Estimation of country-specific tuberculosis resistance antibiograms using pathogen genomics and machine learning.

Autor:	Dixit A; Division of Infectious Diseases, Department of Pediatrics, Boston Children's Hospital, Boston, Massachusetts, USA.; Department of Biomedical Informatics, Harvard Medical School, Boston, Massachusetts, USA., Freschi L; Department of Biomedical Informatics, Harvard Medical School, Boston, Massachusetts, USA., Vargas R; Department of Biomedical Informatics, Harvard Medical School, Boston, Massachusetts, USA.; Center for Computational Biomedicine, Harvard Medical School, Boston, Massachusetts, USA., Gröschel MI; Department of Biomedical Informatics, Harvard Medical School, Boston, Massachusetts, USA., Nakhoul M; Informatics and Analytics Department, Dana-Farber Cancer Institute, Boston, Massachusetts, USA., Tahseen S; National Tuberculosis Control Programme, Islamabad, Pakistan., Alam SMM; Ministry of Health and Family Welfare, Kolkata, West Bengal, India., Kamal SMM; National Institute of Diseases of the Chest and Hospital, Dhaka, Bangladesh., Skrahina A; Republican Scientific and Practical Center for Pulmonology and Tuberculosis, Minsk, Belarus., Basilio RP; Research Institute for Tropical Medicine, Muntinlupa City, Philippines., Lim DR; Research Institute for Tropical Medicine, Muntinlupa City, Philippines., Ismail N; Clinical Microbiology and Infectious Diseases, University of the Witwatersrand Johannesburg Faculty of Health Sciences, Johannesburg, South Africa., Farhat MR; Department of Biomedical Informatics, Harvard Medical School, Boston, Massachusetts, USA Maha_Farhat@hms.harvard.edu.; Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
Jazyk:	angličtina
Zdroj:	BMJ global health [BMJ Glob Health] 2024 Mar 28; Vol. 9 (3). Date of Electronic Publication: 2024 Mar 28.
DOI:	10.1136/bmjgh-2023-013532
Abstrakt:	Background: Global tuberculosis (TB) drug resistance (DR) surveillance focuses on rifampicin. We examined the potential of public and surveillance Mycobacterium tuberculosis ( Mtb ) whole-genome sequencing (WGS) data, to generate expanded country-level resistance prevalence estimates (antibiograms) using in silico resistance prediction. Methods: We curated and quality-controlled Mtb WGS data. We used a validated random forest model to predict phenotypic resistance to 12 drugs and bias-corrected for model performance, outbreak sampling and rifampicin resistance oversampling. Validation leveraged a national DR survey conducted in South Africa. Results: Mtb isolates from 29 countries (n=19 149) met sequence quality criteria. Global marginal genotypic resistance among mono-resistant TB estimates overlapped with the South African DR survey, except for isoniazid, ethionamide and second-line injectables, which were underestimated (n=3134). Among multidrug resistant (MDR) TB (n=268), estimates overlapped for the fluoroquinolones but overestimated other drugs. Globally pooled mono-resistance to isoniazid was 10.9% (95% CI: 10.2-11.7%, n=14 012). Mono-levofloxacin resistance rates were highest in South Asia (Pakistan 3.4% (0.1-11%), n=111 and India 2.8% (0.08-9.4%), n=114). Given the recent interest in drugs enhancing ethionamide activity and their expected activity against isolates with resistance discordance between isoniazid and ethionamide, we measured this rate and found it to be high at 74.4% (IQR: 64.5-79.7%) of isoniazid-resistant isolates predicted to be ethionamide susceptible. The global susceptibility rate to pyrazinamide and levofloxacin among MDR was 15.1% (95% CI: 10.2-19.9%, n=3964). Conclusions: This is the first attempt at global Mtb antibiogram estimation. DR prevalence in Mtb can be reliably estimated using public WGS and phenotypic resistance prediction for key antibiotics, but public WGS data demonstrates oversampling of isolates with higher resistance levels than MDR. Nevertheless, our results raise concerns about the empiric use of short-course fluoroquinolone regimens for drug-susceptible TB in South Asia and indicate underutilisation of ethionamide in MDR treatment. Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
Databáze:	MEDLINE
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