Resistance to Mycobacterium tuberculosis Infection Among Household Contacts: A Multinational Study

Davit Baliashvili, Neel R. Gandhi, Soyeon Kim, Michael Hughes, Vidya Mave, Alberto Mendoza-Ticona, Pedro Gonzales, Kim Narunsky, Poongulali Selvamuthu, Sharlaa Badal-Faesen, Caryn Upton, Linda Naini, Elizabeth Smith, Amita Gupta, Gavin Churchyard, Susan Swindells, Anneke Hesseling, N. Sarita Shah

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)1037-1045
Number of pages9
JournalClinical infectious diseases : an official publication of the Infectious Diseases Society of America
Volume73
Issue number6
DOIs
StatePublished - Sep 15 2021

Keywords

  • exposure
  • infection
  • resisters
  • tuberculosis

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

Fingerprint

Dive into the research topics of 'Resistance to Mycobacterium tuberculosis Infection Among Household Contacts: A Multinational Study'. Together they form a unique fingerprint.

Cite this