Review on Drug Resistant Tuberculosis

Introduction: An estimated 9.9 million people fell ill with tuberculosis globally in 2020 with India and China contribu?ng a major percentage to the burden of TB. India is grouped under high TB, high HIV associated TB and MDR TB burden countries and 1.24 lakh fell ill with drug resistant TB out of which 56000 were started on second line treatment in 2020. Annually India accounts for 27% of missing TB cases. Diagnosis: The major forms of drug resistant TB that are of clinical importance are INH monoresistant TB, mul?drug resistant TB, pre- XDR TB and XDR TB.WHO approved newer molecular tests for MTB detec?on and drug suscep?bility tests. Treatment: Few newer drugs and few previously used drugs are showing promise when used in combina?on which have come up in recent years. Bedaquiline based regimens are showing improved cure rates. Conclusion: Guidelines based regimens should be strictly adhered to by both public and private TB case trea?ng physicians.

Nuevas perspectivas terapéuticas en tuberculosis / New perspectives in tuberculosis treatment

To advance in the control and elimination of tuberculosis (TB) we must achieve a high level of effectiveness in the prevention of TB in populations infected by Mycobacterium tuberculosis. Latent TB prevention success with current therapies (single isoniazid or in combination with rifampicin) is close to 60%. We also must offer a high level of treatment success in first-line drugs sensitive TB patients. With currently available drugs (isoniazid, rifampicin, ethambutol and pyrazinamide) treatment success should reach at least 95%. Drug side reactions together with the lengthen treatment of infection and disease (6 months) decrease the compliance to these therapies. In Multi-Drug-Resistant TB (MDR-TB), therapies are even longer (20 months according to WHO's recommendation) and much less tolerated, with rates of success under 50%. New trials for latent TB using rifapentin and isoniacid; combined fixed-dose offirst-line drugs in sensible TB, and the addition of new drugs (fluorquinolones, bedaquiline, delamanid and linezolid) in multi-drug resistant TB, together with shorter regimens of 12 months duration which include Clofazimine (experience in Cameroon with modification of a 9 months trial previously used in Bangladesh showing 89% cure) are discussed in this article.

Para el control y eliminación de la tuberculosis se debe lograr un alto grado de eficacia en la prevención del desarrollo de tuberculosis en la población infectada por Mycobacterium tuberculosis. Esta prevención, con las terapias actuales de la tuberculosis latente (isoniazida sola o combinada con rifampicina), es cercana al 60%. También debemos alcanzar una alta tasa de curación para los enfermos con tuberculosis sensible a los fármacos de primera línea (vírgenes a tratamiento). Con los fármacos actualmente disponibles (isoniazida, rifampicina, etambutol y pirazinamida) esta curación debería alcanzar a no menos del 95%. La regular tolerancia y reacciones colaterales de los fármacos y el largo tiempo que demandan las terapias de la infección y de la enfermedad (6 meses) atenta contra su adherencia. En el caso de la Tuberculosis Multi-Drogo-Resistente (TB-MDR), los tratamientos son aún más prolongados (20 meses según recomienda la OMS actualmente) y menos tolerados, siendo sus tasas de curación inferiores a 50%. Se analizan nuevos esquemas para el tratamiento de la tuberculosis latente usando rifapentina asociada a isoniacida; dosis fijas combinadas de fármacos de primera línea para tuberculosis sensibles, y asociación de fármacos antiguos y nuevos (fluoroquinolonas, bedaquilina, delamanid y linezolid) para el tratamiento de las tuberculosis multirresistentes. También se presentan nuevos esquemas acortados, de 12 meses de duración, que incluyen clofazimina (experiencia en Camerún con modificación del esquema de 9 meses usado previamente en Bangladesh, con tasas de curación de 89%).

Results of molecular genetic study of m. Tuberculosis strains isolated from specimens of mdr-tb suspects in Ulaanbaatar, Mongolia in 2009-2010 / Монголын Анагаах Ухаан

Bacground: DST by conventional methods takes several weeks, while early diagnosis of the disease and the rapid identification of resistant strains are essential for efficient treatment and control of the MDR strains. Rapid molecular testing of detecting MDR-TB is needed.Objective: The aim of this study was to assess performance of molecular line probe assay, Genotype16 MTBDRp/us, for rapid detection of RIF and INH resistance for M.Tuberculosis in Mongolia. The sensitivity and specificity of Genotype® MTBDRp/us to detect RIF and INH resistance-associated mutations in culture specimens and directly in smear-positive clinical specimens was examined and compared with conventional culture and drug susceptibility testing on solid medium.Material and Methods: The subjects of this study were 218 MDR-TB suspects aged 14-75 years from 8 districts in Ulaanbaatar city. The study was conducted from July 2009 to May 2010. The Genotype M. Tuberculosis drug resistance first line (MTBDR plus) assay (Hain Life-science, Nehren, Germany) was tested on directly on 41 sputum specimens and 109 clinical isolates.Results: The high correlation of the results from Genotype® MTBDRp/us and conventional drug susceptibility testing was obtained from this study. The results clearly show high performance of Genotype® MTBDRp/us with almost 100% accuracy for all the important indicators, such as sensitivity, specificity, positive and negative predictive values of detection of RIF and INH resistance. Some minor discrepancies were obtained in comparison with DNA sequencing results.Our study found that among high proportion for detection of RIF resistance, S531L mutation (MUT3 band) occurred the most commonly, with 80.0% of all RIF-resistant strains (83.6% of MDR) having the mutation. Other mutation in the 530-533 regions was common, as detected by the lack of binding to the WT8 probe in the absence of S531L mutation.In this study we observed that mutations in the promoter region of inhA gene played a major role (67.6 % (63.9% of MDR strains and 90% of INH-mono-resistant strains) had a mutation in the inhA.Conclusion: The Genotype® MTBDRp/us assay was demonstrated as a rapid, reliable and highly accurate tool for early detection of MDR-TB through examining smear positive cases enabling early start of appropriate therapeutic and public health measures to control of the spread of drug resistant M.tuberculosis in the population.

Detection of Rifampin Resistant Mycobacterium tuberculosis complex using Denaturing HPLC / 대한진단검사의학회지

BACKGROUND: Tuberculosis (TB) remains an important cause of morbidity and mortality throughout the world. The surge of TB has been accompanied by an increase in multi-drug-resistant tuberculosis (MDR-TB). In this study, we developed a denaturing HPLC (DHPLC) method for detecting rpoB gene mutation as a rifampin resistance based on sequence. METHODS: In this study, we used 99 mycobacterial isolates grown in Ogawa media. At first, we used a PCR method that can amplify the 235 bp and 136 bp rpoB DNAs of Mycobacterium tuberculosis complex (MTB) and Non-tuberculous mycobacteria (NTM). And then, PCR-restriction fragment length polymorphism (RFLP) of rpoB DNA (342 bp), which comprises the Rif(T) region, was used for the differential identification of Mycobacteria. Finally, we detected these amplicons by DHPLC, compared to PCR-RFLP results, and performed sequencing. RESULTS: Among 99 mycobacterial isolates, 80 (81%) were MTB and 19 (19%) were NTM. NTM were identified to 7 different species by DHPLC and PCR-RFLP. rpoB mutation was detected in 9 (11%) of the MTB specimens. These results were confirmed by using sequencing. CONCLUSIONS: DHPLC provided a rapid, simple, and automatable performance for detection of rifampin resistant Mycobacterium tuberculosis complex and would be helpful as a supplemental method in high-throughput clinical laboratories.