Malaria prophylactic medication exposure and associated maternal, fetal, and infant outcomes

Nearly half of the world’s population is at risk for malaria, a disease caused by an infection with a parasite through a mosquito bite. Millions more are placed at risk due to travel to regions where malaria is common, including United States (U.S.) military Service Members, federal civil servants and families. Pregnant people, young children, and travelers are particularly susceptible to infection and are at high risk of severe malaria. More than 100,000 pregnancies occur annually in the U.S. military health system. Malaria medication as prevention is a strategy to avoid malaria infection during and immediately after travel to areas where malaria is a risk, and is essential for overseas U.S. military Service Members, federal employees, and families. For pregnant travelers, these medications are critical for preventing infection, given complications that include infants born too small, pregnancy loss and maternal death. Despite this need, there are only two approved options for pregnant people and they are both problematic. Chloroquine is well-studied, but its use is very limited due to geographic areas of medication resistance. Mefloquine use shows safety concerns for neurological and psychological adverse effects. Thus, safe, well-tolerated alternative options are an unmet need. The safety of other medications as prevention such as atovaquone/proguanil and doxycycline has not been established for mother and infant because pregnant people are routinely excluded from drug trials. However, pregnancy exposures to these medications do occur, for example, when a person does not yet recognize that they are pregnant. Analysis of a large electronic health records database where pregnancy medications are routinely documented can shed light on this knowledge gap. The rationale for this study is that medication options approved for use in pregnancy are limited, and we suspect that atovaquone/proguanil, a newer option currently approved for non-pregnant travelers, may be safe for use in later trimesters of pregnancy.

Relevance to the Toxic Exposures Research Program (TERP): This study directly addresses TERP Goal 2 and Topical and Focus Areas by determining whether medications to prevent malaria are toxic in pregnancy, and specifically will look at the safety of mefloquine.

Impact: This study will inform global malaria prevention for pregnant travelers, and in particular, U.S. military, federal civil servants, and families. In addition to tens of thousands of military personnel taking malaria medication as prevention, there are 74 U.S. embassies and 32 Peace Corps assignments located in malaria-endemic countries, placing thousands of Americans at risk annually. In the short term, our study will determine whether the timing and length that malaria prevention medication is taken matters for adverse pregnancy outcomes. Longer-term, improved malaria prevention medication options are vital for safe deployment and short-term overseas assignments as the number of Service Women of childbearing age continues to grow. Safe motherhood and healthy infants and children is a readiness issue for active-duty mothers and fathers.

Clinical Applications: It is expected that the research findings will have significant clinical and public health benefits. This research may help establish the safety of alternative medication options than those currently approved for malaria prevention in pregnancy. These findings may also help decrease the use of mefloquine, thereby avoiding potential neurological or psychological effects for the individual patient. Study of health record data for thousands of pregnancies previously exposed to malaria prevention medication poses no risk to the individual.

Drug-based Strategies
Vulnerable Populations

Sep 2023 — Sep 2026

$752,148

United States