Predictors of unfavorable responses to therapy in rifampicin-sensitive pulmonary tuberculosis using an integrated approach of radiological presentation and sputum mycobacterial burden.

<h4>Introduction</h4>Despite the exalted status of sputum mycobacterial load for gauging pulmonary tuberculosis treatment and progress, Chest X-rays supplement valuable information for taking instantaneous therapeutic decisions, especially during the COVID-19 pandemic. Even though litera...

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Autores principales:	Narendran Gopalan, Vignes Anand Srinivasalu, Ponnuraja Chinnayan, Banurekha Velayutham, Adhin Bhaskar, Ramesh Santhanakrishnan, Thirumaran Senguttuvan, Sridhar Rathinam, Mahilmaran Ayyamperumal, Kumar Satagopan, Dhanalakshmi Rajendran, Tamizhselvan Manoharan, Sekar Lakshmanan, Paulkumaran Paramasivam, Dhanalakshmi Angamuthu, Mangalambal Ganesan, John Washington Easudoss Arockia, Ramesh Babu Venkatesan, Venkatesan Lakshmipathy, Shivakumar Shanmugham, Balaji Subramanyam, Shakila Shankar, Jawahar Mohideen Shaheed, Baskaran Dhanaraj, Narayanan Paranji Ramiyengar, Soumya Swaminathan, Padmapriyadarsini Chandrasekaran
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/24bd32c0dc5a4cd3b6c69c8326d74016
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language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Narendran Gopalan Vignes Anand Srinivasalu Ponnuraja Chinnayan Banurekha Velayutham Adhin Bhaskar Ramesh Santhanakrishnan Thirumaran Senguttuvan Sridhar Rathinam Mahilmaran Ayyamperumal Kumar Satagopan Dhanalakshmi Rajendran Tamizhselvan Manoharan Sekar Lakshmanan Paulkumaran Paramasivam Dhanalakshmi Angamuthu Mangalambal Ganesan John Washington Easudoss Arockia Ramesh Babu Venkatesan Venkatesan Lakshmipathy Shivakumar Shanmugham Balaji Subramanyam Shakila Shankar Jawahar Mohideen Shaheed Baskaran Dhanaraj Narayanan Paranji Ramiyengar Soumya Swaminathan Padmapriyadarsini Chandrasekaran Predictors of unfavorable responses to therapy in rifampicin-sensitive pulmonary tuberculosis using an integrated approach of radiological presentation and sputum mycobacterial burden.
description	<h4>Introduction</h4>Despite the exalted status of sputum mycobacterial load for gauging pulmonary tuberculosis treatment and progress, Chest X-rays supplement valuable information for taking instantaneous therapeutic decisions, especially during the COVID-19 pandemic. Even though literature on individual parameters is overwhelming, few studies have explored the interaction between radiographic parameters denoting severity with mycobacterial burden signifying infectivity. By using a sophisticated approach of integrating Chest X-ray parameters with sputum mycobacterial characteristics, evaluated at all the three crucial time points of TB treatment namely pre-treatment, end of intensive phase and completion of treatment, utilizing the interactive Cox Proportional Hazards model, we aimed to precisely deduce predictors of unfavorable response to TB treatment.<h4>Materials and method</h4>We extracted de-identified data from well characterized clinical trial cohorts that recruited rifampicin-sensitive Pulmonary TB patients without any comorbidities, taking their first spell of anti-tuberculosis therapy under supervision and meticulous follow up for 24 months post treatment completion, to accurately predict TB outcomes. Radiographic data independently obtained, interpreted by two experienced pulmonologists was collated with demographic details and, sputum smear and culture grades of participants by an independent statistician and analyzed using the Cox Proportional Hazards model, to not only adjust for confounding factors including treatment effect, but also explore the interaction between radiological and bacteriological parameters for better therapeutic application.<h4>Results</h4>Of 667 TB patients with data available, cavitation, extent of involvement, lower zone involvement, smear and culture grade at baseline were significant parameters predisposing to an unfavorable TB treatment outcome in the univariate analysis. Reduction in radiological lesions in Chest X-ray by at least 50% at 2 months and 75% at the end of treatment helped in averting unfavorable responses. Smear and Culture conversion at the end of 2 months was highly significant as a predictor (p<0.001). In the multivariate analysis, the adjusted hazards ratios (HR) for an unfavorable response to TB therapy for extent of involvement, baseline cavitation and persistence (post treatment) were 1.21 (95% CI: 1.01-1.44), 1.73 (95% CI: 1.05-2.84) and 2.68 (95% CI: 1.4-5.12) respectively. A 3+ smear had an HR of 1.94 (95% CI: 0.81-4.64). Further probing into the interaction, among patients with 3+ and 2+ smears, HRs for cavitation were 3.26 (95% CI: 1.33-8.00) and 1.92 (95% CI: 0.80-4.60) while for >2 zones, were 3.05 (95% CI: 1.12-8.23) and 1.92 (95% CI: 0.72-5.08) respectively. Patients without cavitation, zonal involvement <2, and a smear grade less than 2+ had a better prognosis and constituted minimal disease.<h4>Conclusion</h4>Baseline Cavitation, Opacities occupying >2 zones and 3+ smear grade individually and independently forecasted a poorer TB outcome. The interaction model revealed that Zonal involvement confined to 2 zones, without a cavity and smear grade up to 2+, constituting "minimal disease", had a better prognosis. Radiological clearance >50% along with smear conversion at the end of intensive phase of treatment, observed to be a reasonable alternative to culture conversion in predicting a successful outcome. These parameters may potentially take up key positions as stratification factors for future trials contemplating on shorter TB regimens.
format	article
author	Narendran Gopalan Vignes Anand Srinivasalu Ponnuraja Chinnayan Banurekha Velayutham Adhin Bhaskar Ramesh Santhanakrishnan Thirumaran Senguttuvan Sridhar Rathinam Mahilmaran Ayyamperumal Kumar Satagopan Dhanalakshmi Rajendran Tamizhselvan Manoharan Sekar Lakshmanan Paulkumaran Paramasivam Dhanalakshmi Angamuthu Mangalambal Ganesan John Washington Easudoss Arockia Ramesh Babu Venkatesan Venkatesan Lakshmipathy Shivakumar Shanmugham Balaji Subramanyam Shakila Shankar Jawahar Mohideen Shaheed Baskaran Dhanaraj Narayanan Paranji Ramiyengar Soumya Swaminathan Padmapriyadarsini Chandrasekaran
author_facet	Narendran Gopalan Vignes Anand Srinivasalu Ponnuraja Chinnayan Banurekha Velayutham Adhin Bhaskar Ramesh Santhanakrishnan Thirumaran Senguttuvan Sridhar Rathinam Mahilmaran Ayyamperumal Kumar Satagopan Dhanalakshmi Rajendran Tamizhselvan Manoharan Sekar Lakshmanan Paulkumaran Paramasivam Dhanalakshmi Angamuthu Mangalambal Ganesan John Washington Easudoss Arockia Ramesh Babu Venkatesan Venkatesan Lakshmipathy Shivakumar Shanmugham Balaji Subramanyam Shakila Shankar Jawahar Mohideen Shaheed Baskaran Dhanaraj Narayanan Paranji Ramiyengar Soumya Swaminathan Padmapriyadarsini Chandrasekaran
author_sort	Narendran Gopalan
title	Predictors of unfavorable responses to therapy in rifampicin-sensitive pulmonary tuberculosis using an integrated approach of radiological presentation and sputum mycobacterial burden.
title_short	Predictors of unfavorable responses to therapy in rifampicin-sensitive pulmonary tuberculosis using an integrated approach of radiological presentation and sputum mycobacterial burden.
title_full	Predictors of unfavorable responses to therapy in rifampicin-sensitive pulmonary tuberculosis using an integrated approach of radiological presentation and sputum mycobacterial burden.
title_fullStr	Predictors of unfavorable responses to therapy in rifampicin-sensitive pulmonary tuberculosis using an integrated approach of radiological presentation and sputum mycobacterial burden.
title_full_unstemmed	Predictors of unfavorable responses to therapy in rifampicin-sensitive pulmonary tuberculosis using an integrated approach of radiological presentation and sputum mycobacterial burden.
title_sort	predictors of unfavorable responses to therapy in rifampicin-sensitive pulmonary tuberculosis using an integrated approach of radiological presentation and sputum mycobacterial burden.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/24bd32c0dc5a4cd3b6c69c8326d74016
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spelling	oai:doaj.org-article:24bd32c0dc5a4cd3b6c69c8326d740162021-11-25T06:23:29ZPredictors of unfavorable responses to therapy in rifampicin-sensitive pulmonary tuberculosis using an integrated approach of radiological presentation and sputum mycobacterial burden.1932-620310.1371/journal.pone.0257647https://doaj.org/article/24bd32c0dc5a4cd3b6c69c8326d740162021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0257647https://doaj.org/toc/1932-6203<h4>Introduction</h4>Despite the exalted status of sputum mycobacterial load for gauging pulmonary tuberculosis treatment and progress, Chest X-rays supplement valuable information for taking instantaneous therapeutic decisions, especially during the COVID-19 pandemic. Even though literature on individual parameters is overwhelming, few studies have explored the interaction between radiographic parameters denoting severity with mycobacterial burden signifying infectivity. By using a sophisticated approach of integrating Chest X-ray parameters with sputum mycobacterial characteristics, evaluated at all the three crucial time points of TB treatment namely pre-treatment, end of intensive phase and completion of treatment, utilizing the interactive Cox Proportional Hazards model, we aimed to precisely deduce predictors of unfavorable response to TB treatment.<h4>Materials and method</h4>We extracted de-identified data from well characterized clinical trial cohorts that recruited rifampicin-sensitive Pulmonary TB patients without any comorbidities, taking their first spell of anti-tuberculosis therapy under supervision and meticulous follow up for 24 months post treatment completion, to accurately predict TB outcomes. Radiographic data independently obtained, interpreted by two experienced pulmonologists was collated with demographic details and, sputum smear and culture grades of participants by an independent statistician and analyzed using the Cox Proportional Hazards model, to not only adjust for confounding factors including treatment effect, but also explore the interaction between radiological and bacteriological parameters for better therapeutic application.<h4>Results</h4>Of 667 TB patients with data available, cavitation, extent of involvement, lower zone involvement, smear and culture grade at baseline were significant parameters predisposing to an unfavorable TB treatment outcome in the univariate analysis. Reduction in radiological lesions in Chest X-ray by at least 50% at 2 months and 75% at the end of treatment helped in averting unfavorable responses. Smear and Culture conversion at the end of 2 months was highly significant as a predictor (p<0.001). In the multivariate analysis, the adjusted hazards ratios (HR) for an unfavorable response to TB therapy for extent of involvement, baseline cavitation and persistence (post treatment) were 1.21 (95% CI: 1.01-1.44), 1.73 (95% CI: 1.05-2.84) and 2.68 (95% CI: 1.4-5.12) respectively. A 3+ smear had an HR of 1.94 (95% CI: 0.81-4.64). Further probing into the interaction, among patients with 3+ and 2+ smears, HRs for cavitation were 3.26 (95% CI: 1.33-8.00) and 1.92 (95% CI: 0.80-4.60) while for >2 zones, were 3.05 (95% CI: 1.12-8.23) and 1.92 (95% CI: 0.72-5.08) respectively. Patients without cavitation, zonal involvement <2, and a smear grade less than 2+ had a better prognosis and constituted minimal disease.<h4>Conclusion</h4>Baseline Cavitation, Opacities occupying >2 zones and 3+ smear grade individually and independently forecasted a poorer TB outcome. The interaction model revealed that Zonal involvement confined to 2 zones, without a cavity and smear grade up to 2+, constituting "minimal disease", had a better prognosis. Radiological clearance >50% along with smear conversion at the end of intensive phase of treatment, observed to be a reasonable alternative to culture conversion in predicting a successful outcome. These parameters may potentially take up key positions as stratification factors for future trials contemplating on shorter TB regimens.Narendran GopalanVignes Anand SrinivasaluPonnuraja ChinnayanBanurekha VelayuthamAdhin BhaskarRamesh SanthanakrishnanThirumaran SenguttuvanSridhar RathinamMahilmaran AyyamperumalKumar SatagopanDhanalakshmi RajendranTamizhselvan ManoharanSekar LakshmananPaulkumaran ParamasivamDhanalakshmi AngamuthuMangalambal GanesanJohn Washington Easudoss ArockiaRamesh Babu VenkatesanVenkatesan LakshmipathyShivakumar ShanmughamBalaji SubramanyamShakila ShankarJawahar Mohideen ShaheedBaskaran DhanarajNarayanan Paranji RamiyengarSoumya SwaminathanPadmapriyadarsini ChandrasekaranPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 9, p e0257647 (2021)

Predictors of unfavorable responses to therapy in rifampicin-sensitive pulmonary tuberculosis using an integrated approach of radiological presentation and sputum mycobacterial burden.

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