A 71-year-old man presented to the emergency department with two weeks of recurrent fevers and chills. He had recently returned from a trip to his cabin in northern Minnesota approximately two weeks earlier. He recalled many mosquito bites but no tick bites. Laboratory evaluation showed elevated liver transaminases, mild anemia, and leukopenia. A peripheral smear of his blood is pictured below.
The correct answer is ...
West Nile virus.
This patient is infected with Babesia microti, a protozoan (Apicomplexan) tick-transmitted blood-borne parasite.1 Clinical disease typically begins 1–4 weeks after transmission from an infected tick. Typical symptoms include fatigue, malaise, fever, and chills, and frequent laboratory abnormalities include thrombocytopenia, elevated liver transaminases, and hemolytic anemia. Up to half of patients require hospital admission, and illness is more severe among asplenic and immunocompromised patients.2,3
Diagnostic testing for babesiosis includes direct examination of blood films for parasites and nucleic acid amplification (NAAT) detection. Giemsa-stained thick and thin blood smears should be examined and may detect as little as 0.0002–0.001% parasitemia.4 Microscopic features include delicate, pleomorphic ring forms, multiply‐infected erythrocytes, and extracellular forms.
The classic “Maltese cross” tetrad formation is occasionally seen and is pathognomic (Figure 1). Hemozoin, schizonts, and gametocytes are not seen with Babesia, and the presence of these elements suggests Plasmodium infection. NAATs are considered to have excellent sensitivity and specificity.4 While no NAATs are currently FDA-approved for the clinical diagnosis of babesiosis, reference laboratories may offer laboratory-developed molecular assays. Several NAATs are FDA-approved for testing of donor blood and tissue. Serology may be used for supportive or confirmatory testin; however, it cannot distinguish between recent and prior infection.5
In North America, the primary mode of transmission of Babesia is Ixodes ticks (the blacklegged “deer” tick). These ticks are endemic to the Northeast, upper Midwest, and South United States (I. scapularis) and the west coast (I. pacificus).2,6 Most cases of babesiosis occur during the summer and early fall in endemic areas where ticks and vertebrate reservoirs overlap with human activity.5,7 While B. microti is responsible for most clinical infections in the Unites States, other clinically important species include B. duncani, B. divergens, and B. venatorum. There are several other significant pathogens that may be carried by Ixodes ticks, and co-infection presents a challenge for both diagnostics and clinical management. These pathogens include Borrelia burgdorferi (Lyme disease), B. miyamotoi (hard tick-borne relapsing fever), Anaplasma phagocytophilum (human granulocytic anaplasmosis, HGA), Ehrlichia muris-like agent, and tick-borne flaviviruses including Powassan virus and tick-borne encephalitis virus.6
Co-infection appears to be common in nature, with up to 28% of ticks in endemic areas co-infected with either B. burgdorferi, A. phagocytophilum, or Babesia spp.8 In humans, up to 40% of patients with Lyme disease are co-infected with Babesia spp.6 There is growing evidence that co-infection may have important clinical consequences. Studies indicate that in patients with Lyme disease, co-infection with babesiosis or HGA may exacerbate and prolong symptoms.9,10 Clinicians practicing in endemic areas should maintain a high index of suspicion for co-infections, especially in cases of atypical or severe manifestations, or poor response to therapy.
West Nile virus is a mosquito-transmitted flavivirus maintained in reservoir bird populations. While most human infections with WNV are asymptomatic, around 20% develop fever, and less than 1% develop neurologic disease.2 Neurologic manifestations are diverse and include encephalitis, meningitis, cranial neuropathies, and acute flaccid paralysis. Mortality ranges from 4%–14% among patients with neurologic disease, and long-term sequalae are common.11 The diagnosis is most commonly made by detection of WNV-specific antibodies in acute or convalescent serum or cerebrospinal fluid.12
James Vaillant, M.D., M.S.
Fellow, Clinical Microbiology
Bobbi Pritt, M.D.
Consultant, Laboratory Medicine and Pathology
Consultant and Division Chair, Clinical Microbiology
Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science