Contact investigation of tuberculosis in Brunei Darussalam: Evaluation and risk factor analysis.

INTRODUCTION: We evaluated the yield of tuberculosis (TB) contact investigation in Brunei Darussalam, and identified the associated factors for latent TB infection (LTBI) diagnosis, as well as for initiating and completing LTBI treatment. METHODS: Data were extracted and digitalised for all close contacts of pulmonary TB (PTB) cases at the National TB Coordinating Centre from January 2009 to December 2018. Generalising estimating equations logistic regression models were used to determine the associated factors. Manual matching against electronic health records system was done to identify contacts who had progressed to active TB disease. RESULTS: Among 10 537 contacts, 9.9% (n=1047) were diagnosed as LTBI, out of which 43.0% (n=450) initiated LTBI treatment. Among those who initiated, 74.0% (n=333) completed LTBI treatment. Contact factors associated with LTBI diagnosis include being male (adjusted OR (aOR)=1.18 (95% CI 1.03 to 1.34)), local (aOR=0.70 (95% CI 0.56 to 0.88)) and a household contact (aOR=1.59 (95% CI 1.26 to 1.99)). Contacts of index cases who were <60 years old and diagnosed as smear positive PTB (aOR=1.62 (95% CI 1.19 to 2.20)) had higher odds of being diagnosed with LTBI. Local LTBI cases had higher odds of initiating LTBI treatment (aOR=1.86 (95% CI 1.26 to 2.73)). Also, LTBI cases detected from local (aOR=2.32 (95% CI 1.08 to 4.97)) and smear positive PTB index cases (aOR=2.23 (95% CI 1.09 to 4.55)) had higher odds of completing LTBI treatment. Among 1047 LTBI cases, 5 (0.5%) had progressed to active PTB within 1-8 years post-LTBI diagnosis. DISCUSSION: LTBI burden is disproportionately high towards foreign nationals, with higher odds of LTBI diagnosis but lower odds of treatment initiation. Determining the reasons of not initiating LTBI treatment will be useful to help improve LTBI treatment uptake. Establishing digital databases and building TB laboratory capacity for molecular typing would be useful to determine the contribution of LTBI or reactivation towards TB incidence in Brunei.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Setting-specific Transmission Rates: A Systematic Review and Meta-analysis.

BACKGROUND: Understanding the drivers of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission is crucial for control policies, but evidence of transmission rates in different settings remains limited. METHODS: We conducted a systematic review to estimate secondary attack rates (SARs) and observed reproduction numbers (Robs) in different settings exploring differences by age, symptom status, and duration of exposure. To account for additional study heterogeneity, we employed a beta-binomial model to pool SARs across studies and a negative-binomial model to estimate Robs. RESULTS: Households showed the highest transmission rates, with a pooled SAR of 21.1% (95% confidence interval [CI]:17.4-24.8). SARs were significantly higher where the duration of household exposure exceeded 5 days compared with exposure of ≤5 days. SARs related to contacts at social events with family and friends were higher than those for low-risk casual contacts (5.9% vs 1.2%). Estimates of SARs and Robs for asymptomatic index cases were approximately one-seventh, and for presymptomatic two-thirds of those for symptomatic index cases. We found some evidence for reduced transmission potential both from and to individuals younger than 20 years of age in the household context, which is more limited when examining all settings. CONCLUSIONS: Our results suggest that exposure in settings with familiar contacts increases SARS-CoV-2 transmission potential. Additionally, the differences observed in transmissibility by index case symptom status and duration of exposure have important implications for control strategies, such as contact tracing, testing, and rapid isolation of cases. There were limited data to explore transmission patterns in workplaces, schools, and care homes, highlighting the need for further research in such settings.

Analysis of SARS-CoV-2 Transmission in Different Settings, Brunei.

We report the transmission dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) across different settings in Brunei. An initial cluster of SARS-CoV-2 cases arose from 19 persons who had attended the Tablighi Jama'at gathering in Malaysia, resulting in 52 locally transmitted cases. The highest nonprimary attack rates (14.8%) were observed from a subsequent religious gathering in Brunei and in households of attendees (10.6%). Household attack rates from symptomatic case-patients were higher (14.4%) than from asymptomatic (4.4%) or presymptomatic (6.1%) case-patients. Workplace and social settings had attack rates of <1%. Our analyses highlight that transmission of SARS-CoV-2 varies depending on environmental, behavioral, and host factors. We identify red flags for potential superspreading events, specifically densely populated gatherings with prolonged exposure in enclosed settings, persons with recent travel history to areas with active SARS-CoV-2 infections, and group behaviors. We propose differentiated testing strategies to account for differing transmission risk.

What do we know about SARS-CoV-2 transmission? A systematic review and meta-analysis of the secondary attack rate and associated risk factors.

INTRODUCTION: Current SARS-CoV-2 containment measures rely on controlling viral transmission. Effective prioritization can be determined by understanding SARS-CoV-2 transmission dynamics. We conducted a systematic review and meta-analyses of the secondary attack rate (SAR) in household and healthcare settings. We also examined whether household transmission differed by symptom status of index case, adult and children, and relationship to index case. METHODS: We searched PubMed, medRxiv, and bioRxiv databases between January 1 and July 25, 2020. High-quality studies presenting original data for calculating point estimates and 95% confidence intervals (CI) were included. Random effects models were constructed to pool SAR in household and healthcare settings. Publication bias was assessed by funnel plots and Egger's meta-regression test. RESULTS: 43 studies met the inclusion criteria for household SAR, 18 for healthcare SAR, and 17 for other settings. The pooled household SAR was 18.1% (95% CI: 15.7%, 20.6%), with significant heterogeneity across studies ranging from 3.9% to 54.9%. SAR of symptomatic index cases was higher than asymptomatic cases (RR: 3.23; 95% CI: 1.46, 7.14). Adults showed higher susceptibility to infection than children (RR: 1.71; 95% CI: 1.35, 2.17). Spouses of index cases were more likely to be infected compared to other household contacts (RR: 2.39; 95% CI: 1.79, 3.19). In healthcare settings, SAR was estimated at 0.7% (95% CI: 0.4%, 1.0%). DISCUSSION: While aggressive contact tracing strategies may be appropriate early in an outbreak, as it progresses, measures should transition to account for setting-specific transmission risk. Quarantine may need to cover entire communities while tracing shifts to identifying transmission hotspots and vulnerable populations. Where possible, confirmed cases should be isolated away from the household.

Epidemiological Investigation of the First 135 COVID-19 Cases in Brunei: Implications for Surveillance, Control, and Travel Restrictions.

Studies on the early introduction of SARS-CoV-2 in a naive population have important epidemic control implications. We report findings from the epidemiological investigation of the initial 135 COVID-19 cases in Brunei and describe the impact of control measures and travel restrictions. Epidemiological and clinical information was obtained for all confirmed COVID-19 cases, whose symptom onset was from March 9 to April 5, 2020. The basic reproduction number (R0), incubation period, and serial interval (SI) were calculated. Time-varying R was estimated to assess the effectiveness of control measures. Of the 135 cases detected, 53 (39.3%) were imported. The median age was 36 (range = 0.5-72) years. Forty-one (30.4%) and 13 (9.6%) were presymptomatic and asymptomatic cases, respectively. The median incubation period was 5 days (interquartile range [IQR] = 5, range = 1-11), and the mean SI was 5.4 days (SD = 4.5; 95% CI: 4.3, 6.5). The reproduction number was between 3.9 and 6.0, and the doubling time was 1.3 days. The time-varying reproduction number (Rt) was below one (Rt = 0.91; 95% credible interval: 0.62, 1.32) by the 13th day of the epidemic. Epidemic control was achieved through a combination of public health measures, with emphasis on a test-isolate-trace approach supplemented by travel restrictions and moderate physical distancing measures but no actual lockdown. Regular and ongoing testing of high-risk groups to supplement the existing surveillance program and a phased easing of physical distancing measures has helped maintain suppression of the COVID-19 outbreak in Brunei, as evidenced by the identification of only six additional cases from April 5 to August 5, 2020.