Trends in Mycobacterium Tuberculosis and prevalence of Rifampicin Resistance in Eastern zone, Tigray Region, Northern Ethiopia

Tuberculosis (TB) is an infectious disease usually caused by Mycobacterium tuberculosis (MTB) bacteria. The emergence of Mono or multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis (XDR-TB), poses a considerable challenge to Mycobacterium tuberculosis control programs in the worldwide; however, there has been no reliable and organized data on trends and prevalence drug resistance of Mycobacterium tuberculosis in study area; Therefore, aim of this study to determine the trends of Mycobacterium tuberculosis and prevalence of Rifampicin resistance in eastern zone, Tigray, Northern Ethiopia. retrospective


Introduction
Tuberculosis (TB) is a contagious and airborne caused by the bacillus Mycobacterium tuberculosis (MTB). It typically affects the lungs (pulmonary TB) but can affect other sites as well (extra pulmonary TB). Relatively small proportion of people infected with Mycobacterium tuberculosis will go on to develop TB disease; however, the probability of developing TB is much higher among people with immune debilitated. TB affects mostly adults in the economically productive age groups; around two-thirds of cases are estimated to occur among people aged 15-59 years [1].
About one-quarter of the world's population has latent TB, which means people have been infected with TB bacteria but are not (yet) ill with the disease and cannot transmit the  4.1% of these new TB cases and 19% of the previously treated cases are believed to harbor Drug resistant-TB with an estimated 240, 000 deaths annually due to MDR-TB [3]. World Health Organization (WHO) estimates that 4.5 million people are coinfected with Human Immunodeficiency Virus (HIV) and TB globally [4].
Ethiopia is among the 30 High TB, HIV and multidrug resistance (MDR-TB) Burden Countries, that accounted for 80% of all estimated TB cases worldwide, with an annual estimated TB incidence of 207/100,000 populations and death rate of 33 per 100,000 populations in 2014 [5]. Among the notified TB cases in 2014, 1300 (1.6%) of new TB cases and 11.8% previously treated TB cases [3]. Besides, drug resistance (DR-TB) sentinel report in 2013 shows the MDR-TB prevalence of 2.3% among new and 17.8% among previously retreated TB cases. In the same year notified 119, 592 new TB cases and enrolled 597 drug-resistant TB cases [6]. And many studies showed the prevalence of Mycobacterium tuberculosis with rifampicin resistance in Ethiopia ranged from 4.7-18.3%. Mutations region of 81 base pairs (bp) of rpoB gene has been found in about 96% of rifampicin (RMP) resistant M. Tuberculosis [7][8].
Ethiopia is implementing a comprehensive TB/Leprosy and TB/HIV control programs and has achieved a lot in the past decades and is on track to achieve the MDG (Millennium development goal) targets regarding TB and HIV. However, Tuberculosis (TB) still remain a major public health problem claiming the lives of thousands of Ethiopians every year [9].
The Case detection rate was very low using smear Microscopy. Now the Ethiopian government continued its commitment in the fight against TB by joining the new post-2015 Global TB Strategy called "END TB strategy" by increasing case detection & further reducing the burden of disease. To achieve the strategy Ethiopia endorsed many advanced technologies concordantly with WHO recommendations. One of the technologies is the geneXpert MTB/RIF assay. The assay detects MTB and rifampicin resistance; conferring mutations using three specific primers and five unique molecular probes. It provides results in less than two hours and has minimal bio-safety requirements and training [10].
Ethiopia is one of the high burden countries, reflected both in its TB incidence and the estimated rates of MDRTB. However, there has been no reliable and organized data on trends and prevalence rifampicin resistance of Mycobacterium tuberculosis in Ethiopia. As far as our knowledge, there are no studies conducted concerning document reviewing systematically trends in Mycobacterium tuberculosis and prevalence of rifampicin resistance using Gene expert in Adigrat area. Therefore, this study aimed to determine the trends in Mycobacterium tuberculosis and the prevalence of rifampicin resistance using Gene expert among TB-presumptive cases at Adigrat General Hospital, northern, Ethiopia.

Study Design, Area and Period
Retrospective cross-sectional study design was used to collect the secondary data from June 01-August 30, 2019 in Adigrat General Hospital. The Adigrat General Hospital is found in Tigay, northern Ethiopia and 560 miles far from capital city Addis Ababa. The Adigart General Hospital offers service around one million people, including the catchment health facilities. It gives all service, including directly observed treatment clinic for TB patients.

Inclusion criteria
Those who had completed data in the registration book were included during the study period specified.

Exclusion criteria
Indeterminate and/or invalid GeneXpert results were excluded from the study.

Independent variable
Sex, residence, age, Co-infection, Previously treated, Tuberculosis treatment outcomes and year of diagnosis.

Sample size
Retrospectively all presumptive TB suspected patients from a TB registration book from January 01, 2015 to December 30, 2018 was being included.

Data collection and laboratory methods
The data were collected retrospectively from TB registration books in Adigart General Hospital at The Directly Observed Treatment, short course clinic (DOTS). Data was collected using developed checklist.

Quality of data
The quality of data was maintained by checking the completeness of necessary information, the obtained data were cross-checked and double entered and re-checked to assure the quality of data.

Statistical Analysis and interpretation
Data obtained through the checklist and laboratory test results were double entered into the Epi-info 3.1 software. Data analysis was performed using SPSS 20. Descriptive analysis, frequencies, and Figures were used to explain the findings. Chi-square analysis was used to correlate categorical variables. In all cases, the p-value less than 0.05 were considered statistically significant.

Results
A total of 5944 presumptive TB patients eligible for GeneXpert Mycobacterium Tuberculosis / rifampicin resistance assay were retrospectively included in this study.
Among these the majority was male 3455 (58.1%).The median age of the participants was 40.0 (IQC-57, 26), the majority were in the age group 30-    The trends of positivity in Mycobacterium tuberculosis and rifampicin resistance were  Amplification Technology that overcomes many of the current operational difficulties in TB diagnosis [11].  [19], Zambia (98.3%) [32] &South Africa (> 70%) [33]. The possible explanation for this difference could be due to the fact that HIV infected patients are one of the eligible groups recommended being tested by the Xpertand most likely they have a higher prevalence of HIV.
In this study, Mycobacterium tuberculosis common prevalent in all ages, but has seriously hit the productive age group (30- [18].However, it's much lower than studies conducted in Debremarkos referral Hospital (38% ) [12] & Zimbabwe (37.1%) [36].The discrepancies might be due to in our study we included all presumptive TB and a high number of participants.
According to our study, we found 132 (9.1%) of rifampicin resistance among confirmed TB cases on average. This is comparable with a study conducted in Debremarkos Referral Hospital (10.3%) [12], FelegeHiwot referral Hospital and Debretabor Hospital (9.3%) [19],India (10.5%) [37].In the other hand, it is higher than the studies conducted in different part of Ethiopia (2.9%-5.7%) [6,18,[30][31][32], Nigeria (2.9%) [23] and Zambia (5.9%) [32].The possible explanation for these variation could be due to the fact that this study was included retrospectively four years and difference in study design .However, it lower than study conduct in Gonder 15.8% [13] We also wish to express our sincere thanks and appreciation to Dr. Chernet Gebre medical Trends of Mycobacterium tuberculosis and Rifampicin resistant in Adigrat General Hospital,Tigray,Northern, Ethiopia 2020.