Persistent Babesial Parasitemia
ABSTRACT & COMMENTARY
Synopsis: Untreated, asymptomatic babesial infection may persist for many months. Treatment with clindamycin and quinine reduces the duration of parasitemia, but infections can still recrudesce.
Source: Krause PJ, et al. Persistent parasitemia after acute babesiosis. N Engl J Med 1998;339:160-165.
Krause and associates performed a prospective study from 1991 to 1996 to detect seroconversion and illness among the residents of communities in southeastern Connecticut and Block Island, RI. Forty-six babesia-infected subjects were identified and were monitored every three months for up to 27 months by thin blood smears, polymerase chain reaction (PCR) assays, serology, and questionnaires.
Approximately 25% of infections were detected through a serologic survey, in which the subjects were minimally symptomatic and were not treated. Another 25% of infections were detected in a survey of patients already diagnosed with Lyme disease. These patients did not receive specific antibabesial therapy because their symptoms had improved with treatment for Lyme disease. The remaining 50% of the subjects had symptoms of acute babesiosis and were treated with clindamycin 600 mg and quinine 650 mg orally every eight hours for 1-2 weeks. Almost half of these treated subjects developed drug-related side effects from therapy.
Babesia parasites were initially detectable by microscopy in all treated subjects and two of the untreated subjects, but no parasites could be found one week after the onset of illness. Babesial DNA was detectable for a mean of 16 days in the subjects treated with clindamycin and quinine, compared to 82 days in the untreated subjects. Serology correlated initially with babesial DNA detection but remained positive longer than did babesial DNA. Serology correlated with babesial DNA detection initially but remained positive longer than babesial DNA.
Sixteen of the 46 patients in the study appeared to be coinfected with the Lyme spirochete, and only two received antibabesial therapy. Comparisons of babesial DNA persistence did not show an increase in the subjects coinfected with Lyme disease. However, serum obtained from one subject reacted against the Lyme spirochete as well as the agent of human granulocytic ehrlichiosis; babesial DNA was detectable in this case for 208 days.
Among the subjects who did not receive specific antibabesial treatment, the subjects in whom babesial DNA was detectable for three months or more had symptoms of babesiosis for a mean of 114 days. In the subjects in whom babesial DNA was undetectable at three months, babesial symptoms were only present for a mean of 15 days.
Interestingly, one subject had recrudescent disease after two years. He was initially asymptomatic, but babesial DNA was detected during the 5th and 17th months after microscopic detection of parasites. He then had symptoms of babesiosis, with 3% parasitemia, and responded to a one-week course of clindamycin and quinine. At that time, he was diagnosed with a primary intracapsular renal tumor. Six weeks later (27 months after initial parasitemia), he was found to have 1% parasitemia, and therapy was administered for yet another week with resolution of parasitemia.
COMMENT BY LIN H. CHEN, MD
Babesiosis is a tick-transmitted zoonosis caused by one of several intraerythrocytic protozoa in the genus Babesia. The organisms usually associated with human disease are B. microti (rodents), B. bovis, B. divergens, B. bigemina (cattle), and the recently identified, transfusion-acquired WA-1 strain. Similar to Lyme disease and human granulocyte ehrlichiosis, the organisms are transmitted by Ixodes dammini in the northeastern United States. The most common host for I. dammini is the white-footed mouse, Peromyscus leucopus. The vector for WA-1 is felt to most likely be Ixodes pacificus,1 and the vector for B. divergens, the most commonly involved pathogen in Europe, is thought to be Ixodes ricinus.2 The nymphal form of the tick is the usual vector, and they are most active from May to July.
The majority of babesiosis cases in humans have occurred in the northeastern United States, especially coastal Massachusetts, Connecticut, Rhode Island, and New York.4,8 Sporadic cases have been reported from other states, including Wisconsin, Missouri, Washington, and California.5-7 Rare cases have also been reported from Europe, including France, Great Britain, Ireland, and Yugoslavia (the very first human case in 1957),2 and one case has been reported from Taiwan.10
The clinical manifestations of babesiosis range from an asymptomatic course to a malaria-like illness with hemolysis, fever, and hemoglobinuria.1 Seroepidemiologic studies in the United States have shown most infections to be self-limited and often subclinical.3,9 In contrast, human infections reported from Europe have occurred mainly in asplenic patients, resulting in a fulminant course and a mortality rate higher than 50%.1,2
The diagnosis of babesiosis can be made by detection of parasites in blood smears or quantitative buffy coat methodology, by an indirect immunofluorescent assay for serum antibodies, or by detection of circulating babesia DNA using the PCR technique. Treatment with clindamycin and quinine is usually reserved for the patients with significant symptoms, the elderly, asplenic individuals, and immunocompromised patients.1,4 Severe, fulminant cases are treated with exchange transfusions.1,2
This study by Krause et al makes several important observations. First of all, babesial DNA determination by PCR appeared to be a more sensitive test for detection of infection than microscopic identification of the parasite on blood smears. DNA also persisted longer and correlated with symptoms of babesiosis. Second, treatment with clindamycin and quinine shortened the duration of babesial DNA detection; however, almost half the treated subjects developed side effects related to antimicrobial therapy. Third, coinfection with Borrelia burgdorferi did not appear to prolong the duration of babesial DNA detection, although coinfection with B. burgdorferi and the agent of human granulocyte ehrlichiosis may have prolonged the period of babesial DNA circulation in one subject. Finally, recrudescent disease appeared to be a possibility more than two years after initial infection, as described in one patient.
For the travel medicine practitioner, the following inferences can be made: 1) Babesiosis, often a mild, self-limiting infection, may become more persistent than previously believed; 2) Perhaps patients diagnosed with babesiosis should be treated more aggressively (e.g., even those with only mild symptoms); 3) For those patients with a history of a tick bite and/or patients diagnosed with Lyme disease or human granulocyte ehrlichiosis, one should consider testing for babesiosis to assess whether additional antibabesial therapy might also be appropriate; 4) The asplenic patient poses a greater risk for severe babesiosis and must be vigilant both during and after travel in endemic areas.