Isoniazid and rifapentine treatment effectively reduce persistent M. tuberculosis infection in macaque lungs

• Type of Material: Article
• Authors: Riti Sharan, Southwest National Primate Research Center; Shashank R Ganatra, Southwest National Primate Research Center; Dhiraj K Singh, Southwest National Primate Research Center; Journey Cole, Southwest National Primate Research Center; Taylor W Foreman, National Institute of Allergy and Infectious Diseases; Rajesh Thippeshappa, Southwest National Primate Research Center; Charles A Peloquin, University of Florida; Vinay Shivanna, Southwest National Primate Research Center; Olga Gonzalez, Southwest National Primate Research Center; Cheryl Day, Emory University; Neel Gandhi, Emory University; Edward J Dick, Southwest National Primate Research Center; Shannan Hall-Ursone, Southwest National Primate Research Center; Smriti Mehra, Southwest National Primate Research Center; Larry S Schlesinger, Southwest National Primate Research Center; Jyothi Rengarajan, Emory University; Deepak Kaushal, Southwest National Primate Research Center
• Language: English
• Date: 2022-09-15
• Publisher: AMER SOC CLINICAL INVESTIGATION INC
• Publication Version: Final Published Version
• Copyright Statement: © 2022 Sharan et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1172/JCI161564
• Title of Journal or Parent Work: JOURNAL OF CLINICAL INVESTIGATION
• Volume: 132
• Issue: 18
• Grant/Funding Information: This research was supported by philanthropic funding to Texas Biomedical Research Institute.; This research was supported by institutional grants from the Office of the Director, NIH grant P51OD011133 (to SNPRC), and NIH grant S10OD028732, which provide core support to experiments and were funded by donor funds from the Texas Biomedical Research Institute.
• Keywords: Life Sciences & Biomedicine; Science & Technology; Medicine, Research & Experimental; MODEL; MECHANISMS; Research & Experimental Medicine; LATENT TUBERCULOSIS
• Research Categories: Health Sciences, Medicine and Surgery

Abstract

A once-weekly oral dose of isoniazid and rifapentine for 3 months (3HP) is recommended by the CDC for treatment of latent tuberculosis infection (LTBI). The aim of this study is to assess 3HP-mediated clearance of M. tuberculosis bacteria in macaques with asymptomatic LTBI. Twelve Indian-origin rhesus macaques were infected with a low dose (∼10 CFU) of M. tuberculosis CDC1551 via aerosol. Six animals were treated with 3HP and 6 were left untreated. The animals were imaged via PET/CT at frequent intervals. Upon treatment completion, all animals except 1 were coinfected with SIV to assess reactivation of LTBI to active tuberculosis (ATB). Four of 6 treated macaques showed no evidence of persistent bacilli or extrapulmonary spread until the study end point. PET/CT demonstrated the presence of significantly more granulomas in untreated animals relative to the treated group. The untreated animals harbored persistent bacilli and demonstrated tuberculosis (TB) reactivation following SIV coinfection, while none of the treated animals reactivated to ATB. 3HP treatment effectively reduced persistent infection with M. tuberculosis and prevented reactivation of TB in latently infected macaques. Copyright: