Usefulness of aircraft and airport wastewater for monitoring multiple pathogens including SARS-CoV-2 variants.

BACKGROUND: As global travel resumed in COVID-19 endemicity, the potential of aircraft wastewater monitoring to provide early warning of disease trends for SARS-CoV-2 variants and other infectious diseases, particularly at international air travel hubs, was recognised. We therefore assessed and compared the feasibility of testing wastewater from inbound aircraft and airport terminals for 18 pathogens including SARS-CoV-2 in Singapore, a popular travel hub in Asia. METHODS: Wastewater samples collected from inbound medium- and long-haul flights and airport terminals were tested for SARS-CoV-2. Next Generation Sequencing (NGS) was carried out on positive samples to identify SARS-CoV-2 variants. Airport and aircraft samples were further tested for 17 other pathogens through quantitative reverse transcription polymerase chain reaction (RT-qPCR). RESULTS: The proportion of SARS-CoV-2-positive samples and the average virus load was higher for wastewater samples from aircraft as compared to airport terminals. Cross-correlation analyses indicated that viral load trends from airport wastewater led local COVID-19 case trends by two to five days. A total of ten variants (44 sub-lineages) were successfully identified from aircraft wastewater and airport terminals, and four variants of interest (VOIs) and one variant under monitoring (VUM) were detected in aircraft and airport wastewater 18-31 days prior to detection in local clinical cases. The detection of five respiratory and four enteric viruses in aircraft wastewater samples further underscores the potential to expand aircraft wastewater to monitoring pathogens beyond SARS-CoV-2. CONCLUSION: Our findings demonstrate the feasibility of aircraft wastewater testing for monitoring infectious diseases threats, potentially detecting signals before clinical cases are reported. The triangulation of similar datapoints from aircraft wastewater of international travel nodes could therefore serve as a useful early warning system for global health threats.

Positive association of SARS-CoV-2 RNA concentrations in wastewater and reported COVID-19 cases in Singapore - A study across three populations.

Wastewater testing of SARS-CoV-2 has been adopted globally and has shown to be a useful, non-intrusive surveillance method for monitoring COVID-19 trends. In Singapore, wastewater surveillance has been widely implemented across various sites and has facilitated timely COVID-19 management and response. From April 2020 to February 2022, SARS-CoV-2 RNA concentrations in wastewater monitored across three populations, nationally, in the community, and in High Density Living Environments (HDLEs) were aggregated into indices and compared with reported COVID-19 cases and hospitalisations. Temporal trends and associations of these indices were compared descriptively and quantitatively, using Poisson Generalised Linear Models and Generalised Additive Models. National vaccination rates and vaccine breakthrough infection rates were additionally considered as confounders to shedding. Fitted models quantified the temporal associations between the indices and cases and COVID-related hospitalisations. At the national level, the wastewater index was a leading indicator of COVID-19 cases (p-value <0.001) of one week, and a contemporaneous association with hospitalisations (p-value <0.001) was observed. At finer levels of surveillance, the community index was observed to be contemporaneously associated with COVID-19 cases (p-value <0.001) and had a lagging association of 1-week in HDLEs (p-value <0.001). These temporal differences were attributed to differences in testing routines for different sites during the study period and the timeline of COVID-19 progression in infected persons. Overall, this study demonstrates the utility of wastewater surveillance in understanding underlying COVID-19 transmission and shedding levels, particularly for areas with falling or low case ascertainment. In such settings, wastewater surveillance showed to be a lead indicator of COVID-19 cases. The findings also underscore the potential of wastewater surveillance for monitoring other infectious diseases threats.

Severity of SARS-CoV-2 Omicron XBB subvariants in Singapore.

Several XBB subvariants such as XBB.1.5, XBB.1.9, XBB.1.16 and XBB.2.3 co-circulate in Singapore. Despite the different viral properties of XBB.1.16 as compared to other XBB subvariants, comparison on their severity is limited. In this study, we investigate the outcomes of hospitalisation and severe COVID-19 infection in individuals infected with different XBB subvariants, adjusted for potential confounders such as age and vaccination history. Overall, our preliminary analysis showed that the risk of severe outcomes when infected with XBB.1.16 is higher than that of XBB.1.5 or XBB.1.9 but there is no difference in the risk of hospitalisation across different XBB subvariants.

Serial Intervals and Incubation Periods of SARS-CoV-2 Omicron and Delta Variants, Singapore.

We compared serial intervals and incubation periods for SARS-CoV-2 Omicron BA.1 and BA.2 subvariants and Delta variants in Singapore. Median incubation period was 3 days for BA.1 versus 4 days for Delta. Serial interval was 2 days for BA.1 and 3 days for BA.2 but 4 days for Delta.

The role of health systems for health security: a scoping review revealing the need for improved conceptual and practical linkages.

BACKGROUND: Practical links between health systems and health security are historically prevalent, but the conceptual links between these fields remain under explored, with little on health system strengthening. The need to address this gap gains relevance in light of the COVID-19 pandemic as it demonstrated a crucial relationship between health system capacities and effective health security response. Acknowledging the importance of developing stronger and more resilient health systems globally for health emergency preparedness, the WHO developed a Health Systems for Health Security framework that aims to promote a common understanding of what health systems for health security entails whilst identifying key capacities required. METHODS/ RESULTS: To further explore and analyse the conceptual and practical links between health systems and health security within the peer reviewed literature, a rapid scoping review was carried out to provide an overview of the type, extent and quantity of research available. Studies were included if they had been peer-reviewed and were published in English (seven databases 2000 to 2020). 343 articles were identified, of those 204 discussed health systems and health security (high and medium relevance), 101 discussed just health systems and 47 discussed only health security (low relevance). Within the high and medium relevance articles, several concepts emerged, including the prioritization of health security over health systems, the tendency to treat health security as exceptionalism focusing on acute health emergencies, and a conceptualisation of security as 'state security' not 'human security' or population health. CONCLUSION: Examples of literature exploring links between health systems and health security are provided. We also present recommendations for further research, offering several investments and/or programmes that could reliably lead to maximal gains from both a health system and a health security perspective, and why these should be explored further. This paper could help researchers and funders when deciding upon the scope, nature and design of future research in this area. Additionally, the paper legitimises the necessity of the Health Systems for Health Security framework, with the findings of this paper providing useful insights and evidentiary examples for effective implementation of the framework.

The costs of improving health emergency preparedness: A systematic review and analysis of multi-country studies.

BACKGROUND: Investing in health emergency preparedness is critical to the safety, welfare and stability of communities and countries worldwide. Despite the global push to increase investments, questions remain around how much should be spent and what to focus on. We conducted a systematic review and analysis of studies that costed improvements to health emergency preparedness to help to answer these questions. METHODS: We searched for studies that estimated the costs of improving health emergency preparedness and that were published between 1 January 2000 and 14 May 2021, using PubMed, Web of Science, Google Scholar, EconLit, and National Health Service Economic Evaluation Databases (PROSPERO CRD42021254428). We also searched grey literature repositories and contacted subject experts. We included studies that estimated the costs of improving preparedness at the global level and/or at the national level across at least ten countries, covered two or more technical areas in the WHO Benchmarks for International Health Regulations (IHR) Capacities, and included activities focused on human health. We mapped costs across technical areas in the WHO Benchmarks for IHR Capacities. FINDINGS: Ten studies met our inclusion criteria. Costing methods varied substantially across included studies and cost estimates ranged from US$1·6 billion per year to improve capacities across 139 low- and middle-income countries (LMICs) to US$43 billion per year to support national-level activities worldwide and implement global-level initiatives, such as research and development for health technologies (diagnostics, therapeutics, and vaccines). Two recent studies estimated costs by drawing on IHR Monitoring and Evaluation Framework country capacity data, with one study estimating costs across 67 LMICs of US$15·4 billion per year (US$29·1 billion including upfront capital costs) and the other calculating costs for the 196 States Parties to the IHR of US$24·8 billion per year. Differences in included studies' methods, and the characteristics of countries considered, mean it is difficult to make like-for-like comparisons of the absolute costs or per-capita costs estimated by studies. INTERPRETATION: Improving health emergency preparedness worldwide will require substantial and sustained increases in investments. Further guidance on estimating the size of those investments can help to standardise methods, allowing greater interpretation and comparison across studies/countries. As well as greater transparency and detail in the reporting of methods by studies focused on this topic, this can help support estimates of global resource requirements and facilitate investments towards improving preparedness for future pandemics. FUNDING: None.

Simulation exercises and after action reviews - analysis of outputs during 2016-2019 to strengthen global health emergency preparedness and response.

BACKGROUND: Under the International Health Regulations (2005) [IHR (2005)] Monitoring and Evaluation Framework, after action reviews (AAR) and simulation exercises (SimEx) are two critical components which measure the functionality of a country's health emergency preparedness and response under a "real-life" event or simulated situation. The objective of this study was to describe the AAR and SimEx supported by the World Health Organization (WHO) globally in 2016-2019. METHODS: In 2016-2019, WHO supported 63 AAR and 117 SimEx, of which 42 (66.7%) AAR reports and 56 (47.9%) SimEx reports were available. We extracted key information from these reports and created two central databases for AAR and SimEx, respectively. We conducted descriptive analysis and linked the findings according to the 13 IHR (2005) core capacities. RESULTS: Among the 42 AAR and 56 SimEx available reports, AAR and SimEx were most commonly conducted in the WHO African Region (AAR: n = 32, 76.2%; SimEx: n = 32, 52.5%). The most common public health events reviewed or tested in AAR and SimEx, respectively, were epidemics and pandemics (AAR: n = 38, 90.5%; SimEx: n = 46, 82.1%). For AAR, 10 (76.9%) of the 13 IHR core capacities were reviewed at least once, with no AAR conducted for food safety, chemical events, and radiation emergencies, among the reports available. For SimEx, all 13 (100.0%) IHR capacities were tested at least once. For AAR, the most commonly reviewed IHR core capacities were health services provision (n = 41, 97.6%), risk communication (n = 39, 92.9%), national health emergency framework (n = 39, 92.9%), surveillance (n = 37, 88.1%) and laboratory (n = 35, 83.3%). For SimEx, the most commonly tested IHR core capacity were national health emergency framework (n = 56, 91.1%), followed by risk communication (n = 48, 85.7%), IHR coordination and national IHR focal point functions (n = 45, 80.4%), surveillance (n = 31, 55.4%), and health service provision (n = 29, 51.8%). For AAR, the median timeframe between the end of the event and AAR was 125 days (range = 25-399 days). CONCLUSIONS: WHO has recently published guidance for the planning, execution, and follow-up of AAR and SimEx. Through the guidance and the simplified reporting format provided, we hope to see more countries conduct AAR and SimEx and standardization in their methodology, practice, reporting and follow-up.

Imported Monkeypox, Singapore.

In May 2019, we investigated monkeypox in a traveler from Nigeria to Singapore. The public health response included rapid identification of contacts, use of quarantine, and postexposure smallpox vaccination. No secondary cases were identified. Countries should develop surveillance systems to detect emerging infectious diseases globally.

Using a HIV registry to develop accurate estimates for the HIV care cascade - the Singapore experience.

INTRODUCTION: Achieving UNAIDS 90-90-90 targets is a crucial step towards ending the AIDS epidemic. Many countries have published estimates of care cascades, although often with methodological limitations. We describe an approach that used the national HIV registry as a starting-point to determine the HIV care cascade and resulting UNAIDS 90-90-90 estimates for Singapore in 2014. METHODS: HIV is a legally notifiable disease in Singapore. The anonymized HIV registry data provided for a back-calculation model from the European Centre for Disease Prevention and Control to obtain 2014 estimates for the total number of persons living with HIV (PLHIV), and the count in the registry for proportions diagnosed with HIV and linked to care. Using additional data collected for a simple random sample from the registry, outcomes in 2015 and 2016 were ascertained retrospectively to derive proportions for those retained in care, on antiretroviral therapy, and achieved viral suppression. Findings were extrapolated to derive national estimates and UN90-90-90 estimates. Bootstrapped samples from the model and sample were used to derive 95% confidence intervals. RESULTS: An estimated 6900 (95% CI 6650, 7050) persons were living with HIV and AIDS in 2014. Of these, 4948 were diagnosed with HIV, and 4820 had been linked to care. The random sample of 500 persons was further analysed, and of these, 87.2% were retained in care, 84.6% on antiretroviral therapy, and 79.6% had suppressed viral loads. The proportions of HIV-infected individuals on antiretroviral therapy and achieving viral suppression were 60.7% (95% CI 58.4, 63.6) and 57.1% (95% CI 55.0, 60.5) respectively. The corresponding UNAIDS 90-90-90 estimates were 71.7% (95% CI 70.0, 74.2) of all persons diagnosed; 84.6% (95% CI 81.6, 87.4) of diagnosed persons being on antiretroviral therapy, and 94.1% (95% CI 91.6, 96.2) of persons on therapy having achieved viral suppression. CONCLUSIONS: A national HIV registry, alongside back-calculation and additional data from a sample, can be used to estimate attainment of UNAIDS 90-90-90 targets and identify system gaps. The registry had advantages of providing a well-established, comprehensive capture of diagnosed persons and easily accessible data. The same approach can be used elsewhere if similar data are available.

Investigation of a cluster of multi-drug resistant tuberculosis in a high-rise apartment block in Singapore.

OBJECTIVE: Between February 2012 and May 2016, six residents of an 11-storey apartment block were diagnosed with MDR-TB. Based on initial tests, all isolates had similar genotypic profiles, although there were no identifiable epidemiological transmission patterns between three cases. We present findings from the cluster investigation and results of a mass screening exercise. DESIGN: Free voluntary TB screening was offered to past and current residents of the apartment block, comprising an interview, Chest X-Ray, and Interferon Gamma Release Assay or Tuberculin skin test. Expected latent TB proportions were calculated using a reference population, and whole genome sequencing (WGS) was performed. RESULTS: The index case was involved in a separate gaming centre outbreak involving five patrons. 241 current (67.9% of 355 residents) and 18 past residents were screened. The latent TB proportion was 19.9%, which was at the higher end of the expected range. WGS confirmed relatedness of cases' MDR-TB isolates- eight of 10 isolates were genetically identical, while the remaining two were one Single Nucleotide Polymorphism apart. CONCLUSION: With WGS, TB clusters not apparent through regular activity-based contact tracing may be detected. Mass screening may help inform the extent of transmission, but is limited by participation and difficulties in interpretation.

Risk factors for febrile respiratory illness and mono-viral infections in a semi-closed military environment: a case-control study.

BACKGROUND: Febrile respiratory illness (FRI) results in substantial burden in semi-closed environments. Tackling risk factors may reduce transmission and infection. However, risk factors involved in one setting may not be generalizable in all settings due to differences in climate, residential environment, population genetic and cultural backgrounds. This study aims to identify risk factors of FRI and mono-viral infections in a tropical military environment. METHODS: From year 2009 to 2012, military personnel with temperature ≥37.5 °C, cough and/or sore throat, and personnel with no fever or no respiratory symptoms were recruited as cases and controls, respectively. Subjects provided nasal wash specimens and answered a standardized questionnaire. Resplex assays were used to determine the viral etiologies. Descriptive, univariate and multivariate analyses of the variables were performed using appropriate descriptive tests and logistic regression modelling, respectively, with R program. RESULTS: A total of 7,743 FRI cases and 1,247 non-FRI study controls were recruited. Increasing age [adjusted odds ratio (AOR) = 1.03; 95 % confidence interval (CI) = 1.01-1.05], recruit camp (AOR = 4.67; 95 % CI = 3.99-5.46) and smoker (AOR = 1.31; 95 % CI = 1.13-1.52) were independent risk factors of FRI. Malay ethnicity was positively associated with influenza A(H1N1)pdm09 (AOR = 1.50; 95 % CI = 1.04-2.15) and coxsackie/echovirus (AOR = 1.67; 95 % CI = 1.19-2.36) mono-infection. Significant contact risk factors were stay-out personnel with ill household member (AOR = 4.96; 95 % CI = 3.39-7.24), and stay-in personnel with ill bunkmate and household member (AOR = 3.55; 95 % CI = 2.57-4.91). Staying in camp with none ill in bunk and at home was a protective factor against FRI (AOR = 0.80; 95 % CI = 0.64-0.99). These contact risk factors were similarly observed for the five most common viruses detected, namely adenovirus, rhinoviruses, influenza A and B, and coxsackie/echovirus. CONCLUSION: Increasing age, smoker, recruit-camp, stay-out personnel with ill household members and stay-in personnel with ill bunkmates were independent risk factors of FRI in a semi-closed military environment. Early identification and isolation of ill personnel from their bunk may be effective to prevent and reduce transmission and disease burden.

Clinical differences between respiratory viral and bacterial mono- and dual pathogen detected among Singapore military servicemen with febrile respiratory illness.

BACKGROUND: Although it is known that febrile respiratory illnesses (FRI) may be caused by multiple respiratory pathogens, there are no population-level studies describing its impact on clinical disease. METHODS: Between May 2009 and October 2012, 7733 FRI patients and controls in the Singapore military had clinical data and nasal wash samples collected prospectively and sent for PCR testing. Patients with one pathogen detected (mono-pathogen) were compared with those with two pathogens (dual pathogen) for differences in basic demographics and clinical presentation. RESULTS: In total, 45.8% had one pathogen detected, 20.2% had two pathogens detected, 30.9% had no pathogens detected, and 3.1% had more than two pathogens. Multiple pathogens were associated with recruits, those with asthma and non-smokers. Influenza A (80.0%), influenza B (73.0%) and mycoplasma (70.6%) were most commonly associated with mono-infections, while adenovirus was most commonly associated with dual infections (62.9%). Influenza A paired with S. pneumoniae had higher proportions of chills and rigors than their respective mono-pathogens (P = 0.03, P = 0.009). H. influenzae paired with either enterovirus or parainfluenzae had higher proportions of cough with phlegm than their respective mono-pathogens. Although there were observed differences in mean proportions of body temperature, nasal symptoms, sore throat, body aches and joint pains between viral and bacterial mono-pathogens, there were few differences between distinct dual-pathogen pairs and their respective mono-pathogen counterparts. CONCLUSION: A substantial number of FRI patients have multiple pathogens detected. Observed clinical differences between patients of dual pathogen and mono-pathogen indicate the likely presence of complex microbial interactions between the various pathogens.

Emergence of norovirus GI.2 outbreaks in military camps in Singapore.

BACKGROUND: Simultaneous acute gastroenteritis (AGE) outbreaks occurred at two military camps. This study details the epidemiological findings, explores possible origins, and discusses preventive measures. METHODS: Investigations included attack rate surveys, symptom surveys, hygiene inspections, and the testing of water, food, and stool samples. DNA/RNA was extracted from stool samples and amplified via real-time reverse transcription PCR (RT-PCR). Partial and full-length capsid nucleotide sequences were obtained, phylogenetic relationships inferred, and homology modelling of antigenic sites performed. RESULTS: The military outbreaks involved 775 persons and were preceded by two AGE outbreaks at restaurants in the local community. The outbreak was longer and larger in the bigger camp (21 days, attack rate 15.0%) than the smaller camp (6 days, attack rate 8.3%). Of 198 stool samples, norovirus GI.2 was detected in 32.5% (larger camp) and 28.6% (smaller camp). These were essentially identical to preceding community outbreaks. Antigenic site homology modelling also showed differences between identified and more common AGE outbreak strains (norovirus GII.4). CONCLUSION: Differences observed highlight difficulties in controlling person-to-person outbreaks among large groups in close proximity (e.g., military trainees). Distinct differences in antigenic sites may have contributed to increased immunological susceptibility of the soldiers to infection.

Emerging and re-emerging infectious diseases: challenges and opportunities for militaries.

The communal nature of living and training environments, alongside suboptimal hygiene and stressors in the field, place military personnel at higher risk of contracting emerging infectious diseases. Some of these diseases spread quickly within ranks resulting in large outbreaks, and personnel deployed are also often immunologically naïve to otherwise uncommonly-encountered pathogens. Furthermore, the chance of weaponised biological agents being used in conventional warfare or otherwise remains a very real, albeit often veiled, threat. However, such challenges also provide opportunities for the advancement of preventive and therapeutic military medicine, some of which have been later adopted in civilian settings. Some of these include improved surveillance, new vaccines and drugs, better public health interventions and inter-agency co-operations. The legacy of successes in dealing with infectious diseases is a reminder of the importance in sustaining efforts aimed at ensuring a safer environment for both military and the community at large.

Chinese familial tradition and Western influence: a case study in Singapore on decision making at the end of life.

Decision making for an incompetent patient at the end of life is difficult for both family members and physicians alike. Often, palliative care teams are tasked with weaving through opinions, emotions, and goals in search for an amenable solution. Occasionally, these situations get challenging. We present the case of an elderly Chinese Singaporean with metastatic cancer, whose family and physicians had conflicting goals of care. The former was adamant on treating the patient's disease with an untested drug, whereas the latter aimed to treat his symptoms with more conventional medication. Drug-drug interactions prevented treatment with both. Beginning with a discussion of the patient's best interest, we delve into the Singaporean context to show how culture affects medical decision making. Confucianism and filial piety are the values on which this family's workings were based. In an analysis of what this entails, we attempt to explain the significant and assertive family involvement in the decision-making process and their insistence on using novel medications, having exhausted conventional interventions. Within this mix were Western influences, too. Through the Internet, family members have become more informed and empowered in decision making, wresting the traditional paternalistic role of physicians in favor of "patient autonomy." An understanding of such dynamic facets will help better tailor culturally appropriate approaches to such complex situations.