For the tick-borne infection babesiosis, adding the antimalarial drug tafenoquine may be a lifesaver for vulnerable patients who relapse after standard treatment, according to a new study by researchers at the Yale School of Public Health (YSPH).
“Tafenoquine is going to make a huge difference, I think, in people who are severely immunocompromised,” said Peter J. Krause,MD, a senior research scientist in the YSPH Department of Epidemiology of Microbial Diseases and first author of the study, which was conducted in collaboration with researchers at Brown University and Tufts Medical Center.
Alongside Lyme disease and anaplasmosis, babesiosis is one of the most common tick-borne diseases in the world. It is endemic in the Northeast, upper Midwest, and northeastern China. The infection typically results in fevers as well as soaking sweats, chills, headache, malaise, joint and muscle pain, and/or weakness.
The disease is caused by parasitic microorganisms of the genus Babesia, and has long been known to infect cattle, mice, and other animals. It was first reported in humans in 1957. As with malaria, the parasite invades red blood cells. That similarity intrigued researchers who first considered using tafenoquine in babesiosis.
Tafenoquine is going to make a huge difference ... in people who are severely immunocompromised.
Peter J. Krause, senior research scientist
In most people, babesiosis treatment is straightforward. Weakened immunity due to age (over 50 years), certain cancers, HIV/AIDS, use of immunosuppressant drugs, and/or the lack of a spleen can, however, render a patient vulnerable to relapse after apparent cure. Among those who relapse, as many as one-fifth die.
The new study describes five New England residents with immune deficiencies whose Babesia microti infections were not permanently knocked out by the usual standard of care — a two-drug combination treatment that was established in an earlier study by Krause and collaborating investigators and published in the New England Journal of Medicine in 2000.
Instead, the five patients experienced dangerous relapses.
Krause and colleagues considered treating the patients with tafenoquine, which is normally used to prevent or treat malaria. A study of tafenoquine in hamsters inspired the idea, though the drug had failed in a previously reported human case of relapsing babesiosis.
This time, it worked — again and again. Providers added tafenoquine to the drug regimens of four highly immunocompromised patients with relapsing babesiosis, and all were cured. (A fifth received tafenoquine on its own, which did not clear the infection.)
A higher dose was used than in the previously reported case that failed.
Tafenoquine overcame antimicrobial resistance in the Babesia microti parasite, whose genome had mutated, the researchers found.
By demonstrating treatment success, the results are helping shape a new standard of babesiosis care for these patients.
“This is the first case series, and I think it confirms that tafenoquine can be a very useful adjunct,” Krause said.
The study appears in Clinical Infectious Diseases.
The standard two-drug combination of atovaquone and azithromycin “works in virtually every patient with mild disease,” said co-author Edouard Vannier, an assistant professor in the Division of Geographic Medicine and Infectious Diseases at Tufts Medical Center in Boston, Massachusetts.
Vannier’s role was to test the organism for genetic mutations that could explain drug resistance.
“In patients who are severely ill and severely immunocompromised, because resolution does not happen fast enough, the parasite has a chance to mutate,” Vannier explained. “Very often, atovaquone resistance is noted.”
“Testing for mutations is the future of treating these patients and opens the door to personalized medicine,” Vannier said. Detecting a mutation may allow providers to course-correct to a more effective treatment.
“The whole idea is to tailor the therapy to the patient,” he said.
Several limitations were noted in the study. Tafenoquine treatment is unsafe for patients with the inherited condition G6PD deficiency, and the study was too small to determine the best duration of treatment with tafenoquine. A clinical trial is planned.
Study funding was provided by the Llura A. Gund Laboratory for Vector-borne Disease Research and the Gordon and Llura Gund Foundation, the National Institutes of Health, and funds from the Dammin and Windsor families.
Krause, Vannier and Ralph Rogers of the Division of Infectious Diseases, Warren Alpert Medical School of Brown University in Providence, Rhode Island contributed equally to the project. Other co-authors include, Monika K. Shah of the Infectious Diseases Service, Department of Medicine, Memorial Sloan Kettering Cancer Center (MSKCC) in New York, New York, and of the Department of Medicine, Weill Cornell Medical College, Cornell University in New York, New York; Rich Kodama, also of the Infectious Diseases Service at MSKCC; and HeeEun Kang and Jeffrey Parsonnet, both of the Section of Infectious Diseases and International Health, Dartmouth-Hitchcock Medical Center in Lebanon, New Hampshire.