Immunotherapy with Mycobacterium vaccae in patients with newly diagnosed pulmonary tuberculosis:: a randomised controlled trial

Background Mycobacterium vaccae, an environmental saprophyte, has immunogenic properties that enhance the host immune response. Immunotherapy with M vaccae has been suggested to shorten short-course antituberculosis chemotherapy. We tested the hypothesis that the addition of M vaccae to standard short-course antituberculosis chemotherapy would decrease the time to achieve a negative sputum culture. Methods Patients with newly diagnosed tuberculosis were randomly assigned an injection of saline (placebo) or M vaccae on day 8. All patients received antituberculosis chemotherapy with rifampicin, isoniazid, pyrazinamide, and ethambutol. Sputum samples were checked by microscopy and culture every week for the first 8 weeks and monthly until the end of chemotherapy at 6 months. The primary outcome was the time to a negative sputum culture in the first 8 weeks. Intention-to-treat analysis was used and time to sputum clearance was assessed by log-rank test and Cox's proportional-hazards regression. Findings 172 patients received M vaccae and 175 patients received placebo. At 8 weeks, 70 patients in the M vaccae group and 65 patients in the placebo group had a negative culture; there was no difference between groups in the time to a negative culture (p=0.83). There was no interaction between HIV status and treatment. Interpretation M vaccae immunotherapy has no benefit when added to standard antituberculosis chemotherapy.