Elucidation of the chain of disease transmission and identification of the source of coronavirus disease 2019 (COVID-19) infections are crucial for effective disease containment. We describe an ...epidemiological investigation that, with use of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serological assays, established links between three clusters of COVID-19.
In Singapore, active case-finding and contact tracing were undertaken for all COVID-19 cases. Diagnosis for acute disease was confirmed with RT-PCR testing. When epidemiological information suggested that people might have been nodes of disease transmission but had recovered from illness, SARS-CoV-2 IgG serology testing was used to establish past infection.
Three clusters of COVID-19, comprising 28 locally transmitted cases, were identified in Singapore; these clusters were from two churches (Church A and Church B) and a family gathering. The clusters in Church A and Church B were linked by an individual from Church A (A2), who transmitted SARS-CoV-2 infection to the primary case from Church B (F1) at a family gathering they both attended on Jan 25, 2020. All cases were confirmed by RT-PCR testing because they had active disease, except for A2, who at the time of testing had recovered from their illness and tested negative. This individual was eventually diagnosed with past infection by serological testing. ELISA assays showed an optical density of more than 1·4 for SARS-CoV-2 nucleoprotein and receptor binding domain antigens in titres up to 1/400, and viral neutralisation was noted in titres up to 1/320.
Development and application of a serological assay has helped to establish connections between COVID-19 clusters in Singapore. Serological testing can have a crucial role in identifying convalescent cases or people with milder disease who might have been missed by other surveillance methods.
National Research Foundation (Singapore), National Natural Science Foundation (China), and National Medical Research Council (Singapore).
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Objective
To describe the characteristics of healthcare workers (HCWs) infected with COVID‐19 and to examine their sources of exposure.
Methods
A descriptive cross‐sectional study using data ...extracted from the centralized disease notification system comprising individuals confirmed with COVID‐19 in Singapore between 23 January and 17 April 2020. Occupation of HCWs was categorized into six categories. Their job nature was classified into “frontline” or “back‐end” based on the frequency of direct patient contact, and source of exposure was classified as family/household, social interaction or workplace. Chi‐square and median tests were used to identify differences between categorical groups and sample medians, respectively.
Results
A total of 88 (1.7%) HCWs were identified from 5,050 cases. Their median age was 35 years. Chinese and Indians constituted 42.0% and 31.8%, respectively, and 43.2% were foreigners. The majority (63.6%) was serving at frontlines handling patient‐facing duties, 15.9% were doctors, 11.4% were nurses and 44.3% were ancillary staff. About 81.8% acquired the infection locally, of which 40.3% did not have a clearly identifiable source of exposure. Exposure from the family/household was most common (27.8%), followed by workplace (16.7%) and social interaction (15.3%). All HCWs were discharged well with no mortality; three (3.4%) were ever admitted to intensive care unit and required increased care.
Conclusion
Healthcare workers accounted for a small proportion of COVID‐19 cases in Singapore with favourable outcomes. The possibility of transmission resulting from family/household exposure and social interactions highlights the need to maintain strict vigilance and precautionary measures at all times beyond the workplace.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Early treatment of high‐risk COVID‐19 patients may prevent disease progression. However, there are limited data to support treatment of hospitalized or fully vaccinated patients with mild‐to‐moderate ...disease. In this retrospective cohort study, we studied the effect of early use of sotrovimab and remdesivir in high‐risk hospitalized COVID‐19 patients. We included PCR‐confirmed COVID‐19 patients admitted to the National Centre for Infectious Diseases who presented within the first 5 days of illness, and who were not requiring oxygen or ICU care at presentation. Sotrovimab‐ and remdesivir‐treated groups were compared with control (no early treatment). A multiple propensity‐score adjusted multivariable regression analysis was conducted with a composite primary endpoint of in‐hospital deterioration (oxygen requirement, ICU admission, or mortality). Of 1118 patients, 841 were in the control group, 106 in the sotrovimab group and 169 in the remdesivir group. The median age was 63 years (IQR 46–74 years) and 505 (45.2%) were female. In unvaccinated patients, both remdesivir and sotrovimab treatment were protective (adjusted odds ratio aOR 0.19, 95% CI 0.064–0.60 and 0.18 95% CI 0.066–0.47), respectively. Contrarily, among the vaccinated patients there was no significant treatment effect with early remdesivir treatment (aOR 2.51, 95% CI 0.83–7.57, p = 0.10). Remdesivir and sotrovimab treatment, given early in the disease course to unvaccinated high‐risk patients, was effective in reducing the risk of in‐hospital deterioration and severe disease. This effect was not seen in fully vaccinated patients, which may be due to a small sample size or residual confounding.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The Omicron variant has been reported to present with milder disease compared with Delta, although this may be due to immunity from vaccination and prior exposure. Predictors of severity with recent ...strains have not been well characterized. We retrospectively examined consecutive cases of moderate‐to‐severe COVID‐19 (defined as requiring supplemental oxygenation, intensive care or mortality) admitted to seven tertiary hospitals across Singapore in April 2023. Whole genome sequencing was performed on each isolate to determine the sublineage, while baseline clinical, laboratory data and outcomes were tabulated. We reviewed 182 patients with moderate‐to‐severe illness and 466 controls hospitalized at the same time. Advanced age and presence of chronic kidney disease predicted adverse outcome. Previously reported markers such as radiographic evidence of pneumonia, elevated C‐reactive protein and serum creatinine levels at presentation also correlated with adverse outcomes. There were no observable differences in outcomes with any specific Omicron XBB sublineage. We did not find any specific Omicron XBB sublineage that was associated with worse outcomes. Larger multinational studies would be important to track the clinical evolution of the virus in its current endemic state.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Due to the chronic nature of diabetes along with their complications, they have been recognised as a major health issue, which results in significant economic burden. This study aims to estimate the ...direct medical cost associated with type 2 diabetes mellitus (T2DM) in Singapore in 2010 and to examine both the relationship between demographic and clinical state variables with the total estimated expenditure. The National Healthcare Group (NHG) Chronic Disease Management System (CDMS) database was used to identify patients with T2DM in the year 2010. DM-attributable costs estimated included hospitalisations, accident and emergency (A&E) room visits, outpatient physician visits, medications, laboratory tests and allied health services. All charges and unit costs were provided by the NHG. A total of 500 patients with DM were identified for the analyses. The mean annual direct medical cost was found to be $2,034, of which 61% was accounted for by inpatient services, 35% by outpatient services, and 4% by A&E services. Independent determinants of total costs were DM treatments such as the use of insulin only (p<0.001) and the combination of both oral medications and insulin (p=0.047) as well as having complications such as cerebrovascular disease (p<0.001), cardiovascular disease (p=0.002), peripheral vascular disease (p=0.001), and nephropathy (p=0.041). In this study, the cost of DM treatments and DM-related complications were found to be strong determinants of costs. This finding suggests an imperative need to address the economic burden associated with diabetes with urgency and to reorganise resources required to improve healthcare costs.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Purpose
This retrospective cohort study aims to examine adherence to secondary stroke preventive medications and their association with risk of stroke recurrence and mortality in patients after ...first‐ever ischemic stroke.
Methods
Using data from the National Healthcare Group and Singapore Stroke Registry, patients with first‐ever ischemic stroke between 2010 and 2014 were included, and categorized based on antithrombotic or statin adherence using the proportion of days covered: high (≥75%), intermediate (50%‐74%), low (25%‐49%), and very low (<25%). The primary outcome was first recurrent ischemic stroke within a year after hospital discharge, while the secondary composite outcomes were (a) stroke recurrence and all‐cause mortality and (b) stroke recurrence and cardiovascular mortality. The Cox proportional hazard model was used to examine the association between medication adherence and outcomes. Adjusted hazard ratios (aHRs) and the corresponding 95% confidence intervals (CIs) were reported.
Results
Among ischemic stroke patients prescribed with antithrombotics (n = 1139) or statins (n = 1160) at hospital discharge, about one‐third were highly adherent to their medications. Patients with lower medication adherence tended to be younger, were admitted to private ward classes, and were without hypertension. Compared with the patients with high medication adherence, the risk of stroke recurrence was higher in patients with very low antithrombotic (aHR = 4.65; 95% CI: 1.45‐14.89) or statin (aHR = 3.44; 95% CI: 0.93‐12.74) adherence. Similar findings were observed for the secondary outcomes.
Conclusions
Poor adherence to antithrombotic and statin treatment increases the risk of recurrent stroke and mortality in patients after first‐ever ischemic stroke. Further measures are needed to improve medication adherence among stroke survivors.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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.
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.
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).
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.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
The aim of the present study was to forecast the prevalence and number of adult Singapore residents with prediabetes and diabetes in 2035.
Methods
A dynamic Markov model with nine mutually ...exclusive states was developed based on the clinical course of diabetes using time‐dependent rates and probabilities. A 1‐year cycle over a 25‐year time horizon from 2010 to 2035 was used in the model. With publicly available data and a chronic disease register, the model forecast annual disease burden by simulating transition of cohorts across different health states using prevalence rates, incidence rates, mortality rates, disease transition, disease detection, and complication rates. An aging index was used in the model in anticipation of population aging to minimize risks of underestimating disease burden.
Results
From 2010 to 2035, the number of Singapore residents with prediabetes and diabetes is projected to more than double, from 434 685 to 903 596 and from 373 104 to 823 802, respectively. The prevalence of prediabetes and diabetes will rise steadily from 15.5 % to 24.9 % and from 13.3 % to 22.7 %, respectively. By 2035, a further estimate of 733 174 and 100 250 patients with prediabetes and uncomplicated diabetes, respectively, will remain undiagnosed. The prevalence of detected and undetected complications is forecast to rise from 60.0 % in 2010 to 70.2 % by 2035.
Conclusion
By 2035, the prevalence of prediabetes and diabetes among Singapore residents aged 21+ years is expected to be one in four and one in five, respectively. There is an impetus to adopt more aggressive interventions to contain disease progression.
Highlights
By 2035, the prevalence of prediabetes and diabetes among Singapore residents is expected to be one in four and one in five, respectively.
The prevalence of complications is forecast to rise from 60.0% in 2010 to 70.2% by 2035.
Number of individuals with normoglycemia, prediabetes, and diabetes in Singapore, 2010–35.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
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.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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.
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).
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.
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.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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