Transmission Dynamics of MYCOBACTERIUM TUBERCULOSIS IN Southern Region of Ethiopia
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Date
2020-01
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Addis Ababa University
Abstract
Background: Tuberculosis (TB) is a major global public health problem with countries in sub-Saharan Africa (SSA) including Ethiopia being most affected by the disease. Understanding the epidemiology of TB and the development and spread of drug-resistant TB is limited by scarce molecular epidemiologic data in SSA including Ethiopia. In terms of epidemiology of TB, control of TB in prisons is an important public health priority. In some settings, prisons have been recognized as a reservoir and sites of transmission for TB. Additionally, the spread of TB in rural settings deserves further attention. In rural settings,
several factors may contribute to enhanced transmission of TB including either missed diagnosis or delays in diagnosis.
Objective: To describe the molecular epidemiology and drug resistance pattern of TB to better understand the transmission of TB and the development and spread of drug resistance in different settings of Southern Ethiopia.
Methods: Three studies were conducted, all using a cross-sectional design: a prison study in Hawassa Prison, a health facility-based study at nine health facilities in and around Shashemene areas of Western Arisi Zone (Oromia region) and a community-based study in the rural areas of Hawassa Zuria Woreda (Sidama Zone, Southern Region). In the prison study, incarcerated individuals were screened for TB using a symptom screen; those with a cough of ≥2 weeks had spot and morning sputum samples collected for AFB smear
microscopy and molecular diagnostic testing (Xpert MTB/RIF). The study was conducted from June 15 through July 13, 2015. The health facility study was conducted among sputum smear positive patients with TB visiting nine diagnostic facilities in Southern Ethiopia. Three consecutive sputum samples (spot-morning-spot) per patient were examined using AFB smear microscopy with all smear positive specimens also having AFB cultures performed. Mtb isolates had drug susceptibility testing (DST) performed using the indirect
proportion method and were genotyped with RD9 deletion typing and spoligotyping. Spoligotyping International Types (SIT) and sub-lineages (clades) were assigned according to the SITVITWEB data base. Geographic information system (GIS) was used to map source sites of strains. Whole genome sequencing (WGS) was done on selected Mtb isolates. The study was conducted from June 2015 to May 2016. The population-based survey was conducted in six Kebeles (the lowest administrative units) of Hawassa Zuria Woreda using a community-based active case finding (ACF) strategy. Volunteer women community workers led a symptom screening program to identify community members with TB. Individuals with cough ≥ 2 weeks were asked to provide two sputum samples (spot and morning) for diagnostic testing for TB. AFB smear microscopy and culture and Xpert MTB/RIF were performed. The study was conducted from May 08, 2016 through June 09, 2016.
Results: Among 2068 prisoners, 372 (18%) had a positive cough screen. The median age of these 372 persons was 23 years, 97% were male and 63% were from urban areas. Among them, 8/372 (2%) had a positive AFB sputum smear microscopy result and 31/372 (8%) had a positive Xpert TB/RIF. The point prevalence of pulmonary TB at the prison was 1748 per 100,000 population as defined by Xpert TB/RIF. In the health facility study, among 250 newly diagnosed patients with TB, 154 (52%) were male and 143 (57%) came from rural areas. The prevalence of HIV co-infection was 4%. A total of 230 isolates were obtained from 250 sputum cultures. All 230 isolates were M. tuberculosis strains belonging to three lineages: Euro-American, 187 (81%); East-African-Indian, 31 (14%); and Lineage 7 (Ethiopian lineage), 8 (4%). The 230 isolates could be categorized into 65 different spoligo type patterns, of which 36 (55.0%) were already known in the international data base and 29 (45.0%) were new patterns (orphans). The dominant spoligo types were SIT149(21%), SIT53 (19%) and new strains (16%). One hundred ninety-three (84%) isolates were clustered into 29 spoligotype patterns and the remaining (37, 16%) strains fell into single spoligotypes, and clustering of strains by geographic locations was observed. DST revealed that 14% of Mtb isolates tested were resistant to > 1 first line anti-TB drugs and 11% to isoniazid. SIT 149 was the most prevalent spoligotype among drug resistant isolates. WGS analysis identified different drug resistance mutations in Mtb isolates including on pyrazinamide which was not detected by phenotypic DST. MDR-TB was not identified both by phynotipic DST and WGS analysis. For the community study, all 24,517 adults in the study area had a symptom screen performed using 350 health development armies (HDAs); 544 (2.2%) had cough ≥ 2 weeks. Among persons with a positive symptom screen, 13/544 (2.4%) had a positive sputum AFB smear microscopy, 13/544 (2.4%) a positive culture and 32/544 (5.8%) a positive Xpert MTB/RIF test (including two with rifampin resistance identified). Overall, 34/544 TB cases (6%) were identified by culture and/or Xpert, which corresponds to a prevalence of 139 per 100,000 population (95% CI: 96-194).Conclusion: Epidemiological data on TB including drug resistance in different settings is vital to look at the problem from different perspectives. A high prevalence of TB was detected among inmates at a large Ethiopian prison. Active case finding using cough symptom screening in combination with the Xpert test has high utility as a potential tool to interrupt transmission of M. tuberculosis in correctional facilities in high burden, low- and middle-income countries. The health facility study identified a heterogeneous pool of M. tuberculosis strains with several clusters including lineage 7 strains circulating in Southern Ethiopia. The presence of several clusters and of new strains of M. tuberculosis suggests recent transmission of TB, including of drug-resistant strains in southern Ethiopia. This calls for regular surveillance of drug susceptibility and wider monitoring and geospatial analysis of transmission trends to control TB in the southern Ethiopia. The community study demonstrated the capability of community health workers (volunteer and paid) to rapidly conduct a large-scale population TB screening evaluation and highlighted the high yield of such a program to detect previously undiagnosed cases when combined with XpertMTB/RIF testing. This could be a model to implement in other similar settings. In general, the results of the three study findings could significantly impact the TB control program of the country in improving the prevention and control of the disease and add knowledge to the science.
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Keywords
Tuberculosis ,drug resistance pattern of TB,Mycobacterium Tuberculosis