Malaria parasite infection during pregnancy and at delivery in mother, placenta, and newborn: efficacy of chloroquine and mefloquine in rural Malawi

Abstract

Despite international recommendations to use malaria treatment and prevention in pregnant women in malaria-endemic areas, few studies have evaluated the efficacy of available antimalarial regimens. This issue is of particular concern in the face of spreading chloroquine (CQ)-resistance of Plasmodium falciparum in malarious areas of sub-Saharan Africa. In a prospective trial in rural Malawian pregnant women, we examined three regimens using CQ (including the existing national policy regimen) and one regimen using mefloquine (MQ). The efficacy of the regimens was determined by comparing rates of clearance of initial parasitemia; prevention of breakthrough infection; and parasitemia at delivery in maternal peripheral blood, placental blood, and in infant umbilical cord blood. Among 1,528 parasitemic women at enrollment, 281 (18.4%) had persistent infections; and among 1,852 initially aparasitemic women, 320 (17.3%) had breakthrough parasitemia on one or more follow-up visits. Compared with women on MQ, women on a CQ regimen were at significantly greater risk of persistent and breakthrough infection (odds ratios [OR] = 30.9 and 11.1, respectively, P < 10(-6)). Other significant risk factors for persistent and breakthrough infections in a multivariate model included first pregnancy; enrollment in the rainy or postrainy season; maternal age < or = 25 years; seropositivity to the human immunodeficiency virus (HIV) (persistent infections only); and no use of antimalarial prophylaxis before enrollment (breakthrough infections only). At delivery, compared with women on MQ, women on a CQ regimen were at significantly greater risk of peripheral, placental, or umbilical cord blood parasitemia (OR = 8.7, 7.4, and 4.1, respectively, P < 10(-6)). Additional risk factors for parasitemia at delivery in multivariate models included first pregnancy; delivery in the rainy or postrainy season; HIV-seropositivity; and maternal age < or = 25 years (risk for peripheral and placental blood parasitemia only). Maternal anemia (hematocrit < 30%) at enrollment or at delivery was not associated with persistent or breakthrough parasitemia or parasitemia at deliver in these multivariate models. While factors leading to increased malaria parasite exposure (high transmission seasons) and lowered or altered host immune response (low pregnancy number, young age, and HIV infection) are important risk factors for malaria in pregnant women, the use of an ineffective intervention (CQ in a setting with CQ-resistant parasites) was the most important determinant of P. falciparum parasitemia in these pregnant women. Strategies to reduce the impact of malaria in pregnant women must use efficacious interventions and may need to consider targeting the intervention to the most susceptible women during the seasons of high malaria exposure.

PIP: During September 1987 to June 1990, 3380 pregnant women with parasitemia attending 4 prenatal care clinics in rural Mangochi District, Malawi, were assigned to 1 of 4 regimens of antimalarial treatment and/or prophylaxis. The women were followed through delivery to determine the antimalarial drug efficacy on peripheral parasitemia during pregnancy and parasitemia at the time of delivery in peripheral, placental, and umbilical cord blood. The regimens were 3 regimens for chloroquine (CQ), 1 of which was the current standard of care in Malawi, and a mefloquine (MQ) regimen. Parasite clearance was not achieved in 18.4% of the 1528 women with parasitemia at enrollment. 17.3% of the 1852 women who were aparasitemic at enrollment had breakthrough infections. Women using a CQ regimen faced a significantly greater risk of persistent and breakthrough parasitemia (odds ratio [OR ] = 30.9 and 11.1, respectively; p 0.0000001). The multivariate analysis found other significant risk factors for malaria to be first pregnancy (OR = 3.6 for persistent malaria and 1.5 for breakthrough malaria), enrollment in the rainy or post-rainy season (OR = 2-3.4 for persistent parasitemia and 1.2-2.7 for breakthrough malaria), maternal age of at most 25 years (OR = 2.3 for persistent malaria and 1.6 for breakthrough malaria), and seropositivity to HIV (OR = 1.9 for persistent malaria). At delivery, women on a CQ regimen faced a significantly higher risk of peripheral, placental, or umbilical cord parasitemia than those using MQ (OR = 8.7, 7.4, and 4.1, respectively; p 0.000001). In the multivariate model, other significant risk factors for malaria at delivery were first pregnancy, enrollment in the rainy or post-rainy season, maternal age of at most 25 years, and seropositivity to HIV. The most important determinant of falciparum malaria in pregnant women was use of an ineffective intervention (i.e., CQ in an area with CQ-resistant parasites). Based on these findings, the researchers recommend that antimalarial programs focus on highly efficacious drugs and targeting pregnant women during the season of high malaria exposure.