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Abstract Objectives The objectives of this study were to describe the coronavirus disease caused by SARS-CoV-2 (COVID-19) reinfection evaluation algorithm used in the early phase of the pandemic in Singapore and analyze the clinical and laboratory characteristics of the cases evaluated. Methods We performed a retrospective case-control analysis including all COVID-19 cases evaluated for possible reinfection under the local COVID-19 reinfection evaluation programme between 1 June 2020-30 June 2021. Whole genome sequencing (WGS) was used as confirmatory testing. We compared all reinfection (“RI”) cases against those who were evaluated but eventually assessed not to be reinfection (“non-RI”). Results There were 74 possible reinfection cases evaluated through the programme, of which 32 were subsequently classified as RI. There was strong statistical evidence that RI cases had a longer interval between 1st and 2nd episode (mean 297 days; 95%-confidence interval (CI) 267–327) compared to non-RI cases (mean 186 days; 95%-CI 144–228). The cycle threshold (Ct) value of initial polymerase chain rection (PCR) at 2nd episode was also found to be significantly lower in RI cases (mean 23; 95%-CI 20–26) compared to non-RI cases (mean 34; 95%-CI 32–36). There was no significant difference in the proportion of individuals who had fever, acute respiratory symptoms or asymptomatic in both groups. Delta and beta variants were most commonly identified from WGS and provide indication of re-infection as these were not ‘wild-type’ and were not circulating during the time period of the index infection. Conclusions Using a combination of serologic, microbiologic and genomic criteria to evaluate possible reinfection cases is useful and can provide a framework for evaluation that may be modified for future similar situations.

Abstract Background Since the last local case of diphtheria in 1992, there had not been any case in Singapore until an autochthonous case was reported in 2017. This fatal diphtheria case of a migrant worker raised concerns about the potential re-emergence of locally transmitted toxigenic diphtheria in Singapore. We conducted a seroprevalence study to assess the immunity levels to diphtheria among migrant workers in Singapore. Methods Residual sera from migrant workers who hailed from Bangladesh, China, India, Indonesia, Malaysia, Myanmar and the Philippines were tested for anti-diphtheria toxoid immunoglobulin G (IgG) antibodies. These migrant workers previously participated in a survey between 2016 and 2019 and had provided blood samples as part of the survey procedure. Results A total of 2176 migrant workers were included in the study. Their overall mean age was 27.1 years (standard deviation 5.0), range was 20–43 years. The proportion having at least basic protection against diphtheria (antitoxin titres ≥ 0.01 IU/ml) ranged from 77.9% (95% confidence interval [CI] 72.8 – 82.3%) among migrant workers from Bangladesh to 96.7% (95% CI 92.5 – 98.6%) in those hailing from Malaysia. The proportion showing full protection (antitoxin titres ≥ 0.10 IU/ml) ranged from 10.1% (95% CI 6.5 – 15.4%) in Chinese workers to 23.0% (95% CI 17.1 – 30.3%) in Malaysian workers. There were no significant differences in the proportion with at least basic protection across birth cohorts, except for those from Bangladesh where the seroprevalence was significantly lower in younger migrant workers born after 1989. Conclusions The proportions having at least basic protection against diphtheria in migrant workers from five out of seven Asian countries (India, Indonesia, Malaysia, Myanmar and the Philippines) were higher than 85%, the threshold for diphtheria herd immunity. Seroprevalence surveys should be conducted periodically to assess the level of immunity against diphtheria and other vaccine preventable diseases in migrant worker population, so that appropriate interventions such as booster vaccination can be implemented proactively to prevent sporadic outbreaks.

Abstract Background In 2019, two clusters of measles cases were reported in migrant worker dormitories in Singapore. We conducted a seroprevalence study to measure the level of susceptibility to measles among migrant workers in Singapore. Methods Our study involved residual sera of migrant workers from seven Asian countries (Bangladesh, China, India, Indonesia, Malaysia, Myanmar and the Philippines) who had participated in a survey between 2016 and 2019. Immunoglobulin G (IgG) antibody levels were first measured using a commercial enzyme-linked immunosorbent assay (ELISA) test kit. Those with equivocal or negative IgG results were further evaluated using plaque reduction neutralization test (PRNT). Results A total of 2234 migrant workers aged 20–49 years were included in the study. The overall prevalence of measles IgG antibodies among migrant workers from the seven Asian countries was 90.5% (95% confidence interval 89.2–91.6%). The country-specific seroprevalence ranged from 80.3 to 94.0%. The seroprevalence was significantly higher among migrant workers born in 1965–1989 than those born in 1990–1999 (95.3% vs. 86.6%, p

Abstract Background Early diagnosis is crucial in securing optimal outcomes in the HIV care cascade. Recent HIV infection (RHI) serves as an indicator of early detection in the course of HIV infection. Surveillance of RHI is important in uncovering at-risk groups in which HIV transmission is ongoing. The study objectives are to estimate the proportion of RHI among persons newly-diagnosed in 2013–2017, and to elucidate epidemiological factors associated with RHI in Singapore. Methods As part of the National HIV Molecular Surveillance Programme, residual plasma samples of treatment-naïve HIV-1 positive individuals were tested using the biotinylated peptide-capture enzyme immunoassay with a cutoff of normalized optical density ≤ 0.8 for evidence of RHI. A recent infection testing algorithm was applied for the classification of RHI. We identified risk factors associated with RHI using logistic regression analyses. Results A total of 701 newly-diagnosed HIV-infected persons were included in the study. The median age at HIV diagnosis was 38 years (interquartile range, 28–51). The majority were men (94.2%), and sexual route was the predominant mode of HIV transmission (98.3%). Overall, 133/701 (19.0, 95% confidence interval [CI] 16.2–22.0%) were classified as RHI. The proportions of RHI in 2015 (31.1%) and 2017 (31.0%) were significantly higher than in 2014 (11.2%). A significantly higher proportion of men having sex with men (23.4, 95% CI 19.6–27.6%) had RHI compared with heterosexual men (11.1, 95% CI 7.6–15.9%). Independent factors associated with RHI were: age 15–24 years (adjusted odds ratio [aOR] 4.18, 95% CI 1.69–10.31) compared with ≥55 years; HIV diagnosis in 2015 (aOR 2.36, 95% CI 1.25–4.46) and 2017 (aOR 2.52, 95% CI 1.32–4.80) compared with 2013–2014; detection via voluntary testing (aOR 1.91, 95% CI 1.07–3.43) compared with medical care; and self-reported history of HIV test(s) prior to diagnosis (aOR 1.72, 95% CI 1.06–2.81). Conclusion Although there appears to be an increasing trend towards early diagnosis, persons with RHI remain a minority in Singapore. The strong associations observed between modifiable behaviors (voluntary testing and HIV testing history) and RHI highlight the importance of increasing the accessibility to HIV testing for at-risk groups.

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.

Objectives: The Ministry of Health (MOH), Singapore, conducted the National Paediatric Seroprevalence Survey 2018 (NPSS 2018) to estimate the latest immunity levels against measles, rubella, varicella, diphtheria, tetanus and hepatitis B, and the seroprevalence of chronic hepatitis B virus (HBV) carriage in children and adolescents in Singapore. Methods: The survey involved prospective collection of residual sera from 1,200 children and adolescents aged 1–17 years in two public acute hospitals. Enzyme-linked immunosorbent assays (EIA) or plague reduction neutralisation tests (PRNT) were used to determine the seroprevalence of the vaccine-preventable diseases. Results: Overall prevalence of measles and rubella antibodies among Singaporean children and adolescents aged 1–17 years were 98.2% (95% CI: 91.2–98.8%) and 94.8% (95% CI: 93.4–95.9%) respectively. 97.1% (95% CI: 96.0–97.9%) of subjects had at least basic protection against diphtheria, while 89.3% (95% CI: 87.5–91.0%) were protected against tetanus. The prevalence of chronic HBV carriage was 0.4% (95% CI: 0.2–1.0%), while 45.7% (95% CI: 42.9–48.5%) were immune against HBV. The seroprevalence for varicella antibodies was 52.9% (95% CI: 50.1–55.7%). Concordance between vaccination status and seroprevalence was observed for measles, rubella, diphtheria and tetanus. Conclusion: Singapore’s children and adolescents are well-protected against measles, rubella, diphtheria and tetanus. Continual efforts in ensuring high vaccination coverage should be sustained. Keywords: Seroprevalence, Survey, Vaccine, Immunity, Children, Adolescents, Singapore, Epidemiology, Public health

Abstract Background Influenza disease burden varies by age and this has important public health implications. We compared the proportional distribution of different influenza virus types within age strata using surveillance data from twenty-nine countries during 1999-2014 (N=358,796 influenza cases). Methods For each virus, we calculated a Relative Illness Ratio (defined as the ratio of the percentage of cases in an age group to the percentage of the country population in the same age group) for young children (0-4 years), older children (5-17 years), young adults (18-39 years), older adults (40-64 years), and the elderly (65+ years). We used random-effects meta-analysis models to obtain summary relative illness ratios (sRIRs), and conducted meta-regression and sub-group analyses to explore causes of between-estimates heterogeneity. Results The influenza virus with highest sRIR was A(H1N1) for young children, B for older children, A(H1N1)pdm2009 for adults, and (A(H3N2) for the elderly. As expected, considering the diverse nature of the national surveillance datasets included in our analysis, between-estimates heterogeneity was high (I2>90%) for most sRIRs. The variations of countries’ geographic, demographic and economic characteristics and the proportion of outpatients among reported influenza cases explained only part of the heterogeneity, suggesting that multiple factors were at play. Conclusions These results highlight the importance of presenting burden of disease estimates by age group and virus (sub)type.

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.

Abstract Background From 31 August to 9 September 2015, a total of 150 military personnel at a military institution in Singapore were infected with acute gastroenteritis (AGE) with an attack rate of approximately 3%. This study aimed to determine the epidemiology of the outbreak, investigate its origins, and discuss measures to prevent future occurrences. Methods After the AGE outbreak was declared on 31 August 2015, symptom surveys, hygiene inspections, and the testing of water, food, and stool samples were initiated. We collected 86 stool samples from AGE cases and 58 samples from food-handlers during the course of the outbreak and these stool samples were tested for 8 bacterial pathogens and 2 viral pathogens (i.e., norovirus and sapovirus). Results We detected Sapovirus (SaV), group I Norovirus (NoV GI) and group II Norovirus (NoV GII) from the stool samples of AGE cases. Further sequence analyses showed that the AGE outbreak in August was caused mainly by three rarely reported calicivirus novel genotypes: NoV GI.7, NoV GII.17 and SaV GII.3. Control measures implemented focused on the escalation of personal and environmental hygiene, which included the separation of affected and unaffected soldiers, enforcement of rigorous hand-washing and hygiene, raising awareness of food and water safety, and disinfection of communal areas with bleach. Conclusions This study identified both NoV and SaV as the causative agents for an AGE outbreak at a Singapore military camp in August 2015. This study is also the first to report SaV as one of the main causative agents, highlighting the importance of caliciviruses as causative agents of AGE outbreaks in the Singapore military. As there are no commercially available vaccines against caliciviruses, strict personal hygiene and proper disinfection of environmental surfaces remain crucial to prevent calicivirus outbreak and transmission.

ObjectivesSince the 1990s, Singapore has experienced periodic dengue epidemics of increasing frequency and magnitude. In the aftermath of the 2004-2005 dengue epidemic, hospitals refined their admission criteria for dengue cases to right-site dengue case management and reduce the burden of healthcare utilization and negative outcomes. In this study, we describe the national trends of hospital admissions for dengue and disease severity in terms of length of stay (LOS), admission to the intensive care unit (ICU) and death in hospital, and case fatality rate (CFR) in Singapore.MethodsWe conducted a retrospective study of notified cases and laboratory confirmed dengue patients admitted to all public and private hospitals between 2003 and 2017. Case notifications for dengue and hospitalization records were extracted from national databases.ResultsThe proportion of dengue cases hospitalized was lower in recent years; 28.9% in the 2013-2014 epidemic, compared to 93.2% in the 2004-2005 epidemic, and 58.1% in the 2007 epidemic. Median LOS remained stable over the years; overall LOS was 3 to 4 days and ICU stay was 2 to 3 days. Less than 2% of hospitalized patients were admitted to the ICU. Overall CFR was low and remained below 0.5%. The proportions of dengue cases hospitalized and patients admitted to the ICU were highest in the elderly aged 65 years and older.ConclusionsWhile the proportion of dengue cases hospitalized saw a drastic decline due to more selective admission criteria, there was no concomitant increase in adverse outcomes, suggesting that admission criteria were appropriate to focus on severe dengue cases. Further studies are needed to optimize dengue management in older adults who are more likely to be hospitalized with greater disease severity, given the higher proportions of hospitalizations and severe disease among older adults.

We describe the epidemiological characteristics, pattern of circulation, and geographical distribution of influenza B viruses and its lineages using data from the Global Influenza B Study. We included over 1.8 million influenza cases occurred in thirty-one countries during 2000-2018. We calculated the proportion of cases caused by influenza B and its lineages; determined the timing of influenza A and B epidemics; compared the age distribution of B/Victoria and B/Yamagata cases; and evaluated the frequency of lineage-level mismatch for the trivalent vaccine. The median proportion of influenza cases caused by influenza B virus was 23.4%, with a tendency (borderline statistical significance, p = 0.060) to be higher in tropical vs. temperate countries. Influenza B was the dominant virus type in about one every seven seasons. In temperate countries, influenza B epidemics occurred on average three weeks later than influenza A epidemics; no consistent pattern emerged in the tropics. The two B lineages caused a comparable proportion of influenza B cases globally, however the B/Yamagata was more frequent in temperate countries, and the B/Victoria in the tropics (p = 0.048). B/Yamagata patients were significantly older than B/Victoria patients in almost all countries. A lineage-level vaccine mismatch was observed in over 40% of seasons in temperate countries and in 30% of seasons in the tropics. The type B virus caused a substantial proportion of influenza infections globally in the 21st century, and its two virus lineages differed in terms of age and geographical distribution of patients. These findings will help inform health policy decisions aiming to reduce disease burden associated with seasonal influenza.

During November 2012–July 2013, a marked increase of adenovirus type 7 (Ad7) infections associated with severe disease was documented among pediatric patients in Singapore. Phylogenetic analysis revealed close genetic links with severe Ad7 outbreaks in China, Taiwan, and other parts of Asia.

Studies of influenza-associated hospitalizations in tropical settings are lacking. To increase understanding of the effect of influenza in Singapore, we estimated the age-specific influenza-associated hospitalizations for pneumonia and influenza during 2004–2008 and 2010–2012. The rate of hospitalization was 28.3/100,000 person-years during 2004–2008 and 29.6/100,000 person-years during 2010–2012. The age-specific influenza-associated hospitalization rates followed a J-shaped pattern: rates in persons >75 years of age and in children 47 times and >26 times higher, respectively, than those for persons 25–44 years of age. Across all ages during these 2 study periods, ≈12% of the hospitalizations for pneumonia and influenza were attributable to influenza. The rates and proportions of hospitalizations attributable to influenza, particularly among the very young and the elderly, are considerable in Singapore and highlight the importance of vaccination in protecting populations at risk.