title: Importance of adequate local spatiotemporal transmission measures in malaria cohort studies: application to the relation between placental malaria and first malaria infection in infants.
abstract: According to several studies, infants whose mothers had a malaria-infected placenta (MIP) at delivery are at increased risk of a first malaria infection. Immune tolerance caused by intrauterine contact with the parasite could explain this phenomenon, but it is also known that infants who are highly exposed to Anopheles mosquitoes infected with Plasmodium are at greater risk of contracting malaria. Consequently, local malaria transmission must be taken into account to demonstrate the immune tolerance hypothesis. From data collected between 2007 and 2010 on 545 infants followed from birth to age 18 months in southern Benin, we compared estimates of the effect of MIP on time to first malaria infection obtained through different Cox models. In these models, MIP was adjusted for either 1) "village-like" time-independent exposure variables or 2) spatiotemporal exposure prediction derived from local climatic, environmental, and behavioral factors. Only the use of exposure prediction improved the model's goodness of fit (Bayesian Information Criterion) and led to clear conclusions regarding the effect of placental infection, whereas the models using the village-like variables were less successful than the univariate model. This demonstrated clearly the benefit of adequately taking transmission into account in cohort studies of malaria.
authors.affiliation: Institut de Recherche pour le Développement, Unité Mixte de Recherche 216, Mère et Enfant Face aux Infections Tropicales, 75270 Paris Cedex 6, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Le Port
authors.forename: Gilles
authors.initials: G
authors.lastname: Cottrell
authors.forename: Fabrice
authors.initials: F
authors.lastname: Chandre
authors.forename: Michel
authors.initials: M
authors.lastname: Cot
authors.forename: Achille
authors.initials: A
authors.lastname: Massougbodji
authors.forename: André
authors.initials: A
authors.lastname: Garcia
mesh_terms: D000818:Animals; D000852:Anopheles; D001499:Bayes Theorem; D001541:Benin / Q000453:epidemiology; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical; D053208:Kaplan-Meier Estimate; D016778:Malaria, Falciparum / Q000453:epidemiology* / Q000635:transmission; D015999:Multivariate Analysis; D010920:Placenta / Q000469:parasitology; D011159:Population Surveillance; D011247:Pregnancy; D016016:Proportional Hazards Models; D012307:Risk Factors
keywords: cohort studies; infant; malaria; malaria transmission; placenta