RESUMO

BACKGROUND: The introduction of Wolbachia (wMel strain) into Aedes aegypti mosquitoes reduces their capacity to transmit dengue and other arboviruses. Randomised and non-randomised studies in multiple countries have shown significant reductions in dengue incidence following field releases of wMel-infected Ae. aegypti. We report the public health outcomes from phased, large-scale releases of wMel-Ae. aegypti mosquitoes throughout three contiguous cities in the Aburrá Valley, Colombia. METHODOLOGY/PRINCIPAL FINDINGS: Following pilot releases in 2015-2016, staged city-wide wMel-Ae. aegypti deployments were undertaken in the cities of Bello, Medellín and Itagüí (3.3 million people) between October 2016 and April 2022. The impact of the Wolbachia intervention on dengue incidence was evaluated in two parallel studies. A quasi-experimental study using interrupted time series analysis showed notified dengue case incidence was reduced by 95% in Bello and Medellín and 97% in Itagüí, following establishment of wMel at ≥60% prevalence, compared to the pre-intervention period and after adjusting for seasonal trends. A concurrent clinic-based case-control study with a test-negative design was unable to attain the target sample size of 63 enrolled virologically-confirmed dengue (VCD) cases between May 2019 and December 2021, consistent with low dengue incidence throughout the Aburrá Valley following wMel deployments. Nevertheless, VCD incidence was 45% lower (OR 0.55 [95% CI 0.25, 1.17]) and combined VCD/presumptive dengue incidence was 47% lower (OR 0.53 [95% CI 0.30, 0.93]) among participants resident in wMel-treated versus untreated neighbourhoods. CONCLUSIONS/SIGNIFICANCE: Stable introduction of wMel into local Ae. aegypti populations was associated with a significant and sustained reduction in dengue incidence across three Colombian cities. These results from the largest contiguous Wolbachia releases to-date demonstrate the real-world effectiveness of the method across large urban populations and, alongside previously published results, support the reproducibility of this effectiveness across different ecological settings. TRIAL REGISTRATION: NCT03631719.

Assuntos

Aedes , Vírus da Dengue , Dengue , Wolbachia , Animais , Humanos , Colômbia/epidemiologia , Cidades/epidemiologia , Incidência , Análise de Séries Temporais Interrompida , Estudos de Casos e Controles , Reprodutibilidade dos Testes , Controle Biológico de Vetores/métodos , Dengue/epidemiologia , Dengue/prevenção & controle , Mosquitos Vetores

RESUMO

BACKGROUND: The introduction of the bacterium Wolbachia (wMel strain) into Aedes aegypti mosquitoes reduces their capacity to transmit dengue and other arboviruses. Evidence of a reduction in dengue case incidence following field releases of wMel-infected Ae. aegypti has been reported previously from a cluster randomised controlled trial in Indonesia, and quasi-experimental studies in Indonesia and northern Australia. METHODOLOGY/PRINCIPAL FINDINGS: Following pilot releases in 2015-2016 and a period of intensive community engagement, deployments of adult wMel-infected Ae. aegypti mosquitoes were conducted in Niterói, Brazil during 2017-2019. Deployments were phased across four release zones, with a total area of 83 km2 and a residential population of approximately 373,000. A quasi-experimental design was used to evaluate the effectiveness of wMel deployments in reducing dengue, chikungunya and Zika incidence. An untreated control zone was pre-defined, which was comparable to the intervention area in historical dengue trends. The wMel intervention effect was estimated by controlled interrupted time series analysis of monthly dengue, chikungunya and Zika case notifications to the public health surveillance system before, during and after releases, from release zones and the control zone. Three years after commencement of releases, wMel introgression into local Ae. aegypti populations was heterogeneous throughout Niterói, reaching a high prevalence (>80%) in the earliest release zone, and more moderate levels (prevalence 40-70%) elsewhere. Despite this spatial heterogeneity in entomological outcomes, the wMel intervention was associated with a 69% reduction in dengue incidence (95% confidence interval 54%, 79%), a 56% reduction in chikungunya incidence (95%CI 16%, 77%) and a 37% reduction in Zika incidence (95%CI 1%, 60%), in the aggregate release area compared with the pre-defined control area. This significant intervention effect on dengue was replicated across all four release zones, and in three of four zones for chikungunya, though not in individual release zones for Zika. CONCLUSIONS/SIGNIFICANCE: We demonstrate that wMel Wolbachia can be successfully introgressed into Ae. aegypti populations in a large and complex urban setting, and that a significant public health benefit from reduced incidence of Aedes-borne disease accrues even where the prevalence of wMel in local mosquito populations is moderate and spatially heterogeneous. These findings are consistent with the results of randomised and non-randomised field trials in Indonesia and northern Australia, and are supportive of the Wolbachia biocontrol method as a multivalent intervention against dengue, chikungunya and Zika.

Assuntos

Aedes/microbiologia , Aedes/virologia , Febre de Chikungunya/transmissão , Dengue/transmissão , Controle de Mosquitos/métodos , Wolbachia/fisiologia , Infecção por Zika virus/transmissão , Aedes/fisiologia , Animais , Brasil/epidemiologia , Febre de Chikungunya/epidemiologia , Febre de Chikungunya/virologia , Vírus Chikungunya/fisiologia , Dengue/epidemiologia , Dengue/virologia , Vírus da Dengue/fisiologia , Feminino , Humanos , Incidência , Masculino , Mosquitos Vetores/microbiologia , Mosquitos Vetores/fisiologia , Mosquitos Vetores/virologia , Zika virus/fisiologia , Infecção por Zika virus/epidemiologia , Infecção por Zika virus/virologia

RESUMO

OBJECTIVE: Evaluate how coverage and quality of primary health care (PHC) and a conditional cash transfer (CCT) program associate with child mortality in Brazil. METHODS: Multivariate linear regression models and least absolute shrinkage and selection estimator (LASSO) were utilized with the municipal level child mortality rate as the key dependent variable. PHC quality with PHC and CCT coverage were the independent variables. The quality of the Brazilian PHC was assessed using the Brazilian National Program for Access and Quality Improvement in PHC data. PHC and CCT coverage were calculated based on Brazilian official databases. Human developmental index (HDI), municipality size, and country region were used as control variables. A total of 3441 municipalities were evaluated. RESULTS: We found that ESF (Estratégia Saúde da Família) quality variables PLANNING [Family Health Team Planning activities], CITYSUPPORT [municipality support for Family Health Strategy activities], EXAMS [exams offered and priority groups seen by the family health team], and PRENATAL [prenatal care and exams provided by the family health team], as well as HDI, percentage of PHC coverage, percentage of CCT coverage, and population size have significant and negative relationships with 1-year-old child mortality. LASSO regression results confirmed these associations. Quality is an important element of effective social service provision. CONCLUSION: This exploration represents one of the first investigations into the role of PHC system quality, and how it is related to health outcomes, while also considering PHC and conditional cash transfer program coverage. Quality of PHC, measured by work process variables, plays an important role in child mortality. Efforts on PHC quality and coverage, as well as on CCT program coverage, are important to child mortality reduction. Therefore, this is an important finding to other PHC public health services.

Assuntos

Mortalidade da Criança/tendências , Atenção Primária à Saúde/normas , Assistência Pública/estatística & dados numéricos , Qualidade da Assistência à Saúde/estatística & dados numéricos , Brasil/epidemiologia , Criança , Humanos , Avaliação de Programas e Projetos de Saúde

RESUMO

Background: Rio de Janeiro and Niterói are neighbouring cities in southeastern Brazil which experience large dengue epidemics every 2 to 5 years, with >100,000 cases notified in epidemic years. Costs of vector control and direct and indirect costs due to the Aedes-borne diseases dengue, chikungunya and Zika were estimated to total $650 million USD in 2016, but traditional vector control strategies have not been effective in preventing mosquito-borne disease outbreaks. The Wolbachia method is a novel and self-sustaining approach for the biological control of Aedes-borne diseases, in which the transmission potential of Aedes aegypti mosquitoes is reduced by stably transfecting them with the Wolbachia bacterium ( wMel strain). This paper describes a study protocol for evaluating the effect of large-scale non-randomised releases of Wolbachia--infected mosquitoes on the incidence of dengue, Zika and chikungunya in the two cities of Niterói and Rio de Janeiro. This follows a lead-in period since 2014 involving intensive community engagement, regulatory and public approval, entomological surveys, and small-scale pilot releases. Method: The Wolbachia releases during 2017-2019 covered a combined area of 170 km 2 with a resident population of 1.2 million, across Niterói and Rio de Janeiro. Untreated areas with comparable historical dengue profiles and demographic characteristics have been identified a priori as comparative control areas in each city. The proposed pragmatic epidemiological approach combines a controlled interrupted time series analysis of routinely notified suspected and laboratory-confirmed dengue and chikungunya cases, together with monitoring of Aedes-borne disease activity utilising outbreak signals routinely used in public health disease surveillance. Discussion: If the current project is successful, this model for control of mosquito-borne disease through Wolbachia releases can be expanded nationally and regionally.

Assuntos

Aedes/virologia , Febre de Chikungunya , Dengue , Controle de Mosquitos , Wolbachia , Infecção por Zika virus , Animais , Agentes de Controle Biológico , Brasil/epidemiologia , Febre de Chikungunya/epidemiologia , Febre de Chikungunya/prevenção & controle , Cidades , Dengue/epidemiologia , Dengue/prevenção & controle , Vírus da Dengue , Humanos , Incidência , Análise de Séries Temporais Interrompida , Mosquitos Vetores/virologia , Zika virus , Infecção por Zika virus/epidemiologia , Infecção por Zika virus/prevenção & controle

RESUMO

Background: Dengue, chikungunya and Zika are viral infections transmitted by Aedes aegypti mosquitoes, and present major public health challenges in tropical regions. Traditional vector control methods have been ineffective at halting disease transmission. The World Mosquito Program has developed a novel approach to arbovirus control using Ae. aegypti stably transfected with the Wolbachia bacterium, which have significantly reduced ability to transmit dengue, Zika and chikungunya in laboratory experiments. Field releases in eight countries have demonstrated Wolbachia establishment in local Ae. aegypti populations. Methods: We describe a pragmatic approach to measuring the epidemiological impact of city-wide Wolbachia deployments in Bello and Medellín, Colombia. First, an interrupted time-series analysis will compare the incidence of dengue, chikungunya and Zika case notifications before and after Wolbachia releases, across the two municipalities. Second, a prospective case-control study using a test-negative design will be conducted in one quadrant of Medellín. Three of the six contiguous release zones in the case-control area were allocated to receive the first Wolbachia deployments in the city and three to be treated last, approximating a parallel two-arm trial for the >12-month period during which Wolbachia exposure remains discordant. Allocation, although non-random, aimed to maximise balance between arms in historical dengue incidence and demographics. Arboviral disease cases and arbovirus-negative controls will be enrolled concurrently from febrile patients presenting to primary care, with case/control status classified retrospectively following laboratory diagnostic testing. Intervention effect is estimated from an aggregate odds ratio comparing Wolbachia-exposure odds among test-positive cases versus test-negative controls. Discussion: The study findings will add to an accumulating body of evidence from global field sites on the efficacy of the Wolbachia method in reducing arboviral disease incidence, and can inform decisions on wider public health implementation of this intervention in the Americas and beyond. Trial registration: ClinicalTrials.gov: NCT03631719. Registered on 15 August 2018.