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All About Babesiosis
Information For Professionals
Causal Agent:
Babesiosis is caused by
hemoprotozoan parasites of the genus Babesia. While more than 100 species have been
reported, only a few have been identified as causing human infections. Babesia
microti and Babesia divergens have been identified in most human cases, but
variants (considered different species) have been recently reported in the United States.
Little is known about the occurrence of Babesia species in malaria-endemic areas
where Babesia can easily be misdiagnosed as Plasmodium. Reference:
Herwaldt BL, Persing DH,
Précigout EA, et al. A fatal case of babesiosis in Missouri: Identification of another
piroplasm that infect humans. Ann Int Med 1996; 124:643-65
Life Cycle:
Babesiosis is transmitted by
ixodid (hard-bodied) ticks. The ticks become infected by feeding on an infected
vertebrate animal (rodents, cattle, wild animals) or transovarially (ticks thus can be
vectors as well as reservoirs!). In the ticks, the parasites develop and
multiply. Transmission to the next vertebrate host occurs during a subsequent blood
meal of the tick. Inside the vertebrate host, the parasites invade directly the
erythrocytes (without the exo-erythrocytic liver stage required by human malaria
parasites), where they undergo successive cycles of multiplication and reinvasion.
The cycle is closed when the infected blood is ingested by a tick feeding on the mammalian
host. Babesia can also be acquired by transfusion of blood or blood products.
Geographic
Distribution:
Worldwide, but little is known
about the prevalence of Babesia in malaria-endemic countries, where misdiagnosis as
Plasmodium probably occurs. In Europe, most cases are due to B. divergens and
occur in splenectomized patients. In the United States, B. microti is the
agent most frequently identified (Northeast and Midwest), and can occur in
non-splenectomized individuals. Two variants, arguably different species, have been
reported in the U.S. states of Washington and California (WA1- type parasites) and
Missouri (MO1).
Clinical Features:
Most infections are probably asymptomatic, as indicated by serologic surveys. Manifestations of disease include fever,
chills, sweating, myalgias, fatigue, hepatosplenomegaly, and hemolytic anemia.
Symptoms
typically occur after an incubation period of 1 to 4 weeks, and can last several weeks.
The
disease is more severe in patients who are immunosuppressed, splenectomized, and/or
elderly. Infections due to B. divergens tend to be more severe (frequently fatal)
than those due to B. microti, where clinical recovery usually occurs.
Laboratory Diagnosis:
Diagnosis can be made by
microscopic examination of thick and thin blood smears stained with Giemsa.
Repeated
smears may be needed.
Diagnostic findings:
- Microscopy
-
 |
| A |
A:
Babesia microti infection, Giemsa-stained thin smear. The organisms resemble Plasmodium
falciparum; however Babesia parasites present several distinguishing
features: they vary more in shape and in size; and they do not produce pigment.
A 67
year old woman, status post-splenectomy, infection probably acquired in Long
Island (New
York).
 |
 |
B |
C |
Infection with Babesia.
Giemsa-stained thin smears. Note in B the tetrad (left side of the
image), a dividing form pathognomonic for Babesia. Note also the variation
in size and shape of the ring stage parasites (compare B and C),
and the absence of pigment. A 6 year old girl, status post splenectomy for
hereditary spherocytosis, infection acquired in the US.
- Antibody detection by indirect fluorescent antibody (IFA) test is a complementary diagnostic test
- Antibody
Detection
Diagnosis of Babesia
infection should be made by detection of parasites in patients' blood smears. However,
antibody detection tests are useful for detecting infected individuals with very low
levels of parasitemia (such as asymptomatic blood donors in transfusion-associated cases),
for diagnosis after infection is cleared by therapy, and for discrimination between Plasmodium
falciparum and Babesia infection in patients whose blood smear examinations
are inconclusive and whose travel histories cannot exclude either parasite.
- The indirect fluorescent antibody test
(IFA) is quite sensitive for B. microti infection. IFA antigen slides are
prepared using washed, parasitized erythrocytes produced in hamsters. Patients' titers
generally rise to >1:1024 during the first weeks of illness and decline
gradually over 6 months to titers of 1:16 to1:256, but may remain detectable at low levels
for a year or more. Specificity is 100% in patients with other tick-borne diseases or
persons not exposed to the parasite. Cross-reactions may occur in serum specimens from
patients with malaria infections, but generally titers are highest with the homologous
antigen.
The extent of cross-reactivity
between Babesia species is variable. A negative result with B. microti
antigen for a patient exposed on the West Coast may be a false-negative reaction for Babesia
infection. Individuals whose exposure could have occurred on the West Coast should
be tested also for antibodies to the Babesia WA1 species, because of the lack of
cross-reactivity with B. microti.
Krause PJ, Telford S RI , Ryan
R, et al. Diagnosis of babesiosis: Evaluation of a serologic test for the detection
of Babesia microti antibody. 1994; J Infect Dis 169:923-926.
- Molecular methods
- Molecular
diagnosis
In some
infections with intra-erythrocytic parasites, the morphologic characteristics observed on
microscopic examination of blood smears do not allow an unambiguous differentiation
between Babesia and Plasmodium. In such cases, the diagnosis can be
derived from molecular techniques, such as PCR using the appropriate primers. In addition,
molecular approaches will be valuable for investigating the phylogenetics of new Babesia
variants (or species) observed in recent human infections.
 |
| A |
A: 2% a garose gel analysis of a PCR diagnostic
test for detection of Babesia microti DNA. PCR was performed using primers BAB1 and BAB41.
- Lane 1: Babesia
microti positive blood specimen submitted to the CDC for reference diagnosis by Hernan
R. Chang M.D., Salem Hospital in Salem Massachusetts. The red arrow shows the diagnostic
band for Babesia microti (size: 238bp).
- Lane S: Molecular base
pair standard (50bp ladder). Black arrows show the size of standard bands.
Reference:
- Persing DH, Mathiesen D,
Marshall WF, Telford SR, Spielman A, Thomford JW, Conrad PA. Detection of Babesia
microti by polymerase chain reaction. J Clin Microbiol 1992;30:2097-103.
Isolation of
the organisms by inoculation of patient blood into hamsters or gerbils may also assist in
diagnosis. Animals inoculated with infective blood typically develop parasitemia within
1 to 4 weeks.
Treatment:
The Medical
Letter recommends clindamycin plus quinine as the drug regimen of choice.
It also notes that exchange transfusion has been used in severely ill patients with
high parasitemias, and that combinations including other drugs (such as atovaquone,
azithromycin, pentamidine, and trimethoprim-sulfamethoxazole) may also be effective.
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