Malaria is a major cause of morbidity and mortality. Malaria during pregnancy threatens the health of both the mother and the child, with long-lasting consequences on infant health that may be attributable to the impact of maternal malaria on the fetal immune system. It is unknown what effect different manifestations of pregnancy-associated malaria have on child immunity and health. Moreover, the timing during pregnancy when malaria needs to be prevented to maximize mother-infant health is not known. In a longitudinal study in Malawi we examined the effect of maternal peripheral and placental malaria on infant risk of malaria, by following mother-infant pairs from early in pregnancy through the first two years of the child’s life. We conducted active and passive surveillance for malaria infection and disease. We assessed the concentrations of serum cytokines (IFNγ, IL13, IL12p70, IL10, IL1β, IL2, IL4, IL6, TNFα, CRP and TGFβ) in cord blood, as well as peripheral blood drawn at one year of age.
One in five women was infected with malaria at the first antenatal visit and this frequency decreased immediately following a universal bed net campaign. Children born to mothers with placental malaria, but not children born to mothers with peripheral malaria, were at increased risk of malaria during infancy as compared to those born to mothers with no malaria. Most cases of placental malaria were cleared by delivery. Children born to mothers with chronic placental malaria had elevated levels of TNFα, CRP and IL10 and a significantly decreased TNFα:IL10 ratio as compared to those born to mothers with peripheral malaria or no malaria. These differences in cytokine profile at birth disappeared by one year of age. We found no association between cytokine concentrations at birth and increased risk of malaria in infancy. We hypothesize that placental malaria, even early in pregnancy, causes cytokine dysregulation and induction of long-lived cellular alterations that are maintained in infancy, leading to increased risk of malaria. Our findings have direct public health significance. Interventions need to target all women of childbearing age and prevent all placental malaria in order to maximize the health of mother and child.
|Advisor:||Laufer, Miriam K.|
|Commitee:||Amr, Sania, Cairo, Cristiana, Lyke, Kirsten E., Plowe, Christopher V., Sztein, Marcelo M.|
|School:||University of Maryland, Baltimore|
|Department:||Molecular Microbiology and Immunology|
|School Location:||United States -- Maryland|
|Source:||DAI-B 77/12(E), Dissertation Abstracts International|
|Subjects:||Microbiology, Public health, Immunology|
|Keywords:||Infant, Malaria, Malawi, Pregnancy|
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