Positive association of SARS-CoV-2 RNA concentrations in wastewater and reported COVID-19 cases in Singapore - A study across three populations.

Wastewater testing of SARS-CoV-2 has been adopted globally and has shown to be a useful, non-intrusive surveillance method for monitoring COVID-19 trends. In Singapore, wastewater surveillance has been widely implemented across various sites and has facilitated timely COVID-19 management and response. From April 2020 to February 2022, SARS-CoV-2 RNA concentrations in wastewater monitored across three populations, nationally, in the community, and in High Density Living Environments (HDLEs) were aggregated into indices and compared with reported COVID-19 cases and hospitalisations. Temporal trends and associations of these indices were compared descriptively and quantitatively, using Poisson Generalised Linear Models and Generalised Additive Models. National vaccination rates and vaccine breakthrough infection rates were additionally considered as confounders to shedding. Fitted models quantified the temporal associations between the indices and cases and COVID-related hospitalisations. At the national level, the wastewater index was a leading indicator of COVID-19 cases (p-value <0.001) of one week, and a contemporaneous association with hospitalisations (p-value <0.001) was observed. At finer levels of surveillance, the community index was observed to be contemporaneously associated with COVID-19 cases (p-value <0.001) and had a lagging association of 1-week in HDLEs (p-value <0.001). These temporal differences were attributed to differences in testing routines for different sites during the study period and the timeline of COVID-19 progression in infected persons. Overall, this study demonstrates the utility of wastewater surveillance in understanding underlying COVID-19 transmission and shedding levels, particularly for areas with falling or low case ascertainment. In such settings, wastewater surveillance showed to be a lead indicator of COVID-19 cases. The findings also underscore the potential of wastewater surveillance for monitoring other infectious diseases threats.

Baseline characteristics of participants in the Pre-Diabetes Interventions and Continued Tracking to Ease-out Diabetes (Pre-DICTED) Program.

OBJECTIVE: The Pre-Diabetes Interventions and Continued Tracking to Ease-out Diabetes (Pre-DICTED) Program is a diabetes prevention trial comparing the diabetes conversion rate at 3 years between the intervention group, which receives the incentivized lifestyle intervention program with stepwise addition of metformin, and the control group, which receives the standard of care. We describe the baseline characteristics and compare Pre-DICTED participants with other diabetes prevention trials cohort. RESEARCH DESIGN AND METHODS: Participants were aged between 21 and 64 years, overweight (body mass index (BMI) ≥23.0 kg/m2), and had pre-diabetes (impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT)). RESULTS: A total of 751 participants (53.1% women) were randomized. At baseline, mean (SD) age was 52.5 (8.5) years and mean BMI (SD) was 29.0 (4.6) kg/m2. Twenty-three per cent had both IFG and IGT, 63.9% had isolated IGT, and 13.3% had isolated IFG. Ethnic Asian Indian participants were more likely to report a family history of diabetes and had a higher waist circumference, compared with Chinese and Malay participants. Women were less likely than men to meet the physical activity recommendations (≥150 min of moderate-intensity physical activity per week), and dietary intake varied with both sex and ethnicity. Compared with other Asian diabetes prevention studies, the Pre-DICTED cohort had a higher mean age and BMI. CONCLUSION: The Pre-DICTED cohort represents subjects at high risk of diabetes conversion. The study will evaluate the effectiveness of a community-based incentivized lifestyle intervention program in an urban Asian context.

The Pre-Diabetes Interventions and Continued Tracking to Ease-out Diabetes (Pre-DICTED) program: study protocol for a randomized controlled trial.

BACKGROUND: Community-based diabetes prevention programs varied widely in effectiveness, and the intervention strategy consisting of lifestyle interventions, stepwise addition of metformin, and financial incentives has not been studied in real-world clinical practice settings. The Pre-Diabetes Interventions and Continued Tracking to Ease-out Diabetes (Pre-DICTED) trial is a pragmatic trial that aims to compare the effectiveness of a community-based stepwise diabetes prevention program with added financial incentives (intervention) versus the standard of care (control) in reducing the risk of type 2 diabetes over 3 years among overweight or obese individuals with pre-diabetes. METHODS: This is an open-label, 1:1 randomized controlled trial which aims to recruit 846 adult individuals with isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT), or both IFG and IGT from Singapore. Intervention arm participants attend 12 group-based sessions (2 nutrition workshops, 9 exercise sessions, and a goal-setting workshop) delivered at community sites (weeks 1 to 6), receive weekly physical activity and nutrition recommendations delivered by printed worksheets (weeks 7 to 12), and receive monthly health tips delivered by text messages (months 4 to 36). From month 6 onwards, intervention arm participants who remain at the highest risk of conversion to diabetes are prescribed metformin. Intervention arm participants are also eligible for a payment/rewards program with incentives tied to attendance at the group sessions and achievement of the weight loss target (5% of baseline weight). All participants are assessed at baseline, month 3, month 6, and every 6 months subsequently till month 36. The primary endpoint is the proportion of participants with diabetes at 3 years. Secondary endpoints include the mean change from baseline at 3 years in fasting plasma glucose, 2-hour plasma glucose, HbA1c, body weight, body mass index, physical activity, and dietary intake. DISCUSSION: The Pre-DICTED trial will provide evidence of the effectiveness and feasibility of a community-based stepwise diabetes prevention program with added financial incentives for individuals with pre-diabetes in Singapore. The study will provide data for a future cost-effectiveness analysis, which will be used to inform policymakers of the value of a nationwide implementation of the diabetes prevention program. TRIAL REGISTRATION: ClinicalTrials.gov NCT03503942 . Retrospectively registered on April 20, 2018. Protocol version: 5.0 Date: 1 March 2019.

Nitrates in combination with hydralazine in cardiorenal syndrome: a randomized controlled proof-of-concept study.

AIMS: Cardiorenal syndrome (CRS) is a common problem of great morbidity and mortality. Hydralazine-isosorbide dinitrate (H-ISDN) may be used in renal failure and may improve exercise capacity in heart failure (HF). Our proof-of-concept study aimed to evaluate early evidence of efficacy, safety, and feasibility of H-ISDN compared with standard of care in CRS. METHODS AND RESULTS: This multi-centre, single-blind, randomized trial in Singapore enrolled CRS patients, defined as chronic HF with concomitant renal failure [estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2 ]. The primary outcome was 6 min walk test (6MWT) distance measured at 6 months. Secondary outcomes included study feasibility; efficacy outcomes which included renal, cardiac, and endothelial functions, health-related quality of life using Short Form-36, clinical outcomes; and adverse events. Forty-four patients [71 ± 10 years; 75% male; median (inter-quartile range) N-terminal prohormone brain natriuretic peptide 1346 (481-2272) pg/mL] with CRS (left ventricular ejection fraction 42 ± 12% and eGFR 46 ± 15 ml/min/1.73 m2 ) were randomized into two equal groups. Of these, 39 (89%) had hypertension, 27 (61%) had diabetes mellitus, and 17 (39%) had atrial fibrillation. Six (27%) discontinued H-ISDN owing to intolerance and poor compliance. There was a trend towards improved 6MWT distance with H-ISDN compared with standard of care at 6 months (mean difference 27 m; 95% CI, -12 to 66), with little differences in secondary efficacy outcomes. Giddiness and hypotension occurred more frequently with H-ISDN, but HF hospitalizations and mortality were less. CONCLUSIONS: Our pilot study does not support the addition of H-ISDN on top of standard medical therapy to improve exercise capacity in patients with CRS.

Connecting clusters of COVID-19: an epidemiological and serological investigation.

BACKGROUND: Elucidation of the chain of disease transmission and identification of the source of coronavirus disease 2019 (COVID-19) infections are crucial for effective disease containment. We describe an epidemiological investigation that, with use of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serological assays, established links between three clusters of COVID-19. METHODS: In Singapore, active case-finding and contact tracing were undertaken for all COVID-19 cases. Diagnosis for acute disease was confirmed with RT-PCR testing. When epidemiological information suggested that people might have been nodes of disease transmission but had recovered from illness, SARS-CoV-2 IgG serology testing was used to establish past infection. FINDINGS: Three clusters of COVID-19, comprising 28 locally transmitted cases, were identified in Singapore; these clusters were from two churches (Church A and Church B) and a family gathering. The clusters in Church A and Church B were linked by an individual from Church A (A2), who transmitted SARS-CoV-2 infection to the primary case from Church B (F1) at a family gathering they both attended on Jan 25, 2020. All cases were confirmed by RT-PCR testing because they had active disease, except for A2, who at the time of testing had recovered from their illness and tested negative. This individual was eventually diagnosed with past infection by serological testing. ELISA assays showed an optical density of more than 1·4 for SARS-CoV-2 nucleoprotein and receptor binding domain antigens in titres up to 1/400, and viral neutralisation was noted in titres up to 1/320. INTERPRETATION: Development and application of a serological assay has helped to establish connections between COVID-19 clusters in Singapore. Serological testing can have a crucial role in identifying convalescent cases or people with milder disease who might have been missed by other surveillance methods. FUNDING: National Research Foundation (Singapore), National Natural Science Foundation (China), and National Medical Research Council (Singapore).

Asian Liver Transplant Network Clinical Guidelines on Immunosuppression in Liver Transplantation.

Most management guidelines and much of the available clinical trial evidence for immunosuppressants in liver transplantation (LT) pertain to Western practice. While evidence from Western studies may not translate to Asian settings, there is a paucity of Asian randomized controlled trials of immunosuppression in liver recipients. Nonetheless, there are notable differences in the indications and procedures for LT between Western and Asian settings. The Asian Liver Transplant Network held its inaugural meeting in Singapore in November 2016 and aimed to provide an Asian perspective on aspects of immunosuppression following LT. Because of their importance to outcome following LT, the meeting focused on (1) reducing the impact of renal toxicity, (2) hepatocellular carcinoma recurrence, and (3) nonadherence with immunosuppressant therapy.

Efficacy, Immunogenicity and Safety of a Human Rotavirus Vaccine RIX4414 in Singaporean Infants.

INTRODUCTION: This was the first study conducted to evaluate the efficacy of 2 oral doses of the human rotavirus vaccine, RIX4414 in Singaporean infants during the first 3 years of life. MATERIALS AND METHODS: Healthy infants, 11 to 17 weeks of age were enrolled in this randomised (1:1), double-blinded, placebo-controlled study to receive 2 oral doses of RIX4414 vaccine/placebo following a 0-, 1-month schedule. Vaccine efficacy against severe rotavirus (RV) gastroenteritis (Vesikari score ≥11) caused by wild-type RV strains from a period starting from 2 weeks post-Dose 2 until 2 and 3 years of age was calculated with 95% confidence interval (CI). Immunogenicity and safety of the vaccine were also assessed. RESULTS: Of 6542 infants enrolled, 6466 were included in the efficacy analysis and a subset of 100 infants was included in the immunogenicity analysis. Fewer severe RV gastroenteritis episodes were reported in the RIX4414 group when compared to placebo at both 2 and 3 year follow-up periods. Vaccine efficacy against severe RV gastroenteritis at the respective time points were 93.8% (95% CI, 59.9 to 99.9) and 95.2% (95% CI, 70.5 to 99.9). One to 2 months post-Dose 2 of RIX4414, 97.5% (95% CI, 86.8 to 99.9) of infants seroconverted for anti-RV IgA antibodies. The number of serious adverse events recorded from Dose 1 until 3 years of age was similar in both groups. CONCLUSION: Two oral doses of RIX4414 vaccine was immunogenic and provided high level of protection against severe RV gastroenteritis in Singaporean children, during the first 3 years of life when the disease burden is highest.

Current role of selective internal radiation with yttrium-90 in liver tumors.

An expert panel met to review the evidence for selective internal radiation therapy (SIRT) using yttrium-90 microspheres in hepatocellular carcinoma and metastases from colorectal cancer and neuroendocrine tumors. There is now convincing evidence for the safety and efficacy of SIRT in these situations albeit mostly from retrospective cohort studies. There are a number of ongoing prospective randomized controlled clinical trials investigating the role of SIRT in liver tumors; however, data from these trials are still several years away (although the SIRFLOX study has been recently published). In this evolving environment, published evidence and the authors' experience were used to summarize the current and potential role of SIRT in the management of hepatocellular carcinoma of intermediate or advanced stage and in liver-dominant metastatic colorectal cancer and metastatic neuroendocrine tumors.

A randomised trial to evaluate the immunogenicity, reactogenicity, and safety of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) co-administered with routine childhood vaccines in Singapore and Malaysia.

BACKGROUND: The immunogenicity, reactogenicity, and safety of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) co-administered with routine childhood vaccines were evaluated among infants from Singapore and Malaysia, where PHiD-CV has been licensed. METHODS: In the primary vaccination phase, 298 infants from Singapore and 168 infants from Malaysia were randomised to receive the Phase III Clinical (Clin) or the Commercial (Com) lot of PHiD-CV at 2, 3, and 5 months of age. In the booster vaccination phase, 238 toddlers from Singapore received one dose of the PHiD-CV Commercial lot at 18-21 months of age. Immune responses to pneumococcal polysaccharides were measured using 22F-inhibition enzyme-linked immunosorbent assay (ELISA) and functional opsonophagocytic activity (OPA) assay and to protein D, using ELISA. RESULTS: Immune responses induced by primary vaccination with the PHiD-CV Commercial lot were non-inferior to the Phase III Clinical lot in terms of adjusted antibody geometric mean concentration (GMC) ratios for each vaccine pneumococcal serotype and protein D. For each vaccine pneumococcal serotype, ≥93.6% and ≥88.5% of infants from Malaysia and Singapore had post-primary vaccination antibody concentrations ≥0.2 µg/mL and OPA titres ≥8, in the Clin and Com groups, respectively. For each vaccine pneumococcal serotype, ≥60.8% and ≥98.2% of toddlers from Singapore had pre- and post-booster antibody concentrations ≥0.2 µg/mL, in the Clin and Com groups, respectively. All children, except one, had measurable anti-protein D antibodies and the primary and booster doses of the co-administered vaccines were immunogenic. The incidence of each grade 3 solicited symptom was ≤11.1% in both study phases. No serious adverse events considered causally related to vaccination were reported throughout the study. CONCLUSIONS: PHiD-CV given as three-dose primary vaccination to infants in Singapore and Malaysia and booster vaccination to toddlers in Singapore was shown to be immunogenic with a clinically acceptable-safety profile.This study has been registered at http://www.clinicaltrials.govNCT00808444 and NCT01119625.

A hospital-based surveillance of rotavirus gastroenteritis in children <5 years of age in Singapore.

BACKGROUND: In Singapore, 2 rotavirus vaccines were licensed in October 2005 and July 2007, respectively, for vaccinating infants aged ≥ 6 weeks against rotavirus gastroenteritis. These vaccines are optional and are not included in the National Childhood Immunization Program. This study aimed to determine the incidence of rotavirus gastroenteritis-associated hospitalizations among children <5 years of age. METHODS: Children <5 years, who were hospitalized for acute gastro enteritis, were enrolled between September 2005 and April 2008. Stool samples were tested for the presence and serotyping of rotavirus. Incidence and proportion of gastroenteritis and rotavirus gastroenteritis cases were calculated with 95% confidence intervals. RESULTS: Among 1976 children included in the according-to-protocol cohort, 781 were rotavirus positive with a median age of 24 months (range: 0-59 months). The overall incidence of rotavirus gastroenteritis hospitalizations during the entire study period in children <5 years of age was 4.6 (95% confidence interval: 4.3-4.9) per 1000 person-years with the highest number of cases observed in children 13-24 months of age (26.5%). G1P[8] (18.3%) and G9P[8] (9.9%) were the most common rotavirus types. Rotavirus gastroenteritis hospitalizations peaked between January and March. CONCLUSION: Rotavirus infection was the primary cause of acute gastro enteritis hospitalizations among children <5 years of age, constituting nearly one-third of gastroenteritis hospitalizations in Singapore. The predominant strain observed in Singapore was G1P[8]. Results of this study suggest the need for implementation of rotavirus vaccination into National Childhood Immunization Program in Singapore.

Rotavirus vaccine RIX4414 efficacy sustained during the third year of life: a randomized clinical trial in an Asian population.

RIX4414 (Rotarix™), has shown high efficacy during the first 2-years of life. A 2-year randomized, double-blind, placebo-controlled trial in Singapore, Hong Kong, and Taiwan was extended for another year. Infants (6-17 weeks) received 2-doses (1-2 months apart) of RIX4414 (n=5359) or placebo (n=5349). During the third-year follow-up, 4359 (RIX4414) and 4328 (placebo) infants were monitored. 64 (1.2%) and 2 (0.04%) infants in the placebo and RIX4414 groups, respectively, reported severe rotavirus-gastroenteritis (RVGE), resulting in a vaccine efficacy of 96.9% (95% CI [88.3-99.6]). Efficacy was 100% (67.5-100) in the third-year. RIX4414 was efficacious against G1 (100.0% [84.8-100]) and pooled non-G1 RV types (94.9% [80.2-99.4]). This study shows that the vaccine is highly efficacious, regardless of circulating RV-types, up to the first 3 years of life in affluent Asian urban populations.

Cost-effectiveness of different human papillomavirus vaccines in Singapore.

BACKGROUND: Human papillomavirus (HPV) vaccines are widely available and there have been studies exploring their potential clinical impact and cost-effectiveness. However, few studies have compared the cost-effectiveness among the 2 main vaccines available - a bivalent vaccine against HPV 16/18, and a quadrivalent vaccine against 6/11/16/18. We explore the cost-effectiveness of these two HPV vaccines in tropical Singapore. METHODS: We developed a Markov state-transition model to represent the natural history of cervical cancer to predict HPV infection, cancer incidence, mortality, and costs. Cytologic screening and treatment of different outcomes of HPV infection were incorporated. Vaccination was provided to a cohort of 12-year old females in Singapore, followed up until death. Based on available vaccines on the market, the bivalent vaccine had increased effectiveness against a wider range of HPV types, while the quadrivalent vaccine had effectiveness against genital warts. Incremental cost-effectiveness ratios (ICER) compared vaccination to no-vaccination, and between the two vaccines. Sensitivity analyses explored differences in vaccine effectiveness and uptake, and other key input parameters. RESULTS: For the no vaccination scenario, 229 cervical cancer cases occurred over the cohort's lifetime. The total discounted cost per individual due to HPV infection was SGD$275 with 28.54 discounted life-years. With 100% vaccine coverage, the quadrivalent vaccine reduced cancers by 176, and had an ICER of SGD$12,866 per life-year saved. For the bivalent vaccine, 197 cancers were prevented with an ICER of $12,827 per life-year saved. Comparing the bivalent to the quadrivalent vaccine, the ICER was $12,488 per life-year saved. However, the cost per QALY saved for the quadrivalent vaccine compared to no vaccine was $9,071, while it was $10,392 for the bivalent vaccine, with the quadrivalent vaccine dominating the bivalent vaccine due to the additional QALY effect from reduction in genital warts. The overall outcomes were most sensitive to vaccine cost and coverage. CONCLUSION: HPV vaccination is a cost-effective strategy, and should be considered a possible strategy to reduce the impact of HPV infection.

Safety and reactogenicity of DTPa-HBV-IPV/Hib and DTPa-IPV/I-Hib vaccines in a post-marketing surveillance setting.

Combination vaccines have been shown to improve the timeliness of vaccination and vaccine coverage. Safety and reactogenicity of combined diphtheria-tetanus-acellular pertussis-inactivated poliovirus and Haemophilus influenzae type b vaccine (DTPa-IPV/Hib, Infanrix IPV+Hib, GlaxoSmithKline Biologicals) was assessed in two clinical studies. In Study A, 2,590 subjects received DTPa-IPV/Hib at 3, 4 and 5 months of age with a booster at 18 months. In Study B, 702 subjects received the same schedule but with DTPa-hepatitis B-IPV/Hib (DTPa-HBV-IPV/Hib, Infanrix hexa, GlaxoSmithKline Biologicals) vaccine administered at 5 months of age. Reactogenicity was assessed for four days after each dose using diary cards. Serious adverse events (SAEs) were assessed until 24 months of age. The vaccines were well tolerated. After primary vaccination, irritability was the most frequently reported grade 3 general symptom (0.8% of doses in both studies). Fever (axillary) > 39 degrees C was infrequent (0.3% of doses in Study A; 0.5% of doses in Study B). After the booster dose, the most frequently reported grade 3 symptom was redness (5%) in Study A and pain (0.5%) in Study B. An axillary temperature > 39 degrees C was reported in 1.1% of subjects. Throughout the study period, 646 SAEs were reported, of which 6 SAEs were considered to be vaccination-related. The reactogenicity and safety profile of the combined DTPa-IPV/Hib vaccine was good when used for primary and booster vaccinations in over 3,000 Singaporean infants. Substitution of DTPa-IPV/Hib with DTPa-HBV-IPV/Hib at Month 5 reduced the number of injections required at this age by one.

An update of paediatric intussusception incidence in Singapore: 1997-2007, 11 years of intussusception surveillance.

INTRODUCTION: Understanding baseline epidemiology of intussusception (IS) in different geographical settings is important for the safety assessment of rotavirus vaccines. This paper presents IS surveillance data from Singapore between 1997 and 2007, including the period between November 2005 and December 2007 when rotavirus vaccines (primarily Rotarix) were available to newborns in Singapore. MATERIALS AND METHODS: Case ascertainment, collection, analyses and presentation of IS data was done as per recommendations of the Brighton Collaboration Working Group. For estimating the IS incidence rate in infants, live births for the years of the study were used as denominators, while for incidence in children age <2 years, the expected numbers of infant deaths occurring between 1 and 2 years of age was deducted from the combined live births for the 2 years, to obtain the denominator. RESULTS: The incidence of IS among children aged <1 year throughout this 10-year period was higher than the incidence of IS in children between 1 and 2 years of age. In 2005, 2006 and 2007, the incidence of IS per 100,000 was 39.9, 26.4 and 35.6 in children aged <1 year and 26.2, 23.8 and 28.7 in children <2 years. CONCLUSION: This IS surveillance study provides reassuring preliminary evidence that there is no increase in the incidence of IS in Singapore after the introduction of rotavirus vaccines (including Rotarix) in Singapore.

Immunogenicity and tolerability of an AS03(A)-adjuvanted prepandemic influenza vaccine: a phase III study in a large population of Asian adults.

The immunogenicity and lot-to-lot consistency of an AS03-adjuvanted H5N1 vaccine were evaluated in 1206 Asian adults, randomised to receive two doses of adjuvanted (3.75 microg haemagglutinin) or diluent-mixed vaccines, 21 days apart. Post-Dose 2, 96.0% of vaccinees in the H5N1-AS03 group demonstrated a four-fold increase in neutralising antibody titres against the vaccine strain A/Vietnam/1194/2004 and 91.4% against strain A/Indonesia/05/2005. Haemagglutination-inhibiting antibodies (titre > or = 1:40) against A/Vietnam/1194/2004 and A/Indonesia/05/2005 strains were observed in 94.3% and 50.2% of subjects, respectively. Lot-to-lot consistency of the AS03-adjuvanted vaccine combinations was demonstrated. The AS03-adjuvanted vaccine was well tolerated, induced a high frequency of immune responses to the vaccine strain, allowed antigen sparing and promoted cross-clade immunity. These characteristics make it suitable for presumptive use if an H5N1 pandemic were considered to be imminent.

Immunogenicity, reactogenicity and safety of a diphtheria-tetanus-acellular pertussis-inactivated polio and Haemophilus influenzae type b vaccine in a placebo-controlled rotavirus vaccine study.

INTRODUCTION: In recent years, acellular pertussis combination vaccines have facilitated compliance with and coverage of the national immunisation programme in Singapore. This phase-II study (Rota-007) evaluated the immunogenicity, reactogenicity and safety of a DTPa-IPV/Hib combined vaccine when co-administered with a rotavirus vaccine. MATERIALS AND METHODS: A total of 2464 children aged 3 months were vaccinated with DTPa-IPV/Hib together with a randomised 1:3 ratio of either placebo (n=653) or 1 of 3 different formulations of a rotavirus vaccine. Blood samples were collected for immunogenicity analysis 1 month after the third DTPa-IPV/Hib vaccine dose in a subset of subjects (n = 640). Local and general reactogenicity and unsolicited adverse events were recorded during the follow-up after each vaccination. RESULTS: Serological analysis showed >95% response for all antigens in the co-administered DTPa-IPV/Hib vaccine, with no difference between the rotavirus vaccine and placebo groups. No differences in adverse events and reactogenicity were reported in the rotavirus vaccine and placebo groups. Only 0.2% of the subjects reported Grade 3 adverse events. Three subjects (from the vaccine groups) died during the study, which were assessed by the investigators as unrelated to vaccination. No deaths were reported in the placebo group. CONCLUSION: The combined DTPa- IPV/Hib vaccine is safe, well tolerated and highly immunogenic when given alone or coadministered with the rotavirus vaccine for infants in Singapore.

Four is better than nine. a combined diphtheria-tetanus-pertussis-hepatitis B-Haemophilus influenzae type b vaccine for routine immunization in Malaysia.

Malaysian infants would have to receive nine injections during the first few months of life in order to be protected against disease caused by hepatitis B (HBV), diphtheria, tetanus, pertussis and Haemophilus influenzae type b (Hib) if single HBV and Hib vaccines were used. We evaluated a combined DTPw-HBV/Hib vaccine administered at 1.5, 3 and 5 months after a birth dose of hepatitis B vaccine (HBV). One month after completion of the primary vaccination, 99% of subjects had seroprotective anti-HBV antibody levels, and at least 98% had seroprotective antibodies against diphtheria, tetanus, and Hib, and were seropositive for pertussis antibodies. The immune response to the combined vaccine was comparable to that induced by separate injections with DTPw, HBV and Hib vaccines. Overall, the DTPw-HBV/Hib vaccine was as well tolerated as separate administration of DTPw, HBV and Hib vaccines. The combined DTPw-HBV/Hib vaccine induces protection against five diseases as recommended in the Malaysian routine vaccination schedule. Use of the combined DTPw-HBV/Hib vaccine can reduce the required number of injections from nine to four in the first few months of life.

Cluster of Staphylococcus aureus and dengue co-infection in Singapore.

INTRODUCTION: Singapore saw a resurgence of dengue infections in 2005. Concurrent bacterial co-infections in dengue is rare. CLINICAL PICTURE: We report a cluster of serious methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia or severe soft tissue infection in 5 epidemiologically linked construction workers presenting with dengue and non-resolving fever. TREATMENT: Surgical intervention was indicated in 4 of the 5 patients despite appropriate antistaphylococcal therapy. OUTCOME: All but 1 patient were eventually discharged. Clonality and Panton-Valentine leucocidin genes were not demonstrated. Epidemiological investigations suggested that occupational contact dermatitis could have predisposed the patients to this opportunistic co-infection. CONCLUSION: Clinicians need to be vigilant to unusual manifestations of dengue which may signal a concomitant aetiology.