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• W2912678428 abstract "To determine the effectiveness and degree of implementation of interventions for the control of Aedes aegypti in Latin America and the Caribbean (LAC) as reported in scientific literature. We searched MEDLINE, EMBASE, CENTRAL, SOCINDEX, and LILACS, for experimental and observational studies, economic assessments and qualitative experiences carried out in LAC from 2000 to 2016. We assessed incidence and morbimortality of Aedes aegypti-related diseases and entomological indices: Breteau (containers), House, and Pupae per Person. We used GRADE methodology for assessing quality of evidence. Of 1826 records retrieved, 75 were included and 9 cluster randomised clinical trials could be meta-analysed. We did not identify any intervention supported by a high certainty of evidence. In consistency with qualitative evidence, health education and community engagement probably reduces the entomological indices, as do the use of insecticide-treated materials, indoor residual spraying and the management of containers. There is low certainty of evidence supporting the use of ovitraps or larvitraps, and the integrated epidemiological surveillance strategy to improve indices and reduce the incidence of dengue. The reported degree of implementation of these vector control interventions was variable and most did not extend to whole cities and were not sustained beyond 2 years. We found a general lack of evidence on effectiveness of vector control in the region, despite a few interventions that showed moderate to low certainty of evidence. It is important to engage and educate the community, apart from achieving the implementation of integrated actions between the health and other sectors at national and regional level. Déterminer l'efficacité et le degré d'implémentation des interventions de lutte contre Aedes aegypti en Amérique latine et dans les Caraïbes (ALC), tels que décrits dans la littérature scientifique. Nous avons effectué des recherches dans MEDLINE, EMBASE, CENTRAL, SOCINDEX et LILACS pour des études expérimentales et d'observation, des évaluations économiques et des expériences qualitatives réalisées dans la région ALC de 2000 à 2016. Nous avons évalué l'incidence et la morbimortalité des maladies liées à Aedes aegypti et les indices entomologiques: Breteau (conteneurs), Maison et Pupe par Personne. Nous avons utilisé la méthodologie GRADE pour évaluer la qualité des données. Sur 1.826 articles retrouvés, 75 ont été inclus et 9 essais cliniques randomisés en grappes ont pu être méta-analysés. Nous n'avons identifié aucune intervention étayée par une certitude élevée. De manière cohérente avec les preuves qualitatives, l’éducation pour la santé et la participation de la communauté réduisent probablement les indices entomologiques, de même que l'utilisation de matériaux traités à l'insecticide, la pulvérisation de résidus à l'intérieur et la gestion des conteneurs. Il existe peu de certitude quant aux données soutenant l'utilisation des ovitraps ou des larvitraps et de la stratégie de surveillance épidémiologique intégrée visant à améliorer les indices et à réduire l'incidence de la dengue. Le degré d'implémentation rapporté pour ces interventions de lutte antivectorielle était variable et la plupart ne s’étendaient pas à l'entièreté des villes et ne duraient pas plus de deux ans. Nous avons constaté un manque général de preuves sur l'efficacité de la lutte antivectorielle dans la région, malgré quelques interventions montrant une certitude modérée à faible. Il est important d'impliquer et d’éduquer la communauté, outre la mise en œuvre d'actions intégrées entre le secteur de la santé et d'autres secteurs aux niveaux national et régional. Aedes aegypti is the mosquito that causes the propagation of diseases such as zika, dengue, chikungunya and yellow fever. This mosquito is present both in urban and forest environments, in almost all countries of the American continent except for Canada and Chile 1. The most important macro-determinants for the development of the diseases are population density increase, poor health conditions in the urban areas, deterioration of the public health systems and lack of effective vector control programs, together with environmental factors such as rainfall levels and average temperatures 2. Currently, 61 countries and territories globally report the active transmission of these diseases 3, 4. In the last years their burden and impact in the region have increased, including a reappearance of yellow fever in Brazil 5. In 2015, the Zika virus was introduced in Brazil and it rapidly spread all over the Americas. Since then, there has been a confirmed increase in the rates of microcephaly, placental failure, growth delays and foetal death related to Zika virus infection during pregnancy and an increase in the cases of Guillain-Barre syndrome. Thus WHO declared, on February 1, 2016, a major international public health emergency related to the Zika virus infection, and recommended an increase in surveillance and research activities 6. Meanwhile there are approximately 50–100 million new cases of dengue and about 2500 million people living in endemic areas worldwide 7. Throughout the year, low-level transmission has been observed, but most countries exhibit an epidemic pattern 8. Our group published a systematic review on Dengue epidemiology in Latin America and the Caribbean (LAC) 9, which analysed the incidence trends of both classic and hemorrhagic dengue, mortality and direct health costs attributed to it between 1995 and 2010. In the past, different programs for vector control introduced in Latin America included different approaches, some vertical and others decentralised 10. The world strategy for the prevention and control of dengue has five main components: vector control, based on the principles of vector integrated management; active disease surveillance based on a comprehensive health information system; emergency preparedness; capacity development and training; and vector control research. The Pan-American Health Organization (PAHO) managed in the last 15 years an intensive program called Communication for Behavioral Impact (COMBI) 11 with the objective of ensuring a flow of timely and accurate information to the public. Capacity building was considered the main tool in this program for developing social mobilisation and communication activities focused on behavioral change. The current PAHO strategy is known as EGI-Dengue. Although facing many obstacles, such as lack of continuity, lack of validated behaviour indicators or support from ministries, the program succeeded in achieving health education goals in many countries. Another potential public health strategy is vaccination for the prevention of dengue in high-demand areas, which is currently in the planning stage. With regards to yellow fever, vaccination is recommended for areas at risk of active transmission within the different countries in the region 12, although the current epidemic of yellow fever in the Americas so far does not involve Aedes aegypti. There are no recommendations for chikungunya 13. Although there are many ongoing programs with significant resource allocation, no systematic reviews have been done so far to comprehensively synthesise performance of strategies in the LAC region. The purpose of this study was hence to collect information on effectiveness, cost-effectiveness of the vector control strategies 14 and implementation experiences as reported in scientific literature. This work was part of a wider mixed qualitative 15, 16 and quantitative research. The report of this systematic review and meta-analysis of observational studies follows the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) 17 and the Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) 18 guidelines. Also, it was registered in the PROSPERO (CRD42016038067) database of systematic reviews. The protocol for this work was published in the PAHO journal 14. We performed a systematic search in several databases, including MEDLINE, EMBASE, CENTRAL, SOCINDEX and LILACS from January 2000 to September 2016 (see Appendix S1 for details on the search strategy). We included grey literature through personal contact with the main authors, and by means of generic internet searches. Moreover, we searched the websites of WHO, several NGOs, Google and Google Scholar, specific sites of health ministries for arboviruses, scientific societies, vector congresses, the ISOPS VIII International Symposium on Phlebotomine Sandflies, the Annals of the International Society for Infectious Diseases international congresses, the Pan American Dengue Research Network meeting repositories, the site of the EGI Dengue Integrated Management Strategy and grey literature databases such as Teseo (Spanish theses), Opengray and Sigle. Experimental, quasi-experimental and observational studies, economic assessments and qualitative studies related to control interventions on diseases transmitted by the Aedes aegypti mosquito, such as dengue, zika, chikungunya and yellow fever were considered. Studies conducted since 1995, assessing the control strategies described in Box 1 were included. We excluded mathematic model reports without direct observation, and entomological or epidemiological surveillance studies that were not part of a wider vector control program. The study selection was made by means of EROS® (Early Review Organizing Software, Institute for Clinical Effectiveness and Health Policy [IECS], Buenos Aires), a web platform designed to facilitate the execution of systematic reviews 19. We included articles from any epidemiological design, from LAC countries, reporting about the effectiveness or degree of implementation of vector control interventions of any kind. Independent researchers, in pairs, reviewed all identified studies by title and abstract, and then analysed the full text of all selected articles that fulfilled the above-mentioned inclusion criteria. Disagreements were resolved by consensus within the review team. If the data of the included studies were considered to be unclear or insufficient, the authors were consulted. We used a previously piloted web-based spreadsheet to compile the information. One reviewer extracted the data from the included studies, and another verified them. The following data were included: Continent and country; publication date; effectiveness related to vectoral indices; intervention implementation level and type; type of epidemiological design of the study; rural or urban environment; special population groups (pregnant women, workers) and type of sampling (probabilistic or not). The outcomes under consideration were: incidence and morbimortality of Aedes aegypti-related diseases, larval indices for monitoring the effect of control strategies including Breteau, House index and Pupae per Person index, and degree of implementation or coverage levels by jurisdiction. These density indices are globally the most used in surveillance. We also assessed other vectoral indices such as recipient productivity, adult population estimation and ovitrap positivity rate. Finally, we considered general knowledge of the population on vector control, and the programmatic costs and cost-effectiveness data whenever available. With regards to the risk of bias assessment of observational studies, we used a tool based upon the verification list STROBE 20, two methodological documents, Sanderson et al. 21 and Fowkes and Fulton 22. This tool considered four major criteria (study participant selection methods, methods of exposure measuring and variable results, methods to control the confounding factors and comparability between the groups) and two minor criteria (statistical methods, excluding confounding and conflict of interest) (see Appendix S2). We used the Cochrane Handbook to assess the quality of the evidence from clinical trials, and quasi-experimental studies were assessed with the EPOC group tool of Cochrane 23. In order to assess the quality of economic evaluations, we used the tool proposed by Drummond et al. 24 and for qualitative studies, the Mays et al. checklist 25. Two independent reviewers assessed the methodological quality of all included studies. Discrepancies were resolved by consensus of the whole team. Finally, to assess the quality of evidence provided by each category of interventions, we used the GRADE methodology 26. Briefly, the GRADE quality of evidence can be High, Moderate, Low and Very Low. High quality means that further research is very unlikely to change our confidence in the estimate of effect; moderate quality refers to further research likely to have an important impact on our confidence in the estimate of effect and may change the estimate; low quality implies further research very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate; and very low quality means that we are very uncertain about the estimate. We used simple descriptive statistics when it was not possible to calculate association measurements. Meta-analyses were carried out for analytic studies by using Odds Ratio (OR) and Relative Risks (RR), with their corresponding Confidence Intervals (CI). Additionally, we utilised the method of the inverse of the generic variance in order to combine different effect measurements. To perform these analyses, we used RevMan version 5.3. A DerSimonian-Laird random effect model was selected, taking into account potential differences in methods, result measurement tools and populations as possible sources of heterogeneity 19, assessed by means of the I2 statistic. We planned publication bias analyses by means of funnel graphs, if the number of studies selected for meta-analysis was at least an arbitrary number of ten. Sub-group analyses considered a priori were: area of infestation by mosquitoes by aedic index; flavivirus disease incidence rate and classification of the country's income level according to the World Bank classification. The search strategy yielded 1926 studies in the databases described. Figure 1 shows a flowchart of the selection process. Of the 75 studies included, which met the inclusion criteria for data synthesis, 51 were quantitative with varied epidemiological designs and 24 were of a qualitative-type. The most frequent reason for exclusion was the lack of sufficient description of the implemented control strategies. A total number of nine cluster randomised controlled trials (RCTs), of 15 relevant trials, could be meta-analysed. Most epidemiological studies were from Cuba (N = 11), Brazil (N = 10), Colombia (N = 6), Mexico (N = 4), Peru (N = 4) and multiple countries (N = 4) (Table 1). Other countries represented were Argentina, Costa Rica, Guatemala, Honduras and Puerto Rico. Main characteristics and results are shown in Table 1. Colonia Delicia, Misiones. 4750 inhabitants Moreno, Pernambuco. 56 650 inhabitants Boa Vista, Roraima. Nearly 285 000 inhabitants La Dorada. 228 people, heads of household Bucaramanga four neighborhoods with high incidence of dengue. Santiago. 20 neighborhoods Questionnaire to assess people's involvement in the decision-making, implementation and evaluation of dengue control activities Routine entomological surveillance data collected by the National Vector Control Program. Breteau Index Guantanamo. 12 clusters (500 homes approximately) La Lisa, Havana. 16 intervention clusters (389 houses) Container Index. Breteau Index. Entomological indicators: Household index Production of the Aedes control program: houses inspected/treated. Health services: number of fever cases detected, laboratory tests carried out, hospitalised patients. Hospital indicators: number of admissions due to dengue, number of discharges, average length of stay, number of diagnostic tests performed Guantanamo. 12 clusters of 500 houses each Poptun. 10 experimental clusters and 10 control clusters. 2357 houses Comayaguela. Four schools, two experimental and two control Comayaguela. Teachers and students. 10 marginal communities. 6740 households and 36 800 inhabitants Colima. 187 houses grouped into 4 blocks Acapulco. 20 clusters 60 clusters in Nicaragua and 90 in Mexico. In Mexico, the population is from Costa Grande, Acapulco and Costa Chica. In Nicaragua, the population is from Managua Specific dengue infection rate (saliva samples) in children aged 3–9 years. House, Container, Breteau and Pupae per Person Indices Iquitos. 2800 households Iquitos. Two comparable neighbourhoods with 2500 inhabitants each Breteau index. House index Container index Girardot. Nine schools Breteau index. Pupae index Breteau index. Pupae index. Regarding the methodological quality and bias risk, of the 51 quantitative studies included, 15 used a cluster RCT design; nine were non-randomised controlled field trials; four were interrupted time-series; 10 were before-after studies, six were descriptive or ecological observational studies, and seven were economic evaluations. In Appendix S3, a graphical report of the methodological quality of the studies identified can be found, according to their epidemiological design. RCTs are of moderate or low methodological quality in most domains explored, except for the domain related to blinding of evaluators, where the risk of bias was generally low. In non-randomised clinical trials, the risk of bias was generally high in most domains, except for incomplete or selective reporting of data and conflicts of interest. Interrupted time series showed a moderate risk of bias in most domains, except for how to address the effects of secular trends, where bias risk was high. Before/after studies lacked description of some domains, such as baseline measurements or of those characteristics of studies used as control and showed low risk of information bias but entailed relatively moderate detection bias. Qualitative studies showed a low-to-moderate risk of bias, except for the process of research and sampling, where a high risk of bias was frequent. In health economic evaluations, the risk of bias was moderate, in general. Differential adjustment by time and characterisation of uncertainty of costs and health consequences were the domains with the worst performance; in general, the rest of the domains showed moderate-to-low risk of bias. Finally, in observational studies, the risk of bias was globally moderate, with a worse performance in the domain of control of confounders. Appendix S4 shows the characteristics and main findings for the remaining 24 qualitative research studies. Five cluster RCTs that evaluated insecticide-treated materials (ITM) were identified 58, 60, 65, 66, 76, 77, two of them from the same experience in Cuba 65, 77. Regarding treated bednets and/or curtains, a non-significant reduction in the Breteau Index was observed after the evaluation period (Risk Difference −5.00; CI 95%: −11.69 to 1.69; sub-studies = 2 (66)), similar to the House Index (Mean Difference, inverse variance, of −0.04; CI 95%: −0.14 to +0.06; studies = 1 (58)). As for treated water covers, Tun-Lin et al. 76 in Venezuela reported that the BI showed a non-significant reduction (Risk Difference 0.84; CI 95%: −8.94 to 10.62) and the Pupae per person index (PPI) showed an also non-significant OR of 0.98; CI 95%: 0.47–2.02. Considering both types of ITMs in combination, the PPI showed a non-significant reduction of 0.84 CI 95%: 0.61–1.16; studies = 3 60, 76, 77), although Che-Mendoza et al. 77. found statistically significant evidence of reduction in the House Index (OR 0.44 CI 95%: 0.26–0.74). Acceptance for interventions was high in Venezuela and Mexico, with more than 87–95% of respective households in the cities with interventions using treated curtains, and to a lesser extent, water jar covers. Similarly, a high coverage of the population was achieved in the Guatemala study by Rizzo et al. 60. The effect of ITMs lasted at least 24 months in Mexico as reported by Che-Mendoza et al. 77, but dropped to 50% in the Venezuelan study by Tun Lin 76. Two large quasi-experimental studies conducted in Venezuela 74, 75 reported similar results (Table 2 of non-randomised studies). As for the use of larvicides in breeding sites, in Peru Tun Lin in 2009 76 showed non-significant results (OR 1.44, CI 95%: 0.97–2.14) in the reduction of larval indices for active vs. non-active arms, after 5 months of follow up. In two of the non-randomised studies conducted in Brazil 30, 35, a multifaceted intervention including control of breeding sites and the mass collection of eggs in one of the sites prevented the occurrence of a hypothetical Aedes population outbreak (Table 2). Another study in Colombia reported a reduction in the incidence of dengue cases (RR 0.19; CI 95%: 0.12–0.30, P < 0.001) 45. Two cluster RCT assessed the use of indoor residual spraying 63, 76. No statistically significant benefits were found in any of the assessed indices, OR of 0.84 [0.59, 1.19] for Espinoza-Gomez [35] in the House Index. No RCT was identified testing the effectiveness of outdoor fogging. The level of coverage of the population of western Colima by Espinoza-Gomez 35 was of 3% of households. Two non-randomised studies conducted in Argentina and Peru were identified 27, 71. These studies reported a reduction in larval indices with the use of insecticide spraying in houses. A cross-sectional study in Brazil 37 with multiple surveys assessed insecticide resistance for various agents in the state of Sao Paulo. The authors found evidence of resistance and suggested that management of resistance development needs to be adopted when insect populations show reduced susceptibility. No randomised clinical trials were found. Three non-randomised trials and two before/after studies 31, 46, 69, 70, 72 carried out in Brazil, Colombia, Peru and Puerto Rico were identified, which reported a reduction in vector densities by means of the use of lethal oviposition trap-based mass interventions, for example ALOT ovitraps and CDC autocidal ovitraps. In one of these studies, it was suggested that the association with the use of deltamethrin was effective 46. In Wesson's study, apart from reduction in indices, a reduction in the incidence of dengue was also found. Finally, the aforementioned studies of mixed interventions 30, 35 also used traps. (Table 2) One single cluster RCT, Tun Lin 2009 – Mexico 76, evaluated the usefulness of reservoir reduction in mosquito control, reporting a statistically non-significant reduction in the Breteau index (−12.65; IC 95%: −28.77 to +3.47). A statistically significant reduction in the pupae per person index (−0.529; CI 95%: −1.034 to −0.024) was mentioned. A quasi-experimental study 48 performed in Costa Rica reported a sharp decline in larval indices with an adequate reservoir management (Table 2). Four cluster RCTs assessed the implementation of health education strategies and the incentive of community engagement 51, 55, 67, 76. These studies demonstrated a significant reduction in the Breteau Index (pooled OR 0.58; CI 95%: 0.46–0.72; studies = 4, Figure 2), in the House Index (OR 0.53; CI 95%: 0.32–0.86; studies = 2) and in the Pupae Index (OR 0.38; CI 95%: 0.18–0.78; studies = 2). High levels of coverage of interventions were achieved by the Camino Verde study in Nicaragua and Mexico 67, being community-based trials. Among six additional non-randomised studies 43, 49, 56, 61, 62, 73 carried out in Colombia, Venezuela and Cuba two found a reduction in the larval indices, one showed a reduction in the number of reservoirs and two studies that assessed knowledge and attitudes related to mosquito prevention reported a reduction in mosquitoes. Table 2 shows the main results of non-experimental studies. Under this topic we frame multifaceted studies using an integrated approach and part of a vector control program. We found a single non-randomised clinical trial performed in Cuba 52. Their community empowerment intervention targeted five participatory processes: training, community dengue surveillance, social communications, behavioral change and participation assessment, and showed the achievement of adequate behavioral pattern with a reduction in BI. In Colombia, in the city of La Dorada, in 2010, Pacheco Coral et al. 42. described a study that utilised cluster sampling in neighborhoods with the highest number of cases of Aedes aegypti-borne diseases and the highest density of mosquitoes reported in previous years, and where the Information, Education and Communication (IEC) strategy had been implemented needing surveillance. Within these neighbourhoods, 228 houses were randomly selected. Reservoirs were tested. There were also no larvae or pupae in homes where people had knowledge about dengue disease and its transmission. Almost 80% of the people in the target area were educated on the topic thanks to this strategy. Also in Colombia, in 2002, Romero Vivas et al. 41. described a method to identify the most productive containers (surveillance), but also to avoid oviposition mechanically by using netted lids built with local materials. The intervention consisted of mechanical barriers (lids) fitted on the most productive breeding sites. Although no correlation was observed between temporal fluctuation of populations of larval Aedes aegypti and monthly rainfall, the barriers were effective. Finally, in Peru, Machaca et al. 68 described in 2002 a surveillance study based on planned and periodic campaigns for the washing of water recipients for human and/or animal consumption (reservoirs, cylinders, buckets, clay pots, flowerpots, tires, etc.). The aedic index decreased from 46% to 3.3% in 20 days. The remaining RCTs we found 38, 44, 47, 51, 54, 64 could not be included in pooled analyses due to lack of detail, data duplication, or lack of controlled comparisons. The summarised findings for other non-randomised studies, quasi-experimental designs and health economic evaluations are shown in Table 1. The evidence found for other interventions, such as surveillance programs, school programs or training of community leaders is shown in Table 2. For some other interventions, such as advocacy, biogents, mosquito repellent or coils or media campaigns, we found no evidence on effectiveness in the LAC region. We identified 25 qualitative studies regarding different topics related to Aedes aegypti control (see Appendix S4). In general, the risk of bias in those studies was low or moderate. Methodologies were varied, including surveys, structured interviews, and focus groups; mainly done in general population, although health professionals and decision makers were also interviewed in some of them. The main topics mentioned were: the need for community commitment; the partial knowledge about the real health risk that dengue disease entails and the relatively broad knowledge of the measures to control the vector, but with a lack of application. Contradictory results were found in relation to the perception of the usefulness of fumigation. The risk of vector multiplication in favourable environments for their dissemination, such as abandoned houses, vacant lots and streams, was better known than the perception of risk within the household. Some studies revealed the perception that actions carried out by the government were insufficient or uncoordinated. An important barrier to control was observed due to the need to store water in tanks without the possibility of keeping them free of larvae, as well as some resistance to the implementation of bednets and curtains impregnated with insecticides due to their maintenance and feeling of insecurity. Details are found in Appendix S4. The PRISMA Checklist is in Appendix S5. This study summarises the information identified in the LAC region regarding the interventions for the control of Aedes aegypti for over 15 years. A comprehensive literature review and an assessment of the methodological quality of the studies included was conducted. Most of the available data were from Brazil, Argentina, Cuba, Mexico and Peru. The RCTs were of moderate or low methodological quality. The main findings were that in the LAC region, there is an important knowledge gap; that few types of interventions were supported by evidence on their effectiveness, and that many others showed low effectiveness. As previously mentioned, for most interventions listed in Chart 1, however, we found no (or very scarce) scientifically sound evidence on effectiveness. ITMs may reduce the entomological indices, both in experimental and quasi-experimental studies, although trials’ estimates did not reach statistical significance. For insecticides in breeding sites, although a few non-randomised studies showed some degree of effectiveness, RCTs showed non-significant results. No statistically significant benefits were found in any of the assessed indices for indoor residual spraying; yet some low-quality evidence showed reduction in larval indices. No RCT was identified which tested the performance of outdoor fogging. Regarding trap-based mass interventions, no RCTs were found. However, three non-randomised studies reported effectiveness. For the management of containers, we found only one RCT, with mixed results, and a quasi-experimental study showing a sharp reduction in indices with adequate reservoir management. Epidemiological surveillance as part of integrated control programs showed some degree of effectiveness coming from non-randomised studies. Vector control integrated strategies not always increase efficacy. The Integrative Vector Management strategy (IVM) has been pointed out as the ultimate action of governments and public health departments to mitigate disease transmission. Even a combined approach might have little impact if community engagement is not an integral part of IVM strategy. Regarding health education and community engagemen" @default.
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• W2912678428 title "Interventions for the control of <i>Aedes aegypti</i> in Latin America and the Caribbean: systematic review and meta‐analysis" @default.
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