Malaria treatment and prevention in pregnancy: indications for use and adverse events associated with use of chloroquine or mefloquine.

In sub-Saharan Africa, women frequently report a variety of symptoms during pregnancy, some of which indicate possible illness. Given the adverse impact of malaria in pregnancy, these events may be important for at least two reasons: it may be possible to use reported fever illness as a determinant of which women need an antimalarial intervention, and, it is possible that adverse symptoms following the antimalarial intervention may be important determinants of continued adherence to the prevention regimen. In a cohort of pregnant women enrolled at first antenatal clinic visit in rural Malawi, we evaluated reported fever, determined parasitemia, and placed the women on antimalarial regimens containing chloroquine (CQ) or mefloquine (MQ). We then systematically evaluated reported symptoms following antimalarial drug use after initial therapeutic doses and subsequent prophylactic doses, and monitored women throughout their pregnancy and at delivery. Among 4,187 enrolled women, 1,048 (25%) reported at least one febrile episode during pregnancy before their first antenatal clinic visit. Factors associated with this reported fever included low parity, enrollment in the rainy season, human immunodeficiency virus seropositivity, use of antimalarial prophylaxis before enrollment, high socioeconomic status, normal (compared to low) maternal height and weight, and literacy. Fever before the first antenatal clinic visit was reported by 24.4% of parasitemic women and 25.4% of aparasitemic women; the sensitivity and specificity of fever to identify parasitemic women was 24% and 71%, respectively. In contrast, the sensitivity and specificity of first or second pregnancy to identify parasitemic women was 71% and 57%, respectively. Among women on a CQ or MQ regimen, approximately 60% reported side effects (e.g., itching, dizziness, and gastrointestinal disturbances) after a treatment dose and approximately 25% reported side effects after a prophylactic dose; rates and types of symptoms reported were similar in the CQ and MQ groups. Few serious side effects were observed and rates of fetal loss were low and similar in the groups. Reliance on fever illness will be wholly inadequate to identify parasitemic women; therefore, our findings support existing World Health Organization recommendations that presumptive treatment and prevention regimens should be offered to all pregnant women. When resources are inadequate to offer antimalarial prophylaxis to all pregnant women, women in their first or second pregnancy may be a more appropriate target group than pregnant women with reported fever. Education regarding expected minor side effects may reduce rates of poor compliance and improve the effectiveness of the prevention effort.