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

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.

List of scientific papers

I. Bereczky S, Liljander A, Rooth I, Granath F, Carpenter D, Shaw MA, Montgomery SM, Farnert A (2005). The impact of diversity of Plasmodium falciparum infections on malaria morbidity. [Manuscript]

II. Bereczky S, Montgomery SM, Troye-Blomberg M, Rooth I, Shaw MA, Farnert A (2004). Elevated anti-malarial IgE in asymptomatic individuals is associated with reduced risk for subsequent clinical malaria. Int J Parasitol. 34(8): 935-42.
https://doi.org/10.1016/j.ijpara.2004.04.007

III. Zakeri S, Bereczky S, Naimi P, Pedro Gil J, Djadid ND, Farnert A, Snounou G, Bjorkman A (2005). Multiple genotypes of the merozoite surface proteins 1 and 2 in Plasmodium falciparum infections in a hypoendemic area in Iran. Trop Med Int Health. 10(10): 1060-4.
https://doi.org/10.1111/j.1365-3156.2005.01477.x

IV. Bereczky S, Martensson A, Gil JP, Farnert A (2005). Short report: Rapid DNA extraction from archive blood spots on filter paper for genotyping of Plasmodium falciparum. Am J Trop Med Hyg. 72(3): 249-51.
https://pubmed.ncbi.nlm.nih.gov/15772315

V. Bereczky S, Dolo A, Maiga B, Hayano M, Granath F, Montgomery SM, Daou M, Arama C, Troye-Blomberg M, Doumbo O, Farnert A (2005). Spleen enlargement and genetic diversity of P. falciparum infection in two ethnic groups with different malaria susceptibility in Mali, West Africa. Transactions of the Royal Society of Tropical Medicine and Hygiene. [Accepted]
https://doi.org/10.1016/j.trstmh.2005.03.011