Isoniazid and rifapentine treatment effectively reduces persistent M. tuberculosis infection in macaque lungs
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 rhes...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Clinical Investigation
2022-09-01
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| Series: | The Journal of Clinical Investigation |
| Subjects: | |
| Online Access: | https://doi.org/10.1172/JCI161564 |
| _version_ | 1797634588712894464 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Riti Sharan |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T12:09:44Z |
| format | Article |
| id | doaj.art-659732e8266a421b8e6775d23db444b0 |
| institution | Directory Open Access Journal |
| issn | 1558-8238 |
| language | English |
| last_indexed | 2024-03-11T12:09:44Z |
| publishDate | 2022-09-01 |
| publisher | American Society for Clinical Investigation |
| record_format | Article |
| series | The Journal of Clinical Investigation |
| spelling | doaj.art-659732e8266a421b8e6775d23db444b02023-11-07T16:19:20ZengAmerican Society for Clinical InvestigationThe Journal of Clinical Investigation1558-82382022-09-0113218Isoniazid and rifapentine treatment effectively reduces persistent M. tuberculosis infection in macaque lungsRiti SharanShashank R. GanatraDhiraj K. SinghJourney ColeTaylor W. ForemanRajesh ThippeshappaCharles A. PeloquinVinay ShivannaOlga GonzalezCheryl L. DayNeel R. GandhiEdward J. Dick Jr.Shannan Hall-UrsoneSmriti MehraLarry S. SchlesingerJyothi RengarajanDeepak KaushalA 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.https://doi.org/10.1172/JCI161564Infectious disease |
| spellingShingle | 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 Isoniazid and rifapentine treatment effectively reduces persistent M. tuberculosis infection in macaque lungs The Journal of Clinical Investigation Infectious disease |
| title | Isoniazid and rifapentine treatment effectively reduces persistent M. tuberculosis infection in macaque lungs |
| title_full | Isoniazid and rifapentine treatment effectively reduces persistent M. tuberculosis infection in macaque lungs |
| title_fullStr | Isoniazid and rifapentine treatment effectively reduces persistent M. tuberculosis infection in macaque lungs |
| title_full_unstemmed | Isoniazid and rifapentine treatment effectively reduces persistent M. tuberculosis infection in macaque lungs |
| title_short | Isoniazid and rifapentine treatment effectively reduces persistent M. tuberculosis infection in macaque lungs |
| title_sort | isoniazid and rifapentine treatment effectively reduces persistent m tuberculosis infection in macaque lungs |
| topic | Infectious disease |
| url | https://doi.org/10.1172/JCI161564 |
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