2023
DOI: 10.7554/elife.85140
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Plasmodium falciparum adapts its investment into replication versus transmission according to the host environment

Abstract: The malaria parasite life cycle includes asexual replication in human blood, with a proportion of parasites differentiating to gametocytes required for transmission to mosquitoes. Commitment to differentiate into gametocytes, which is marked by activation of the parasite transcription factor ap2-g, is known to be influenced by host factors but a comprehensive model remains uncertain. Here we analyze data from 828 children in Kilifi, Kenya with severe, uncomplicated, and asymptomatic malaria infection over 18 y… Show more

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Cited by 20 publications
(7 citation statements)
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“…Although multiplication rates seen here in the clinical isolates from The Gambia were lower than those from an area of higher endemicity in Ghana, it is unknown whether such rates vary depending on local transmission conditions as previously suggested [25]. One study of parasite gene expression has suggested that there may be increased commitment to parasite sexual stages required to infect mosquitoes when overall transmission rates are lower [26]. However, the substantial variation in asexual multiplication rates in the present and previous studies is not explainable by varying proportions of parasites undergoing sexual commitment, as these are normally only a small minority of parasites per cycle [13, 27].…”
Section: Discussionmentioning
confidence: 77%
“…Although multiplication rates seen here in the clinical isolates from The Gambia were lower than those from an area of higher endemicity in Ghana, it is unknown whether such rates vary depending on local transmission conditions as previously suggested [25]. One study of parasite gene expression has suggested that there may be increased commitment to parasite sexual stages required to infect mosquitoes when overall transmission rates are lower [26]. However, the substantial variation in asexual multiplication rates in the present and previous studies is not explainable by varying proportions of parasites undergoing sexual commitment, as these are normally only a small minority of parasites per cycle [13, 27].…”
Section: Discussionmentioning
confidence: 77%
“…The P. falciparum clinical isolates used here from southern Africa are attuned to either replication or reproduction, with an anticorrelated relationship observed in the sample set. Such preferences for either replication or reproduction have been seen also on a population level associated with changes in environmental conditions ( 62 , 63 ) and within-host factors including declining immunity ( 64 ) and nutritional depletion ( 65 67 ). As a result, reproduction (as increased gametocyte prevalence) is prioritized to ensure transmission efficiency ( 68 ).…”
Section: Discussionmentioning
confidence: 99%
“…Early after infection (day 4 PI), plasma levels of IFN-γ, TNF-α, IL-3, IL-17, IL-1β, and IL-4 were increased in baso IL-18R (−) mice ( 16 ) but not in basophil-depleted mice ( 15 ). These cytokines are markers of a hyperinflammatory state, with IFN-γ negatively associated with gametocyte commitment and parasite transmission ( 63 ). Infected baso IL-4/IL-13 (−) mice exhibited cytokine trends similar to those observed in baso IL-18R (−) mice, but plasma levels in baso IL-4/IL-13 (−) mice were not significantly different from those in baso IL-4/IL-13 (+) mice ( Supplemental Fig.…”
Section: Discussionmentioning
confidence: 99%