Davit Baliashvili1, Neel R Gandhi1,2, Soyeon Kim3, Michael Hughes4, Vidya Mave5, Alberto Mendoza-Ticona6, Pedro Gonzales6, Kim Narunsky7, Poongulali Selvamuthu8, Sharlaa Badal-Faesen9, Caryn Upton10, Linda Naini11, Elizabeth Smith12, Amita Gupta13, Gavin Churchyard14,15, Susan Swindells16, Anneke Hesseling17, N Sarita Shah1,2. 1. Emory Rollins School of Public Health, Atlanta, Georgia, USA. 2. Emory School of Medicine, Atlanta, Georgia, USA. 3. Frontier Science Foundation, Brookline, Massachusetts, USA. 4. Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA. 5. Byramjee Jeejeebhoy Government Medical College-Johns Hopkins University Clinical Research Site, Pune, Maharashtra, India. 6. Asociacion Civil Impacta Salud y Educacion, Lima, Peru. 7. UCT Lung Institute, Cape Town, South Africa. 8. Chennai Antiviral Research and Treatment (CART) Clinical Research Site, Infectious Diseases Medical Center, Voluntary Health Services, Chennai, India. 9. Clinical HIV Research Unit, Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa. 10. TASK Applied Science, Cape Town, South Africa. 11. Social and Scientific Systems, Inc., Silver Spring, Maryland, USA. 12. National Institutes of Health, Bethesda, Maryland, USA. 13. Johns Hopkins University, Department of Medicine, Baltimore, Maryland, USA. 14. Aurum Institute, Parktown, South Africa. 15. School of Public Health, University of Witwatersrand, Johannesburg, South Africa. 16. University of Nebraska Medical Center, Omaha, Nebraska, USA. 17. Desmond Tutu TB Centre, Stellenbosch University, Tygerberg, South Africa.
Abstract
BACKGROUND: Some contacts of patients with tuberculosis remain negative on tests for tuberculosis infection, despite prolonged exposure, suggesting they might be resistant to Mycobacterium tuberculosis infection. The objective of this multinational study was to estimate the proportion of household contacts resistant to M. tuberculosis (resisters). METHODS: We conducted a longitudinal study enrolling index patients enrolled in treatment for pulmonary multidrug- or rifampin-resistant tuberculosis and their household contacts. Contacts were tested for tuberculosis infection with a tuberculin skin test (TST) and interferon-gamma release assay (IGRA) at baseline and after 1 year. Exposure was quantified based on index patients' infectiousness, index patient and household contact interaction, and age. We explored multiple definitions of resistance to tuberculosis infection by varying TST negativity cutoffs (0 vs <5 mm), classification of missing test results, and exposure level. RESULTS: In total, 1016 contacts were evaluated from 284 households; 572 contacts aged ≥5 years had TST and longitudinal IGRA results available. And 77 (13%) or 71 (12%) contacts were classified as resisters with a <5 mm or 0 mm TST threshold, respectively. Among 263 highly exposed contacts, 29 (11%) or 26 (10%) were classified as resisters using TST cutoffs of <5 mm and 0 mm, respectively. The prevalence of resisters did not differ substantially by sex, age, human immunodeficiency virus (HIV) coinfection, or comorbid conditions. CONCLUSIONS: At least 10% of household contacts can be classified as resistant to tuberculosis infection, depending on the definition used, including those with high exposure. Further studies to understand genetic or immunologic mechanisms underlying the resister phenotype may inform novel strategies for therapeutics and vaccines.
BACKGROUND: Some contacts of patients with tuberculosis remain negative on tests for tuberculosis infection, despite prolonged exposure, suggesting they might be resistant to Mycobacterium tuberculosis infection. The objective of this multinational study was to estimate the proportion of household contacts resistant to M. tuberculosis (resisters). METHODS: We conducted a longitudinal study enrolling index patients enrolled in treatment for pulmonary multidrug- or rifampin-resistant tuberculosis and their household contacts. Contacts were tested for tuberculosis infection with a tuberculin skin test (TST) and interferon-gamma release assay (IGRA) at baseline and after 1 year. Exposure was quantified based on index patients' infectiousness, index patient and household contact interaction, and age. We explored multiple definitions of resistance to tuberculosis infection by varying TST negativity cutoffs (0 vs <5 mm), classification of missing test results, and exposure level. RESULTS: In total, 1016 contacts were evaluated from 284 households; 572 contacts aged ≥5 years had TST and longitudinal IGRA results available. And 77 (13%) or 71 (12%) contacts were classified as resisters with a <5 mm or 0 mm TST threshold, respectively. Among 263 highly exposed contacts, 29 (11%) or 26 (10%) were classified as resisters using TST cutoffs of <5 mm and 0 mm, respectively. The prevalence of resisters did not differ substantially by sex, age, human immunodeficiency virus (HIV) coinfection, or comorbid conditions. CONCLUSIONS: At least 10% of household contacts can be classified as resistant to tuberculosis infection, depending on the definition used, including those with high exposure. Further studies to understand genetic or immunologic mechanisms underlying the resister phenotype may inform novel strategies for therapeutics and vaccines.
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