Diversity and dynamics of Plasmodium falciparum malaria

Sammanfattning: The epidemiology of genetic diversity of malaria parasites in relation to clinical parameters, acquisition of immunity and malaria transmission has implications for the development and evaluation of control measures such as vaccines and drugs. The diversity and dynamics of Plasmodium falciparum infections were therefore studied with a polymerase chain reaction (PCR)-based genotyping method targeting three highly polymorphic genes coding for potential vaccine candidate antigens: the two merozoite surface proteins msp1 block 2 and msp2 and the glutamine rich protein (glurp). The methodology was evaluated with regards to sampling and storage of blood samples as well as reproducibility and comparability between different laboratories. P. falciparum infections were found to be highly dynamic in asymptomatic children in a holoendemic area in Tanzania. Fluctuations of parasite densities and detection of different genotypes on consecutive days, many appearing only every 48 hours, suggested highly synchronised sequestration of parasite populations in asymptomatic infection. Parasites detected in an single blood sample thus only partly represent the total parasite population in an individual. In contrast, no synchronicity was observed in symptomatic infections during treatment in non-immune travellers, suggesting that P. falciparum populations are asynchronous in the early phase of infection. In a cohort of children followed for four years, parasite prevalence and genetic diversity varied substantially between the children but showed a high degree of consistency within the individual child. A reverse correlation was found between both parasite prevalence and multiplicity and the number of clinical episodes, suggesting that asymptomatic, especially multiclonal, P falciparum infections protect against clinical disease. Malaria infections in travellers returning from malaria endemic areas were found to be composed of several P. falciparum genotypes despite short term travel, suggesting that single mosquito inoculations transmit multiple clones. P. falciparum infections are highly genetically diverse and dynamic. The diversity may be of protective value for the human host and needs to be considered in relation to malaria prevention and treatment.