Rodent activity in municipal waste collection premises in Singapore: an analysis of risk factors using mixed-effects modelling.

Refuse storage and collection systems are potential sources of food and harbourage areas for rodents which transmit pathogens. We examined the factors associated with rodent activity in public housing municipal waste collection premises in a highly urbanized city-state. We analysed data from April 2019 to March 2020 in mixed-effects logistic regression models to examine the independent factors associated with rodent activity in central refuse chute rooms (CRCs), individual refuse chute (IRC) bin chambers and bin centres. We accounted for within-year patterns, repeated measures and nested effects. We observed a heterogeneous spatial distribution of rodent activity. Rodent droppings were strongly associated with rodent activity in CRCs (aOR: 6.20, 95% CI: 4.20-9.15), bin centres (aOR: 3.61, 95% CI: 1.70-7.64) and IRC bin chambers (aOR: 90.84, 95% CI: 70.13-117.67). Gnaw marks were positively associated with rodent activity in CRCs (aOR: 5.61, 95% CI: 3.55-8.97) and IRC bin chambers (aOR: 2.05, 95% CI: 1.43-2.95), as were rub marks in CRCs (aOR: 5.04, 95% CI: 3.44-7.37) and IRC bin chambers (aOR: 3.07, 95% CI: 1.74-5.42). Each burrow increased the odds of rodent sightings in bin centres (aOR: 1.03, 95% CI: 1.00-1.06). The odds of rodent sightings in an IRC bin chamber increased with every additional bin chute chamber within the same block (aOR: 1.04, 95% CI: 1.01-1.07). We identified several factors that well predicted rodent activity in waste collection premises. Municipal estate managers with limited resources can adopt a risk-based approach in tailoring the focus of their rodent control interventions.

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.

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).

Ambient temperature and hospital admissions for non-ST segment elevation myocardial infarction in the tropics.

BACKGROUND: Myocardial infarction is an important cause of cardiovascular mortality and can be precipitated by climatic factors. The temperature dependence of myocardial infarction risk has been well examined in temperate settings. Fewer studies have investigated this in the tropics where thermal amplitudes are narrower. This study investigated how ambient temperature influenced the risk of non-ST segment elevation myocardial infarction (NSTEMI), an increasingly common type of myocardial infarction, in the tropical city-state of Singapore. METHODS: All nationally reported NSTEMI cases from 2009 to 2018 were included and assessed for its short-term association with ambient temperature using conditional Poisson regression models that comprised a three-way interaction term with year, month and day of the week and adjusted for relative humidity. The Distributed Lag Non-Linear Modelling (DLNM) was used to account for the immediate and lagged effects of environmental exposures. Stratified analysis by sex and age groups was undertaken to assess potential effect modification. RESULTS: There were 60,643 reports of NSTEMI. Temperature decline (cool effect) was associated with a delayed cumulative, non-linear increase in NSTEMI risk over 10 days post exposure [Relative Risk (RRlag0-10, 10th percentile: 1.12, 95%CI: 1.02-1.24)]. Those aged 65 years and above were potentially more susceptible (RR lag0-10, 10th percentile: 1.19, 95 % CI: 1.06-1.33) to the cool effect compared to those below that age (RRlag0-10, 10th percentile: 1.00, 95 % CI: 0.85-1.18) (p-value for difference = 0.087). CONCLUSION: Short-term temperature fluctuations were independently associated with NSTEMI incidence in the tropics, with age as a potential effect modifier of this association. An increase in the frequency of climate change driven temperature events may trigger more instances of NSTEMI in tropical cosmopolitan cities.

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.

The use of anticoagulants for rodent control in a mixed-use urban environmefent in Singapore: A controlled interrupted time series analysis.

Vector control remains an important strategy in preventing rodent-borne diseases. Studies quantifying the impact of anticoagulant bait use on rodent populations are scarce in tropical settings. This study examined the impact of anticoagulant bait use on three measures of rodent activity in Singapore to inform rodent-borne disease control strategies. Using a controlled interrupted time-series analytical design with negative binomial and linear regression models, the average rodent activity levels were compared in the pre- and post-intervention periods. There was a 62.7% (Incidence Rate Ratio (IRR): 0.373, 95% CI: [0.224, 0.620]) reduction in the number of rodents caught, a 25.8-unit (coefficient = -25.829, 95% CI: [-29.855, -21.804]) reduction in the number of 30 g/unit baits consumed and a 61.9% (IRR: 0.381, 95% CI: [0.218, 0.665]) reduction in the number of marred bait stations relative to the pre-intervention period. There was a rise in all three outcome measures within four months after the post-intervention period. This study provided strong evidence that anticoagulant baits substantially reduces rodent activity. The population resurgence after the post-intervention period reinforces the importance of timing the resumption of control measures aimed at reducing rodent-borne disease transmission.

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.

Climate variability and seasonal patterns of paediatric parainfluenza infections in the tropics: An ecological study in Singapore.

OBJECTIVES: Evidence of the relationship between climate variability, air pollution and human parainfluenza virus (HPIV) infections has been inconsistent. We assessed this in a paediatric population from a highly urbanized tropical city-state. METHODS: We analysed all reports of HPIV infections in children <5 years old obtained from a major specialist women and children's hospital in Singapore. Assuming a negative binomial distribution and using multivariable fractional polynomial modelling, we examined the relations between climate variability, air quality and the risk of HPIV infections, adjusting for time-varying confounders. RESULTS: We identified 6393 laboratory-confirmed HPIV infections from 2009 to 2019. Every 1 °C decline in temperature was associated with a 5.8% increase (RR: 0.943, 95% Confidence Interval [95% CI]: 0.903-0.984) in HPIV infection risk 6 days later. Every 10% decrease in relative humidity was associated with a 15.8% cumulative increase in HPIV risk over the next 6 days (cumulative RR: 0.842, 95% CI: 0.771-0.919). Rainfall was positively associated with HPIV risk 2 days later (RR: 1.021, 95% CI: 1.000-1.043). A within-year seasonal rise of HPIV was driven by HPIV-3 and HPIV-1 and preceded by a seasonal decline in temperature. Gender was an effect modifier of the climate-HPIV relationship. Air quality was not associated with HPIV risk. CONCLUSIONS: This study demonstrates a close association between HPIV infection risk and tropical climate variability. The climate dependence and seasonal predictability of HPIV can inform the timing of community campaigns aimed at reducing infection risk and the development of hospital resources and climate adaption plans.

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.

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.

The abundance of Culex mosquito vectors for West Nile Virus and other flaviviruses: A time-series analysis of rainfall and temperature dependence in Singapore.

Culex mosquitoes are important vectors of West Nile Virus (WNV), St. Louis Encephalitis Virus (SLEV) and Japanese Encephalitis Virus (JEV). Climate change is expected to alter their ability to spread diseases in human populations. Studies examining the influence of climate variability on Culex mosquitoes in South East Asia are scarce. We examined the influence of climate variability on reported Culex mosquito larval habitats from 2009 to 2018 in Singapore. We analysed the non-linear immediate and lagged weather dependence of Culex habitats over 5 weeks in negative binomial regression models using nationally representative data. We adjusted for the effects of long-term trend, seasonality, public holidays and autocorrelation. There were 41,170 reported Culex larval habitats over the study period. Non-residential premises were associated with more reports of habitats compared to residential premises [Rate Ratio (RR): 113.9, 95% CI: 110.9, 116.9]. Larvae in more than 90% of these habitats were entomologically identified as Culex quinquefasciatus. In residences, every 10 mm increase in rainfall above a 90 mm threshold was associated with a 10.1% [Incidence Rate Ratio (IRR): 0.899, 95% CI: 0.836, 0.968] cumulative decline in larval habitats. Public holidays were not significantly included in the model analysing larval habitats in residences. In non-residences, a 1 °C increase in the ambient air temperature with respect to the mean was associated with a 36.0% (IRR: 1.360, 95% CI: 1.057, 1.749) cumulative increase in Culex larval habitats. Public holidays were associated with a decline in Culex larval habitats in the same week. Our study provides evidence of how ambient air temperature and rainfall variability influences the abundance of Culex mosquito larval habitats. Our findings support the utility of using weather data in predictive models to inform the timing of vector control measures aimed at reducing the risk of WNV and other Culex-borne flavivirus transmission in urban areas.