Medicine and Health Sciences Commons^™

Diagnostic Accuracy Of Different Cut-Off Values Of Adenosine Deaminase Levels In Tuberculous Pleural Effusion, Kiran Iqbal Masood, Shayan Shahid, Kauser Jabeen, Joveria Farooqi, Sabeika Raza Kerawala, Muhammad Irfan

Department of Pathology and Laboratory Medicine

Objective: To assess the diagnostic accuracy of different cut-off values of pleural fluid adenosine deaminase levels as a diagnostic method for tuberculous pleural effusion.
Method: 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. Data was analysed using IBM SPSS (Statistical Package for Social Sciences) version 21.0 (IBM Corp., Armonk, …

Characterisation Of Drug-Resistant Mycobacterium Tuberculosis Mutations And Transmission In Pakistan, Gary Napier, Anwar Sheed Khan, Abdul Jabbar, Muhammad Tahir Khan, Sajid Ali, Muhammad Qasim, Noor Mohammad, Rumina Hasan, Zahra Hasan, Susana Campino

Department of Pathology and Laboratory Medicine

Tuberculosis, 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. Here we analyse WGS data on 535 M. tuberculosis isolates sourced across Pakistan between years 2003 and 2020, to understand the circulating strain-types and mutations related to 12 anti-TB drugs, as well as identify transmission clusters. Most isolates belonged to lineage 3 (n = 397; 74.2%) strain-types, and were MDR (n = …

Molecular Epidemiology Of Mycobacterium Tuberculosis Complex Strains In Urban And Slum Settings Of Nairobi, Kenya, Glennah Kerubo, Perpetua Ndungu, Yassir Adam Shuaib, Evans Amukoye, Gunturu Revathi, Susanne Homolka, Samuel Kariuki, Matthias Merker, Stefan Niemann

Pathology, East Africa

Kenya is a country with a high tuberculosis (TB) burden. However, knowledge on the genetic diversity of Mycobacterium tuberculosis complex (MTBC) strains and their transmission dynamics is sparsely available. Hence, we used whole-genome sequencing (WGS) to depict the genetic diversity, molecular markers of drug resistance, and possible transmission clusters among MTBC strains in urban and slum settings of Nairobi. We analyzed 385 clinical MTBC isolates collected between 2010 and 2015 in combination with patients’ demographics. We showed that the MTBC population mainly comprises strains of four lineages (L1–L4). The two dominating lineages were L4 with 55.8% (n = 215) and …

A Prospective Observational Study Of Community Acquired Pneumonia In Kenya: The Role Of Viral Pathogens, Jamila Nambafu, Mary Achakolong, Fridah Mwendwa, Jumaa Bwika, Felix Riunga, Samuel Gitau, Hanika Patel, Rodney Adam

Internal Medicine, East Africa

Background: Lower respiratory tract infections continue to contribute significantly to morbidity and mortality across all age groups globally. In sub-Saharan Africa, many studies of community acquired pneumonia in adults have focused on HIV-infected patients and little attention has been given to risk factors and etiologic agents in an urban area with a more moderate HIV prevalence.

Methods: We prospectively enrolled 77 patients admitted to a 280 bed teaching hospital in Kenya with radiographically confirmed community acquired pneumonia from May 2019 to March 2020. The patients were followed for etiology and clinical outcomes. Viral PCR testing was performed using …

Post Tuberculosis Treatment Infectious Complications, Desmond Hsu, Muhammad Irfan, Kauser Jabeen, Nousheen Iqbal, Rumina Hasan, Giovanni Battista Migliori, Alimuddin Zumla, Dina Visca, Rosella Centis, Simon Tiberi

Department of Pathology and Laboratory Medicine

Following greater attention and follow-up of patients with treated pulmonary tuberculosis (TB), it has emerged that infections are more likely to occur in this cohort of patients. This comes as no surprise, as pulmonary TB is a destructive process that leads to cicatrization, alteration of parenchyma, bronchiectasis, and scarring of the lung, with reduction of lung volumes and an impact on pulmonary function. In addition to relapse and re-infection with TB, other pathogens are increasingly recognized in post-TB patients. This paper serves as a summary and guide on how to approach the post-TB patient with new signs and symptoms of …

Raised Levels Of Ifn-Gamma And Il-13 Are Associated With Pre-Diabetes Amongst Newly Diagnosed Patients With Tuberculosis, Zahra Hasan, Muhammad Irfan, Qamar Masood, Owais Ahmed, Shoaib Rao, Umme Salama Moosajee, Naseem Salahuddin

Department of Pathology and Laboratory Medicine

Objective: To investigate pre-diabetes and diabetes in newly-diagnosed tuberculosis patients and to assess the association of serum cytokine levels with diabetes status.
Methods: The cross-sectional study was conducted at Indus Hospital and The Aga Khan University Hospital, Karachi from May to November 2015, and included patients of either gender aged 18 years or more with a confirmed diagnosis of tuberculosis who were either newly diagnosed or had received up to 1 month of anti-tuberculosis therapy were included. Patients were enrolled from among those presenting to the clinics at Indus Hospital, Karachi, and the Department of Medicine, Aga Khan University Hospital …

Tuberculous Granuloma On Bone Marrow Trephine, Farheen Karim, Hira Qadir

Department of Pathology and Laboratory Medicine

Bone marrow examination is a useful tool for diagnosis of many diseases. The utility of bone marrow examination in workup of pyrexia of unknown origin cannot be undermined. Bone trephine of patients presenting with pyrexia of unknown origin must be carefully looked upon for granulomas for evaluation of tuberculosis. In this case, bone marrow trephine aided in timely diagnosis of tuberculosis in a patient.

Tuberculosis In Vulnerable Populations In Eastern Mediterranean Region-Implications For Control, Sadia Shakoor, Rumina Hasan

Department of Pathology and Laboratory Medicine

Objectives: Socially and economically disadvantaged or "vulnerable" people are at high risk of tuberculosis (TB) and also contribute to active chains of TB transmission. Included in such vulnerable populations are children, women, prisoners, people living with human immunodeficiency virus, the homeless, and displaced people. The ongoing active transmission of TB among such populations is made more difficult to assess and control by difficult access, health inequities, poverty, and other chronic and debilitating health conditions at individual, domestic, and community levels.
Methods: The 22 Eastern Mediterranean Region member states encompass diverse sociopolitical and socioeconomic situations with far-reaching effects on vulnerable populations …

Cerebral Aspergillosis And Pulmonary Tuberculosis In A Child With Chronic Granulomatous Disease, Muhammad Waqas, Sidra Zafar, Tooba Rehman, Muhammed Riyaz, Muhammad Ehsan Bari, Romana Idress

Section of Neurosurgery

Background: Chronic granulomatous disease (CGD) is an immune disorder that affects phagocytes. It is characterized by recurrent or persistent bacterial and fungal infections. Reports of tuberculosis (TB) in patients with CGD are rare. In developing countries, where TB is endemic, possibility of other chronic infections is often overlooked by physicians.
Case description: We report the case of a 4-year-old boy who had recurrent respiratory infections and episodes of headache. He was put on antituberculosis (ATT) drugs without microbiological or pathological evidence 2 months prior to presentation. The child did not improve and was brought to our hospital where a computed …

Mycobacterium Tuberculosis Lineage 4 Comprises Globally Distributed And Geographically Restricted Sublineages, David Stucki, Daniela Brites, Leïla Jeljeli, Mireia Coscolla, Gunturu Revathi

Pathology, East Africa

Generalist and specialist species differ in the breadth of their ecological niches. Little is known about the niche width of obligate human pathogens. Here we analyzed a global collection of Mycobacterium tuberculosis lineage 4 clinical isolates, the most geographically widespread cause of human tuberculosis. We show that lineage 4 comprises globally distributed and geographically restricted sublineages, suggesting a distinction between generalists and specialists. Population genomic analyses showed that, whereas the majority of human T cell epitopes were conserved in all sublineages, the proportion of variable epitopes was higher in generalists. Our data further support a European origin for the most …

Interplay Of Chemo Attractant Peptides (Cathelicidin And Chemerin) With Vitamin-D In Patients With Pulmonary Tuberculosis, Najeeha Talat Iqbal, Syeda Sadia Fatima, Rabia Hussain, Nisar Ahmed Rao, Narius Virji, Bushra Jamil, Muhammad Irfan

Department of Paediatrics and Child Health

Aim: Both Cathelicidin and Chemerin are chemoattractant proteins and possess antimicrobial activity.Sufficient level of Vitamin D is important for optimum response of Cathelicidin for its antimycobacterial activity. Studies on the role of these antimicrobial peptides and their relationship withVitamin D level are limited in tuberculosis. The aim of this study was to investigate an associationof Vitamin D with antimicrobial peptide (Cathelicidin) and an adipokine (Chemerin) in patients with pulmonary tuberculosis (TB). Methods: In a case control study we estimated level of Vitamin D, Chemerin, Cathelicidin and TNFα in pulmonary TB patients (n=22) and healthy endemic controls (n=17) using sandwich ELISA …

Drug Resistant Tuberculosis: Challenges Of Urbanization, Rumina Hasan

Department of Pathology and Laboratory Medicine

No abstract provided.

Histologic Findings In Biopsies/Resection Specimens From The Small Intestine With Special Emphasis On Celiac Disease: Experience From A Developing Country In South Asia, Huma Arshad, Zubair Ahmad

Department of Pathology and Laboratory Medicine

Biopsies from the small intestine especially the duodenum are now being performed much more frequently than in the past. The most frequent reason for performing duodenal biopsies is to evaluate for malabsorption. In the last few years, increased awareness has resulted in more biopsies sent for evaluation of malabsorption, especially celiac disease (CD). In the duodenum, features of malabsorption (increased intraepithelial lymphocytes, villous shortening, and atrophy) were the most common histologic finding seen in 63.4% of cases. Serum tTG levels were available for correlation in 52.8% of cases. In patients with confirmed CD, 53.4% were MARSH IIIb, and 29.5% were …

Line Probe Assay For Detection Of Rifampicin And Isoniazid Resistant Tuberculosis In Pakistan, Joveria Qais Farooqi, Erum Khan, Syed Muhammed Zaheer Alam, Asho Ali, Zahra Hasan, Rumina Hasan

Department of Pathology and Laboratory Medicine

Objective:
To assess the efficacy of a line-probe assay delta (LiPA) as rapid diagnostic test for early detection of drug-resistant tuberculosis compared to conventional susceptibility methods in Pakistan.
Methods:
Resistance to rifampicin (RIF) and isoniazid (INH) in 108 smear-positive pulmonary tuberculosis samples was detected using a line-probe assay [GenoType MTBDRplus (Hain Lifescience, GmbH, Nehren, Germany)] at the clinical microbiology laboratory of Aga Khan University Hospital in May, 2009. Results were compared with susceptibilities performed while using agar proportion.
Results:
In comparison to the agar proportion method, the detection rate and specificity of resistance using MTBDR plus was 92.5% and 98.2% …

Resistance Patterns Of Mycobacterium Tuberculosis Isolates From Pulmonary Tuberculosis Patients In Nairobi, Perpetual Wangui Ndung’U, Samuel Kariuki, Zipporah Ng’Ang’A, Gunturu Revathi

Pathology, East Africa

Introduction: In Kenya, which ranks thirteenth of 27 high tuberculosis burden countries, diagnosis is based on Ziehl-Neelsen staining alone and patients are treated without information on sensitivity patterns. This study aimed to determine resistance patterns of Mycobacterium tuberculosis isolated from pulmonary samples.

Methodology: Pulmonary tuberculosis patients in Nairobi were randomly sampled after informed consent and recruited into the study using a structured questionnaire. Specimens were cultured in liquid and solid media, and drug susceptibility tests were performed for first-line drugs including (isoniazid, rifampin, streptomycin, ethambutol and pyrazinamide).

Results: Eighty-six (30%) of 286 isolates were resistant to at least one of …

Presence Of Rd149 Deletions In M. Tuberculosis Central Asian Strain 1 Isolates Affect Growth And Tnfalpha Induction In Thp-1 Monocytes., Akber Kanji, Zahra Hasan, Mehnaz Tanveer, Raunaq Mahboob, Sana Jafri, Rumina Hasan

Department of Pathology and Laboratory Medicine

Central Asian Strain 1 (CAS1) is the prevalent Mycobacterium tuberculosis genogroup in South Asia. CAS1 strains carry deletions in RD149 and RD152 regions. Significance of these deletions is as yet unknown. We compared CAS1 strains with RD149 and concurrent RD149-RD152 deletions with CAS1 strains without deletions and with the laboratory reference strain, M. tuberculosis H37Rv for growth and for induction of TNFα, IL6, CCL2 and IL10 in THP-1 cells. Growth of CAS1 strains with deletions was slower in broth (RD149; p = 0.024 and RD149-RD152; p = 0.025) than that of strains without deletions. CAS1 strains with RD149 deletion strains …

Esat6-Induced Ifngamma And Cxcl9 Can Differentiate Severity Of Tuberculosis., Zahra Hasan, Bushra Jamil, Mussarat Ashraf, Muniba Islam, Muhammad S Yusuf, Javaid A Khan, Rabia Hussain

Department of Pathology and Laboratory Medicine

Background: Protective responses against Mycobacterium tuberculosis are dependent on appropriate T cell and macrophage activation. Mycobacterial antigen six kDa early secreted antigenic target (ESAT6) and culture filtrate protein 10 (CFP10) can detect M. tuberculosis specific IFNgamma responses. However, most studies have been performed in non-endemic regions and to study pulmonary tuberculosis (PTB). We have studied ESAT6 and CFP10 induced cytokine and chemokines responses in PTB and extrapulmonary (EPul) TB.
Methodology: IFNgamma, IL10, CXCL9 and CCL2 responses were determined using an ex vivo whole blood assay system in PTB (n = 30) and EPulTB Patients with limited (LNTB, n = …

Cytokine Gene Polymorphisms Across Tuberculosis Clinical Spectrum In Pakistani Patients., Ambreen Ansari, Najeeha Talat, Bushra Jamil, Zahra Hasan, Tashmeem Razzaki, Ghaffar Dawood, Rabia Hussain

Department of Pathology and Laboratory Medicine

Background:Pakistan ranks 7(th) globally in terms of tuberculosis (TB) disease burden (incidence 181/100000 pop./yr, prevalence of 329/pop./yr). Reports from different populations show variable associations of TB susceptibility and severity with cytokine gene polymorphisms. Tuberculosis clinical severity is multi-factorial and cytokines play a pivotal role in the modulation of disease severity. We have recently reported that the ratio of two key cytokines (IFNgamma and IL10) show significant correlation with the severity spectrum of tuberculosis. The objective of the current study was to analyze the frequency of cytokine gene polymorphisms linked to high and low responder phenotypes (IFNgamma +874 T(hi)-->A(lo) …

A Case Of Histoplasmosis Mimicking Tuberculosis, Asim Qureshi

Department of Pathology and Laboratory Medicine

Drug resistance to Tuberculosis is an emerging problem but proper exhaustive workup needs to be done before confirming the diagnosis. The case of a 5 year old male child who presented with low grade fever and lymphadenopathy and was being treated with anti TB drugs with no satisfactory response is presented. A detail workup including a biopsy gave the diagnosis of histoplasmosis.

Elevated Ex Vivo Monocyte Chemotactic Protein-1 (Ccl2) In Pulmonary As Compared With Extra-Pulmonary Tuberculosis, Zahra Hasan, Irfan Zaidi, Bushra Jamil, M Aslam Khan, Akber Kanji, Rabia Hussain

Department of Pathology and Laboratory Medicine

Background: Tuberculosis causes 3 million deaths annually. The most common site of tuberculosis is pulmonary however; extra-pulmonary forms of the disease also remain prevalent. Restriction of Mycobacterium tuberculosis depends on effective recruitment and subsequent activation of T lymphocytes, mononuclear and polymorphonuclear cells to the site of infection. Tumor necrosis factor (TNF)-α is essential for granuloma formation and is a potent activator of monocyte chemotactic protein (MCP-1, CCL2). CCL2 is essential for recruitment of monocytes and T cells and has been shown to play a role in protection against tuberculosis. Interleukin -8 (CXCL8) is a potent activator of neutrophils. Increased …

Localized Tuberculosis And Myelofibrosis With Myeloid Metaplasia : An Extremely Unusual Presentation, Suhail Muzaffar

Department of Pathology and Laboratory Medicine

Myelofibrosis with myeloid metaplasia (MMM) is usually considered primary agnogenic, however, it may be secondary to various diseases, The association of tuberculosis with MMIM is exceedingly rare, however, the pathogenetic relationship between the two is difficult to define. We present a case report showing simultaneous presentation of localized active tuberculosis and MMM The literature on the subject is also reviewed with special emphasis on pathogenic relation­ship between the two.