Advances and Perspectives in the Study of the Malaria Mosquito Anopheles funestus

International audienc

Distance sampling for epidemiology: an interactive tool for estimating under-reporting of cases from clinic data

Background: Distance sampling methods are widely used in ecology to estimate and map the abundance of animal and plant populations from spatial survey data. The key underlying concept in distance sampling is the detection function, the probability of detecting the occurrence of an event as a function of its distance from the observer, as well as other covariates that may influence detection. In epidemiology, the burden and distribution of infectious disease is often inferred from cases that are reported at clinics and hospitals. In areas with few public health facilities and low accessibility, the probability of detecting a case is also a function of the distance between an infected person and the “observer” (e.g. a health centre). While the problem of distance-related under-reporting is acknowledged in public health; there are few quantitative methods for assessing and correcting for this bias when mapping disease incidence. Here, we develop a modified version of distance sampling for prediction of infectious disease incidence by relaxing some of the framework’s fundamental assumptions. We illustrate the utility of this approach using as our example malaria distribution in rural Burkina Faso, where there is a large population at risk but relatively low accessibility of health facilities. Results: The modified distance-sampling framework was used to predict the probability of reporting malaria infection at 8 rural clinics, based on road-travel distances from villages. The rate at which reporting probability dropped with distance varied between clinics, depending on road and clinic positions. The probability of case detection was estimated as 0.3–1 in the immediate vicinity of the clinic, dropping to 0.1–0.6 at a travel distance of 10 km, and effectively zero at distances > 30–40 km. Conclusions: To enhance the method’s strategic impact, we provide an interactive mapping tool (as a self-contained R Shiny app) that can be used by non-specialists to interrogate model outputs and visualize how the overall probability of under-reporting and the catchment area of each clinic is influenced by changing the number and spatial allocation of health centres

Detection of G119S ace-1 R mutation in field-collected Anopheles gambiae mosquitoes using allele-specific loop-mediated isothermal amplification (AS-LAMP) method

Background Malaria vectors have developed resistance to the four families of insecticides available for public health purposes. For example, the kdr mutation is associated with organochlorines and pyrethroids resistance. It is of particular concern that organophosphate and carbamate resistance associated with the G119S ace-1 R mutation has recently increased in West Africa in extent and frequency, and is now spreading through the Anopheles gambiae malaria vector population. There is an urgent need to improve resistance management using existing insecticides and new tools to quickly assess resistance level for rapid decision-making. Methods DNA extracted from field-collected mosquitoes was used to develop the method. Specific primers were designed manually to match the mutation region and an additional mismatched nucleotide in the penultimate position to increase specificity. Other primers used are common to both wild and mutant types. The allele specific (AS)-LAMP method was compared to the PCR restriction fragment length polymorphism (PCR-RFLP) and real-time PCR (RT-PCR) methods using the genomic DNA of 104 field-collected mosquitoes. Results The primers designed for LAMP were able to distinguish between the wild type (ace-1 S ) and mutated type allele (ace-1 R ). Detection time was 50 min for the wild type homozygous and 64 min for the heterozygous. No amplification of the resistant allele took place within the 75-min test period when using the wild type primers. For the ace-1 R resistant type, detection time was 51 min for the resistant homozygous and 55 min for the heterozygous. No amplification of the wild type allele took place within the 75-min test period when using the resistant type primers. Gel electrophoresis of LAMP products confirmed that amplification was primer-DNA specific, i.e., primers could only amplify their target specific DNA. AS-LAMP, PCR-RFLP, and RT-PCR showed no significant difference in the sensitivity and specificity of their ace-1 R detection ability. Conclusions The AS-LAMP method could detect the ace-1 R mutation within 60 min, which is faster than conventional PCR-RFLP. This method may be used to quickly detect the ace-1 R mutation for rapid decision-making, even in less well-equipped laboratories

Insecticide resistance in Anopheles gambiae: data from the first year of a multi-country study highlight the extent of the problem

<p>Abstract</p> <p>Background</p> <p>Insecticide resistance in malaria vectors is a growing concern in many countries which requires immediate attention because of the limited chemical arsenal available for vector control. The current extent and distribution of this resistance in many parts of the continent is unknown and yet such information is essential for the planning of effective malaria control interventions.</p> <p>Methods</p> <p>In 2008, a network was established, with financial support from WHO/TDR, to investigate the extent of insecticide resistance in malaria vectors in five African countries. Here, the results of bioassays on <it>Anopheles gambiae sensu lato </it>from two rounds of monitoring from 12 sentinel sites in three of the partner countries are reported.</p> <p>Results</p> <p>Resistance is very heterogeneous even over relatively small distances. Furthermore, in some sites, large differences in mortality rates were observed during the course of the malaria transmission season. Using WHO diagnostic doses, all populations from Burkina Faso and Chad and two of the four populations from Sudan were classified as resistant to permethrin and/or deltamethrin. Very high frequencies of DDT resistance were found in urban areas in Burkina Faso and Sudan and in a cotton-growing district in Chad. In areas where both <it>An. gambiae s.s</it>. and <it>Anopheles arabiensis </it>were present, resistance was found in both species, although generally at a higher frequency in <it>An gambiae s.s</it>. <it>Anopheles gambiae s.l</it>. remains largely susceptible to the organophosphate fenitrothion and the carbamate bendiocarb in the majority of the sentinel sites with the exception of two sites in Burkina Faso. In the cotton-growing region of Soumousso in Burkina Faso, the vector population is resistant to all four classes of insecticide available for malaria control.</p> <p>Conclusions</p> <p>Possible factors influencing the frequency of resistant individuals observed in the sentinel sites are discussed. The results of this study highlight the importance of standardized longitudinal insecticide resistance monitoring and the urgent need for studies to monitor the impact of this resistance on malaria vector control activities.</p

Behavioural plasticity of Anopheles coluzzii and Anopheles arabiensis undermines LLIN community protective effect in a Sudanese-savannah village in Burkina Faso

Background Despite the overall major impact of long-lasting insecticide treated nets (LLINs) in eliciting individual and collective protection to malaria infections, some sub-Saharan countries, including Burkina Faso, still carry a disproportionately high share of the global malaria burden. This study aims to analyse the possible entomological bases of LLIN limited impact, focusing on a LLIN-protected village in the Plateau Central region of Burkina Faso. Methods Human landing catches (HLCs) were carried out in 2015 for 12 nights both indoors and outdoors at different time windows during the highest biting activity phase for Anopheles gambiae (s.l.). Collected specimens were morphologically and molecularly identified and processed for Plasmodium detection and L1014F insecticide-resistance allele genotyping. Results Almost 2000 unfed An. gambiae (s.l.) (54% Anopheles coluzzii and 44% Anopheles arabiensis) females landing on human volunteers were collected, corresponding to a median number of 23.5 females/person/hour. No significant differences were observed in median numbers of mosquitoes collected indoors and outdoors, nor between sporozoite rates in An. coluzzii (6.1%) and An. arabiensis (5.5%). The estimated median hourly entomological inoculation rate (EIR) on volunteers was 1.4 infective bites/person/hour. Results do not show evidence of the biting peak during night hours typical for An. gambiae (s.l.) in the absence of bednet protection. The frequency of the L1014F resistant allele (n = 285) was 66% in An. coluzzii and 38% in An. arabiensis. Conclusions The observed biting rate and sporozoite rates are in line with the literature data available for An. gambiae (s.l.) in the same geographical area before LLIN implementation and highlight high levels of malaria transmission in the study village. Homogeneous biting rate throughout the night and lack of preference for indoor-biting activity, suggest the capacity of both An. coluzzii and An. arabiensis to adjust their host-seeking behaviour to bite humans despite bednet protection, accounting for the maintenance of high rates of mosquito infectivity and malaria transmission. These results, despite being limited to a local situation in Burkina Faso, represent a paradigmatic example of how high densities and behavioural plasticity in the vector populations may contribute to explaining the limited impact of LLINs on malaria transmission in holo-endemic Sudanese savannah areas in West Africa

Anopheline species composition and the 1014F-genotype in different ecological settings of Burkina Faso in relation to malaria transmission

Background: A three-year longitudinal study was conducted in four sentinel sites from different ecological settings in Burkina Faso, between 2008 and 2010 to identify longitudinal changes in insecticide resistance within Anopheles gambiae complex species based on larval collection. During this study, adult mosquitoes were also collected indoor and outdoor using several methods of collection. The present study reports the diversity of malaria vectors and the 1014F-genotype from this adult collection and investigates the association between this 1014F-genotype and sporozoite rate. Methods: Adult mosquitoes were collected from July to August (corresponding to the start of rainy season) and October to November (corresponding to the end of rainy season) over 3 years (2008–2010) at four sites across the country, using pyrethrum spray catches (PSC), exit traps and pit shelters. Anopheles gambiae complex mosquitoes were identified to species and genotyped for the L1014F kdr mutation by PCR using genomic DNA. The circumsporozoite antigen of Plasmodium falciparum was detected in mosquitoes using sandwich ELISA. Results: Overall 9212 anopheline mosquitoes were collected during the study period. Of those, 6767 mosquitoes were identified as Anopheles gambiae sensu lato (s.l.). Anopheles arabiensis, Anopheles coluzzii, Anopheles gambiae and or Anopheles funestus were incriminated as vectors of P. falciparum in the study area with an average sporozoite rate of 5%, (95% CI 4.14–5.99%). The kdr1014F-genotype frequencies were 11.44% (95% CI 2.5–39.85%), 19.2% (95% CI 4.53–53.73%) and 89.9 (95% CI 63.14–97.45%), respectively for An. arabiensis, An. coluzzii and An. gambiae. The proportion of the 1014F-genotype varied between sporozoite-infected and uninfected An. gambiae s.l. group. There was no significant difference in the 1014F-genotype frequency between infected and uninfected mosquitoes. Conclusion: The current study shows the diversity of malaria vectors and significant interaction between species composition and kdr1014F-genotype in An. gambiae complex mosquitoes from Burkina Faso. In this study, no associations were found between the 1014F-genotype and P. falciparum infection in the major malaria vector An. gambiae s.l

A cohort study to identify risk factors for Plasmodium falciparum infection in Burkinabe children: implications for other high burden high impact countries

Background: Progress in controlling malaria has stalled in recent years. Today the malaria burden is increasingly concentrated in a few countries, including Burkina Faso, where malaria is not declining. A cohort study was conducted to identify risk factors for malaria infection in children in southwest Burkina Faso, an area with high insecticide-treated net (ITN) coverage and insecticide-resistant vectors. Methods: Incidence of Plasmodium falciparum infection was measured in 252 children aged 5 to 15 years, using active and passive detection, during the 2017 transmission season, following clearance of infection. Demographic, socio-economic, environmental, and entomological risk factors, including use of ITNs and insecticide resistance were monitored. Results: During the six-month follow-up period, the overall incidence of P. falciparum infection was 2.78 episodes per child (95% CI = 2.66–2.91) by microscopy, and 3.11 (95% CI = 2.95–3.28) by polymerase chain reaction (PCR). The entomological inoculation rate (EIR) was 80.4 infective bites per child over the six-month malaria transmission season. At baseline, 80.6% of children were reported as sleeping under an ITN the previous night, although at the last survey, 23.3% of nets were in poor condition and considered no longer protective. No association was found between the rate of P. falciparum infection and either EIR (incidence rate ratio (IRR): 1.00, 95% CI: 1.00–1.00, p = 0.08) or mortality in WHO tube tests when vectors were exposed to 0.05% deltamethrin (IRR: 1.05, 95% CI: 0.73–1.50, p = 0.79). Travel history (IRR: 1.52, 95% CI: 1.45–1.59, p < 0.001) and higher socio-economic status were associated with an increased risk of P. falciparum infection (IRR: 1.05, 95% CI: 1.00–1.11, p = 0.04). Conclusions: Incidence of P. falciparum infection remains overwhelmingly high in the study area. The study findings suggest that because of the exceptionally high levels of malaria transmission in the study area, malaria elimination cannot be achieved solely by mass deployment of ITNs and additional control measures are needed

Ampleur de la dengue dans la ville de Ouagadougou, Burkina-Faso, 2016: Magnitude of dengue fever in the city of Ouagadougou, Burkina-Faso, 2016

Introduction: En Octobre 2016, le Burkina Faso a connu une flambée de cas de dengue dont l’ampleur est peu connue. Aussi aucune étude n’a été réalisée durant les dix dernières années, donnant lieu à un manque d’information actualisée sur sa prévalence et son incidence. Cette étude avait pour objectif de déterminer l’ampleur de la dengue à Ouagadougou et le type de virus circulant. Méthodes: Nous avons mené une étude transversale sur les cas de dengue enregistrés dans les formations sanitaires (FS) de la ville de Ouagadougou du 1er août au 31 décembre 2016. Un cas de dengue était défini comme toute personne résident dans la ville de Ouagadougou présentant une maladie fébrile aiguë (2-7 jours), avec au moins deux des symptômes suivants : céphalées, douleur rétro-orbitale, myalgie, arthralgie, éruption cutanée, manifestations hémorragiques, syndrome de choc et un test biologique positif à la PCR ou avec TDR-Dengue positif ayant un lien épidémiologique avec un cas confirmé. Nous avons réalisé une recherche active des cas à travers une revue documentaire des registres de laboratoire, consultation et/ou d’hospitalisation des FS, Une fiche de collecte a été utilisée pour recueillir les caractéristiques sociodémographiques, cliniques, biologiques des cas. Résultats: Au total, 5094 cas de dengue ont été enregistrés dans les FS. L’âge médian était de 27 ans avec un intervalle interquartile de 16 à 37 ans. Quinze cas (51,72%) ont été testés positifs à la PCR dont 10 (66,67%) au DENV2 et 5 (33,33%) au DENV3. Parmi les cas, 2569 (50,76%) étaient de sexe féminin et 1494 (28,16%) cas avaient été hospitalisés. Sur les cas recensés, 73% avaient été notifiés par les structures privées et 3174 (88,88%) étaient des éleves/étudiants ou fonctionnaires ou commerçants. Le taux d’attaque global était de 201 cas (5094/2532311) pour 100000 habitants. Le taux de létalité était de 35/5094 (0,69%). Conclusion: Le taux d’attaque global de la dengue en 2016 était de 201 cas pour 100000 habitants. La dengue touchait plus les adultes jeunes surtout les élèves/étudiants et les fonctionnaires et était causée par les types 2 et 3. Les cas étaient plus notifiés par les structures privées. Une surveillance hebdomadaire associée à une surveil-lance sentinelle et la sensibilisation de la population sur la dengue contribueraient à endiguer ce fléau au Burki-na Faso. Background: In October 2016, Burkina Faso experienced an outbreak of dengue fever that the magnitude is little known. Also, no studies have been performed in the past ten years, giving rise to a lack of updated information on its prevalence and incidence. We conducted an investigation to determine the magnitude of dengue fever in Ouagadougou’s city and the type of virus circulating. Methods: We conducted a cross-sectional study on the cases of dengue recorded in health facilities (HF) in Ouagadougou’s city from August 1st to December 31st, 2016. We defined a case of dengue as any person resident in the city of Ouagadougou with acute febrile illness (2-7days), with at least two of the following symptoms (headache, retro-orbital pain, myalgia, arthralgia, rash, hemorrhagic manifestations, shock syndrome) and a positive PCR test or with dengue-RDT positive, having an epidemiological link with a confirmed case. We carried out an active search for cases through a documentary review of laboratory, consultation and/or hospitalization registers of HF, used a file to collect the socio-demographic, clinical and biological characteristics of the cases. Results: A total of 5094 cases of dengue fever were recorded in the HF. The median age was 27 years with an interquartile range of 16 to 37 years old. Fifteen (51.72%) cases tested positive with PCR including 10(66.67%) for DENV2 and 5(33.33%) for DENV3. Among the cases, 2,569(50.76%) were female and 1,494(28.16%) cases were hospitalized. Of the cases listed, 73% were notified by private’s hospitals and 3,174 (88.88%) were pupils/students or civil servants or traders. The overall attack rate was 201 cases (5094/2532311) per 100,000 populations. The case fatality rate was 35/5094 (0.69%). Conclusion: The overall dengue attack rate in 2016 was 201 cases per 100,000 populations. Dengue more affected young adults especially the pupils/students or civil servants and was caused by types 2 and 3. The cases were more notified by the private hospitals. We recommend weekly surveillance, sentinel surveillance and public awareness of dengue fever

Efficacy of Olyset Duo, a bednet containing pyriproxyfen and permethrin, versus a permethrin-only net against clinical malaria in an area with highly pyrethroid-resistant vectors in rural Burkina Faso: a cluster-randomised controlled trial

Background Substantial reductions in malaria incidence in sub-Saharan Africa have been achieved with massive deployment of long-lasting insecticidal nets (LLINs), but pyrethroid resistance threatens control. Burkina Faso is an area with intense malaria transmission and highly pyrethroid-resistant vectors. We assessed the effectiveness of bednets containing permethrin, a pyrethroid, and pyriproxyfen, an insect growth regulator, versus permethrin-only (standard) LLINs against clinical malaria in children younger than 5 years in Banfora, Burkina Faso. Methods In this two-group, step-wedge, cluster-randomised, controlled, superiority trial, standard LLINs were incrementally replaced with LLINs treated with permethrin plus pyriproxyfen (PPF) in 40 rural clusters in Burkina Faso. In each cluster, 50 children (aged 6 months to 5 years) were followed up by passive case detection for clinical malaria. Cross-sectional surveys were done at the start and the end of the transmission seasons in 2014 and 2015. We did monthly collections from indoor light traps to estimate vector densities. Primary endpoints were the incidence of clinical malaria, measured by passive case detection, and the entomological inoculation rate. Analyses were adjusted for clustering and for month and health centre. This trial is registered as ISRCTN21853394. Findings 1980 children were enrolled in the cohort in 2014 and 2157 in 2015. At the end of the study, more than 99% of children slept under a bednet. The incidence of clinical malaria was 2·0 episodes per child-year in the standard LLIN group and 1·5 episodes per child-year in the PPF-treated LLIN group (incidence rate ratio 0·88 [95% CI 0·77–0·99; p=0·04]). The entomological inoculation rate was 85 (95% CI 63–108) infective bites per transmission season in the standard LLIN group versus 42 (32–52) infective bites per transmission season in the PPF-treated LLIN group (rate ratio 0·49, 95% CI 0·32–0·66; p<0·0001). Interpretation PPF-treated LLINs provide greater protection against clinical malaria than do standard LLINs and could be used as an alternative to standard LLINs in areas with intense transmission of Plasmodium falciparum malaria and highly pyrethroid-resistant vectors. Funding EU Seventh Framework Programme