Etude des politiques relatives aux stratégies de gestion de la chimiorésistance dans le cadre de la lutte contre la trypanosomose en Afrique de l'Ouest: cas du Mali

Discussion sur l’etude des politiques relatives aux stratégies de gestion de la chimiorésistance dans le cadre de la lutte contre la trypanosomose en Afrique de l’Ouest, Mali. Le projet a pour objectif d’assurer l’efficacité des trypanocides comme une composante effective des strategies intégrées et améliorées de contrôle de Ia trypanosomose animale dans Ia region ouest-africaine. Pour atteindre cet objectif, des organisations nationales de recherche et de developpement, des institutions internationales et régionales de recherche, et des universités allemandes travaillent en partenariat afin de développer aux niveaux local et regional des strategies de reduction de risque de Ia chimiorésistance. L’accent est mis principalement sur l‘information et des supports techniques aux paysans, aux prestataires de service en sante animale, aux vétérinaires professionnels et aux décideurs politiques. Les informations et supports techniques ont pour but de promouvoir Ia lutte intégrée et l’utilisation rationnelle des trypanocides afin de réduire les risques a long terme de Ia chimiorésistance sans compromettre Ia capacité des éleveurs a pouvoir protéger leurs animaux contre les effets néfastes de la trypanosomose animale. Le projet est réalisé au Burkina Faso, au Mali et en Guinée par l’lnstitut International de Recherche sur l’Elevage (lLRl) en collaboration avec d’autres organisations. Des approaches de solutions sont alors proposees de maniere a apporter une solution durable au phenomene de la chimioresistance

Genetic structure of Anopheles gambiae populations on islands in northwestern Lake Victoria, Uganda

BACKGROUND: Alternative means of malaria control are urgently needed. Evaluating the effectiveness of measures that involve genetic manipulation of vector populations will be facilitated by identifying small, genetically isolated vector populations. The study was designed to use variation in microsatellite markers to look at genetic structure across four Lake Victoria islands and two surrounding mainland populations and for evidence of any restriction to free gene flow. METHODS: Four Islands (from 20–50 km apart) and two surrounding mainland populations (96 km apart) were studied. Samples of indoor resting adult mosquitoes, collected over two consecutive years, were genotyped at microsatellite loci distributed broadly throughout the genome and analysed for genetic structure, effective migration (Nem) and effective population size (Ne). RESULTS: Ne estimates showed island populations to consist of smaller demes compared to the mainland ones. Most populations were significantly differentiated geographically, and from one year to the other. Average geographic pair-wise FST ranged from 0.014–0.105 and several pairs of populations had Ne m < 3. The loci showed broad heterogeneity at capturing or estimating population differences. CONCLUSION: These island populations are significantly genetically differentiated. Differences reoccurred over the study period, between the two mainland populations and between each other. This appears to be the product of their separation by water, dynamics of small populations and local adaptation. With further characterisation these islands could become possible sites for applying measures evaluating effectiveness of control by genetic manipulation

A De Novo Expression Profiling of Anopheles funestus, Malaria Vector in Africa, Using 454 Pyrosequencing

BACKGROUND: Anopheles funestus is one of the major malaria vectors in Africa and yet there are few genomic tools available for this species compared to An. gambiae. To start to close this knowledge gap, we sequenced the An. funestus transcriptome using cDNA libraries developed from a pyrethroid resistant laboratory strain and a pyrethroid susceptible field strain from Mali. RESULTS: Using a pool of life stages (pupae, larvae, adults: females and males) for each strain, 454 sequencing generated 375,619 reads (average length of 182 bp). De novo assembly generated 18,103 contigs with average length of 253 bp. The average depth of coverage of these contigs was 8.3. In total 20.8% of all reads were novel when compared to reference databases. The sequencing of the field strain generated 204,758 reads compared to 170,861 from the insecticide resistant laboratory strain. The contigs most differentially represented in the resistant strain belong to the P450 gene family and cuticular genes which correlates with previous studies implicating both of these gene families in pyrethroid resistance. qPCR carried out on six contigs indicates that these ESTs could be suitable for gene expression studies such as microarray. 31,000 sites were estimated to contain Single Nucleotide Polymorphisms (SNPs) and analysis of SNPs from 20 contigs suggested that most of these SNPs are likely to be true SNPs. Gene conservation analysis confirmed the close phylogenetic relationship between An. funestus and An. gambiae. CONCLUSION: This study represents a significant advance for the genetics and genomics of An. funestus since it provides an extensive set of both Expressed Sequence Tags (ESTs) and SNPs which can be readily adopted for the design of new genomic tools such as microarray or SNP platforms

Comparative Analysis of the Global Transcriptome of Anopheles funestus from Mali, West Africa

Background: Anopheles funestus is a principal vector of malaria across much of tropical Africa and is considered one of the most efficient of its kind, yet studies of this species have lagged behind those of its broadly sympatric congener, An. gambiae. In aid of future genomic sequencing of An. funestus, we explored the whole body transcriptome, derived from mixed stage progeny of wild-caught females from Mali, West Africa. Principal Findings: Here we report the functional annotation and comparative genomics of 2,005 expressed sequence tags (ESTs) from An. funestus, which were assembled with a previous EST set from adult female salivary glands from the same mosquito. The assembled ESTs provided for a nonredundant catalog of 1,035 transcripts excluding mitochondrial sequences. Conclusions/Significance: Comparison of the An. funestus and An. gambiae transcriptomes using computational and macroarray approaches revealed a high degree of sequence identity despite an estimated 20–80 MY divergence time between lineages. A phylogenetically broader comparative genomic analysis indicated that the most rapidly evolving proteins – those involved in immunity, hematophagy, formation of extracellular structures, and hypothetical conserved proteins – are those that probably play important roles in how mosquitoes adapt to their nutritional and externa

Utilizing direct skin feeding assays for development of vaccines that interrupt malaria transmission: A systematic review of methods and case study.

Shifting the malaria priorities from a paradigm of control and elimination to a goal of global eradication calls for renewed attention to the interruption of malaria transmission. Sustained progress toward eradication will require both improved understanding of infectious reservoirs and efficient development of novel transmission-blocking interventions, such as rapidly acting and highly efficacious therapeutics and vaccines. Here, we review the direct skin feeding assay (DSF), which has been proposed as a valuable tool for measuring the in natura transmission of malaria parasites from human hosts to mosquito vectors across heterogeneous populations. To capture the methodological breadth of this assay's use, we first systematically review and qualitatively synthesize previously published investigations using DSFs to study malaria transmission in humans. Then, using a recent Phase 1 trial in Mali of the Pfs25H-EPA/Alhydrogel® vaccine candidate (NCT01867463) designed to interrupt Plasmodium falciparum transmission as a case study, we describe the potential opportunities and current limitations of utilizing the endpoints measured by DSF in making early clinical decisions for individually randomized transmission-interrupting intervention candidates. Using simulations based on the data collected in the clinical trial, we demonstrate that the capacity of the DSF to serve as an evaluative tool is limited by the statistical power constraints of the "effective sample size" (i.e. the number of subjects that are capable of transmitting at the time of feeding). Altogether, our findings suggest DSFs have great potential utility for assessing the public health impacts of emerging antimalarial tools, but additional research is needed to address issues of scalability and to establish correlation with community-wide clinical endpoints as well as complementary in vitro measures, such as standard membrane feeding assays

Intestinal parasitic infections in schoolchildren in different settings of Côte d'Ivoire : effect of diagnostic approach and implications for control

BACKGROUND: Social-ecological systems govern parasitic infections in humans. Within the frame of assessing the accuracy of a rapid diagnostic test for Schistosoma mansoni in Cote d'Ivoire, three different endemicity settings had to be identified and schoolchildren's intestinal parasitic infection profiles were characterized. METHODS: In September 2010, a rapid screening was conducted in 11 schools in the Azaguie district, south Cote d'Ivoire. In each school, 25 children were examined for S. mansoni and S. haematobium. Based on predefined schistosome endemicity levels, three settings were selected, where schoolchildren aged 8-12 years were asked to provide three stool and three urine samples for an in-depth appraisal of parasitic infections. Triplicate Kato-Katz thick smears were prepared from each stool sample for S. mansoni and soil-transmitted helminth diagnosis, whereas urine samples were subjected to a filtration method for S. haematobium diagnosis. Additionally, a formol-ether concentration method was employed on one stool sample for the diagnosis of helminths and intestinal protozoa. Multivariable logistic regression models were employed to analyse associations between schoolchildren's parasitic infections, age, sex and study setting. RESULTS: The prevalences of S. mansoni and S. haematobium infections in the initial screening ranged from nil to 88% and from nil to 56%, respectively. The rapid screening in the three selected areas revealed prevalences of S. mansoni of 16%, 33% and 78%. Based on a more rigorous diagnostic approach, the respective prevalences increased to 92%, 53% and 33%. S. haematobium prevalences were 0.8%, 4% and 65%. Prevalence and intensity of Schistosoma spp., soil-transmitted helminths and intestinal protozoan infections showed setting-specific patterns. Infections with two or more species concurrently were most common in the rural setting (84%), followed by the peri-urban (28.3%) and urban setting (18.2%). CONCLUSIONS: More sensitive diagnostic tools or rigorous sampling approaches are needed to select endemicity settings with high fidelity. The observed small-scale heterogeneity of helminths and intestinal protozoan infections has important implications for contro

Management of insecticide resistance in the major Aedes vectors of arboviruses Advances and challenges

Background The landscape of mosquito-borne disease risk has changed dramatically in recent decades, due to the emergence and reemergence of urban transmission cycles driven by invasive Aedes aegypti and Ae. albopictus. Insecticide resistance is already widespread in the yellow fever mosquito, Ae. Aegypti; is emerging in the Asian tiger mosquito Ae. Albopictus; and is now threatening the global fight against human arboviral diseases such as dengue, yellow fever, chikungunya, and Zika. Because the panel of insecticides available for public health is limited, it is of primary importance to preserve the efficacy of existing and upcoming active ingredients. Timely implementation of insecticide resistance management (IRM) is crucial to maintain the arsenal of effective public health insecticides and sustain arbovirus vector control. Methodology and principal findings This Review is one of a series being generated by the Worldwide Insecticide resistance Network (WIN) and aims at defining the principles and concepts underlying IRM, identifying the main factors affecting the evolution of resistance, and evaluating the value of existing tools for resistance monitoring. Based on the lessons taken from resistance strategies used for other vector species and agricultural pests, we propose a framework for the implementation of IRM strategies for Aedes mosquito vectors. Conclusions and significance Although IRM should be a fixture of all vector control programs, it is currently often absent from the strategic plans to control mosquito-borne diseases, especially arboviruses. Experiences from other public health disease vectors and agricultural pests underscore the need for urgent action in implementing IRM for invasive Aedes mosquitoes. Based on a plan developed for malaria vectors, here we propose some key activities to establish a global plan for IRM in Aedes spp. Author summary Arthropod-borne viruses transmitted by Aedes aegypti and Ae. albopictus represent a major public health concern at a global scale. The insecticidal treatments exerted on both species have selected for various resistance mechanisms within wild populations. Although the impact of insecticide resistance on the efficacy of vector control operations remains broadly unknown, it is of primary importance to implement strategies for preserving the efficacy of treatments and reducing the pathogen transmission during epidemics. For this purpose, there are urgent needs for new tools for vector control and insecticide resistance monitoring to improve the management of insecticide resistance in Aedes species

Epidemiology of intestinal parasite infections in three departments of south-central Côte d’Ivoire before the implementation of a cluster-randomised trial

Hundreds of millions of people are infected with helminths and intestinal protozoa, particularly children in low- and middle-income countries. Preventive chemotherapy is the main strategy to control helminthiases. However, rapid re-infection occurs in settings where there is a lack of clean water, sanitation and hygiene. In August and September 2014, we conducted a cross-sectional epidemiological survey in 56 communities of three departments of south-central Côte d’Ivoire. Study participants were invited to provide stool and urine samples. Stool samples were examined for helminth and intestinal protozoa infections using the Kato-Katz technique and a formalin-ether concentration method. Urine samples were subjected to a filtration method for the diagnosis of Schistosoma haematobium. Information on sociodemographic characteristics, knowledge, attitude, practices and beliefs with regard to hygiene, sanitation and intestinal parasitic diseases were collected using a questionnaire administered to household heads. Multivariable logistic regression models were employed to analyse associations between parasite infections and risk factors. Overall, 4,305 participants had complete parasitological and questionnaire data. Hookworm was the predominant helminth species (21.2%), while Ascaris lumbricoides, Trichuris trichiura, Schistosoma mansoni and S. haematobium showed prevalences below 10%. Infections with pathogenic intestinal protozoa (e.g. Entamoeba histolytica/E. dispar and Giardia intestinalis) were similarly prevalent in the three departments. Hookworm infection was associated with open defecation and participants' age and sex. Entamoeba coli infection was negatively associated with the use of tap water at home (odds ratio (OR) = 0.66; p = 0.032). Disposal of garbage in close proximity to people’s home was positively associated with G. intestinalis (OR = 1.30; p = 0.015). Taken together, helminth and intestinal protozoa infections affected a considerable proportion of rural dwellers in south-central Côte d’Ivoire at the onset of a cluster-randomised intervention trial. Our results will serve as baseline to monitor the effect of a package of interventions, including preventive chemotherapy, sanitation and health education on re-infection with helminths and intestinal protozoa