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This study describes the evolution of knockdown resistance (kdr) haplotypes in Aedes aegypti in response to pyrethroid insecticide use over the course of 18 years in Iquitos, Peru. Based on the duration and intensiveness of sampling (~10,000 samples), this is the most thorough study of kdr population genetics in Ae. aegypti to date within a city. We provide evidence for the direct connection between programmatic citywide pyrethroid spraying and the increase in frequency of specific kdr haplotypes by identifying two evolutionary events in the population. The relatively high selection coefficients, even under infrequent insecticide pressure, emphasize how quickly Ae. aegypti populations can evolve. In our examination of the literature on mosquitoes and other insect pests, we could find no cases where a pest evolved so quickly to so few exposures to low or nonresidual insecticide applications. The observed rapid increase in frequency of resistance alleles might have been aided by the incomplete dominance of resistance-conferring alleles over corresponding susceptibility alleles. In addition to dramatic temporal shifts, spatial suppression experiments reveal that genetic heterogeneity existed not only at the citywide scale, but also on a very fine scale within the city.

Dengue is one of the most important vector-borne diseases, resulting in an estimated hundreds of millions of infections annually throughout the tropics. Control of dengue is heavily dependent upon control of its primary mosquito vector, Aedes aegypti. Innovative interventions that are effective at targeting the adult stage of the mosquito are needed to increase the options for effective control. The use of insecticide-treated curtains (ITCs) has previously been shown to significantly reduce the abundance of Ae. aegypti in and around homes, but the impact of ITCs on dengue virus (DENV) transmission has not been rigorously quantified. A parallel arm cluster-randomized controlled trial was conducted in Iquitos, Peru to quantify the impact of ITCs on DENV seroconversion as measured through plaque-reduction neutralization tests. Seroconversion data showed that individuals living in the clusters that received ITCs were at greater risk to seroconverting to DENV, with an average seroconversion rate of 50.6 per 100 person-years (PY) (CI: 29.9-71.9), while those in the control arm had an average seroconversion rate of 37.4 per 100 PY (CI: 15.2-51.7). ITCs lost their insecticidal efficacy within 6 months of deployment, necessitating re-treatment with insecticide. Entomological indicators did not show statistically significant differences between ITC and non-ITC clusters. It's unclear how the lack of protective efficacy reported here is attributable to simple failure of the intervention to protect against Ae. aegypti bites, or the presence of a faulty intervention during much of the follow-up period. The higher risk of dengue seroconversion that was detected in the ITC clusters may have arisen due to a false sense of security that inadvertently led to less routine protective behaviors on the part of households that received the ITCs. Our study provides important lessons learned for conducting cluster randomized trials for vector control interventions against Aedes-transmitted virus infections.

Aedes mosquito-borne viruses (ABVs) place a substantial strain on public health resources in the Americas. Vector control of Aedes mosquitoes is an important public health strategy to decrease or prevent spread of ABVs. The ongoing Targeted Indoor Residual Spraying (TIRS) trial is an NIH-sponsored clinical trial to study the efficacy of a novel, proactive vector control technique to prevent dengue virus (DENV), Zika virus (ZIKV), and chikungunya virus (CHIKV) infections in the endemic city of Merida, Yucatan, Mexico. The primary outcome of the trial is laboratory-confirmed ABV infections in neighborhood clusters. Despite the difficulties caused by the COVID-19 pandemic, by early 2021 the TIRS trial completed enrollment of 4,792 children aged 2–15 years in 50 neighborhood clusters which were allocated to control or intervention arms via a covariate-constrained randomization algorithm. Here, we describe the makeup and ABV seroprevalence of participants and mosquito population characteristics in both arms before TIRS administration. Baseline surveys showed similar distribution of age, sex, and socio-economic factors between the arms. Serum samples from 1,399 children were tested by commercially available ELISAs for presence of anti-ABV antibodies. We found that 45.1% of children were seropositive for one or more flaviviruses and 24.0% were seropositive for CHIKV. Of the flavivirus-positive participants, most were positive for ZIKV-neutralizing antibodies by focus reduction neutralization testing which indicated a higher proportion of participants with previous ZIKV than DENV infections within the cohort. Both study arms had statistically similar seroprevalence for all viruses tested, similar socio-demographic compositions, similar levels of Ae. aegypti infestation, and similar observed mosquito susceptibility to insecticides. These findings describe a population with a high rate of previous exposure to ZIKV and lower titers of neutralizing antibodies against DENV serotypes, suggesting susceptibility to future outbreaks of flaviviruses is possible, but proactive vector control may mitigate these risks. [ABSTRACT FROM AUTHOR]

Water-related diseases such as diarrhoeal diseases from viral, bacterial and parasitic organisms and Aedes-borne arboviral diseases are major global health problems. We believe that these two disease groups share common risk factors, namely inadequate household water management, poor sanitation and solid waste management. Where water provision is inadequate, water storage is essential. Aedes mosquitoes commonly breed in household water storage containers, which can hold water contaminated with enteric disease-causing organisms. Microbiological contamination of water between source and point-of-use is a major cause of reduced drinking-water quality. Inadequate sanitation and solid waste management increase not only risk of water contamination, but also the availability of mosquito larval habitats. In this article we discuss integrated interventions that interrupt mosquito breeding while also providing sanitary environments and clean water. Specific interventions include improving storage container design, placement and maintenance and scaling up access to piped water. Vector control can be integrated into sanitation projects that target sewers and drains to avoid accumulation of stagnant water. Better management of garbage and solid waste can reduce the availability of mosquito habitats while improving human living conditions. Our proposed integration of disease interventions is consistent with strategies promoted in several global health frameworks, such as the sustainable development goals, the global vector control response, behavioural change, and water, sanitation and hygiene initiatives. Future research should address how interventions targeting water, sanitation, hygiene and community waste disposal also benefit Aedes-borne disease control. The projected effects of climate change mean that integrated management and control strategies will become increasingly important. Gestion integree des maladies: arboviroses et diarrhees liees a l'eau Diarrhees provoquees par la presence d'organismes viraux, bacteriens et parasites, arboviroses vehiculees par les moustiques Aedes: les maladies liees a l'eau constituent un probleme de sante majeur dans le monde. Nous pensons que ces deux groupes de maladies partagent les memes facteurs de risque, a savoir une mauvaise gestion de l'eau au sein du foyer ainsi qu'un manque d'assainissement et de traitement des dechets solides. Dans les endroits oU l'approvisionnement en eau est insuffisant, les conditions de conservation sont essentielles. Les moustiques Aedes se reproduisent frequemment dans les reservoirs d'eau a domicile, qui peuvent des lors contenir de l'eau contaminee par des organismes responsables d'infections enteriques. La contamination microbiologique de l'eau, entre la source et le moment oU elle est consommee, represente l'une des causes principales d'alteration de la qualite de l'eau potable. Le manque d'assainissement et de traitement des dechets solides fait augmenter le risque de contamination de l'eau, mais aussi le nombre de biotopes disponibles pour les larves de moustique. Dans cet article, nous parlons des interventions integrees qui permettent d'interrompre la reproduction des moustiques tout en creant des environnements sanitaires adaptes et de l'eau propre. Ces interventions specifiques prevoient notamment une optimisation de la conception, du placement et de l'entretien des reservoirs, ainsi qu'un meilleur acces a l'eau courante. La lutte contre les vecteurs peut etre incorporee dans des projets d'assainissement qui ciblent les egouts et canalisations, afin d'eviter toute accumulation d'eau stagnante. Une meilleure gestion des ordures menageres et des dechets solides peut reduire le nombre de biotopes disponibles pour les moustiques, mais aussi ameliorer les conditions de vie de la population. Nous proposons une gestion integree des maladies coherente avec les strategies mises en avant dans plusieurs cadres de sante mondiaux tels que les objectifs de developpement durable, l'action mondiale pour lutter contre les vecteurs, le changement de comportement ainsi que les initiatives relatives a l'approvisionnement en eau, l'assainissement et l'hygiene. Les futures recherches devraient etudier la facon dont les interventions dediees a l'eau, a l'assainissement, a l'hygiene et a l'elimination des dechets au sein des communautes contribuent egalement a la lutte contre les maladies vehiculees par les moustiques Aedes. Compte tenu des effets attendus du changement climatique, les strategies de lutte et de gestion integree vont gagner en importance. Gestion integrada de enfermedades: infecciones arbovirales y diarreas transmitidas por el agua Las enfermedades relacionadas con el agua, como las enfermedades diarreicas por organismos viricos, bacterianos y parasitarios, y las enfermedades arbovirales transmitidas por el Aedes, son importantes problemas sanitarios a nivel mundial. Creemos que estos dos grupos de enfermedades comparten factores de riesgo comunes, es decir, una gestion inadecuada del agua en los hogares, un saneamiento deficiente y la gestion de los residuos solidos. Cuando el suministro de agua es inadecuado, el almacenamiento de agua es esencial. Los mosquitos Aedes suelen criar en los recipientes de almacenamiento de agua de los hogares, que pueden contener agua contaminada con organismos causantes de enfermedades entericas. La contaminacion microbiologica del agua entre la fuente y el punto de uso es una de las principales causas de la reduccion de la calidad del agua potable. Un saneamiento y una gestion de residuos solidos inadecuados no solo aumentan el riesgo de contaminacion del agua, sino tambien la disponibilidad de habitats para las larvas de mosquitos. En este articulo se analizan las intervenciones integradas que interrumpen la cria de mosquitos al tiempo que proporcionan entornos sanitarios y agua limpia. Las intervenciones especificas incluyen la mejora del diseno, la colocacion y el mantenimiento de los contenedores de almacenamiento y la ampliacion del acceso al agua corriente. El control de los vectores puede integrarse en proyectos de saneamiento dirigidos a las alcantarillas y los desagues para evitar la acumulacion de agua estancada. Una mejor gestion de la basura y los residuos solidos puede reducir la disponibilidad de habitats para los mosquitos y mejorar las condiciones de vida de las personas. Nuestra propuesta de integracion de las intervenciones contra la enfermedad es coherente con las estrategias promovidas en varios marcos sanitarios mundiales, como los objetivos de desarrollo sostenible, la respuesta mundial de control de vectores, el cambio de comportamiento y las iniciativas de agua, saneamiento e higiene. La investigacion futura deberia abordar como las intervenciones dirigidas al agua, el saneamiento, la higiene y la eliminacion de residuos de la comunidad tambien benefician al control de las enfermedades transmitidas por el Aedes. Los efectos previstos del cambio climatico significan que las estrategias de gestion y control integrados seran cada vez mas importantes., Introduction Water-related diseases such as diarrhoeal diseases from viral, bacterial and parasitic organisms and Aedes-borne arboviral diseases are major global health problems (Box 1; Table 1). The effects of water [...]

BackgroundDengue is an arthropod-borne viral disease responsible for approximately 400 million infections annually; the only available method of prevention is vector control. It has been previously demonstrated that insecticide treated curtains (ITCs) can lower dengue vector infestations in and around houses. As part of a larger trial examining whether ITCs could reduce dengue transmission in Iquitos, Peru, the objective of this study was to characterize the participants' experience with the ITCs using qualitative methods.MethodsKnowledge, attitudes, and practices (KAP) surveys (at baseline, and 9 and 27 months post-ITC distribution, with n = 593, 595 and 511, respectively), focus group discussions (at 6 and 12 months post-ITC distribution, with n = 18 and 33, respectively), and 11 one-on-one interviews (at 12 months post-distribution) were conducted with 605 participants who received ITCs as part of a cluster-randomized trial.ResultsFocus groups at 6 months post-ITC distribution revealed that individuals had observed their ITCs to function for approximately 3 months, after which they reported the ITCs were no longer working. Follow up revealed that the ITCs required re-treatment with insecticide at approximately 1 year post-distribution. Over half (55.3 %, n = 329) of participants at 9 months post-ITC distribution and over a third (34.8 %, n = 177) at 27 months post-ITC distribution reported perceiving a decrease in the number of mosquitoes in their home. The percentage of participants who would recommend ITCs to their family or friends in the future remained high throughout the study (94.3 %, n = 561 at 9 months and 94.6 %, n = 488 at 27 months post-distribution). When asked why, participants reported that ITCs were effective at reducing mosquitoes (81.6 and 37.8 %, at 9 and 27 months respectively), that they prevent dengue (5.7 and 51.2 %, at 9 and 27 months), that they are "beautiful" (5.9 and 3.1 %), as well as other reasons (6.9 and 2.5 %).ConclusionITCs have substantial potential for long term dengue vector control because they are liked by users, both for their perceived effectiveness and for aesthetic reasons, and because they require little proactive behavioral effort on the part of the users. Our results highlight the importance of gathering process (as opposed to outcome) data during vector control studies, without which researchers would not have become aware that the ITCs had lost effectiveness early in the trial.

Dengue is an arthropod-borne virus of great public health importance, and control of its mosquito vectors is currently the only available method for prevention. Previous research has suggested that insecticide treated curtains (ITCs) can lower dengue vector infestations in houses. This observational study investigated individual and household-level socio-demographic factors associated with correct and consistent use of ITCs in Iquitos, Peru. A baseline knowledge, attitudes, and practices (KAP) survey was administered to 1,333 study participants, and ITCs were then distributed to 593 households as part of a cluster-randomized trial. Follow up KAP surveys and ITC-monitoring checklists were conducted at 9, 18, and 27 months post-ITC distribution. At 9 months post-distribution, almost 70% of ITCs were hanging properly (e.g. hanging fully extended or tied up), particularly those hung on walls compared to other locations. Proper ITC hanging dropped at 18 months to 45.7%. The odds of hanging ITCs correctly and consistently were significantly greater among those participants who were housewives, knew three or more correct symptoms of dengue and at least one correct treatment for dengue, knew a relative or close friend who had had dengue, had children sleeping under a mosquito net, or perceived a change in the amount of mosquitoes in the home. Additionally, the odds of recommending ITCs in the future were significantly greater among those who perceived a change in the amount of mosquitoes in the home (e.g. perceived the ITCs to be effective). Despite various challenges associated with the sustained effectiveness of the selected ITCs, almost half of the ITCs were still hanging at 18 months, suggesting a feasible vector control strategy for sustained community use.

As part of a cluster-randomized trial to evaluate insecticide-treated curtains for dengue prevention in Iquitos, Peru, we surveyed 1,333 study participants to examine knowledge and reported practices associated with dengue and its prevention. Entomological data from 1,133 of these households were linked to the survey. Most participants knew that dengue was transmitted by mosquito bite (85.6%), but only few (18.6%) knew that dengue vectors bite during daytime. Most commonly recognized dengue symptoms were fever (86.6%), headache (76.4%), and muscle/joint pain (67.9%). Most commonly reported correct practices for mosquito control were cleaning homes (61.6%), using insecticide sprays (23%), and avoiding having standing water at home (12.3%). Higher education was associated with higher knowledge about dengue, including transmission and vector control. Higher socioeconomic status was associated with increased reported use of preventive practices requiring money expenditure. We were less likely to find Aedes aegypti eggs, larvae, or pupae in households that had < 5-year-old children at home. Although dengue has been transmitted in Iquitos since the 1990s and the Regional Health Authority routinely fumigates households, treats domestic water containers with larvicide, and issues health education messages through mass media, knowledge of dengue transmission and household practices for prevention could be improved.

Zika virus (ZIKV), a flavivirus that can cause birth defects and is associated with Guillain-Barre syndrome, has rapidly spread throughout the Western Hemisphere (1-3). The virus is spread primarily by [...]

Infectious disease models play a key role in public health planning. These models rely on accurate estimates of key transmission parameters such as the force of infection (FoI), which is the per-capita risk of a susceptible person being infected. The FoI captures the fundamental dynamics of transmission and is crucial for gauging control efforts, such as identifying vaccination targets. Dengue virus (DENV) is a mosquito-borne, multiserotype pathogen that currently infects ∼390 million people a year. Existing estimates of the DENV FoI are inaccurate because they rely on the unrealistic assumption that risk is constant over time. Dengue models are thus unreliable for designing vaccine deployment strategies. Here, we present to our knowledge the first time-varying (daily), serotype-specific estimates of DENV FoIs using a spline-based fitting procedure designed to examine a 12-y, longitudinal DENV serological dataset from Iquitos, Peru (11,703 individuals, 38,416 samples, and 22,301 serotype-specific DENV infections from 1999 to 2010). The yearly DENV FoI varied markedly across time and serotypes (0-0.33), as did daily basic reproductive numbers (0.49-4.72). During specific time periods, the FoI fluctuations correlated across serotypes, indicating that different DENV serotypes shared common transmission drivers. The marked variation in transmission intensity that we detected indicates that intervention targets based on one-time estimates of the FoI could underestimate the level of effort needed to prevent disease. Our description of dengue virus transmission dynamics is unprecedented in detail, providing a basis for understanding the persistence of this rapidly emerging pathogen and improving disease prevention programs.

The first case of autochthonous Zika virus infection in the Western Hemisphere was reported in Brazil in 2015, followed by reports from 26 countries and territories in the Caribbean and [...]