Phenotypic and genotypic drug sensitivity profiles of  Mycobacterium tuberculosis  infection and associated factors in northeastern Ethiopia

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Abstract

Background

Tuberculosis is a devastating and a deadly disease despite the novel advances in its diagnostic tools and drug therapy. Drug resistant Mycobacterium contributes a great share to tuberculosis mortality. Status of drug resistance and patients’ awareness toward the disease is unknown in northeastern Ethiopia. Thus, the aim of this study was to determine the phenotypic and genotypic drug sensitivity patterns and associated factors in Oromia Special Zone and Dessie Town, northeastern Ethiopia.

Methods

In a cross-sectional study, 384 smear positive tuberculosis cases were recruited and Löwenstein-Jensen culture was done. The performance of GenoTypic MTBDR plus assay using the conventional BACTEC MGIT 960 as a “gold standard” was determined. Drug resistant strains were identified using spoligotyping. Pearson Chi-square test was used to determine the association of drug sensitivity test and tuberculosis type, lineages, dominant strains and clustering of the isolates.

Results

The 384 smear positive Mycobacterium samples were cultured on LJ media of which 29.2% (112/384) as culture positive. A fair agreement was found between MTBDR plus assay and the conventional MGIT test in detecting the Mycobacterium tuberculosis with sensitivity, specificity, positive and negative predictive value of 94.2, 30.2, 68.4 and 76.5%, respectively. Among LJ culture positive samples 95 of them gave valid result for MTBDR plus assay and 16.8% (16/95) as drug resistant. Similarly, MGIT subculture was made for the 112 isolates and 69 of them gave positive result with 15.9% (11/69) as drug resistant. Cohen’s kappa value showed almost a perfect agreement between the two testing methods in detecting rifampicin (sensitivity 100% and specificity 98.3%) and multi-drug resistance (sensitivity 83.3% and specificity 100%). Spoligotyping identified 76.5% (13/17) of the drug resistant isolates as Euro-American and family 33 as the predominant family. Significant association was observed between drug resistant isolates and the dominant strains (χ2: 34.861; p = 0.040) of the Mycobacterium.

Conclusion

Higher magnitude of drug resistance was found in the study area. The GenoTypic MDRTB plus assay had an acceptable drug sensitivity testing performance.

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Most cited references 31

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Interrater reliability: the kappa statistic

Mary L McHugh (2012)

The kappa statistic is frequently used to test interrater reliability. The importance of rater reliability lies in the fact that it represents the extent to which the data collected in the study are correct representations of the variables measured. Measurement of the extent to which data collectors (raters) assign the same score to the same variable is called interrater reliability. While there have been a variety of methods to measure interrater reliability, traditionally it was measured as percent agreement, calculated as the number of agreement scores divided by the total number of scores. In 1960, Jacob Cohen critiqued use of percent agreement due to its inability to account for chance agreement. He introduced the Cohen’s kappa, developed to account for the possibility that raters actually guess on at least some variables due to uncertainty. Like most correlation statistics, the kappa can range from −1 to +1. While the kappa is one of the most commonly used statistics to test interrater reliability, it has limitations. Judgments about what level of kappa should be acceptable for health research are questioned. Cohen’s suggested interpretation may be too lenient for health related studies because it implies that a score as low as 0.41 might be acceptable. Kappa and percent agreement are compared, and levels for both kappa and percent agreement that should be demanded in healthcare studies are suggested.

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Rapid molecular detection of tuberculosis and rifampin resistance.

Catharina C. Boehme, Pamela Nabeta, Doris Hillemann … (2010)

Global control of tuberculosis is hampered by slow, insensitive diagnostic methods, particularly for the detection of drug-resistant forms and in patients with human immunodeficiency virus infection. Early detection is essential to reduce the death rate and interrupt transmission, but the complexity and infrastructure needs of sensitive methods limit their accessibility and effect. We assessed the performance of Xpert MTB/RIF, an automated molecular test for Mycobacterium tuberculosis (MTB) and resistance to rifampin (RIF), with fully integrated sample processing in 1730 patients with suspected drug-sensitive or multidrug-resistant pulmonary tuberculosis. Eligible patients in Peru, Azerbaijan, South Africa, and India provided three sputum specimens each. Two specimens were processed with N-acetyl-L-cysteine and sodium hydroxide before microscopy, solid and liquid culture, and the MTB/RIF test, and one specimen was used for direct testing with microscopy and the MTB/RIF test. Among culture-positive patients, a single, direct MTB/RIF test identified 551 of 561 patients with smear-positive tuberculosis (98.2%) and 124 of 171 with smear-negative tuberculosis (72.5%). The test was specific in 604 of 609 patients without tuberculosis (99.2%). Among patients with smear-negative, culture-positive tuberculosis, the addition of a second MTB/RIF test increased sensitivity by 12.6 percentage points and a third by 5.1 percentage points, to a total of 90.2%. As compared with phenotypic drug-susceptibility testing, MTB/RIF testing correctly identified 200 of 205 patients (97.6%) with rifampin-resistant bacteria and 504 of 514 (98.1%) with rifampin-sensitive bacteria. Sequencing resolved all but two cases in favor of the MTB/RIF assay. The MTB/RIF test provided sensitive detection of tuberculosis and rifampin resistance directly from untreated sputum in less than 2 hours with minimal hands-on time. (Funded by the Foundation for Innovative New Diagnostics.)

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The history of tuberculosis.

Roy Daniel (2006)

Tuberculosis has claimed its victims throughout much of known human history. It reached epidemic proportions in Europe and North America during the 18th and 19th centuries, earning the sobriquet, "Captain Among these Men of Death." Then it began to decline. Understanding of the pathogenesis of tuberculosis began with the work of Théophile Laennec at the beginning of the 19th century and was further advanced by the demonstration of the transmissibility of Mycobacterium tuberculosis infection by Jean-Antoine Villemin in 1865 and the identification of the tubercle bacillus as the etiologic agent by Robert Koch in 1882. Clemens von Pirquet developed the tuberculin skin test in 1907 and 3 years later used it to demonstrate latent tuberculous infection in asymptomatic children. In the late 19th and early 20th centuries sanatoria developed for the treatment of patients with tuberculosis. The rest provided there was supplemented with pulmonary collapse procedures designed to rest infected parts of lungs and to close cavities. Public Health measures to combat the spread of tuberculosis emerged following the discovery of its bacterial cause. BCG vaccination was widely employed following World War I. The modern era of tuberculosis treatment and control was heralded by the discovery of streptomycin in 1944 and isoniazid in 1952.

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Author and article information

Contributors

Fikru Gashaw: fikrug2012@gmail.com

Berhanu Erko: berhanue@yahoo.com

Yalemtsehay Mekonnen: yalemtmek55@gmail.com

Bazezew Yenew: bazezewyenew@yahoo.com

Misikir Amare: misikiramare.ma@gmail.com

Balako Gumi: balako.gumi@yahoo.com

Gobena Ameni: gobenachimdi2009@yahoo.co.uk

Journal

Journal ID (nlm-ta): BMC Infect Dis

Journal ID (iso-abbrev): BMC Infect Dis

Title: BMC Infectious Diseases

Publisher: BioMed Central (London )

ISSN (Electronic): 1471-2334

Publication date (Electronic): 12 March 2021

Publication date PMC-release: 12 March 2021

Publication date Collection: 2021

Volume: 21

Electronic Location Identifier: 261

Affiliations

[1 ]GRID grid.7123.7, ISNI 0000 0001 1250 5688, Aklilu Lemma Institute of Pathobiology, , Addis Ababa University, ; P.O. Box 1176, Addis Ababa, Ethiopia

[2 ]GRID grid.7123.7, ISNI 0000 0001 1250 5688, Department of Microbial, Cellular and Molecular Biology, , College of Natural Sciences, Addis Ababa University, ; P.O. Box 1176, Addis Ababa, Ethiopia

[3 ]GRID grid.493105.a, ISNI 0000 0000 9089 2970, Department of Biology, College of Natural and Computational Sciences, , Kotebe Metropolitan University, ; P.O. Box 31248, Addis Ababa, Ethiopia

[4 ]GRID grid.452387.f, Ethiopian Public Health Institute, ; P.O. Box 1242, Addis Ababa, Ethiopia

[5 ]GRID grid.43519.3a, ISNI 0000 0001 2193 6666, Department of Veterinary Medicine, College of Food and Agriculture, , United Arab Emirates University, ; Al Ain, P.O. Box 15551 Abu Dhabi United Arab Emirates

Article

Publisher ID: 5961

DOI: 10.1186/s12879-021-05961-8

PMC ID: 7953820

PubMed ID: 33711936

SO-VID: 97218ac1-e20a-4280-8d0a-63c6196a0231

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 12 December 2020

Date accepted : 2 March 2021

Custom metadata

ScienceOpen disciplines: Infectious disease & Microbiology

Keywords: mycobacterium tuberculosis,drug resistance,bactec mgit 960,mtbdrplus assay,northeastern ethiopia

Data availability:

ScienceOpen disciplines: Infectious disease & Microbiology

Keywords: mycobacterium tuberculosis, drug resistance, bactec mgit 960, mtbdrplus assay, northeastern ethiopia

Phenotypic and genotypic drug sensitivity profiles of Mycobacterium tuberculosis infection and associated factors in northeastern Ethiopia

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Abstract

Background

Methods

Results

Conclusion

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Point-Of-Care Testing for Tuberculosis

Most cited references 31

Interrater reliability: the kappa statistic

Rapid molecular detection of tuberculosis and rifampin resistance.

The history of tuberculosis.

Author and article information

Contributors

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Article

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