SARS-CoV-2 variants of concern (VOC) have been associated with increased viral transmission and disease severity. We investigated the mechanisms of pathogenesis caused by variants using a host blood transcriptome profiling approach. We analysed transcriptional signatures of COVID-19 patients comparing those infected with wildtype (wt), alpha, delta or omicron strains seeking insights into infection in Asymptomatic cases.
View Article and Find Full Text PDFBackground: Pakistan reported 1.57 million COVID-19 cases between 2020 and 2022, based on approximately 30.6 million SARS-CoV-2 RT-PCR (reverse-transcription polymerase chain reaction) tests conducted.
View Article and Find Full Text PDFTuberculosis (TB) and sarcoidosis are both granulomatous diseases. Here, we compared the immunological microenvironments of granulomas from TB and sarcoidosis patients using sequencing (ISS) transcriptomic analysis and multiplexed immunolabeling of tissue sections. TB lesions consisted of large necrotic and cellular granulomas, whereas "multifocal" granulomas with macrophages or epitheloid cell core and a T-cell rim were observed in sarcoidosis samples.
View Article and Find Full Text PDFBackground: Protection against SARS-CoV-2 is mediated by humoral and T cell responses. Pakistan faced relatively low morbidity and mortality from COVID-19 through the pandemic. To examine the role of prior immunity in the population, we studied IgG antibody response levels, virus neutralizing activity and T cell reactivity to Spike protein in a healthy control group (HG) as compared with COVID-19 cases and individuals from the pre-pandemic period (PP).
View Article and Find Full Text PDFBackground And Aims: COVID-19 vaccinations have reduced morbidity and mortality from the disease. Antibodies against severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) have been associated with immune protection. Seroprevalence studies revealed high immunoglobulin G (IgG) antibody levels to SARS-CoV-2 in the Pakistani population before vaccinations.
View Article and Find Full Text PDFCOVID-19 resulted in extensive morbidity and mortality worldwide. SARS-CoV-2 evolved rapidly, with increasing transmission due to Variants of Concern (VOC). Identifying VOC became important but genome submissions from low-middle income countries (LMIC) remained low leading to gaps in genomic epidemiology.
View Article and Find Full Text PDFObjectives: To assess the diagnostic accuracy of different cut-off values of pleural fluid adenosine deaminase levels as a diagnostic method for tuberculous pleural effusion.
Methods: The prospective study was conducted from 2014 to 2016 at the Aga Khan University Hospital, Karachi, and comprised pleural fluid samples of adult patients with and without tuberculosis which were tested for adenosine deaminase levels, and divided into tuberculosis group A and non-tuberculosis group B. Sensitivity, specificity, negative predictive value and positive predictive value were calculated using different cut-offs.
(MTB) is the causative agent of TB. TB incidence is high in many low resource settings where limited health systems make it difficult for screening of co-morbid conditions. Susceptibility to TB is increased with coincident diabetes mellitus (DM) or prediabetes.
View Article and Find Full Text PDFIntroduction: An estimated 1.5 million cases were reported in Pakistan until 23 March, 2022. However, SARS-CoV-2 PCR testing capacity has been limited and the incidence of COVID-19 infections is unknown.
View Article and Find Full Text PDFTuberculosis (TB) outcomes are worsened by type II diabetes mellitus (DM). Protective immunity against Mycobacterium tuberculosis (MTB) is driven by cytokines. Latent TB (LTBi) is common but its effect on the diabetic host is not well understood.
View Article and Find Full Text PDFObjectives: This study aimed to explore mechanism of colistin resistance amongst Klebsiella pneumoniae isolates through plasmid mediated mcr-1 gene in Pakistan. Carbapenem and Colistin resistant K. pneumoniae isolates (n = 34) stored at - 80 °C as part of the Aga Khan University Clinical Laboratory strain bank were randomly selected and subjected to mcr-1 gene PCR.
View Article and Find Full Text PDFUnderstanding key host protective mechanisms against SARS-CoV-2 infection can help improve treatment modalities for COVID-19. We used a blood transcriptome approach to study biomarkers associated with differing severity of COVID-19, comparing severe and mild Symptomatic disease with Asymptomatic COVID-19 and uninfected Controls. There was suppression of antigen presentation but upregulation of inflammatory and viral mRNA translation associated pathways in Symptomatic as compared with Asymptomatic cases.
View Article and Find Full Text PDFBackground: We investigated the genome diversity of SARS-CoV-2 associated with the early COVID-19 period to investigate evolution of the virus in Pakistan.
Materials And Methods: We studied ninety SARS-CoV-2 strains isolated between March and October 2020. Whole genome sequences from our laboratory and available genomes were used to investigate phylogeny, genetic variantion and mutation rates of SARS-CoV-2 strains in Pakistan.
Introduction: There were 10 million new cases of tuberculosis (TB) in 2017. To eliminate TB, it is necessary to diagnose active TB and latent tuberculosis infection (LTBI). Diagnosis of paucibacillary disease and in extrapulmonary TB (EPTB) remains challenging; low mycobacterial load can be missed by microbiological or molecular based confirmation; EPTB, can be misdiagnosed due to absence of site specific specimens for testing.
View Article and Find Full Text PDFBackground And Objectives: Dengue virus infections (Dengue) have become increasingly common in Pakistan and can result in case fatalities if not managed appropriately. Patients with Dengue virus infection may be asymptomatic or present with Dengue fever (DF), Dengue with warning signs (DWS) or severe Dengue (SD). Severity in Dengue is coincident with an exacerbated production of lymphocyte-induced cytokines and chemokines which are associated with plasma leakage.
View Article and Find Full Text PDFIntroduction: Pakistan ranks fifth in high tuberculosis (TB)-burden countries and seventh among countries with high prevalence rates of diabetes mellitus (DM). DM is a risk factor for TB and worsens disease outcomes. Furthermore, Mycobacterium tuberculosis (MTB) infection can induce glucose intolerance and worsen glycemic control in diabetes.
View Article and Find Full Text PDFWe investigated the role of suppressor of cytokine signaling-1 (SOCS1) and SOCS3 molecules in lymph nodes from tuberculous lymphadenitis patients (LNTB). Fewer T cells were noted in LNTB cases, which also had raised chemokine (C-X-C motif) receptor 3 (CXCR3) levels. In addition, we observed a positive correlation between CXCR3 and SOCS1 expression.
View Article and Find Full Text PDFIntroduction: Expression of Suppressor of cytokine signaling (SOCS)-1 molecules is increased in patients with tuberculosis (TB). Early Secreted Antigen Target (ESAT)-6 kDa - induced IFN-γ responses indicate Mycobacterium tuberculosis infection. The effect of ESAT6- stimulation on SOCS1 in the host is not known.
View Article and Find Full Text PDFBackground: Appropriate immune activation of T cells and macrophages is central for the control of Mycobacterium tuberculosis infections. IFN-γ stimulated responses are lowered in tuberculosis (TB), while expression of Suppressor of Cytokine Signaling (SOCS) molecules - 1 and 3 and CD4+CD25+FoxP3+T regulatory cells is increased. Here we investigated the association of these molecules in regard to clinical severity of TB.
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