Malaria vector control: Can repurposed agricultural insecticides offer solutions to resistance issues?

The ongoing Zika virus outbreak, which briefly threatened to put a stop to the 2016 Olympic Games in Brazil, has again focused attention on the threat of vector‐borne diseases. One efficient strategy to battle such diseases, now underway in Brazil to fight the Zika virus, is to kill the insects that carry the pathogen. Vector control has been practised with varying effectiveness for at least half a century, especially for malaria; the Brazil outbreak again highlights the need for integrating existing methods including the use of insecticides, vaccines, drugs and low technology such as sanitation to keep insect vectors at bay. In addition, new approaches are being developed based on sophisticated methods such as genome editing of the insect vector and deliberate infection of mosquitoes with the Wolbachia bacteria. However, attempts to scale up these new methods from field trials to deployment have been slowed down or halted by environmental concerns or public resistance against genetically modified organisms. The Zika outbreak in South America has stimulated cross‐border collaboration of public health authorities and increased pressure to use new integrative approaches that are essential for combatting vector‐borne diseases. The irony is that the Zika virus itself has a minimal global impact compared with other insect‐borne pathogens, but it has attracted enormous publicity because of the risk of causing microcephaly in unborn children, combined with the coincidence of the outbreak during the Olympic year. The exact risk for the foetus is as yet unknown [1], but it is clear that Zika is otherwise a relatively mild disease with no symptoms in the majority of cases (http://www.cdc.gov/zika/symptoms/index.html). By contrast, other mosquito‐borne diseases, including malaria, yellow fever, dengue and chikungunya (CHIKV), are major causes of both mortality and morbidity, responsible for hundreds of millions of cases each year and millions of deaths …

Since the start of Roll Back Malaria (RBM) in 1998 funding for malaria control has increased dramatically, resulting in the current peak of $2.5billion spent on global malaria control annually. Vector control has been a major source of expenditure, with the focus in sub-Saharan Africa being free Long-Lasting Insecticidal Net (LLIN) distribution and Indoor Residual Spraying (IRS). Use of pyrethroid insecticides in agriculture and rapid scaling up of pyrethroid LLINs and IRS for malaria vector control has led to the development and spread of pyrethroid resistance in Anopheles gambiae malaria vectors. In community use, the level of insecticide resistance at which malaria control is compromised remains uncertain, but experimental hut trials in Benin, an area of high frequency pyrethroid resistance, showed that holed pyrethroid Insecticide Treated Nets (ITNs) failed to protect sleepers from being bitten and no longer had a mass killing effect on malaria vectors. If LLINs and IRS are to remain effective it is essential that new public health insecticides are developed to address the growing problem of resistance. All insecticides that are currently recommended by the World Health Organization Pesticide Evaluation Scheme (WHOPES) for LLIN or IRS belong to just four classes of chemistry that act on nerve and muscle targets; namely pyrethroid, organophosphate (OP), carbamate, and organochlorine (DDT). The Global Plan for Insecticide Resistance Management (GPIRM) states that in areas of pyrethroid resistance or high LLIN coverage, alternative insecticide classes should be used for IRS in a rotation. Rotation of insecticides is very difficult to implement due to a lack of new public health insecticides. The Stockholm Convention on Persistent Organic Pollutants (POPs) came into effect in 2004, yet the use of DDT (classified as a POP) for malaria control has been allowed to continue under exemption since then due to a perceived absence of equally effective and efficient alternatives. Alternative classes of insecticide for IRS such as pirimiphos-methyl (OP) and bendiocarb (carbamate) have a relatively short residual duration of action (2-6 months according to WHOPES). In areas of year-round transmission, multiple spray cycles are required resulting in significantly higher costs for malaria control programs and user fatigue. For continued cost-effectiveness of IRS programs it is important to develop new longer-lasting formulations of currently available insecticides, while also developing insecticides with new modes of action. Pyrethroids are the only insecticides that are currently recommended by WHOPES for LLIN. Therefore, it is essential to develop and evaluate new insecticides for LLIN before effectiveness of pyrethroid LLIN is compromised.
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\nThis thesis consisted of a sequence of tests to evaluate the efficacy of several new formulations of WHOPES recommended insecticides and novel insecticides both in the laboratory and against wild mosquitoes entering experimental huts.
\nSpecifically these studies have shown that:
\n Addition of eave baffles in experimental huts succeeded in reducing the potential for mosquito escape and is preferable to the assumption of doubling veranda catch to allow for unrecorded escapes (research paper 2).
\n A Capsule Suspension (CS) formulation of pirmiphos-methyl used for IRS showed a significant improvement in terms of longevity on mud, concrete and plywood when compared with the previously recommended Emulsifiable Concentrate (EC) formulation in laboratory and experimental hut bioassays (research paper 3).
\n A new formulation of deltamethrin with polymeric binder (SC-PE) for IRS showed only a slight improvement over the existing Water Dispersible Granules (WG) formulation in bioassays, but both formulations equalled DDT in experimental huts and should provide annual mosquito control. Deltamethrin SC-PE or WG should only be considered for use by malaria control programs where there is low pyrethroid LLIN coverage (research paper 4).
\n In experimental hut trials, chlorfenapyr (pyrrole) IRS was equivalent to alphacypermethrin against pyrethroid susceptible An. arabiensis but superior against pyrethroid-resistant Cx. quinquefasciatus. The unique non-neurological mode of action shows no cross-resistance to existing resistance mechanisms and should be successful for control of pyrethroid resistant mosquitoes (research paper 5).
\n In experimental hut trials, chlorfenapyr ITNs produced relatively high mortality rates of pyrethroid susceptible An. arabiensis but due to low irritability there was only a small reduction in blood-feeding (research paper 8). Mortality rates were similar to those produced by deltamethrin ITN.
\n Unlike neurotoxic insecticides, such as pyrethroids and carbamates, chlorfenapyr owes its toxicity to the disruption of molecular pathways which enable cellular respiration to occur. Conventional 3 minute contact bioassay based on WHOPES guidelines is suitable for pyrethroids but does not predict field performance of
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\nchlorfenapyr, which is metabolic in nature and sensitive to temperature and the phase of the insect’s circadian activity rhythm (research paper 9).
\n Combining chlorfenapyr with a more excito-repellent pyrethroid on mosquito nets produced higher levels of blood-feeding inhibition than chlorfenapyr alone, in tunnel tests with both pyrethroid susceptible and resistant strains of Cx. quinquefasciatus (research paper 10).
\n Restricting insecticide to particular surfaces of the nets (top only or sides only) indicated that An. arabiensis contacts both the top and sides of a mosquito net during host-seeking behaviour. These results support the rationale behind the ‘2-in-1’ mosquito net, in which the top of the net is treated with a non-pyrethroid insecticide and the sides with pyrethroid (research paper 11).

Current vector control challenges in the fight against malaria

Background and Aim: Malaria control programs in Indonesia heavily rely on insecticide-based interventions such as long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS). However, the effectiveness of these strategies is increasingly compromised by the emergence of insecticide resistance, particularly in high-transmission regions like Papua Province. The mechanisms underlying pyrethroid resistance in local vector populations remain inadequately characterized. This study aimed to assess the permethrin resistance status and characterize the frequency of L1014F/S knockdown resistance (kdr) alleles in Anopheles punctulatus group mosquitoes in Keerom, Papua, to inform region-specific malaria vector control strategies. Materials and Methods: An entomological and molecular investigation was conducted in five villages across three districts of Keerom Regency. Larval and adult Anopheles mosquitoes were collected through standard World Health Organization techniques. Insecticide susceptibility was evaluated using 0.75% permethrin bioassays. Molecular identification and detection of kdr mutations (L1014F/S) were performed using species-specific polymerase chain reaction and sequencing protocols. Allele frequencies were analyzed using Hardy–Weinberg equilibrium models, and statistical comparisons were made using one-way analysis of variance. Results: Among 163 mosquitoes tested, permethrin resistance was confirmed across all districts, with mortality rates ranging from 50% to 68.66%. Molecular analyses identified Anopheles koliensis, A. punctulatus, and A. peditaeniatus. High frequencies of the L1014S mutation were detected in A. koliensis (0.87) and A. punctulatus (0.66), whereas A. peditaeniatus exhibited only wild-type alleles. No L1014F mutations were observed. The high prevalence of homozygous resistant genotypes indicates intense selection pressure, potentially linked to LLIN and agricultural insecticide use. Conclusion: This study provides the first molecular evidence of widespread permethrin resistance mediated by L1014S mutations in the A. punctulatus group in Papua. These findings underscore the urgent need for enhanced resistance monitoring and the integration of alternative insecticides and non-chemical vector control methods to sustain malaria control efforts in the region. Keywords: Anopheles punctulatus, knockdown resistance, L1014S, malaria vector control, Papua, pyrethroid resistance.

Preface. 1. Executive summary. 2. Report of the working-group meeting, Christos Louis and Bart G.J. Knols.- Lessons learnt and anticipated benefits: 3. Review of previous applications of genetics to vector control, Chris F. Curtis. 4. Genomics and expected benefits for vector entomology, Christos Louis.- Current state and future needs of laboratory and field science: 5. Genetic approaches for malaria control, Marcelo Jacobs-Lorena. 6. Current thoughts about the integration of field and laboratory sciences in genetic control of disease vectors, Thomas W. Scott. 7. Genetic approaches in Aedes aegypti for control of dengue: an overview, Kenneth Olsen et al. Regional situation reports: malaria and dengue: 8. Malaria and dengue vector biology and control in West and Central Africa, Didier Fontenille and Pierre Carnevale. 9. Malaria and dengue vector biology and control in Southern and Eastern Africa, Maureen Coetzee. 10. Malaria and dengue vector biology and control in Southeast Asia, Pattamaporn Kittayapong. 11. Malaria and dengue vector biology and control in Latin America, Mario H. Rodriguez.- Integration: 12. Transition from the laboratory to the field and effective interplay, Christos Louis. 13. Evaluation of drive mechanisms (including transgenes and drivers) in different environmental conditions and genetic backgrounds, Anthony A. James et al. 14. Tools for monitoring the genetic structure and stability of mosquito populations, Gregory C. Lanzaro et al. 15. What are relevant assays for refractoriness? George K. Christophides et al.- 16. Fitness studies: developing a consensus methodology, Thomas W. Scott et al.- 17. Mosquito mating behaviour: 18. Pathogen evolution issues in genetically modified mosquito vector strategies, Mario H. Rodriguez. 19. Models to investigate some issues regarding the feasibility of driving refractoriness genes into mosquito vector populations, Chris F. Curtis. 20. Identification and characterization of field sitesfor genetic control of disease vectors, Bart G.J. Knols. 21. Application of genetically modified mosquitoes in national vector control programmes: thoughts on integrated control, Abraham Mnzava et al. 22. Entomological correlates of epidemiological impacts: how do we know it is working? Andrew Githeko. 23. Ethical, legal and social issues in the use of genetically modified vectors for disease control, Yeya T. Toure and Lucien Manga.- List of participants.

The work of Pooda et al. published in Malaria Journal [1] provides encouraging evidence of the potential use of systemic insecticides in cattle as a complementary means to further reduce residual malaria transmission that persists despite high coverage of current front-line vector measures, namely long-lasting insecticidal nets (LLINs) and indoor residual sprays (IRS). LLINs and IRS interventions are responsible for most of the remarkable reductions in malaria burden achieved in this century [2], but even more ambitious new vector control measures will be required to achieve elimination of transmission from most endemic areas in the years ahead [3–5]. This is because LLINs and IRS leave two obvious spatial and temporal gaps wherever vector mosquitoes attack people outdoors, especially in the evenings and mornings, or rest outdoors before and after feeding [3–5]. There is, however, a third gap that does not usually receive as much attention, specifically their failure to kill mosquitoes that feed on animals rather than humans. Zoophagic vectors that feed predominantly on animals can sustain malaria transmission even if they only bite humans infrequently [6]. Even with near-complete coverage of human sleeping spaces and houses, LLINs and IRS cannot be reasonably expected to have any meaningful impact upon the density or longevity of zoophagic vector populations, because they achieve no insecticidal coverage of the animals that constitute their main source of protein [4, 6]. Fortunately, by far the most common source of blood for most zoophagic malaria vectors are domesticated livestock, cattle in particular [7], so it is also possible to control the malaria transmission they mediate through veterinary applications of insecticides [8], the most exciting of which may be the systemic insecticides which the mosquito actually ingests along with its blood meal. Fritz et al. first described increased mortality of Anopheles gambiae feeding on ivermectin-treated cattle and suggested a potential role of this strategy for integrated vector management [9]. These findings have since been extended to Anopheles culicifacies and Anopheles stephensi, the main malaria vectors of Pakistan [10], and more recently to an important African vector of residual transmission, Anopheles arabiensis [11]. This latest report by Pooda et al. [1] now demonstrates similar increased mortality and reduced fertility of Anopheles coluzzii, a widely distributed vector species which maintains robust malaria transmission all across west and central Africa [12]. Interestingly, the lethal effect of ivermectin was seen even when the colony used had high prevalence of the kdr mutation which contributes to pyrethroid resistance in many parts of Africa. Although the evidence base is growing fast, the full potential of ivermectin for malaria vector and transmission control remains to be established, but most discourse thus far has focused on medical delivery to human beings [13]. However, the alternative strategy of veterinary delivery to livestock has several advantages: Long-lasting injectable veterinary formulations of ivermectin already exist that can dramatically increase the effectiveness of this approach, by not only targeting a more important blood source for vector populations than humans, but also by achieving far longer duration of efficacy than is possible with the oral formulations available for human pharmaceutical delivery. A much greater diversity of different endectocides are available for cattle and other livestock, which offers an opportunity to combine drugs with different mechanisms of action, especially if ivermectin is to be used for mass drug administration to humans. Integrating an endectocide into traditional zooprophylaxis strategies [14] removes potential risks of accidentally increasing malaria transmission by increasing vector survival and reproduction [15], because mosquitoes attracted to feeding on animals could be killed rather than merely diverted away from humans. Endectocides can contribute to an overall One Health strategy by simultaneously improving livestock and human health. Nonzoonotic livestock parasites pose an important burden on human health by reducing economic output and nutrient availability. In addition to preventing malaria transmission, broadening the use of veterinary endectocides also offers an excellent opportunity to alleviate poverty and malnutrition by reducing the burden of livestock parasites on the health and economic resilience of their human owners [16]. Plasmodium falciparum and Plasmodium vivax are both strict anthroponoses, so it is understandable that ivermectin mass drug administration for malaria control and elimination is usually viewed primarily as an intervention for human populations. However, the use of veterinary antiparasitic drugs with insecticidal proprieties in domesticated livestock could perhaps achieve greater impact in many settings where persisting transmission is mediated by zoophagic vectors, and contribute to human health in previously unforeseen ways.

SummaryBackgroundProgress in malaria control is under threat by wide-scale insecticide resistance in malaria vectors. Two recent vector control products have been developed: a long-lasting insecticidal net that incorporates a synergist piperonyl butoxide (PBO) and a long-lasting indoor residual spraying formulation of the insecticide pirimiphos-methyl. We evaluated the effectiveness of PBO long-lasting insecticidal nets versus standard long-lasting insecticidal nets as single interventions and in combination with the indoor residual spraying of pirimiphos-methyl.MethodsWe did a four-group cluster randomised controlled trial using a two-by-two factorial design of 48 clusters derived from 40 villages in Muleba (Kagera, Tanzania). We randomly assigned these clusters using restricted randomisation to four groups: standard long-lasting insecticidal nets, PBO long-lasting insecticidal nets, standard long-lasting insecticidal nets plus indoor residual spraying, or PBO long-lasting insecticidal nets plus indoor residual spraying. Both standard and PBO nets were distributed in 2015. Indoor residual spraying was applied only once in 2015. We masked the inhabitants of each cluster to the type of nets received, as well as field staff who took blood samples. Neither the investigators nor the participants were masked to indoor residual spraying. The primary outcome was the prevalence of malaria infection in children aged 6 months to 14 years assessed by cross-sectional surveys at 4, 9, 16, and 21 months after intervention. The endpoint for assessment of indoor residual spraying was 9 months and PBO long-lasting insecticidal nets was 21 months. This trial is registered with ClinicalTrials.gov, number NCT02288637.Findings7184 (68·0%) of 10 560 households were selected for post-intervention survey, and 15 469 (89·0%) of 17 377 eligible children from the four surveys were included in the intention-to-treat analysis. Of the 878 households visited in the two indoor residual spraying groups, 827 (94%) had been sprayed. Reported use of long-lasting insecticidal nets, across all groups, was 15 341 (77·3%) of 19 852 residents after 1 year, decreasing to 12 503 (59·2%) of 21 105 in the second year. Malaria infection prevalence after 9 months was lower in the two groups that received PBO long-lasting insecticidal nets than in the two groups that received standard long-lasting insecticidal nets (531 [29%] of 1852 children vs 767 [42%] of 1809; odds ratio [OR] 0·37, 95% CI 0·21–0·65; p=0·0011). At the same timepoint, malaria prevalence in the two groups that received indoor residual spraying was lower than in groups that did not receive indoor residual spraying (508 [28%] of 1846 children vs 790 [44%] of 1815; OR 0·33, 95% CI 0·19–0·55; p<0·0001) and there was evidence of an interaction between PBO long-lasting insecticidal nets and indoor residual spraying (OR 2·43, 95% CI 1·19–4·97; p=0·0158), indicating redundancy when combined. The PBO long-lasting insecticidal net effect was sustained after 21 months with a lower malaria prevalence than the standard long-lasting insecticidal net (865 [45%] of 1930 children vs 1255 [62%] of 2034; OR 0·40, 0·20–0·81; p=0·0122).InterpretationThe PBO long-lasting insecticidal net and non-pyrethroid indoor residual spraying interventions showed improved control of malaria transmission compared with standard long-lasting insecticidal nets where pyrethroid resistance is prevalent and either intervention could be deployed to good effect. As a result, WHO has since recommended to increase coverage of PBO long-lasting insecticidal nets. Combining indoor residual spraying with pirimiphos-methyl and PBO long-lasting insecticidal nets provided no additional benefit compared with PBO long-lasting insecticidal nets alone or standard long-lasting insecticidal nets plus indoor residual spraying.FundingUK Department for International Development, Medical Research Council, and Wellcome Trust.

BackgroundAfter three years with no local transmission of malaria, an outbreak occurred in Iran in 2022. Key malaria control methods in Iran are including indoor residual spraying (IRS), long-lasting insecticide-treated nets (LLINs), and prompt diagnosis and treatment of malaria cases. Anopheles sacharovi is one of the main malaria vectors in Iran. This study aimed to determine the insecticides resistance status of An. sacharovi in northwestern Iran, to inform effective vector control programs in this region.MethodsLarval stages of An. sacharovi were collected from various larval habitats located in the villages along the Aras River. Adult susceptibility tests were performed on An. sacharovi using diagnostic doses of insecticides accordance to World Health Organization (WHO) guidelines. The study also evaluated agricultural insecticide and fertilizer usage alongside the presence of natural mosquito predators in breeding sites in the study area.ResultsAlongside various chemicals such as silica, humic acid, superphosphate, sulfur, urea, and solupotasse at different dose levels, organophosphorus and pyrethroid insecticides are commonly used in rice fields and orchards. Anopheles sacharovi displayed diverse reactions to insecticides, demonstrating resistance to DDT but sensitivity to malathion, and showing similar reactions to carbamate and pyrethroid insecticides.ConclusionsThese results provide significant insights into agricultural practices and the presence of mosquito larvae in the study area. The extensive use of a specific herbicide illustrates its popularity among farmers for weed control, while other agricultural products focus on enhancing soil fertility and productivity. The absence of mosquito larvae in habitats with predators indicates the usefulness of these predators in controlling the population of mosquitoes. The resistance of mosquitoes to certain insecticides highlights the need for careful selection and intermittent use of insecticides in vector control programs. These findings can inform the development of targeted strategies to reduce malaria transmission risks. Further research is essential for assessing the effectiveness of these interventions.

BACKGROUND: Primary malaria prevention on a large scale depends on two vector control interventions: indoor residual spraying (IRS) and insecticide-treated mosquito nets (ITNs). Historically, IRS has reduced malaria transmission in many settings in the world, but the health effects of IRS have never been properly quantified. This is important, and will help compare IRS with other vector control interventions. OBJECTIVES: To quantify the impact of IRS alone, and to compare the relative impacts of IRS and ITNs, on key malariological parameters. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group Specialized Register (September 2009), CENTRAL (The Cochrane Library 2009, Issue 3), MEDLINE (1966 to September 2009), EMBASE (1974 to September 2009), LILACS (1982 to September 2009), mRCT (September 2009), reference lists, and conference abstracts. We also contacted researchers in the field, organizations, and manufacturers of insecticides (June 2007). SELECTION CRITERIA: Cluster randomized controlled trials (RCTs), controlled before-and-after studies (CBA) and interrupted time series (ITS) of IRS compared to no IRS or ITNs. Studies examining the impact of IRS on special groups not representative of the general population, or using insecticides and dosages not recommended by the World Health Organization (WHO) were excluded. DATA COLLECTION AND ANALYSIS: Two authors independently reviewed trials for inclusion. Two authors extracted data, assessed risk of bias and analysed the data. Where possible, we adjusted confidence intervals (CIs) for clustering. Studies were grouped into those comparing IRS with no IRS, and IRS compared with ITNs, and then stratified by malaria endemicity. MAIN RESULTS: IRS versus no IRSStable malaria (entomological inoculation rate (EIR) 1): Two studies; for incidence and prevalence, the malaria rates were higher in the IRS group compared to the ITN group in one study. Malaria incidence was higher in the IRS arm in India (risk ratio IRS:ITN = 1.48) and in South Africa (risk ratio 1.34 but the cluster unadjusted CIs included 1). For malaria prevalence, ITNs appeared to give better protection against any infection compared to IRS in India (risk ratio IRS:ITN = 1.70) and also for both P. falciparum (risk ratio IRS:ITN = 1.78) and P. vivax (risk ratio IRS:ITN = 1.37). AUTHORS' CONCLUSIONS: Historical and programme documentation has clearly established the impact of IRS. However, the number of high-quality trials are too few to quantify the size of effect in different transmission settings. The evidence from randomized comparisons of IRS versus no IRS confirms that IRS reduces malaria incidence in unstable malaria settings, but randomized trial data from stable malaria settings is very limited. Some limited data suggest that ITN give better protection than IRS in unstable areas, but more trials are needed to compare the effects of ITNs with IRS, as well as to quantify their combined effects

BackgroundProgress in reducing the malaria disease burden through the substantial scale up of insecticide-based vector control in recent years could be reversed by the widespread emergence of insecticide resistance. The impact of insecticide resistance on the protective effectiveness of insecticide-treated nets (ITN) and indoor residual spraying (IRS) is not known. A multi-country study was undertaken in Sudan, Kenya, India, Cameroon and Benin to quantify the potential loss of epidemiological effectiveness of ITNs and IRS due to decreased susceptibility of malaria vectors to insecticides. The design of the study is described in this paper.MethodsMalaria disease incidence rates by active case detection in cohorts of children, and indicators of insecticide resistance in local vectors were monitored in each of approximately 300 separate locations (clusters) with high coverage of malaria vector control over multiple malaria seasons. Phenotypic and genotypic resistance was assessed annually. In two countries, Sudan and India, clusters were randomly assigned to receive universal coverage of ITNs only, or universal coverage of ITNs combined with high coverage of IRS. Association between malaria incidence and insecticide resistance, and protective effectiveness of vector control methods and insecticide resistance were estimated, respectively.ResultsCohorts have been set up in all five countries, and phenotypic resistance data have been collected in all clusters. In Sudan, Kenya, Cameroon and Benin data collection is due to be completed in 2015. In India data collection will be completed in 2016.DiscussionThe paper discusses challenges faced in the design and execution of the study, the analysis plan, the strengths and weaknesses, and the possible alternatives to the chosen study design.

BackgroundNew classes of insecticides with novel modes of action, which can provide effective and prolonged control of insecticide-resistant malaria vector populations, are urgently needed for indoor residual spraying. Such insecticides can be included in a rotation plan to manage and prevent further development of resistance in mosquito vectors of malaria. Chlorfenapyr, a novel pyrrole insecticide with a unique mode of action, is being developed as a long-lasting IRS formulation.MethodsThe efficacy of several formulations of chlorfenapyr alone and as mixtures with alpha-cypermethrin were evaluated in an experimental hut trial against wild pyrethroid-resistant Anopheles gambiae sensu lato in Cové, Benin, in an attempt to identify the most effective and long-lasting formulations for IRS. The trial lasted 12 months. A comparison was made with alpha-cypermethrin and bendiocarb formulations. CDC bottle bioassays were performed to investigate cross-resistance to chlorfenapyr in the local vector population.ResultsMortality rates in World Health Organization (WHO) cylinder bioassays were < 5% with pyrethroids due to high levels of pyrethroid resistance, but > 95% with bendiocarb thus confirming susceptibility to carbamates in the vector population. CDC bottle bioassays showed no cross-resistance between pyrethroids and chlorfenapyr. Overall mortality of free-flying mosquitoes entering the experimental huts over the 12-month trial was 4% with alpha-cypermethrin and 12% with bendiocarb. The chlorfenapyr solo-formulations induced significantly higher levels of mortality (38–46%) compared to the bendiocarb (12% P < 0.001) and to the mixture formulations (18–22%, P < 0.05). The original Sylando 240SC formulation of chlorfenapyr was more efficacious than all other novel chlorfenapyr formulations tested. Bendiocarb induced > 80% mortality in the first month, but this declined sharply to < 20% by the third month while the mortality rates achieved with the chlorfenapyr formulations (38–46%) were persistent lasting 7–10 months. The mixtures induced significantly lower percentage mortality than chlorfenapyr-solo formulations. Wall cone bioassays only showed mortality rates that were consistent with chlorfenapyr IRS treated huts when the exposure time was increased to 2 h.ConclusionIndoor residual spraying with chlorfenapyr (Sylando® 240SC) provides moderate but prolonged control of pyrethroid-resistant malaria vectors compared to pyrethroid and bendiocarb IRS. Wall cone bioassays on chlorfenapyr-treated walls required longer exposure times of 2 h than the customary 30 min indicating that WHO guidelines on residual cone bioassays need to be more insecticide-specific.

The implementation of a vector control strategy needs to be adapted to both socioculturaland environmental contexts. The determination of National Malaria Control Program (NMCP) to fight effectively against malaria resulted in their decision to implement indoor residual spraying (IRS) in the department of Atacora in the Northwest of Benin. This study assessed community knowledge, perceptions and practices about malaria prevention especially about Indoor Residual Spraying (IRS), as well as data related to the type of human dwellings. Cross-sectional study was conducted between September and October, 2010. The results of a total of 7,878 respondents show little knowledge of populations about malaria. There was however a variety of protective measures against mosquito bitesincluding bednets which are the most used. Moreover, IRS was accepted by 98.74% of respondents. Most (79.84%) of the walls were smooth and lend themselves well to the insecticide treatment. Key words: Malaria prevention, community, knowledge, perceptions, practices, physical environment aspect, indoor residual spraying (IRS), Benin.

Malaria vector control technology has remained largely static for decades and there is a pressing need for innovative control tools and methodology to radically improve the quality and efficiency of current vector control practices. This report summarizes a workshop jointly organized by the Innovative Vector Control Consortium (IVCC) and the Armed Forces Pest Management Board (AFPMB) focused on public health pesticide application technology. Three main topics were discussed: the limitations with current tools and techniques used for indoor residual spraying (IRS), technology innovation to improve efficacy of IRS programmes, and truly disruptive application technology beyond IRS. The group identified several opportunities to improve application technology to include: insuring all IRS programmes are using constant flow valves and erosion resistant tips; introducing compression sprayer improvements that help minimize pesticide waste and human error; and moving beyond IRS by embracing the potential for new larval source management techniques and next generation technology such as unmanned “smart” spray systems. The meeting served to lay the foundation for broader collaboration between the IVCC and AFPMB and partners in industry, the World Health Organization, the Bill and Melinda Gates Foundation and others.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-015-0907-9) contains supplementary material, which is available to authorized users.

The letter “DDT and Malaria Control” (Tren and Roberts 2010) is the latest in a long string of opinion pieces placed by authors associated with Africa Fighting Malaria (AFM). Appearing in both the popular media (e.g., AFM 2006; Bate 2009; Bate and De Lorenzo 2007; Roberts 2007a; Tren 2002) and scientific literature (e.g., Attaran et al. 2000; Roberts 2001, 2007b; Roberts et al. 2000, 2004; Tren 2009), these articles and letters reduce the complex issue of malaria control to a single, dichotomous choice between DDT and malaria. Framing the issue in this manner is a dangerous oversimplification and an distraction from the critical dialog on how to effectively combat malaria around the world—particularly in African communities. The question that AFM and malaria control experts must ask is not “Which is worse, malaria or DDT?” but rather “What are the best tools to deploy for malaria control in a given situation, taking into account the on-the-ground challenges and needs, efficacy, cost, and collateral effects—both positive and negative—to human health and the environment, as well as the uncertainties associated with all these considerations?” Tren and Roberts (2010) briefly acknowledged that alternatives to DDT exist (while denigrating them as “supposed solutions”), but in typical fashion they focused most of their letter on the chemical, arguing that the health effects of malaria are much worse that those of DDT exposure. As malaria professionals we are well aware of the dire health consequences of malaria, but also of DDT. The challenge before us is therefore to determine how much weight to give to vector control within the broader context of a malaria control program; within vector control, how much weight to allot to nets versus indoor residual spraying (IRS); and within IRS, how much weight to give to DDT or some other chemical. These decisions are indeed complex and location specific. In this regard, van den Berg’s commentary, “Global Status of DDT and Its Alternatives for Use in Vector Control to Prevent Disease” (van den Berg 2009), is a most useful contribution. In contrast, Tren and Roberts’ (2010) advice that “van den Berg’s concerns should be ignored” strikes us as reckless and irresponsible. In 2006, Allan Schapira, former coordinator of vector control and prevention of World Health Organization’s Global Malaria Programme, observed that malaria control discussions had become “polluted,” and warned, “The renewed interest in indoor residual spraying could lead to interminable debates in countries about the pros and cons of DDT” (Schapira 2006). However well intentioned, Tren and Roberts (2010)—as with much of AFM’s output—do more to fuel those “interminable debates” than to meaningfully inform decisions that will save people’s lives.

Background: Indoor residual spraying (IRS) is a core insecticide-based vector control tool employed in most malaria-affected settings globally. However, mosquito vectors have developed resistance to nearly all of the insecticides currently used in IRS. This has necessitated a transition to new classes of insecticides, from mostly using dichlorodiphenyltrichloroethane (DDT) and pyrethroids from 1997 to 2010 to carbamates in 2011 and organophosphates in 2013. In addition, other vector control measures, like the use of long-lasting insecticide-treated bed nets (LLINs), have also been employed for malaria control. Despite the implementation of these mosquito vector control interventions, malaria remains a disease of public health concern, especially in sub-Saharan Africa, which bears over 90% of the disease burden. This review will thus collate evidence on the effectiveness of IRS for malaria control in sub-Saharan Africa. Methods and analysis: The systematic review will be conducted following a priori criteria developed using the PRISMA guidelines. Articles will be obtained through a search of the Web of Science, Google Scholar, Medline via PubMed, Scopus and Embase databases. Mesh terms and Boolean operators (“AND”, “OR”) will be used in the article search. Additionally, websites of malaria research institutions will be searched. The article search will be conducted by two independent librarians (AAK and RS). All identified articles will be transferred to EPPI-reviewer v6.15.1.0 software. Article screening and data abstraction will be performed in duplicate by four reviewers (KOO, LN, GK and MO), and any further disagreements will be resolved through discussion and consensus. We shall extract data on the country, region, study design, insecticide combination, season, susceptibility procedure used, vector control interventions, population, mosquito species, malaria incidence or prevalence, insecticide efficacy, susceptibility, genotypic resistance, vector mortality and knockdown effect. Data analysis will be performed using STATA v17.0. Effect sizes will be statistically pooled using inverse-variance-weighted random-effects meta-analysis. Heterogeneity and publication bias in the articles will be assessed using the I2 statistic and a funnel plot, respectively. For the studies that will not be included in the meta-analysis, a narrative synthesis will be written following the Cochrane Consumer and Communication Review Group format. Results: The findings of this review will help generate evidence on the effectiveness of indoor residual spraying using WHO pre-qualified insecticides in malaria control in sub-Saharan Africa. This protocol was registered in PROSPERO, registration number CRD42024517119.