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. METHODS: This was a case-control study where 24 INH-DILI cases and 79 controls were recruited from the TB control unit in a tertiary hospital. Logistic regression was used to test for the association between candidate SNPs and INH-DILI. NAT2 acetylator status was inferred from genotypes and tested for association with INH-DILI. Finally, clinical validity measures were estimated for significant variants. RESULTS: Two SNPs in NAT2 (rs1041983 and rs1495741) and NAT2 slow acetylators (SA) were significantly associated with INH-DILI (OR (95% CI) = 13.86 (4.30-44.70), 0.10 (0.03-0.33) and 9.98 (3.32-33.80), respectively). Based on an INH-DILI prevalence of 10%, the sensitivity, specificity, positive and negative predictive values of NAT2 SA were 75%, 78%, 28% and 97%, respectively. The population attributable fraction (PAF) and number needed to test (NNT) for NAT2 SA were estimated to be 0.67 and 4.08, respectively. A model with clinical and NAT2 acetylator status provided significantly better prediction for INH-DILI than a clinical model alone (area under receiver operating characteristic curve = 0.863 vs. 0.766, respectively, p = 0.027). CONCLUSIONS: We show the association between NAT2 SA and INH-DILI in a Singaporean population and demonstrated its clinical utility in the prediction of INH-DILI.

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. Approximately 9% of patients with MDR-TB had extensively drug-resistant (XDR)-TB. A 30-year-old Vietnamese woman previously treated for TB in her home country presented with 5 months of cough and shortness of breath 1 year after migrating to Singapore. Xpert MTB/Rif testing showed rpoB gene mutation. Phenotypic drug susceptibility testing revealed XDR-TB. Second and third-line TB drugs were commenced. To strengthen the efficacy of her treatment regimen, the novel anti-TB drug bedaquiline was obtained for the patient on compassionate grounds. We report the first use in Singapore of bedaquiline for the treatment of XDR-TB.

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). This study aimed to determine the effect of this incentive scheme on treatment completion rates and to report the characteristics of patients who were non-adherent to the scheme. METHODS: This descriptive study used data from the TBCU medical social worker database and the National TB Registry. RESULTS: From July 2009 to December 2012, a total of 883 TB patients were enrolled in the scheme. The overall treatment completion rates of the patients before (July 2006-June 2009) and after (July 2009-December 2012) the implementation of the scheme improved from 85.3% to 87.2% (p = 0.02). Patients under this scheme had a higher treatment completion rate (90.0%) than those not under this scheme (86.4%) (p < 0.01). It was found that the non-adherent patients were more likely to be of Malay ethnicity, younger and unemployed. CONCLUSION: We demonstrate the salutary effect of a non-governmental organisation-funded grocery voucher incentive scheme for low-income TB patients on DOT in Singapore.