Synthetic repellents based on di-ethyl 3-methyl benzamide (DEET) are a popular method of obtaining protection from mosquitoes and yet clear evidence for a protective effect against malaria has hitherto never been convincingly demonstrated. A household randomized trial was undertaken among a study population of 127 families (25%) in an Afghan refugee village in Pakistan to compare the efficacy of repellent soap (Mosbar containing 20% DEET and 0.5% permethrin) vs. a placebo lotion. Cases of falciparum and vivax malaria were detected by passive case detection at the camp's clinic. At the end of the 6 month trial 3.7% (23 of 618) of individuals in the Mosbar group had presented with one or more episodes of falciparum malaria compared with 8.9% (47 of 530) of the placebo group (odds ratio 0.44, 95% CI 0.25-0.76). 16.7% of the Mosbar group (103 of 618) presented with vivax malaria compared with 11.7% (62 of 530) of the placebo group, and thus no effect was shown against vivax malaria (odds ratio 1.29, 95% CI 0.86-1.94). A considerable proportion of individuals (22%) had presented with vivax malaria during the 7 months leading up to the trial and thus any intervention effect would be partially masked by relapsed infections. The distribution of mosquitoes among households was broadly similar between Mosbar and placebo groups. The repellent was popularly received and very few side-effects were reported. There is a case for giving repellents more prominence in public health as a preventive measure in regions where vectors bite in the early evening or in emergency situations such as epidemics or newly established refugee camps.
BACKGROUND: The World Health Organization has yet to endorse deployment of topical repellents for malaria prevention as part of public health campaigns. We aimed to quantify the effectiveness of repellent distributed by the village health volunteer (VHV) network in the Greater Mekong Subregion (GMS) in reducing malaria in order to advance regional malaria elimination.
METHODS AND FINDINGS: Between April 2015 and June 2016, a 15-month stepped-wedge cluster randomised trial was conducted in 116 villages in Myanmar (stepped monthly in blocks) to test the effectiveness of 12% N,N-diethylbenzamide w/w cream distributed by VHVs, on Plasmodium spp. infection. The median age of participants was 18 years, approximately half were female, and the majority were either village residents (46%) or forest dwellers (40%). No adverse events were reported during the study. Generalised linear mixed modelling estimated the effect of repellent on infection detected by rapid diagnostic test (RDT) (primary outcome) and polymerase chain reaction (PCR) (secondary outcome). Overall Plasmodium infection detected by RDT was low (0.16%; 50/32,194), but infection detected by PCR was higher (3%; 419/13,157). There was no significant protection against RDT-detectable infection (adjusted odds ratio [AOR] = 0.25, 95% CI 0.004-15.2, p = 0.512). In Plasmodium-species-specific analyses, repellent protected against PCR-detectable P. falciparum (adjusted relative risk ratio [ARRR] = 0.67, 95% CI 0.47-0.95, p = 0.026), but not P. vivax infection (ARRR = 1.41, 95% CI 0.80-2.47, p = 0.233). Repellent effects were similar when delayed effects were modelled, across risk groups, and regardless of village-level and temporal heterogeneity in malaria prevalence. The incremental cost-effectiveness ratio was US$256 per PCR-detectable infection averted. Study limitations were a lower than expected Plasmodium spp. infection rate and potential geographic dilution of the intervention.
CONCLUSIONS: In this study, we observed apparent protection against new infections associated with the large-scale distribution of repellent by VHVs. Incorporation of repellent into national strategies, particularly in areas where bed nets are less effective, may contribute to the interruption of malaria transmission. Further studies are warranted across different transmission settings and populations, from the GMS and beyond, to inform WHO public health policy on the deployment of topical repellents for malaria prevention.
TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry (ACTRN12616001434482).
<b>BACKGROUND: </b>To combat emerging drug resistance in the Greater Mekong Sub-region (GMS) the World Health Organization and GMS countries have committed to eliminating malaria in the region by 2030. The overall approach includes providing universal access to diagnosis and treatment of malaria, and sustainable preventive measures, including vector control. Topical repellents are an intervention that can be used to target residual malaria transmission not covered by long lasting insecticide nets and indoor residual spraying. Although there is strong evidence that topical repellents protect against mosquito bites, evidence is not well established for the effectiveness of repellents distributed as part of malaria control activities in protecting against episodes of malaria. A common approach to deliver malaria services is to assign Village Health Volunteers (VHVs) to villages, particularly where limited or no services exist. The proposed trial aims to provide evidence for the effectiveness of repellent distributed through VHVs in reducing malaria.<b>METHODS: </b>The study is an open stepped-wedge cluster-randomised controlled trial randomised at the village level. Using this approach, repellent (N,N-diethyl-benzamide - 12% w/w, cream) is distributed by VHVs in villages sequentially throughout the malaria transmission season. Villages will be grouped into blocks, with blocks transitioned monthly from control (no repellent) to intervention states (to receive repellent) across 14 monthly intervals in random order). This follows a 4-week baseline period where all villages do not receive repellent. The primary endpoint is defined as the number of individuals positive for Plasmodium falciparum and Plasmodium vivax infections diagnosed by a rapid diagnostic test. Secondary endpoints include symptomatic malaria, Polymerase Chain Reaction (PCR)-detectable Plasmodium spp. infections, molecular markers of drug resistance and antibodies specific for Plasmodium spp. parasites.<b>DISCUSSION: </b>This study has been approved by relevant institutional ethics committees in Myanmar and Australia. Results will be disseminated through workshops, conferences and peer-reviewed publications. Findings will contribute to a better understanding of the optimal distribution mechanisms of repellent, context specific effectiveness and inform policy makers and implementers of malaria elimination programs in the GMS.<b>Trial Registration: </b>Australian and New Zealand Clinical Trials Registry ( ACTRN12616001434482 ). Retrospectively registered 14th October 2016.
BACKGROUND: While community distribution of topical repellents has been proposed as an additional malaria control intervention, the safety of this intervention at the population level remains poorly evaluated. We describe the safety of mass distribution of the picaridin repellent during a cluster-randomised trial in rural Cambodia in 2012-2013.
METHODS: The repellent was distributed among 57 intervention villages with around 25,000 inhabitants by a team of village distributors. Information on individual adverse events, reported by phone by the village distributors, was obtained through home visits. Information on perceived side effects, reported at the family level, was obtained during two-weekly bottle exchange. Adverse events were classified as adverse reactions (events likely linked to the repellent), cases of repellent abuse and events not related to the repellent use, and classified as per Common Terminology Criteria for Adverse Events.
FINDINGS: Of the 41 adverse events notified by phone by the village distributors, there were 22 adverse reactions, 11 cases of repellent abuse (6 accidental, 5 suicide attempts) and 8 non-related events. All adverse reactions were mild, occurred in the first few months of use, and mainly manifested as skin conditions. Of the 11 cases of abuse, 2 were moderate and 2 life-threatening. All cases with adverse reactions and repellent abuse recovered completely. 20% of families reported perceived side effects, mainly itching, headache, dizziness and bad smell, but few discontinued repellent use.
CONCLUSIONS: Adverse reactions and abuse during mass use of picaridin were uncommon and generally mild, supporting the safety of the picaridin repellent for malaria control.
<b>BACKGROUND: </b>Although effective topical repellents provide personal protection against malaria, whether mass use of topical repellents in addition to long-lasting insecticidal nets can contribute to a further decline of malaria is not known, particularly in areas where outdoor transmission occurs. We aimed to assess the epidemiological efficacy of a highly effective topical repellent in addition to long-lasting insecticidal nets in reducing malaria prevalence in this setting.<b>METHODS: </b>A cluster randomised controlled trial was done in the 117 most endemic villages in Ratanakiri province, Cambodia, to assess the efficacy of topical repellents in addition to long-lasting insecticidal nets in controlling malaria in a low-endemic setting. We did a pre-trial assessment of village accessibility and excluded four villages because of their inaccessibility during the rainy season. Another 25 villages were grouped because of their proximity to each other, resulting in 98 study clusters (comprising either a single village or multiple neighbouring villages). Clusters were randomly assigned (1:1) to either a control (long-lasting insecticidal nets) or intervention (long-lasting insecticidal nets plus topical repellent) study group after a restricted randomisation. All clusters received one long-lasting insecticidal net per individual, whereas those in the intervention group also received safe and effective topical repellents (picaridin KBR3023, SC Johnson, Racine, WI, USA), along with instruction and promotion of its daily use. Cross-sectional surveys of 65 randomly selected individuals per cluster were done at the beginning and end of the malaria transmission season in 2012 and 2013. The primary outcome was Plasmodium species-specific prevalence in participants obtained by real-time PCR, assessed in the intention-to-treat population. Complete safety analysis data will be published seperately; any ad-hoc adverse events are reported here. This trial is registered with ClinicalTrials.gov, number NCT01663831.<b>FINDINGS: </b>Of the 98 clusters that villages were split into, 49 were assigned to the control group and 49 were assigned to the intervention group. Despite having a successful distribution system, the daily use of repellents was suboptimum. No post-intervention differences in PCR plasmodium prevalence were observed between study groups in 2012 (4·91% in the control group vs 4·86% in the intervention group; adjusted odds ratio [aOR] 1·01 [95% CI 0·60-1·70]; p=0·975) or in 2013 (2·96% in the control group vs 3·85% in the intervention group; aOR 1·31 [0·81-2·11]; p=0·266). Similar results were obtained according to Plasmodium species (1·33% of participants in the intervention group vs 1·10% in the intervention group were infected with Plasmodium falciparum; aOR 0·83 [0·44-1·56]; p=0·561; and 1·85% in the control group vs 2·67% in the intervention group were infected with Plasmodium vivax; aOR 1·51 [0·88-2·57]; p=0·133). 41 adverse event notifications from nine villages were received, of which 33 were classified as adverse reactions (11 of these 33 were cases of repellent abuse through oral ingestion, either accidental or not). All participants with adverse reactions fully recovered and 17 were advised to permanently stop using the repellent.<b>INTERPRETATION: </b>Mass distribution of highly effective topical repellents in resource-sufficient conditions did not contribute to a further decline in malaria endemicity in a pre-elimination setting in the Greater Mekong subregion. Daily compliance and appropriate use of the repellents remains the main obstacle.<b>Funding: </b>Bill & Melinda Gates Foundation.
BACKGROUND: As many neglected tropical diseases are co-endemic and have common risk factors, integrated control can efficiently reduce disease burden and relieve resource-strained public health budgets. Diarrheal diseases and dengue fever are major global health problems sharing common risk factors in water storage containers. Where provision of clean water is inadequate, water storage is crucial. Fecal contamination of stored water is a common source of diarrheal illness, but stored water also provides breeding sites for dengue vector mosquitoes. Integrating improved water management and educational strategies for both diseases in the school environment can potentially improve the health situation for students and the larger community. The objective of this trial was to investigate whether interventions targeting diarrhea and dengue risk factors would significantly reduce absence due to diarrheal disease and dengue entomological risk factors in schools.
METHODOLOGY/PRINCIPAL FINDINGS: A factorial cluster randomized controlled trial was carried out in 34 rural primary schools (1,301 pupils) in La Mesa and Anapoima municipalities, Cundinamarca, Colombia. Schools were randomized to one of four study arms: diarrhea interventions (DIA), dengue interventions (DEN), combined diarrhea and dengue interventions (DIADEN), and control (CON). Interventions had no apparent effect on pupil school absence due to diarrheal disease (p = 0.45) or on adult female Aedes aegypti density (p = 0.32) (primary outcomes). However, the dengue interventions reduced the Breteau Index on average by 78% (p = 0.029), with Breteau indices of 10.8 and 6.2 in the DEN and DIADEN arms, respectively compared to 37.5 and 46.9 in the DIA and CON arms, respectively. The diarrhea interventions improved water quality as assessed by the amount of Escherichia coli colony forming units (CFU); the ratio of Williams mean E. coli CFU being 0.22, or 78% reduction (p = 0.008).
CONCLUSIONS/SIGNIFICANCE: Integrated control of dengue and diarrhea has never been conducted before. This trial presents an example for application of control strategies that may affect both diseases and the first study to apply such an approach in school settings. The interventions were well received and highly appreciated by students and teachers. An apparent absence of effect in primary outcome indicators could be the result of pupils being exposed to risk factors outside the school area and mosquitoes flying in from nearby uncontrolled breeding sites. Integrated interventions targeting these diseases in a school context remain promising because of the reduced mosquito breeding and improved water quality, as well as educational benefits. However, to improve outcomes in future integrated approaches, simultaneous interventions in communities, in addition to schools, should be considered; using appropriate combinations of site-specific, effective, acceptable, and affordable interventions.
TRIAL REGISTRATION: ClinicalTrials.gov no. ISRCTN40195031.
BACKGROUND: Uruguay is located at the southern border of Aedes aegypti distribution on the South American sub-continent. The reported dengue cases in the country are all imported from surrounding countries. One of the cities at higher risk of local dengue transmission is Salto, a border city with heavy traffic from dengue endemic areas.
METHODS: We completed an intervention study using a cluster randomized trial design in 20 randomly selected 'clusters' in Salto. The clusters were located in neighborhoods of differing geography and economic, cultural and social aspects.
RESULTS: Entomological surveys were carried out to measure the impact of the intervention on vector densities. Through participatory processes of all stakeholders, an appropriate ecosystem management intervention was defined. Residents collected the abundant small water holding containers and the Ministry of Public Health and the Municipality of Salto were responsible for collecting and eliminating them. Additional vector breeding places were large water tanks; they were either altered so that they could not hold water any more or covered so that oviposition by mosquitoes could not take place.
CONCLUSIONS: The response from the community and national programme managers was encouraging. The intervention evidenced opportunities for cost savings and reducing dengue vector densities (although not to statistically significant levels). The observed low vector density limits the potential reduction due to the intervention. A larger sample size is needed to obtain a statistically significant difference.
BACKGROUND: Long-lasting insecticide-treated net (LLIN) window and door curtains alone or in combination with LLIN water container covers were analysed regarding effectiveness in reducing dengue vector density, and feasibility of the intervention.
METHODS: A cluster randomised trial was conducted in an urban area of Colombia comparing 10 randomly selected control and 10 intervention clusters. In control clusters, routine vector control activities were performed. The intervention delivered first, LLIN curtains (from July to August 2013) and secondly, water container covers (from October to March 2014). Cross-sectional entomological surveys were carried out at baseline (February 2013 to June 2013), 9 weeks after the first intervention (August to October 2013), and 4-6 weeks after the second intervention (March to April 2014).
RESULTS: Curtains were installed in 922 households and water container covers in 303 households. The Breteau index (BI) fell from 14 to 6 in the intervention group and from 8 to 5 in the control group. The additional intervention with LLIN covers for water containers showed a significant reduction in pupae per person index (PPI) (p=0.01). In the intervention group, the PPI index showed a clear decline of 71% compared with 25% in the control group. Costs were high but options for cost savings were identified.
CONCLUSIONS: Short term impact evaluation indicates that the intervention package can reduce dengue vector density but sustained effect will depend on multiple factors.
OBJETIVOS: se acumulan y analizar la viabilidad, el proceso, y la eficacia de un ecosistema de intervención de gestión alianza impulsada en la reducción de la cría del vector del dengue y la construcción de alianzas sostenibles entre múltiples partes interesadas. MÉTODOS: Un estudio de intervención basado en la comunidad se llevó a cabo a partir de mayo 2009-enero 2010 en la ciudad de Yangon. Seis de alto riesgo y seis grupos de bajo riesgo fueron asignados al azar y se asignan como áreas de intervención y servicios de rutina, respectivamente. Para cada grupo, 100 hogares fueron cubiertos. Se llevaron a cabo evaluaciones bimensuales entomológicos (es decir, de larva y pupa) encuestas y estudios de aceptabilidad de los hogares al final del período de intervención de 6 meses, complementado con evaluaciones cualitativas. Descripción Intervención: Las estrategias incluyen grupos ecológicos asociados múltiples partes interesadas (Thingaha) y voluntarios de la sala, la toma de decisiones informada de los cabezas de familia, seguido de enfoque de gestión integrada de vectores. RESULTADOS: Las pupas por Índice persona (IPP) disminuyó en la última evaluación por 5Â · 7% (0Â · 35-0Â · 33) en grupos de alto riesgo. Pero en grupos de bajo riesgo, PPI notablemente disminuyó 63A · 6% (0Â · 33-0Â · 12). En el área de servicio de rutina, PPI también disminuyó debido a la disponibilidad de Temephos después del ciclón Nargis. En cuanto a número total de pupas en todos los contenedores, cuando se compara con la evaluación 1, hubo una reducción de 18º · 6% en la evaluación 2 y 44A · 1% en la evaluación 3 en la zona de intervención. Sin embargo, en el área de servicio de rutina, se observó más reducción. Todas las herramientas de intervención se encontraron como aceptables, siendo factible implementar por grupos asociados con múltiples partes interesadas. Conclusiones: La eficacia de las intervenciones de asociación impulsada controlados por la comunidad resultó ser superior al enfoque vertical en términos de sostenibilidad y empoderamiento de la comunidad.
BACKGROUND: Long-lasting insecticidal net screens (LLIS) fitted to domestic windows and doors in combination with targeted treatment (TT) of the most productive Aedes aegypti breeding sites were evaluated for their impact on dengue vector indices in a cluster-randomised trial in Mexico between 2011 and 2013.
METHODS: Sequentially over 2 years, LLIS and TT were deployed in 10 treatment clusters (100 houses/cluster) and followed up over 24 months. Cross-sectional surveys quantified infestations of adult mosquitoes, immature stages at baseline (pre-intervention) and in four post-intervention samples at 6-monthly intervals. Identical surveys were carried out in 10 control clusters that received no treatment.
RESULTS: LLIS clusters had significantly lower infestations compared to control clusters at 5 and 12 months after installation, as measured by adult (male and female) and pupal-based vector indices. After addition of TT to the intervention houses in intervention clusters, indices remained significantly lower in the treated clusters until 18 (immature and adult stage indices) and 24 months (adult indices only) post-intervention.
CONCLUSIONS: These safe, simple affordable vector control tools were well-accepted by study participants and are potentially suitable in many regions at risk from dengue worldwide.
Synthetic repellents based on di-ethyl 3-methyl benzamide (DEET) are a popular method of obtaining protection from mosquitoes and yet clear evidence for a protective effect against malaria has hitherto never been convincingly demonstrated. A household randomized trial was undertaken among a study population of 127 families (25%) in an Afghan refugee village in Pakistan to compare the efficacy of repellent soap (Mosbar containing 20% DEET and 0.5% permethrin) vs. a placebo lotion. Cases of falciparum and vivax malaria were detected by passive case detection at the camp's clinic. At the end of the 6 month trial 3.7% (23 of 618) of individuals in the Mosbar group had presented with one or more episodes of falciparum malaria compared with 8.9% (47 of 530) of the placebo group (odds ratio 0.44, 95% CI 0.25-0.76). 16.7% of the Mosbar group (103 of 618) presented with vivax malaria compared with 11.7% (62 of 530) of the placebo group, and thus no effect was shown against vivax malaria (odds ratio 1.29, 95% CI 0.86-1.94). A considerable proportion of individuals (22%) had presented with vivax malaria during the 7 months leading up to the trial and thus any intervention effect would be partially masked by relapsed infections. The distribution of mosquitoes among households was broadly similar between Mosbar and placebo groups. The repellent was popularly received and very few side-effects were reported. There is a case for giving repellents more prominence in public health as a preventive measure in regions where vectors bite in the early evening or in emergency situations such as epidemics or newly established refugee camps.
