Pre- and post-exposure prophylaxis of tick-transmitted babesiosis by the antimalarial drug tafenoquine

The National Institute of Allergy and Infectious Diseases awarded Tufts Medical Center Parent, Inc. (doing business as Tufts Medical Center) $506,415 on February 9, 2026, for research on pre- and post-exposure prophylaxis of tick-transmitted babesiosis using the antimalarial drug tafenoquine under the Allergy and Infectious Diseases Research program (CFDA 93.855).

The research evaluates tafenoquine's potential to prevent Babesia microti infection transmitted by Ixodes scapularis nymphs. The investigator will test whether tafenoquine administered as a three-day pre-exposure regimen prevents liver-stage sporozoite infection and whether the same regimen provides post-exposure prophylaxis against blood-stage merozoites. Work proceeds by analogy to tafenoquine's established pre-exposure prophylaxis mechanism against malaria and its known action via reactive oxygen species, with the hypothesis that this non-specific mechanism extends to B. microti sporozoites.

Performance occurs in Boston, Massachusetts, with a period of performance through January 31, 2028. Trustees of Tufts College, doing business as Tufts University School of Medicine, serves as sub-recipient and maintains tick-transmitted stabilates of the RM/NS strain of B. microti, providing Tufts Medical Center with B. microti-infected Ixodes scapularis nymphs and supporting manuscript preparation as needed. The sub-award was dated February 17, 2026.

Abstract

Human babesiosis caused by babesia microti is an emerging infectious disease in the united states. The primary vector is the nymph of the deer tick, ixodes scapularis. If infected, nymphs release b. Microti sporozoites from their salivary glands as they feed on humans. Sporozoites invade red blood cells where they undergo asexual replication to yield merozoites. Merozoites egress their host cells, causing their lysis, only to invade other red blood cells. Symptoms appear 1 to 4 weeks after the nymph has FED to repletion and typically consist of fever, chills, sweats, headache, myalgia and anorexia. Severe disease requires hospital admission and often occurs in patients with high parasitemia due to splenectomy or severe immune suppression. Despite antimicrobial therapy, complications such as severe anemia, adult respiratory distress syndrome and renal insufficiency or failure can develop. Death occurs in 2-3% of hospitalized cases. Preventive measures, which are limited to endemic area avoidance and tick exposure reduction, have failed to contain the emergence of babesiosis. No prophylaxis is available. Tafenoquine is approved for pre-exposure prophylaxis of malaria. The regimen consists of a loading dose taken for three consecutive days prior to travel and a weekly maintenance dose thereafter. In preliminary studies, we established that a three-day regimen of tafenoquine is sufficient for post-exposure prophylaxis of mice infected with blood-stage b. Microti (merozoites). In a mouse model of malaria, tafenoquine prevents liver stage infection when given prior to intravenous delivery of sporozoites. Proceeding by analogy and aware that tafenoquine acts via reactive oxygen species, i.e., in a non-specific manner, we postulate that tafenoquine is effective against b. Microti sporozoites. Accordingly, we hypothesize that tafenoquine can be used for pre-exposure and post-exposure prophylaxis of tick-transmitted babesiosis. In aim #1, we will initiate three-day regimens of tafenoquine on day 1 or day 3 after nymph repletion. Daily doses will be those identified in our preliminary studies. We will monitor parasitemia on day 2 post-repletion and every 2-4 days until day 60. We will obtain plasma every 4 days and monitor antibody titers, thereby testing whether prophylaxis is uncoupled from humoral immunity. On day 60, to confirm eradication of infection, we will perform an adoptive transfer of blood cells to RAG-deficient mice. We will seek to identify a regimen of tafenoquine that confers post-exposure prophylaxis to RAG-deficient mice, which experience severe, persistent infection, and to splenectomized mice, which experience severe, life-threatening infection. In aim #2, we will initiate three-day regimens of tafenoquine on the day of, but prior to nymph exposure. We will identify the daily dose that protects RAG-deficient mice and splenectomized mice. If successful, our work will serve as foundation for a trial of tafenoquine for post-exposure prophylaxis of tick-transmitted babesiosis. Our work may also support off- label use of tafenoquine for prophylaxis of babesiosis, particularly to individuals at risk of severe disease.