Changing from single-drug to fixed-dose combinations: Experience from Fiji

Abstract

T uberculosis (TB) is a major cause of morbidity and mortality worldwide, with the highest prevalence in resource-limited countries. Fiji reported a TB case notification rate of 24 per 100 000 population in 2012, and this compares to a case notification rate of 31/100 000 in 1990. 1 TB control is an ongoing challenge, with 614 new and relapse TB cases reported to the World Health Organization (WHO) from 2010 to end 2012. Reported treatment success rates, an important indicator of TB control, have been variable over the last decade, ranging from 62% to 90%. 1 There are many possible reasons for inadequate treatment outcomes, some of which may relate directly to medication, such as interrupted anti-tuberculosis drug supplies or poor patient adherence. To improve adherence, the WHO and the International Union Against Tuberculosis and Lung Disease (The Union) now recommend the use of fixed-dose combinations (FDCs) for first-line treatment of drug-susceptible TB. 2 TB patients were previously treated with a combination of single-drug preparations of isoniazid (H, INH), rifampicin (R, RMP), pyrazinamide (Z, PZA) and ethambutol (E, EMB). Prospective, randomised trials covering multiple sites in TB-endemic settings have concluded that treatment outcomes were not inferior when using FDCs than when using single-drug preparations. 3,4 Since FDCs were introduced into the Fiji National Tuberculosis Programme (NTP) in November 2011, it has been observed anecdotally that the sputum conversion rate among new sputum smear-positive TB patients is lower than when treatment consisted of single-drug preparations. Although the WHO TB treatment guidelines limit the intensive phase of treatment for new patients to 2 months, this perception resulted in clinicians occasionally prolonging the intensive phase of treatment in patients receiving FDCs. This observation of lower sputum conversion rates has not, however, been evaluated or quantified.We therefore aimed to evaluate whether the introduction of FDCs had affected treatment response among TB patients in Fiji. METHODS Study settingThis was a retrospective cohort study comparing anti-tuberculosis treatment outcomes between those receiving FDCs and those receiving single-drug preparations undertaken at all three NTP TB treatment centres in Fiji. The Fiji NTP was established in 1951, and the DOTS strategy was introduced in 1997. 5 The case detection rate rose from an estimated 28% in 1990 to 79% in 2010. 1 The three TB treatment centres are the only providers of anti-tuberculosis drugs in Fiji. Sputum smear microscopy with Ziehl-Neelsen staining for acid-fast bacilli (AFB) is undertaken for initial diagnosis and after 2 months of standard first-line treatment for all sputum smear-positive cases to assess smear conversion to sputum smear-negative. For those patients who do not convert by 2 months, follow-up smear examination is carried out monthly. Results are recorded in the AFB register.TB has been treated according to the Fiji NTP guidelines since before 2010: standard first-line trea...