Pre-Extensively Drug Resistant Tuberculosis (Pre-XDR-TB) among Pulmonary Multidrug Resistant Tuberculosis (MDR-TB) Patients in Bangladesh

Background & Objectives: Emergence of drug resistant Tuberculosis (TB) is a major obstacle in the TB control programme of Bangladesh. This study was carried out to detect pre-extensively drug resistant TB (pre-XDR-TB) cases among the multidrug resistant TB (MDR-TB) patients in Bangladesh, as the early detection of pre-XDR-TB can guide clinicians in the appropriate modification of MDR-TB treatment regimen with effective drugs to prevent treatment failure. Methodology: A total of 68 MDR-TB cases were enrolled in this study. Multiplex Real-time PCR was done to detect pre-XDR-TB cases directly from sputum samples of MDR-TB patients. Results: Out of 68 MDR-TB cases 11 (16.18%) cases were detected as pre-XDR-TB. The resistant profile of the 11 pre-XDR-TB revealed 9 (81.82%) cases of fluoroquinolone (FLQ) resistant pre-XDR-TB and 2 (18.18%) cases of injectable second line (ISL) agent resistant pre-XDR-TB. Out of 11 pre-XDR-TB cases 7 (63.64%) cases had history of taking treatment for MDR-TB regularly, 1 (9.09%) case had history of taking treatment for MDR-TB irregularly and 3 (27.27%) cases had no history of taking treatment for MDR-TB. Conclusion: This study encountered a high rate of pre-XDR-TB cases along with a significant number of primarily resistant bacilli which is of concern in the management of MDR-TB. It is evident that Bangladesh is in urgent need to device strategies for rapid and early detection of pre-XDR-TB in order to prevent treatment failure of MDR-TB cases and also to halt the progression of MDR-TB cases to extensively drug resistant TB (XDR-TB), which is not only difficult but also very expensive to treat. How to cite this paper: Tasnim, T., Tarafder, S., Alam, F.M., Sattar, H. and Mostofa Kamal, S.M. (2018) Pre-Extensively Drug Resistant Tuberculosis (Pre-XDR-TB) among Pulmonary Multidrug Resistant Tuberculosis (MDR-TB) Patients in Bangladesh. Journal of Tuberculosis Research, 6, 199-206. https://doi.org/10.4236/jtr.2018.63018 Received: June 25, 2018 Accepted: July 21, 2018 Published: July 24, 2018 Copyright © 2018 by authors and Scientific Research Publishing Inc. This work is licensed under the Creative Commons Attribution International License (CC BY 4.0). http://creativecommons.org/licenses/by/4.0/ Open Access


Introduction
Tuberculosis (TB) is a major public health problem in Bangladesh. The estimated incidence rates for all forms of TB in 2015 were 225 per 100,000. An estimated 45 per 100,000 died of TB in the same year. The prevalence of MDR-TB (Multi drug resistant TB) in Bangladesh in new cases is 1.6% and in re-treatment cases is 29% [1].
Pre-extensively drug resistant tuberculosis (pre-XDR-TB) is a comparatively new term and is defined as TB with resistance to rifampicin (RMP) and isoniazide (INH) with additional resistance to either a FLQ (Fluoroquinolone) or ISL (Injectable second line) agent but not against both these drugs simultaneously [2]. Thus pre-XDR-TB cases with FLQ or ISL resistance receive less number of effective drugs under standard MDR-TB regimen. It may amplify further resistance to the effective drugs and progression towards XDR-TB (Extensively drug resistant TB).
XDR-TB is defined as TB resistant to RMP and INH (MDR-TB) with additional resistance to second line anti-TB drugs i.e. to any FLQs, and to at least one of the three injectable second-line drugs (ISL) naming amikacin, kanamycine and capreomycin [3]. The prevalence of XDR-TB is 9.5% worldwide [4]. Treatment of XDR-TB is complicated, as it requires the use of second-line drugs that are less effective and more toxic, thus demanding longer treatment duration.
Detection of pre-XDR-TB cases among MDR-TB patients is an important step in the prevention of treatment failure of MDR-TB and in addition, it helps to take appropriate measures to halt the progression towards XDR-TB.
So far no data is available regarding the status of pre-XDR-TB in Bangladesh.
Neighboring countries like India, Pakistan and Nepal have reported high prevalence of pre-XDR-TB cases. In India 55.65% pre-XDR-TB cases were found among pulmonary MDR-TB patients in a tertiary care hospital in Mumbai [3].
From Pakistan, two separate studies, one from Multan and the other from Karachi found the prevalence of pre-XDR-TB among MDR-TB patients to be 32.2% and 39.5% respectively [5] [6]. Nepal has reported 28% pre-XDR-TB cases among drug resistant Tuberculosis (DR-TB) cases [7]. Therefore the aim of our study was to detect the rate of pre-XDR-TB cases among pulmonary MDR-TB patients, admitted at the National Institute of Diseases of the Chest and Hospital (NIDCH), Dhaka, Bangladesh.

Clinical Samples
A total of 68 pulmonary MDR-TB patients (both newly diagnosed cases and patients under MDR-TB treatment regimen) attending the NIDCH were recruited in this study.
Inclusion criteria: Pulmonary MDR-TB patients diagnosed by Xpert MTB/RIF assay (Cepheid Inc, USA), which detected rifampicin resistance and by the conventional DST (drug susceptibility testing), which detected rifampicin and isoniazide resistance were selected.
Exclusion criteria: Extra pulmonary MDR-TB patients.

Sample Collection and Processing
Sputum samples were collected following standard protocol then digested and decontaminated by NALC-NaHO method [8].

Results
Out of the 68 MDR-TB patients, 11 (16.18%) were detected as pre-XDR-TB cases. Age-wise distribution of pre-XDR-TB cases shows highest number of cases were in the age group of 21 -30 years followed by 3 cases in the age group of ≤20 years. The 11 pre-XDR-TB cases were consisted of 7 males and 4 females cases (Table 2).

Discussion
This study was conducted to observe the rate of pre-XDR-TB cases among

MDR-TB patients varies between countries and is some cases variations occur
within the same county in different regions. These differences may be the result of different anti-TB regimens adopted by the different countries. Other contributing factors may be due to low socio-economic condition, poor health infrastructure and lack of sufficient medications in those regions.
The current study also detected higher number of FLQ resistant pre-XDR-TB (13.24%) cases, than ISL resistant pre-XDR-TB (2.94%) cases. Data from previous studies suggests that the incidence of FLQ resistant MDR-TB (pre-XDR-TB) is increasing worldwide [12]. The current study found a higher number of pre-XDR-TB cases in the age group of 21 -30 years. Similarly two separate studies, one from India and the other from Nigeria also found higher numbers of pre-XDR cases among the young adult group, with ages ranging from 18 -25 years and 15 -29 years respectively [3] [13]. The probable cause of the higher numbers of drug resistant TB in the active age group may be due to their frequent movement, greater exposure to the environment, coming in contact with more people outdoors and higher case notification due to greater health awareness and concern among young adults.
The treatment status of the 11 pre-XDR-TB cases were also observed in this study, of which 7 (63.64%) cases had history of taking MDR-TB drugs regularly,

Limitations
The data regarding pre-XDR-TB does not represent that of the entire population because the study was done among MDR-TB patients, which was not a repre-

Conclusion
This study encountered a higher rate of pre-XDR-TB among pulmonary MDR-TB patients in Bangladesh. It can be concluded that Bangladesh is in urgent need to put in action strategies for rapid and early detection of pre-XDR-TB cases among the MDR-TB patients. Identification of pre-XDR-TB cases is an important step in the prevention of treatment failure of patients suffering from MDR-TB in addition to halting the progression towards XDR-TB. Standard MDR-TB treatment regimen in pre-XDR-TB cases is of no worth rather it can amplify further resistance to the drugs that are effective. It is prudent to find out the cause for significant numbers of pre-XDR-TB cases among those with a history of regular MDR-TB treatment. If there is an ongoing high rate of transmission of primary resistant bacilli, it demands serious attention.