Safety and effectiveness of switching to Abacavir/Lamivudine plus rilpivirine for maintenance therapy in virologically suppressed HIV-1 individuals in Singapore (SEALS).

BACKGROUND: The efficacy and tolerability of an antiretroviral regimen are important considerations for selection of HIV-1 infection maintenance therapy. Abacavir/lamivudine plus rilpivirine (ABC/3TC + RPV) has been shown in international studies to be effective and well-tolerated in virologically suppressed individuals. This study evaluated the effectiveness and safety of switching to ABC/3TC + RPV as maintenance therapy in virologically suppressed HIV-1 infected individuals in Singapore. METHODS: In this retrospective, single-centre study, we included individuals who were prescribed ABC/3TC + RPV, had HIV-1 viral load (VL) < 50 copies/ml immediately pre-switch, and had no documented history of resistance mutations or virologic failure to any of the components. The follow-up period was 48 ± 12 weeks. The primary outcome was the proportion of individuals who maintained virologic suppression of HIV-1 VL < 50 copies/ml at the end of follow-up period based on on-treatment analysis. The secondary outcomes were the resistance profiles associated with virologic failure, changes in immunologic and metabolic parameters, and the safety profile of ABC/3TC + RPV. RESULTS: A total of 222 individuals were included in the study. The primary outcome was achieved in 197 individuals [88.8%, 95% confidence interval: 83.7-92.4%]. There were 21 individuals (9.5%) who discontinued treatment for non-virologic reasons. The remaining 4 individuals experienced virologic failure, of whom, 3 of these individuals had developed emergent antiretroviral resistance and had HIV-1 VL > 500 copies/ml at the end of the 48 ± 12 weeks follow-up period. The remaining individual experienced sustained low level viremia and subsequently achieved viral suppression without undergoing resistance testing. A total of 49 adverse events were observed in 31 out of 222 individuals (14.0%), which led to 13 individuals discontinuing therapy. Neuropsychiatric adverse events were most commonly observed (53.1%). A statistically significant increase in CD4 was observed (p < 0.01), with a median absolute change of 31 cells/uL (interquartile range: - 31.50 to 140.75). No significant changes in lipid profiles were detected. CONCLUSION: ABC/3TC + RPV is a safe and effective switch option for maintenance therapy in virologically suppressed HIV-1 individuals with in Singapore.

Influenza vaccine failure in the tropics: a retrospective cohort study of waning effectiveness.

Influenza vaccine effectiveness (VE) wanes over the course of a temperate climate winter season but little data are available from tropical countries with year-round influenza virus activity. In Singapore, a retrospective cohort study of adults vaccinated from 2013 to 2017 was conducted. Influenza vaccine failure was defined as hospital admission with polymerase chain reaction-confirmed influenza infection 2-49 weeks after vaccination. Relative VE was calculated by splitting the follow-up period into 8-week episodes (Lexis expansion) and the odds of influenza infection in the first 8-week period after vaccination (weeks 2-9) compared with subsequent 8-week periods using multivariable logistic regression adjusting for patient factors and influenza virus activity. Records of 19 298 influenza vaccinations were analysed with 617 (3.2%) influenza infections. Relative VE was stable for the first 26 weeks post-vaccination, but then declined for all three influenza types/subtypes to 69% at weeks 42-49 (95% confidence interval (CI) 52-92%, P = 0.011). VE declined fastest in older adults, in individuals with chronic pulmonary disease and in those who had been previously vaccinated within the last 2 years. Vaccine failure was significantly associated with a change in recommended vaccine strains between vaccination and observation period (adjusted odds ratio 1.26, 95% CI 1.06-1.50, P = 0.010).

Reproductive factors and risk of total knee replacement due to severe knee osteoarthritis in women, the Singapore Chinese Health Study.

OBJECTIVES: Knee osteoarthritis (OA) is more common in women, and may be related to reproductive or hormonal factors. We evaluated these factors with the risk of total knee replacement (TKR) for severe knee OA among women. METHODS: The Singapore Chinese Health Study recruited 63,257 Chinese aged 45-74 years from 1993 to 1998, and among them, 35,298 were women. Information on height, weight, lifestyle factors, number of biological children, ages at menarche and menopause, and use of hormonal therapies was collected through interviews. Incident cases of TKR were identified via linkage with nationwide database. RESULTS: There were 1,645 women with TKR after mean follow-up of 14.8 years. Higher parity was associated with increased TKR risk in a stepwise manner (P for trend <0.001). Compared to nulliparous women, those with ≥5 children had the highest risk [hazard ratio (HR) 2.01, 95% confidence intervals (CIs) 1.50-2.70]. The effect of parity on TKR risk was significantly stronger among lean women compared to heavier women; HRs (95% CIs) for highest parity was 4.86 (2.22-10.63) for women with body mass index (BMI) <23 kg/m2 and 1.57 (1.14-2.14) for those ≥23 kg/m2 (P for interaction = 0.001). Earlier age at menarche and use of oral contraceptives were significantly associated with TKR in a stepwise manner (P for trend ≤0.002). Age at menopause and use of hormonal therapy were not associated with TKR risk. CONCLUSION: Higher parity, earlier age of menarche and use of oral contraceptives were associated with increased risk of TKR for severe knee OA among women.

Epidemiology of tuberculosis and HIV coinfections in Singapore, 2000-2014.

Cross-matching of records between Singapore's tuberculosis and HIV registries showed that 3.3% of individuals with tuberculosis (TB) were coinfected with HIV (2000-2014), the TB incidence among individuals with HIV infection was 1.65 per 100 person-years, and 53% of coinfections were diagnosed within 1 month of each other. The findings supported joint prevention programmes for early diagnosis and treatment.

Gout and risk of knee replacement for severe knee osteoarthritis in the Singapore Chinese Health Study.

OBJECTIVE: While cross-sectional and retrospective case-control studies suggest that gout is associated with knee osteoarthritis (KOA), no prospective study has evaluated the risk of total knee replacement (TKR) for KOA in association with gout. We prospectively evaluated the association between gout and the risk of TKR due to severe KOA. DESIGN: We used data from the Singapore Chinese Health Study (SCHS), a prospective cohort with 63,257 Chinese adults aged 45-74 years at recruitment (1993-1998). Self-report of physician-diagnosed gout was enquired at follow-up I interview (1999-2004) from 52,322 subjects. TKR cases for KOA after follow-up I were identified via linkage with nationwide hospital discharge database through 31 December 2011. Multivariable Cox proportional hazards regression model was applied with adjustment for potential risk factors of KOA. RESULTS: Among 51,858 subjects (22,180 men and 29,678 women) included in this analysis, after average 9.7 follow-up years, there were 1,435 cases of TKR. Gout was associated with 39% higher risk of TKR in women [hazard ratio (HR) 1.39; 95% confidence interval (CI) 1.08-1.79] but not in men (HR 0.78; 95% CI 0.49-1.23). The positive gout-TKR association in women remained after excluding participants with self-reported history of arthritis (HR 1.57; 95% CI 1.04-2.37). This association was stronger in women who were lean (body mass index [BMI] < 23 kg/m2) (HR 2.17; 95% CI 1.30-3.64) compared to their heavier counterparts (Pinteraction = 0.016). CONCLUSION: Gout is associated with risk of severe KOA, especially in lean women, suggesting the crystal arthritis may play a role in the pathogenesis or progression of OA.

Factors associated with influenza vaccine uptake in older adults living in the community in Singapore.

In Singapore, influenza vaccination is recommended for persons at higher risk of complications of seasonal influenza, including those with chronic medical conditions and the elderly (individuals aged ⩾65 years). We investigated the factors associated with influenza vaccine uptake based on a nationally representative sample of community-dwelling adults aged >50 years. The data for this study were obtained from the National Health Surveillance Survey (NHSS) 2013. The association between influenza vaccine uptake and socio-demographic and health-related variables was analysed using univariable and multivariable logistic regression models. Of 3700 respondents aged ⩾50 years in the NHSS, 15·2% had received seasonal influenza vaccination in the past year. Older age, single marital status and economic inactivity were the socio-demographic variables independently associated with vaccine uptake. Health-related factors which were predictive of influenza vaccine uptake were sufficient total physical activity, better self-rated health, having at least one medical condition at risk of influenza complications and a regular family doctor/general practitioner. Influenza vaccine uptake in community-dwelling older adults was low. Our findings are of relevance in the formulation of public health policies and targeted health promotion strategies to increase vaccine uptake in this population group.

A large common-source outbreak of norovirus gastroenteritis in a hotel in Singapore, 2012.

An outbreak of gastroenteritis affected 453 attendees (attack rate 28·5%) of six separate events held at a hotel in Singapore. Active case detection, case-control studies, hygiene inspections and microbial analysis of food, environmental and stool samples were conducted to determine the aetiology of the outbreak and the modes of transmission. The only commonality was the food, crockery and cutlery provided and/or handled by the hotel's Chinese banquet kitchen. Stool specimens from 34 cases and 15 food handlers were positive for norovirus genogroup II. The putative index case was one of eight norovirus-positive food handlers who had worked while they were symptomatic. Several food samples and remnants tested positive for Escherichia coli or high faecal coliforms, aerobic plate counts and/or total coliforms, indicating poor food hygiene. This large common-source outbreak of norovirus gastroenteritis was caused by the consumption of contaminated food and/or contact with contaminated crockery or cutlery provided or handled by the hotel's Chinese banquet kitchen.

Basic reproduction number of coxsackievirus type A6 and A16 and enterovirus 71: estimates from outbreaks of hand, foot and mouth disease in Singapore, a tropical city-state.

Coxsackievirus A6 (CV-A6), coxsackievirus A16 (CV-A16) and enterovirus 71 (EV-A71) were the major enteroviruses causing nationwide hand, foot and mouth disease (HFMD) epidemics in Singapore in the last decade. We estimated the basic reproduction number (R 0) of these enteroviruses to obtain a better understanding of their transmission dynamics. We merged records of cases from HFMD outbreaks reported between 2007 and 2012 with laboratory results from virological surveillance. R 0 was estimated based on the cumulative number of reported cases in the initial growth phase of each outbreak associated with the particular enterovirus type. A total of 33 HFMD outbreaks were selected based on the inclusion criteria specified for our study, of which five were associated with CV-A6, 13 with CV-A16, and 15 with EV-A71. The median R 0 was estimated to be 5·04 [interquartile range (IQR) 3·57-5·16] for CV-A6, 2·42 (IQR 1·85-3·36) for CV-A16, and 3·50 (IQR 2·36-4·53) for EV-A71. R 0 was not significantly associated with number of infected children (P = 0·86), number of exposed children (P = 0·94), and duration of the outbreak (P = 0·05). These enterovirus-specific R 0 estimates will be helpful in providing insights into the potential growth of future HFMD epidemics and outbreaks for timely implementation of disease control measures, together with disease dynamics such as severity of the cases.

Prevalence of diphtheria and tetanus antibodies among adults in Singapore: a national serological study to identify most susceptible population groups.

BACKGROUND: In view of waning antitoxin titres over time after the last vaccine dose against diphtheria and tetanus, we determined the immunity levels in adults to identify most susceptible groups for protection in Singapore. METHODS: Our study involved residual sera from 3293 adults aged 18-79 who had participated in a national health survey in 2010. IgG antibody levels were determined using commercial enzyme-linked immunosorbent assay. RESULTS: Overall, 92.0% (95% confidence interval [CI]: 91.1-92.9%) had at least basic protection against diphtheria (antibody levels ≥0.01 IU/ml), while 71.4% (95% CI: 69.8-72.9%) had at least short-term protection against tetanus (antibody levels >0.1 IU/ml). The seroprevalence declined significantly with age for both diseases; the drop was most marked in the 50- to 59-year age group for diphtheria and 60- to 69-year age group for tetanus. There was a significant difference in seroprevalence by residency for diphtheria (92.8% among Singapore citizens versus 87.1% among permanent residents; P = 0.001). The seroprevalence for tetanus was significantly higher among males (83.2%) than females (62.4%) (P < 0.0005). CONCLUSIONS: It may be of value to consider additional vaccination efforts to protect older adults at higher risk for exposure against diphtheria and tetanus, particularly those travelling to areas where diphtheria is endemic or epidemic.

Influenza A(H1N1)pdm09 infection in pregnant and non-pregnant women hospitalized in Singapore, May - December 2009.

OBJECTIVES: The aim of this study was to compare the demographic and clinical characteristics of pregnant women and non-pregnant women of childbearing age hospitalized with laboratory-confirmed influenza A(H1N1)pdm09 infection in Singapore, and to assess whether pregnancy was a risk factor associated with the development of influenza-related complications. STUDY DESIGN: Retrospective observational study. METHODS: We retrospectively identified and collected information from available medical records of all women admitted to three tertiary hospitals between 26 May 2009 and 31 December 2009 with laboratory-confirmed influenza A(H1N1)pdm09 infection who were either pregnant or non-pregnant and of childbearing age between 15 and 50 years. RESULTS: A total of 222 women, of whom 81 (36.5%) were pregnant, were hospitalized during the study period. Pregnant women were significantly more likely to be hospitalized with influenza A(H1N1)pdm09 infection than non-pregnant women of childbearing age (relative risk 26.3; 95% confidence interval: 20.1-34.6). Among those hospitalized, the proportion of pregnant women having at least one underlying medical condition that could predispose them to influenza-related complications was significantly lower than that of non-pregnant women (32.1% versus 56.0%, P < 0.001). The median time from onset of symptoms to administration of anti-viral drugs was significantly shorter among pregnant women than among non-pregnant women (three days versus five days, P < 0.001). The median length of stay in hospital was also significantly shorter among pregnant women than that of non-pregnant women (two days versus three days, P = 0.002). About 4.9% of pregnant women developed influenza-related complications, compared with 12.8% among non-pregnant women (P = 0.066). CONCLUSIONS: Pregnant women with influenza A(H1N1)pdm09 infection were at a higher risk of hospitalization. Upon hospitalization, they were not at a higher risk of developing influenza-related complications.

Association between change in body weight after midlife and risk of hip fracture-the Singapore Chinese Health Study.

UNLABELLED: The relationship between change in body weight and risk of fractures is inconsistent in epidemiologic studies. In this cohort of middle-aged to elderly Chinese in Singapore, compared to stable weight, weight loss ≥10 % over an average of 6 years is associated with nearly 40 % increase in risk of hip fracture. INTRODUCTION: Findings on the relationship between change in body weight and risk of hip fracture are inconsistent. In this study, we examined this association among middle-aged and elderly Chinese in Singapore. METHODS: We used prospective data from the Singapore Chinese Health Study, a population-based cohort of 63,257 Chinese men and women aged 45-74 years at recruitment in 1993-1998. Body weight and height were self-reported at recruitment and reassessed during follow-up interview in 1999-2004. Percent in weight change was computed based on the weight difference over an average of 6 years, and categorized as loss ≥10 %, loss 5 to <10 %, loss or gain <5 % (stable weight), gain 5 to <10 %, and gain ≥10 %. Multivariable Cox proportional hazards regression model was applied with adjustment for risk factors for hip fracture and body mass index (BMI) reported at follow-up interview. RESULTS: About 12 % experienced weight loss ≥10 %, and another 12 % had weight gain ≥10 %. After a mean follow-up of 9.0 years, we identified 775 incident hip fractures among 42,149 eligible participants. Compared to stable weight, weight loss ≥10 % was associated with 39 % increased risk (hazard ratio 1.39; 95 % confidence interval 1.14, 1.69). Such elevated risk with weight loss ≥10 % was observed in both genders and age groups at follow-up (≤65 and >65 years) and in those with baseline BMI ≥20 kg/m(2).There was no significant association with weight gain. CONCLUSIONS: Our findings provide evidence that substantial weight loss is an important risk factor for osteoporotic hip fractures among the middle-aged to elderly Chinese.

Association between body mass index and risk of total knee replacement, the Singapore Chinese Health Study.

PURPOSE: Data on the association between body mass index (BMI) and risk of knee osteoarthritis (KOA) are sparse for Asian populations who are leaner than Western populations. We evaluated the association between BMI and risk of total knee replacement (TKR) due to severe KOA among Chinese in Singapore. METHODS: We used data from the Singapore Chinese Health Study (SCHS), a population-based prospective cohort of 63,257 Chinese men and women, aged 45-74 years at enrollment from 1993 to 1998. Information on height, weight, diet and lifestyle factors were obtained via in-person interviews. TKR cases for severe KOA were identified via linkage with the nationwide hospital discharge database through 2011. Cox regression and weighted least squares regression were used in the analysis. RESULTS: The mean BMI among cohort participants was 23.1 kg/m(2), and more than two-thirds had BMI below 25 kg/m(2). A total of 1649 had TKR attributable to severe KOA. Risk of TKR increased in a strong dose-dependent manner with increasing BMI throughout the 15-32 kg/m(2) range and became less clear at BMI >32 kg/m(2). In the BMI range 16-27 kg/m(2), there was a 27% increase in TKR risk for each unit increase in BMI (P for trend < 0.001). Compared to BMI 19-20 kg/m(2), the risk estimates of TKR were all statistically significant with increasing unit of BMI ≥21 kg/m(2). Results were similar for men and women. CONCLUSION: Our results provided evidence for a constant mechanical mechanism underlying BMI and KOA initiation and/or progression.

Seroepidemiology of dengue virus infection in the adult population in tropical Singapore.

To assess the impact of past dengue epidemics in Singapore, we undertook a national seroepidemiological study to determine the prevalence of past dengue virus (DENV) infection in the adult population in 2010 and make comparisons with the seroprevalence in 2004. The study involved residual sera from 3293 adults aged 18-79 years who participated in a national health survey in 2010. The overall prevalence of anti-DENV IgG antibodies was 56·8% (95% confidence interval 55·1-58·5) in 2010. The seroprevalence increased significantly with age. Males had significantly higher seroprevalence than females (61·5% vs. 53·2%). Among the three major ethnic groups, Malays had the lowest seroprevalence (50·2%) compared to Chinese (57·0%) and Indians (62·0%). The age-standardized seroprevalence in adults was significantly lower in 2010 (54·4%) compared to 2004 (63·1%). Older age, male gender, Indian ethnicity, permanent residency and being home-bound were independent risk factors significantly associated with seropositivity. About 43% of the Singapore adult resident population remain susceptible to DENV infection as a result of the successful implementation of a comprehensive nationwide Aedes surveillance and control programme since the 1970s. Vector suppression and concerted efforts of all stakeholders in the community remain the key strategy in the prevention and control of dengue.

Cigarette smoking and risk of total knee replacement for severe osteoarthritis among Chinese in Singapore--the Singapore Chinese health study.

PURPOSE: Data on the effects of cigarette smoking with osteoarthritis (OA) are inconsistent and no study has examined the effect of smoking cessation. We examined smoking status, duration, dosage and cessation in association with risk of total knee replacement (TKR) for severe knee OA among elderly Chinese in Singapore. METHODS: We used data from the Singapore Chinese Health Study, a population-based prospective cohort of 63,257 Chinese men and women aged 45-74 years during enrollment between 1993 and 1998. Detailed information on smoking, current diet and lifestyle factors were obtained through in person interviews. As of 31 December 2011, 1,973 incident TKR cases for severe knee OA had been identified via linkage with nationwide hospital discharge database. We used Cox regression methods to examine smoking in relation to TKR risk with adjustment for age, gender, education, body mass index (BMI), comorbidities and physical activity level. RESULTS: Compared to never smokers, current smokers had a 51% decrease in risk of TKR [Hazards ratio (HR) = 0.49; 95% confidence interval (CI) = 0.40-0.60]. Among current smokers, there was a very strong dose-dependent association between increasing duration and dosage of smoking with decreasing risk of TKR (P for trend <0.0001). Among former smokers, there was a dose-dependent response between decrease in duration of smoking cessation and reduction in TKR risk (P for trend = 0.034). CONCLUSION: Our findings strongly implicate smoking as a protective factor for TKR indicated for severe knee OA. This concurs with experimental data that nicotine promotes proliferation and collagen synthesis in chondrocytes.

Prevalence of antibodies against measles, mumps and rubella in the childhood population in Singapore, 2008-2010.

We undertook a national paediatric seroprevalence survey of measles, mumps and rubella (MMR) in Singapore to assess the impact of the national childhood immunization programme against these three diseases after introduction of the trivalent MMR vaccine in 1990. The survey involved 1200 residual sera of Singapore residents aged 1-17 years collected from two hospitals between 2008 and 2010. The overall prevalence of antibodies against measles, mumps and rubella was 83∙1% [95% confidence interval (CI) 80∙9-85∙1], 71.8% (95% CI 69∙1-74∙2) and 88∙5% (95% CI 86∙6-90∙2), respectively. For all three diseases, the lowest prevalence was in children aged 1 year (47∙8-62∙3%). The seroprevalence of the vaccinated children declined over time. The national MMR immunization programme is effective in raising the herd immunity of the childhood population, although certain age groups are more susceptible to infection, in particular, those who are not eligible for vaccination at age <15 months.

Dietary B vitamin intake and risk of hip fracture: the Singapore Chinese Health Study.

UNLABELLED: This prospective cohort study that comprehensively examined effects of different B vitamins in an Asian population showed an inverse relationship between dietary intake of pyridoxine and hip fracture risk in elderly women. These findings suggest that maintaining sufficient pyridoxine intake may be beneficial in preserving bone health in postmenopausal women. INTRODUCTION: B vitamins have recently been investigated for their possible roles in maintaining bone health. Incidence of osteoporotic hip fracture has been rising in Asia, but epidemiological data on dietary B vitamins and risk of osteoporotic fractures are sparse. We aimed to examine the association between dietary intakes of B vitamins (thiamin, riboflavin, niacin, pyridoxine, folate, and cobalamin) and hip fracture risk among elderly Chinese in Singapore. METHODS: The current study was conducted in the Singapore Chinese Health Study, which is a population-based cohort prospective study that enrolled a total of 63,257 men and women aged 45-74 years between 1993 and 1998. Dietary intakes of B vitamins were derived from a validated food frequency questionnaire and the Singapore Food Composition Database. RESULTS: After a mean follow-up period of 13.8 years, 1,630 hip fracture incident cases were identified. A statistically significant inverse relationship between dietary pyridoxine intake and hip fracture risk was observed among women (p for trend = 0.002) but not among men. Compared to women in the lowest quartile intake (0.37-0.61 mg/1,000 kcal/day), women in the highest quartile intake (0.78-1.76 mg/1,000 kcal/day) had a 22 % reduction in hip fracture risk (hazard ratio 0.78, 95 % confidence interval 0.66-0.93). Dietary intakes of the other B vitamins of interest were not related to hip fracture risk. CONCLUSIONS: Our findings suggest that maintaining adequate intake of pyridoxine may prevent osteoporotic fractures among elderly women.

All-cause and cause-specific mortality after hip fracture among Chinese women and men: the Singapore Chinese Health Study.

UNLABELLED: All-cause mortality risk persisted for 5 years after hip fractures in both men and women. There may be gender-specific differences in effect and duration of excess risk for cause-specific mortality after hip fracture. INTRODUCTION: To determine all-cause and cause-specific mortality risk in the first 5 years after hip fracture in an Asian Chinese population. METHODS: The Singapore Chinese Health Study is a population-based cohort of 63,257 middle-aged and elderly Chinese men and women in Singapore recruited between 1993 and 1998. This cohort was followed up for hip fracture and death via linkage with nationwide hospital discharge database and death registry. As of 31 December 2008, we identified 1,166 hip fracture cases and matched five non-fracture cohort subjects by age and gender for each fracture case. Cox proportional hazards and competing risks regression models with hip fracture as a time-dependent covariate were used to determine all-cause and cause-specific mortality risk, respectively. RESULTS: Increase in all-cause mortality risk persisted till 5 years after hip fracture (adjusted hazard ratio, aHR = 1.58 [95 % CI, 1.35-1.86] for females and aHR = 1.64 [95 % CI, 1.30-2.06] for males). Men had higher mortality risk after hip fracture than women for deaths from stroke and cancer up to 1 year post-fracture but women with hip fracture had higher coronary artery mortality risk than men for 5 years post-fracture. Men had higher risk of death from pneumonia while women had increased risk of death from urinary tract infections. There was no difference in mortality risk by types of hip fracture surgery. CONCLUSIONS: All-cause mortality risk persisted for 5 years after hip fractures in men and women. There are gender-specific differences in effect size and duration of excess mortality risk from hip fractures between specific causes of death.

Comparative seroepidemiology of pertussis, diphtheria and poliovirus antibodies in Singapore: waning pertussis immunity in a highly immunized population and the need for adolescent booster doses.

BACKGROUND: We assessed the seroepidemiology of pertussis, diphtheria and poliovirus antibodies in a cohort of highly immunized children, together with the burden of these diseases in Singapore. METHODS: Hospital residual sera collected between August 2008 and July 2010 from 1200 children aged 1-17 years were tested for the prevalence of IgG antibodies against Bordetella pertussis, diphtheria toxoid, and all three poliovirus types by enzyme-linked immunosorbent assays. RESULTS: We found an overall seroprevalence of 99.4% (95% CI 98.8-99.7%) for diphtheria, and 92.3% (95% CI 90.6-93.6%) for poliomyelitis, along with no indigenous cases of these diseases since 1993. However, the seroprevalence for pertussis was 60.8% (95% CI 58.0-63.5%) only. Among the subjects who had completed three doses of pertussis vaccination by the age of 2 years (n=1092), the pertussis seroprevalence was 85.0% (95% CI 79.7-89.2%) in those who received the last vaccination within a year before the study, and it decreased to 75.0% (95% CI 64.5-83.2%) and 63.1% (95% CI 50.9-73.8%) in those who had the last vaccination 1 year and 2 years before the study, respectively. The seroprevalence remained at about 50% for those whose last pertussis vaccination was administered 4 years and longer before the study. CONCLUSIONS: The high seroprevalence for poliomyelitis and diphtheria confer solid herd immunity to eliminate these diseases in Singapore. In contrast, immunity against pertussis waned considerably over time, and routine boosters should be given to adolescents to ensure sustained immunity against pertussis.

Mortality among tuberculosis patients on treatment in Singapore.

OBJECTIVE: To identify the risk factors associated with mortality among tuberculosis (TB) patients on treatment in Singapore. DESIGN: A retrospective cohort study of 7433 TB patients notified and started on TB treatment from 2000 to 2006 was conducted. Cox regression analysis was used to determine independent risk factors for mortality. RESULTS: Of 7433 patients who started TB treatment between 2000 and 2006, there were 884 deaths (11.9%) from any cause. Older age, male sex, being in a long-term care facility, having comorbidity, absence of cough, more than one site of TB, bacteriologically confirmed laboratory results, resistance to at least isoniazid (INH) and rifampicin (RMP) and absence of cavity were strongly associated with all-cause mortality among TB patients. A total of 203 patients (2.7%) died of TB. Risk factors for death due to TB were older age, male sex, Malay ethnicity, being in a long-term care facility, absence of cough, more than one site of TB, bacteriologically confirmed laboratory results and resistance to at least INH and RMP or to at least INH but not RMP. CONCLUSION: It is important to identify TB patients with risk factors related to mortality so that appropriate and timely interventions can be instituted to prevent deaths among TB patients.