Modeling the impact of Plasmodium falciparum sexual stage immunity on the composition and dynamics of the human infectious reservoir for malaria in natural settings
Submicroscopic gametocyte infections are efficiently transmitted from humans to mosquitoes in settings with efficient malaria vectors and may pose challenges for malaria control and elimination efforts. Our understanding of what mechanisms contribute to submicroscopic gametocytes infectiousness remains limited. Here we assess the impact of naturally acquired anti-gametocyte antibodies on malaria transmission to mosquitoes and on the age-dependent composition of the infectious reservoir and seasonal dynamics. Anti-gametocyte immunity significantly reduces the infectiousness of high gametocyte density infections, contributes to explain the age-related profiles of the infectious reservoir in the study area, whilst submicroscopic gametocyte infections that present with lower anti-Pfs48/45 and anti-Pfs230 antibody responses commonly remain transmissible to mosquitoes. Our findings indicate that sexual stage immunity needs to be incorporated in transmission models to better understand transmission dynamics. Furthermore, tools that boost sexual stage immunity may reduce transmission to mosquitoes and thus aid elimination strategies.
By investigating the interactions between oocyst counts and antibody densities, adjusting for gametocyte density, we were able to estimate the transmission reducing activity (TRA) of specific antibody densities.
Fig 4 illustrates TRA in relation to Pfs230, Pfs48/45 and NANP6 antibodies at various gametocyte densities determined by QT-NASBA.
Distribution of oocyst intensity in the presence and absence of Pfs230 (a), Pfs48/45 (b) or NANP6 (c) antibody at different gametocyte densities.