The occurrence and frequency of genomic mutations that mediate Isoniazid and Rifampicin resistance in Mycobacterium tuberculosis isolates from untreated pulmonary Tuberculosis cases in urban Blantyre, Malawi

Geoffrey P. Kumwenda; Geoffrey Chipungu; Derek J. Sloan; Yankho Kaimila; Kondwani Chiumya; Harry Pangani

doi:10.4314/mmj.v30i1.1

The occurrence and frequency of genomic mutations that mediate Isoniazid and Rifampicin resistance in Mycobacterium tuberculosis isolates from untreated pulmonary Tuberculosis cases in urban Blantyre, Malawi

Geoffrey P. Kumwenda^*, Geoffrey Chipungu, Derek J. Sloan, Yankho Kaimila, Kondwani Chiumya, Harry Pangani

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

Background

The emergence and spread of drug-resistant Tuberculosis (TB) is a major public health threat. TB resistance originates in the course of treatment due to genomic mutations in Mycobacterium tuberculosis (MTB). An increase in new cases with drug-resistant TB could be an indicator of high levels of circulating resistant strains. This study was conducted to determine the occurrence and frequency of genomic mutations that mediate Isoniazid (INH) and Rifampicin (RIF) resistance among isolates from untreated TB cases in urban Blantyre, Malawi.

Methods

A cross-sectional retrospective study was conducted on a panel of 141(n=141) MTB clinical isolates recovered between June 2010 and January 2012 from ≥2+ Ziehl-Neelsen smear positive new pulmonary-TB patients with no history of treatment. Frozen isolates were revived using the BACTEC MGIT detection system. DNA was extracted using GenoLyse DNA extraction kit and detection of genomic mutations was carried out using the GenoType MTBDRplus Ver 2.0 assay.

Results

Out of the 141 isolates studied, 3 (2.1%) were found carrying mutations in the katG gene that confer resistance to Isoniazid (INH). No mutations were detected in the inhA promoter region gene that confer weak INH resistance or in the rpoB gene that confer Rifampicin resistance. All katG mutant genes had a S315T1 single point mutation, a genomic alteration that mediates high INH resistance.

Conclusion

The katG mutant gene conferring resistance to INH was the only genomic mutation observed among the isolates studied and the frequency of occurrence was low. Our findings suggest low levels of circulating drug-resistant MTB strains in urban Blantyre, Malawi.

Original language	English
Pages (from-to)	1-5
Number of pages	5
Journal	Malawi Medical Journal
Volume	30
Issue number	1
Early online date	26 Mar 2018
DOIs	https://doi.org/10.4314/mmj.v30i1.1
Publication status	Published - Mar 2018

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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Kumwenda, G. P., Chipungu, G., Sloan, D. J., Kaimila, Y., Chiumya, K., & Pangani, H. (2018). The occurrence and frequency of genomic mutations that mediate Isoniazid and Rifampicin resistance in Mycobacterium tuberculosis isolates from untreated pulmonary Tuberculosis cases in urban Blantyre, Malawi. Malawi Medical Journal, 30(1), 1-5. https://doi.org/10.4314/mmj.v30i1.1

@article{fb5a5e69ce1b4b1cb4e9d9d256af7cc6,

title = "The occurrence and frequency of genomic mutations that mediate Isoniazid and Rifampicin resistance in Mycobacterium tuberculosis isolates from untreated pulmonary Tuberculosis cases in urban Blantyre, Malawi",

abstract = "BackgroundThe emergence and spread of drug-resistant Tuberculosis (TB) is a major public health threat. TB resistance originates in the course of treatment due to genomic mutations in Mycobacterium tuberculosis (MTB). An increase in new cases with drug-resistant TB could be an indicator of high levels of circulating resistant strains. This study was conducted to determine the occurrence and frequency of genomic mutations that mediate Isoniazid (INH) and Rifampicin (RIF) resistance among isolates from untreated TB cases in urban Blantyre, Malawi.MethodsA cross-sectional retrospective study was conducted on a panel of 141(n=141) MTB clinical isolates recovered between June 2010 and January 2012 from ≥2+ Ziehl-Neelsen smear positive new pulmonary-TB patients with no history of treatment. Frozen isolates were revived using the BACTEC MGIT detection system. DNA was extracted using GenoLyse DNA extraction kit and detection of genomic mutations was carried out using the GenoType MTBDRplus Ver 2.0 assay.ResultsOut of the 141 isolates studied, 3 (2.1%) were found carrying mutations in the katG gene that confer resistance to Isoniazid (INH). No mutations were detected in the inhA promoter region gene that confer weak INH resistance or in the rpoB gene that confer Rifampicin resistance. All katG mutant genes had a S315T1 single point mutation, a genomic alteration that mediates high INH resistance.ConclusionThe katG mutant gene conferring resistance to INH was the only genomic mutation observed among the isolates studied and the frequency of occurrence was low. Our findings suggest low levels of circulating drug-resistant MTB strains in urban Blantyre, Malawi.",

author = "Kumwenda, {Geoffrey P.} and Geoffrey Chipungu and Sloan, {Derek J.} and Yankho Kaimila and Kondwani Chiumya and Harry Pangani",

note = "This study was funded by the Helse Nord Tuberculosis Initiative (HNTI), a College of Medicine grant supported by the Helse Nord RHF and the University of Tromso.",

year = "2018",

month = mar,

doi = "10.4314/mmj.v30i1.1",

language = "English",

volume = "30",

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Kumwenda, GP, Chipungu, G, Sloan, DJ, Kaimila, Y, Chiumya, K & Pangani, H 2018, 'The occurrence and frequency of genomic mutations that mediate Isoniazid and Rifampicin resistance in Mycobacterium tuberculosis isolates from untreated pulmonary Tuberculosis cases in urban Blantyre, Malawi', Malawi Medical Journal, vol. 30, no. 1, pp. 1-5. https://doi.org/10.4314/mmj.v30i1.1

The occurrence and frequency of genomic mutations that mediate Isoniazid and Rifampicin resistance in Mycobacterium tuberculosis isolates from untreated pulmonary Tuberculosis cases in urban Blantyre, Malawi. / Kumwenda, Geoffrey P.; Chipungu, Geoffrey; Sloan, Derek J. et al.
In: Malawi Medical Journal, Vol. 30, No. 1, 03.2018, p. 1-5.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - The occurrence and frequency of genomic mutations that mediate Isoniazid and Rifampicin resistance in Mycobacterium tuberculosis isolates from untreated pulmonary Tuberculosis cases in urban Blantyre, Malawi

AU - Kumwenda, Geoffrey P.

AU - Chipungu, Geoffrey

AU - Sloan, Derek J.

AU - Kaimila, Yankho

AU - Chiumya, Kondwani

AU - Pangani, Harry

N1 - This study was funded by the Helse Nord Tuberculosis Initiative (HNTI), a College of Medicine grant supported by the Helse Nord RHF and the University of Tromso.

PY - 2018/3

Y1 - 2018/3

N2 - BackgroundThe emergence and spread of drug-resistant Tuberculosis (TB) is a major public health threat. TB resistance originates in the course of treatment due to genomic mutations in Mycobacterium tuberculosis (MTB). An increase in new cases with drug-resistant TB could be an indicator of high levels of circulating resistant strains. This study was conducted to determine the occurrence and frequency of genomic mutations that mediate Isoniazid (INH) and Rifampicin (RIF) resistance among isolates from untreated TB cases in urban Blantyre, Malawi.MethodsA cross-sectional retrospective study was conducted on a panel of 141(n=141) MTB clinical isolates recovered between June 2010 and January 2012 from ≥2+ Ziehl-Neelsen smear positive new pulmonary-TB patients with no history of treatment. Frozen isolates were revived using the BACTEC MGIT detection system. DNA was extracted using GenoLyse DNA extraction kit and detection of genomic mutations was carried out using the GenoType MTBDRplus Ver 2.0 assay.ResultsOut of the 141 isolates studied, 3 (2.1%) were found carrying mutations in the katG gene that confer resistance to Isoniazid (INH). No mutations were detected in the inhA promoter region gene that confer weak INH resistance or in the rpoB gene that confer Rifampicin resistance. All katG mutant genes had a S315T1 single point mutation, a genomic alteration that mediates high INH resistance.ConclusionThe katG mutant gene conferring resistance to INH was the only genomic mutation observed among the isolates studied and the frequency of occurrence was low. Our findings suggest low levels of circulating drug-resistant MTB strains in urban Blantyre, Malawi.

AB - BackgroundThe emergence and spread of drug-resistant Tuberculosis (TB) is a major public health threat. TB resistance originates in the course of treatment due to genomic mutations in Mycobacterium tuberculosis (MTB). An increase in new cases with drug-resistant TB could be an indicator of high levels of circulating resistant strains. This study was conducted to determine the occurrence and frequency of genomic mutations that mediate Isoniazid (INH) and Rifampicin (RIF) resistance among isolates from untreated TB cases in urban Blantyre, Malawi.MethodsA cross-sectional retrospective study was conducted on a panel of 141(n=141) MTB clinical isolates recovered between June 2010 and January 2012 from ≥2+ Ziehl-Neelsen smear positive new pulmonary-TB patients with no history of treatment. Frozen isolates were revived using the BACTEC MGIT detection system. DNA was extracted using GenoLyse DNA extraction kit and detection of genomic mutations was carried out using the GenoType MTBDRplus Ver 2.0 assay.ResultsOut of the 141 isolates studied, 3 (2.1%) were found carrying mutations in the katG gene that confer resistance to Isoniazid (INH). No mutations were detected in the inhA promoter region gene that confer weak INH resistance or in the rpoB gene that confer Rifampicin resistance. All katG mutant genes had a S315T1 single point mutation, a genomic alteration that mediates high INH resistance.ConclusionThe katG mutant gene conferring resistance to INH was the only genomic mutation observed among the isolates studied and the frequency of occurrence was low. Our findings suggest low levels of circulating drug-resistant MTB strains in urban Blantyre, Malawi.

U2 - 10.4314/mmj.v30i1.1

DO - 10.4314/mmj.v30i1.1

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SN - 1995-7262

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JO - Malawi Medical Journal

JF - Malawi Medical Journal

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