Peace Corps offers window into long-term impacts of malaria drugs

WASHINGTON — A new report on potential long-term health effects of malaria drugs reached few definitive conclusions. Researchers were clear on one point though: There has not been enough good research into potential links between malaria prophylactics and a variety of health outcomes experienced by people who have taken them.

The study, published Tuesday by the National Academies of Sciences, Engineering, and Medicine, sought to respond to questions raised mainly by advocates for U.S. military personnel deployed in malaria-endemic countries. They wondered if some health conditions experienced by service members — particularly neurologic and psychiatric outcomes — might have been precipitated by their exposure to malaria drugs at some time in the past.

David Savitz, chair of the review committee and a professor at Brown University, thinks it’s a question worthy of continued exploration.

“The evidence base to make a determination is really quite limited, but as far as the question being a reasonable and appropriate one to ask, we think that is the case,” Savitz told Devex.

The implications of that question are not limited to American military personnel. Half the world’s population lives in places where malaria is present, leading to over 220 million cases, and more than 400,000 deaths per year.

In addition to military personnel and others deployed overseas, the researchers looked at available research on malaria drug use and effects among U.S. Peace Corps volunteers, many of whom serve in malaria-endemic countries, and who are required to take malaria prevention medication.

Approximately 10% of malaria cases reported annually in U.S. citizens by the Centers for Disease Control and Prevention occur in Peace Corps volunteers, according to the report. Most of these originate in Africa. Two people in Peace Corps have died from malaria since 2000, with both cases occurring in people who were “non adherent” with prophylaxis, according to the report.

There are currently six malaria prophylactic drugs approved by the U.S. Food and Drug Administration: chloroquine, primaquine, mefloquine, doxycycline, atovaquone/proguanil, and tafenoquine. Each of these comes with recommendations for who should take them and the concurrent and short-term adverse effects of taking them — those that occur during the drug course — are well documented.

The researchers looked at the available evidence for associations between specific malaria drugs and persistent health outcomes — those that appear during the period of the medication and persist after the course has ended — as well as latent health outcomes — those that appear after use is completed.

The review was only able to find sufficient evidence between one malaria medication and one persistent health outcome, and it should probably not be cause for great concern, Savitz said.

The researchers found that the drug tafenoquine was associated with a condition called vortex keratopathy, which results in deposits in the cornea of the eye that disappear after the drug course ends and cause no functional vision changes.

The report’s more significant conclusion, Savitz said, relates to the weaknesses of the evidence base for long-term effects of malaria medication.

Most of the health outcomes the researchers examined — including post-traumatic stress disorder; neurologic and psychiatric events; and cardiovascular events — fell under the category of “inadequate or insufficient evidence of an association.” The researchers concluded that seven of the 30 possible associations they included in this category presented an “empirical basis for additional research.”

“I wish we had clearer answers, but there’s no getting around the observation that the body of research to inform this issue is both limited in volume and in quality, and there’s really, we think, a case to be made for looking further into it,” Savitz said.

The researchers pointed to some elements of future studies that might make them better suited for drawing clearer conclusions about long-term health outcomes and malaria drugs. These should include better documentation of the antimalarial dosage used and a clear timeline of both antimalarial drug use and symptom or event occurrence. The studies should also be large enough to detect any associations with rare events, according to the report.

According to Savitz, Peace Corps might offer one potential avenue for this kind of research to move forward.

“There won’t be a population or database that does all that perfectly, but there is some basic criteria for doing informative research, and certainly it’s plausible that organizations like the Peace Corps would have the necessary sort of elements in place,” he said.