Isoniazid and Rifapentine Treatment Eradicates Persistent Mycobacterium tuberculosis in Macaques.
Am J Respir Crit Care Med
; 201(4): 469-477, 2020 02 15.
Article
en En
| MEDLINE
| ID: mdl-31647877
ABSTRACT
Rationale Direct evidence for persistence of Mycobacterium tuberculosis (Mtb) during asymptomatic latent tuberculosis infection (LTBI) in humans is currently lacking. Moreover, although a 12-week regimen of once-weekly isoniazid and rifapentine (3HP) is currently recommended by the CDC as treatment for LTBI, experimental evidence for 3HP-mediated clearance of persistent Mtb infection in human lungs has not been established.Objectives:
Using a nonhuman primate (NHP) model of TB, we sought to assess 3HP treatment-mediated clearance of Mtb infection in latently infected macaques.Methods:
Sixteen NHPs were infected via inhalation with â¼10 cfu of Mtb CDC1551, after which asymptomatic animals were either treated with 3HP or left untreated. Pharmacokinetics of the 3HP regimen were measured. Following treatment, animals were coinfected with simian immunodeficiency virus to assess reactivation of LTBI and development of active TB disease.Measurements and MainResults:
Fourteen NHPs remained free of clinical signs or microbiological evidence of active TB following infection with Mtb and were subsequently either treated with 3HP (n = 7) or left untreated (n = 7). Untreated NHPs were asymptomatic for 7 months but harbored persistent Mtb infection, as shown by reactivation of latent infection following simian immunodeficiency virus coinfection. However, none of the treated animals developed TB reactivation disease, and they remained without clinical or microbiological evidence of persistent bacilli, suggesting treatment-mediated clearance of bacteria.Conclusions:
Mtb can persist in asymptomatic macaques for at least 7 months. Furthermore, 3HP treatment effectively cleared bacteria and prevented reactivation of TB in latently infected macaques.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
1_ASSA2030
/
2_ODS3
Problema de salud:
1_doencas_transmissiveis
/
2_enfermedades_transmissibles
Asunto principal:
Rifampin
/
Tuberculosis
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Tuberculosis Latente
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Isoniazida
/
Antibióticos Antituberculosos
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Mycobacterium tuberculosis
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Antituberculosos
Límite:
Animals
Idioma:
En
Revista:
Am J Respir Crit Care Med
Asunto de la revista:
TERAPIA INTENSIVA
Año:
2020
Tipo del documento:
Article