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Avoidance of tick bites remains the mainstay of prevention, and patients should be educated to use insect repellents as directed. Diagnosis

Patients who remain asymptomatic following a tick bite do not require evaluation as there is no prophylaxis for babesiosis, HME, or HGA, and treating asymptomatic individuals even if they test positive for these diseases is not recommended by the Infectious Diseases Society of America (IDSA).Antibiotic prophylaxis for Lyme disease is generally not recommended by IDSA, except under certain circumstances.12 Due to limitations in diagnostic testing, clinical diagnosis that takes into consideration epidemiologic, geographic, and laboratory features is most practical. For example, exposure to ticks in an endemic area during spring or summer in a patient who develops febrile illness, leukopenia, or thrombocytopenia is strongly suggestive of HME and is sufficient justification for treatment.4 Testing for Lyme disease should be considered in patients diagnosed with babesiosis and HGA as coinfection with the Ixodes tick vector is common. In symptomatic individuals, the standard to diagnose babesiosis, HME, and HGA is light microscopy of Giemsa-stained peripheral blood smears. Babesia can be seen within erythrocytes in its ringform trophozoite and tear drop-shaped merozoite stages, which classically but rarely appear as a “Maltese-cross” tetrad. The observation of extracellular ring forms is also suggestive of Babesia.10 The presence of characteristic intracytoplasmic morulae (membrane-bound vacuoles with irregular edges containing clustered purple or blue colonies of gram-negative bacteria) on buffy coat examination are highly suggestive of HME (if in monocytes) or HGA (in granulocytes). Absence of morulae does not rule out infection as they are present in 1% to 20% of patients with HME and in 20% to 80% of patients with HGA.4 If initial smears are negative but clinical suspicion is high, subsequent smears may be obtained over a period of days to increase yield. Polymerase chain reaction (PCR) testing is available for Babesia, HME, and HGA. It is more sensitive than microscopy so is useful when parasitemia is very low; it can also distinguish between Babesia species.3 The reported sensitivity of PCR for HGA varies from 60% to 70% and from 52% to 87% for HME.4 If symptoms persist but microscopy has been negative, repeat blood smear and PCR testing should be performed. Of note, parasite DNA may be detectable by PCR for several months following completion of antibiotic therapy and resolution of symptoms.3 The preferred and most widely available method of diagnosis of HME and HGA is the indirect fluorescent antibody (IFA) test that can be obtained through state health departments.4 The IFA test is 94% to 100% sensitive if the second

sample is obtained 2 weeks after the onset of symptoms; a 4-fold rise is considered positive.4 An important limitation of the test is that antibodies first become detectable 2 to 3 weeks after the onset of the illness. Enzyme-linked immunosorbent assay (ELISA) testing is also available. Serology is of limited use in acute disease but provides retrospective evidence of infection; a 4-fold rise in titers confirms recent infection. Because serologic cross reactivity can occasionally occur between E chaffeensis and A phagocytophilum, it is not possible to reliably differentiate between these 2 infections with a single serologic assay.4 Treatment

The preferred treatment of babesiosis for adults is azithromycin 500 mg orally on day 1, followed by 250 mg orally plus atovaquone 750 mg orally every 12 hours to complete 7 to 10 days of therapy. The therapy is weight-based for children.An alternative regimen includes clindamycin plus quinine, which has the same efficacy but with a higher side effect profile. Symptoms usually begin to improve within 48 hours of initiating antimicrobial therapy and resolve within 1 to 2 weeks. Management of severe babesiosis consists of hospitalization, antimicrobial therapy, and, in some cases, red blood cell exchange transfusion for parasitemia >10%, severe hemolysis, or organ failure.4 Treatment should be initiated in all patients suspected of having HME or HGA.The medication of choice in all patients, including children and pregnant women, is doxycycline.This is also the preferred therapy for spotted fever rickettsiosis, the disorder most frequently confused with HME and Lyme disease.4 Doxycycline can be given orally or intravenously at 100 mg twice daily for 10 days or for 3 to 5 days after fever abates.4 Patients who have intolerance or allergy to tetracyclines can be treated with rifampin 300 mg twice daily for 7 to 10 days. Prognosis

Mild to moderate babesiosis in immunocompetent patients is usually associated with <4% parasitemia and does not require hospital admission.3 Severe babesiosis is often associated with parasitemia ≥4% and is more likely to lead to complications and/or persistent or relapsing disease. Of 34 cases of babesiosis on Long Island, acute respiratory failure and DIC proved to be the 2 most common complications, occurring in 7 out of 34 cases and 6 out of 34 cases, respectively.13 In HME and HGA, delay in treatment with doxycycline was associated with increased rates of mechanical ventilation and prolonged hospitalization.3 Estimated mortality rates have been 2% to 5% for HME and as high as 7% to 10% for HGA.4 Life-threatening • THE CLINICAL ADVISOR • JUNE 2019 35

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June 2019 Clinical Advisor  

June 2019 Clinical Advisor