J Infect Public Health
September 2023
Background: The IL-12/23/ISG15-IFN-γ pathway is the main immunological pathway for controlling intra-macrophagic microorganisms such as Mycobacteria, Salmonella, and Leishmania spp. Consequently, upon mutations in genes of the IL-12/23/ISG15-IFN-γ pathway cause increased susceptibility to intra-macrophagic pathogens, particularly to Mycobacteria. Therefore, the purpose of this study was to characterize the mutations in genes of the IL-12/23/ISG15-IFN-γ pathway in severe tuberculosis (TB) patients.
View Article and Find Full Text PDFTuberculosis (TB) is a global health problem caused by the complex (MTBC). These bacteria secrete various proteins involved in the pathogenesis and persistence of MTBC. Among the secretory proteins, MPT64 (Rv1980C) is highly conserved and is also known as a major culture filtrate that is used in rapid diagnosis of MTBC.
View Article and Find Full Text PDFTuberculosis, caused by Mycobacterium tuberculosis, is a major public health issue in Pakistan. Isoniazid is a first-line pro-drug that requires activation through an enzyme called catalase peroxidase, but is subject to widespread resistance, driven by mutations in katG and inhA genes and other loci with compensatory effects (e.g.
View Article and Find Full Text PDFTuberculosis, caused by Mycobacterium tuberculosis, is a high-burden disease in Pakistan, with multi-drug (MDR) and extensive-drug (XDR) resistance, complicating infection control. Whole genome sequencing (WGS) of M. tuberculosis is being used to infer lineages (strain-types), drug resistance mutations, and transmission patterns-all informing infection control and clinical decision making.
View Article and Find Full Text PDFTuberculosis (TB), caused by Mycobacterium tuberculosis, is endemic in Pakistan. Resistance to both firstline rifampicin and isoniazid drugs (multidrug-resistant TB; MDR-TB) is hampering disease control. Rifampicin resistance is attributed to rpoB gene mutations, but rpoA and rpoC loci may also be involved.
View Article and Find Full Text PDFObjective: To explore the burden of drug-resistant tuberculosis in Khyber Pakhtunkhwa, Pakistan.
Methods: The cross-sectional study was conducted from March 1, 2016, to February 28, 2017, at the Khyber Pakhtunkhwa Tuberculosis Reference Laboratory, Hayatabad Medical Complex, Peshawar, Pakistan, and comprised referred suspected tuberculosis patient samples. Drug Susceptibility testing on all Mycobacterium tuberculosis complex strains was performed and data was subjected to statistical analysis.
Whole genome sequencing (WGS) is one of the most reliable methods for detection of drug resistance, genetic diversity in other virulence factor and also evolutionary dynamics of Mycobacterium tuberculosis complex (MTBC). First-line anti-tuberculosis drugs are the major weapons against Mycobacterium tuberculosis (MTB). However, the emergence of drug resistance remained a major obstacle towards global tuberculosis (TB) control program 2030, especially in high burden countries including Pakistan.
View Article and Find Full Text PDFAmong viral outbreaks, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is one of the deadliest ones, and it has triggered the global COVID-19 pandemic. In Pakistan, until 5th September 2020, a total of 6342 deaths have been reported, of which 1255 were from the Khyber Pakhtunkhwa (KPK) province. To understand the disease progression and control and also to produce vaccines and therapeutic efforts, whole genome sequence analysis is important.
View Article and Find Full Text PDFRegardless of a plethora of advanced diagnostics, TB and drug resistance remains a principal killer. We proposed gold nanoparticles (AuNPs) attached with probes to enhance the efficiency of GeneXpert MTB/RIF assay instead of conventional dye probes for molecular detection. A total of 15,000 samples were collected from TB suspects and subjected to Xpert MTB/RIF assay, where 6800 (45.
View Article and Find Full Text PDFBackground: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) epidemic has resulted in thousands of infections and deaths worldwide. Several therapies are currently undergoing clinical trials for the treatment of SARS-CoV-2 infection. However, the development of new drugs and the repositioning of existing drugs can only be achieved after the identification of potential therapeutic targets within structures, as this strategy provides the most precise solution for developing treatments for sudden epidemic infectious diseases.
View Article and Find Full Text PDFFluoroquinolones (FQs) are broad-spectrum second-line antimicrobial drugs commonly used in the treatment of tuberculosis (TB). Data on FQ resistance in the Khyber Pakhtunkhwa (KP) province of Pakistan, a high-burden country, are scarce. This study aimed to analyze the resistance to FQs in this specific geographic area.
View Article and Find Full Text PDFSevere acute respiratory syndrome virus 2 (SARS-CoV-2) belongs to the single-stranded positive-sense RNA family. The virus contains a large genome that encodes four structural proteins, small envelope (E), matrix (M), nucleocapsid phosphoprotein (N), spike (S), and 16 nonstructural proteins (nsp1-16) that together, ensure replication of the virus in the host cell. Among these proteins, the interactions of N and Nsp3 are essential that links the viral genome for processing.
View Article and Find Full Text PDFAnti-tuberculosis therapy involves the combination of drugs to hamper the growth of (MTB). The emergence of multidrug-resistant tuberculosis (MDR-TB) is a global concern. Pakistan has been ranked 5 position in terms of a high burden of MDR-TB in the world.
View Article and Find Full Text PDFLipases with high tolerance to temperature play a significant role in industry from food manufacturing to waste management systems. Thus, there is a need to investigate these enzymes from different geographical areas to look out for a more thermo-stable one. Characterization of lipases through experimental approaches is time consuming process and sometimes the results are ambiguous due to errors.
View Article and Find Full Text PDFPyrazinamide (PZA) is one of the main FDA approved drugs to be used as the first line of defense against (MTB). It is activated into pyrazinoic acid (POA) via MTB's gene-encoded pyrazinamidase (PZase). Mutations are most commonly responsible for PZA-resistance in nearly 70% of the resistant samples.
View Article and Find Full Text PDFSpoligotyping is a reproducible, reverse hybridization approach for genotyping of complex (MTBC). Molecular typing of MTBC is helpful for understanding and controlling tuberculosis epidemics. Spoligotyping was performed on 166 clinical isolates of (MTB) collected from 25 districts of Khyber Pakhtunkhwa, Pakistan.
View Article and Find Full Text PDFBackground: Pyrazinamide (PZA) is an important component of first-line drugs because of its distinctive capability to kill subpopulations of persistent Mycobacterium tuberculosis (MTB). The prodrug (PZA) is converted to its active form, pyrazinoic acid (POA) by MTB pncA-encoded pyrazinamidase (PZase). Mutation in pncA is the most common and primary cause of PZA resistance.
View Article and Find Full Text PDFGeneXpert is one of the recent technological instruments used to diagnose tuberculosis in a short span of time. In this study, the performance of GeneXpert MTB/RIF assay for the diagnosis of extrapulmonary tuberculosis (EPTB) was compared with light-emitting diode Fluorescent Microscopy (LED-FM) in Khyber Pakhtunkhwa, Pakistan. A total of 737 EPTB samples were collected from tuberculosis (TB) suspected patients.
View Article and Find Full Text PDFMicrob Drug Resist
November 2018
Aims: Pyrazinamide (PZA) is an important component of first-line tuberculosis (TB) treatment because of its distinctive capability to kill subpopulations of persister Mycobacterium tuberculosis (MTB). The significance of PZA can be understood by its inclusion in the most recent World Health Organization-recommended multidrug-resistant (MDR) TB regimen. Very little information is available about the prevalence of PZA-resistant TB from geographically distinct regions of high burden countries, including Khyber Pakhtunkhwa (KPK), Pakistan, because drug susceptibility testing (DST) of PZA is not regularly performed due to the complexity.
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