Number and proportion of P. falciparum gametocytes vary from acute infection to chronic parasite carriage despite unaltered sexual commitment rate

Introduction In areas of seasonal malaria, resuming transmission every wet season relies on persistent asexual parasites during dry season that maintain the ability to produce gametocytes until the mosquito population resurges following the start of annual rains. Although human asymptomatic P. falciparum reservoirs in the dry season are widely recognized, the longitudinal dynamics of parasite sexual commitment and gametocytogenesis remain unclear. Methods We compared the expression of genes related with sexual commitment and gametocytogenesis of P. falciparum , the density and proportion of P. falciparum gametocytes, and the blood concentrations of phospholipids potentially involved in gametocytogenesis from asymptomatic subjects at the end of the dry season versus subjects with symptomatic malaria in the wet season. Furthermore, we verified whether number and proportion of gametocytes in asymptomatic vs clinical cases had similar trends in areas of seasonal and perennial transmission settings. Finally, we adapted a within-host mathematical model considering asexual parasites, sexually committed parasites, and gametocytes to infer the dynamics of gametocyte number and proportion as P. falciparum infections progress. Results We found that transcripts of genes specific of late-stage gametocytes were predominantly upregulated in asymptomatic infections at the end of the dry season, which also showed increased proportions of circulating mature gametocytes compared to clinical malaria cases. On the other hand, blood densities of gametocytes and asexual parasites were lower in chronic asymptomatic individuals compared to clinical malaria. In addition, the levels of parasite transcripts involved in sexual commitment were unaltered throughout the year. Discussion Our experimental data in combination with mathematical modelling support a scenario in which gametocyte density and proportion diverge as infections progress from recent transmission to chronic carriage, without significant alterations in the rate of sexual commitment over time. ### Competing Interest Statement The authors have declared no competing interest.