Micobacterium vaccae immunotherapy for tuberculosis in rural KwaZulu, South Africa

It is estimated that one third of the world's population are infected with M. tuberculosis and that tuberculosis causes 7% of all deaths together with 26% of preventable deaths. Despite well-established six or nine month chemotherapy regimens problems continue with failure of tuberculosis control programmes, incomplete patient compliance, dual infection with Human Immunodeficiency Virus and multi-drug resistance. Potential new modes of therapy require examination. Pilot studies with killed Mycobacterium vaccae as an immunotherapeutic agent together with standard chemotherapy have shown promise in improving on standard chemotherapy. This thesis represents a double blind controlled field trial of 204 patients with tuberculosis at Mseleni and Manguzi Hospitals in KwaZulu, South Africa. M. vaccae was administered intradermally alongside established six-month quadruple chemotherapy, tetanus toxoid was utilised as placebo. M. vaccae recipients gained 0.81 kg/week compared with 0.53 kg/week for placebo patients (p=0.055), the greatest advantage of rate of weight gain occurred in the first two months of treatment. Amongst weight gainers the active group gained 1.04 kg/week compared with the placebo group's gain of 0.67 kg/week (p=0.011). Clinically assessed cure rates were 71.4% and 80.0% for M. vaccae and placebo groups respectively, with corresponding relapse rates 20.0% and 11.4% (p=0.577). At eight weeks sputum culture conversion to negative was unexpectedly low at 44.8% and 38.8% in active and placebo cases respectively (p=0.676). No difference was identified on analysing chest radiography or erythrocyte sedimentation rate. Case fatalities at six months were higher than expected at 7.1% in each treatment arm. Patients were followed-up three to four years after treatment, the health status for 60.1% of cases was ascertained. Tuberculosis deaths rose to 14.5% in the M. vaccae group and 16.1% in the placebo patients, overall mortality was 25.8% and 21.0% respectively. Outcome measurement criteria and the case for M. vaccae immunotherapy are discussed