Inter-individuele variatie van de vatbaarheid van zuigelingen voor malaria: de rol van het in utero milieu en immunogenetische factoren
13 december 2018
UAntwerpen, Stadscampus, De Kapel - Lange Sint Annastraat 7 - 2000 Antwerpen (route: UAntwerpen, Stadscampus
14 - 16 uur
Hamtandi Magloire Natama
Luc Kestens, Anna Rosanas Urgell
Doctoraatsverdediging Hamtandi Magloire Natama - Departement Biomedische Wetenschappen
The hallmark of P. falciparum parasite is the complexity of its interaction with the human host and, the multiplicity of factors driving differential risk of infection resulting in an interindividual variation in disease manifestation. In this PhD project we aimed to investigate the role of in utero environment and host immunogenetic factors in modulating the risk of
malaria in infancy.
In the first part (Chapters II-III), we determined malaria incidence and prevalence in a birth cohort of 734 infants living in Nanoro (Burkina Faso) and we explored the clinical relevance
of cord blood malaria infections. We found high and marked age and seasonal-dependency of malaria infections (17.7% at 3 months to 31.3% at 12 months of age) and disease (incidence of 0.27 to 1.92 episodes per child-year at 0-3 months and 9-12 months of age, respectively), calling for intensified efforts to control malaria in rural Burkina Faso (Chapter II). These P. falciparum infections were more likely to be acquired postnatally given the non-clinical relevance of cord blood infections from birth to 59 days of life (Chapter III).
In the second part, we investigated factors that could modulate the risk of malaria during the first year of life (Chapters IV-V-VI). The factors examined include: (1) malaria in pregnancy
(MiP) preventive treatments; (2) types of prenatal malaria exposure (PME i.e. maternal peripheral infection and placental acute, chronic and past infections) and (3) genetic variations in genes driving innate immune responses. Firstly, we provided evidence that MiP preventive treatments may provide additional protection against both malaria and nonmalarial fevers (NMFs) during the first year of life, suggesting that effective malaria control strategies in pregnancy could have long-term benefits in infants (Chapter IV). In addition, we demonstrated that past placental infections have a profound effect on fetal immune system, and that the differential alterations of innate immune responses by PME categories might drive heterogeneity between individuals to clinical malaria susceptibility during the first year of life (Chapter V). Finally, the genetic association analysis revealed that, polymorphisms in the immune system genes such as IL-1β (rs1143634) and FcγRIIA/CD32 (rs1801274), condition malaria susceptibility during the first months of life, possibly by modulating production of inflammatory mediators (Chapter VI).
Overall, these findings provide new insight on how MiP impacts malaria risk in infants and might help to develop rational strategies and/or new tools for preventing malaria cases and related-deaths in infancy.