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

Riti Sharan1, Shashank R Ganatra1, Dhiraj K Singh1

  • 1Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, Texas, USA.

The Journal of Clinical Investigation
|July 21, 2022
PubMed

Insights

Once-weekly isoniazid and rifapentine (3HP) effectively clears tuberculosis bacteria in macaques with latent infection. This treatment prevented tuberculosis reactivation, showing its potential for latent tuberculosis infection management.

Area of Science:

  • Microbiology
  • Infectious Diseases
  • Pharmacology

Background:

  • Latent tuberculosis infection (LTBI) is a significant global health concern.
  • The CDC recommends a 3-month once-weekly oral regimen of isoniazid and rifapentine (3HP) for LTBI treatment.
  • Assessing the efficacy of 3HP in a preclinical model is crucial for understanding its impact on Mycobacterium tuberculosis clearance.

Purpose of the Study:

  • To evaluate the efficacy of 3HP in clearing M. tuberculosis in macaques with asymptomatic LTBI.
  • To assess the preventative effect of 3HP on LTBI reactivation to active tuberculosis (ATB).

Main Methods:

  • Twelve Indian-origin rhesus macaques were infected with M. tuberculosis via aerosol.
  • Six macaques received 3HP treatment; six served as untreated controls.
  • Positron emission tomography/computed tomography (PET/CT) imaging was used for monitoring.
  • Following treatment, most animals were coinfected with SIV to assess LTBI reactivation.

Main Results:

  • Four out of six 3HP-treated macaques showed no persistent bacilli or extrapulmonary spread.
  • PET/CT imaging revealed significantly fewer granulomas in treated animals compared to controls.
  • Untreated animals exhibited persistent bacilli and TB reactivation after SIV coinfection.
  • No treated animals reactivated to active tuberculosis.

Conclusions:

  • 3HP treatment significantly reduces persistent M. tuberculosis infection in a macaque model.
  • 3HP effectively prevents the reactivation of latent tuberculosis infection to active disease.
  • This study supports the use of 3HP for managing latent tuberculosis infection.
Keywords:
Infectious diseaseTuberculosis

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