Malaria in Burkina Faso: A comprehensive analysis of spatiotemporal distribution of incidence and environmental drivers, and implications for control strategies.

BACKGROUND: The number of malaria cases worldwide has increased, with over 241 million cases and 69,000 more deaths in 2020 compared to 2019. Burkina Faso recorded over 11 million malaria cases in 2020, resulting in nearly 4,000 deaths. The overall incidence of malaria in Burkina Faso has been steadily increasing since 2016. This study investigates the spatiotemporal pattern and environmental and meteorological determinants of malaria incidence in Burkina Faso. METHODS: We described the temporal dynamics of malaria cases by detecting the transmission periods and the evolution trend from 2013 to 2018. We detected hotspots using spatial scan statistics. We assessed different environmental zones through a hierarchical clustering and analyzed the environmental and climatic data to identify their association with malaria incidence at the national and at the district's levels through generalized additive models. We also assessed the time lag between malaria peaks onset and the rainfall at the district level. The environmental and climatic data were synthetized into indicators. RESULTS: The study found that malaria incidence had a seasonal pattern, with high transmission occurring during the rainy seasons. We also found an increasing trend in the incidence. The highest-risk districts for malaria incidence were identified, with a significant expansion of high-risk areas from less than half of the districts in 2013-2014 to nearly 90% of the districts in 2017-2018. We identified three classes of health districts based on environmental and climatic data, with the northern, south-western, and western districts forming separate clusters. Additionally, we found that the time lag between malaria peaks onset and the rainfall at the district level varied from 7 weeks to 17 weeks with a median at 10 weeks. Environmental and climatic factors have been found to be associated with the number of cases both at global and districts levels. CONCLUSION: The study provides important insights into the environmental and spatiotemporal patterns of malaria in Burkina Faso by assessing the spatio temporal dynamics of Malaria cases but also linking those dynamics to the environmental and climatic factors. The findings highlight the importance of targeted control strategies to reduce the burden of malaria in high-risk areas as we found that Malaria epidemiology is complex and linked to many factors that make some regions more at risk than others.

Durability of the deltamethrin-treated polypropylene long-lasting net LifeNet® in a pyrethroid resistance area in south western Benin: A phase III trial.

BACKGROUND: Long-lasting insecticidal bed nets (LLINs) are a key measure for preventing malaria and their evaluation is coordinated by the World Health Organization Pesticide Evaluation Scheme (WHOPES). LifeNet® was granted WHOPES time-limited interim recommendation in 2011 after successful Phase I and Phase II evaluations. Here, we evaluated the durability and community acceptance of LifeNet® in a Phase III trial from June 2014 to June 2017 in Benin rural area. METHODS: A prospective longitudinal, cluster-randomized, controlled trial with households as the unit of observation was designed to assess the performance of LifeNet® over a three-year period, using a WHOPES fully recommended LLIN (PermaNet® 2.0) as a positive control. The primary outcomes were the bioassay performance using WHO cone assays and tunnel tests, the insecticide content and physical integrity. RESULTS: At baseline, 100% of LLINs were within the tolerance limits of their target deltamethrin concentrations. By 36 months only 17.3% of LifeNet® and 8.5% of PermaNet® LLINs still were within their target deltamethrin concentrations. Despite these low rates, 100% of both LLINs meet WHO efficacy criteria (≥ 80% mortality or ≥ 95% knockdown or tunnel test criteria of ≥ 80% mortality or ≥ 90% blood-feeding inhibition) after 36 months using WHO cone bio-assays and tunnel tests. The proportion of LLINs in good physical condition was 33% for LifeNet® and 29% for PermaNet® after 36 months. After 36 M the survivorship was 21% and 26% for LifeNet® and PermaNet® respectively. Although both LLINs were well accepted by the population, complaints of side effects were significantly higher among LifeNet® users than PermaNet® ones. CONCLUSION: LifeNet® LLINs did meet WHO criteria for bio-efficacy throughout the study period and were well accepted by the population. This is an important step towards getting a full WHO recommendation for use in malaria endemic countries.

Anopheles sampling collections in the health districts of Korhogo (Côte d'Ivoire) and Diébougou (Burkina Faso) between 2016 and 2018.

Characterizing the entomological profile of malaria transmission at fine spatiotemporal scales is essential for developing and implementing effective vector control strategies. Here, we present a fine-grained dataset of Anopheles mosquitoes (Diptera: Culicidae) collected in 55 villages of the rural districts of Korhogo (Northern Côte d'Ivoire) and Diébougou (South-West Burkina Faso) between 2016 and 2018. In the framework of a randomized controlled trial, Anopheles mosquitoes were periodically collected by Human Landing Catches experts inside and outside households, and analyzed individually to identify the genus and, for a subsample, species, insecticide resistance genetic mutations, Plasmodium falciparum infection, and parity status. More than 3,000 collection sessions were carried out, achieving about 45,000 h of sampling efforts. Over 60,000 Anopheles were collected (mainly A. gambiae s.s., A. coluzzii, and A. funestus). The dataset is published as a Darwin Core archive in the Global Biodiversity Information Facility, comprising four files: events, occurrences, mosquito characterizations, and environmental data.

Influence of the sickle cell trait on Plasmodium falciparum infectivity from naturally infected gametocyte carriers.

BACKGROUND: Sickle cell trait (SCT) refers to the carriage of one abnormal copy of the ß-globin gene, the HbS allele. SCT offers protection against malaria, controlling parasite density and preventing progression to symptomatic malaria. However, it remains unclear whether SCT also affects transmission stages and mosquito infection parameters. Deciphering the impact of the SCT on human to mosquito malaria transmission is key to understanding mechanisms that maintain the trait in malaria endemic areas. METHODS: The study was conducted from June to July 2017 among asymptomatic children living in the locality of Mfou, Cameroon. Blood samples were collected from asymptomatic children to perform malaria diagnosis by microscopy, Plasmodium species by PCR and hemoglobin typing by RFLP. Infectiousness of gametocytes to mosquitoes was assessed by membrane feeding assays using blood from gametocyte carriers of HbAA and HbAS genotypes. A zero-inflated model was fitted to predict distribution of oocysts in mosquitoes according to hemoglobin genotype of the gametocyte source. RESULTS: Among the 1557 children enrolled in the study, 314 (20.16%) were of the HbAS genotype. The prevalence of children with P. falciparum gametocytes was 18.47% in HbAS individuals and 13.57% in HbAA, and the difference is significant (χ2 = 4.61, P = 0.032). Multiplicity of infection was lower in HbAS gametocyte carriers (median = 2 genotypes/carrier in HbAS versus 3.5 genotypes/carrier in HbAA, Wilcoxon sum rank test = 188, P = 0.032). Gametocyte densities in the blood donor significantly influenced mosquito infection prevalence in both HbAS and HbAA individuals. The HbAS genotype had no significant effect on mosquito infection outcomes when using immune or naïve serum in feeding assays. In AB replacement feeding experiments, the odds ratio of mosquito infection for HbAA blood as compared to HbAS was 0.56 (95% CI 0.29-1.10), indicating a twice higher risk of infection in mosquitoes fed on gametocyte-containing blood of HbAS genotype. CONCLUSION: Plasmodium transmission stages were more prevalent in SCT individuals. This may reflect the parasite's enhanced investment in the sexual stage to increase their survival rate when asexual replication is impeded. The public health impact of our results points the need for intensive malaria control interventions in areas with high prevalence of HbAS. The similar infection parameters in feeding experiments where mosquitoes received the original serum from the blood donor indicated that immune responses to gametocyte surface proteins occur in both HbAS and HbAA individuals. The higher risk of infection in mosquitoes fed on HbAS blood depleted of immune factors suggests that changes in the membrane properties in HbAS erythrocytes may impact on the maturation process of gametocytes within circulating red blood cells.

Proof-of-concept study for a long-acting formulation of ivermectin injected in cattle as a complementary malaria vector control tool.

BACKGROUND: Domesticated animals play a role in maintaining residual transmission of Plasmodium parasites of humans, by offering alternative blood meal sources for malaria vectors to survive on. However, the blood of animals treated with veterinary formulations of the anti-helminthic drug ivermectin can have an insecticidal effect on adult malaria vector mosquitoes. This study therefore assessed the effects of treating cattle with long-acting injectable formulations of ivermectin on the survival of an important malaria vector species, to determine whether it has potential as a complementary vector control measure. METHODS: Eight head of a local breed of cattle were randomly assigned to either one of two treatment arms (2 × 2 cattle injected with one of two long-acting formulations of ivermectin with the BEPO® technology at the therapeutic dose of 1.2 mg/kg), or one of two control arms (2 × 2 cattle injected with the vehicles of the formulations). The lethality of the formulations was evaluated on 3-5-day-old Anopheles coluzzii mosquitoes through direct skin-feeding assays, from 1 to 210 days after treatment. The efficacy of each formulation was evaluated and compared using Cox proportional hazards survival models, Kaplan-Meier survival estimates, and log-logistic regression on cumulative mortality. RESULTS: Both formulations released mosquitocidal concentrations of ivermectin until 210 days post-treatment (hazard ratio > 1). The treatments significantly reduced mosquito survival, with average median survival time of 4-5 days post-feeding. The lethal concentrations to kill 50% of the Anopheles (LC50) before they became infectious (10 days after an infectious blood meal) were maintained for 210 days post-injection for both formulations. CONCLUSIONS: This long-lasting formulation of ivermectin injected in cattle could complement insecticide-treated nets by suppressing field populations of zoophagic mosquitoes that are responsible, at least in part, for residual malaria transmission. The impact of this approach will of course depend on the field epidemiological context. Complementary studies will be necessary to characterize ivermectin withdrawal times and potential environmental toxicity.

Entomological drivers of uneven malaria transmission in urban lowland areas in Bouaké, Côte d'Ivoire.

BACKGROUND: The use of urban lowlands for agriculture contributes to the food security of city- dwellers, but promotes malaria transmission. The objective of the study was to characterize the entomological drivers of malaria transmission in two lowlands (N'Gattakro and Odiennekourani) in the city of Bouaké, Côte d'Ivoire. METHODS: The human landing catch technique was used to capture mosquitoes in houses located at the edge of two lowlands in Bouaké from February to December 2019. Cultivated surfaces were calculated monthly in both lowlands for each crop type (rice and market gardening) using images acquired by a drone. The different mosquito species were identified morphologically and by PCR analysis for the Anopheles gambiae complex. Anopheles infection by Plasmodium parasites was assessed by quantitative PCR. Mosquito diversity, biting behaviour and rhythmicity, and malaria transmission were determined in each lowland and compared. RESULTS: Anopheles gambiae sensu lato (s.l.) was predominant in N'Gattakro and Culex quinquefasciatus in Odiennekourani. Four Anopheles species were identified: An. gambiae s.l. and Anopheles funestus s.l. in both lowlands, Anopheles pharoensis in N'Gattakro, and Anopheles ziemanni in Odiennekourani. Within the An. gambiae complex, three species were caught: An. gambiae sensu stricto (s.s.), Anopheles coluzzii, and Anopheles arabiensis for the first time in Côte d'Ivoire (30.1%, 69.9% and 0% in N'Gattakro, and 45.1%, 52.6% and 2.4% in Odiennekourani, respectively). Anopheles gambiae s.l. species exhibited a significant exophagic behaviour in N'Gattakro (77.1% of outdoor bites versus 52.2% in Odiennekourani). In N'Gattakro, 12.6% of captures occurred before bedtime (09.00 pm) and after waking up (05.00 am), 15.1% in Odiennekourani. The mean human biting rate was higher in N'Gattakro than in Odiennekourani (61.6 versus 15.5 bites per person per night). Overall, Anopheles infection rate was 0.68%, with 0.539 and 0.029 infected bites per person per night in N'Gattakro and Odiennekourani, respectively. CONCLUSION: The risk of malaria in urban agricultural lowland areas is uneven. The role of agricultural developments and irrigation patterns in the production of larval habitat should be explored. The exophagic behaviour of Anopheles vectors raises the question of the residual transmission that needs to be assessed to implement appropriate control strategies.

First detection of the malaria vector Anopheles arabiensis in Côte d'Ivoire: urbanization in question.

BACKGROUND: Previous studies have revealed high malaria transmission in Bouaké, Côte d'Ivoire. The sociopolitical crisis in the country and the resulting environmental changes have raised the need to update existing knowledge on mosquito vector species and malaria transmission. METHODS: Adult mosquitoes were caught using the human landing catch (HLC) sampling method in Bouaké. They were collected in six districts representative of the diversity in urban landscapes. Sampling points were selected along the water network crossing the city and monitored from 2020 to 2021 to detect the presence of anopheline larvae. PCR techniques were used to ascertain the species of the Anopheles gambiae complex, Plasmodium falciparum sporozoite infection in a subset of Anopheles vectors, and insecticide resistance mechanisms in Anopheles arabiensis only. RESULTS: A total of 4599 Anopheles mosquitoes were collected and then identified. Anopheles gambiae sensu lato (s.l.) made up the majority of the whole collection (99%) while Anopheles funestus (0.7%), Anopheles ziemanni (0.2%), Anopheles pharoensis (0.2%) represented the remaining proportion of collection. Among the Anopheles gambiae complex, three species were identified namely An. gambiae sensu stricto (45.9%), Anopheles coluzzii (52.2%), and Anopheles arabiensis (1.9%). The first two species had already been collected in Bouaké, however this is the first time that An. arabiensis is reported in Côte d'Ivoire. Anopheles arabiensis was also collected during the larval surveys in a similar proportion (1.1%) in the same areas as the adults. CONCLUSIONS: This study detected the presence of An. arabiensis for the first time in Côte d'Ivoire. This species was found quite far from its usual geographic area and its expansion could be linked to the urbanization process. Although no An. arabiensis was found to be infected by Plasmodium sp., its role in malaria transmission in Bouaké has to be explored, particularly since its exophagic behaviour raises the issue of control measures and the use of insecticide-impregnated nets. The spread of this species in Côte d'Ivoire should be assessed through further research in additional towns in the country.

Spatio-temporal analysis and prediction of malaria cases using remote sensing meteorological data in Diébougou health district, Burkina Faso, 2016-2017.

Malaria control and prevention programs are more efficient and cost-effective when they target hotspots or select the best periods of year to implement interventions. This study aimed to identify the spatial distribution of malaria hotspots at the village level in Diébougou health district, Burkina Faso, and to model the temporal dynamics of malaria cases as a function of meteorological conditions and of the distance between villages and health centres (HCs). Case data for 27 villages were collected in 13 HCs. Meteorological data were obtained through remote sensing. Two synthetic meteorological indicators (SMIs) were created to summarize meteorological variables. Spatial hotspots were detected using the Kulldorf scanning method. A General Additive Model was used to determine the time lag between cases and SMIs and to evaluate the effect of SMIs and distance to HC on the temporal evolution of malaria cases. The multivariate model was fitted with data from the epidemic year to predict the number of cases in the following outbreak. Overall, the incidence rate in the area was 429.13 cases per 1000 person-year with important spatial and temporal heterogeneities. Four spatial hotspots, involving 7 of the 27 villages, were detected, for an incidence rate of 854.02 cases per 1000 person-year. The hotspot with the highest risk (relative risk = 4.06) consisted of a single village, with an incidence rate of 1750.75 cases per 1000 person-years. The multivariate analysis found greater variability in incidence between HCs than between villages linked to the same HC. The time lag that generated the better predictions of cases was 9 weeks for SMI1 (positively correlated with precipitation variables) and 16 weeks for SMI2 (positively correlated with temperature variables. The prediction followed the overall pattern of the time series of reported cases and predicted the onset of the following outbreak with a precision of less than 3 weeks. This analysis of malaria cases in Diébougou health district, Burkina Faso, provides a powerful prospective method for identifying and predicting high-risk areas and high-transmission periods that could be targeted in future malaria control and prevention campaigns.

Effects of insemination and blood-feeding on locomotor activity of wild-derived females of the malaria mosquito Anopheles coluzzii.

BACKGROUND: Behavioural shifts in the canonical location and timing of biting have been reported in natural populations of anopheline malaria vectors following the implementation of insecticide-based indoor vector control interventions. These modifications increase the likelihood of human-vector contact and allow mosquitoes to avoid insecticides, both conditions being favourable to residual transmission of the malarial parasites. The biting behaviour of mosquitoes follows rhythms that are under the control of biological clocks and environmental conditions, modulated by physiological states. In this work we explore modifications of spontaneous locomotor activity expressed by mosquitoes in different physiological states to highlight phenotypic variability associated to circadian control that may contribute to explain residual transmission in the field. METHODS: The F10 generation progeny of field-collected Anopheles coluzzii from southwestern Burkina Faso was tested using an automated recording apparatus (Locomotor Activity Monitor, TriKinetics Inc.) under LD 12:12 or DD light regimens in laboratory-controlled conditions. Activity recordings of each test were carried out for a week with 6-day-old females belonging to four experimental treatments, representing factorial combinations of two physiological variables: insemination status (virgin vs inseminated) and gonotrophic status (glucose fed vs blood fed). Chronobiological features of rhythmicity in locomotor activity were explored using periodograms, diversity indices, and generalized linear mixed modelling. RESULTS: The average strength of activity, onset of activity, and acrophase were modulated by both nutritional and insemination status as well as by the light regimen. Inseminated females showed a significant excess of arrhythmic activity under DD. When rhythmicity was observed in DD, females displayed sustained activity also during the subjective day. CONCLUSIONS: Insemination and gonotrophic status influence the underlying light and circadian control of chronobiological features of locomotor activity. Overrepresentation of arrhythmic chronotypes as well as the sustained activity of inseminated females during the subjective day under DD conditions suggests potential activity of natural populations of A. coluzzii during daytime under dim conditions, with implications for residual transmission of malarial parasites.

Evaluation of Yahe® and Panda® 2.0 long-lasting insecticidal nets against wild pyrethroid-resistant Anopheles gambiae s.l. from Côte d'Ivoire: an experimental hut trial.

BACKGROUND: Long-lasting insecticidal nets (LLINs) have played an important role in reducing the global malaria burden since 2000. They are a core prevention tool used widely by people at risk of malaria. The Vector Control Prequalification mechanism of the Word Health Organization (WHO-Vector Control PQ) established the testing and evaluation guidelines for LLINs before registration for public use. In the present study, two new brands of deltamethrin-impregnated nets (Yahe® LN and Panda® Net 2.0) were evaluated in an experimental hut against wild pyrethroid-resistant Anopheles gambiae s.l. in M'Bé nearby Bouaké, central Côte d'Ivoire. METHODS: The performance of Yahe® LN and Panda® Net 2.0 was compared with that of PermaNet 2.0, conventionally treated nets (CTN), and untreated net to assess the blood-feeding inhibition, deterrence, induced exophily, and mortality. RESULTS: Cone bioassay results showed that Panda® Net 2.0, PermaNet 2.0 and Yahe® LN (both unwashed and washed 20 times) induced > 95% knockdown or > 80% mortality of the susceptible Anopheles gambiae Kisumu strain. With the pyrethroid-resistant M'Bé strain, mortality rate for all treated nets did not exceed 70%. There was a significant reduction in entry and blood feeding (p < 0.05) and an increase in exophily and mortality rates (p < 0.05) with all treatments compared to untreated nets, except the CTNs. However, the personal protection induced by these treated nets decreased significantly after 20 washes. The performance of Panda® Net 2.0 was equal to PermaNet® 2.0 in terms of inhibiting blood feeding, but better than PermaNet® 2.0 in terms of mortality. CONCLUSION: This study showed that Yahe® LN and Panda® Net 2.0 met the WHO Pesticide Evaluation Scheme (WHOPES) criteria to undergo phase III trial at the community level. Due to an increasing spread and development of pyrethroid resistance in malaria vectors, control of malaria transmission must evolve into an integrated vector management relying on a large variety of efficient control tools.

Data-driven and interpretable machine-learning modeling to explore the fine-scale environmental determinants of malaria vectors biting rates in rural Burkina Faso.

BACKGROUND: Improving the knowledge and understanding of the environmental determinants of malaria vector abundance at fine spatiotemporal scales is essential to design locally tailored vector control intervention. This work is aimed at exploring the environmental tenets of human-biting activity in the main malaria vectors (Anopheles gambiae s.s., Anopheles coluzzii and Anopheles funestus) in the health district of Diébougou, rural Burkina Faso. METHODS: Anopheles human-biting activity was monitored in 27 villages during 15 months (in 2017-2018), and environmental variables (meteorological and landscape) were extracted from high-resolution satellite imagery. A two-step data-driven modeling study was then carried out. Correlation coefficients between the biting rates of each vector species and the environmental variables taken at various temporal lags and spatial distances from the biting events were first calculated. Then, multivariate machine-learning models were generated and interpreted to (i) pinpoint primary and secondary environmental drivers of variation in the biting rates of each species and (ii) identify complex associations between the environmental conditions and the biting rates. RESULTS: Meteorological and landscape variables were often significantly correlated with the vectors' biting rates. Many nonlinear associations and thresholds were unveiled by the multivariate models, for both meteorological and landscape variables. From these results, several aspects of the bio-ecology of the main malaria vectors were identified or hypothesized for the Diébougou area, including breeding site typologies, development and survival rates in relation to weather, flight ranges from breeding sites and dispersal related to landscape openness. CONCLUSIONS: Using high-resolution data in an interpretable machine-learning modeling framework proved to be an efficient way to enhance the knowledge of the complex links between the environment and the malaria vectors at a local scale. More broadly, the emerging field of interpretable machine learning has significant potential to help improve our understanding of the complex processes leading to malaria transmission, and to aid in developing operational tools to support the fight against the disease (e.g. vector control intervention plans, seasonal maps of predicted biting rates, early warning systems).

Malaria vectors diversity, insecticide resistance and transmission during the rainy season in peri-urban villages of south-western Burkina Faso.

BACKGROUND: This study reports an updated description on malaria vector diversity, behaviour, insecticide resistance and malaria transmission in the Diébougou and Dano peri-urban areas, Burkina Faso. METHODS: Mosquitoes were caught monthly using CDC light traps and pyrethrum spray catches. Mosquitoes were identified using morphological taxonomic keys. PCR techniques were used to identify the species of the Anopheles gambiae complex and insecticide resistance mechanisms in a subset of Anopheles vectors. The Plasmodium sporozoite infection status and origins of blood meals of female mosquitoes were determined by ELISA methods. Larvae were collected, breed in the insectary and tested for phenotypic resistance against four insecticides using WHO bioassays. RESULTS: This study contributed to update the entomological data in two peri-urban areas of Southwest Burkina Faso. Anopheles populations were mostly anthropophilic and endophilic in both areas and exhibit high susceptibility to an organophosphate insecticide. This offers an alternative for the control of these pyrethroid-resistant populations. These data might help the National Malaria Control Programme for decision-making about vector control planning and resistance management. CONCLUSIONS: This study contributed to update the entomological data in two peri-urban areas of Southwest Burkina Faso. Anopheles populations were mostly anthropophilic and endophilic in both areas and exhibit high susceptibility to an organophosphate insecticide. This offers an alternative for the control of these pyrethroid-resistant populations. These data might help the National Malaria Control Programme for decision-making about vector control planning and resistance management.

Insecticide resistance status of malaria vectors Anopheles gambiae (s.l.) of southwest Burkina Faso and residual efficacy of indoor residual spraying with microencapsulated pirimiphos-methyl insecticide.

BACKGROUND: The rapid spread of insecticide resistance in malaria vectors and the rebound in malaria cases observed recently in some endemic areas underscore the urgent need to evaluate and deploy new effective control interventions. A randomized control trial (RCT) was conducted with the aim to investigate the benefit of deploying complementary strategies, including indoor residual spraying (IRS) with pirimiphos-methyl in addition to long-lasting insecticidal nets (LLINs) in Diébougou, southwest Burkina Faso. METHODS: We measured the susceptibility of the Anopheles gambiae (s.l.) population from Diébougou to conventional insecticides. We further monitored the efficacy and residual activity of pirimiphos-methyl on both cement and mud walls using a laboratory susceptible strain (Kisumu) and the local An. gambiae (s.l.) population. RESULTS: An. gambiae (s.l.) from Diébougou was resistant to DDT, pyrethroids (deltamethrin, permethrin and alphacypermethrin) and bendiocarb but showed susceptibility to organophosphates (pirimiphos-methyl and chlorpyrimiphos-methyl). A mixed-effect generalized linear model predicted that pirimiphos-methyl applied on cement or mud walls was effective for 210 days against the laboratory susceptible strain and 247 days against the local population. The residual efficacy of pirimiphos-methyl against the local population on walls made of mud was similar to that of cement (OR = 0.792, [0.55-1.12], Tukey's test p-value = 0.19). CONCLUSIONS: If data on malaria transmission and malaria cases (as measured trough the RCT) are consistent with data on residual activity of pirimiphos-methyl regardless of the type of wall, one round of IRS with pirimiphos-methyl would have the potential to control malaria in a context of multi-resistant An. gambiae (s.l.) for at least 7 months.

Anopheles bionomics, insecticide resistance and malaria transmission in southwest Burkina Faso: A pre-intervention study.

BACKGROUND: Twenty-seven villages were selected in southwest Burkina Faso to implement new vector control strategies in addition to long lasting insecticidal nets (LLINs) through a Randomized Controlled Trial (RCT). We conducted entomological surveys in the villages during the dry cold season (January 2017), dry hot season (March 2017) and rainy season (June 2017) to describe malaria vectors bionomics, insecticide resistance and transmission prior to this trial. METHODS: We carried out hourly catches (from 17:00 to 09:00) inside and outside 4 houses in each village using the Human Landing Catch technique. Mosquitoes were identified using morphological taxonomic keys. Specimens belonging to the Anopheles gambiae complex and Anopheles funestus group were identified using molecular techniques as well as detection of Plasmodium falciparum infection and insecticide resistance target-site mutations. RESULTS: Eight Anopheles species were detected in the area. Anopheles funestus s.s was the main vector during the dry cold season. It was replaced by Anopheles coluzzii during the dry hot season whereas An. coluzzii and An. gambiae s.s. were the dominant species during the rainy season. Species composition of the Anopheles population varied significantly among seasons. All insecticide resistance mechanisms (kdr-w, kdr-e and ace-1 target site mutations) investigated were found in each members of the An. gambiae complex but at different frequencies. We observed early and late biting phenotypes in the main malaria vector species. Entomological inoculation rates were 2.61, 2.67 and 11.25 infected bites per human per month during dry cold season, dry hot season and rainy season, respectively. CONCLUSION: The entomological indicators of malaria transmission were high despite the universal coverage with LLINs. We detected early and late biting phenotypes in the main malaria vector species as well as physiological insecticide resistance mechanisms. These data will be used to evaluate the impact of complementary tools to LLINs in an upcoming RCT.

Anopheles bionomics, insecticide resistance mechanisms, and malaria transmission in the Korhogo area, northern Côte d'Ivoire: a pre-intervention study.

A better understanding of malaria transmission at a local scale is essential for developing and implementing effective control strategies. In the framework of a randomized controlled trial (RCT), we aimed to provide an updated description of malaria transmission in the Korhogo area, northern Côte d'Ivoire, and to obtain baseline data for the trial. We performed human landing collections (HLCs) in 26 villages in the Korhogo area during the rainy season (September-October 2016, April-May 2017) and the dry season (November-December 2016, February-March 2017). We used PCR techniques to ascertain the species of the Anopheles gambiae complex, Plasmodium falciparum sporozoite infection, and insecticide resistance mechanisms in a subset of Anopheles vectors. Anopheles gambiae s.l. was the predominant malaria vector in the Korhogo area. Overall, more vectors were collected outdoors than indoors (p < 0.001). Of the 774 An. gambiae s.l. tested in the laboratory, 89.65% were An. gambiae s.s. and 10.35% were An. coluzzii. The frequencies of the kdr allele were very high in An. gambiae s.s. but the ace-1 allele was found at moderate frequencies. An unprotected individual living in the Korhogo area received an average of 9.04, 0.63, 0.06 and 0.12 infected bites per night in September-October, November-December, February-March, and April-May, respectively. These results demonstrate that the intensity of malaria transmission is extremely high in the Korhogo area, especially during the rainy season. Malaria control in highly endemic areas such as Korhogo needs to be strengthened with complementary tools in order to reduce the burden of the disease.

Behavioural adaptations of mosquito vectors to insecticide control.

Behavioural resistance to insecticides may be an important factor restraining the efficacy of vector control against mosquito-transmitted diseases. However, our understanding of the mechanisms underlying such behavioural resistance remains sparse. In this review, we focus on the behavioural adaptations of mosquito vectors in response to the use of insecticides and provide a general framework for guiding future investigations. We present our review of vector behaviour in the field and a conceptual classification of behavioural adaptations to insecticides. We emphasise that behavioural adaptations can result from constitutive or induced (i.e. phenotypically plastic) traits. Lastly, we identify gaps in knowledge limiting a better understanding of how mosquito behavioural adaptations may affect the fight against vector-borne diseases.

High level of soluble human leukocyte antigen (HLA)-G at beginning of pregnancy as predictor of risk of malaria during infancy.

Placental malaria has been associated with an immune tolerance phenomenon and a higher susceptibility to malaria infection during infancy. HLA-G is involved in fetal maternal immune tolerance by inhibiting maternal immunity. During infections HLA-G can be involved in immune escape of pathogens by creating a tolerogenic environment. Recent studies have shown an association between the risk of malaria and HLA-G at both genetic and protein levels. Moreover, women with placental malaria have a higher probability of giving birth to children exhibiting high sHLA-G, independently of their own level during pregnancy. Our aim was to explore the association between the level of maternal soluble HLA-G and the risk of malaria infection in their newborns. Here, 400 pregnant women and their children were actively followed-up during 24 months. The results show a significant association between the level of sHLA-G at the first antenatal visit and the time to first malaria infection during infancy adjusted to the risk of exposure to vector bites (aHR = 1.02, 95%CI [1.01-1.03], p = 0.014). The level of sHLA-G is a significant predictor of the occurrence of malaria infection during infancy consistent with the hypothesis that mother sHLA-G could be a biomarker of malaria susceptibility in children.

Efficacy of vector control tools against malaria-infected mosquitoes.

Within mosquito vector populations, infectious mosquitoes are the ones completing the transmission of pathogens to susceptible hosts and they are, consequently, of great epidemiological interest. Mosquito infection by malaria parasites has been shown to affect several traits of mosquito physiology and behavior, and could interplay with the efficacy of control tools. In this study, we evaluated, in pyrethroid resistant Anopheles gambiae, the effect of mosquito infection with the human malaria parasite Plasmodium falciparum on the efficacy of nets treated with either the insecticide deltamethrin or the repellent DEET, measuring (i) mosquito success to pass through the net, (ii) blood-feeding on a host and (iii) chemicals-induced mortality. Infection of mosquitoes at non-infectious stage did not affect their success to pass through the net, to blood-feed, nor chemicals-induced mortality. At infectious stage, depending on replicates, infected mosquitoes had higher mortality rates than uninfected mosquitoes, with stronger effect in presence of DEET. This data evidenced a cost of infection on mosquito survival at transmissible stages of infection, which could have significant consequences for both malaria epidemiology and vector control. This stresses the need for understanding the combined effects of insecticide resistance and infection on the efficacy on control tools.

Identification and characterization of Anopheles spp. breeding habitats in the Korhogo area in northern Côte d'Ivoire: a study prior to a Bti-based larviciding intervention.

BACKGROUND: Although larviciding may be a valuable tool to supplement long-lasting insecticide nets (LLINs) in West Africa in different ecological settings, its actual impact on malaria burden and transmission has yet to be demonstrated. A randomized controlled trial was therefore undertaken to assess the effectiveness of larviciding using Bacillus thuringiensis israeliensis (Bti) in addition to the use of LLINs. In order to optimally implement such a larviciding intervention, we first aimed to identify and to characterize the breeding habitats of Anopheles spp. in the entire study area located in the vicinity of Korhogo in northern Côte d'Ivoire. METHODS: We conducted two surveys during the rainy and the dry season, respectively, in the thirty villages around Korhogo involved in the study. In each survey, water bodies located within a 2 km radius around each village were identified and assessed for the presence of mosquito larvae. We morphologically identified the larvae to the genus level and we characterized all of the habitats positive for Anopheles spp. larvae based on a predefined set of criteria. RESULTS: Overall, 620 and 188 water bodies positive for Anopheles spp. larvae were sampled in the rainy and the dry season, respectively. A broad range of habitat types were identified. Rice paddies accounted for 61% and 57% of the habitats encountered in the rainy and the dry season, respectively. In the rainy season, edges of rivers and streams (12%) were the second most abundant habitats for Anopheles spp. larvae. More than 90% of the Anopheles spp. breeding habitats were surrounded by green areas. Dams, ponds and drains produced higher numbers of Anopheles spp. larvae per square meter than rice paddies (RR = 1.51; 95% CI: 1.18-1.94; P = 0.0010). The density of Anopheles spp. larvae was significantly higher in habitats surrounded by low-density housing (RR = 4.81; 95% CI: 1.84-12.60; P = 0.0014) and green areas (RR = 3.96; 95% CI: 1.92-8.16; P = 0.0002] than habitats surrounded by high-density housing. Turbid water [RR = 1.42 (95% CI: 1.15-1.76; P = 0.0012) was associated with higher densities of Anopheles spp. larvae. The likelihood of finding mosquito pupae in Anopheles spp. breeding habitats was higher in the dry season (OR = 5.92; 95% CI: 2.11-16.63; P = 0.0007) than in the rainy season. CONCLUSIONS: Rice paddies represented the most frequent habitat type for Anopheles spp. larvae in the Korhogo area during both the rainy and the dry seasons. Anopheles spp. breeding habitats covered a very large and dynamic area in the rainy season whereas they were fewer in number in the dry season. In this context, implementing a larviciding strategy from the end of the rainy season to the dry season is presumably the most cost-effective strategy.