MALARIA PARASITE INFECTION DURING PREGNANCY AND AT DELIVERY IN MOTHER, PLACENTA, AND NEWBORN - EFFICACY OF CHLOROQUINE AND MEFLOQUINE IN RURAL MALAWI

Despite international recommendations to use malaria treatment and pre vention in pregnant women in malaria-endemic areas, few studies have e valuated the efficacy of available antimalarial regimens. This issue i s of particular concern in the face of spreading chloroquine (CQ)-resi stance of Plasmodium falciparum in malarious areas of sub-Saharan Afri ca. In a prospective trial in rural Malawian pregnant women, we examin ed three regimens using CQ (including the existing national policy reg imen) and one regimen using mefloquine (MQ). The efficacy of the regim ens was determined by comparing rates of clearance of initial parasite mia; prevention of breakthrough infection; and parasitemia at delivery in maternal peripheral blood, placental blood, and in infant umbilica l cord blood. Among 1,528 parasitemic women at enrollment, 281 (18.4%) had persistent infections, and among 1,852 initially aparasitemic wom en, 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 signi ficantly greater risk of persistent and breakthrough infection (odds r atios [OR] = 30.9 and 11.1, respectively, P < 10(-6)). Other significa nt risk factors for persistent and breakthrough infections in a multiv ariate model included first pregnancy; enrollment in the rainy or post rainy season; maternal age less than or equal to 25 years; seropositiv ity to the human immunodeficiency virus (HIV) (persistent infections o nly); and no use of antimalarial prophylaxis before enrollment (breakt hrough infections only). At delivery, compared with women on MQ, women on a CQ regimen were at significantly greater risk of peripheral, pla cental, or umbilical cord blood parasitemia (OR = 8.7, 7.4, and 4.1, r espectively, P < 10(-6)). Additional risk factors for parasitemia at d elivery in multivariate models included first pregnancy; delivery in t he rainy or postrainy season; HIV-seropositivity; and maternal age les s than or equal to 25 years (risk for peripheral and placental blood p arasitemia only). Maternal anemia (hematocrit < 30%) at enrollment or at delivery was not associated with persistent or breakthrough parasit emia or parasitemia at delivery in these multivariate models. While fa ctors leading to increased malaria parasite exposure (high transmissio n seasons) and lowered or altered host immune response (low pregnancy number, young age, and HIV infection) are important risk factors for m alaria in pregnant women, the use of an ineffective intervention (CQ i n a setting with CQ-resistant parasites) was the most important determ inant of P. falciparum parasitemia in these pregnant women. Strategies to reduce the impact of malaria in pregnant women must use efficaciou s interventions and may need to consider targeting the intervention to the most susceptible women during the seasons of high malaria exposur e.