scholarly journals Pyrethroid Resistance Aggravation in Ugandan Malaria Vectors Is Reducing Bednet Efficacy

Pathogens ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 415
Author(s):  
Magellan Tchouakui ◽  
Leon M. J. Mugenzi ◽  
Benjamin D. Menze ◽  
Jude N. T. Khaukha ◽  
Williams Tchapga ◽  
...  
Keyword(s):  
High Intensity ◽  
Pyrethroid Resistance ◽  
Anopheles Funestus ◽  
Resistance Mechanisms ◽  
Malaria Vectors ◽  
Insecticide Treated Nets ◽  
Over Expression ◽  
Cytochrome P450 Genes ◽  
Long Lasting Insecticidal Nets ◽  
Urgent Action

Monitoring cases of insecticide resistance aggravation and the effect on the efficacy of control tools is crucial for successful malaria control. In this study, the resistance intensity of major malaria vectors from Uganda was characterised and its impact on the performance of various insecticide-treated nets elucidated. High intensity of resistance to the discriminating concentration (DC), 5× DC, and 10× DC of pyrethroids was observed in both Anopheles funestus and Anopheles gambiae in Mayuge and Busia leading to significant reduced performance of long-lasting insecticidal nets (LLINs) including the piperonyl butoxide (PBO)-based nets (Olyset Plus). Molecular analysis revealed significant over-expression of cytochrome P450 genes (CYP9K1 and CYP6P9a/b). However, the expression of these genes was not associated with resistance escalation as no difference was observed in the level of expression in mosquitoes resistant to 5× DC and 10× DC compared to 1× DC suggesting that other resistance mechanisms are involved. Such high intensity of pyrethroid resistance in Uganda could have terrible consequences on the effectiveness of insecticide-based interventions and urgent action should be taken to prevent the spread of super-resistance in malaria vectors.

scholarly journals Escalation of Pyrethroid Resistance in the Malaria Vector Anopheles funestus Induces a Loss of Efficacy of Piperonyl Butoxide–Based Insecticide-Treated Nets in Mozambique

2019 ◽  
Vol 220 (3) ◽  
pp. 467-475 ◽  
Author(s):  
Jacob M Riveron ◽  
Silvie Huijben ◽  
Williams Tchapga ◽  
Magellan Tchouakui ◽  
Murielle J Wondji ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Pyrethroid Resistance ◽  
Anopheles Funestus ◽  
Resistance Mechanisms ◽  
Piperonyl Butoxide ◽  
Insecticide Treated Nets ◽  
Molecular Analyses ◽  
Cytochrome P450 Genes ◽  
High Degree ◽  
Long Lasting Insecticidal Nets

Abstract Background Insecticide resistance poses a serious threat to insecticide-based interventions in Africa. There is a fear that resistance escalation could jeopardize malaria control efforts. Monitoring of cases of aggravation of resistance intensity and its impact on the efficacy of control tools is crucial to predict consequences of resistance. Methods The resistance levels of an Anopheles funestus population from Palmeira, southern Mozambique, were characterized and their impact on the efficacy of various insecticide-treated nets established. Results A dramatic loss of efficacy of all long-lasting insecticidal nets (LLINs), including piperonyl butoxide (PBO)–based nets (Olyset Plus), was observed. This An. funestus population consistently (2016, 2017, and 2018) exhibited a high degree of pyrethroid resistance. Molecular analyses revealed that this resistance escalation was associated with a massive overexpression of the duplicated cytochrome P450 genes CYP6P9a and CYP6P9b, and also the fixation of the resistance CYP6P9a_R allele in this population in 2016 (100%) in contrast to 2002 (5%). However, the low recovery of susceptibility after PBO synergist assay suggests that other resistance mechanisms could be involved. Conclusions The loss of efficacy of pyrethroid-based LLINs with and without PBO is a concern for the effectiveness of insecticide-based interventions, and action should be taken to prevent the spread of such super-resistance.

scholarly journals Evaluating the Evidence from Molecular Structure and Population Studies for Cross-Resistance to the Pyrethroids Used in Malaria Vector Control

2020 ◽  
Author(s):  
Catherine L. Moyes ◽  
Rosemary S. Lees ◽  
Cristina Yunta ◽  
Kyle J. Walker ◽  
Kay Hemmings ◽  
...  
Keyword(s):  
Binding Affinity ◽  
Malaria Vector ◽  
Pyrethroid Resistance ◽  
Anopheles Funestus ◽  
Malaria Vectors ◽  
Cross Resistance ◽  
Malaria Vector Control ◽  
Insecticide Treated Nets ◽  
The Common ◽  
The Impact

Abstract The primary malaria control intervention in high burden countries is the deployment of long-lasting insecticide-treated nets (LLINs) treated with pyrethroids, alone or in combination with a second active ingredient or synergist. It is essential to understand whether the impact of pyrethroid resistance can be mitigated by switching between different pyrethroids or whether cross-resistance precludes this. Structural diversity within the pyrethroids could mean some compounds are better able to counteract the resistance mechanisms that have evolved in malaria vectors. Here we consider variation in vulnerability to the P450 enzymes that confer metabolic pyrethroid resistance in Anopheles gambiae s.l. and Anopheles funestus. We assess the relationships among pyrethroids in terms of their binding affinity to key P450s and the percent dep­letion by these P450s, in order to identify which pyrethroids diverge from the others. We then investigate whether these same pyrethroids also diverge from the others in terms of resistance in vector populations. We found that etofenprox, which lacks the common structural moiety of other pyrethroids, potentially diverges from the commonly deployed pyrethroids in terms of P450 binding affinity and resistance in malaria vector populations, but not depletion by the P450s tested. These results are supplemented by an analysis of resistance to the same pyrethroids in Aedes aegypti populations, which also found etofenprox diverges from the other pyrethroids in terms of resistance in wild populations. In addition, we found that bifenthrin, which also lacks the common structural moiety of most pyrethroids, diverges from the commonly deployed pyrethroids in terms of P450 binding affinity and depletion by P450s. However, resistance to bifenthrin in vector populations is largely untested. The prevalence of resistance to the pyrethroids α-cypermethrin, cyfluthrin, deltamethrin, λ-cyhalothrin, and permethrin was correlated across malaria vector populations and switching between these compounds as a tool to mitigate against pyrethroid resistance is not advised without strong evidence supporting a true difference in resistance.

scholarly journals Cis-regulatory CYP6P9b P450 variants associated with loss of insecticide-treated bed net efficacy against Anopheles funestus

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Leon M. J. Mugenzi ◽  
Benjamin D. Menze ◽  
Magellan Tchouakui ◽  
Murielle J. Wondji ◽  
Helen Irving ◽  
...  
Keyword(s):  
Pyrethroid Resistance ◽  
Resistance Management ◽  
Anopheles Funestus ◽  
Central Africa ◽  
Malaria Vectors ◽  
Insecticide Treated Nets ◽  
Metabolic Resistance ◽  
P450 Gene ◽  
Regulatory Variants ◽  
The Impact

Abstract Elucidating the genetic basis of metabolic resistance to insecticides in malaria vectors is crucial to prolonging the effectiveness of insecticide-based control tools including long lasting insecticidal nets (LLINs). Here, we show that cis-regulatory variants of the cytochrome P450 gene, CYP6P9b, are associated with pyrethroid resistance in the African malaria vector Anopheles funestus. A DNA-based assay is designed to track this resistance that occurs near fixation in southern Africa but not in West/Central Africa. Applying this assay we demonstrate, using semi-field experimental huts, that CYP6P9b-mediated resistance associates with reduced effectiveness of LLINs. Furthermore, we establish that CYP6P9b combines with another P450, CYP6P9a, to additively exacerbate the reduced efficacy of insecticide-treated nets. Double homozygote resistant mosquitoes (RR/RR) significantly survive exposure to insecticide-treated nets and successfully blood feed more than other genotypes. This study provides tools to track and assess the impact of multi-gene driven metabolic resistance to pyrethroids, helping improve resistance management.

scholarly journals Anopheles funestus mosquitoes from rural south-eastern Tanzania may have stronger resistance to pyrethroids than the other malaria vector, Anopheles arabiensis

2020 ◽  
Author(s):  
Polius Gerazi Pinda ◽  
Claudia Eichenberger ◽  
Halfan S Ngowo ◽  
Dickson S Msaky ◽  
Said Abbasi ◽  
...  
Keyword(s):  
Malaria Transmission ◽  
Anopheles Arabiensis ◽  
Pyrethroid Resistance ◽  
Anopheles Funestus ◽  
Indoor Residual Spraying ◽  
The Other ◽  
Sub Saharan Africa ◽  
Malaria Vectors ◽  
Insecticide Treated Nets ◽  
South Eastern

Abstract Background: Long-lasting insecticide-treated nets (LLINs) and indoor residual spraying (IRS) have greatly reduced malaria transmission in sub-Saharan Africa, but are threatened by insecticide resistance. In south-eastern Tanzania, pyrethroid-resistant Anopheles funestus are now implicated in > 80% of malaria infections, even in villages where the species occurs at lower densities than the other vector species, Anopheles arabiensis. This study compared the intensities of resistance between the two malaria vectors, so as to improve options for control. Methods: The study used WHO assays with 1×, 5× and 10× insecticide doses to assess levels of resistance, followed by synergist bioassays to understand possible mechanisms of the observed resistance phenotypes. The tests involved adult mosquitoes collected from villages across two districts in south-eastern Tanzania and identified using morphological and molecular approaches.Findings: At baseline doses (1×), both species were resistant to the two pyrethroids (permethrin and deltamethrin) but susceptible to the organophosphate (pirimiphos-methyl). An. funestus, but not An. arabiensis was also resistant to the carbamate (bendiocarb) at baseline doses. Both species were generally resistant to DDT, except An.arabiensis from one village. An. funestus showed strong resistance to pyrethroids, surviving the 5× and 10× doses except in one village. Pre-exposure to the synergist, piperonyl butoxide (PBO), enhanced the potency of pyrethroid in both An. arabiensis and An. funestus achieving mortalities >98%, except for An. funestus from two villages for which permethrin-associated mortalities exceeded 90% but not 98%. Conclusions: In these communities where An. funestus dominates malaria transmission, this study may suggest that the species also have much stronger resistance to pyrethroids than its counterpart, An. arabiensis and can survive more classes of insecticides, including carbamates. The pyrethroid resistance in both species appears to be mostly metabolic and may be temporarily addressed using synergists, e.g. PBO. These findings may explain the continued persistence and dominance of An. funestus despite widespread use of pyrethroid-treated LLINs, and inform new choices of interventions to tackle malaria transmission in such settings. These may include PBO-based LLINs or improved IRS with compounds to which the vectors are susceptible. Additional field validation of these indications will be necessary using age-synchronized mosquitoes.

scholarly journals Evidence of pyrethroid resistance in Anopheles amharicus and Anopheles arabiensis from Arjo-Didessa irrigation scheme, Ethiopia

PLoS ONE ◽  
2022 ◽  
Vol 17 (1) ◽  
pp. e0261713
Author(s):  
Assalif Demissew ◽  
Abebe Animut ◽  
Solomon Kibret ◽  
Arega Tsegaye ◽  
Dawit Hawaria ◽  
...  
Keyword(s):  
Malaria Control ◽  
Pyrethroid Resistance ◽  
Management Strategies ◽  
Resistance Management ◽  
Indoor Residual Spraying ◽  
Resistance Mechanisms ◽  
Malaria Vectors ◽  
Insecticide Treated Nets ◽  
Irrigation Area ◽  
Specific Pcr

Background Indoor residual spraying and insecticide-treated nets are among the key malaria control intervention tools. However, their efficacy is declining due to the development and spread of insecticide resistant vectors. In Ethiopia, several studies reported resistance of An. arabiensis to multiple insecticide classes. However, such data is scarce in irrigated areas of the country where insecticides, pesticides and herbicides are intensively used. Susceptibility of An. gambiae s.l. to existing and new insecticides and resistance mechanisms were assessed in Arjo-Didessa sugarcane plantation area, southwestern Ethiopia. Methods Adult An. gambiae s.l. reared from larval/pupal collections of Arjo-Didessa sugarcane irrigation area and its surrounding were tested for their susceptibility to selected insecticides. Randomly selected An. gambiae s.l. (dead and survived) samples were identified to species using species-specific polymerase chain reaction (PCR) and were further analyzed for the presence of knockdown resistance (kdr) alleles using allele-specific PCR. Results Among the 214 An. gambiae s.l. samples analyzed by PCR, 89% (n = 190) were An. amharicus and 9% (n = 20) were An. arabiensis. Mortality rates of the An. gambiae s.l. exposed to deltamethrin and alphacypermethrin were 85% and 86.8%, respectively. On the other hand, mortalities against pirmiphos-methyl, bendiocarb, propoxur and clothianidin were 100%, 99%, 100% and 100%, respectively. Of those sub-samples (An. amharicus and An. arabiensis) examined for presence of kdr gene, none of them were found to carry the L1014F (West African) allelic mutation. Conclusion Anopheles amharicus and An. arabiensis from Arjo-Didessa sugarcane irrigation area were resistant to pyrethroids which might be synergized by extensive use of agricultural chemicals. Occurrence of pyrethroid resistant malaria vectors could challenge the ongoing malaria control and elimination program in the area unless resistance management strategies are implemented. Given the resistance of An. amharicus to pyrethroids, its behavior and vectorial capacity should be further investigated.

scholarly journals The dominant malaria vector, Anopheles funestus from rural south-eastern Tanzania, is more strongly resistant to insecticides than Anopheles arabiensis

2020 ◽  
Author(s):  
Polius Gerazi Pinda ◽  
Claudia Eichenberger ◽  
Halfan S Ngowo ◽  
Dickson S Msaky ◽  
Said Abbasi ◽  
...  
Keyword(s):  
Malaria Transmission ◽  
Pyrethroid Resistance ◽  
Mosquito Species ◽  
Anopheles Funestus ◽  
Indoor Residual Spraying ◽  
Sub Saharan Africa ◽  
Malaria Vectors ◽  
Insecticide Treated Nets ◽  
South Eastern ◽  
Sub Saharan

Abstract Background: Long-lasting insecticide-treated nets (LLINs) and indoor residual spraying (IRS) have greatly reduced malaria transmission in sub-Saharan Africa, but are threatened by insecticide resistance in dominant malaria vectors. In south-eastern Tanzania, pyrethroid-resistant Anopheles funestus now transmit more than 80% of malaria infections even in villages where the species occurs at far lower densities than other vectors such as Anopheles arabiensis.Methods: To better understand the dominance of An. funestus in these settings and improve options for its control, this study compared intensities of resistance between females of this species and those of An. arabiensis , using WHO assays with 1×, 5× and 10× insecticide doses. Additional tests were done to assess the reversibility of such resistance using synergists. The mosquitoes were collected from villages across two districts in south-eastern Tanzania.Findings: Both species were resistant to the two pyrethroids (permethrin and deltamethrin) and the organochloride (DDT) but susceptible to the organophosphate (pirimiphos-methyl) at standard baseline doses (1×). However, An. funestus as opposed to An. arabiensis was also resistant to the carbamate (bendiocarb) at standard doses (1×). An. funestus showed strong resistance to pyrethroids, surviving the 5× doses and 10× doses except in one village. Pre-exposure to the synergist, piperonyl butoxide (PBO), reversed the pyrethroid-resistance in both An. arabiensis and An. funestus achieving mortalities >98%, except for An. funestus from two villages for which permethrin-associated mortalities exceeded 90% but not 98%.Conclusions : In these communities where An. funestus now dominates malaria transmission, the species also displays much stronger resistance to pyrethroids than its counterpart, An. arabiensis, and can readily survive more classes of insecticides, including carbamates. The resistance to pyrethroids in both mosquito species appears to be mostly metabolic and can be reversed significantly using synergists such as PBO. These findings may explain the continued persistence and dominance of An. funestus despite widespread use of pyrethroid-treated LLINs, and will also inform future choices of interventions to tackle malaria transmission in this area and other similar settings. Such interventions may include PBO-based LLINs or improved IRS with compounds such as organophosphates against which the vectors are still susceptible.

scholarly journals Creating mosquito-free outdoor spaces using transfluthrin-treated chairs and ribbons

2019 ◽  
Author(s):  
John Paliga Masalu ◽  
Marceline Finda ◽  
Gerry F. Killeen ◽  
Halfan S. Ngowo ◽  
Polius G. Pinda ◽  
...  
Keyword(s):  
Anopheles Funestus ◽  
Indoor Residual Spraying ◽  
Malaria Vectors ◽  
Insecticide Treated Nets ◽  
Domestic Spaces ◽  
Host Seeking ◽  
Outdoor Spaces ◽  
Outdoor Biting ◽  
Outdoor Environments ◽  
Almost All

Abstract Background Residents of malaria-endemic communities spend several hours outdoors performing different activities, e.g. cooking, story-telling or eating, thereby exposing themselves to potentially-infectious mosquitoes. This compromises effectiveness of indoor interventions, notably long-lasting insecticide-treated nets (LLINs) and indoor residual spraying (IRS). This study characterized common peri-domestic spaces in rural south-eastern Tanzania, and assessed protective efficacies of hessian fabric mats and ribbons treated with the spatial repellent, transfluthrin and respectively fitted to chairs and outdoor kitchens, against mosquitoes.Methods Two hundred households were surveyed, and their most-used peri-domestic spaces physically characterized. Protective efficacies of locally-made transfluthrin-emanating chairs and hessian ribbons were tested in outdoor environments of eight households using volunteer-occupied exposure-free double net traps. CDC light traps were used to estimate host-seeking mosquito densities within open-structure outdoor kitchens. Field-collected Anopheles arabiensis and Anopheles funestus mosquitoes were exposed underneath the chairs to estimate 24h-mortality. Finally, WHO insecticide susceptibility tests were conducted on wild-caught Anopheles from the villages.Results Approximately half (52%) of houses had verandas. Aside from these verandas, most houses also had peri-domestic spaces where residents stayed most times (67% of houses with verandas and 94% of non-veranda houses). Two-thirds of these spaces were sited under trees, and only one third (34.4%) were built-up. The outdoor structures were usually makeshift kitchens having roofs and partial walls. Transfluthrin-treated chairs reduced outdoor-biting An. arabiensis densities by 70-76% while transfluthrin-treated hessian ribbons fitted to the outdoor kitchens caused 81% reduction in the general peri-domestic area. Almost all the field-collected An. arabiensis (99.4%) and An. funestus (100%) exposed under transfluthrin-treated chairs died. The An. arabiensis were susceptible to non-pyrethroids (pirimiphos methyl & bendiocarb) but resistant to pyrethroids commonly used on LLINs (deltamethrin & permethrin).Conclusion Most houses had actively-used peri-domestic outdoor spaces where exposure to mosquitoes occurred. The transfluthrin-treated chair and ribbons reduced outdoor-biting malaria vectors in these peri-domestic spaces, and also elicited significant mortality among pyrethroid-resistant field-caught malaria vectors. These two new prototype formats for transfluthrin emanators, if developed further, may constitute new options for complementing LLINs and IRS with outdoor protection against malaria and other mosquito-borne pathogens in areas where peri-domestic human activities are common.

scholarly journals Investigation of the influence of a glutathione S-transferase metabolic resistance to pyrethroids/DDT on mating competitiveness in males of the African malaria vector, Anopheles funestus

2019 ◽  
Vol 4 ◽  
pp. 13 ◽  
Author(s):  
Magellan Tchouakui ◽  
Billy Tene Fossog ◽  
Brigitte Vanessa Ngannang ◽  
Doumani Djonabaye ◽  
Williams Tchapga ◽  
...  
Keyword(s):  
Natural Populations ◽  
Anopheles Funestus ◽  
Resistance Mechanisms ◽  
Malaria Vectors ◽  
Glutathione S Transferase ◽  
Metabolic Resistance ◽  
Mating Competitiveness ◽  
Metabolic Marker ◽  
Susceptible Allele ◽  
Permanet 3.0

Background: Metabolic resistance is a serious challenge to current insecticide-based interventions. The extent to which it affects natural populations of mosquitoes including their reproduction ability remains uncharacterised. Here, we investigated the potential impact of the glutathione S-transferase L119F-GSTe2 resistance on the mating competitiveness of male Anopheles funestus, in Cameroon. Methods: Swarms and indoor resting collections took place in March, 2018 in Tibati, Cameroon. WHO tube and cone assays were performed on F1 mosquitoes from indoor collected females to assess the susceptibility profile of malaria vectors. Mosquitoes mated and unmated males collected in the swarms were genotyped for the L119F metabolic marker to assess its association with mating male competitiveness. Results: Susceptibility and synergist assays, showed that this population was multiple resistant to pyrethroids, DDT and carbamates, likely driven by metabolic resistance mechanisms. Cone assays revealed a reduced efficacy of standard pyrethroid-nets (Olyset and PermaNet 2.0) with low mortality (<25%) whereas synergist PBO-Nets (Olyset Plus and PermaNet 3.0) retained greater efficacy with higher mortality (>80%). The L119F-GSTe2 mutation, conferring pyrethroid/DDT resistance, was detected in this An. funestus population at a frequency of 28.8%. In addition, a total of 15 mating swarms were identified and 21 An. funestus couples were isolated from those swarms.  A comparative genotyping of the L119F-GSTe2 mutation between mated and unmated males revealed that heterozygote males 119L/F-RS were less able to mate than homozygote susceptible (OR=7.2, P<0.0001). Surprisingly, heterozygote mosquitoes were also less able to mate than homozygote resistant (OR=4.2, P=0.010) suggesting the presence of a heterozygote disadvantage effect. Overall, mosquitoes bearing the L119-S susceptible allele were significantly more able to mate than those with 119F-R resistant allele (OR=2.1, P=0.03). Conclusion: This study provides preliminary evidences that metabolic resistance potentially exerts a fitness cost on mating competiveness in resistant mosquitoes.

scholarly journals An Experimental Hut Evaluation of PBO-Based and Pyrethroid-Only Nets against the Malaria Vector Anopheles funestus Reveals a Loss of Bed Nets Efficacy Associated with GSTe2 Metabolic Resistance

Genes ◽  
2020 ◽  
Vol 11 (2) ◽  
pp. 143 ◽  
Author(s):  
Benjamin D. Menze ◽  
Mersimine F. Kouamo ◽  
Murielle J. Wondji ◽  
Williams Tchapga ◽  
Micareme Tchoupo ◽  
...  
Keyword(s):  
Anopheles Funestus ◽  
Blood Feeding ◽  
Malaria Vectors ◽  
Bed Nets ◽  
Glutathione S Transferase ◽  
Metabolic Resistance ◽  
Experimental Hut ◽  
The Impact ◽  
Long Lasting Insecticidal Nets ◽  
Permanet 3.0

Growing insecticide resistance in malaria vectors is threatening the effectiveness of insecticide-based interventions, including Long Lasting Insecticidal Nets (LLINs). However, the impact of metabolic resistance on the effectiveness of these tools remains poorly characterized. Using experimental hut trials and genotyping of a glutathione S-transferase resistance marker (L119F-GSTe2), we established that GST-mediated resistance is reducing the efficacy of LLINs against Anopheles funestus. Hut trials performed in Cameroon revealed that Piperonyl butoxide (PBO)-based nets induced a significantly higher mortality against pyrethroid resistant An. funestus than pyrethroid-only nets. Blood feeding rate and deterrence were significantly higher in all LLINs than control. Genotyping the L119F-GSTe2 mutation revealed that, for permethrin-based nets, 119F-GSTe2 resistant mosquitoes have a greater ability to blood feed than susceptible while the opposite effect is observed for deltamethrin-based nets. For Olyset Plus, a significant association with exophily was observed in resistant mosquitoes (OR = 11.7; p < 0.01). Furthermore, GSTe2-resistant mosquitoes (cone assays) significantly survived with PermaNet 2.0 (OR = 2.1; p < 0.01) and PermaNet 3.0 (side) (OR = 30.1; p < 0.001) but not for Olyset Plus. This study shows that the efficacy of PBO-based nets (e.g., blood feeding inhibition) against pyrethroid resistant malaria vectors could be impacted by other mechanisms including GST-mediated metabolic resistance not affected by the synergistic action of PBO. Mosaic LLINs incorporating a GST inhibitor (diethyl maleate) could help improve their efficacy in areas of GST-mediated resistance.

scholarly journals Sub-lethal aquatic doses of pyriproxyfen may increase pyrethroid resistance in malaria mosquitoes

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0248538
Author(s):  
Mercy A. Opiyo ◽  
Halfan S. Ngowo ◽  
Salum A. Mapua ◽  
Monica Mpingwa ◽  
Nuru Nchimbi ◽  
...  
Keyword(s):  
Pyrethroid Resistance ◽  
Mortality Rates ◽  
Malaria Vectors ◽  
Bed Nets ◽  
Insecticide Treated Nets ◽  
Biochemical Basis ◽  
Larval Habitats ◽  
Emergent Adults ◽  
Malaria Mosquitoes ◽  
Lethal Doses

Background Pyriproxyfen (PPF), an insect growth hormone mimic is widely used as a larvicide and in some second-generation bed nets, where it is combined with pyrethroids to improve impact. It has also been evaluated as a candidate for auto-dissemination by adult mosquitoes to control Aedes and Anopheles species. We examined whether PPF added to larval habitats of pyrethroid-resistant malaria vectors can modulate levels of resistance among emergent adult mosquitoes. Methodology Third-instar larvae of pyrethroid-resistant Anopheles arabiensis (both laboratory-reared and field-collected) were reared in different PPF concentrations, between 1×10−9 milligrams active ingredient per litre of water (mgAI/L) and 1×10−4 mgAI/L, or no PPF at all. Emergent adults escaping these sub-lethal exposures were tested using WHO-standard susceptibility assays on pyrethroids (0.75% permethrin and 0.05% deltamethrin), carbamates (0.1% bendiocarb) and organochlorides (4% DDT). Biochemical basis of pyrethroid resistance was investigated by pre-exposure to 4% PBO. Bio-efficacies of long-lasting insecticide-treated nets, Olyset® and PermaNet 2.0 were also examined against adult mosquitoes with or without previous aquatic exposure to PPF. Results Addition of sub-lethal doses of PPF to larval habitats of pyrethroid-resistant An. arabiensis, consistently resulted in significantly reduced mortalities of emergent adults when exposed to pyrethroids, but not to bendiocarb or DDT. Mortality rates after exposure to Olyset® nets, but not PermaNet 2.0 were also reduced following aquatic exposures to PPF. Pre-exposure to PBO followed by permethrin or deltamethrin resulted in significant increases in mortality, compared to either insecticide alone. Conclusions Partially-resistant mosquitoes exposed to sub-lethal aquatic concentrations of PPF may become more resistant to pyrethroids than they already are without such pre-exposures. Studies should be conducted to examine whether field applications of PPF, either by larviciding or other means actually exacerbates pyrethroid-resistance in areas where signs of such resistance already exist in wild the vector populations. The studies should also investigate mechanisms underlying such magnification of resistance, and how this may impact the potential of PPF-based interventions in areas with pyrethroid resistance.

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