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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. 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. 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.

The emergence of chikungunya virus (CHIKV) has raised serious concerns due to the virus' rapid dissemination into new geographic areas and the clinical features associated with infection. To better understand CHIKV dynamics in Rio de Janeiro, we generated 11 near-complete genomes by means of real-time portable nanopore sequencing of virus isolates obtained directly from clinical samples. To better understand CHIKV dynamics in Rio de Janeiro, we generated 11 near-complete genomes by means of real-time portable nanopore sequencing of virus isolates obtained directly from clinical samples. Our phylogenetic reconstructions indicated the circulation of the East-Central-South-African (ECSA) lineage in Rio de Janeiro. Time-measured phylogenetic analysis combined with CHIKV notified case numbers revealed the ECSA lineage was introduced in Rio de Janeiro around June 2015 (95% Bayesian credible interval: May to July 2015) indicating the virus was circulating unnoticed for 5 months before the first reports of CHIKV autochthonous transmissions in Rio de Janeiro, in November 2015. These findings reinforce that continued genomic surveillance strategies are needed to assist in the monitoring and understanding of arbovirus epidemics, which might help to attenuate public health impact of infectious diseases.

Targeted indoor residual spraying focuses insecticide applications on common resting surfaces of mosquitoes (an arboviral disease vector) in houses, such as exposed lower sections of walls and under furniture. We conducted a two-group, parallel, unblinded, cluster-randomized trial in Merida, Mexico, to quantify the efficacy of targeted indoor residual spraying for preventing aedes-borne diseases (chikungunya, dengue, or Zika). Children 2 to 15 years of age were enrolled from households in 50 clusters of five-by-five city blocks. Households in 25 clusters received an annual application of targeted indoor residual spraying (intervention) before each season of aedes-borne disease (July through December). All clusters received routine Ministry of Health vector control. The primary end point was laboratory-confirmed, symptomatic aedes-borne disease. Community effects were assessed with the use of geolocated national surveillance data. A total of 4461 children were monitored for up to three seasons (2021, 2022, and 2023). The indoor density of mosquitoes was 59% (95% confidence interval [CI], 51 to 65) lower with the intervention than with control. A total of 422 cases of aedes-borne disease were confirmed, primarily dengue in 2023. In the per-protocol analysis of cluster centers, 91 cases occurred among 1038 participants in the intervention group and 89 cases among 1037 participants in the control group (efficacy, -12.8%; 95% CI, -60.7 to 23.0). In an intention-to-treat analysis of entire clusters, 198 cases occurred among 2239 participants in the intervention group and 199 cases among 2222 participants in the control group (efficacy, 3.9%; 95% CI, -28.1 to 26.7). Adjustment of analyses for mobility or demographic characteristics did not change results. On the basis of 150 cases in the intervention clusters and 202 in the control clusters that were geolocated, the estimated community effect of the intervention was 24.0% (95% CI, 6.0 to 38.6). Two cases of multisymptom adverse events (e.g., nausea, watery eyes, diarrhea, and vomiting) were associated with the intervention. Despite lower entomologic indexes with targeted indoor residual spraying than with routine vector control, the cumulative incidence of aedes-borne diseases was not significantly lower with targeted indoor residual spraying. (Funded by the National Institutes of Health and the Innovative Vector Control Consortium; ClinicalTrials.gov number, NCT04343521.).

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.

Chikungunya is an arbovirus, transmitted by Aedes mosquitoes, which emerged in the Americas in 2013 and spread rapidly to almost every country on this continent. In Brazil, where the first cases were detected in 2014, it currently has reached all regions of this country and more than 900,000 cases were reported. The clinical spectrum of chikungunya ranges from an acute self-limiting form to disabling chronic forms. The purpose of this study was to estimate the seroprevalence of chikungunya infection in a large Brazilian city and investigate the association between viral circulation and living condition. We conducted a population-based ecological study in selected Sentinel Areas (SA) through household interviews and a serologic survey in 2016/2017. The sample was of 1,981 individuals randomly selected. The CHIKV seroprevalence was 22.1% (17.1 IgG, 2.3 IgM, and 1.4 IgG and IgM) and varied between SA from 2.0% to 70.5%. The seroprevalence was significantly lower in SA with high living conditions compared to SA with low living condition. There was a positive association between CHIKV seroprevalence and population density (r = 0.2389; p = 0.02033). The seroprevalence in this city was 2.6 times lower than the 57% observed in a study conducted in the epicentre of the CHIKV epidemic of this same urban centre. So, the herd immunity in this general population, after four years of circulation of this agent is relatively low. It indicates that CHIKV transmission may persist in that city, either in endemic form or in the form of a new epidemic, because the vector infestation is persistent. Besides, the significantly lower seroprevalences in SA of higher Living Condition suggest that beyond the surveillance of the disease, vector control and specific actions of basic sanitation, the reduction of the incidence of this infection also depends on the improvement of the general living conditions of the population.

There is a need for effective methods to control Aedes aegypti and prevent the transmission of dengue, chikungunya, yellow fever and Zika viruses. Insecticide treated screening (ITS) is a promising approach, particularly as it targets adult mosquitoes to reduce human-mosquito contact. A cluster-randomised controlled trial evaluated the entomological efficacy of ITS based intervention, which consisted of the installation of pyrethroid-impregnated long-lasting insecticide-treated netting material fixed as framed screens on external doors and windows. A total of 10 treatment and 10 control clusters (100 houses/cluster) were distributed throughout the city of Merida, Mexico. Cross-sectional entomological surveys quantified indoor adult mosquito infestation at baseline (pre-intervention) and throughout four post-intervention (PI) surveys spaced at 6-month intervals corresponding to dry/rainy seasons over two years (2012-2014). A total of 844 households from intervention clusters (86% coverage) were protected with ITS at the start of the trial. Significant reductions in the indoor presence and abundance of Ae. aegypti adults (OR = 0.48 and IRR = 0.45, P<0.05 respectively) and the indoor presence and abundance of Ae. aegypti female mosquitoes (OR = 0.47 and IRR = 0.44, P<0.05 respectively) were detected in intervention clusters compared to controls. This high level of protective effect was sustained for up to 24 months PI. Insecticidal activity of the ITS material declined with time, with ~70% mortality being demonstrated in susceptible mosquito cohorts up to 24 months after installation. The strong and sustained entomological impact observed in this study demonstrates the potential of house screening as a feasible, alternative approach to a sustained long-term impact on household infestations of Ae. aegypti. Larger trials quantifying the effectiveness of ITS on epidemiological endpoints are warranted and therefore recommended.

In Senegal, chikungunya virus (CHIKV) is maintained in a sylvatic cycle and causes sporadic cases or small outbreaks in rural areas. However, little is known about the influence of the environment on its transmission. To address the question, 120 villages were randomly selected in the Kedougou region of southeastern Senegal. In each selected village, 10 persons by randomly selected household were sampled and tested for specific anti-CHIKV IgG antibodies by ELISA. We investigated the association of CHIKV seroprevalence with environmental variables using logistic regression analysis and the spatial correlation of village seroprevalence based on semivariogram analysis. Fifty-four percent (51%–57%) of individuals sampled during the survey tested positive for CHIKV-specific IgG. CHIKV seroprevalence was significantly higher in populations living close to forested areas (Normalized Difference Vegetation Index (NDVI), Odds Ratio (OR) = 1.90 (1.42–2.57)), and was negatively associated with population density (OR = 0.76 (0.69–0.84)). In contrast, in gold mining sites where population density was >400 people per km2, seroprevalence peaked significantly among adults (46% (27%–67%)) compared to all other individuals (20% (12%–31%)). However, traditional gold mining activities significantly modify the transmission dynamic of CHIKV, leading to a potential increase of the risk of human exposition in the region.

Chikungunya virus (CHIKV), a reemerging arbovirus, causes a crippling musculoskeletal inflammatory disease in humans characterized by fever, polyarthralgia, myalgia, rash, and headache. CHIKV is transmitted by Aedes species of mosquitoes and is capable of an epidemic, urban transmission cycle with high rates of infection. Since 2004, CHIKV has spread to new areas, causing disease on a global scale, and the potential for CHIKV epidemics remains high. Although CHIKV has caused millions of cases of disease and significant economic burden in affected areas, no licensed vaccines or antiviral therapies are available. In this Review, we describe CHIKV epidemiology, replication cycle, pathogenesis and host immune responses, and prospects for effective vaccines and highlight important questions for future research.

Chikungunya virus (CHIKV) emerged in the Americas in late 2013 to cause substantial acute and chronic morbidity. About 1.1 million cases of chikungunya were reported within a year, including severe cases and deaths. The burden of chikungunya is unclear owing to inadequate disease surveillance and underdiagnosis. Virus evolution, globalization, and climate change may further CHIKV spread. No approved vaccine or antiviral therapeutics exist. Early detection and appropriate management could reduce the burden of severe atypical and chronic arthritic disease. Improved surveillance and risk assessment are needed to mitigate the impact of chikungunya.

Chikungunya virus (CHIKV) is transmitted by Aedes aegypti and Aedes albopictus mosquitoes and causes febrile illness with severe arthralgia in humans. There are 3 circulating CHIKV genotypes, Asia, East/Central/South Africa, and West Africa. CHIKV was first reported in 1953 in Tanzania, and up until the early 2000s, a few outbreaks and sporadic cases of CHIKV were mainly reported in Africa and Asia. However, from 2004 to 2005, a large epidemic spanned from Kenya over to the southwestern Indian Ocean region, India, and Southeast Asia. Identified in 2005, the E1 glycoprotein A226V mutation of the East/Central/South Africa genotype conferred enhanced transmission by the A. albopictus mosquito and has been implicated in CHIKV's further spread in the last decade. In 2013, the Asian CHIKV genotype emerged in the Caribbean and quickly took the Americas by storm. This review will discuss the history of CHIKV as well as its expanding geographic distribution.