Association between exposure to ambient air pollution, meteorological factors and atopic dermatitis consultations in Singapore-a stratified nationwide time-series analysis.

Atopic dermatitis (AD) is a chronic inflammatory skin disease affecting approximately 20% of children globally. While studies have been conducted elsewhere, air pollution and weather variability is not well studied in the tropics. This time-series study examines the association between air pollution and meteorological factors with the incidence of outpatient visits for AD obtained from the National Skin Centre (NSC) in Singapore. The total number of 1,440,844 consultation visits from the NSC from 2009 to 2019 was analysed. Using the distributed lag non-linear model and assuming a negative binomial distribution, the short-term temporal association between outpatient visits for AD and air quality and meteorological variability on a weekly time-scale were examined, while adjusting for long-term trends, seasonality and autocorrelation. The analysis was also stratified by gender and age to assess potential effect modification. The risk of AD consultation visits was 14% lower (RR10th percentile: 0.86, 95% CI 0.78-0.96) at the 10th percentile (11.9 µg/m3) of PM2.5 and 10% higher (RR90th percentile: 1.10, 95% CI 1.01-1.19) at the 90th percentile (24.4 µg/m3) compared to the median value (16.1 µg/m3). Similar results were observed for PM10 with lower risk at the 10th percentile and higher risk at the 90th percentile (RR10th percentile: 0.86, 95% CI 0.78-0.95, RR90th percentile: 1.10, 95% CI 1.01-1.19). For rainfall for values above the median, the risk of consultation visits was higher up to 7.4 mm in the PM2.5 model (RR74th percentile: 1.07, 95% CI 1.00-1.14) and up to 9 mm in the PM10 model (RR80th percentile: 1.12, 95% CI 1.00-1.25). This study found a close association between outpatient visits for AD with ambient particulate matter concentrations and rainfall. Seasonal variations in particulate matter and rainfall may be used to alert healthcare providers on the anticipated rise in AD cases and to time preventive measures to reduce the associated health burden.

Singapore's 5 decades of dengue prevention and control-Implications for global dengue control.

This paper summarises the lessons learnt in dengue epidemiology, risk factors, and prevention in Singapore over the last half a century, during which Singapore evolved from a city of 1.9 million people to a highly urban globalised city-state with a population of 5.6 million. Set in a tropical climate, urbanisation among green foliage has created ideal conditions for the proliferation of Aedes aegypti and Aedes albopictus, the mosquito vectors that transmit dengue. A vector control programme, largely for malaria, was initiated as early as 1921, but it was only in 1966 that the Vector Control Unit (VCU) was established to additionally tackle dengue haemorrhagic fever (DHF) that was first documented in the 1960s. Centred on source reduction and public education, and based on research into the bionomics and ecology of the vectors, the programme successfully reduced the Aedes House Index (HI) from 48% in 1966 to <5% in the 1970s. Further enhancement of the programme, including through legislation, suppressed the Aedes HI to around 1% from the 1990s. The current programme is characterised by 4 key features: (i) proactive inter-epidemic surveillance and control that is stepped up during outbreaks; (ii) risk-based prevention and intervention strategies based on advanced data analytics; (iii) coordinated inter-sectoral cooperation between the public, private, and people sectors; and (iv) evidence-based adoption of new tools and strategies. Dengue seroprevalence and force of infection (FOI) among residents have substantially and continuously declined over the 5 decades. This is consistent with the observation that dengue incidence has been delayed to adulthood, with severity highest among the elderly. Paradoxically, the number of reported dengue cases and outbreaks has increased since the 1990s with record-breaking epidemics. We propose that Singapore's increased vulnerability to outbreaks is due to low levels of immunity in the population, constant introduction of new viral variants, expanding urban centres, and increasing human density. The growing magnitude of reported outbreaks could also be attributed to improved diagnostics and surveillance, which at least partially explains the discord between rising trend in cases and the continuous reduction in dengue seroprevalence. Changing global and local landscapes, including climate change, increasing urbanisation and global physical connectivity are expected to make dengue control even more challenging. The adoption of new vector surveillance and control tools, such as the Gravitrap and Wolbachia technology, is important to impede the growing threat of dengue and other Aedes-borne diseases.

Assessing the efficacy of male Wolbachia-infected mosquito deployments to reduce dengue incidence in Singapore: study protocol for a cluster-randomized controlled trial.

BACKGROUND: Dengue is a severe environmental public health challenge in tropical and subtropical regions. In Singapore, decreasing seroprevalence and herd immunity due to successful vector control has paradoxically led to increased transmission potential of the dengue virus. We have previously demonstrated that incompatible insect technique coupled with sterile insect technique (IIT-SIT), which involves the release of X-ray-irradiated male Wolbachia-infected mosquitoes, reduced the Aedes aegypti population by 98% and dengue incidence by 88%. This novel vector control tool is expected to be able to complement current vector control to mitigate the increasing threat of dengue on a larger scale. We propose a multi-site protocol to study the efficacy of IIT-SIT at reducing dengue incidence. METHODS/DESIGN: The study is designed as a parallel, two-arm, non-blinded cluster-randomized (CR) controlled trial to be conducted in high-rise public housing estates in Singapore, an equatorial city-state. The aim is to determine whether large-scale deployment of male Wolbachia-infected Ae. aegypti mosquitoes can significantly reduce dengue incidence in intervention clusters. We will use the CR design, with the study area comprising 15 clusters with a total area of 10.9 km2, covering approximately 722,204 residents in 1713 apartment blocks. Eight clusters will be randomly selected to receive the intervention, while the other seven will serve as non-intervention clusters. Intervention efficacy will be estimated through two primary endpoints: (1) odds ratio of Wolbachia exposure distribution (i.e., probability of living in an intervention cluster) among laboratory-confirmed reported dengue cases compared to test-negative controls and (2) laboratory-confirmed reported dengue counts normalized by population size in intervention versus non-intervention clusters. DISCUSSION: This study will provide evidence from a multi-site, randomized controlled trial for the efficacy of IIT-SIT in reducing dengue incidence. The trial will provide valuable information to estimate intervention efficacy for this novel vector control approach and guide plans for integration into national vector control programs in dengue-endemic settings. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT05505682 . Registered on 16 August 2022. Retrospectively registered.

Spatial Methods for Inferring Extremes in Dengue Outbreak Risk in Singapore.

Dengue is a major vector-borne disease worldwide. Here, we examined the spatial distribution of extreme weekly dengue outbreak risk in Singapore from 2007 to 2020. We divided Singapore into equal-sized hexagons with a circumradius of 165 m and obtained the weekly number of dengue cases and the surface characteristics of each hexagon. We accounted for spatial heterogeneity using max-stable processes. The 5-, 10-, 20-, and 30-year return levels, or the weekly dengue case counts expected to be exceeded once every 5, 10, 20, and 30 years, respectively, were determined for each hexagon conditional on their surface characteristics remaining constant over time. The return levels were higher in the country's east, with the maximum weekly dengue cases per hexagon expected to exceed 51 at least once in 30 years in many areas. The surface characteristics with the largest impact on outbreak risk were the age of public apartments and the percentage of impervious surfaces, where a 3-year and 10% increase in each characteristic resulted in a 3.8% and 3.3% increase in risk, respectively. Vector control efforts should be prioritized in older residential estates and places with large contiguous masses of built-up environments. Our findings indicate the likely scale of outbreaks in the long term.

Geographical clusters of dengue outbreak in Singapore during the Covid-19 nationwide lockdown of 2020.

Dengue, a mosquito-transmitted viral disease, has posed a public health challenge to Singaporean residents over the years. In 2020, Singapore experienced an unprecedented dengue outbreak. We collected a dataset of geographical dengue clusters reported by the National Environment Agency (NEA) from 15 February to 9 July in 2020, covering the nationwide lockdown associated with Covid-19 during the period from 7 April to 1 June. NEA regularly updates the dengue clusters during which an infected person may be tagged to one cluster based on the most probable infection location (residential apartment or workplace address), which is further matched to fine-grained spatial units with an average coverage of about 1.35 km2. Such dengue cluster dataset helps not only reveal the dengue transmission patterns, but also reflect the effects of lockdown on dengue spreading dynamics. The resulting data records are released in simple formats for easy access to facilitate studies on dengue epidemics.

Perfluoroalkyl substances and lipid concentrations in the blood: A systematic review of epidemiological studies.

BACKGROUND: Perfluoroalkyl substances (PFAS) are widely used synthetic aliphatic compounds. This systematic review aims to assess PFAS associations with low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), total cholesterol (TC) and total triglyceride (TG) concentrations in human populations. METHOD: We systematically searched four online databases, PubMed, Scopus, Embase, and Cochrane Library for relevant peer-reviewed English language articles published until July 2021. Additional relevant articles identified were also included in the search results. We categorised populations into adults (≥18 years old) and children. Primary findings were the associations between PFAS concentrations and LDL, HDL, TC, and TG concentrations in the serum, plasma, or whole blood; secondary findings were the associations between PFAS concentrations and the odds of lipid-related health outcomes. Quantitative synthesis was done by vote counting of the effect directions between concentrations of PFAS and lipids/health outcomes, repeated on articles with sample size >1000. Sign tests were performed to assess the statistical significance of the differences between positive and negative associations. Sensitivity analysis was performed by separating out articles with populations having high concentrations of perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS). Quality was assessed with the STROBE checklist and NHBLI Study Quality Assessment Tool. RESULTS: A total of 58 articles were included for review. There was evidence that PFAS exposure is associated with higher concentrations of LDL, HDL, and TC, particularly for PFOA-LDL, PFOA-TC, PFOS-TC, and PFNA-LDL. Associations between PFAS and TG tended to be negative, especially for perfluoroundecanoic acid (PFUnDA). Associations between PFAS concentration and the odds of secondary outcomes generally supported a positive association between PFAS and cholesterol concentrations. CONCLUSION: We found evidence of associations between the concentrations of some PFAS-lipid pairs in human populations. Future research should be conducted on the less well-studied PFAS to explore their effects on human health and in regions where such studies are currently lacking. (300 words).

Strategies to Mitigate Establishment under the Wolbachia Incompatible Insect Technique.

The Incompatible Insect Technique (IIT) strategy involves the release of male mosquitoes infected with the bacterium Wolbachia. Regular releases of male Wolbachia-infected mosquitoes can lead to the suppression of mosquito populations, thereby reducing the risk of transmission of vector-borne diseases such as dengue. However, due to imperfect sex-sorting under IIT, fertile Wolbachia-infected female mosquitoes may potentially be unintentionally released into the environment, which may result in replacement and failure to suppress the mosquito populations. As such, mitigating Wolbachia establishment requires a combination of IIT with other strategies. We introduced a simple compartmental model to simulate ex-ante mosquito population dynamics subjected to a Wolbachia-IIT programme. In silico, we explored the risk of replacement, and strategies that could mitigate the establishment of the released Wolbachia strain in the mosquito population. Our results suggest that mitigation may be achieved through the application of a sterile insect technique. Our simulations indicate that these interventions do not override the intended wild type suppression of the IIT approach. These findings will inform policy makers of possible ways to mitigate the potential establishment of Wolbachia using the IIT population control strategy.

Fine-scale estimation of effective reproduction numbers for dengue surveillance.

The effective reproduction number Rt is an epidemiological quantity that provides an instantaneous measure of transmission potential of an infectious disease. While dengue is an increasingly important vector-borne disease, few have used Rt as a measure to inform public health operations and policy for dengue. This study demonstrates the utility of Rt for real time dengue surveillance. Using nationally representative, geo-located dengue case data from Singapore over 2010-2020, we estimated Rt by modifying methods from Bayesian (EpiEstim) and filtering (EpiFilter) approaches, at both the national and local levels. We conducted model assessment of Rt from each proposed method and determined exogenous temporal and spatial drivers for Rt in relation to a wide range of environmental and anthropogenic factors. At the national level, both methods achieved satisfactory model performance (R2EpiEstim = 0.95, R2EpiFilter = 0.97), but disparities in performance were large at finer spatial scales when case counts are low (MASE EpiEstim = 1.23, MASEEpiFilter = 0.59). Impervious surfaces and vegetation with structure dominated by human management (without tree canopy) were positively associated with increased transmission intensity. Vegetation with structure dominated by human management (with tree canopy), on the other hand, was associated with lower dengue transmission intensity. We showed that dengue outbreaks were preceded by sustained periods of high transmissibility, demonstrating the potential of Rt as a dengue surveillance tool for detecting large rises in dengue cases. Real time estimation of Rt at the fine scale can assist public health agencies in identifying high transmission risk areas and facilitating localised outbreak preparedness and response.

Hyperendemicity associated with increased dengue burden.

Over 105 million dengue infections are estimated to occur annually. Understanding the disease dynamics of dengue is often difficult due to multiple strains circulating within a population. Interactions between dengue serotype dynamics may result in complex cross-immunity dynamics at the population level and create difficulties in terms of formulating intervention strategies for the disease. In this study, a nationally representative 16-year time series with over 43 000 serotyped dengue infections was used to infer the long-run effects of between and within strain interactions and their impacts on past outbreaks. We used a novel identification strategy incorporating sign-identified Bayesian vector autoregressions, using structural impulse responses, historical decompositions and counterfactual analysis to conduct inference on dengue dynamics post-estimation. We found that on the population level: (i) across-serotype interactions on the population level were highly persistent, with a one time increase in any other serotype associated with long run decreases in the serotype of interest (range: 0.5-2.5 years) and (ii) over 38.7% of dengue cases of any serotype were associated with across-serotype interactions. The findings in this paper will substantially impact public health policy interventions with respect to dengue.

Short Report: Adult Aedes abundance and risk of dengue transmission.

Dengue is transmitted mainly by the adult female Aedes aegypti mosquito. However, little is known about the impact of adult Aedes abundance on the risk of dengue transmission. Here we analysed nationally representative dengue case and vector surveillance data collected from Singapore, to determine the effect of adult Aedes abundance on the risk of dengue transmission. A case was an area with active dengue transmission as indicated by the presence of dengue cluster. A control was an area where no dengue cluster was reported. Using multivariate logistic regression, we analysed 88 cases and 602 controls and estimated the odds of dengue cluster formation at various adult Aedes abundance levels, estimated by the mean number of adult female Aedes per Gravitrap per week and categorised into Low, Moderate, High and Very High abundance level. We found that the risk of dengue cluster formation was positively associated with adult Ae. aegypti abundance. We observed a three to four-fold increase in the odds of dengue clusters forming in areas with High (AOR: 3.40, 95% CI: 2.09, 5.52) and Very High (AOR: 3.99, 95% CI: 2.46, 6.46) adult Aedes aegypti abundance level compared to those with low Ae. aegypti abundance level. Our study strengthens the evidence for the use of adult Aedes indices for dengue risk assessment and early warning for dengue outbreaks. Entomological indicators of adult Ae. aegypti could be used to anticipate and prioritize areas for dengue control.

Spatio-temporal analysis of the main dengue vector populations in Singapore.

BACKGROUND: Despite the licensure of the world's first dengue vaccine and the current development of additional vaccine candidates, successful Aedes control remains critical to the reduction of dengue virus transmission. To date, there is still limited literature that attempts to explain the spatio-temporal population dynamics of Aedes mosquitoes within a single city, which hinders the development of more effective citywide vector control strategies. Narrowing this knowledge gap requires consistent and longitudinal measurement of Aedes abundance across the city as well as examination of relationships between variables on a much finer scale. METHODS: We utilized a high-resolution longitudinal dataset generated from Singapore's islandwide Gravitrap surveillance system over a 2-year period and built a Bayesian hierarchical model to explain the spatio-temporal dynamics of Aedes aegypti and Aedes albopictus in relation to a wide range of environmental and anthropogenic variables. We also created a baseline during our model assessment to serve as a benchmark to be compared with the model's out-of-sample prediction/forecast accuracy as measured by the mean absolute error. RESULTS: For both Aedes species, building age and nearby managed vegetation cover were found to have a significant positive association with the mean mosquito abundance, with the former being the strongest predictor. We also observed substantial evidence of a nonlinear effect of weekly maximum temperature on the Aedes abundance. Our models generally yielded modest but statistically significant reductions in the out-of-sample prediction/forecast error relative to the baseline. CONCLUSIONS: Our findings suggest that public residential estates with older buildings and more nearby managed vegetation should be prioritized for vector control inspections and community advocacy to reduce the abundance of Aedes mosquitoes and the risk of dengue transmission.

Decreased dengue transmission in migrant worker populations in Singapore attributable to SARS-CoV-2 quarantine measures.

BACKGROUND: We examined the impact of SARS-CoV-2 social distancing and quarantine policies on dengue transmission in the general and migrant worker populations in Singapore. METHODS: We utilized all nationally reported dengue cases in the general and migrant worker populations from 1 January 2013 to 31 May 2020. A difference-in-difference identification strategy was used to determine the effects of social distancing and quarantine policies on reported dengue case counts over time, whilst controlling for weather patterns, seasonality, age and population size. RESULTS: A reduction of 4.8 dengue cases per age band among migrant workers was attributable to quarantine policies, corresponding to a total reduction of around 432 reported dengue cases over 10 weeks. In the general working population, an increase of 14.5 dengue cases per age band was observed, which corresponds to a total increase of around 1450 reported dengue cases in the same time period. There is an expected relative risk reduction in dengue transmission for the migrant worker population at 0.635 due to quarantine policy and a relative risk increase for the general working population due to social distancing policies at 0.685. CONCLUSIONS: Migrant workers experienced a reduced risk of dengue when they were confined to their dormitories as part of the COVID-19 social distancing measures. Our study highlights the vulnerability of migrant workers under normal working conditions.

Economic impact of dengue in Singapore from 2010 to 2020 and the cost-effectiveness of Wolbachia interventions.

The release of Wolbachia-infected mosquitoes is a promising disease intervention strategy that aims to control dengue and other arboviral infections. While early field trials and modelling studies suggest promising epidemiological and entomological outcomes, the overall cost effectiveness of the technology is not well studied in a resource rich setting nor under the suppression approach that aims to suppress the wild-type mosquito population through the release of Wolbachia-infected males. We used economical and epidemiological data from 2010 to 2020 to first ascertain the economic and health costs of dengue in Singapore, a high income nation where dengue is hyper-endemic. The hypothetical cost effectiveness of a national Wolbachia suppression program was then evaluated historically from 2010 to 2020. We estimated that the average economic impact of dengue in Singapore from 2010 to 2020 in constant 2010US$ ranged from $1.014 to $2.265 Billion. Using empirically derived disability weights, we estimated a disease burden of 7,645-21,262 DALYs from 2010-2020. Under an assumed steady-state running cost of a national Wolbachia suppression program in Singapore, we conservatively estimate that Wolbachia would cost an estimated $50,453-$100,907 per DALYs averted and would lead to an estimated $329.40 Million saved in economic costs over 2010 to 2020 under 40% intervention efficacy. Wolbachia releases in Singapore are expected to be highly cost-effective and its rollout must be prioritised to reduce the onward spread of dengue.

Increased Dengue Transmissions in Singapore Attributable to SARS-CoV-2 Social Distancing Measures.

Social distancing (SD) measures aimed at curbing the spread of SARS-CoV-2 remain an important public health intervention. Little is known about the collateral impact of reduced mobility on the risk of other communicable diseases. We used differences in dengue case counts pre- and post implementation of SD measures and exploited heterogeneity in SD treatment effects among different age groups in Singapore to identify the spillover effects of SD measures. SD policy caused an increase of over 37.2% in dengue cases from baseline. Additional measures to preemptively mitigate the risk of other communicable diseases must be considered before the implementation/reimplementation of SARS-CoV-2 SD measures.

Gravitrap deployment for adult Aedes aegypti surveillance and its impact on dengue cases.

House Index, Container Index, and Breteau Index are the most commonly used indices for dengue vector surveillance. However, these larval indices are a poor proxy for measuring the adult population-which is responsible for disease transmission. Information on the adult distribution and density are important for assessing transmission risk as well as for developing effective control strategies. This study introduces a new entomological index, Gravitrap aegypti index (GAI), which estimates the adult female Aedes aegypti population in the community and presents its association with dengue cases. Gravitraps were deployed across 34 treatment sites in Singapore from September 2013 to September 2016. The GAI, derived from the Gravitrap surveillance data, was analysed to investigate the spatio-temporal patterns of the Ae. aegypti population in Singapore. The index was further categorised into low, moderate, and high-risk groups and its association with dengue cases were examined. A Before-After Control Impact analysis was performed to evaluate the epidemiology impact of Gravitrap system on dengue transmission. The Ae. aegypti population exhibits a seasonal pattern, and spatial heterogeneity in Ae. aegypti abundance was observed among treatment sites. The Ae. aegypti population was also found to be unevenly distributed among floors of an apartment block, with low floors (floors 1-4) having a higher abundance of mosquitoes trapped than mid (floors 5-8) and high (floors ≥9) floors. Areas with high GAI were shown to have higher dengue case count. Gravitrap has also demonstrated to be a good dengue control tool. The contribution of cases by treatment sites to the national numbers was lower after Gravitraps deployment. The GAI, which is of better relevance to dengue transmission risk, could be recommended as an indicator for decision making in vector control efforts, and to monitor the spatio-temporal variability of the adult Aedes population in the country. In addition, findings from this study indicate that Gravitraps can be used as a dengue control tool to reduce dengue transmission.

Distribution and seasonal fluctuations of Ae. aegypti and Ae. albopictus larval and pupae in residential areas in an urban landscape.

Dengue, a vector-borne disease spread by Aedes mosquitoes, is a global threat. In the absence of an efficacious dengue vaccine, vector control is the key intervention tool in Singapore. A good understanding of vector habitats is essential to formulate operational strategies. We examined the distribution, long-term trend and seasonality of Aedes data collected during regulatory inspections in residences and public areas from 2008 to 2017. We also studied the seasonality of climate factors to understand their influence on the detection of Aedes-positive containers. The most frequently reported Aedes-positive containers were domestic containers, drains, discarded receptacles, ornamental containers, flower pot plates/trays, plants, gully traps, canvas/plastic sheet, bins, ground puddle, inspection chambers and roof tops/gutters. We found more Ae. aegypti and Ae. albopictus-positive containers per inspection in residences and public areas, respectively. The seasonality of Ae. aegypti-positive containers in residences and public areas coincided with that of mean temperature. However, the seasonality of Ae. albopictus-positive containers lagged by one month compared to that of mean temperature. Our study demonstrates the seasonal fluctuations of Aedes-positive containers in an urban environment. Understanding the distribution and seasonality of Aedes breeding helps to facilitate resource planning and community awareness to moderate dengue transmission.

The effects of climate variability and seasonal influence on diarrhoeal disease in the tropical city-state of Singapore - A time-series analysis.

BACKGROUND: Diarrhoeal disease is common and imposes substantial health and economic burdens across the globe, especially in the African and Southeast Asian regions. Besides causing high mortality and morbidity, diarrhoeal disease has also been associated with growth and cognitive shortfalls in children in low-resource settings. Extreme weather events brought about by climate change may increase diarrhoeal disease and impact vulnerable populations in countries regardless of levels of development. We examined the seasonal and climatic influences of acute diarrhoeal disease reports in Singapore, a city-state located in Southeast Asia. METHODS: We used a time-series analysis, adjusting for time-varying potential confounders in a negative binomial regression model and fitting fractional polynomials to investigate the relationship between climatic factors (temperature, relative humidity and rainfall) and reported diarrhoeal disease. RESULTS: We included 1,798,198 reports of diarrhoeal disease from 2005 to 2018. We observed annual trimodal peaks in the number of reports. Every 10% increase in relative humidity in the present week was positively associated with an increase in reports one week later [Incidence Rate Ratio (IRR): 1.030, 95% CI 1.004-1.057] and negatively associated with a decrease in reports six weeks later (IRR: 0.979, 95% CI 0.961-0.997). We observed effect modification of relative humidity on the risk of diarrhoeal disease in the first calendar quarter (January to March). There was weak evidence of a delayed effect of ambient air temperature on reports of diarrhoeal disease one week later (IRR: 1.013, 95% CI 0.998-1.027). No threshold effects of climatic factors were observed. Each week of school holidays was associated with a 14.4% reduction in diarrhoeal disease reports (IRR: 0.856, 95% CI: 0.840 to 0.871). Public holidays were associated with a reduction in reports in the same week and an increase a week later. CONCLUSIONS: Diarrhoeal disease is highly seasonal and is associated with climate variability. Food safety and primary healthcare resource mitigation could be timed in anticipation of seasonal and climate driven increases in disease reports.

Using Human Movement Data to Identify Potential Areas of Zika Transmission: Case Study of the Largest Zika Cluster in Singapore.

Singapore experienced its first Zika virus (ZIKV) cluster in August 2016. To understand the implication of human movement on disease spread, a retrospective study was conducted using aggregated and anonymized mobile phone data to examine movement from the cluster to identify areas of possible transmission. An origin⁻destination model was developed based on the movement of three groups of individuals: (i) construction workers, (ii) residents and (iii) visitors out of the cluster locality to other parts of the island. The odds ratio of ZIKV cases in a hexagon visited by an individual from the cluster, independent of the group of individuals, is 3.20 (95% CI: 2.65⁻3.87, p-value < 0.05), reflecting a higher count of ZIKV cases when there is a movement into a hexagon from the cluster locality. A comparison of independent ROC curves tested the statistical significance of the difference between the areas under the curves of the three groups of individuals. Visitors (difference in AUC = 0.119) and residents (difference in AUC = 0.124) have a significantly larger difference in area under the curve compared to the construction workers (p-value < 0.05). This study supports the proof of concept of using mobile phone data to approximate population movement, thus identifying areas at risk of disease transmission.

A novel entomological index, Aedes aegypti Breeding Percentage, reveals the geographical spread of the dengue vector in Singapore and serves as a spatial risk indicator for dengue.

BACKGROUND: Aedes aegypti is an efficient primary vector of dengue, and has a heterogeneous distribution in Singapore. Aedes albopictus, a poor vector of dengue, is native and ubiquitous on the island. Though dengue risk follows the dispersal of Ae. aegypti, the spatial distribution of the vector is often poorly characterized. Here, based on the ubiquitous presence of Ae. albopictus, we developed a novel entomological index, Ae. aegypti Breeding Percentage (BP), to demonstrate the expansion of Ae. aegypti into new territories that redefined the dengue burden map in Singapore. We also determined the thresholds of BP that render the specific area higher risk of dengue transmission. METHODS: We performed analysis of dengue fever incidence and Aedes mosquito breeding in Singapore by utilizing island-wide dengue cases and vector surveillance data from 2003 to 2013. The percentage of Ae. aegypti breeding among the total Aedes breeding habitats (BP), and the reported number of dengue fever cases in each year were calculated for each residential grid. RESULTS: The BP of grids, for every year over the 11-year study period, had a consistent positive correlation with the annual case counts. Our findings suggest that the geographical expansion of Ae. aegypti to previously "non-dengue" areas have contributed substantially to the recent dengue fever incidence in Singapore. Our analysis further indicated that non-endemic areas in Singapore are likely to be at risk of dengue fever outbreaks beyond an Ae. aegypti BP of 20%. CONCLUSIONS: Our analyses indicate areas with increasing Ae. aegypti BP are likely to become more vulnerable to dengue outbreaks. We propose the usage of Ae. aegypti BP as a factor for spatial risk stratification of dengue fever in endemic countries. The Ae. aegypti BP could be recommended as an indicator for decision making in vector control efforts, and also be used to monitor the geographical expansion of Ae. aegypti.

Highly Selective Transmission Success of Dengue Virus Type 1 Lineages in a Dynamic Virus Population: An Evolutionary and Fitness Perspective.

Arbovirus transmission is modulated by host, vector, virus, and environmental factors. Even though viral fitness plays a salient role in host and vector adaptation, the transmission success of individual strains in a heterogeneous population may be stochastic. Our large-scale molecular epidemiological analyses of a dengue virus type 1 population revealed that only a subset of strains (16.7%; n = 6) were able to sustain transmission, despite the population being widely dispersed, dynamic, and heterogeneous. The overall dominance was variable even among the "established" lineages, albeit sharing comparable evolutionary characteristics and replication profiles. These findings indicated that virological parameters alone were unlikely to have a profound effect on the survival of viral lineages, suggesting an important role for non-viral factors in the transmission success of lineages. Our observations, therefore, emphasize the strategic importance of a holistic understanding of vector, human host, and viral factors in the control of vector-borne diseases.