Genetic Diversity and Drug Sensitivity Profile of Mycobacterium Tuberculosis Among Children in Ethiopia
Hilina Mollalign, Muluwork Getahun, Getu Diriba, Ayinalem Alemu, Dawit Chala, Begna Tulu, Gobena Ameni
Abstract
Background
Worldwide, tuberculosis (TB) affects about one million children every year. The burden of the disease is higher in developing countries. However, there is limited information on the lineages and drug sensitivity patterns of Mycobacterium tuberculosis (M. tuberculosis) infecting children in these countries, including Ethiopia. Thus, this study aimed to characterize the different lineages of the M. tuberculosis complex causing childhood pulmonary tuberculosis and evaluate the drug-sensitivity patterns to the first-line anti-TB drugs.
Introduction
Tuberculosis (TB) is among the oldest recorded human infection, which continues to cause illness and death in humans despite the worldwide use of the Bacille Calmette Guérin (BCG) vaccines and different anti-TB drugs [1]. According to the 2020 global TB report by the world health organization(WHO), there were 10 million incident cases of TB, of which 12% occurred among children under the age of 15 [2]. Challenges in bacteriologic confirmation and the poor practice of documentation and underreporting have made the actual estimate of the incidence difficult [3]. These challenges also contribute to the minimal attention for the investigations of TB in children [4].
Materials and method
Study area and source of the isolates
This study was conducted at the Ethiopian Public Health Institute (EPHI), National Tuberculosis Reference Laboratory (NTRL) on stored MTBC isolates. Samples from which the isolates were harvested were collected from selected health facilities in Addis Ababa, Oromia, Amhara and Southern nations and nationalities and peoples (SNNP) of Ethiopia for another study (not published).
Result
Demographic and clinical characteristics of study participants
Data describing gender and age is available for 51 and 50 participants respectively. Among these 21 (41.2%) isolates were obtained from female participants. The mean age of the study participants was 10.78 (5–15) years. Most of the positive isolates were obtained from Oromia, accounting for 38.9% (21/54). Most culture-positive study participants (80.4%) were in the age group of 8 to 15 years, as compared to participants in the age group of 5–7 (19.6%) (Table 1).
Discussion
In the present study, the lineages of M.tuberculosis infecting children in the study settings were identified and their drug sensitivity testing profiles were described. In this study, we have identified three major lineages through the Conformal Bayesian Network (CBN). These are the EA, EAI, and M.Africanum lineages. Drug susceptibility testing by the phenotypic method has identified mono resistance for two cases while one MDR-TB in which re-culturing failed to recover live bacteria and was identified by the molecular method. In this MDR isolate, mutation of the WT3 and MUT2B gene conferred resistance for RIF and there was high dose INH resistance. The overall prevalence of any resistance was 7.8% and the prevalence of MDR-TB was 2.6%.
Conclusion
In conclusion, the present study showed predominant lineages infecting children appear like the dominant lineages identified from adult populations in different parts of the country. This genotype represents the most common circulating lineages in Ethiopia. Despite the tiny fraction of isolates tested, drug resistance in children is rare. A larger study is required to provide a comprehensive description of the molecular epidemiology of MTBC genotypes in children.
Acknowledgments
We acknowledged the Ethiopian public health institute, National Tuberculosis Reference Laboratory, and Addis Ababa University, Aklilu Lemma Institute of Pathobiology.
Citation: Mollalign H, Getahun M, Diriba G, Alemu A, Chala D, Tulu B, et al. (2023) Genetic diversity and drug sensitivity profile of Mycobacterium tuberculosis among children in Ethiopia. PLoS ONE 18(7): e0284363. https://doi.org/10.1371/journal.pone.0284363
Editor: Leonid Chindelevitch, Imperial College London, UNITED KINGDOM
Received: April 27, 2022; Accepted: March 29, 2023; Published: July 28, 2023
Copyright: © 2023 Mollalign et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All the important information is available within the manuscript and its supplementary files.
Funding: The authors received no specific funding for this work.
Competing interests: The authors have declared that no competing interests exist.
Abbreviations: BA, Blood agar plate; BCG, Bacille Calmette Guérin; CI, Confidence interval; DRTB, Drug-resistant tuberculosis; DST, Drug susceptibility test; EPHI, Ethiopian public health institute; HIV, Human immunodeficiency virus; INH, Isoniazid; MDR-TB, Multidrug-resistant tuberculosis; MTB, Mycobacterium tuberculosis; MGIT, Mycobacteria Growth Indicator Tube; NTM, Nontuberculosis mycobacteria; ODAC, Oleic acid Dextrose Albumin and Catalase; PCR, Polymerase chain reaction; PTB, Pulmonary tuberculosis; PZA, Pyrazinamide; QC, Quality control; RD, Region of difference; RR, Rifampicin resistant; SIT, Spoligotype Shared International Type; STM, Streptomycin; TB, Tuberculosis; WHO, World Health Organization; XDR- TB, Extensively drug-resistant tuberculosis
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0284363#abstract0
