scholarly journals Efficacy evaluation of Veeralin LN, a PBO-incorporated alpha-cypermethrin long-lasting insecticidal net against Anopheles culicifacies in experimental huts in Odisha State

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Gunasekaran Kasinathan ◽  
Sudhansu Sekhar Sahu ◽  
Nallan Krishnamoorthy ◽  
Mohammed Mustafa Baig ◽  
Sonia Thankachy ◽  
...  

Abstract Background The success of malaria control using long-lasting insecticidal nets (LLINs) is threatened by pyrethroid resistance developed by the malaria vectors, worldwide. To combat the resistance, synergist piperonyl butoxide (PBO) incorporated LLINs is one of the available options. In the current phase II hut trial, the efficacy of Veeralin®LN (an alpha-cypermethrin and PBO-incorporated net) was evaluated against Anopheles culicifacies, a pyrethroid resistant malaria vector. Methods The performance of Veeralin®LN was compared with MAGNet®LN and untreated net in reducing the entry, induced exit, mortality and blood feeding inhibition of target vector species. Results The performance of Veeralin was equal to MAGNet in terms of reducing hut entry, inhibiting blood feeding and inducing exophily, and with regard to causing mortality Veeralin was better than MAGNet. When compared to untreated net, a significant reduction in hut entry and blood feeding and an increase in exophily and mortality were observed with Veeralin. In cone bioassays, unwashed Veeralin caused > 80% mortality of An. culicifacies. Conclusions Veeralin performed equal to (entry, exit, feeding) or better than (mortality in huts and cone bioassays) MAGNet and could be an effective tool against pyrethroid resistant malaria vectors.

Genes ◽  
2020 ◽  
Vol 11 (2) ◽  
pp. 143 ◽  
Author(s):  
Benjamin D. Menze ◽  
Mersimine F. Kouamo ◽  
Murielle J. Wondji ◽  
Williams Tchapga ◽  
Micareme Tchoupo ◽  
...  

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.


2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Eliningaya J. Kweka ◽  
Patrick K. Tungu ◽  
Aneth M. Mahande ◽  
Humphrey D. Mazigo ◽  
Subira Sayumwe ◽  
...  

Abstract Background The decline in malaria cases and vectors is major milestone in fighting against malaria. The efficacy of MAGNet long-lasting insecticidal nets (MAGNet LLIN), an alpha-cypermethrin incorporated long-lasting net, with the target dose ± 25% of 5.8 g active ingredient (AI)/kg (4.35–7.25 g AI/kg) was evaluated in six veranda-trap experimental huts in Muheza, Tanzania against freely flying wild population of Anopheles funestus. Methods MAGNet LLINs were tested against wild, free-flying, host-seeking An. funestus mosquitoes over a period of 6 weeks (total of 36 nights in the huts). MAGNet LLIN efficacy was determined in terms of mosquito mortality, blood-feeding inhibition, deterrence, induced exiting, personal protection, and insecticidal killing over 20 washes according to WHO standardized procedures. Efficacy was compared with reference to a WHOPES recommended approved LLINs (DuraNet) and to a net conventionally treated (CTN) treated with alpha-cypermethrin at WHO-recommended dose and washed to just before cut-off point. The efficacy of MAGNet was evaluated in experimental huts against wild, free-flying, pyrethroid-resistant An. funestus. The WHO-susceptibility method was used to detect resistance in wild Anopheles exposed to 0.75% permethrin. Mosquito mortality, blood-feeding inhibition and personal protection were compared between untreated nets and standard LLINs. Blood-feeding rates were recorded and compared between the 20 times washed; blood-feeding rates between 20 times washed MAGNet LLIN and 20 times washed WHOPES-approved piperonyl butoxide (PBO)/pyrethroid were not statistically different (p > 0.05). Results The results have evidently shown that MAGNet LLIN provides similar blood-feeding inhibition, exophily, mortality, and deterrence to the standard approved LLIN, thus meeting the WHOPES criteria for blood feeding. The significantly high feeding inhibition and personal protection over pyrethroid-resistant An. funestus recorded by both unwashed and 20 times washed MAGNet compared to the unwashed DuraNet, the WHOPES-approved standard pyrethroid-only LLIN provides proof of MAGNet meeting Phase II WHOPES criteria for a LLIN. Conclusion Based on this study, MAGNet has been shown to have a promising impact on protection when 20 times washed against a highly resistant population of An. funestus.


2017 ◽  
Vol 2 ◽  
pp. 112 ◽  
Author(s):  
Arnold S. Mmbando ◽  
Halfan S. Ngowo ◽  
Masoud Kilalangongono ◽  
Said Abbas ◽  
Nancy S. Matowo ◽  
...  

Background: Despite high coverage of indoor interventions like insecticide-treated nets, mosquito-borne infections persist, partly because of outdoor-biting, early-biting and insecticide-resistant vectors. Push-pull systems, where mosquitoes are repelled from humans and attracted to nearby lethal targets, may constitute effective complementary interventions. Methods: A partially randomized cross-over design was used to test efficacy of push-pull in four experimental huts and four local houses, in an area with high pyrethroid resistance in Tanzania. The push-pull system consisted of 1.1% or 2.2% w/v transfluthrin repellent dispensers and an outdoor lure-and-kill device (odour-baited mosquito landing box). Matching controls were set up without push-pull. Adult male volunteers collected mosquitoes attempting to bite them outdoors, but collections were also done indoors using exit traps in experimental huts and by volunteers in the local houses. The collections were done hourly (1830hrs-0730hrs) and mosquito catches compared between push-pull and controls. An. gambiae s.l. and An. funestus s.l. were assessed by PCR to identify sibling species, and ELISA to detect Plasmodium falciparum and blood meal sources. Results: Push-pull in experimental huts reduced outdoor-biting for An. arabiensis and Mansonia species by 30% and 41.5% respectively. However, the reductions were marginal and insignificant for An. funestus (12.2%; p>0.05) and Culex (5%; p>0.05). Highest protection against all species occurred before 2200hrs. There was no significant difference in number of mosquitoes inside exit traps in huts with or without push-pull. In local households, push-pull significantly reduced indoor and outdoor-biting of An. arabiensis by 48% and 25% respectively, but had no effect on other species. Conclusion: This push-pull system offered modest protection against outdoor-biting An. arabiensis, without increasing indoor mosquito densities. Additional experimentation is required to assess how transfluthrin-based products affect mosquito blood-feeding and mortality in push-pull contexts. This approach, if optimised, could potentially complement existing malaria interventions even in areas with high pyrethroid resistance.


Pathogens ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 415
Author(s):  
Magellan Tchouakui ◽  
Leon M. J. Mugenzi ◽  
Benjamin D. Menze ◽  
Jude N. T. Khaukha ◽  
Williams Tchapga ◽  
...  

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.


2020 ◽  
Author(s):  
Jackline Martin ◽  
Franklin W Mosha ◽  
Eliud Lukole ◽  
Mark Rowland ◽  
Jim Todd ◽  
...  

Abstract Background: The spread of pyrethroid resistance in malaria vectors threatens the effectiveness of standard long-lasting insecticidal nets (LLIN). Synergist nets combine pyrethroid (Py) and piperonyl-butoxide (PBO) to enhance potency against resistance mediated by mono-oxygenase mechanisms. Our project assessed personal protection of WHO first-in-class PBO-Py treated nets (Olyset Plus) versus standard LLIN (Olyset net) against pyrethroid resistant Anopheles gambiae and An. funestus in North West Tanzania after 20 months of household use.Methods: From household survey, 39 standard Olyset net and 39 Olyset Plus houses were selected, physical integrity and hole index (HI) of nets assessed, resting mosquitoes collected from inside nets and from room walls, indoor abundance estimated using CDC light traps and species identified using PCR. Residual bio-efficacy of PBO and standard LLINs was assessed using 30 min cylinder bioassays.Results: Of 2397 Anopheles collected, 8.9% (n=213) were resting inside standard Olyset nets while none were found inside Olyset Plus PBO-Py nets of any HI category. Resting density of blood fed mosquitoes was higher on walls of sleeping rooms with Olyset net compared to Olyset Plus (0.62 vs 0.10, density ratio: 0.03, 95% CI: 0.01-0.13, p<0.001). Mosquitoes were found inside Olyset nets of all WHO HI categories but more were collected inside the more damaged (HI≥ 643) nets than in less damaged (HI 0-64) nets (DR: 6.4, 95% CI: 1.1-36.0, p=0.037). In residual bioassay, mortality of An. gambiae s.l was higher with Olyset Plus than with Olyset net for new nets (76.8% vs 27.5%) and 20 months’ nets (56.8% vs 12.8%); similar trends were observed with An. funestus. Conclusion: The PBO-Py treated net provided improved protection after 20 months of household use, as demonstrated by the higher bioassay mortality and absence of pyrethroid resistant An. gambiae s.s. and An. funestus collected from inside Olyset Plus, irrespective of hole index category, as compared to Olyset nets.


2003 ◽  
Vol 93 (6) ◽  
pp. 491-498 ◽  
Author(s):  
J.-M. Hougard ◽  
V. Corbel ◽  
R. N'Guessan ◽  
F. Darriet ◽  
F. Chandre ◽  
...  

AbstractOnly pyrethroid insecticides have so far been recommended for the treatment of mosquito nets for malaria control. Increasing resistance of malaria vectors to pyrethroids threatens to reduce the potency of this important method of vector control. Among the strategies proposed for resistance management is to use a pyrethroid and a non-pyrethroid insecticide in combination on the same mosquito net, either separately or as a mixture. Mixtures are particularly promising if there is potentiation between the two insecticides as this would make it possible to lower the dosage of each, as has been demonstrated under laboratory conditions for a mixture of bifenthrin (pyrethroid) and carbosulfan (carbamate). The effect of these types of treatment were compared in experimental huts on wild populations of Anopheles gambiae Giles and the nuisance mosquito Culex quinquefasciatus Say, both of which are multi-resistant. Four treatments were evaluated in experimental huts over six months: the recommended dosage of 50 mg m−2 bifenthrin, 300 mg m−2 carbosulfan, a mosaic of 300 mg m−2 carbosulfan on the ceiling and 50 mg m−2 bifenthrin on the sides, and a mixture of 6.25 mg m−2 carbosulfan and 25 mg m−2 bifenthrin. The mixture and mosaic treatments did not differ significantly in effectiveness from carbosulfan and bifenthrin alone against anophelines in terms of deterrency, induced exophily, blood feeding inhibition and overall mortality, but were more effective than in earlier tests with deltamethrin. These results are considered encouraging, as the combination of different classes of insecticides might be a potential tool for resistance management. The mixture might have an advantage in terms of lower cost and toxicity.


2019 ◽  
Vol 220 (3) ◽  
pp. 467-475 ◽  
Author(s):  
Jacob M Riveron ◽  
Silvie Huijben ◽  
Williams Tchapga ◽  
Magellan Tchouakui ◽  
Murielle J Wondji ◽  
...  

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.


2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Joseph M. Wagman ◽  
Kenyssony Varela ◽  
Rose Zulliger ◽  
Abuchahama Saifodine ◽  
Rodaly Muthoni ◽  
...  

Abstract Background The need to develop new products and novel approaches for malaria vector control is recognized as a global health priority. One approach to meeting this need has been the development of new products for indoor residual spraying (IRS) with novel active ingredients for public health. While initial results showing the impact of several of these next-generation IRS products have been encouraging, questions remain about how to best deploy them for maximum impact. To help address these questions, a 2-year cluster-randomized controlled trial to measure the impact of IRS with a microencapsulated formulation of pirimiphos-methyl (PM) in an area with high ownership of long-lasting insecticidal nets (LLINs) was conducted in a high-transmission district of central Mozambique with pyrethroid resistant vectors. Presented here are the results of the vector surveillance component of the trial. Methods The 2 year, two-armed trial was conducted in Mopeia District, Zambezia Province, Mozambique. In ten sentinel villages, five that received IRS with PM in October–November 2016 and again in October–November 2017 and five that received no IRS, indoor light trap collections and paired indoor-outdoor human landing collections catches (HLCs) were conducted monthly from September 2016 through October 2018. A universal coverage campaign in June 2017, just prior to the second spray round, distributed 131,540 standard alpha-cypermethrin LLINs across all study villages and increased overall net usage rates in children under 5 years old to over 90%. Results The primary malaria vector during the trial was Anopheles funestus sensu lato (s.l.), and standard World Health Organization (WHO) tube tests with this population indicated variable but increasing resistance to pyrethroids (including alpha-cypermethrin, from > 85% mortality in 2017 to 7% mortality in 2018) and uniform susceptibility to PM (100% mortality in both years). Over the entire duration of the study, IRS reduced An. funestus s.l. densities by 48% (CI95 33–59%; p < 0.001) in indoor light traps and by 74% (CI95 38–90%; p = 0.010) during indoor and outdoor HLC, though in each study year reductions in vector density were consistently greatest in those months immediately following the IRS campaigns and waned over time. Overall there was no strong preference for An. funestus to feed indoors or outdoors, and these biting behaviours did not differ significantly across study arms: observed indoor-outdoor biting ratios were 1.10 (CI95 1.00–1.21) in no-IRS villages and 0.88 (CI95 0.67–1.15) in IRS villages. The impact of IRS was consistent in reducing HLC exposures both indoors (75% reduction: CI95 47–88%; p = 0. < 0.001) and outdoors (68% reduction: CI95 22–87%; p = 0.012). While substantially fewer Anopheles gambiae s.l. were collected during the study, trends show a similar impact of IRS on this key vector group as well, with a 33% (CI95 7–53%; p = 0.019) reduction in mosquitoes collected in light traps and a non-statistically significant 39% reduction (p = 0.249) in HLC landing rates. Conclusion IRS with PM used in addition to pyrethroid-only LLINs substantially reduced human exposures to malaria vectors during both years of the cluster-randomized controlled trial in Mopeia—a high-burden district where the primary vector, An. funestus s.l., was equally likely to feed indoors or outdoors and demonstrated increasing resistance to pyrethroids. Findings suggest that IRS with PM can provide effective vector control, including in some settings where pyrethroid-only ITNs are widely used. Trial registrationclinicaltrials.gov, NCT02910934. Registered 22 September 2016, https://www.clinicaltrials.gov/ct2/show/NCT02910934.


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