Malarial Immunity in Pregnant Cameroonian Women

Plasmodium falciparum malaria is one of the three major infectious diseases in the world today. Infants in endemic areas are born with transplacentally-acquired antibodies (Ab) that help to protect them against severe infections. Once this passive-immunity wanes, infants become susceptible to severe disease. Asymptomatic and clinical malaria are more common in pregnant women, creating a health problem for both mother and developing fetus. Malaria increases maternal anemia, mortality at parturition and the risk of having low birth weight (LBW) babies. This study plans to enroll a total of 1,160 pregnant women, ages 15 to 50 years, including 920 pregnant women who reside in the city of Yaounde and 240 women who reside in the rural villages of Ngali II and Ntouessong. In addition, 216 babies born residing in Ngali II and Ntouessong will be enrolled. Women will receive physical exams, participate in blood sample collection, and will be followed monthly through their pregnancy. Participants will receive sulfadoxine - pyrimethamine (SP) every other month until term, as recommended by the World Health Organization (WHO). During the 2nd or 3rd visit, pregnant women will be asked to provide a stool sample for detection of intestinal parasites. At delivery, the following will be collected: 2-3 cc of maternal venous blood, information on the newborn, a biopsy of the placenta for histology, blood from the intervillous space of the placenta (IVS) for cytokines, and fetal cord blood for Ab and primed T and B cells. To determine how malarial infection during the 2nd and 3rd trimesters influences malarial infection in infants, mothers in the above study as well as additional mothers who received Intermittent Preventive Therapy (IPT)-SP during the 2nd and 3rd trimester and women who received less than the recommended dose will be recruited during their last trimester of pregnancy and asked to enroll their newborns. The levels of antimalarial cellular and humoral immunity at birth will be recorded for each infant. The newborn will be followed to determine when they 1st become positive for P. falciparum and the number and severity of infections. In addition, the decline of maternal Ab and acquisition of Ab (IgM and IgG) by infants to vaccine-candidate antigen (Ag) will be monitored throughout the 1st year using blood samples collected monthly. The goals of this study are to determine if the absence of malaria during the 2nd and 3rd trimesters (due to the use of IPT) does the following: alters the development of pregnancy-associated immunity in the mother; reduces placental pathology; and increases the susceptibility of babies to malaria. The primary outcome measures will be to determine: at delivery, the proportion of primigravidae with Ab to variant antigen identified by Salanti (VAR2csa) will be significantly reduced if pregnant women are not infected during the 3rd trimester of pregnancy; prevalence of presence of severe pathology will be compared among the groups; and the number of babies who have malaria during the first 6 months of life. The secondary outcome measures of this study will include: determining if maternal P. falciparum infection during the 2nd or 3rd trimester reduces the transfer of malaria-specific IgG to the fetus; determining if the proportion of babies who are born with primed T cells is the same in those whose mothers had malaria during the 2nd or 3rd trimester compared to those who did not; presence of primed B cells in cord blood will be detected by culturing cord blood mononuclear cells MNC in vitro culture for 5 days; and plasma collected from babies when they experience their 1st P. falciparum infection will be screened for the presence of IgG and IgM Abs against the panel of Ag. The duration of the entire study is 5 years.