Managing insecticide resistance in malaria vectors by combining carbamate-treated plastic wall sheeting and pyrethroid-treated bed nets

Abstract Background Insecticide resistance is threatening the effectiveness of efforts to control malaria vectors in Benin. This study explores the levels and mechanisms of insecticide resistance in An. gambiae s.l. to pyrethroids. Methods Larvae were collected from August 2017 to July 2018 in five communes in southern Benin (Adjohoun, Allada, Bohicon, Cotonou, and Porto-Novo) representing diverse ecological regions, and were reared in Benin’s insectary. Two- to five-day-old female mosquitoes from each district were exposed to multiple doses of deltamethrin and permethrin (1×, 2×, 5×, and 10×) using the WHO insecticide resistance intensity bioassay. The effect of pre-exposure to the synergist, piperonyl butoxide (PBO), was also tested at different pyrethroid doses. Molecular allele frequencies of kdr (1014F) and ace-1R (119S) insecticide resistance mutations and levels of detoxification enzymes were determined for mosquitoes sampled from each study area. Results An. gambiae s.l. were resistant to pyrethroid-only exposure up to 10× the diagnostic doses in all the study sites for both deltamethrin and permethrin. Mortality was significantly higher in An. gambiae s.l. pre-exposed to PBO followed by exposure to deltamethrin or permethrin compared to mosquitoes exposed to deltamethrin or permethrin only (p < 0.001). The difference in mortality between deltamethrin only and PBO plus deltamethrin was the smallest in Cotonou (16–64%) and the greatest in Bohicon (12–93%). The mortality difference between permethrin only and PBO plus permethrin was the smallest in Cotonou (44–75%) and the greatest in Bohicon (22–72%). In all the study sites, the kdr resistance allele (1014F) frequency was high (75–100%), while the ace-1 resistance allele (G119S) frequency was low (0–3%). Analysis of the metabolic enzymatic activity of An. gambiae s.l. showed overexpression of nonspecific esterases and glutathione S-transferases (GST) in all study sites. In contrast to the PBO results, oxidase expression was low and was similar to the susceptible An. gambiae s.s. Kisumu strain in all sites. Conclusion There is high-intensity resistance to pyrethroids in southern Benin. However, pre-exposure to PBO significantly increased susceptibility to the pyrethroids in the different An. gambiae s.l. populations sampled. The use of PBO insecticide-treated bed nets may help maintain the gains in An. gambiae (s.l.) control in southern Benin. Graphical Abstract

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Status of insecticide susceptibility in Anopheles arabiensis and detection of the knockdown resistance mutation (kdr) concerning agricultural practices from Northern Sudan state, Sudan

Journal of Genetic Engineering and Biotechnology ◽

10.1186/s43141-021-00142-1 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

M. Y. Korti ◽

T. B. Ageep ◽

A. I. Adam ◽

K. B. Shitta ◽

A. A. Hassan ◽

...

Keyword(s):

Insecticide Resistance ◽

Vector Control ◽

Anopheles Arabiensis ◽

Resistance Mutation ◽

Indoor Residual Spraying ◽

Mortality Rates ◽

Malaria Vectors ◽

Bed Nets ◽

Knockdown Resistance ◽

Insecticide Susceptibility

Abstract Background Chemical control has been the most efficient method in mosquito control, the development of insecticide resistance in target populations has a significant impact on vector control. The use of agricultural pesticides may have a profound impact on the development of resistance in the field populations of malaria vectors. Our study focused on insecticide resistance and knockdown resistance (kdr) of Anopheles arabiensis populations from Northern Sudan, related to agricultural pesticide usage. Results Anopheles arabiensis from urban and rural localities (Merowe and Al-hamadab) were fully susceptible to bendiocarb 0.1% and permethrin 0.75% insecticides while resistant to DDT 4% and malathion 5%. The population of laboratory reference colony F189 from Dongola showed a mortality of 91% to DDT (4%) and fully susceptible to others. GLM analysis indicated that insecticides, sites, site type, and their interaction were determinant factors on mortality rates (P < 0.01). Except for malathion, mortality rates of all insecticides were not significant (P > 0.05) according to sites. Mortality rates of malathion and DDT were varied significantly (P < 0.0001 and P < 0.05 respectively) by site types, while mortality rates of bendiocarb and permethrin were not significant (P >0.05). The West African kdr mutation (L1014F) was found in urban and rural sites. Even though, the low-moderate frequency of kdr (L1014F) mutation was observed. The findings presented here for An. arabiensis showed no correlation between the resistant phenotype as ascertained by bioassay and the presence of the kdr mutation, with all individuals tested except the Merowe site which showed a moderate association with DDT (OR= 6 in allelic test), suggesting that kdr genotype would be a poor indicator of phenotypic resistance. Conclusion The results provide critical pieces of information regarding the insecticide susceptibility status of An. arabiensis in northern Sudan. The usage of the same pesticides in agricultural areas seemed to affect the Anopheles susceptibility when they are exposed to those insecticides in the field. The kdr mutation might have a less role than normally expected in pyrethroids resistance; however, other resistance genes should be in focus. These pieces of information will help to improve the surveillance system and The implication of different vector control programs employing any of these insecticides either in the treatment of bed nets or for indoor residual spraying would achieve satisfactory success rates.

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Accounting for heterogeneity in wild adult samples to measure insecticide resistance in Anopheles malaria vectors

10.1101/2021.08.13.456216 ◽

2021 ◽

Author(s):

Inga E. Holmdahl ◽

Caroline O. Buckee ◽

Lauren M. Childs

Keyword(s):

Spatial Structure ◽

Insecticide Resistance ◽

Gold Standard ◽

Time Frame ◽

Malaria Vectors ◽

Bed Nets ◽

Insecticide Exposure ◽

Mosquito Collection ◽

The Impact

Background Systematic, long-term, and spatially representative monitoring of insecticide resistance in mosquito populations is urgently needed to quantify its impact on malaria transmission, and to combat failing interventions when resistance emerges. Resistance assays on wild-caught adult mosquitoes (known as adult-capture) offer an alternative to the current protocols, and can be done cheaply, in a shorter time frame, and in the absence of an insectary. However, quantitative assessments of the performance of these assays relative to the gold standard, which involves rearing larvae in an insectary, are lacking. Methodology/Principal findings We developed a discrete-time deterministic mosquito lifecycle model to simulate insecticide resistance assays from adult-captured mosquito collection in a heterogeneous environment compared to the gold standard larval capture methods, and to quantify possible biases in the results. We incorporated non-lethal effects of insecticide exposure that have been demonstrated in laboratory experiments, spatial structure, and the impact of multiple exposure to insecticides and natural ageing on mosquito death rates during the assay. Using output from this model, we compared the results of these assays to true resistance as measured by the presence of the resistance allele. In simulated samples of 100 test mosquitoes, reflecting WHO-recommended sample sizes, we found that compared to adult-captured assays (MSE = 0.0059), larval-captured assays were a better measure of true resistance (MSE = 0.0018). Using a correction model, we were able to improve the accuracy of the adult-captured assay results (MSE = 0.0038). Bias in the adult-capture assays was dependent on the level of insecticide resistance rather than coverage of bed nets or spatial structure. Conclusions/Significance Using adult-captured mosquitoes for resistance assays has logistical advantages over the standard larval-capture collection, and may be a more accurate sample of the mosquito population. These results show that adult-captured assays can be improved using a simple mathematical approach and used to inform resistance monitoring programs.

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Adaptive introgression in an African malaria mosquito coincident with the increased usage of insecticide-treated bed nets

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1418892112 ◽

2015 ◽

Vol 112 (3) ◽

pp. 815-820 ◽

Cited By ~ 128

Author(s):

Laura C. Norris ◽

Bradley J. Main ◽

Yoosook Lee ◽

Travis C. Collier ◽

Abdrahamane Fofana ◽

...

Keyword(s):

Insecticide Resistance ◽

Assortative Mating ◽

Animal Species ◽

Temporal Dynamics ◽

Fitness Landscape ◽

Malaria Vectors ◽

Bed Nets ◽

Alternative Mechanism ◽

Anopheles Coluzzii ◽

Adaptive Introgression

Animal species adapt to changes in their environment, including man-made changes such as the introduction of insecticides, through selection for advantageous genes already present in populations or newly arisen through mutation. A possible alternative mechanism is the acquisition of adaptive genes from related species via a process known as adaptive introgression. Differing levels of insecticide resistance between two African malaria vectors, Anopheles coluzzii and Anopheles gambiae, have been attributed to assortative mating between the two species. In a previous study, we reported two bouts of hybridization observed in the town of Selinkenyi, Mali in 2002 and 2006. These hybridization events did not appear to be directly associated with insecticide-resistance genes. We demonstrate that during a brief breakdown in assortative mating in 2006, A. coluzzii inherited the entire A. gambiae-associated 2L divergence island, which includes a suite of insecticide-resistance alleles. In this case, introgression was coincident with the start of a major insecticide-treated bed net distribution campaign in Mali. This suggests that insecticide exposure altered the fitness landscape, favoring the survival of A. coluzzii/A. gambiae hybrids, and provided selection pressure that swept the 2L divergence island through A. coluzzii populations in Mali. We propose that the work described herein presents a unique description of the temporal dynamics of adaptive introgression in an animal species and represents a mechanism for the rapid evolution of insecticide resistance in this important vector of human malaria in Africa.

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Mapping insecticide resistance in malaria vectors: Latest updates from IR Mapper

10.1603/ice.2016.117689 ◽

2016 ◽

Author(s):

Melinda P Hadi

Keyword(s):

Insecticide Resistance ◽

Malaria Vectors

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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

Parasites & Vectors ◽

10.1186/s13071-020-04563-8 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Dieudonné Diloma Soma ◽

Barnabas Zogo ◽

Domonbabele François de Sales Hien ◽

Aristide Sawdetuo Hien ◽

Didier Alexandre Kaboré ◽

...

Keyword(s):

Insecticide Resistance ◽

Burkina Faso ◽

Anopheles Gambiae ◽

Local Population ◽

Residual Activity ◽

Indoor Residual Spraying ◽

Susceptible Strain ◽

Malaria Vectors ◽

Pirimiphos Methyl ◽

Residual Efficacy

Abstract 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.

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Insecticide resistance status of Anopheles arabiensis in irrigated and non-irrigated areas in western Kenya

Parasites & Vectors ◽

10.1186/s13071-021-04833-z ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Pauline Winnie Orondo ◽

Steven G. Nyanjom ◽

Harrysone Atieli ◽

John Githure ◽

Benyl M. Ondeto ◽

...

Keyword(s):

Insecticide Resistance ◽

Vector Control ◽

Anopheles Arabiensis ◽

Crop Protection ◽

Indoor Residual Spraying ◽

Malaria Vectors ◽

Western Kenya ◽

Animal Protection ◽

Selection Of ◽

Selection Of Resistance

Abstract Background Malaria control in Kenya is based on case management and vector control using long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS). However, the development of insecticide resistance compromises the effectiveness of insecticide-based vector control programs. The use of pesticides for agricultural purposes has been implicated as one of the sources driving the selection of resistance. The current study was undertaken to assess the status and mechanism of insecticide resistance in malaria vectors in irrigated and non-irrigated areas with varying agrochemical use in western Kenya. Methods The study was carried out in 2018–2019 in Homa Bay County, western Kenya. The bioassay was performed on adults reared from larvae collected from irrigated and non-irrigated fields in order to assess the susceptibility of malaria vectors to different classes of insecticides following the standard WHO guidelines. Characterization of knockdown resistance (kdr) and acetylcholinesterase-inhibiting enzyme/angiotensin-converting enzyme (Ace-1) mutations within Anopheles gambiae s.l. species was performed using the polymerase chain reaction (PCR) method. To determine the agricultural and public health insecticide usage pattern, a questionnaire was administered to farmers, households, and veterinary officers in the study area. Results Anopheles arabiensis was the predominant species in the irrigated (100%, n = 154) area and the dominant species in the non-irrigated areas (97.5%, n = 162), the rest being An. gambiae sensu stricto. In 2018, Anopheles arabiensis in the irrigated region were susceptible to all insecticides tested, while in the non-irrigated region reduced mortality was observed (84%) against deltamethrin. In 2019, phenotypic mortality was decreased (97.8–84% to 83.3–78.2%). In contrast, high mortality from malathion (100%), DDT (98.98%), and piperonyl butoxide (PBO)-deltamethrin (100%) was observed. Molecular analysis of the vectors from the irrigated and non-irrigated areas revealed low levels of leucine-serine/phenylalanine substitution at position 1014 (L1014S/L1014F), with mutation frequencies of 1–16%, and low-frequency mutation in the Ace-1R gene (0.7%). In addition to very high coverage of LLINs impregnated with pyrethroids and IRS with organophosphate insecticides, pyrethroids were the predominant chemical class of pesticides used for crop and animal protection. Conclusion Anopheles arabiensis from irrigated areas showed increased phenotypic resistance, and the intensive use of pesticides for crop protection in this region may have contributed to the selection of resistance genes observed. The susceptibility of these malaria vectors to organophosphates and PBO synergists in pyrethroids offers a promising future for IRS and insecticide-treated net-based vector control interventions. These findings emphasize the need for integrated vector control strategies, with particular attention to agricultural practices to mitigate mosquito resistance to insecticides. Graphic abstract

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Insecticide resistance in Anopheles stephensi in Somali Region, eastern Ethiopia

10.21203/rs.2.18020/v3 ◽

2020 ◽

Author(s):

Solomon Yared ◽

Araya Gebressielasie ◽

Lambodhar Damodaran ◽

Victoria Bonnell ◽

Karen Lopez ◽

...

Keyword(s):

Insecticide Resistance ◽

Anopheles Stephensi ◽

Mortality Rates ◽

Resistance Mechanisms ◽

World Health ◽

Malaria Vectors ◽

Resistance Locus ◽

Eastern Ethiopia ◽

Pyrethroid Insecticides ◽

Pirimiphos Methyl

Abstract Background The movement of malaria vectors into new areas is a growing concern in the efforts to control malaria. The recent report of Anopheles stephensi in eastern Ethiopia has raised the necessity to understand the insecticide resistance status of the vector in the region to better inform vector-based interventions. The aim of this study was to evaluate insecticide resistance in An. stephensi in eastern Ethiopia using two approaches: 1) World Health Organization (WHO) bioassay tests in An. stephensi; and 2) genetic analysis of insecticide resistance genes in An. stephensi in eastern Ethiopia. Methods Mosquito larvae and pupae were collected from Kebri Dehar. Insecticide susceptibility of An. stephensi was tested withmalathion 5%, bendiocarb 0.1%, propoxur 0.1%, deltamethrin 0.05%, permethrin 0.75%, Pirimiphos-methyl 0.25% and DDT 4%, according to WHO standard protocols. In this study, the knockdown resistance locus (kdr) in the voltage gated sodium channel (vgsc) and ace1R locus in the acetylcholinesterase gene (ace-1) were analysed in An. stephensi. Results All An. stephensi samples were resistant to carbamates, with mortality rates of 23% and 21% for bendiocarb and propoxur, respectively. Adult An. stephensi was also resistant to pyrethroid insecticides with mortality rates 67% for deltamethrin and 53% for permethrin. Resistance to DDT and malathion was detected in An. stephensi with mortality rates of 32% as well as An. stephensi was resistance to pirimiphos-methyl with mortality rates 14%. Analysis of the insecticide resistance loci revealed the absence of kdr L1014F and L1014S mutations and the ace1R G119S mutation. Conclusion Overall, these findings support that An. stephensi is resistant to several classes of insecticides, most notably pyrethroids. However, the absence of the kdr L1014 gene may suggest non-target site resistance mechanisms. Continuous insecticide resistance monitoring should be carried out in the region to confirm the documented resistance and exploring mechanisms conferring resistance in An. stephensi in Ethiopia.

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Community Knowledge, Perceptions, And Practices Regarding Malaria and Its Control In Jabi Tehnan District, Amhara Region, Northwest Ethiopia

10.21203/rs.3.rs-489446/v1 ◽

2021 ◽

Author(s):

Abebe Asale ◽

Zewdu Abro ◽

Bayu Enchalew ◽

Alayu Tesager ◽

Aklilu Belay ◽

...

Keyword(s):

Vector Control ◽

Malaria Control ◽

Community Education ◽

Indoor Residual Spraying ◽

Community Empowerment ◽

Malaria Episode ◽

Malaria Vectors ◽

Bed Nets ◽

Health Seeking ◽

Malaria Parasites

Abstract Background: Key program components of malaria control in Ethiopia include community empowerment and mobilization, vector control using long-lasting insecticidal nets (LLINs), indoor residual spraying (IRS), prompt diagnosis and treatment, and disease surveillance. However, the effectiveness of these interventions is often undermined by various challenges, including insecticide and drug resistance, the plasticity of malaria vectors feeding and biting behavior, and certain household factors that lead to misuse and poor utilization of LLINs. The primary objective of this study was to document households’ perceptions towards malaria and assess the prevalence of the disease and the constraints related to the ongoing interventions in Ethiopia (LLINs, IRS, community mobilization house screening). Method: The study was conducted in Jabi Tehnan district, Northwestern Ethiopi,a from November 2019 to March 2020. A total of 3,010 households distributed over 38 kebeles (villages) were randomly selected for socio-economic and demographic survey. Focus group discussions (FGDs) were conducted in 11 different health clusters taking into account agro-ecological differences. A total of 1,256 children under 10 years of age were screened for malaria parasites using microscopy in order to determine malaria prevalence. Furthermore, five-year malaria trend analysis was undertaken based on data obtained from the district health office to understand the disease dynamics.Result: Malaria knowledge in the area was high as all FGD participants correctly identified mosquito bites during the night as sources of malaria transmission. Delayed health seeking behavior remains a key behavioral challenge in malaria control as it took patients on average 4 days before reporting the case at the nearby health facility. On average households lost 2.53 working days per person-per malaria episode and theey spent US$ 18 per person perepisode. Out of the 1,256 randomly selected under 10 children tested for malaria parasites, 11 (0.89%) were found to be positive. Malaria disproportionately affected the adult segment of the population more, 50% of the total cases reported from households whose age was 15 and beyond. The second most affected group was the age group between 5 and 14 years followed by children under 10, with 31% and 14% burden,respectively.Conclusion: Despite the achievement of universal coverage in terms of LLINs access, utilization of vector control interventions in the area remained low.Using bed nets for unintended purposes remained a major challenge. Therefore, continued community education and communication work should be prioritised in the study area to bring about the desired behavioral changes.

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Impact of insecticide resistance in Anopheles arabiensis on malaria incidence and prevalence in Sudan and the costs of mitigation

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1713814114 ◽

2017 ◽

Vol 114 (52) ◽

pp. E11267-E11275 ◽

Cited By ~ 12

Author(s):

Hmooda Toto Kafy ◽

Bashir Adam Ismail ◽

Abraham Peter Mnzava ◽

Jonathan Lines ◽

Mogahid Shiekh Eldin Abdin ◽

...

Keyword(s):

Insecticide Resistance ◽

Pyrethroid Resistance ◽

Malaria Incidence ◽

Disease Incidence ◽

Indoor Residual Spraying ◽

Sub Saharan Africa ◽

Malaria Vectors ◽

Incidence And Mortality ◽

Additional Protection ◽

The Impact

Insecticide-based interventions have contributed to ∼78% of the reduction in the malaria burden in sub-Saharan Africa since 2000. Insecticide resistance in malaria vectors could presage a catastrophic rebound in disease incidence and mortality. A major impediment to the implementation of insecticide resistance management strategies is that evidence of the impact of resistance on malaria disease burden is limited. A cluster randomized trial was conducted in Sudan with pyrethroid-resistant and carbamate-susceptible malaria vectors. Clusters were randomly allocated to receive either long-lasting insecticidal nets (LLINs) alone or LLINs in combination with indoor residual spraying (IRS) with a pyrethroid (deltamethrin) insecticide in the first year and a carbamate (bendiocarb) insecticide in the two subsequent years. Malaria incidence was monitored for 3 y through active case detection in cohorts of children aged 1 to <10 y. When deltamethrin was used for IRS, incidence rates in the LLIN + IRS arm and the LLIN-only arm were similar, with the IRS providing no additional protection [incidence rate ratio (IRR) = 1.0 (95% confidence interval [CI]: 0.36–3.0; P = 0.96)]. When bendiocarb was used for IRS, there was some evidence of additional protection [interaction IRR = 0.55 (95% CI: 0.40–0.76; P < 0.001)]. In conclusion, pyrethroid resistance may have had an impact on pyrethroid-based IRS. The study was not designed to assess whether resistance had an impact on LLINs. These data alone should not be used as the basis for any policy change in vector control interventions.

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