2. Introduction History Classification Structure Lifecycle
Epidemiology Pathogenesis Clinical features Diagnosis Treatment
Animal models Prevention 3. Introduction Infection due to parasites
belonging to genus Babesia B. microti B. divergens B. duncani WA-1
MO-1 KO -1 EU-1 Obligate intracellular: RBCs Requires both a
competent vertebrate and nonvertebratehost to maintain transmission
cycles Transmitted by ixodid ticks to their vertebrate hosts 4.
HistoryTheobald Smith (July 31, 1859 December 10, 1934) Along with
Kilbourne Discovered arthropod borne transmission in 1893 Cattle
Febrile heamturia : Bloodied waters of Egypt 5. History 1957- 1st
human case- Yugoslavian farmer 1968- 1st recognized in California
(USA) 1976- Ixodes dammini identified as vector for B.microti 1993-
1st description of WA-1 1996- 1st description of MO-1 6.
Classification Taxonomic Classification phylum Apicomplexa (also
called Sporozoa), class Aconoidasida (Piroplasmea) order
Piroplasmida families Babesiidae and Theileriidae; absence of a
preerythrocytic cycle in Babesia and the absence of transovarial
transmission in Theileria. 7. Initially, Babesia species identified
- morphologicalparameters of the intraerythrocytic forms (i.e.,
trophozoites) This analysis, along with host specificity, has
provided> 100 species of Babesia 7 spp. affect humans 8.
Large(2.5-5m) TransovarialSmall (1.02.5m) TransstadialBabesiosis,
HOMER et.al. CMR, July 2000, p. 451469 9. Structure 10.
LifecycleReservoir White tailed deerFor all except B. meri
ornithodorrus 11. Epidemiology WA-1B. microti 300 cases Temperate
climatesB. divergens 12. Epidemiology Frequency of B. microti &
WA-1 in US > reported cases because self- limiting & mild in
humans Mortality in USA 5% Survey in California 16% prevalence WA-1
Survey of Blood donors - 3-8% prevalence B. microti Human cases of
B. microti reported Coastal areas of southern New England Eastern
Long Island Minnesota Winsconsin WA-1 throughout pacific coasts
Babesiosis, HOMER et.al. CMR, July 2000, p. 451469 13. Contd..
Sporadic cases Europe (France & British Isles),Africa, Asia
Cattle Babesia (B. divergens, B. microti) 83% Babesiosis in Europe
- B. divergens Mortality rate 42% Europe Few cases reported China,
Taiwan, Egypt, S. Africa,Mexico Transfusion- acquired Babesia
several cases in USA, but none in Europe & elsewhere 14. India
Single case report 51 year old patient from Madhya Pradesh History
Working nursing home in gwalior Fever, vomiting, headache,
arthralgia No h/o tick bite or visit to endemic area No other
family member No h/o splenectomy or blood transfusion IJMM
2005;23:267-9 15. O/E Liver and spleen palpable Scleral icterus,
passed dark coloured urine Investigations WBC count 1,900/cumm
Platelet count 55,000/cumm LDH raised 16. Peripheral blood smear
ring forms varied greatlyconfused P. Falciparum Antimalarial
treatment no response Smear reviewed pear shaped, tetrad -
babesiosis suspected HRP II negative Quinine + clindamycin Pt.
afebrile within 2 days 17. Pathogenesis EnvHost Agent 18.
Modification and rupture of RBCs Replication neoAg`s d/t membrane
alteration Docking sites for IgG and complement phagocytosis in
spleen Anemia Lack of periodicity: Asynchronous replication More
severe manifestations in immunosuppresed andelderly 19.
establishment stage antibodies (IgG) play a role inpreventing
erythrocyte infection by binding the free sporozoites. progression
stage organisms invade erythrocyte innate immune system control
growth rate of the merozoites NK cells and macrophages - soluble
factors: IFN-g by NKcells and TNF-a, nitric oxide (NO), and ROSs by
macrophages (Mf). resolution stage decrease in parasite numbers
-intracellular degeneration inside the erythrocyte, as evidenced by
the appearance of crisis forms. 20. Clinical features Disease
manifestations asexual reproductive stage Predisposing factors +/
Mild to severe illness Generalized weakness Fever Gastrointestinal
symptoms (anorexia, nausea, abdominal pain, vomiting, diarrhea,
etc.) Headache Myalgia Weight loss Arthralgia Respiratory symptoms
(cough, shortness of breath, etc.) Dark urine 21. Clinical
examination Hepatomegaly and splenomegaly Hemolytic anemia - lasts
from several days to fewmonths occur in clinically severe cases,
most commonly in asplenic or elderly 22. Pulmonary manifestations -
rare in babesiosis, butnon-cardiogenic pulmonary edema (NCPE) is
the most frequent manifestation not related degree of parasitemia
splenic function and its onset may be early or late 16 reported
cases - reviewing the literature on thepulmonary complications 23.
Common Complications Acute respiratory distress syndrome Anemia
requiring transfusion Congestive heart failure Disseminated
intravascular coagulation Hypotension/shock Myocardial infarction
Renal failure 24. HUMAN COINFECTION Coinfection with B. microti
& other tick-bornepathogens, particularly B. burgdorferi (Lymes
disease) serosurveys - 13% of Lyme disease patients in
babesia-endemic areas are coinfected with B. microti B. microti is
transmitted by the same Ixodes tick thatperpetuates the agents of
Lyme disease human granulocytic ehrlichiosis novel Bartonella
species P. leucopus is also the vertebrate reservoir for at
leastthree of the known pathogens 25. Patients coinfected with B.
microti and B. burgdorferiexperience more severe symptoms,
resulting in fatality in rare cases persistence of postinfectious
fatigue. B. burgdorferi DNA persisted for prolonged periods B.
microti - no significant effect on the duration ofparasitemia 26.
Blood transfusionSplenectomyTick biteTravel history Clinical
presentationDiagnosisAge 27. A positive Coombs test in combination
with hemolyticanemia & elevated procalcitonin levels is highly
suspicious of babesiosis Laboratory tests examination of stained
blood smears serologic evaluation with indirect (immuno)
fluorescentantibody tests (IFATs) PCR 28. Examination of thin
bloodsmears most frequently used technique Wrights or Giemsa stain
simple rings (annular), pear-shaped (pyriform), Maltese cross
(tetrad form) High parasitemia present duringacute infections
varying from 5 to 80% of erythrocytes 29. Duration of detectable
parasitemia on blood smearsvaries 3 weeks to 12 weeks with the
longest duration of smear positivity being 7 months for a
splenectomized patient Quantitative buffy coat system (QBC)
Merozoitesstained with acridine orange Simple & rapid Showed
100% correlation with blood smear exam. (Mattia et al, 1993) 30.
Distinguishing features differentiate the twoorganisms. Babesial
organisms usually form tetrads ("Maltesecross"), Do not have
hemozoin pigments within the affected red blood cells Have
extracellular merozoites 31. Serodiagnosis IFATs - B. microti
infections, chronic infections Hamster-derived B. microti Ag
Distinguish between B. microti, WA-1, B. divergens Specific and
sensitive Diagnostic titers above 1:64 Higher cutoff titers (1:128
to 1:256) greater diagnostic specificity IgM and IgG Problematic in
HIV, splenectomy Time consuming & labor intensive 32. IFAT
Antibody titers can remain elevated for as long as 13months to 6
years after infection Although persistence of antibody does not
necessarily reflect a measurable infection, levels of IgG antibody
decline less rapidly in persistently infected patients 33. ELISA
ELISA Recombinant antigen - 4 antigens used rBMN1-2 rBMN1-15
rBMN1-17 rMN-10- 27/40 - 27/40 - 27/40 - 27/40 Showed high
sensitivity & specificity Soluble whole parasite antigen (B.
divergens)Loades et al, 2000 34. Problem associated with
serological tests Relationship between antibody titers, the
presence of parasites, and the state of protective immunity is not
clearAntibodies may persist for long periods after the disease
hascleared Overestimate of disease prevalenceAntibody titers may be
observed in the absence of protective immunity 35. PCR assay Based
on universal primer amplification of a fragmentof the small subunit
rRNA gene Highly conserved among babesias Heterologous between
Babesia spp. and other intraerythrocytic protozoal parasites as
well as within the genus Babesia itself Distinguishes readily
between B. divergens, B. microti, and Plasmodium spp., it provides
a valuable adjunctive 36. Advantages over IFA testing. Less time
consuming conducted by generalist technicians more readily be
standardized sensitivity and specificity comparable to those of
conventional IFAs 37. MASP(microaerophilous stationary phase)
culture technique Quantities of parasite nucleic acid needed for
defining phylogenetic relationships of these species,Methods for
detection of the parasite in otherwise asymptomatic
individualsProducing parasite antigensAttenuated strains of Babesia
- immunization. 38. Laboratory diagnosis B. microti immunoblot kits
Animal Inoculation 2-4 weeks Sensitive (300 org./ml blood) Time
consuming, expensive 39. Animal models Rats BALB/ c mice
Splenectomized calves Gerbils 40. Treatment 41. Imidocarb and the
combination of oxomemazine andphenamidine were most effective in
vitro Imidocarb, although not licensed for human use, mosteffective
agent for treating B. divergens infections incattle other
pharmacologic interventions -chloroquine, tetracycline, primaquine,
sulfadiazine, and pyrimethamine 42. Prevention Avoidance of or
minimization of exposure to tick infested areas Ase of tick
repellents before entering a tick-infested area thorough
examination of skin after exposure. Ticks found before attachment
-removed, and Ticks found after attachment removed within 24 h
limit the possibility of transmission Application of pesticide to
host nests and on the coats of reservoir hosts can interrupt
transmission 43. Vaccines Live vaccines living parasites cattle
Recombinant vaccines B. bovis & B. bigemina vaccine cattle
Soluble parasite antigen (SPA) No effective B. microti vaccine
Human vaccines Expt. Stage MRA gene (Maltase cross form-related
antigen) 37 kDa glycoprotein (Bd37) 44. Summary Emerging disease
Common in the Americas Can be confused with plasmodium
falciparuminfection Diagnosis requires high index of suspicion
Treatment involves use of At or Az or Clin + Quin 45. Thank you
