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Author Notes:

Deepak Kaushal, Southwest National Primate Research Center, Texas Biomedical Research Institute, 8715 W. Military Drive, San Antonio, Texas 78227, USA. Phone: 210.258.9209; Email: dkaushal@txbiomed.org

Jyothi Rengarajan, Emory Vaccine Center 954 Gatewood Road, Room 1022, Atlanta, Georgia 30329, USA. Phone: 404.727.8174; Email: jrengar@emory.edu

DK and JR conceptualized and funded this research. DK, RS, JR, SM, TWF, and CLD designed the experiments. RS, SRG, DKS, JC, RT, CAP, VS, OG, EJD, SHU, and SM performed the experiments. RS, SRG, TWF, RT, CAP, VS, OG, EJD, SHU, SM, DK, and JR analyzed the results. RS, DK, NG, LSS, and JR wrote the manuscript.

The authors acknowledge the invaluable contribution of the Veterinary and Pathology services and staff; Renee Escalona, Jesse Martinez, and Colin Chubafor histology support; Dedra Brown, Karla Valle, and Mariana Rodriguez for necropsy support at SNPRC and Texas Biomedical Research Institute.

The authors have declared that no conflict of interest exists.

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Research Funding:

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.

This research was supported by philanthropic funding to Texas Biomedical Research Institute.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Medicine, Research & Experimental
  • Research & Experimental Medicine
  • LATENT TUBERCULOSIS
  • MECHANISMS
  • MODEL

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

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Journal Title:

JOURNAL OF CLINICAL INVESTIGATION

Volume:

Volume 132, Number 18

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Type of Work:

Article | Final Publisher PDF

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:

Copyright information:

© 2022 Sharan et al.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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