TY - JOUR
T1 - Resistance to Mycobacterium tuberculosis Infection Among Household Contacts
T2 - A Multinational Study
AU - A5300/2003 PHOENIx Feasibility study team
AU - Baliashvili, Davit
AU - Gandhi, Neel R.
AU - Kim, Soyeon
AU - Hughes, Michael
AU - Mave, Vidya
AU - Mendoza-Ticon, Alberto
AU - Gonzales, Pedro
AU - Narunsky, Kim
AU - Selvamuthu, Poongulali
AU - Badal-Faese, Sharlaa
AU - Upton, Caryn
AU - Naini, Linda
AU - Smith, Elizabeth
AU - Gupta, Amita
AU - Churchyard, Gavin
AU - Swindells, Susan
AU - Hesseling, Anneke
AU - Shah, N. Sarita
N1 - Funding Information:
This work was supported by the National Institute of Allergy and Infectious Diseases, with cofunding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and the National Institute of Mental Health (NIMH), all components of the National Institutes of Health, under award numbers UM1AI068634, UM1AI068636 UM1AI106701, UM1A1068616, UM1AI068632, UM1AI068616, UM1AI106716, and by NICHD contract number HHSN275201800001I and R01AI139406 (PI Gandhi). This work was supported in part by the NIH Fogarty International Center Global Infectious Diseases grant number D43TW007124 to D. B.; K24AI114444, Emory TB Research Unit grant number U19AI111211 and Emory Center for AIDS Research grant P30AI051519 to N. G.; grant numbers UM1AI069465, R01HD081929, and R01AI39406 to A. G., and the National South African Research Foundation through a SARCHi Chair to A. H. C. U. reports that ACTG provided institutional grant support and was sponsor of the original feasibility study. G. C. reports that the Aurum Institute received a grant from ACTG/DAIDS to implement the PHOENIx Feasibility study.
Publisher Copyright:
© The Author(s) 2021.
PY - 2021/9/15
Y1 - 2021/9/15
N2 - 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.
AB - 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.
KW - Tuberculosis
KW - exposure
KW - infection
KW - resisters
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U2 - 10.1093/cid/ciab269
DO - 10.1093/cid/ciab269
M3 - Article
C2 - 33772550
AN - SCOPUS:85116958717
VL - 73
SP - 1037
EP - 1045
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
SN - 1058-4838
IS - 6
ER -