One-year mortality of tuberculosis patients on isoniazid-based treatment and its association with rapid acetylator NAT2 genotypes
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 tre...
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Elsevier
2025-06-01
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| Series: | International Journal of Infectious Diseases |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1201971225001183 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Ayu Kasamatsu |
| collection | DOAJ |
| description | 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 (0.67–2.37) 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. |
| format | Article |
| id | doaj-art-1db839ef3a4143009d5650e7b69103e3 |
| institution | OA Journals |
| issn | 1201-9712 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | International Journal of Infectious Diseases |
| spelling | doaj-art-1db839ef3a4143009d5650e7b69103e32025-08-20T01:49:19ZengElsevierInternational Journal of Infectious Diseases1201-97122025-06-0115510789510.1016/j.ijid.2025.107895One-year mortality of tuberculosis patients on isoniazid-based treatment and its association with rapid acetylator NAT2 genotypesAyu Kasamatsu0Reiko Miyahara1Daisuke Yoneoka2Licht Toyo-oka3Boonchai Chiyasirinroje4Worarat Imsanguan5Supharat Suvichapanich6Hideki Yanai7Sukanya Wattnapokayakit8Supalert Nedsuwan9Manon Boonbangyang10Prasit Palittapongarnpim11Katsushi Tokunaga12Taisei Mushiroda13Surakameth Mahasirimongkol14Center for Surveillance, Immunization, and Epidemiologic Research, National Institute of Infectious Diseases, Tokyo, JapanCenter for Surveillance, Immunization, and Epidemiologic Research, National Institute of Infectious Diseases, Tokyo, Japan; Corresponding author: Reiko Miyahara, Chief, International Research Unit, Center for Surveillance, Immunization, and Epidemiologic Research, National Institute of Infectious Diseases, J1601 Iidabashi Plano Stage Building 2-7-2 Fujimi, Chiyoda-ku, Tokyo, 102-0071, Japan.Center for Surveillance, Immunization, and Epidemiologic Research, National Institute of Infectious Diseases, Tokyo, JapanFaculty of Contemporary Society, Toyama University of International Studies, Toyama, JapanTB/HIV Research Foundation, Chiang Rai, ThailandChiangrai Prachanukroh Hospital, Ministry of Public Health, Chiang Rai, ThailandDepartment of Biochemistry, Faculty of Pharmacy, Mahidol University, Bangkok, ThailandJapan Anti-Tuberculosis Association, Kiyose, JapanDepartment of Medical Sciences, Ministry of Public Health, Nonthaburi, ThailandChiangrai Prachanukroh Hospital, Ministry of Public Health, Chiang Rai, ThailandPornchai Matangkasombut Center for Microbial Genomics (CENMIG), Department of Microbiology, Faculty of Science, Mahidol University, Bangkok, ThailandPornchai Matangkasombut Center for Microbial Genomics (CENMIG), Department of Microbiology, Faculty of Science, Mahidol University, Bangkok, ThailandGenome Medical Science Project, National Center for Global Health and Medicine, Tokyo, JapanLaboratory for Pharmacogenomics, RIKEN Center for Integrative Medical Sciences, Yokohama, JapanInformation and Communication Technology Center, Office of Permanent Secretary, Ministry of Public Health, Nonthaburi, ThailandBackground: 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 (0.67–2.37) 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.http://www.sciencedirect.com/science/article/pii/S1201971225001183TuberculosisSurvivalPharmacokineticsIsoniazidNAT2 genotypeDrug resistance |
| spellingShingle | 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 One-year mortality of tuberculosis patients on isoniazid-based treatment and its association with rapid acetylator NAT2 genotypes International Journal of Infectious Diseases Tuberculosis Survival Pharmacokinetics Isoniazid NAT2 genotype Drug resistance |
| title | One-year mortality of tuberculosis patients on isoniazid-based treatment and its association with rapid acetylator NAT2 genotypes |
| title_full | One-year mortality of tuberculosis patients on isoniazid-based treatment and its association with rapid acetylator NAT2 genotypes |
| title_fullStr | One-year mortality of tuberculosis patients on isoniazid-based treatment and its association with rapid acetylator NAT2 genotypes |
| title_full_unstemmed | One-year mortality of tuberculosis patients on isoniazid-based treatment and its association with rapid acetylator NAT2 genotypes |
| title_short | One-year mortality of tuberculosis patients on isoniazid-based treatment and its association with rapid acetylator NAT2 genotypes |
| title_sort | one year mortality of tuberculosis patients on isoniazid based treatment and its association with rapid acetylator nat2 genotypes |
| topic | Tuberculosis Survival Pharmacokinetics Isoniazid NAT2 genotype Drug resistance |
| url | http://www.sciencedirect.com/science/article/pii/S1201971225001183 |
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