scholarly journals Comparative efficacy of two pyrethroid-piperonyl butoxide nets (Olyset Plus and PermaNet 3.0) against pyrethroid resistant malaria vectors: a non-inferiority assessment

2022 ◽  
Vol 21 (1) ◽  
Author(s):  
Corine Ngufor ◽  
Josias Fagbohoun ◽  
Abel Agbevo ◽  
Hanafy Ismail ◽  
Joseph D. Challenger ◽  
...  

Abstract Background Pyrethroid-PBO nets were conditionally recommended for control of malaria transmitted by mosquitoes with oxidase-based pyrethroid-resistance based on epidemiological evidence of additional protective effect with Olyset Plus compared to a pyrethroid-only net (Olyset Net). Entomological studies can be used to assess the comparative performance of other brands of pyrethroid-PBO ITNs to Olyset Plus. Methods An experimental hut trial was performed in Cové, Benin to compare PermaNet 3.0 (deltamethrin plus PBO on roof panel only) to Olyset Plus (permethrin plus PBO on all panels) against wild pyrethroid-resistant Anopheles gambiae sensu lato (s.l.) following World Health Organization (WHO) guidelines. Both nets were tested unwashed and after 20 standardized washes compared to Olyset Net. Laboratory bioassays were also performed to help explain findings in the experimental huts. Results With unwashed nets, mosquito mortality was higher in huts with PermaNet 3.0 compared to Olyset Plus (41% vs. 28%, P < 0.001). After 20 washes, mortality declined significantly with PermaNet 3.0 (41% unwashed vs. 17% after washing P < 0.001), but not with Olyset Plus (28% unwashed vs. 24% after washing P = 0.433); Olyset Plus induced significantly higher mortality than PermaNet 3.0 and Olyset Net after 20 washes. PermaNet 3.0 showed a higher wash retention of PBO compared to Olyset Plus. A non-inferiority analysis performed with data from unwashed and washed nets together using a margin recommended by the WHO, showed that PermaNet 3.0 was non-inferior to Olyset Plus in terms of mosquito mortality (25% with Olyset Plus vs. 27% with PermaNet 3.0, OR = 1.528, 95%CI = 1.02–2.29) but not in reducing mosquito feeding (25% with Olyset Plus vs. 30% with PermaNet 3.0, OR = 1.192, 95%CI = 0.77–1.84). Both pyrethroid-PBO nets were superior to Olyset Net. Conclusion Olyset Plus outperformed PermaNet 3.0 in terms of its ability to cause greater margins of improved mosquito mortality compared to a standard pyrethroid net, after multiple standardized washes. However, using a margin of non-inferiority defined by the WHO, PermaNet 3.0 was non-inferior to Olyset Plus in inducing mosquito mortality. Considering the low levels of mortality observed and increasing pyrethroid-resistance in West Africa, it is unclear whether either of these nets would demonstrate the same epidemiological impact observed in community trials in East Africa.

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Jackline L. 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 the World Health Organization first-in-class PBO-Py LLIN (Olyset Plus) versus the standard LLIN (Olyset net) against pyrethroid-resistant Anopheles gambiae sensu lato (s.l.) and An. funestus in North-West Tanzania after 20 months of household use. Methods From a household survey, 39 standard Olyset net and 39 Olyset Plus houses were selected. The physical integrity and hole index (HI) of the nets were assessed, and resting mosquitoes were collected from inside nets and from room walls. The indoor abundance was estimated using CDC light traps and species identified using PCR. The bioefficacy of PBO and standard LLINs against wild Anopheles was assessed using 30-minute cylinder bioassays. Results Of 2397 Anopheles collected, 8.9% (n = 213) were resting inside standard Olyset nets, while none were found inside Olyset Plus nets (PBO-Py LLINs) of any HI category. Resting density of blood-fed mosquitoes was higher on walls of sleeping rooms with Olyset nets compared to Olyset Plus (0.62 vs 0.10, density ratio [DR]: 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 nets (HI ≥ 643) than in less damaged (HI 0–64) nets (DR: 6.4, 95% CI 1.1–36.0, p = 0.037). In bioassay, mortality of An. gambiae s.l. was higher with Olyset Plus than with Olyset nets for new nets (76.8% vs 27.5%) and nets used for 20 months (56.8% vs 12.8%); similar trends were observed with An. funestus. Conclusion The PBO-Py LLINs provided improved protection after 20 months of household use, as demonstrated by the higher bioassay mortality and absence of pyrethroid-resistant An. gambiae sensu stricto (s.s.) and An. funestus collected from inside Olyset Plus nets, irrespective of HI category, as compared to Olyset nets.


2021 ◽  
Author(s):  
Johnson Matowo ◽  
David Weetman ◽  
Patricia Pignatell ◽  
Alexandra Wright ◽  
Jacques Charlwood ◽  
...  

Long lasting insecticidal nets (LLINs) are a proven tool to reduce malaria transmission, but in Africa efficacy is being reduced by pyrethroid resistance in the major vectors. A cluster randomized trial in Muleba district, Tanzania demonstrated that permethrin LLINs co-treated with piperonyl butoxide (PBO), a synergist that can block pyrethroid-metabolizing enzymes in the mosquito, had much greater efficacy than pyrethroid-only nets. Insecticide resistance profiles and underlying mechanisms were investigated in Anopheles gambiae and An. funestus from Muleba during the trial. Diagnostic dose bioassays using permethrin, together with intensity assays, suggest pyrethroid resistance that is both strong and very common, but not extreme. Transcriptomic analysis found multiple P450 genes over expressed including CYP6M2, CYP6Z3, CYP6P3, CYP6P4, CYP6AA1 and CYP9K1 in An. gambiae and CYP6N1, CYP6M7, CYP6M1 and CYP6Z3 in An. funestus. Indeed, very similar suites of P450 enzymes commonly associated with resistant populations elsewhere in Africa were detected as over expressed suggesting a convergence of mechanisms across Sub-Saharan African malaria vectors. The findings give insight into factors that may correlate with pyrethroid PBO LLIN success, broadly supporting model predictions, but revision to guidelines previously issued by the World Health Organization is warranted.


Author(s):  
Solomon Yared ◽  
Araya Gebressielasie ◽  
Lambodhar Damodaran ◽  
Victoria Bonnell ◽  
Karen Lopez ◽  
...  

Abstract Background: The movement of malaria vectors into new areas is a growing concern in the efforts to control malaria. The recent report of Anopheles stephensi in eastern Ethiopia has raised the necessity to understand the insecticide resistance status of the vector in the region to better inform vector-based interventions. The aim of this study was to evaluate insecticide resistance in An. stephensi in eastern Ethiopia using two approaches: 1) World Health Organization (WHO) bioassay tests in An. stephensi and 2) genetic analysis of insecticide resistance genes in An. stephensi in eastern Ethiopia. Methods: Mosquito larvae and pupae were collected from Kebridehar. Insecticide susceptibility of An. stephensi was tested with malathion 5%, bendiocarb 0.1%, propoxur 0.1%, deltamethrin 0.05%, permethrin 0.75%, Pirimiphos-methyl 0.25% and DDT 4%, according to WHO standard protocols. Results: All An. stephensi samples were resistant to carbamates, with mortality rates 23% and 21% for bendiocarb and propoxur, respectively. Adult An. stephensi was also resistant to pyrethroid insecticides with mortality rates 67% for deltamethrin and 53% for permethrin. Resistance to DDT and malathion was detected in An. stephensi with mortality rates of 32% as well as An. stephensi was resistance to pirimiphos-methyl with mortality rates 14%. Analysis of the voltage gate sodium channel gene (vgsc) revealed the absence of kdr L1014 mutations. Conclusion: Overall, these findings support that An. stephensi is resistant to several classes of insecticides, most notably pyrethroids. However, the absence of the kdr L1014 gene may suggest non-target site resistance mechanisms. Continuous insecticide resistance monitoring should be carried out in the region to confirm the documented resistance and exploring mechanisms conferring resistance in An. stephensi in Ethiopia.


2020 ◽  
Vol 117 (36) ◽  
pp. 22042-22050 ◽  
Author(s):  
Catherine L. Moyes ◽  
Duncan K. Athinya ◽  
Tara Seethaler ◽  
Katherine E. Battle ◽  
Marianne Sinka ◽  
...  

Malaria vector control may be compromised by resistance to insecticides in vector populations. Actions to mitigate against resistance rely on surveillance using standard susceptibility tests, but there are large gaps in the monitoring data across Africa. Using a published geostatistical ensemble model, we have generated maps that bridge these gaps and consider the likelihood that resistance exceeds recommended thresholds. Our results show that this model provides more accurate next-year predictions than two simpler approaches. We have used the model to generate district-level maps for the probability that pyrethroid resistance inAnopheles gambiaes.l. exceeds the World Health Organization thresholds for susceptibility and confirmed resistance. In addition, we have mapped the three criteria for the deployment of piperonyl butoxide-treated nets that mitigate against the effects of metabolic resistance to pyrethroids. This includes a critical review of the evidence for presence of cytochrome P450-mediated metabolic resistance mechanisms across Africa. The maps for pyrethroid resistance are available on the IR Mapper website, where they can be viewed alongside the latest survey data.


2020 ◽  
Vol 16 (2) ◽  
Author(s):  
Rosilawati R ◽  
Lee HL ◽  
Nazni WA ◽  
Nurulhusna AH ◽  
Roziah A ◽  
...  

Vector control is still the principal method to control dengue and chemical insecticides, especially the pyrethroids such as permethrin are the forerunners of mosquito control agent. Intensive and extensive use of pyrethroids often result in resistance, thereby hampering control efforts. The present study was conducted to evaluate the susceptible status of Aedes aegypti, the primary vector of dengue against permethrin. A nationwide mosquito sampling via ovitrapping was conducted in 12 dengue hotspots across 5 states in Peninsular Malaysia. Field collected Aedes eggs were hatched and reared until L3 larval and further identified it species. Adult F0 Aedes aegypti were reared until F1 progeny and the female were used in adult assay, performed according to World Health Organization (WHO) protocol as to determine the resistance level. The laboratory strain maintained for more than 1000 generations that were susceptible to permethrin served as the control strain. Evaluation of resistance ratio was assessed by comparing the knockdown rate with laboratory susceptible strain. In this present study, 70% ofAe. aegypti population from dengue hotspots was highly resistance to permethrin. The study clearly demonstrated that widespread of permethrin resistant Ae. aegypti in Malaysian mosquito’s population, indicating the need of implementing an efficient pyrethroid resistance management.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Yong Wei ◽  
Xueli Zheng ◽  
Song He ◽  
Xuli Xin ◽  
Jiachun Zhang ◽  
...  

Abstract Background Aedes (Stegomyia) albopictus (Skuse, 1894) is the main vector of dengue virus in China. The resistance to insecticides is a huge obstacle for the control of this species, and determining its resistance status and mechanisms in China is essential for the implementation of vector management strategies. Methods We have investigated the larval and adult resistance status of Ae. albopictus to deltamethrin in eight field populations in China. Mutations at the voltage-gated sodium channel gene, related to the knockdown resistance (kdr) effect, were detected by sequencing of PCR products. The eight field populations were examined for pyrethroid resistance using the World Health Organization standard bioassays, and the association between the mutations and phenotypic resistance was tested. Results The eight field populations of larvae of Ae. albopictus in China exhibited high resistance to deltamethrin; the RR50 values ranged from 12 (ZJ) to 44 (GZ). Adult bioassay revealed that Ae. albopictus populations were resistant to deltamethrin (mortality rate < 90%), except ZJ population (probably resistant, mortality rate = 93.5%). Long knockdown time in the field populations was consistent with low mortality rates in adult bioassay. F1534S mutation showed increased protection against deltamethrin in all populations except BJ and SJZ populations, whereas I1532T mutation showed increased protection against deltamethrin in only BJ population. Conclusion There were different degrees of resistance to deltamethrin in field Ae. albopictus populations in China. The longest knockdown time and lowest mortality rate observed in Ae. albopictus population in Guangzhou indicate the severity of high resistance to deltamethrin. The patchy distribution of deltamethrin resistance and kdr mutations in Ae. albopictus mosquitoes suggests the necessity for resistance management and developing counter measures to mitigate the spread of resistance. Graphical Abstract


2020 ◽  
Vol 31 (1) ◽  
pp. 2-4
Author(s):  
Mark Rowland

Much of the dramatic decline in malaria in sub-Saharan Africa since 2000 is due to the massive investment in long-lasting insecticide treated nets (LLIN). According to the latest figures from the World Health Organization (WHO), over half of Africa's population now has access to LLIN, increasing from 33% in 2010 to 57% in 2019 (WHO 2019). In 2018 alone, 197 million LLINs were delivered to Africa by manufacturers. Despite this, LLIN coverage has improved only marginally since 2015. The malaria burden worldwide has fallen only slightly from an estimated 231 million cases of malaria in 2017 to 228 million in 2018, and is at a standstill in Africa. WHO policy is to assess candidate 2nd-in-class products for entomological efficacy only. Due to the significant variation in the specifications of the candidates, to generate the required assurance of comparative performance to 1st in class, WHO has designed a non-inferiority trial design to demonstrate whether each candidate 2nd-in-class test product is no worse in experimental hut trials.


2021 ◽  
Vol 53 (03) ◽  
pp. 33-50
Author(s):  
RK Singh ◽  

Background and Objective: The current study was undertaken to determine insecticide susceptibility of malaria vectors in various villages of high malaria endemic PHCs of Gadchiroli district of Maharashtra. Methods: Adult malaria vectors were collected from the human dwellings/ cattle sheds of 156 villages of 18 malaria endemic PHCs. Susceptibility tests were carried out for different insecticides against An. culicifacies and An. fluviatilis mosquitoes as per the World Health Organization (WHO) procedure. Cone bioassays were also done to assess the quality and efficacy of indoor residual spray. Results:An. fluviatilis could be collected from 23 villages only and all the populations were fully susceptible to synthetic pyrethroid (deltamethrin) while being tolerant to organophosphorous (malathion). Susceptibility of An. culicifacies from 156 villages indicated that only 3 populations of An. culicifacies were resistant to deltamethrin while 57 populations were fully susceptible and other 96 populations were tolerant to deltamethrin. Resistance was recorded in 25 populations of An. culicifacies against malathion and 30 populations were tolerant to malathion insecticide. Remaining populations of An. fluviatilis and An. culicifacies were highly resistant to organochlorine. Results of cone bioassay revealed the mortality ranged from 32.5-51.1% on cemented and 27.5-43.3% on the mud wall sprayed with lambda cyhalothrin. Conclusion: The current study indicates that resistance has developed to synthetic pyrethroids in the major malaria vector An. culicifacies. Therefore, there is an urgent need for the evaluation of new insecticide molecules for better control of malaria vectors.


2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Polius G. Pinda ◽  
Claudia Eichenberger ◽  
Halfan S. Ngowo ◽  
Dickson S. Msaky ◽  
Said Abbasi ◽  
...  

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, Anopheles arabiensis. This study compared the insecticide resistance phenotypes between the two malaria vectors in an area where pyrethroid-LLINs are widely used. Methods The study used the World Health Organization (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 three villages across two districts in south-eastern Tanzania and included four insecticide classes. Findings At baseline doses (1×), both species were resistant to the two candidate pyrethroids (permethrin and deltamethrin), but susceptible to the organophosphate (pirimiphos-methyl). Anopheles funestus, but not An. arabiensis was also resistant to the carbamate (bendiocarb). Both species were resistant to DDT in all villages except in one village where An. arabiensis was susceptible. Anopheles funestus showed strong resistance to pyrethroids, surviving the 5× and 10× doses, while An. arabiensis reverted to susceptibility at the 5× dose. Pre-exposure to the synergist, piperonyl butoxide (PBO), enhanced the potency of the pyrethroids against both species and resulted in full susceptibility of An. arabiensis (> 98% mortality). However, for An. funestus from two villages, permethrin-associated mortalities after pre-exposure to PBO only exceeded 90% but not 98%. Conclusions In south-eastern Tanzania, where An. funestus dominates malaria transmission, the species also has much stronger resistance to pyrethroids than its counterpart, An. arabiensis, and can survive more classes of insecticides. The pyrethroid resistance in both species appears to be mostly metabolic and may be partially 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 intervention choices for such settings. In short and medium-term, these may include PBO-based LLINs or improved IRS with compounds to which the vectors are still susceptible.


1960 ◽  
Vol 14 (4) ◽  
pp. 673-674

The thirteenth session of the Assembly of the World Health Organization (WHO) was held in Geneva, from May 3 to 20, 1960. In his inaugural address, the President of the Assembly, Dr. H. B. Turbott, spoke of the ground gained by the idea of world health since the early days of WHO, of the new and growing challenges with which the Assembly would have to deal in discussing the 1961 program—such as the control of pestilential diseases, protection against radiation hazards, the evaluation of live poliomyelitis vaccine, extended nutrition programs, and the world shortage of competent health personnel—and of the problems of particular concern to the more developed countries, such as heart, cancer, and mental illness. Dr. Turbott also described the integration of preventive and curative services as one field to which WHO should devote more attention. The Director-General, presenting his report on the work of WHO during 1959, stressed the urgency of the world-wide malaria eradication campaign, pointing out that malaria was the most important single obstacle to the development of the economic and social potentials of the underdeveloped areas of the world. The year 1959, he continued, had witnessed intensified research activities by the Organization, an increase in experts trained under WHO's fellowship program, and improved coordination between inter-country and inter-regional projects, but the problem of the resistance of malaria vectors to insecticides remained an obstacle to malaria eradication, and the question of funds for international technical assistance was still unsolved. In concluding, the Director-General predicted diat, at die present rate of progress, malaria could be eradicated, at least from Europe, the Americas, North Africa, and large parts of Asia, within perhaps the next ten years.


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