scholarly journals A high throughput multi-locus insecticide resistance marker panel for tracking resistance emergence and spread in Anopheles gambiae

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Eric R. Lucas ◽  
Kirk A. Rockett ◽  
Amy Lynd ◽  
John Essandoh ◽  
Nelson Grisales ◽  
...  
Keyword(s):  
Insecticide Resistance ◽  
Anopheles Gambiae ◽  
High Throughput ◽  
Democratic Republic Of Congo ◽  
Novel Mutation ◽  
Sub Saharan Africa ◽  
Wild Type Counterpart ◽  
Control Programmes ◽  
Resistance Markers ◽  
Sub Saharan

Abstract The spread of resistance to insecticides in disease-carrying mosquitoes poses a threat to the effectiveness of control programmes, which rely largely on insecticide-based interventions. Monitoring mosquito populations is essential, but obtaining phenotypic measurements of resistance is laborious and error-prone. High-throughput genotyping offers the prospect of quick and repeatable estimates of resistance, while also allowing resistance markers to be tracked and studied. To demonstrate the potential of highly-mulitplexed genotypic screening for measuring resistance-association of mutations and tracking their spread, we developed a panel of 28 known or putative resistance markers in the major malaria vector Anopheles gambiae, which we used to screen mosquitoes from a wide swathe of Sub-Saharan Africa (Burkina Faso, Ghana, Democratic Republic of Congo (DRC) and Kenya). We found resistance association in four markers, including a novel mutation in the detoxification gene Gste2 (Gste2-119V). We also identified a duplication in Gste2 combining a resistance-associated mutation with its wild-type counterpart, potentially alleviating the costs of resistance. Finally, we describe the distribution of the multiple origins of kdr resistance, finding unprecedented diversity in the DRC. This panel represents the first step towards a quantitative genotypic model of insecticide resistance that can be used to predict resistance status in An. gambiae.

scholarly journals A high throughput multi-locus insecticide resistance marker panel for tracking resistance emergence and spread inAnopheles gambiae

2019 ◽  
Author(s):  
Eric R. Lucas ◽  
Kirk A. Rockett ◽  
Amy Lynd ◽  
John Essandoh ◽  
Nelson Grisales ◽  
...  
Keyword(s):  
Insecticide Resistance ◽  
High Throughput ◽  
Democratic Republic Of Congo ◽  
Novel Mutation ◽  
Sub Saharan Africa ◽  
Mutant Form ◽  
Evolutionary Origins ◽  
Wild Type Counterpart ◽  
Control Programmes ◽  
Sub Saharan

AbstractThe spread of resistance to insecticides in the mosquito vectors of diseases such as malaria and dengue poses a threat to the effectiveness of control programmes, which rely largely on insecticide-based interventions. Monitoring the resistance status of mosquito populations is therefore essential, but obtaining direct phenotypic measurements of resistance is laborious and error-prone. In contrast, high-throughput genotyping offers the prospect of quick and repeatable estimates of resistance, while also allowing the genotypic markers of resistance to be tracked and studied. We developed a panel of 28 known or putative markers of resistance in the major malaria vectorAnopheles gambiae, which we use to test the association of these markers with resistance and to study their geographic distribution. We screened resistance-phenotypedAn.gambiaefrom populations from a wide swathe of Sub-Saharan Africa (Burkina Faso, Ghana, Democratic Republic of Congo (DRC) and Kenya), and found evidence of resistance association for four mutations, including a novel mutation in the detoxification geneGste2(Gste2-119V). We also identified a gene duplication inGste2which combines a resistance-associated mutant form of the gene with its wild-type counterpart, potentially alleviating the costs of resistance. Finally, we describe the distribution of the multiple evolutionary origins ofkdrresistance, finding unprecedented levels of diversity in the DRC. This panel represents the first step towards developing a quantitative predictive genotypic model of insecticide resistance that can be used to screenAn.gambiaepopulations and predict resistance status.

First Incidence of CYP9K1, CYP6P4 and CYP6Z1 in Anopheles gambiae ss from Nigeria

2020 ◽  
Author(s):  
Ada Sylvester Haruna ◽  
Konstantinos Mavridis ◽  
John Vontas ◽  
Joseph Effiong Eyo
Keyword(s):  
Anopheles Gambiae ◽  
Statistical Significance ◽  
Sub Saharan Africa ◽  
Breeding Sites ◽  
Anopheles Mosquitoes ◽  
Genes Expression ◽  
Control Programmes ◽  
Pirimiphos Methyl ◽  
Sub Saharan ◽  
High Level

Abstract Background: Anopheles resistance to insecticides is an impediment to the success of malaria control programmes in sub-Saharan Africa. This study addresses the enzymes that play the key role in insecticide resistance in Kogi State, Nigeria.Methods: Anopheles immature stages were collected from breeding sites across four LGAs in Kogi State, Nigeria. Adult anophelines were identified morphologically and molecularly to species level using the polymerase chain reaction. Adult Anopheles mosquitoes were exposed to eight different insecticides belonging to organochlorine, organophosphate, carbamate and pyrethroids. Newly developed and integrable to the LabDisk automated diagnostic platform quantitative Reverse Transcription-real-time PCR (qRT-PCR) 3-plex TaqMan® assays were used to quantify 7 detoxification genes’ expression. Fold-changes, 95% CIs and statistical significance were performed according to the Pfaffl methods. Results: An. gambiae sl were susceptible to pirimiphos methyl in all the LGAs, but resistance to alphacypermethrin, permethrin, DDT, bendiocarb, propoxur, lambdacyhalothrin and deltamethrin. The detoxification genes CYP6P3(1.6), CYP6M2(36 folds), CYP9K1(6.4 folds), CYP6P4(5.3), CYP6Z1(4.8 folds), GSTE2(4.1 fold), CYP6P1(0.50 folds) and CYP4G16 (2.36 folds) were encountered but only CYP6M2, CYP9K1, CYP6P4 and CYP6Z1 were found to be up regulated in the Dekina multi resistant (pyrethroids, DDT, bendiocarb) population compared to two susceptible (Kisumu and G3) laboratory strains. Resistance was observed in seven out of the eight insecticides tested. Very high level of resistance was observed in DDT across the three LGAs. The CYP6M2, CYP9K1, CYP6P4 and CYP6Z1 were up regulated genes that confer resistance to different insecticides. Conclusion: This study recorded for the first time CYP9K1, CYP6P4 and CYP6Z1 detoxification genes in wild Anopheles gambiae ss populations from Nigeria. In light of the absence of iAche mutations in our results, carbamate (bendiocarb and propoxur) resistance could be associated with the expression of CYP6P4 that has been previously implicated.

scholarly journals A pyrethroïd-treated bed net increases host attractiveness for Anopheles gambiae s.s. carrying the kdr allele in a dual-choice olfactometer

2016 ◽  
Author(s):  
Angélique Porciani ◽  
Malal Diop ◽  
Nicolas Moiroux ◽  
Tatiana Kadoke-Lambi ◽  
Anna Cohuet ◽  
...  
Keyword(s):  
Insecticide Resistance ◽  
Anopheles Gambiae ◽  
Sub Saharan Africa ◽  
Malaria Vectors ◽  
Malaria Vector Control ◽  
Anopheles Gambiae S.S ◽  
Host Seeking ◽  
Seeking Behavior ◽  
Sub Saharan ◽  
The Impact

AbstractThe use of long lasting insecticide nets (LLINs) treated with pyrethroïd is known for its major contribution in malaria control. However, LLINs are suspected to induce behavioral changes in malaria vectors, which may in turn drastically affect their efficacy against Plasmodium sp. transmission. In sub Saharan Africa, where malaria imposes the heaviest burden, the main malaria vectors are widely resistant to pyrethroïds, the insecticide family used on LLINs, which also threatens LLIN efficiency. There is therefore a crucial need for deciphering how insecticide-impregnated materials might affect the host-seeking behavior of malaria vectors in regards to insecticide resistance. In this study, we explored the impact of permethrin-impregnated net on the host attractiveness for Anopheles gambiae mosquitoes, either susceptible to insecticides, or carrying the insecticide resistance conferring allele kdr. Groups of female mosquitoes were released in a dual-choice olfactometer and their movements towards an attractive odor source (a rabbit) protected by insecticide-treated (ITN) or untreated nets (UTN) were monitored. Kdr homozygous mosquitoes, resistant to insecticides, were more attracted by a host behind an ITN than an UTN, while the presence of insecticide on the net did not affect the choice of susceptible mosquitoes. These results suggest that permethrin-impregnated net is detectable by malaria vectors and that the kdr mutation impacts their response to a LLIN protected host. We discuss the implication of these results for malaria vector control.

scholarly journals Investigating the relationship between insecticide resistance, underlying molecular mechanisms and malaria prevalence in Anopheles gambiae s.l. from Guinea

2018 ◽  
Author(s):  
Emma Collins ◽  
Natasha M. Vaselli ◽  
Moussa Sylla ◽  
Abdoul H. Beavogui ◽  
James Orsborne ◽  
...  
Keyword(s):  
Insecticide Resistance ◽  
Anopheles Gambiae ◽  
Molecular Mechanisms ◽  
Pyrethroid Resistance ◽  
Resistance Mechanisms ◽  
Malaria Prevalence ◽  
Sub Saharan Africa ◽  
Malaria Vector Control ◽  
Partial Restoration ◽  
Sub Saharan

AbstractThe threat of insecticide resistance across sub-Saharan Africa is anticipated to severely impact the continued effectiveness of malaria vector control. We investigated the effect of carbamate and pyrethroid resistance on Anopheles gambiae s.l age, Plasmodium falciparum infection and characterized molecular resistance mechanisms in Guinea. Pyrethroid resistance was intense, with survivors of ten times the insecticidal concentration required to kill susceptible individuals. The L1014F kdr allele was significantly associated with mosquito survival following deltamethrin or permethrin treatment (p=0.003 and p=0.04, respectively). N1575Y and I1527T mutations were identified in 13% and 10% of individuals, respectively, but neither conferred increased pyrethroid tolerance. Partial restoration of pyrethroid susceptibility following synergist pre-exposure suggest a role for mixed-function oxidases. Carbamate resistance was lower and significantly associated with the G119S Ace-1 mutation (p=0.001). Oocyst rates were 6.8% and 4.2% among resistant and susceptible mosquitoes, respectively; survivors of bendiocarb exposure were significantly more likely to be infected (p=0.03). Resistant mosquitoes had significantly lower parity rates; however, a subset of intensely pyrethroid-resistant vectors were more likely to be parous (p=0.042 and p=0.045, for survivors of five and ten times the diagnostic dose of insecticides, respectively). Our findings emphasize the need for additional studies directly assessing the influence of insecticide resistance on mosquito fitness.

scholarly journals Fanconi Bickel syndrome: clinical phenotypes and genetics in a cohort of Sudanese children

2020 ◽  
Vol 2020 (1) ◽  
Author(s):  
Salwa A. Musa ◽  
Areej A. Ibrahim ◽  
Samar S. Hassan ◽  
Matthew B Johnson ◽  
Asmahan T. Basheer ◽  
...  
Keyword(s):  
Glucose Transporter ◽  
Novel Mutation ◽  
Wide Spectrum ◽  
Rare Condition ◽  
Neonatal Diabetes ◽  
Abdominal Ultrasound ◽  
Sub Saharan Africa ◽  
High Rate ◽  
Genetic Characteristics ◽  
Sub Saharan

Abstract Background Fanconi-Bickel syndrome (FBS) is a rare condition of carbohydrate metabolism, caused by a recessive defect in the facilitative glucose transporter GLUT2 encoded by the SLC2A2 gene and characterized by a wide spectrum of phenotypical features. There is a paucity of reported data on FBS from Sub-Saharan Africa. Here, we describe the clinical, biochemical and genetic characteristics of our patients with FBS from Sudan, a country with a high consanguinity rate. Patients & methods Eleven patients from ten unrelated Sudanese families were included. Clinical & biochemical data were documented and imaging studies done including bone survey and abdominal ultrasound. Liver biopsy was done to confirm the pathological diagnosis in 45% of cases and molecular genetics was performed through contribution with the Exeter genomics laboratory for ten patients. Results Reported consanguinity was 70% among our patients. Growth was significantly impaired at presentation with mean weights of (-5.3 ± 1.8) SD and heights (-5.4 ± 2.5) SD. Severe chest deformity was present in (27%) and all patients showed features of rickets at presentation. Three patients had neonatal diabetes requiring insulin therapy of which one has been reported before. Six families lost undiagnosed siblings with similar clinical presentations. We identified a total of four homozygous pathogenic SLC2A2 variants in our patients, one of whom had a novel mutation. Conclusions FBS is not uncommon in Sudan where there is a high rate of consanguinity. Many cases are likely missed because of variable presentation and lack of public and professionals’ awareness. This is the first series to describe this condition from Sub-Saharan Africa.

scholarly journals Competing interests, clashing ideas and institutionalizing influence: insights into the political economy of malaria control from seven African countries

2020 ◽  
Author(s):  
Justin Parkhurst ◽  
Ludovica Ghilardi ◽  
Jayne Webster ◽  
Robert W Snow ◽  
Caroline A Lynch
Keyword(s):  
Decision Making ◽  
Malaria Control ◽  
Qualitative Interviews ◽  
Sub Saharan Africa ◽  
African Countries ◽  
Health Community ◽  
Control Programmes ◽  
Control Decision ◽  
Sub Saharan ◽  
Economic Considerations

Abstract This article explores how malaria control in sub-Saharan Africa is shaped in important ways by political and economic considerations within the contexts of aid-recipient nations and the global health community. Malaria control is often assumed to be a technically driven exercise: the remit of public health experts and epidemiologists who utilize available data to select the most effective package of activities given available resources. Yet research conducted with national and international stakeholders shows how the realities of malaria control decision-making are often more nuanced. Hegemonic ideas and interests of global actors, as well as the national and global institutional arrangements through which malaria control is funded and implemented, can all influence how national actors respond to malaria. Results from qualitative interviews in seven malaria-endemic countries indicate that malaria decision-making is constrained or directed by multiple competing objectives, including a need to balance overarching global goals with local realities, as well as a need for National Malaria Control Programmes to manage and coordinate a range of non-state stakeholders who may divide up regions and tasks within countries. Finally, beyond the influence that political and economic concerns have over programmatic decisions and action, our analysis further finds that malaria control efforts have institutionalized systems, structures and processes that may have implications for local capacity development.

scholarly journals Characterizing Permethrin and Etofenprox Resistance in Two Common Laboratory Strains of Anopheles gambiae (Diptera: Culicidae)

Insects ◽  
2018 ◽  
Vol 9 (4) ◽  
pp. 146 ◽  
Author(s):  
Aaron Gross ◽  
Jeffrey Bloomquist
Keyword(s):  
Anopheles Gambiae ◽  
Pyrethroid Resistance ◽  
Laboratory Strain ◽  
Pyrethroid Insecticide ◽  
Sub Saharan Africa ◽  
Cross Resistance ◽  
Type I ◽  
Mosquito Vector ◽  
Sub Saharan ◽  
Anopheles Gambiae Giles

Anopheles gambiae Giles (Diptera: Culicidae) is the most prolific malaria vector in sub-Saharan Africa, where widespread insecticide resistance has been reported. An. gambiae laboratory strains are commonly used to study the basic biology of this important mosquito vector, and also in new insecticide discovery programs, where insecticide-susceptible and -resistant strains are often used to screen new molecules for potency and cross-resistance, respectively. This study investigated the toxicity of permethrin, a Type-I pyrethroid insecticide, and etofenprox, a non-ester containing pyrethroid insecticide, against An. gambiae at three life stages. This characterization was performed with susceptible (G3; MRA-112) and resistant (Akdr; MRA-1280) An. gambiae strains; the Akdr strain is known to contain the L1014F mutation in the voltage-sensitive sodium channel. Surprisingly, etofenprox displays a lower level of resistance than permethrin against all stages of mosquitoes, except in a headless larval paralysis assay designed to minimize penetration factors. In first-instar An. gambiae larvae, permethrin had significant resistance, determined by the resistance ratio (RR50 = 5), but etofenprox was not significantly different (RR50 = 3.4) from the wild-type strain. Fourth-instar larvae displayed the highest level of resistance for permethrin (RR50 = 108) and etofenprox (RR50 = 35). Permethrin (PC50 = 2 ppb) and etofenprox (PC50 = 9 ppb) resulted in headless larval paralysis (5-h), but resistance, albeit lower, was still present for permethrin (RR50 = 5) and etofenprox (RR50 = 6.9). In adult female mosquitoes, permethrin displayed higher resistance (RR50 = 14) compared to etofenprox (RR50 = 4.3). The level of etofenprox resistance was different from that previously reported for a similar Akron An. gambiae laboratory strain (MRA-913). The chemical synergists piperonyl butoxide (PBO) and diethyl maleate (DEM) were able to synergize permethrin, but not etofenprox in the resistant strain (Akdr). In conclusion, multiple mechanisms are likely involved in pyrethroid resistance, but resistance profiles are dependent upon selection. Etofenprox is an effective insecticide against An. gambiae in the lab but will likely suffer from resistance in the field.

scholarly journals Evaluating survey designs for targeting preventive chemotherapy against Schistosoma haematobium and Schistosoma mansoni across Sub-Saharan Africa: a geostatistical analysis and modelling study

2020 ◽  
Author(s):  
Kimberly Fornace ◽  
Claudio Fronterrè ◽  
Fiona M Fleming ◽  
Hope Simpson ◽  
Honorat Zoure ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Schistosoma Haematobium ◽  
Sampling Strategy ◽  
Sub Saharan Africa ◽  
Spatial Distributions ◽  
Preventive Chemotherapy ◽  
School Based ◽  
Control Programmes ◽  
Sub Saharan ◽  
Survey Designs

Abstract Background: Schistosomiasis control programmes primarily use school-based surveys to identify areas for mass drug administration of preventive chemotherapy. However, as the spatial distribution of schistosomiasis can be highly focal, transmission may not be detected by surveys implemented at districts or larger spatial units. Improved mapping strategies are required to accurately and cost-effectively target preventive chemotherapy to remaining foci across all possible spatial distributions of schistosomiasis. Methods: Here, we use geostatistical models to quantify the spatial heterogeneity of Schistosoma haematobium and S. mansoni across sub-Saharan Africa using the most comprehensive dataset available on school-based surveys. Applying this information to parameterise simulations, we assess the accuracy and cost of targeting alternative implementation unit sizes across the range of plausible schistosomiasis distributions. We evaluate the consequences of decisions based on survey designs implemented at district and subdistrict levels sampling different numbers of schools. Cost data were obtained from field surveys conducted across multiple countries and years, with cost effectiveness evaluated as the cost per correctly identified school. Results: Models identified marked differences in prevalence and spatial distributions between countries and species; however, results suggest implementing surveys at subdistrict level increase the accuracy of treatment classifications across most scenarios. While sampling intensively at the subdistrict level resulted in the highest classification accuracy, this sampling strategy resulted in the highest costs. Alternatively, sampling the same numbers of schools currently recommended at the district level but stratifying by subdistrict increased cost effectiveness.Conclusions: This study provides a new tool to evaluate schistosomiasis survey designs across a range of transmission settings. Results highlight the importance of considering spatial structure when designing sampling strategies, illustrating that a substantial proportion of children may be undertreated even when an implementation unit is correctly classified. Control programmes need to weigh the increased accuracy of more detailed mapping strategies against the survey costs and treatment priorities.

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