Biology subjects

Toure, M.

Publications and source records attributed to Toure, M..

3 recordsLinked to original sources

bioRxiv2025

Phenotypic assessment and genetic validation of Plasmodium falciparum molecular markers associated with malaria chemoprevention in Senegal

Drug resistance in Plasmodium falciparum threatens to undermine malaria control and elimination efforts. Senegal is a malaria-endemic country that has implemented successive antimalarial and chemopreventive drug-based strategies for two decades. Sulfadoxine-pyrimethamine (SP) is used for chemoprevention in Senegal for intermittent preventive treatment in pregnancy (since 2004) and SP plus amodiaquine (AQ) is used for seasonal malaria chemoprevention (SMC, since 2013). Using whole genome sequence (WGS) data from malaria patient samples from health facilities across Senegal (2006 - 2022), we observed near fixation of Pfdhfr triple mutant and fluctuation in Pfdhps and Pfcrt mutation frequencies over time. It is unclear how these mutations influence drug resistance and fitness phenotypes in natural isolates; therefore, we evaluated natural parasite isolates with different Pfcrt, Pfmdr1, Pfdhps, and Pfdhfr haplotypes. Parasites were culture-adapted and phenotyped for antimalarial drug susceptibility and competitive growth (fitness). Pfcrt CVIET + A220S + Q271E + N326S + R371I and Pfcrt CVIET + A220S + Q271E + I356T + R371I mutants were significantly more resistant to monodesethyl-amodiaquine (md-AQ) compared to Pfcrt wild-type (WT) and Pfcrt CVIET + A220S + Q271E + R371I mutants. Pfdhfr triple mutants were significantly more pyrimethamine (PYR) resistant than Pfdhfr WT and revealed a range of phenotypes, but this was not explained by Pfgch1 copy-number. Pfdhps A437G parasites were significantly more sulfadoxine (SDX) resistant compared to Pfdhps wild-type and Pfdhps S436A mutants, suggesting that A437G is a key mutation for SDX resistance. Competitive growth assays between Pfdhfr-Pfdhps mutants revealed that Pfdhps mutations do not always result in fitness costs. Ongoing phenotypic assessment and genetic validation of these mutations in a Senegalese background is necessary to assess the impact of drug pressure, identify evolving genetic determinants of drug resistance, and provide molecular markers for ongoing surveillance to monitor and guide the use of drug-based interventions. AUTHOR SUMMARYDrug resistance is a major concern for both preventing and treating malaria, especially in Africa where most malaria cases and deaths occur. Since 2013, Senegal has been giving children under 10 years old a combination of sulfadoxine-pyrimethamine plus amodiaquine to prevent malaria during the transmission season, called Seasonal Malaria Chemoprevention (SMC), and plans to continue expanding its use. However, there is evidence from genetic surveillance that drug resistance mutations are present in Senegal which could render this antimalarial drug combination ineffective. Here we use natural P. falciparum isolates obtained from Senegalese patients that represent the extant parasite population to evaluate the consequences of evolving mutations on antimalarial drug resistance and fitness phenotypes. This study is one of the first to use natural parasites to assess the impact of naturally derived mutations on drug resistance and fitness phenotypes. Our results provide evidence that certain combinations of drug resistance mutations impact both parasite drug resistance and fitness, and therefore need to be closely monitored and can inform optimal antimalarial combinations for the prevention or treatment of malaria. This work informs the ongoing evolution of resistance and fitness phenotypes in malaria endemic settings that are introducing new multi first line therapies (MFTs) and SMC interventions that have been used for decades in Senegal. Our approach creates a framework for using genetic surveillance data to form a hypothesis, which can then be phenotypically tested by measuring the resistance and fitness levels of genetically diverse natural parasite isolates.

molecular biology↗

bioRxiv2025

Patterns of Aedes aegypti immature ecology and arboviral epidemic risks in peri-urban and intra-urban villages of Cocody-Bingerville, Cote d'Ivoire: insights from a dengue outbreak

BackgroundIn Cote dIvoire, Aedes vector studies and arboviral outbreak responses have mostly focused on urbanized neighborhoods including intra-urban villages, but have often neglected peripheral villages. We assessed and compared Aedes aegypti population dynamics and dengue (DEN) and yellow fever (YF) epidemic risks among peri-urban and intra-urban villages during the 2023-2024 DEN outbreaks in Cocody-Bingerville, southern Cote dIvoire. MethodsFrom August 2023 to July 2024, we sampled Aedes eggs, larvae and pupae in the domestic and peridomestic ecozones of three peri-urban and three intra-urban villages. We compared Ae. aegypti larval infestation, container productivity, Stegomyia indices (house index: HI, container index: CI, and Breteau index: BI) and pupal indices (pupae per house index: PHI, pupae per container index: PCI, and pupae per person index: PPI) between the study villages. ResultsAedes aegypti widely dominated Aedes fauna in both peri-urban (98.1%) and intra-urban (99.8%) villages. Immatures were sampled from seven container types. However, the most productive containers were small containers, tires and medium containers which produced 81.8% of all the pupae in the peri-urban villages, and tires and small containers yielding 83.2% in the intra-urban villages. These key containers produced substantially more pupae in the domestic ecozones (70.9%) in the peri-urban villages, but equitably between the domestic (48.8%) and peridomestic (51.2%) ecozones in the intra-urban villages. In each study village, they yielded around 90% and 80% of pupae during the short dry and long rainy seasons, respectively. CI, HI and BI were comparable between the peri-urban (29.9%, 35.9% and 41.4) and intra-urban (36.7%, 48.0% and 56.2) villages, and surpassed the World Health Organization (WHO) DEN and YF epidemic thresholds. PCI (1.26 vs. 3.38 pupae/container) and PHI (1.75 vs. 5.18 pupae/house) were lower in the peri-urban than in the intra-urban villages, while PPI (0.54 vs. 1.25 pupae/person) was similar between the villages. Unlike temperature and relative humidity, all indices were strongly associated with rainfall in all the study villages. ConclusionIn Cocody-Bingerville, all sampled peri-urban and intra-urban villages exhibited high densities of Ae. aegypti immatures and habitats. Although larval habitats were diverse, a limited number of container types accounted for over 80% of pupal production. Stegomyia indices remained consistently elevated, exceeding WHO epidemic thresholds for DEN and YF across all study villages, potentially contributing to ongoing DEN outbreaks. Therefore, vector surveillance and outbreak responses should be extended to peri-urban villages, as they could act as arbovirus re-introduction sources. Community-based interventions targeting the identified key containers could help control the outbreaks. This study provides a baseline for strategically reducing human exposure to arboviruses in the study villages.

ecology↗

bioRxiv2025

Assessing the oviposition and larval ecologies of mosquitoes and Stegomyia indices along an urban-rural gradient during ongoing dengue outbreaks in the arboviral hotspots of Cocody-Bingerville, southeastern Cote d'Ivoire

BackgroundCote dIvoire (West Africa) has recurrently faced multiple outbreaks of Aedes mosquito-transmitted arboviral diseases (e.g., dengue (DEN) and yellow fever (YF)), mainly in the health district of Cocody-Bingerville subjected to rapid urbanization. Thus, this study assessed the ecology of mosquito immatures and Stegomyia indices along an urban-rural gradient during ongoing dengue outbreaks within arboviral hotspots in Cocody-Bingerville. MethodsBetween August 2023 and July 2024, we collected mosquito eggs and larvae in urban, suburban and rural areas of Cocody-Bingerville using standard ovitraps and larval surveys. Collections were done in the domestic and peridomestic ecozones, and during rainy and dry seasons. Species composition, oviposition indices (ovitrap positive index (OPI), mean egg counts per ovitrap (MEO) and egg density index (EDI)) and Stegomyia indices (house index (HI), container index (CI) and Breteau index (BI)) were compared across the study areas, ecozones and seasons, and with the World Health Organization (WHO) DEN and YF epidemic thresholds. ResultsOverall, all the study areas were highly infested with diversified mosquito species, with the highest Stegomyia risk indices recorded in the urban areas. We identified (individuals: species) in the all study (70,550: 15), urban (32,331: 10), suburban (19,768: 14) and rural (18,451: 15) areas. Mosquitoes were mostly abundant in the domestic ecozones and rainy seasons. Larvae bred mainly in tires in the urban and suburban, and small containers in the rural areas. Wild Aedes species (Aedes dendrophilus, Aedes lilii, Aedes fraseri, Aedes luteocephalus, Aedes metallicus and Aedes vittatus) were mostly restricted in the suburban and rural areas, as well as mosquito predatory larvae (Lutzia tigripes, Toxorhynchites and Eretmapodites). However, Aedes aegypti spread and dominated throughout, showing highest proportions in the urban (90.2%), followed by the suburban (68.6%) and rural (68.5%) areas. OPI, MEO (egg/ovitrap/week) and EDI (egg/ovitrap/week) values were higher in the urban areas (53.0%, 8.7 and 16.4) than in the suburban (43.1%, 5.56 and 12.9) and rural (33.7%, 4.4 and 13.0) areas, respectively, and correlated with Stegomyia indices. HI, CI and BI were higher in the urban (48.0%, 40.4% and 61.8) compared with the suburban (37.8%, 32.0% and 43.3) and rural (34.5%, 28.87% and 39.8) areas. Stegomyia indices corresponded to the WHO-density scales of 6-8 in the urban and 5-7 in the suburban and rural areas. Stegomyia indices were all above the WHO epidemic thresholds: YF risk was high the urban and moderate in the suburban and rural areas, while people were permanently exposed to high risk of DEN outbreaks in all the areas. Conclusions/significanceIn Cocody-Bingerville, urbanization shifts mosquito biodiversity, with restriction of wild Aedes and predatory species in the rural and suburban areas and dominance of Ae. aegypti in the urban areas. Stegomyia indices exceeded the WHO DEN and YF epidemic thresholds in all the areas, with highest risks in the urban areas. This could explain the current DEN outbreaks in urban Cocody-Bingerville. Our study provides a baseline for raising local community awareness and guiding appropriate preventive actions, including managing identified larval habitats to contain ongoing dengue outbreaks in Cote dIvoire. Author summaryCote dIvoire has experienced several epidemics of dengue and yellow fever transmitted by Aedes mosquitoes. Over 80-90% of dengue and yellow fever cases were reported in the urban areas of the health district of Cocody-Bingerville, southeastern Cote dIvoire. The increase in the frequency, magnitude and burden of these outbreaks has paralleled to the fast and uncontrolled urbanization. However, data are still lacking on how urbanization influences the ecology of the local mosquito vectors and the risks of transmission of dengue and yellow fever, thus compromising adequate planning of preventive actions. Therefore, we assessed the mosquito species composition and larval breeding sites, and Stegomyia indices in urban, suburban and rural areas within the disease hotspots during ongoing dengue outbreaks in the Cocody-Bingerville. Our results showed that mosquito species diversity altered considerably from urban to rural areas, leading to a dominance of the main vector Aedes aegypti in all the study areas. Moreover, Aedes aegypti showed the highest proportions in the urban areas that contained more larval breeding sites (e.g., tires and small containers). Stegomyia indices were very high and above the World Health Organization (WHO) epidemic thresholds, suggesting that people were exposed to high dengue risks and moderate yellow fever risks in all the study areas, but were more exposed to both diseases in the urban areas. This could explain the recurrent and present dengue outbreaks in urban Cocody-Bingerville. A community-based management of identified larval habitats might help to control the ongoing dengue outbreaks in Cocody-Bingerville, and more widely in similar settings.

ecology↗