Effectiveness and safety of a treatment regimen based on isoniazid plus vaccination with Mycobacterium tuberculosis cells' fragments: field-study with naturally Mycobacterium caprae-infected goats.
The identification of a herd of goats with tuberculosis let us test a new treatment regimen against latent tuberculosis infection (LTBI). Using large animal experimental models allows a better approach to understanding human tuberculosis according to immunopathological parameters. Based on an initial study showing a correlation between the ESAT-6-specific interferon (IFN)-gamma secretion and the severity of pulmonary lesions, this parameter was used in combination with an X-ray examination to screen the animals to be included in the efficacy and safety studies. All the animals proved to be infected with Mycobacterium caprae. The efficacy study was run in animals distributed in three experimental groups according to treatment: untreated (CT), treated with isoniazid (INH), and treated with INH + RUTI (a vaccine based on M. tuberculosis cell fragments) inoculated twice. RUTI temporarily increased the IFN-gamma production after stimulating the peripheral blood with ESAT-6, purified protein derivative and RUTI in vitro. The INH chemotherapy reduced both pulmonary and extra pulmonary affectation, but not disease in pulmonary lymph nodes. The addition of RUTI may have decreased extrapulmonary disease further but had no benefit to lung or lung lymph-nodes itself. Safety studies showed that inoculation of RUTI caused a temporary increase of rectal temperature (1-2 degrees C) and local swelling, both adverse effects being well tolerated. Neither systemic toxicity nor mortality was induced by the vaccination. The control of goats' infection by the therapeutic regimen consisting in INH chemotherapy + RUTI as well as its safety, represented a further step towards testing its effects in human LTBI in a future.
Centre de Recerca en Sanitat Animal, UAB-IRTA, Bellaterra, Catalonia, Spain.
M
M
Domingo
O
O
Gil
E
E
Serrano
E
E
Guirado
M
M
Nofrarias
M
M
Grassa
N
N
Cáceres
B
B
Pérez
C
C
Vilaplana
P-J
PJ
Cardona
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology / Q000627:therapeutic use; D000995:Antitubercular Agents / Q000627:therapeutic use*; D005260:Female; D006041:Goats; D007371:Interferon-gamma / Q000096:biosynthesis; D007538:Isoniazid / Q000627:therapeutic use*; D009161:Mycobacterium / Q000276:immunology*; D014376:Tuberculosis / Q000473:pathology / Q000628:therapy* / Q000662:veterinary*; D032581:Tuberculosis Vaccines / Q000276:immunology*
D000942:Antigens, Bacterial; D000995:Antitubercular Agents; D032581:Tuberculosis Vaccines; D007371:Interferon-gamma; D007538:Isoniazid