Efficacy of pyriproxyfen-pyrethroid long-lasting insecticidal nets (LLINs) and chlorfenapyr-pyrethroid LLINs compared with pyrethroid-only LLINs for malaria control in Benin: a cluster-randomised, superiority trial

Accrombessi, Manfred; Cook, Jackie; Dangbénon, Edouard; Yovogan, Boulais; Akpovi, Hilaire; Sovi, Arthur; Adoha, Constantin; Assongba, Landry; Aboubacar, Sidick; Akinro, Bruno; Ossè, Razaki; Tokponnon, Filémon; Aïkpon, Rock; Ogouyèmi-Hounto, Aurore; Padonou, Germain Gil; Kleinschmidt, Immo; Messenger, Louisa A.; Rowland, Mark; Ngufor, Corine; Protopopoff, Natacha; Akogbéto, Martin

doi:10.1016/s0140-6736(22)02319-4

Cited by 87 publications

(130 citation statements)

References 24 publications

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“…This is mostly due to susceptibility of the Covè vector population to chlorfenapyr as demonstrated in bottle bioassays. This superior performance of pyrethroid-chlorfenapyr ITNs confirms previous findings in experimental hut studies in Benin [22,44] and across Africa [23][24][25] and recent cRCTs in Benin [27] Tanzania [28], reiterating the importance of this innovative ITN technology for improving the control of pyrethroid-resistant malaria vector populations. PermaNet® Dual was also non-inferior to Interceptor® G2 for the primary endpoint of mortality thus providing necessary evidence for the candidate ITN to be covered by WHO policy recommendations for deployment of pyrethroidchlorfenapyr nets, pending their availability.…”

Section: Discussionsupporting

confidence: 86%

“…Evidence of epidemiological impact is also emerging from large-scale trials and pilot distribution schemes in several countries. Most notably, cRCTs in Benin [27] and Tanzania [28] showed that Interceptor® G2 reduced child malaria incidence by 46% and 44% respectively over 2 years relative to standard pyrethroid-only ITNs. Pyrethroid-chlorfenapyr ITNs are soon expected to receive a WHO endorsement and policy recommendation, pending proof of improved public health impact from a second ongoing cRCT in Benin [29].…”

Section: Introductionmentioning

confidence: 99%

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PermaNet® Dual, a new deltamethrin-chlorfenapyr mixture net, shows improved efficacy against pyrethroid-resistantAnopheles gambiae sensu latoin southern Benin

Syme

N’dombidjé

Gbegbo

et al. 2023

Preprint

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Pyrethroid-chlorfenapyr nets have demonstrated improved entomological and epidemiological impact in trials across Africa. This is driving increased demand for this novel net class in malaria endemic countries. PermaNet® Dual is a new deltamethrin-chlorfenapyr net developed by Vestergaard Sàrl to provide more options to malaria control programmes. We performed an experimental hut trial to evaluate the efficacy of PermaNet® Dual against wild, free-flying pyrethroid-resistantAnopheles gambiae sensu latoin Covè, Benin. PermaNet® Dual induced superior levels of mosquito mortality compared to a pyrethroid-only net and a pyrethroid-piperonyl butoxide net both when unwashed (77% with PermaNet® Dual vs. 23% with PermaNet® 2.0 and 56% with PermaNet® 3.0, p<0.001) and after 20 standardised washes (75% with PermaNet® Dual vs. 14% with PermaNet® 2.0 and 30% with PermaNet® 3.0, p<0.001). Using a provisional non-inferiority margin defined by the World Health Organisation, PermaNet® Dual was also non-inferior to a pyrethroid-chlorfenapyr net that has demonstrated improved public health value (Interceptor® G2), for vector mortality (79% vs. 76%, OR=0.854, 95% CIs: 0.703-1.038) but not for blood-feeding protection (35% vs. 26%, OR=1.445, 95% CIs: 1.203-1.735). PermaNet® Dual presents an additional option of this highly effective net class for improved control of malaria transmitted by pyrethroid-resistant mosquitoes.

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Section: Discussionsupporting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

PermaNet® Dual, a new deltamethrin-chlorfenapyr mixture net, shows improved efficacy against pyrethroid-resistantAnopheles gambiae sensu latoin southern Benin

Syme

N’dombidjé

Gbegbo

et al. 2023

Preprint

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“…gambiae s.l. exposed to the control nets had fully developed their eggs to Christopher's stage V. While these study results would suggest that Royal Guard® or other pyriproxyfen-based products may potentially lead to a significant reduction in malaria transmission, studies in randomized control trials in Tanzania [29] and Benin [55] have demonstrated that Royal Guard® ITNs show no greater impact on epidemiological indicators than standard pyrethroid only ITNs.…”

Section: Discussionmentioning

confidence: 77%

“…Ngufor et al 2017, showed, in a study conducted in Covè (southern Benin), that indoor residual spraying with CFP in households with standard LLINs provided additional levels of transmission control and personal protection thus revealing the potential of CFP to manage pyrethroid resistance in the context of an expanding LLIN/IRS strategy [18]. Recently, there have been two studies, one in Benin [55] and one in Tanzania [29], which have demonstrated a high reduction in human malaria indicators in the Interceptor® G2 net arm compared to the standard pyrethroid-only net arm in randomized control trials after two years of use. All these studies continue to provide evidence of the potential efficacy of chlorfenapyr-based products for vector control.…”

Section: Discussionmentioning

confidence: 99%

Assessing the susceptibility and efficacy of three public health, insecticides, chlorfenapyr, clothianidin, and pyriproxyfen, on wild pyrethroid-resistant populations of Anopheles gambiae s.l. from southern Benin

Zoungbédji¹,

Padonou²,

Konkon³

et al. 2023

Preprint

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Background: The objective of this study was to determine the susceptibility of wild Anopheles gambiaes.l. from southern Benin to the new insecticides (chlorfenapyr (CFP), pyriproxyfen (PPF), and clothianidin (CTD)) and assess the efficacy of insecticide-treated bed nets (ITNs) that contain these new products. Methods: Wild Anopheles gambiae s.l. from the Benin communes of Allada, Ifangni, Akpro-Missérété, and Porto-Novo were tested for their susceptibility to CFP and PPF using the WHO bottle tests, and pyrethroids (alpha-cypermethrin, deltamethrin, and permethrin) and CTD using WHO tube tests. WHO cone tests were used to evaluate the efficacy of Interceptor® (which contains alpha-cypermethrin (ACM) only), Interceptor® G2, (CFP + ACM), and Royal Guard® nets (PPF + ACM). The ovaries of blood-fed Anopheles gambiae s.l. from Ifangni exposed to a new PPF net were dissected, and egg development status was examined using Christopher’s stages to determine the fertility status of the mosquitoes. Using a standardized protocol, the oviposition rate and oviposition inhibition rate were calculated from live blood-fed Anopheles gambiae s.l. placed in oviposition chambers after exposure to PPF. Results. In all four mosquito populations, pyrethroid mortality ranged from 5% to 80%, while chlorfenapyr and clothianidin mortality ranged from 98% to 100%. At Ifangni, all mosquitoes exposed to Royal Guard® nets were infertile (100%) while the majority (74.9%) of mosquitoes exposed to Interceptor® nets had fully developed their eggs to Christopher’s stage V. The oviposition inhibition rate after exposure of the mosquitoes to the PPF was 99% for the wild population of Anopheles gambiaes.l. and the susceptible laboratory strain, Anopheles gambiae Kisumu. Conclusions: The results of this study suggest that pyrethroid-resistant Anopheles gambiaes.l. from the selected communes in southern Benin are susceptible to chlorfenapyr, clothianidin, and pyriproxyfen. In addition, based on bioassay results, Interceptor® G2 and Royal Guard® nets are probably effective in Ifangni. Despite the availability of new effective insecticides, continued vigilance is needed in Benin. Therefore, monitoring of resistance to these insecticides will continue to periodically update the Benin national insecticide resistance database and management plan.

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“…In contrast, we observed markedly improved mortality rates with both types of pyrethroid-CFP ITN compared to pyrethroid-PBO and pyrethroid-only ITNs which can be attributed to the susceptibility of the Covè vector population to CFP. The superiority of pyrethroid-CFP ITNs over other ITN types is supported by recent experimental hut trials (29,34,35,36) and cRCTs in Benin (37) and Tanzania (14), and was formally acknowledged in recently revised WHO guidelines recommending them over pyrethroid-only and pyrethroid-PBO ITNs (10).…”

Section: Discussionmentioning

confidence: 95%

Can the performance of pyrethroid-chlorfenapyr nets be reduced when combined with pyrethroid-piperonyl butoxide (PBO) nets?

Syme

Nounagnon²,

N’dombidjé³

et al. 2023

Preprint

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Background Pyrethroid-chlorfenapyr (CFP) and pyrethroid-piperonyl butoxide (PBO) nets are being scaled across endemic countries to improve control of malaria transmitted by pyrethroid-resistant mosquitoes. CFP is a pro-insecticide requiring activation by mosquito cytochrome P450 monooxygenase enzymes (P450s) while PBO improves pyrethroid potency by inhibiting the action of these enzymes in pyrethroid-resistant mosquitoes. The inhibitory action of PBO against P450s may thus reduce the efficacy of pyrethroid-CFP nets when applied inside the same household as pyrethroid-PBO nets. Methods We performed two experimental hut trials to evaluate the entomological impact of two different types of pyrethroid-CFP ITN (Interceptor® G2, PermaNet®Dual) when applied alone and in combination with pyrethroid-PBO ITNs (DuraNet®Plus, PermaNet®3.0) against a pyrethroid-resistant vector population in southern Benin. In both trials, all net types were tested as single and double net treatments. We also performed bioassays to assess the resistance profile of the vector population at the hut site and investigate interactions between CFP and PBO. Results The vector population was susceptible to CFP but exhibited a high intensity of pyrethroid resistance that was overcame by PBO pre-exposure. Vector mortality was significantly lower in huts with combinations of pyrethroid-CFP nets plus pyrethroid-PBO nets compared to huts with two pyrethroid-CFP nets (57–75% vs. 83–85%, p<0.001). PBO pre-exposure reduced the toxicity of CFP in bottle bioassays suggesting this effect may be partly attributable to antagonism between CFP and PBO. We observed higher levels of vector mortality in huts with net combinations that included pyrethroid-CFP nets compared to those that did not and highest mortality was achieved when pyrethroid-CFP nets were applied alone as a single net (68–82%) and as two nets together (83–85%). Conclusions This study shows evidence of a reduced performance of pyrethroid-CFP nets when combined with pyrethroid-PBO ITNs compared to when applied alone and higher efficacy with net combinations that included pyrethroid-CFP nets. Our findings therefore suggest that in similar contexts, prioritising distribution of pyrethroid-CFP nets over other net types would maximise vector control impact.

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Efficacy of pyriproxyfen-pyrethroid long-lasting insecticidal nets (LLINs) and chlorfenapyr-pyrethroid LLINs compared with pyrethroid-only LLINs for malaria control in Benin: a cluster-randomised, superiority trial

Cited by 87 publications

References 24 publications

PermaNet® Dual, a new deltamethrin-chlorfenapyr mixture net, shows improved efficacy against pyrethroid-resistantAnopheles gambiae sensu latoin southern Benin

PermaNet® Dual, a new deltamethrin-chlorfenapyr mixture net, shows improved efficacy against pyrethroid-resistantAnopheles gambiae sensu latoin southern Benin

Assessing the susceptibility and efficacy of three public health, insecticides, chlorfenapyr, clothianidin, and pyriproxyfen, on wild pyrethroid-resistant populations of Anopheles gambiae s.l. from southern Benin

Can the performance of pyrethroid-chlorfenapyr nets be reduced when combined with pyrethroid-piperonyl butoxide (PBO) nets?

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