Evaluating quasi-experimental approaches for estimating epidemiological efficacy of non-randomised field trials: applications in Wolbachia interventions for dengue.

BACKGROUND: Wolbachia symbiosis in Aedes aegypti is an emerging biocontrol measure against dengue. However, assessing its real-world efficacy is challenging due to the non-randomised, field-based nature of most intervention studies. This research re-evaluates the spatial-temporal impact of Wolbachia interventions on dengue incidence using a large battery of quasi-experimental methods and assesses each method's validity. METHODS: A systematic search for Wolbachia intervention data was conducted via PUBMED. Efficacy was reassessed using commonly-used quasi-experimental approaches with extensive robustness checks, including geospatial placebo tests and a simulation study. Intervention efficacies across multiple study sites were computed using high-resolution aggregations to examine heterogeneities across sites and study periods. We further designed a stochastic simulation framework to assess the methods' ability to estimate intervention efficacies (IE). RESULTS: Wolbachia interventions in Singapore, Malaysia, and Brazil significantly decreased dengue incidence, with reductions ranging from 48.17% to 69.19%. IEs varied with location and duration. Malaysia showed increasing efficacy over time, while Brazil exhibited initial success with subsequent decline, hinting at operational challenges. Singapore's strategy was highly effective despite partial saturation. Simulations identified Synthetic Control Methods (SCM) and its variant, count Synthetic Control Method (cSCM), as superior in precision, with the smallest percentage errors in efficacy estimation. These methods also demonstrated robustness in placebo tests. CONCLUSIONS: Wolbachia interventions exhibit consistent protective effects against dengue. SCM and cSCM provided the most precise and robust estimates of IEs, validated across simulated and real-world settings.

Effects of Recent Prior Dengue Infection on Risk and Severity of Subsequent SARS-CoV-2 Infection: A Retrospective Cohort Study.

Background and Aims: Elucidating whether prior dengue potentially confers cross-protection against COVID-19 is of public health importance in tropical countries at risk of overlapping dengue and COVID-19 epidemics. However, studies to date have yielded conflicting results. We aimed to assess effects of recent prior dengue infection on risk and severity of subsequent SARS-CoV-2 infection among adult Singaporeans. Methods: A retrospective cohort study including all adult Singaporeans aged ≥18 years was conducted from 1 July 2021 through 31 October 2022, when a dengue outbreak driven by the DENV3 serotype preceded subsequent waves of SARS-CoV-2 Delta/Omicron transmission in Singapore. SARS-CoV-2 and dengue infection status were classified using national registries. Cox regression models adjusted for demographics, COVID-19 vaccination status, comorbidity, and socioeconomic-status were used to assess risks and severity (hospitalization, severe illness) of SARS-CoV-2 infection occurring after previous recorded dengue infection. Results: A total of 3 366 399 individuals were included, contributing 1 399 696 530 person-days of observation. A total of 13 434 dengue infections and 1 253 520 subsequent SARS-CoV-2 infections were recorded; with an average of 94.7 days (standard deviation = 83.8) between dengue infection and SARS-CoV-2 infection. Preceding dengue infection was associated with a modest increase in risk of subsequent SARS-CoV-2 infection (adjusted hazards ratio [aHR] = 1.13; 95% confidence interval [CI], 1.08-1.17), and significantly elevated risk of subsequent COVID-19 hospitalization (aHR = 3.25; 95% CI, 2.78-3.82) and severe COVID-19 (aHR = 3.39; 95% CI, 2.29-5.03). Conclusions: Increased risk of SARS-CoV-2 infection and adverse COVID-19 outcomes were observed following preceding dengue infection in a national population-based cohort of adult Singaporeans. This observation is of significance in tropical countries with overlapping dengue and COVID-19 outbreaks.

Assessing Wolbachia-mediated Sterility for Dengue Control: Emulation of a Cluster Randomized Target Trial in Singapore.

BACKGROUND: Matings between male Aedes aegypti mosquitoes infected with wAlbB strain of Wolbachia and wildtype females yield non-viable eggs. We evaluated the efficacy of releasing wAlbB-infected Ae. aegypti male mosquitoes to suppress dengue. METHODS: We specified the protocol of a two-arm cluster-randomized test-negative controlled trial (cRCT) and emulated it using a nationally representative test-negative/positive database of individuals reporting for febrile illness to any public hospital, general practitioner or polyclinic. We retrospectively built a cohort of individuals who reside in Wolbachia locations versus a comparator control group who do not reside in Wolbachia locations, using a nationally representative database of all individuals whom report for febrile illness and were tested for dengue at the Environmental Health Institute/hospital laboratories/commercial diagnostic laboratories, through general practitioner clinic, polyclinic or public/private hospital from EW1 2019-EW 262022. We emulated a constrained randomization protocol used in cRCTs to balance dengue risk between intervention and control arms in the pre-intervention period. We used the inverse-probability weighting approach to further balance the intervention and control groups using a battery of algorithmically selected sociodemographic, environmental and anthropogenic variables. Intention-to-treat analyses was conducted to estimate the risk reduction of dengue given Wolbachia exposure. RESULTS: Intention-to-treat analyses revealed that, compared with controls, Wolbachia releases for 3, 6, 12 or more months was associated to 47%(95%CI:25-69%), 44%(33-77%) and 61%(38-78%) protective efficacy against dengue, respectively. When exposed to 12 or more months of Wolbachia releases, protective efficacies ranged from 49%(13-72%) to 77%(60-94%) across years. The proportion of virologically confirmed dengue cases was lower overall in the intervention arm. Protective efficacies were found across all years, age and sex subgroups, with higher durations of Wolbachia exposure associated to greater risk reductions of dengue. CONCLUSION: Results demonstrated that Wolbachia-mediated sterility can strengthen dengue control in tropical cities, where dengue burden is the greatest.

The epidemiologic and economic burden of dengue in Singapore: A systematic review.

BACKGROUND: Despite its well-regarded vector control program, Singapore remains susceptible to dengue epidemics. To assist evaluation of dengue interventions, we aimed to synthesize current data on the epidemiologic and economic burden of dengue in Singapore. METHODOLOGY: We used multiple databases (PubMed, Embase, Cochrane, international/national repositories, surveillance) to search for published and gray literature (2000-2022). We included observational and cost studies, and two interventional studies, reporting Singapore-specific data on our co-primary outcomes, dengue incidence and dengue-related costs. Quality was assessed using the Newcastle-Ottawa Scale and an adapted cost-of-illness evaluation checklist. We performed a narrative synthesis and grouped studies according to reported outcomes and available stratified analyses. FINDINGS: In total, 333 reports (330 epidemiological, 3 economic) were included. Most published epidemiological studies (89%) and all economic studies were of good quality. All gray literature reports were from the Ministry of Health or National Environment Agency. Based predominantly on surveillance data, Singapore experienced multiple outbreaks in 2000-2021, attaining peak incidence rate in 2020 (621.1 cases/100,000 person-years). Stratified analyses revealed the highest incidence rates in DENV-2 and DENV-3 serotypes and the 15-44 age group. Among dengue cases, the risk of hospitalization has been highest in the ≥45-year-old age groups while the risks of dengue hemorrhagic fever and death have generally been low (both <1%) for the last decade. Our search yielded limited data on deaths by age, severity, and infection type (primary, secondary, post-secondary). Seroprevalence (dengue immunoglobulin G) increases with age but has remained <50% in the general population. Comprising 21-63% indirect costs, dengue-related total costs were higher in 2010-2020 (SGD 148 million) versus the preceding decade (SGD 58-110 million). CONCLUSION: Despite abundant passive surveillance data, more stratified and up-to-date data on the epidemiologic and economic burden of dengue are warranted in Singapore to continuously assess prevention and management strategies.

Update to: Assessing the efficacy of male Wolbachia-infected mosquito deployments to reduce dengue incidence in Singapore.

BACKGROUND: This trial is a parallel, two-arm, non-blinded cluster randomised controlled trial that is under way in Singapore, with the aim of measuring the efficacy of male Wolbachia-infected Aedes aegypti deployments in reducing dengue incidence in an endemic setting with all four dengue serotypes in circulation. The trial commenced in July 2022 and is expected to conclude in September 2024. The original study protocol was published in December 2022. Here, we describe amendments that have been made to the study protocol since commencement of the trial. METHODS: The key protocol amendments are (1) addition of an explicit definition of Wolbachia exposure for residents residing in intervention sites based on the duration of Wolbachia exposure at point of testing, (2) incorporation of a high-dimensional set of anthropogenic and environmental characteristics in the analysis plan to adjust for baseline risk factors of dengue transmission, and (3) addition of alternative statistical analyses for endpoints to control for post hoc imbalance in cluster-based environmental and anthropogenic characteristics. DISCUSSION: The findings from this study will provide the first experimental evidence for the efficacy of releasing male-Wolbachia infected mosquitoes to reduce dengue incidence in a cluster-randomised controlled trial. The trial will conclude in 2024 and results will be reported shortly thereafter. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT05505682. Registered on 16 August 2022. Retrospectively registered. Last updated 11 November 2023.

Receptiveness to monkeypox vaccines and public health communication strategies among gay, bisexual and other men who have sex with men in Singapore: cross-sectional quantitative and qualitative insights.

OBJECTIVES: Monkeypox (mpox) was declared as a global health emergency by the WHO, with most reported cases disproportionately involving gay, bisexual and other men who have sex with men (GBMSM). This study explored the willingness of Singaporean GBMSM to receive mpox vaccines and engage in changes to sexual behaviour, and analysed the factors influencing both decisions. METHODS: An online cross-sectional study was disseminated through community groups and Grindr from September to October 2022 among GBMSM in Singapore, where we surveyed respondents' demographics, stigma associated with mpox, perceived risks of sexually transmitted infections (STIs) and changes to sexual behaviours in response to mpox. Descriptive statistics and multivariable linear and logistics regression analyses, as well as thematic analysis of data, were also conducted. RESULTS: 237 GBMSM community members responded to the survey, with the majority being receptive to vaccine and 67.5% indicating changes to sexual behaviour in view of rising mpox infections. Predictors of vaccine receptivity among GBMSM included self-perceived mpox risk (adjusted OR (aOR)=0.44, 95% CI 0.07, 0.82) and self-perceived STI risk (aOR=0.39, 95% CI 0.03, 0.76). Predictors for changes to sexual behaviour included self-perceived mpox stigma (aOR=1.17, 95% CI 1.08, 1.27), self-perceived mpox risk (aOR=1.22, 95% CI 1.03,1.44), age (aOR=0.96, 95% CI 0.93, 1.00) and race (aOR=0.31, 95% CI 0.10, 0.93). In the thematic analysis, respondents raised concerns about vaccine effectiveness, side effects, cost and privacy. CONCLUSIONS: Our findings suggest that the rise in mpox infections have prompted changes to GBMSM's sexual practices. In general, GBMSM are willing to receive the mpox vaccine but are concerned about the physical and social consequences of uptake. These concerns should be addressed when vaccines are released.

Feasibility of wastewater-based detection of emergent pandemics through a global network of airports.

Wastewater-based surveillance has been put into practice during the pandemic. Persistence of SARS-CoV-2 in faeces of infected individuals, and high volume of passengers travelling by air, make it possible to detect virus from aircraft wastewater, lending itself to the potential identification of a novel pathogen prior to clinical diagnosis. In this study, we estimated the likelihood of detecting the virus through aircraft wastewater from the probabilities of air travel, viral shedding, defecation, testing sensitivity, and sampling. We considered various hypothetical scenarios, with diverse sampling proportions of inbound flights, surveillance airports, and sources of outbreaks. Our calculations showed that the probability of detecting SARS-CoV-2 would increase exponentially against time in the early phase of the pandemic, and would be much higher if the 20 major airports in Asia, Europe, and North America cooperated to perform aircraft wastewater surveillance. We also found other contributors to early detection, including high sampling proportion of inbound flight at destination airports, small population size of the epicentre relative to the travel volume, and large volume of outbound travelers to major airports around the globe. We concluded that routine aircraft wastewater monitoring could be a feasible approach for early identification and tracking of an emerging pathogen with high faecal shedding rates, particularly when implemented through a global surveillance network of major airports.

Efficacy of Wolbachia-mediated sterility to reduce the incidence of dengue: a synthetic control study in Singapore.

BACKGROUND: Due to the absence of available therapeutics and good vaccines, vector control solutions are needed to mitigate the spread of dengue. Matings between male Aedes aegypti mosquitoes infected with the wAlbB strain of Wolbachia and wildtype females yield non-viable eggs. We evaluated the efficacy of releasing wAlbB-infected A aegypti male mosquitoes to suppress dengue incidence. METHODS: In this synthetic control study, we conducted large-scale field trials in Singapore involving release of wAlbB-infected A aegypti male mosquitoes for dengue control via vector population suppression, from epidemiological week (EW) 27, 2018, to EW 26, 2022. We selected two large towns (Yishun and Tampines) to adopt an expanding release strategy and two smaller towns (Bukit Batok and Choa Chu Kang) to adopt a targeted-release approach. Releases were conducted two times a week in high-rise public housing estates. All intervention and control locations practised the same baseline dengue control protocol. The main outcome was weekly dengue incidence rate caused by any dengue virus serotype. We used incidence data collected by the Singapore Ministry of Health to assess the efficacy of the interventions. To compare interventions, we used the synthetic control method to generate appropriate counterfactuals for the intervention towns using a weighted combination of 30 control towns between EW 1, 2014 and EW 26, 2022. FINDINGS: Our study comprised an at-risk population of 607 872 individuals living in intervention sites and 3 894 544 individuals living in control sites. Interventions demonstrated up to 77·28% (121/156, 95% CI 75·81-78·58) intervention efficacy despite incomplete coverage across all towns until EW 26, 2022. Intervention efficacies increased as release coverage increased across all intervention sites. Releases led to 2242 (95% CI 2092-2391) fewer cases per 100 000 people in intervention sites during the study period. Secondary analysis showed that these intervention effects were replicated across all age groups and both sexes for intervention sites. INTERPRETATION: Our results demonstrated the potential of Wolbachia-mediated incompatible insect technique for strengthening dengue control in tropical cities, where dengue burden is the greatest. FUNDING: Singapore Ministry of Finance, Ministry of Sustainability, and the National Environment Agency, and the Singapore National Robotics Program.

The need for pre-emptive control strategies for mpox in Asia and Oceania.

Introduction: The transmission dynamics of the recent mpox outbreak highlights the lack of infrastructure available to rapidly respond to novel STI outbreaks, of which Asia and Oceania remains particularly susceptible. Here, we simulate outbreaks in this setting and propose the use of pre-emptive vaccination within the men who have sex with men (MSM) community before the arrival and establishment of the virus. Materials and methods: Using data driven heterogeneous sexual contact networks, we simulated outbreaks of mpox in Singapore, Hong Kong, and Sydney. An individual based SEIR compartmental model was used to simulate epidemic trajectories and the impact of different vaccination uptakes was assessed in their ability to avert or suppress outbreaks upon the arrival of mpox within the MSM populations. Results: The highly dense sexual networks of Singapore and Sydney experience rapid outbreaks, with infection peaks occurring at day 41 and 23 respectively, compared to Hong Kong which occurs at day 77. Across the simulations with no vaccination, 68.2%-89.7% of the MSM community will become infected with mpox across the different cities, over a simulation period of 1 year. By implementing vaccination strategies, the infection rate across the cities can be reduced to as low as 3.1% of the population (range: 3.1%-82.2%) depending on the implementation and uptake of the vaccine. Vaccination is also extremely effective in slowing the start of the epidemic, delaying the epidemic peak by 36-50 days in Hong Kong, or even preventing the outbreak of mpox. Discussion: With extremely dense and well-connected sexual contact networks, where 65.2%-83.2% of the population are connected to a super-spreader in the different contact networks, pre-emptive or immediate vaccination upon identification of the first case is strongly recommended to help better manage the outbreak of mpox and prevent potential straining of healthcare systems.

Long-term neuropsychiatric sequelae of Delta versus Omicron SARS-CoV-2 infection.

OBJECTIVES: Studies have reported increased rates of long-term neuropsychiatric sequelae after SARS-CoV-2 infection using electronic health-record (EHR) data; however, the majority were conducted before Omicron and booster rollout. We estimated the long-term risks and excess burdens of pre-specified new-incident neuropsychiatric diagnoses after Delta versus Omicron BA.1/2 infection in a highly-vaccinated and boosted cohort of adult Singaporeans. METHODS: The national SARS-CoV-2 testing registry was used to construct cohorts of Singaporean adults infected during periods of Delta and Omicron BA.1/2 predominance and a contemporaneous test-negative control group. New-incident neuropsychiatric diagnoses recorded in the national health care claims database were identified up to 300 days postinfection. Risks and excess burden were estimated using a doubly robust competing-risks survival analysis. RESULTS: 104 179 and 375 903 infected cases were assigned to Delta and Omicron cohorts and compared against test-negative controls (Delta: N = 666 575 and Omicron: N = 619 379). Elevated risk of cognition or memory disorders was consistently reported across Omicron (Adjusted hazards ratio [aHR], 1.24; 95% CI, 1.12-1.38) and Delta cohorts (aHR, 1.63; 95% CI, 1.39-1.92). Delta-variant infection was associated with an increased risk of anosmia or dysgeusia (aHR, 4.53; 95% CI, 2.78-7.41) and psychosis (aHR, 1.65; 95% CI, 1.22-2.22). By contrast, Omicron-variant infection was associated with a risk of abnormal involuntary movements (aHR, 1.93; 95% CI, 1.32-2.83). Risks of neuropsychiatric sequelae predominantly accrued in hospitalized individuals. DISCUSSIONS: A modestly increased risk of cognition and memory disorders at 300 days after SARS-CoV-2 infection was observed among adult Singaporeans infected during the Delta/Omicron BA.1/2 transmission. There was no overall increased risk of neuropsychiatric sequelae observed across other domains. Variant-specific differences were also observed in individual neuropsychiatric sequelae, including an elevated risk of anosmia or dysgeusia after Delta-variant infection.

Non-linear associations between meteorological factors, ambient air pollutants and major mosquito-borne diseases in Thailand.

BACKGROUND: Transmission intensity for mosquito-borne diseases are highly heterogenous and multi-factorial. Understanding risk factors associated to disease transmission allow the optimization of vector control. This study sets out to understand and compare the combined anthropogenic and environmental risk factors of four major mosquito-borne diseases, dengue, malaria, chikungunya and Japanese encephalitis in Thailand. METHODS: An integrated analysis of mosquito-borne diseases, meteorological and ambient air pollutants of 76 provinces of Thailand was conducted over 2003-2021. We explored the use of generalized linear models and generalized additive models to consider both linear and non-linear associations between meteorological factors, ambient air pollutants and mosquito-borne disease incidence. Different assumptions on spatio-temporal dependence and nonlinearity were considered through province-specific and panel models, as well as different spline functions. Disease-specific model evidence was assessed to select best-fit models for epidemiological inference downstream. RESULTS: Analyses indicated several findings which can be generally applied to all diseases explored: (1) higher AH above mean values was positively associated with disease case counts (2) higher total precipitation above mean values was positively associated with disease case counts (3) extremely high temperatures were negatively associated with disease case counts (4) higher SO2 and PM2.5 surface concentrations were negatively associated with disease case counts. However, the relationships between disease and RH, non-extreme temperatures and CO surface concentration were more mixed, with directions of associations changing across the different diseases considered. CONCLUSIONS: This study found protective and enhancing effects of meteorological and ambient air pollutant factors on mosquito-borne diseases burdens in Thailand. Further studies should employ these factors to understand and predict risk factors associated with mosquito-borne disease transmission.

Understanding knowledge, attitudes and behaviours related to dietary sodium intake in a multi-ethnic population in Singapore.

OBJECTIVE: This study aimed to fill the current gap in the understanding of the knowledge, attitudes and behaviours (KAB) related to dietary Na among adult residents in Singapore. DESIGN: A cross-sectional online survey was conducted between October and December 2020 on 955 participants selected through random sampling. SETTING: The survey was conducted in Singapore. PARTICIPANTS: Participants were recruited from the Singapore Population Health Study Online Panel. RESULTS: Participants' mean age was 46·6 ± 14·1 years old and 58 % of them were females. Most of the participants were Chinese (82·1 %), 10·5 % were Indian and 4·5 % were Malay. Findings from the weighted data showed that most participants were aware of the health impact of high Na consumption. However, many participants were unaware of the recommended intake for salt (68%) and Na (83%), had misconceptions, and were unable to correctly use food labels to assess NA content (69%). Findings also alluded to the presence of knowledge gaps in the sources of Na in their diet. While 59 % of the participants reported to be limiting their consumption of Na, many reported facing barriers such as not knowing how to limit their Na intake. Participants also felt that there were limited options for low-Na foods when eating out and were lacking awareness of low-Na products. CONCLUSIONS: Findings highlighted substantial gaps in participants' knowledge and skills in managing their Na consumption. This suggests the need for more public education and improvements in the food environment.

Associations between Dengue Incidence, Ecological Factors, and Anthropogenic Factors in Singapore.

Singapore experiences endemic dengue. Vector control remains the primary means to reduce transmission due to the lack of available therapeutics. Resource limitations mean that vector-control tools need to be optimized, which can be achieved by studying risk factors related to disease transmission. We developed a statistical modelling framework which can account for a high-resolution and high-dimensional set of covariates to delineate spatio-temporal characteristics that are associated with dengue transmission from 2014 to 2020 in Singapore. We applied the proposed framework to two distinct datasets, stratified based on the primary type of housing within each spatial unit. Generalized additive models reveal non-linear exposure responses between a large range of ecological and anthropogenic factors as well as dengue incidence rates. At values below their mean, lesser mean total daily rainfall (Incidence rate ratio (IRR): 3.75, 95% CI: 1.00-14.05, Mean: 4.40 mm), decreased mean windspeed (IRR: 3.65, 95% CI: 1.87-7.10, Mean: 4.53 km/h), and lower building heights (IRR: 2.62, 95% CI: 1.44-4.77, Mean: 6.5 m) displayed positive associations, while higher than average annual NO2 concentrations (IRR: 0.35, 95% CI: 0.18-0.66, Mean: 13.8 ppb) were estimated to be negatively associated with dengue incidence rates. Our study provides an understanding of associations between ecological and anthropogenic characteristics with dengue transmission. These findings help us understand high-risk areas of dengue transmission, and allows for land-use planning and formulation of vector control policies.

Acculturation as a Determinant of Obesity and Related Lifestyle Behaviors in a Multi-Ethnic Asian Population.

Limited attention has been given to the role of cultural orientation towards different ethnic groups in multi-ethnic settings without a dominant host culture. We evaluated whether acculturation levels, reflecting cultural orientation towards other ethnic groups, were associated with obesity and related lifestyle behaviors in a cosmopolitan Asian population. We conducted the current study based on data from the Singapore Multi-Ethnic Cohort (N = 10,622) consisting of ethnic Chinese, Malays, and Indians aged 21 to 75 years. Multivariable linear and logistic regression analyses were used to examine associations between the acculturation level (z-score), obesity, and related lifestyle behaviors, including dietary habits and physical activity. A higher acculturation level was directly associated with a higher prevalence of obesity among Chinese, whereas an inverse association was found for ethnic Indians, and no significant association in Malays. In ethnic Malays, greater acculturation was significantly associated with higher dietary quality and less sedentary time. Furthermore, a high acculturation level was significantly associated with higher sugar-sweetened beverage consumption and more leisure-time PA in all ethnic groups. Our findings suggest that greater cultural orientation towards other ethnic groups was associated with convergence in obesity levels. More research is required to understand how acculturation affects obesity-related lifestyle factors in multi-ethnic settings.

EpiMix: A novel method to estimate effective reproduction number.

Transmission potential of a pathogen, often quantified by the time-varying reproduction number Rt, provides the current pace of infection for a disease and indicates whether an emerging epidemic is under control. In this study, we proposed a novel method, EpiMix, for Rt estimation, wherein we incorporated the impacts of exogenous factors and random effects under a Bayesian regression framework. Using Integrated Nested Laplace Approximation, EpiMix is able to efficiently generate reliable, deterministic Rt estimates. In the simulations and case studies performed, we further demonstrated the method's robustness in low-incidence scenarios, together with other merits, including its flexibility in selecting variables and tolerance of varying reporting rates. All these make EpiMix a potentially useful tool for real-time Rt estimation provided that the serial interval distribution, time series of case counts and external influencing factors are available.

Density forecasting of conjunctivitis burden using high-dimensional environmental time series data.

As one of the most common eye conditions being presented at clinics, acute conjunctivitis puts substantial strain on primary health resources. To reduce this public health burden, it is important to forecast and provide forward guidance to policymakers by estimating conjunctivitis trends, taking into account factors which influence transmission. Using a high-dimensional set of ambient air pollution and meteorological data, this study describes new approaches to point and probabilistic forecasting of conjunctivitis burden which can be readily translated to other infectious diseases. Over the period of 2012 - 2022, we show that simple models without environmental data provided better point forecasts but the more complex models which optimized predictive accuracy and combined multiple predictors demonstrated superior density forecast performance. These results were shown to be consistent over periods with and without structural breaks in transmission. Furthermore, ecological analysis using post-selection inference showed that increases in SO2, O3 surface concentration and total precipitation were associated to increased conjunctivitis attendance. The methods proposed can provide rich and informative forward guidance for outbreak preparedness and help guide healthcare resource planning in both stable periods of transmission and periods where structural breaks in data occur.

Use of Bluetooth contact tracing technology to model COVID-19 quarantine policies in high-risk closed populations.

Containment measures in high-risk closed settings, like migrant worker (MW) dormitories, are critical for mitigating emerging infectious disease outbreaks and protecting potentially vulnerable populations in outbreaks such as coronavirus disease 2019 (COVID-19). The direct impact of social distancing measures can be assessed through wearable contact tracing devices. Here, we developed an individual-based model using data collected through a Bluetooth wearable device that collected 33.6M and 52.8M contact events in two dormitories in Singapore, one apartment style and the other a barrack style, to assess the impact of measures to reduce the social contact of cases and their contacts. The simulation of highly detailed contact networks accounts for different infrastructural levels, including room, floor, block, and dormitory, and intensity in terms of being regular or transient. Via a branching process model, we then simulated outbreaks that matched the prevalence during the COVID-19 outbreak in the two dormitories and explored alternative scenarios for control. We found that strict isolation of all cases and quarantine of all contacts would lead to very low prevalence but that quarantining only regular contacts would lead to only marginally higher prevalence but substantially fewer total man-hours lost in quarantine. Reducing the density of contacts by 30% through the construction of additional dormitories was modelled to reduce the prevalence by 14 and 9% under smaller and larger outbreaks, respectively. Wearable contact tracing devices may be used not just for contact tracing efforts but also to inform alternative containment measures in high-risk closed settings.

Association between ambient air pollutants and upper respiratory tract infection and pneumonia disease burden in Thailand from 2000 to 2022: a high frequency ecological analysis.

BACKGROUND: A pertinent risk factor of upper respiratory tract infections (URTIs) and pneumonia is the exposure to major ambient air pollutants, with short term exposures to different air pollutants being shown to exacerbate several respiratory conditions. METHODS: Here, using disease surveillance data comprising of reported disease case counts at the province level, high frequency ambient air pollutant and climate data in Thailand, we delineated the association between ambient air pollution and URTI/Pneumonia burden in Thailand from 2000 - 2022. We developed mixed-data sampling methods and estimation strategies to account for the high frequency nature of ambient air pollutant concentration data. This was used to evaluate the effects past concentrations of fine particulate matter (PM2.5), sulphur dioxide (SO2), and carbon monoxide (CO) and the number of disease case count, after controlling for the confounding meteorological and disease factors. RESULTS: Across provinces, we found that past increases in CO, SO2, and PM2.5 concentration were associated to changes in URTI and pneumonia case counts, but the direction of their association mixed. The contributive burden of past ambient air pollutants on contemporaneous disease burden was also found to be larger than meteorological factors, and comparable to that of disease related factors. CONCLUSIONS: By developing a novel statistical methodology, we prevented subjective variable selection and discretization bias to detect associations, and provided a robust estimate on the effect of ambient air pollutants on URTI and pneumonia burden over a large spatial scale.

Border Control for Infectious Respiratory Disease Pandemics: A Modelling Study for H1N1 and Four Strains of SARS-CoV-2.

Post-pandemic economic recovery relies on border control for safe cross-border movement. Following the COVID-19 pandemic, we investigate whether effective strategies generalize across diseases and variants. For four SARS-CoV-2 variants and influenza A-H1N1, we simulated 21 strategy families of varying test types and frequencies, quantifying expected transmission risk, relative to no control, by strategy family and quarantine length. We also determined minimum quarantine lengths to suppress relative risk below given thresholds. SARS-CoV-2 variants showed similar relative risk across strategy families and quarantine lengths, with at most 2 days' between-variant difference in minimum quarantine lengths. ART-based and PCR-based strategies showed comparable effectiveness, with regular testing strategies requiring at most 9 days. For influenza A-H1N1, ART-based strategies were ineffective. Daily ART testing reduced relative risk only 9% faster than without regular testing. PCR-based strategies were moderately effective, with daily PCR (0-day delay) testing requiring 16 days for the second-most stringent threshold. Viruses with high typical viral loads and low transmission risk given low viral loads, such as SARS-CoV-2, are effectively controlled with moderate-sensitivity tests (ARTs) and modest quarantine periods. Viruses with low typical viral loads and substantial transmission risk at low viral loads, such as influenza A-H1N1, require high-sensitivity tests (PCR) and longer quarantine periods.