scholarly journals Transfluthrin eave-positioned targeted insecticide (EPTI) reduces human landing rate (HLR) of pyrethroid resistant and susceptible malaria vectors in a semi-field simulated peridomestic space

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Mgeni M. Tambwe ◽  
Sarah Moore ◽  
Lorenz Hofer ◽  
Ummi A. Kibondo ◽  
Adam Saddler

Abstract Background Volatile pyrethroids (VPs) are proven to reduce human–vector contact for mosquito vectors. With increasing resistance to pyrethroids in mosquitoes, the efficacy of VPs, such as transfluthrin, may be compromised. Therefore, experiments were conducted to determine if the efficacy of transfluthrin eave-positioned targeted insecticide (EPTI) depends on the resistance status of malaria vectors. Methods Ribbons treated with 5.25 g transfluthrin or untreated controls were used around the eaves of an experimental hut as EPTI inside a semi-field system. Mosquito strains with different levels of pyrethroid resistance were released simultaneously, recaptured by means of human landing catches (HLCs) and monitored for 24-h mortality. Technical-grade (TG) transfluthrin was used, followed by emulsifiable concentrate (EC) transfluthrin and additional mosquito strains. Generalized linear mixed models with binomial distribution were used to determine the impact of transfluthrin and mosquito strain on mosquito landing rates and 24-h mortality. Results EPTI treated with 5.25 g of either TG or EC transfluthrin significantly reduced HLR of all susceptible and resistant Anopheles mosquitoes (Odds Ratio (OR) ranging from 0.14 (95% Confidence Interval (CI) [0.11–0.17], P < 0.001) to 0.57, (CI [0.42–0.78] P < 0.001). Both TG and EC EPTI had less impact on landing for the resistant Anopheles arabiensis (Mbita strain) compared to the susceptible Anopheles gambiae (Ifakara strain) (OR 1.50 [95% CI 1.18–1.91] P < 0.001) and (OR 1.67 [95% CI 1.29–2.17] P < 0.001), respectively. The EC EPTI also had less impact on the resistant An. arabiensis (Kingani strain) (OR 2.29 [95% CI 1.78–2.94] P < 0.001) compared to the control however the TG EPTI was equally effective against the resistant Kingani strain and susceptible Ifakara strain (OR 1.03 [95% CI 0.82–1.32] P = 0.75). Finally the EC EPTI was equally effective against the susceptible An. gambiae (Kisumu strain) and the resistant An. gambiae (Kisumu-kdr strain) (OR 0.98 [95% CI 0.74–1.30] P = 0.90). Conclusions Transfluthrin-treated EPTI could be useful in areas with pyrethroid-resistant mosquitoes, but it remains unclear whether stronger resistance to pyrethroids will undermine the efficacy of transfluthrin. At this dosage, transfluthrin EPTI cannot be used to kill exposed mosquitoes.

2021 ◽  
Author(s):  
Mgeni Tambwe ◽  
Sarah J Moore ◽  
Lorenz Hofer ◽  
Ummi Abdul Kibondo ◽  
Adam Saddler

Abstract Introduction: Volatile pyrethroids (VPs) are proven to reduce human–vector contact for mosquito vectors. With increasing resistance to pyrethroids in mosquitoes, the efficacy of VPs such as transfluthrin may be compromised. Therefore, experiments were conducted to determine if the efficacy of transfluthrin eave-positioned targeted insecticide (EPTI) depends on the resistance status of malaria vectors.Methods: Ribbons treated with 5.25 g transfluthrin or untreated controls were used around the eaves of an experimental hut as EPTI inside a semi-field system. Mosquito strains with different levels of pyrethroid resistance were released simultaneously, recaptured by means of human landing catches (HLCs) conducted 2.5 m outside the hut, and monitored for 24-hour mortality. Technical-grade (TG) transfluthrin was used, followed by emulsifiable concentrate (EC) transfluthrin and additional mosquito strains. Generalised linear mixed models with binomial distribution were used to determine the impact of transfluthrin and mosquito strain on mosquito landing rates and 24-hour mortality. Results: A significant interaction between strain and treatment indicated that the effect of the transfluthrin EPTI varied between three strains under investigation (P < 0.001). Whether TG or EC, EPTI significantly reduced the odds of landing of pyrethroid-susceptible mosquitoes Anopheles gambiae (Ifakara) and An. gambiae (Kisumu) and of pyrethroid-resistant mosquitoes An. arabiensis (Mbita), An. gambiae Kisumu knockdown-resistant (Kisumu-kdr) and An. arabiensis (Kingani), with PE > 40% for all strains (P < 0.001). In the control, An. gambiae mosquitoes were more likely to land than An. arabiensis (P < 0.05). Conclusions: This study confirms that the efficacy of EPTI was not dependent on mosquito pyrethroid resistance status. However, it remains unclear whether resistance to pyrethroids undermines the efficacy of transfluthrin for bite prevention. It is important to consider mosquito anthropophagy, strain, years of colonisation and fitness when assessing vector control interventions. Overall, these findings suggest that transfluthrin-treated EPTI could be useful in areas with highly pyrethroid-resistant mosquitoes. At this dosage, transfluthrin EPTI cannot be used to kill exposed mosquitoes.


2017 ◽  
Vol 114 (52) ◽  
pp. E11267-E11275 ◽  
Author(s):  
Hmooda Toto Kafy ◽  
Bashir Adam Ismail ◽  
Abraham Peter Mnzava ◽  
Jonathan Lines ◽  
Mogahid Shiekh Eldin Abdin ◽  
...  

Insecticide-based interventions have contributed to ∼78% of the reduction in the malaria burden in sub-Saharan Africa since 2000. Insecticide resistance in malaria vectors could presage a catastrophic rebound in disease incidence and mortality. A major impediment to the implementation of insecticide resistance management strategies is that evidence of the impact of resistance on malaria disease burden is limited. A cluster randomized trial was conducted in Sudan with pyrethroid-resistant and carbamate-susceptible malaria vectors. Clusters were randomly allocated to receive either long-lasting insecticidal nets (LLINs) alone or LLINs in combination with indoor residual spraying (IRS) with a pyrethroid (deltamethrin) insecticide in the first year and a carbamate (bendiocarb) insecticide in the two subsequent years. Malaria incidence was monitored for 3 y through active case detection in cohorts of children aged 1 to <10 y. When deltamethrin was used for IRS, incidence rates in the LLIN + IRS arm and the LLIN-only arm were similar, with the IRS providing no additional protection [incidence rate ratio (IRR) = 1.0 (95% confidence interval [CI]: 0.36–3.0; P = 0.96)]. When bendiocarb was used for IRS, there was some evidence of additional protection [interaction IRR = 0.55 (95% CI: 0.40–0.76; P < 0.001)]. In conclusion, pyrethroid resistance may have had an impact on pyrethroid-based IRS. The study was not designed to assess whether resistance had an impact on LLINs. These data alone should not be used as the basis for any policy change in vector control interventions.


2019 ◽  
Vol 4 ◽  
pp. 11
Author(s):  
Sunisa Sawasdichai ◽  
Victor Chaumeau ◽  
Tee Dah ◽  
Thithiworada Kulabkeeree ◽  
Ladda Kajeechiwa ◽  
...  

Background: Natural Wolbachia infections in malaria mosquitoes were recently reported in Africa, and negatively correlated with the development of Plasmodium falciparum in the vectors. The occurrence and effects of Wolbachia infections outside Africa have not been described and may have been underestimated. Methods: Mosquitoes were collected by human-landing catch during May and June 2017 in ten villages in Kayin state, Myanmar. Closely related species of malaria vectors were identified with molecular assays. Wolbachia infection rates were assessed with quantitative real-time PCR. Results: Low titer of Wolbachia DNA was detected in 13/370 samples in six malaria vector species. Phylogenetic analysis based on 16S rRNA sequences revealed a high diversity of Wolbachia strains and identified lineages different from those described in the African malaria mosquitoes. Conclusion: These low-density genetically diverse natural Wolbachia infections question the ecology and biology of Wolbachia-Anopheles interactions in Southeast Asia. Their effects on malaria transmission and mosquito vectors are yet to be determined.


2020 ◽  
Author(s):  
Melkam Abiye Zeru ◽  
Simon Shibru ◽  
Fekadu Massebo

Abstract Background The early and outdoor biting behaviors of malaria vectors are among the key challenges in malaria control. Hence, understanding the host-seeking behavior and the peak biting time of malaria vectors is important in malaria vector control programs. This study assessed the host-seeking behavior and hourly biting activity of malaria mosquitoes in Chano Mille village in Arba Minch district, southwest Ethiopia. Methods The first trial was done by keeping cattle together with human that collects the entered mosquitoes in tent, while the other was done by keeping cattle outside a 1 m distance from human collector inside a tent. In both trials, mosquito collation was done inside tents baited by cattle and human using human landing catches (HLC) techniques. Four human volunteers’ were recruited and trained to collect mosquitoes in the four tents from 18:00-24:00 for three months. Two tents were selected randomly for human alone and two for cattle baited collections in the first night and then rotated to minimize the variation due to location of tents and collectors skill. The tent trial was done close to the shore of the Lake Abaya to minimize the interference of other animals on mosquito movement. The peak biting hour of malaria vectors was assessed within a Chano village from 18:00-6:00. Mosquito collation was done both indoor and outdoor by HLC. Morphological speciation of Anopheles mosquitoes was done. The sporozoite infectivity status of Anopheles pharoensis was examined using enzyme-linked immuno-sorbent assay technique. The data was analyzed using a Generalized Estimating Equations with a negative binomial distribution. Results An. pharoensis, An. gambiae complex and An. tenebrosus were the three species documented during the trial. Keeping cattle together with human collector inside the tent attracted 42% ( P < 0.001) more An. pharoensis compared to human alone tent. Also, keeping cattle outside near to a tent with human at 1 m distance, attracted the entering An. pharoensis into the tent inside with human by 46% ( P = 0.002) than human in a tent with no cattle outside the same tent. The impact was not significant for An. gambiae complex and An. tenebrosus. Anopheles pharoensis and An. gambiae complex showed early night biting activity with peak biting from 19.00-20:00 which was significant for both An. gambiae complex ( P < 0.001) and An. pharoensis ( P = 0.015). Anopheles gambiae complex was mainly biting humans outdoor in the village. Conclusions Finally, keeping cattle within and close to human dwellings could increase malaria vectors bite exposure particularly to the zoophilic malaria vector An. pharoensis and, hence deployment of cattle far from human residence could be recommended to reduce the human exposure. The outdoor and early hours biting behavior of the An. gambiae complex could be a threat for success of current indoor based interventions and hence, tools could be designed to reduce this threat.


2020 ◽  
Author(s):  
Catherine L. Moyes ◽  
Rosemary S. Lees ◽  
Cristina Yunta ◽  
Kyle J. Walker ◽  
Kay Hemmings ◽  
...  

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.


2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Angela Hughes ◽  
Natalie Lissenden ◽  
Mafalda Viana ◽  
Kobié Hyacinthe Toé ◽  
Hilary Ranson

Abstract Background The efficacy of long-lasting insecticidal nets (LLINs) in preventing malaria in Africa is threatened by insecticide resistance. Bioassays assessing 24-hour mortality post-LLIN exposure have established that resistance to the concentration of pyrethroids used in LLINs is widespread. However, although mosquitoes may no longer be rapidly killed by LLIN exposure, a delayed mortality effect has been shown to reduce the transmission potential of mosquitoes exposed to nets. This has been postulated to partially explain the continued efficacy of LLINs against pyrethroid-resistant populations. Burkina Faso is one of a number of countries with very high malaria burdens and pyrethroid-resistant vectors, where progress in controlling this disease has stagnated. We measured the impact of LLIN exposure on mosquito longevity in an area of the country with intense pyrethroid resistance to establish whether pyrethroid exposure was still shortening mosquito lifespan in this setting. Methods We quantified the immediate and delayed mortality effects of LLIN exposure using standard laboratory WHO cone tests, tube bioassays and experimental hut trials on Anopheles gambiae populations originating from the Cascades region of Burkina Faso using survival analysis and a Bayesian state-space model. Results Following single and multiple exposures to a PermaNet 2.0 LLIN only one of the four mosquito populations tested showed evidence of delayed mortality. No delayed mortality was seen in experimental hut studies using LLINs. A delayed mortality effect was only observed in WHO tube bioassays when deltamethrin concentration was increased above the standard diagnostic dose. Conclusions As mosquito pyrethroid-resistance increases in intensity, delayed effects from LLIN exposure are substantially reduced or absent. Given the rapid increase in resistance occurring in malaria vectors across Africa it is important to determine whether the failure of LLINs to shorten mosquito lifespan is now a widespread phenomenon as this will have important implications for the future of this pivotal malaria control tool.


2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Leon M. J. Mugenzi ◽  
Benjamin D. Menze ◽  
Magellan Tchouakui ◽  
Murielle J. Wondji ◽  
Helen Irving ◽  
...  

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.


2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Joseph Wagman ◽  
Idrissa Cissé ◽  
Diakalkia Kone ◽  
Seydou Fomba ◽  
Erin Eckert ◽  
...  

Abstract Background The National Malaria Control Programme (NMCP) of Mali has had recent success decreasing malaria transmission using 3rd generation indoor residual spraying (IRS) products in areas with pyrethroid resistance, primarily in Ségou and Koulikoro Regions. In 2015, national survey data showed that Mopti Region had the highest under 5-year-old (u5) malaria prevalence at 54%—nearly twice the national average—despite having high access to long-lasting insecticidal nets (LLINs) and seasonal malaria chemoprevention (SMC). Accordingly, in 2016 the NMCP and other stakeholders shifted IRS activities from Ségou to Mopti. Here, the results of a series of observational analyses utilizing routine malaria indicators to evaluate the impact of this switch are presented. Methods A set of retrospective, eco-observational time-series analyses were performed using monthly incidence rates of rapid diagnostic test (RDT)-confirmed malaria cases reported in the District Health Information System 2 (DHIS2) from January 2016 until February 2018. Comparisons of case incidence rates were made between health facility catchments from the same region that differed in IRS status (IRS vs. no-IRS) to describe the general impact of the 2016 and 2017 IRS campaigns, and a difference-in-differences approach comparing changes in incidence from year-to-year was used to describe the effect of suspending IRS operations in Ségou and introducing IRS operations in Mopti in 2017. Results Compared to communities with no IRS, cumulative case incidence rates in IRS communities were reduced 16% in Ségou Region during the 6 months following the 2016 campaign and 31% in Mopti Region during the 6 months following the 2017 campaign, likely averting a total of more than 22,000 cases of malaria that otherwise would have been expected during peak transmission months. Across all comparator health facilities (HFs) where there was no IRS in either year, peak malaria case incidence rates fell by an average of 22% (CI95 18–30%) from 2016 to 2017. At HFs in communities of Mopti where IRS was introduced in 2017, peak incidence fell by an average of 42% (CI95 31–63%) between these years, a significantly greater decrease (p = 0.040) almost double what was seen in the comparator HFCAs. The opposite effect was observed in Ségou Region, where peak incidence at those HFs where IRS was withdrawn after the 2016 campaign increased by an average of 106% (CI95 63–150%) from year to year, also a significant difference-in-differences compared to the comparator no-IRS HFs (p < 0.0001). Conclusion Annual IRS campaigns continue to make dramatic contributions to the seasonal reduction of malaria transmission in communities across central Mali, where IRS campaigns were timed in advance of peak seasonal transmission and utilized a micro-encapsulated product with an active ingredient that was of a different class than the one found on the LLINs used throughout the region and to which local malaria vectors were shown to be susceptible. Strategies to help mitigate the resurgence of malaria cases that can be expected should be prioritized whenever the suspension of IRS activities in a particular region is considered.


2021 ◽  
Author(s):  
Narenrit Wamaket ◽  
Oranicha Khamprapa ◽  
Sittinont Chainarin ◽  
Panisa Thamsawet ◽  
Ubolrat Ninsaeng ◽  
...  

Abstract Background: Ivermectin mass drug administration (MDA) could accelerate malaria elimination in the Greater Mekong Subregion. This study was performed to characterize the bionomics of Anopheles in Surat Thani province, Thailand.Methods: Mosquitoes were collected via human landing collections, February - October of 2019. Anopheles were morphologically identified to species. Primary Anopheles malaria vectors were dissected to assess parity status and a subset evaluated for molecular identification and Plasmodium detection.Results: A total of 17,348 mosquitoes were collected. Of 5,777 Anopheles mosquitoes, 15 species were identified morphologically. The most abundant Anopheles were Anopheles minimus s.l. (87.87%, n = 5,035), Anopheles dirus s.l. (7.05%, n = 407), and Anopheles barbirostris s.l. (2.86%, n = 165). Molecular identification confirmed that of An. minimus s.l., 99.80% were An. minimus s.s. (n=484) and 0.2% An. aconitus (n = 1), of An. dirus s.l., 100% were An. baimaii (n = 348), and of An. maculatus s.l., 93.62% were An. maculatus s.s. (n = 44) and 6.38% An. sawadwongporni (n = 3). No Anopheles were Plasmodium positive (n = 879). An average of 11.46 Anopheles were captured per collector per night. There were differences between species in hour of collection (Kruskal-Wallis = 80.89, P < 0.0001, n = 5,666), with more An. barbirostris s.l. and An. maculatus s.l. caught earlier compared to An. minimus s.l. (P = 0.0001, P < 0.0001, respectively) and An. dirus s.l. (P = 0.0082, P < 0.001, respectively). The proportion of parous An. minimus s.l. captured by hour increased throughout the night (Wald Chi-square = 17.31, P=0.000, odds ratio = 1.0535 [1.0279 – 1.0796] 95% CI (n = 3,400). Overall, An. minimus s.l. parity was 67.68% (2,375/3,509) with an intra cluster correlation of 0.0378. A power calculation determined that an An. minimus s.l. parity reduction treatment effect size = 34%, with four clusters per treatment arm, a minimum of 300 mosquitoes dissected per cluster at an α= 0.05 will provide 82% power to detect a significant difference following ivermectin MDA. Conclusions: The study area in Surat Thani province is an ideal location to evaluate the impact of ivermectin MDA on An. minimus parity.


Author(s):  
Sulaiman S. Ibrahim ◽  
Muhammad M. Mukhtar ◽  
Abdullahi Muhammad ◽  
Charles S. Wondji

Climate change is impacting the spread/intensity of vector-borne diseases, including malaria, and accelerating evolutionary/adaptive changes in vector species. These changes including chromoso-mal inversions and overexpression and/or changes in allele frequencies of thermotoler-ance-associated genes, may facilitate insecticide resistance through pleiotropy. This study investi-gated the impact of thermotolerance on pyrethroid resistance in four populations of malaria vector An. gambiae, from savanna/sub-Sahel of northern Nigeria. Anopheles coluzzii and An. gambiae were the only malaria vectors found, sympatric in all the sites, with the former species predominant. High thermotolerance was observed, with no mortality at 38&deg;C, and LT50 of ~44&deg;C. Significantly high permethrin resistance was observed (mortality &lt;50%) in heat-hardened (44&deg;C) larvae from two sites, BUK and Pantami, compared with control, and heat-hardened adult females from Auyo (mortality = 3.00%&plusmn;1.20, &chi;2 = 5.83, p&lt;0.01) compared with control (12.00%&plusmn;4.65). The 2La chromosomal inver-sion was detected at ~50% in larvae and 58% in adult females. Significant association was observed (OR = 7.2, p&lt;0.03) between permethrin resistance and 2La/+a rearrangement compared with 2L+a/+a, in BUK larvae. For all sites permethrin resistance correlated with 2La/a homozygosity in adult fe-males [OR = 5.02, p=0.01). qRT-PCR identified 6 genes commonly induced/overexpressed, including heat shock protein 70 (AGAP004581) which was 2468x and 5x overexpressed in heat-hardened and permethrin-resistant females, respectively, trehalose-6-phosphate synthase (AGAP008227), and ionotropic glutamate receptor genes, IR25a (AGAP010272) and IR21a (AGAP008511). This study highlights challenges associated with insecticide-based malaria vector control, and the epidemiological significance of taking climate variables into account for design/choice of control measures.


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