Transmissibility and potential for disease progression of drug resistant Mycobacterium tuberculosis: prospective cohort study

BMJ. 2019 Oct 24;367:l5894. doi: 10.1136/bmj.l5894.

Abstract

Objective: To measure the association between phenotypic drug resistance and the risk of tuberculosis infection and disease among household contacts of patients with pulmonary tuberculosis.

Setting: 106 district health centers in Lima, Peru between September 2009 and September 2012.

Design: Prospective cohort study.

Participants: 10 160 household contacts of 3339 index patients with tuberculosis were classified on the basis of the drug resistance profile of the patient: 6189 were exposed to drug susceptible strains of Mycobacterium tuberculosis, 1659 to strains resistant to isoniazid or rifampicin, and 1541 to strains that were multidrug resistant (resistant to isoniazid and rifampicin).

Main outcome measures: Tuberculosis infection (positive tuberculin skin test) and the incidence of active disease (diagnosed by positive sputum smear or chest radiograph) after 12 months of follow-up.

Results: Household contacts exposed to patients with multidrug resistant tuberculosis had an 8% (95% confidence interval 4% to 13%) higher risk of infection by the end of follow-up compared with household contacts of patients with drug sensitive tuberculosis. The relative hazard of incident tuberculosis disease did not differ among household contacts exposed to multidrug resistant tuberculosis and those exposed to drug sensitive tuberculosis (adjusted hazard ratio 1.28, 95% confidence interval 0.9 to 1.83).

Conclusion: Household contacts of patients with multidrug resistant tuberculosis were at higher risk of tuberculosis infection than contacts exposed to drug sensitive tuberculosis. The risk of developing tuberculosis disease did not differ among contacts in both groups. The evidence invites guideline producers to take action by targeting drug resistant and drug sensitive tuberculosis, such as early detection and effective treatment of infection and disease.

Trial registration: ClinicalTrials.gov NCT00676754.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antitubercular Agents / pharmacology
  • Antitubercular Agents / therapeutic use
  • Child
  • Child, Preschool
  • Contact Tracing / methods
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Humans
  • Incidence
  • Infant
  • Infant, Newborn
  • Isoniazid / pharmacology
  • Isoniazid / therapeutic use
  • Kaplan-Meier Estimate
  • Male
  • Microbial Sensitivity Tests / methods
  • Middle Aged
  • Mycobacterium tuberculosis / drug effects
  • Mycobacterium tuberculosis / isolation & purification
  • Peru / epidemiology
  • Prospective Studies
  • Rifampin / pharmacology
  • Rifampin / therapeutic use
  • Sputum / microbiology
  • Tuberculin Test
  • Tuberculosis, Multidrug-Resistant / drug therapy
  • Tuberculosis, Multidrug-Resistant / epidemiology
  • Tuberculosis, Multidrug-Resistant / transmission*
  • Tuberculosis, Pulmonary / drug therapy
  • Tuberculosis, Pulmonary / epidemiology
  • Tuberculosis, Pulmonary / microbiology
  • Tuberculosis, Pulmonary / transmission*
  • Young Adult

Substances

  • Antitubercular Agents
  • Isoniazid
  • Rifampin

Associated data

  • ClinicalTrials.gov/NCT00676754