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World TB Day 2019: Global WACh’s emerging research contributes to global efforts to end TB

World TB Day, held each year on March 24, aims to raise public awareness about the devastating health, social, and economic consequences of tuberculosis (TB) and to step up efforts to end the global TB epidemic.  The theme of World TB Day 2019 – “It’s Time” – urges global health organizations and government leaders to accelerate the TB response and ensure access to care.

Global WACh researchers are working hard to discover more effective diagnostic, treatment, and prevention measures for a TB-free world.  They are collaborating with investigators on a number of studies, including HIV/TB immunopathogenesis and protection in infants and pregnant women, improved TB screening and novel non-sputum based diagnostics in HIV-infected and HIV-uninfected children and adults, and implementation of TB prevention in adolescents.  Continue reading for a summary of studies and a collection of publications.

Ongoing Studies

Preventing Mycobacterium tuberculosis infection in HIV exposed infants (Thrasher Research Fund)
PIs: Grace John-Stewart, Thomas Hawn; Co-I: Sylvia LaCourse, Lisa Cranmer (Emory), John Kinuthia (Kenyatta National Hospital), Lisa Maleche-Obimbo (University of Nairobi)
This randomized controlled trial aims to determine if isoniazid preventative therapy (IPT) prevents primary Mycobacterium tuberculosis (Mtb) infection in HIV-exposed uninfected infants in Kenya.

The effect of HIV exposure and infection on immunity to TB in children (NIAID R01)
PIs: Grace John-Stewart, Cheryl Day (Emory) Co-I: Sylvia LaCourse, Lisa Cranmer (Emory) 
This study will utilize specimens from unique cohorts of HIV-infected, -exposed, and -unexposed children to determine predictors of anti-mycobacterial immunity (including HIV exposure, HIV infection, antiretroviral treatment, and other factors), the influence of HIV exposure or infection on ‘trained immunity’, and the effects of this immunity on susceptibility to TB.  Read our latest posting on the project.

Impact of maternal HIV on Mycobacterium tuberculosis (Mtb) infection among peripartum women and their infants (NIH/NIAID K23)
PI: Sylvia LaCourse; Mentors: Grace John-Stewart, Amita Gupta (Johns Hopkins), John Kinuthia (Kenyatta National Hospital)
This is a prospective observational cohort study enrolling HIV-infected and uninfected pregnant women and their infants to determine the effect of maternal HIV on risk and timing of maternal peripartum Mtb infection (Aim1), influence of maternal HIV on risk of infant Mtb infection (Aim 2), and effect of maternal HIV status and peripartum stage on latent TB infection diagnostics (Aim 3).

NanoDisk-MS measured Mtb antigen peptides for TB diagnosis and treatment monitoring in HIV-infected children (NIH/NIAID R21)
PI: Sylvia LaCourse; Co-I Ye Hu (Arizona State University), Grace John-Stewart, Lurdes Inoue; Collaborators: Dalton Wamalwa, Lisa Maleche-Obimbo
The goal of this study is to evaluate the performance of a novel blood-based diagnostic (NanoDisk-MS) to detect M. tuberculosis antigens for TB diagnosis (Aim 1), mortality prognosis (Aim 2), and treatment response in HIV-infected children (Aim 3).

Oral swab analysis (OSA) for TB diagnosis in women, adolescents, and HIV-infected individuals (UW/Fred Hutch CFAR)
PI: Sylvia LaCourse; Co-I: Gerard Cangelosi, Collaborators: KEMRI/CDC
This is a pilot study to determine diagnostic performance of OSA versus Xpert/culture for detection of TB in women, adolescents, and HIV-infected individuals and cofactors associated with missed TB diagnoses in western Kenya.

TB screening and prevention cascade among adolescent PLHIV (NICHD R01 Diversity Supplement)
PI: Danae Black; Mentors: Grace John-Stewart, Sylvia LaCourse
This research seeks to define and describe the TB cascade of care and identify facility and individual level determinants to isoniazid preventive therapy initiation, continuation, and completion among HIV-infected adolescents in Kenya.

Pediatric Urgent Start of HAART (PUSH) (NIH NICHD R01)
PIs: Grace John-Stewart, Dalton Walmalwa
Within the completed parent pediatric ART initiation trial, a number of nested studies have evaluated the performance of non-sputum based diagnostics for pediatric TB, including stool Xpert, urine LAM, and blood monocyte-to-lymphocyte ratio.

Article Collection

 AIDS

American Journal of Tropical Medicine and Hygiene

Clinical Infectious Diseases

Cochrane Database of Systematic Reviews

European Respiratory Society Journal

  • WHO guidelines for the programmatic management of drug-resistant tuberculosis: 2011 update
    Falzon D, Jaramillo E, Schünemann HJ, Arentz M, Bauer M, Bayona J, Blanc L, Caminero JA, Daley CL, Duncombe C, Fitzpatrick C, Gebhard A, Getahun H, Henkens M, Holtz TH, Keravec J, Keshavjee S, Khan AJ, Kulier R, Leimane V, Lienhardt C, Lu C, Mariandyshev A, Migliori GB, Mirzayev F, Mitnick CD, Nunn P, Nwagboniwe G, Oxlade O, Palmero D, Pavlinac P, Quelapio MI, Raviglione MC, Rich ML, Royce S, Rüsch-Gerdes S, Salakaia A, Sarin R, Sculier D, Varaine F, Vitoria M, Walson JL, Wares F, Weyer K, White RA, Zignol M

Infectious Diseases in Obstetrics and Gynecology

International Journal of Tuberculosis and Lung Disease

Journal of Acquired Immune Deficiency Syndromes

Journal of Infectious Diseases

Pediatrics Infectious Diseases Journal

PLoS One

Stigma Health