Persistent Plasmodium falciparum infections enhance transmission-reducing immunity development

Abstract

Subclinical infections that serve as reservoir populations to drive transmission remain a hurdle to malaria control. Data on infection dynamics in a geographical area is required to strategically design and implement malaria interventions. In a longitudinal cohort, we monitored Plasmodium falciparum infection prevalence and persistence, and anti-parasite immunity to gametocyte and asexual antigens for 10 weeks. Of the 100 participants, only 11 were never infected, whilst 16 had persistent infections detected by reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR), and one participant had microscopic parasites at all visits. Over 70% of the participants were infected three or more times, and submicroscopic gametocyte prevalence was high, ≥ 48% of the parasite carriers. Naturally induced responses against recombinant Pfs48/45.6C, Pfs230proC, and EBA175RIII–V antigens were not associated with either infection status or gametocyte carriage, but the antigen-specific IgG titers inversely correlated with parasite and gametocyte densities consistent with partial immunity. Longitudinal analysis of gametocyte diversity indicated at least four distinct clones circulated throughout the study period. The high prevalence of children infected with distinct gametocyte clones coupled with marked variation in infection status at the individual level suggests ongoing transmission and should be targeted in malaria control programs.

Potent transmission-blocking monoclonal antibodies from naturally exposed individuals target a conserved epitope on Plasmodium falciparum Pfs230

“… 20 , 54 Importantly, the humoral response to gametocyte TBV immunogens such as Pfs230 may be reinforced by prior and/or subsequent natural infection. 55 Humoral responses against Pfs230 are common in malaria endemic regions, 56 , 57 and we have recently shown that affinity-purified Pfs230-specific antibodies can indeed block transmission. 21 LMIV230-01 is the only other human-derived mAb reported to date with observed TRA 18 ( Figure 5 C) and is encoded by IGHV1-69 and IGKV1-5 , which were the most common germline genes identified from the memory B cells sequences obtained from the eight vaccinees in Coelho et al.…”

Comparative study of Plasmodium falciparum msp-1 and msp-2 Genetic Diversity in Isolates from Rural and Urban Areas in the South of Brazzaville, Republic of Congo

“…The MOI is an important parameter for the evaluation of level of malaria transmission and human immunity in a given locality [ 23 ]. In this study, the multiple infection rate and mean of MOI varied between study sites and were higher in rural areas than in urban areas.…”

B-Cell Epitope Mapping of the Plasmodium falciparum Malaria Vaccine Candidate GMZ2.6c in a Naturally Exposed Population of the Brazilian Amazon

“…Specific antibodies against sexual-stage antigens are also related to age and serve as markers of exposure, increasing according to gametocyte densities [ 62 , 74 , 75 ], but no correlation with epidemiological parameters was found in this study. This finding is not surprising since, in malaria-endemic areas, infections are determined by microscopic parasite counts, and gametocytes normally occur at low densities.…”