Results from a systematic programme of evaluating COVID-19 reinfection cases in the early phase of the pandemic, Singapore.

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.

The first imported case of monkeypox in Singapore during the 2022 outbreak - Reflections and lessons.

On June 21, 2022, Singapore reported its second ever case of imported monkeypox and first linked to the ongoing multi-country outbreak that has since been declared a public health emergency of international concern. There was quick initiation of public health measures including identification and quarantine of contacts, with post-exposure smallpox vaccination.

Seroprevalence of IgG antibodies against diphtheria antitoxin among migrant workers in Singapore, 2016-2019.

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.

Prevalence of measles antibodies among migrant workers in Singapore: a serological study to identify susceptible population subgroups.

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.

Living with COVID-19: The road ahead.

INTRODUCTION: The COVID-19 pandemic has affected the world for more than a year, with multiple waves of infections resulting in morbidity, mortality and disruption to the economy and society. Response measures employed to control it have generally been effective but are unlikely to be sustainable over the long term. METHODS: We examined the evidence for a vaccine-driven COVID-19 exit strategy including academic papers, governmental reports and epidemiological data, and discuss the shift from the current pandemic footing to an endemic approach similar to influenza and other respiratory infectious diseases. RESULTS: A desired endemic state is characterised by a baseline prevalence of infections with a generally mild disease profile that can be sustainably managed by the healthcare system, together with the resumption of near normalcy in human activities. Such an endemic state is attainable for COVID-19 given the promising data around vaccine efficacy, although uncertainty remains around vaccine immunity escape in emergent variants of concern. Maintenance of non-pharmaceutical interventions remains crucial until high vaccination coverage is attained to avoid runaway outbreaks. It may also be worthwhile to de-escalate measures in phases, before standing down most measures for an endemic state. If a variant that substantially evades immunity emerges, it will need to be managed akin to a new disease threat, with pandemic preparedness and response plans. CONCLUSION: An endemic state for COVID-19, characterised by sustainable disease control measures, is likely attainable through vaccination.

The Global Epidemiology of RSV in Community and Hospitalized Care: Findings From 15 Countries.

BACKGROUND: Respiratory syncytial virus (RSV) is one of the leading causes of acute respiratory tract infections. To optimize control strategies, a better understanding of the global epidemiology of RSV is critical. To this end, we initiated the Global Epidemiology of RSV in Hospitalized and Community care study (GERi). METHODS: Focal points from 44 countries were approached to join GERi and share detailed RSV surveillance data. Countries completed a questionnaire on the characteristics of their surveillance system. RESULTS: Fifteen countries provided granular surveillance data and information on their surveillance system. A median (interquartile range) of 1641 (552-2415) RSV cases per season were reported from 2000 and 2020. The majority (55%) of RSV cases occurred in the <1-year-olds, with 8% of cases reported in those aged ≥65 years. Hospitalized cases were younger than those in community care. We found no age difference between RSV subtypes and no clear pattern of dominant subtypes. CONCLUSIONS: The high number of cases in the <1-year-olds indicates a need to focus prevention efforts in this group. The minimal differences between RSV subtypes and their co-circulation implies that prevention needs to target both subtypes. Importantly, there appears to be a lack of RSV surveillance data in the elderly.

Defining the seasonality of respiratory syncytial virus around the world: National and subnational surveillance data from 12 countries.

BACKGROUND: Respiratory syncytial virus (RSV) infections are one of the leading causes of lower respiratory tract infections and have a major burden on society. For prevention and control to be deployed effectively, an improved understanding of the seasonality of RSV is necessary. OBJECTIVES: The main objective of this study was to contribute to a better understanding of RSV seasonality by examining the GERi multi-country surveillance dataset. METHODS: RSV seasons were included in the analysis if they contained ≥100 cases. Seasonality was determined using the "average annual percentage" method. Analyses were performed at a subnational level for the United States and Brazil. RESULTS: We included 601 425 RSV cases from 12 countries. Most temperate countries experienced RSV epidemics in the winter, with a median duration of 10-21 weeks. Not all epidemics fit this pattern in a consistent manner, with some occurring later or in an irregular manner. More variation in timing was observed in (sub)tropical countries, and we found substantial differences in seasonality at a subnational level. No association was found between the timing of the epidemic and the dominant RSV subtype. CONCLUSIONS: Our findings suggest that geographical location or climatic characteristics cannot be used as a definitive predictor for the timing of RSV epidemics and highlight the need for (sub)national data collection and analysis.

Short-term mortality from HIV-infected persons diagnosed from 2012 to 2016: Impact of late diagnosis of HIV infection.

ABSTRACT: 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.

Non-intrusive wastewater surveillance for monitoring of a residential building for COVID-19 cases.

Wastewater-based surveillance for SARS-CoV-2 has been used for the early warning of transmission or objective trending of the population-level disease prevalence. Here, we describe a new use-case of conducting targeted wastewater surveillance to complement clinical testing for case identification in a small community at risk of COVID-19 transmission. On 2 July 2020, a cluster of COVID-19 cases in two unrelated households residing on different floors in the same stack of an apartment building was reported in Singapore. After cases were conveyed to healthcare facilities and six healthy household contacts were quarantined in their respective apartments, wastewater surveillance was implemented for the entire residential block. SARS-CoV-2 was subsequently detected in wastewaters in an increasing frequency and concentration, despite the absence of confirmed COVID-19 cases, suggesting the presence of fresh case/s in the building. Phone interviews of six residents in quarantine revealed that no one was symptomatic (fever/respiratory illness). However, when nasopharyngeal swabs from six quarantined residents were tested by PCR tests, one was positive for SARS-CoV-2. The positive case reported episodes of diarrhea and the case's stool sample was also positive for SARS-CoV-2, explaining the SARS-CoV-2 spikes observed in wastewaters. After the case was conveyed to a healthcare facility, wastewaters continued to yield positive signals for five days, though with a decreasing intensity. This was attributed to the return of recovered cases, who had continued to shed the virus. Our findings demonstrate the utility of wastewater surveillance as a non-intrusive tool to monitor high-risk COVID-19 premises, which is able to trigger individual tests for case detection, highlighting a new use-case for wastewater testing.

Epidemiological factors associated with recent HIV infection among newly-diagnosed cases in Singapore, 2013-2017.

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.

Healthcare workers in Singapore infected with COVID-19: 23 January-17 April 2020.

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.

Coronavirus Disease 2019 (COVID-19): The Singapore Experience. A Review of the First Eight Months.

As of 27 October 2020, there have been 57,980 confirmed cases of COVID-19 in Singapore, with 28 fatalities. To summarise the Singapore experience in managing and containing COVID-19 based on available published data and from relevant sources, a review of literature using research databases such as PubMed and OVID Medline, along with non-peer-reviewed articles and other sources, was conducted with the search terms 'COVID-19' and 'Singapore'. Research conducted in Singapore has provided insight into the clinical manifestations and period of infectivity of COVID-19, demonstrated evidence of pre-symptomatic transmission, linked infection clusters using serological tools, and highlighted aspects of hospital-based environmental contamination. It has also provided guidance for diagnostic testing and has described immune and virologic correlates with disease severity. Evidence of effectiveness of containment measures such as early border control, rigorous contact training, and calibrated social distancing measures have also been demonstrated. Singapore's multipronged strategy has been largely successful at containing COVID-19 and minimising fatalities, but the risk of re-emergence is high.

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.

Epidemiologic Features and Clinical Course of Patients Infected With SARS-CoV-2 in Singapore.

Importance: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China, in December 2019 and has spread globally with sustained human-to-human transmission outside China. Objective: To report the initial experience in Singapore with the epidemiologic investigation of this outbreak, clinical features, and management. Design, Setting, and Participants: Descriptive case series of the first 18 patients diagnosed with polymerase chain reaction (PCR)-confirmed SARS-CoV-2 infection at 4 hospitals in Singapore from January 23 to February 3, 2020; final follow-up date was February 25, 2020. Exposures: Confirmed SARS-CoV-2 infection. Main Outcomes and Measures: Clinical, laboratory, and radiologic data were collected, including PCR cycle threshold values from nasopharyngeal swabs and viral shedding in blood, urine, and stool. Clinical course was summarized, including requirement for supplemental oxygen and intensive care and use of empirical treatment with lopinavir-ritonavir. Results: Among the 18 hospitalized patients with PCR-confirmed SARS-CoV-2 infection (median age, 47 years; 9 [50%] women), clinical presentation was an upper respiratory tract infection in 12 (67%), and viral shedding from the nasopharynx was prolonged for 7 days or longer among 15 (83%). Six individuals (33%) required supplemental oxygen; of these, 2 required intensive care. There were no deaths. Virus was detectable in the stool (4/8 [50%]) and blood (1/12 [8%]) by PCR but not in urine. Five individuals requiring supplemental oxygen were treated with lopinavir-ritonavir. For 3 of the 5 patients, fever resolved and supplemental oxygen requirement was reduced within 3 days, whereas 2 deteriorated with progressive respiratory failure. Four of the 5 patients treated with lopinavir-ritonavir developed nausea, vomiting, and/or diarrhea, and 3 developed abnormal liver function test results. Conclusions and Relevance: Among the first 18 patients diagnosed with SARS-CoV-2 infection in Singapore, clinical presentation was frequently a mild respiratory tract infection. Some patients required supplemental oxygen and had variable clinical outcomes following treatment with an antiretroviral agent.

Characterisation of respiratory syncytial virus activity in children and adults presenting with acute respiratory illness at primary care clinics in Singapore, 2014-2018.

BACKGROUND: Respiratory syncytial virus (RSV) is an important respiratory pathogen that affects people of all ages. OBJECTIVES: We examined the patterns of RSV circulation in 2014-2018, and investigated their age-specific differences in tropical Singapore. METHODS: Nasopharyngeal and/or throat swabs were taken from outpatient attendees for the national influenza virological surveillance among those who presented with acute respiratory illness in the community. Specimens tested negative for influenza were then tested for RSV and other respiratory pathogens. RESULTS: Among 8436 influenza-negative specimens tested during the five-year period, 5.8% (95% confidence interval 5.3%-6.3%) were positive for RSV. The peak of RSV activity occurred around middle of the year. The age-specific proportion of RSV detections showed a reverse J-shaped pattern; RSV positivity was the highest in young children ≤2 years of age (10.9%), followed by those aged 3-5 years (6.4%) and persons aged ≥65 years (5.3%), while the nadir was observed in the age group of 15-24 years (1.2%). RSV type A was predominantly circulating in children ≤5 years of age from 2014 to 2015 and 2017, whereas in 2016, they were more affected by type B. CONCLUSION: Respiratory syncytial virus was more frequently detected among the two age groups that have been recommended for influenza vaccination; persons ≥65 years of age and children 6 months to <5 years of age. Characterisation of RSV activity in the community helps to better inform public health policies for effective prevention and control interventions.

Implementing the World Health Organization Pandemic Influenza Severity Assessment framework-Singapore's experience.

BACKGROUND: We report our experience in evaluating the severity of local influenza epidemics using the World Health Organization Pandemic Influenza Severity Assessment framework. METHODS: We assessed the severity of influenza by monitoring indicators of influenza transmissibility, seriousness of disease and impact on healthcare resource utilisation. Indicators were described by various parameters collected weekly from eight government hospitals, 20 government and 30 private primary care clinics, and the national public health laboratory. Transmissibility and seriousness of disease indicators were each represented by multiple parameters, and alert thresholds were set at the 70th and 90th percentile of a parameter's past 2-year surveillance data. We derived a collective measure for each indicator using the average percentile rank of the related parameters. Alert thresholds for the single impact parameter were set at predefined values and evaluated for its sensitivity, specificity and positive predictive value. RESULTS: For the transmissibility and seriousness of disease parameters, calculation of the percentile rank was simple and independent of a parameter's underlying distribution. For the impact parameter, predefined alert thresholds had high sensitivity and specificity (>80%) but low positive predictive value (15%-30%). Assessment scales were used to qualitatively classify the activity of an indicator as low, moderate or high together with a confidence level. CONCLUSION: We applied different methods for threshold setting depending on the attributes of each parameter and indicator. For indicators represented by multiple parameters, an aggregated assessment of the indicator's level of activity and confidence level of the assessment was needed for effective reporting.

Seroprevalence of vaccine-preventable diseases among children and adolescents in Singapore: Results from the National Paediatric Seroprevalence Survey 2018.

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.

The epidemiological signature of influenza B virus and its B/Victoria and B/Yamagata lineages in the 21st century.

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.

Evaluating the effectiveness of the influenza vaccine during respiratory outbreaks in Singapore's long term care facilities, 2017.

Influenza outbreaks occur periodically in Long Term Care Facilities (LTCFs) and vaccination is critical in preventing influenza infections. We evaluated the influenza vaccine effectiveness (VE) during respiratory outbreaks in LTCFs reported to the Ministry of Health, Singapore in 2017. A test-negative design was used to estimate the ratio of the odds of testing positive for influenza among vaccinated individuals to the odds among unvaccinated individuals. The VE was calculated as (1-odds ratio) × 100%. For adjusted VE, the estimates were derived using logistic regression adjusted for age group, gender, month of illness, and number of days from date of illness onset till to swab collection date. Estimates by influenza subtypes and post-vaccination time periods (15-180 days & 181-365 days) were also calculated using stratified data. 264 individuals, with 118 laboratory-confirmed influenza cases [32 A(H1N1)pdm09, 75 A(H3N2), 11 A(untypable)], were included in the analysis. No one was identified to be infected with influenza B. The overall adjusted VE estimate was 40.5% (95% CI: -12.2-68.5%), while the subtype-specific adjusted VE estimates were -43.4% (95% CI: -312.4-50.2%) against A(H1N1)pdm09 and 57.1% (95% CI: 5.7-80.5%) against A(H3N2). At 15-180 days post-vaccination period, the adjusted VEs were 59.3% (95% CI: 18.0-79.8%) against all influenza, 35.4% (95% CI: -123.5-81.3%) against A(H1N1)pdm09 and 67.9% (95% CI: 22.5-86.7%) against A(H3N2). Estimates were not significant at 181-365 days post-vaccination. The influenza vaccine showed varying effectiveness among individuals in Singapore's LTCFs in 2017, with a higher effectiveness among those who were more recently vaccinated. It remains an important tool in preventing influenza infections, especially for those who are at high risk of influenza-related complications.

A 15-year review of dengue hospitalizations in Singapore: Reducing admissions without adverse consequences, 2003 to 2017.

OBJECTIVES: Since 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. METHODS: We 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. RESULTS: The 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. CONCLUSIONS: While 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.