Effectiveness and cost-effectiveness against malaria of three types of dual-active-ingredient long-lasting insecticidal nets (LLINs) compared with pyrethroid-only LLINs in Tanzania: a four-arm, cluster-randomised trial.
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SUBMITTER: Mosha JF
PROVIDER: S-EPMC8971961 | biostudies-literature | 2022 Mar
REPOSITORIES: biostudies-literature
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Effectiveness and cost-effectiveness against malaria of three types of dual-active-ingredient long-lasting insecticidal nets (LLINs) compared with pyrethroid-only LLINs in Tanzania: a four-arm, cluster-randomised trial.
Mosha Jacklin F JF Kulkarni Manisha A MA Lukole Eliud E Matowo Nancy S NS Pitt Catherine C Messenger Louisa A LA Mallya Elizabeth E Jumanne Mohamed M Aziz Tatu T Kaaya Robert R Shirima Boniface A BA Isaya Gladness G Taljaard Monica M Martin Jacklin J Hashim Ramadhan R Thickstun Charles C Manjurano Alphaxard A Kleinschmidt Immo I Mosha Franklin W FW Rowland Mark M Protopopoff Natacha N
Lancet (London, England) 20220301 10331
<h4>Background</h4>Long-lasting insecticidal nets (LLINs) have successfully reduced malaria in sub-Saharan Africa, but their effectiveness is now partly compromised by widespread resistance to insecticides among vectors. We evaluated new classes of LLINs with two active ingredients with differing modes of action against resistant malaria vectors.<h4>Methods</h4>We did a four-arm, cluster-randomised trial in Misungwi, Tanzania. Clusters were villages, or groups of hamlets, with at least 119 house ...[more]
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Project description:IntroductionThe massive scale-up of long-lasting insecticidal nets (LLINs) has led to major reductions in malaria burden in many sub-Saharan African countries. This progress is threatened by widespread insecticide resistance among malaria vectors. This cluster-randomised controlled trial (c-RCT) compares three of the most promising dual active ingredients LLINs (dual-AI LLINs), which incorporate mixtures of insecticides or insecticide synergists to standard LLINs in an area of pyrethroid insecticide resistance.MethodsA four-arm, single-blinded, c-RCT will evaluate the effectiveness of three types of dual-AI LLINs (1) Royal Guard, combining two insecticides, pyriproxyfen and the pyrethroid alpha-cypermethrin; (2) Interceptor G2, combining chlorfenapyr and alpha-cypermethrin; (3) Olyset Plus, an LLIN combining a synergist, piperonyl butoxide and the pyrethroid permethrin, compared with; (4) Interceptor LN, a standard LLIN containing the pyrethroid alpha-cypermethrin as the sole AI. The primary outcomes are malaria infection prevalence in children aged 6 months-14 years and entomological inoculation rate (EIR), as a standard measure of malaria transmission at 24 months postintervention and cost-effectiveness.Ethics and disseminationEthical approval was received from the institutional review boards of the Tanzanian National Institute for Medical Research, Kilimanjaro Christian Medical University College, London School of Hygiene and Tropical Medicine, and University of Ottawa. Study findings will be actively disseminated via reports and presentations to stakeholders, local community leaders, and relevant national and international policy makers as well as through conferences, and peer-reviewed publications.Trial registration numberNCT03554616.
| S-EPMC7942254 | biostudies-literature
Project description:BackgroundThe massive scale-up of long-lasting insecticidal nets (LLIN) has led to a major reduction in malaria burden in many sub-Saharan African (SSA) countries. The World Health Organization (WHO) has recently issued a strong recommendation for the use of chlorfenapyr-pyrethroid LLINs compared to standard pyrethroid-only LLINs in areas of high insecticide resistance intensity. However, there is still a lack of conclusive evidence on the efficacy of piperonyl butoxide-pyrethroid (PBO-py) LLINs, especially in West Africa, where vector composition and resistance mechanisms may be different from vectors in East Africa.MethodsThis is a three-arm, superiority, triple-blinded, cluster randomised trial, with village as the unit of randomisation. This study conducted in Côte d'Ivoire will evaluate the efficacy on epidemiological and entomological outcomes of (1) the control arm: MAGNet® LN, which contains the pyrethroid, alpha-cypermethrin, (2) VEERALIN® LN, a net combining the synergist PBO and alpha-cypermethrin, and (3) Interceptor® G2 LN, which incorporates chlorfenapyr and alpha-cypermethrin, two adulticides with different mechanisms of action. A total of 33 villages with an average of 200 households per village will be identified, mapped, and randomised in a ratio of 1:1:1. Nets will be distributed at a central point following national guidelines with 1 net for every 2 people. The primary outcome of the trial will be incidence of malaria cases (confirmed by rapid diagnostic test (RDT)) in a cohort of 50 children aged 6 months to 10 years in each cluster, followed for 12 months (active case detection). Secondary outcomes are cross-sectional community prevalence of malaria infection (confirmed by RDT) in the study population at 6 and 12 months post-intervention (50 randomly selected persons per cluster), vector density, entomological inoculation rate (EIR), and phenotypic and genotypic insecticide resistance at baseline and 12 months post-intervention in 3 sentinel villages in each treatment arm.DiscussionIn addition to generating further evidence for next-generation LLINs, this study will also provide the first evidence for pyrethroid-PBO nets in a West African setting. This could further inform WHO recommendations on the pragmatic use of pyrethroid-PBO nets.Trial registrationClinicalTrials.gov NCT05796193. Registered on April 3, 2023.
| S-EPMC10900640 | biostudies-literature
Project description:BackgroundAfter decades of success in reducing malaria through the scale-up of pyrethroid long-lasting insecticidal nets (LLINs), the decline in the malaria burden has stalled, coinciding with the rapid spread of pyrethroid resistance. In a previously reported study, nets treated with a pyrethroid and a synergist, piperonyl butoxide (PBO), demonstrated superior efficacy compared to standard pyrethroid LLINs (std-LLINs) against malaria. Evidence was used to support the public health recommendation of PBO-Pyrethroid-LLIN by the World Health Organization in 2018. This study looks at the third year of rollout of these nets in Muleba district, Tanzania to inform whether policy guidelines need to be updated.MethodsA four-group cluster randomized trial (CRT) using a two-by-two factorial design was carried out between January 2014 and December 2017. A total of 48 clusters, were randomized in a 1:1:1:1 ratio to the following treatment groups, each intervention being provided once in 2015: 1/std-LLIN; 2/PBO-pyrethroid LLIN; 3/std-LLIN + Indoor Residual Spraying (IRS) and 4/PBO-Pyrethroid-LLIN + IRS. During the third year follow-up, malaria infection prevalence in 80 children per cluster, aged 6 months to 14 years, was measured at 28- and 33-months post-intervention and analysed as intention-to-treat (ITT) and per protocol (PP). Mosquito collections were performed monthly in all clusters, using CDC light traps in 7 randomly selected houses per cluster.ResultsAt 28 and 33 months, study net usage among household participants was only 47% and 31%, respectively. In ITT analysis, after 28 months malaria infection prevalence among 7471 children was 80.9% in the two std-LLIN groups compared to 69.3% in the two PBO-Pyrethroid-LLIN (Odds Ratio: 0.45, 95% Confidence Interval: 0.21-0.95, p-value: 0.0364). After 33 months the effect was weaker in the ITT analysis (prevalence 59.6% versus 49.9%, OR: 0.60, 95%CI:0.32-1.13, p-value: 0.1131) but still evident in the PP analysis (57.2% versus 44.2%, OR: 0.34, 95%CI: 0.16-0.71, p-value: 0.0051). Mean number of Anopheles per night collected per house was similar between PBO-Pyrethroid-LLIN groups (5.48) and std-LLIN groups (5.24) during the third year.ConclusionsDespite low usage of PBO- Pyrethroid LLIN, a small impact of those nets on malaria infection prevalence was still observed in the 3rd year with the most protection offered to children still using them. To maximize impact, it is essential that net re-distribution cycles are aligned with this LLIN lifespan to maintain maximum coverage.Trial registrationThe trial was registered with ClinicalTrials.gov (registration number NCT02288637).
| S-EPMC10548685 | biostudies-literature
Project description:Understanding long-lasting insecticidal nets (LLINs) utilization is important in monitoring and quantifying the impact of past and current prevention and control efforts of malaria. A cross-sectional study was carried out on a sample of 409 households in Mogadishu, to estimate the LLIN use and assess barriers to its utilization. A standardized questionnaire was used to collect data on demographics, malaria-related knowledge, and the use of preventive measures. LLINs use was assessed using multivariable generalized estimating equations with adjustment for clustering of study participants within the same household. Out of 409 households only 155 (37.9%) owned LLINs. Out of 237 owned LLINs, 199 (84.0%) were used. Median household size being 6.0 (3.0), intra-household net accessibility was low, with one net (42.6%) frequent. Most nets were from mass distribution (55.7%) and obtained '12 months ago'. Un-partnered respondents (unadjusted odds ratio [OR] 0.34, 95% CI 0.14, 0.82; p = 0.017) compared with partnered (married) respondents, large-sized household (adjusted OR 0.83, 96% CI 0.74-0.94; p = 0.002). There was marginal evidence of a greater odds of LLIN utilization among respondents knowledgeable of the correct cause of malaria, that is, mosquito bites (AOR 3.19, 95% CI 0.77, 13.2; p = 0.11) but was not statistically significant. Among households owning nets, most of the LLINs were hung the night prior to the survey (7.9% versus 98%) and was associated with greater marginal odds of utilization (p<0.001). Ownership of LLINs is insufficient in Mogadishu districts affecting household-level access and utilization. If this is not checked, this could weaken the progress made on malaria control efforts. LLIN utilization was modest and largely driven by recently acquired nets showing a desire to utilize them despite low coverage. These imply that mass and facility-based distribution, and awareness campaigns will remain relevant, but efforts for willingness-to-pay for LLINs should be strengthened to sustain coverage and replacements of worn-out nets.
| S-EPMC10019640 | biostudies-literature
Project description:BackgroundThe effectiveness of insecticide-treated nets in preventing malaria is threatened by developing resistance against pyrethroids. Little is known about how strongly this affects the effectiveness of vector control programmes.MethodsData from experimental hut studies on the effects of long-lasting, insecticidal nets (LLINs) on nine anopheline mosquito populations, with varying levels of mortality in World Health Organization susceptibility tests, were used to parameterize malaria models. Both simple static models predicting population-level insecticidal effectiveness and protection against blood feeding, and complex dynamic epidemiological models, where LLINs decayed over time, were used. The epidemiological models, implemented in OpenMalaria, were employed to study the impact of a single mass distribution of LLINs on malaria, both in terms of episodes prevented during the effective lifetime of the batch of LLINs, and in terms of net health benefits (NHB) expressed in disability-adjusted life years (DALYs) averted during that period, depending on net type (standard pyrethroid-only LLIN or pyrethroid-piperonyl butoxide combination LLIN), resistance status, coverage and pre-intervention transmission level.ResultsThere were strong positive correlations between insecticide susceptibility status and predicted population level insecticidal effectiveness of and protection against blood feeding by LLIN intervention programmes. With the most resistant mosquito population, the LLIN mass distribution averted up to about 40% fewer episodes and DALYs during the effective lifetime of the batch than with fully susceptible populations. However, cost effectiveness of LLINs was more sensitive to the pre-intervention transmission level and coverage than to susceptibility status. For four out of the six Anopheles gambiae sensu lato populations where direct comparisons between standard LLINs and combination LLINs were possible, combination nets were more cost effective, despite being more expensive. With one resistant population, both net types were equally effective, and with one of the two susceptible populations, standard LLINs were more cost effective.ConclusionDespite being less effective when compared to areas with susceptible mosquito populations, standard and combination LLINs are likely to (still) be cost effective against malaria even in areas with strong pyrethroid resistance. Combination nets are likely to be more cost effective than standard nets in areas with resistant mosquito populations.
| S-EPMC3598792 | biostudies-literature
Project description:BackgroundLong-lasting insecticidal nets (LLINs) were once fully effective for the prevention of malaria; however, mosquitoes have developed resistance to pyrethroids, the main class of insecticides used on nets. Dual active ingredient LLINs (dual-AI LLINs) have been rolled out as an alternative to pyrethroid (PY)-only LLINs to counteract this. Understanding the minimum community usage at which these LLINs elicit an effect that also benefits non-users against malaria infection is important.MethodsWe conducted a secondary analysis of a 3-year randomized controlled trial (RCT) in 84 clusters in North-western Tanzania to evaluate the effectiveness of three dual-AI LLINs: pyriproxyfen and alpha(α)-cypermethrin, chlorfenapyr and α-cypermethrin, and the piperonyl-butoxide (PBO) and permethrin compared to α-cypermethrin only LLINs. We measured malaria infection prevalence using 5 cross-sectional surveys between 2020 and 2022. We assessed net usage at the cluster level and malaria infection in children aged from 6 months to 14 years in 45 households per cluster. The trial was registered as a clinical trial on www.Clinicaltrialsgov : ClinicalTrials.gov (NCT03554616) on 2018-06-13.ResultsA total of 22,479 children from 12,654 households were tested for malaria using rapid diagnostic tests in January 2020, 2021, & 2022 and July 2020 & 2021. Among non-users, community-level usage of > 40% of dual-AI LLIN was significantly associated with protection against malaria infection: chlorfenapyr arm (OR: 0.44 (95% CI: 0.27-0.71), p = 0.0009), PBO arm (OR: 0.55 (95% CI: 0.33-0.94), p = 0.0277) and pyriproxyfen arm (OR: 0.61 (95% CI: 0.37-0.99), p = 0.0470) compared with non-users in clusters with > 40% usage of pyrethroid-only LLINs. There were indications of some protection against malaria infection to non-users in the chlorfenapyr arm when community-level usage was ≤ 40% (OR: 0.65 (95% CI: 0.42-1.01), p = 0.0528) compared to those living in clusters with > 40% usage of pyrethroid-only LLINs.ConclusionOur study demonstrated that at a community usage of 40% or more of dual-AI LLINs non-users benefited from the presence of these nets. Noticeably, even when usage was ≤ 40% in the chlorfenapyr arm, non-users were better protected than non-users in the higher coverage pyrethroid-only arm. The greater difference in malaria risk observed between users and non-users indicates that LLINs play a crucial role in providing personal protection against malaria infection for the people using the net.
| S-EPMC11773712 | biostudies-literature
Project description:BackgroundLong-lasting insecticidal nets (LLINs) are the most widely used malaria prevention and control intervention in Africa. However, their effectiveness may vary depending on their local geographic coverage, ownership and use at household level. This study aimed at assessing LLINs ownership and use following mass distribution campaign in western Kenya.MethodsA cross-sectional study was conducted in November 2017. A total of 160 households were randomly selected from 16 villages. Structured questionnaires were used to collect data on households' knowledge on malaria, LLINs ownership, utilization and their perceived benefits. Data was analyzed using IBM Statistical Package for Social Sciences (SPSS) version 21 for windows. Variables were presented as proportions and associations between variables tested using Pearson's chi-square test.ResultsMalaria was reported to be the most frequently occurring disease (87.5%) in the area. Children under 5 years of age were reported to be at higher risks of malaria infection (28.6%). Around 31% of the respondents reported to have at least one member of the household sick with malaria a week before the interview. Commonly cited signs and symptoms of malaria were; fever (24.1%), headache (17.7%), vomiting (14.5%) feeling cold (12.6%) and loss of appetite (10%). There were 382 reported LLINs among 753 occupants in the 160 households surveyed. The average LLIN ownership was 2.4 nets per household and 1.97 persons per LLIN. Among the surveyed households, 96.9% owned at least one LLIN and 64.1% owned at least one LLIN for every two people. Among those who owned LLINs, 98.1% reported using them the previous night. Ownership per household ranged from 0 to 6 with a mean of 2.39. More than three quarter of the nets were acquired through free mass distribution campaigns and 80% were acquired less than 6 months prior to the survey.ConclusionDespite high net coverage and use, a number of households experienced malaria episodes in the study area. There is need to investigate the likelihood of outdoor malaria transmission and assess the physical integrity of the existing LLINs and their insecticidal effectiveness in protecting household members against malaria.
| S-EPMC8173981 | biostudies-literature
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.
| S-EPMC7842967 | biostudies-literature
Project description:New classes of long-lasting insecticidal nets (LLINs), have been recommended by the World Health Organization (WHO) to control malaria vectors resistant to pyrethroid insecticides. This study was nested in a large-scale cluster-randomized controlled trial conducted (cRCT) in Tanzania. A series of experimental hut trials (EHTs) aimed to evaluate the bio-efficacy of trial LLINs on mosquito indicators most pertinent to malaria transmission over 3 years of use in the community in order to better understand the outcomes of the cRCT. The following field-collected LLINs were assessed: 1) Olyset Plus (combining piperonyl butoxide synergist and permethrin), 2) Interceptor G2 (chlorfenapyr and alpha-cypermethrin), 3) Royal Guard (pyriproxyfen and alpha-cypermethrin), 4) Interceptor (alpha-cypermethrin only) conducted in parallel with 5) a new Interceptor, and 6) an untreated net. Thirty nets of each type were withdrawn from the community at 12, 24, and 36 months after distribution and used for the EHTs. Pre-specified outcomes were 72-hour mortality for Interceptor G2, 24-hour mortality for Olyset Plus, and fertility based on egg development stage for Royal Guard. Overall, Interceptor G2 LLINs induced higher 72-hour mortality compared to standard LLINs of the same age up to12 months (44% vs 21%, OR: 3.5, 95% CI: 1.9-6.6, p-value < 0.001), and 24-hour mortality was only significantly higher in Olyset Plus when new (OR: 13.6, 95%CI: 4.4-41.3, p-value < 0.001) compared to standard LLINs but not at 12 months (17% vs 13%; OR: 2.1, 95% CI: 1.0-4.3; p-value = 0.112). A small, non-significant effect of pyriproxyfen on Anopheles fertility was observed for Royal Guard up to 12 months (75% vs 98%, OR: 1.1, 95% CI: 0.0-24.9, p-value = 0.951). There was no evidence of a difference in the main outcomes for any of the new classes of LLINs at 24 and 36 months compared to standard LLINs. Interceptor G2 LLINs showed superior bio-efficacy compared to standard LLINs only up to 12 months, and the effect of Olyset Plus was observed when new for all species and 12 months for An. gambiae s.l. only. The pyriproxyfen component of Royal Guard had a short and limited effect on fertility. The decrease in effectiveness of Olyset Plus and Royal Guard LLINs in the EHTs aligns with findings from the cRCT, whereas efficacy of Interceptor G2 lasted for a longer period in the cRCT compared to the EHT. Further investigations are needed to understand the complete scope of chlorfenapyr mode of action. Additional EHT in various contexts will help confirm the residual efficacy of the dual active ingredient LLINs and support the development of longer-lasting nets.
| S-EPMC11451999 | biostudies-literature
Project description:BackgroundProgress achieved by long-lasting insecticidal nets (LLINs) against malaria is threatened by widespread selection of pyrethroid resistance among vector populations. LLINs with non-pyrethroid insecticides are urgently needed. This study aims to assess the insecticide and textile durability of three classes of dual-active ingredient (A.I.) LLINs using techniques derived from established WHO LLIN testing methods to set new standards of evaluation.MethodsA WHO Phase 3 active ingredients and textile durability study will be carried out within a cluster randomized controlled trial in 40 clusters in Misungwi district, Tanzania. The following treatments will be evaluated: (1) Interceptor®G2 combining chlorfenapyr and the pyrethroid alpha-cypermethrin, (2) Royal Guard® treated with pyriproxyfen and alpha-cypermethrin, (3) Olyset™ Plus which incorporates a synergist piperonyl butoxide and the pyrethroid permethrin, and (4) a reference standard alpha-cypermethrin only LLIN (Interceptor®). 750 nets will be followed in 5 clusters per intervention arm at 6, 12, 24 and 36 months post distribution for survivorship and hole index assessment. A second cohort of 1950 nets per net type will be identified in 10 clusters, of which 30 LLINs will be withdrawn for bio-efficacy and chemical analysis every 6 months up to 36 months and another 30 collected for experimental hut trials every year. Bio-efficacy will be assessed using cone bioassays and tunnel tests against susceptible and resistant laboratory strains of Anopheles gambiae sensu stricto. Efficacy of field-collected nets will be compared in six experimental huts. The main outcomes will be Anopheles mortality up to 72 h post exposure, blood feeding and egg maturation using ovary dissection to assess impact on fecundity.ConclusionsStudy findings will help develop bio-efficacy and physical durability criteria for partner A.I., in relation to the cRCT epidemiological and entomological outcomes, and refine preferred product characteristics of each class of LLIN. If suitable, the bioassay and hut outcomes will be fitted to transmission models to estimate correlation with cRCT outcomes.Trial registration numberNCT03554616.
| S-EPMC8934498 | biostudies-literature