The evidence based treatment of tuberculosis: where and why are we failing?
- Professor Lawrence L Peter Ormerod, Royal Blackburn Hospital, Lancs BB2 3HH, UK; Lawrence.Ormerod{at}elht.nhs.uk
THE SCALE OF THE PROBLEM
Tuberculosis is increasing both globally and nationally, so its management is becoming even more important. Globally, it is estimated that there are at least 7.96 million (95% confidence interval 6.3–11.1) clinical cases, with 3.52 million (2.8–4.1) sputum microscopy positive cases, and 1.87 million (1.4–2.8) deaths.1 This gives a case fatality rate of 23%. In addition, 32% of the world’s population (1.86 billion) are infected, as judged by a positive tuberculin skin test.1 In England and Wales after a nadir of 5000 cases per year, numbers have reached over 8000.2
THE SCIENTIFIC BASIS FOR SHORT COURSE CHEMOTHERAPY
Each of the antituberculosis drugs vary in their abilities to kill organisms, to sterilise lesions and to prevent the emergence of drug resistance.3 Isoniazid is the best drug for killing rapidly dividing organisms, followed by rifampicin and then streptomycin and ethambutol. Rifampicin is best for dormant organisms with occasional spurts of metabolism, and pyrazinamide is best for organisms in an intracellular (acid) environment. Multiple controlled clinical trials have been carried out in a number of countries.3 These show that a 6 month regimen comprising a 2 month phase of rifampicin (R), isoniazid (H), pyrazinamide (Z) and ethambutol (E), followed by a 4 month continuation phase of rifampicin and isoniazid, designated 2RHZE/4HR, gives a greater than 95% cure rate, and a relapse rate of less than 5%. This applies whether the drugs are given daily throughout treatment, daily in the initial phase with an intermittent (thrice weekly) continuation phase or fully intermittent throughout.3 If the regimen is shortened to 4 months by a shortened continuation phase, relapse rates rise to over 10%.4 The 6 month short course regimen also performs well in the presence of a proportion of isoniazid and/or streptomycin resistance, but much less well if there is initial rifampicin resistance.5 The fourth …
