Multiplicity of infections and level of recrudescence in Plasmodium falciparum malaria in Mlimba, Tanzania

Polymorphism and antigenic variation are important biological survival strategies of malaria parasites determining the episode, outcome and implications of treatment interventions. In P. falciparum, polymorphic antigens are associated with the asexual blood-stage; merozoite surface protein 2 (MSP2). The MSP2 genes have been invaluable in post-treatment discrimination of parasite resurgence fromnew infection, especially in high transmission areas. We performed polymerase chain reaction (PCR) on DNA extracted from blood samples of 141 malaria-infected infants, followed by restriction fragmentlength polymorphism (RFLP) of PCR products. The findings showed multiplicity of infections of single to six infections with an average of 2.58 infections per patient. Single infections of either 3D7 or FC27allelic families of the MSP2 gene occurred in 51 patients (50.5%) out of all PCR-RFLP successful samples (n = 101). Out of 15 (10.6%) follow up samples with resurgent parasitaemia, 3 (20%) sampleshad recrudescent infections while 12 (80%) had variable results. Our findings provide an insight on the prevalence of the genetic determinants of suphadoxine-pyrimethamine (SP) resistance in Mlimba during the study period, and in the face of rapidly spreading resistance, calls for the periodic surveillance in order to timely detect early warning signal of the deteriorating SP cure rate

Structural diversity and African origin of the 17q21.31 inversion polymorphism.(*First two authors contributed equally to this work)

The 17q21.31 inversion polymorphism exists either as direct (H1) or inverted (H2) haplotypes with differential predispositions to disease and selection. We investigated its genetic diversity in 2,700 individuals, with an emphasis on African populations. We characterize eight structural haplotypes due to complex rearrangements that vary in size from 1.08-1.49 Mb and provide evidence for a 30-kb H1-H2 double recombination event. We show that recurrent partial duplications of the KANSL1 gene have occurred on both the H1 and H2 haplotypes and have risen to high frequency in European populations. We identify a likely ancestral H2 haplotype (H2') lacking these duplications that is enriched among African hunter-gatherer groups yet essentially absent from West African populations. Whereas H1 and H2 segmental duplications arose independently and before human migration out of Africa, they have reached high frequencies recently among Europeans, either because of extraordinary genetic drift or selective sweeps