{"title":"One-year mortality of tuberculosis patients on isoniazid-based treatment and its association with rapid acetylator NAT2 genotypes.","authors":"Ayu Kasamatsu, Reiko Miyahara, Daisuke Yoneoka, Licht Toyo-Oka, Boonchai Chiyasirinroje, Worarat Imsanguan, Supharat Suvichapanich, Hideki Yanai, Sukanya Wattnapokayakit, Supalert Nedsuwan, Manon Boonbangyang, Prasit Palittapongarnpim, Katsushi Tokunaga, Taisei Mushiroda, Surakameth Mahasirimongkol","doi":"10.1016/j.ijid.2025.107895","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>NAT2 polymorphisms affect isoniazid metabolism, but their effect on mortality among individuals with tuberculosis (TB) remains unclear.</p><p><strong>Methods: </strong>This study used data from two TB cohorts (2005-2011, 2014-2020) and death certificate records in Thailand. Newly diagnosed Thai individuals treated with isoniazid-containing regimens were included. NAT2 genotypes-rapid, intermediate, and slow acetylator (RA, IA, SA)-were classified via haplotype inference. The primary outcome was 1-year all-cause mortality, while secondary outcomes included TB-related mortality, TB+respiratory disease-related mortality recorded in the vital registration system, and death as a TB treatment outcome. Adjusted hazard ratios (aHRs) relative to the IA type were estimated using stratified Cox proportional hazards models. Subgroup analyses targeted individuals with isoniazid-resistant TB and HIV infection.</p><p><strong>Results: </strong>A total of 1,065 individuals (766 males; mean age=51 years) were analyzed. Individuals with RA had a 1.70-fold greater all-cause mortality risk (95% CI: 1.03-2.80) than IA. The aHRs for RA were 1.14 (0.43-3.03) for TB-related mortality, 1.59 (0.80-3.18) for TB+respiratory disease-related mortality, and 1.26 (0.67-2.14) for TB treatment outcome death. Among individuals with isoniazid-resistant TB, those with RA had a 4.68-fold (1.14-19.12) greater aHR for all-cause mortality.</p><p><strong>Conclusion: </strong>The RA type is associated with increased 1-year all-cause mortality.</p>","PeriodicalId":14006,"journal":{"name":"International Journal of Infectious Diseases","volume":" ","pages":"107895"},"PeriodicalIF":4.8000,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Infectious Diseases","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.ijid.2025.107895","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"INFECTIOUS DISEASES","Score":null,"Total":0}
引用次数: 0
Abstract
Background: NAT2 polymorphisms affect isoniazid metabolism, but their effect on mortality among individuals with tuberculosis (TB) remains unclear.
Methods: This study used data from two TB cohorts (2005-2011, 2014-2020) and death certificate records in Thailand. Newly diagnosed Thai individuals treated with isoniazid-containing regimens were included. NAT2 genotypes-rapid, intermediate, and slow acetylator (RA, IA, SA)-were classified via haplotype inference. The primary outcome was 1-year all-cause mortality, while secondary outcomes included TB-related mortality, TB+respiratory disease-related mortality recorded in the vital registration system, and death as a TB treatment outcome. Adjusted hazard ratios (aHRs) relative to the IA type were estimated using stratified Cox proportional hazards models. Subgroup analyses targeted individuals with isoniazid-resistant TB and HIV infection.
Results: A total of 1,065 individuals (766 males; mean age=51 years) were analyzed. Individuals with RA had a 1.70-fold greater all-cause mortality risk (95% CI: 1.03-2.80) than IA. The aHRs for RA were 1.14 (0.43-3.03) for TB-related mortality, 1.59 (0.80-3.18) for TB+respiratory disease-related mortality, and 1.26 (0.67-2.14) for TB treatment outcome death. Among individuals with isoniazid-resistant TB, those with RA had a 4.68-fold (1.14-19.12) greater aHR for all-cause mortality.
Conclusion: The RA type is associated with increased 1-year all-cause mortality.
期刊介绍:
International Journal of Infectious Diseases (IJID)
Publisher: International Society for Infectious Diseases
Publication Frequency: Monthly
Type: Peer-reviewed, Open Access
Scope:
Publishes original clinical and laboratory-based research.
Reports clinical trials, reviews, and some case reports.
Focuses on epidemiology, clinical diagnosis, treatment, and control of infectious diseases.
Emphasizes diseases common in under-resourced countries.