Dataset Information

Reduced exposure to malaria vectors following indoor residual spraying of pirimiphos-methyl in a high-burden district of rural Mozambique with high ownership of long-lasting insecticidal nets: entomological surveillance results from a cluster-randomized trial.

ABSTRACT:

Background

The need to develop new products and novel approaches for malaria vector control is recognized as a global health priority. One approach to meeting this need has been the development of new products for indoor residual spraying (IRS) with novel active ingredients for public health. While initial results showing the impact of several of these next-generation IRS products have been encouraging, questions remain about how to best deploy them for maximum impact. To help address these questions, a 2-year cluster-randomized controlled trial to measure the impact of IRS with a microencapsulated formulation of pirimiphos-methyl (PM) in an area with high ownership of long-lasting insecticidal nets (LLINs) was conducted in a high-transmission district of central Mozambique with pyrethroid resistant vectors. Presented here are the results of the vector surveillance component of the trial.

Methods

The 2 year, two-armed trial was conducted in Mopeia District, Zambezia Province, Mozambique. In ten sentinel villages, five that received IRS with PM in October-November 2016 and again in October-November 2017 and five that received no IRS, indoor light trap collections and paired indoor-outdoor human landing collections catches (HLCs) were conducted monthly from September 2016 through October 2018. A universal coverage campaign in June 2017, just prior to the second spray round, distributed 131,540 standard alpha-cypermethrin LLINs across all study villages and increased overall net usage rates in children under 5 years old to over 90%.

Results

The primary malaria vector during the trial was Anopheles funestus sensu lato (s.l.), and standard World Health Organization (WHO) tube tests with this population indicated variable but increasing resistance to pyrethroids (including alpha-cypermethrin, from?>?85% mortality in 2017 to 7% mortality in 2018) and uniform susceptibility to PM (100% mortality in both years). Over the entire duration of the study, IRS reduced An. funestus s.l. densities by 48% (CI₉₅ 33-59%; p?95 38-90%; p?=?0.010) during indoor and outdoor HLC, though in each study year reductions in vector density were consistently greatest in those months immediately following the IRS campaigns and waned over time. Overall there was no strong preference for An. funestus to feed indoors or outdoors, and these biting behaviours did not differ significantly across study arms: observed indoor-outdoor biting ratios were 1.10 (CI₉₅ 1.00-1.21) in no-IRS villages and 0.88 (CI₉₅ 0.67-1.15) in IRS villages. The impact of IRS was consistent in reducing HLC exposures both indoors (75% reduction: CI₉₅ 47-88%; p?=?0.?95 22-87%; p?=?0.012). While substantially fewer Anopheles gambiae s.l. were collected during the study, trends show a similar impact of IRS on this key vector group as well, with a 33% (CI₉₅ 7-53%; p?=?0.019) reduction in mosquitoes collected in light traps and a non-statistically significant 39% reduction (p?=?0.249) in HLC landing rates.

Conclusion

IRS with PM used in addition to pyrethroid-only LLINs substantially reduced human exposures to malaria vectors during both years of the cluster-randomized controlled trial in Mopeia-a high-burden district where the primary vector, An. funestus s.l., was equally likely to feed indoors or outdoors and demonstrated increasing resistance to pyrethroids. Findings suggest that IRS with PM can provide effective vector control, including in some settings where pyrethroid-only ITNs are widely used. Trial registration clinicaltrials.gov , NCT02910934. Registered 22 September 2016, https://www.clinicaltrials.gov/ct2/show/NCT02910934.

SUBMITTER: Wagman JM

PROVIDER: S-EPMC7819201 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Reduced exposure to malaria vectors following indoor residual spraying of pirimiphos-methyl in a high-burden district of rural Mozambique with high ownership of long-lasting insecticidal nets: entomological surveillance results from a cluster-randomized trial.

Wagman Joseph M JM Varela Kenyssony K Zulliger Rose R Saifodine Abuchahama A Muthoni Rodaly R Magesa Stephen S Chaccour Carlos C Gogue Christelle C Tynuv Kenzie K Seyoum Aklilu A Dengela Dereje D Saúte Francisco F Richardson Jason H JH Fornadel Christen C Linton Yvonne-Marie YM Slutsker Laurence L Candrinho Baltazar B Robertson Molly M

Malaria journal 20210121 1

<h4>Background</h4>The need to develop new products and novel approaches for malaria vector control is recognized as a global health priority. One approach to meeting this need has been the development of new products for indoor residual spraying (IRS) with novel active ingredients for public health. While initial results showing the impact of several of these next-generation IRS products have been encouraging, questions remain about how to best deploy them for maximum impact. To help address th ...[more]

PMID: 33478533

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Project description:BackgroundAs malaria cases increase in some of the highest burden countries, more strategic deployment of new and proven interventions must be evaluated to meet global malaria reduction goals.MethodsThe cost and cost-effectiveness of indoor residual spraying (IRS) with pirimiphos-methyl (Actellic®300 CS) were assessed in a high transmission district (Mopeia) with high access to pyrethroid insecticide-treated nets (ITNs), compared to ITNs alone. The major mosquito vectors in the area were susceptible to primiphos-methyl, but resistant to pyrethoids. A decision analysis approach was followed to conduct deterministic and probabilistic sensitivity analyses in a theoretical cohort of 10,000 children under five years of age (U5) and 10,000 individuals of all ages, separately. Model parameters and distributions were based on prospectively collected cost and epidemiological data from a cluster-randomized control trial and a literature review. The primary analysis used health facility-malaria incidence, while community cohort incidence and cross-sectional prevalence rates were used in sensitivity analyses. Lifetime costs, malaria cases, deaths and disability-adjusted life-years (DALYs) were calculated to determine the incremental costs per DALY averted through IRS.ResultsThe average IRS cost per person protected was US$8.26 and 51% of the cost was insecticide. IRS averted 46,609 (95% CI 46,570-46,646) uncomplicated and 242 (95% CI 241-243) severe lifetime cases in a theoretical children U5 cohort, yielding an incremental cost-effectiveness ratio (ICER) of US$400 (95% CI 399-402) per DALY averted. In the all-age cohort, the ICER was higher: US$1,860 (95% CI 1,852-1,868) per DALY averted. Deterministic and probabilistic results were consistent. When adding the community protective effect of IRS, the cost per person protected decreased (US$7.06) and IRS was highly cost-effective in children U5 (ICER = US$312) and cost-effective in individuals of all ages (ICER = US$1,431), compared to ITNs alone.ConclusionThis study provides robust evidence that IRS with pirimiphos-methyl can be cost-effective in high transmission regions with high pyrethroid ITN coverage where the major vector is susceptible to pirimiphos-methyl but resistant to pyrethroids. The finding that insecticide cost is the main driver of IRS costs highlights the need to reduce the insecticide price without jeopardizing effectiveness.Trial registrationClinicalTrials.gov identifier NCT02910934 (Registered 22 September 2016). https://clinicaltrials.gov/ct2/show/NCT02910934?term=NCT02910934&draw=2&rank=1.

Project description:Malaria control today is threatened by widespread insecticide resistance in vector populations. The World Health Organization (WHO) recommends the use of a mixture of unrelated insecticides for indoor residual spraying (IRS) and long-lasting insecticidal nets (LNs) or as a combination of interventions for improved vector control and insecticide resistance management. Studies investigating the efficacy of these different strategies are necessary.The efficacy of Interceptor® G2 LN, a newly developed LN treated with a mixture of chlorfenapyr (a pyrrole) and alpha-cypermethrin (a pyrethroid), was compared to a combined chlorfenapyr IRS and Interceptor® LN (a standard alpha-cypermethrin LN) intervention in experimental huts in Cove Southern Benin, against wild, free-flying, pyrethroid-resistant Anopheles gambiae s.l. A direct comparison was also made with a pyrethroid-only net (Interceptor® LN) alone and chorfenapyr IRS alone.WHO resistance bioassays performed during the trial demonstrated a pyrethroid resistance frequency of >90% in the wild An. gambiae s.l. from the Cove hut site. Mortality in the control (untreated net) hut was 5%. Mortality with Interceptor® LN (24%) was lower than with chlorfenapyr IRS alone (59%, P < 0.001). The combined Interceptor® LN and chlorfenapyr IRS intervention and the mixture net (Interceptor® G2 LN) provided significantly higher mortality rates (73 and 76%, respectively) and these did not differ significantly between both treatments (P = 0.15). Interceptor LN induced 46% blood-feeding inhibition compared to the control untreated net, while chlorfenapyr IRS alone provided none. Both mixture/combination strategies also induced substantial levels of blood-feeding inhibition (38% with combined interventions and 30% with Interceptor® G2 LN). A similar trend of improved mortality of pyrethroid-resistant An. gambiae s.l. from Cove was observed with Interceptor® G2 LN (79%) compared to Interceptor LN (42%, P < 0.001) in WHO tunnel tests.The use of chlorfenapyr and alpha-cypermethrin together as a mixture on nets (Interceptor® G2 LN) or a combined chlorfenapyr IRS and pyrethroid LN intervention provides improved control of pyrethroid-resistant malaria vectors by inducing significantly higher levels of mortality through the chlorfenapyr component and providing personal protection through the pyrethroid component. Both strategies are comparable in their potential to improve the control of malaria transmitted by pyrethroid resistant mosquito vectors.

Project description:BackgroundWhere resources are available, non-pyrethroid IRS can be deployed to complement standard pyrethroid LLINs with the aim of achieving improved vector control and managing insecticide resistance. The impact of the combination may however depend on the type of IRS insecticide deployed. Studies comparing combinations of pyrethroid LLINs with different types of non-pyrethroid IRS products will be necessary for decision making.MethodsThe efficacy of combining a standard pyrethroid LLIN (DuraNet®) with IRS insecticides from three chemical classes (bendiocarb, chlorfenapyr and pirimiphos-methyl CS) was evaluated in an experimental hut trial against wild pyrethroid-resistant Anopheles gambiae s.l. in Cové, Benin. The combinations were also compared to each intervention alone. WHO cylinder and CDC bottle bioassays were performed to assess susceptibility of the local An. gambiae s.l. vector population at the Cové hut site to insecticides used in the combinations.ResultsSusceptibility bioassays revealed that the vector population at Cové, was resistant to pyrethroids (<20% mortality) but susceptible to carbamates, chlorfenapyr and organophosphates (≥98% mortality). Mortality of wild free-flying pyrethroid resistant An. gambiae s.l. entering the hut with the untreated net control (4%) did not differ significantly from DuraNet® alone (8%, p = 0.169). Pirimiphos-methyl CS IRS induced the highest mortality both on its own (85%) and in combination with DuraNet® (81%). Mortality with the DuraNet® + chlorfenapyr IRS combination was significantly higher than each intervention alone (46% vs. 33% and 8%, p<0.05) demonstrating an additive effect. The DuraNet® + bendiocarb IRS combination induced significantly lower mortality compared to the other combinations (32%, p<0.05). Blood-feeding inhibition was very low with the IRS treatments alone (3-5%) but increased significantly when they were combined with DuraNet® (61% - 71%, p<0.05). Blood-feeding rates in the combinations were similar to the net alone. Adding bendiocarb IRS to DuraNet® induced significantly lower levels of mosquito feeding compared to adding chlorfenapyr IRS (28% vs. 37%, p = 0.015).ConclusionsAdding non-pyrethroid IRS to standard pyrethroid-only LLINs against a pyrethroid-resistant vector population which is susceptible to the IRS insecticide, can provide higher levels of vector mosquito control compared to the pyrethroid net alone or IRS alone. Adding pirimiphos-methyl CS IRS may provide substantial improvements in vector control while adding chlorfenapyr IRS can demonstrate an additive effect relative to both interventions alone. Adding bendiocarb IRS may show limited enhancements in vector control owing to its short residual effect.

Project description:BackgroundSignificant progress in malaria prevention during the past two decades has prompted increasing global dialogue on malaria elimination. Recent reviews on malaria strategies have focused mainly on long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS), with little emphasis on other prevention methods. This article is a scoping review of literature on malaria prevention methods beyond LLINs and IRS in low- and middle-income countries (LMICs).MethodsThis scoping review found articles published between from 1994 to 2020. Studies were obtained from a search of the PubMed, the Cochrane Library and Social Science abstracts. Grey literature and manual search of secondary references was also done. The search strategy included all study designs but limited only to English. Three independent reviewers performed the selection and characterization of articles, and the data collected were synthesized qualitatively.ResultsA total of 10,112 studies were identified among which 31 met the inclusion criteria. The results were grouped by the 3 emerging themes of: housing design; mosquito repellents; and integrated vector control. Housing design strategies included closing eves, screening of houses including windows, doors and ceilings, while mosquito repellents were mainly spatial repellents, use of repellent plants, and use of plant-based oils. Integrated vector control included larvae source management. Evidence consistently shows that improving housing design reduced mosquito entry and malaria prevalence. Spatial repellents also showed promising results in field experiments, while evidence on repellent plants is limited and still emerging. Recent literature shows that IVM has been largely ignored in recent years in many LMICs. Some malaria prevention methods such as spatial repellents and IVM are shown to have the potential to target both indoor and outdoor transmission of malaria, which are both important aspects to consider to achieve malaria elimination in LMICs.ConclusionThe scoping review shows that other malaria prevention strategies beyond LLINs and IRS have increasingly become important in LMICs. These methods have a significant role in contributing to malaria elimination in endemic countries if they are adequately promoted alongside other conventional approaches.

Project description:BackgroundLong-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) are the main malaria vector control measures deployed in Kenya. Widespread pyrethroid resistance among the primary vectors in Western Kenya has necessitated the re-introduction of IRS using an organophosphate insecticide, pirimiphos-methyl (Actellic® 300CS), as a pyrethroid resistance management strategy. Evaluation of the effectiveness of the combined use of non-pyrethroid IRS and LLINs has yielded varied results. We aimed to evaluate the effect of non-pyrethroid IRS and LLINs on malaria indicators in a high malaria transmission area.MethodsWe reviewed records and tallied monthly aggregate of outpatient department (OPD) attendance, suspected malaria cases, those tested for malaria and those testing positive for malaria at two health facilities, one from Nyatike, an intervention sub-county, and one from Suba, a comparison sub-county, both located in Western Kenya, from February 1, 2016, through March 31, 2018. The first round of IRS was conducted in February-March 2017 in Nyatike sub-county and the second round one year later in both Nyatike and Suba sub-counties. The mass distribution of LLINs has been conducted in both locations. We performed descriptive analysis and estimated the effect of the interventions and temporal changes of malaria indicators using Poisson regression for a period before and after the first round of IRS.ResultsA higher reduction in the intervention area in total OPD, the proportion of OPD visits due to suspected malaria, testing positivity rate and annual malaria incidences were observed except for the total OPD visits among the under 5 children (59% decrease observed in the comparison area vs 33% decrease in the intervention area, net change -27%, P <0.001). The percentage decline in annual malaria incidence observed in the intervention area was more than twice the observed percentage decline in the comparison area across all the age groups. A marked decline in the monthly testing positivity rate (TPR) was noticed in the intervention area, while no major changes were observed in the comparison area. The monthly TPR reduced from 46% in February 2016 to 11% in February 2018, representing a 76% absolute decrease in TPR among all ages (RR = 0.24, 95% CI 0.12-0.46). In the comparison area, TPR was 16% in both February 2016 and February 2018 (RR = 1.0, 95% CI 0.52-2.09). A month-by-month comparison revealed lower TPR in Year 2 compared to Year 1 in the intervention area for most of the one year after the introduction of the IRS.ConclusionsOur findings demonstrated a reduced malaria burden among populations protected by both non-pyrethroid IRS and LLINs implying a possible additional benefit afforded by the combined intervention in the malaria-endemic zone.

Project description:BackgroundMost of the reduction in malaria prevalence seen in Africa since 2000 has been attributed to vector control interventions. Yet increases in the distribution and intensity of insecticide resistance and higher costs of newer insecticides pose a challenge to sustaining these gains. Thus, endemic countries face challenging decisions regarding the choice of vector control interventions.MethodsA cluster randomised trial is being carried out in Mopeia District in the Zambezia Province of Mozambique, where malaria prevalence in children under 5 is high (68% in 2015), despite continuous and campaign distribution of long-lasting insecticide-treated nets (LLINs). Study arm 1 will continue to use the standard, LLIN-based National Malaria Control Programme vector control strategy (LLINs only), while study arm 2 will receive indoor residual spraying (IRS) once a year for 2 years with a microencapsulated formulation of pirimiphos-methyl (Actellic 300 CS), in addition to the standard LLIN strategy (LLINs+IRS). Prior to the 2016 IRS implementation (the first of two IRS campaigns in this study), 146 clusters were defined and stratified per number of households. Clusters were then randomised 1:1 into the two study arms. The public health impact and cost-effectiveness of IRS intervention will be evaluated over 2 years using multiple methods: (1) monthly active malaria case detection in a cohort of 1548 total children aged 6-59 months; (2) enhanced passive surveillance at health facilities and with community health workers; (3) annual cross-sectional surveys; and (4) entomological surveillance. Prospective microcosting of the intervention and provider and societal costs will be conducted. Insecticide resistance status pattern and changes in local Anopheline populations will be included as important supportive outcomes.DiscussionBy evaluating the public health impact and cost-effectiveness of IRS with a non-pyrethroid insecticide in a high-transmission setting with high LLIN ownership, it is expected that this study will provide programmatic and policy-relevant data to guide national and global vector control strategies.Trial registration numberNCT02910934.

Project description:BackgroundTo eliminate malaria in southern Mozambique, the National Malaria Control Programme and its partners are scaling up indoor residual spraying (IRS) activities in two provinces, Gaza and Inhambane. An entomological surveillance planning tool (ESPT) was used to answer the programmatic question of whether IRS would be effective in target geographies, given limited information on local vector bionomics.MethodsEntomological intelligence was collected in six sentinel sites at the end of the rainy season (April-May 2018) and the beginning of the dry season (June-July 2018). The primary objective was to provide an 'entomological snapshot' by collecting question-based, timely and high-quality data within one single week in each location. Host-seeking behaviour (both indoors and outdoors) was monitored by human-baited tent traps. Indoor resting behaviour was quantified by pyrethrum spray catches and window exit traps.ResultsFive different species or species groups were identified: Anopheles funestus sensu lato (s.l.) (66.0%), Anopheles gambiae s.l. (14.0%), Anopheles pharoensis (1.4%), Anopheles tenebrosus (14.1%) and Anopheles ziemanni (4.5%). Anopheles funestus sensu stricto (s.s.) was the major vector among its sibling species, and 1.9% were positive for Plasmodium falciparum infections. Anopheles arabiensis was the most abundant vector species within the An. gambiae complex, but none tested positive for P. falciparum infections. Some An. tenebrosus were positive for P. falciparum (1.3%). When evaluating behaviours that impact IRS efficacy, i.e. endophily, the known primary vector An. funestus s.s., was found to rest indoors-demonstrating at least part of its population will be impacted by the intervention if insecticides are selected to which this vector is susceptible. However, other vector species, including An. gambiae s.l., An. tenebrosus, An. pharoensis and An. ziemanni, showed exophilic and exophagic behaviours in several of the districts surveilled.ConclusionThe targeted approach to entomological surveillance was successful in collecting question-based entomological intelligence to inform decision-making about the use of IRS in specific districts. Endophilic An. funestus s.s. was documented as being the most prevalent and primary malaria vector suggesting that IRS can reduce malaria transmission, but the presence of other vector species both indoors and outdoors suggests that alternative vector control interventions that target these gaps in protection may increase the impact of vector control in southern Mozambique.

Project description:Indoor residual spraying (IRS) of insecticides is a major vector control strategy for malaria prevention. We evaluated the impact of a single round of IRS with the organophosphate, pirimiphos-methyl (Actellic 300CS), on entomological and parasitological parameters of malaria in Migori County, western Kenya in 2017, in an area where primary vectors are resistant to pyrethroids but susceptible to the IRS compound. Entomological monitoring was conducted by indoor CDC light trap, pyrethrum spray catches (PSC) and human landing collection (HLC) before and after IRS. The residual effect of the insecticide was assessed monthly by exposing susceptible An. gambiae s.s. Kisumu strain to sprayed surfaces in cone assays and measuring mortality at 24 hours. Malaria case burden data were extracted from laboratory records of four health facilities within the sprayed area and two adjacent unsprayed areas. IRS was associated with reductions in An. funestus numbers in the intervention areas compared to non-intervention areas by 88% with light traps (risk ratio [RR] 0.12, 95% CI 0.07-0.21, p < 0.001) and 93% with PSC collections (RR = 0.07, 0.03-0.17, p < 0.001). The corresponding reductions in the numbers of An. arabiensis collected by PSC were 69% in the intervention compared to the non-intervention areas (RR = 0.31, 0.14-0.68, p = 0.006), but there was no significant difference with light traps (RR = 0.45, 0.21-0.96, p = 0.05). Before IRS, An. funestus accounted for over 80% of Anopheles mosquitoes collected by light trap and PSC in all sites. After IRS, An. arabiensis accounted for 86% of Anopheles collected by PSC and 66% by CDC light trap in the sprayed sites while the proportion in non-intervention sites remained unchanged. No sporozoite infections were detected in intervention areas after IRS and biting rates by An. funestus were reduced to near zero. Anopheles funestus and An. arabiensis were fully susceptible to pirimiphos-methyl and resistant to pyrethroids. The residual effect of Actellic 300CS lasted ten months on mud and concrete walls. Malaria case counts among febrile patients within IRS areas was lower post- compared to pre-IRS by 44%, 65% and 47% in Rongo, Uriri and Nyatike health facilities respectively. A single application of IRS with Actellic 300CS in Migori County provided ten months protection and resulted in the near elimination of the primary malaria vector An. funestus and a corresponding reduction of malaria case count among out-patients. The impact was less on An. arabiensis, most likely due to their exophilic nature.

Dataset Information

Reduced exposure to malaria vectors following indoor residual spraying of pirimiphos-methyl in a high-burden district of rural Mozambique with high ownership of long-lasting insecticidal nets: entomological surveillance results from a cluster-randomized trial.

Background

Methods

Results

Conclusion

Publications

Reduced exposure to malaria vectors following indoor residual spraying of pirimiphos-methyl in a high-burden district of rural Mozambique with high ownership of long-lasting insecticidal nets: entomological surveillance results from a cluster-randomized trial.

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