Tuberculosis (TB) is the second greatest worldwide infectious killer. According to the World Health Organization (WHO), 37 million lives were treated between 2000 and 2013. In 2014, 9.6 million people fell ill with TB [
1]. Qatar is a peninsula located between the Persian Gulf and Saudi Arabia [
2]. In January 2016, the population was estimated to be over 2.3 million compared to around 220 thousands in the mid-1980s. This increase was primarily driven by the expatriate workforce traveling to Qatar. In 2013, number of foreign labors constituted around 85.7% of the population and up to 94.1% of the country’s workforce [
3]. The majority of this workforce is from Asian countries with high TB prevalence such as India (31%), Nepal (23%), Bangladesh (4.8%) leading to an increase in the total number of TB [
3]. In Qatar, all cases of TB are registered at the Communicable Disease Control and Prevention Section in the Supreme Council of Health [
4]. TB cases have increased from 184 cases in 1990 to 728 cases in 2012 with a decrease in the incidence rate from 44/100,000 to 41/100,000. A decrease in the incidence of TB was recorded at 40/100,000 with 511 new cases [
5].
Mycobacterium tuberculosis is the bacteria responsible for TB and it spreads through the air leading to lung infection which is the most common TB infection. Even though TB is preventable and curable, achieving a high cure rate is challenging and critical. The usual TB treatment regimen is a standard 2-month regimen of isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), and ethambutol (EMB), followed by a 4-month regimen of isoniazid and rifampin. This classic regimen is associated with poor compliance and adherence which leads to the development of resistant strains and multidrug resistant bacilli [
6]. Several methods have been explored to improve compliance and reduce errors such as the fixed-dose combination (FDC). The rationale of FDC is that the presence of all these drugs combined in one tablet can facilitate dosage calculation, prevent prescribing errors, increases patient’s acceptance, and decreases pill burden [
7‐
9]. During the 1980s and 1990s, health care providers were concerned about the quality of FDCs where poor bioavailability of the rifampin component of the tablet was an issue [
10,
11]. However, current FDCs are fully bioequivalent, stable and efficacious even after 6 months in tropical conditions [
7,
12‐
17]. Common fixed-dose combinations (FDCs) are of two anti-tuberculosis drugs (2FDCs, usually [RIF] + [INH]), three drugs (3FDCs, RIF + INH + [PZA]) and four drugs (4FDCs, RIF + INH + PZA + [EMB]). Several studies tested the safety and efficacy in different parts of the world using different brands of FDC regimens. However, no similar studies were performed in Qatar.
The objective of this study is to compare the FDC using Rifafour® for the first time as part of an FDC regimen and compare it to the regimens of separate tablets (ST) during the initial phase of TB treatment in Qatar, while assessing the safety and effectiveness of both regimens in terms of adverse events and time to negative sputum smear, respectively. The secondary objective is to compare FDC to ST regimens in terms of safety and efficacy in patients with diabetes treated for TB.