| Autor: |
Uddin MKM; Infectious Diseases Division, icddr,b, Dhaka, Bangladesh., Cabibbe AM; Emerging Bacterial Pathogens Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy., Nasrin R; Infectious Diseases Division, icddr,b, Dhaka, Bangladesh., Ghodousi A; Emerging Bacterial Pathogens Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy., Nobel FA; Infectious Diseases Division, icddr,b, Dhaka, Bangladesh., Rahman SMM; Infectious Diseases Division, icddr,b, Dhaka, Bangladesh., Ahmed S; Infectious Diseases Division, icddr,b, Dhaka, Bangladesh., Ather MF; Infectious Diseases Division, icddr,b, Dhaka, Bangladesh., Razzaque SMA; National Institute of Disease of the Chest and Hospital, Dhaka, Bangladesh., Raihan MA; 250 bed TB Hospital, Dhaka, Bangladesh., Modak PK; National Tuberculosis Control Programme, Bangladesh., Berland JL; Fondation Merieux, Lyon, France., Gemert WV; Stop TB Partnership, Switzerland., Mohsin SMI; Office of Population, Health, and Nutrition, U.S. Agency for International Development (USAID), Bangladesh., Cirillo DM; Emerging Bacterial Pathogens Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy., Banu S; Infectious Diseases Division, icddr,b, Dhaka, Bangladesh. |
| Abstrakt: |
Lack of appropriate early diagnostic tools for drug-resistant tuberculosis (DR-TB) and their incomplete drug susceptibility testing (DST) profiling is concerning for TB disease control. Existing methods, such as phenotypic DST (pDST), are time-consuming, while Xpert MTB/RIF (Xpert) and line probe assay (LPA) are limited to detecting resistance to few drugs. Targeted next-generation sequencing (tNGS) has been recently approved by WHO as an alternative approach for rapid and comprehensive DST. We aimed to investigate the performance and feasibility of tNGS for detecting DR-TB directly from clinical samples in Bangladesh. pDST, LPA and tNGS were performed among 264 sputum samples, either rifampicin-resistant (RR) or rifampicin-sensitive (RS) TB cases confirmed by Xpert assay. Resistotypes of tNGS were compared with pDST, LPA and composite reference standard (CRS, resistant if either pDST or LPA showed a resistant result). tNGS results revealed higher sensitivities for rifampicin (RIF) (99.3%), isoniazid (INH) (96.3%), fluoroquinolones (FQs) (94.4%), and aminoglycosides (AMGs) (100%) but comparatively lower for ethambutol (76.6%), streptomycin (68.7%), ethionamide (56.0%) and pyrazinamide (50.7%) when compared with pDST. The sensitivities of tNGS for INH, RIF, FQs and AMGs were 93.0%, 96.6%, 90.9%, and 100%, respectively and the specificities ranged from 91.3 to 100% when compared with CRS. This proof of concept study, conducted in a high-burden setting demonstrated that tNGS is a valuable tool for identifying DR-TB directly from the clinical specimens. Its feasibility in our laboratory suggests potential implementation and moving tNGS from research settings into clinical settings. |
