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Human Babesiosis – An Update Patricia J. Holman Department of Veterinary Pathobiology College of Veterinary Medicine and Biomedical Sciences Texas A&M.

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Presentation on theme: "Human Babesiosis – An Update Patricia J. Holman Department of Veterinary Pathobiology College of Veterinary Medicine and Biomedical Sciences Texas A&M."— Presentation transcript:

1 Human Babesiosis – An Update Patricia J. Holman Department of Veterinary Pathobiology College of Veterinary Medicine and Biomedical Sciences Texas A&M University College Station, TX

2 Babesiosis Emerging tick-borne disease Zoonosis caused by intraerythrocytic protozoan parasites Infections may range from asymptomatic to severe, or even fatal Most cases occur in the U.S.; worldwide where ticks occur

3 Phylum – Apicomplexa –Babesia, Plasmodium, Toxoplasma, Cryptosporidium –Unique organelles comprise apical complex Electron micrograph courtesy of Dr. R.E. Droleskey USDA College Station, TX

4 Babesia - Two-host life cycle Sexual reproduction in the vector tick Asexual reproduction in mammalian red blood cells


6 Babesia divergens Tick transovarial transmission

7 Babesiosis Symptoms 1-6 wks after tick feeds Variable –Asymptomatic infection –Mild to moderate illness –Severe disease – usually immunosuppressed Medication Splenectomy HIV co-infection Malignancy

8 Babesiosis Symptoms –Fatigue –Intermittent fever Chills, sweats, headache, arthralgia, anorexia, cough, nausea Asymptomatic infection Clinical Presentation –Fever, pallor –Splenomegaly –Hepatomegaly May last a week or months Prolonged recovery; persistent parasitemia

9 Babesiosis – Severe form Most common complications –Respiratory failure –Congestive heart failure –DIC –Liver and kidney failure –Splenic rupture –Immunocompromised – 21% mortality

10 Diagnosis CBC –Hemolytic anemia with elevated reticulocytes –Thrombocytopenia –Normal to slightly decreased leukocyte count Blood chemistry –Elevated serum liver enzymes (~ ½ of patients) –Proteinuria, elevated blood urea nitrogen and serum creatinine

11 Diagnosis Microscopic identification –Giemsa stained thick or thin blood films –Babesia ring forms can be mistaken for malaria Serology - IFA –B. microti B. duncani does not cross-react –B. divergens Sera from B. divergens or B. ventorum patients cross react

12 Diagnosis Polymerase chain reaction –Highly sensitive and specific –Useful for extremely low parasitemias Confirm infection Determine species FISH –Detects Babesia DNA in patient blood film –Specific probe binds to DNA –Highly specific; not as sensitive as PCR IGeneX

13 Diagnosis Subinoculation into laboratory animals –2-4 weeks for parasites to appear in circulation –Hamster – Babesia microti –No known laboratory host for all of the human Babesia spp.

14 Treatment Atovoquone/azithromycin 7-10 days –B. microti infections –15% adverse reactions –Diarrhea and rash Clindamycin/quinine 7-10 days –Recommended for severe babesiosis –72% adverse reactions –Diarrhea; tinnitus and hearing loss Exchange transfusion - severe illness

15 Prevention Avoid areas with ticks, mice and deer –Especially May-October –Especially immune compromised people Anti-tick strategies –Long sleeves, long pants tuck cuffs into socks –Pyrethrins on clothing –DEET on exposed skin –Check for and remove ticks promptly after possible exposure

16 Prevention II Property –Keep grass short –Remove leaf litter –Discourage mice Seal potential den holes Pyrethrin treated cotton –Discourage deer Deer proof plants Fencing

17 Prevention III Transfusion risk –No FDA approved test for donated blood –Agencies prohibit donations by people who live in or visit endemic areas –Research ongoing for ways to inactivate organisms in blood

18 Zoonotic Babesia spp. Europe –Babesia divergens - France, Ireland, Great Britain (cattle production) –Babesia venatorum – Austria, Italy, Germany –Babesia microti Asia, Africa, and South America –Babesia microti-like –B. divergens-like –Ovine Babesia-like

19 Babesia divergens Most cases occur in France & British Isles –30 reported human cases –Associated with cattle –84% asplenic patients; 42% fatality rate –Infection is considered a medical emergency Hosts –Cattle, small mammals –Ixodes ricinus

20 Babesia venatorum Three documented cases –All asplenic and > 50 years –Mild to severe, but not fatal Parasites – typical paired pyriform Hosts –Roe deer –Ixodes ricinus

21 Zoonotic Babesia spp. United States –Babesia microti - Northeast and upper midwest –Babesia duncani – Washington state (WA1-3) –California CA1-6 (similar to B. duncani ?) –Babesia divergens-like – MO-1 and KY (Nantucket Island) –Babesia divergens-like – Washington state

22 Babesia microti Most cases occur in the U.S. –> 300 known cases – not a reportable disease –Variable severity of disease Most symptomatic cases mild and self-limiting Immune suppressed or >50 yrs at higher risk of severe disease 5% mortality rate –Tick transmission May-October –Transfusion or blood product associated cases –Neonatal cases

23 Babesia microti U.S. endemic regions –Ixodes scapularis –White footed mouse –White-tailed deer maintain the vector tick –B. microti cannot infect deer Parasites in tetrads in paired form

24 Babesia microti Not considered a major human pathogen in Europe –High prevalence in rodents –Ixodes trianguliceps vector tick – nest dwelling –Ixodes ricinus

25 Babesia duncani Washington and California Five cases –Spleen intact individuals –Subclinical to severe illness –2 were acquired via transfusion Seroprevalence 4 to 17% Tick vector and reservoir host unknown Parasites in tetrads in paired form

26 Babesia divergens-like One case in Washington state –Asplenic, > 50 years –Similar molecularly to Babesia divergens –Tick and reservoir host not known

27 Babesia divergens-like Two cases - MO-1 and KY –Both asplenic, > 50 years –Both severe disease, 1 death –Parasite endemic on Nantucket Island Eastern cottontail rabbits Ixodes dentatus Not infective to cattle No human cases on Nantucket Island

28 Babesia divergens-like cases of Human Babesiosis KY isolate –Critically ill man admitted to emergency room in Kentucky Fever Chills Bloody urine Immediately started on doxycycline – Ehrlichiosis ?

29 Babesia divergens-like KY Blood smear - Numerous babesia organisms History –Splenectomy 9 years previously –Tick exposure Recreational hunter WTD and cottontail rabbits

30 Diagnosis and Treatment Negative for Ehrlichia and Babesia microti *** Babesia divergens *** (Beattie et al. 2002) Pathology - Asplenic Morphology 18S rRNA gene sequence Hospitalized for 12 days TX: Clindamycin, quinine, and doxycycline

31 MO-1 –Fever, chills, headache, sore throat, and joint pain –No improvement with erythromycin –Fatal infection (Herwaldt et al, 1996) –MO-1 18S rRNA gene identical to KY B. divergens-like MO-1

32 Nantucket (rabbit isolate) –KY/MO-1 18S rRNA gene identical to NR (Goethert & Telford 2003) –16% of rabbits positive by PCR –Ixodes dentatus ticks, larval to nymphal stage 4% + B. divergens-like NR


34 Babesia divergens Discrepancies Tick vector ? Neither patient had traveled outside of the US No known infection in U.S. cattle despite high cattle population in Kentucky and dairies on Nantucket Island

35 rRNA ITS1 & ITS2 Percent Identities KYNRBdiv KY100 94 NR 100 94 Bdiv 90 100 SSUrRNAITS15.8SITS2LSUrRNA

36 Infection Studies Source of parasites needed –No blood from the case Rabbits –Limited by extremely low circulating parasitemias In vitro culture –Produce quantities for additional characterization –Collaboration with Goethert and Telford, Tufts University

37 Host erythrocyte specificity in vitro ParasiteHost RBCSerum supplement Nantucket Rabbit (NR774) B. divergens Human Bovine Cottontail rabbit Human Bovine Cottontail rabbit Human Bovine Human Bovine Human Growth Yes No Yes No

38 Results - Morphometric ParasiteHost RBCSize Stddev NR Human Cottontail rabbit Bovine 4.3 µm ± 0.48 4.2 µm ± 0.56 N/A Bdiv Human Bovine Cottontail rabbit 3.1 µm* ± 0.53 2.2 µm ± 0.36 N/A KY Human (blood) 4.1 µm ± 0.58

39 Cattle Infection Study

40 Conclusions KY and NR are conspecific –Identical 18S rRNA gene sequence –Identical ITS1 / ITS2 sequences –Size - large babesia –Morphology B. divergens distinct –ITS1 and ITS2 sequences vary from KY/NR –Size - small babesia in natural host –Morphology –Infective for cattle –Culture – Bovine RBC, not cottontail rabbit

41 Babesia divergens is not endemic in the U.S.

42 Acknowledgements Dr. Andy Allen, Washington State University, Pullman, WA Dr. Jim Beattie, Bowling Green Associated Pathologists, KY Dr. Bob Droleskey, USDA, College Station, TX Dr. Heidi Goethert, Tufts University, MA Dr. Sam Telford, Tufts University, MA Dr. Will Goff, USDA, Pullman, WA Dr. Don Knowles, USDA, Pullman, WA Angela Spencer & Lorien Schoelkopf Funding: NIH RO3, USDA/ARS, Texas Agricultural Experiment Station

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