This dissertation represents the first formal investigation of malaria during pregnancy in the hypoendemic regions of the Peruvian Amazon lowlands. The three manuscripts presented demonstrate a progression in the assessment of malaria among pregnant women in this region, and provides new insight into the characteristics of malarial infection during pregnancy. The first manuscript used passive and active surveillance to investigate the prevalence of symptomatic clinical malaria and incidence of malarial infection of pregnant women in communities surrounding Iquitos, Peru. The results demonstrated that pregnant women in this region have an increased risk of P. falciparum infection, and not P. vivax infection, compared to non-pregnant women of the same age group [OR=2.3, 95% CI (1.3, 3.9) p = 0.004]. The second manuscript reports the frequency of malarial infection as detected by microscopy, PCR, and serologic responses in a hospital-based cross-sectional study of pregnant women at delivery. A low frequency of enrolled subjects were parasitemic at time of delivery, however 87% demonstrated an IgG or IgM response to the merozoite surface protein of either P. vivax or P. falciparum. Specific IgM responses to P. vivax were significantly associated with decreased infant birthweight and gestational age (p = 0.01 and p = 0.06). The third manuscript describes the frequency of placental infection in the study population, and compared the placental pathology between infected and non-infected in a case-control analysis. None of the placentas were parasitemic at the time of delivery, but 23% had malaria pigment, indicating past placental infection. Cases with placental hemozoin had increased monocytes in the intervillous space compared to controls with no hemozoin (44.7 vs. 25.5, p=0.012). Pigmented monocytes were found in fetal vessels of 33% of cases indicating that parasites may breach the placental barrier, and that congenital infection may occur frequently. In conclusion, this dissertation provides evidence for a high frequency of subclinical malarial infection during pregnancy, indicating that pregnant women in this region may have developed a protective immunity to clinical malaria. Further studies are necessary to gain a greater understanding of the factors associated with subclinical malarial infection during pregnancy and the apparent protection from clinical disease
