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We conducted a study among healthcare workers (HCWs) exposed to patients with severe acute respiratory syndrome (SARS) before infection control measures were instituted. Of all exposed HCWs, 7.5% had asymptomatic SARS-positive cases. Asymptomatic SARS was associated with lower SARS antibody titers and higher use of masks when compared to pneumonic SARS.

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 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

Objectives: To examine the prevalence and characteristics of HIV-tuberculosis (TB) co-infected patients in Singapore, an intermediate TB-burden country.Methods: Retrospective data across 11 years was obtained from the National University Hospital (NUH), a quaternary hospital and the National Centre for Infectious Diseases (NCID), the national HIV center.Results: From December 2005 to December 2016, 4015 HIV-infected patients were managed at NUH and NCID, of whom, respectively, 48 and 272 were diagnosed with active TB disease. Only 2 patients (0.6%) were screened for latent TB infection on HIV diagnosis. Mean CD4 count at TB diagnosis was 125.0 ± 153.9 cells/mm3. More patients with HIV diagnosed ≥6 weeks before TB (41%) were associated with CD4 counts >200 cells/mm3 than patients with TB diagnosed ≥6 weeks before HIV (2%). Of 124 (38.6%) HIV-TB patients with CD4 count ≤50 cells/mm3, only 18 (14.2%) started anti-retroviral therapy (ART) in

Abstract Surveillance of nosocomial infections, like catheter-associated urinary tract infection (CAUTI), central line-associated bloodstream infection, possible ventilator-associated pneumonia and secondary bloodstream infections were observed to study the impact of COVID-19 outbreak in ICUs from Tan Tock Seng Hospital and National Centre for Infectious Diseases, Singapore between February and June 2020. Higher nosocomial infection rates were observed in COVID-19 patients, although it was not statistically significant. Moreover, COVID-19 patients seem to be more predisposed to CAUTI despite a higher proportion of non-COVID-19 patients having urinary catheters. Thus, continued vigilance to ensure adherence to IPC measures is needed.

Dengue virus (DENV) and Zika virus (ZIKV) belong to the Flaviviridae family of viruses spread by Aedes aegypti mosquitoes in tropical and subtropical areas. Accurate diagnostic tests to differentiate the 2 infections are necessary for patient management and disease control. Using characterized ZIKV and DENV patient plasma in a blind manner, we validated an ELISA and a rapid immunochromatographic test for ZIKV detection. We engineered the ZIKV nonstructural protein 1 (NS1) for sensitive serologic detection with low cross reactivity against dengue and developed monoclonal antibodies specific for the ZIKV NS1 antigen. As expected, the serologic assays performed better with convalescent than acute plasma samples; the sensitivity ranged from 71% to 88%, depending on the performance of individual tests (IgM/IgG/NS1). Although serologic tests were generally less sensitive with acute samples, our ZIKV NS1 antibodies were able to complement the serologic tests to achieve greater sensitivity for detecting early infections.

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.

Background: This study compared the genomes of influenza viruses that caused mild infections among outpatients and severe infections among hospitalized patients in Singapore, and characterized their molecular evolution and receptor-binding specificity. Methods: The complete genomes of influenza A/H1N1, A/H3N2 and B viruses that caused mild infections among outpatients and severe infections among inpatients in Singapore during 2012–2015 were sequenced and characterized. Using various bioinformatics approaches, we elucidated their evolutionary, mutational and structural patterns against the background of global and vaccine strains. Results: The phylogenetic trees of the 8 gene segments revealed that the outpatient and inpatient strains overlapped with representative global and vaccine strains. We observed a cluster of inpatients with A/H3N2 strains that were closely related to vaccine strain A/Texas/50/2012(H3N2). Several protein sites could accurately discriminate between outpatient versus inpatient strains, with site 221 in neuraminidase (NA) achieving the highest accuracy for A/H3N2. Interestingly, amino acid residues of inpatient but not outpatient isolates at those sites generally matched the corresponding residues in vaccine strains, except at site 145 of hemagglutinin (HA). This would be especially relevant for future surveillance of A/H3N2 strains in relation to their antigenicity and virulence. Furthermore, we observed a trend in which the HA proteins of influenza A/H3N2 and A/H1N1 exhibited enhanced ability to bind both avian and human host cell receptors. In contrast, the binding ability to each receptor was relatively stable for the HA of influenza B. Conclusions: Overall, our findings extend our understanding of the molecular and structural evolution of influenza virus strains in Singapore within the global context of these dynamic viruses. Keywords: Influenza, A/H1N1 viruses, A/H3N2 viruses, Influenza B, Evolution, Mutations, Receptor binding, Severity, Singapore

ABSTRACTDespite initial findings indicating that SARS-CoV and SARS-CoV-2 are genetically related belonging to the same virus species and that the two viruses used the same entry receptor, angiotensin-converting enzyme 2 (ACE2), our data demonstrated that there is no detectable cross-neutralization by SARS patient sera against SARS-CoV-2. We also found that there are significant levels of neutralizing antibodies in recovered SARS patients 9–17 years after initial infection. These findings will be of significant use in guiding the development of serologic tests, formulating convalescent plasma therapy strategies, and assessing the longevity of protective immunity for SARS-related coronaviruses in general as well as vaccine efficacy.

Dengue virus and Zika virus coexist in tropical regions in Asia where healthcare resources are limited; differentiating the 2 viruses is challenging. We showed in a case–control discovery cohort, and replicated in a validation cohort, that the diagnostic indices of conjunctivitis, platelet count, and monocyte count reliably distinguished between these viruses.

Abstract Background The first autochthonous Zika virus (ZIKV) outbreak in Singapore was detected in August 2016. We report an analysis of the correlation of clinical illness with viremia and laboratory parameters in this Asian cohort. Methods We conducted a prospective longitudinal cohort study of patients with a positive blood ZIKV polymerase chain reaction (PCR) result who were admitted to Tan Tock Seng Hospital, Singapore, for isolation and management. Results We included 40 patients in our study. Rash was present in all patients, while 80% (32/40) had fever, 62.5% (25/40) myalgia, 60% (24/40) conjunctivitis and 38% (15/40) arthralgia. The median duration of viremia was 3.5 days (IQR: 3–5 days). Patients with viremia of ≥4 days were more likely to have prolonged fever compared to those with viremia of less than 4 days (95% versus 63%, p = 0.01), but had no significant correlation with other clinical signs and symptoms, or laboratory investigations. However, 21 patients (53%) had hypokalemia despite the absence of gastrointestinal symptoms. Conclusion Although fever correlated with duration of viremia, 30% of patients remained viremic despite defervescence. Laboratory abnormalities such as leukopenia or thrombocytopenia were not prominent in this cohort but about half the patients were noted to have hypokalemia.

Singapore experienced its first documented Zika virus outbreak in 2016. We identified clinical and laboratory parameters that increase the probability for Zika or dengue virus infection. Early during the illness, combinations of key parameters obtained through clinical assessment and hematologic tests can help distinguish between these infections.

Abstract Background In the aftermath of an upsurge in the number of dengue cases in 2013 and 2014, the SD BIOLINE Dengue Duo rapid diagnostic Point-of-Care Test (POCT) kit was introduced in Tan Tock Seng Hospital, Singapore in June 2013. It is known that the success of POCT usage is contingent on its implementation within the health system. We evaluated health services delivery and the Dengue Duo rapid diagnostic test kit application in Singapore from healthcare workers’ perspectives and patient experiences of dengue at surge times. Methods Focus group discussions were conducted with dengue patients, from before and after the POCT implementation period. In-depth interviews with semi-structured components with healthcare workers were carried out. A patient centred process mapping technique was used for evaluation, which mapped the patient’s journey and was mirrored from the healthcare worker’s perspective. Results Patients and healthcare workers confirmed a wide range of symptoms in adults, making it challenging to determine diagnosis. There were multiple routes to help seeking, and no ‘typical patient journey’, with patients either presenting directly to the hospital emergency department, or being referred there by a primary care provider. Patients groups diagnosed before and after POCT implementation expressed some differences between speed of diagnoses and attitudes of doctors, yet shared negative feelings about waiting times and a lack of communication and poor information delivery. However, the POCT did not in its current implementation do much to help waiting times. Healthcare workers expressed that public perceptions of dengue in recent years was a major factor in changing patient management, and that the POCT kit was helpful in improving the speed and accuracy of diagnoses. Conclusions Health service delivery for dengue patients in Singapore was overall perceived to be of an acceptable clinical standard, which was enhanced by the introduction of the POCT. However, improvements can be focused on Adapting to outbreaks by reducing and rendering Waiting experiences more comfortable; Advancing education about symptom recognition, while also Recognising better communication strategies; and Expanding follow-up care options. This is presented as the Dengue AWARE model of care delivery.

Abstract Background Dengue results in high morbidity and mortality globally. The knowledge, attitude and practices (KAP) of dengue management, including diagnosis, among primary care physicians (PCPs) are important to reduce dengue transmission and burden. However, there is a lack of understanding on the impact of dengue epidemic on dengue management. Hence, the aim of this study is to examine the changes in KAP on dengue management among PCPs before and after the largest dengue epidemic in 2013 in Singapore. Methods Surveys were mailed to 2000 and 1514 PCPs registered under the Singapore Medical Council in March of year 2011 and 2014, respectively. Survey data were then collected between April and June of that year. Chi-square or Fisher’s exact test was used for comparing categorical variables. A multivariate logistic regression model was implemented to determine independent factors for frequent use of dengue diagnostic tests (DDTs). All tests were conducted at 5% level of significance. Adjusted odds ratio and corresponding 95% confidence intervals were reported, where applicable. Qualitative data were descriptively coded for themes and analysis. Results Among PCPs surveyed in 2011 and 2014, 89.9% and 86% had good knowledge on dengue management respectively. The usage of DDTs had increased significantly in 2014 (N = 164;56%) as compared to 2011 (N = 107;29.5%) in both private and public clinics (p

An outbreak of invasive group B Streptococcus (GBS) disease occurred in Singapore in mid-2015. We conducted a case–control study of 22 adults with invasive GBS infections during June 21–November 21, 2015. Consumption of raw fish was strongly associated with invasive sequence type 283 infections, but not with non–sequence type 283 infections.

A total of 828 community-dwelling adults were studied during the course of the pandemic (H1N1) 2009 outbreak in Singapore during June–September 2009. Baseline blood samples were obtained before the outbreak, and 2 additional samples were obtained during follow-up. Seroconversion was defined as a >4-fold increase in antibody titers to pandemic (H1N1) 2009, determined by using hemagglutination inhibition. Men were more likely than women to seroconvert (mean adjusted hazards ratio [HR] 2.23, mean 95% confidence interval [CI] 1.26–3.93); Malays were more likely than Chinese to seroconvert (HR 2.67, 95% CI 1.04–6.91). Travel outside Singapore during the study period was associated with seroconversion (HR 1.76, 95% CI 1.11–2.78) as was use of public transport (HR 1.81, 95% CI 1.05–3.09). High baseline antibody titers were associated with reduced seroconversion. This study suggests possible areas for intervention to reduce transmission during future influenza outbreaks.

We describe incidence and risk factors for pandemic (H1N1) 2009 virus infection in healthcare personnel during the June–September 2009 epidemic in Singapore. Personnel contributed 3 serologic samples during June–October 2009, with seroconversion defined as a >4-fold increase in hemagglutination inhibition titers to pandemic (H1N1) 2009. Of 531 participants, 35 showed evidence of seroconversion. Seroconversion rates were highest in nurses (28/290) and lowest in allied health staff (2/116). Significant risk factors on multivariate analysis were being a nurse (adjusted odds ratio [aOR] 4.5, 95% confidence interval [CI] 1.0–19.6) and working in pandemic (H1N1) 2009 isolation wards (aOR 4.5, 95% CI 1.3–15.6). Contact with pandemic (H1N1) 2009–infected colleagues (aOR 2.5, 95% CI 0.9–6.6) and larger household size (aOR 1.2, 95% CI 1.0–1.4) were of borderline significance. Our study suggests that seroconversion was associated with occupational and nonoccupational risk factors.

In June 2009, during Singapore’s pandemic influenza plan containment phase, pandemic (H1N1) 2009 was introduced into the country through imported cases. To understand how travel patterns affected the initial outbreak, we examined epidemiologic and travel data for the first 116 case-patients admitted to Tan Tock Seng Hospital, Singapore, with travel-associated infection. Sixty-one percent and 54% of patients, respectively, met US Centers for Disease Control and Prevention and World Health Organization temperature criteria for influenza-like illness. One fourth of the case-patients traveled after illness onset, and 15% became ill while traveling. Regions of exposure for imported infections changed rapidly; case-patients initially arrived from North America, followed by Australasia and Southeast Asia. Case-patients on longer flights were more likely to become ill before arrival; those with shorter flights tended to become ill after arrival. Thermal scanners detected fevers in 12% of the arriving case-patients, resulting in a shorter time to isolation.

We compared strategies for stockpiling neuraminidase inhibitors to treat and prevent influenza in Singapore. Cost-benefit and cost-effectiveness analyses, with Monte Carlo simulations, were used to determine economic outcomes. A pandemic in a population of 4.2 million would result in an estimated 525–1,775 deaths, 10,700–38,600 hospitalization days, and economic costs of $0.7 to $2.2 billion Singapore dollars. The treatment-only strategy had optimal economic benefits: stockpiles of antiviral agents for 40% of the population would save an estimated 418 lives and $414 million, at a cost of $52.6 million per shelf-life cycle of the stockpile. Prophylaxis was economically beneficial in high-risk subpopulations, which account for 78% of deaths, and in pandemics in which the death rate was >0.6%. Prophylaxis for pandemics with a 5% case-fatality rate would save 50,000 lives and $81 billion. These models can help policymakers weigh the options for pandemic planning.

Severe acute respiratory syndrome (SARS) is caused by a novel coronavirus (SARS-CoV). In a longitudinal cross-sectional study, we determined the prevalence of virus in bodily excretions and time of seroconversion in discharged patients with SARS. Conjunctival, throat, stool, and urine specimens were collected weekly from 64 patients and tested for SARS-CoV RNA by real-time polymerase chain reaction; serum samples were collected weekly and tested for SARS-CoV antibody with indirect enzyme immunoassay and immunofluorescence assay. In total, 126 conjunctival, 124 throat swab, 116 stool, and 124 urine specimens were analyzed. Five patients had positive stool samples, collected weeks 5–9. Two patients seroconverted in weeks 7 and 8; the others were seropositive at the first serum sample collection. In this study, 5 (7.8%) of 64 patients continued to shed viral RNA in stool samples only, for up to week 8 of illness. Most seroconversions occurred by week 6 of illness.

An outbreak of severe acute respiratory syndrome (SARS) was detected in Singapore at the beginning of March 2003. The outbreak, initiated by a traveler to Hong Kong in late February 2003, led to sequential spread of SARS to three major acute care hospitals in Singapore. The critical factor in containing this outbreak was early detection and complete assessment of movements and follow-up of patients, healthcare workers, and visitors who were contacts. Visitor records were important in helping identify exposed persons who could carry the infection into the community. In the three hospital outbreaks, three different containment strategies were used to contain spread of infection: closing an entire hospital, removing all potentially infected persons to a dedicated SARS hospital, and managing exposed persons in place. On the basis of this experience, if a nosocomial outbreak is detected late, a hospital may need to be closed in order to contain spread of the disease. Outbreaks detected early can be managed by either removing all exposed persons to a designated location or isolating and managing them in place.

We report a case of naturally acquired Plasmodium knowlesi in Singapore, a malaria-free country. Diagnosis was confirmed by PCR with validated species-specific primers. In industrialized countries, free-ranging primates are a potential source of P. knowlesi human infection. P. knowlesi infection is a differential diagnosis of febrile illness acquired in Singapore.