The yield of tuberculosis contact investigation on relapsed TB patients and analysis of associated risk factors: Singapore's experience.

The yield of contact investigation on relapsed tuberculosis (TB) cases can guide strategies and resource allocation in the TB control programme. We conducted a retrospective cohort study to review the yield of contact investigation in relapsed TB cases and identify factors associated with TB infection (TBI) among close contacts of relapsed TB cases notified between 2018 and 2022 in Singapore. TB infection positivity was higher among contacts of relapsed cases which were culture-positive for Mycobacterium tuberculosis complex compared to those who were only polymerase chain reaction (PCR)-positive (14.8% vs. 12.3%). On multivariate analysis, after adjusting for age and gender of the index, gender, and existing comorbidities of contacts, factors independently associated with TBI were culture and smear positivity of the index (AOR 1.41, 95%CI 1.02-1.94), higher odds with every 10 years of increase in age compared to contacts below aged 30, contacts who were not Singapore residents (AOR 2.09, 95%CI 1.46-2.97), and household contacts (AOR 2.19, 95%CI 1.44-3.34). Although the yield of screening was higher for those who were culture-positive compared to only PCR-positive relapsed cases, contact tracing for only PCR-positive cases may still be important in a country with moderate TB incidence, should resources allow.

Epidemiological characteristics associated with uptake of pneumococcal vaccine among older adults living in the community in Singapore: Results from the National Health Surveillance Survey 2013.

AIMS: In Singapore, pneumococcal vaccination is recommended for the elderly (i.e. those ≥65 years of age) and people with chronic medical conditions. We investigated epidemiological characteristics associated with the uptake of pneumococcal vaccine based on a nationally representative cross-sectional sample of community-living adults aged ≥50 years. METHODS: The data were obtained from the National Health Surveillance Survey (NHSS) 2013. Associations between pneumococcal vaccination and sociodemographic and health-related variables were analysed using univariable and multivariable logistic regression models. RESULTS: Among 3672 respondents aged ≥50 years in the NHSS, 7.8% had taken the pneumococcal vaccination. A higher level of education and higher monthly household income were sociodemographic characteristics independently associated with pneumococcal vaccine uptake. Health-related characteristics predictive of pneumococcal vaccine uptake were better self-rated health and having a regular family doctor/general practitioner. Among those who responded to the two questions on vaccinations, 3.9% had been vaccinated against both seasonal influenza and pneumococcal infection, while 11.1% had taken only seasonal influenza vaccination in the past year. CONCLUSIONS: There is a need to boost pneumococcal vaccination coverage among community-dwelling older adults. These findings provide insights into reviewing and tailoring public-health strategies and programmes to increase vaccine uptake in at-risk population groups.

Influenza-Associated Hospitalizations for Cardiovascular Diseases in the Tropics.

Influenza is a major cause of mortality and morbidity. We aimed to examine the influenza-associated hospitalization rates and proportions for cardiovascular disease (CVD) in tropical Singapore. Hospital admissions for ischemic heart disease (IHD), congestive heart failure (CHF), and overall CVD were obtained from the national inpatient database for the period of 2010-2014. We used, as the key indicator of influenza virus activity, the overall proportion of specimens from outpatients with influenza-like illness in the community that tested positive for influenza as part of the national influenza surveillance program. The annual influenza-associated hospitalization rates per 100,000 person-years ranged from 9.5 to 12.2 for IHD, 7.7 to 9.1 for CHF, and 15.8 to 19.2 for overall CVD. The influenza-associated hospitalization rates increased with increasing age. Influenza was significantly associated with excess hospitalizations in elderly persons aged ≥80 years, with an excess hospitalization rate per 100,000 person-years of 242.7 for IHD (P = 0.02), 271.8 for CHF (P = 0.01), and 497.2 for overall CVD (P < 0.001). In the tropics, influenza accounts for excess cardiovascular-related hospitalizations, especially in the elderly.

Group B Streptococcus Serotype III Sequence Type 283 Bacteremia Associated with Consumption of Raw Fish, Singapore.

We conducted a retrospective study of 40 case-patients and 58 controls as part of a nationwide investigation of a group B Streptococcus outbreak in Singapore in 2015. Eating a Chinese-style raw fish dish (yusheng) was a major risk factor for bacteremia, particularly caused by serotype III sequence type 283.

The inevitable colonisation of Singapore by Zika virus.

Singapore is endemic for Dengue virus, with approximately 10,000 to 20,000 annual cases reported in recent years. In 2012, Chikungunya was introduced, although the numbers of cases reported is much fewer. The current Zika virus pandemic originating in Brazil represents a threat to all regions with Aedes mosquitoes, particularly those well connected by travellers. In this respect, it was felt inevitable that Singapore would eventually realise its third endemic flavivirus. In late August 2016, a primary care practitioner observed a cluster of geographically linked patients attending with fever and rash. This resulted in the first identification of locally transmitted Zika in Singapore on August 27, 2016. This prompted a robust response in an attempt to stop further spread, which continued for approximately 10 days until a large number of laboratory-confirmed cases were found as a result of active case finding. Surprisingly, the strain was later identified to be of Asian lineage and distinct from that originating in the Americas, prompting speculation over the epidemiology of this under recognised virus in Asia.

Characterization of influenza activity based on virological surveillance of influenza-like illness in tropical Singapore, 2010-2014.

Singapore is situated in the tropics where the seasonality of influenza is not as well defined as that of temperate countries. We examined the circulation of influenza viruses in the community in terms of the characteristics of influenza activity. We reviewed laboratory-confirmed virological data collected between 2010 and 2014 under the national influenza surveillance programme. Influenza activity was measured by the proportion of specimens from outpatients with influenza-like illness tested positive for influenza virus based on 4-weekly moving interval. Seasonal epidemics occurred around the end of previous year or the beginning and middle of the year. Increases in influenza positivity were more pronounced when there was a change in the predominant circulating influenza virus type/subtype to influenza A(H3N2). Influenza epidemics lasted about 12 weeks on average, with longer duration when there was a change in the predominant influenza type/subtype and especially when it was associated with influenza A(H3N2). Continuous influenza surveillance is important as it could provide early warning of imminent surges in virus transmission, and allow for timely implementation of public health prevention and control interventions to minimize influenza-associated disease burden. J. Med. Virol. 88:2069-2077, 2016. © 2016 Wiley Periodicals, Inc.

Epidemic resurgence of dengue fever in Singapore in 2013-2014: A virological and entomological perspective.

BACKGROUND: Dengue resurged in Singapore during 2013-14, causing an outbreak with unprecedented number of cases in the country. In the present study, we summarise the epidemiological, virological and entomological findings gathered through the dengue surveillance programme and highlight the drivers of the epidemic. We also describe how the surveillance system facilitated the preparedness to moderate epidemic transmission of dengue in the country. METHODS: The case surveillance was based on a mandatory notification system that requires all medical practitioners to report clinically-suspected and laboratory-confirmed cases within 24 hours. The circulating Dengue virus (DENV) populations were monitored through an island wide virus surveillance programme aimed at determining the serotypes and genotypes of circulating virus strains. Entomological surveillance included adult Aedes surveillance as well as premise checks for larval breeding. RESULTS: A switch in the dominant serotype from DENV-2 to DENV-1 in March 2013 signalled a potential spike in cases, and the alert was corroborated by an increase in average Aedes house index. The alert triggered preparedness and early response to moderate the impending outbreak. The two-year outbreak led to 22,170 cases in 2013 and 18,338 in 2014, corresponding to an incidence rate of 410.6 and 335.0 per 100,000 population, respectively. DENV-1 was the dominant serotype in 2013 (61.7 %, n = 5,071) and 2014 (79.2 %, n = 5,226), contributed largely by a newly-introduced DENV-1 genotype III strain. The percentage of houses with Ae. aegypti breeding increased significantly (p < 0.001) from 2012 (annual average of 0.07 %) to 2013 (annual average of 0.14 %), followed by a drop in 2014 (annual average of 0.10 %). Aedes breeding data further showed a wide spread distribution of Ae. aegypti in the country that corresponded with the dengue case distribution pattern in 2013 and 2014. The adult Aedes data from 34 gravitrap sentinel sites revealed that approximately 1/3 of the monitored sites remained at high risk of DENV transmission in 2013. CONCLUSIONS: The culmination of the latest epidemic is likely to be due to a number of demographic, social, virological, entomological, immunological, climatic and ecological factors that contribute to DENV transmission. A multi-pronged approach backed by the epidemiological, virological and entomological understanding paved way to moderate the case burden through an integrated vector management approach.

Seroprevalence of past dengue virus infection among children and adolescents in Singapore.

We conducted a pediatric seroprevalence study of dengue virus (DENV) infection in Singapore, a dengue endemic city-state. Residual sera from 1,200 Singapore residents aged 1-17 years seen in two hospitals between 2008 and 2010 were tested for anti-DENV IgG antibodies. The overall seroprevalence was 10.4% (95%CI: 8.7-12.1%). There had been a marked decline in seroprevalence in the 15-19-year age group over the last three decades, while the prevalence in the 1-5-year olds (12.6%) was significantly higher than that of the 1996-1997 pediatric survey (0.8%). The overall dengue seroprevalence in children and adolescents remained low.

Influenza-associated hospitalizations, Singapore, 2004-2008 and 2010-2012.

Studies of influenza-associated hospitalizations in tropical settings are lacking. To increase understanding of the effect of influenza in Singapore, we estimated the age-specific influenza-associated hospitalizations for pneumonia and influenza during 2004-2008 and 2010-2012. The rate of hospitalization was 28.3/100,000 person-years during 2004-2008 and 29.6/100,000 person-years during 2010-2012. The age-specific influenza-associated hospitalization rates followed a J-shaped pattern: rates in persons >75 years of age and in children <6 months of age were >47 times and >26 times higher, respectively, than those for persons 25-44 years of age. Across all ages during these 2 study periods, ≈12% of the hospitalizations for pneumonia and influenza were attributable to influenza. The rates and proportions of hospitalizations for influenza, particularly among the very young and the elderly, are considerable in Singapore and highlight the importance of vaccination in protecting populations at risk.

"Risk factors for tuberculosis among close IGRA-negative contacts of persons with infectious tuberculosis in Singapore".

BACKGROUND: Contacts of infectious TB cases testing positive on Interferon-Gamma Release Assay (IGRA) are followed up to exclude active disease. However, factors that predispose IGRA-negative contacts to TB could improve screening and follow-up strategies in a medium TB burden country like Singapore. METHODS: We conducted a retrospective study of IGRA-negative contacts aged ≥2 years identified during contact investigation between January 2014 and December 2022. We examined the risk factors associated with developing active TB among contacts previously testing IGRA-negative, using univariate and multivariable logistic regression and odds ratios (OR) with 95% confidence intervals (CI). RESULTS: Of 60,377 IGRA-negative contacts, 150 developed TB disease and half were notified within 23 months of index diagnosis. IGRA-negative contacts of a smear-positive index were more likely to develop TB. Independent risk factors for TB were being over 50, Malay, having Diabetes or End-Stage Renal Failure, a "family" relationship with the index or exposure in a dormitory or nursing home. CONCLUSION: Certain risk factors could help optimize follow-up strategies and preventive treatment in IGRA-negative individuals. The incidence of TB in this group was 150/100,000 population, substantially higher than in the community, with a median 92 weeks to develop disease. Findings suggest that follow-up be extended to 24 months for contacts with these risk factors.

Microsporidial keratoconjunctivitis after rugby tournament, Singapore.

We investigated an outbreak of 47 probable and 6 confirmed cases of microsporidial keratoconjunctivitis involving participants of an international rugby tournament in Singapore in April 2012.The mode of transmission was eye contact with soil. Vittaforma corneae was identified in 4 of 6 corneal scrapings and in 1 of 12 soil water samples.

Seroprevalence of hepatitis B virus infection among children and adolescents in Singapore, 2008-2010.

A national pediatric survey was undertaken to determine the prevalence of hepatitis B virus markers in Singapore. The aim was to assess the impact of the national childhood immunization program against hepatitis B implemented for all newborns since 1987. The survey involved prospective collection of residual sera from Singapore residents aged 1-17 years attending inpatient services or day surgery in two public hospitals between August 2008 and July 2010. A total of 1,200 sera were collected comprising 400 in each of the three age groups of 1-6, 7-12, and 13-17 years. The sera were tested for hepatitis B surface antigen (HBsAg) and antibody to HBsAg (anti-HBs). Four of the 1,200 samples tested positive for HBsAg, giving an overall prevalence of 0.3%. One and three in the 7-12 years and 13-17 years age groups, respectively, were positive for HBsAg. About 40% possessed anti-HBs (≥10 mIU/ml); the antibody prevalence decreased significantly from 63.8% in children aged 1-6 years to 32.8% in 7-12 year olds, and 23.5% in 13-17 year olds (P < 0.0005). The successful implementation of the national childhood hepatitis B immunization program over the last two decades has resulted in a low prevalence of HBsAg among children and adolescents. Singapore has achieved the World Health Organization Western Pacific Region's goal in reducing the prevalence of chronic HBV infection to below 2% among children aged 5 years and older by 2012 and to below 1% by 2017.

Implementation of national whole-genome sequencing of Mycobacterium tuberculosis, National Public Health Laboratory, Singapore, 2019-2022.

The National Tuberculosis Programme (NTBP) monitors the occurrence and spread of tuberculosis (TB) and multidrug-resistant TB (MDR-TB) in Singapore. Since 2020, whole-genome sequencing (WGS) of Mycobacterium tuberculosis isolates has been performed at the National Public Health Laboratory (NPHL) for genomic surveillance, replacing spoligotyping and mycobacterial interspersed repetitive unit-variable number tandem repeats analysis (MIRU-VNTR). Four thousand three hundred and seven samples were sequenced from 2014 to January 2023, initially as research projects and later developed into a comprehensive public health surveillance programme. Currently, all newly diagnosed culture-positive cases of TB in Singapore are prospectively sent for WGS, which is used to perform lineage classification, predict drug resistance profiles and infer genetic relationships between TB isolates. This paper describes NPHL's operational and technical experiences with implementing the WGS service in an urban TB-endemic setting, focusing on cluster detection and genomic drug susceptibility testing (DST). Cluster detection: WGS has been used to guide contact tracing by detecting clusters and discovering unknown transmission networks. Examples have been clusters in a daycare centre, housing apartment blocks and a horse-racing betting centre. Genomic DST: genomic DST prediction (gDST) identifies mutations in core genes known to be associated with TB drug resistance catalogued in the TBProfiler drug resistance mutation database. Mutations are reported with confidence scores according to a standardized approach referencing NPHL's internal gDST confidence database, which is adapted from the World Health Organization (WHO) TB drug mutation catalogue. Phenotypic-genomic concordance was observed for the first-line drugs ranging from 2959/2998 (98.7 %) (ethambutol) to 2983/2996 (99.6 %) (rifampicin). Aspects of internal database management, reporting standards and caveats in results interpretation are discussed.

Teacher led school-based surveillance can allow accurate tracking of emerging infectious diseases - evidence from serial cross-sectional surveys of febrile respiratory illness during the H1N1 2009 influenza pandemic in Singapore.

BACKGROUND: Schools are important foci of influenza transmission and potential targets for surveillance and interventions. We compared several school-based influenza monitoring systems with clinic-based influenza-like illness (ILI) surveillance, and assessed the variation in illness rates between and within schools. METHODS: During the initial wave of pandemic H1N1 (pdmH1N1) infections from June to Sept 2009 in Singapore, we collected data on nation-wide laboratory confirmed cases (Sch-LCC) and daily temperature monitoring (Sch-DTM), and teacher-led febrile respiratory illness reporting in 6 sentinel schools (Sch-FRI). Comparisons were made against age-stratified clinic-based influenza-like illness (ILI) data from 23 primary care clinics (GP-ILI) and proportions of ILI testing positive for pdmH1N1 (Lab-ILI) by computing the fraction of cumulative incidence occurring by epidemiological week 30 (when GP-ILI incidence peaked); and cumulative incidence rates between school-based indicators and sero-epidemiological pdmH1N1 incidence (estimated from changes in prevalence of A/California/7/2009 H1N1 hemagglutination inhibition titers ≥ 40 between pre-epidemic and post-epidemic sera). Variation in Sch-FRI rates in the 6 schools was also investigated through a Bayesian hierarchical model. RESULTS: By week 30, for primary and secondary school children respectively, 63% and 79% of incidence for Sch-LCC had occurred, compared with 50% and 52% for GP-ILI data, and 48% and 53% for Sch-FRI. There were 1,187 notified cases and 7,588 episodes in the Sch-LCC and Sch-DTM systems; given school enrollment of 485,723 children, this represented 0.24 cases and 1.6 episodes per 100 children respectively. Mean Sch-FRI rate was 28.8 per 100 children (95% CI: 27.7 to 29.9) in the 6 schools. We estimate from serology that 41.8% (95% CI: 30.2% to 55.9%) of primary and 43.2% (95% CI: 28.2% to 60.8%) of secondary school-aged children were infected. Sch-FRI rates were similar across the 6 schools (23 to 34 episodes per 100 children), but there was widespread variation by classrooms; in the hierarchical model, omitting age and school effects was inconsequential but neglecting classroom level effects led to highly significant reductions in goodness of fit. CONCLUSIONS: Epidemic curves from Sch-FRI were comparable to GP-ILI data, and Sch-FRI detected substantially more infections than Sch-LCC and Sch-DTM. Variability in classroom attack rates suggests localized class-room transmission.

The changing seroepidemiology of enterovirus 71 infection among children and adolescents in Singapore.

BACKGROUND: Enterovirus 71 (EV71) has caused recurrent epidemics of hand, foot and mouth disease among children in Singapore. Between August 2008 and July 2010, we conducted a survey to estimate the seroprevalence of EV71 infection among children and adolescents aged 1-17 years. We compared our EV71 seroepidemiologic findings with a previous study conducted in 1996-1997. METHODS: The survey involved the prospective collection of 1,200 residual sera from Singapore residents aged 1-17 years in two hospitals. Neutralizing antibodies to EV71 were detected by the microneutralization test. The geometric mean titer (GMT) of EV71 antibodies and 95% confidence intervals (CI) were calculated and compared by age groups. Statistical significance was taken as P < 0.05. RESULTS: The overall EV71 antibody prevalence was 26.9% (95% CI: 24.5-29.5%). It increased significantly from 14.3% in children aged 1-6 years to 27.8% in those aged 7-12 years, and reached 38.8% in adolescents aged 13-17 years. The seroconversion rate differed by about 12% between the consecutive age groups. The GMT of EV71 antibodies was higher among primary school children aged 7-12 years in our study than that among the 6-12 year age group in the 1996-1997 study. CONCLUSIONS: Higher antibody titers were observed in children aged 1-6 years than those in the other two age groups, indicating that most of the infections had been acquired during early childhood. EV71 infection is common among children and adolescents in Singapore, with 39% infected by the time they are in secondary school (13-17 years of age).

Epidemiological, Clinical, and Phylogenetic Characteristics of the First SARS-CoV-2 Transmission in a Nursing Home of Singapore: A Prospective Observational Investigation.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission has resulted in a significant burden among nursing home facilities globally. This prospective observational cohort study aims to define the potential sources of introduction and characteristics of SARS-CoV-2 transmission of the first nursing home facility in Singapore. An epidemiological serial point-prevalence survey of SARS-CoV-2 was conducted among 108 residents and 56 healthcare staff (HCS). In the current study, 14 (13%) residents and two (3.6%) HCS were diagnosed with coronavirus disease 2019 (COVID-19), with a case fatality rate (CFR) of 28.6% (4/14) among the residents. The median age of the infected residents was 86.5 [interquartile range (IQR) 78.5-88] and 85.7% were women. Five residents were symptomatic (35.7%) and the others were asymptomatic (64.3%). A higher proportion of residents who succumbed to COVID-19 had hypertension than those who recovered. The SARS-CoV-2 whole-genome sequencing showed lineage B.6 which is rare globally but common regionally during the early phase of the pandemic. Household transmission is a potential source of introduction into the nursing home, with at least six epidemiologically linked secondary cases. Male residents were less implicated due to the staff segregation plan by block. Among residents, a higher proportion of the non-survivors were asymptomatic and had hypertension compared with survivors.

The influenza A (H1N1-2009) experience at the inaugural Asian Youth Games Singapore 2009: mass gathering during a developing pandemic.

From 29 June to 7 July 2009, Singapore hosted the inaugural Asian Youth Games (AYG), which brought 1210 athletes and 810 officials from 43 participating countries. On 11 June, just 1 week before the Games Village Medical Centre started operations, the World Health Organization officially declared a global H1N1 2009 pandemic. Working in close partnership with the Olympic Council of Asia Medical Commission, Singapore AYG Organising Committee and other government agencies, the AYG Medical Services Committee was successful in preventing the local transmission of H1N1, which would have been a threat to the games, as it could have led to the cancellation of these games. This article describes the experience and valuable lessons learnt from managing a sports-related mass gathering during the developing pandemic.

Assessment of the risk posed to Singapore by the emergence of artemisinin-resistant malaria in the Greater Mekong Subregion.

OBJECTIVE: To assess the public health risk to Singapore posed by the emergence of artemisinin-resistant (ART-R) malaria in the Greater Mekong Subregion (GMS). METHODS: We assessed the likelihood of importation of drug-resistant malaria into Singapore and the impact on public health of its subsequent secondary spread in Singapore. Literature on the epidemiology and contextual factors associated with ART-R malaria was reviewed. The epidemiology of malaria cases in Singapore was analysed. The vulnerability and receptivity of Singapore were examined, including the connectivity with countries reporting ART-R malaria, as well as the preparedness of Singaporean health authorities. Sources of information include international journals, World Health Organization guidelines, data from the Singapore Ministry of Health and National Public Health Laboratory of the National Centre for Infectious Diseases, and the International Air Transport Association. RESULTS: The importation of ART-R malaria into Singapore is possible given the close proximity and significant travel volume between Singapore and the GMS countries reporting artemisinin resistance. Singapore's vulnerability is further enhanced by the presence of foreign workers from neighbouring endemic countries. Nonetheless, the overall likelihood of such an event is low based on the rarity and decreasing trend of imported malaria incidence.​: With the presence of Anopheles vectors in Singapore, imported cases of drug-resistant malaria could cause secondary transmission. Nevertheless, the risk of sustained spread is likely to be mitigated by the comprehensive surveillance and control system in place for both infected vectors and human cases. DISCUSSION: This risk assessment highlights the need for a continued high degree of vigilance of ART-R malaria locally and globally to minimize the risk and public health impact of drug-resistant malaria in Singapore.