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.
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.
- Stool Xpert MTB/RIF and urine lipoarabinomannan for the diagnosis of tuberculosis in hospitalized HIV-infected children
LaCourse SM, Pavlinac PB, Cranmer LM, Njuguna IN, Mugo C, Gatimu J, Stern J, Walson JL, Maleche-Obimbo E, Oyugi J, Wamalwa D, John-Stewart G
American Journal of Tropical Medicine and Hygiene
- Mycobacterium tuberculosis Bacteremia Among Acutely Febrile Children in Western Kenya
Pavlinac PB, Naulikha JM, John-Stewart GC, Onchiri FM, Okumu AO, Sitati RR.
Clinical Infectious Diseases
- Urine Tuberculosis Lipoarabinomannan Predicts Mortality in Hospitalized Human Immunodeficiency Virus-Infected Children
LaCourse SM, Cranmer LM, Njuguna IN, Gatimu J, Stern J, Maleche-Obimbo E, Walson JL, Wamalwa D, John-Stewart GC, Pavlinac PB
Cochrane Database of Systematic Reviews
- Symptom screening for active tuberculosis in pregnant women living with HIV
LaCourse SM, Cranmer LM, Bekker A, Steingart KR, Black D, Horne DJ, Oren E
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
- Consistency of Mycobacterium tuberculosis-specific interferon-gamma responses in HIV-1-infected women during pregnancy and postpartum
Jonnalagadda SR, Brown E, Lohman-Payne B, Wamalwa D, Farquhar C, Tapia K, Cranmer LM, John-Stewart GC
- Risk of Adverse Infant Outcomes Associated with Maternal Tuberculosis in a Low Burden Setting: A Population-Based Retrospective Cohort Study
LaCourse SM, Greene SA, Dawson-Hahn EE, Hawes SE
International Journal of Tuberculosis and Lung Disease
- Incidence and correlates of tuberculosis IGRA conversion among HIV-infected postpartum women
Jonnalagadda S, LaCourse SM, Otieno P, Lohman-Payne B, Maleche-Obimbo E, Cranmer LM, John-Stewart GC
- Diagnostic accuracy of nucleic acid amplification tests in urine for pulmonary tuberculosis: a meta-analysis
Marangu D, Devine B, John-Stewart G
- Mycobacterium tuberculosis bacteremia in adults and children: a systematic review and meta-analysis
Pavlinac PB, Lokken EM, Walson JL, Richardson BA, Crump JA, John-Stewart GC
- Integrating tuberculosis screening in Kenyan Prevention of Mother-To-Child Transmission programs
Cranmer LM, Langat A, Ronen K, McGrath CJ, LaCourse S, Pintye J, Odeny B, Singa B, Katana A, Nganga L, Kinuthia J, John-Stewart G
- Predictive value of interferon-gamma release assays for postpartum active tuberculosis in HIV-1-infected women
Jonnalagadda SR, Brown E, Lohman-Payne B, Wamalwa D, Farquhar C, John-Stewart GC
Journal of Acquired Immune Deficiency Syndromes
- Monocyte-to-Lymphocyte Ratio Is Associated With Tuberculosis Disease and Declines
Choudhary RK, Wall KM, Njuguna I, Pavlinac PB, LaCourse SM, Otieno V, Gatimu J, Stern J, Maleche-Obimbo E, Wamalwa D, John-Stewart G, Cranmer LM
- Tuberculosis Case Finding in HIV-Infected Pregnant Women in Kenya Reveals Poor Performance of Symptom Screening and Rapid Diagnostic Tests
LaCourse SM, Cranmer LM, Matemo D, Kinuthia J, Richardson BA, John-Stewart G, Horne DJ
- Evaluation of the Isoniazid Preventive Therapy Care Cascade Among HIV-Positive Female Sex Workers in Mombasa, Kenya
LaCourse SM, Deya RW, Graham SM, Masese LN, Jaoko W, Mandaliya KN, Overbaugh J, McClelland RS
- Effect of Pregnancy on Interferon Gamma Release Assay and Tuberculin Skin Test Detection of Latent TB Infection Among HIV-Infected Women in a High Burden Setting
LaCourse SM, Cranmer LM, Matemo D, Kinuthia J, Richardson BA, Horne DJ, John-Stewart G
Journal of Infectious Diseases
- Latent tuberculosis detection by interferon γ release assay during pregnancy predicts active tuberculosis and mortality in human immunodeficiency virus type 1-infected women and their children
Jonnalagadda S, Lohman Payne B, Brown E, Wamalwa D, Maleche Obimbo E, Majiwa M, Farquhar C, Otieno P, Mbori-Ngacha D, John-Stewart G
Pediatrics Infectious Diseases Journal
- Use of Xpert for the diagnosis of pulmonary tuberculosis in severely malnourished hospitalized Malawian children
LaCourse SM, Chester FM, Preidis G, McCrary LM, Arscott-Mills T, Maliwichi M, James G, McCollum ED, Hosseinipour MC
- High prevalence of tuberculosis infection in HIV-1 exposed Kenyan infants
Cranmer LM, Kanyugo M, Jonnalagadda SR, Lohman-Payne B, Sorensen B, Maleche Obimbo E, Wamalwa D, John-Stewart GC
- Stakeholder perspectives for optimization of tuberculosis contact investigation in a high-burden setting
Marangu D, Mwaniki H, Nduku S, Maleche-Obimbo E, Jaoko W, Babigumira J, John-Stewart G, Rao D
- Use of anti-retroviral therapy in tuberculosis patients on second-line anti-TB regimens: a systematic review
Arentz M, Pavlinac P, Kimerling ME, Horne DJ, Falzon D, Schünemann HJ, Royce S, Dheda K, Walson JL; ART study group
- Mycobacterium tuberculosis bacteremia in a cohort of HIV-infected patients hospitalized with severe sepsis in Uganda–High frequency, low clinical suspicion [corrected] and derivation of a clinical prediction score
Jacob ST, Pavlinac PB, Nakiyingi L, Banura P, Baeten JM, Morgan K, Magaret A, Manabe Y, Reynolds SJ, Liles WC, Wald A, Joloba ML, Mayanja-Kizza H, Scheld WM
- Adapting a stigma scale for assessment of tuberculosis-related stigma among English/Swahili-speaking patients in an African Setting
Marangu D, Mwaniki H, Nduku S, Maleche-Obimbo E, Jaoko W, Babigumira J, John-Stewart G, Rao D