Higher gametocyte production and mosquito infectivity in chronic compared to incident Plasmodium falciparum infections

Abstract

Plasmodium falciparum gametocyte kinetics and infectivity may differ between chronic and incident infections. In the current study, we assess parasite kinetics and infectivity to mosquitoes among children (aged 5–10 years) from Burkina Faso with (a) incident infections following parasite clearance (n = 48) and (b) chronic asymptomatic infections (n = 60). In the incident infection cohort, 92% (44/48) of children develop symptoms within 35 days, compared to 23% (14/60) in the chronic cohort. All individuals with chronic infection carried gametocytes or developed them during follow-up, whereas only 35% (17/48) in the incident cohort produce gametocytes before becoming symptomatic and receiving treatment. Parasite multiplication rate (PMR) and the relative abundance of ap2-g and gexp-5 transcripts are positively associated with gametocyte production. Antibody responses are higher and PMR lower in chronic infections. The presence of symptoms and sexual stage immune responses are associated with reductions in gametocyte infectivity to mosquitoes. We observe that most incident infections require treatment before the density of mature gametocytes is sufficient to infect mosquitoes. In contrast, chronic, asymptomatic infections represent a significant source of mosquito infections. Our observations support the notion that malaria transmission reduction may be expedited by enhanced case management, involving both symptom-screening and infection detection.

Infectivity of patent Plasmodium falciparum gametocyte carriers to mosquitoes: establishing capacity to investigate the infectious reservoir of malaria in a low-transmission setting in The Gambia

“…Gametocyte infectiousness was lower among gametocyte carriers with confirmed fever (T≥37.5°C) at the moment of mosquito feeding, as shown elsewhere. 32 This apparent decrease in mosquito infection rates has been associated with cytokine-mediated inactivation of gametocytes. 9…”

Cross-sectional survey of asymptomatic malaria in Dak Nong province in the Central Highlands of Vietnam for the malaria elimination roadmap

“…A recent study in Western Kenya, in an area of high malaria transmission, revealed that asymptomatic infections were responsible for 94.6% of malaria transmission [ 9 ]. Even though in low transmission areas asymptomatic low-density parasite infections are associated with lower gametocyte densities [ 14 ], they still contribute to malaria transmission [ 10 , 13 , 15 , 16 ]. Studies in Vietnam and Lao-PDR have provided evidence of persisting and oscillating submicroscopic malaria infections that frequently led to high-density infections, thus sustaining malaria transmission [ 7 , 8 ].…”

The Dynamic Change of Immune Responses Between Acute and Recurrence Stages of Rodent Malaria Infection

“…With frequent recrudescence, human malaria infection persists for several months or years and serves as a major reservoir for malaria transmission ( Okell et al, 2012 ; Churcher et al, 2015 ; Lin et al, 2016 ; Slater et al, 2019 ; Barry et al, 2021 ). If our finding that innate immune responses were critical for the control of parasite recrudescence could be confirmed in human malaria, it will help us to design novel strategy to control parasite recrudescence and to block malaria transmission.…”

“…However, some parasite clones are able to evade the host immune attack by switching their variant antigens, such as var , repetitive interspersed family ( rif ), and subtelomeric variant open reading frame ( stevor ), resulting in frequent recrudescence ( Scherf et al, 2008 ). Thus, after the acute infection stage, malaria infection persists at low levels for several months or years, and this has been regarded as a reservoir for malaria transmission ( Ouedraogo et al, 2009 ; Okell et al, 2012 ; Churcher et al, 2015 ; Barry et al, 2021 ). Understanding the underlying mechanisms involved in the host control of malaria recrudescence will provide us with novel clues for designing immune intervention measures against malaria parasites and blocking malaria transmission.…”