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

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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.

Authors

Riti Sharan, Shashank R. Ganatra, Dhiraj K. Singh, Journey Cole, Taylor W. Foreman, Rajesh Thippeshappa, Charles A. Peloquin, Vinay Shivanna, Olga Gonzalez, Cheryl L. Day, Neel R. Gandhi, Edward J. Dick Jr., Shannan Hall-Ursone, Smriti Mehra, Larry S. Schlesinger, Jyothi Rengarajan, Deepak Kaushal