Li Wei Ang

Background: We previously reviewed methods for estimating the timing of respiratory syncytial virus (RSV) epidemics. This study examines the impact of various estimation methods on determining the start, end, duration, and capture rate of RSV epidemics.Methods: We applied eight estimation methods to RSV surveillance data from the Global Epidemiology of RSV (GERi) study, covering Chile, New Zealand, Singapore, South Africa, Spain, and the United States: 3% and 10% positivity rate, moving epidemic method (MEM), mean positivity, 1.2% total detections, mean and 60% mean number, and 75% average annual percentage (AAP). We compared the median start, end, duration, and capture rate of RSV epidemics obtained from these methods.Results: Within countries, the median duration of RSV epidemics varied by over 10 weeks, and the median capture rates ranged from > 95 to < 60%, depending on the estimation method. Generally, the 3% positivity rate method identified the longest RSV epidemics (earliest median start and latest end, and highest capture rate). The 10% positivity rate, MEM, and 75% AAP methods indicated the shortest RSV epidemics with the lowest capture rate. The remaining four methods produced intermediate results.Conclusions: These findings underscore the importance of selecting estimation methods suited to the surveillance system and the intended use, whether for outbreak alert, planning, or targeted interventions.

Objective: Abnormal liver tests have been associated with worse clinical outcomes in patients infected with COVID-19. This retrospective observational study from Singapore aims to elucidate simple clinical predictors of abnormal alanine aminotransferase (ALT) in COVID-19 infections. Design: 717 patients hospitalised with COVID-19 at the National Centre for Infectious Diseases (NCID), Singapore, from 23 January–15 April 2020 were screened, of which 163 patients with baseline normal alanine transferase (ALT) and at least two subsequent ALTs performed were included in the final analysis. Information on baseline demographics, clinical characteristics and biochemical laboratory tests were collected. Results: 30.7% of patients developed abnormal ALT. They were more likely to be older (60 vs. 55, p = 0.022) and have comorbidities of hyperlipidaemia and hypertension. The multivariate logistic regression showed that R-factor ≥1 on admission (adjusted odds ratio (aOR) 3.13, 95% Confidence Interval (CI) 1.41–6.95) and hypoxia (aOR 3.54, 95% CI 1.29–9.69) were independent risk factors for developing abnormal ALT. The patients who developed abnormal ALT also ran a more severe course of illness with a greater proportion needing supplementary oxygen (58% vs. 18.6%, p < 0.0005), admission to the Intensive Care Unit (ICU)/High Dependency Unit (HDU) (32% vs. 11.5%, p = 0.003) and intubation (20% vs. 2.7%, p < 0.0005). There was no difference in death rate between the two groups. Conclusions: Liver injury is associated with poor clinical outcomes in patients with COVID-19. R-factor ≥1 on admission and hypoxia are independent simple clinical predictors for developing abnormal ALT in COVID-19.

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 < 0.0005), whereas there was no significant difference by gender (90.8% in men vs. 89.9% in women, p = 0.508). 195 out of 213 samples with equivocal or negative ELISA results were tested positive using PRNT.Conclusion: The IgG seroprevalence in migrant workers was below the herd immunity threshold of 95% for measles. Sporadic outbreaks may occur in susceptible individuals due to high transmissibility of measles virus. Seroprevalence surveys can help identify susceptible subgroups for vaccination.

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. 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. 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. 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.

Objective To assess the temporal trend and identify risk factors associated with the absence of previous HIV testing prior to their diagnosis among HIV-positive persons in Singapore. Study design Cross-sectional. Setting and participants We analysed data of HIV-positive persons infected via sexual transmission, who were notified to the National HIV Registry in 2012–2017. Outcomes Epidemiological factors associated with the absence of HIV testing prior to diagnosis were determined separately for two groups of HIV-positive persons: early and late stages of HIV infection at diagnosis. Results 2188 HIV-positive persons with information on HIV testing history and CD4 cell count were included in the study. The median age at HIV diagnosis was 40 years (IQR 30–51). Nearly half (45.1%) had never been tested for HIV prior to their diagnosis. The most common reason cited for no previous HIV testing was ‘not necessary to test’ (73.7%). The proportion diagnosed at late-stage HIV infection was significantly higher among HIV-positive persons who had never been tested for HIV (63.9%) compared with those who had undergone previous HIV tests (29.0%). Common risk factors associated with no previous HIV testing in multivariable logistic regression analysis stratified by stage of HIV infection were: older age at HIV diagnosis, lower educational level, detection via medical care and HIV infection via heterosexual transmission. In the stratified analysis for persons diagnosed at early-stage of HIV infection, in addition to the four risk factors, women and those of Malay ethnicity were also less likely to have previous HIV testing prior to their diagnosis. Conclusion Targeted prevention efforts and strategies are needed to raise the level of awareness of HIV/AIDS and to encourage early and regular screening among the at-risk groups by making HIV testing more accessible.

Objectives We aimed to evaluate the association between fibre intake and its food sources, and the risk of total knee replacement (TKR) due to severe knee osteoarthritis (KOA). Methods We used data from the Singapore Chinese Health Study, a prospective cohort study that recruited 63 257 participants aged 45–74 years from 1993 to 1998. At baseline, we assessed diet using a validated 165-item semiquantitative food frequency questionnaire, together with body mass index (BMI) and lifestyle factors. Incident TKR cases were identified via record linkage with nationwide hospital discharge database through 2017. Results There were 2816 cases of incident TKR due to severe KOA. The total fibre intake at baseline was not associated with the risk of TKR after adjustment for confounders. Among the food sources of fibre, higher intake of legumes was associated with a lower risk of TKR in a dose-dependent manner; compared with those having the lowest quartile intake, HR (95% CI) was 0.86 (0.76, 0.96) for those having the highest quartile intake (p for trend=0.004). This association was consistent after including BMI in the model and homogeneous across BMI categories. The consumption of other fibre sources, namely grain products, nuts and seeds, soy food, fruits and vegetables, was not associated with the risk of TKR. Conclusion Intake of legumes, but not total fibre, was associated with a reduced risk of TKR. Further research is needed to replicate our findings and to evaluate possible biological mechanisms that could explain the effect of dietary legumes on pathogenesis or progression of KOA.

We investigated the temporal trends of short-term mortality (death within 1 year of diagnosis) and cause-specific deaths in human immunodeficiency virus (HIV)-infected persons by stage of HIV infection at diagnosis. We also assessed the impact of late diagnosis (LD) on short-term mortality. Epidemiological records of HIV-infected Singapore residents from the National HIV Registry were linked to death records from the Registry of Births and Deaths for observational analyses. Newly-diagnosed HIV cases with available cluster of differentiation 4 count at time of diagnosis in a 5-year period from 2012 to 2016 were included in the study. Hazard ratios (HRs) and 95% confidence interval (CI) of LD for all deaths excluding suicides and self-inflicted or accidental injuries, and HIV/ acquired immunodeficiency syndrome (AIDS)-related deaths occurring within 1 year post-diagnosis were calculated using Cox proportional hazards regression models with adjustment for age at HIV/AIDS diagnosis. Population attributable risk proportions (PARPs) were then calculated using the adjusted HRs. Of the 1990 newly-diagnosed HIV cases included in the study, 7.2% had died by end of 2017, giving an overall mortality rate of 2.16 per 100 person-years (PY) (95% CI 1.82–2.54). The mortality rate was 3.81 per 100 PY (95% CI 3.15–4.56) in HIV cases with LD, compared with 0.71 (95% CI 0.46–1.05) in non-LD (nLD) cases. Short-term mortality was significantly higher in LD (9.1%) than nLD cases (1.1%). Of the 143 deaths reported between 2012 and 2017, 58.0% were HIV/AIDS-related (nLD 28.0% vs LD 64.4%). HIV/AIDS-related causes represented 70.4% of all deaths which occurred during the first year of diagnosis (nLD 36.4% vs LD 74.7%). The PARP of short-term mortality due to LD was 77.8% for all deaths by natural causes, and 87.8% for HIV/AIDS-related deaths. The mortality rate of HIV-infected persons with LD was higher than nLD, especially within 1 year of diagnosis, and HIV/AIDS-related causes constituted majority of these deaths. To reduce short-term mortality, persons at high risk of late-stage HIV infection should be targeted in outreach efforts to promote health screening and remove barriers to HIV testing and treatment.

Background: The epidemiology of hepatitis C virus (HCV) infection in people living with HIV has been evolving, with increasing evidence of permucosal (sexual) transmission identified predominantly in HIV-positive men who have sex with men (MSM). The aim of this study was to estimate the incidence rate and elucidate epidemiological factors associated with HCV infection among HIV-infected men in Singapore from 2006 to 2018. Methods: A retrospective cohort study was conducted using a clinical database maintained by the Clinical HIV Program at the National Centre for Infectious Diseases, Singapore. Factors associated with incident HCV infections were identified using Cox proportional hazards regression analyses. Results: Among 1348 HIV-infected male patients who were HCV seronegative at baseline, 64 (4.7%) subsequently tested positive for HCV, giving an incidence of 0.88 per 100 person-years of follow-up (PYFU) (95% confidence interval (CI) 0.69–1.13). The incidence rate of HCV seroconversion increased from 0.33 (95% CI 0.12–0.71) per 100 PYFU in 2010–2012 to 1.93 (95% CI 1.36–2.67) in 2016–2018. Independent factors associated with incident HCV infection were younger age groups at HIV diagnosis versus ≥45 years, HIV acquisition via MSM or via both sexual contact and intravenous drug use versus heterosexual transmission, HIV diagnosis in later periods versus 2006–2009, and recent syphilis acquisition. Conclusions: An increasing trend of incident HCV infection was seen in HIV-infected men, particularly for MSM. Preventive and behavioural interventions should be targeted at HIV-infected individuals engaged in high-risk sexual behaviour.

Background: While the use of combination antiretroviral therapy (cART) has conferred significant reduction in morbidity and mortality, there are growing concerns about the metabolic complications of antiretroviral regimens in HIV-infected patients. The aim of this study was to estimate the prevalence of metabolic syndrome (MetS) among people living with HIV (PLHIV) in Singapore.Methods: We conducted a retrospective study using the clinical database maintained by the Clinical HIV Programme at the National Centre for Infectious Diseases, Singapore. Treatment-experienced PLHIV on follow-up during 2015–2017 were included. MetS was defined as having three or more of the following five abnormalities: hypertriglyceridemia, HDL hypocholesterolemia, hypertension, obesity, and diabetes.Results: A total of 2,231 PLHIV were included in this study. 93.9% were men, and the median age at latest follow-up was 48 years. The median duration of HIV infection and duration of exposure to cART was 6.8 years and 5.7 years, respectively. All had been exposed to nucleoside reverse transcriptase inhibitors (NRTIs) as the first line of treatment, 93.9% to non-NRTIs, 28.6% to protease inhibitors (PIs) and 12.8% to integrase strand transfer inhibitors. The most common metabolic abnormality among PLHIV was HDL hypocholesterolemia (60.2%) followed by hypertriglyceridemia (45.5%). Of all the 2,231 individuals, 68.8% had at least one component of MetS. The overall prevalence of MetS was 23.6% (95% confidence interval 21.9%–25.4%). Of the 526 with MetS, the most common combination was HDL hypocholesterolemia, hypertriglyceridemia and hypertension (51.0%), followed by HDL hypocholesterolemia, hypertriglyceridemia, hypertension and diabetes (25.1%). Compared with PLHIV without MetS, a significantly higher proportion of those with MetS were ever on protease inhibitors (33.5% vs. 27.1%).Conclusion: MetS is common in PLHIV. In view of the progressive aging of HIV-infected population and long-term use of cART, regular monitoring for metabolic abnormalities, surveillance of drug effects and behavioural interventions are needed to optimize management and prevention of metabolic disorders in PLHIV.