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To determine immunologic and epidemiologic correlates of acute Mycobacterium tuberculosis infection in household contacts of infectious tuberculosis cases, we performed a prospective, community-based cohort study of index cases and their household contacts in Kampala, Uganda. Contacts were evaluated for tuberculin skin test (TST) conversion over two years. Interferon-
expression was measured using a whole blood assay after stimulating with M. tuberculosis culture-filtrate. In 222 contacts with a TST less than 5 mm at baseline, the one-year rate of TST conversion was 27%. The TST conversion was associated with the infectiousness of the index case and proximity of contact. Interferon- levels at baseline were greater among TST converters compared with those who did not convert. The risk of TST conversion increased four-fold as the baseline interferon- increased 10-fold, but only in contacts with BCG vaccination. In household contacts of tuberculosis, interferon- responses to non-specific mycobacterial antigens may be used to make an early diagnosis of tuberculosis infection, especially in resource-limited settings where bacille Calmette-Guérin vaccination is commonly used.
Received September 22, 2005. Accepted for publication March 22, 2006.
Acknowledgments: We acknowledge the invaluable contribution made by the study medical officers, health visitors and data personnel: Dr. David Guwatudde, Dr. Margaret Nakakeeto, Dr. Love Nakende, Mark Breda, Albert Maganda, Deborah Nsamba, Barbara Kyeyune, Margaret Nansumba, Faith Kintu, Gladys Mpalanyi, Philo Nassozi, and Augustine Banyanga. We thank Dr. Francis Adatu Engwau (Head of the Uganda National Tuberculosis and Leprosy Program) for his support of this project. We also acknowledge 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. We also thank Dr. Robert Wallis for providing culture filtrate used in these studies and Drs. Jerrold Ellner, Zahra Toossi, and Gilbert Bukenya for their advice and guidance with the conduct of the study.
Financial support: This study was supported by Tuberculosis Prevention and Control Research Unit (AI-45244-95383), the AIDS International Training and Research Program of the Fogarty International Center (TW-00011), and the Center for AIDS Research (AI 36219) at the National Institutes of Allergy and Infectious Diseases, the National Institutes of Health.
Disclosure: None of the authors has a conflict of interest with the publication of this research.
* Address correspondence to Christopher C. Whalen, Department of Epidemiology and Biostatistics, Case Western Reserve University School of Medicine, WG-37, 10900 Euclid Avenue, Cleveland, OH 44106. E-mail: ccw{at}case.edu
Authors’ addresses: Christopher C. Whalen, Department of Epidemiology and Biostatistics, Case Western Reserve University School of Medicine, Cleveland, OH 44106. Allan Chiunda, Christina Hirsch, Pierre Peters, and W. Henry Boom, Department of Medicine, Case Western Reserve University School of Medicine and University Hospitals of Cleveland, Cleveland, OH 44106. Sarah Zalwango, Lorna Nshuti, and Roy D. Mugerwa, Department of Medicine, Makerere University Medical School, Kampala Uganda. Edward Jones-Lopez, Department of Medicine, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103. Alphonse Okwera, National Tuberculosis and Leprosy Control Programme, Kampala, Uganda.
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