Abstract
Human babesiosis is an emerging tick-borne disease caused by apicomplexan parasites of the genus Babesia Clinical cases caused by Babesia duncani have been associated with high parasite burden, severe pathology, and death. In both mice and hamsters, the parasite causes uncontrolled fulminant infections, which ultimately lead to death. Resolving these infections requires knowledge of B. duncani biology, virulence, and susceptibility to anti-infectives, but little is known and further research is hindered by a lack of relevant model systems. Here, we report the first continuous in vitro culture of B. duncani in human red blood cells. We show that during its asexual cycle within human erythrocytes, B. duncani develops and divides to form four daughter parasites with parasitemia doubling every ∼22 h. Using this in vitro culture assay, we found that B. duncani has low susceptibility to the four drugs recommended for treatment of human babesiosis, atovaquone, azithromycin, clindamycin, and quinine, with IC50 values ranging between 500 nm and 20 μm These data suggest that current practices are of limited effect in treating the disease. We anticipate this new disease model will set the stage for a better understanding of the biology of this parasite and will help guide better therapeutic strategies to treat B. duncani-associated babesiosis.
Highlights
Human babesiosis is an emerging tick-borne disease caused by apicomplexan parasites of the genus Babesia
Using this in vitro culture assay, we found that B. duncani has low susceptibility to the four drugs recommended for treatment of human babesiosis, atovaquone, azithromycin, clindamycin, and quinine, with IC50 values ranging between 500 nM and 20 M
Human babesiosis is an emerging disease caused by apicomplexan Babesia parasites that are closely related to Plasmodium and Theileria species, the agents of malaria and theileriosis, respectively
Summary
Human babesiosis is an emerging tick-borne disease caused by apicomplexan parasites of the genus Babesia. Clinical cases caused by Babesia duncani have been associated with high parasite burden, severe pathology, and death. We show that during its asexual cycle within human erythrocytes, B. duncani develops and divides to form four daughter parasites with parasitemia doubling every ϳ22 h Using this in vitro culture assay, we found that B. duncani has low susceptibility to the four drugs recommended for treatment of human babesiosis, atovaquone, azithromycin, clindamycin, and quinine, with IC50 values ranging between 500 nM and 20 M. The first clinical cases of human babesiosis caused by B. duncani were reported in Washington State and California in 1991 and 1991–1993, respectively [12, 13] The majority of these cases were transmitted by an arthropod vector, whereas three cases were due to blood transfusion (14 –16). Whereas B. microti infections in immunocompetent hosts start with an initial phase of high parasitemia, anemia, and splenomegaly and end with a decline in parasitemia and recovery [17, 18], infections with B. duncani result in a rapid increase in par-
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