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Back To Vidyya 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

    • B. microti
      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).

      Babesia tetrads Babesia

      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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