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Isoniazid and rifapentine treatment effectively reduces persistent M. tuberculosis infection in macaque lungs
The Journal of Clinical Investigation ( IF 13.3 ) Pub Date : 2022 , DOI: 10.1172/jci161564
Riti Sharan 1 , Shashank R Ganatra 1 , Dhiraj K Singh 1 , Journey Cole 1 , Taylor W Foreman 2 , Rajesh Thippeshappa 1 , Charles A Peloquin 3 , Vinay Shivanna 1 , Olga Gonzalez 1 , Cheryl L Day 4 , Neel R Gandhi 4, 5, 6 , Edward J Dick 1 , Shannan Hall-Ursone 1 , Smriti Mehra 1 , Larry S Schlesinger 1 , Jyothi Rengarajan 4, 5, 6 , Deepak Kaushal 1
Affiliation  

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.

中文翻译:


异烟肼和利福喷丁治疗可有效减少猕猴肺部的持续结核分枝杆菌感染



CDC 建议每周一次口服异烟肼和利福喷丁,持续 3 个月 (3HP),用于治疗潜伏性结核感染 (LTBI)。本研究的目的是评估 3HP 介导的无症状 LTBI 猕猴中结核分枝杆菌的清除情况。 12 只印度恒河猴通过气溶胶感染了低剂量 (~10 CFU)结核分枝杆菌CDC1551。六只动物接受了 3HP 治疗,六只动物未接受治疗。通过 PET/CT 定期对动物进行成像。治疗完成后,除 1 只动物外,所有动物均同时感染 SIV,以评估 LTBI 重新激活为活动性结核病 (ATB)。 6 只接受治疗的猕猴中,有 4 只在研究结束前没有显示出持续性杆菌或肺外传播的证据。 PET/CT 表明,与治疗组相比,未经治疗的动物存在明显更多的肉芽肿。未经治疗的动物体内含有持久性杆菌,并在 SIV 合并感染后表现出结核病 (TB) 重新激活,而接受治疗的动物均未重新激活 ATB。 3HP 治疗可有效减少结核分枝杆菌的持续感染,并防止潜伏感染的猕猴中结核病的重新激活。
更新日期:2022-09-16
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