Host and Parasite Genetic Factors that affect Plasmodium Falciparum Gametocytogenesis and Malaria Transmission in Southern Ghana

Abstract

Several factors affect gametocyte production and are proposed to vary in different endemic settings and seasons. The current study assessed gametocyte production rates in P. falciparum isolates from malaria patients in ex vivo assays. Effect of host (G6PD, HBB and ABO blood groups) and parasite (msp2 and Pfg377 diversity, and drug resistant strains) factors on gametocyte prevalence were assessed in asymptomatic infections. Study participants were children aged one to twelve years living in Obom and Cape Coast. In an ex vivo assay, 54% of the P. falciparum isolates produced gametocytes by day three with the mean production rate of less than 1%. High P. falciparum prevalence was observed, in up to 60% and 86% of children harbouring the parasites at microscopic and submicroscopic levels respectively. The parasite prevalence in Obom exhibited an extensive seasonal variation (P < 0.001) in microscopic and submicroscopic infections. Neither HBB, G6DP variants nor any of the ABO blood groups was associated with gametocyte prevalence; but participants with heterozygous or homozygous HbC had more gametocytes than the other HBB genotypes. Low P. falciparum sexual and asexual diversities (MOI<1.5) were observed and gametocyte positivity was significantly (P = 0.001) higher in individuals with msp2 dimorphic infections. Different levels of drug mutant P. falciparum strains with crt 76T (< 23%), Pfindrl 86Y (< 18%), dhfr S108N (< 40%) and Pfdhps A437G (> 3%) were observed. Low frequencies (2.1%) of K13 (C469C and A558S) mutant parasite strains were recorded. Plasmodium falciparum infections with both the mutant and wild type drug resistant strains also had msp2 dimorphic alleles and this will result in the formation of new parasite strains in the Anopheles vector for onward transmission.