Explore the vast range of titles available.

Background Information on non-tuberculosis mycobacterial (NTM) diseases remains limited in Singapore and other Southeast Asian countries. This study aimed to delineate epidemiological and clinical features of pulmonary NTM disease. Methods A retrospective review was performed on all NTM isolates identified in Singapore General Hospital from 2012 to 2016 using the 2007 ATS/IDSA diagnostic criteria. Results A total of 2026 NTM isolates from 852 patients were identified. M. abscessus-chelonae group (1010, 49.9%) was the most commonly isolated and implicated in pulmonary NTM disease. Pulmonary cases (352, 76%) had the highest prevalence among patients diagnosed with NTM diseases (465/852, 54.6%) with no gender difference. Male patients were older (68.5 years, P  = 0.014) with a higher incidence of chronic obstructive pulmonary disease (COPD) (23.6%, P  < 0.001) and recurrent cough with phlegm production (51.6%, P  = 0.035). In contrast, more female patients had bronchiectasis (50%, P  < 0.001) and haemoptysis (37.6%, P  = 0.042). Age and COPD were associated with multiple NTM species isolation per patient. Conclusions M. abscessus-chelonae group was the commonest NTM species isolated in Singapore. Pulmonary NTM infection has the highest frequency with male and female patients associated with a higher incidence of COPD and bronchiectasis respectively. Age and COPD were associated with multiple NTM species isolation per patient.

There were 290 multidrug-resistant (MDR)-TB cases diagnosed in Singapore from 2006 to 2018. Eighty-one percent were foreign-born. Spoligotyping and MIRU-VNTR methods identified 108 patients in 24 clusters. The Beijing spoligotype accounted for 22 clusters. Whole genome sequencing (WGS) analysis reduced the number of clustered patients and clusters to 43 and nine respectively. One MIRU cluster was redefined into three WGS clusters. All the clusters had foreign-born source cases. Forty percent of local-born, versus 9% of foreign-born, MDR-TB cases belonged to WGS clusters. WGS more accurately elucidated potential MDR-TB transmission which was overestimated by conventional genotyping methods in Singapore.

Abstract Background Previously treated (ie, recurrent) tuberculosis (TB) cases account for approximately 7%–8% of incident TB globally and in Singapore. Molecular fingerprinting has enabled the differentiation of these patients into relapsed or reinfection cases. Methods Patient demographics, disease characteristics, and treatment information were obtained from the national TB notification registry and TB Control Unit. We performed a retrospective, case-control study to evaluate factors associated with recurrent TB disease in Singapore citizens and permanent residents with culture-positive TB from 2006 to 2013 and who developed a second episode of culture-positive TB up to 2016 using multivariable logistic regression analyses. Results Ninety-one cases with culture-positive first and recurrent TB disease episodes were identified. Recurrent TB was associated with age ≥60 years (adjusted odds ratio [aOR], 1.98 [95% confidence interval {CI}, 1.09–3.61), male sex (aOR, 2.29 [95% CI, 1.22–4.51]), having concomitant pulmonary and extrapulmonary TB (aOR, 3.10 [95% CI, 1.59–6.10]) and extrapulmonary TB alone (aOR, 3.82 [95% CI, 1.12–13.31]), and was less likely in non-Malays (aOR, 0.52 [95% CI, .27–.99]). DNA fingerprinting results for both episodes in 49 cases differentiated these into 28 relapsed and 21 reinfection cases. Relapse was associated with having concomitant pulmonary and extrapulmonary TB (aOR, 9.24 [95% CI, 2.50–42.42]) and positive sputum acid-fast bacilli smear (aOR, 3.95 [95% CI, 1.36–13.10]). Conclusions Relapse and reinfection contributed to 57% and 43%, respectively, of recurrent TB in Singapore. Our study highlights the underappreciated association of concomitant pulmonary and extrapulmonary TB as a significant risk factor for disease relapse. Relapse and reinfection contributed to 57% and 43%, respectively, of recurrent tuberculosis (TB) cases in Singapore, a densely populated country with intermediate TB incidence. Positive sputum smear and concomitant pulmonary and extrapulmonary TB disease were significantly associated with risk of relapse.

Tuberculosis remains common in Singapore, increasing in incidence since 2008. We attempted to determine the molecular epidemiology of Mycobacterium tuberculosis complex (MTC) isolates locally, identifying major circulating genotypes and obtaining a glimpse of transmission dynamics. Non-duplicate MTC isolates archived between 2006 and 2012 at the larger clinical tuberculosis laboratory in Singapore were sampled for spoligotyping and MIRU-VNTR typing, with case data obtained from the Singapore Tuberculosis Elimination Program registry database. Isolates between 2008 and 2012 were selected because of either multidrug-resistance or potential epidemiological linkage, whereas earlier isolates were randomly selected. Separate analyses were performed for the early (2006-2007) and later (2008-2012) study phases in view of potential selection bias. A total of 1,612 MTC isolates were typed, constituting 13.1% of all culture-positive tuberculosis cases during this period. Multidrug-resistance was present in 91 (5.6%) isolates - higher than the national prevalence in view of selection bias. The majority of isolates belonged to the Beijing (45.8%) and EAI (22.8%) lineages. There were 347 (30.7%) and 133 (27.5%) cases clustered by combined spoligotyping and MIRU-VNTR typing from the earlier and later phases respectively. Patients within these clusters tended to be of Chinese ethnicity, Singapore resident, and have isolates belonging to the Beijing lineage. A review of prior contact investigation results for all patients with clustered isolates failed to reveal epidemiological links for the majority, suggesting either unknown transmission networks or inadequate specificity of the molecular typing methods in a country with a moderate incidence of tuberculosis. Our work demonstrates that Singapore has a large and heterogeneous distribution of MTC strains, and with possible cross-transmission over the past few years based on our molecular typing results. A universal MTC typing program coupled with enhanced contact investigations may be useful in further understanding the transmission dynamics of tuberculosis locally.

Thierry Wirth, Philip Supply, Stefan Niemann and colleagues analyze 4,987 Mycobacterium tuberculosis strains of the Beijing lineage isolated from 99 countries. They report whole-genome sequencing of 110 representative strains, characterize global population structure and reconstruct the evolutionary history of this lineage. Mycobacterium tuberculosis strains of the Beijing lineage are globally distributed and are associated with the massive spread of multidrug-resistant (MDR) tuberculosis in Eurasia. Here we reconstructed the biogeographical structure and evolutionary history of this lineage by genetic analysis of 4,987 isolates from 99 countries and whole-genome sequencing of 110 representative isolates. We show that this lineage initially originated in the Far East, from where it radiated worldwide in several waves. We detected successive increases in population size for this pathogen over the last 200 years, practically coinciding with the Industrial Revolution, the First World War and HIV epidemics. Two MDR clones of this lineage started to spread throughout central Asia and Russia concomitantly with the collapse of the public health system in the former Soviet Union. Mutations identified in genes putatively under positive selection and associated with virulence might have favored the expansion of the most successful branches of the lineage.

Background Tuberculosis remains common in Singapore, increasing in incidence since 2008. We attempted to determine the molecular epidemiology of Mycobacterium tuberculosis complex (MTC) isolates locally, identifying major circulating genotypes and obtaining a glimpse of transmission dynamics. Methodology Non-duplicate MTC isolates archived between 2006 and 2012 at the larger clinical tuberculosis laboratory in Singapore were sampled for spoligotyping and MIRU-VNTR typing, with case data obtained from the Singapore Tuberculosis Elimination Program registry database. Isolates between 2008 and 2012 were selected because of either multidrug-resistance or potential epidemiological linkage, whereas earlier isolates were randomly selected. Separate analyses were performed for the early (2006-2007) and later (2008-2012) study phases in view of potential selection bias. Principal Findings A total of 1,612 MTC isolates were typed, constituting 13.1% of all culture-positive tuberculosis cases during this period. Multidrug-resistance was present in 91 (5.6%) isolates - higher than the national prevalence in view of selection bias. The majority of isolates belonged to the Beijing (45.8%) and EAI (22.8%) lineages. There were 347 (30.7%) and 133 (27.5%) cases clustered by combined spoligotyping and MIRU-VNTR typing from the earlier and later phases respectively. Patients within these clusters tended to be of Chinese ethnicity, Singapore resident, and have isolates belonging to the Beijing lineage. A review of prior contact investigation results for all patients with clustered isolates failed to reveal epidemiological links for the majority, suggesting either unknown transmission networks or inadequate specificity of the molecular typing methods in a country with a moderate incidence of tuberculosis. Conclusion Our work demonstrates that Singapore has a large and heterogeneous distribution of MTC strains, and with possible cross-transmission over the past few years based on our molecular typing results. A universal MTC typing program coupled with enhanced contact investigations may be useful in further understanding the transmission dynamics of tuberculosis locally.