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Biology subjects

Yerbanga, S. R.

Publications and source records attributed to Yerbanga, S. R..

5 recordsLinked to original sources

The dynamic transcriptome of Plasmodium malariae in the mosquito

To survive and multiply in different host niches, malaria parasites require sets of proteins that are expressed during the life cycle in a timely manner. Plasmodium malariae is a human malaria parasite that is present in most malaria-endemic regions. However, this species remains enigmatic because it is very challenging to culture, its low parasitaemia in human infections, and frequent co-infection with other malarias. We investigate the transcriptome of P. malariae during transmission in the vector by analyzing RNA-seq data from midgut and salivary gland parasite stages obtained in two experimental mosquito infections with field P. malariae isolates. Our analysis resulted in 3,699 expressed genes, of which 263 are developmentally regulated and 1,338 are P. malariae specific, including genes with unknown functions and without orthologs in other Plasmodium. We detected unique expression patterns of the ApiAP2 family of transcription factors, many of which appear to function as master regulators during sporogony. We found expressed several members of multigene families, like PIR, PHIST, fam-l, and described new families potentially showing transcriptional heterogeneity. Our findings point to the uniqueness of the P. malariae transcriptome, probably related to different transmission traits in the vector, and the lower pathogenicity and virulence in the human.

microbiology↗

Intervention reducing malaria parasite load in vector mosquitoes: no impact on Plasmodium falciparum extrinsic incubation period and the survival of Anopheles gambiae

In the fight against malaria, transmission blocking interventions (TBIs) are promising approaches to complement conventional tools. They aim to prevent the infection of the vectors and thereby reduce the subsequent exposure of a human population to infectious mosquitoes. The effectiveness of these approaches has been shown to depend on the initial intensity of infection in mosquitoes, often measured as the mean number of oocysts resulting from an infectious blood meal prior to intervention. In mosquitoes exposed to a high infection load, current TBI candidates are expected to be ineffective at completely blocking infection but will decrease parasite load and therefore, potentially also affect key parameters of vector transmission. The present study aims to investigate the consequences of changes in oocyst intensity on downstream parasite development and mosquito survival. To address this, we experimentally produced different infection intensities in Anopheles gambiae females by diluting gametocytes from natural Plasmodium falciparum isolates and used a newly developed non-destructive method based on the exploitation of mosquito sugar feeding to track parasite and mosquito life history traits throughout sporogonic development. Our results indicate that P. falciparum extrinsic incubation period (EIP) and mosquito survival did not vary with parasite density but differed significantly between parasite isolates. Our results do not identify here unintended consequences of the decrease of parasite loads in mosquitoes on the parasite incubation period or on mosquito survival, two key parameters of vectorial capacity, and hence support the transmission blocking strategies to control malaria. Author summaryIn the fight against malaria, it is recognized that the use of several complementary strategies is necessary to significantly reduce transmission and improve human health. Among these, transmission blocking strategies aim at blocking the development of the parasites within the mosquito vectors. This approach should prevent infection in most of mosquitoes feeding on infectious hosts and thus block the transmission. However, in some cases it may only reduce parasite load without fully clearing the infection. Here we identified potential risks: if reducing parasite load would reduce the incubation period of the parasite in the mosquitoes or increase the longevity of the mosquitoes, undesirable consequences may occur with an increased efficiency of these mosquitoes to transmit parasites to human. We therefore tested these hypotheses and experimentally produced different infection loads in vector mosquitoes Anopheles gambiae by using dilutions of Plasmodium falciparum isolates from naturally infected human donors. We observed that the longevity of the mosquitoes and the incubation period of the parasites were not affected by the parasite load. This is not consistent with the unintended risks that we investigated and thus strengthens the potential of transmission blocking interventions in the toolbox to combat malaria.

evolutionary biology↗

Antimalarials in mosquitoes overcome Anopheles and Plasmodium resistance to malaria control strategies

The spread of insecticide resistance in Anopheles mosquitoes and drug resistance in Plasmodium parasites is contributing to a global resurgence of malaria, making the generation of control tools that can overcome these issues an urgent public health priority. We recently showed that the transmission of Plasmodium falciparum parasites can be efficiently blocked when exposing Anopheles gambiae females to antimalarials deposited on a treated surface, with no negative consequences on mosquito fitness. Here, we demonstrate this approach can overcome the hurdles of insecticide resistance in mosquitoes and drug resistant in parasites. We show that the transmission-blocking efficacy of mosquito-targeted antimalarials is maintained when field-derived, insecticide resistant Anopheles are exposed to the potent cytochrome b inhibitor atovaquone, demonstrating that this drug escapes insecticide resistance mechanisms that could potentially interfere with its function. Moreover, this approach prevents transmission of field-derived, artemisinin resistant P. falciparum parasites (Kelch13 C580Y mutant), proving that this strategy could be used to prevent the spread of parasite mutations that induce resistance to front-line antimalarials. Atovaquone is also highly effective at limiting parasite development when ingested by mosquitoes in sugar solutions, including in ongoing infections. These data support the use of mosquito-targeted antimalarials as a promising tool to complement and extend the efficacy of current malaria control interventions. Significance StatementEffective control of malaria is hampered by resistance to vector-targeted insecticides and parasite-targeted drugs. This situation is exacerbated by a critical lack of chemical diversity in both interventions and, as such, new interventions are badly needed. Recent laboratory studies have shown that an alternative approach based on treating Anopheles mosquitoes directly with antimalarial compounds can render the vector incapable of transmitting the Plasmodium parasites that cause malaria. While promising, showing that mosquito-targeted antimalarials remain effective against wild parasites and mosquitoes, including drug- and insecticide-resistant populations, respectively, is crucial to the future viability of this approach. In this study, carried out in the US and Burkina Faso, we show that antimalarial exposure is highly effective, even against extremely resistant mosquitoes, and can block transmission of drug-resistant parasites. By combining lab, and field-based studies in this way we have demonstrated that this novel approach can be effective in areas where conventional control measures are no longer as effective.

microbiology↗

Opening Pandora’s Box: Distribution of Plasmodium gametocytes in bloodstream

Malaria, a vector borne disease caused by Plasmodium spp., remains a major global cause of morbidity and mortality. Optimization of the disease control strategies requires a thorough understanding of the fundamental processes underlying parasite transmission. Although the number of transmissible stages of Plasmodium (gametocyte) in human blood is frequently used as an indicator of human-to-mosquito transmission potential, this relationship is not always clear. Important efforts have been made to develop molecular tools to fine-tune gametocyte densities estimation and therefore improve the prediction of mosquito infection rates, but a significant level of uncertainty around this estimate remains. Here we show with both human and avian malaria system that the within-vertebrate host distribution of gametocytes could explain much of this uncertainty. By comparing gametocyte densities in bloodstream between different body parts, we found a difference by nearly 50% in humans and by more than 15% in birds. An estimation of gametocyte density from only one blood sample, as is usually the case, could therefore drastically over- or underestimated the infectivity of gametocyte carriers. This might have important consequences on the epidemiology of the disease since we show, using the avian malaria system, that this variation influences the transmission of the parasite to the mosquito vector. In the light of our results, we argue that it is essential to consider the heterogeneous distribution of gametocyte to improve human diagnosis, identify infectious reservoirs and to test new malaria control strategies.

evolutionary biology↗

High Plasmodium infection intensity in naturally infected malaria vectors in Africa

The population dynamics of human-to-mosquito malaria transmission in the field has important implications for the genetics, epidemiology and control of malaria. The number of oocysts in oocysts positive mosquitoes developing from a single, naturally acquired infectious blood meal (herein referred to as parasite exposure) greatly influence the effectiveness of transmission blocking interventions but still remains poorly documented. During a year-long analysis of malaria parasite transmission in Burkina Faso we caught and dissected wild malaria vectors to assess Plasmodium oocysts prevalence and load (the number of oocysts counted in mosquitoes with detectable oocysts) and the prevalence of salivary gland sporozoites. This was compared to malaria endemicity in the human population assessed in cross-sectional surveys. Data was analyzed using a novel transmission mathematical model to estimate the per-bite transmission probability and the average parasite exposure of mosquitoes for each location. Observed oocysts load and estimated parasite exposure in naturally infected mosquitoes is substantially higher than previous estimates (ranging from 3.2 to 24.5 according to seasons and locations) and indicates a strong positive association between parasite exposure of mosquitoes and parasite prevalence in human. This work suggests that highly infected mosquitoes may have a greater influence on the epidemiology and genetics of the parasite and that novel partially effective transmission blocking interventions may become more effective at halting transmission as parasite exposure is diminished.

ecology↗