3. Introduction
• Infection due to parasites belonging to genus Babesia
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B. microti
B. divergens
B. duncani
WA-1
MO-1
KO -1
EU-1
• Obligate intracellular: RBCs
• Requires both a competent vertebrate and nonvertebrate
host to maintain transmission cycles
• Transmitted by ixodid ticks to their vertebrate hosts
4. History
Theobald 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 - morphological
parameters of the intraerythrocytic forms
(i.e., trophozoites)
• This analysis, along with host specificity, has provided
> 100 species of Babesia
• 7 spp. affect humans
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. 451–469
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
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 and
elderly
19.
20. • establishment stage antibodies (IgG) play a role in
preventing 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 NK
cells 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.
21. Clinical features
• Disease manifestations asexual reproductive stage
• Predisposing factors +/• Mild to severe illness
– Generalized weakness
– Fever
– Gastrointestinal symptoms (anorexia, nausea, abdominal
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pain, vomiting, diarrhea, etc.)
Headache
Myalgia
Weight loss
Arthralgia
Respiratory symptoms (cough, shortness of breath, etc.)
Dark urine
22. Clinical examination
Hepatomegaly and splenomegaly
Hemolytic anemia - lasts from several days to few
months occur in clinically severe cases, most
commonly in asplenic or elderly
23. Pulmonary manifestations - rare in babesiosis, but
non-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 the
pulmonary complications
25. HUMAN COINFECTION
• Coinfection with B. microti & other tick-borne
pathogens, particularly B. burgdorferi (Lymes disease)
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serosurveys - 13% of Lyme disease patients in babesia-endemic
areas are coinfected with B. microti
• B. microti is transmitted by the same Ixodes tick that
perpetuates the agents of
Lyme disease
• human granulocytic ehrlichiosis
• novel Bartonella species
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• P. leucopus is also the vertebrate reservoir for at least
three of the known pathogens
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27. • Patients coinfected with B. microti and B. burgdorferi
experience
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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 of
parasitemia
29. A positive Coombs test in combination with hemolytic
anemia & elevated procalcitonin levels is highly
suspicious of babesiosis
Laboratory tests
examination of stained blood smears
serologic evaluation with indirect (immuno) fluorescent
antibody tests (IFATs)
PCR
30. Examination of thin blood
smears
most frequently used technique
Wright’s or Giemsa stain
simple rings (annular),
pear-shaped (pyriform),
Maltese cross (tetrad form)
High parasitemia present during
acute infections
varying from 5 to 80% of
erythrocytes
31. • Duration of detectable parasitemia on blood smears
varies
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3 weeks to 12 weeks with the longest duration of smear
positivity being 7 months for a splenectomized patient
• Quantitative buffy coat system (QBC) – Merozoites
stained with acridine orange
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Simple & rapid
Showed 100% correlation with blood smear exam.
(Mattia et al, 1993)
32. Distinguishing features differentiate the two
organisms.
Babesial organisms usually form tetrads ("Maltese
cross"),
Do not have hemozoin pigments within the affected red
blood cells
Have extracellular merozoites
33. 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
34. IFAT
Antibody titers can remain elevated for as long as 13
months 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
36. Problem associated with
serological tests
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Relationship between antibody titers, the presence of
parasites, and the state of protective immunity is not clear
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Antibodies may persist for long periods after the disease has
cleared
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Overestimate of disease prevalence
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Antibody titers may be observed in the absence of protective
immunity
37. PCR assay
• Based on universal primer amplification of a fragment
of 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
38. Advantages over IFA testing.
Less time consuming
conducted by generalist technicians
more readily be standardized
sensitivity and specificity comparable to those of
conventional IFAs
39. 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 individuals
Producing parasite antigens
Attenuated strains of Babesia - immunization.
43. Imidocarb and the combination of oxomemazine and
phenamidine were most effective in vitro
Imidocarb, although not licensed for human use, most
effective agent for treating B. divergens infections in
cattle
other pharmacologic interventions -
chloroquine, tetracycline, primaquine, sulfadiazine, an
d pyrimethamine
44. Prevention
• Avoidance of or minimization of exposure to tick•
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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
45. 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)
46. Summary
Emerging disease
Common in the Americas
Can be confused with plasmodium falciparum
infection
Diagnosis requires high index of suspicion
Treatment involves use of At or Az or Clin + Quin