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Full-Text Articles in Pathology
Methylation In Mycobacterium Tuberculosis Is Lineage Specific With Associated Mutations Present Globally, Jody Phelan, Paola Florez De Sessions, Leopold Tientcheu, Joao Perdigao, Diana Machado, Rumina Hasan, Zahra Hasan, Indra L. Bergval, Richard Anthony, Ruth Mcnerney
Methylation In Mycobacterium Tuberculosis Is Lineage Specific With Associated Mutations Present Globally, Jody Phelan, Paola Florez De Sessions, Leopold Tientcheu, Joao Perdigao, Diana Machado, Rumina Hasan, Zahra Hasan, Indra L. Bergval, Richard Anthony, Ruth Mcnerney
Department of Pathology and Laboratory Medicine
DNA methylation is an epigenetic modification of the genome involved in regulating crucial cellular processes, including transcription and chromosome stability. Advances in PacBio sequencing technologies can be used to robustly reveal methylation sites. The methylome of the Mycobacterium tuberculosis complex is poorly understood but may be involved in virulence, hypoxic survival and the emergence of drug resistance. In the most extensive study to date, we characterise the methylome across the 4 major lineages of M. tuberculosis and 2 lineages of M. africanum, the leading causes of tuberculosis disease in humans. We reveal lineage-specific methylated motifs and strain-specific mutations that are …
Single Nucleotide Polymorphisms In Efflux Pumps Genes In Extensively Drug Resistant Mycobacterium Tuberculosis Isolates From Pakistan, Akbar Kanji, Rumina Hasan, Asho Ali, Ambreen Zaver, Ying Zhang, Kehkashan Imtiaz, Wanliang Shi, Taane G. Clark, Ruth Mcnerney, Jody Phelan
Single Nucleotide Polymorphisms In Efflux Pumps Genes In Extensively Drug Resistant Mycobacterium Tuberculosis Isolates From Pakistan, Akbar Kanji, Rumina Hasan, Asho Ali, Ambreen Zaver, Ying Zhang, Kehkashan Imtiaz, Wanliang Shi, Taane G. Clark, Ruth Mcnerney, Jody Phelan
Department of Pathology and Laboratory Medicine
It is challenging to understand mechanisms of drug resistance in Mycobacterium tuberculosis (MTB) due to the large variability in resistance associated genes. Efflux pump genes contribute to drug resistance and thus add to this complexity. Efflux pump gene protein superfamilies have been characterized by genome analysis of drug resistant strains and through invitro transcriptional studies. However, there is limited information regarding efflux pump genes in extensively drug resistant (XDR) tuberculosis (TB) isolates. Whole genome sequencing (WGS) based analysis of 37 extensively drug resistant (XDR) and five drug sensitive (DS) MTB clinical isolates was performed. Single nucleotide polymorphisms (SNPs) in efflux …
Phenotypic Low-Level Isoniazid Resistance As A Marker To Predict Ethionamide Resistance In Mycobacterium Tuberculosis, Salima Qamar, Joveria Q. Farooqi, Kausar Jabeen, Rumina Hasan
Phenotypic Low-Level Isoniazid Resistance As A Marker To Predict Ethionamide Resistance In Mycobacterium Tuberculosis, Salima Qamar, Joveria Q. Farooqi, Kausar Jabeen, Rumina Hasan
Department of Pathology and Laboratory Medicine
Background: Tuberculosis is one of the most prevalent diseases in Pakistan. Pakistan has the highest burden of MDR-TB in the Eastern Mediterranean region. Ethionamide is an anti-tuberculous drug frequently used to treat MDR-TB. Its drug susceptibility testing is not easily available in resource limited settings. Since it acts on the same target protein as isoniazid (inhA protein encoded by inhA gene), we sought to find out if phenotypic isoniazid resistance can be a marker of ethionamide resistance.
Materials and Methods: This was a retrospective observational study conducted at the Aga Khan University hospital section of microbiology. Data was retrieved between …
Mycobacterial Contamination Of Bronchoscopes: Challenges And Possible Solutions In Low Resource Settings, Dania Khalid Saeed, Sadia Shakoor, Seema Irfan, Rumina Hasan
Mycobacterial Contamination Of Bronchoscopes: Challenges And Possible Solutions In Low Resource Settings, Dania Khalid Saeed, Sadia Shakoor, Seema Irfan, Rumina Hasan
Department of Pathology and Laboratory Medicine
The use of bronchoscopes has increased in tuberculosis (TB) diagnostics to circumvent the diagnostic challenges that are associated with low sputum volume and smear-negative TB. In healthcare facilities situated in low income countries that have a high burden of TB, adequate decontamination of bronchoscopes is a challenge and often overlooked to save on time and costs. This amplifies the risk of outbreaks and pseudo-outbreaks due to Mycobacterium tuberculosis and nontuberculosis mycobacteria. In this minireview, we review published literature of contaminated bronchoscopes causing pseudo-outbreaks of M. tuberculosis and nontuberculosis mycobacteria in an effort to determine common sources, and possible mitigation strategies …
Mycobacterium Tuberculosis Central Asian Strain (Cas) Lineage Strains In Pakistan Reveal Lower Diversity Of Miru Loci Than Other Strains, Asho Ali, Zahra Hasan, Sana Jafri, Raunaq Inayat, Rumina Hasan
Mycobacterium Tuberculosis Central Asian Strain (Cas) Lineage Strains In Pakistan Reveal Lower Diversity Of Miru Loci Than Other Strains, Asho Ali, Zahra Hasan, Sana Jafri, Raunaq Inayat, Rumina Hasan
Department of Pathology and Laboratory Medicine
Mycobacterium tuberculosis (MTB) Central Asian Strain (CAS) lineage strains are predominant in South Asia. Mycobacterial interspersed repetitive units-variable number of tandem repeats (MIRU-VNTR) typing is an effective way of determining genetic diversity of strains. A maximum of 24 loci-based MIRU-VNTR typing can be used, however, it is important to investigate the relevance of specific MIRU loci for regional strains for more cost-effective MIRU typing. MIRU-VNTR typing was performed on MTB strains from Pakistan. Strains were comprised of CAS (n=113) and non-CAS lineages (n=87) - both multi-drug resistant (MDR) and drug susceptible. Hunter Gaston Discriminatory Index (HGDI) for each MIRU loci …
High Isoniazid Resistance Rates In Rifampicin Susceptible Mycobacterium Tuberculosis Pulmonary Isolates From Pakistan, Naima Fasih, Yasraba Rafiq, Kausar Jabeen, Rumina Hasan
High Isoniazid Resistance Rates In Rifampicin Susceptible Mycobacterium Tuberculosis Pulmonary Isolates From Pakistan, Naima Fasih, Yasraba Rafiq, Kausar Jabeen, Rumina Hasan
Department of Pathology and Laboratory Medicine
Background:
Rapid new diagnostic methods (including Xpert MTB/RIF assay) use rifampicin resistance as a surrogate marker for multidrug resistant tuberculosis. Patients infected with rifampicin susceptible strains are prescribed first line anti-tuberculosis therapy. The roll out of such methods raises a concern that strains with resistance to other first line anti-tuberculosis drugs including isoniazid will be missed and inappropriate treatment given. To evaluate implications of using such methods review of resistance data from high burden settings such as ours is essential.
Objective:
To determine resistance to first line anti-tuberculosis drugs amongst rifampicin susceptible pulmonary Mycobacterium tuberculosis (MTB) isolates from Pakistan.
Material …