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Babesia 2012 Treatment Update

Do you wonder what are the best current treatments for Babesia?

Do you feel that we need new and better options to heal you?

Are you aware new Babesia species are being found for which no test exists for their species?

Below are a vast range of science articles to start a basic reading of treatments for Babesia. In the coming months, I will be doing an updated treatment textbook based on a vast number of articles.

I wish you see some of the hopeful pearls and ideas these fine researchers have published.

I hope you find your healing and healers devoted to ongoing aggressive learning.

Dr. J

1. Pediatrics. 2011 Oct;128(4):e1019-24. Epub 2011 Sep 2.

Clinical presentation and treatment of transfusion-associated babesiosis in premature infants.

Simonsen KA, Harwell JI, Lainwala S.

Pediatric Infectious Diseases, University of Nebraska Medical Center, 982162 Nebraska Medical Center, Omaha, Nebraska 68198-2162, USA.

We review here 7 cases of neonatal transfusion-associated babesiosis at a NICU in the northeast United States. Transfusion from 2 infected units of blood resulted in the 7 cases described. The clinical presentation was highly variable in this cohort; the extremely low birth weight neonates were the most severely affected. Antibiotic therapy was effective in neonates with mild and asymptomatic infection; however, double-volume exchange blood transfusion with prolonged multidrug treatment was required for the 2 most severe cases. The risk of Babesia microti infection is not eliminated through current blood-bank practices. Neonatologists in endemic areas should have a high index of suspicion for babesiosis in premature infants exposed to blood transfusions.

PMID: 21890833 [PubMed - indexed for MEDLINE]

2. Curr Issues Mol Biol. 2011 Jul 26;14(1):9-26. [Epub ahead of print]

Ribonucleotide Reductase as a Target to Control Apicomplexan Diseases.

Munro JB, Silva JC.

Department of Microbiology and Immunology and Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD 21201, USA.

Malaria is caused by species in the apicomplexan genus Plasmodium, which infect hundreds of millions of people each year and kill close to one million. While malaria is the most notorious of the apicomplexan-caused diseases, other members of eukaryotic phylum Apicomplexa are responsible for additional, albeit less well-known, diseases in humans, economically important livestock, and a variety of other vertebrates. Diseases such as babesiosis (hemolytic anemia), theileriosis and East Coast Fever, cryptosporidiosis, and toxoplasmosis are caused by the apicomplexans Babesia, Theileria, Cryptosporidium and Toxoplasma, respectively. In addition to the loss of human life, these diseases are responsible for losses of billions of dollars annually. Hence, the research into new drug targets remains a high priority. Ribonucleotide reductase (RNR) is an essential enzyme found in all domains of life. It is the only means by which de novo synthesis of deoxyribonucleotides occurs, without which DNA replication and repair cannot proceed. RNR has long been the target of antiviral, antibacterial and anti-cancer therapeutics. Herein, we review the chemotherapeutic methods used to inhibit RNR, with particular emphasis on the role of RNR inhibition in Apicomplexa, and in light of the novel RNR R2_e2 subunit recently identified in apicomplexan parasites.

PMID: 21791713 [PubMed - as supplied by publisher]

3. Ticks Tick Borne Dis. 2011 Mar;2(1):55-61. Epub 2011 Jan 26.

A campaign to eradicate bovine babesiosis from New Caledonia.

Barré N, Happold J, Delathière JM, Desoutter D, Salery M, de Vos A, Marchal C, Perrot R, Grailles M, Mortelecque A.

Institut Agronomique néo-Calédonien/Centre de Coopération Internationale en Recherche Agronomique pour le Développement (IAC/CIRAD), New Caledonia, France.

In December 2007, Babesia bovis was introduced to New Caledonia through the importation of cattle that had been vaccinated with a live tick fever (babesiosis and anaplasmosis) vaccine. Although the tick Rhipicephalus (Boophilus) microplus is common in New Caledonia, the territory had previously been free of tick-borne diseases of cattle. This paper describes the initial extent of the outbreak, the measures and rationale for disease control, and the progress to date of the eradication campaign. Initially, 22 properties were affected involving approximately 2300 cattle in 'high risk' zones and 1600 in adjoining 'suspect' zones. Rather than slaughtering infected herds or attempting to eliminate the tick vector, the campaign was based on quarantine of affected properties, and aggressive tick control in conjunction with 3-monthly treatments of the high risk cattle with the antiprotozoal drug imidocarb dipropionate. Subsequent surveillance by ELISA and PCR showed a progressive and dramatic decline in seroprevalence among infected herds and the absence of new infections. All 22 properties were considered to be free of Babesia within 12 months of the start of the disease control program. These results indicate that the strategy was effective in eliminating Babesia from infected herds and feasible as an eradication strategy on a moderately large scale. Unfortunately, early in the campaign, babesiosis spread to a herd of feral cattle on a property in the 'suspect' zone, and this reservoir of infection subsequently resulted in the infection (or reinfection) of cattle on several neighbouring commercial farms. The eradication campaign in New Caledonia is currently focussed on destocking the feral cattle - extensive surveillance suggests that this is the only remaining nidus of infection.

2010 Elsevier GmbH. All rights reserved.

PMID: 21771538 [PubMed - in process]

4. Am J Med. 2011 Sep;124(9):800-5. Epub 2011 Jun 16.

Transfusion-transmitted babesiosis in an immunocompromised patient: a case report and review.

Wudhikarn K, Perry EH, Kemperman M, Jensen KA, Kline SE.

Department of Medicine, University of Minnesota, Minneapolis, USA.

Babesiosis is a tick- and transfusion-borne disease caused by intraerythrocytic Babesia parasites. In 2009, a 61-year-old Minnesota woman with chronic lymphocytic leukemia and a history of recent chemotherapy and numerous blood transfusions for gastrointestinal bleeding became febrile and anemic 12 days postsplenectomy. Babesia were visualized on blood smears, confirmed by polymerase chain reaction as B. microti. She developed respiratory failure despite initiation of clindamycin and quinine, and required 12 weeks of azithromycin and atovaquone before blood smear and polymerase chain reaction findings were negative. Serologic evidence of B. microti infection was identified in 1 associated blood donor and 1 other recipient of that donor's blood. Babesia infection can be asymptomatic or cause mild to fulminant disease resulting in multiorgan failure or death. Patients with advanced age, asplenia, or other immune compromise are at risk for severe babesiosis and may require prolonged treatment to eradicate parasitemia. Incidence of transfusion-transmitted babesiosis has increased over the past decade.

Copyright © 2011 Elsevier Inc. All rights reserved.

PMID: 21683324 [PubMed - indexed for MEDLINE]

5. Wiad Parazytol. 2011;57(2):77-81.

Babesia spp. infections transmitted through blood transfusion.

Siński E, Welc-Faleciak R, Pogłód R.

Department of Parasitology, Faculty of Biology, University of Warsaw, 1 Miecznikowa Street, 02-096 Warsaw.

Babesiosis in humans is caused by infection with various species of Babesia (Apicomplexa, Piroplasmida), mainly transmitted by an arthropod vector--Ixodes spp. ticks. This review will focus on blood transfusion as another mode of Babesia transmission, especially in endemic areas, as well as the impact of human babesiosis on transfusion medicine.

PMID: 21682090 [PubMed - indexed for MEDLINE]

6. J Signal Transduct. 2011;2011:971968. Epub 2011 Feb 27.

Parasite mitogen-activated protein kinases as drug discovery targets to treat human protozoan pathogens.

Brumlik MJ, Pandeswara S, Ludwig SM, Murthy K, Curiel TJ.

Department of Medicine, School of Medicine, and Program in Immunology and Microbiology, Graduate School of Biomedical Sciences, University of Texas Health Science Center, San Antonio, TX 78229, USA.

Protozoan pathogens are a highly diverse group of unicellular organisms, several of which are significant human pathogens. One group of protozoan pathogens includes obligate intracellular parasites such as agents of malaria, leishmaniasis, babesiosis, and toxoplasmosis. The other group includes extracellular pathogens such as agents of giardiasis and amebiasis. An unfortunate unifying theme for most human protozoan pathogens is that highly effective treatments for them are generally lacking. We will review targeting protozoan mitogen-activated protein kinases (MAPKs) as a novel drug discovery approach towards developing better therapies, focusing on Plasmodia, Leishmania, and Toxoplasma, about which the most is known.

PMCID: PMC3100106 PMID: 21637385 [PubMed]

7. Emerg Infect Dis. 2011 May;17(5):843-7.

Babesiosis in Lower Hudson Valley, New York, USA.

Joseph JT, Roy SS, Shams N, Visintainer P, Nadelman RB, Hosur S, Nelson J, Wormser GP.

Division of Infectious Diseases, New York Medical College, Valhalla, New York 10595, USA.

Although Lyme disease has been endemic to parts of the Lower Hudson Valley of New York, United States, for >2 decades, babesiosis has emerged there only since 2001. The number of Lower Hudson Valley residents in whom babesiosis was diagnosed increased 20-fold, from 6 to 119 cases per year during 2001-2008, compared with an ≈1.6-fold increase for the rest of New York. During 2002-2009, a total of 19 patients with babesiosis were hospitalized on 22 occasions at the regional tertiary care center. Concurrent conditions included advanced age, malignancies, splenectomy, and AIDS. Two patients acquired the infection from blood transfusions and 1 from perinatal exposure, rather than from a tick bite. One patient died. Clinicians should consider babesiosis in persons with fever and hemolytic anemia who have had tick exposure or have received blood products.

PMID: 21529393 [PubMed - indexed for MEDLINE]

8. J Vasc Interv Radiol. 2011 May;22(5):732-4.

Spontaneous splenic rupture secondary to Babesia microti infection: treatment with splenic artery embolization.

Reis SP, Maddineni S, Rozenblit G, Allen D.

PMID: 21514529 [PubMed - indexed for MEDLINE]

9. Conn Med. 2011 Mar;75(3):143-6.

Successful conservative treatment of spontaneous splenic rupture secondary to Babesiosis: a case report and literature review.

Abbas HM, Brenes RA, Ajemian MS, Scholand SJ.

The Stanley J. Dudrick Department of Surgery, Saint Mary's Hospital, Waterbury, USA.

Babesiosis is caused by a protozoan parasite of the genus Babesia. In the United States, the usual infective organism Babesia microti, is most commonly transmitted through the bite of an infected Ixodestick. While the majority of patients exhibit sub-clinical signs and symptoms, significant illness can result. Spontaneous splenic rupture is a life-threatening complication of some viral and protozoan infections. We present a case of Babesiosis with spontaneous splenic rupture in which conservative management with blood transfusions and hospital-based care were successful, and the patient was spared splenectomy. To our knowledge, this is the first reported case treated without splenectomy. Our successful experience suggests conservative management may be appropriate for some patients.

PMID: 21500704 [PubMed - indexed for MEDLINE]

10. Am Surg. 2011 Mar;77(3):345-7.

Babesiosis as a cause of fever in patients undergoing a splenectomy.

Wormser GP, Lombardo G, Silverblatt F, El Khoury MY, Prasad A, Yelon JA, Sanda A, Karim S, Coku L, Savino JA.

Department of Medicine, New York Medical College, Valhalla, New York 10595, USA.

Babesiosis is an emerging infection most commonly acquired from a tick bite. We describe three hospitalized patients with fever attributable to babesiosis after a splenectomy. Splenectomy was done because of splenic enlargement due to unsuspected babesia infection in one patient and because of splenic perforation due to babesiosis in a second patient. The third patient underwent splenectomy for trauma and acquired babesiosis postoperatively from a blood transfusion. Our cases demonstrate the need to be vigilant for babesiosis in patients undergoing splenectomy.

PMID: 21375849 [PubMed - indexed for MEDLINE]

11. Infect Disord Drug Targets. 2011 Feb;11(1):45-56.

Approaches to minimize infection risk in blood banking and transfusion practice.

Lindholm PF, Annen K, Ramsey G.

Department of Pathology, Northwestern University, Feinberg School of Medicine, 303 East Chicago Avenue, Chicago, IL 60611, USA.

The use of blood donor history and state-of-the-art FDA-licensed serological and nucleic acid testing (NAT) assays have greatly reduced the "infectious window" for several transfusion-transmitted pathogens. Currently transmission of human immunodeficiency virus (HIV), Human T-cell Lymphotropic Virus (HTLV), hepatitis viruses and West Nile Virus are rare events. The seroprevalence of cytomegalovirus in the donor population is high and cytomegalovirus infection can cause significant complications for immunocompromised recipients of blood transfusion. Careful use of CMV seronegative blood resources and leukoreduction of blood products are able to prevent most CMV infections in these patients. Currently, bacterial contamination of platelet concentrates is the greatest remaining infectious disease risk in blood transfusion. Specialized donor collection procedures reduce the risk of bacterial contamination of blood products; blood culture and surrogate testing procedures are used to detect potential bacterially contaminated platelet products prior to transfusion. A rapid quantitative immunoassay is now available to test for the presence of lipotechoic acid and lipopolysaccharide bacterial products prior to platelet transfusion. Attention has now turned to emerging infectious diseases including variant Creutzfeldt-Jakob disease, dengue, babesiosis, Chagas' disease and malaria. Challenges are presented to identify and prevent transmission of these agents. Several methods are being used or in development to reduce infectivity of blood products, including solvent-detergent processing of plasma and nucleic acid cross-linking via photochemical reactions with methylene blue, riboflavin, psoralen and alkylating agents. Several opportunities exist to further improve blood safety through advances in infectious disease screening and pathogen inactivation methods.

PMID: 21303341 [PubMed - indexed for MEDLINE]

12. Clin Microbiol Rev. 2011 Jan;24(1):14-28.

Transfusion-transmitted Babesia spp.: bull's-eye on Babesia microti.

Leiby DA.

Transmissible Diseases Department, American Red Cross Holland Laboratory, 15601 Crabbs Branch Way, Rockville, MD 20855, USA.

Babesia spp. are intraerythrocytic protozoan parasites of animals and humans that cause babesiosis, a zoonotic disease transmitted primarily by tick vectors. Although a variety of species or types of Babesia have been described in the literature as causing infection in humans, the rodent parasite Babesia microti has emerged as the focal point of human disease, especially in the United States. Not only has B. microti become established as a public health concern, this agent is increasingly being transmitted by blood transfusion: estimates suggest that between 70 and 100 cases of transfusion-transmitted Babesia (TTB) have occurred over the last 30 years. A recent upsurge in TTB cases attributable to B. microti, coupled with at least 12 fatalities in transfusion recipients diagnosed with babesiosis, has elevated TTB to a key policy issue in transfusion medicine. Despite clarity on a need to mitigate transmission risk, few options are currently available to prevent the transmission of B. microti by blood transfusion. Future mitigation efforts may stress serological screening of blood donors in regionalized areas of endemicity, with adjunct nucleic acid testing during the summer months, when acute infections are prevalent. However, several hurdles remain, including the absence of a licensed blood screening assay and a thorough cost-benefit analysis of proposed interventions. Despite current obstacles, continued discussion of TTB without proactive intervention is no longer a viable alternative.

PMCID: PMC3021205 [Available on 2012/1/1] PMID: 21233506 [PubMed - indexed for MEDLINE]

13. Leuk Res. 2011 Jun;35(6):e77-8. Epub 2010 Dec 24.

Persistent babesiosis in a stem cell transplant recipient.

Lubin AS, Snydman DR, Miller KB.

PMCID: PMC3085102 [Available on 2012/6/1] PMID: 21185598 [PubMed - indexed for MEDLINE]

14. Congenit Heart Dis. 2010 Nov-Dec;5(6):607-13. doi: 10.1111/j.1747-0803.2010.00384.x.

Transfusion-associated babesiosis in a 7-month-old infant after bidirectional Glenn procedure.

Nicholson GT, Walsh CA, Madan RP.

Department of Pediatrics, Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY, USA.

We describe a case of transfusion-associated babesiosis following bidirectional Glenn procedure. This unique case highlights the importance of including babesiosis and other typically vector-borne infections in the differential diagnosis for patients with recent blood transfusions and fever without obvious source.

© 2010 Copyright the Authors. Congenital Heart Disease © 2010 Wiley Periodicals, Inc.

PMID: 21106022 [PubMed - indexed for MEDLINE]

15. J Clin Apher. 2010;25(6):358-61. doi: 10.1002/jca.20262. Epub 2010 Sep 7.

Autoimmunity in transfusion babesiosis: a spectrum of clinical presentations.

Herman JH, Ayache S, Olkowska D.

Transfusion Medicine Department, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania 19107, USA.

Transfusion-acquired babesiosis can be an asymptomatic or self-limited febrile hemolytic illness in a healthy host. A persistent, relapsing, and/or fulminant course with the development of life-threatening complications may be seen in immunocompromised or splenectomized patients. As in malaria, erythrocyte parasitemia is often associated with nonimmune hemolysis, and can be treated with erythrocytapheresis. Just as warm autoantibodies have been reported in malaria infection, the development of autoantibody-mediated immune hemolysis has been reported in babesiosis. We treated a previously healthy male with multiple injuries from a motor vehicle accident necessitating massive transfusion. Late in the hospitalization, his blood smear revealed Babesia microti, confirmed by PCR study and serology. This was eventually traced to a unit of blood from an asymptomatic blood donor that was transfused during his initial trauma care. Specific antibiotic therapy was begun, and severe hemolysis from a high parasite burden required red blood cell exchange which led to rapid abatement of the hemolysis. He had a positive DAT (IgG with a pan-reactive eluate) but no serum autoantibody. This persisted for 10 days following cessation of hemolysis, and became negative while still on antibiotics while his parasite burden became undetectable. Reports of autoimmunity associated with community acquired babesiosis often have severe hemolysis from their autoantibodies, but our case shows that autoantibodies may also follow transfusion-acquired babesiosis. The nature of the autoantigen is unknown.

Copyright © 2010 Wiley-Liss, Inc.

PMID: 20824620 [PubMed - indexed for MEDLINE]

16. Transfusion. 2010 Oct;50(10):2080-99.

Transfusion-associated infections: 50 years of relentless challenges and remarkable progress.

Perkins HA, Busch MP.

Blood Systems Research Institute, Blood Centers of the Pacific, University of California, San Francisco, California 94118, USA.

PMID: 20738828 [PubMed - indexed for MEDLINE]

17. Exp Parasitol. 2011 Jan;127(1):287-93. Epub 2010 Jun 25.

Babesia microti: molecular and antigenic characterizations of a novel 94-kDa protein (BmP94).

Ooka H, Terkawi MA, Goo YK, Luo Y, Li Y, Yamagishi J, Nishikawa Y, Igarashi I, Xuan X.

National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido 080-8555, Japan.

A novel gene, BmP94, encoding 94-kDa protein of Babesia microti was identified by immunoscreening of the cDNA expression library. The full-length of BmP94 was expressed in Escherichia coli (rBmP94), which resulted in insoluble form with low yield, and the truncated hydrophilic C-terminus region of the gene was expressed as a soluble protein (rBmP94/CT) with improved productivity. Antiserum raised against rBmP94/CT recognized the 94-kDa native protein in the parasite extract by Western blot analysis. Next, an ELISA using rBmP94/CT was evaluated for diagnostic use, and it demonstrated high sensitivity and specificity when tested with the sera from mice experimentally infected with B. microti and closely related parasites. Moreover, the immunoprotective property of rBmP94/CT as a subunit vaccine was evaluated in BALB/c mice against a B. microti challenge, but no significant protection was observed. Our data suggest that the immunodominant antigen BmP94 could be a promising candidate for diagnostic use for human babesiosis.

Copyright © 2010 Elsevier Inc. All rights reserved.

PMID: 20599995 [PubMed - indexed for MEDLINE]

18. J S Afr Vet Assoc. 2009 Dec;80(4):215-9.

The intravenous pharmacokinetics of diminazene in healthy dogs.

Naidoo V, Mulders MS, Swan GE.

Department of Paraclinical Sciences, Faculty of Veterinary Science, University of Pretoria, Private Bag X04, Onderstepoort, 0110 South Africa.

Diminazene remains one of South Africa's most commonly used antiprotozoal agents for the management of babesiosis in dogs. Although the drug has been on the market for over 40 years, its intravenous pharmacokinetics are poorly known. To better understand the pharmacokinetics of the drug Berenil, it was reconstituted in sterile water and administered intravenously to 6 adult German shepherd dogs. All 6 dogs demonstrated the previously described secondary peak in the plasma concentration versus time profile. The plasma pharmacokinetics for diminazene are described by both non-compartmental and compartmental models. From non-compartmental analysis, the area under curve to the last sample point (AUClast), clearance (CL) and volume of distribution (Vz) were 4.65 +/- 1.95 ng/ml/h, 0.77 +/- 0.18 l/kg/h and 2.28 +/- 0.60 l/kg, respectively. For compartmental modelling, the plasma concentrations were fitted to both a 2-compartmental open model and a recirculatory enterohepatic model. From the recirculation model, the rate of release and re-entry into the central compartment varied markedly with the rate of release from the gall bladder (Ttom) being estimated at 27 +/- 20.90 h. Once released, drug re-entry into the central compartment was variable at 9.70 +/- 5.48 h. With normal biliary excretion time being about 2 h, this indicates that the redistribution cannot be occurring physiologically from the bile. Although it was not possible to identify the site from which sequestration and delayed release is occurring, it is believed that it is most likely from the liver. The study therefore showed that the secondary peak described for the pharmacokinetics of intramuscular administered diminazene in the dog is not related to biphasic absorption.

PMID: 20458860 [PubMed - indexed for MEDLINE]

19. Acta Vet Scand. 2010 Apr 24;52:27.

Use of a doxycycline-enrofloxacin-metronidazole combination with/without diminazene diaceturate to treat naturally occurring canine babesiosis caused by Babesia gibsoni.

Lin MY, Huang HP.

Section of Small Animal Internal Medicine, National Taiwan University Veterinary Hospital, Taipei, Taiwan.

Canine babesiosis is an important worldwide, tick-borne disease caused by hemoprotozoan parasites of the genus Babesia. Babesia gibsoni is the predominant species that causes canine babesiosis in Taipei, Taiwan. It is a small pleomorphic intraerythrocytic parasite that can cause erythrocyte destruction and hemolytic anemia. Efficacy of oral administration of a doxycycline-enrofloxacin-metronidazole combination with and without injections of diminazene diaceturate in the management of naturally occurring canine babesiosis caused by B. gibsoni was evaluated retrospectively. The overall efficacy of this combination of doxycycline-enrofloxacin-metronidazole in conjunction with and without administration of diminazene diaceturate was 85.7% and 83.3%, respectively; with a mean recovery time of 24.2 and 23.5 days, respectively. Concomitant use of intramuscular diminazene diaceturate may not improve the efficacy of a doxycycline-enrofloxacin-metronidazole combination in management of canine babesiosis caused by B. gibsoni.

PMCID: PMC2874561 PMID: 20416095 [PubMed - indexed for MEDLINE]

20. Clin Vaccine Immunol. 2010 Jun;17(6):954-65. Epub 2010 Apr 21.

Cloning and characterization of the acidic ribosomal protein P2 of Cryptosporidium parvum, a new 17-kilodalton antigen.

Priest JW, Kwon JP, Montgomery JM, Bern C, Moss DM, Freeman AR, Jones CC, Arrowood MJ, Won KY, Lammie PJ, Gilman RH, Mead JR.

Division of Parasitic Diseases, Centers for Disease Control and Prevention, 4770 Buford Highway, NE, Mail Stop F-13, Atlanta, GA 30341, USA.

Cryptosporidium infection is commonly observed among children and immunocompromised individuals in developing countries, but large-scale outbreaks of disease among adults have not been reported. In contrast, outbreaks of cryptosporidiosis in the United States and Canada are increasingly common among patients of all ages. Thus, it seems likely that residents of regions where Cryptosporidium is highly endemic acquire some level of immunity, while residents of the developed world do not. A new immunodominant Cryptosporidium parvum antigen in the 15- to 17-kDa size range was identified as the Cryptosporidium parvum 60S acidic ribosomal protein P2 (CpP2). We developed a recombinant protein-based enzyme-linked immunosorbent assay for serologic population surveillance for antibodies that was 89% sensitive and 92% specific relative to the results of the large-format Western blot assay. The human IgG response is directed almost exclusively toward the highly conserved, carboxy-terminal 15 amino acids of the protein. Although IgG antibody cross-reactivity was documented with sera from patients with acute babesiosis, the development of an anti-CpP2 antibody response in our Peru study population correlated better with Cryptosporidium infection than with infection by any other parasitic protozoan. In Haiti, the prevalence of antibodies to CpP2 plateaus at 11 to 20 years of age. Because anti-CpP2 IgG antibodies were found only among residents of countries in the developing world where Cryptosporidium infection occurs early and often, we propose that this response may be a proxy for the intensity of infection and for acquired immunity.

PMCID: PMC2884433 PMID: 20410328 [PubMed - indexed for MEDLINE]

21. Transfusion. 2010 Feb;50(2):290-1.

Transfusion medicine illustrated. The expanding range and severity of babesiosis.

Weld ED, Eimer KM, Saharia K, Orenstein A, Hess JR.

University of Maryland Medical Center, Baltimore, Maryland, USA.

PMID: 20233358 [PubMed - indexed for MEDLINE]

22. Vet Parasitol. 2010 May 28;170(1-2):30-6. Epub 2010 Feb 18.

Serological responses to Babesia bovis vaccination in cattle previously infected with Babesia bigemina.

Combrink MP, Troskie PC, Du Plessis F, Latif AA.

Parasites, Vectors and Vector-borne Diseases (PVVD), ARC-Onderstepoort Veterinary Institute, Private Bag X05, 100 Old Soutpan Road, Onderstepoort 0110, Pretoria, South Africa.

Serological responses of field cattle (260) on a farm in KwaZulu-Natal, South Africa were determined before and after vaccination with the commercial Babesia bovis live-blood vaccine, using the indirect fluorescent antibody test (IFAT). All the cattle tested negative for B. bovis antibodies before vaccination while 83% of them had significant antibody titres (>or=1/80) to Babesia bigemina, indicating a high degree of natural exposure to the latter parasite. By Day 60 post-vaccination only 53% of the cattle had seroconverted to B. bovis. This raised the question as to why only half of the vaccinated cattle had seroconverted. The possibility of previous exposure to B. bigemina infection interfering with the development of detectable antibodies to B. bovis was therefore investigated under controlled conditions. It was found that simultaneous vaccination with B. bigemina and B. bovis (n=6), and B. bigemina vaccination followed by B. bovis vaccination (n=12), had no effect on the animals' immune responses to B. bovis vaccination. All of these cattle developed a significant antibody response. However, only 58% of cattle (n=12) which had previously been inoculated with the B. bigemina field isolate, obtained from the trial farm, seroconverted (>or=1/80) after B. bovis vaccination, yet parasites for B. bovis could be demonstrated microscopically in all of the animals in this group. These findings confirmed the serology results from the field trial. When challenged with a B. bovis field isolate, cattle in this group did not show clinical reactions compared with an unvaccinated control group. The judicious use of IFAT to establish vaccination success obtained with the current South African B. bovis vaccine is indicated.

(c) 2010 Elsevier B.V. All rights reserved.

PMID: 20207488 [PubMed - indexed for MEDLINE]

23. Transfusion. 2009 Dec;49(12):2548-50.

The problem of transfusion-transmitted babesiosis.

Young C, Krause PJ.

PMID: 20163687 [PubMed - indexed for MEDLINE]

24. Clin Infect Dis. 2010 Feb 1;50(3):381-6.

Emergence of resistance to azithromycin-atovaquone in immunocompromised patients with Babesia microti infection.

Wormser GP, Prasad A, Neuhaus E, Joshi S, Nowakowski J, Nelson J, Mittleman A, Aguero-Rosenfeld M, Topal J, Krause PJ.

Divisions of 1Infectious Diseases, Departments of Medicine and 3Pathology, New York Medical College, Valhalla, NY 10595, USA.

BACKGROUND: Babesiosis is an emerging tickborne malaria-like infection principally caused by Babesia microti. This infection typically resolves either spontaneously or after administration of a 7-10-day course of azithromycin plus atovaquone or clindamycin plus quinine. Although certain highly immunocompromised patients may respond suboptimally to these drug regimens, unlike the situation with malaria there has been no reported evidence that the cause of treatment failure is infection with drug-resistant strains of B. microti. METHODS: Emergence of drug resistance in B. microti was defined as the development of a microbiologic relapse (recurrent parasitemia or a marked increase in parasitemia) in association with both clinical and laboratory abnormalities indicative of active babesiosis in a patient after 28 days of uninterrupted antibabesia drug therapy and while still receiving treatment. RESULTS: The clinical case histories of 3 highly immunocompromised patients who received a subcurative course of azithromycin-atovaquone associated with the eventual development of resistance to this drug regimen are described. One of the 3 patients died of complications related to babesiosis. CONCLUSIONS: B. microti may become resistant to azithromycin-atovaquone during the treatment of babesiosis with this combined drug regimen in highly immunocompromised patients. Although research is needed to determine the optimal therapy for highly immunocompromised patients with babesiosis, reducing the level of immunosuppression when possible would appear to be a desirable strategy.

PMID: 20047477 [PubMed - indexed for MEDLINE]

25. Transfusion. 2010 May;50(5):1019-27. Epub 2009 Dec 18.

Evaluation of the Mirasol pathogen [corrected] reduction technology system against Babesia microti in apheresis platelets and plasma.

Tonnetti L, Proctor MC, Reddy HL, Goodrich RP, Leiby DA.

Transmissible Diseases Department, Jerome H. Holland Laboratory, American Red Cross, Rockville, Maryland 20855, USA.

Erratum in Transfusion. 2010 Jul;50(7):1594.

BACKGROUND: Babesia microti is an intraerythrocytic parasite, transmitted naturally to humans by infected ixodid ticks, that causes babesiosis. In recent years, B. microti has been identified as a growing public health concern that has also emerged as a critical blood safety issue in the absence of appropriate interventions to reduce transmission by blood transfusion. Thus, we evaluated the ability of the Mirasol pathogen reduction technology (PRT; CaridianBCT), which uses riboflavin (RB) and ultraviolet (UV) light, to diminish the presence of B. microti in apheresis plasma and platelets (PLTs). STUDY DESIGN AND METHODS: Apheresis plasma and PLT units were spiked with B. microti-infected hamster blood and subsequently treated using the Mirasol PRT system. Control and experimental samples were collected at different stages during the treatment process and injected into hamsters to detect the presence of viable parasites. Four weeks postinoculation, hamster blood was tested for B. microti infection by blood smear and real-time polymerase chain reaction analysis. RESULTS: None of the blood smears from animals injected with samples from PRT-treated plasma or PLT units were positive by microscopy, while all the non-PRT-treated plasma and PLT units were demonstrably parasitemic. Parasite load reduction in hamsters ranged between 4 and 5 log in all PRT-treated units compared to untreated controls. CONCLUSION: The data indicate that the use of RB and UV light efficiently reduces the presence of viable B. microti in apheresis plasma and PLT products, thereby reducing the risk of transfusion-transmitted Babesia potentially associated with these products. Based on this observed "proof of principle," future studies will determine the efficacy of the Mirasol PRT in whole blood.

PMID: 20030791 [PubMed - indexed for MEDLINE]

26. Transfusion. 2009 Dec;49(12):2583-7. Epub 2009 Nov 9.

A fatal case of transfusion-transmitted babesiosis in the State of Delaware.

Zhao Y, Love KR, Hall SW, Beardell FV.

Department of Pathology and the Department of Medicine, Christiana Care Health System, Newark, Delaware 19718, USA.

BACKGROUND: Most cases of human babesiosis in North America are caused by Babesia microti, which is endemic in the northeastern and upper midwestern United States. Although the disease is usually transmitted by a tick bite, there has been an increase in the number of transfusion-transmitted cases reported. We describe a fatal case of transfusion-transmitted babesiosis in a nonendemic state, Delaware. CASE REPORT: The patient was a 43-year-old Caucasian woman with history of transfusion-dependent Diamond-Blackfan syndrome, hepatitis C, and splenectomy. She was admitted initially for presumptive pneumonia. The next day, a routine examination of the peripheral blood smears revealed numerous intraerythrocytic ring forms, consistent with Babesia. The parasitemia was approximately 5% to 6%. The diagnosis was confirmed by positive polymerase chain reaction (PCR) for B. microti DNA and high titer of antibody to B. microti (1:2048). Despite aggressive therapy including clindamycin and quinine antibiotics, the patient expired 3 days after admission. Subsequently, 13 blood donors were tested for B. microti. All tested donors were negative by PCR. However, one donor living in New Jersey had a significant elevated B. microti antibody titer (1:1024). CONCLUSIONS: We believe that this is the first reported case of transfusion-transmitted babesiosis in Delaware, a nonendemic state. Our case illustrates that clinicians should consider babesiosis in the differential diagnosis of immunocompromised patients who have fever and recent transfusion history, even in areas where babesiosis is not endemic. It also demonstrates the need for better preventive strategies including more sensitive, specific, and rapid blood donor screening tests to prevent transfusion-transmitted babesiosis.

PMID: 19906041 [PubMed - indexed for MEDLINE]

27. J S Afr Vet Assoc. 2009 Jun;80(2):87-91.

C-reactive protein in canine babesiosis caused by Babesia rossi and its association with outcome.

Köster LS, Van Schoor M, Goddard A, Thompson PN, Matjila PT, Kjelgaard-Hansen M.

Department of Companion Animal Clinical Studies, Faculty of Veterinary Science, University of Pretoria, Private Bag X04, Onderstepoort 0110, South Africa.

C-reactive protein (CRP) is a positive major acute-phase protein in dogs and can be used as a predictive marker for risk of disease and to monitor the response to treatment. Increased concentrations in certain diseases are associated with poor outcome. This cross-sectional, observational study of 75 dogs naturally infected with Babesia rossi was designed to examine the relationship between outcome and CRP concentration at admission and the magnitude of CRP change 24 hours after admission. Diagnosis was confirmed by polymerase chain reaction (PCR) and reverse line blot. CRP concentrations were determined by an automated human CRP Turbidometric Immunoassay, previously validated for use in dogs. There was no significant difference in mean CRP concentration between survivors (n = 57), 107.5 +/- 49.5 mg/l and non-survivors (n = 11), 122.1 +/- 64.6 mg/l at admission and using the exact logistic regression, adjusting for age and sex, there was no association with outcome (P = 0.53). Multiple regression analysis failed to show a significant relationship between admission CRP concentration and number of days of hospitalisation in the survivors, adjusting for age and sex (P = 0.65). Similarly, no significance was found in the relationship between the magnitude of change in CRP concentration 24 hours after admission, and the number of days of hospitalisation in survivors, (P = 0.34). It is concluded that CRP concentration, as a measure of the acute phase response, is not associated with outcome in canine babesiosis, and inflammation is unlikely to be the only cause of severity of disease.

PMID: 19831269 [PubMed - indexed for MEDLINE]

28. J S Afr Vet Assoc. 2009 Jun;80(2):75-8.

Comparison of Babesia rossi and Babesia canis isolates with emphasis on effects of vaccination with soluble parasite antigens: a review.

Schetters TP, Moubri K, Cooke BM.

Microbiology R&D Department, Intervet/Schering-Plough Animal Health, Boxmeer, The Netherlands.

Babesia canis and B. rossi are large Babesia species that infect dogs and cause clinical disease. The spectrum of disease is highly diverse with either parasite, but upon evaluation of field cases it has been suggested that in general B. rossi is more virulent than B. canis. This difference was also found in experimental infections using B. canis and B. rossi isolates and appeared to be related to a difference in parasitaemia. Whether this difference reflects the essential difference between B. canis and B. rossi species in general, or merely reflects the variability in virulence of individual isolates cannot be discerned. Comparative in vitro and in vivo studies revealed a number of qualitative differences between the B. canis and B. rossi isolates studied; however, more research is required to determine any causal relationship between in vitro and in vivo characteristics. Vaccination with a bivalent vaccine (containing soluble parasite antigen [SPA] from supernatants of in vitro cultures of B. canis and B. rossi) induced protection against clinical babesiosis upon challenge infection with either parasite. The dynamics of parasitaemia upon challenge infection of vaccinated animals indicated a biological difference between the B. canis and B. rossi isolates studied. Vaccinated dogs that were challenged with B. rossi parasites (2 isolates tested) effectively controlled parasitaemia. By contrast, in vaccinated dogs that were challenged with B. canis isolates (2 isolates tested) there was little or no effect on parasitaemia but levels of SPA in plasma were reduced. Apparently the nature of vaccine-induced immunity differs with respect to the challenge species.

PMID: 19831266 [PubMed - indexed for MEDLINE]

29. Jpn J Vet Res. 2009 Aug;57(2):101-8.

Preliminary studies on the effects of orally-administered Transforming Growth Factor-beta on protozoan diseases in mice.

Namangala B, Inoue N, Sugimoto C.

National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Japan.

Transforming growth factor beta-1 (TGF-beta1) is a pleiotropic cytokine with both pro- and antiinflammatory properties, depending on its environment and concentration. The present study evaluated the effects of orally-delivered TGF-beta1 on mice parenterally-infected with various protozoan parasites. We report that while orally-administered TGF-beta1 seems to confer partial protection against murine chronic babesiosis and acute trypanosomosis, no beneficial clinical effects were observed against acute babesiosis, malaria or toxoplasmosis. Taken together, these preliminary data suggest that the systemic effects conferred by exogenous TGF-beta1 could be parasite species-specific. The variations in different parasitic infections could be due to (i) intrinsic differences between parasite species and/or strains in their ability to induce production of immunosuppressive molecules and/or (ii) differences in mechanisms governing host protection against different parasitic infections.

PMID: 19827745 [PubMed - indexed for MEDLINE]

30. Transfusion. 2009 Dec;49(12):2759-71. Epub 2009 Oct 10.

Transfusion-transmitted babesiosis in the United States: summary of a workshop.

Gubernot DM, Nakhasi HL, Mied PA, Asher DM, Epstein JS, Kumar S.

Office of Blood Research and Review, Center for Biologics Evaluation and Research, US Food and Drug Administration, Rockville, Maryland 20852, USA.

Infections of humans with intraerythrocytic parasites of the genus Babesia can be locally prevalent in diverse regions of the United States. Transfusion of blood and blood products collected from donors infected with Babesia may result in a serious illness that can be fatal. In September 2008, the Food and Drug Administration organized a public workshop to discuss the various aspects of transfusion-transmitted babesiosis in the United States including the possible strategies to identify and defer blood donors who may have been infected with Babesia. Discussions were also held on the biology, pathogenesis, and epidemiology of Babesia species. In this article, we summarize the scientific presentations and panel discussions that took place during the workshop.

PMID: 19821952 [PubMed - indexed for MEDLINE]

31. Transfusion. 2009 Dec;49(12):2574-82. Epub 2009 Oct 10.

Seroprevalence of Babesia microti in blood donors from Babesia-endemic areas of the northeastern United States: 2000 through 2007.

Johnson ST, Cable RG, Tonnetti L, Spencer B, Rios J, Leiby DA.

Transmissible Diseases Department, Jerome H Holland Laboratory, and Biomedical Services, American Red Cross, Farmington, Connecticut 06032, USA.

BACKGROUND: Current estimates of 70 cases of transfusion-transmitted Babesia microti, with 12 associated deaths, suggest that Babesia is a growing blood safety concern. The extent of Babesia infections among blood donors has not been well defined. To determine how common exposure to B. microti is among blood donors, a seroprevalence study was undertaken in the American Red Cross Northeast Division. STUDY DESIGN AND METHODS: Blood donations at selected blood drives in Connecticut and Massachusetts (2000 through 2007) were tested for the presence of immunoglobulin (Ig)G antibodies to B. microti using immunofluorescence assay. Geographic and temporal trends of B. microti seroprevalence were estimated for donor's zip code of residence. RESULTS: Overall, a 1.1% seroprevalence was identified in Connecticut, with the highest levels found in two Southeastern counties (Middlesex and New London). Observed seroprevalence for offshore islands of Massachusetts was 1.4%. Seropositive donations were identified from donors residing in all eight counties in Connecticut and three counties in Massachusetts. Although a seasonal peak was found between July and September, seropositive donations were identified in every month of the year. CONCLUSIONS: Foci of statistically higher B. microti seroprevalence among blood donors were observed; however, B. microti transfusion transmission risk exists for blood collected throughout Connecticut and portions of Massachusetts. Similarly, a seasonal peak was identified; nevertheless, seropositive donations were found year-round. Thus, geographic and/or seasonal exclusion methods are insufficient to fully safeguard the blood supply from Babesia transmission. Steps should be taken to reduce risk of transfusion-transmitted B. microti, perhaps through implementation of year-round, regional testing.

PMID: 19821951 [PubMed - indexed for MEDLINE]

32. Transfusion. 2009 Dec;49(12):2564-73. Epub 2009 Sep 16.

Transfusion-transmitted babesiosis in Rhode Island.

Asad S, Sweeney J, Mermel LA.

Division of Infectious Diseases, Department of Medicine, and Transfusion Medicine, Rhode Island Hospital, Providence, RI 02903, USA.

BACKGROUND: Babesiosis is caused by an intraerythrocytic protozoan transmitted by ticks. Blood transfusion is another mode of transmission. STUDY DESIGN AND METHODS: This was a retrospective study based on babesiosis cases reported to the Rhode Island Department of Health between 1999 and 2007. Additional cases were also identified. RESULTS: Twenty-one cases of transfusion-transmitted babesiosis (TTB) were identified from 1999 through 2007. From 2005 through 2007, the incidence approached one case per 9000 units of blood transfused. One of 21 (5%) TTB cases was diagnosed in July, in sharp contrast to 65 of 152 (43%) of the total babesiosis cases diagnosed during July in Rhode Island. Many cases were identified when a complete blood count with a differential was routinely requested and parasites were noted by laboratory technologists. Most patients with TTB had underlying conditions known to predispose to symptomatic infection. CONCLUSION: Blood transfusion is an important mode of Babesia transmission. The current screening method of omitting donors with a history of babesiosis may be effective in preventing some, but not all, cases of TTB and current processing of blood products does not eradicate this parasite. Thus, a better screening test is needed. Alternatively, pathogen reduction technology could be utilized to prevent this mode of transmission.

PMID: 19761547 [PubMed - indexed for MEDLINE]

33. Exp Parasitol. 2009 Dec;123(4):296-301. Epub 2009 Aug 25.

Immunogenicity and growth inhibitory efficacy of the prime-boost immunization regime with DNA followed by recombinant vaccinia virus carrying the P29 gene of Babesia gibsoni in dogs.

Fukumoto S, Tamaki Y, Igarashi I, Suzuki H, Xuan X.

National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido 080-8555, Japan.

In recent studies, heterologous prime-boost approaches, employing plasmid DNA and viral vector pathogen-delivering sequences, have been considered an effective protection strategy for intracellular parasite infections. Here, we evaluated the efficacy of such a strategy against the canine Babesia gibsoni infection. The DNA (pCAGGS-P29) and recombinant vaccinia virus (vvP29) both encoding the P29 of B. gibsoni were used in this study. The dogs were immunized 3 times with priming DNA and boosted once with recombinant virus. The dogs immunized with P29 developed a significant level of IgG2 antibody against P29. The response was strongly boosted by the inoculation of vvP29. The peripheral IFN-gamma responses of the dogs immunized with P29 were significantly higher than those of controls after the parasite inoculation. Moreover, the P29 immunized group showed a significantly low level of parasitemia. In conclusion, this study supports the efficacy of a prime-boost strategy for dogs against canine B. gibsoni infection.

PMID: 19712674 [PubMed - indexed for MEDLINE]

34. J Vet Emerg Crit Care (San Antonio). 2009 Feb;19(1):102-12.

A prospective, randomized comparison of Oxyglobin (HB-200) and packed red blood cell transfusion for canine babesiosis.

Zambelli AB, Leisewitz AL.

Department of Companion Animal Clinical Studies, University of Pretoria, Pretoria, South Africa.

OBJECTIVE: To establish the efficacy of Oxyglobin (HB-200) in canine babesiosis and compare it to standard therapy, packed red blood cell transfusion (pRBCT) with respect to improvements in specific parameters of blood gas, acid-base, blood pressure, and subjective evaluations. DESIGN: Prospective, randomized, clinical trial. SETTING: Onderstepoort Veterinary Academic Hospital. ANIMALS: Twelve dogs (8-25 kg) naturally infected with Babesia rossi and a hematocrit of 0.1-0.2 L/L (10-20%). INTERVENTIONS: Treatment groups were randomized to receive either 20 mL/kg of Oxyglobin or pRBCT over 4 hours via a central venous catheter. Transfusions were followed by lactated Ringer's solution infusion. Rectal temperature, femoral arterial and mixed venous blood sampling, oscillometric blood pressure, and subjective assessment of patient status (habitus), and appetite were performed at time points 0, 1, 4, 8, 24, 48, and 72 hours. MAIN RESULTS: Dogs presented with a hypoalbuminemic alkalosis; hyperchloremic, dilutional acidosis; normotensive tachycardia; pyrexia; depression; and anorexia. Both treatments produced similar results, with the exception of significant differences in pH (4 h); PCO(2) (4 h); hemoglobin (8 h, 24 h); mean arterial pressure (48 h); albumin (4 h, 8 h); habitus (8 h, 48 h); and appetite (24 h). Arterial O(2) content was higher for pRBCT than Oxyglobin at 72 hours, but central venous PO(2) did not differ between groups or over time and was consistently subnormal. CONCLUSIONS: Oxyglobin provides similar overall improvements to pRBCT in dogs with anemia from babesiosis, with respect to blood gas, acid-base and blood pressure, although patients receiving packed cells tended to have more rapid normalization of habitus and appetite.

PMID: 19691591 [PubMed - indexed for MEDLINE]

35. Transfusion. 2009 Dec;49(12):2557-63. Epub 2009 Jul 16.

Transfusion-transmitted Babesia microti identified through hemovigilance.

Tonnetti L, Eder AF, Dy B, Kennedy J, Pisciotto P, Benjamin RJ, Leiby DA.

Transmissible Diseases Department, Jerome H. Holland Laboratory, American Red Cross, Rockville, Maryland 20855, USA.

BACKGROUND: Babesia microti, the primary cause of human babesiosis in the United States, is an intraerythrocytic parasite endemic to the Northeast and upper Midwest. Published studies indicate that B. microti increasingly poses a blood safety risk. The American Red Cross Hemovigilance Program herein describes the donor and recipient characteristics of suspected transfusion-transmitted B. microti cases reported between 2005 and 2007. STUDY DESIGN AND METHODS: Suspected transfusion-transmitted Babesia infections were reported by transfusion services or were discovered through recipient-tracing investigations of prior donations from donors with a positive test for B. microti in a serologic study. Follow-up samples from involved donors were tested by Babesia-specific immunofluorescence assay, Western blot, and/or real-time polymerase chain reaction analysis. RESULTS: Eighteen definite or probable B. microti infections, including five fatalities, were identified in transfusion recipients, 16 from hospital-reported cases and two through serologic lookback studies. Thirteen recipients were 61 to 84 years old and two were 2 years old or younger. Two recipients had sickle cell disease and four were known to be asplenic, including one with sickle cell disease. Seventeen antibody-positive donors were implicated; 11 (65%) were residents in Babesia-endemic areas, while four (24%) nonresident donors had a history of travel to endemic areas. CONCLUSIONS: Transfusion-transmitted B. microti can be a significant cause of transfusion-related morbidity and mortality, especially in infant, elderly, and asplenic blood recipients. These data demonstrate the need for interventions, in both endemic and nonendemic areas of the United States, to reduce patient risk.

PMID: 19624607 [PubMed - indexed for MEDLINE]

36. Nursing. 2009 Jun;39(6):55.

Babesiosis: another tick-borne disease.

Snow M.

Weber State University's College of Health Professions in Kaysville, Utah, USA.

PMID: 19474614 [PubMed - indexed for MEDLINE]

37. Emerg Infect Dis. 2009 May;15(5):785-7.

Babesiosis acquired through blood transfusion, California, USA.

Ngo V, Civen R.

Los Angeles County Department of Public Health, CA 90012, USA.

Babesiosis was reported in a California resident who received a transfusion of blood products collected in the disease-endemic northeastern region of the United States. Babesiosis should be considered year-round in the diagnosis of febrile and afebrile patients with abnormal blood cell counts who have received blood products from disease-endemic areas.

PMCID: PMC2687036 PMID: 19402969 [PubMed - indexed for MEDLINE]

38. Vet Parasitol. 2009 Jul 7;163(1-2):144-7. Epub 2009 Mar 31.

Viability assays of intra-erythrocytic organisms using fluorescent dyes.

Fletcher TI, Wigg JL, Rolls PJ, de Vos AJ.

Tick Fever Centre, Department of Primary Industries and Fisheries, 280 Grindle Road, Wacol 4076, Australia.

Three intra-erythrocytic tick fever organisms of cattle (Babesia bovis, Babesia bigemina and Anaplasma centrale) were subjected to a range of stressors, including heat, storage over time, specific chemotherapy and cryopreservation. Various stains, both alone and in combination, were used in an attempt to assess viability of these organisms before and after the stressors were applied. Carboxyfluorescein diacetate succinimidyl ester (CFSE) stained live Babesia spp. very well while fluorescein diacetate (FDA) stained A. centrale successfully. Propidium iodide (PI) and ethidium-homodimer-1 (Eth-D) were used as counter stains to identify dead organisms. Stain combinations allowed differentiation between living and dead Babesia organisms after exposure to heat and after chemotherapy. PI and Eth-D as counter stains were of little value after deglycerolisation of cryopreserved organisms. Possible reasons for this limited success in determining death or viability of tick fever organisms after some treatments include the impermeability of red blood cells to PI and Eth-D counter stains or the loss of live and/or dead organisms during sample processing.

PMID: 19380205 [PubMed - indexed for MEDLINE]

39. J Clin Apher. 2009;24(3):97-105.

Red cell exchange transfusion for babesiosis in Rhode Island.

Spaete J, Patrozou E, Rich JD, Sweeney JD.

Division of Infectious Diseases, Miriam and Rhode Island Hospitals, Warren Alpert Medical School of Brown University, Providence, Rhode Island 02906, USA.

We report four cases of clinically severe tick borne babesiosis treated with chemotherapy and adjunctive red cell exchange (RCE) at two Rhode Island hospitals from 2004 to 2007. All RCE procedures were performed using a Cobe Spectra device and were well tolerated without complications. The volume of allogeneic red cells used in the exchange was determined using the algorithm in the apheresis device with the input variables of preprocedure hematocrit, weight, height, an assumed allogeneic red cell hematocrit of 55 and a desired post procedure hematocrit of 27. The preprocedure level of parasitemia varied between 2.4% and 24% and the postprocedure level of parasitemia between 0.4 and 5.5% with an average overall percent reduction in parasitemia of 74%. Retrospectively, application of a new formula to calculate red cell mass appeared to correlate better with the percent reduction in parasitemia. Previous reports of RCE in babesiosis were reviewed. The reported reduction in parasitemia varied from 50% to >90%. Although a preprocedure level of parasitemia of 10% is sometimes used as a threshold for RCE in clinically severe babesiosis, this threshold does not have a firm empirical basis. No postprocedure desired level of parasitemia is indicated nor the mass of allogeneic red cells needed to achieve such a level. We conclude that current estimates of the dose of allogeneic red cells used in RCE are probably inaccurate, advocate a new formula to estimate this dose and suggest that a 90% reduction in parasitemia should be the minimally desired target of RCE in babesiosis.

PMID: 19291782 [PubMed - indexed for MEDLINE]

40. J Vet Med Sci. 2009 Jan;71(1):33-41.

Evaluation of efficacy of bruceine A, a natural quassinoid compound extracted from a medicinal plant, Brucea javanica, for canine babesiosis.

Nakao R, Mizukami C, Kawamura Y, Subeki, Bawm S, Yamasaki M, Maede Y, Matsuura H, Nabeta K, Nonaka N, Oku Y, Katakura K.

Laboratory of Parasitology, Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 8, Sapporo, Japan.

Bruceine A, a natural quassinoid compound extracted from the dried fruits of Brucea javanica (L.) Merr., was evaluated for its antibabesial activity in vitro and in vivo. Bruceine A inhibited the in vitro growth of Babesia gibsoni in canine erythrocytes at lower concentration compared with the standard antibabesial drug diminazene aceturate and killed the parasites within 24 hr at a concentration of 25 nM. Oral administration of bruceine A at a dosage of 6.4 mg/kg/day for 5 days resulted in no clinical findings in a dog with normal ranges of hematological and biochemical values in the blood. Three dogs were infected with B. gibsoni and two of them were treated with bruceine A at a dosage of 6.4 mg/kg/day for 6 days from day 5 post-infection. An untreated dog developed typical acute babesiosis symptoms including severe anemia, high fever, and complete loss of appetite and movement. However, the two bruceine A-treated dogs maintained their healthy conditions throughout the experimental period of 4 weeks although complete elimination of parasites from the peripheral blood was not achieved and decreases in the packed cell volume and the erythrocyte and platelet counts were observed. Since natural quassinoid compounds have been used as traditional medicines for the treatment of various ailments including cancer and malaria, the present results suggest that bruceine A or other related compounds are potential candidates for the treatment of canine babesiosis.

PMID: 19194074 [PubMed - indexed for MEDLINE]

41. Vaccine. 2008 Dec 19;26 Suppl 6:G29-33.

Vaccination of cattle against B. bovis infection with live attenuated parasites and non-viable immunogens.

Fish L, Leibovich B, Krigel Y, McElwain T, Shkap V.

Division of Parasitology, Kimron Veterinary Institute, Bet Dagan 50250, Israel.

Susceptible dairy cattle were immunized with attenuated, live calf-derived, in vitro-cultured or biologically cloned Babesia bovis, with non-viable exoantigens, or with recombinant rhoptry-associated protein 1 (rRAP1). Antibody response assessed by the indirect fluorescent assay (IFA) and by the growth inhibition activity in vitro showed that seroconversion correlated with neutralization activity in vitro in all immunized groups, but not with protective immunity in vivo. The protective responses elicited by immunization with completely avirulent biologically cloned live parasites, or by the exoantigens were sufficient for highly susceptible dairy cattle, in which prime immunization with blood-derived attenuated parasites cause clinical babesiosis. Upon challenge with virulent live parasites all immunized calves were solidly protected, but only partial protective immunity was acquired by rRAP1 immunization.

PMID: 19178890 [PubMed - indexed for MEDLINE]

42. Vox Sang. 2008 Nov;95(4):331-4.

Transmission of Babesia microti by blood transfusion in Texas.

Cangelosi JJ, Sarvat B, Sarria JC, Herwaldt BL, Indrikovs AJ.

Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555-0435, USA.

In the USA, seasonal tickborne transmission of Babesia microti occurs in the Northeast and upper Midwest. A resident of Texas became infected through a red blood cell transfusion from an asymptomatic local donor who had summered in Massachusetts. The patient's infection was diagnosed by blood smear examination in January, 7 weeks post-transfusion. He died 1 week later from variceal haemorrhage complicated by haemolysis. Premortem patient specimens and archived blood from the donor unit tested positive for B. microti antibodies and DNA. Babesiosis should be included in the differential diagnosis of post-transfusion haemolytic anaemia or thrombocytopenia, regardless of the geographical region or season.

PMID: 19138264 [PubMed - indexed for MEDLINE]

43. Immunohematology. 2009;25(4):179-85.

The American Red Cross Hemovigilance Program: advancing the safety of blood donation and transfusion.

Eder AF, Dy BA, Barton J, Kennedy JM, Benjamin RJ.

American Red Cross, National Headquarters, Biomedical Services, Medical Office, 15601 Crabbs Branch Way, Rockville, MD 20855, USA.

PMID: 20406027 [PubMed - indexed for MEDLINE]

44. J Parasitol. 2009 Jun;95(3):598-603.

Mediterranean theileriosis and other tick transmitted piroplasmoses in cattle in Minorca (Balearic Islands, Spain): the effect of tick control on prevalence levels analyzed by reverse line blot (RLB) macroarrays.

Almerìa S, Delgado-Neira Y, Adelantado C, Huguet M, Vinent J, Nicolàs A.

Centre de Recerca en Sanitat Animal (CReSA), UAB-IRTA and Departament de Sanitat i Anatomia Animals, Campus de la Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain.

Mediterranean theileriosis, caused by Theileria annulata, is endemic in Minorca (Balearic Islands, Spain). The present study analyzes the prevalence of piroplasm infections in cattle in Minorca using reverse line blot (RLB) macroarrays, as well as the effect of herd tick control on those prevalence levels. One hundred and nineteen animals from 12 herds were sampled in representative areas of the island. Information was gathered regarding tick control for the animals (frequency and acaricide used) in each herd. More than 87% of the animals were positive for the presence of piroplasm species. Theileria annulata and Theileria buffeli were observed in all sampled herds (mean prevalence 53.3% for T. annulata and 69.75% for T. buffeli). The mean prevalence was 5.7% for Babesia bigemina. A significantly higher prevalence of Theileria spp. was observed in herds that grazed in, or near, forested areas. Theileria annulata prevalence was significantly lower in herds that followed tick control and was related to the frequency of the applied treatments. Theileria buffeli and B. bigemina prevalences were not affected by tick control for the herds. The results indicate that despite tick control, Mediterranean theileriosis remains endemic in Minorca. Adequate control measures and vaccination approaches are required to improve the situation of Mediterranean theileriosis on the island.

PMID: 19086744 [PubMed - indexed for MEDLINE]

45. Clin Infect Dis. 2009 Jan 1;48(1):25-30.

Babesia infection through blood transfusions: reports received by the US Food and Drug Administration, 1997-2007.

Gubernot DM, Lucey CT, Lee KC, Conley GB, Holness LG, Wise RP.

Office of Blood Research and Review, Center for Biologics Evaluation and Research, US Food and Drug Administration, Rockville, Maryland 20852-1448, USA.

Comment in Clin Infect Dis. 2009 Jul 1;49(1):166-7.

BACKGROUND: Human babesiosis is an illness with clinical manifestations that range from asymptomatic to fatal. Although babesiosis is not nationally notifiable, the US incidence appears to be increasing. Babesia infection is a transfusion-transmissable disease. An estimated 70 cases were reported during 1979-2007; most of these cases were reported during the past decade. METHODS: We queried the 3 following US Food and Drug Administration safety surveillance systems to assess trends in babesiosis reporting since 1997: fatality reports for blood donors and transfusion recipients, the Adverse Event Reporting System (which includes MedWatch), and the Biological Product Deviations Reporting system.We analyzed fatality reports for time frames, clinical presentations, and patient and donor demographic characteristics. RESULTS: Eight of 9 deaths due to transfusion-transmitted babesiosis that were reported since 1997 occurred within the past 3 years (2005-2007). Four implicated donors and 5 patients lived in areas where Babesia infection is not endemic. Increasing numbers of Biological Product Deviations Reports were submitted to the US Food and Drug Administration over the past decade; the Adverse Event Reporting System received no reports. CONCLUSIONS: After nearly a decade with no reported death due to transfusion-transmitted babesiosis, the US Food and Drug Administration received 8 reports from November 2005 onward. The increased numbers of deaths reported and Biological Product Deviations Reports suggest an increasing incidence of transfusion-transmitted babesiosis. Physicians should consider babesiosis in the differential diagnosis in immunocompromised, febrile patients with a history of recent transfusion, even in areas where Babesia infection is not endemic. Accurate and timely reporting of babesiosis-related donor and transfusion events assists the US Food and Drug Administration in developing appropriate public health-control measures.

PMID: 19035776 [PubMed - indexed for MEDLINE]

46. Heart Lung. 2008 Nov-Dec;37(6):481-4. Epub 2008 Sep 30.

Fever of unknown origin (FUO) due to babesiosis in a immunocompetent host.

Cunha BA, Cohen YZ, McDermott B.

Infectious Disease Division, Winthrop-University Hospital, Mineola, New York 11501, USA.

Fevers of unknown origin (FUOs) are defined as prolonged fevers of 101 degrees F or greater lasting 3 or more weeks that remain undiagnosed after comprehensive inpatient/outpatient laboratory testing. Tick-borne infections are uncommon causes of FUOs. Any infectious disease accompanied by prolonged fevers can present as an FUO if the diagnosis is not suspected or if specific laboratory testing is not done to confirm the diagnosis. Babesiosis is transmitted by the Ixodes scapularis ticks endemic to areas in the northeastern United States. We present the case of a 73-year-old, non-human immunodeficiency virus, male from Long Island who presented with FUO for 6 weeks. As with malaria, there are usually few or no localizing signs in babesiosis. During the patient's hospitalization, babesiosis was suspected on the basis of nonspecific laboratory findings, that is, relative lymphopenia, thrombocytopenia, thrombocytopenia, and an elevated lactate dehydrogenase. When babesiosis was considered in the differential diagnosis, stained blood smears demonstrated the red blood cell inclusions of babesiosis. In the hospital, the patient developed noncardiac pulmonary edema, which rapidly resolved which has been described as a rare complication of babesiosis. He also had an elevated immunoglobulin-M Lyme titer indicating coinfection with Lyme disease. Although his hemolytic anemia persisted for weeks, he only had 3% parasitemia and intact splenic function. We believe this to be the first case of babesiosis presenting as an FUO in a normal host.

PMID: 18992633 [PubMed - indexed for MEDLINE]

47. Vet Parasitol. 2008 Nov 7;157(3-4):203-10. Epub 2008 Aug 5.

Efficiency of a recombinant MSA-2c-based ELISA to establish the persistence of antibodies in cattle vaccinated with Babesia bovis.

Bono MF, Mangold AJ, Baravalle ME, Valentini BS, Thompson CS, Wilkowsky SE, Echaide IE, Farber MD, Torioni de Echaide SM.

Universidad Nacional del Litoral, Reverendo P. Kreder 2805, CP 3080, Esperanza, Santa Fe, Argentina.

Bovine babesiosis is caused by Babesia bovis and B. bigemina in Argentina. These protozoans are prevalent north of parallel 30 degrees S, where their natural vector Rhipicephalus (Boophilus) microplus is widespread. To prevent babesiosis outbreaks in endemic areas, an increasing population of 4-10-month-old calves are vaccinated with low virulence B. bovis R1A (BboR1A) and B. bigemina S1A (BbiS1A) strains. In non-endemic areas, an additional calf population is also vaccinated and boostered as adults, before they are relocated to R. microplus-endemic areas of the country. Serological tests are currently utilized not only to determine the status of natural Babesia spp. infections, but also to confirm the infection caused by vaccine strains. For this purpose, an indirect enzyme immunoassay (ELISA) based on the recombinant major surface antigen-2c (rMSA-2c) of B. bovis expressed in Escherichia coli, was standardized using sera from Babesia spp. experimentally infected cattle. ELISA(rMSA-2c) was validated using sera obtained weekly during 336 days from steers primed and boostered with BboR1A and/or BbiS1A on days 0 and 154, then compared with the immunofluorescent-antibody test (IFAT). Western blot (WB) protein analysis was used to confirm the specificity of the immune response to rMSA-2c. The sensitivity and specificity for ELISA(rMSA-2c) were 92 and 96% after the Babesia spp. priming and 88 and 73% after the boostering immunization, respectively. The sensitivity and specificity for IFAT were 99 and 90% after priming and 92 and 98% after boostering, respectively. Unlike IFAT, ELISA(rMSA-2c) detected a remarkable delayed booster response and a significant drop in specificity between 35 and 84 days after the booster immunization. Simultaneously, 87.5% of cattle boostered with B. bigemina showed cross-reactions in the ELISA(rMSA-2c), particularly between 63 and 77 days after the inoculation. A reaction against E. coli was observed, since bands of approximately 40 and/or 42kDa were detected using sera from cattle before and after Babesia spp. inoculations. ELISA(rMSA-2c) showed to be useful between 42 and 98 days after priming with Babesia spp. live vaccine to evaluate the success of infecting cattle. However, after boostering the test showed low specificity.

PMID: 18783887 [PubMed - indexed for MEDLINE]

48. Transfusion. 2009 Jan;49(1):8. Epub 2008 Aug 6.

Fatal transfusion-transmitted Babesia microti in the Midwest.

Blue D, Graves V, McCarthy L, Cruz J, Gregurek S, Smith D.

Indiana University Medical Center, Clarian Health, and the Indiana Blood Center, Indianapolis, Indiana 46202, USA.

PMID: 18694463 [PubMed - indexed for MEDLINE]

49. Parasite Immunol. 2008 Jun-Jul;30(6-7):365-70.

C3 contributes to the cross-protective immunity induced by Babesia gibsoni phosphoriboprotein P0 against a lethal B. rodhaini infection.

Terkawi MA, Zhang G, Jia H, Aboge G, Goo YK, Nishikawa Y, Yokoyama N, Igarashi I, Kawazu SI, Fujisaki K, Xuan X.

National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido 080-8555, Japan.

We have studied the impact of complement component 3 (C3) deficiency on the progression of lethal Babesia rodhaini infection in immune mice. A B. gibsoni ribosomal phosphoprotein P0 (BgP0) previously reported to be a cross-protective antigen against Babesia infection was used to immunize C57BL/6 wild-type (WT) and C3-deficient (C3-/-) mice. Test mice were immunized intraperitoneally (i.p.) with recombinant BgP0 (rBgP0), while controls either were immunized with PBS or did not receive any immunization. Following the immunization regime, test WT mice induced a specifically strong humoral response consisting of mixed immunoglobulins IgG1 and IgG2 associated with high production of IFN-gamma in the supernatant of splenocytes. While test C3-/- mice had significantly decreased total IgG, IgG1 and IgG2b responses, the secretions of IL-12 and IFN-gamma tended to be lower than those in WT mice. Furthermore, partial protection was only observed in rBgP0-immunized WT mice but not in C3-/- mice or controls. Indeed, rBgP0-immunized WT mice showed significant reductions in the initiation of parasitaemia correlated with delayed mortalities and considerable survival rates. Taken together, our results indicate that cross-protection was impaired in C3-/- mice in view of the decrease in the antibody responses and cytokine production and the high susceptibility to infection.

PMID: 18533933 [PubMed - indexed for MEDLINE]

50. Transfusion. 2008 Aug;48(8):1676-84. Epub 2008 May 22.

Photochemical inactivation with amotosalen and long-wavelength ultraviolet light of Plasmodium and Babesia in platelet and plasma components.

Grellier P, Benach J, Labaied M, Charneau S, Gil H, Monsalve G, Alfonso R, Sawyer L, Lin L, Steiert M, Dupuis K.

Biologie Fonctionnelle des Protozoaires, Muséum National d'Histoire Naturelle, Paris, France.

BACKGROUND: Transfusion-transmitted cases of malaria and babesiosis have been well documented. Current efforts to screen out contaminated blood products result in component wastage due to the lack of specific detection methods while donor deferral does not always guarantee safe blood products. This study evaluated the efficacy of a photochemical treatment (PCT) method with amotosalen and long-wavelength ultraviolet light (UVA) to inactivate these agents in red blood cells (RBCs) contaminating platelet (PLT) and plasma components. STUDY DESIGN AND METHODS: Plasmodium falciparum- and Babesia microti-contaminated RBCs seeded into PLT and plasma components were treated with 150 micromol per L amotosalen and 3 J per cm2 UVA. The viability of both pathogens before and after treatment was measured with infectivity assays. Treatment with 150 micromol per L amotosalen and 1 J per cm2 UVA was used to assess the robustness of the PCT system. RESULTS: No viable B. microti was detected in PLTs or plasma after treatment with 150 mol per L amotosalen and 3 J per cm2 UVA, demonstrating a mean inactivation of greater than 5.3 log in PLTs and greater than 5.3 log in plasma. After the same treatment, viable P. falciparum was either absent or below the limit of quantification in three of four replicate experiments both in PLTs and in plasma demonstrating a mean inactivation of at least 6.0 log in PLTs and at least 6.9 log in plasma. Reducing UVA dose to 1 J per cm2 did not significantly affect the level of inactivation. CONCLUSION: P. falciparum and B. microti were highly sensitive to inactivation by PCT. Pathogen inactivation approaches could reduce the risk of transfusion-transmitted parasitic infections and avoid unnecessary donor exclusions.

PMID: 18503613 [PubMed - indexed for MEDLINE]

51. Rev Biol Trop. 2007 Mar;55(1):127-33.

[Isolation of a field strain of Babesia bigemina (Piroplasma: Babesiidae) and establishment of in vitro culture for antigen production].

[Article in Spanish]

Rodríguez-Vivas RI, Quiñones-Avila FJ, Ramírez-Cruz GT, Cruz D, Wagner G.

Departamento de Parasitología, Facultad de Medicina Veterinaria y Zootecnia, Universidad Autónoma de Yucatán.

Isolation of a field strain of Babesia bigemina (Piroplasma: Babesiidae) and establishment of in vitro culture for antigen production. Bovine b abesiosis, caused by Babesia bigemina, is a barrier for livestock development; it results in high economic loss to Mexican livestock. Control requires adequate antigens for diagnosis and vaccination programs. However, because of antigenic variation among Babesia strains, it is necessary to use antigens prepared from local strains. The purpose of the present study was to isolate a local field strain and to establish the in vitro culture of B. bigemina by the evaluation of the constituent's concentration of culture media. Thirty engorged female Boophilus microplus were collected from cattle suffering clinical babesiosis (B. bigemina) in Yucatan state, Mexico. These ticks were sent to the laboratory for detection of Babesia sp. vermicules. Eggs were kept at 83-85 % humidity and 27 degrees C until hatching. Larvae were transferred to an esplenectomized calf (B-1). The resulting nymphs were transferred to an esplenectomized calf (B-2). Twelve days later, B. bigemina (local strain) was detected in calf B-2 and its infected blood was frozen in liquid nitrogen to initiate the in vitro culture. The Microaerophilus Stationary Phase (MASP) in vitro culture method was used to reactivate the parasite. Three different concentrations of culture media (70, 60 and 50%), serum (30, 40 and 50%) and uninfected red blood cells (5, 10 and 15 %) were used in order to know the convenient concentrations to obtain the highest percentage of infected red blood cells (PEI). The cultured strain was used to prepare antigens for the Immunofluorescence Antibody Test (IFAT) and several concentrations of serum and conjugate were tested. Strain isolation was successful; 30 days were needed to obtain a PEI of 1.5%. The isolated strain was frozen in liquid nitrogen and the parasites were reactivated with the in vitro culture MASP method. The concentration of culture media that produced the highest PEI (14%) (p < 0.05) was 30% serum, 70% M199 and 5%. Uninfected Red Blood cells antigens were successfully used in the IFAT and the best dilutions to differentiate between positive and negative controls were serum 1:80 and conjugate 1:80. The isolated B. bigemina local strain requires particular conditions of in vitro culture by the MASP method to reach high numbers of infected red blood cells, needed to prepare and provide high quality antigens for serological diagnosis of B. bigemina.

PMID: 18457120 [PubMed - indexed for MEDLINE]

52. Int J Parasitol. 2008 Sep;38(11):1219-37. Epub 2008 Mar 20.

Babesiosis: recent insights into an ancient disease.

Hunfeld KP, Hildebrandt A, Gray JS.

Institute of Medical Microbiology & Infection Control, Hospital of the Johann Wolfgang Goethe-University Frankfurt am Main, Department of Serology and Molecular Diagnostics, Frankfurt/Main, Germany.

Ever since the discovery of parasitic inclusions in erythrocytes of cattle in Romania by Victor Babes at the end of the 19th century, newly recognised babesial pathogens continue to emerge around the world and the substantial public health impact of babesiosis on livestock and man is ongoing. Babesia are transmitted by ixodid ticks and infection of the host causes a host-mediated pathology and erythrocyte lysis, resulting in anemia, hyperbilirubinuria, hemoglobinuria, and possibly organ failure. Recently obtained molecular data, particularly for the 18S rRNA gene, has contributed significantly to a better understanding of the sometimes puzzling phylogenetic situation of the genus Babesia and new information has been added to help determine the taxonomic position of many species. Moreover, it seems that owing to higher medical awareness the number of reported cases in humans is rising steadily. Hitherto unknown zoonotic babesias are now being reported from geographical areas where babesiosis was not known to occur and the growing numbers of immunocompromised individuals suggest that the frequency of cases will continue to rise. This review covers recent insights into human babesiosis with regard to phylogeny, diagnostics and treatment in order to provide new information on well known as well as recently discovered parasites with zoonotic potential.

PMID: 18440005 [PubMed - indexed for MEDLINE]

53. Clin Infect Dis. 2008 May 1;46(9):e92-5.

Spontaneous splenic rupture caused by Babesia microti infection.

Kuwayama DP, Briones RJ.

Department of Surgery, The Johns Hopkins Hospital, Baltimore, Maryland 21205, USA.

Babesiosis has not been previously associated with spontaneous splenic rupture. We describe an otherwise healthy 61-year-old man with symptomatic babesiosis whose spleen ruptured during hospitalization. Although this complication is rare, practitioners who commonly treat patients with babesiosis should be aware of its potential occurrence.

PMID: 18419430 [PubMed - indexed for MEDLINE]

54. Med Klin (Munich). 2008 Feb 15;103(2):104-7.

[Babesiosis in an immunocompromised German patient].

[Article in German]

Häselbarth K, Kurz M, Hunfeld KP, Krieger G.

II. Medizinische Klinik, Hegau-Klinikum Singen, Virchowstrasse 10, Singen.

BACKGROUND: Babesiosis is a tick-borne zoonosis. Human cases of babesiosis occur worldwide but have been mainly described in North America and rarely in Europe. The disease manifestations show a broad clinical spectrum including a malaria-like syndrome. Fulminant and life-threatening infections have been described in the setting of asplenia and/or immunosuppression. CASE REPORT: A 63-year-old splenectomized patient had been treated with rituximab because of B cell lymphoma. 4 weeks later, he developed signs of infection, anemia, subicterus, and dark urine. Laboratory investigation revealed hemolytic anemia, hemoglobinuria, and renal insufficiency. Blood smears showed Plasmodium-like intraerythrocytic parasites. He had not been exposed to malaria. He had taken frequent walks in the woods around Lake Constance in the south of Germany, where tick-borne diseases are endemic. Babesiosis was confirmed by polymerase chain reaction (PCR) and the parasite was identified as EU1. Serology was negative. Therapy with clindamycin and quinine induced remission. Following a relapse, retreatment with atovaquone and azithromycin was initiated. After several months, seroconversion occurred and the patient cleared the parasite 8 months after first admission. CONCLUSION: Human babesiosis does occur in Germany. Patients with splenectomy and/or immunosuppression and malaria-like symptoms should be evaluated for babesiosis by blood smear and PCR.

PMID: 18270666 [PubMed - indexed for MEDLINE]

55. Clin Infect Dis. 2008 Feb 1;46(3):370-6.

Persistent and relapsing babesiosis in immunocompromised patients.

Krause PJ, Gewurz BE, Hill D, Marty FM, Vannier E, Foppa IM, Furman RR, Neuhaus E, Skowron G, Gupta S, McCalla C, Pesanti EL, Young M, Heiman D, Hsue G, Gelfand JA, Wormser GP, Dickason J, Bia FJ, Hartman B, Telford SR 3rd, Christianson D, Dardick K, Coleman M, Girotto JE, Spielman A.

Division of Infectious Diseases, Connecticut Children's Medical Center, and Department of Pediatrics, University of Connecticut School of Medicine, Farmington, Connecticut 06106, USA.

BACKGROUND: Human babesiosis is a tickborne malaria-like illness that generally resolves without complication after administration of atovaquone and azithromycin or clindamycin and quinine. Although patients experiencing babesiosis that is unresponsive to standard antimicrobial therapy have been described, the pathogenesis, clinical course, and optimal treatment regimen of such cases remain uncertain. METHODS: We compared the immunologic status, clinical course, and treatment of 14 case patients who experienced morbidity or death after persistence of Babesia microti infection, despite repeated courses of antibabesial treatment, with those of 46 control subjects whose infection resolved after a single course of standard therapy. This retrospective case-control study was performed in southern New England, New York, and Wisconsin. RESULTS: All case patients were immunosuppressed at the time of acute babesiosis, compared with <10% of the control subjects. Most case patients experienced B cell lymphoma and were asplenic or had received rituximab before babesial illness. The case patients were more likely than control subjects to experience complications, and 3 died. Resolution of persistent infection occurred in 11 patients after 2-10 courses of therapy, including administration of a final antimicrobial regimen for at least 2 weeks after babesia were no longer seen on blood smear. CONCLUSIONS: Immunocompromised people who are infected by B. microti are at risk of persistent relapsing illness. Such patients generally require antibabesial treatment for >or=6 weeks to achieve cure, including 2 weeks after parasites are no longer detected on blood smear.

PMID: 18181735 [PubMed - indexed for MEDLINE]

56. J Am Board Fam Med. 2008 Jan-Feb;21(1):75-7.

Complications of coinfection with Babesia and Lyme disease after splenectomy.

Abrams Y.

Department of Family and Community Medicine, University of Pittsburgh, PA 15217, USA.

PMID: 18178707 [PubMed - indexed for MEDLINE]

57. Rev Bras Parasitol Vet. 2007 Jul-Sep;16(3):163-5.

[Natural infection by hemoparasites in calves submitted to chemoprophylaxis at 30 days of age].

[Article in Portuguese]

da Silva RA, Corrêa Fdo N, Botteon Rde C, Botteon Pde T.

Empresa de Pesquisa Agropecuária de Minas Gerais, Instituto Técnicoem Agropecuária e Cooperativismo, Pitangui, MG 35650-00, Brasil.

The tick-borne disease (TBD) brings great damages to cattle breeding. The most important etiologic agents are Babesia bigemina, B. bovis and Anaplasma marginale, being the tick Boophilus microplus the main vector. This work reports the occurrence of natural infection by hemoparasites of TBD in 36 calves with high ticks natural infestation submitted to chemoprophylaxis with 30 days year-old. The blood smears from animals of different ages were analized and were found B. bigemina (33.3%), B. bovis (11.1%) and A. marginale (13.9%). Six animals had clinical symptoms (16.7%) and one dead (2.8%). The number of clinical cases ocurred in consequence of an association of factors as high infestation of ticks and low passive immunity in period that calves had not developed enough active immunity.

PMID: 18078605 [PubMed - indexed for MEDLINE]

58. Transfus Med Rev. 2008 Jan;22(1):1-34.

Proceedings of a Consensus Conference: pathogen inactivation-making decisions about new technologies.

Webert KE, Cserti CM, Hannon J, Lin Y, Pavenski K, Pendergrast JM, Blajchman MA.

Medical, Scientific, and Research Affairs, Canadian Blood Services, Hamilton, Edmonton and Toronto, Canada.

Significant progress has been made in reducing the risk of pathogen transmission to transfusion recipients. Nonetheless, there remains a continuing risk of transmission of viruses, bacteria, protozoa, and prions to recipients. These include many of the viruses for which specific screening tests exist as well as pathogens for which testing is currently not being done, including various species of bacteria, babesiosis, variant Creutzfeld-Jacob disease, hepatitis A virus, human herpes virus 8, chikungunya virus, Chagas disease, and malaria. Pathogen inactivation (PI) technologies potentially provide an additional way to protect the blood supply from emerging agents and also provide additional protection against both known and as-yet-unidentified agents. However, the impact of PI on product quality and recipient safety remains to be determined. The purpose of this consensus conference was to bring together international experts in an effort to consider the following issues with respect to PI: implementation criteria; licensing requirements; blood service and clinical issues; risk management issues; cost-benefit impact; and research requirements. These proceedings are provided to make available to the transfusion medicine community the considerable amount of important information presented at this consensus conference.

PMID: 18063190 [PubMed - indexed for MEDLINE]

59. Curr Opin Hematol. 2007 Nov;14(6):671-6.

Current risk for transfusion transmitted infections.

Dodd RY.

Research and Development, American Red Cross, Rockville, Maryland 20855, USA.

PURPOSE OF REVIEW: Blood safety is a topic of continuing concern, and much effort is expended on measures to decrease the risk for transmission of infectious agents via transfusion. At the same time, emerging infections may threaten this safety. A periodic review of risk is therefore appropriate. RECENT FINDINGS: The risk for major transfusion transmissible infections continues to decline as a result of continually strengthening interventions and because of more general improvements in public health. More attention is being paid to emerging infections, and recently donor testing has been implemented for West Nile virus and Trypanosoma cruzi. Within the period covered by this review, the transmission of variant Creutzfeldt-Jakob disease by transfusion has been confirmed. Our understanding of other agents is improving. SUMMARY: The estimated risk for transfusion transmitted hepatitis viruses and retroviruses is now vanishingly small, but clinicians should be alert to the possibility of infection with emerging infectious agents, because preventive measures may not be available in all cases.

PMID: 17898573 [PubMed - indexed for MEDLINE]

60. Parassitologia. 2007 May;49 Suppl 1:19-22.

Advances in the development of molecular tools for the control of bovine babesiosis in Mexico.

Mosqueda J, Figueroa JV, Alvarez A, Bautista R, Falcon A, Ramos A, Canto G, Vega CA.

Bovine Babesiosis Laboratory, National Center for Disciplinary Research in Veterinary Parasitology (CENID-PAVET)-INIFAP, Jiutepec, Morelos, Mexico.

The severe negative impact that bovine babesiosis has in the Mexican cattle industry has not been ameliorated basically due to the lack of safe and effective commercially available vaccines and sensitive and reliable diagnostic tests. In recent years, the Bovine Babesiosis Laboratory at the National Center for Disciplinary Research in Veterinary Parasitology-INIFAP in Morelos State, Mexico has been directing efforts towards three main research areas: (1) The development of in vitro culture-derived, improved and safer live vaccines. This has been done in two ways: using gamma-irradiated bovine serum and erythrocytes for the in vitro culture of vaccine strains, which reduces the risk of contaminating pathogens, and improving the immune response, by the addition of L. casei, a strong stimulant of the innate immune system. (2) The study of antigens considered as vaccine candidates with the goal of developing a recombinant vaccine that suits the country's needs. Knowing their degree of conservation or variation in Mexican isolates, their phylogenetic relationship and their protective, immuno-stimulatory properties, are first steps towards that goal. (3) The development of new tools for diagnosis, detection and discrimination of bovine babesiosis is the third area. Developing variants of ELISA, which are more reliable than the currently used IFAT, are a priority, and finally, taking advantage of the genomes of Babesia bigemina, and B. bovis, we are identifying genes than allow us to discriminate isolates using molecular tools.

PMID: 17691602 [PubMed - indexed for MEDLINE]

61. Parassitologia. 2007 May;49 Suppl 1:13-7.

Vaccination against large Babesia species from dogs.

Schetters TP, Kleuskens J, Carcy B, Gorenflot A, Vermeulen A.

Parasitology R&D Department, Intervet International BV Boxmeer, The Netherlands.

The original observation of Sibinovic that soluble parasite antigens (SPA) of B. canis could be used to protect dogs against challenge infection formed the starting point for the development of an effective vaccine. With the advent of in vitro cultivation techniques for haemoprotozoan parasites an important tool became available for the commercial production of the vaccine antigens. A first generation vaccine was developed for dogs, but it appeared that the level of protection induced was not complete. In contrast to what was found with the SPA from serum/plasma of infected animals, protection induced with SPA from a single Babesia canis strain protected against a homologous challenge infection only. Further research led to the discovery that a combination of SPA of B. canis and SPA of B. rossi induced a broad spectrum of immunity. This improved vaccine, Nobivac Piro, not only induces protection against heterologous B. canis infection, but also against heterologous B. rossi infection.

PMID: 17691601 [PubMed - indexed for MEDLINE]

62. Parassitologia. 2007 May;49 Suppl 1:9-12.

Search for Babesia bovis vaccine candidates.

Florin-Christensen M, Schnittger L, Dominguez M, Mesplet M, Rodríguez A, Ferreri L, Asenzo G, Wilkowsky S, Farber M, Echaide I, Suarez C.

Institute of Pathobiology, CICVyA, INTA-Castelar, Buenos Aires, Argentina.

Babesia bovis is a tick-borne apicomplexan pathogen that remains an important constrain for the development of cattle industries worldwide. Effective control can be achieved by vaccination with live attenuated forms of the parasite, but they have several drawbacks and thus the development of alternative subunit vaccines, either based in recombinant versions of full size proteins or in recombinant or synthetic peptides containing combinations of protective B-cell and T-cell epitopes is needed. Our current strategies for the identification of vaccine candidate antigens include the identification of functionally relevant antigens, bioinformatics, and comparative genomics using the recently sequenced B. bovis genome. These led us to the functional and immunological characterization of members of the VMSA gene family, a group of well conserved putative cysteine and serine proteases, and to the definition of a surface exposed B-cell epitope present in the Merozoite Surface Antigen-2c. Work in progress is focused in defining additional epitopes, and to determine whether they are neutralization-sensitive. These approaches might unravel useful vaccine candidates for B. bovis, and will increase our understanding of the pathogenicity mechanisms of these and related hemoparasites.

PMID: 17691600 [PubMed - indexed for MEDLINE]

63. J S Afr Vet Assoc. 2007 Mar;78(1):2-5.

Molecular characterisation of Babesia gibsoni infection from a pit-bull terrier pup recently imported into South Africa.

Matjila PT, Penzhorn BL, Leisewitz AL, Bhoora R, Barker R.

Department of Veterinary Tropical Diseases, Faculty of Veterinary Science, University of Pretoria, Onderstepoort, 0110 South Africa.

Canine babesiosis caused by Babesia gibsoni was diagnosed in a 3-month-old Pit-bull pup during a routine clinical examination. Diagnosis was confirmed by way of smear examination, PCR, Reverse Line Blot (RLB) and sequence analysis which showed 100% homology with B. gibsoni (Japan AB118032) and Babesia sp. (Oklahoma) (AF205636). Haematology showed moderate anaemia and severe thrombocytopenia. Treatment was initiated with diminazene aceturate (Berenil RTU) followed by 2 doses of imidocarb diproprionate (Forray-65) 3 days and 14 days later, respectively. Babesia gibsoni DNA was still detectable 2 weeks post-treatment on the PCR/RLB test. A 10-day course of combination drug therapy using atovaquone and azithromycin was initiated. Blood samples taken on Day 1 and Day 40 after completion of treatment were negative for B. gibsoni DNA on PCR/RLB test. The implications of a possible introduction of B. gibsoni into South Africa are discussed.

PMID: 17665757 [PubMed - indexed for MEDLINE]

64. Chest. 2007 Jul;132(1):347-50.

A 57-year-old man with abdominal pain, jaundice, and a history of blood transfusion.

Babu RV, Sharma G.

Allergy, Pulmonary, Immunology, Critical Care, and Sleep (APICS) Division, 301 University Blvd, JSA-5.112, UTMB, Galveston, TX 77555-0561, USA.

PMID: 17625097 [PubMed - indexed for MEDLINE]

65. Eur J Clin Microbiol Infect Dis. 2007 Aug;26(8):595-601.

First confirmed autochthonous case of human Babesia microti infection in Europe.

Hildebrandt A, Hunfeld KP, Baier M, Krumbholz A, Sachse S, Lorenzen T, Kiehntopf M, Fricke HJ, Straube E.

Institute of Medical Microbiology, Friedrich Schiller University, Semmelweiss Str. 4, 07743, Jena, Germany.

A 42-year-old female patient with acute myeloid leukemia presented with fever and heavy chest pain after her first cycle of specific chemotherapy. Acute myocardial infarction was excluded, but surprisingly, parasitic inclusions in erythrocytes became obvious in Pappenheim and Giemsa-stained peripheral blood smears. The patient did not remember a tick bite but acknowledged having received several blood transfusions in her recent medical history. Suspicion of malaria was ruled out by use of a dip-stick test. The diagnosis of Babesia microti infection was finally established by specific polymerase chain reaction (PCR). Six weeks after initiation of specific treatment, PCR turned negative and a positive immunoflourescence assay (IFA) with an IgG titer of 1:128 indicated seroconversion. Subsequent screening of donors involved in the transfusion of blood products to the patient demonstrated borderline reactivity for Babesia microti (IgG-titer 1:32) in 1 out of 44 individuals. Neither the patient nor the positively tested blood donor had travelled to North America or Asia. Therefore, this is the first confirmed autochthonous human infection in Europe.

PMID: 17587072 [PubMed - indexed for MEDLINE]

66. J Vet Med Sci. 2007 May;69(5):563-8.

A Possible treatment strategy and clinical factors to estimate the treatment response in Bebesia gibsoni infection.

Suzuki K, Wakabayashi H, Takahashi M, Fukushima K, Yabuki A, Endo Y.

Laboratory of Veterinary Internal Medicine, Faculty of Agriculture, Kagoshivma University, Korimoto, Kagoshima, Japan.

The effectiveness of combination therapy using clindamycin, metronidazole and doxycycline against canine babesiosis, and the usefulness of platelet count and the plasma C-reactive protein (CRP) concentration as an estimation factor for treatment, were evaluated in four dogs experimentally infected with Babesia gibsoni. The combination therapy successfully eliminated B. gibsoni in peripheral blood in 3 of 4 dogs, however the remaining dog showed obvious uncontrolled relapse after a temporary recovery. In addition, it was shown that CRP levels decreased in an inverse relationship to the recovery of packed cell volume and therefore CRP levels could be used as an optional clinical marker to estimate the response to treatment.

PMID: 17551236 [PubMed - indexed for MEDLINE]

67. N Engl J Med. 2007 May 31;356(22):2313-9.

Case records of the Massachusetts General Hospital. Case 17-2007. A 25-year-old woman with relapsing fevers and recent onset of dyspnea.

Stowell CP, Gelfand JA, Shepard JA, Kratz A.

Blood Transfusion Service, Massachusetts General Hospital, USA.

PMID: 17538091 [PubMed - indexed for MEDLINE]

68. Dev Biol (Basel). 2007;127:17-41.

Parasitic infections in the blood supply: assessing and countering the threat.

Wendel S, Leiby DA.

Blood Bank, Hospital Sirio Libanês, São Paulo, Brazil.

PMID: 17486879 [PubMed - indexed for MEDLINE]

69. Homeopathy. 2007 Apr;96(2):90-4.

Clinical management of babesiosis in dogs with homeopathic Crotalus horridus 200C.

Chaudhuri S, Varshney JP.

Clinical Diagnosis laboratory, Referral Veterinary Polyclinic, Indian Veterinary Research Institute, Izatnagar 243122 UP, India.

Homeopathic Crotalus horridus 200C was evaluated in 13 clinical cases of babesiosis in dogs, compared with another 20 clinical cases treated with diminazine. Babesiosis is an important tropical tick-borne haemoprotozoan disease in dogs clinically manifested by anorexia, dehydration, temperature, dullness/depression, diarrhoea/constipation, pale mucosa, hepatomegaly, vomiting/nausea, splenomegaly, distended abdomen/ascites, yellow coloured urine, emaciation/weight loss, and occular discharge. The diagnosis of babesiosis was based on cytological evidence of Babesia gibsoni in freshly prepared blood smears. The dogs were treated with oral C. horridus 200C, 4 pills four times daily for 14 days (n=13) or diminazine aceturate 5 mg/kg single intramuscularly dose (n=20). All the dogs were administered 5% Dextrose normal saline at 60 ml/kg intravenously for 4 days. Initial clinical scores were similar in both groups and showed similar progressive improvement with the two treatments over 14 days. Parasitaemia also improved in both groups, but haematological values showed no change. No untoward reactions were observed. It appears that C. horridus is as effective in causing clinical recovery in moderate cases of canine babesiosis caused by Babesia gibsoni as the standard drug diminazine. Large scale randomized trials are indicated for more conclusive results.

PMID: 17437935 [PubMed - indexed for MEDLINE]

70. J Parasitol. 2007 Feb;93(1):208-11.

Modification of host erythrocyte membranes by trypsin and chymotrypsin treatments and effects on the in vitro growth of bovine and equine Babesia parasites.

Okamura M, Yokoyama N, Takabatake N, Okubo K, Ikehara Y, Igarashi I.

National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido 080-8555, Japan.

In the present study, we investigated the effects of protease pretreatments of host erythrocytes (RBC) on the in vitro growth of bovine Babesia parasites (Babesia bovis and B. bigemina) and equine Babesia parasites (B. equi and B. caballi). The selected proteases, trypsin and chymotrypsin, clearly modified several membrane proteins of both bovine and equine RBC, as demonstrated by SDS-PAGE analysis; however, the protease treatments also modified the sialic acid content exclusively in bovine RBC, as demonstrated by lectin blot analysis. An in vitro growth assay using the protease-treated RBC showed that the trypsin-treated bovine RBC, but not the chymotrypsin-treated ones, significantly reduced the growth of B. bovis and B. bigemina as compared to the control. In contrast, the growth of B. equi and B. caballi was not affected by any of these proteases. Thus, the bovine, but not the equine, Babesia parasites require the trypsin-sensitive membrane (sialoglyco) proteins to infect the RBC.

PMID: 17436968 [PubMed - indexed for MEDLINE]

71. Xenotransplantation. 2007 Mar;14(2):162-5.

Babesia as a complication of immunosuppression following pig-to-baboon heart transplantation.

Ezzelarab M, Yeh P, Wagner R, Cooper DK.

Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA 15261, USA. [corrected]

Erratum in Xenotransplantation. 2007 Jul;14(4):374.

We report a baboon that developed anemia, leukocytosis, fever, and anorexia while immunosuppressed following a pig heart transplant. Blood smears indicated babesia infection of the erythrocytes, and this was confirmed by polymerase chain reaction. A 1-week course of treatment with doxycycline successfully eradicated the organism. Babesia, a widespread blood parasite that can infect humans, has been reported to be present in the erythrocytes of approximately a third of baboons housed in facilities in the USA, without overt signs of infection. Immunosuppression can reduce the host's immune system, and result in proliferation of the parasite, leading to hemolysis and other features of infection, sometimes with fatal outcome.

PMID: 17381691 [PubMed - indexed for MEDLINE]

72. Vet Parasitol. 2007 May 31;146(3-4):221-6. Epub 2007 Mar 26.

Babesia bigemina: attenuation of an Uzbek isolate for immunization of cattle with live calf- or culture-derived parasites.

Shkap V, Rasulov I, Abdurasulov S, Fish L, Leibovitz B, Krigel Y, Molad T, Mazuz ML, Savitsky I.

Kimron Veterinary Institute, P.O. Box 12, Bet Dagan 50250, Israel.

The virulence of an Uzbek isolate of Babesia bigemina, obtained from infected Boophilus annulatus ticks from an endemic area in Uzbekistan, was attenuated for immunization of cattle with autochthonous calf- or culture-derived parasites in Uzbekistan. After four "slow passages" in vivo the virulence was reduced, as evidenced by the response of calves inoculated with an experimental live frozen vaccine produced from the following passage. The vaccine was safe and protective against homologous virulent challenge under laboratory conditions. The culture-derived experimental vaccine was produced from cultures initiated after 3 passages in vivo followed by 22 passages in vitro. The cultured parasites did not elicit any clinical sign, but inoculated calves seroconverted following vaccination and were protected against the virulent homologous challenge. Both calf- and culture-derived vaccines were safe for cattle grazing in an endemic area in Uzbekistan. Despite the high polymorphism of B. bigemina, as reported from various geographical regions, the Central Asian strain was attenuated similarly to those that form the basis of the existing live B. bigemina vaccines in other parts of the world.

PMID: 17368728 [PubMed - indexed for MEDLINE]

73. Pediatr Infect Dis J. 2007 Feb;26(2):181-3.

Atovaquone and azithromycin treatment for babesiosis in an infant.

Raju M, Salazar JC, Leopold H, Krause PJ.

Division of Infectious Diseases, Department of Medicine, University of Connecticut Health Center, Farmington, CT, USA.

An 8-month-old infant with cyanotic heart disease and transfusion-associated Babesia microti infection is reported here. At initial presentation, she was ill appearing, febrile and cyanotic. Laboratory tests revealed severe anemia, thrombocytopenia and an increase in hepatic enzymes. The diagnosis was made by the presence of intraerythrocytic parasites on thin blood smear and confirmed by serology and polymerase chain reaction. The infant was treated successfully with a combination of oral azithromycin and atovaquone. This combination is an alternative to clindamycin and quinine for the treatment of children with babesiosis.

PMID: 17259886 [PubMed - indexed for MEDLINE]

74. Vaccine. 2007 Mar 1;25(11):2027-35. Epub 2006 Dec 8.

Babesia gibsoni ribosomal phosphoprotein P0 induces cross-protective immunity against B. microti infection in mice.

Terkawi MA, Jia H, Zhou J, Lee EG, Igarashi I, Fujisaki K, Nishikawa Y, Xuan X.

National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido 080-8555, Japan.

Babesia gibsoni ribosomal phosphoprotein P0 (BgP0) was identified as an immunodominant cross-reactive antigen with B. microti. The BgP0 gene is a single copy with a predicted open reading frame of 942 bp and 314 amino acids. The BgP0 was expressed as a glutathione S-transferase fusion protein in Escherichia coli. The serum raised in mice with the recombinant BgP0 showed a specific band with a 34-kDa molecular mass in the extracts of B. gibsoni and B. microti merozoites. Furthermore, the intraperitoneal (i.p.) immunization of rBgP0 and Freund's adjuvant induced strong humoral response consisting of mixed immunoglobulins IgG1 and IgG2a in BALB/c mice. Following the challenge with B. microti, these mice delayed the onset of parasites and significantly reduced the peripheral parasitemia. On the other hand, passive-transfer of purified anti-BgP0 IgG into SCID mice showed partial protection against B. microti challenge infection. It was only effective in restricting the initial parasitemia but not later during its progress. Taken together, the immunological response elicited by rBgP0 protected the mice against B. microti challenge infection. These data suggest that BgP0 is a potentially universal vaccine candidate for both B. gibsoni and B. microti infections.

PMID: 17229504 [PubMed - indexed for MEDLINE]

75. Ann N Y Acad Sci. 2006 Oct;1081:405-16.

Bovine babesiosis live vaccine production: use of gamma irradiation on the substrate.

Rojas C, Figueroa JV, Alvarado A, Mejia P, Mosqueda JJ, Falcon A, Vega CA, Alvarez A.

CENID Parasitología Veterinaria, INIFAP, Morelos, C.P. 62500, Mexico.

Gamma irradiation on bovine serum and red blood cells (RBC) allows proliferation and growth of in vitro-cultured Babesia sp., and has potential application to inactivate contaminating viruses and bacteria from the substrate. Gamma irradiation with 25 kGy in a source of (60)Co was able to inactivate infectious bovine rinotracheitis (IBR) and bovine viral diarrhea (BVD) viruses in artificially contaminated serum; besides, bacteria were also eliminated. In vitro culture of Babesia bovis (B. bovis) in modified substrate, by adding irradiated serum with (60)Co at 25 kGy was propagated from 24-well culture plates to 225 cm(2) tissue culture flasks, and percentages of parasitized erythrocytes (PPE) from 2.4% to 8.8% were obtained. Infected RBC adapted to Irrad S were transferred to the irradiated substrate in vitro culture system, by using serum irradiated at 25 kGy and RBC from 10 to 70 Gy. The PPE ranged from 3.1 to 11. Culture of Babesia bigemina (B. bigemina) was established with Irrad S (25 kGy); its propagation was achieved in tissue culture flasks reaching PPE from 0.5 to 4.3 with no statistical difference (P > 0.05) when compared to the nonirradiated control culture (1.2-4.8). B. bigemina-infected RBCs were transferred to the modified culture system by adding irradiated serum and RBC (25 kGy and 70 Gy, respectively). PPE obtained in culture flasks were from 0.8 to 4.2. The results indicate that gamma irradiation is a suitable method to inactivate potential viral contamination and eliminate bacteria from bovine serum, to produce a live attenuated vaccine through the in vitro culture.

PMID: 17135544 [PubMed - indexed for MEDLINE]

76. Ann N Y Acad Sci. 2006 Oct;1081:397-404.

Evaluation of cattle inoculated with Babesia bovis clones adhesive in vitro to bovine brain endothelial cells.

Canto GJ, Figueroa JV, Ramos JA, Rojas EE, Garcia-Tapia D, Alvarez JA, Allred DR, Carson CA.

CENID-Fisiologia Animal, INIFAP, Ajuchitlan, Qro., 76280 Mexico.

A comparative assessment of the virulence of Babesia bovis clones that adhere or not to bovine brain endothelial cells was done using two clones of B. bovis: (1) a clone phenotypically characterized as virulent (2F8) and (2) a clone of reduced virulence (RAD). Of these subpopulations, we selected those that had adhesive characteristics (a) or nonadhesive characteristics (na) in cultured endothelial cells. Twenty Holstein cattle, 12 months of age or older, were used in this study, and these cattle were randomly assigned to five groups of four animals each. The clones and their respective subpopulations were inoculated via intramuscular injection at a 0.5 x 10(7) infected erythrocyte dosage. Group A was inoculated with aRAD, group B with naRAD, group C with a2F8, group D with na2F8, and group E remained as a control. All inoculated animals showed a decrease in the packed cell volume (PCV), with group D showing the largest decrease (39.53%) and longest time (7 days) with rectal temperature above 39.5 degrees C. Babesia was observed in stained blood smears from only six cattle. While the four parasite subpopulations were pathogenic, significant differences were not noted among them, despite that the subpopulations considered to be virulent caused the greatest reduction in PCV per individual.

PMID: 17135543 [PubMed - indexed for MEDLINE]

77. Vet Parasitol. 2007 Mar 15;144(1-2):10-9. Epub 2006 Oct 23.

Immunity against Babesia rossi infection in dogs vaccinated with antigens from culture supernatants.

Schetters TP, Strydom T, Crafford D, Kleuskens JA, van de Crommert J, Vermeulen AN.

Parasitology R&D Department, Intervet International B.V., P.O. Box 31, 5830 AA Boxmeer, The Netherlands.

Soluble parasite antigens (SPA) from different Babesia species have been shown earlier to induce protective immunity when used as vaccine. However, initial attempts to produce such vaccine against Babesia rossi infection using SPA from B. rossi culture supernatants were not or only partially successful. Here we show that when dogs were vaccinated with a vaccine comprising SPA from B. rossi combined with SPA from Babesia canis protective immunity against experimental challenge infection was induced. Immunity was reflected in reduced clinical signs that resolved spontaneously, and reduction of parasitaemia and SPA in the blood. Not a single infected erythrocyte could be found in blood smears of dogs that had been repeatedly boosted (three vaccinations in total). In contrast, three out of four control dogs required chemotherapeutic treatment to prevent death. The fourth control dog showed a transient parasitaemia that resolved spontaneously. Vaccination did not prevent the development of a transient anaemia. It is concluded that a vaccine containing a mixture of SPA obtained from in vitro culture supernatants of B. rossi and B. canis induces protection in dogs against heterologous challenge infection with B. canis (as shown before) or B. rossi.

PMID: 17056181 [PubMed - indexed for MEDLINE]

78. Vaccine. 2007 Jan 26;25(7):1334-41. Epub 2006 Oct 10.

Prime-boost immunization with DNA followed by a recombinant vaccinia virus expressing P50 induced protective immunity against Babesia gibsoni infection in dogs.

Fukumoto S, Tamaki Y, Okamura M, Bannai H, Yokoyama N, Suzuki T, Igarashi I, Suzuki H, Xuan X.

Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.

A heterologous prime-boost immunization regime with priming DNA followed by recombinant vaccinia virus expressing relevant antigens has been shown to induce effective immune responses against several infectious pathogens. In this study, we constructed a recombinant plasmid and vaccinia virus, both of which expressed P50 of Babesia gibsoni, to investigate the immunogenicity and protective efficacy of a heterologous prime-boost immunization against canine babesiosis. The dogs immunized with the prime-boost regime developed a significantly high level of specific antibody against P50 when compared with the control groups, and the antibody level was strongly increased after a booster immunization with a recombinant vaccinia virus. The prime-boost immunization regime induced a specific IgG2 antibody response and IFN-gamma production in dogs. Two weeks after the booster immunization with a recombinant vaccinia virus expressing P50, the dogs were challenged with B. gibsoni patasites. The dogs immunized with the prime-boost regime showed partial protection, manifested as a significantly low level of parasitemia and a 2-day delay of the peak parasitemia. These results indicated that such a heterologous prime-boost immunization approach might be useful against B. gibsoni infection in dogs.

PMID: 17055131 [PubMed - indexed for MEDLINE]

79. Adv Ther. 2006 Jan-Feb;23(1):1-11.

Atovaquone plus cholestyramine in patients coinfected with Babesia microti and Borrelia burgdorferi refractory to other treatment.

Shoemaker RC, Hudnell HK, House DE, Van Kempen A, Pakes GE; COL40155 Study Team.

Center for Research on Biotoxin-Associated Illnesses Pocomoke City, Maryland 21851, USA.

Ten percent of US patients with Lyme disease are coinfected with Babesia microti. A double-blind, placebo-controlled, crossover trial enrolled 25 patients with confirmed Borrelia burgdorferi/B microti coinfection, abnormal visual contrast sensitivity (VCS), and persistent symptoms despite prior treatment with atovaquone and azithromycin. Patients were randomly assigned to atovaquone suspension or placebo plus cholestyramine for 3 weeks, were crossed over for 3 weeks, and then received open-label atovaquone and cholestyramine for 6 weeks. Symptoms and VCS scores were recorded at baseline and after weeks 3, 6, 9, and 12. Improvements in symptoms and VCS deficits were observed only after at least 9 weeks of treatment. At week 12, 5 patients were asymptomatic, and 16 had a notable reduction in the number of symptoms. The entire cohort demonstrated significant increases in VCS scores. Adverse effects were rare. Patients coinfected with B burgdorferi and B microti derive measurable clinical benefit from prolonged treatment with atovaquone and cholestyramine. Longer-term combination therapy may be indicated.

PMID: 16644602 [PubMed - indexed for MEDLINE]

80. Acta Vet Hung. 2006 Mar;54(1):19-33.

Clinicopathological changes and effect of imidocarb therapy in dogs experimentally infected with Babesia canis.

Máthé A, Vörös K, Németh T, Biksi I, Hetyey C, Manczur F, Tekes L.

Department and Clinic of Internal Medicine, Faculty of Veterinary Science, Szent István University, H-1078 Budapest, Hungary.

In this study one spleen-intact dog (A) and two splenectomised dogs (BSE, CSE) were infected with Babesia canis. All animals developed an acute disease characterised by fever, haemoglobinuria and anaemia, the latter being more severe in the splenectomised dogs. Fever and parasitised red blood cells were detected for three days after imidocarb treatment in the splenectomised animals. Haematological abnormalities included regenerative anaemia, thrombocytopenia and leukopenia (due to neutropenia and lymphopenia) in the acute phase, soon followed by leukocytosis, neutrophilia and left shift a few days later. Acute hepatopathy was detected in all dogs with elevated ALT activity, which was more seriously altered in the splenectomised dogs. Diffuse changes in liver structure and hepatomegaly were seen by ultrasonography. Liver biopsy and histology revealed acute, non-purulent hepatitis in the splenectomised dogs. Both splenectomised dogs were successfully cured after collection of 400 ml highly parasitised blood, proving that large-amount antigen production is possible with rescuing the experimental animals. Whole blood transfusion, imidocarb and supportive care with infusions, antipyretics, glucocorticoids and diuretics were applied. The spleen-intact dog clinically recovered after receiving supportive treatment, with no imidocarb therapy. Microbial infections developed in both splenectomised animals (BSE: haemobartonellosis, CSE: osteomyelitis caused by Escherichia coli), probably as a consequence of immunosuppression after splenectomy and glucocorticoid therapy.

PMID: 16613023 [PubMed - indexed for MEDLINE]

81. Vet Parasitol. 2006 May 31;138(1-2):118-25. Epub 2006 Feb 28.

Canine babesiosis in France.

Bourdoiseau G.

Unité de Parasitologie-Mycologie-Maladies Parasitaires, Ecole Nationale Vétérinaire de Lyon, 1 av. Bourgelat, 69280 Marcy l'Etoile, France.

Canine babesiosis has a high prevalence in France and continues to constitute a diagnostic challenge. This paper presents essential data derived from epidemiological surveys in order to define the main features of this disease. Atypical forms are frequent, the diagnosis must be confirmed by blood smears and treatment is based on the use of imidocarb. Prophylaxis currently remains insufficient.

PMID: 16507334 [PubMed - indexed for MEDLINE]

82. Vox Sang. 2006 Apr;90(3):157-65.

Babesiosis and blood transfusion: flying under the radar.

Leiby DA.

Department of Transmissible Diseases, Jerome H. Holland Laboratory for the Biomedical Sciences, American Red Cross, Rockville, MD 20855, USA.

Infectious agents of disease continue to plague transfusion medicine as an increasing number of pathogens are described that pose a potential blood safety risk. While the recent focus has been on newly emerged agents, several well-established pathogens provide timely reminders that other agents continue to pose threats, but invariably 'fly under the radar', thereby failing to elicit adequate measures to prevent their transmission by blood transfusion. Perhaps foremost among this group of agents are the Babesia spp., which have been known to cause human disease, in the USA, for close to 40 years. B. microti, B. divergens and several Babesia-like agents are responsible for a growing number of human babesiosis infections. Concomitantly, in the USA, there has been a sharp rise in the number of transfusion-transmitted infections of Babesia spp., attributable almost exclusively to B. microti. Despite the obvious public health issues posed by Babesia spp., options for preventing their transmission by blood transfusion remain limited. However, recognition that the Babesia spp. are indeed an ongoing and expanding blood safety threat will probably prove instrumental in the development of viable interventions to limit transmission of these agents.

PMID: 16507014 [PubMed - indexed for MEDLINE]

83. Vet Parasitol. 2006 May 31;138(1-2):88-96. Epub 2006 Feb 28.

Live vaccines against bovine babesiosis.

de Waal DT, Combrink MP.

Department of Veterinary Microbiology and Parasitology, Faculty of Veterinary Medicine, University College Dublin, Belfield, Dublin 4, Ireland.

Bovine babesiosis is an important tick-borne disease caused by Babesia bovis, B. bigemina and B. divergens. The first steps taken in the development of an effective vaccination strategy against bovine babesiosis followed the observations that animals, recovered from natural infection with Babesia were strongly protected against subsequent challenge. Further investigation indicated that the use of donor blood from recovered animals to infect recipient animals did not produce the severe form of the disease. The past century has seen a refinement of this original carrier-donor system to one using attenuated less virulent strains with standardized doses of known parasite concentration to ensure reliability. With the implementation of good manufacturing practices further changes were necessary in the production of these vaccines, such as freezing for long-term storage to allow sufficient time for pre-release safety and effectivity testing. Regardless of these improvements the vaccines are not without problems and breakdowns and breakthroughs occur from time to time. Despite considerable research efforts into the development of alternative more consumer friendly vaccines, none is immediately forthcoming and the live attenuated babesiosis vaccines are still used in many countries.

PMID: 16504404 [PubMed - indexed for MEDLINE]

84. Vet Parasitol. 2006 May 31;138(1-2):147-60. Epub 2006 Feb 28.

Chemotherapy against babesiosis.

Vial HJ, Gorenflot A.

Dynamique Moléculaire des Interactions Membranaires, UMR 5539 CNRS/Université Montpellier II, Case 107, Place Eugène bataillon, F-34095 Montpellier Cedex 5, France.

Babesiosis is caused by a haemotropic protozoal parasite of the genus Babesia, member of the phylum Apicomplexa and transmitted by the bite of an infected tick. There are many Babesia species affecting livestock, dogs, horses and rodents which are of economic significance. Infections can occur without producing symptoms, but babesiosis may also be severe and sometimes fatal caused by the intraerythrocytic parasite development. The disease can cause fever, fatigue and haemolytic anemia lasting from several days to several months. There are a number of effective babesiacides, but imidocarb dipropionate (which consistently clears the parasitaemia; often the only available drug on the market) and diminazene aceturate are the most widely used. Some Babesia spp. can infect humans, particularly Babesia microti and Babesia divergens, and human babesiosis is a significant emerging tick-borne zoonotic disease. Clinical manifestations differ markedly between European and North American diseases. In clinical cases, a combination of clindamycin and quinine is administered as the standard treatment, but also administration of atovaquone-azithromycin is successful. Supportive therapy such as intravenous fluids and blood transfusions are employed when necessary. More specific fast-acting new treatments for babesiosis have now to be developed. This should be facilitated by the knowledge of the Babesia spp. genome and increased interest for this malaria-like parasite.

PMID: 16504402 [PubMed - indexed for MEDLINE]

85. Chemotherapy. 2006;52(2):53-9. Epub 2006 Feb 22.

Lyme disease: the quest for magic bullets.

Stricker RB, Lautin A, Burrascano JJ.

California Pacific Medical Center, San Francisco, CA 94108, USA.

Lyme disease represents a growing public health threat. Recent molecular and genetic studies have confirmed that Borrelia burgdorferi, the spirochetal agent of Lyme disease, is one of the most complex bacteria known to man. Affinity for multiple cell types and the presence of non-replicating forms of B. burgdorferi have contributed to persistent infection and failure of simple antibiotic regimens. The controversial clinical science of Lyme disease has impeded reliable diagnosis and effective treatment of this protean illness. Two major clinical hurdles are the absence of a therapeutic endpoint in treating Lyme disease and the presence of tick-borne coinfections that may complicate the course of the illness. New strategies for the diagnosis, treatment and prevention of Lyme disease are urgently needed.

Copyright 2006 S. Karger AG, Basel.

PMID: 16498239 [PubMed - indexed for MEDLINE]

86. Pediatr Infect Dis J. 2006 Feb;25(2):169-73.

Neonatal babesiosis: case report and review of the literature.

Fox LM, Wingerter S, Ahmed A, Arnold A, Chou J, Rhein L, Levy O.

Division of Infectious Diseases, Children's Hospital Boston, Harvard Medical School, Boston, MA.

Comment in Pediatr Infect Dis J. 2010 Feb;29(2):188.

A case of transfusion-associated neonatal babesiosis is presented. Jaundice, hepatosplenomegaly, anemia and conjugated hyperbilirubinemia developed in this preterm infant. The diagnosis was eventually made by blood smear, serology and polymerase chain reaction. The patient was treated with clindamycin and quinine and made a favorable recovery. Of neonatal babesiosis reported in the literature, 9 other cases are reviewed, including 6 that were transfusion-associated, 2 congenital and 2 tick transmitted.

PMID: 16462298 [PubMed - indexed for MEDLINE]

87. Behav Processes. 2006 Mar;72(1):74-83. Epub 2006 Jan 26.

Odour learning and immunity costs in mice.

Barnard CJ, Collins SA, Daisley JN, Behnke JM.

Animal Behaviour Research Group, School of Biology, University of Nottingham, University Park, Nottingham NG7 2RD, UK.

There is accumulating evidence that learning is metabolically costly. One way in which this may manifest itself is in trade-offs between learning effort and immune function, with learning increasing susceptibility to infection. We tested this idea in the context of odour learning using outbred (BKW) male laboratory mice. Mice were exposed to three experimental treatments in which they were required to learn different numbers of urinary odours. While treatment affected the extent to which mice habituated to test odours during training, differences were not a simple function of the number of odours. The fact that there was also no significant effect of treatment on the degree of preference for novel over familiar odours in subsequent tests suggests mice retained learned odour profiles equally well regardless of the number of odours. That subsequent infection with Babesia microti increased with the number of odours mice had to learn is then consistent with an increased cost to learning effort when more odours were presented. Analysis within treatments, and relationships with the change in corticosterone concentration over the period of the experiment, suggested that it was a failure to learn, rather than maintaining learning performance, in more difficult learning tasks that led to greater infection. As in a previous study of maze learning in the strain, there was no direct relationship between infection and measures of peripheral antibody (total IgG) titre. The results are discussed in relation to studies in other learning contexts and reported relationships between glucocorticoid hormones and learning outcomes.

PMID: 16442748 [PubMed - indexed for MEDLINE]

88. Tijdschr Diergeneeskd. 2005 Dec 1;130(23):726-31.

[A literature review of equine piroplasmosis after an episode of acute babesiosis in a Dutch Standardbred foal after a stay in Normandy].

[Article in Dutch]

Butler CM, van Gils JA, van der Kolk JH.

Hoofdafdeling Gezondheidszorg Paard, Discipline Inwendige Ziekten, Faculteit der Diergeneeskunde, Universiteit Utrecht, Yalelaan 16, 3508 TD Utrecht.

Comment in Tijdschr Diergeneeskd. 2006 Jan 15;131(2):44.

Piroplasmosis, a disease endemic to most tropical and subtropical areas, appears to be spreading to more temperate zones. This article gives a review of equine piroplasmosis and describes an acute case of infection with Babesia caballi in a Dutch Standard bred foal after a short stay at a stud in Normandy (France). A 3-month-old stallion foal was presented with lethargy, fever of 41 degrees C, and pale mucosal membranes. Haematology revealed a low packed cell volume (14 l/l) leucytosis (25 G/l) and a high blood urea nitrogen concentration (20.1mmol/l). Infection with B. caballi was diagnosed on the basis of Giemsa staining blood smears and was confirmed by polymerase chain reaction in combination with RLB. Treatment with imidocarb dipropionate and a blood transfusion resolved the haemolytic crisis.

PMID: 16363205 [PubMed - indexed for MEDLINE]

89. Clin Adv Hematol Oncol. 2003 May;1(5):307-13.

Risks of blood transfusion and their prevention.

Sandler SG, Yu H, Rassai N.

Georgetown University Medical Center, Washington, DC 20007, USA.

As a result of significant progress in reducing the risks of transfusion-transmitted viral infections, bacterial contamination of platelet components (1:2,000) and sepsis (1:50,000) are now the most frequent infectious complications of blood transfusions. Sepsis from bacterial contamination of red cell components is less frequent (1:500,000), because red blood cells, unlike platelet components, can be stored at refrigerated temperatures (1 degrees C-4 degrees C). Current risks for transfusion-transmitted viral diseases (per blood component transfused) are: human immunodeficiency virus, 1:2,135,000; hepatitis C virus, 1:1,935,000; hepatitis B virus, 1:205,000; and human T-lymphotropic viruses, 1:2,993,000. Transfusion-transmitted babesiosis has increased morbidity and mortality for splenectomized patients. Immunocompromised recipients are at increased risk of developing Chagas disease from blood contaminated by Trypanosoma cruzi. Reports of transfusion-related acute lunge injury and transfusion-associated graft-versus-host disease increase each year as physicians become increasingly aware of their varied clinical presentations. While strategies for preventing infections complications focus primarily on blood donor services, individual physicians can reduce risks to their patients by maintaining conservative "triggers" for transfusions, prescribing pharmacologic agents to reduce bleeding (antifibrinolytic drugs, serine protease inhibitors, fibrin sealants), and using epoetin alpha to reduce transfusion of red cells in selected patients.

PMID: 16224428 [PubMed - indexed for MEDLINE]

90. Parasitol Res. 2005 Dec;97(6):472-7. Epub 2005 Sep 17.

The treatment of mice with Lactobacillus casei induces protection against Babesia microti infection.

Bautista-Garfias CR, Gómez MB, Aguilar BR, Ixta O, Martínez F, Mosqueda J.

CENID-PAVET, INIFAP Apdo, Postal 206, CIVAC, 62500 Estado de Morelos, México.

In this study, we report that administration of Lactobacillus casei confers protection to mice against the intracellular protozoan Babesia microti. Mice treated with L. casei orally or intraperitoneally were inoculated 7 days later with an infectious dose of B. microti. Mice treated with lactobacilli showed significant reduction in the percentage of parasitized erythrocytes (PPE) compared to untreated mice. When mice were inoculated intraperitoneally with L. casei 3 or 0 days before challenge with B. microti, the PPE was significantly lower compared to untreated mice and there were no differences between treated mice and mice immune to B. microti infection. When mice treated with live or dead L. casei were compared to mice inoculated with Freund Complete Adjuvant before a B. microti infection, a significant reduction of PPE was observed. These results show the protective effect of L. casei administered to mice against a B. microti infection and suggest that it might act by stimulating the innate immune system.

PMID: 16170567 [PubMed - indexed for MEDLINE]

91. Vet J. 2007 Mar;173(2):384-90. Epub 2005 Oct 5.

Epidemiological aspects and economic impact of bovine theileriosis (East Coast fever) and its control: a preliminary assessment with special reference to Kibaha district, Tanzania.

Kivaria FM, Ruheta MR, Mkonyi PA, Malamsha PC.

Animal Diseases Research Institute, P.O. Box 9254, Dar es Salaam, Tanzania.

Comment in Vet J. 2007 Mar;173(2):248-9.

A cross-sectional study based on clinical examination, inspection of herd health records and a questionnaire was designed to determine the epidemiology, economics and potential impact of immunisation against theileriosis in Tanzania. The results showed annual theileriosis costs to be US$ 205.40 per head, whereas the introduction of immunisation reduced this by 40-68% depending on the post immunisation dipping strategy adopted. Morbidity risk due to theileriosis was 0.048 in immunised and 0.235 in non-immunised cattle, and the difference was significant (chi(2)=66.7; P=0.000). The questionnaire results indicated that immunised cattle had a significantly (chi(2)=6; P=0.015) higher risk of anaplasmosis compared with non-immunised cattle, whereas the risk of bovine babesiosis did not differ significantly (chi(2)=0.06; P=0.807) between the two groups. Mortality risk due to anaplasmosis was 0.046 in immunised and 0.018 in non-immunised cattle and this difference was statistically significant (chi(2)=4.48; P=0.043). The theileriosis mortality risk was 0.203 in the non-immunised cattle, while the risk was 0.009 in the immunised cattle and these differences were also significant (chi(2)=103; P=0.000). It was concluded that farmers who have immunised their cattle may cautiously cut down acaricide application by 50% for extensively grazed herds and by 75% for zero grazed animals depending on the level of tick challenge at the herd level.

PMID: 16169755 [PubMed - indexed for MEDLINE]

92. Paediatr Drugs. 2005;7(3):163-76.

Tick-borne infections in children: epidemiology, clinical manifestations, and optimal management strategies.

Buckingham SC.

Department of Pediatrics, Division of Infectious Disease, University of Tennessee Health Science Center and Children's Foundation Research Center at Le Bonheur Children's Medical Center, Memphis, Tennessee, USA.

Ticks can transmit bacterial, protozoal, and viral infections to humans. Specific therapy is available for several of these infections. Doxycycline is the antimicrobial treatment of choice for all patients, regardless of age, with Rocky Mountain spotted fever, human monocytic ehrlichiosis, or human granulocytic ehrlichiosis. Chloramphenicol has been used to treat these infections in children but is demonstrably inferior to doxycycline. In patients with Mediterranean spotted fever, doxycycline, chloramphenicol, and newer macrolides all appear to be effective therapies. Therapy of Lyme disease depends on the age of the child and stage of the disease. For early localized disease, amoxicillin (for those aged <8 years) or doxycycline (for those aged >/=8 years) is effective. Doxycycline, penicillin V (phenoxymethylpenicillin) or penicillin G (benzylpenicillin) preparations, and erythromycin are all effective treatments for tick-borne relapsing fever. Hospitalized patients with tularemia should receive gentamicin or streptomycin. Doxycycline and ciprofloxacin have each been investigated for the treatment of tularemia in outpatients; however, these agents do not yet have established roles in the treatment of this disease in children. Combination therapy with clindamycin and quinine is preferred for children with babesiosis; the combination of azithromycin and atovaquone also appears promising. Ribavirin has been recently shown to markedly improve survival in patients with Crimean-Congo hemorrhagic fever. The role of antiviral therapy in the treatment of other tick-borne viral infections, including other hemorrhagic fevers and tick-borne encephalitis, is not yet defined.

PMID: 15977962 [PubMed - indexed for MEDLINE]

93. Planta Med. 2005 May;71(5):482-4.

Anti-babesial compounds from Curcuma zedoaria.

Kasahara K, Nomura S, Subeki, Matsuura H, Yamasaki M, Yamato O, Maede Y, Katakura K, Suzuki M, Trimurningsih, Chairul, Yoshihara T.

Laboratory of Bioorganic Chemistry, Division of Applied Bioscience, Graduate School of Agriculture, Hokkaido University, Sapporo, Japan.

Anti-babesial activity was confirmed in an extract of the bark of Curcuma zedoaria. The active ingredients were isolated, and their chemical structures were determined to be zedoalactones A, B, and C based on spectral data. Zedoalactone C is a hitherto unreported compound. The IC50 vales of these active compounds against Babesia gibsoni were compared with a standard drug, diminazene aceturate. The IC50 value of diminazene aceturate was 0.6 microg/mL, while those of zedoalactones A, B, and C were 16.5, 1.6 and 4.2 microg/mL, respectively.

PMID: 15977324 [PubMed - indexed for MEDLINE]

94. Parasitology. 2004;129 Suppl:S247-69.

Babesiosis of cattle.

Bock R, Jackson L, de Vos A, Jorgensen W.

Tock Fever Centre, Animal and Plant Health Service, Queensland Department of Primary Industries & Fisheries, 280 Grindle Road, Wacol Qld 4076, Australia.

Tick fever or cattle fever (babesiosis) is economically the most important arthropod-borne disease of cattle worldwide with vast areas of Australia, Africa, South and Central America and the United States continuously under threat. Tick fever was the first disease for which transmission by an arthropod to a mammal was implicated at the turn of the twentieth century and is the first disease to be eradicated from a continent (North America). This review describes the biology of Babesia spp. in the host and the tick, the scale of the problem to the cattle industry, the various components of control programmes, epidemiology, pathogenesis, immunity, vaccination and future research. The emphasis is on Babesia bovis and Babesia bigemina.

PMID: 15938514 [PubMed - indexed for MEDLINE]

95. Planta Med. 2005 May;71(5):420-3.

Anti-babesial activity of some central kalimantan plant extracts and active oligostilbenoids from Shorea balangeran.

Subeki, Nomura S, Matsuura H, Yamasaki M, Yamato O, Maede Y, Katakura K, Suzuki M, Trimurningsih, Chairul, Yoshihara T.

Division of Applied Bioscience, Graduate School of Agriculture, Hokkaido University, Sapporo, Japan.

Bark extracts from a total of 22 species of Central Kalimantan plants were evaluated for their anti-babesial activity against Babesia gibsoni in vitro. Of these plant species, extracts of Calophyllum tetrapterum, Garcinia rigida, Lithocarpus sp., Sandoricum emarginatum, and Shorea balangeran showed more than 90% inhibition of the parasite growth at a test concentration of 1000 microg/mL. Activity-guided fractionation of the bark of S. balangeran (Dipterocarpaceae) led to the reisolation of oligostilbenoids, vaticanol A(1), B(2), and G(3). The structures were determined on the basis of spectral evidence. Compounds 1 and 3 showed complete inhibition on the growth of Babesia gibsoni in vitro at a concentration of 25 microg/mL, and compound 2 at concentration of 50 microg/mL.

PMID: 15931579 [PubMed - indexed for MEDLINE]

96. Mil Med. 2005 Apr;170(4):295-6.

Transfusion-acquired babesiosis in a nonendemic area.

Della-Giustina D, Laird TW Jr, Smith T.

Department of Emergency Medicine, Madigan Army Medical Center, Tacoma, WA 98431, USA.

Babesiosis is a tick-borne illness endemic to the coastal areas of southern New England. Despite the enormous safety measures that transfusion and blood bank services perform for each product, transfusion of blood products is not without risk. The majority of transfusion-related reactions and complications are recognized soon after transfusion. We report a case of transfusion-acquired babesiosis in Washington State that presented 4 weeks after transfusion of a blood product from a donor living in a babesiosis-endemic area.

PMID: 15916297 [PubMed - indexed for MEDLINE]

97. J S Afr Vet Assoc. 2005 Mar;76(1):26-32.

Clinical and clinicopathological changes in 6 healthy ponies following intramuscular administration of multiple doses of imidocarb dipropionate.

Meyer C, Guthrie AJ, Stevens KB.

Equis Veterinary Practice, PO Box 2155, Hillcrest 3650, South Africa.

Haematological variables and selected serum indices, particularly those affected by changes in renal and hepatic function, were examined in 6 healthy ponies following 4 intramuscular doses of 4 mg/kg imidocarb dipropionate administered every 72 hours. This treatment regime has been reported to sterilise experimental Babesia equi infections in horses and may have value in preventing the spread of this disease during exportation of possible carrier horses to non-endemic countries. Serum bile acids and serum gamma glutamyltransferase activity were measured to evaluate the effect of this treatment regime on hepatic function. Owing to the absence of any increase in these variables it was concluded that this treatment regime had no clinically detectable deleterious effect on hepatic function in healthy ponies. Urinary gamma glutamyltransferase : creatinine ratios (IU/g), serum creatinine and fractional clearance of sodium, potassium and phosphate (%) were calculated as a measure of renal function. Urinary GGT and urinary GGT : creatinine ratios were significantly elevated on Day 5 of the trial, with 2 of the trial animals also exhibiting mild azotaemia indicative of changes in renal function. The changes in urine GGT : urine creatinine ratios observed in this study also provides evidence of the value of this ratio for the early detection of renal toxicity, following exposure to nephrotoxic agents.

PMID: 15900897 [PubMed - indexed for MEDLINE]

98. J Emerg Nurs. 2005 Apr;31(2):137-8.

A 56-year-old woman with fever, generalized body aches, and anemia after a tick bite.

Bradbury-Golas K, Washart C.

Emergency Department, Shore Memorial Hospital, 1 East New York Avenue, Somers Point, NJ 08244, USA.

PMID: 15856537 [PubMed - indexed for MEDLINE]

99. Vet Parasitol. 2005 May 15;129(3-4):235-42.

Vaccination of older Bos taurus bulls against bovine babesiosis.

Shkap V, Leibovitz B, Krigel Y, Hammerschlag J, Marcovics A, Fish L, Molad T, Savitsky I, Mazuz M.

Division of Parasitology, Kimron Veterinary Institute, P.O. Box 12, Bet Dagan 50250, Israel.

Two separate groups of Bos taurus bulls, one of 106 and the second of 27 animals, imported to Israel from areas free of Babesia bovis and Babesia bigemina, were vaccinated against babesiosis with a bivalent live attenuated vaccine. In light of the fact that routine vaccination is recommended at the weaning age, these bulls--of highly susceptible breeds--were kept under close surveillance to prevent losses that might be caused by severe clinical reactions to their vaccination at the age of 16-18 months. Seven days after vaccination, about one-third of the 106 bulls in the first group developed clinical signs of B. bigemina infection, which peaked at day 9, and then diminished from day 11, when the patent period known for B. bovis infection was observed. Because of the severe clinical responses a total of 36% of the bulls required babesicidal treatment. Despite the treatment Babesia were not sterilized: 33 and 68% of the animals remained PCR positive for B. bigemina and B. bovis, respectively. To mitigate the severe responses to vaccination, the 27 bulls of the second group were vaccinated in two-steps: they were inoculated initially with avirulent culture-derived parasites and then vaccinated with the conventional donor-derived vaccine a month later. None of the bulls in the latter group developed clinical babesiosis, all were serologically positive to B. bigemina, and 67% showed seroconversion to B. bovis. In light of the experience described here, it is suggested that sensitive older cattle be vaccinated against babesiosis by priming them with avirulent in vitro-cultured parasites and then inoculating them with the conventional donor-derived vaccines.

PMID: 15845278 [PubMed - indexed for MEDLINE]

100. Clin Diagn Lab Immunol. 2005 Apr;12(4):557-9.

Immunization with recombinant surface antigen P50 of Babesia gibsoni expressed in insect cells induced parasite growth inhibition in dogs.

Fukumoto S, Tamaki Y, Shirafuji H, Harakawa S, Suzuki H, Xuan X.

National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido, Japan.

This is a report of a vaccine trial directed against Babesia gibsoni infection in dogs with the use of the recombinant antigen P50. Dogs immunized with P50 showed partial protection manifested as a significantly low level of parasitemia. The results indicated that P50 is a primary vaccine candidate molecule against canine B. gibsoni infection.

PMCID: PMC1074387 PMID: 15817768 [PubMed - indexed for MEDLINE]

101. Transfus Clin Biol. 2005 Feb;12(1):1-4.

European strategies against the parasite transfusion risk.

Reesink HW.

Sanquin Blood Bank North-West Region, Sanquin Diagnostic Services, P.O. Box 9137, NL - 1006 AC Amsterdam, The Netherlands.

Protozoal infections are endemic in mainly tropical low income countries, affecting millions of people. Malaria, American trypanosomiasis (Trypanosoma cruzi/Chagas disease) and protozoal tickborne diseases (e.g. Babesia) can be efficiently transmitted by transfusion of cellular blood components. In non-endemic areas like Europe malaria, Chagas disease and Babesia are imported diseases resulting of travelling to endemic areas and migration of autochthons from these endemic areas. A recent International Forum showed that in Europe, as well as the USA, prevention of transfusion-associated protozoal infections depend mainly on selection of donors using questionnaires. Most countries divide donors at risk for malaria in two groups: individuals who have lived in the first 5 years of their life in malaria endemic areas and those who are borne and residing in non-endemic areas and visited the endemic area(s). The first category of donors is rejected for 3 years after their last visit to the endemic area, and in one country such donors are permanently rejected. In some countries such donors are accepted after 4 months-3 years, provided a test for malaria is non-reactive. Persons from non-endemic areas, who visited the malaria endemic area, are rejected for 4-12 months. Some countries reject these donors for 3 years or permanently when they resided for more than 6 months in the endemic area. The rejection rate of donors for malaria risk in the various countries was 0.003-0.43% of all donations. Over the last decade only a few cases of TT-malaria were reported in the various countries. In several countries donors are questioned for risk of T. cruzi infection. In some countries donors are excluded when they (or their mothers) were born in South or Central America, if they received a blood transfusion in these areas and if they lived in rural areas in these endemic countries for more than 4 weeks. In none of the countries donors are asked if they had Babesia or Leishmania. At present implemented measures to prevent TT-malaria in the European countries are probably highly effective. More research is needed to establish the theoretical risk of TT-T. cruzi and TT-Leishmania infection in Europe, before preventive measures may be considered.

PMID: 15814284 [PubMed - indexed for MEDLINE]

102. Trends Parasitol. 2005 Apr;21(4):179-84.

Vaccination against canine babesiosis.

Schetters T.

Parasitology Research and Development Department, Intervet International, PO Box 31, 5830 AA Boxmeer, The Netherlands.

It has been known for several decades that the soluble parasite antigen (SPA) of several Babesia species can be used as a vaccine against the clinical manifestations of babesiosis. Originally observed in the plasma of infected animals, SPA can also be recovered from the supernatants of in vitro cultures of these parasites. Variable success has been reported for vaccines against the bovine and canine Babesia parasites, which seems to be related to antigenic diversity within Babesia species. In this article, an overview is presented of the development of such vaccines for dogs, and additional research that has led to improvement of an SPA-based vaccine against Babesia canis in dogs.

PMID: 15780840 [PubMed - indexed for MEDLINE]

103. Onderstepoort J Vet Res. 2004 Dec;71(4):333-6.

Progression towards endemic stability to bovine babesiosis in cattle introduced onto a game ranch.

Regassa A, Penzhorn BL, Bryson NR.

Department of Veterinary Tropical Diseases, Faculty of Veterinary Science, University of Pretoria, Private Bag X04, Onderstepoort 0110, South Africa.

An opportunity to study progression toward endemic stability to Babesia bigemina arose when cattle were reintroduced onto a game ranch in 1999 after an absence of three years. The study was conducted between August 2000 and June 2001. The unvaccinated breeding cows were sampled only once. Calves born during October 1999 were initially vaccinated against B. bigemina and Babesia bovis at the age of 4 months and were then bled at 10, 17 and 20 months of age. Calves born during 2000 were bled at 7 and 8 months of age. Sera were collected from all the cattle sampled and later tested for antibodies against B. bigemina and B. bovis using the indirect fluorescent antibody (IFA) test. Although endemic stability to B. bigemina had not been achieved at Nooitgedacht 2 years after resumption of cattle ranching, the high seroprevalence in the unvaccinated 8-month-old calves suggested that the situation was approaching stability and that calf vaccination against bovine babesiosis was not required. Tick control should therefore be restricted to prevent excessive tick worry. Only vaccinated cattle were positive to B. bovis and it was concluded that the parasite was absent from the ranch.

PMID: 15732461 [PubMed - indexed for MEDLINE]

104. Exp Appl Acarol. 2004;34(3-4):375-82.

Integrated control of Boophilus microplus ticks in Cuba based on vaccination with the anti-tick vaccine Gavac.

Valle MR, Mèndez L, Valdez M, Redondo M, Espinosa CM, Vargas M, Cruz RL, Barrios HP, Seoane G, Ramirez ES, Boue O, Vigil JL, Machado H, Nordelo CB, Piñeiro MJ.

Centro de Ingeniería Genéticay Biotecnología, Cubanacan, Playa, Havana, Cuba.

Boophilus microplus has developed resistance against a range of chemical acaricides which has stimulated the development of alternative methods such as vaccination against ticks. In Cuba, the Bm86-based recombinant vaccine Gavac has been successfully used in a number of controlled laboratory and field trials in cattle against B. microplus. In this paper, we have evaluated Gavac in a large scale field trial wherein 588,573 dairy cattle were vaccinated with the aim to reduce the number of acaricidal treatments. It was found that the number of acaricidal treatments could be reduced by 87% over a period of 8 years (1995--2003). Prior to the introduction of the vaccine, 54 clinical cases of babesiosis and six fatal cases were reported per 1000 animals. Six years later, the incidence of babesiosis was reduced to 1.9 cases per 1000 cattle and mortality reduced to 0.18 per 1000. The national consumption of acaricides in Cuba could be reduced by 82% after the implementation of the integrated anti-B. microplus control program.

PMID: 15651533 [PubMed - indexed for MEDLINE]

105. Can J Public Health. 2004 Nov-Dec;95(6):451-5.

Physician survey on knowledge and reporting practices of transfusion-transmitted infections in Canada.

Farzad E, Cator M, Giulivi A, Zhang J.

Office of Community Medicine, First Nation and Inuit Health Branch, Health Canada.

OBJECTIVE: To assess physicians' knowledge and reporting practices of transfusion-transmitted infections (TTI). DESIGN: Cross-sectional postal survey. TARGET POPULATION: Family physicians and specialists. METHODS: A survey questionnaire was sent by mail to 1,359 randomly selected physicians across Canada, and was followed up by a reminder telephone call. RESULTS: A total of 546 (40%) physicians completed and returned the questionnaire. The data from 512 eligible practitioners across Canada were analyzed. Almost all physicians were knowledgeable on the transmission of HIV, HBV and HCV through blood and plasma derivatives. However, physicians' knowledge, particularly the family physicians', was generally lower for less well-known TTIs. For example, only 7.2% of family physicians recognized Babesiosis as a TTI. Of the total 318 physicians who have encountered patients with possible TTI, 50% of them reported such cases to public health or other authorities and many reported to more than one organization. Of the total 159 non-reporting physicians, 91.1% explained that the cases were already reported by laboratories or other physicians. More than 90% of respondents think that it is important or very important that physicians report the cases of TTI to public health authorities for the purpose of surveillance, and more than 80% of them think that it is important or very important to include TTI as a separate entity in the communicable diseases surveillance systems. CONCLUSION: The majority of physicians recognize the more common TTIs and only 50% of them reported such cases. The majority of physicians support the reporting of TTI to public health authorities for surveillance. Recommendations are made to increase physicians' knowledge and reporting of TTI.

PMID: 15622796 [PubMed - indexed for MEDLINE]

106. Eur J Clin Microbiol Infect Dis. 2005 Jan;24(1):74-5.

Role of quinine in life-threatening Babesia divergens infection successfully treated with clindamycin.

Corpelet C, Vacher P, Coudore F, Laurichesse H, Conort N, Souweine B.

Department of Pharmacology, CHU Gabriel Montpied, Clermont-Ferrand Cedex 1, France.

PMID: 15616840 [PubMed - indexed for MEDLINE]

107. Ann N Y Acad Sci. 2004 Oct;1026:312-8.

Reduced incidence of Babesia bigemina infection in cattle immunized against the cattle tick, Boophilus microplus.

Jittapalapong S, Jansawan W, Barriga OO, Stich RW.

Department of Parasitology, Kasetsart University, Bangkok 10903, Thailand.

Boophilus microplus is an important vector of bovine disease agents having a major economic impact on cattle production in many tropical and subtropical countries. Components of tick saliva that enable ticks to feed may also facilitate establishment of tick-borne pathogens in the vertebrate host. It has been suggested that acquired resistance against molecules in tick saliva could inhibit parasite transmission, and there is increasing evidence to support this hypothesis. The effect of immune resistance to B. microplus on the incidence of tick-transmitted pathogens was the focus of this experiment. Groups of four dairy cows were injected with antigen extracts of tick salivary glands, midgut, adjuvant only, or PBS, prior to a grazing period in a pasture in Thailand where ticks are abundant and babesiosis is enzootic. These animals were then observed for evidence of babesiosis throughout the rainy season. A reduction in the incidence of clinical babesiosis was observed among cattle immunized with salivary gland preparations compared to nonimmunized controls (P < 0.05). Immunization with midgut or adjuvant only both resulted in a slight reduction in observed disease compared to the same negative control group. B. bigemina was detected in fewer ticks (24.43%) collected from salivary gland-immunized cattle than those collected from the remaining groups (> or =44.57%). These results indicated that immunization with salivary gland antigens could affect pathogen transmission and appears promising for control of tick-borne diseases of cattle.

PMID: 15604511 [PubMed - indexed for MEDLINE]

108. Ann N Y Acad Sci. 2004 Oct;1026:277-83.

Field challenge of cattle vaccinated with a combined Babesia bovis and Babesia bigemina frozen immunogen.

Alvarez JA, Ramos JA, Rojas EE, Mosqueda JJ, Vega CA, Olvera AM, Figueroa JV, Cantó GJ.

CENID-Parasitología Veterinaria, INIFAP, Morelos, C.P. 62500. Mexico.

To determine the optimal dose of a combined, frozen immunogen containing in vitro culture-derived strains of Babesia bovis and Babesia bigemina, twenty-four 14-month-old Bos taurus steers from a Boophilus microplus-free area in Northern Mexico were used in this experiment. Cattle were randomly allocated into six groups with four animals each, and were intramuscularly inoculated as follows: group 1 (control animals) were administered with normal bovine erythrocytes; group 2 received 1 x 10(7) B. bovis- and B. bigemina-infected erythrocytes as a combined fresh immunogen. Groups 3-6 were inoculated with a combined frozen immunogen containing (previous to cryopreservation at -196 degrees C) 1 x 10(7), 5 x 10(7), 1 x 10(8), and 5 x 10(8) infected erythrocytes of each parasite species, respectively. Four months after immunization, principal and control animals were translocated to a bovine babesiosis endemic zone for field challenge. This was carried out by introducing the experimental cattle to tick-infested pastures for 30 days without ixodicide treatment. Cattle were monitored from day 8 postintroduction to the field (PIF) by recording the manifestation of clinical disease, rectal temperature values (RT), packed cell volume index (PCV), and percent of parasitized erythrocytes (PPE). At challenge, all experimental cattle became infected with both Babesia bovis and B. bigemina. However, except for two animals from group 6, none of the vaccinated animals showed signs of acute clinical babesiosis; therefore, no treatment was instituted. Out of six animals showing acute clinical babesiosis (four group 1 controls and two group 6 vaccinates), two animals (one from each group) died, despite babesiacide treatment, as they manifested classical cerebral babesiosis caused by B. bovis. Regardless of the dose or type of immunogen used (combined fresh or frozen), 90% of vaccinated cattle were determined to be protected against the virulent Babesia sp. field isolates. Nevertheless, by evaluating clinical parameters, such as average of maximum drop in PVC index (28.5%), average duration of parasitemia (3 days for B. bovis; 8.5 days for B. bigemina), and average duration of RT values > or = 39.5 degrees C (2 days), animals receiving 1 x 10(8) infected erythrocytes, as combined frozen immunogen, were more efficaciously protected against challenge with virulent B. bovis and B. bigemina field isolates.

PMID: 15604506 [PubMed - indexed for MEDLINE]

109. Vet Parasitol. 2004 Sep 20;124(1-2):9-18.

Efficacy of atovaquone against Babesia gibsoni in vivo and in vitro.

Matsuu A, Koshida Y, Kawahara M, Inoue K, Ikadai H, Hikasa Y, Okano S, Higuchi S.

Department of Small Animal Medicine, School of Veterinary Medicine and Animal Sciences, Kitasato University, Towada, Aomori 034-8628, Japan.

The therapeutic efficacy of atovaquone against Babesia gibsoni was examined in three dogs experimentally infected with B. gibsoni isolated from naturally infected dogs in Aomori Prefecture, Japan. Once parasitemia reached 10%, atovaquone was administered orally (30 mg/kg twice daily for 7 days). Within 2 days of atovaquone treatment, the parasite disappeared from blood smears without any clinical side effects. Anemia and thrombocytopenia were significantly improved in all the dogs. However, a polymerase chain reaction assay revealed that a B. gibsoni marker gene was intermittently present in peripheral blood after atovaquone therapy, indicating that the organism had not been eliminated, and parasites reappeared in blood smears 33 days after the last treatment. To investigate the change in sensitivity against atovaquone, an in vitro sensitivity test was performed using peripheral blood obtained from an untreated dog that was infected with the original parasite isolate, and from two of the experimentally infected and atovaquone-treated animals (blood was collected at the time of the post-treatment recurrence of the B. gibsoni infection). Atovaquone was added to the culture medium to final concentrations of 0.1, 1, 10, 100, and 1000 nM. For the untreated parasites, complete growth inhibition occurred at 1000 nM of atovaquone, whereas the recurrent parasites were inhibited by only 39.52 +/- 8.34% and 31.31 +/- 8.14% at this concentration after 48 h of incubation. Thus, the recurring parasites were less sensitive to atovaquone than the untreated originally isolated parasites.

PMID: 15350657 [PubMed - indexed for MEDLINE]

110. J Vet Intern Med. 2004 Jul-Aug;18(4):494-8.

Efficacy of combined atovaquone and azithromycin for therapy of chronic Babesia gibsoni (Asian genotype) infections in dogs.

Birkenheuer AJ, Levy MG, Breitschwerdt EB.

Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USA.

Babesiosis caused by Babesia gibsoni (Asian genotype) is an emerging disease in dogs in the United States. To date, no drugs have been shown to eliminate B. gibsoni (Asian genotype) infections from dogs. Twenty-two dogs that remained persistently infected with B. gibsoni (Asian genotype) after either imidocarb diproprionate and or diminazine aceturate therapy were identified and randomly and evenly distributed into 2 groups. One group was treated with atovaquone and azithromycin combination therapy, and the other group received a placebo. Eight of 10 dogs in the treatment group had no detectable B. gibsoni (Asian genotype) DNA, as determined by a sensitive and specific polymerase chain reaction (PCR) assay, in any of their posttreatment samples. In contrast, B. gibsoni (Asian genotype) DNA was detectable by PCR in the posttreatment samples from 11 of 11 of the placebo-treated dogs. One dog in the treatment group was excluded from the treatment outcome analysis. This dog had 2 consecutive negative PCR assay results and was euthanized because of ongoing degenerative joint disease prior to completion of the study. No adverse effects of treatment were reported in any dog during the study period. A combination of atovaquone and azithromycin is the 1st described treatment that will either eliminate B. gibsoni (Asian genotype) infections or suppress the parasitemia below the limit of detection in the majority of treated dogs.

PMID: 15320586 [PubMed - indexed for MEDLINE]

111. J Egypt Soc Parasitol. 2004 Aug;34(2):407-22.

The protective activity of serum and fractionated serum from rats against Babesia divergens.

Ben Musa N, Dawoud HA.

Department of Medical Parasitology, Faculty of Medicine, Great Al-Fatah University for Medical Sciences, Tripoli, Libya.

The rat adapted strain of bovine Babesia, B. divergens was used as a model to investigate the mechanisms of immunity to this parasite. The participation of humoral factors in acquired immunity to B. divergens was investigated in splenectomised rats. Antibodies to B. divergens were detected by IFA test in sera collected during infection and at different times after recovery. The protective activity of the same serum was tested in vivo by passive transfer and compared with the antibody levels as measured by IFA test. The role of antibody in protection was confirmed after fractionating IgM and IgG from immune and hyper-immune sera. The protective activity of sera collected immediately after recovery was mainly due to IgM antibodies. The protective activity of sera collected 3-4 days after recovery and of hyper-immune sera was mainly due to IgG antibodies. In hyper-immune serum IgM antibodies were partially protective.

PMID: 15287167 [PubMed - indexed for MEDLINE]

112. Vox Sang. 2004 Jul;87 Suppl 2:120-2.

Threats to blood safety posed by emerging protozoan pathogens.

Leiby DA.

Transmissible Diseases Department, Jerome H. Holland Laboratory for the Biomedical Sciences, Rockville, MD 20855, USA.

PMID: 15209895 [PubMed - indexed for MEDLINE]

113. Clin Tech Small Anim Pract. 2004 May;19(2):68-74.

Infection and blood transfusion: a guide to donor screening.

Reine NJ.

Bobst Hospital, Jaqua Transfusion Medicine Service, Animal Medical Center, 510 East 62nd Street, New York, NY 10021, USA.

In recent years, blood-component therapy has become more accessible in veterinary practice. As with human medicine, care must be taken to minimize the risk of disease transmission from donor to recipient. Determining the appropriate diseases to screen for is complicated by regional variations in disease incidence, the existence of chronic carrier states for some diseases, the difficulty in screening-test selection, and testing cost. The feline diseases considered include retroviral infections, feline coronaviruses, ehrlichiosis (Ehrlichia canis-like), anaplasmosis (Anaplasma phagocytophilum), neorickettsiosis (Neorickettsia risticii), hemoplasmosis (Mycoplasma hemofelis and M. hemominutum, previously feline hemobartonellosis), and cytauxzoonosis (Cytauxzoon felis). The canine diseases considered in this paper include babesiosis (Babesia canis and B. gibsonii,) ehrlichiosis (E. canis and E. ewingii), anaplasmosis (A. phagocytophilum), neorickettsiosis (N. risticii var. atypicalis), leishmaniasis (Leishmania donovani complex), brucellosis (Brucella canis), hemoplasmosis (M. hemocanis, previously canine hemobartonellosis), and bartonellosis (Bartonella vinsonii).

PMID: 15179926 [PubMed - indexed for MEDLINE]

114. Curr Microbiol. 2004 Jun;48(6):435-7.

Babesia microti infection in Europe.

Meer-Scherrer L, Adelson M, Mordechai E, Lottaz B, Tilton R.

Medical Diagnostic Laboratories, Mt. Laurel, NJ, USA.

The majority of babesia infections in Europe are life-threatening and caused by Babesia divergens and B. bovis. Although Babesia microti has been detected in ticks from Switzerland, few if any cases of babesiosis have been caused by B. microti. This first reported case, diagnosed by serology, DNA detection, and microscopy, is additionally interesting because there appears to be coinfection with the Lyme disease organism, Borrelia burgdorferi.

PMID: 15170239 [PubMed - indexed for MEDLINE]

115. J Pediatr Hematol Oncol. 2004 Mar;26(3):213.

Asymptomatic babesiosis in a child with hepatoblastoma.

Rech A, Bittar CM, de Castro CG, Azevedo KR, dos Santos RP, Machado AR, Schwartsmann G, Goldani L, Brunetto AL.

Pediatric Oncology Unit, Hospital de Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul. Porto Alegre, Brazil.

PMID: 15125618 [PubMed - indexed for MEDLINE]

116. Aust Vet J. 2003 Mar;81(3):147-52.

Serological evidence of exposure to tick fever organisms in young cattle on Queensland dairy farms.

Sserugga JN, Jonsson NN, Bock RE, More SJ.

School of Veterinary Science, The University of Queensland, PO Box 125, Kenmore, Queensland 4069.

OBJECTIVES: To compare the features of farms on which the exposure of young cattle to tick fever organisms is sufficient to ensure that immunity is high and the risk of clinical disease is low (endemic stability) with those of farms on which exposure is insufficient to induce widespread immunity (hence without endemic stability); to examine the relationships between the management of ticks and tick fever, and endemic stability to Babesia bovis, B. bigemina and Anaplasma marginale. DESIGN: Cross-sectional study of 874 cattle between the ages of 6 and 15 months on 64 dairy farms, from three centres in south-eastern Queensland (Mutdapilly, Dayboro and Kenilworth) and one centre in far-north Queensland (Malanda). PROCEDURE: Blood samples collected from between 5 and 20 calves from each farm were submitted for serological assay to determine exposure to B. bovis, B. bigemina and A. marginale. A questionnaire about the farm characteristics and the management of ticks and tick fever was completed with each farmer. RESULTS: On 73% of farms, confirmed clinical cases of tick fever were recalled by the farmer, indicating that tick fever was a threat on most farms. The majority of herds in the study (54 of 64) did not have sufficient numbers of seropositive animals aged between 6 and 15 months to have a low risk of tick fever. Region had an effect on the likelihood of endemic stability for all tick fever organisms. Cattle near Malanda in Far-north Queensland were more likely to be seropositive to B. bovis and B. bigemina. The method, strategy and intensity of tick control were not related to the likelihood of endemic stability when the effect of region was considered. The decision to leave a few ticks on cattle in an effort to induce endemic stability did increase the likelihood of endemic stability to A. marginale. However, in practical terms, it was ineffective, because only 26% of these farms had endemic stability against all three organisms. CONCLUSIONS: Given the low proportion of farms that have endemic stability to the tick fever organisms and the high likelihood of clinical disease, vaccination is recommended to protect dairy cattle from tick fever throughout the tick infested area of Queensland. However, further work is required to determine the economic value of vaccination, taking into account the costs of vaccination, of outbreaks and the protective value of vaccination.

PMID: 15080428 [PubMed - indexed for MEDLINE]

117. J S Afr Vet Assoc. 2003 Sep;74(3):69-71.

The effects of diminazene aceturate on systemic blood pressure in clinically healthy adult dogs.

Joubert KE, Kettner F, Lobetti RG, Miller DM.

Department of Companion Animal Clinical Studies, Faculty of Veterinary Science, University of Pretoria, Private Bag X04, Onderstepoort 0110, South Africa.

Diminazene aceturate is a commonly used antibabesial agent. It has been postulated that diminazine may induce a decrease in blood pressure and exacerbate the hypotension presented in dogs with babesiosis. This study was undertaken to assess the effect of diminazine aceturate on the blood pressure of healthy dogs. Six healthy German shepherd dogs between 18 and 24 months of age with a mean weight of 30.4 +/- 2.75 kg were used. Blood pressure was directly measured at the following time intervals: -5, 0, 5, 10, 15, 20, 25, 30, 35, 40, 50, 60, 90 and 120 minutes after treatment with diminazine aceturate (4.2 mg/kg) intramuscularly. No statistical difference (P > 0.05) was found in blood pressure between any of the time intervals. An increase in heart rate was seen 5 minutes after the administration of diminazine aceturate but no change in blood pressure was evident. This study concluded that diminazene aceturate in its current formulation with antipyrine does not alter blood pressure in healthy adult dogs.

PMID: 15029949 [PubMed - indexed for MEDLINE]

118. Lancet. 2004 Feb 28;363(9410):704.

Babesiosis and HIV.

Froberg MK, Dannen D, Bakken JS.

Department of Pathology, Laboratory Medicine, Medical Microbiology, and Immunology, University of Minnesota, Duluth School of Medicine, Duluth, MN 55812, USA.

PMID: 15001329 [PubMed - indexed for MEDLINE]

119. Infect Immun. 2004 Mar;72(3):1795-8.

Inhibitory effect of antiserum to surface antigen P50 of Babesia gibsoni on growth of parasites in severe combined immunodeficiency mice given canine red blood cells.

Fukumoto S, Xuan X, Takabatake N, Igarashi I, Sugimoto C, Fujisaki K, Nagasawa H, Mikami T, Suzuki H.

National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido 080-8555, Japan.

The inhibitory effect of an antiserum to surface protein P50 of Babesia gibsoni on the growth of the parasite was determined with severe combined immunodeficiency mice given canine red blood cells. The antiserum to the recombinant P50 protein significantly inhibited the parasite growth, indicating that P50 might be a useful vaccine candidate.

PMCID: PMC356003 PMID: 14977989 [PubMed - indexed for MEDLINE]

120. J Vet Med Sci. 2003 Nov;65(11):1171-7.

In-vivo therapeutic efficacy trial with artemisinin derivative, buparvaquone and imidocarb dipropionate against Babesia equi infection in donkeys.

Kumar S, Gupta AK, Pal Y, Dwivedi SK.

National Research Centre on Equines, Haryana, India.

The therapeutic efficacy of imidocarb, artesunate, arteether, buparvaquone and arteether+buparvaquone combination was evaluated against Babesia equi of Indian origin in splenectomised donkeys with experimentally induced acute infection. Efficacies of these drugs were tested by administering each drug or drug combination to groups of donkeys (having three donkeys each group). One group of donkey was kept as untreated control for comparing the results. Parasitaemia, haematology (WBC, RBC, PCV, granulocytes and haemoglobin), biochemical parameters (SAST, SALT, alkaline phosphatase, albumin/globulin ratio) were monitored at regular intervals. Individually, arteether and buparvaquone were found to have no parasite clearing efficacy and the treated animals died within 5-6 days after showing high parasitaemia and clinical symptoms of the disease. However, artesunate treated animals were able to restrict the parasite multiplication but only during the treatment period. Animals treated with imidocarb and arteether+buparvaquone combination were able to clear the parasite from the blood circulation after 2-5 days post-treatment (PT). After 55-58 days PT, recrudescence of B. equi parasite was observed in both these groups and a mean survival period of 66 days and 69 days, respectively, was recorded in these groups. Results of haemato-biochemical parameters had shown that imidocarb had deleterious effect on the liver function while on the other hand arteether+buparvaquone combination was found to be safe. This limited study indicates that arteether+buparvaquone combination could be a better choice than imidocarb for treating B. equi infection, but further trials are required in detail.

PMID: 14665744 [PubMed - indexed for MEDLINE]

121. Clin Lab Sci. 2003 Fall;16(4):239-45, 251.

Transfusion-transmitted parasites.

Smith LA, Wright-Kanuth MS.

Department of Clinical Laboratory Sciences, University of Texas Health Science Center at San Antonio, 78229-3900, USA.

PMID: 14626442 [PubMed - indexed for MEDLINE]

122. Exp Appl Acarol. 2003;29(1-2):141-9.

Immunity against Boophilus annulatus induced by the Bm86 (Tick-GARD) vaccine.

Pipano E, Alekceev E, Galker F, Fish L, Samish M, Shkap V.

Veterinary Services and Animal Health, Kimron Veterinary Institute, Ministry of Agriculture and Rural Development, POB 12, 50250 Bet Dagan, Israel.

Friesian cattle were immunized with two inoculations of anti-tick Bm86 (Tick-GARD) vaccine and were challenged 30 or 90 d later with Boophilus annulatus larvae derived from 1.2 g of eggs. No nymphs or adult ticks were found on the immunized cattle during four weeks after challenge. Repeated infestations (2 to 4) with larvae on three other calves during a period of 160 and 390 d after the immunization did not result in development of nymphal and adult stages. In control, non-immunized cattle infested with corresponding batches of larvae 1380 to 4653 replete adult female ticks were collected. Larvae issued from Babesia bovis-infected female ticks transmitted the infection to Bm86-immunized cattle, but the progeny of B. bigemina-infected females did not. Since B. bigemina is transmitted exclusively by nymphal stages of Bo. annulatus these results support the observation that immunity induced by Bm86 affects the larval stage of this tick.

PMID: 14580066 [PubMed - indexed for MEDLINE]

123. Curr Opin Hematol. 2003 Nov;10(6):405-11.

Risk and prevention of transfusion-transmitted babesiosis and other tick-borne diseases.

Cable RG, Leiby DA.

American Red Cross, Connecticut Blood Services, Farmington, and University of Connecticut Health Center, Farmington, Connecticut 06032, USA.

PURPOSE OF REVIEW: Tick-borne diseases have increasingly been recognized in the United States as public health problems. The importance of tick-borne diseases has been accelerated by increases in animal populations, as well as increased human recreation in wooded environments that are conducive to tick bites. Babesiosis, usually caused by the intraerythrocytic parasite, Babesia microti and transmitted by the same tick as Lyme disease, has important transfusion implications. Although Lyme disease has not been reported from blood transfusion, newly identified tick-borne diseases such as ehrlichiosis raise additional questions about the role of the tick in transfusion-transmitted diseases. RECENT FINDINGS: The risk of transfusion-transmitted babesiosis is higher than usually appreciated and in endemic areas represents a major threat to the blood supply. Furthermore, the geographic range of B. microti is expanding, other Babesia spp. have been implicated in transfusion transmission in the western United States, and the movement of blood donors and donated blood components may result in the appearance of transfusion babesiosis in areas less familiar with these parasites. Consequently, a higher degree of clinical suspicion will allow early recognition and treatment of this important transfusion complication. SUMMARY: In endemic areas transfusion-transmitted babesiosis is more prevalent than usually believed. The extension of the geographic range of various Babesia spp. and the movement of donors and blood products around the United States has resulted in the risk extending to non-endemic areas. Clinicians should maintain a high degree of clinical suspicion for transfusion-transmitted babesiosis.

PMID: 14564169 [PubMed - indexed for MEDLINE]

124. Curr Hematol Rep. 2003 Nov;2(6):511-7.

Vector-borne illnesses and the safety of the blood supply.

Becker JL.

Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA.

The protection of patients from diseases carried in blood transfusions is an ongoing effort. The viruses that cause long-term human infection and death have received much of the attention in the United States and testing has significantly diminished the risk of infection from a transfusion. As the risk of these diseases has decreased, other transfusion-transmitted organisms with a lower incidence in the community or newer diseases with rapidly expanding endemic areas are receiving additional attention. One group of these infections are infections in which the normal route of human infection is a vector.

PMID: 14561396 [PubMed - indexed for MEDLINE]

125. Vet Parasitol. 2003 Jul 29;115(3):213-22.

Overcoming constraints to meeting increased demand for Babesia bigemina vaccine in Australia.

Standfast NF, Bock RE, Wiecek MM, deVos AJ, Jorgensen WK, Kingston TG.

Department of Primary Industries, Tick Fever Research Centre, Queensland, 280 Grindle Road, Wacol 4076, Qld, Australia.

Demand for live trivalent tick fever vaccine containing Babesia bovis, Babesia bigemina and Anaplasma centrale produced by the Department of Primary Industries, Queensland, has increased from less than 10,000 doses in 1988 to 500,000 doses in 2001. This paper describes a series of trials aimed at overcoming certain constraints to obtain B. bigemina parasitised erythrocytes (PEs) on a large enough scale from infected splenectomised calves to meet the demand. Passage through a series of splenectomised calves failed to increase the yield per calf but we showed that the dose rate of infected cells could be reduced from the long-time standard of 1x10(7) to 2.5x10(6) without affecting immunogenicity and still leaving a safety margin of at least 50-fold for infectivity. This change quadrupled the potential yield of doses per calf and allowed the DPI to meet the increased demand for B bigemina in vaccine. Due to the high cost and limited availability of suitable, health tested donors, calves previously infected with B. bovis or A. centrale were used to provide B. bigemina organisms but the practice resulted in red cell agglutination in some batches of prepared vaccine. A trial is described where B. bigemina-infected red cells were washed by centrifugation to remove agglutinating antibodies. Washing had no effect on parasite viability and this method is now in routine use in the production of trivalent vaccine.

PMID: 12935736 [PubMed - indexed for MEDLINE]

126. Clin Diagn Lab Immunol. 2003 Jul;10(4):596-601.

High-level expression of truncated surface antigen P50 of Babesia gibsoni in insect cells by baculovirus and evaluation of its immunogenicity and antigenicity.

Fukumoto S, Xuan X, Kadota K, Igarashi I, Sugimoto C, Fujisaki K, Nagasawa H, Mikami T, Suzuki H.

National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido 080-8555, Japan.

Previously, we identified an immunodominant antigen, P50 of Babesia gibsoni. In the present study, the gene encoding the truncated P50 (rP50t) without a C-terminal hydrophobic region (29 amino acids [aa]) was expressed in insect cells by a recombinant baculovirus. The highly hydrophobic C-terminal 20-aa regions seems to be a transmembrane region, which was evidenced by the fact that rP50t was effectively secreted into the supernatant of insect cells infected with the recombinant baculovirus. N-terminal amino acid sequence analysis of rP50t indicated that N-terminal 19 aa function as a signal peptide. The expression level of rP50t reached up to 2 mg per 10(8) cells infected with the recombinant baculovirus. The immunogenic property of rP50t was evaluated by an immunization test in mice. Mice immunized with rP50t induced a high-level antibody titer against the B. gibsoni merozoite. Monoclonal antibodies (MAbs) to rP50t were produced in mice to determine the immunogenic regions of P50. The epitope(s) recognized by all five MAbs were located between aa 190 and 273, suggesting that the central part of P50 is a highly immunogenic region. The diagnostic potential of rP50t was evaluated using an enzyme-linked immunosorbent assay (ELISA). The ELISA was able to differentiate clearly (P < 0.0001) between B. gibsoni-infected dog serum and B. canis-infected dog serum or noninfected dog serum. Our results indicated that the rP50t may provide a useful potential immunogenic reagent for use in diagnosis and as a subunit vaccine to control B. gibsoni infection in dogs.

PMCID: PMC164249 PMID: 12853391 [PubMed - indexed for MEDLINE]

127. Nihon Rinsho. 2003 Feb;61 Suppl 2:623-8.


[Article in Japanese]

Saito-Ito A, Dantrakool A, Kawai A, Yano Y, Takada N.

Section of Parasitology, Department of Genome Sciences, Faculty of Medical Sciences, Kobe University Graduate School of Medicine.

PMID: 12722292 [PubMed - indexed for MEDLINE]

128. J Am Vet Med Assoc. 2003 Apr 1;222(7):959-63, 952.

Transfusion-associated Babesia gibsoni infection in a dog.

Stegeman JR, Birkenheuer AJ, Kruger JM, Breitschwerdt EB.

Department of Small Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USA.

A 2.5-year-old spayed female German Shepherd Dog was referred for evaluation of progressive anemia, lethargy, and weight loss. Seventeen days earlier, the dog had received a whole blood transfusion to manage hemorrhage after ovariohysterectomy. Mild fever, splenomegaly, and thrombocytopenia were also identified. Von Willebrand disease and Babesia gibsoni infection were diagnosed. Because of the serologic cross-reactivity of B gibsoni and B canis in the immunofluorescent antibody assay for IgG antibodies against these organisms, polymerase chain reaction amplification of parasite DNA was required to identify the infecting Babesia sp. The source of the B gibsoni infection was traced to an apparently healthy American Pit Bull Terrier blood donor. Despite resolution of clinical signs in the dog of this report, a series of antiparasitic treatments failed to eliminate the B gibsoni infection. Screening of potential blood donor dogs for Babesia spp is becoming increasingly important in the United States.

PMID: 12685786 [PubMed - indexed for MEDLINE]

129. J Small Anim Pract. 2003 Mar;44(3):132-4.

Dermatitis associated with Dirofilaria repens microfilariae in three dogs in Saudi Arabia.

Tarello W.

Thaliah International Veterinary Clinic, PO Box 20690, Jeddah 21465, Saudi Arabia.

The presence of microfilariae of the zoonotic nematode Dirofilaria repens is reported in three dogs from Saudi Arabia, manifesting as pruritic dermatitis with signs including erythema, alopecia, papules, crusting and hyperkeratosis. All dogs were found to have concurrent babesiosis. Specific treatments against the two conditions led to complete clinical recovery and disappearance of microfilariae from the blood one month later.

PMID: 12653329 [PubMed - indexed for MEDLINE]

130. Vet Parasitol. 2003 Feb 28;112(1-2):75-89.

Factors related to cattle infestation level and resistance to acaricides in Boophilus microplus tick populations in New Caledonia.

Bianchi MW, Barré N, Messad S.

IAC-CIRAD, BP 25, Paita, New Caledonia.

Boophilus microplus, even in the absence of babesiosis, is a major disease of the cattle in New Caledonia where the particular farming system associates continental European breeds and a tropical climate tempered by the Pacific Ocean. In order to have a better understanding of the factors involved in cattle tick infestation, to decrease the possible wastage and use of chemicals and to increase the lifetime of the acaricides, the veterinary authorities investigated the conditions of the chemical treatments. A survey among 148 cattle farms of the whole of New Caledonia was carried out and factors that explain the development of tick resistance and cattle infestation have been determined. From this survey, three typologies for the main characteristics of the farms have been set up, the technical practices of the farmers and the tick control measures applied by the farmers, respectively. Some variables are significantly associated with the tick resistance to deltamethrin but their contribution to the explanation model is always moderate: farms in the south, with a positive resistance gradient from east to west, absence of bush fire and membership to a cattle farmers organization. The more the farmers have intensified their breeding-male castration, weaning, heifer separation, drenching, etc.-and pasture-high stock rate, mowing, extra feeding of the cows, many paddocks, etc.-techniques, the higher was the probability for the ticks in their farm to be resistant to deltamethrin. The technical details of the acaricide treatment had a low contribution to the explanation model. However, the use of a spray generated more resistance than a dip. Furthermore, there is a negative resistance gradient when the farmers increased the treatment interval average. Considering infestation, none of the variables from the three typologies were associated with the two infestation variables (1: semi-engorged tick females and 2: other ticks) at the herd level. However, the seven studied variables-the three typologies, breed, age, body condition score and breeding status-affected significantly the two infestation variables at the cow level, but their predictive ability remained very low (R(2)<3.5%). This result-individual effect more important than herd effect on the infestation-is confirmed by the importance of the variance of the intra-farm factors (99%) when compared with inter-farm factors (1%). Cows of Charolais breed, in poor body condition, old, pregnant or lactating, and those of the farms with irrational and high pressure control of ticks are the most infested.

PMID: 12581586 [PubMed - indexed for MEDLINE]

131. Emerg Infect Dis. 2003 Jan;9(1):116-9.

Transfusion-associated babesiosis after heart transplant.

Lux JZ, Weiss D, Linden JV, Kessler D, Herwaldt BL, Wong SJ, Keithly J, Della-Latta P, Scully BE.

Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.

We describe a 54-year-old spleen-intact man with transfusion-associated Babesia microti infection after a heart transplant. Adult respiratory distress syndrome developed in the patient, and he required mechanical ventilation. Our experiences with this patient suggest that babesiosis should be considered in the differential diagnosis of transplant patients who have fever and hemolytic anemia.

PMCID: PMC2873739 PMID: 12533293 [PubMed - indexed for MEDLINE]

132. Transfusion. 2002 Dec;42(12):1585-91.

Relationship between tick bites and the seroprevalence of Babesia microti and Anaplasma phagocytophila (previously Ehrlichia sp.) in blood donors.

Leiby DA, Chung AP, Cable RG, Trouern-Trend J, McCullough J, Homer MJ, Reynolds LD, Houghton RL, Lodes MJ, Persing DH.

Transmissible Diseases Department, American Red Cross, Rockville, MD 20855, USA.

BACKGROUND: Tick-borne diseases, particularly babesiosis and ehrlichiosis, represent recently emerging infections. Despite an increased recognition of the threat tick-borne agents pose to blood safety, our understanding of the prevalence and transmissibility of these agents in blood donors is limited. STUDY DESIGN AND METHODS: Babesia microti and Anaplasma phagocytophila (previously Ehrlichia sp.) seroprevalence was determined in random Connecticut and Wisconsin donors, and subsequently in Connecticut donors reporting tick bites. In the interim, a postcard survey regarding tick bites during the previous 6 months was sent to 6,000 random donors in six geographically distinct collection regions. RESULTS: In total, 3 of 999 Wisconsin donors (0.3%) and 6 of 1,007 Connecticut donors (0.6%) had antibodies to B. microti. Of 992 donors tested for A. phagocytophila, 5 Wisconsin donors (0.5%) and 35 Connecticut donors (3.5%) were seropositive. A total of 2,482 donors (41.4%) completed the survey; 103 (4.1%) reported a tick bite. Of 848 Connecticut donors (0.4%) reporting tick bites, 3 had B. microti antibodies, while 8 (0.9%) had A. phagocytophila antibodies. These rates were not significantly different from control donors. CONCLUSION: Blood donors seropositive for B. microti and A. phagocytophila are present in Connecticut and Wisconsin. Donors readily recall previous tick bites, but self-reported bites are not reliable indicators of serologic status. The exposure of blood donors to tick-borne pathogens does suggest a need to better understand the transfusion transmission potential of these agents.

PMID: 12473139 [PubMed - indexed for MEDLINE]

133. Transfusion. 2002 Sep;42(9):1154-8.

Transmission of Babesia microti in Minnesota through four blood donations from the same donor over a 6-month period.

Herwaldt BL, Neitzel DF, Gorlin JB, Jensen KA, Perry EH, Peglow WR, Slemenda SB, Won KY, Nace EK, Pieniazek NJ, Wilson M.

Division of Parasitic Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30341-3724, USA.

BACKGROUND: Babesiosis is a tick-borne zoonosis caused by intraerythrocytic protozoa. More than 40 US cases of Babesia microti infection acquired by blood transfusion have been reported. This report describes the identification of a transfusion-associated case of babesiosis and the subsequent identification of the infected blood donor and three other infected recipients of cellular blood components from three other donations by this donor. STUDY DESIGN AND METHODS: Serum specimens from the donors of blood that had been made into cellular components received by the index recipient and from other recipients of such components from the implicated donor were tested by the indirect fluorescent antibody (IFA) assay for antibodies to B. microti. Whole blood from IFA-positive persons was tested by PCR for B. microti DNA. RESULTS: IFA testing of serum from 31 of 36 donors implicated a 45-year-old man (titer, 1 in 256), whose donation had been used for RBCs. He likely became infected when bitten by ticks while camping in Minnesota in June 1999 and had donated blood four times thereafter. As demonstrated by PCR, he remained parasitemic for at least 10 months. Of the five other surviving recipients of cellular blood components from the implicated donor, three recipients (one for each of the three other donations) had become infected through either RBC or platelet transfusions. CONCLUSIONS: Babesiosis should be included in the differential diagnosis of posttransfusion febrile illness, and effective means for preventing transmission by blood transfusion are needed.

PMID: 12430672 [PubMed - indexed for MEDLINE]

134. Transfusion. 2002 Nov;42(11):1482-7.

Investigation of transfusion transmission of a WA1-type babesial parasite to a premature infant in California.

Kjemtrup AM, Lee B, Fritz CL, Evans C, Chervenak M, Conrad PA.

Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California, Davis 95616-8745, USA.

BACKGROUND: A premature infant in California developed respiratory distress associated with infection with a protozoal parasite, Babesia. The infant had received two blood transfusions, one from the father and one from an anonymous donor (Donor A). This study describes the follow-up required to identify the source and species of Babesia that infected the infant. STUDY DESIGN AND METHODS: At the time of the infant's illness, whole blood from the infant, father, and mother was evaluated for Babesia infection. Similar evaluation of whole blood from Donor A was performed 2 months after the suspected donation to the infant. Samples were tested using blood smear examination, serology, PCR, and hamster inoculation. Identity of the recovered Babesia parasites was confirmed by DNA amplification by PCR, genetic sequencing of the 18S gene, and phylogenetic analysis. RESULTS: WA1-type Babesia was recovered from the infant. Neither parent was the source of infection. Serology and hamster inoculation confirmed WA1-type Babesia infection in Donor A. DNA sequences of the 18S gene from the infant and donor isolates were 100% identical. CONCLUSION: WA1-type Babesia infections may be difficult to detect among blood donors because such infections can be subclinical. This is the second WA1-type Babesia transmission via blood transfusion and the first in an infant. Physicians in the western United States should consider Babesia as a possible cause of nonspecific febrile illness after a blood transfusion.

PMID: 12421222 [PubMed - indexed for MEDLINE]

135. Vet J. 2002 Jul;164(1):64-8.

Babesia bovis and B. bigemina: Persistence of infection in friesian cows following vaccination with live antibabesial vaccines.

Pipano E, Shkap V, Kriegel Y, Leibovitz B, Savitsky I, Fish L.

Division of Parasitology, The Kimron Veterinary Institute, Bet Dagan 50250, Israel.

The persistence of Babesia bovis and B. bigemina infection in Friesian cows, following vaccination with attenuated live vaccines, was assessed by subinoculation of blood into splenectomized calves. Subinoculation tests showed that B. bigemina persisted in two out of 20 cows vaccinated 10 and 46 months previously, and that B. bovis persisted in 11 out of 22 cows vaccinated 10 to 47 months previously. Antibody was detected in five B. bigemina - and 15B. bovis -vaccinated cows. Parasites of both species persisted among the serologically negative cows, whereas blood obtained from serologically positive cows failed to transmit infection. It is concluded that in the absence of reinfection Friesian cattle may spontaneously eliminate B. bigemina and B. bovis infection after various periods following vaccination.

PMID: 12359486 [PubMed - indexed for MEDLINE]

136. Vet Dermatol. 2002 Oct;13(5):267-74.

Cutaneous lesions in dogs with Dirofilaria (Nochtiella) repens infestation and concurrent tick-borne transmitted diseases.

Tarello W.

Centro Veterinario Alessandrino, via Amendola 1, Alessandria, Italy.

A pruritic dermatitis characterized by the presence of erythema, papules, focal or multifocal alopecia, crusting and nodules was seen in 28 dogs with Dirofilaria repens microfilariae infestation in an endemic area in north-west Italy. Previous unsuccessful nonspecific antipruritic treatments, flea control and restricted diet were recorded in 53.6% of the patients. Both the Knott and the antigen tests were negative for Dirofilaria immitis and Acanthocheilonema reconditum. Concurrent babesiosis and/or canine granulocytic ehrlichiosis was also diagnosed in many affected dogs. Preliminary treatment of the concurrent diseases was followed by specific filaricide treatment. The cutaneous lesions, although slightly improved with the initial treatment, resolved completely with macro- and microfilaricide treatment. Although D. repens may be an opportunistic pathogen, this parasite should not be considered as harmless as previously thought and its potential pathogenic role in causing cutaneous lesions in dogs should be considered. Furthermore, it has a zoonotic importance as human cases have been reported worldwide.

PMID: 12358611 [PubMed - indexed for MEDLINE]

137. Equine Vet J. 2002 Sep;34(6):625-9.

Pharmacokinetics of imidocarb dipropionate in horses after intramuscular administration.

Belloli C, Crescenzo G, Lai O, Carofiglio V, Marang O, Ormas P.

Department of Animal Health and Welfare, University of Bari Valenzano, Italy.

The objective of this study was to determine the pharmacokinetic behaviour of imidocarb in horses following a single i.m. injection at the dose commonly administered to treat Babesia caballi infections or to prevent babesiosis. Eight horses were injected i.m. with a single dose of 2.4 mg imidocarb dipropionate/kg bwt and blood, faecal, urine and milk samples were collected. For imidocarb determination, a high-performance liquid chromatographic method (HPLC) was used after weak cation-exchange solid phase, or liquid-liquid, extraction procedures. Twelve hours after treatment, no detectable plasma concentrations were recorded in any of the treated animals. The distribution and elimination patterns of the drug suggested that it is quickly sequestrated in some storage tissues and remains in the body for a long time. Its prolonged presence in the body may confer a reservoir effect to imidocarb in some tissues, therefore making it undetectable in the plasma of animals but sufficient to produce its described therapeutic and prophylactic activities.

PMID: 12358005 [PubMed - indexed for MEDLINE]

138. Vet Parasitol. 2002 Aug 22;107(4):295-301.

Identification of immunoreactive polypeptides of Babesia equi parasite during immunization.

Kumar S, Malhotra DV, Nichani AK.

All India Coordinated Research Project on Blood Protista, College of Veterinary Sciences, CCS Haryana Agricultural University, Haryana, India.

This study was carried out to identify immunoreactive polypeptides in Babesia equi merozoite antigen. Three fractions of killed B. equi merozoite antigen viz.; whole merozoite (WM), cell membrane (CM) and high speed supernatant (HSS) antigens were prepared from the parasite infected erythrocytes. These antigenic preparations along with ghost antigen from non-infected erythrocytes were fractionated on 12% sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotted with sera showing high antibody titres. On SDS-PAGE, 16 polypeptides with molecular weight (Mr) in the range of 112-17kDa were obtained from the WM and CM antigens. But only six polypeptides were detected (96.5-28kDa) in the HSS antigen. On immunoblotting with high titred serum collected from donkeys following two immunizations with a killed B. equi merozoite immunogen, 11 polypeptides were observed in the WM and CM antigens (Mr 112-18kDa). Of these, four polypeptides (Mr 112, 45, 33 and 18kDa) were identified as most immunoreactive. Besides these, a 28kDa was observed as strong immunoreactive protein in WM and CM antigens. The HSS antigen showed only six polypeptides and one peptide (28kDa) was identified as immunoreactive. When high titred serum collected from immunized donkeys following challenge with B. equi infected blood and was used for immunoblotting, the protein profile of WM and CM antigens remained the same. However, three additional polypeptides (Mr 81, 54.5 and 39kDa) were detected in HSS antigen.

PMID: 12163241 [PubMed - indexed for MEDLINE]

139. Expert Opin Pharmacother. 2002 Aug;3(8):1109-15.

Babesiosis in humans: a treatment review.

Weiss LM.

Division of Infectious Diseases, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Room 504 Forchheimer Building, Bronx, New York, 10461, USA.

Comment in Expert Opin Pharmacother. 2002 Nov;3(11):1541-2.

Human infections with Babesia species, in particular Babesia microti, are tick-borne illnesses that are being recognised with increased frequency. Coinfection with ehrlichiosis and Lyme disease is also being recognised as an important feature of these tick-borne illnesses. Despite the superficial resemblance of Babesia to malaria, these piroplasms do not respond to chloroquine or other similar drugs. However, the treatment of babesiosis using a clindamycin-quinine combination has been successful. Data in animal models and case-reports in humans have suggested that an atovaquone-azithromycin combination is also effective. This was confirmed in a recent prospective, open, randomised trial of clindamycin-quinine versus azithromycin-atovaquone. This paper reviews the literature on the treatment of human babesiosis and the animal models of these human pathogens.

PMID: 12150690 [PubMed - indexed for MEDLINE]

140. Int J Med Microbiol. 2002 Jun;291 Suppl 33:22-9.

Foci of tick-borne diseases in southwest Germany.

Oehme R, Hartelt K, Backe H, Brockmann S, Kimmig P.

State Health Office Baden-Wuerttemberg, Stuttgart, Germany.

Presently known tick-borne diseases in Germany include Lyme borreliosis, tick-borne encephalitis (TBE-virus, western subtype), Q-fever, babesiosis and presumably ehrlichiosis. Blood samples of 4,368 forestry workers in the State of Baden-Wuerttemberg (B-W), southwestern Germany, were tested for the presence of antibodies against Borrelia burgdorferi sensu lato, TBE-virus and Ehrlichia spp. (genogroup E. phagocytophila). Furthermore 12,327 ticks (Ixodes ricinus) collected in various areas of B-W were analysed by PCR and genotyping for the prevalence of pathogen RNA and DNA. The human seroprevalence rates of antibodies to B. burgdorferi sensu lato ranged from 18% to 52%, for TBE-virus from 0% to 43% and for Ehrlichia spp. from 5% to 16% in various counties of the State. The foci of B. burgdorferi and TBE-virus as indicated by antibody prevalence in humans are only partly overlapping with each other. The highest rates of TBE-virus antibodies are in concordance with available clinical data. However antibody prevalence up to 27% in areas with no reports of clinical cases was found, suggesting that TBE occurs throughout the State of B-W. The prevalence of Ehrlichia spp. antibodies suggests that ehrlichiosis plays a role as a tick-borne disease in Germany, but as long as no clinical data are available, this will remain unclear. Investigations of ticks for TBE-virus (n = 9,189) by nested PCR showed prevalence rates from 0% to 2.3% and for Ehrlichia spp. (n = 1,963) from 2.6% to 3.1%. Examination of ticks (n = 3,138) for the presence of B. burgdorferi sensu lato DNA was performed by PCR and revealed prevalence rates from 13.9% up to 24%. Furthermore 1,106 samples positive for B. burgdorferi sensu lato were used for genotyping. B. afzelii DNA was found in 407 ticks (36.8%), followed by B. garinii (21.9%), B. valaisiana (13.7%), and B. burgdorferi sensu stricto (9.9%). Double infection was found in 6.4% and triple infection in 0.8% of the ticks. 10.5% of the positive samples could not be classified. Prevention of tick-borne diseases has to focus on behavioural intervention to reduce individual tick exposure by proper behaviour in the environment, as a large-scale control of the tick population seems impossible and thus reduction of Lyme borreliosis and TBE through tick control is unlikely. Vaccination against TBE-virus should not only be recommended for high endemic areas but also for persons with a high individual risk.

PMID: 12141751 [PubMed - indexed for MEDLINE]

141. Transfus Med Rev. 2002 Jul;16(3):239-50.

Exchange transfusion for malaria and Babesia infection.

Powell VI, Grima K.

New York Blood Center, New York, NY 10605, USA.

Malaria accounts for about 2 million deaths per year. Although most cases occur in children in sub-Saharian Africa, fatal infections are seen increasingly in industrialized countries. In 1992, over 900 malaria cases were reported in the United States and a third of these were caused by Plasmodium falciparum. Fatal infections are related to the magnitude of the parasitemia and the immune status of the host. P falciparum poses the greatest threat of death because it invades red cells of all ages, is often drug resistant, and is the only one of the plasmodia species that produces microvascular disease. The risk of death is correlated with the parasite load in immune naive individuals. Babesiosis is generally a subclinical infection in most normal hosts, but it can be life threatening in asplenic patients, older, or immunocompromised individuals. The role of exchange transfusion (ET) in the treatment of these infections is controversial. The Centers for Disease Control recommends that ET be performed in P falciparum infection when parasitemia is equal or greater than 10%. In patients with coma, renal failure, or adult respiratory distress syndrome, ET is recommended regardless of the level of parasitemia even if less than 10%. ET has been advocated to reduce the level of parasitized red blood cells (RBCs), to remove cytokines, and to improve the rheologic properties of the blood. Dramatic improvement has been reported, but there are conflicting reports that question the need for exchange transfusion. This review examines the pathophysiology of severe infection and its treatment, with an emphasis on the role of exchange transfusion.

Copyright 2002, Elsevier Science (USA). All rights reserved.

PMID: 12075561 [PubMed - indexed for MEDLINE]

142. Acta Vet Hung. 2002;50(1):63-78.

Dermatitis associated with Dirofilaria (Nochtiella) repens microfilariae in dogs from central Italy.

Tarello W.

Pruritic dermatitis associated with Dirofilaria (Nochtiella) repens microfilariae in the blood was diagnosed in 22 dogs from Fermo (Central Italy). According to the history, previous unsuccessful treatments with corticosteroids, antibiotics, restricted diet, flea control, levamisole and ivermectin were recorded in 17 dogs (77.3%). The combined filtration tests and antigen tests, performed during the study, were negative for Dirofilaria immitis and Acanthocheilonema reconditum in each case. Dermatological lesions included erythema, papules, single or multifocal alopecia, eczema, lichenification, crusting and nodules. All dogs had pruritus. Concurrent babesiosis was diagnosed in the blood smears of each case (100%), and 60% of the dogs were found to be carriers of canine granulocytic ehrlichiosis (CGE). Three dogs (13.6%) were positive for leishmaniosis. Eradication of the concurrent infections followed by specific macro- and microfilaricide treatment led to complete recovery from the dermatological syndrome. The main conclusion of the study is that D. repens infection can be more pathogenic than is currently considered, and it is apparently an opportunistic disease with serious dermatological consequences.

PMID: 12061238 [PubMed - indexed for MEDLINE]

143. Berl Munch Tierarztl Wochenschr. 2002 May-Jun;115(5-6):167-72.

[Isoimmune haemolytic icterus in neonatal calves as a consequence of vaccination against piroplasmosis].

[Article in German]

Sipos W, Schmoll F, Bagó Z, Hobbiger A, Wodak E.

II. Medizinische Universitätsklinik für Klauentiere, Veterinärmedizinischen Universität Wien.

The article refers about several cases of isoimmunohaemolytic icterus in neonatal calves from different farms, whose dams had all been vaccinated against piroplasmosis. Clinical signs of immunomediated icterus neonatorum gravis, results of blood chemistry (with special regard to liver-specific parameters in the neonatal calf and results of haematology) as well as gross pathology and pathohistology are to be discussed. It is summarized, that the most relevant indicators for a hepatopathy in the newborn calf are total-bilirubin and the glutamate-dehydrogenase. Today, the production of piroplasmosis-vaccines out of blood of splenectomized animals is referred to as the only practicable method of harvesting sufficient amounts of vaccine-antigen.

PMID: 12058589 [PubMed - indexed for MEDLINE]

144. Parasitol Res. 2002 May;88(13 Suppl 1):S38-40.

Culture-derived Babesia orientalis exoantigens used as a vaccine against buffalo babesiosis.

Zhao JL, Liu ZL, Yao BA, Ma LH.

Institute of Animal Science and Veterinary Medicine, Huazhong Agricultural University, Wuhan Hubei, The People's Republic of China.

Buffalo babesiosis represents a major problem for the livestock industry in China. The pathogen of this disease was isolated and identified as Babesia orientalis and subsequently propagated in vitro, using the microaerophilus stationary phase culture system. The aim of this study was to determine the efficacy of exoantigens derived from B. orientalis cultures to induce a protective immunity against challenge exposure to virulent organisms in laboratory and field. The results showed that exoantigens of B. orientalis could induce a high degree of protection against challenge with a virulent B. orientalis strain. The animals in the vaccinated group exhibited a slight decrease in haemoglobin levels and blood cell counts, whereas animals in the control group showed typical clinical symptoms and died between days 11 and 16 after challenge. In another approach, 82 buffaloes kept in B. orientalis-endemic areas were injected with exoantigens plus Freund's adjuvant in two doses at an interval of 2 weeks, one month before the endemic period. An additional 86 buffaloes served as unvaccinated controls. During the endemic period, the clinical signs of all buffaloes were monitored and the antibody response was investigated, using the latex agglutination test. During the endemic period, none of the vaccinated buffaloes showed clinical signs or died, whereas five control buffaloes showed clinical signs and two of them died. The mean antibody titre of vaccinated animals was higher than that of the control animals. These results showed that the culture-derived exoantigens of B. orientalis could be used as a vaccine to prevent buffalo babesiosis.

PMID: 12051606 [PubMed - indexed for MEDLINE]

145. Vet Parasitol. 2002 May 30;106(1):19-33.

Vaccination of donkeys against Babesia equi using killed merozoite immunogen.

Kumar S, Malhotra DV, Dhar S, Nichani AK.

All India Coordinated Research Project on Blood Protista, CCS Haryana Agricultural University, Hisar, India.

Protective efficacy of a killed Babesia equi immunogen was assessed in donkeys. The immunogen was prepared from B. equi infected blood so as to contain lysate of 2 x 10(10) parasitised erythrocytes per dose. The immunogen was mixed with an adjuvant Quil A (3mg) and inoculated into four susceptible donkeys (group I). A booster inoculation was given after 21 days of first inoculation followed by challenge with fresh infected blood containing 1x10(11) parasitised erythrocytes 14 days later. Two groups of two donkey each were included as adjuvant only control (group II) and uninoculated control (group III), respectively. After challenge, donkeys were observed for a period of 4 weeks. The immunised donkeys (group I) showed significantly high (P<0.05%) enzyme linked immunosorbant assay (ELISA) antibody titres and significantly high (P<0.05%) stimulation indices (SI) in lymphocyte proliferation assay (LPA) than that of groups II and III donkeys from day 14 PI and day 7 PI onwards, respectively. All the immunised donkeys withstood lethal challenge, whereas, control donkeys died within 10 days post-challenge (PC). Parasitaemia rose to mean maximum 8.0+/-6.0% for 5-7 days in group I donkeys after challenge, whereas, it rose to 55.5% in control groups. The percent rise in rectal temperature, total leucocyte count (TLC), fall in haemoglobin (Hb) was less severe in immunised group as compared to the control groups. Two immunised-challenged donkeys were splenectomised recovery. No parasites appeared in the blood during the observation period following splenectomy 4-week. Three times increase in skin-fold thickness at 24h of intradermal inoculation prior to challenge in group I donkeys was observed, thus, indicating a good in vivo cell mediated immunity. It can be concluded that the B. equi immunogen along with adjuvant Quil A, used in the present study, was optimum to elicit a strong immune response against B. equi in experimental donkeys.

PMID: 11992708 [PubMed - indexed for MEDLINE]

146. Med Clin North Am. 2002 Mar;86(2):361-73.


Krause PJ.

University of Connecticut School of Medicine, Department of Pediatrics, Connecticut Children's Medical Center, Hartford, Connecticut, USA.

Babesiosis is an emerging infection caused by protozoal parasites and transmitted by the same tick that transmits Lyme disease. Babesiosis is found throughout the world, but most cases have been described from the northeastern and northern midwestern United States. Patients experience a flulike illness that usually lasts for 1 or 2 weeks but may require hospital admission. Those at greatest risk of fatal disease include individuals older than age 50 years; asplenic individuals; and immunocompromised individuals as a result of immunosuppressive drugs, malignancy, or HIV infection. Specific diagnosis is made through examination of a Giemsa-stained thin blood smear, DNA amplification using polymerase chain reaction, or detection of specific antibody. Treatment consists of clindamycin and quinine or atovaquone and azithromycin and, in severe cases, exchange transfusion.

PMID: 11982307 [PubMed - indexed for MEDLINE]

147. Transfus Med Rev. 2002 Apr;16(2):131-43.

The impact of babesiosis on transfusion medicine.

Pantanowitz L, Telford SR 3rd, Cannon ME.

Department of Pathology, Beth Israel Deaconess Medical Center, Harvard School of Public Health, 330 Brookline Avenue, Boston, MA 02215, USA.

Babesiosis is an emerging zoonotic disease that has begun to have a noticeable impact on transfusion medicine. This is reflected in the growing medical literature on the topic. There has been no review to summarize the various ways in which babesiosis influences transfusion medicine. Babesiosis is the most frequently reported tick-borne pathogen to be transmitted by blood transmission. Until recently, it has been an underrecognized complication of blood transfusion. However, the increased use of blood products for an ever-increasing elderly and immunodeficient patient population has heightened awareness about this disease. Fortunately, the risk of acquiring a symptomatic infection through a blood transfusion is surprisingly low. Nevertheless, babesiosis should be included in the differential diagnosis of a febrile hemolytic illness in recipients of blood transfusions. Infected individuals who become chronic carriers and donate blood during asymptomatic periods pose the greatest risk to the blood supply. The exact risk that this parasite poses to our blood supply remains to be accurately assessed. Reported cases of transmission, to date, have involved only the transfusion of red blood cells (RBCs) and, more rarely, platelets. Transmission of these piroplasms through plasma alone has not been documented. Much of our understanding about this organism evoked host responses and its requirements for in vitro survival has come from studies on non-human vertebrates. These studies have shown that antigenic variation may play a significant role in the development of prolonged parasitemia, that complement-induced changes to erythrocytes are pivotal in facilitating protozoan entry into host RBCs, and that autoimmunity contributes to disease. Severe infections may require lifesaving exchange transfusions and even plasmapheresis. Controlled studies to clearly define specific indications, benefits, and objectives of this therapy are still needed. Despite the development of novel and improved diagnostic tests, these tests are not readily available for the mass screening of blood donors. Improved strategies to assess and prevent transfusion-associated babesiosis are required. Current measures cannot be relied on to identify infected donors with a high degree of sensitivity or to protect susceptible recipients from this parasite.

Copyright 2002, Elsevier Science (USA). All rights reserved.

PMID: 11941575 [PubMed - indexed for MEDLINE]

148. Exp Parasitol. 2001 Nov;99(3):168-74.

Babesia bovis: culture of laboratory-adapted parasite lines and clinical isolates in a chemically defined medium.

Jackson LA, Waldron SJ, Weier HM, Nicoll CL, Cooke BM.

Tick Fever Research Centre, Queensland Department of Primary Industries, 280 Grindle Road, Wacol, Queensland 4076, Australia.

Babesiosis caused by Babesia spp. is a disease of both veterinary and human importance. Here, we describe a method to continuously culture laboratory lines and field isolates of Babesia bovis in vitro in a chemically defined medium using (ALBU)MAX II as an alternative to bovine serum. Further, we have successfully cultured parasite isolates directly from cattle that failed to grow in traditional serum-containing medium. Variation of atmospheric gas composition and culture volumes to determine optimal growth conditions revealed that a 600-microl culture in an atmosphere comprising 5% O(2), 5% CO(2), and 90% N(2) achieved a significantly higher percentage of parasitized red blood cells than any other combination tested. The process could be scaled up to reliably produce large volumes of parasites. Supplementation of the culture medium with hypoxanthine further improved parasite growth. B. bovis cultured in this way could be the basis of an alternative, safer vaccine and a reliable source of parasites and exoantigens for parasitological research.

Copyright 2001 Elsevier Science (USA).

PMID: 11846527 [PubMed - indexed for MEDLINE]

149. Aust Vet J. 2001 Dec;79(12):832-9.

Immunity following use of Australian tick fever vaccine: a review of the evidence.

Bock RE, de Vos AJ.

Tick Fever Research Centre, Animal and Plant Health Service, Queensland Department of Primary Industries, Wacol.

OBJECTIVE: To review the evidence available on the degree and duration of immunity provided by Australian tick fever vaccines against Babesia bovis, B. bigemina and Anaplasma marginale infections in Australia and overseas. BACKGROUND: Vaccines containing attenuated strains of B bovis and B bigemina as well as A. centrale grown in splenectomised calves have been used in Australia since 1964 to immunise cattle against tick fever. About 800,000 doses of vaccine are supplied annually and much of the evidence for protection is field evidence rather than conventional immunological measures or pen trials. CONCLUSIONS: Immunity to Babesia bovis and B. bigemina--A single inoculation generally provides sound, long-lasting protection both in Australia and overseas. No evidence was found of a loss of immunity with time. Vaccine failures to B. bovis do occur, but are uncommon and evidently caused by a number of factors, including immune responsiveness of the vaccinated animals, and immunogenicity of the vaccine strain. Immunity to Anaplasma marginale--The vaccine containing A. centrale provides partial, variable protection against A. marginale. Protection against challenge in Australia is adequate in most cases to prevent disease and use of the vaccine in this country appears to be justified. Protection against antigenically diverse, highly virulent stocks of A. marginale in other countries is, at times, clearly inadequate and better vaccines are required in situations where the challenge is severe.

PMID: 11837905 [PubMed - indexed for MEDLINE]

150. Onderstepoort J Vet Res. 2001 Sep;68(3):217-23.

Immunization of cattle against East Coast fever using Theileria parva (Marikebuni) and relaxation of tick control in North Rift, Kenya.

Wanjohi JM, Ngeranwa JN, Rumberia RM, Muraguri GR, Mbogo SK.

Kenya Agricultural Research Institute, National Veterinary Research Centre Muguga, Kikuyu.

A total of 90 animals was immunized against East Coast fever (ECF) using Theileria parva (Marikebuni) stock on three large-scale farms in Kiminini Division, Trans-Nzoia District, North Rift, Kenya. Another 90 cattle served as non-immunized controls. Following immunization the number of cattle with significant indirect fluorescent antibody (IFA) titres increased from 43.9% to 84.4% and 6.7% of the cattle developed clinical ECF reactions. Two months after immunization, the immunized and non-immunized cattle were divided into two groups one of which was dipped every 3 weeks and the other dipped when total full body tick counts reached 100. All the animals were monitored for 51 weeks for incidences of ECF and other tick-borne diseases. Twenty-four cases of ECF were diagnosed among the non-immunized cattle compared to four cases among the immunized cattle; a difference that was significant (P > 0.05). There was no significant difference in the incidences of babesiosis and anaplasmosis between the immunized and non-immunized cattle.

PMID: 11769354 [PubMed - indexed for MEDLINE]

151. Adv Parasitol. 2001;50:1-86.

The malaria-infected red blood cell: structural and functional changes.

Cooke BM, Mohandas N, Coppel RL.

Department of Microbiology, P.O. Box 53, Monash University, Victoria 3800, Australia.

The asexual stage of malaria parasites of the genus Plasmodium invade red blood cells of various species including humans. After parasite invasion, red blood cells progressively acquire a new set of properties and are converted into more typical, although still simpler, eukaryotic cells by the appearance of new structures in the red blood cell cytoplasm, and new proteins at the red blood cell membrane skeleton. The red blood cell undergoes striking morphological alterations and its rheological properties are considerably altered, manifesting as red blood cells with increased membrane rigidity, reduced deformability and increased adhesiveness for a number of other cells including the vascular endothelium. Elucidation of the structural changes in the red blood cell induced by parasite invasion and maturation and an understanding of the accompanying functional alterations have the ability to considerably extend our knowledge of structure-function relationships in the normal red blood cell. Furthermore, interference with these interactions may lead to previously unsuspected means of reducing parasite virulence and may lead to the development of novel antimalarial therapeutics.

PMID: 11757330 [PubMed - indexed for MEDLINE]

152. Int J Parasitol. 2001 Dec;31(14):1673-9.

Characterisation of the gene encoding a protective antigen from Babesia microti identified it as eta subunit of chaperonin containing T-complex protein 1.

Nishisaka M, Yokoyama N, Xuan X, Inoue N, Nagasawa H, Fujisaki K, Mikami T, Igarashi I.

National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido 080-8555, Japan.

Passive immunisations with a monoclonal antibody termed 1-5H showed a partial but significant inhibition of parasitaemia against Babesia microti challenge infection. By immunoscreening with 1-5H, a clone (termed p58 gene) was obtained from a cDNA expression library of B. microti and the complete nucleotide sequence was determined. A protein homology search showed significant amino acid identities to the eta subunit of the chaperonin containing T-complex protein 1 (CCT) of human (59%), mouse (58%) and Plasmodium falciparum (62%). Genomic analyses indicated that the p58 gene is present as a single copy gene and contains a total of approximately 400-bp introns in the genome of B. microti. The mAb 1-5H recognised a 58-kDa protein of B. microti and was found to cross-react with a 60-kDa protein of Babesia rodhaini. These results suggest the possibility that the p58 protein is the CCT eta subunit of B. microti and functions as a chaperonin.

PMID: 11730795 [PubMed - indexed for MEDLINE]

153. Hematology Am Soc Hematol Educ Program. 2001:433-42.

Reducing the risk of blood transfusion.

Snyder EL, Dodd RY.

Blood Bank, Yale-New Haven Hospital, CT 06504-1001, USA.

There are continuing concerns over the safety of the nation's and the world's blood supply. The allogeneic blood supply is tested for antibodies to HIV1/2, HTLVI/II, hepatitis B, hepatitis C (HCV) and syphilis. Testing is also performed for donor ALT (SGOT) levels, for the presence of hepatitis B surface antigen, human immunodeficiency virus (HIV) p24 antigen and, using nucleic acid amplification testing (NAT), for HIV and HCV nucleic acids. Still, there are concerns regarding other pathogenic agents. Dr. Roger Dodd addresses a series of pathogens that are already known to be transmissible by transfusion. These include malaria, Chagas' disease, babesiosis, bacteria and some viral agents. The need for new donor screening assays to protect the integrity and purity of the blood supply must be balanced against the loss of potential donors and the cost of developing and implementing these new screening assays. This issue will be highlighted. Dr. Edward Snyder reviews the status of research into development of systems for pathogen inactivation (PI) of blood and its components. A proactive technology wherein PI reagents such as psoralen, riboflavin, dimethylmethylene blue or inactine are added to blood collection bags could assure multiple log reduction of a variety of pathogens including viruses, bacteria, protozoa and fungi without the need to initially pre-screen the blood for a specific pathogen. Such a program could also cover new pathogens as they enter the blood supply. As a key issue relates to the toxicology of these agents, Dr. Snyder provides data on a novel carcinogenicity assay that uses a heterozygous p53 knock-out mouse model. The criteria likely to be needed for PI technology to be adopted by the transfusion community are summarized.

PMID: 11722997 [PubMed - indexed for MEDLINE]

154. Vet Parasitol. 2001 Nov 22;101(3-4):233-48.

Molecular approaches to elucidating innate and acquired immune responses to Babesia bovis, a protozoan parasite that causes persistent infection.

Brown WC.

Department of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman, WA 99164-7040, USA.

For many vector-transmitted protozoal parasites, immunological control of acute infection leads to a state of persistent infection during which parasitemias may cycle unnoticed in infected but otherwise clinically healthy animals. Achieving persistent infection is a strategy that favors parasitism, since both host and, therefore, parasite survive, and endemically infected animal populations provide a reservoir of parasites continually available for subsequent transmission. Examples of the major economically important protozoan pathogens that cause persistent infection in mammals include the related Theileria and Babesia parasites as well as Trypanosoma species. Control of acute infection and maintenance of clinical immunity against subsequent infection are determined by the interplay of innate and acquired immune responses. This review will focus on approaches taken to gain an understanding of the molecular basis for innate and acquired immunity against the hemoprotozoan parasite of cattle, Babesia bovis. Knowledge of mechanisms used by the parasite to survive within infected cattle from acute to persistent infection combined with definition of the correlates of protective immunity in cattle should be applicable to designing effective vaccines.

PMID: 11707299 [PubMed - indexed for MEDLINE]

155. Vet Parasitol. 2001 Sep 12;100(1-2):75-86.

Vaccination of dogs against heterologous Babesia canis infection using antigens from culture supernatants.

Schetters TP, Kleuskens JA, Scholtes NC, Gorenflot A, Moubri K, Vermeulen AN.

Parasitology R&D Department, Intervet International B.V., P.O. Box 315830, AA Boxmeer, The Netherlands.

Soluble parasite antigens (SPA) from European Babesia canis can be used to protect dogs against a homologous but not heterologous challenge infection. In this study it is shown that when dogs are vaccinated with a mixture of SPA from both, a European B. canis isolate and a South African Babesia rossi isolate, protective immunity against heterologous B. canis infection is induced. Three groups of five beagle dogs each were vaccinated twice with graded doses of SPA derived from in vitro cultures of B. canis and B. rossi, with a 3-week interval. Saponin was used as adjuvant. Three weeks after booster vaccination immunological responsiveness against heterologous B. canis antigen was measured by seroconversion against infected erythrocytes and lymphocyte transformation using SPA. Upon vaccination dogs produced antibodies against infected erythrocytes and lymphoblastogenic responses against SPA in a dose-dependent manner. Dogs were then challenged with heterologous B. canis parasites. Dogs appeared to be protected against challenge infection, which was reflected in less severe decrease of packed cell volume (PCV) and reduced clinical signs. The level of protection to clinical signs (but not excessive PCV drop) was related to the level of SPA in plasma and spleen size, and not related to peripheral parasitaemia. The results suggest that vaccination with this bivalent vaccine primes T-helper cells that recognise common epitopes on SPA from an antigenically distinct B. canis isolate. These cells provide the essential Th signal to mount an effective and timely antibody response against SPA and parasites or parasitised erythrocytes, which prevents the further development of clinical babesiosis.

PMID: 11522408 [PubMed - indexed for MEDLINE]

156. Clin Infect Dis. 2001 Sep 1;33(5):676-85. Epub 2001 Aug 6.

Coinfecting deer-associated zoonoses: Lyme disease, babesiosis, and ehrlichiosis.

Thompson C, Spielman A, Krause PJ.

Department of Pediatrics, University of Connecticut School of Medicine, Farmington, Connecticut, USA.

The heightened worldwide recognition of the health burden of tickborne infection derives largely from the increasing incidence of Lyme disease, human babesiosis, and human granulocytic ehrlichiosis, both individually and in concert. Because these infections share the same rodent reservoir and tick vector hosts, they can be cotransmitted to human hosts. Indeed, human coinfections involving various combinations of these pathogens are common, and some tend to be particularly severe. Diagnostic procedures and clinical management of the resulting disease syndrome is rendered complex by the diversity of pathogens involved and by the unusual diversity and duration of symptoms.

PMID: 11486290 [PubMed - indexed for MEDLINE]

157. CMAJ. 2001 Jun 12;164(12):1721-3.

Transfusion-transmitted babesiosis in Ontario: first reported case in Canada.

Kain KC, Jassoum SB, Fong IW, Hannach B.

Centre for Travel and Tropical Medicine, Division of Infectious Diseases, Department of Medicine, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Ont.

Babesiosis has only recently been reported in Canada, but a number of transfusion-transmitted cases of this infection have been reported from the United States. We present a case of transfusion-transmitted babesiosis that occurred in Canada. Canadian physicians must consider babesiosis in the differential diagnosis of patients who experience fever or a hemolytic reaction after blood transfusion. Prompt recognition and treatment are important, because Babesia infections can be severe or fatal in certain risk groups. Better strategies to prevent transfusion-transmitted babesiosis are required.

PMCID: PMC81161 PMID: 11450217 [PubMed - indexed for MEDLINE]

158. Am Fam Physician. 2001 May 15;63(10):1969-74.

When to suspect and how to monitor babesiosis.

Mylonakis E.

Infectious Diseases Division, Massachusetts General Hospital, Boston 02114, USA.

In the past decade, cases of babesiosis in humans have been reported with increasing frequency, especially in the northeastern United States. Babesia microti (in the United States) and bovine strains (in Europe) cause most infections in humans. Most cases are tick-borne, although cases of transfusion-associated and transplacental/perinatal transmission have also been reported. Factors associated with more severe disease include advanced age, previous splenectomy and immunodeficient states. Symptoms include high fever, chills, diaphoresis, weakness, anorexia and headache. Later in the course of the illness, the patient may develop jaundice. Congestive heart failure, renal failure and acute respiratory distress syndrome are the most common complications. Therapy using the combination of quinine sulfate and clindamycin was the most commonly used treatment; however, atovaquone suspension plus azithromycin was recently reported an equally effective and less toxic therapy. Exchange transfusion, together with antibabesial chemotherapy, may be necessary in critically ill patients.

PMID: 11388711 [PubMed - indexed for MEDLINE]

159. J Clin Microbiol. 2001 Jun;39(6):2178-83.

Human babesiosis in Japan: isolation of Babesia microti-like parasites from an asymptomatic transfusion donor and from a rodent from an area where babesiosis is endemic.

Wei Q, Tsuji M, Zamoto A, Kohsaki M, Matsui T, Shiota T, Telford SR 3rd, Ishihara C.

School of Veterinary Medicine, Rakuno-Gakuen University, 582-1 Bunkyodai-Midorima-chi, Ebetsu 069-8501, Japan.

To determine the source of infection for the Japanese index case of human babesiosis, we analyzed blood samples from an asymptomatic individual whose blood had been transfused into the patient. In addition, we surveyed rodents collected from near the donor's residence. Examination by microscopy and PCR failed to detect the parasite in the donor's blood obtained 8 months after the donation of the blood that was transfused. However, we were able to isolate Babesia parasites by inoculating the blood sample into SCID mice whose circulating red blood cells (RBCs) had been replaced with human RBCs. A Babesia parasite capable of propagating in human RBCs was also isolated from a field mouse (Apodemus speciosus) captured near the donor's residential area. Follow-up surveys over a 1-year period revealed that the donor continued to be asymptomatic but had consistently high immunoglobulin G (IgG) titers in serum and low levels of parasitemia which were microscopically undetectable yet which were repeatedly demonstrable by inoculation into animals. The index case patient's sera contained high titers of IgM and, subsequently, rising titers of IgG antibodies, both of which gradually diminished with the disappearance of the parasitemia. Analysis of the parasite's rRNA gene (rDNA) sequence and immunodominant antigens revealed the similarity between donor and patient isolates. The rodent isolate also had an rDNA sequence that was identical to that of the human isolates but that differed slightly from that of the human isolates by Western blot analysis. We conclude that the index case patient acquired infection by transfusion from a donor who became infected in Japan, that parasitemia in an asymptomatic carrier can persist for more than a year, and that A. speciosus serves as a reservoir of an agent of human babesiosis in Japan.

PMCID: PMC88108 PMID: 11376054 [PubMed - indexed for MEDLINE]

160. Int J Parasitol. 2001 Feb;31(2):179-86.

Identification of antigenic differences that discriminate between cattle vaccinated with Anaplasma centrale and cattle naturally infected with Anaplasma marginale.

Molloy JB, Bock RE, Templeton JM, Bruyeres AG, Bowles PM, Blight GW, Jorgensen WK.

Queensland Department of Primary Industries, Agency for Food and Fibre Science, Animal Research Institute, Yeerongpilly, Australia.

Monoclonal antibodies were raised against the vaccine strain of Anaplasma centrale used in Australia. A monoclonal antibody that reacted with an 80 kDa antigen was used to develop an A. centrale-specific fluorescent antibody test that will be useful for confirming species identity in patent infections. Another monoclonal antibody that reacted with a 116 kDa antigen was used to develop an A. centrale-specific competitive inhibition enzyme-linked immunosorbent assay (ELISA) for the serological identification of vaccinated cattle. The sensitivity of the ELISA was 100% in cattle experimentally infected with A. centrale, 97.1% in a vaccinated beef herd and 98.3% in a vaccinated dairy herd. The specificity of the ELISA was 98.6% in non-vaccinated cattle outside the Anaplasma marginale-endemic area, 97.9% in non-vaccinated cattle within the A. marginale-endemic area and 100% in cattle experimentally infected with A. marginale. The ELISA detected antibodies to A. centrale in cattle up to 9 years after vaccination with no apparent decrease in sensitivity. The assay has proved extremely valuable in Australia for investigating reported failures of multivalent live vaccines used to protect cattle against anaplasmosis and babesiosis, and should be similarly useful elsewhere in the world where these types of vaccines are used, e.g. Israel and South America.

PMID: 11239938 [PubMed - indexed for MEDLINE]

161. N Engl J Med. 2001 Mar 8;344(10):773-4.

The treatment of babesiosis.

Ranque S.

Comment on N Engl J Med. 2000 Nov 16;343(20):1454-8.

PMID: 11236790 [PubMed - indexed for MEDLINE]

162. N Engl J Med. 2001 Mar 8;344(10):773.

The treatment of babesiosis.

Weiss LM, Wittner M, Tanowitz HB.

Comment on N Engl J Med. 2000 Nov 16;343(20):1454-8.

PMID: 11236789 [PubMed - indexed for MEDLINE]

163. Ann N Y Acad Sci. 2000;916:540-5.

Vaccination against bovine babesiosis.

De Vos AJ, Bock RE.

Tick Fever Research Centre, Department of Primary Industries, Wacol, Queensland 4076, Australia.

Bovine babesiosis is an important disease caused by Babesia bovis, B. bigemina, and B. divergens. Solid immunity develops after infection and this feature has been exploited with the use of live attenuated organisms as immunogens. Attributes of live vaccines include a durable immunity to heterologous challenge after one vaccination. To overcome disadvantages relating to poor quality control (risk of contamination and adverse reactions), production procedures have been modified to meet the requirements of codes of good manufacturing practice. This includes development of methods to allow production of cryopreserved vaccine and limit antigenic drift. Killed vaccines have also been used on a limited basis and consist of antigens extracted from cultured material or blood of infected calves, and given with adjuvant. The degree and duration of immunity against heterologous challenge is not well documented. Attempts are being made to develop subunit vaccines but the progress has been slow. A better understanding of the mechanisms involved in the expression of protective immunity against Babesia spp will aid in the identification of protective antigens.

PMID: 11193669 [PubMed - indexed for MEDLINE]

164. J Emerg Med. 2001 Jan;20(1):21-4.


Filbin MR, Mylonakis EE, Callegari L, Legome E.

Harvard Affiliated Emergency Medicine Residency, Massachusetts General Hospital, Boston, Massachusetts 02114-2696, USA.

A case of human babesiosis is presented. This case emphasizes the need to consider tick-borne disease in anyone who presents with prolonged and undulating fevers, chills, headache, myalgias, and arthralgias. This holds true particularly in areas endemic for tick-borne diseases, even in the absence of a history of tick bite. These symptoms, associated with signs of intravascular hemolysis, thrombocytopenia, and renal insufficiency in a patient who resides in, or with recent travel to, the Northeastern United States, strongly suggest a diagnosis of babesiosis.

PMID: 11165832 [PubMed - indexed for MEDLINE]

165. J Parasitol. 2000 Oct;86(5):956-8.

Morphological changes of Babesia gibsoni grown in canine red blood cell-substituted severe combined immune deficiency mice.

Fukumoto S, Xuan X, Igarashi I, Zhang S, Mugisha J, Ogata T, Nagasawa H, Fujisaki K, Suzuki N, Mikami T.

The National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Hokkaido, Japan.

Canine red blood cell-substituted severe combined immune deficiency (Ca-RBC-SCID) mice were prepared for canine Babesia gibsoni infection. The Ca-RBC-SCID mice infected with B. gibsoni developed a high level of parasitemia, and showed clinical symptoms such as anemia and hemoglobinuria, which are similar to those observed in dogs infected with B. gibsoni. The B. gibsoni parasites grown in Ca-RBC-SCID mice showed marked morphological changes, including a significantly larger size of parasites than those in dogs and abundant RBCs containing 4, 8, 16, and 32 parasites. The multiple infection may have resulted from 1 parasite because the posterior end of each parasite in a multiply infected cell was connected. The parasites grown in SCID mice retained their infectivity and virulence to dogs and their morphology was dramatically restored to the original state when they were returned to dogs.

PMID: 11128518 [PubMed - indexed for MEDLINE]

166. J Clin Microbiol. 2000 Dec;38(12):4511-6.

Transfusion-acquired, autochthonous human babesiosis in Japan: isolation of Babesia microti-like parasites with hu-RBC-SCID mice.

Saito-Ito A, Tsuji M, Wei Q, He S, Matsui T, Kohsaki M, Arai S, Kamiyama T, Hioki K, Ishihara C.

Department of Medical Zoology, Kobe 650-0017, School of Veterinary Medicine, Rakuno-gakuen University, Ebetsu 069-8501, Japan.

We have isolated piroplasms from a patient who developed the first case of human babesiosis in Japan by using NOD/shi-scid mice whose circulating erythrocytes (RBCs) had been replaced with human RBCs (hu-RBC-SCID mice). Following inoculation of the patient's blood specimen into hu-RBC-SCID mice, parasites proliferated within the human RBCs in the mice, resulting in a high level of parasitemia. Parasite DNA was prepared from blood samples of the patient and the mice, and the nuclear small-subunit rRNA gene (rDNA) was amplified and sequenced. Both DNA samples gave rise to identical sequences which showed the highest degree of homology (99.2%) with the Babesia microti rDNA. Because the patient had received a blood transfusion before the onset of babesiosis, we investigated the eight donors who were involved. Their archived blood samples were analyzed for specific antibody and parasite DNA; only a single donor was found to be positive by both tests, and the parasite rDNA sequence from the donor coincided with that derived from the patient. The donor's serum exhibited a high antibody titer against the isolate from the patient, whereas it exhibited only a weak cross-reaction against B. microti strains isolated in the United States. We conclude that the first Japanese babesiosis case occurred due to a blood transfusion and that the etiological agent is an indigenous Japanese parasite which may be a geographical variant of B. microti. Our results also demonstrated the usefulness of hu-RBC-SCID mice for isolation of parasites from humans and for maintenance of the parasite infectivity for human RBCs.

PMCID: PMC87629 PMID: 11101588 [PubMed - indexed for MEDLINE]

167. N Engl J Med. 2000 Nov 16;343(20):1454-8.

Atovaquone and azithromycin for the treatment of babesiosis.

Krause PJ, Lepore T, Sikand VK, Gadbaw J Jr, Burke G, Telford SR 3rd, Brassard P, Pearl D, Azlanzadeh J, Christianson D, McGrath D, Spielman A.

Division of Infectious Diseases, Connecticut Children's Medical Center and the University of Connecticut School of Medicine, Hartford 06106, USA.

Comment in N Engl J Med. 2001 Mar 8;344(10):773. N Engl J Med. 2001 Mar 8;344(10):773-4.

BACKGROUND: Babesiosis is a tick-borne, malaria-like illness known to be enzootic in southern New England. A course of clindamycin and quinine is the standard treatment, but this regimen frequently causes adverse reactions and occasionally fails. A promising alternative treatment is atovaquone plus azithromycin. METHODS: We conducted a prospective, nonblinded, randomized trial of the two regimens in 58 subjects with non-life-threatening babesiosis on Nantucket, on Block Island, and in southern Connecticut. The subjects were assigned to receive either atovaquone (750 mg every 12 hours) and azithromycin (500 mg on day 1 and 250 mg per day thereafter) for seven days (40 subjects) or clindamycin (600 mg every 8 hours) and quinine (650 mg every 8 hours) for seven days (18 subjects). RESULTS: Adverse effects were reported by 15 percent of the subjects who received atovaquone and azithromycin, as compared with 72 percent of those who received clindamycin and quinine (P<0.001). The most common adverse effects with atovaquone and azithromycin were diarrhea and rash (each in 8 percent of the subjects); with clindamycin and quinine the most common adverse effects were tinnitus (39 percent), diarrhea (33 percent), and decreased hearing (28 percent). Symptoms had resolved three months after the start of therapy in 65 percent of those who received atovaquone and azithromycin and 73 percent of those who received clindamycin and quinine (P=0.66), and after six months no patient in either group had symptoms. Three months after the completion of the assigned regimen, no parasites could be seen on microscopy, and no Babesia microti DNA was detected in the blood of any subject. CONCLUSIONS: For the treatment of babesiosis, a regimen of atovaquone and azithromycin is as effective as a regimen of clindamycin and quinine and is associated with fewer adverse reactions.

PMID: 11078770 [PubMed - indexed for MEDLINE]

168. Nurse Pract. 2000 Oct;25(10):38-40, 43-4, 47-8 passim; quiz 56-7.

An update on Lyme disease and other tick-borne illnesses.

Fell E.

Lyme disease, the most common vector-borne illness in North America, is a multisystem, multistage infectious disease caused by the tick-transmitted spirochete Borrelia burgdorferi. Although Lyme disease is not fatal, it can cause musculoskeletal, neurological, and cardiovascular manifestations that may be difficult to treat. Clinicians must also be aware of other potentially fatal tick-borne diseases such as babesiosis, ehrlichiosis, and Rocky Mountain spotted fever. Early identification and treatment of tick-borne diseases are crucial to preventing devastating sequelae.

PMID: 11068777 [PubMed - indexed for MEDLINE]

169. Rinsho Ketsueki. 2000 Aug;41(8):628-34.

[First documentation of transfusion-associated babesiosis in Japan].

[Article in Japanese]

Matsui T, Inoue R, Kajimoto K, Tamekane A, Okamura A, Katayama Y, Shimoyama M, Chihara K, Saito-Ito A, Tsuji M.

Department of Medicine, Kobe University School of Medicine.

A 40-year-old man received blood transfusion in December 1998 because of gastric bleeding from a peptic ulcer. One month later, he developed febrile hemolytic anemia. Administration of high doses of glucocorticoid significantly reduced the hemolysis, but did not cure the disease. To investigate the cause of the hemolysis, the patient was transferred to our hospital in May 1999. Giemsa-stained peripheral blood smears showed Babesia parasites in the red blood cells (RBC), and PCR analysis confirmed the presence of Babesia microti DNA. The parasitemia disappeared hematologically after 2 weeks of quinine and clindamycin therapy. However, parasite DNA was still detectable in the RBC. Although treatment with oral atovaquone was given for 2 weeks, parasitemia and febrile hemolysis recurred within a month after the last treatment. Fortunately, complete remission was obtained after a second 12-week course of therapy with quinine and clindamycin. PCR analysis revealed asymptomatic Babesia infection in one of eight samples from the original blood donor. The initial steroid therapy given to the patient without an accurate diagnosis seemed to have delayed augmentation of the specific antibodies (IgG) against Babesia microti, thus prolonging the parasitemia after the initial acute stage of babesiosis.

PMID: 11020989 [PubMed - indexed for MEDLINE]

170. J Vet Med Sci. 2000 Aug;62(8):835-9.

Therapeutic effect of clindamycin and tetracycline on Babesia rodhaini infection in mouse model.

Wijaya A, Wulansari R, Ano H, Inokuma H, Makimura S.

Department of Veterinary Science, Faculty of Agriculture, Miyazaki University, Japan.

In order to identify the alternative effective chemotherapeutic agents for murine babesiosis, some selected drugs were examined for their efficacy against protozoan infection in the mouse-Babesia rodhaini (B. rodhaini) model. Clindamycin was not completely effective for elimination of parasites in a dose of 50 mg or 100 mg/kg BW/day b.i.d. but effective to prolong the life span of hosts, while it completely cured B. rodhaini infections in a dose of 200 mg. On the other hand, a double therapy consisting of 2 treatments with 100 mg clindamycin and 100 mg clindamycin and with 100 mg clindamycin and 100 mg tetracycline; respectively, and a single therapy with 100 mg tetracycline or 200 mg clindamycin, had a possibility to clear away B. rodhaini organisms from hosts. However, almost all the treatment groups, had a relapse of the infection within 10 days post treatment or re-treatment. Cured mice by treatment with clindamycin and clindamycin, or clindamycin and tetracycline showed complete resistance against challenge with B. rodhaini, while mice cured by administration of clindamycin at 200 mg or tetracycline at 100 mg showed incomplete resistance to challenge infection. The present data suggest that the two former chemotherapies can induce effective protective immunity (premunization), but the latter two chemotherapies induce incomplete premunization.

PMID: 10993180 [PubMed - indexed for MEDLINE]

171. Rev Latinoam Microbiol. 1998 Jan-Jun;40(1-2):39-44.

Use of a duplex PCR/DNA probe assay to monitor Babesia bovis and Babesia bigemina in cattle during a vaccination trial.

Figueroa JV, Alvarez JA, Rojas EE, Ramos JA, Mosqueda JJ, Cantó GJ, Vega CA, Buening GM.


Erratum in Rev Latinoam Microbiol 1999 Jan-Mar;41(1):43-5.

A Duplex Polymerase Chain Reaction (DPCR)/DNA probe assay was used to detect Babesia bovis and B. bigemina DNA in cattle undergoing immunization trials. Blood samples were collected from 15 non-splenectomized, 1-2 years old bulls, inoculated with 1 x 10(7) each of culture-derived B. bovis- and B. bigemina-infected erythrocytes. 15 bulls inoculated with normal erythrocytes served as a control group. All cattle were field exposed to tick-transmitted Babesia 21 days (20 animals, Group I) and 60 days (10 animals, Group II) post-inoculation (PI). After immunization, the DPCR/DNA probe assay detected B. bigemina and B. bovis parasite DNA in all inoculated animals from days 4 to 14 PI. At challenge, B. bovis DNA was detected in all control animals as early as day 8 (Group I), or day 11 (Group II) post-introduction to a tick-infested area. The immunized bulls showed B. bovis positive PCR/DNA probe signals from day 0 (Group II) and day 8 (group I), up to day 32 post-exposure to ticks. Positive B. bigemina signals were detected from day 0 (Group I) and day 8 (Group II), up to day 36 post-exposure to ticks. During challenge, it was not possible to clearly define whether the PCR/DNA probe signals detected in the blood from immunized cattle were a result of amplified DNA from the culture-derived parasites, from the tick-transmitted parasites, or both.

PMID: 10932733 [PubMed - indexed for MEDLINE]

172. Transplantation. 2000 Jul 15;70(1):205-8.

Babesiosis in a renal transplant recipient acquired through blood transfusion.

Perdrizet GA, Olson NH, Krause PJ, Banever GT, Spielman A, Cable RG.

Department of Surgery, Hartford Hospital, CT 06102, USA.

BACKGROUND: The success of organ-replacement therapies has resulted in a population of chronically immunosuppressed but active people who experience increased vulnerability to tick-borne zoonoses. Several of these infections may be life threatening. Human babesiosis is an emerging zoonosis that is transmitted by the same tick that transmits Lyme disease and human granulocytic ehrlichiosis. METHODS: We briefly review these zoonoses and present a case of a renal transplant recipient who survived infection by Babesia microti contracted through blood transfusion. RESULTS: A recipient of a living-related renal transplant developed acute postoperative hemolytic anemia. The etiology of this anemia was diagnosed by peripheral red blood cell smear as Babesia microti. The patient was managed by a reduction in transplant immunosuppressive therapy and administration of clindamycin and quinine antimicrobials. CONCLUSIONS: Transplant patients may contract babesiosis after tick exposure and/or via blood transfusion. The diagnosis of babesiosis may be confused with malaria and should be included in the differential diagnosis of posttransplant hemolytic-uremic syndrome in organ transplant patients.

PMID: 10919602 [PubMed - indexed for MEDLINE]

173. J S Afr Vet Assoc. 1999 Jun;70(2):90-1.

Could treatment of pregnant mares prevent abortions due to equine piroplasmosis?

Lewis BD, Penzhorn BL, Volkmann DH.

Department of Biology, Medical University of Southern Africa, Medunsa, South Africa.

Treatment of pregnant mares to prevent abortions due to equine piroplasmosis is a novel idea practised empirically at some Thoroughbred studs in South Africa. This paper presents the results of an investigation to ascertain whether imidocarb dipropionate crosses the equine placenta. Three pregnant mares were injected intramuscularly with imidocarb and their foetuses were mechanically aborted at varying time intervals thereafter. Imidocarb was found in foetal blood at a level similar to that in the dam's blood, suggesting that imidocarb administered to the dam would be available for anti-parasitic activity in the foetal circulation. Uncertainty concerning the time of treatment to achieve the desired effect currently makes this a questionable exercise.

PMID: 10855828 [PubMed - indexed for MEDLINE]

174. Transfus Sci. 2000 Jun;22(3):183-94.

Clinical application of therapeutic erythrocytapheresis (TEA).

Valbonesi M, Bruni R.

Immunohematology Services, San Martino University Hospital, Largo Rosana Benzi 10, 16132, Genoa, Italy.

Therapeutic erythrocytapheresis (TEA) has been used in different diseases such as polycythemia vera (PV), secondary erythrocytosis or hemochromatosis as a process of the less cumbersome but more expensive phlebotomy. TEA is preferred in emergency conditions such as thrombocytosis or in conditions such as porphyria cutanea tarda (PCT) or erythropoietic porphyria when plasma exchange (PEX) is often combined with TEA to reduce extracellular levels of uroporphyrin which contribute to plasma hyperviscosity. TEA is often combined with drug therapy that varies from etoposide in PV to EPO and desferoxamine which are used to mobilize and reduce iron stores in hemochromatosis. Benefits from this combination may be more long lasting than expected. Nonetheless for TEA, there is no standard protocol and, clinical experience with this therapy remains highly anecdotal. Therapeutic red cell-exchange (TREX) has been used with much interest over the years, starting with the management of hemolytic disease of the newborn and later used to correct severe anemia in thalassemia patients thereby preventing iron overload. It has also been used for the management of complications of sickle cell disease such as priapism, chest syndrome, stroke, retinal, bone, splenic and hepatic infarction or in preparation for surgery by reducing HbS to less than 30%. Automated apheresis has also favored the use of TREX in conditions such as paroxysmal nocturnal hemoglobinuria and aniline poisoning, arsenic poisoning, Na chlorate intoxications and CO intoxications, hemoglobinopathies, autoimmune hemolytic anemia, reactions due to ABO incompatibility, in preparation for ABO incompatible bone marrow transplantation or for preventing anti-D immunization after the transfusion of D(+) cells to D(-) recipients. Another field of application has been in the emergency management of intraerythrocytic parasite infections such as malaria and babesiosis. Application of TREX may be wide but its real use remains limited. In our personal experience, in 16 years, only 167 TREX procedures have been carried out in a total of 13,747 therapeutic procedures. This represents only 1.21% of the total.

PMID: 10831921 [PubMed - indexed for MEDLINE]

175. J Clin Apher. 2000;15(1-2):28-52.

Therapeutic apheresis in hematological and oncological diseases.

Grima KM.

Clinical Services, New York Blood Center, Valhalla, NY 10595, USA.

PMID: 10767050 [PubMed - indexed for MEDLINE]

176. Transfusion. 2000 Mar;40(3):375-80.

Fulminant babesiosis treated with clindamycin, quinine, and whole-blood exchange transfusion.

Dorman SE, Cannon ME, Telford SR 3rd, Frank KM, Churchill WH.

Division of Hematology, Department of Medicine, and the Department of Pathology, Brigham and Women's Hospital, Boston, MA 02215, USA.

BACKGROUND: Babesiosis is an increasingly recognized parasitic infection with manifestations that range from a subclinical or mild flu-like illness to life-threatening disease. Risk factors that may be associated with a more severe clinical course include immunosuppression, splenectomy, and advanced age. The most effective chemotherapeutic regimen, clindamycin plus quinine, is sometimes ineffective in cases of severe disease. CASE REPORT: A previously healthy, 58-year-old man was infected by Babesia microti, presumably through a tick bite. He developed fulminant disease characterized by severe hemolytic anemia, disseminated intravascular coagulation, acute renal failure, and respiratory failure. There was no history of splenectomy or immunodeficiency. He was given oral clindamycin (300 mg/4x/day) 2 days before admission. Oral quinine (650 mg/3x/day) was added upon hospitalization. There was no clinical improvement despite antibiotic therapy with clindamycin and quinine. On the second hospital day, a whole-blood exchange transfusion was performed to simultaneously lower the parasite load and replace the patient's plasma. With an automated blood cell separator, 87 percent of the patient's total blood volume was exchanged. As replacement fluid, 6.7 L of packed RBCs reconstituted with FFP (average Hct, 33%) was used. The patient's Hct increased from 26.9 percent before the exchange to 28.3 percent after the exchange. The percentage of parasitized RBCs decreased from 13.8 percent just before exchange to 4.2 percent immediately after exchange. There was rapid clinical improvement after the whole-blood exchange transfusion. The patient's subsequent clinical course was marked by a disappearance of the parasitemia and continued slow, general improvement. Therapy with clindamycin was continued for 14 days after the exchange transfusion and quinine for 17 days. CONCLUSION: In cases of severe babesiosis, prompt institution of whole-blood exchange transfusion, in combination with appropriate antimicrobial therapy, can be life-saving.

PMID: 10738042 [PubMed - indexed for MEDLINE]

177. Transfusion. 2000 Mar;40(3):285-9.

Transfusion-associated transmission of babesiosis in New York State.

Linden JV, Wong SJ, Chu FK, Schmidt GB, Bianco C.

Wadsworth Center, New York State Department of Health, Albany, New York 12201-0509, USA.

BACKGROUND: Babesiosis can be life-threatening in immunocompromised individuals. Although the disease is usually transmitted by tick bite, more than 20 cases have been reported of infection transmitted by transfusion of blood or blood components obtained from apparently healthy donors from endemic areas in the United States. This report describes several recent cases of transfusion-transmitted babesiosis in New York State. STUDY DESIGN AND METHODS: Transfusion-associated incidents of babesiosis infection were identified and investigated. Seroprevalence of babesiosis in healthy blood donors in a highly endemic area was ascertained. RESULTS: In three incidents, babesiosis was diagnosed in five of eight patients given infected blood: two premature infants, an elderly patient with gastrointestinal bleeding, and two patients with thalassemia. Seroprevalence in blood donors on Shelter Island (Suffolk County, eastern Long Island), a highly endemic area, was 4.3 percent in May 1998. CONCLUSIONS: Infected donors lived in endemic areas and were asymptomatic with no history of tick bite. Blood collected in January 1997 from one donor was infectious. Those transfusion recipients who were infected were neonatal, elderly, or chronically transfused patients. Babesiosis should be included in the differential diagnosis of febrile illness in immunocompromised recipients of blood transfusion, particularly in the Northeastern United States.

PMID: 10738027 [PubMed - indexed for MEDLINE]

178. Transfusion. 2000 Mar;40(3):274-84.

Transmission of tick-borne agents of disease by blood transfusion: a review of known and potential risks in the United States.

McQuiston JH, Childs JE, Chamberland ME, Tabor E.

Erratum in Transfusion 2000 Jul;40(7):891.

PMID: 10738026 [PubMed - indexed for MEDLINE]

179. Can Commun Dis Rep. 2000 Jan 15;26(2):9-13.

Transfusion-transmitted babesiosis in Ontario: first reported case in Canada.

[Article in English, French]

Bu Jassoum S, Fong IW, Hannach B, Kain KC.

Department of Medicine, St. Michael's Hospital.

PMID: 10680253 [PubMed - indexed for MEDLINE]

180. Kansenshogaku Zasshi. 1999 Nov;73(11):1163-4.

[First demonstration of Babesia parasitizing in human in Japan].

[Article in Japanese]

Saitoito A, Rai SK, He S, Kohsaki M, Tsuji M, Ishihara C.

Department of Medical Zoology, Kobe University School of Medicine.

PMID: 10624098 [PubMed - indexed for MEDLINE]

181. Genet Anal. 1999 Nov;15(3-5):143-8.

Vaccination against ticks (Boophilus spp.): the experience with the Bm86-based vaccine Gavac.

de la Fuente J, Rodríguez M, Montero C, Redondo M, García-García JC, Méndez L, Serrano E, Valdés M, Enríquez A, Canales M, Ramos E, Boué O, Machado H, Lleonart R.

Division of Mammalian Cell Genetics, Centro de Ingeniería Genética y Biotecnologia, Havana, Cuba.

The control of tick infestations and the transmission of tick-borne diseases remain a challenge for the cattle industry in tropical and subtropical areas of the world. Traditional control methods have been only partially successful and the parasites continue to result in significant losses for the cattle industry. Recently, vaccines containing the recombinant B. microplus gut antigen Bm86 have been developed. Our vaccine formulation (Gavac, Heber Biotec S.A., Havana, Cuba) has been registered and is commercially available in Cuba, Colombia, Dominican Republic, Brazil and Mexico. In controlled pen trials, Gavac has been effective for the control of artificial infestations of B. annulatus, B. decoloratus and chemical-sensitive and resistant B. microplus strains from Australia, Africa, America and Iran. In controlled field trials in Cuba, Brazil, Argentina and Mexico, Gavac has shown a 55-100% efficacy in the control of B. microplus infestations in grazing cattle 12-36 weeks after the first vaccination. Field trials under production conditions have been conducted in Cuba, Colombia, Brazil and Mexico in pure and cross-bred cattle herds. The application of Gavac has increased the time between acaricide treatments by an average of 32 /-21 days (P = 0.0005) resulting in important savings for the cattle industry. In Cuba, a cost-effectiveness analysis was conducted in more than 260000 animals. The cost-effectiveness analysis showed a 60% reduction in the number of acaricide treatments, together with the control of tick infestations and transmission of babesiosis, which resulted in savings of 23.4 dollars animal(-1) year (-1). These results clearly demonstrate the advantage of vaccination and support the application of Gavac for the control of Boophilus spp. infestations.

PMID: 10596754 [PubMed - indexed for MEDLINE]

182. Aust Vet J. 1999 Oct;77(10):657-9.

Transmission of Babesia spp by the cattle tick (Boophilus microplus) to cattle treated with injectable or pour-on formulations of ivermectin and moxidectin.

Waldron SJ, Jorgensen WK.

Queensland Department of Primary Industries, Tick Fever Research Centre, Wacol.

OBJECTIVE: To assess the efficacy of ivermectin and moxidectin to prevent transmission of Babesia bovis and Babesia bigemina by Boophilus microplus to cattle under conditions of relatively intense experimental challenge. DESIGN: Naive Bos taurus calves were treated with either pour-on or injectable formulations of either ivermectin or moxidectin and then exposed to larvae of B microplus infected with B bovis or larvae or adults of B microplus infected with B bigemina. One calf was used for each combination of haemoparasite, B microplus life stage, drug and application route. PROCEDURE: Groups of calves were treated with the test drugs in either pour-on or injectable formulation and then infested with B microplus larvae infected with B bovis or B bigemina. B bigemina infected adult male ticks grown on an untreated calf were later transferred to a fourth group of animals. Infections were monitored via peripheral blood smears to determine haemoparasite transmission. RESULTS: Cattle treated with either pour-on or injectable formulations of ivermectin and moxidectin became infected with B bovis after infestation with infected larvae. Similarly, larvae infected with B bigemina survived to the nymphal stage to transmit the haemoparasite to animals treated with each drug preparation. Cattle treated with pour-on formulations of ivermectin and moxidectin then infested with adult male ticks infected with B bigemina did not become infected with B bigemina whereas those treated with the injectable formulations of ivermectin and moxidectin did show a parasitaemia. CONCLUSIONS: Injectable or pour-on formulations of ivermectin and moxidectin do not prevent transmission of Babesia to cattle by B microplus. Use of these drugs can therefore not be recommended as a primary means of protecting susceptible cattle from the risk of Babesia infection.

PMID: 10590793 [PubMed - indexed for MEDLINE]

183. Mayo Clin Proc. 1999 Nov;74(11):1161-75.

Antiparasitic agents.

Rosenblatt JE.

Division of Clinical Microbiology, Mayo Clinic Rochester, Minnesota 55905, USA.

Several important developments have occurred in recent years in the chemotherapy for and prophylaxis of parasitic infections. Although mefloquine is clearly the most effective agent for prevention of chloroquine-resistant falciparum malaria, its use has been compromised by side effects, both real and imagined. Well-designed studies have shown that side effects occur no more frequently with low-dose mefloquine than with chloroquine. Use of mefloquine in pregnant women has not been associated with birth defects, but the incidence of stillbirths may be increased. Malarone is a new agent that combines atovaquone and proguanil, and it may be as effective as mefloquine; however, it is not yet available in the United States. Several newer agents have appeared in response to the development of multidrug resistant Plasmodium falciparum, especially in Southeast Asia. Halofantrine is available for the treatment of mild to moderate malaria due to P. falciparum and for P. vivax infections. Because of severe toxic effects, use of halofantrine should be restricted to only those unusual and rare situations in which other agents cannot be used. Artemisinin (an extract of the Chinese herbal remedy qinghaosu) and two derivatives, artesunate and artemether, are active against multidrug resistant P. falciparum and are widely used in Asia in oral, parenteral, and rectal forms. The antibacterial azithromycin in combination with atovaquone or quinine has now been reported to treat babesiosis effectively in experimental animals and in a few patients. Azithromycin in combination with paromomycin has also shown promise in the treatment of cryptosporidiosis (and toxoplasmosis when combined with pyrimethamine) in patients with the acquired immunodeficiency syndrome (AIDS). Albendazole is currently the only systemic agent available for treatment of microsporidiosis, an infection primarily of patients with AIDS. In addition, albendazole and ivermectin have emerged as effective broad-spectrum antihelminthics, with albendazole becoming the drug of choice for hydatid disease (echinococcosis), neurocysticercosis, and most intestinal nematode infections (except strongyloidiasis and trichuriasis). Liposomal amphotericin B is the first drug approved by the Food and Drug Administration for the treatment of visceral leishmaniasis.

PMID: 10560606 [PubMed - indexed for MEDLINE]

184. Trop Anim Health Prod. 1999 Aug;31(4):215-22.

The effect of short-interval deltamethrin applications to control tsetse on the seroprevalence of babesiosis in cattle.

Van den Bossche P, Mudenge D.

Regional Tsetse and Trypanosomosis Control Programme, Harare, Zimbabwe.

For the past decade, treatment of cattle with 0.00375% deltamethrin (Decatix, Coopers) at two-weekly intervals has been part of an integrated approach to counteract continuous invasion of Zimbabwe by tsetse from the Mozambique fly-belt. To determine the effect of these regular deltamethrin treatments on the epidemiology of babesiosis, a survey was conducted to estimate the prevalence of antibodies against Babesia bigemina in adult communal cattle. The seroprevalence of antibodies against B. bigemina in adjacent areas, where cattle are treated with short-residual acaricides, was also determined for comparison. The prevalence of antibodies to B. bigemina was much higher in areas where dipping with a non-pyrethroid acaricide was conducted. This was attributed to the successful control of Boophilus spp. and hence a very low level of B. bigemina transmission in the 'deltamethrin treatment zone'. This low level of disease transmission was confirmed by the low prevalence of antibodies against B. bigemina in sentinel cattle that were introduced to the 'deltamethrin treatment zone'. The potential adverse effects of severely reducing the tick population should be taken into consideration at the onset of tsetse control operations in which cattle are to be treated with deltamethrin at short treatment intervals.

PMID: 10504101 [PubMed - indexed for MEDLINE]

185. Exp Parasitol. 1999 Oct;93(2):105-8.

Babesia bigemina: immunization with purified rhoptries induces protection against acute parasitemia.

Machado RZ, McElwain TF, Pancracio HP, Freschi CR, Palmer GH.

Departmento de Patologia Veterinaria, Universidade de Estadual de Sao Paulo, Jaboticabal, Sao Paulo, Brazil.

PMID: 10502474 [PubMed - indexed for MEDLINE]

186. J Parasitol. 1999 Aug;85(4):723-8.

Activity of atovaquone against Babesia microti in the Mongolian gerbil, Meriones unguiculatus.

Gray JS, Pudney M.

Department of Environmental Resource Management, University College Dublin, Republic of Ireland.

The hydroxynaphthoquinone, atovaquone (Wellvone, Glaxo-Wellcome Ltd.) was found to have significant activity against Babesia microti, the main cause of human babesiosis in the U.S.A. This activity compares well with that of the most effective babesicide currently available for use in animals, imidocarb dipropionate, that unlike atovaquone is not licensed for use in humans. Treatment with well tolerated doses of atovaquone results in a rapid reduction in parasitemias and an early disappearance of parasites from blood smears. However, in common with all the other babesicides tested, atovaquone did not sterilize gerbils of infection, even at very high daily doses administered for up to 10 days. A combination of atovaquone and clindamycin was more effective than atovaquone alone in the treatment of both acute and chronic infections but failed to eliminate parasites completely.

PMID: 10461956 [PubMed - indexed for MEDLINE]

187. Infect Immun. 1999 Aug;67(8):4143-8.

Roles of CD4(+) T cells and gamma interferon in protective immunity against Babesia microti infection in mice.

Igarashi I, Suzuki R, Waki S, Tagawa Y, Seng S, Tum S, Omata Y, Saito A, Nagasawa H, Iwakura Y, Suzuki N, Mikami T, Toyoda Y.

The Research Center for Protozoan Molecular Immunology, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido, Maebashi, The University of Tokyo, Tokyo, Japan.

Babesia microti produces a self-limiting infection in mice, and recovered mice are resistant to reinfection. In the present study, the role of T cells in protective immunity against challenge infection was examined. BALB/c mice which recovered from primary infection showed strong protective immunity against challenge infection. In contrast, nude mice which failed to control the primary infection and were cured with an antibabesial drug did not show protection against challenge infection. Treatment of immune mice with anti-CD4 monoclonal antibody (MAb) diminished the protective immunity against challenge infection, but treatment with anti-CD8 MAb had no effect on the protection. Transfer of CD4(+) T-cell-depleted spleen cells resulted in higher parasitemia than transfer of CD8(+) T-cell-depleted spleen cells. A high level of gamma interferon (IFN-gamma), which was produced by CD4(+) T cells, was observed for the culture supernatant of spleen cells from immune mice, and treatment of immune mice with anti-IFN-gamma MAb partially reduced the protection. Moreover, no protection against challenge infection was found in IFN-gamma-deficient mice. On the other hand, treatment of immune mice with MAbs against interleukin-2 (IL-2), IL-4, or tumor necrosis factor alpha did not affect protective immunity. These results suggest essential requirements for CD4(+) T cells and IFN-gamma in protective immunity against challenge infection with B. microti.

PMCID: PMC96718 PMID: 10417185 [PubMed - indexed for MEDLINE]

188. Vet Parasitol. 1999 Mar 22;82(1):11-7.

Detection of IgM antibodies against Babesia bovis in cattle.

Gonçalves PM, Passos LM, Ribeiro MF.

Escola de Veterinária, Universidade Federal de Minas Gerais, Brazil.

The diagnosis of acute babesiosis by direct examination of blood smears has some limitations and the indirect serological methods currently in use are designed for detection of IgG, which may not be detectable at an early stage of infection. There is a need, therefore, for rapid and reliable procedures to diagnose acute infections. An ELISA system using a crude antigenic preparation of Babesia bovis was standardized for the detection of IgM antibodies. Optimal dilutions of the antigen, using positive and negative reference sera, were determined by checkerboard titrations. Serum samples of cattle imported from tick-free areas collected before and during an immunization process were used to validate the tests. The specificity was 94% and sensitivity 100%. Specific IgM antibodies against B. bovis first appeared on the 11th day post-inoculation (p.i.) in animals infested with Boophilus microplus ticks and on the 19th day p.i. in animals which had been inoculated with infected blood. Antibody titers decreased after Day 33; however, all animals remained positive until the end of the experiment (124 days).

PMID: 10223346 [PubMed - indexed for MEDLINE]

189. Int J Parasitol. 1999 Feb;29(2):263-6.

Immunogenicity of recombinant Babesia microti hsp70 homologue in mice.

Erol E, Kumar N, Carson CA.

Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia 62511, USA.

A Babesia microti hsp70 homologue was cloned, expressed in a prokaryotic system and tested in a pilot study for protection against lethal challenge. Results showed that 30% of the mice inoculated with recombinant protein (rBm hsp70) survived challenge, while all of the controls died. Evidence of antibody response to the hsp homologue was detected by Western blot analysis, but no protection was imparted through passive transfer of convalescent serum. Passively transferred spleen cells, from mice which survived challenge, also failed to impart protection. The mechanism of partial immunity suggested by these observations remains to be elucidated.

PMID: 10221626 [PubMed - indexed for MEDLINE]

190. JAMA. 1999 Mar 10;281(10):927-30.

A cluster of transfusion-associated babesiosis cases traced to a single asymptomatic donor.

Dobroszycki J, Herwaldt BL, Boctor F, Miller JR, Linden J, Eberhard ML, Yoon JJ, Ali NM, Tanowitz HB, Graham F, Weiss LM, Wittner M.

Department of Pediatrics, Bronx-Lebanon Hospital Center, NY, USA.

CONTEXT: The risk of acquiring babesiosis by blood transfusion is largely unknown since in areas where it is endemic it is often an asymptomatic infection. OBJECTIVE: To investigate and treat a cluster of blood transfusion-associated babesiosis cases. DESIGN: Case series and epidemiologic investigation. SETTING: Urban inner-city hospital. PATIENTS: Six persons who received Babesia microti-infected blood components from a donor. MAIN OUTCOME MEASURE: Diagnosis and successful therapy of babesiosis following transfusion. RESULTS: Six individuals (1 adult, 1 child, and 4 neonates) were exposed to products from a single blood donation by an asymptomatic Babesia-infected donor. Three of the 6 exposed patients became parasitemic. Polymerase chain reaction testing, animal inoculation studies, and indirect immunofluorescent antibody testing were used to confirm the presence of Babesia microti in the donor's blood and to establish the presence of infection in 3 of the 6 recipients. The 3 infected recipients and 1 additional recipient were treated without incident. CONCLUSION: Physicians should consider babesiosis in the differential diagnosis of a febrile hemolytic disorder after blood transfusion. Prompt diagnosis is important since babesiosis is responsive to antibiotic therapy and, untreated, can be a fatal disease in certain risk groups.

PMID: 10078490 [PubMed - indexed for MEDLINE]

191. Heart Lung. 1998 Nov-Dec;27(6):424-8.

Life-threatening babesiosis in an asplenic patient treated with exchange transfusion, azithromycin, and atovaquone.

Bonoan JT, Johnson DH, Cunha BA.

Infectious Disease Division, Winthrop-University Hospital, Mineola, NY 11501, USA.

PMID: 9835673 [PubMed - indexed for MEDLINE]

192. Arch Intern Med. 1998 Oct 26;158(19):2149-54.

Human babesiosis in New York State: Review of 139 hospitalized cases and analysis of prognostic factors.

White DJ, Talarico J, Chang HG, Birkhead GS, Heimberger T, Morse DL.

Division of Infectious Disease, Wadsworth Center, New York State Department of Health, Albany 12201-0509, USA.

BACKGROUND: Babesiosis infections are infrequent, occur in limited geographic locations, and range from asymptomatic infection to severe illness and death. METHODS: Descriptive clinical and epidemiological information on human babesiosis cases was collated from state communicable disease reports and medical records of patients hospitalized from 1982 to 1993. Univariate and multivariate analyses were performed to determine prognostic factors associated with severe disease outcome (hospitalization ending in death, duration of hospitalization > 14 days, or intensive care unit stay > 2 days). RESULTS: Between 1982 and 1993, 139 patients were hospitalized with babesiosis in New York State. Nine patients (6.5%) died, 35 (25.2%) were admitted to the intensive care unit, and 35 (25.2%) required hospitalization for more than 14 days. Mean age at first hospitalization was 62.5 years. Sixty-two percent were male, and 91% resided in Suffolk County, Long Island. The most common symptoms were fatigue/malaise/weakness (91%), fever (91%), shaking chills (77%), and diaphoresis (69%). Past medical records showed that 52% of patients had a history of chronic disease; 12% had a history of Lyme disease; 12% had undergone a splenectomy; and 2% had undergone a blood transfusion. There was a 12- to 14-day delay between onset of symptoms and initiation of appropriate antibiotic treatment. Univariate analyses showed alkaline phosphatase levels greater than 125 U/L, white blood cell counts greater than 5 x 10(9)/L, history of cardiac abnormality, history of splenectomy, presence of heart murmur, and parasitemia values of 0.04 or higher to be significantly associated with disease severity. Multiple logistic regression analyses indicated that male sex, alkaline phosphatase values greater than 125 U/L, and white blood cell counts greater than 5 x 10(9)/L remained strong predictors of severe outcome. CONCLUSIONS: Human babesiosis is a rare but debilitating and potentially fatal illness, especially in the elderly. Prompt disease diagnosis and treatment are essential but are often delayed, as seen in our series. This delay reinforces the need for enhanced public and physician education targeted toward residents and visitors to the few high-risk geographic areas where disease and Ixodes scapularis ticks are endemic. Patients presenting with certain prognostic indicators (male sex, alkaline phosphatase values > 125 U/L, and white blood cell counts >5 x 10(9)/L) require comprehensive and aggressive medical care to prevent further deterioration. Since babesiosis is only 1 of 3 currently recognized diseases transmitted by I scapularis ticks, primary prevention recommendations will also reduce human exposure to Lyme disease and human granulocytic ehrlichiosis.

PMID: 9801183 [PubMed - indexed for MEDLINE]

193. Am J Trop Med Hyg. 1998 Oct;59(4):509-12.

Ability of azithromycin in combination with quinine for the elimination of babesial infection in humans.

Shih CM, Wang CC.

Department of Parasitology and Tropical Medicine, National Defense Medical Center, Taipei, Taiwan, Republic of China.

We report the ability of azithromycin in combination with quinine to eliminate the Babesia infection in a native Taiwanese woman. Failure of elimination of the babesial infection was observed two weeks after treating with standard regimen of oral quinine plus intravenous clindamycin for a 10-day course of therapy. Azithromycin in place of clindamycin was administered for another 10-day course of therapy two months following initial treatment. Clearance of Babesia parasites was observed and verified by hamster inoculation. These results suggest that azithromycin plus quinine should be considered as an alternative therapy for human babesiosis, especially in the failure of treatment with standard regimens.

PMID: 9790419 [PubMed - indexed for MEDLINE]

194. Int J Parasitol. 1998 Sep;28(9):1429-35.

Babesia canis infection in canine-red blood cell-substituted SCID mice.

Arai S, Tsuji M, Kim SJ, Nakade T, Kanno Y, Ishihara C.

School of Veterinary Medicine, Rakuno-gakuen University, Ebetsu, Japan.

We have developed a mouse model for Babesia canis infection using severe combined immunodeficiency (SCID) mice whose circulating red blood cells had been substituted with canine red blood cells. Substitution of red blood cells in SCID mice was achieved by repetitive transfusions of canine red blood cells, together with administration of an antimouse red blood cell monoclonal antibody. Following inoculation of canine-red blood cell-SCID mice with B. canis, parasites proliferated in the canine red blood cells that had been transfused into the SCID mice, resulting in much higher parasitaemia than that observed in dogs. In an attempt to demonstrate the utility of this mouse model, three antiprotozoal drugs, diminazene diaceturate, clindamycin and oxytetracycline, were examined for their efficacy to inhibit the growth of B. canis in canine-red blood cell-SCID mice. The mouse model clearly showed that diminazene diaceturate and oxytetracycline were capable of eliminating B. canis from the canine-red blood cell-SCID mice, whereas clindamycin exhibited only a static effect as parasitaemia relapsed upon cessation of drug administration.

PMID: 9770629 [PubMed - indexed for MEDLINE]

195. Vox Sang. 1998;74 Suppl 2:161-3.

Transmission of parasites by blood transfusion.

Dodd RY.

Transmissible Diseases Department, American Red Cross, Jerome H. Holland Laboratory, Rockville, MD 20855, USA.

A number of parasitic diseases are known, or suspected to be transmitted by blood transfusion. Of greatest concern are malaria and Chagas' disease, but babesia, leishmania and toxoplasmosis also offer risk in particular locations or circumstances. Some of these parasites may be imported into non-endemic areas as a result of population movements and in some cases, the natural range of the parasite is increasing as a result of environmental change. Recent research, particularly on Chagas disease and babesiosis will be discussed, along with measures to minimize transmission of these and other parasites via transfusion.

PMID: 9704440 [PubMed - indexed for MEDLINE]

196. Ann Trop Med Parasitol. 1998 Jun;92(4):513-9.

Parasite localization and dissemination in the Babesia-infected host.

Schetters TP, Kleuskens J, Scholtes N, Gorenflot A.

Parasitology R & D Department, Intervet Int. b.v., Boxmeer, The Netherlands.

Babesia bovis infections in cattle and B. canis infections in dogs are characterized by non-haemolytic anaemia and low parasitaemia during the acute phase of the disease. In this phase of the disease, animals suffer from hypotension followed by disturbances of the coagulation system. This review discusses the hypothesis that may explain the process of parasite localization in the host, and the consequences of such localization. It is suggested that hypotension favours the interaction between infected erythrocytes and the endothelial lining, thus facilitating localization of the infection. In addition, activation of the coagulation system by a parasite-derived molecule (one associated with the surface of infected erythrocytes or a soluble antigen) might consolidate this situation by causing cellular plugs to form. The continued proliferation of parasites in such plugs may then result in the occurrence of capillaries that are particularly heavily parasitised. An explanation is also suggested for the protective effect of vaccines against clinical babesiosis, based on the soluble parasite antigens that are released into the medium in cultures of babesial parasites.

PMID: 9683902 [PubMed - indexed for MEDLINE]

197. Ann Trop Med Parasitol. 1998 Jun;92(4):489-501.

Human babesiosis.

Gorenflot A, Moubri K, Precigout E, Carcy B, Schetters TP.

Laboratoire de Biologie Cellulaire et Moléculaire, UFR Pharmacie, Université Montpellier I, France.

The first demonstrated case of human babesiosis in the world was reported in Europe, in 1957. Since then, a further 28 babesial infections in man have been reported in Europe. Most (83%) of the infections were in asplenic individuals and most (76%) were with Babesia divergens, a cattle parasite. Parasitaemias varied from 1%-80% of red blood cells. The usual clinical manifestations of severe B. divergens infection were severe intravascular haemolysis with haemoglobinuria. The most efficient treatment consisted of a massive blood-exchange transfusion, followed immediately by chemotherapy with clindamycin. Hundreds of cases of human infection with Babesia spp. have been reported in the U.S.A. Most cases were infected by ticks carrying the rodent parasite B. microti, but other emerging. Babesia spp. (currently known as WA1, CA1, and MO1) are increasingly involved. Several cases were the result of blood transfusion. In terms of clinical manifestations, human infections with B. microti varied widely, from asymptomatic infection to a severe, rapidly fatal disease. Parasitaemia ranged between <1% and 85%. The splenectomized, the elderly, the immunocompromised and HIV-infected patients were predisposed to severe infection. Infection with B. microti often remained subclinical or asymptomatic and were only detected through serological surveys. The currently recommended treatment of symptomatic cases is quinine plus clindamycin. A few other cases of human babesial infection have been described in China, Egypt, Mexico, South Africa and Taiwan.

PMID: 9683900 [PubMed - indexed for MEDLINE]

198. N Engl J Med. 1998 Jul 16;339(3):160-5.

Persistent parasitemia after acute babesiosis.

Krause PJ, Spielman A, Telford SR 3rd, Sikand VK, McKay K, Christianson D, Pollack RJ, Brassard P, Magera J, Ryan R, Persing DH.

Department of Pediatrics, Connecticut Children's Medical Center and University of Connecticut School of Medicine, Hartford 06106, USA.

BACKGROUND: Babesiosis, a zoonosis caused by the protozoan Babesia microti, is usually not treated when the symptoms are mild, because the parasitemia appears to be transient. However, the microscopical methods used to diagnose this infection are insensitive, and few infected people have been followed longitudinally. We compared the duration of parasitemia in people who had received specific antibabesial therapy with that in silently infected people who had not been treated. METHODS: Forty-six babesia-infected subjects were identified from 1991 through 1996 in a prospective, community-based study designed to detect episodes of illness and of seroconversion among the residents of southeastern Connecticut and Block Island, Rhode Island. Subjects with acute babesial illness were monitored every 3 months for up to 27 months by means of thin blood smears, Bab. microti polymerase-chain-reaction assays, serologic tests, and questionnaires. RESULTS: Babesial DNA persisted in the blood for a mean of 82 days in 24 infected subjects without specific symptoms who received no specific therapy. Babesial DNA persisted for 16 days in 22 acutely ill subjects who received clindamycin and quinine therapy (P=0.03), of whom 9 had side effects from the treatment. Among the subjects who did not receive specific therapy, symptoms of babesiosis persisted for a mean of 114 days in five subjects with babesial DNA present for 3 or more months and for only 15 days in seven others in whom the DNA was detectable for less than 3 months (P<0.05); one subject had recrudescent disease after two years. CONCLUSIONS: When left untreated, silent babesial infection may persist for months or even years. Although treatment with clindamycin and quinine reduces the duration of parasitemia, infection may still persist and recrudesce and side effects are common. Improved treatments are needed.

PMID: 9664092 [PubMed - indexed for MEDLINE]

199. Lakartidningen. 1998 Jun 3;95(23):2695-700.

[Ticks--a medical topic of current interest which sticks].

[Article in Swedish]

Berglund J.

Samhällsmedicinska institutionen, Lunds universitet.

Comment in Lakartidningen. 1998 Aug 5;95(32-33):3397.

PMID: 9656623 [PubMed - indexed for MEDLINE]

200. Vaccine. 1998 Feb;16(4):366-73.

Field studies and cost-effectiveness analysis of vaccination with Gavac against the cattle tick Boophilus microplus.

de la Fuente J, Rodríguez M, Redondo M, Montero C, García-García JC, Méndez L, Serrano E, Valdés M, Enriquez A, Canales M, Ramos E, Boué O, Machado H, Lleonart R, de Armas CA, Rey S, Rodríguez JL, Artiles M, García L.

Division of Mammalian Cell Genetics, Centro de Ingeniería Genética y Biotecnología, Havana, Cuba.

The control of tick infestations and the transmission of tick-borne diseases remains a challenge for the cattle industry in tropical and subtropical areas of the world. Traditional control methods have been only partially successful and the parasites continue to result in significant losses for the cattle industry. Recently, vaccines containing the recombinant Boophilus microplus gut antigen Bm86 have been developed. These vaccines have been shown to control tick infestations in the field. However, extensive field studies investigating the efficacy and cost-effectiveness of vaccination have not been reported and are needed to appraise the effect of this new approach for tick control. Here is reported the results of the application of Gavac in a field trial including more than 260,000 animals in Cuba. In this study the correlation between the antibody response to vaccination and the effect on ticks fertility is determined. Physiological status of the animals was found to affect the primary response to vaccination but not the antibody titers after revaccination. A cost-effectiveness analysis showed a 60% reduction in the number acaricide treatments, together with the control of tick infestations and transmission of babesiosis, which resulted in savings of $23.4 animal-1 year-1. These results clearly demonstrate the advantage of vaccination and support the application of Gavac for tick control.

PMID: 9607057 [PubMed - indexed for MEDLINE]

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