Investigation of a cluster of multi-drug resistant tuberculosis in a high-rise apartment block in Singapore

Ho, Zheng Jie Marc; Chee, Cynthia Bin Eng; Ong, Rick Twee Hee; Sng, Li-Hwei; Peh, Woei Ling Justine; Cook, Alex R.; Hsu, Li Yang; Wang, Yee Tang; Koh, Han Fang; Lee, Vernon Jian Ming

doi:10.1016/j.ijid.2017.12.010

Cited by 9 publications

(5 citation statements)

References 23 publications

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“…Of note, one of the intermediate contacts was not only infected with TB but also developed TB disease, suggesting contact of even fewer than 10 hours may result in TB infection. Thus, the scope of TB contact investigations may have to be expanded, ( 14 ) particularly in school settings. ( 13 )…”

Section: Discussionmentioning

confidence: 99%

A tuberculosis contact investigation involving a large number of contacts tested with interferon-gamma release assay at a nursing school: Kanagawa, Japan, 2012

Tasaka

Shimamura

Iwata³

et al. 2018

WPSAR

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In May 2012, a teacher of a nursing school with about 300 staff members and students in Japan was diagnosed with sputum smear-positive pulmonary tuberculosis (TB), leading to an investigation involving nearly 300 contacts. We describe the contacts’ closeness to the index TB patient and the likelihood of TB infection and disease.A case of TB was defined as an individual with positive bacteriological tests or by a physician diagnosis of TB. A latent TB infection (LTBI) case was defined as an individual who had a positive interferon-gamma release assay (IGRA).A total of 283 persons screened with IGRA were analysed. Eight persons (2.8%, 95% confidence interval [CI]: 1.2–5.4) tested positive by IGRA; one student who had intermediate (less than 10 hours) contact with the index patient was found to have pulmonary TB by chest X-ray. The positivity in IGRA among staff members with very close contact with the index patient (4 of 21, 19%, 95% CI: 5.4–42%) with a statistically significant relative risk of 17 (95% CI: 2.0–140) was high compared with that of the intermediate contacts (1 of 88, 1.1% [95% CI: 0.028–6.2]). There was a statistically significant trend in the risk of TB infection and closeness with the index patient among the staff members and students (P < 0.00022).In congregate settings such as schools, the scope of contact investigation may have to be expanded to detect a TB case among those who had brief contact with the index patient.

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Section: Discussionmentioning

confidence: 99%

A tuberculosis contact investigation involving a large number of contacts tested with interferon-gamma release assay at a nursing school: Kanagawa, Japan, 2012

Tasaka

Shimamura

Iwata³

et al. 2018

WPSAR

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“…Local spread of MDR-TB between migrants and residents had previously been reported in a correctional setting [ 5 ], and a local adolescent with no travel or contact history was diagnosed with MDR-TB in 2011 [ 6 ]. There have also been reports of MDR-TB clusters related to two gaming centres in 2012 [ 7 ] and an 11-storey apartment block between 2012 and 2016 [ 8 ].…”

Section: Background Of Tuberculosis Surveillance In Singaporementioning

confidence: 99%

“…During the research phase, 499 retrospective MDR-TB and suspected outbreak samples of TB DNA were sent to Polaris in the Genome Institute of Singapore for sequencing followed by SSHSPH-NUS for bioinformatics analysis. The WGS results were utilized by STEP for cluster investigation and treatment of MDR-TB cases [ 12 , 8 ].…”

Section: Role Of the National Public Health Laboratory In Tuberculosi...mentioning

confidence: 99%

“…WGS had also confirmed the presence of TB clusters within public housing blocks. A mass screening exercise was undertaken in response to a cluster of MDR-TB in a single 11-storey apartment block [ 8 ]. In a 4 year period, six residents were diagnosed with MDR-TB but none of them had any epidemiological links.…”

Section: Public Health Applications Of Tuberculosis Wgs Phylogenymentioning

confidence: 99%

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Implementation of national whole-genome sequencing of Mycobacterium tuberculosis, National Public Health Laboratory, Singapore, 2019—2022

Lim,

Ang,

Cho

et al. 2023

Microbial Genomics

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The National Tuberculosis Programme (NTBP) monitors the occurrence and spread of tuberculosis (TB) and multidrug-resistant TB (MDR-TB) in Singapore. Since 2020, whole-genome sequencing (WGS) of Mycobacterium tuberculosis isolates has been performed at the National Public Health Laboratory (NPHL) for genomic surveillance, replacing spoligotyping and mycobacterial interspersed repetitive unit-variable number tandem repeats analysis (MIRU-VNTR). Four thousand three hundred and seven samples were sequenced from 2014 to January 2023, initially as research projects and later developed into a comprehensive public health surveillance programme. Currently, all newly diagnosed culture-positive cases of TB in Singapore are prospectively sent for WGS, which is used to perform lineage classification, predict drug resistance profiles and infer genetic relationships between TB isolates. This paper describes NPHL’s operational and technical experiences with implementing the WGS service in an urban TB-endemic setting, focusing on cluster detection and genomic drug susceptibility testing (DST). Cluster detection: WGS has been used to guide contact tracing by detecting clusters and discovering unknown transmission networks. Examples have been clusters in a daycare centre, housing apartment blocks and a horse-racing betting centre. Genomic DST: genomic DST prediction (gDST) identifies mutations in core genes known to be associated with TB drug resistance catalogued in the TBProfiler drug resistance mutation database. Mutations are reported with confidence scores according to a standardized approach referencing NPHL’s internal gDST confidence database, which is adapted from the World Health Organization (WHO) TB drug mutation catalogue. Phenotypic–genomic concordance was observed for the first-line drugs ranging from 2959/2998 (98.7 %) (ethambutol) to 2983/2996 (99.6 %) (rifampicin). Aspects of internal database management, reporting standards and caveats in results interpretation are discussed.

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“…The pervasiveness of drug-resistant bacterial infections is a global health issue with significant healthcare, economic, and societal burdens. − Community-acquired and nosocomial infections, caused by drug-resistant microbes such as methicillin-resistant Staphylococcus aureus (MRSA), multidrug-resistant Pseudomonas aeruginosa (P. aeruginosa), and vancomycin-resistant Enterococci (VRE) have become increasingly prevalent. − Another confounding issue is the pervasive use of antimicrobial agents in personal care products, sanitizers, and hospital cleaners, where a major concern is the development of cross- and co-resistance with clinically used antibiotics, especially in hospital settings. , Current antibiotic therapies are also inefficient to treat biofilm protected and intracellular infections such as Mycobacterium tuberculosis ( Mtb ) and non-tuberculous mycobacteria, allowing bacteria to establish chronic drug-resistant infections. − Given the reduction of effective treatment options for tuberculosis (TB) and other drug-resistant pathogens coupled with a diminished antibiotic discovery and development pipeline, a new therapeutic development paradigm is needed for treatment of increasingly drug-resistant bacterial infections. , …”

Section: Introductionmentioning

confidence: 99%

Upcycling Poly(ethylene terephthalate) Refuse to Advanced Therapeutics for the Treatment of Nosocomial and Mycobacterial Infections

Tan

Park

et al. 2019

Macromolecules

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The discovery of antibiotics was one of the crowning achievements of the 20th century, revolutionizing the treatment of infectious disease. However, widespread improper use of antibiotics has led to the development of antibiotic-resistant bacteria, resulting in a healthcare crisis and the urgent need to develop new effective antibiotics. Moreover, current antibiotic therapies are inefficient in treating biofilm-protected and intracellular organisms such as Mycobacterium tuberculosis (Mtb) and non-tuberculous mycobacteria. Herein, we present a strategy for the construction of macromolecular antimicrobial compounds using a catalyst-free, polyaddition polymerization process of monomers derived from poly(ethylene terephthalate) (PET) refuse. The initial depolymerization of PET refuse via aminolysis is highly amenable and scalable process to access a broad array of functional tertiary amine-containing terephthalamide polymer-grade monomers. This new monomer platform was subsequently used to construct antimicrobial cationic polyionenes via a polyaddition polymerization. The composition and structure of the antimicrobial polyionenes were varied to study their antimicrobial activity against a broad spectrum of pathogenic microbes including Mtb. Polymers with optimized compositions have potent antimicrobial activity with low minimum inhibitory concentrations of 3.9–15.8 μg/mL against microbes including Mtb and high selectivity for microbes over mammalian cells. Similarly, activity against Mtb ranged from 2 to 16 μg/mL, while values for Mycobacterium avium and Mycobacterium abscessus were higher. In addition, antimicrobial polyionenes were able to target and kill M. avium residing inside human macrophages. Overall, PET refuse was successfully used as a feedstock to generate new functional terephthalamide monomers for new macromolecular antimicrobial polyionenes. These polyionenes are promising candidate agents to treat difficult-to-treat bacterial and mycobacterial infections that are currently resistant to existing antibiotics.

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Investigation of a cluster of multi-drug resistant tuberculosis in a high-rise apartment block in Singapore

Abstract: With WGS, TB clusters not apparent through regular activity-based contact tracing may be detected. Mass screening may help inform the extent of transmission, but is limited by participation and difficulties in interpretation.

Cited by 9 publications

References 23 publications

A tuberculosis contact investigation involving a large number of contacts tested with interferon-gamma release assay at a nursing school: Kanagawa, Japan, 2012

A tuberculosis contact investigation involving a large number of contacts tested with interferon-gamma release assay at a nursing school: Kanagawa, Japan, 2012

Implementation of national whole-genome sequencing of Mycobacterium tuberculosis, National Public Health Laboratory, Singapore, 2019—2022

Upcycling Poly(ethylene terephthalate) Refuse to Advanced Therapeutics for the Treatment of Nosocomial and Mycobacterial Infections

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