RT Journal Article SR Electronic T1 P. falciparum gametocyte density and infectivity in peripheral blood and skin tissue of naturally infected parasite carriers JF bioRxiv FD Cold Spring Harbor Laboratory SP 803296 DO 10.1101/803296 A1 Elamaran Meibalan A1 Aissata Barry A1 Matthew P. Gibbins A1 Shehu Awandu A1 Lisette Meerstein-Kessel A1 Fiona Achcar A1 Selina Bopp A1 Christopher Moxon A1 Amidou Diarra A1 Siaka Debe A1 Nicolas Ouédraogo A1 Ines Barry-Some A1 Emilie Badoum A1 Traoré Fagnima A1 Kjerstin Lanke A1 Bronner P. Gonçalves A1 John Bradley A1 Dyann Wirth A1 Chris Drakeley A1 Wamdaogo Moussa Guelbeogo A1 Alfred B. Tiono A1 Matthias Marti A1 Teun Bousema YR 2019 UL http://biorxiv.org/content/early/2019/10/14/803296.abstract AB Transmission of Plasmodium falciparum depends on the presence of mature gametocytes that can be ingested by mosquitoes taking a bloodmeal when feeding on human skin. It has long been hypothesised that skin sequestration contributes to efficient transmission. Although skin sequestration would have major implications for our understanding of transmission biology and the suitability of mosquito feeding methodologies to measure the human infectious reservoir, it has never been formally tested. In two populations of naturally infected gametocyte carriers from Burkina Faso, we assessed transmission potential to mosquitoes and directly quantified male and female gametocytes and asexual parasites in: i) finger prick blood, ii) venous blood, iii) skin biopsies, and in pools of mosquitoes that fed iv) on venous blood or, v) directly on the skin. Whilst more mosquitoes became infected when feeding directly on the skin compared to venous blood, concentrations of gametocytes in the subdermal skin vasculature were identical to that in other blood compartments. Asexual parasite densities, gametocyte densities and sex ratios were identical in the mosquito blood meals taken directly from the skin of parasite carriers and their venous blood.We also observed sparse gametocytes in skin biopsies from legs and arms of gametocyte carriers by microscopy. Taken together, we provide conclusive evidence for the absence of significant skin sequestration of P. falciparum gametocytes. Gametocyte densities in peripheral blood are thus informative for predicting onward transmission potential to mosquitoes. Quantifying this human malaria transmission potential is of pivotal importance for the deployment and monitoring of malaria elimination initiatives.IMPORTANCE Our observations settle a long-standing question in the malaria field and close a major knowledge gap in the parasite cycle. By deploying mosquito feeding experiments and stage-specific molecular and immunofluorescence parasite detection methodologies in two populations of naturally infected parasite carriers, we conclusively reject the hypothesis of gametocyte skin sequestration. Our findings provide novel insights in parasite stage composition in human blood compartments, mosquito bloodmeals and their implications for transmission potential. We demonstrate that gametocyte levels in venous or finger prick blood can be used to predict onward transmission potential to mosquitoes. Our findings thus pave the way for methodologies to quantify the human infectious reservoir based on conventional blood sampling approaches to support the deployment and monitoring of malaria elimination efforts for maximum public health impact.