scholarly journals Reduced long-lasting insecticidal net efficacy and pyrethroid insecticide resistance are associated with over-expression of CYP6P4, CYP6P3 and CYP6Z1 in populations of Anopheles coluzzii from South-East Côte d’Ivoire

2020 ◽  
Author(s):  
Anne Meiwald ◽  
Emma Clark ◽  
Mojca Kristan ◽  
Constant Edi ◽  
Claire L. Jeffries ◽  
...  

AbstractBackgroundResistance to major public health insecticides in Côte d’Ivoire has intensified and now threatens the long-term effectiveness of malaria vector control interventions.MethodsThis study evaluated the bioefficacy of conventional and next-generation long-lasting insecticidal nets (LLINs), determined resistance profiles, and characterized molecular and metabolic mechanisms in wild Anopheles coluzzii from South-East Côte d’Ivoire in 2019.ResultsPhenotypic resistance was intense: more than 25% of mosquitoes survived exposure to ten times the doses of pyrethroids required to kill susceptible populations. Similarly, 24-hour mortality to deltamethrin-only LLINs was very low and not significantly different to an untreated net. Sub-lethal pyrethroid exposure did not induce significant delayed vector mortality 72 hours later. In contrast, LLINs containing the synergist piperonyl butoxide (PBO), or new insecticides, clothianidin and chlorfenapyr, were highly toxic to An. coluzzii. Pyrethroid-susceptible An. coluzzii were significantly more likely to be infected with malaria, compared to those that survived insecticidal exposure. Pyrethroid resistance was associated with significant over-expression of CYP6P4, CPY6Z1 and CYP6P3.ConclusionsStudy findings raise concerns regarding the operational failure of standard LLINs and support the urgent deployment of vector control interventions incorporating PBO, chlorfenapyr or clothianidin in areas of high resistance intensity in Côte d’Ivoire.

Author(s):  
Anne Meiwald ◽  
Emma Clark ◽  
Mojca Kristan ◽  
Constant Edi ◽  
Claire L Jeffries ◽  
...  

Abstract Background Resistance to major public health insecticides in Côte d’Ivoire has intensified and now threatens the long-term effectiveness of malaria vector control interventions. Methods This study evaluated the bioefficacy of conventional and next-generation long-lasting insecticidal nets (LLINs), determined resistance profiles, and characterized molecular and metabolic mechanisms in wild Anopheles coluzzii from Southeast Côte d’Ivoire in 2019. Results Phenotypic resistance was intense: >25% of mosquitoes survived exposure to 10 times the doses of pyrethroids required to kill susceptible populations. Similarly, the 24-hour mortality rate with deltamethrin-only LLINs was very low and not significantly different from that with an untreated net. Sublethal pyrethroid exposure did not induce significant delayed vector mortality effects 72 hours later. In contrast, LLINs containing the synergist piperonyl butoxide, or new insecticides clothianidin and chlorfenapyr, were highly toxic to A. coluzzii. Pyrethroid-susceptible A. coluzzii were significantly more likely to be infected with malaria, compared with those that survived insecticidal exposure. Pyrethroid resistance was associated with significant overexpression of CYP6P4, CYP6P3, and CYP6Z1. Conclusions Study findings raise concerns regarding the operational failure of standard LLINs and support the urgent deployment of vector control interventions incorporating piperonyl butoxide, chlorfenapyr, or clothianidin in areas of high resistance intensity in Côte d’Ivoire.


Author(s):  
Lucien Yao Konan ◽  
Welbeck Achille Oumbouke ◽  
Urbain Garhapié Silué ◽  
Ibrahima Zanakoungo Coulibaly ◽  
Jean-Claude Tokou Ziogba ◽  
...  

Abstract From 2008 to 2017, the city of Abidjan, Côte d’Ivoire experienced several Aedes-borne disease epidemics which required control of the vector mosquito population based on the reduction of larval habitats and insecticidal sprays for adult mosquitoes. This study was undertaken to assess the insecticide susceptibility status of Aedes aegypti (Linnaeus) in the city of Abidjan. Immature Ae. aegypti were sampled from several larval habitats within seven communes of Abidjan and reared to adults. Three to five days old F1 emerged adults were tested for susceptibility using insecticide-impregnated papers and the synergist piperonyl butoxide (PBO) following WHO bioassay guidelines. The results showed that Ae. aegypti populations from Abidjan were resistant to 0.1% propoxur, and 1% fenitrothion, with mortality rates ranging from 0% to 54.2%. Reduced susceptibility (93.4–97.5% mortality) was observed to 0.05% deltamethrin, 0.75% permethrin, 0.05% lambda-cyhalothrin, 5% malathion, and 0.8% chlorpyrifos-methyl. This reduced susceptibility varied depending on the insecticide and the collection site. The restoration of mortality when the mosquitoes were pre-exposed to the synergist PBO suggests that increased activity of oxidases could be contributing to resistance. Three kdr mutations (V410L, V1016I, and F1534C) were present in populations tested, with low frequencies for the Leu410 (0.28) and Ile1016 (0.32) alleles and high frequencies for the Cys1534 allele (0.96). These findings will be used to inform future arbovirus vector control activities in Abidjan.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Welbeck A. Oumbouke ◽  
Patricia Pignatelli ◽  
Antoine M. G. Barreaux ◽  
Innocent Z. Tia ◽  
Alphonsine A. Koffi ◽  
...  

Abstract Routine monitoring of occurrence, levels and mechanisms of insecticide resistance informs effective management strategies, and should be used to assess the effect of new tools on resistance. As part of a cluster randomised controlled trial evaluating a novel insecticide-based intervention in central Côte d’Ivoire, we assessed resistance and its underlying mechanisms in Anopheles gambiae populations from a subset of trial villages. Resistance to multiple insecticides in An. gambiae s.s. and An. coluzzii was detected across villages, with dose–response assays demonstrating extremely high resistance intensity to the pyrethroid deltamethrin (> 1,500-fold), and mortality following exposure to pyrethroid-treated bednets was low (< 30% mortality in cone bioassays). The 1014F kdr mutation was almost fixed (≥ 90%) in all villages but the 1575Y kdr-amplifying mutation was relatively rare (< 15%). The carbamate and organophosphate resistance-associated Ace-1 G119S mutation was also detected at moderate frequencies (22–43%). Transcriptome analysis identified overexpression of P450 genes known to confer pyrethroid resistance (Cyp9K1, Cyp6P3, and Cyp6M2), and also a carboxylesterase (COEAE1F) as major candidates. Cyp6P3 expression was high but variable (up to 33-fold) and correlated positively with deltamethrin resistance intensity across villages (r2 = 0.78, P = 0.02). Tools and strategies to mitigate the extreme and multiple resistance provided by these mechanisms are required in this area to avoid future control failures.


2019 ◽  
Vol 4 ◽  
pp. 31 ◽  
Author(s):  
Chouaïbou Seïdou Mouhamadou ◽  
Prisca Bédjou N’Dri ◽  
Behi Kouadio Fodjo ◽  
Christabelle Gba Sadia ◽  
France-Paraudie Kouadio Affoue ◽  
...  

Malaria morbidity and mortality rates in Sub-Saharan Africa are increasing. The scale-up of long-lasting insecticidal nets and indoor residual spraying have been the major contributors to the decrease of malaria burden. These tools are now threatened by insecticide resistance in malaria vectors, which is spreading dramatically. After two different real-time polymerase chain reaction molecular characterizations carried out on 70 mosquitoes sampled in the locality of Elibou in southern Côte d’Ivoire, results revealed that 9 mosquitoes from Anopheles coluzzi harbored the double East- and West-African knockdown resistance mutations. In the previous year, only 1 mosquito out of 150 sampled from 10 regions of the country had the same genotype. These results show the rapid spread of insecticide resistance in malaria vectors and highlight the urgent need to diversify the methods of vector control in order to avoid the failure of insecticide-based vector control tools which may favor malaria fatalities.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Cyntia-Muriel Y. Clegban ◽  
Soromane Camara ◽  
A. Alphonsine Koffi ◽  
Ludovic P. Ahoua Alou ◽  
Jean-Paul Kabran Kouame ◽  
...  

Abstract Background Long-lasting insecticidal nets (LLINs) have played an important role in reducing the global malaria burden since 2000. They are a core prevention tool used widely by people at risk of malaria. The Vector Control Prequalification mechanism of the Word Health Organization (WHO-Vector Control PQ) established the testing and evaluation guidelines for LLINs before registration for public use. In the present study, two new brands of deltamethrin-impregnated nets (Yahe® LN and Panda® Net 2.0) were evaluated in an experimental hut against wild pyrethroid-resistant Anopheles gambiae s.l. in M’Bé nearby Bouaké, central Côte d’Ivoire. Methods The performance of Yahe® LN and Panda® Net 2.0 was compared with that of PermaNet 2.0, conventionally treated nets (CTN), and untreated net to assess the blood-feeding inhibition, deterrence, induced exophily, and mortality. Results Cone bioassay results showed that Panda® Net 2.0, PermaNet 2.0 and Yahe® LN (both unwashed and washed 20 times) induced > 95% knockdown or > 80% mortality of the susceptible Anopheles gambiae Kisumu strain. With the pyrethroid-resistant M’Bé strain, mortality rate for all treated nets did not exceed 70%. There was a significant reduction in entry and blood feeding (p < 0.05) and an increase in exophily and mortality rates (p < 0.05) with all treatments compared to untreated nets, except the CTNs. However, the personal protection induced by these treated nets decreased significantly after 20 washes. The performance of Panda® Net 2.0 was equal to PermaNet® 2.0 in terms of inhibiting blood feeding, but better than PermaNet® 2.0 in terms of mortality. Conclusion This study showed that Yahe® LN and Panda® Net 2.0 met the WHO Pesticide Evaluation Scheme (WHOPES) criteria to undergo phase III trial at the community level. Due to an increasing spread and development of pyrethroid resistance in malaria vectors, control of malaria transmission must evolve into an integrated vector management relying on a large variety of efficient control tools. Graphical Abstract


Parasite ◽  
2018 ◽  
Vol 25 ◽  
pp. 42 ◽  
Author(s):  
Soromane Camara ◽  
Ludovic Phamien Ahoua Alou ◽  
Alphonsine Amanan Koffi ◽  
Yao Cyntia Muriel Clegban ◽  
Jean-Paul Kabran ◽  
...  

Background: The widespread insecticide resistance in malaria vector populations is a serious threat to the efficacy of vector control tools. As a result, the World Health Organization (WHO) supports the development of alternative tools that combine several insecticides with the aim of improving vector control and the management of insecticide resistance. In the present study, a long-lasting insecticidal net treated with a mixture of chlorfenapyr and alphacypermethrin was evaluated against wild pyrethroid-resistant Anopheles gambiae s.s in M’bé, Côte d’Ivoire. Centers for Disease Control and Prevention (CDC) bottle tests were carried out with resistant An. gambiae s.s. of M’bé and the susceptible strain, to assess the resistance level to chlorfenapyr and alphacypermethrin. Results: CDC bottle bioassays revealed a high level of resistance of An. gambiae s.s. population from M’bé to alphacypermethrin, whereas they revealed low resistance to chlorfenapyr. In experimental huts, Interceptor® G2 that was unwashed or washed 20 times killed 87% and 82% of An. gambiae s.s., respectively, whereas Interceptor® LN that was either unwashed or washed 20 times killed only about 10% of the mosquitoes. The blood-feeding inhibition induced by Interceptor® was not significantly different compared to untreated nets, whereas Interceptor® G2 that was unwashed or washed 20 times induced 42% and 34% inhibition of blood-feeding, respectively. Conclusion: Interceptor® G2 met the WHOPES criteria to undergo a phase III study. Investigation of its efficacy at a community level and the conduct of randomized controlled trials dealing with epidemiological outputs are warranted in order to study the potential of Interceptor® G2 to better protect communities.


2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Welbeck A. Oumbouke ◽  
Mark Rowland ◽  
Alphonsine A. Koffi ◽  
Ludovic P. A. Alou ◽  
Soromane Camara ◽  
...  

Abstract Background Long-lasting insecticidal nets (LLINs) are the primary method of malaria prevention. However, the widespread resistance to pyrethroids among major malaria vector species represents a significant threat to the continued efficacy of pyrethroid LLIN. Piperonyl butoxide (PBO) is a synergist that inhibits the activity of metabolic enzymes of the cytochrome P450 family known to detoxify insecticides including pyrethroids. Synergist LLIN incorporating PBO and a pyrethroid may provide improved control compared to pyrethroid-only LLIN. Methods The efficacy of VEERALIN® LN (VKA polymers Pvt Ltd, India), an alpha-cypermethrin PBO synergist net was evaluated in experimental huts in M’bé, central Côte d’Ivoire against wild pyrethroid resistant Anopheles gambiae s.s. Comparison was made with a standard alpha-cypermethrin-treated net (MAGNet® LN, VKA polymers Pvt Ltd, India). Nets were tested unwashed and after 20 standardized washes. Results VEERALIN® LN demonstrated improved efficacy compared to MAGNet® LN against wild free-flying pyrethroid-resistant An. gambiae s.s. Before washing, VEERALIN® LN produced mortality of An. gambiae s.s. (51%) significantly higher than the standard pyrethroid-only net (29%) (P < 0.0001). Although there was a significant reduction in mortality with both LLINs after 20 washes, VEERALIN® LN remained superior in efficacy to MAGNet® LN (38 vs 17%) (P < 0.0001). Blood-feeding was significantly inhibited with both types of insecticide-treated nets relative to the untreated control net (P < 0.0001). Unwashed VEERALIN® LN induced significantly higher blood-feeding inhibition of An. gambiae s.s. (62.6%) compared to MAGNet® LN (35.4%) (P < 0.001). The difference persisted after washing, as there was no indication that either LLIN lost protection against biting or blood-feeding. The level of personal protection derived from the use of VEERALIN® LN was high (87%) compared to MAGNet® LN (66–69%) whether unwashed or washed. The AI content of VEERALIN® LN after 20 washes decreased from 6.75 to 6.03 g/kg for alpha-cypermethrin and from 2.95 to 2.64 g/kg for PBO, corresponding to an overall retention of 89% for each compound. Conclusions The addition of the synergist PBO to pyrethroid net greatly improved protection and control of pyrethroid-resistant An. gambiae s.s. The pyrethroid-PBO VEERALIN® LN has the potential to reduce transmission in areas compromised by pyrethroid resistance.


2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Joanna E. C. Furnival-Adams ◽  
Soromane Camara ◽  
Mark Rowland ◽  
Alphonsine A. Koffi ◽  
Ludovic P. Ahoua Alou ◽  
...  

Abstract Background Indoor attractive toxic sugar bait (ATSB) has potential as a supplementary vector-control and resistance-management tool, offering an alternative mode of insecticide delivery to current core vector-control interventions, with potential to deliver novel insecticides. Given the high long-lasting insecticidal bed net (LLIN) coverage across Africa, it is crucial that the efficacy of indoor ATSB in combination with LLINs is established before it is considered for wider use in public health. Methods An experimental hut trial to evaluate the efficacy of indoor ATSB traps treated with 4% boric acid (BA ATSB) or 1% chlorfenapyr (CFP ATSB) in combination with untreated nets or LLINs (holed or intact), took place at the M’bé field station in central Côte d’Ivoire against pyrethroid resistant Anopheles gambiae sensu lato. Results The addition of ATSB to LLINs increased the mortality rates of wild pyrethroid-resistant An. gambiae from 19% with LLIN alone to 28% with added BA ATSB and to 39% with added CFP ATSB (p < 0.001). Anopheles gambiae mortality with combined ATSB and untreated net was similar to that of combined ATSB and LLIN regardless of which insecticide was used in the ATSB. The presence of holes in the LLIN did not significantly affect ATSB-induced An. gambiae mortality. Comparative tests against pyrethroid resistant and susceptible strains using oral application of ATSB treated with pyrethroid demonstrated 66% higher survival rate among pyrethroid-resistant mosquitoes. Conclusion Indoor ATSB traps in combination with LLINs enhanced the control of pyrethroid-resistant An. gambiae. However, many host-seeking An. gambiae entering experimental huts with indoor ATSB exited into the verandah trap without sugar feeding when restricted from a host by a LLIN. Although ATSB has potential for making effective use of classes of insecticide otherwise unsuited to vector control, it does not exempt potential selection of resistance via this route.


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