Prevalence of rifampicin resistant Mycobacterium tuberculosis among presumptive tuberculosis patients in selected governmental hospitals in Addis Ababa, Ethiopia

The emergence and spread of multidrug-resistant tuberculosis (MDR-TB) is threat, which complicate diagnosis, treatment and control of the disease [1]. On average, 4.1% of newly diagnosed and 19% previously treated TB patients are estimated to MDR-TB worldwide in 2017 [2].

Empirical TB treatment without drug susceptibility testing (DST), which is a common practice in many developing countries, is believed to increase the day to day risk of transmission of drug resistant strains [3, 4]. Therefore, routine testing of all patients with TB is widely recognized as the most appropriate surveillance approach for monitoring trends in drug resistant TB [5].

WHO endorsed the Xpert MTB/RIF assay, which is a rapid and automated molecular system that detects both M.tuberculosis DNA and rifampicin-resistance (RR) associated mutations simultaneously. Research recognized that RR can be a surrogate marker for MDR-TB in more than 90% of the cases [6]. Hence, WHO recommends that RR-TB patients should be treated like patients with MDR-TB [7]. Initially, this technique was indicated for patients with TB/HIV co-infection, presumptive MDR-TB and paediatrics TB patients [8] but 3 years later of its implementation, it was recommended for all patients suspected of having TB [9]. Ethiopia ranks 10th among the high-TB-pandemic countries and 15th among the 27 high MDR-TB countries with more than 5000 estimated MDR-TB patients each year [10]. A recent national drug resistance survey conducted in Ethiopia reported a 2 and 11% prevalence of MDR-TB among new and pretreatment cases, respectively [11]. In addition, a meta-analysis and systematic review conducted in our country reported that drug resistant TB rates were stable in the last 10 years [12]. Drug resistant TB treatment is more complex than susceptible TB due to longer treatment time, increased toxicity and costs [13].

In Ethiopia, sputum smear microscopy is the commonly used laboratory diagnostics technique for TB. Mycobacterium tuberculosis culture, the gold standard test, is limited only to regional laboratories and primarily used for research purposes. The Xpert MTB/RIF assay is now going to be implemented in all health facilities, mainly in referral hospitals across the country since 2014, as per the recommendation of WHO [14]. This survey assessed the prevalence of RR-TB among presumptive TB patients diagnosed using Xpert MTB/RIF assay in selected governmental hospitals in the capital city of Ethiopia.

In the present study, the prevalence of M. tuberculosis infection was found to be 15.11%. Other several studies reported quite a diverse magnitude of M. tuberculosis (15.4–25% [15‐19] in the different parts of the country. This might be related to variation in risk for HIV acquisition, geographical variation, method of diagnosis, study setting or TB control practice.

The prevalence of M.tuberclosis among pediatrics TB Patients (13.6%) in the current study is comparable to a report from South Africa (13%) [20] and Uganda 14% [21]. Yet, it is lower than a study done in Southwest Ethiopia (31.7%) [22]. This substantial difference can be owing to the methods of diagnosis. While we used only Xpert MTB/RIF assay, the other study applied microscopy and culture and other molecular techniques for identification.

The existence of RR-TB is a serious health problem in the study population. The prevalence of RR-TB in this study is in line with previous studies in Ethiopia (9–10.3%) [17, 19] and Nigeria (12.1%) [23]. However, other studies in the country reported a lower (5.7–7.5%) [24, 25] and a higher (15.8–33.3%) [18, 26, 27] level of RR-TB. The variation of RR-TB across the country might be related to differences in patient selection, sample size (small sampling could generate higher resistance rate).

In the present study, the proportion of RR-MTB (7.9%) among paediatrics TB patients was consistent to two studies in China (6.9–8.3) [28, 29] yet higher than a study in Uganda (5.7%) [21] and in Thailand (5.1%) [30]. This study also found no significant differences (P > 0.05) for the presence of RR-TB among pediatrics (< 15) and adults. In the same way, other studies [31, 32] also support our findings. Since the largest source of drug resistance TB comes from adults, it seems reasonable to treat the paediatrics in similar regimen as of their contacts [33, 34]. However, children can acquire infection independently in the community [35], in case of TB high burden settings. Therefore, molecular typing of isolates from pediatrics TB patients and their potential contacts is essential to determine the source of transmission.

In the present study, RR-TB was significantly higher among previously treated patients compared to treatment naïve patients. This is in agreement with other studies in Ethiopia (18–19). However, the level of RR-TB among previously untreated cases (7.6%) in the analysis is higher than that reported in the latest Ethiopia national survey report (2%) [36], other study in the country (6.7%) [19], and in the WHO 2017 report (4.1%) [2]. The high prevalence of RR-TB among new TB cases in the current study suggests the existence of active person-to-person transmission or the existence of undiagnosed new RR-TB cases. In addition, drug resistance among previously untreated cases indicate the performance of TB control program in the past. The strict practice of direct observed therapy (DOTS) and DOTS-plus program currently run-through in Ethiopia is questionable.

According to our study, being female was identified as an independent risk factor for RR-TB. This is in agreement with the report from previous study in Ethiopia [27], another study in Georgia [37], Russia [38] and Estonian patients [39]. The prevalence of RR-TB among females might be related to socioeconomic factors, probably due to lack of control of financial resources at household levels), poor knowledge regarding TB as seen in other studies in country [40] and delay and poor health seeking behavior in females [41]. Since mothers are primary care giver of children in our country, it may increase risk of RR-TB among children. This is very valuable and instructive, and could aid in comprehension for health professionals and policy makers to address the problem. In this study we could not do microbiological confirmation of tuberculosis, phenotypic rifampicin resistance and resistance to other anti-TB drugs.

In our setting, RR-MTB is prevalent both among adult and paediatric TB patients. Being female and previous treatment with anti-TB drugs was found significantly associated with rifampicin resistance. The strong association of rifampicin resistance with previous treatment suggests the need of an improved monitoring of treatment to limit the emergence of drug resistant MTB strains.