Safety and efficacy of human rotavirus vaccine during the first 2 years of life in Asian infants: randomised, double-blind, controlled study.

This study evaluates the safety and efficacy against severe rotavirus gastroenteritis of the oral live attenuated human rotavirus vaccine RIX4414 (Rotarix) during the first 2 years of life in Asian infants from high-income countries. Healthy infants were enrolled to receive 2 doses of RIX4414 (N=5,359) or placebo (N=5,349). From 2 weeks post-dose 2 to 2 years of age, vaccine efficacy was 96.1% (95%CI:85.1%; 99.5%) against severe rotavirus gastroenteritis, 100% (95%CI:80.8%; 100%) against wild-type G1P[8] and 93.6% (95%CI:74.7%; 99.3%) against circulating non-G1 rotavirus types. No intussusception cases were reported within 31 days post-vaccination. RIX4414 shows a good safety profile and offers high protection during the first 2 years of life with potentially significant public health impact in this population.

Treatment outcome of Singapore residents with pulmonary tuberculosis in the first year after introduction of a computerised treatment surveillance module.

INTRODUCTION: A key intervention of the Singapore Tuberculosis Elimination Programme (STEP) was the introduction in 2001 of a computerised treatment surveillance module (TSM) for the real-time monitoring of the treatment progress of the country's notified tuberculosis (TB) cases until a final outcome. We report the treatment outcome as at December 31, 2002 for the cohort of Singapore residents with new and relapsed pulmonary TB in whom treatment was commenced in 2001. METHODS: Each TB notification will activate the TSM, which requires a return on the patient's treatment progress, treatment delivery mode and the treating physician's management decision at each clinic visit to the STEP Registry until an outcome is reached. RESULTS: There were 1,354 Singapore residents with new or relapsed pulmonary TB who started treatment in 2001. Of these, 620 (45.8 percent) underwent directly-observed therapy (DOT) at their nearest polyclinic. As at December 31, 2002 , 79 percent of patients completed treatment, nine percent died (two percent from TB), nine percent interrupted treatment (they were either lost to follow-up or refused treatment), 1.8 percent were still on treatment, 0.6 percent left the country, and 0.5 percent had permanent cessation of treatment due to drug reactions. Factors associated with treatment completion were Chinese ethnicity (odds-ratio [OR] 1.5, 95 percent confidence interval [Cl] 1.1-2, p-value is 0.02), age younger than 65 years (OR 1.8, 95 percent Cl 1.3-3.0, p-value is 0.003) and the use of DOT (OR 3.1, 95 percent Cl 2.3-4.1, p-value is less than 0.05). CONCLUSION: The findings from the TSM's first year provide a baseline for future programme evaluation.

Contact screening and latent TB infection treatment in Singapore correctional facilities.

SETTING: Singapore, a city-state with a tuberculosis (TB) incidence rate of 47 per 100000 population in 2000. OBJECTIVES: 1) To report our experience with contact investigation and latent TB infection (LTBI) treatment in high-risk contacts with unknown human immunodeficiency virus (HIV) status in correctional facilities (CFs) (prisons/drug rehabilitation centres); and 2) to compare the yield of contact screening in this setting with that in the community (household/family) setting. METHODS: The tuberculin skin test (TST) readings of 704 CF contacts screened from 1999 to 2001 were compared with those of 2729 household/family contacts who underwent screening in 2000. RESULTS: Respectively eight (1.1%) and 20 (0.7%) active TB cases were detected among the CF and community contacts. A significantly higher proportion of CF contacts had first (non-conversion) TST readings > or =15 mm (39% vs. 22%, OR 2.3; 95%CI 1.9-2.7; P < 0.001), and 10-14 mm (26% vs. 18%, OR 1.6; 95%CI 1.3-2.0; P < 0.001) and TST conversion (43% vs. 20%, OR 2.9; 95%CI 1.7-4.9; P < 0.001). LTBI treatment was started in 65% of the CF contacts screened; 87% completed treatment. CONCLUSION: We found a high LTBI rate among CF contacts, presenting an opportunity for intervention.

Factors associated with transmission of severe acute respiratory syndrome among health-care workers in Singapore.

Between 1 and 22 March 2003, a nosocomial outbreak of Severe Acute Respiratory Syndrome (SARS) occurred at the Communicable Disease Centre in Tan Tock Seng Hospital, Singapore, the national treatment and isolation facility for patients with SARS. A case-control study with 36 cases and 50 controls was conducted of factors associated with the transmission of SARS within the hospital. In univariate analysis, contact with respiratory secretions elevated the odds ratio to 6.9 (95 % CI 1.4-34.6, P= 0.02). Protection was conferred by hand washing (OR 0.06, 95% CI 0.007-0.5, P=0.03) and wearing of N95 masks (OR 0.1, 95% CI 0.03-0.4, P=0.001). Use of gloves and gowns had no effect. Multivariate analysis confirmed the strong role of contact with respiratory secretions (adjusted OR 21.8, 95 % CI 1.7 274.8, P=0.017). Both hand washing (adjusted OR 0.07, 95 % CI 0.008-0.66, P=0.02) and wearing of N95 masks (adjusted OR 0.1, 95% CI 0.02-0.86, P=0.04) remained strongly protective but gowns and gloves had no effect.

Treatment of latent TB infection for close contacts as a complementary TB control strategy in Singapore.

OBJECTIVE: To describe our initial experience with treatment of latent tuberculosis infection (LTBI) for close contacts of infectious TB cases in Singapore, an intermediate TB burden country with mass BCG (re)vaccination since the 1950s. METHODS: Screening of 5699 contacts of 1374 index cases notified in 1998 was carried out at the TB Control Unit. RESULTS: Seventy-five per cent (4239) completed tuberculin skin testing (TST). Fifty-three cases of TB disease were detected (0.9% yield). Twenty-one per cent (895/4239) of the TST-screened contacts were started on LTBI treatment, comprising 92% (810/883) of contacts with TST > or = 15 mm, 5% (64/1195) of those with TST 10-14 mm and 1% (21/2161) of those with TST < 10 mm. The regimen utilized was isoniazid for 6 months in adults and 9 months in children. Eighty-one per cent completed treatment. The incidence of isoniazid-induced hepatitis was 0.45%. Over the ensuing 4 years, one case of active TB was reported among those treated for LTBI, and 10 cases (five without TST readings) were notified among contacts who did not receive treatment. CONCLUSIONS: Where good case-finding and treatment of TB disease exist, and where resources permit, LTBI treatment for close contacts is feasible as a complementary TB control strategy in an intermediate TB burden country with a BCG-vaccinated population.

Interpretation of the tuberculin skin test in Mycobacterium bovis BCG-vaccinated Singaporean schoolchildren.

Tuberculin skin test (TST) interpretation in Singapore is confounded by universal BCG vaccination at birth and by a revaccination policy for schoolchildren who are tuberculin nonreactors (TST < 10 mm, using 1 TU PPD RT 23) at 12 or 16 yr old, with not more than two BCG vaccinations given to any child. School health records for birth cohorts 1978 to 1984 indicate that 82.8% were revaccinated at age 12 yr. By collation with the national database of tuberculosis (TB) notifications, we examined the risk of TB disease in these cohorts for the 4 yr subsequent to TST reading at ages 12 and 16 yr respectively, in intervals of 0-4, 5-9, 10-14, 15-17, and >/= 18 mm. Receiver-operating curves (ROCs) were constructed to ascertain the optimum TST cutoffs in screening for the likelihood of development of TB disease. A cutoff of 10 mm performed best for the group tested at age 12 yr, whereas 16 mm was found to be optimum in those tested at age 16 yr (> 80% of whom were BCG revaccinated 4 yr earlier). We have extrapolated these findings to the screening of contacts, and utilized these cutoff points to guide the treatment of latent TB infection in this high-risk group.

Patient and disease characteristics, and outcome of treatment defaulters from the Singapore TB control unit--a one-year retrospective survey.

SETTING: The Singapore Tuberculosis Control Unit. OBJECTIVES: 1) To identify any demographic, social, disease or treatment-related characteristics which may be predictive of patients defaulting from treatment; 2) to assess the effectiveness of home visits as a means of defaulter recall; 3) to ascertain outcome in these patients. DESIGN: A retrospective, case-controlled study of TB treatment defaulters, defined as patients who missed their scheduled appointments and required a home visit to recall for treatment. Controls were randomly selected, non-defaulting patients who started treatment on the same dates as the defaulters. RESULTS: Forty-four patients required home visits in 1996. Compared to controls, defaulters were more likely to be non-Chinese, and to live on their own or with friends. There was no significant association of defaulting with age, sex, marital or employment status, disease characteristics, or treatment-related factors. Seventy per cent defaulted during the continuation phase of treatment. Home visits did not result in contact with the patient (or any other person) 41% of the time. Although 48% of the defaulters remained lost to follow-up at the time of the survey, all but one of the sputum-positive patients had bacteriologically converted by the time of default. CONCLUSION: Non-Chinese ethnicity and lack of family support were found to be factors strongly predictive of default. Age, sex, marital and employment status, treatment-related factors and disease characteristics were not significant in distinguishing those at risk for defaulting.

Temporomandibular disorders in rheumatoid arthritis.

OBJECTIVE: To determine the frequency and character of temporomandibular disorders (TMD) in Oriental patients with rheumatoid arthritis (RA) and to investigate the relationship between TMD and RA in a tertiary referral center. METHODS: Symptoms and signs related to TMD were investigated in 80 patients (67 female, 13 male) who fulfilled the American College of Rheumatology 1987 revised criteria for RA. Diagnoses of TMD including muscle, disk displacement, or temporomandibular joint (TMJ) disorders were made based on clinical assessment. TMJ disorder was then correlated with the clinical, laboratory, and radiological features of RA. RESULTS: The mean age of the study population was 49.7 years and the mean duration of RA was 86.9 months. Eleven patients (13.8%) had active RA at the time of TMD assessment. About 76% of the study population had seropositive disease and 62% had peripheral joint erosions. Osteoarthrosis of the TMJ was the most common TMD in this Oriental population. Joint sounds on opening (35%), joint sounds on moving sideways or forward (27.5%), and pain in jaw joints (23.7%) were common TMD symptoms. Deviated mouth opening (45%) and coarse crepitus (15-21.3%) were most prevalent on examination. CONCLUSION: Patients with RA who had prolonged disease duration of RA and active peripheral joints tended to have osteoarthrosis of the TMJ. Presence of rheumatoid factor or peripheral joint erosions was not associated with TMJ osteoarthrosis.

Drug-resistant tuberculosis in Singapore, 1995 to 1996.

Singapore's tuberculosis incidence of 49 to 57 per 100,000 population for 1987 to 1996 presents a picture that is intermediate between developed and developing countries. The proportion of drug-resistant isolates has remained stable at 4.3% to 5.5% from 1992 to 1996 despite rising HIV rates. From 1995 to 1996, of the 199 consecutive drug-resistant isolates at the Central Tuberculosis Laboratory, 66% were mono-resistant, 22% dual-resistant and 12% resistant to more than two drugs. Isoniazid resistance was most prevalent, being found in 72% of isolates, followed by streptomycin resistance in 45%. Resistance to isoniazid and streptomycin (21%) was more common than to isoniazid and rifampicin, i.e. multidrug resistance (MDR) (14%). The small numbers indicated by the low overall prevalence of resistance and the predominance of single-drug resistance support the current initial choice of the standard short course with its three-drug initial phase. Of the 170 cases with matching National Tuberculosis Registry data, 72% of drug-resistant cases represented initial and 28% acquired resistance; testifying to the effectiveness of present day treatment regimens in suppressing resistance when compliance is assured. Case-control analysis using 244 drug-sensitive controls randomly selected from notifications in 1995 to 1996 showed an odds ratio for drug-resistance between subjects with a previous history and no previous history of tuberculosis of 2.47 (95% CI 1.40 to 4.37; P = 0.0007). With each increment in the number of episodes of tuberculosis experienced, there was a trend of resistance to progressively more drugs (P = 0.000004). This association remained even when a logistic regression model including all predictor variables was fitted. No associations were found with age, history of contact with tuberculosis, cavitary disease and, most notably, with human immunodeficiency virus infection. This study reaffirms that a history of previous tuberculosis should increase clinicians' index of suspicion for drug resistance, the urgency with which culture and sensitivity results are sought and the vigour with which patients are followed-up and compliance monitored.