Different Factors Drive Initiation of Gametocytogenesis Versus Gametocyte Carriage in Plasmodium falciparum Infections.

BACKGROUND

Gametocyte carriage varies across Plasmodium falciparum infections. The extent to which this variation reflects differences in the initiation of gametocytogenesis and/or gametocyte maturation remains unclear. We investigated determinants of initiation of gametocytogenesis and gametocyte carriage in P. falciparum infections from Malawi.

METHODS

A total of 1108 P. falciparum infections from a cohort study conducted in Malawi between 2019 and 2020 underwent ccp4 and pfmget qRT-PCR to measure gametocyte carriage, ap2-g and sbp1 RT-PCR to quantify gametocytogenesis initiation in ring-stage parasites, and pfs230 DNA amplicon sequencing to estimate infection complexity. Mixed-effects logistic regression was used to evaluate predictors of gametocytogenesis initiation and gametocyte carriage, and mixed-effects linear regression was used to evaluate predictors of ap2-g gene transcript abundance and gametocyte density.

RESULTS

Gametocyte marker transcripts were detected in 54% (594/1108) of infections and ap2-g transcripts were detected in 41% (429/1047) of infections with detectable ring-stage parasites. Parasite density was positively associated with ap2-g expression, and ap2-g expression was more likely in polyclonal compared to monoclonal infections. Children <6 years old had lower ap2-g transcript abundance than adults but were more likely to carry gametocytes and have higher gametocyte density. Asymptomatic infections showed higher ap2-g transcript abundance and greater gametocyte prevalence and density than symptomatic infections.

CONCLUSIONS

Our findings suggest that infection complexity and parasite density may play a role in the initiation of gametocytogenesis, whereas host immunity and duration of infection may play a larger role in gametocyte carriage in P. falciparum infections.