Increased gametocyte production and mosquito infectivity in chronic versus incident Plasmodium falciparum infections

Abstract

30We longitudinally assessed P. falciparum parasite kinetics, gametocyte production and infectivity 31 in incident infections that were naturally acquired following infection clearance and in chronic 32 asymptomatic infections in Burkina Faso. 92% (44/48) of the incident cohort developed symptoms 33 and were treated within 35 days, compared to 23% (14/60) of the chronic cohort. All but two 34 individuals with chronic infection were gametocytaemic at enrollment, whereas only 35% (17/48) 35in the incident cohort developed gametocytes within 35 days. The relative abundance of ap2-g 36 transcripts was positively associated with conversion to gametocyte production (i.e. the ratio of 37 gametocytes at day 14 to ring stage parasites at baseline) and was higher in chronic infections. 38Parasite multiplication rate, assessed by daily molecular parasite quantification, was positively 39 associated with prospective gametocyte production. Most incident infections were cleared before 40 gametocyte density was sufficiently high to infect mosquitoes. In contrast, chronic, asymptomatic 41 infections represented a significant source of mosquito infections. If present, gametocytes were 42 significantly less infectious if concurrent with malaria symptoms. Our observations support the 43 notion that malaria transmission reduction may be expediated by enhanced case management, 44 involving both symptom-screening and infection detection.45 46 47 48The epidemiology of P. falciparum transmission stages, gametocytes, is poorly understood. 50Molecular diagnostics show that low density gametocyte carriage is highly prevalent in endemic 51 populations 1 and that many low density infections are infectious to mosquitoes 2 , explaining 52 observations from the 1950s that gametocyte free individuals (as determined by microscopy) 53 frequently infected mosquitoes 3 . Few assessments of the population infectious reservoir of 54 malaria parasites have been undertaken 4,5 , particularly with tools capable of detecting low 55 parasite and gametocyte densities 6,7 . Fewer still have been able to assess the association of 56 infectivity with factors other than parasite density, despite clear evidence that gametocyte 57 maturity 8,9 , intrinsic parasite factors 10,11 , human genetic factors 12 , and human clinical and immune 58 responses 13-15 can have significant influence on the effectiveness of parasite transmission. 59The association between malaria symptoms and gametocyte dynamics is particularly poorly 60 understood. Among similarly immune individuals, higher densities of pathogenic, asexual stage 61 malaria parasites are commonly associated with the presentation of symptoms 16 . Because 62 gametocytes develop from asexual parasites, individuals with clinical malaria and higher parasite 63 densities may have more gametocytes and be more likely to infect mosquitoes 17,18 . On the other 64 hand, the slower development of gametocytes may result in higher densities later in infections. 65This would result in higher gametocyte densities in infecti...

Relative contribution of low-density and asymptomatic infections to Plasmodium vivax transmission in the Amazon: pooled analysis of individual participant data from population-based cross-sectional surveys

“…gambiae mosquitoes than patients with clinical symptoms, after adjusting for gametocyte density, possibly due to gametocyte inactivation during and shortly after malaria paroxysms by circulating inflammatory cytokines and reactive intermediates. 29 In contrast, asymptomatic P vivax carriers appear to be little infectious to local An dirus mosquitoes in Thailand, although the estimated transmissibility threshold for that vector 30 was one order of magnitude lower than that estimated for An darlingi ( Figure 5 ). Our results imply that asymptomatic carriers, many of them harbouring patent parasitaemia, constitute a critical infectious reservoir of P vivax in the Amazon that should be targeted by active case detection strategies.…”

A descriptive analysis of the data availability statements accompanying medRxiv preprints and a comparison with their published counterparts

“…The system was based on the "Findability" and "Accessibility" elements of the FAIR framework [34], the categories used by previous effort to categorize published data availability statements [4,11], our own experience of medRxiv data availability statements, and discussion with colleagues. Illustrative examples of each category were taken from preprints included in our sample [35][36][37][38][39][40][41][42][43].…”

Impact of school-based malaria screening and treatment onP. falciparuminfection and anemia prevalence in two transmission settings in Malawi

“…32,33 Increasing evidence suggests both school-age children and persistent infections contribute significantly to malaria transmission. [34][35][36] As such, studies of school-based malaria control interventions should also measure the indirect effects on malaria transmission in the community.…”