Genetic diversity of Plasmodium falciparum infections : influence on protective malaria immunity

Abstract

Detailed knowledge of the interaction between the human host and the antigenic and genetic diversity of Plasmodium falciparum infections is a prerequisite for understanding the mechanisms underlying acquisition of immunity to malaria. This thesis assessed the diversity of P. falciparum by genotyping the highly polymorphic vaccine candidate antigen merozoite surface protein 2 (msp2 ) gene in different transmission areas. Factors influencing the number of genotypes and the relation between level of diversity and morbidity were investigated, as well as potential immunological markers of protection.

In a high endemic area in Tanzania, where a large part of the population harbours asymptomatic P. falciparum infections, the diversity was highest in children aged 6 to 10 years. Time to previous antimalarial treatment influenced the diversity of infections suggesting accumulation of genotypes with time. Individual exposure, assessed by anti-circumsporozoite protein antibody levels, did however not affect the number of concurrent genotypes. Asymptomatic multiclonal infections were associated with a reduced risk for subsequent febrile malaria without affecting hemoglobin levels. The number of msp2 genotypes did not affect the crude anti-malarial IgG and IgE antibody levels. However, high anti-malarial IgE levels per se were associated with a reduced risk for subsequent malaria episode.

In a mesoendemic area in Mali, ethnic difference in malaria susceptibility was not reflected in the diversity of P. falciparum but rather in different patterns of splenomegaly. In a low endemic area in Iran, the genetic diversity of P. falciparum in patients was higher than expected, suggesting a more intense transmission than previously reported. A new Tris-EDTA buffer-based DNA extraction method was developed and found to be useful for long term stored filter paper field samples.

The thesis contributes to a further understanding of the molecular epidemiology of the highly polymorphic P. falciparum parasite and highlights interesting interactions between the human host and multiclonal infections that may have to be considered in future strategies of malaria control.