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Empirical and theoretical investigation into the potential impacts of insecticide resistance on the effectiveness of insecticide-treated bed nets.

ABSTRACT: In spite of widespread insecticide resistance in vector mosquitoes throughout Africa, there is limited evidence that long-lasting insecticidal bed nets (LLINs) are failing to protect against malaria. Here, we showed that LLIN contact in the course of host-seeking resulted in higher mortality of resistant Anopheles spp. mosquitoes than predicted from standard laboratory exposures with the same net. We also found that sublethal contact with an LLIN caused a reduction in blood feeding and subsequent host-seeking success in multiple lines of resistant mosquitoes from the laboratory and the field. Using a transmission model, we showed that when these LLIN-related lethal and sublethal effects were accrued over mosquito lifetimes, they greatly reduced the impact of resistance on malaria transmission potential under conditions of high net coverage. If coverage falls, the epidemiological impact is far more pronounced. Similarly, if the intensity of resistance intensifies, the loss of malaria control increases nonlinearly. Our findings help explain why insecticide resistance has not yet led to wide-scale failure of LLINs, but reinforce the call for alternative control tools and informed resistance management strategies.

SUBMITTER: Glunt KD

PROVIDER: S-EPMC5891045 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Empirical and theoretical investigation into the potential impacts of insecticide resistance on the effectiveness of insecticide-treated bed nets.

Glunt Katey D KD Coetzee Maureen M Huijben Silvie S Koffi A Alphonsine AA Lynch Penelope A PA N'Guessan Raphael R Oumbouke Welbeck A WA Sternberg Eleanore D ED Thomas Matthew B MB

Evolutionary applications 20171204 4

In spite of widespread insecticide resistance in vector mosquitoes throughout Africa, there is limited evidence that long-lasting insecticidal bed nets (LLINs) are failing to protect against malaria. Here, we showed that LLIN contact in the course of host-seeking resulted in higher mortality of resistant <i>Anopheles spp</i>. mosquitoes than predicted from standard laboratory exposures with the same net. We also found that sublethal contact with an LLIN caused a reduction in blood feeding and su ...[more]

PMID: 29636797

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Project description:BackgroundDespite widespread use of long-lasting insecticidal nets (LLINs) and other tools, malaria caused 409,000 deaths worldwide in 2019. While indoor residual spraying (IRS) is an effective supplement, IRS is moderately expensive and logistically challenging. In endemic areas, IRS requires yearly application just before the main rainy season and potential interim reapplications. A new technology, insecticide-treated wall liner (ITWL), might overcome these challenges.MethodsWe conducted a 44-cluster two-arm randomized controlled trial in Muheza, Tanzania from 2015 to 2016 to evaluate the cost and efficacy of a non-pyrethroid ITWL to supplement LLINs, analyzing operational changes over three installation phases. The estimated efficacy (with 95% confidence intervals) of IRS as a supplement to LLINs came mainly from a published randomized trial in Muleba, Tanzania. We obtained financial costs of IRS from published reports and conducted a household survey of a similar IRS program near Muleba to determine household costs. The costs of ITWL were amortized over its 4-year expected lifetime and converted to 2019 US dollars using Tanzania's GDP deflator and market exchange rates.ResultsOperational improvements from phases 1 to 3 raised ITWL coverage from 35.1 to 67.1% of initially targeted households while reducing economic cost from $34.18 to $30.56 per person covered. However, 90 days after installing ITWL in 5666 households, the randomized trial was terminated prematurely because cone bioassay tests showed that ITWL no longer killed mosquitoes and therefore could not prevent malaria. The ITWL cost $10.11 per person per year compared to $5.69 for IRS. With an efficacy of 57% (3-81%), IRS averted 1162 (61-1651) disability-adjusted life years (DALYs) per 100,000 population yearly. Its incremental cost-effectiveness ratio (ICER) per DALY averted was $490 (45% of Tanzania's per capita gross national income).ConclusionsThese findings provide design specifications for future ITWL development and implementation. It would need to be efficacious and more effective and/or less costly than IRS, so more persons could be protected with a given budget. The durability of a previous ITWL, progress in non-pyrethroid tools, economies of scale and competition (as occurred with LLINs), strengthened community engagement, and more efficient installation and management procedures all offer promise of achieving these goals. Therefore, ITWLs merit ongoing study.First posted2015 ( NCT02533336 ).

Project description:BackgroundPyrethroid insecticide-treated bed nets (ITNs) help contribute to reducing malaria deaths in Africa, but their efficacy is threatened by insecticide resistance in some malaria mosquito vectors. We therefore assessed the evidence that resistance is attenuating the effect of ITNs on entomological outcomes.Methods and findingsWe included laboratory and field studies of African malaria vectors that measured resistance at the time of the study and used World Health Organization-recommended impregnation regimens. We reported mosquito mortality, blood feeding, induced exophily (premature exit of mosquitoes from the hut), deterrence, time to 50% or 95% knock-down, and percentage knock-down at 60 min. Publications were searched from 1 January 1980 to 31 December 2013 using MEDLINE, Cochrane Central Register of Controlled Trials, Science Citation Index Expanded, Social Sciences Citation Index, African Index Medicus, and CAB Abstracts. We stratified studies into three levels of insecticide resistance, and ITNs were compared with untreated bed nets (UTNs) using the risk difference (RD). Heterogeneity was explored visually and statistically. Included were 36 laboratory and 24 field studies, reported in 25 records. Studies tested and reported resistance inconsistently. Based on the meta-analytic results, the difference in mosquito mortality risk for ITNs compared to UTNs was lower in higher resistance categories. However, mortality risk was significantly higher for ITNs compared to UTNs regardless of resistance. For cone tests: low resistance, risk difference (RD) 0.86 (95% CI 0.72 to 1.01); moderate resistance, RD 0.71 (95% CI 0.53 to 0.88); high resistance, RD 0.56 (95% CI 0.17 to 0.95). For tunnel tests: low resistance, RD 0.74 (95% CI 0.61 to 0.87); moderate resistance, RD 0.50 (95% CI 0.40 to 0.60); high resistance, RD 0.39 (95% CI 0.24 to 0.54). For hut studies: low resistance, RD 0.56 (95% CI 0.43 to 0.68); moderate resistance, RD 0.39 (95% CI 0.16 to 0.61); high resistance, RD 0.35 (95% CI 0.27 to 0.43). However, with the exception of the moderate resistance category for tunnel tests, there was extremely high heterogeneity across studies in each resistance category (chi-squared test, p<0.00001, I² varied from 95% to 100%).ConclusionsThis meta-analysis found that ITNs are more effective than UTNs regardless of resistance. There appears to be a relationship between resistance and the RD for mosquito mortality in laboratory and field studies. However, the substantive heterogeneity in the studies' results and design may mask the true relationship between resistance and the RD, and the results need to be interpreted with caution. Our analysis suggests the potential for cumulative meta-analysis in entomological trials, but further field research in this area will require specialists in the field to work together to improve the quality of trials, and to standardise designs, assessment, and reporting of both resistance and entomological outcomes.

Dataset Information

Empirical and theoretical investigation into the potential impacts of insecticide resistance on the effectiveness of insecticide-treated bed nets.

Publications

Empirical and theoretical investigation into the potential impacts of insecticide resistance on the effectiveness of insecticide-treated bed nets.

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