Histone acetylome-wide associations in immune cells from individuals with active Mycobacterium tuberculosis infection.

Host cell chromatin changes are thought to play an important role in the pathogenesis of infectious diseases. Here we describe a histone acetylome-wide association study (HAWAS) of an infectious disease, on the basis of genome-wide H3K27 acetylation profiling of peripheral blood granulocytes and monocytes from persons with active Mycobacterium tuberculosis (Mtb) infection and healthy controls. We detected >2,000 differentially acetylated loci in either cell type in a Singapore Chinese discovery cohort (n = 46), which were validated in a subsequent multi-ethnic Singapore cohort (n = 29), as well as a longitudinal cohort from South Africa (n = 26), thus demonstrating that HAWAS can be independently corroborated.

Smear-positive pulmonary tuberculosis patients with previously abnormal chest radiographs: missed opportunities for early diagnosis.

Introduction: It is vital to diagnose and treat pulmonary tuberculosis (PTB) early, in the interests of the patient and public health. At the Singapore Tuberculosis Control Unit (TBCU), it was not uncommon to discover abnormal chest radiographs (CXRs) predating their PTB diagnosis by months to years in the electronic medical records (EMRs) of sputum acid-fast bacilli smear-positive patients. Our study explored this observation.

Sub-clinical abnormalities detected by PET/MRI in household tuberculosis contacts.

Background: The understanding of early events following TB exposure is limited by traditional tests that rely on detection of an immune response to infection, which is delayed, or on imaging tests with low sensitivity for early disease. We investigated for evidence of lung abnormalities in heavily exposed TB contacts using PET/MRI.

Methods: 30 household contacts of 20 index patients underwent clinical assessment, IGRA testing, chest x-ray and PET/MRI scan using 18-F-FDG.

Clofazimine drug susceptibility testing for Mycobacterium tuberculosis: the case of using the right diluent.

Accurate and reliable drug susceptibility testing (DST) is essential for the effective treatment and control of tuberculosis. With the increase in drug-resistant organisms, newer and less conventional antimicrobial agents are used for treatment. Recently, we found an unprecedented rise in the number of clofazimine-resistant Mycobacterium tuberculosis isolates in our laboratory.

Prevalence of and risk factors associated with latent tuberculosis in Singapore: A cross-sectional survey.

Objectives: This first cross-sectional survey on latent tuberculosis infection (LTBI) in Singapore was performed by utilizing the QuantiFERON Gold In-tube (QFT-GIT) assay to collect data on the prevalence of LTBI and to identify potential risk factors associated with LTBI.

Methods: Nationwide household addresses were selected randomly for enumeration, and Singaporeans or Permanent Residents aged 18-79 years were identified. One eligible member per household was selected using the Kish grid.

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

Objective: Between February 2012 and May 2016, six residents of an 11-storey apartment block were diagnosed with MDR-TB. Based on initial tests, all isolates had similar genotypic profiles, although there were no identifiable epidemiological transmission patterns between three cases. We present findings from the cluster investigation and results of a mass screening exercise.

Alcohol drinking and cigarette smoking in relation to risk of active tuberculosis: prospective cohort study.

Introduction: Heavy alcohol consumption increases the risk of active tuberculosis (TB). However, the relation between lower levels of alcohol intake and TB risk remains unclear. We aimed to evaluate the association between alcohol intake and risk of active TB and assess whether the associations were modified by smoking status, which is another risk factor for active TB.

Association and clinical utility of NAT2 in the prediction of isoniazid-induced liver injury in Singaporean patients.

Background And Aims: Isoniazid (INH) is part of the first-line-therapy for tuberculosis (TB) but can cause drug-induced liver injury (DILI). Several candidate single nucleotide polymorphisms (SNPs) have been previously identified but the clinical utility of these SNPs in the prediction of INH-DILI remains uncertain. The aim of this study was to assess the association between selected candidate SNPs and the risk of INH-DILI and to assess the clinical validity of associated variants in a Singaporean population.

Tea Drinking and Its Association with Active Tuberculosis Incidence among Middle-Aged and Elderly Adults: The Singapore Chinese Health Study.

Experimental studies showed that tea polyphenols may inhibit growth of . However, no prospective epidemiologic study has investigated tea drinking and the risk of active tuberculosis. We investigated this association in the Singapore Chinese Health Study, a prospective population-based cohort of 63,257 Chinese aged 45-74 years recruited between 1993 and 1998 in Singapore.

Spatial dynamics of TB within a highly urbanised Asian metropolis using point patterns.

Singapore is a high-income country in a region with a high prevalence of tuberculosis. The Singapore Tuberculosis (TB) Elimination Program (STEP) was set up in 1997, and the better surveillance and clinical management practices initiated under STEP led to a decade-long decline in the incidence levels. However, incidence rates started to rise again since 2008.

Ministry of Health Clinical Practice Guidelines: Prevention, Diagnosis and Management of Tuberculosis.

The Ministry of Health (MOH) has developed the clinical practice guidelines on Prevention, Diagnosis and Management of Tuberculosis to provide doctors and patients in Singapore with evidence-based treatment for tuberculosis. This article reproduces the introduction and executive summary (with recommendations from the guidelines) from the MOH clinical practice guidelines on Prevention, Diagnosis and Management of Tuberculosis, for the information of SMJ readers. The chapters and page numbers mentioned in the reproduced extract refer to the full text of the guidelines, which are available from the Ministry of Health website: http://www.

Management of latent Mycobacterium tuberculosis infection: WHO guidelines for low tuberculosis burden countries.

Latent tuberculosis infection (LTBI) is characterised by the presence of immune responses to previously acquired Mycobacterium tuberculosis infection without clinical evidence of active tuberculosis (TB). Here we report evidence-based guidelines from the World Health Organization for a public health approach to the management of LTBI in high risk individuals in countries with high or middle upper income and TB incidence of <100 per 100 000 per year. The guidelines strongly recommend systematic testing and treatment of LTBI in people living with HIV, adult and child contacts of pulmonary TB cases, patients initiating anti-tumour necrosis factor treatment, patients receiving dialysis, patients preparing for organ or haematological transplantation, and patients with silicosis.

First use of bedaquiline in a patient with XDR-TB in Singapore.

Drug-resistant tuberculosis (TB) continues to pose a threat to global control of TB: 3.5% of new and 20.5% of previously treated TB cases were estimated to have multidrug-resistant (MDR)-TB in 2013.

Outcome of a grocery voucher incentive scheme for low-income tuberculosis patients on directly observed therapy in Singapore.

Introduction: The 'DOT & Shop' scheme is sponsored by SATA CommHealth, a local non-governmental organisation. It was launched in July 2009, in collaboration with Singapore's Tuberculosis Control Unit (TBCU). Under this scheme, grocery vouchers are disbursed to low-income patients with tuberculosis (TB) at each clinic visit if they have been adherent to directly observed therapy (DOT).

Measurement of phenotype and absolute number of circulating heparin-binding hemagglutinin, ESAT-6 and CFP-10, and purified protein derivative antigen-specific CD4 T cells can discriminate active from latent tuberculosis infection.

The tuberculin skin test (TST) and interferon gamma (IFN-γ) release assays (IGRAs) are used as adjunctive tests for the evaluation of suspected cases of active tuberculosis (TB). However, a positive test does not differentiate latent from active TB. We investigated whether flow cytometric measurement of novel combinations of intracellular cytokines and surface makers on CD4 T cells could differentiate between active and latent TB after stimulation with Mycobacterium tuberculosis-specific proteins.

Time series analysis of demographic and temporal trends of tuberculosis in Singapore.

Background: Singapore is an intermediate tuberculosis (TB) incidence country, with a recent rise in TB incidence from 2008, after a fall in incidence since 1998. This study identified population characteristics that were associated with the recent increase in TB cases, and built a predictive model of TB risk in Singapore.

Methods: Retrospective time series analysis was used to study TB notification data collected from 1995 to 2011 from the Singapore Tuberculosis Elimination Program (STEP) registry.

Molecular epidemiology of Mycobacterium tuberculosis complex in Singapore, 2006-2012.

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.

Diagnosis and treatment of latent infection with Mycobacterium tuberculosis.

In clinical practice, latent infection with Mycobacterium tuberculosis is defined by the presence of an M. tuberculosis-specific immune response in the absence of active tuberculosis. Targeted testing of individuals from risk groups with the tuberculin skin test or an interferon-γ release assay is currently the best method to identify those with the highest risk for progression to tuberculosis.

The imminent threat of multidrug-resistant tuberculosis in Singapore.

The global emergence of multidrugresistant (MDR) tuberculosis (TB) and extensively drug-resistant (XDR)-TB threatens to derail the efforts of TB control programmes worldwide. From 2000 to 2010, 161 pulmonary MDR-TB cases (including six XDR-TB cases) were reported in Singapore, and of these, 80% occurred among the foreign-born, with an increasing trend seen after 2004. Among new pulmonary TB cases, the highest incidence of MDR-TB occurred among patients from Myanmar (8%), followed by Vietnam (4.

TB control in Singapore: where do we go from here?

The total number of new tuberculosis (TB) cases notified in Singapore among citizens, permanent residents and foreigners rose by 46% from 2004 to 2010. During this period, the proportion of foreigners increased from 29% to 47% of the total case burden. In 2008, the TB incidence rate among Singapore citizens and permanent residents increased for the first time in ten years, despite the on-going efforts of the Singapore TB Elimination Programme.