Years of Innovation in the treatment of latent tuberculosis infection: A comparison between standard and short course therapies in directly observed therapy1

Objectives: The main aim of the study is to compare the acceptance, adherence, tolerance and safety of short course therapies in comparison to a standard 9 month treatment for latent tuberculosis infection (LTBI) in directly observed therapy (DOT) and contrast this with previous results from a standard therapy in patient self-administered treatment. Materials and methods: Retrospective longitudinal study carried out at a medium sized prison. Period of inclusion covers 10 years, from January 2000 to December 2009. The Centers for Disease Control and Prevention (CDC) inclusion and exclusion criteria were used, as well as the ones included in the Program for Tuberculosis Prevention and Control in the Prison Environment. 4 LTBI therapies according to the preference of the patient and possible interactions with other treatments were utilised. Therapy I consisted of isoniazid (H) in doses of 300 mg/day for 9 months (9H), therapy II with rifampicin for 2 months, twice a week, (2R2Z2) therapy III with rifampicin and isoniazid for 3 months (3RH) and therapy IV with rifampicin for four months (4R). Treatment was administered under strict DOT conditions by nursing staff. Results: 902 patients were included, of which 810 accepted the treatment (89.90%), distributed as follows: 400 in the 9H therapy, and 410 with short course therapies (316 in the 2R2Z2, 82 in the 3RH therapy and 12 in the 4R therapy). 92 patients (10.20%) did not accept LTBI therapy, 271 patients (67.75%) concluded the LTBI treatment with 9H, and 314 (76.60%) with short courses. 232 patients (73.42%) concluded the 2R2Z2, 85.40% with the 3RH 70 therapy and 12 (100%) with the 4R treatment. 129 patients (32.25%) did not complete the LTBI 9H therapy (63 due to voluntary withdrawal, 35 due to adverse reactions, 26 for release or transfer, 2 for unknown reasons, 1 due to tuberculosis in a HIVpatient and 1 due to suicide). 96 patients (23.41%) did not conclude the short course therapies (36 due to voluntary withdrawal, 54 due to adverse reactions, 1 due to release or transfer, 3 for unknown reasons, 1 due to a psychotic episode, and 1 due to hepatitis of unknown aetiology). Significant differences could be discerned in the LTBI therapy conclusion rates when comparing the standard 9H and short course therapies. A greater, statistically significant, probability is observed with the short course therapies: p: 0.006; Odds Ration: 1.56 (LC95%: 1.14-2.12). This difference is a result of the 9H therapy presenting a greater number of voluntary withdrawals for no apparent reason (p: 0.002; OR: 2.03 [1.30-3.15]) and a greater number of withdrawals as a result of transfers to another prison or release (p<0.0001; OR 30.22 [4.07-224.29]), with no significant differences being found in withdrawals for adverse reactions between the 9H therapy and the short course treatments as a whole. The 2R2Z2 therapy shows a higher probability of withdrawals for adverse reactions (p: 0.006; OR: 1.87 [(1.21-2.88]) than the other therapies. Conclusion: Greater acceptance of initiating therapy was observed in all the DOT therapies. The 3RH, 2R2Z2 and 4R short course therapies favoured better adherence, with significantly lower ratios of withdrawal than the 9H therapy for the treatment of latent tuberculosis infection. Tolerance and safety of the short course therapies was very similar to the standard 9H treatment, with a significantly higher percentage of adverse reactions in the 2R2Z2 therapy in comparison to others. Our data backs up the safety and adherence of a short course 3RH therapy in DOT for treating latent tuberculosis infection and its preferential use in the prison environment in comparison to isoniazid due to the greater number of patients concluding treatment. (1): 2010 5th Prison Health Research Award-Winning Article.