Digital Commons Network^™

Lung Epithelial Signaling Mediates Early Vaccine-Induced Cd4 + T Cell Activation And Mycobacterium Tuberculosis Control, Shibali Das, Nancy D Marin, Ekaterina Esaulova, Mushtaq Ahmed, Amanda Swain, Bruce A Rosa, Makedonka Mitreva, Javier Rangel-Moreno, Mihai G Netea, Luis B Barreiro, Maziar Divangahi, Maxim N Artyomov, Deepak Kaushal, Shabaana A Khader

Open Access Publications

Tuberculosis (TB) is one of the leading causes of death due to a single infectious agent. The development of a TB vaccine that induces durable and effective immunity to Mycobacterium tuberculosis (

Perceptions And Challenges Experienced By African Physicians When Prescribing Methotrexate For Rheumatic Disease: An Exploratory Study, Carol A Hitchon, Girsh M Mody, Candace H Feldman, Yan Lau, Steven Shi, Michele Meltzer, Rosie Scuccimarri, Michael E Weinblatt, Ines Colmegna

Department of Medicine Faculty Papers

OBJECTIVE: Guidelines for methotrexate (MTX) use in rheumatic disease may not be feasible for physicians practicing in the least developed countries. We aimed to understand the experiences of MTX prescribers relating to MTX use for rheumatic disease in African countries to inform the development of culturally and geographically appropriate recommendations.

METHODS: African physicians who self-identified as MTX prescribers from countries classified as having a low versus a medium or high Human Development Index (L-HDI versus MH-HDI) participated in semistructured interviews between August 2016 and September 2017. Interviews were transcribed verbatim, coded thematically, and stratified by HDI.

RESULTS: Physicians (23 rheumatologists; …

Oral Manifestations Of Tuberculosis, Diana V. Macri, Sandra Castellanos, Elvir Dincer

Publications and Research

This article will update the reader on tuberculosis and its oral manifestations.

After decades of decreasing incidence, tuberculosis resurgence is being seen in some global regions due to factors that include the human immunodeficiency virus (HIV) epidemic, increased immigration from countries with endemic tuberculosis, transmission of tuberculosis in crowded or unsanitary environments, and poor healthcare infrastructure. Additionally, this review is especially prescient considering the increasing prevalence of drug-resistant tuberculosis.

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 …

Profiling Pretomanid As A Therapeutic Option For Tb Infection: Evidence To Date., Stephani L. Stancil, Fuad Mirzayev, Susan M. Abdel-Rahman

Manuscripts, Articles, Book Chapters and Other Papers

Tuberculosis (TB) is the most deadly infectious disease globally. Although most individuals achieve a cure, a substantial portion develop multi-drug resistant TB which is exceedingly difficult to treat, and the number of effective agents is dwindling. Development of new anti-tubercular medications is imperative to combat existing drug resistance and accelerate global eradication of TB. Pretomanid (PA-824) represents one of the newest drug classes (ie, nitroimidazooxazines) approved in 2019 by the United States Food and Drug Administration as part of a multi-drug regimen (with bedaquiline and linezolid, BPaL) and recommended by the World Health Organization (WHO) to treat extensively-resistant (XR-TB) and …

Transfer Transcriptomic Signatures For Infectious Diseases, Julia Di Iulio, Istvan Bartha, Roberto Spreafico, Herbert W Virgin, Amalio Telenti

2020-Current year OA Pubs

The modulation of the transcriptome is among the earliest responses to infection. However, defining the transcriptomic signatures of disease is challenging because logistic, technical, and cost factors limit the size and representativeness of samples in clinical studies. These limitations lead to a poor performance of signatures when applied to new datasets. Although the study focuses on infection, the central hypothesis of the work is the generalization of sets of signatures across diseases. We use a machine learning approach to identify common elements in datasets and then test empirically whether they are informative about a second dataset from a disease or …

Application Of Optimal Control To Tuberculosis Model With Parameter Estimations: Bayesian Approach, Goodluck M Mlay, Alfred K Hugo

Tanzania Journal of Science

In this paper, one-strain tuberculosis (TB) model with two control mechanisms, education campaigns and chemoprophylaxis of TB-infected patients, was studied to determine their effects on the reduction of latent and active TB cases. In the case of analysis, boundedness and positivity of the model solutions were carried out to determine the biological feasibility of the study. Besides, the calibration of the parameters by utilizing the identifiability technique through the Markov chain Monte Carlo (MCMC) was thoroughly analysed. The optimum conditions for controlling TB were derived from the Pontryagin Maximum Principle. The numerical simulations were carried out using the forward-back sweep …

Exploring The Interaction Of Amphiphilic Mycobacterial Lipoarabinomannan With Lipoproteins: Implications For Blood-Based Diagnosis, Shailja Jakhar

Biomedical Sciences ETDs

Currently, over one-third of the global population is infected with tuberculosis (TB), one of the world’s most deadly infectious diseases. The current gold standard for TB diagnosis is microbiological culture, which can take up to 6-8 weeks, which is not conducive to timely treatment. There are no reliable diagnostics for TB. Disease manifestation and outcome of diagnostic tests for TB are influenced by co-morbidities such as HIV co-infection, further complicating diagnostics development. Thus, there is a need for reliable diagnostics for TB. This is especially true in pediatric populations where the differential disease presentation further complicates outcomes.

This dissertation describes …

Cloning Of Pe11 (Lipx, Rv1169c) Gene Of Mycobacterium Tuberculosis Beijing Strain To Pcdna3.1 Plasmid Vector, Lulut Azmi Supardi, Andriansjah Rukmana, Fithriyah Sjatha

Makara Journal of Science

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis. It is a persistent global health problem with a high mortality rate. Currently, TB is controlled by administering the Bacillus Calmette-Guerin (BCG) vaccine, but the effectiveness of its protection varies among individuals in a population. The pe/ppe gene family comprises a typical group of genes that play a role in avoiding the host immune response and inducing persistent TB infection. Based on in silico analysis, the pe11 gene has estimated immunogenicity and potential as a TB seed vaccine candidate. The pe11 gene from an Indonesian isolate of an M. …

Pioneer Science And The Great Plagues: How Microbes, War, And Public Health Shaped Animal Health, Norman F. Cheville, Purdue University Press

Purdue University Press Books

Pioneer Science and the Great Plagues covers the century when infectious plagues—anthrax, tuberculosis, tetanus, plague, smallpox, and polio—were conquered, and details the important role that veterinary scientists played. The narrative is driven by astonishing events that centered on animal disease: the influenza pandemic of 1872, discovery of the causes of anthrax and tuberculosis in the 1880s, conquest of Texas cattle fever and then yellow fever, German anthrax attacks on the United States during World War I, the tuberculin war of 1931, Japanese biological warfare in the 1940s, and today’s bioterror dangers.

Veterinary science in the rural Midwest arose from agriculture, …

Tuberculosis And Non-Communicable Disease Multimorbidity: An Analysis Of The World Health Survey In 48 Low- And Middle-Income Countries, Brendon Stubbs, Kamran Siddiqi, Helen Elsey, Najma Siddiqi, Ruimin Ma, Eugenia Romano, Sameen Siddiqi, Ai Koyanagi

Community Health Sciences

Tuberculosis (TB) is a leading cause of mortality in low- and middle-income countries (LMICs). TB multimorbidity [TB and ≥1 non-communicable diseases (NCDs)] is common, but studies are sparse. Cross-sectional, community-based data including adults from 21 low-income countries and 27 middle-income countries were utilized from the World Health Survey. Associations between 9 NCDs and TB were assessed with multivariable logistic regression analysis. Years lived with disability (YLDs) were calculated using disability weights provided by the 2017 Global Burden of Disease Study. Eight out of 9 NCDs (all except visual impairment) were associated with TB (odds ratio (OR) ranging from 1.38-4.0). Prevalence …

Cancers As Rare Diseases: Terminological, Theoretical, And Methodological Biases, Carina Marques, Charlotte Roberts, Vitor M. J. Matos, Jane E. Buikstra

Anthropology Faculty Publications

Objective

Was cancer a rare disease in the past? Our objective is to consider the various terminological, theoretical, and methodological biases that may affect perceptions of the rarity of cancer in the past.

Materials and methods

We discuss relevant malignant neoplastic biomedical and paleopathological literature and evaluate skeletal data. We selected 108 archaeological sites (n = 151 cancer cases) with published malignant neoplasms and that were amenable to calculating cancer crude prevalence. Furthermore, datasets from four medieval/postmedieval Portuguese and 12 postmedieval UK sites were used to compare age-adjusted rates for metastatic bone disease and tuberculosis.

Results

In the literature review, …

Drug Susceptibility Patterns Of Mycobacterium Tuberculosis From Adults With Multidrug-Resistant Tuberculosis And Implications For A Household Contact Preventive Therapy Trial, Anne-Marie Demers, Soyeon Kim, Sara Mccallum, Kathleen Eisenach, Michael Hughes, Linda Naini, Alberto Mendoza-Ticona, Neeta Pradhan, Kim Narunsky, Selvamuthu Poongulali, Sharlaa Badal-Faesen, Caryn Upton, Elizabeth Smith, N Sarita Shah, Gavin Churchyard, Amita Gupta, Anneke Hesseling, Susan Swindells, Actg A5300/Impaact I2003 Phoenix Feasibility Study Team

Journal Articles: Internal Medicine

BACKGROUND: Drug susceptibility testing (DST) patterns of Mycobacterium tuberculosis (MTB) from patients with rifampicin-resistant tuberculosis (RR-TB) or multidrug-resistant TB (MDR-TB; or resistant to rifampicin and isoniazid (INH)), are important to guide preventive therapy for their household contacts (HHCs).

METHODS: As part of a feasibility study done in preparation for an MDR-TB preventive therapy trial in HHCs, smear, Xpert MTB/RIF, Hain MTBDRplus, culture and DST results of index MDR-TB patients were obtained from routine TB programs. A sputum sample was collected at study entry and evaluated by the same tests. Not all tests were performed on all specimens due to variations …

Disparities In Tuberculosis Rates In New England: 2011, 2014-2018, Etienne Bobe Leta

Muskie School Capstones and Dissertations

Purpose. The purpose of this study was to assess whether decreases in tuberculosis (TB) incidence have been followed by reductions in TB disparities in New England during 2011 and from 2014 to 2018.

Background. Tuberculosis is a potentially serious infectious disease which, without treatment, can be fatal. In the United States, 8,920 new cases were temporarily reported in 2019, showing a decrease of 1.1% from 2018. Similarly, TB incidence declined to 2.7 cases per 100,000 persons, accounting for 1.6% decrease from 2018 (CDC, 2020). Although this improvement, disparities in rates of tuberculosis disease between Whites and minority groups continue to …

The Phosphodiesterase, Rv0805, Is An Unheralded Component Of Tb Complex Mycobacterial Physiology In And Beyond Camp Homeostasis, James R. Mcdowell

Legacy Theses & Dissertations (2009 - 2024)

Phosphodiesterases (PDEs) are integral components of 3’,5’-cyclic adenosine monophosphate (cAMP) signaling pathways by degrading cAMP to modulate the concentration, duration, and localization of the cAMP signal which maintains the specificity of cAMP pathways. The human pathogen, Mycobacterium tuberculosis (Mtb) has a unique cAMP network architecture with at least 15 adenylyl cyclases (ACs) that generate cAMP, but only one characterized PDE, Rv0805, which is found exclusively in pathogenic mycobacteria. Rv0805 can influence Mtb cAMP levels but the absence of Rv0805 orthologs in non-pathogenic mycobacteria and apparent separation of Rv0805 from cAMP directed roles led to numerous questions surrounding PDE function in …

Prediction Tool To Identify Children At Highest Risk Of Tuberculosis Disease Progression Among Those Exposed At Home, Meredith B. Brooks, Leonid Lecca, Carmen Contreras, Roger Calderon, Rosa Yataco, Jerome Galea, Chuan-Chin Huang, Megan B. Murray, Mercedes C. Becerra

Social Work Faculty Publications

Background: There is a dearth of research to understand which children, among those who are exposed at home to tuberculosis (TB), are at the highest risk of TB disease, to tailor care. We sought to identify predictors of TB progression in children.

Methods: We conducted a prospective cohort study of children living with adults with pulmonary TB in Lima, Peru (2009–2012). We applied classification and regression tree analysis to examine potential predictors of incident TB disease during 12 months in 3 age groups (0–4, 5–9, and 10–14 years). We calculated the relative risk (RR) for top predictors in each age …

Risk Of Tuberculosis Is Increased In Behçet's Disease Compared To Other Rheumatologicaldisorders After Anti-Tnf∝ Treatments: A Case Series And Review Of The Literature, Ümmügülsüm Gazel, Derya Kocakaya, İrem Hi̇cret Topçu, Hakan Ömer Karataş, Murat Karabacak, Mehmet Pami̇r Atagündüz, Güzi̇de Nevsun İnanç, Fatma Ali̇baz Öner, Rafi̇ Haner Di̇reskeneli̇

Turkish Journal of Medical Sciences

Background/aim: Tumor necrosis factor-alfa (TNF-a) antagonists are extensively utilized in the treatment of inflammatory rheumatic diseases and also shown to be effective in Behçet's disease (BD) patients with major organ involvement. In this study, we aimed to reevaluate the incidence of tuberculosis (TB) infection after anti-TNFa treatments and to reveal the risk of TB in BD. Methods: Data of patients who received anti-TNFa treatment between 2005 and 2018 were assessed retrospectively. Demographic features, TNF-a antagonist type/treatment time, tuberculosis skin test (TST) and QuantiFERON results, isoniazid prophylaxis status, and concomitant corticosteroid (CS) treatments were collected. Results: A total of 1277 (male/female …

Human Monocyte-Derived Macrophage Responses To M. Tuberculosis Differ By The Host’S Tuberculosis, Diabetes Or Obesity Status, And Are Enhanced By Rapamycin, Blanca I. Restrepo, Arshad Khan, Vipul K. Singh, Erica De Leon, Genesis P. Aguillón-Durán, Eder Ledezma-Campos, David H. Canaday, Chinnaswamy Jagannath

School of Medicine Publications

Human macrophages play a major role in controlling tuberculosis (TB), but their anti-mycobacterial mechanisms remain unclear among individuals with metabolic alterations like obesity (TB protective) or diabetes (TB risk). To help discern this, we aimed to: i) Evaluate the impact of the host’s TB status or their comorbidities on the anti-mycobacterial responses of their monocyte-derived macrophages (MDMs), and ii) determine if the autophagy inducer rapamycin, can enhance these responses. We used MDMs from newly diagnosed TB patients, their close contacts and unexposed controls. The MDMs from TB patients had a reduced capacity to activate T cells (surrogate for antigen presentation) …

Finding The Missing Millions: Lessons From 10 Active Case Finding Interventions In High Tuberculosis Burden Countries, Tripti Pande, Nathaly Aguilera Vasquez, Danielle Cazabon, Jacob Creswell

Open Access archive

No abstract provided.

Research From Around The World: Hiv/Aids In Africa And The Us, Jason E. Farley

SigmaCast [Podcast]

This episode we will be discussing the body of nursing research from Jason E. Farley, PhD, MPH, ANP-BC, FAAN, FAANP, AACRN, a Sigma International Nurse Researcher Hall of Fame inductee in July of 2020 and a professor at Johns Hopkins University School of Nursing

Host: Matt Howard, DNP, RN, CEN, TCRN, CPEN, CPN: Director of Scholarship Resources, Sigma Theta Tau International, Indianapolis, Indiana, USA

Cultural And Religious Belief Approaches Of A Tuberculosis Program For Hard-To-Reach Populations In Mentawai And Solok West Sumatera, Indonesia, Rizanda Machmud, Irvan Medison, Finny Fitry Yani

Kesmas

Tuberculosis (TB) is a leading public health concern in Indonesia. It ranks second on the list of high-burden TB countries. In West Sumatra, 47% of TB cases are undetected, late diagnosed, and received incomplete treatment because of low-level awareness and knowledge and stigma, especially among the hardest to reach populations. The study aims to identify the best communication channel to reach those who live in vulnerable and remote areas. This study was a qualitative study applying in-depth interviews to the informal leaders, health officers, cultural artists, and religious leaders across districts in Mentawai and Solok Districts, which are remote and …

Antibody Fc Glycosylation Discriminates Between Latent And Active Tuberculosis, Lenette L. Lu, Jishnu Das, Patricia S. Grace, Sarah M. Fortune, Blanca I. Restrepo, Galit Alter

School of Medicine Publications

Background. Mycobacterium tuberculosis remains a global health problem and clinical management is complicated by difficulty in discriminating between latent infection and active disease. While M. tuberculosis-reactive antibody levels are heterogeneous, studies suggest that levels of IgG glycosylation differ between disease states. Here we extend this observation across antibody domains and M. tuberculosis specificities to define changes with the greatest resolving power.

Methods. Capillary electrophoretic glycan analysis was performed on bulk non-antigen–specific IgG, bulk Fc domain, bulk Fab domain, and purified protein derivative (PPD)- and Ag85A-specific IgG from subjects with latent (n = 10) and active (n = 20) tuberculosis. PPD-specific …

Tuberculosis, Human Rights, And Law Reform: Addressing The Lack Of Progress In The Global Tuberculosis Response, Matthew M. Kavanagh, Lawrence O. Gostin, John Stephens

Georgetown Law Faculty Publications and Other Works

In 2018, the United Nations General Assembly convened the first-ever high-level meeting (HLM) on tuberculosis (TB). Since that time news on the world’s most lethal infectious disease is not good—the 2019 WHO TB report shows 1.2 million people died from TB, a number that has fallen just 11% since 2015, less than one-third of the way towards the End TB Strategy milestone of a 35% reduction (to about 850 million deaths) by 2020. The same number of people, 10.0 million, are estimated to have fallen ill with TB in 2018 as in 2017. The stubborn persistence of TB is attributable …

Accuracy Of The Tuberculosis Point-Of-Care Alere Determine Lipoarabinomannan Antigen Diagnostic Test Using Α-Mannosidase Treated And Untreated Urine In A Cohort Of People Living With Hiv In Guatemala, Juan Ignacio García, Carlos Mejía-Chew, Et Al.

2020-Current year OA Pubs

BACKGROUND: Improved point-of-care diagnostic tests for tuberculosis (TB) in severe immune suppressed people living with HIV (PLWH) are needed to decrease morbidity and mortality outcomes. The aim of the study is to evaluate the performance of the lipoarabinomannan antigen test (LAM-test) with and without α-mannosidase pre-treated urine in a cohort of PLWH in primary care clinics in Guatemala. We further determined TB incidence, and mortality rates and its risk factors in PLWH with TB symptoms.

METHODS: Prospective longitudinal study of PLWH with TB symptoms. Urine samples were collected at 2 HIV sites to test the sensitivity of the LAM-test in …

Differential Yield Of Universal Versus Selective Drug Susceptibility Testing Of Patients With Tuberculosis In High-Burden Countries: A Systematic Review And Meta-Analysis, Anita Svadzian, Giorgia Sulis, Genevieve Gore, Madhukar Pai

Open Access archive

Introduction Although universal drug susceptibility testing (DST) is a component of the End-TB Strategy, over 70% of drug-resistant tuberculosis (DR-TB) cases globally remain undetected. This detection gap reflects difficulties in DST scale-up and substantial heterogeneity in policies and implemented practices. We conducted a systematic review and meta-analysis to assess whether implementation of universal DST yields increased DR-TB detection compared with only selectively testing high-risk groups. Methods PubMed, Embase, Global Health, Cochrane Library and Web of Science Core Collection were searched for publications reporting on the differential yield of universal versus selective DST implementation on the proportion of DR-TB, from January …

Advances In Molecular Diagnosis Of Tuberculosis, Emily Maclean, Mikashmi Kohli, Stefan F. Weber, Anita Suresh

Open Access archive

Molecular tests for tuberculosis (TB) have the potential to help reach the three million people with TB who are undiagnosed or not reported each year and to improve the quality of care TB patients receive by providing accurate, quick results, including rapid drug-susceptibility testing. The World Health Organization (WHO) has recommended the use of molecular nucleic acid amplification tests (NAATs) tests for TB detection instead of smear microscopy, as they are able to detect TB more accurately, particularly in patients with paucibacillary disease and in people living with HIV. Importantly, some of these WHO-endorsed tests can detect mycobacterial gene mutations …

Two Clinical Prediction Tools To Improve Tuberculosis Contact Investigation, Ruoran Li, Francesco Nordio, Chuan-Chin Huang, Carmen Contreras, Roger Calderon, Rosa Yataco, Jerome Galea, Zibiao Zhang, Mercedes C. Becerra, Leonid Lecca, Megan B. Murray

Social Work Faculty Publications

Background: Efficient contact investigation strategies are needed for the early diagnosis of TB disease and treatment of latent TB infections.

Methods: Between September 2009 and August 2012, we conducted a prospective cohort study in Lima, Peru in which we enrolled and followed 14,044 household contacts of adult pulmonary TB patients. We used information from a subset of this cohort to derive two clinical prediction tools that identify contacts of TB patients at elevated risk of progressing to active disease by training multivariable models that predict (1) co-prevalent TB among all household contacts and (2) one-year incident TB among adult contacts. …

Prevalence Of Tuberculosis In District Haveli, Azad Jammu And Kashmir, Abu Ul Hassan Faiz, Ghazal Tariq, Ayesha Faiz, Lariab Zahra Faiz

Journal of Bioresource Management

Tuberculosis is an infectious disease with a common occurrence in population of Azad Jammu and Kashmir. The current study was designed to find out the prevalence of TB among the general population of a less developed District Haveli. Samples were collected from different hospitals and TB centers located in district Haveli and tested through sputum smear microscopy for conformation of positive for TB. The three-year (2015 to 2018) study was conducted to record prevalence of tuberculosis in selected area of Azad Jammu and Kashmir. The trend line of prevalence was made by using (SPSS software). Results produced linear trends yearly …

Tuberculosis Of The Flexor Carpi Radialis Muscle - A Case Report, Shah Fahad, Naveed Baloch, Nasir Ud Din

Section of Orthopaedic Surgery

Tuberculosis involving almost any organ of the body is a major problem in developing countries. The most commonly affected site in tuberculosis is the lung. Of the extra pulmonary tuberculosis, musculoskeletal involvement accounts for 1-5% of the cases. Muscular involvement in tuberculosis is a rare manifestation of extra pulmonary tuberculosis. Unusual presentations often go undetected and are associated with a diagnostic and therapeutic delay. This case report presents tuberculosis of the flexor carpi radialis.

Previous And Active Tuberculosis Increases Risk Of Death And Prolongs Recovery In Patients With Covid-19, Karla Therese L. Sy, Nel Jason L. Haw, Jhanna Uy

Health Sciences Faculty Publications

Background: There is a growing literature on the association of SARS-CoV-2 and other chronic conditions, such as noncommunicable diseases. However, little is known about the impact of coinfection with tuberculosis. We aimed to compare the risk of death and recovery, as well as time-to-death and time-to-recovery, in COVID-19 patients with and without tuberculosis.

Methods: We created a 4:1 propensity score matched sample of COVID-19 patients without and with tuberculosis, using COVID-19 surveillance data in the Philippines. We conducted a longitudinal cohort analysis of matched COVID-19 patients as of May 17, 2020, following them until June 15, 2020. The …