TY - JOUR
T1 - Resistance and Susceptibility to Mycobacterium tuberculosis Infection and Disease in Tuberculosis Households in Kampala, Uganda
AU - Stein, Catherine M.
AU - Zalwango, Sarah
AU - Malone, Lashaunda L.
AU - Thiel, Bonnie
AU - Mupere, Ezekiel
AU - Nsereko, Mary
AU - Okware, Brenda
AU - Kisingo, Hussein
AU - Lancioni, Christina L.
AU - Bark, Charles M.
AU - Whalen, Christopher C.
AU - Joloba, Moses L.
AU - Boom, W. Henry
AU - Mayanja-Kizza, Harriet
N1 - Funding Information:
Bioinformatics, Case Western Reserve University School of Medicine, Cleveland, Ohio (Catherine M. Stein); Tuberculosis Research Unit, Case Western Reserve University School of Medicine, Cleveland, Ohio (Catherine M. Stein, LaShaunda L. Malone, Bonnie Thiel, Charles M. Bark, W. Henry Boom); Kampala Department of Public Health, Kampala, Uganda (Sarah Zalwango); Departments of Pediatrics and Child Health, and Medicine, School of Medicine, Makerere University and Mulago Hospital, Kampala, Uganda (Ezekiel Mupere, Harriet Mayanja-Kizza); Uganda-CWRU Research Collaboration, Kampala, Uganda (Mary Nsereko, Brenda Okware, Hussein Kisingo); Department of Pediatrics, Oregon Health Sciences University, Portland, Oregon (Christina L. Lancioni); Department of Epidemiology and Biostatistics, College of Public Health, University of Georgia, Athens, Georgia (Christopher C. Whalen); and School for Biomedical Sciences, College of Health Sciences, Makerere University, Kampala, Uganda (Moses L. Joloba). Funding for this work was provided by the Tuberculosis Research Unit at the National Institutes of Health (grant N01-AI95383) and the National Institute of Allergy and Infectious Diseases (grant HHSN266200700022C/N01-AI70022). We thank the senior physicians, medical officers, health visitors, and laboratory and data personnel for their contributions: Dr. Lorna Nshuti, Dr. Roy Mugerwa, Dr. Alphonse Okwera, Dr. Deo Mulindwa, Denise Johnson, Dr. Allan Chiunda, Mark Breda, Dennis Dobbs, Mary Rutaro, Albert Muganda, Richard Bamuhimbisa, Yusuf Mulumba, Deborah Nsamba, Barbara Kyeyune, Faith Kintu, Gladys Mpalanyi, Janet Mukose, Grace Tumusiime, Pierre Peters, Annet Kawuma, Saidah Menya, Joan Nassuna, Keith Chervenak, Karen Morgan, Alfred Etwom, Micheal Angel Mugerwa, Emily Hellwig, and Lisa Kucharski. We also thank Dr. Francis Adatu Engwau, former Head of the Uganda National Tuberculosis and Leprosy Program, for supporting this project. We also thank the medical officers, nurses and counselors at the National Tuberculosis Treatment Centre, Mulago Hospital, the Ugandan National Tuberculosis and Leprosy Program and the Uganda Tuberculosis Investigation Bacteriological Unit, Wandegeya, for their contributions to this study. Finally, we thank Dr. Christine Sizemore, National Institutes of Health, for her support of this project. Conflict of interest: none declared.
Publisher Copyright:
© The Author(s) 2018.
PY - 2018/7/1
Y1 - 2018/7/1
N2 - Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a major public health problem. Household contact studies identify children and adults along the spectrum from Mtb exposure to disease. In the Kawempe Community Health Study (conducted in Kampala, Uganda), 872 culture-confirmed pulmonary TB cases and their 2,585 contacts were enrolled during 2002-2012 and followed for up to 2 years each. Risk factors identified by time-to-event analysis for secondary TB differed among children, women, and men. Younger age (P = 0.0061), human immunodeficiency virus (HIV) (P = 0.0002), thinness (P = 0.01), absent bacille Calmette-Guérin vaccination (P = 0.002), and epidemiologic risk score (P < 0.0001) were risks for children. For women, risks were HIV (P < 0.0001), thinness (World Health Organization criteria; P < 0.0001), and epidemiologic risk score (P = 0.003). For men, HIV (P = 0.0007) and low body mass index (P = 0.008) resulted in faster progression to TB. Tuberculin skin testing (TST) identified contacts with Mtb infection and those with persistently negative TST. Risks for faster time to Mtb infection were identified, and included age (P = 0.0007), baseline TST induration (P < 0.0001), and epidemiologic risk score (P < 0.0001) only in children. Those with persistently negative TST comprised 10% of contacts but had no unique epidemiologic characteristics among adults. The burden of Mtb infection and disease is high in TB households, and risk factors for progression from exposure to infection and disease differ among children, women, and men.
AB - Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a major public health problem. Household contact studies identify children and adults along the spectrum from Mtb exposure to disease. In the Kawempe Community Health Study (conducted in Kampala, Uganda), 872 culture-confirmed pulmonary TB cases and their 2,585 contacts were enrolled during 2002-2012 and followed for up to 2 years each. Risk factors identified by time-to-event analysis for secondary TB differed among children, women, and men. Younger age (P = 0.0061), human immunodeficiency virus (HIV) (P = 0.0002), thinness (P = 0.01), absent bacille Calmette-Guérin vaccination (P = 0.002), and epidemiologic risk score (P < 0.0001) were risks for children. For women, risks were HIV (P < 0.0001), thinness (World Health Organization criteria; P < 0.0001), and epidemiologic risk score (P = 0.003). For men, HIV (P = 0.0007) and low body mass index (P = 0.008) resulted in faster progression to TB. Tuberculin skin testing (TST) identified contacts with Mtb infection and those with persistently negative TST. Risks for faster time to Mtb infection were identified, and included age (P = 0.0007), baseline TST induration (P < 0.0001), and epidemiologic risk score (P < 0.0001) only in children. Those with persistently negative TST comprised 10% of contacts but had no unique epidemiologic characteristics among adults. The burden of Mtb infection and disease is high in TB households, and risk factors for progression from exposure to infection and disease differ among children, women, and men.
KW - Mtb infection
KW - case finding
KW - case-contact study
KW - infectious disease epidemiology
KW - pediatric TB
KW - resistance to infection
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U2 - 10.1093/aje/kwx380
DO - 10.1093/aje/kwx380
M3 - Article
C2 - 29304247
AN - SCOPUS:85047838429
SN - 0002-9262
VL - 187
SP - 1477
EP - 1489
JO - American Journal of Epidemiology
JF - American Journal of Epidemiology
IS - 7
ER -