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NEW JERSEY LYME DISEASE, BABESIA, ERLICHIA AND BARTONELLA AND TREATMENT

PART THREE

A REVIEW OF MAJOR STUDIES

Recently a troubled and agitated New Jersey pseudo expert in Lyme disease seemed to report no interest in treating Babesia, and since her old protocols were questionable anyway, I suppose it was just as well. Others are treating her failures. She had one tool and one way to treat. In 2008 this is 1990's medicine. I believe one must read very widely, and just because past IV treatment has helped some patients does not mean one tool is the only option in the tool box.

So let's look at a small sample of the PUBLISHED DATA on New Jersey. But as real researchers and seasoned clinicians know, the best information is not even published yet. This is one reason to have expert clinicians and researchers to be close and talking back and forth. I recall one article I wrote for the Journal of the American Medical Association which was accepted and yet was not published for a year. In tick and flea-infection science at this time, a year is 10 years.

Here are some sample material relating only to New Jersey Lyme Disease

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[Dogs babesiosis--still actually problem]

[Article in Polish]

Adaszek , Winiarczyk S.

Katedra Epizootiologii i Klinika Chorób Zakaznych, Wydzial Medycyny Weterynaryjnej, Akademia Rolnicza, ul. Gleboka 30, 20-612 Lublin. ukaszek0@wp.pl

Babesiosis (piroplasmosis) is a tick-borne disease with a symptoms of hemolytic anemia. For the first time babesiosis was described in dogs in United States in 1934. The etiological factor of this disease in Poland is protozoa Babesia canis, and its vector--Dermacentor-tick. The most common symptoms of babesiosis are: icterus, hemoglobinuria, occasionally vomits and diarrhea. The biochemical examination of blood serum from sick animals can reveal the increase of activity of AST, ALT, the increase of total bilirubine, urea and creatynine concentrations. The results of hematological examinations can show anemia, leucopenia and thrombocytopenia. The diagnosis of babesiosis bases on anamnesis, clinical examinations of dogs, microscopical examinations of blood smears from sick animals; IF-assay and PCR can also be helpful for the diagnosis of babesiosis. Till now does not exist the effective immunoprophylaxis against this disease. Babesiosis is well-known disease, however there are still problems with therapy of infected animals. Most effective drug in therapy of dog piroplasmosis is imidocarb, but sometimes can be observed side effects after it application. It is possible that the genetically differences which are detected in subspecies may have an influence on the severity of disease and the effectiveness of therapy.

Publication Types:
PMID: 18702315 [PubMed - in process]

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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.

Publication Types:
PMID: 18533933 [PubMed - indexed for MEDLINE]

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The response of the pituitary-adrenal and pituitary-thyroidal axes to the plasma glucose perturbations in Babesia canis rossi babesiosis.

Schoeman JP, Herrtage ME.

Department of Companion Animal Clinical Studies, Faculty of Veterinary Science, University of Pretoria, Onderstepoort, 0110 South Africa. johanp.schoeman@up.ac.za

This prospective, cross-sectional, interventional study was designed to determine the association between the hormones of the pituitary-adrenal and pituitary-thyroid axes and other clinical parameters with the blood glucose perturbations in dogs with naturally occurring Babesia canis rossi babesiosis. Thirty-six dogs with canine babesiosis were studied. Blood samples were obtained from the jugular vein in each dog prior to treatment at admission to hospital and serum endogenous adrenocorticotrophic hormone (ACTH), pre-ACTH cortisol, thyroxine, free thyroxine and TSH concentrations were measured. Immediately thereafter each dog was injected intravenously with 5 microg/kg of ACTH (tetracosactrin). A 2nd blood sample was taken 1 hour later for serum post-ACTH cortisol measurement. Three patient groups were recruited: hypoglycaemic dogs (glucose < 3.3 mmol/l, n = 12); normoglycaemic dogs (glucose 3.3-5.5 mmol/l, n = 12); hyperglycaemic dogs (glucose > 5.5 mmol/l, n = 12). Basal and post-ACTH serum cortisol concentrations were significantly higher in hypoglycaemic dogs, whereas body temperature, serum thyroxine and free thyroxine were significantly lower in hypoglycaemic dogs. Haematocrit was significantly lower in both hypo-and hyperglycaemic dogs compared with normoglycaemic dogs. Low blood glucose concentrations were significantly associated with high basal and post-ACTH cortisol concentrations and with low serum thyroxine and free thyroxine concentrations in dogs suffering from B. canis rossi babesiosis.

Publication Types:
PMID: 18507221 [PubMed - indexed for MEDLINE]

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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 cm(2) 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 cm(2) 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 cm(2) 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 cm(2) 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 - as supplied by publisher]

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The plastid-like organelle of apicomplexan parasites as drug target.

Wiesner J, Reichenberg A, Heinrich S, Schlitzer M, Jomaa H.

Institut für Klinische Chemie und Pathobiochemie, Justus-Liebig-Universität Giessen, Giessen, Germany.

Apicomplexan parasites infectious to humans include Plasmodium spp., Babesia spp., Toxoplasma gondii, Cryptosporidium spp., Isospora belli and Cyclospora cayetanensis. With exception of Cryptosporidium spp., these parasites possess a non-photosynthetic plastid-like organelle called apicoplast. The apicoplast possesses a small circular genome and harbours prokaryotic-type biochemical pathways. As the most important metabolic functions, the mevalonate independent 1-deoxy-D-xylulose 5-phosphate pathway of isoprenoid synthesis and the type II fatty acid synthesis system are operative inside the apicoplast. Classical antibacterial drugs such as ciprofloxacin, tetracycline, doxycycline, clindamycin and spiramycin inhibit the apicoplast-located gyrase and translation machinery, respectively, and are currently used in the clinic for the treatment of infections with apicomplexan parasites. As an inhibitor of isoprenoid synthesis, fosmidomycin was proven to be effective against acute P. falciparum malaria in clinical phase II studies. Triclosan, an inhibitor of fatty acid synthesis, was active in a malaria mouse model. In vitro antimalarial activity was shown for inhibitors of peptide deformylase and the import of apicoplast-targeted proteins. Work on various other inhibitors of apicoplast-located biochemical processes is ongoing.

Publication Types:
PMID: 18473835 [PubMed - indexed for MEDLINE]

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Adrenal response to the low dose ACTH stimulation test and the cortisol-to-adrenocorticotrophic hormone ratio in canine babesiosis.

Schoeman JP, Herrtage ME.

Department of Companion Animal Clinical Studies, Faculty of Veterinary Science, University of Pretoria, Onderstepoort 0110, South Africa. johanp.schoeman@up.ac.za <johanp.schoeman@up.ac.za>

This prospective, interventional, case-controlled study sought to determine the association between adrenocortical function and mortality in dogs with naturally occurring Babesia rossi babesiosis. Sixty-eight dogs with canine babesiosis were studied and fifteen normal dogs were used as controls. Blood samples were obtained from the jugular vein in each dog prior to treatment, at admission to hospital, for the measurement of basal plasma ACTH (adrenocorticotrophic hormone) and serum cortisol concentrations. Immediately thereafter, each dog was injected intravenously with 5 microg/kg of ACTH (tetracosactrin). A second blood sample was taken 1h later for serum ACTH-stimulated cortisol measurement and the resultant calculation of delta cortisol by subtracting basal from ACTH-stimulated cortisol. Diagnosis of babesiosis was confirmed by polymerase chain reaction (PCR) and reverse line blot (RLB). Three outcomes were defined: hospitalization with subsequent death (n=4); hospitalization followed by recovery (n=48); and treatment as an outpatient (n=16). Basal cortisol, but not ACTH-stimulated cortisol, was significantly higher in patients compared to control dogs. Basal- and ACTH-stimulated serum cortisol concentrations were significantly higher in the dogs that died, compared to hospitalized dogs that survived and compared to dogs treated as outpatients. There was no significant difference in delta cortisol concentrations or cortisol to ACTH ratios across outcome groups in dogs suffering from B. rossi babesiosis However, dogs with delta cortisol concentrations below 83 nmol/l had significantly higher cortisol to ACTH ratios compared to dogs with delta cortisol concentrations above 83 nmol/l. These findings of increased basal- and ACTH-stimulated cortisol and increased cortisol to ACTH ratios confirm the absence of adrenal insufficiency and concur with those in human malaria.

Publication Types:
PMID: 18468798 [PubMed - in process]

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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, Paul-Ehrlich-Str. 40, D-60596 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 - in process]

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Spontaneous splenic rupture caused by Babesia microti infection.

Kuwayama DP, Briones RJ.

Department of Surgery, The Johns Hopkins Hospital, Baltimore, Maryland 21205, USA. david.kuwayama@jhu.edu

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.

Publication Types:
PMID: 18419430 [PubMed - indexed for MEDLINE]

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An unusual form of canine babesiosis.

Van de Maele I, Savary-Bataille K, Gielen I, Daminet S.

Faculty of Veterinary Medicine, Department of Medicine and Clinical Biology of Small Animals, Ghent University, Salisburylaan 133, B-9820 Merelbeke, Belgium. isabelvandemaele@hotmail.com

An Akita Inu, living in Belgium, was presented with unusual clinical manifestations of acute babesiosis that included neurological signs and pancytopenia. Diagnosis was made by identifying Babesia canis in the blood smear. Neurological signs resolved after treatment with imidocarb diproprionate. Normalization of hematological abnormalities was gradual over 5 months.

Publication Types:
PMID: 18390102 [PubMed - indexed for MEDLINE]

PMCID: PMC2249724


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Flow cytometry to evaluate the level of Babesia gibsoni parasitemia in vivo and in vitro by using the fluorescent nucleic acid stain SYTO16.

Yamasaki M, Hwang SJ, Ohta H, Yamato O, Maede Y, Takiguchi M.

Laboratory of Internal Medicine, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan. masayama@vetmed.hokudai.ac.jp

In the present study, we employed flow cytometry to evaluate the level of parasitemia of Babesia gibsoni infecting canine erythrocytes in vivo and in vitro by using fluorescent nucleic acid staining. Peripheral blood samples from a B. gibsoni-infected dog and cultured B. gibsoni parasitizing in canine erythrocytes were stained with a membrane-permeable fluorescent nucleic acid stain, SYTO16. In this study, we utilized normal canine erythrocytes (LK erythrocytes) and canine erythrocytes containing high concentrations of potassium, reduced glutathione, and some free amino acids (HK erythrocytes) as host cells for culture. Parasitized cells in vive were discriminated completely from unparasitized cells and a correlation (r = 0.998) between the percentage of SYTO16-positive cells and parasitemia in vivo was observed. On the other hand, erythrocytes in vitro could not be divided clearly into parasitized and unparasitized cells. However, when LK erythrocytes were used as host cells, the percentage of SYTO16-positive cells was almost the same as, and was well correlated (r = 0.932) with, the level of parasitemia. When HK erythrocytes were used as host cells, the percentage of SYTO16-positive cells was almost half of, but was correlated (r = 0.982) with, the level of parasitemia. Therefore, we attempted to observe the changes in the percentage of parasitized cells after treatment with antiprotozoal drug or mitochondria inhibitors by using flow cytometry. The changes in the percentage of SYTO16-positive cells corresponded well with the changes of the level of parasitemia when the parasites in HK erythrocytes were cultured with each compound. The present results suggest that flow cytometric detection using SYTO16 is a rapid and reliable method for monitoring parasitemia both in vive and in vitro.

Publication Types:
PMID: 18380154 [PubMed - indexed for MEDLINE]

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Babesia divergens: identification and characterization of BdHSP-20, a small heat shock protein.

Montero E, Rodriguez M, Gonzalez LM, Lobo CA.

Department of Blood-Borne Parasites, Lindsley Kimball Research Institute, The New York Blood Center, 310 E. 67th Street, New York, NY 10021, USA.

This study describes the identification and characterization of the Babesia divergens alpha-crystallin/small heat shock protein 20 (BdHSP-20). BdHSP-20 was recognized by the DG7 monoclonal antibody (DG7 mAb) originally produced by Precigout et al. [Precigout, E., Valentin, A., Carcy, B., Gorenflot, A., Nakamura, K., Aikawa, M., Schrevel, J. 1993. Babesia divergens: characterization of a 17-kDa merozoite membrane protein. Experimental Parasitology 77, 425-434] against B. divergens merozoites. We used DG7 mAb to immunoscreen a B. divergens cDNA library to clone the gene encoding the small heat shock protein. Bdhsp-20 is a single copy gene interrupted by one intron. The deduced gene product (BdHSP-20) clearly belongs to the alpha-crystallin family and shows significant homology to Babesia bovis, Plasmodium falciparum and Toxoplasma gondii sHSPs, with the highest degree of sequence identity around the catalytic domain. Nutritient stress (serum depletion) treatment of the parasites induced the upregulation of BdHSP-20 gene expression observed by semi-quantitative PCR and immunoprecipitation. This regulation pattern suggests that BdHSP-20 could probably be of importance for parasite survival in the case of environmental stress. BdHSP-20 has previously been shown to be highly conserved among different strains and antibodies against the protein drastically reduce parasitemia in vitro.

Publication Types:
PMID: 18346739 [PubMed - indexed for MEDLINE]

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The brown dog tick, Rhipicephalus sanguineus (Latreille, 1806) (Acari: Ixodidae): from taxonomy to control.

Dantas-Torres F.

Departamento de Imunologia, Centro de Pesquisas Aggeu Magalhčes, Fundaćčo Oswaldo Cruz, Caixa Postal 7472, Avenida Professor Moraes Rego s/n, Campus UFPE, Recife, Pernambuco, Brazil. fdt@cpqam.fiocruz.br

Rhipicephalus sanguineus, commonly known as the brown dog tick, is a three-host tick that feeds primarily on dogs and occasionally on other hosts, including humans. R. sanguineus ticks are widely distributed around the world and they are known vectors of pathogens, such as Babesia canis, Ehrlichia canis, and Rickettsia conorii. The increasing number of cases of human parasitism by R. sanguineus ticks reported in the literature indicates that the interaction between humans and R. sanguineus ticks may be more common than it is actually recognized. The indiscriminate use of acaricides is an emerging problem worldwide and has led to the selection of acaricide resistant tick strains. In this article, the medical and veterinary importance, taxonomy, biology, and ecology of R. sanguineus ticks around the world are reviewed. It also discusses the current strategies for the control of R. sanguineus, highlighting the potential risks associated to the improper use of acaricides, such as environmental pollution and toxicity to humans and other non-target organisms (e.g., tick predators).

Publication Types:
PMID: 18280045 [PubMed - indexed for MEDLINE]

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Histological and ultrastructural studies of renal lesions in Babesia canis infected dogs treated with imidocarb.

Máthé A, Dobos-Kovács M, Vörös K.

Department and Clinic of Internal Medicine, Faculty of Veterinary Science, Szent Istvdn University, H-1078 Budapest, Istvin u. 2, Hungary. Mathe.Akos@aotk.szie.hu

Histological and electron microscopic examinations of the kidneys of 8 dogs suffering from fatal, naturally acquired Babesia canis infection and nephropathy are presented. Seven animals were treated with imidocarb dipropionate on average 4.5 days prior to death. Severe anaemia was present only in 2 cases. Degenerative histological changes observed mostly in the proximal convoluted tubules included vacuolar-hydropic degeneration, necrosis and detachment of renal tubular epithelial (RTE) cells from the basement membrane. Necrotic debris occasionally formed acidophilic casts within the tubules. In some cases, necrosis of the whole tubule was observed. Haemoglobin casts in the tubules and haemoglobin droplets in RTE cells seldom appeared. No significant histological changes were seen in the glomeruli. Ultrastructural lesions in RTE cells included nuclear membrane hyperchromatosis, karyopyknosis, karyolysis, swelling or collapse of mitochondria with fragmentation of cristae and vacuolar-hydropic degeneration in the endoplasmic reticulum and microvilli. Nuclear oedema was also observed. Many RTE cells exhibiting necrosis collapsed. Vacuolar-hydropic degeneration and necrosis were also observed in the glomerular and interstitial capillary endothelium. The severe acute tubular necrosis described in this study is probably the result of hypoxic renal injury. Systemic hypotension leading to vasoconstriction in the kidneys might be the most important cause of renal hypoxia in B. canis infections, but anaemia may also contribute to inadequate oxygenation. Imidocarb should be applied with caution in patients with possible renal involvement until further data become available on its potential nephrotoxicity in dogs.

PMID: 18277710 [PubMed - indexed for MEDLINE]

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Ticks of small ruminants in China.

Yin H, Luo J.

State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, PR China. yinhong@public.lz.gs.cn

The importance of ticks and tick-borne diseases of small ruminants in China is discussed. Of the 109 species of ticks identified to date in China, 45 species infest small ruminants. Five species have been proved to be involved, or possibly involved, in the transmission of tick-borne diseases. Anaplasma ovis, Babesia motasi, Babesia ovis and two unidentified species of Theileria, have been recorded in small ruminants in China. The diseases caused by these organisms are widespread in China, causing great economic losses, estimated at approximately 70 million USD per annum. Anaplasmosis occurs from September to March in Inner Mongolia and during spring in other areas. Babesiosis and theileriosis occur in March to June in northwestern China. The vectors of A. ovis are Dermacentor nuttalli, Hyalomma asiaticum and Rhipicephalus pumilio. These three species of ticks do not appear to transmit A. ovis transstadially or transovarially, but rather through movement of partially engorged, infected adult ticks from A. ovis carrier animals. The vector ticks of the two species of Babesia have not been very well documented, but at least two species of Haemaphysalis are thought to transmit them. Haemaphysalis qinghaiensis transmits the two as yet unidentified species of Theileria transstadially. Priorities for future research on these diseases are summarised.

Publication Types:
PMID: 17823826 [PubMed - indexed for MEDLINE]

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Treatment of refractory Babesia microti infection with atovaquone-proguanil in an HIV-infected patient: case report.

Vyas JM, Telford SR, Robbins GK.

Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA. jvyas@partners.org

A patient with acquired immune deficiency syndrome presented with babesiosis 6 months after presumed tick exposure. Despite initial treatment with azithromycin and atovaquone, followed by quinine and clindamycin, he experienced an increasing parasite load. Finally, red blood cell exchange transfusion, anti-Babesia therapy, and the addition of atovaquone-proguanil to the treatment regimen led to symptomatic improvement and elimination of parasitemia. Low-level parasitemia recurred 20 weeks later and was eradicated by administration of atovaquone-proguanil monotherapy. Atovaquone-proguanil appears to have activity against babesiosis and should be studied as a potential therapy for patients with refractory babesiosis.

Publication Types:
PMID: 18190320 [PubMed - indexed for MEDLINE]

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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. PKrause@ccmckids.org

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.

Publication Types:
PMID: 18181735 [PubMed - indexed for MEDLINE]

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Complications of coinfection with Babesia and Lyme disease after splenectomy.

Abrams Y.

Department of Family and Community Medicine, University of Pittsburgh, PA 15217, USA. abramsym@upmc.edu

Publication Types:
PMID: 18178707 [PubMed - indexed for MEDLINE]

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Babesia: the protective effects of killed Propionibacterium acnes on the infections of two rodent Babesia parasites in mice.

Iseki H, Takabatake N, Ota N, Ishigame T, Yokoyama N, Igarashi I.

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

In the present study, we investigated the protective effects of killed Propionibacterium acnes on the infections of two rodent Babesia parasites in mice. Pre-treatment with "EqStim" (a commercially available immunostimulant containing killed P. acnes) showed significant resistance to both infections. To elucidate the immunological status in the mice, the concentrations of multiple cytokines were measured in serum collected from infected mice. After B. microti infection, the levels of interleukin (IL)-2, IL-4, IL-5, IL-10, IL-12p70, and tumor necrosis factor (TNF)-alpha in the treated group were significantly lower than in the control group. In contrast, after B. rodhaini infection, only IL-12p70 and TNF-alpha were detectable at significantly higher levels in the treated group than in the control group. The present findings indicated the protective effects of killed P. acnes on rodent babesiosis even with different immune responses between the B. microti and B. rodhaini infections. Killed P. acnes might be a powerful tool for the control of serious livestock babesiosis.

Publication Types:
PMID: 18164706 [PubMed - indexed for MEDLINE]

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Plasma insulin concentrations in hypoglycaemic dogs with Babesia canis rossi infection.

Rees P, Schoeman JP.

Department of Companion Animal Clinical Studies, Faculty of Veterinary Science, University of Pretoria, Pretoria, Onderstepoort 0110, South Africa. phil.rees@up.ac.za

Hypoglycaemia has been identified as a life-threatening metabolic complication in almost 20% of severely ill dogs suffering from babesiosis due to Babesia canis rossi infection, and has been correlated with mortality. Hyperinsulinaemia as a result of inappropriate insulin secretion may precipitate hypoglycaemia, and has been suggested as a possible cause of hypoglycaemia in human and murine malaria. This prospective, cross-sectional, observational study, including 94 dogs with naturally occurring virulent babesiosis, sought to identify the presence of inappropriate insulin secretion in hypoglycaemic canine babesiosis. Pre-treatment jugular blood samples were collected for simultaneous determination of plasma glucose and insulin concentrations. Animals were retrospectively divided into three groups: hypoglycaemic (BG<3.3 mmol/L; n=16), normoglycaemic (BG 3.3-5.5 mmol/L; n=62), and hyperglycaemic (BG>5.5 mmol/L; n=16). The median insulin concentrations for the hypoglycaemic, normoglycaemic, and hyperglycaemic groups were 10.7 pmol/L, 10.7 pmol/L, and 21.7 pmol/L, respectively. Statistical analysis revealed no significant difference in insulin concentration between the three groups. Additionally, the median insulin concentration in the hypoglycaemic and normoglycaemic groups was below the detection limit of the assay, suggesting that insulin secretion was appropriately low (i.e. undetectable) in these cases. Only two dogs had inappropriately elevated insulin concentrations. One of these dogs was hypoglycaemic. We conclude that hyperinsulinaemia is an infrequent cause of hypoglycaemia in virulent canine babesiosis. Other causes of hypoglycaemia, such as increased glucose consumption, depletion of hepatic glycogen stores, and hepatic dysfunction with impaired gluconeogenesis, are speculated to play more important roles in the pathophysiology of hypoglycaemia in canine babesiosis.

Publication Types:
PMID: 18164550 [PubMed - indexed for MEDLINE]

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Repeated high dose imidocarb dipropionate treatment did not eliminate Babesia caballi from naturally infected horses as determined by PCR-reverse line blot hybridization.

Butler CM, Nijhof AM, van der Kolk JH, de Haseth OB, Taoufik A, Jongejan F, Houwers DJ.

Department of Equine Sciences, Medicine Section, Utrecht University, PO Box 80.153, 3508 TD Utrecht, The Netherlands. c.m.butler@uu.nl

Imidocarb treatment of horses infected with Babesia caballi is supposed to eliminate the infection, but data on the efficacy of this treatment is scarce. The study presented here concerns four Paso Fino horses, which were imported into the island of Curacao on the basis of a piroplasmosis negative complement fixation test (CFT). Upon re-testing with an indirect fluorescent antibody test immediately after arrival in Curacao, two horses appeared to have antibodies to B. caballi and all horses had antibodies to Theileria equi. Subsequent testing with polymerase chain reaction combined with a reverse line blot yielded positive results for both agents in all four horses. Treatment with five consecutive doses of imidocarb dipropionate (4.7 mg/kg BW im q 72 h), temporarily resulted in negative results, but B. caballi and T. equi were detected again in the samples taken at 6 and 18 weeks after completion of the treatment. These results confirm that the CFT is not a suitable test for pre-import testing and that even high dose treatment with imidocarb may not be capable of eliminating B. caballi and T. equi infections from healthy carriers.

Publication Types:
PMID: 18160222 [PubMed - in process]


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

[Article in Portuguese]

da Silva RA, Corrźa 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. rosangelarural@yahoo.com.br

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.

Publication Types:
PMID: 18078605 [PubMed - indexed for MEDLINE]

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[Babesiosis, a little known zoonosis]

[Article in Czech]

Dvoraková HM, Dvorácková M.

Mikrobiologicky ustav LF MU a FN u sv. Anny v Brne. monika.heroldova@fnusa.cz

Babesiosis is an emerging tick borne zoonotic disease caused by intraerythrocytic parasites of the genus Babesia. Babesiosis is one of the most common infections of free-living animals worldwide but is perhaps most prevalent in rodents, carnivores, and cattle. This fact increases the concern about the emerging zoonosis. Like the malaria agent Plasmodium, the parasite Babesia attacks and damages the host's red cells. Babesia microti and Babesia divergens cause human infections. In the USA, an endemic region of this infection, most human cases are due to Babesia microti. In Europe, babesiosis is considerably rare and is caused by Babesia divergens, with splenectomized patients being at highest risk. The spectrum of disease is broad, ranging from an apparently silent infection to a fulminant, malaria-like disease. Symptoms include fever, chills and icterus. The treatment of choice is clindamycin and quinine. The laboratory diagnosis is based on direct detection of the parasite from blood smears. Due to increasing international travel, even relatively uncommon parasitic infections can be found in the Czech Republic and babesiosis is just one of them.

Publication Types:
PMID: 18072299 [PubMed - indexed for MEDLINE]

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Involvement of a host erythrocyte sialic acid content in Babesia bovis infection.

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

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

Host sialic acid (SA) has recently been suggested to play an important role in erythrocyte (RBC) infection by Babesia spp. The present study attempted to further determine the specific type of SAs important in the RBC invasion. Bovine RBC was found to bear abundant alpha2-3-linked SA residues but not alpha2-6-linked SA in nature, confirmed by flow cytometric analysis of the neuraminidase (Nm)-treated RBCs. Lectin-blot analyses revealed the removal of alpha2-3-linked SAs from the 97-, 33-, and 31-kDa bands by the Nm treatment. Addition of the Nm-treated RBCs into an in vitro culture of B. bovis resulted in a decreased population of the parasitized RBCs. The thin smear samples from the cultures were then observed under a confocal laser scanning microscope after staining with the alpha2-3-linked SA-specific lectin: a selective invasion of B. bovis was found only in the intact RBCs bearing the SAs, but not in the desialylated RBCs. Furthermore, a significant reduction of the parasitized RBCs was also observed in the culture supplemented with exogenous 3'-sialyllactose containing the alpha2-3-linked SAs. However, the complete inhibition of parasite proliferation was not achieved in the culture. These findings indicate that while the alpha2-3-linked SA-dependent pathway is needed for highly efficient invasion of host RBCs by B. bovis, there might also be other potential alternative pathways.

Publication Types:
PMID: 17984585 [PubMed - indexed for MEDLINE]

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A field trial evaluation of the prophylactic efficacy of amitraz-impregnated collars against canine babesiosis (Babesia canis rossi) in South Africa.

Last RD, Hill JM, Matjila PT, RŹme CA.

Vetdiagnostix-Veterinary Pathology Services, P.O. Box 13624, Cascades, 3202, South Africa. vetdiagnostix@futurenet.co.za

South African canine babesiosis caused by Babesia canis rossi is a common clinical disease in dogs in South Africa and remains a significant cause of domestic dog mortality. To determine whether tick-repellent, 9% amitraz-impregnated tick collars (Preventic-Virbac) could prevent tick-borne exposure to B. canis rossi, 50 dogs were assigned to two groups. Group 1 (20 dogs), polymerase chain reaction (PCR)--and reverse line blot (RLB)-negative for B. canis rossi, were fitted with amitraz collars and blood samples collected monthly, over a 6-month period, and analysed for B. canis rossi. Group 2 (30 dogs) included 5 dogs selected on a month-by-month basis from a population of dogs from the same geographical area as the group 1 dogs, but with no history of previous tick control, which were blood-sampled together with the treatment group and analysed for B. canis rossi by PCR and RLB, to serve as the control group. Eight of the 30 control dogs (26.6%) were PCR/RLB positive for B. canis rossi, indicating high pathogen exposure during the trial period. All twenty of the treatment group dogs remained negative for B. canis rossi throughout the 6 months of the trial. These results suggest that the use of amitraz-impregnated collars had a significant effect on reducing infection with B. canis rossi.

PMID: 17941596 [PubMed - indexed for MEDLINE]

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Update on clindamycin in the management of bacterial, fungal and protozoal infections.

Guay D.

University of Minnesota, College of Pharmacy, Weaver-Densford Hall 7-148, 308 Harvard Street SE, Minneapolis, MN 55455, USA. guayx001@umn.edu

Lincomycin and clindamycin are the only members of the relatively small lincosamide antimicrobial class marketed for use in humans. This paper only reviews data regarding clindamycin, with an emphasis on data published over the last decade. Clindamycin exhibits a broad spectrum of antimicrobial activity, including Gram-positive aerobes/anaerobes, Gram-negative anaerobes and select protozoa (Toxoplasma gondii, Plasmodium falciparum, Babesia spp.) and fungi (Pneumocystis jiroveci). It still enjoys use in the therapy and prophylaxis of a large number of bacterial, protozoal and fungal infections, despite > 40 years of clinical use. However, the spectre of resistance by an increasing number of microorganisms is beginning to cast a shadow over the future use of this valuable agent. With the emergence and spread of infections due to community-acquired methicillin-resistant Staphylococci (for which clindamycin is a first-line agent), it is hoped that the issues of resistance can be mitigated and the use of clindamycin extended for at least the foreseeable future.

Publication Types:
PMID: 17927492 [PubMed - indexed for MEDLINE]

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Molecular evaluation of the incidence of Ehrlichia canis, Anaplasma platys and Babesia spp. in dogs from Ribeirčo Preto, Brazil.

Santos F, Coppede JS, Pereira AL, Oliveira LP, Roberto PG, Benedetti RB, Zucoloto LB, Lucas F, Sobreira L, Marins M.

Unidade de Biotecnologia, Universidade de Ribeirčo Preto (UNAERP), Ribeirčo Preto, SP, Brazil.

Canine monocytic ehrlichiosis caused by Ehrlichia canis is endemic in many regions of Brazil. Since thrombocytopenia is a common finding in infected dogs, many clinicians tend to use it as an indication for antibiotic treatment. Polymerase chain reaction (PCR) and nested PCR were used to study the presence of E. canis, Anaplasma platys and Babesia spp. in thrombocytopenic and non-thrombocytopenic dogs from Ribeirčo Preto, Brazil. Despite the high prevalence of E. canis infection among thrombocytopenic dogs, 46.7% of the thrombocytopenic dogs studied were either infected with Babesia spp. or A. platys or not infected with any of the three pathogens. There was a high incidence (25.4%) of E. canis infection in non-thrombocytopenic dogs. Although infection with E. canis should be considered in thrombocytopenic dogs, the final diagnosis needs to be confirmed by complementary tests such as blood smears and PCR to avoid the unnecessary use of antibiotics.

PMID: 17920967 [PubMed - as supplied by publisher]

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Differential Bos taurus cattle response to Babesia bovis infection.

Benavides MV, Sacco AM.

South Embrapa Cattle & Sheep Research Centre, BR 153 km 595 P.O. Box 242, Bagé, RS 96401-970, Brazil. magda@cppsul.embrapa.br

Bovine babesiosis is a tick-borne disease caused by Babesia spp. haemoprotozoans. The disease is of great importance at tick enzootic unstable areas and hampers cattle production in several developing countries. The available immunisation alternatives are pre-immunition and attenuated vaccines. Despite being efficient and protective, they are unsafe as they use cattle blood cells as inoculum and may potentially spread other diseases. Another alternative to help in babesiosis control would be the identification of genetically resistant cattle to Babesia bovis infection. The objective of this work was to phenotype cattle based on primary response against B. bovis infection. Two-hundred and forty half-sib Hereford and Aberdeen Angus heifers (120 animals from each breed), 12-18-month-old naēve cattle, originated from a tick-free area in Southern Brazil, were used in the experiment. Animals were monitored following an inoculation with 1x10(7)B. bovis parasitised erythrocytes. Results showed three different phenotypes: 1-'susceptible', animals with babesiosis clinical signs that received treatment to avoid death; 2-'intermediate', animals with clinical signs: parasitaemia, >or=21.5% reduction in packed cell volume (PCV) and increase in body temperature when compared to their pre-challenge physiological parameters, no specific treatment was needed as animals self recovered from the disease, and 3-'resistant', animals without clinical signs that showed B. bovis presence in blood smears, <21.5% PCV reductions, with little or no increase in body temperature and no need for babesiosis treatment. The frequencies of each phenotype were: 45.4, 26.7, and 27.9%, respectively, demonstrating the existence of phenotypic variation for B. bovis in Bos taurus cattle.

Publication Types:
PMID: 17919816 [PubMed - indexed for MEDLINE]

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[Cattle babesiosis]

[Article in Polish]

Sawczuk M.

Katedra Genetyki, Uniwersytet Szczecinski, Al. Piastów 40B, Szczecin 71-045. sawczukm@univ.szczecin.pl

Babesia parasites are intraerytrocytic Protozoa that infect wide range of domestic and wild animals and occasionally man causing babesiosis (piroplasmosis). Babesiosis also known in cattle as tick fever or red water fever is most important arthropod-borne disease of bovinae ungulates worldwide with areas of Africa, Asia, South and Central America, Australia and finally Europe. Since Smith and Kilborne had first described potential role of ticks in spread of piroplasmosis within animals, only United States till end of 50 of XX century eradicated the disease from the continent. In other, especially African countries, the problem seems to be of great economic importance. In this review all species of Babesia known to date to be infective to cattle are described with emphasis on geographical distribution of piroplasmosis, tick vector and pathogenicity of particular species and strains.

Publication Types:
PMID: 17912800 [PubMed - indexed for MEDLINE]

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Babesiosis: CT and hematologic findings.

Dodd JD, Aquino SL, Sharma A.

Department of Radiology, Massachusetts General Hospital, Boston, MA, USA. jonniedodd@gmail.com

Babesiosis is a tick-borne illness caused by the protozoan Babesia microti. Most patients are asymptomatic but the infection may produce a spectrum of symptoms in immunocomprimised patients, especially asplenic patients. These range from mild fever, sweats, fatigue, and myalgias to severe multiorgan failure, including acute respiratory distress syndrome and death. Radiographic appearances include bilateral patchy air space and interstitial opacities. We report the radiographic, high-resolution computed tomography (HRCT), and hematologic appearances in a 63-year-old man presenting with acute babesisois. HRCT images revealed smooth septal thickening and intralobular lines superimposed on ground glass opacities in both upper lobes. Follow-up HRCT after 2 weeks of therapy demonstrated resolution of the pulmonary parenchymal abnormalities.

Publication Types:
PMID: 17721341 [PubMed - indexed for MEDLINE]

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Therapeutic and prophylactic efficacy of imidocarb dipropionate on experimental Babesia ovis infection of lambs.

Sevinc F, Turgut K, Sevinc M, Ekici OD, Coskun A, Koc Y, Erol M, Ica A.

University of Selcuk, Department of Parasitology, Faculty of Veterinary Medicine, Konya, Turkey. fsevinc@selcuk.edu.tr

The objective of this study was to evaluate the therapeutic and prophylactic efficacy of imidocarb dipropionate (IMDP) against babesiosis and to determine specific antibodies against Babesia ovis in experimentally infected lambs. Thirty-six 6-month-old splenectomized lambs were used. The lambs were randomly divided into six groups with six animals each, and were intravenously inoculated with 50 mL B. ovis-infected erythrocytes as follows: group I (therapy group) was treated with IMDP (1.2 mg/kg body weight) starting on the day of onset of clinical signs of babesiosis after the inoculation; group II (untreated control animals) was not treated with any therapeutic treatment after the inoculation; groups III, IV, V and VI (prophylaxis groups) were administered IMDP (2.4 mg/kg body weight) 1, 2, 3 and 4 weeks before the inoculation, respectively. The animals were housed in a tick-proof room with water and food ad libitum up to the 30th day post-inoculation (PI). The lambs were monitored from the first day PI by recording the manifestation of clinical disease, rectal temperature, and the degree of parasitaemia. All the lambs became infected with B. ovis, except five animals from group III, which were treated 1 week prior to experimental infection. Other animals showed signs of acute clinical babesiosis. The animals treated with IMDP (group I) were able to clear the parasite from the blood circulation after 48 h post-treatment. The recrudescence of B. ovis was observed in two lambs 7 days after treatment, and they were treated with the second similar dose of the drug. Six lambs (1, 1, 2 and 2 lambs in group III, IV, V and VI, respectively) from the prophylaxis groups died within 7-17 days after showing high parasitaemia and clinical symptoms of the disease. Regardless of the clinical symptoms, 83.30% and 66.66% of the lambs which were administered IMDP 1-2 and 3-4 weeks before, were determined to be protected against the virulent field strain of B. ovis.

Publication Types:
PMID: 17709209 [PubMed - in process]

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Resolution of chronic hepatitis C following parasitosis.

Byrnes V, Chopra S, Koziel MJ.

Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.

An inefficient cellular immune response likely leads to chronic hepatitis C virus (HCV) infection. Resolution of chronic HCV infection in the absence of treatment is a rare occurrence. We report the case of a 39-year old white male with a 17-year history of chronic HCV infection, who eradicated HCV following a serious illness due to co-infection with Babesia (babesiosis), Borriela Borgdorferi (Lyme disease) and Ehrlichia (human granulocytic ehrlichiosis). We hypothesize that the cellular immune response mounted by this patient in response to his infection with all three agents but in particular Babesia was sufficient to eradicate HCV.

Publication Types:
PMID: 17696260 [PubMed - indexed for MEDLINE]

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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. mosqueda.juanjoel@inifap.gob.mx

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.

Publication Types:
PMID: 17691602 [PubMed - indexed for MEDLINE]

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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. theo.schetters@intervet.com

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.

Publication Types:
PMID: 17691601 [PubMed - indexed for MEDLINE]

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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. mflorin@cnia.inta.gov.ar

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.

Publication Types:
PMID: 17691600 [PubMed - indexed for MEDLINE]

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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. tshepo.matjila@up.ac.za

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.

Publication Types:
PMID: 17665757 [PubMed - indexed for MEDLINE]

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Attenuated vaccines for tropical theileriosis, babesiosis and heartwater: the continuing necessity.

Shkap V, de Vos AJ, Zweygarth E, Jongejan F.

Division of Parasitology, Kimron Veterinary Institute, Bet Dagan, Israel. shkapv@int.gov.il

Overwhelming evidence has accumulated of the effectiveness of immunization with live attenuated vaccines to control tick-borne diseases of livestock. Despite several disadvantages, vaccination with live attenuated organisms against tropical theileriosis, babesiosis and possibly heartwater constitutes one of the most cost-effective intervention strategies. Although great advances have been made through genomics and proteomics research, this has not yet translated into effective non-living vaccines. As a result, there is a continuing necessity to use available live vaccines in tick and tick-borne disease-control strategies adapted to conditions prevailing in many parts of the world.

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PMID: 17656155 [PubMed - indexed for MEDLINE]

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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.

Publication Types:
PMID: 17625097 [PubMed - indexed for MEDLINE]

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Endocrine predictors of mortality in canine babesiosis caused by Babesia canis rossi.

Schoeman JP, Rees P, Herrtage ME.

Department of Companion Animal Clinical Studies, Faculty of Veterinary Science, University of Pretoria, Onderstepoort 0110, South Africa. johanp.schoeman@up.ac.za

This prospective, cross-sectional, observational study was designed to determine the association between the hormones of the pituitary-adrenal and pituitary-thyroid axes and outcome in dogs with naturally occurring Babesia canis rossi babesiosis. Ninety-five dogs with canine babesiosis were studied and blood samples were obtained from the jugular vein in each dog prior to treatment at admission to hospital. Serum cortisol, adrenocorticotrophic hormone (ACTH), thyroxine, free thyroxine and thyrotropin (TSH) concentrations were measured. Diagnosis was confirmed by polymerase chain reaction and reverse line blot and dogs infected with Babesia canis vogeli or Ehrlichia canis were excluded. Three outcomes were defined: hospitalization with subsequent death (n=7); hospitalization followed by recovery (n=56); and treatment as an outpatient (n=32). Serum cortisol and ACTH concentrations were significantly higher in the dogs that died, compared to hospitalized dogs that survived and compared to dogs treated as outpatients. Serum T4 and free T4 concentrations were significantly lower in the dogs that died, compared to the hospitalized dogs that survived and compared to dogs treated as outpatients. Serum TSH concentrations were not significantly different between any of the groups. Mortality was significantly associated with high cortisol and high ACTH concentrations and with low T4 and fT4 concentrations in dogs suffering from B. canis rossi babesiosis.

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PMID: 17614201 [PubMed - indexed for MEDLINE]

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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. anke.hildebrandt@med.uni-jena.de

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.

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PMID: 17587072 [PubMed - indexed for MEDLINE]

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Comment on:
Counterpoint: long-term antibiotic therapy improves persistent symptoms associated with lyme disease.

Stricker RB.

International Lyme and Associated Diseases Society, Bethesda, MD, USA. rstricker@usmamed.com

BACKGROUND: Controversy exists regarding the diagnosis and treatment of Lyme disease. Patients with persistent symptoms after standard (2-4-week) antibiotic therapy for this tickborne illness have been denied further antibiotic treatment as a result of the perception that long-term infection with the Lyme spirochete, Borrelia burgdorferi, and associated tickborne pathogens is rare or nonexistent. METHODS: I review the pathophysiology of B. burgdorferi infection and the peer-reviewed literature on diagnostic Lyme disease testing, standard treatment results, and coinfection with tickborne agents, such as Babesia, Anaplasma, Ehrlichia, and Bartonella species. I also examine uncontrolled and controlled trials of prolonged antibiotic therapy in patients with persistent symptoms of Lyme disease. RESULTS: The complex "stealth" pathology of B. burgdorferi allows the spirochete to invade diverse tissues, elude the immune response, and establish long-term infection. Commercial testing for Lyme disease is highly specific but relatively insensitive, especially during the later stages of disease. Numerous studies have documented the failure of standard antibiotic therapy in patients with Lyme disease. Previous uncontrolled trials and recent placebo-controlled trials suggest that prolonged antibiotic therapy (duration, >4 weeks) may be beneficial for patients with persistent Lyme disease symptoms. Tickborne coinfections may increase the severity and duration of infection with B. burgdorferi. CONCLUSIONS: Prolonged antibiotic therapy may be useful and justifiable in patients with persistent symptoms of Lyme disease and coinfection with tickborne agents.

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PMID: 17578772 [PubMed - indexed for MEDLINE]

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Pulmonary complications of babesiosis: case report and literature review.

Cunha BA, Nausheen S, Szalda D.

Infectious Disease Division, Winthrop-University Hospital, Mineola, New York, NY 11501, USA. EMcCaffrey@winthrop.org

Reported here is a rare case of babesiosis with pulmonary complications followed by a review of the literature. Babesiosis presents clinically as a malaria-like illness with fever, chills, headache, fatigue with lymphopenia, atypical lymphocytes, mildly or transiently elevated serum transaminases, thrombocytopenia, and increased lactate dehydrogenase (LDH) levels. The diagnosis of babesiosis is based on identification of Babesia spp. on a peripheral blood smear. Babesiosis is usually mild in normal hosts, but it may be severe or even fatal in asplenic patients. Pulmonary manifestations are rare in babesiosis, but non-cardiogenic pulmonary edema (NCPE) is the most frequent manifestation. NCPE in babesiosis does not appear to be related to the degree of parasitemia or splenic function and its onset may be early or late. NCPE usually resolves rapidly with supportive treatment; it is rarely fatal. Clinicians should suspect NCPE in patients with babesiosis who acutely develop shortness of breath and have chest radiograph findings compatible with acute pulmonary edema without cardiomegaly or pleural effusions.

Publication Types:
PMID: 17558489 [PubMed - indexed for MEDLINE]

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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.

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PMID: 17551236 [PubMed - indexed for MEDLINE]

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Babesia gibsoni: detection during experimental infections and after combined atovaquone and azithromycin therapy.

Jefferies R, Ryan UM, Jardine J, Robertson ID, Irwin PJ.

Australasian Centre for Companion Animal Research, Division of Health Sciences, Murdoch University, WA 6150, Australia.

Babesia gibsoni is a protozoan parasite of dogs worldwide yet both an effective treatment and a reliable method for detecting subclinical cases of this emerging infection remain elusive. Experimental B. gibsoni infections were established in vivo to investigate the efficacy of combined atovaquone and azithromycin drug therapy and to determine the detection limits of a nested-PCR, IFAT and microscopy during various stages of infection. While atovaquone and azithromycin produced a reduction in parasitaemia, it did not eliminate the parasite and drug resistance appeared to develop in one dog. Polymerase chain reaction was found to be most useful in detecting infection in the pre-acute and acute stages, while IFAT was most reliable during chronic infections. Microscopy is suggested to be only effective for detecting acute stage infections. This study also describes the detection of B. gibsoni in tissue samples during chronic infections for the first time, suggesting possible sequestration of this parasite.

PMID: 17543304 [PubMed - indexed for MEDLINE]

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Label-free detection of Babesia bovis infected red blood cells using impedance spectroscopy on a microfabricated flow cytometer.

Küttel C, Nascimento E, Demierre N, Silva T, Braschler T, Renaud P, Oliva AG.

Laboratory of Microsystems, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland. kuettel@nano.mavt.ethz.ch

Impedance spectroscopy is a powerful tool for label-free analysis and characterisation of living cells. In this work, we achieved the detection of Babesia bovis infected red blood cells using impedance spectroscopy on a microfabricated flow cytometer. The cellular modifications caused by the intracellular parasite result in a shift in impedance which can be measured dielectrically. Thus, a rapid cell-by-cell detection with microliter amounts of reagents is possible. Unlike other diagnostic tests, this method does not depend on extensive sample pre-treatment or expensive chemicals and equipment.

Publication Types:
PMID: 17451631 [PubMed - indexed for MEDLINE]

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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. drshubhamitra@gmail.com

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.

Publication Types:
PMID: 17437935 [PubMed - indexed for MEDLINE]

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Are various Babesia species a missed cause for hypereosinophilia? A follow-up on the first reported case of imatinib mesylate for idiopathic hypereosinophilia.

Schaller JL, Burkland GA, Langhoff PJ.

INTRODUCTION: In 2001 we reported the first case of use of imatinib mesylate (Gleevec) for treatment of idiopathic hypereosinophilia syndrome (HES). These findings have been replicated in some patients with HES. After 1 year of taking imatinib, the patient stopped this medication, and during the last 5 years the patient has not experienced a relapse. He has, however, recently been diagnosed with babesiosis. This new diagnosis might relate to his HES. METHODS: After 6 years we decided to follow up on this patient's treatment. We interviewed the patient, his son, his aunt, and 2 consulting physicians and also reviewed relevant laboratory results to determine whether his HES had returned and whether his residual morbidity had changed. RESULTS: The patient has had no relapse of HES and his eosinophil counts have remained low-normal. He was recently diagnosed with babesiosis, and was prescribed atovaquone and azithromycin with a significant decrease in morbidity. His eosinophil cationic protein levels have also fallen to low-normal since starting atovaquone and azithromycin. DISCUSSION: New Babesia species are emerging as human infections. Most do not have available antibody or polymerase chain reaction diagnostic testing at this time. Manual differential examinations are of variable utility due to low numbers of infected red blood cells, suboptimal technique, and limited experience. Therefore, a diagnosis might need to be empirical at times, and should be based on signs and symptoms. CONCLUSION: The patient has not relapsed in the 5 years that he has not been taking imatinib. Babesiosis should be added to the many possible causes of HES. It is unknown how often babesiosis causes HES as well as what percentage of HES patients have babesiosis.

Publication Types:
PMID: 17435644 [PubMed - indexed for MEDLINE]

PMCID: PMC1925019


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

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. ezzelarabmb@upmc.edu [corrected]

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.

Publication Types:
PMID: 17381691 [PubMed - indexed for MEDLINE]

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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. shkapv@int.gov.il

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.

Publication Types:
PMID: 17368728 [PubMed - indexed for MEDLINE]

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First case of human babesiosis in Germany - Clinical presentation and molecular characterisation of the pathogen.

Häselbarth K, Tenter AM, Brade V, Krieger G, Hunfeld KP.

Department of Internal Medicine II, Hegau-Bodensee-Medical Center, Singen, Germany.

Babesiosis is a common infection of animals and is gaining increasing attention as an emerging tick-borne zoonosis of humans in Europe. Here we report on the first case of human babesiosis in Germany in a 63-year-old splenectomised German patient with a relapse of nodular lymphocyte-predominant Hodgkin's lymphoma. After treatment with a chimeric anti-CD20 antibody preparation (Rituximab), the patient was hospitalised because of anaemia and dark urine from haemoglobinuria. Presumptive diagnosis of babesiosis was made based on piriform parasitic erythrocytic inclusions in peripheral blood smears and confirmed by Babesia-specific 18S rDNA PCR. Sequence analysis revealed a >99% homology of the amplicon with the recently described EU1 organism clustering within the Babesia divergens/Babesia odocoilei complex. Despite treatment with quinine and clindamycin the patient relapsed and developed chronic parasitaemia requiring re-treatment and long-term maintenance therapy with atovaquone before he eventually seroconverted and the parasite was cleared. Our findings suggest that human babesiosis occurs in Germany and can take a chronic course in immunocompromised individuals.

Publication Types:
PMID: 17350888 [PubMed - indexed for MEDLINE]

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Babesia divergens becoming extinct in cattle of Northeast Hungary: new data on the past and present situation.

Hornok S, Edelhofer R, Szotáczky I, Hajtós I.

Department of Parasitology and Zoology, Faculty of Veterinary Science, Szent István University, H-1078 Budapest, István u. 2, Hungary. Hornok.Sandor@aotk.szie.hu

Previously unpublished data from 1958 to 1967 attest the occurrence of Babesia divergens in cattle in several endemic foci of Northeast Hungary. During that period the number of clinical cases showed fluctuation with intervals of 4-5 years and monophasic seasonality (peaking in June). In order to assess the current status of bovine babesiosis in that region, blood samples were collected from 654 cattle on 44 farms of 36 settlements in or near the endemic area during 2005, and serum levels of IgG antibodies to B. divergens were measured by indirect fluorescent antibody test (IFAT). Only 2 samples (0.3%) showed positivity. In one village clinical babesiosis was observed over the past few years. Animals brought into the endemic area during the spring developed haemoglobinuria in the summer of the same year, but those introduced during the summer or autumn showed clinical signs only after two years. Sampled animals born and raised locally had neither haemoglobinuria nor seroconversion. Reduction in the number of cases during the past decades may have been influenced by the availability of hosts (i.e. decrease of cattle breeding) and the activity of vectors associated with climate-related changes (e.g. increase of annual sunlight hours in the endemic area). This is the first report on the prevalence of antibodies to B. divergens in cattle in Hungary.

Publication Types:
PMID: 17278721 [PubMed - indexed for MEDLINE]

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Can tumor necrosis factor alpha blockade predispose to severe babesiosis?

Taiwo B, Lee C, Venkat D, Tambar S, Sutton SH.

Northwestern University, Feinberg School of Medicine, Chicago, Illinois, USA. b-taiwo@northwestern.edu

Publication Types:
PMID: 17266091 [PubMed - indexed for MEDLINE]

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[Importance of PCR for the diagnostics of canine babesiosis]

[Article in German]

Schaarschmidt D, Trächsel M, Achermann R, Hartelt K, Oehme R, Müller W.

Labor ALOMED, Radolfzell. schaarschmidt@alomed.de

Clinical standards to confirm babesiosis in dogs include the direct identification of the infectious agent in blood smears and serological assays for Babesia canis-specific antibodies. Here, we demonstrate in seven cases (with data on anamnesis, clinics, laboratory diagnostics, and therapeutic outcomes) that a new diagnostic procedure is required. This is the molecular-genetic identification of babesia by real time PCR allowing an unequivocal identification of the infectious agents. Indeed, all seven patients presenting severe clinical symptoms were PCR-positive, but only two of them had specific antibodies and showed babesia in their bloodstream. Six of the dogs appeared to have acquired babesiosis while travelling abroad, and one in the Swiss canton of Schaffhausen.

Publication Types:
PMID: 17263080 [PubMed - indexed for MEDLINE]

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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.

Publication Types:
PMID: 17259886 [PubMed - indexed for MEDLINE]

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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.

Publication Types:
PMID: 17229504 [PubMed - indexed for MEDLINE]

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Comment in:
Motor neuron disease recovery associated with IV ceftriaxone and anti-Babesia therapy.

Harvey WT, Martz D.

Rocky Mountain Chronic Disease Specialists, L.L.C., North Circle Drive, Colorado Springs, CO 80909, USA. wth928@aol.com

This report summarizes what we believe to be the first verifiable case of a significant and progressive motor neuron disease (MND) consistent with amyotrophic lateral sclerosis that resolved during treatment with i.v. ceftriaxone plus oral atovaquone and mefloquine. The rationale for use of these antibiotics was (i) positive testing for Borrelia burgdorferi and (ii) red blood cell ring forms consistent with Babesia species infection. The patient has continued to be free of MND signs and symptoms for 15 months, although some symptoms consistent with disseminated Borreliosis remain.

Publication Types:
PMID: 17212618 [PubMed - indexed for MEDLINE]

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Emerging infectious diseases that threaten the blood supply.

Alter HJ, Stramer SL, Dodd RY.

Infectious Diseases Section and Department of Transfusion Medicine, National Institutes of Health, Bethesda, MD 20892, USA. halter@dtm.cc.nih.gov

Following the devastating effects of blood-transmitted human immunodeficiency virus (HIV), blood establishments have become increasingly vigilant for the emergence or re-emergence of new threats to the safety of the blood supply. Many agents have fulfilled the broad definition of emerging blood-transmitted infections, including West Nile virus (WNV), Trypanosoma cruzi, Plasmodium spp., Babesia spp., parvovirus B19, dengue virus, and the prions that cause variant Creutzfeld-Jacob disease (vCJD). Other agents such as human herpes virus-8 (HHV-8-Kaposi's sarcoma virus) and Borellia (Lyme disease) and, perhaps, avian flu virus, are known to have a viremic phase, but have not yet been proved to be transfusion-transmitted. In the wake of these threats, transfusion services use a variety of donor screening interventions, including serologic assays, nucleic acid assays, and geographic exclusions based on potential exposure. The ultimate safeguard may be a pre-emptive pathogen inactivation strategy that will disrupt all nucleic acid-containing agents (though not prions). Considerable effort and resources have been invested in this arena, but currently no single technique is effective for inactivation of both liquid and cellular blood products and toxicity issues have not been completely resolved. The blood supply is remarkably safe with the risk of major pathogens such as hepatitis C virus (HCV) and HIV now reduced to less than one transmission per 2 to 3 million exposures. However, to approach near-zero infectious disease risk for emerging and re-emerging pathogens, new strategies such as pathogen inactivation or multi-pathogen microarray technology will need to be developed or refined.

Publication Types:
PMID: 17198845 [PubMed - indexed for MEDLINE]

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Amount of cholesterol in host membrane affects erythrocyte invasion and replication by Babesia bovis.

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

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

Cholesterol is a major component of the erythrocyte membrane. In the present study, we investigated the effects of cholesterol reduction in host bovine erythrocytes (RBC) on the growth of Babesia bovis, a major bovine haemoprotozoon. An in vitro growth assay with bovine RBC that had been prepared by pre-treatment with a cholesterol depletion agent (methyl-beta-cyclodextrin, MCD) showed that the culture with 5 mM MCD-treated RBC inhibited the growth of B. bovis significantly as compared with that with the control RBC. In further experiments, the treatment with 5 mM MCD was proved to suppress both activities of the parasite, erythrocyte invasion and replication within the infected RBC. In contrast, a slight reduction in the membrane cholesterol by 1 mM MCD treatment promoted both their growth and erythrocyte invasion activity. These results indicate that erythrocyte invasion and replication by B. bovis are affected by the amount of cholesterol in the host erythrocyte membrane.

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PMID: 17147838 [PubMed - indexed for MEDLINE]

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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.

Publication Types:
PMID: 17135544 [PubMed - indexed for MEDLINE]

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Evidence of an acute phase response in dogs naturally infected with Babesia canis.

Matijatko V, Mrljak V, Kis I, Kucer N, Forsek J, Zivicnjak T, Romic Z, Simec Z, Ceron JJ.

Clinic for Internal Diseases, Faculty of Veterinary Medicine, University of Zagreb, Heinzelova 55, 10000 Zagreb, Croatia. vmatijatko@vip.hr

The erythrocyte sedimentation rate (ESR), white blood cell count (WBC), haematocrit (HCT) and platelet number (PLT) were quantified and compared with the acute phase proteins (APPs) in dogs naturally infected with Babesia canis and healthy dogs. Both groups were treated with imidocarb dipropionate on the day of admission and both groups were monitored for all parameters on the admission day and on the first, second, third, fourth and seventh days in order to determine the presence of an acute phase reaction, to assess the diagnostic value of these markers in uncomplicated canine babesiosis and to evaluate the use of APPs in treatment monitoring. It was demonstrated that an acute phase response occurs in dogs naturally infected with Babesia canis, with significant increases in the concentration of major acute phase proteins. The serum concentration of C-reactive protein (CRP), serum amyloid A (SAA) and the erythrocyte sedimentation rate (ESR) decreased daily after treatment and approached reference range values by the eighth day. PLT and haematocrit (HCT) increased daily after treatment and approached reference range values by the fourth day. WBC and haptoglobin increased after treatment and then decreased from the third and fourth days, respectively, to the eighth day. The diagnostic sensitivity of CRP, SAA and PLT was significantly higher compared to haptoglobin, ESR, HCT and the WBC count. CRP and SAA were of clinical use in monitoring the response to antibabesial treatment.

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PMID: 17116368 [PubMed - indexed for MEDLINE]

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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. theo.schetters@intervet.com

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]

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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.

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PMID: 17055131 [PubMed - indexed for MEDLINE]

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Recombinant protein Bd37 protected gerbils against heterologous challenges with isolates of Babesia divergens polymorphic for the bd37 gene.

Hadj-Kaddour K, Carcy B, Vallet A, Randazzo S, Delbecq S, Kleuskens J, Schetters T, Gorenflot A, Precigout E.

Laboratoire Biologie Cellulaire and Moléculaire, ERT 1038 'Vaccination anti-parasitaire', UFR Pharmacie, Université Montpellier I, 15 Avenue Charles Flahault, B.P. 14491, 34093 Montpellier Cedex 5, France. kamel.hadj-kaddour@univ-montp1.fr

The Bd37gene encoding for a glycosyl-phosphatidyl-inositol anchored protein of Babesia divergens displays genetic polymorphisms among isolates. Five major polymorphic groups (clades) were shown by PCR-RFLP among different B. divergens isolates. Each group has been characterized according to a reference Bd37 gene (Rouen87, W8843, Y5, 6303E and 1705B). Recombinant (GST fusion) protein (Bd37r) expressed from the Bd37 gene, was used as antigen in a saponin-based formulation and was able to protect gerbils, after 2 injections at low dose vaccine concentration (1 mug per dose), against a virulent challenge with the B. divergens Rouen87 isolate. In spite of polymorphism of Bd37 gene, Bd37r induced complete immunoprotection against challenges with each of the 5 reference isolate groups defined by PCR-RFLP.

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PMID: 17038236 [PubMed - indexed for MEDLINE]

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[Human babesiosis]

[Article in French]

Meliani P, Khatibi S, Randazzo S, Gorenflot A, Marchou B.

Service des maladies infectieuses et tropicales, hôpital Purpan, place du Docteur-Baylac, 31059 Toulouse, France. p.meliani@voila.fr

Babesia is one of the most ubiquitous and widespread blood parasite in the world based on numbers and distribution of species in animals. The clinical presentation may vary according to the incriminated species. In some states of the USA this kind of infection is endemic; the number of cases reported in Europe is inferior but more life-threatening. A better understanding of parasite specificities such as cycle and pathogenicity allowed to suggest treatment guidelines adapted to the different clinical and microbiological situations.

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PMID: 17027216 [PubMed - indexed for MEDLINE]

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Clinical manifestations of canine babesiosis in Hungary (63 cases).

Máthé A, Vörös K, Papp L, Reiczigel J.

Department and Clinic of Internal Medicine, Faculty of Veterinary Science, Szent István University, H-1400 Budapest, P.O. Box 2, Hungary. Mathe.Akos@aotk.szie.hu

Clinical observations of Babesia canis infection in 63 dogs during a 1-year period are summarised, demonstrating the pathogenicity of the Babesia strain endemic in Hungary. Most patients had babesiosis in the spring and autumn, correlating with the seasonal activity of ticks. Male animals appeared in higher numbers, probably due to an overrepresentation of outdoor dogs. Uncomplicated babesiosis was diagnosed in 32 cases. The disease affected dogs of any age in this study. Symptoms were similar to those published from other parts of the world: lethargy, fever, splenomegaly, pallor, icterus, haemoglobinuria and presence of ticks were the most common observations. Thrombocytopenia, lymphopenia and neutropenia were frequent haemogram changes. Imidocarb appeared to be highly effective in eliminating the Babesia infection. Thirty-one animals demonstrated babesiosis with complications. Most Rottweilers (7/9) developed complicated disease. Old age was a risk factor for multiple complications. Multiple organ manifestations had poor prognosis. Hepatopathy (44%), pancreatitis (33%), acute renal failure (ARF; 31%) and disseminated intravascular coagulation (DIC; 24%) were frequent complications, while immune-mediated haemolytic anaemia (IMHA; 10%), acute respiratory distress syndrome (ARDS; 6%) and cerebral babesiosis (3%) were rarely observed. There was a significant difference between the mean age of dogs having uncomplicated disease, babesiosis with a single complication and babesiosis with multiple complications (3.4, 4.8 and 8.6 years, respectively, p < 0.001). The recovery rate (78, 68 and 25%, respectively, p = 0.005) and mortality rate (3, 21 and 67%, respectively, p < 0.001) also tended to differ significantly in these groups. Systemic inflammatory response syndrome (SIRS) and DIC are two possible pathways leading to multiple organ dysfunction syndrome (MODS) in babesiosis. DIC was found to predict MODS more sensitively in this study than SIRS: there were 6 animals developing MODS out of 11 identified with DIC, while only 5 dogs developed MODS out of 22 having SIRS.

PMID: 17020140 [PubMed - indexed for MEDLINE]

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Potent antihematozoan activity of novel bisthiazolium drug T16: evidence for inhibition of phosphatidylcholine metabolism in erythrocytes infected with Babesia and Plasmodium spp.

Richier E, Biagini GA, Wein S, Boudou F, Bray PG, Ward SA, Precigout E, Calas M, Dubremetz JF, Vial HJ.

Centre National de la Recherche Scientifique, Unité Mixte de Recherche UMR 5539, CNRS University Montpellier II, F-34095 Montpellier Cedex 5, France.

A leading bisthiazolium drug, T16, designed to mimic choline, was shown to exert potent antibabesial activity, with 50% inhibitory concentrations of 28 and 7 nM against Babesia divergens and B. canis, respectively. T16 accumulated inside Babesia-infected erythrocytes (cellular accumulation ratio, >60) by a saturable process with an apparent K(m) of 0.65 microM. Subcellular fractionation of Babesia parasites revealed the accumulation of T16 into a low-density fraction, while in malaria-infected erythrocytes a significant fraction of the drug was associated with heme malaria pigment. T16 exerts an early and specific inhibition of the de novo biosynthesis of phosphatidylcholine both in B. divergens- and Plasmodium falciparum-infected erythrocytes. Choline accumulation into isolated Babesia parasites was highly sensitive to inhibition by T16. These data are consistent with the hypothesis that bisthiazolium drugs target the de novo phosphatidylcholine biosynthesis of intraerythrocytic hematozoan parasites. In malaria parasites, which generate ferriprotoporphyrin IX during hemoglobin digestion, T16 binding to heme may enhance the accumulation and activity of the drug. The selectivity of accumulation and potent activity of this class of drug into parasite-infected erythrocytes offers unique advantages over more traditional antihematozoan drugs.

Publication Types:
PMID: 17005821 [PubMed - indexed for MEDLINE]

PMCID: PMC1610066


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Erratum in:
  • Vet Parasitol. 2007 Sep 1;148(2):185. dosage error in text.

Canine babesiosis: a Brazilian perspective.

Dantas-Torres F, Figueredo LA.

Departamento de Imunologia, Centro de Pesquisas Aggeu Magalhčes, Fundaćčo Oswaldo Cruz, C.P. 7472, Recife 50670-420, Pernambuco, Brazil. fdt@cpqam.fiocruz.br

Canine babesiosis is highly endemic in Brazil, caused by Babesia canis and Babesia gibsoni, both transmitted by Rhipicephalus sanguineus ticks. The present review argues for a more adequate method of characterizing the Babesia species infecting dogs and cats in different Brazilian endemic zones. It advocates for a comprehensive understanding of the biology of R. sanguineus ticks under Brazilian conditions in order to define the more effective preventive strategies against canine babesiosis and calls for partnerships between the public and private sectors for research on canine babesiosis and other vector-borne diseases in Brazil.

Publication Types:
PMID: 16962707 [PubMed - indexed for MEDLINE]

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Ixodes frontalis and avian tick-related syndrome in the United Kingdom.

Monks D, Fisher M, Forbes NA.

Great Western Referrals, Unit 10 Berkshire House, County Park Business Park, Shrivenham Road, Swindon, Wilts SN1 2NR.

OBJECTIVES: This study aimed to characterise tick species responsible for avian tick infestations in the UK, to analyse various risk factors for tick-related syndrome in tick-infested birds and to test samples for the presence of certain tick-transmitted pathogens. METHODS: Ticks, blood, splenic tissue and tick attachment site tissue from birds with attached ticks were requested from veterinarians and wildlife sanctuaries around the UK. Ticks were identified according to standard keys, and samples were analysed via DNA PCR test for Borrelia burgdorferi sensu lato, Babesia species, Bartonella species and Ehrlichia species. RESULTS: Ixodes frontalis was the most commonly identified tick, and an association of adult female I frontalis with tick-related syndrome in birds was demonstrated. Tick infestation was markedly seasonal. I frontalis was found on 32 species of birds. DNA PCR testing was uniformly negative. Of the birds known to have been treated, 75 per cent (nine of 12) survived. CLINICAL SIGNIFICANCE: Tick-related syndrome is a poorly understood syndrome, with sporadic distribution, both geographically and seasonally. This study confirms I frontalis as the most common cause of this syndrome in the UK and identifies some features of the tick life cycle in this country. The benefit of treatment in affected birds is highlighted. Risk factors for tick-related syndrome are examined and preventive strategies discussed.

Publication Types:
PMID: 16911113 [PubMed - indexed for MEDLINE]

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Prospects for recombinant vaccines against Babesia bovis and related parasites.

Brown WC, Norimine J, Goff WL, Suarez CE, McElwain TF.

Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164-7040, USA. wbrown@vetmed.wsu.edu

Babesial parasites infect cattle in tropical and temperate regions of the world and cause significant morbidity and mortality. Discovery of protective antigens that could be used in a killed vaccine has been slow and to date there are few promising vaccine candidates for cattle Babesia. This review describes mechanisms of protective innate and adaptive immune responses to babesial parasites and different strategies to identify potentially protective protein antigens of B. bovis, B. bigemina, and B. divergens. Successful parasites often cause persistent infection, and this paper also discusses how B. bovis evades and regulates the immune response to promote survival of parasite and host. Development of successful non-living recombinant vaccines will depend on increased understanding of protective immune mechanisms and availability of parasite genomes.

Publication Types:
PMID: 16842268 [PubMed - indexed for MEDLINE]

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Photochemical treatment of plasma with amotosalen and long-wavelength ultraviolet light inactivates pathogens while retaining coagulation function.

Singh Y, Sawyer LS, Pinkoski LS, Dupuis KW, Hsu JC, Lin L, Corash L.

Cerus Corp., Concord, California 94520, USA. yasmin_singh@cerus.com

BACKGROUND: The INTERCEPT Blood System, a photochemical treatment (PCT) process, has been developed to inactivate pathogens in platelet concentrates. These studies evaluated the efficacy of PCT to inactivate pathogens in plasma and the effect of PCT on plasma function. STUDY DESIGN AND METHODS: Jumbo (600 mL) plasma units were inoculated with high titers of test pathogens and treated with 150 micromol per L amotosalen and 3 J per cm(2) long-wavelength ultraviolet light. The viability of each pathogen before and after treatment was measured with biological assays. Plasma function was evaluated through measurement of coagulation factors and antithrombotic protein activities. RESULTS: The levels of inactivation expressed as log-reduction were as follows: cell-free human immunodeficiency virus-1 (HIV-1), greater than 6.8; cell-associated HIV-1, greater than 6.4; human T-lymphotropic virus-I (HTLV-I), 4.5; HTLV-II, greater than 5.7; hepatitis B virus (HBV) and hepatitis C virus, greater than 4.5; duck HBV, 4.4 to 4.5; bovine viral diarrhea virus, 6.0; severe acute respiratory syndrome coronavirus, 5.5; West Nile virus, 6.8; bluetongue virus, 5.1; human adenovirus 5, 6.8; Klebsiella pneumoniae, greater than 7.4; Staphylococcus epidermidis and Yersinia enterocolitica, greater than 7.3; Treponema pallidum, greater than 5.9; Borrelia burgdorferi, greater than 10.6; Plasmodium falciparum, 6.9; Trypanosoma cruzi, greater than 5.0; and Babesia microti, greater than 5.3. Retention of coagulation factor activity after PCT was expressed as the proportion of pretreatment (baseline) activity. Retention was 72 to 73 percent of baseline fibrinogen and Factor (F)VIII activity and 78 to 98 percent for FII, FV, FVII, F IX, FX, FXI, FXIII, protein C, protein S, antithrombin, and alpha2-antiplasmin. CONCLUSION: PCT of plasma inactivated high levels of a wide range of pathogens while maintaining adequate coagulation function. PCT has the potential to reduce the risk of transfusion-transmitted diseases in patients requiring plasma transfusion support.

Publication Types:
PMID: 16836564 [PubMed - indexed for MEDLINE]

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A 38-kDa protein from Babesia gibsoni and its antibody response in an experimentally infected dog.

Zhou J, Zhang G, Nishikawa Y, Fujisaki K, Xuan X.

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

A cDNA encoding the Babesia bovis 12D3 antigen homologue was obtained by immunoscreening the expression library prepared from Babesia gibsoni merozoite mRNA. The complete nucleotide sequence of the gene was 1406 bp. Computer analysis suggested that the sequence contains an open reading frame of 1052 bp encoding an expected protein with a molecular weight of 36kDa. Based on homology analysis, this putative protein was designated as the B. gibsoni 12D3 antigen (Bg12D3). The Bg12D3 gene was expressed in the Escherichia coli BL21 strain, and the chronically infected dog serum reacted with the recombinant protein. The antiserum against the recombinant Bg12D3 protein can recognize a 38-kDa native protein, which is consistent with its expected size. Moreover, the purified recombinant proteins were used as the antigen to detect the antibody response in an experimentally infected dog by the enzyme-linked immunosorbent assay (ELISA). Our results indicated that the Bg12D3 protein was recognized by the host immune system and that it induced an antibody response in chronic B. gibsoni infection. These results allowed us to identify a new member of the 12D3 antigens and its characteristic immune response in canine B. gibsoni infection.

Publication Types:
PMID: 16815635 [PubMed - indexed for MEDLINE]

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Capillary and venous Babesia canis rossi parasitaemias and their association with outcome of infection and circulatory compromise.

Böhm M, Leisewitz AL, Thompson PN, Schoeman JP.

Department of Companion Animal Clinical Studies, Faculty of Veterinary Science, University of Pretoria, Onderstepoort, Pretoria, South Africa. marlies.bohm@up.ac.za

This observational study of 100 dogs naturally infected with Babesia canis rossi determined whether severity of parasitaemia was associated with outcome of infection and documented the relative distribution of parasitised red blood cells (pRBC) in capillary and venous circulation. The association between increased parasitaemias and outcome with a clinically compromised circulation was also investigated. Outcome was defined as either hospitalisation with death, or hospitalisation with eventual recovery or treatment as an outpatient. Dogs were enrolled if large babesias were found on stained thin capillary blood smears made from an ear prick. Thin venous smears were prepared from jugular or cephalic blood. Parasitaemias were manually counted and expressed as the percent pRBC. Ten dogs died, 50 recovered after hospitalisation and 40 were treated as outpatients. Venous sampling site did not affect venous parasitaemia (P=0.6). Both capillary and venous parasitaemias of dogs that died were significantly higher than those of dogs that recovered after hospitalisation (P=0.002) and dogs that were treated as outpatients (P<0.0001). When assessing the whole group, capillary parasitaemia (median 0.61%, range <0.05-71.6%, interquartile range (IQR) 0.22-3.75%) was significantly higher than venous parasitaemia (median 0.14%, range 0-30.6%, IQR 0.046-0.52%) with P<0.0001. The 21 dogs with a clinically compromised circulation were more likely to die (P<0.0001) and had significantly higher capillary (median 5.98%, range 0.09-71.6%, IQR 2.44-19.41%) and venous (median 2.81%, range <0.05-30.6%, IQR 0.17-9.03%) parasitaemias than the 79 dogs with a clinically normal circulation (capillary median parasitaemia 0.38%, range <0.05-12.87%, IQR 0.16-1.42%; venous median parasitaemia 0.096%, range 0-6.13%, IQR <0.05-0.33%; P<0.0001). This study shows that high parasitaemia is significantly associated with death in B c rossi infected dogs. The previous clinical suspicion that capillary parasitaemias are usually higher than venous parasitaemias is confirmed. Thus capillary samples are the most appropriate diagnostic samples. Prior observations that a clinically compromised circulation is associated with death are confirmed. Despite the highly significant association between compromised circulation and higher parasitaemia, it is thought unlikely that parasite burden is the sole trigger for circulatory collapse.

Publication Types:
PMID: 16806713 [PubMed - indexed for MEDLINE]

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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.

Publication Types:
PMID: 16644602 [PubMed - indexed for MEDLINE]

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The impact of 2 dipping systems on endemic stability to bovine babesiosis and anaplasmosis in cattle in 4 communally grazed areas in Limpopo Province, South Africa.

Rikhotso BO, Stoltsz WH, Bryson NR, Sommerville JE.

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

A 12-month study was conducted in 4 communal grazing areas in the Bushbuckridge region, Limpopo Province, South Africa. The main objective was to investigate the impact of reduced acaricide application on endemic stability to bovine babesiosis (Babesia bigemina and Babesia bovis) and anaplasmosis (Anaplasma marginale) in the local cattle population. To this end 60 cattle in each communal grazing area were bled at the beginning and the conclusion of the experimental period and their sera were assayed for B. bovis, B. bigemina and Anaplasma antibodies. Cattle in the intensively dipped group were dipped 26 times and maintained on a 14-day dipping interval throughout the study, whereas cattle in the strategically dipped group were dipped only 13 times. Three cattle, from which adult ticks were collected, were selected from each village, while immature ticks were collected by drag-sampling the surrounding vegetation. During the dipping process, a questionnaire aimed at assessing the prevalence of clinical cases of tick-borne disease, abscesses and mortalities was completed by an Animal Health Technician at each diptank. An increase in seroprevalence to B. bovis and B. bigemina and a decrease in seroprevalence to Anaplasma was detected in the strategically dipped group while in the intensively dipped group the converse was true. Amblyomma hebraeum was the most numerous tick species on the cattle, and Rhipicephalus (Boophilus) microplus was more plentiful than Rhipicephalus (Boophilus) decoloratus. Drag samples yielded more immature stages of A. hebraeum than of Rhipicephalus (Boophilus) spp. The incidence of clinical cases of tick-borne disease and of abscesses increased in the strategically dipped group at the start of the survey.

Publication Types:
PMID: 16642719 [PubMed - indexed for MEDLINE]

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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. Mathe.Akos@aotk.szie.hu

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]

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Short report: cloning of the Babesia gibsoni cytochrome B gene and isolation of three single nucleotide polymorphisms from parasites present after atovaquone treatment.

Matsuu A, Miyamoto K, Ikadai H, Okano S, Higuchi S.

Department of Small Animal Internal Medicine 1, School of Veterinary Medicine and Animal Sciences, Kitasato University, Towada, Aomori, Japan. matsuu@umas.kitasato-u.ac.jp

We determined the nucleotide sequence of the Babesia gibsoni cytochrome b (cytb) gene. DNA was extracted from B. gibsoni isolated from Aomori Prefecture, Japan, and 1,288 basepairs of the cytb gene, including 1,071 basepairs of the open reading frame, were sequenced. The cytb gene of B. gibsoni obtained from three dogs that had been experimentally infected with B. gibsoni and treated with atovaquone was also sequenced. The B. gibsoni cytb gene obtained from all three atovaquone-treated dogs contained a single polymorphism resulting in an amino acid change in one of the putative ubiquinone-binding sites of Plasmodium falciparum. This polymorphism was homologous to mutations in other apicomplexan protozoa that exhibit resistance to atovaquone. Two other single polymorphisms were identified in parasites isolated from two of the dogs. These results indicate that single nucleotide polymorphisms in the sequence for mitochondrial cytb gene may be associated with decreased susceptibility of Babesia species to atovaquone.

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PMID: 16606990 [PubMed - indexed for MEDLINE]

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Comparison of different direct diagnostic methods to identify Babesia bovis and Babesia bigemina in animals vaccinated with live attenuated parasites.

Costa-Júnior LM, Rabelo EM, Martins Filho OA, Ribeiro MF.

Universidade Federal de Minas Gerais, Instituto de Ciźncias Biológicas, Departamento de Parasitologia, Av. Antônio Carlos 6627, CEP 31270-901 Belo Horizonte, Minas Gerais, Brazil.

Blood smear examination, flow cytometry, duplex Polymerase Chain Reaction (PCR), and duplex nested PCR (nPCR) were evaluated for detection of Babesia bigemina and Babesia bovis infections in cattle vaccinated with live attenuated strains. Two groups of four cattle were immunized with either B. bigemina (Bi) or B. bovis (Bo). On day 23 post inoculation (PI), Bi cattle were vaccinated with B. bovis (BiBo) and Bo cattle were vaccinated with B. bigemina (BoBi). Babesia bigemina was first detected by blood smear examination 7.5+/-3.5 days PI in the Bi group and 32.2+/-1.7 days PI in the BoBi group. The first occurrence of B. bovis in blood smears was 8.0 days PI in the Bo group and 36.0+/-2.6 days PI in the BiBo group. Flow cytometry detected parasitized erythrocytes on day 1.7+/-1.5 and 2.2+/-1.5 PI in the Bi and Bo groups, respectively, but did not discriminate between the two Babesia spp. Duplex PCR detected B. bigemina on day 4.0+/-0.8 and 26.0+/-0.8 PI in the Bi and BoBi groups, respectively, and B. bovis on day 4.0 and 25.3+/-0.5 PI in the Bo and BiBo groups, respectively. The duplex nPCR detected B. bigemina on 3.0+/-0.8 and 25.0+/-0.0 days PI in the Bi and BoBi groups, respectively, and 4.7+/-1.7 and 27.7+/-6.2 days PI in the Bo and BiBo groups, respectively. Duplex nPCR outperformed the other tests in terms of specificity and sensitivity, indicating that it is the most useful method for identifying Babesia spp. in cattle following vaccination.

Publication Types:
PMID: 16580136 [PubMed - indexed for MEDLINE]

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Genetic basis for GPI-anchor merozoite surface antigen polymorphism of Babesia and resulting antigenic diversity.

Carcy B, Précigout E, Schetters T, Gorenflot A.

Laboratoire de Biologie Cellulaire et Moléculaire, EA MESR 2413, ERT 1038 Vaccination antiparasitaire, UFR des Sciences Pharmaceutiques et Biologiques, BP 14491, F-34093 Montpellier Cedex 5, France. bcarcy@ww3.pharma.univ-montp1.fr

Glycosyl-phosphatidylinositol anchor merozoite surface antigens (GPI-anchor MSA) are proposed to act in the invasion process of infective merozoites of Babesia into host erythrocytes. Because of their essential function in the survival of Babesia parasites, they constitute good candidates for the development of vaccines against babesiosis and they have been extensively analyzed. These include Babesia bovis variable MSA (VMSA) and Babesia bigemina gp45/gp55 proteins of the agents of bovine babesiosis from tropical and subtropical countries, and the Babesia divergens Bd37 and Babesia canis Bc28 proteins of the main agents of bovine and canine babesiosis in Europe, respectively. However, these are very polymorphic antigens and Babesia parasites have evolved molecular mechanisms that enable these antigens to evade the host immune system as a survival strategy. This review focuses on the genetic basis of GPI-anchor MSA polymorphism and the antigenic diversity of B-cell epitopes that might be generated in each of these Babesia species. The picture is incomplete and no Babesia genome sequence is yet available. However, the available sequences suggest that two distinct, non cross-reactive GPI-anchor MSA (i.e., with unique B-cell epitopes) may be required by all Babesia species for invasion, and that these two distinct GPI-anchor MSA would be encoded by a multigene family. Furthermore, the data are consistent with the ability of biological clones from Babesia to use these multigene families for the expression of GPI-anchor MSA, either conserved (B. canis and B. bovis) or polymorphic (B. divergens and B. bigemina) in their amino acid sequence. Moreover, as a consequence for successful parasitism, the data suggest that both conserved and polymorphic GPI-anchor MSA would present unique B-cell epitopes.

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PMID: 16551492 [PubMed - indexed for MEDLINE]

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Antigenic variation as an exploitable weakness of babesial parasites.

Allred DR, Al-Khedery B.

Department of Pathobiology, University of Florida, Gainesville, FL 32611-0880, USA. allredd@ufl.edu

Babesia bovis and its bovine host interact in many ways, resulting in a range of disease and infection phenotypes. Host responses to the parasite elicit or select for a variety of responses on the part of the parasite, the full range of which is not yet known. One well-established phenomenon, thought to aid parasite survival by evasion of host adaptive immune responses, is the sequential expansion of antigenically variant populations during an infection, a phenomenon referred to as "antigenic variation". Antigenic variation in B. bovis, like that in the human malarial parasite, Plasmodium falciparum, is intimately linked to a second survival mechanism, cytoadhesion. In cytoadhesion, mature parasite-containing erythrocytes bind to the capillary and post-capillary venous endothelium through parasite-derived ligands. The reliance of these parasites on both functions, and on their linkage, may provide opportunities to develop anti-babesial and, perhaps, anti-malarial protection strategies. The development of inhibitors of DNA metabolism in B. bovis may be used to abrogate the process of antigenic variation, whereas small molecular mimics may provide the means to vaccinate against a wide range of variants or to prevent the surface export of variant antigen ligands. In this article, aspects of antigenic variation and cytoadhesion in bovine babesiosis are explored, with a discussion of opportunities for prophylactic or therapeutic intervention in these intertwined processes.

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PMID: 16517078 [PubMed - indexed for MEDLINE]

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Immune control of Babesia bovis infection.

Brown WC, Norimine J, Knowles DP, Goff WL.

Program in Vector-borne Disease, Department of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman, WA 99164-7040, USA. wbrown@vetmed.wsu.edu

Babesia bovis causes an acute and often fatal infection in adult cattle, which if resolved, leads to a state of persistent infection in otherwise clinically healthy cattle. Persistently infected cattle are generally resistant to reinfection with related parasite strains, and this resistance in the face of infection is termed concomitant immunity. Young animals are generally more resistant than adults to B. bovis infection, which is dependent on the spleen. Despite the discovery of B. bovis over a century ago, there are still no safe and effective vaccines that protect cattle against this most virulent of babesial pathogens. Immunodominant antigens identified by serological reactivity and dominant T-cell antigens have failed to protect cattle against challenge. This review describes the innate and acquired immune mechanisms that define resistance in young calves and correlate with the development of concomitant immunity in older cattle following recovery from clinical disease. The first sections will discuss the innate immune responses by peripheral blood- and spleen-derived macrophages in cattle induced by B. bovis merozoites and their products that limit parasite replication, and comparison of natural killer cell responses in the spleens of young (resistant) and adult (susceptible) cattle. Later sections will describe a proteomic approach to discover novel antigens, especially those recognized by immune CD4+ T lymphocytes. Because immunodominant antigens have failed to stimulate protective immunity, identification of subdominant antigens may prove to be important for effective vaccines. Identification of CD4+ T-cell immunogenic proteins and their epitopes, together with the MHC class II restricting elements, now makes possible the development of MHC class II tetramers and application of this technology to both quantify antigen-specific lymphocytes during infection and discover novel antigenic epitopes. Finally, with the imminent completion of the B. bovis genome-sequencing project, strategies using combined genomic and proteomic approaches to identify novel vaccine candidates will be reviewed. The availability of an annotated B. bovis genome will, for the first time, enable identification of non-immunodominant proteins that may stimulate protective immunity.

Publication Types:
PMID: 16510249 [PubMed - indexed for MEDLINE]

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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. g.bourdoiseau@vet-lyon.fr

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.

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PMID: 16507334 [PubMed - indexed for MEDLINE]

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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. leibyd@usa.redcross.org

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.

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PMID: 16507014 [PubMed - indexed for MEDLINE]

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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. theo.dewaal@ucd.ie

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.

Publication Types:
PMID: 16504404 [PubMed - indexed for MEDLINE]

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Erythrocyte invasion by Babesia parasites: current advances in the elucidation of the molecular interactions between the protozoan ligands and host receptors in the invasion stage.

Yokoyama N, Okamura M, Igarashi I.

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

During an asexual growth cycle of Babesia parasites in a natural host, the extracellular merozoites invade (i.e., attach to, penetrate, and internalize) the host erythrocytes (RBC) via multiple adhesive interactions of several protozoan ligands with the target receptors on the host cell surface. After internalizing the host RBC, they asexually multiply, egress from the RBC by rupturing the host cells, and then invade the new RBC again. In the invasion stage, several surface-coating molecules of merozoites might be involved in the initial attachment to the RBC, while proteins secreted from apical organelles (rhoptry, microneme, and spherical body) are proposed to play roles mainly in erythrocyte penetration or internalization. On the other hand, several components located on the surface of the RBC, such as sialic acid residues, protease-sensitive proteins, or sulphated glycosaminoglycans, are identified or suspected as the host receptors of erythrocyte invasion by Babesia parasites. The detailed molecular interactions between Babesia merozoites and the host RBC are incompletely understood. In this review, these identified or suspected molecules (protozoan ligands/erythrocyte receptors) are described by especially focusing on Babesia bovis.

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PMID: 16504403 [PubMed - indexed for MEDLINE]

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Chemotherapy against babesiosis.

Vial HJ, Gorenflot A.

Dynamique Moléculaire des Interactions Membranaires, UMR 5539 CNRS/Université Montpellier II, Case 107, Place EugŹne bataillon, F-34095 Montpellier Cedex 5, France. vial-h@univ-montp2.fr

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.

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PMID: 16504402 [PubMed - indexed for MEDLINE]

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Onset and duration of immunity against Babesia canis infection in dogs vaccinated with antigens from culture supernatants.

Schetters TP, Kleuskens JA, Scholtes NC, van de Crommert J, Krijnen E, Moubri K, Gorenflot A, Vermeulen AN.

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

It has previously been shown that dogs can be vaccinated against heterologous Babesia canis infection using a vaccine containing soluble parasite antigens (SPA) from in vitro cultures of B. canis and B. rossi that are adjuvanted with saponin. In the present study the onset and duration of immunity of vaccinated dogs were studied. Results showed that 3-26 weeks after initial vaccination, dogs effectively limit the level of SPA in plasma upon challenge infection, which was reflected in limited duration and extent of clinical manifestations. There was no statistically significant effect of vaccination on the parasite load in the circulation, which was determined from blood smears. It was further shown that the level of immunity of primary vaccinated dogs (priming and booster vaccination with a 6-week interval) and that of repeatedly vaccinated dogs (a single additional vaccination 6 months after primary vaccination) is comparable. From this study it is concluded that vaccination with this preparation induces protective immunity against clinical babesiosis from 3 weeks after booster vaccination onwards, and remains effective for a period of at least another 6 months. A single booster vaccination is sufficient to maintain immunity for at least another 6 months.

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PMID: 16504401 [PubMed - indexed for MEDLINE]

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Effective imidocarb dipropionate therapy for Babesia shortti in falcons.

Tarello W.

International Veterinary Hospital, PO Box 9275, 61003 Ahmadi, Kuwait.

PMID: 16489163 [PubMed - indexed for MEDLINE]

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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. leanne.fox@childrens.harvard.edu

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.

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PMID: 16462298 [PubMed - indexed for MEDLINE]

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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. christopher.barnard@nottingham.ac.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.

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PMID: 16442748 [PubMed - indexed for MEDLINE]

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[Rickettsia helvetica: an emerging tick-borne pathogen in Hungary and Europe]

[Article in Hungarian]

Sréter T, Sréterné Lancz Z, Széll Z, Egyed L.

Országos Allategészségügyi Intézet, Bakteriológiai Fosztály. sretert@oai.hu

Rickettsia helvetica belonging to spotted fever group rickettsiae was recently detected by polymerase chain reaction followed by sequencing in European sheep ticks (Ixodes ricinus) from Hungary. Current knowledge on these rickettsiae and the clinical and diagnostic aspects of R. helvetica infection is summarized. In acute cases, R. helvetica is generally responsible for flu-like symptoms. Nevertheless, recent data indicate that in chronic cases, these rickettsiae can be responsible for perimyocarditis resulting sudden cardiac death and might play a role in the pathogenesis of aortic valve disease. The diagnosis can be based on serological, molecular and histological methods. A summary of the information available from Hungary and neighbouring countries on the prevalence of tick-borne encephalitis virus, Anaplasma, Borrelia, Francisella, Rickettsia and Babesia infections in I. ricinus is also presented.

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PMID: 16440500 [PubMed - indexed for MEDLINE]

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New diseases and increased risk of diseases in companion animals and horses due to transport.

Englund L, Pringle J.

Department of Small Animals, National Veterinary Institute, Uppsala, Sweden.

Dogs and horses are transported within the European Union for a number of reasons. The transport per se may cause physical problems, exemplified by hyperthermia in dogs and pleuropneumonia in horses, and the stress may reactivate latent infections such as canine herpesvirus-1 and equine herpesvirus-1. Preventive treatments are vital to protect dogs from ticks and mosquitoes transmitting their potentially lethal infectious agents, such as Leishmania donovani infantum, Babesia canis, Ehrlichia canis, and Dirofilaria immitis. However, records show that the travelling dogs are not fully protected since cases occur in non-endemic regions. The brown dog tick also poses a risk for humans by transmitting Rickettsia conorii causing Mediterranean spotted fever. Further, the trade in stray dogs from southern Europe has placed a particular focus on the occurrence of vector-borne diseases in the Mediterranean basin. The unknown origin of strays also poses a risk for rabies. With respect to horses, those transported to southern Europe may be exposed to Theileria equi and Babesia caballi, both of which are transmitted by ticks. Horses with antibodies against these parasites are not permitted to enter the USA. Additionally, viral diseases such as African horse sickness, transmitted by midges, and Borna disease, of the mode of transmission is yet unclear, may also pose a risk for horses travelling to potentially endemic regions.

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PMID: 16429803 [PubMed - indexed for MEDLINE]

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[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.

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.

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PMID: 16363205 [PubMed - indexed for MEDLINE]

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Human babesiosis--a case report.

Marathe A, Tripathi J, Handa V, Date V.

Pranav Pathology Laboratory, Raopura, Baroda - 390 001, Gujarat, India. anantmarathe@hotmail.com.

Babesiosis is an emerging, tick-transmitted, zoonotic disease caused by hematotropic parasites of the genus Babesia. Most cases of Babesial infections in humans have been acquired in temperate regions of the United States, Europe, France and England. A few cases of Babesiosis have been described in other parts of the world, including China, Taiwan, Egypt, South Africa, and Mexico.1,2 We report the first case of human Babesiosis, in a normosplenic, previously healthy individual from India.

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PMID: 16327127 [PubMed - indexed for MEDLINE]

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Babesia canis vogeli: a novel PCR for its detection in dogs in Australia.

Martin AR, Dunstan RH, Roberts TK, Brown GK.

Discipline of Biological Sciences, School of Environmental and Life Sciences, University of Newcastle, University Drive, Callaghan, NSW 2308, Australia.

Babesia canis vogeli is known to cause disease in dogs in Australia, and the rapid detection of various subspecies would enable effective treatment and management. A 21 bp oligonucleotide, "Bab-f" was proposed for the production of larger PCR products with high species specificity that would enable effective sequence analyses to yield subspecies identification. The new forward primer when paired with a previously reported "Babesia common" reverse primer generated a 394 bp product which was successfully amplified and provided subspecies differentiation by sequence analyses. Specificity and sensitivity were reported at 100% on a cohort of 55 dogs.

PMID: 16256109 [PubMed - indexed for MEDLINE]

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Potential for recombinant Babesia bovis antigens to protect against a highly virulent isolate.

Hope M, Riding G, Menzies M, Colditz I, Reverter A, Willadsen P.

CSIRO Livestock Industries, Queensland Bioscience Precinct, St Lucia, Australia. shelly.hope@csiro.au

Two antigens from Babesia bovis,12D3 and 11C5, were expressed and purified as recombinant proteins in Escherichia coli and used to vaccinate groups of six Babesia-susceptible cattle. These were subsequently challenged with a highly virulent strain of B. bovis. All cattle showed symptoms of disease and most required treatment. Cattle vaccination groups receiving either 12D3 or 11C5 or a combination of both, reduced parasitaemia by approximately fourfold and a number of individual animals appeared to control the parasite infection. Control of parasites correlated with high monocyte numbers late in infection. The results thus confirm the potential usefulness of both antigens but also demonstrate the limitations of current formulations.

PMID: 16255742 [PubMed - indexed for MEDLINE]


[In vitro pathogenicity of fungic formulation on nymphs and adults of Rhipicephalus sanguineus (Latreile, 1806) (Acari:Ixodidae)]

[Article in Portuguese]

Reis RC, Melo DR, Perinotto WM, Bittencourt VR.

Universidade Federal Rural do Rio de Janeiro, Seropédica, RJ, Brazil.

Rhipicephalus sanguineus is responsible for transmitting several pathogenic agents, such as: Babesia sp. and Ehrlichia sp.. This species is known as the brown dog tick and has wide geographical distribution. The purpose of this work was to evaluate the pathogenicity of biological formulations of Beauveria bassiana and Metarhizium anisopliae applied to the fed nymphs and adults of R. sanguineus under laboratory conditions. The following treatments were evaluated: control, distilled water with tween 80, emulsible concentrated, cellulose polymerized gel, fungus mixed with emulsible concentrated, fungus mixed with cellulose polymerized gel and fungus mixed with emulsible concentrated and cellulose polymerized gel. Each treatment was repeated ten times. The survival of fed nymphs and unfed adults was evaluated on the 5th, 10th, 15th and the 20th days after treatments. Significant differences were observed between the treatments (p<0.05). The treatment with M. anisopliae mixed with emulsible concentrated and cellulose polymerized gel showed the lower survival on the 15th and 20th days after treatment. We can conclude that the fungi formulation is harmful to fed nymphs and unfed adults of R. sanguineus in vitro, on this account it is suggested its use for the microbial control of this tick.

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PMID: 16229753 [PubMed - indexed for MEDLINE]

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Efficacy of imidacloprid/permethrin and fipronil/(S)-methoprene combinations against Haemaphysalis longicornis ticks evaluated under in vitro and in vivo conditions.

Hagimori I, Machida H, Goi R, Mencke N.

Narita Animal Science Laboratory Co., Ltd., 680 Tokura, Tomisato-city, Chiba 286-0212, Japan.

Haemaphysalis longicornis is one of the most important ticks infesting a wide range of mammals including dogs in Japan. H. longicornis is recorded to be a vector of, for example, Babesia gibsoni. It was the aim of the study presented here to evaluate the efficacy of imidacloprid/permethrin and fipronil/(S)-methoprene against larval, nymphal and adult stages of H. longicornis under in vitro as well as in vivo conditions. In the in vitro part of the study, ticks showed avoidance behaviour to imidacloprid/permethrin-treated filter papers. The onset of acaricidal efficacy in the imidacloprid/permethrin group was recorded earlier than in the fipronil/(S)-methoprene group. In the in vivo experiment three beagles per group were treated with either imidacloprid/permethrin, fipronil/(S)-methoprene or left untreated. Each dog was infested with 30 adult female H. longicornis. Ticks were place on a shaved area of skin of the treated dogs and behaviour of the ticks was recorded as before. After 3 h all ticks were removed and placed in Petri dishes. Ticks were further examined until day 4 post-treatment (p.t.). All ticks recovered from the untreated dogs survived. At 4 h p.t. (1 h post-removal) 40 of the 90 ticks exposed to the imidacloprid/permethrin treatment and 25 of the 90 ticks in the fipronil/(S)-methoprene-treated group were found dead. At day 1 p.t., 61 ticks in the imidacloprid/permethrin- and 81 ticks in the fipronil/(S)-methoprene-treated group were recorded dead. At the final examination day 4 p.t., all 90 ticks were found dead in the imidacloprid/permethrin group, while five ticks remained alive in the fipronil/(S)-methoprene group.

PMID: 16228268 [PubMed - in process]

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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. bautista.carlos@inifap.gob.mx

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.

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PMID: 16170567 [PubMed - indexed for MEDLINE]

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Hemorrhagic disease in dogs infected with an unclassified intraendothelial piroplasm in southern Brazil.

Loretti AP, Barros SS.

Section of Veterinary Pathology, Department of Veterinary Clinical Pathology, Faculty of Veterinary Medicine, Federal University of Rio Grande do Sul UFRGS, CEP 91540-000, Porto Alegre, RS, Brazil. aloretti@uoguelph.ca

A hemorrhagic disease affecting dogs in Brazil, referred to popularly as "nambiuvú" (bloody ears) and believed to be transmitted by ticks, has been observed in animals infected with an organism described originally in 1910 as a piroplasm, and known locally as Rangelia vitalli. In this series of 10 cases, the disease was characterized by anaemia, jaundice, fever, spleno- and lymphadenomegaly, hemorrhage in the gastrointestinal tract, and persistent bleeding from the nose, oral cavity and tips, margins and outer surface of the pinnae. The ixodid ticks Rhipicephalus sanguineus and Amblyomma aureolatum infested affected dogs from suburban and rural areas, respectively. Laboratory findings included regenerative anaemia, spherocytosis, icteric plasma and bilirubinuria. Those intracellular organisms were found in bone marrow smears but not in blood smears. Microscopically, zoites were seen within the cytoplasm of blood capillary endothelial cells. Parasitized and non-parasitized endothelial cells were positive immunohistochemically for von Willebrand factor (vWF). Langhans-type multinucleate giant cells were observed in the lymph nodes and choroid plexus. There was prominent erythrophagocytosis by macrophages in the lymph node sinuses and infiltration of the medullary cords by numerous plasma cells. Ultrastructurally, this organism had an apical complex that included a polar ring and rhoptries but no conoid. This parasite was contained within a parasitophorous vacuole that had a trilaminar membrane with villar protrusions and was situated in the cytoplasm of capillary endothelial cells. This organism tested positive by immunohistochemistry for Babesia microti. This pathogen was also positive by in situ hybridization for B. microti. Tentative clinical diagnosis in these cases was based on the history, clinical picture, haemogram and favorable response to therapy, and confirmed through microscopic examination of smears from the bone marrow or histological sections of multiple tissues, especially lymph nodes where zoites were most frequently found. The disease was reproduced by intravenous inoculation of blood from a naturally infected dog into an experimental dog. The authors demonstrate in this study that this organism is a protozoa of the phylum Apicomplexa, order Piroplasmorida. This piroplasm seems to be different from Babesia since it has an intraendothelial stage. Molecular phylogenetic analysis is necessary to better characterize this parasite and clarify its taxonomic status.

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PMID: 16153781 [PubMed - indexed for MEDLINE]

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Evaluation of the inhibitory activities of the extracts of Indonesian traditional medicinal plants against Plasmodium falciparum and Babesia gibsoni.

Murnigsih T, Subeki , Matsuura H, Takahashi K, Yamasaki M, Yamato O, Maede Y, Katakura K, Suzuki M, Kobayashi S, Chairul , Yoshihara T.

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

Twenty-four kinds of water extracts derived from 22 plants that are traditionally used for the treatment of malaria on Java Island, Indonesia, were screened for their antibabesial and antimalarial activities. Among the extracts, 8 extracts displayed strong antimalarial activity, with an inhibition range from 89.6 to 100%, and 15 showed strong antibabesial activity, with an inhibition range from 84.2 to 98.1%. The extracts of Achillea millefolium, Baeckea frutenscens, Brucea javanica, Curcuma xanthorrhiza, Strychnos lucida and Swietenia macrophylla showed both strong antibabesial and antimalarial activities. The antimalarial activities paralleled the antibabesial activities, but the converse was not true.

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PMID: 16141673 [PubMed - indexed for MEDLINE]

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Determination of prevalence and risk factors of infection with Babesia in small ruminants from Greece by polymerase chain reaction amplification.

Theodoropoulos G, Gazouli M, Ikonomopoulos JA, Kantzoura V, Kominakis A.

Department of Anatomy and Physiology of Farm Animals, Faculty of Animal Science, Agricultural University of Athens, 75 Iera Odos Street, Votanikos, 11855 Athens, Greece. gtheo@aua.gr

A total of 124 blood samples were collected from 92 sheep and 32 goats from 21 randomly selected herds located in two regions of Greece. Data on the characteristics of the animals (species, gender, age, tick burden, presence of haemoglobinuria, prior treatment for babesiosis) and the herd (location, size, species of animals, dogs associated with the herds, tick burden of dogs associated with the herds) were collected through questionnaires. Nineteen animals (15%) produced the DNA fragment specific for Babesia of which 16 were sheep and three were goats. Nucleotide sequence of PCR products revealed 100% homology with Babesia ovis 18S rRNA gene. Nine farms (43%) were found positive for B. ovis. The percentage of positive animals in each farm varied between 10 and 61%. The relative risk of the presence of ticks in sheep and goats (p<0.01) and farm dogs (p<0.01) for PCR-positive results for B. ovis in sheep and goats was found 6.63 and 4.14, respectively.

PMID: 16139956 [PubMed - indexed for MEDLINE]


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