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 Pyrethroid resistance in Anopheles gambiae not associated with insecticide-treated mosquito net effectiveness across sub-Saharan Africa

2020 ◽  
Author(s):  
David A. Larsen ◽  
Rachael L. Church
Keyword(s):  
Anopheles Gambiae ◽  
Malaria Vector ◽  
Malaria Infection ◽  
Pyrethroid Resistance ◽  
Sub Saharan Africa ◽  
Malaria Vector Control ◽  
Lr Test ◽  
Meta Regression ◽  
Sub Saharan ◽  
The Impact

AbstractBackgroundPyrethroid resistance is a major concern for malaria vector control programs that predominantly rely on insecticide-treated mosquito nets (ITN). Contradictory results of the impact of resistance have been observed in field studies.MethodsWe combined continent-wide estimates of pyrethroid resistance in Anopheles gambiae from 2006-2017 with continent-wide survey data to assess the effect of increasing pyrethroid resistance on the effectiveness of ITNs to prevent malaria infections in sub-Saharan Africa. We utilized both a pooled-data approach and meta-regression of survey regions to assess how pyrethroid resistance affects the association between ITN ownership and malaria outcomes in children aged 6-59 months.FindingsITN ownership reduced the risk of malaria outcomes in both pooled and meta-regression approaches. In the pooled analysis, there was no observed interaction between ITN ownership and estimated level of pyrethroid resistance (Likelihood ratio [LR] test = 1.127 for the outcome of rapid diagnostic test confirmed malaria infection, p = 0.2885; LR test = 0.161 for the outcome of microscopy confirmed malaria infection, p = 0.161; LR test = 0.646 for the outcome of moderate or severe anemia, p = 0.4215). In the meta-regression approach the level of pyrethroid resistance did not explain any of the variance in subnational estimates of ITN effectiveness for any of the outcomes.InterpretationITNs decreased risk of malaria outcomes independent of the levels of pyrethroid resistance in the malaria vector populations.FundingDAL did not receive funding and RC received a SOURCE grant from Syracuse University for this project.

scholarly journals Evolution of the Pyrethroids Target-Site Resistance Mechanisms in Senegal: Early Stage of the Vgsc-1014F and Vgsc-1014S Allelic Frequencies Shift

Genes ◽  
2021 ◽  
Vol 12 (12) ◽  
pp. 1948
Author(s):  
Moussa Diallo ◽  
Majidah Hamid-Adiamoh ◽  
Ousmane Sy ◽  
Pape Cheikh Sarr ◽  
Jarra Manneh ◽  
...  
Keyword(s):  
Insecticide Resistance ◽  
Anopheles Gambiae ◽  
Pyrethroid Resistance ◽  
Early Stage ◽  
Resistance Mechanisms ◽  
Sub Saharan Africa ◽  
Malaria Vectors ◽  
Malaria Control Programme ◽  
Anopheles Coluzzii ◽  
Resistance Mutations

The evolution and spread of insecticide resistance mechanisms amongst malaria vectors across the sub-Saharan Africa threaten the effectiveness and sustainability of current insecticide-based vector control interventions. However, a successful insecticide resistance management plan relies strongly on evidence of historical and contemporary mechanisms circulating. This study aims to retrospectively determine the evolution and spread of pyrethroid resistance mechanisms among natural Anopheles gambiae s.l. populations in Senegal. Samples were randomly drawn from an existing mosquito sample, collected in 2013, 2017, and 2018 from 10 sentinel sites monitored by the Senegalese National Malaria Control Programme (NMCP). Molecular species of An. gambiae s.l. and the resistance mutations at the Voltage-gated Sodium Channel 1014 (Vgsc-1014) locus were characterised using PCR-based assays. The genetic diversity of the Vgsc gene was further analyzed by sequencing. The overall species composition revealed the predominance of Anopheles arabiensis (73.08%) followed by An. gambiae s.s. (14.48%), Anopheles coluzzii (10.94%) and Anopheles gambiae–coluzii hybrids (1.48%). Both Vgsc-1014F and Vgsc-1014S mutations were found in all studied populations with a spatial variation of allele frequencies from 3% to 90%; and 7% to 41%, respectively. The two mutations have been detected since 2013 across all the selected health districts, with Vgsc-L1014S frequency increasing over the years while Vgsc-1014F decreasing. At species level, the Vgsc-1014F and Vgsc-1014S alleles were more frequent amongst An. gambiae s.s. (70%) and An. arabiensis (20%). The Vgsc gene was found to be highly diversified with eight different haplotypes shared between Vgsc-1014F and Vgsc-1014S. The observed co-occurrence of Vgsc-1014F and Vgsc-1014S mutations suggest that pyrethroid resistance is becoming a widespread phenomenon amongst malaria vector populations, and the NMCP needs to address this issue to sustain the gain made in controlling malaria.

scholarly journals Pyrethroid Resistance in Anopheles gambiae Not Associated with Insecticide-Treated Mosquito Net Effectiveness Across Sub-Saharan Africa

2021 ◽  
Author(s):  
David A. Larsen ◽  
Rachael L. Church
Keyword(s):  
Anopheles Gambiae ◽  
Malaria Vector ◽  
Malaria Infection ◽  
Pyrethroid Resistance ◽  
Sub Saharan Africa ◽  
Malaria Vector Control ◽  
Lr Test ◽  
Meta Regression ◽  
Sub Saharan ◽  
The Impact

Pyrethroid resistance is a major concern for malaria vector control programs that predominantly rely on insecticide-treated mosquito nets (ITNs). Contradictory results of the impact of resistance have been observed during field studies. We combined continent-wide estimates of pyrethroid resistance in Anopheles gambiae from 2006 to 2017, with continent-wide survey data to assess the effect of increasing pyrethroid resistance on the effectiveness of ITNs to prevent malaria infections in sub-Saharan Africa. We used a pooled-data approach and a meta-regression of survey regions to assess how pyrethroid resistance affects the association between ITN ownership and malaria outcomes for children 6 to 59 months of age. ITN ownership reduced the risk of malaria outcomes according to both the pooled and meta-regression approaches. According to the pooled analysis, there was no observed interaction between ITN ownership and estimated level of pyrethroid resistance (likelihood ratio [LR] test, 1.127 for malaria infection confirmed by the rapid diagnostic test, P = 0.2885; LR test = 0.161 for microscopy-confirmed malaria infection, P = 0.161; LR test = 0.646 for moderate or severe anemia, P = 0.4215). Using the meta-regression approach to determine the level of pyrethroid resistance did not explain any of the variance in subnational estimates of ITN effectiveness for any of the outcomes. ITNs decreased the risk of malaria independent of the levels of pyrethroid resistance in malaria vector populations.

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 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 Functional genetic validation of key genes conferring insecticide resistance in the major African malaria vector, Anopheles gambiae

2019 ◽  
Author(s):  
Adriana Adolfi ◽  
Beth Poulton ◽  
Amalia Anthousi ◽  
Stephanie Macilwee ◽  
Hilary Ranson ◽  
...  
Keyword(s):  
Public Health ◽  
Insecticide Resistance ◽  
Anopheles Gambiae ◽  
Pyrethroid Resistance ◽  
Control Strategies ◽  
Resistance Mechanisms ◽  
Effective Control ◽  
Cross Resistance ◽  
Toxic Metabolite ◽  
Control Programs

ABSTRACTResistance in Anopheles gambiae to members of all four major classes (pyrethroids, carbamates, organochlorines and organophosphates) of public health insecticides limits effective control of malaria transmission in Africa. Increased expression of detoxifying enzymes has been associated with resistance, but direct functional validation in An. gambiae has been lacking. Here we perform transgenic analysis using the GAL4/UAS system to examine insecticide resistance phenotypes conferred by increased expression of the three genes - Cyp6m2, Cyp6p3 and Gste2 - most often found upregulated in resistant An. gambiae. We report the first evidence in An. gambiae that organophosphate and organochlorine resistance is conferred by overexpression of GSTE2 in a broad tissue profile. Pyrethroid and carbamate resistance is bestowed by similar Cyp6p3 overexpression, and Cyp6m2 confers only pyrethroid resistance when overexpressed in the same tissues. Conversely, such Cyp6m2 overexpression increases susceptibility to the organophosphate malathion, presumably due to conversion to a more toxic metabolite. No resistant phenotypes are conferred when either Cyp6 gene overexpression is restricted to the midgut or oenocytes, answering long standing questions related to the importance of these tissues in resistance to contact insecticides. Validation of genes conferring resistance provides markers to guide control strategies, and the observed negative cross-resistance due to Cyp6m2 gives credence to proposed dual insecticide strategies to overcome pyrethroid resistance. These trasnsgenic An. gambiae resistant lines are being used to test potential liabilities in new active compounds early in development.SIGNIFICANCE STATEMENTInsecticide resistance in Anopheles gambiae mosquitoes can derail malaria control programs, and to overcome it we need to discover the underlying molecular basis. Here, for the first time, we characterise three genes most often associated with insecticide resistance directly by their overproduction in genetically modified An. gambiae. We show that overexpression of each gene confers resistance to representatives of at least one insecticide class and, taken together, the three genes provide cross-resistance to all four major insecticide classes currently used in public health. These data validate the candidate genes as markers to monitor the spread of resistance in mosquito populations. The modified mosquitoes produced are also valuable tools to pre-screen new insecticides for potential liabilities to existing resistance mechanisms.

scholarly journals Development of an Insecticide-Free Trapping Bednet to Control Mosquitoes and Manage Resistance in Malaria Vector Control: A New Way of Thinking

Insects ◽  
2020 ◽  
Vol 11 (11) ◽  
pp. 732
Author(s):  
Chouaibou S. Mouhamadou ◽  
Kun Luan ◽  
Behi K. Fodjo ◽  
Andre J. West ◽  
Marian G. McCord ◽  
...  
Keyword(s):  
Mosquito Control ◽  
Pyrethroid Resistance ◽  
Three Dimensional ◽  
Field Testing ◽  
Sub Saharan Africa ◽  
Malaria Vector Control ◽  
Worst Case ◽  
Crowd Modeling ◽  
Single Chemical ◽  
Sub Saharan

Mosquito-borne malaria kills 429,000 people each year with the problem being acute in sub-Saharan Africa. The successes gained with long-lasting pyrethroid-treated bednets are now in jeopardy because of wide-spread, pyrethroid resistance in mosquitoes. Using crowd modeling theory normalized for standard bednet architecture, we were able to design an attract–trap–kill technology for mosquitoes that does not require insecticides. Using three-dimensional polyester knitting and heat fixation, trap funnels were developed with high capture efficacy with no egression under worst-case laboratory conditions. Field testing in Africa in WHO huts with Gen1-3 T (trap)-Nets validated our model, and as predicted, Gen3 had the highest efficacy with a 4.3-fold greater trap–kill rate with no deterrence or repellency compared to Permanet 2.0, the most common bednet in Africa. A T-Net population model was developed based on field data to predict community-level mosquito control compared to a pyrethroid bednet. This model showed the Gen3 non-insecticidal T-Net under field conditions in Africa against pyrethroid resistant mosquitoes was 12.7-fold more efficacious than single chemical, pyrethroid-treated nets.

scholarly journals Evidence supporting deployment of next generation insecticide treated nets in Burkina Faso: bioassays with either chlorfenapyr or piperonyl butoxide increase mortality of pyrethroid-resistant Anopheles gambiae s.l.

2021 ◽  
Author(s):  
Sawdetuo Aristide HIEN ◽  
Dieudonné D. Soma ◽  
Dramane Coulibaly ◽  
Abdoulaye Diabaté ◽  
Allison Belemvire ◽  
...  
Keyword(s):  
Burkina Faso ◽  
Anopheles Gambiae ◽  
High Intensity ◽  
Large Scale ◽  
Pyrethroid Resistance ◽  
Piperonyl Butoxide ◽  
Sub Saharan Africa ◽  
Insecticide Treated Nets ◽  
Bobo Dioulasso ◽  
Sub Saharan

Abstract Background Pyrethroid resistance poses a major threat to the efficacy of insecticide treated nets (ITNs) in Burkina Faso and throughout sub-Saharan Africa, particularly when resistance is present at high intensity. For such areas there are alternative ITNs available, including the synergist piperonyl butoxide (PBO)-based ITNs and dual active ingredient ITNs such as Interceptor G2 (treated with chlorfenapyr and alpha-cypermethrin). Before deploying alternative ITNs on a large scale it is crucial to characterize the resistance profiles of primary malaria vector species for evidence-based decision making Methods Larvae from the predominant vector, Anopheles gambiae s.l., were collected from 15 sites located throughout Burkina Faso and reared to adults for bioassays to assess insecticide resistance status. Resistance intensity assays were conducted using WHO tube tests to determine the level of resistance to pyrethroids commonly used on ITNs at 1x, 5x and 10x times the diagnostic dose. WHO tube tests were also used for PBO synergist bioassays with deltamethrin and permethrin. Bottle bioassays were conducted to determine susceptibility to chlorfenapyr at a dose of 100µg/bottle. Results WHO tube tests revealed high intensity resistance in An. gambiae s.l. to deltamethrin and alpha-cypermethrin in all sites tested. Resistance intensity to permethrin was either moderate or high in 13 sites. PBO pre-exposure followed by deltamethrin restored full susceptibility in 1 site but partially restored susceptibility in all but one of the remaining sites (often reaching mortality greater than 80%). PBO pre-exposure followed by permethrin partially restored susceptibility in 12 sites. There was no significant increase in permethrin mortality after PBO pre-exposure in Kampti, Karangasso-Vigué or Mangodara; while in Seguenega, Orodara and Bobo-Dioulasso there was a significant increase in mortality, but rates remained below 50%. Susceptibility to chlorfenapyr was confirmed in 14 sites. Conclusion High pyrethroid resistance intensity in An. gambiae s.l. is widespread across Burkina Faso and may be a predictor of reduced pyrethroid ITN effectiveness. PBO + deltamethrin ITNs would likely provide greater control than pyrethroid nets. However, since susceptibility in bioassays was not restored in most sites following pre-exposure to PBO, Interceptor G2 may be a better long-term solution as susceptibility was recorded to chlorfenapyr in nearly all sites. This study provides evidence supporting the introduction of both Interceptor G2 nets and PBO nets, which were distributed in Burkina Faso in 2019 as part of a mass campaign.

scholarly journals Investigating molecular mechanisms of insecticide resistance in the Eastern Democratic Republic of the Congo

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Janvier Bandibabone ◽  
Charles McLoughlin ◽  
Sévérin N’Do ◽  
Chimanuka Bantuzeko ◽  
Vital Byabushi ◽  
...  
Keyword(s):  
Insecticide Resistance ◽  
Vector Control ◽  
Access To Health Care ◽  
Molecular Mechanisms ◽  
Democratic Republic ◽  
Resistance Mechanisms ◽  
Malaria Vector Control ◽  
Malaria Control Programme ◽  
Triple Mutant ◽  
Republic Of The Congo

Abstract Background Malaria vector control in the Democratic Republic of the Congo is plagued by several major challenges, including inadequate infrastructure, lack of access to health care systems and preventative measures, and more recently the widespread emergence of insecticide resistance among Anopheles mosquitoes. Across 26 provinces, insecticide resistance has been reported from multiple sentinel sites. However, to date, investigation of molecular resistance mechanisms among Anopheles vector populations in DRC has been more limited. Methods Adult Anopheles gambiae sensu lato (s.l.) and Anopheles funestus s.l. were collected from two sites in Sud-Kivu province and one site in Haut-Uélé province and PCR-screened for the presence of 11 resistance mutations, to provide additional information on frequency of resistance mechanisms in the eastern DRC, and to critically evaluate the utility of these markers for prospective country-wide resistance monitoring. Results L1014F-kdr and L1014S-kdr were present in 75.9% and 56.7% of An. gambiae s.l. screened, respectively, with some individuals harbouring both resistant alleles. Across the three study sites, L43F-CYP4J5 allele frequency ranged from 0.42 to 0.52, with evidence for ongoing selection. G119S-ace1 was also identified in all sites but at lower levels. A triple mutant haplotype (comprising the point mutation CYP6P4-I236M, the insertion of a partial Zanzibar-like transposable element and duplication of CYP6AA1) was present at high frequencies. In An. funestus s.l. cis-regulatory polymorphisms in CYP6P9a and CYP6P9b were detected, with allele frequencies ranging from 0.82 to 0.98 and 0.65 to 0.83, respectively. Conclusions This study screened the most up-to-date panel of DNA-based resistance markers in An. gambiae s.l. and An. funestus s.l. from the eastern DRC, where resistance data is lacking. Several new candidate markers (CYP4J5, G119S-ace1, the triple mutant, CYP6P9a and CYP6P9b) were identified, which are diagnostic of resistance to major insecticide classes, and warrant future, larger-scale monitoring in the DRC to inform vector control decisions by the National Malaria Control Programme.

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