Abstract
BackgroundThe relative fitness of organisms causing drug-susceptible (DS) and multidrug-resistant (MDR) tuberculosis (TB) is unclear. We compared the risk of TB infection and TB disease in young child household contacts of adults with confirmed DS-TB and MDR-TB.MethodsIn this cross-sectional analysis we included data from two community-based contact cohort investigation studies conducted in parallel in Cape Town, South Africa. Children <5 years of age with household exposure to an infectious TB case were included between August 2008 to June 2011. Children completed investigation for TB infection (tuberculin skin test) and TB disease (symptom evaluation, chest radiograph, bacteriology) in both studies using standard approaches. The impact of MDR-TB exposure on each covariate of TB infection and TB disease was assessed using univariable and multivariable logistic regression.ResultsOf 538 children included, 312 had DS-TB and 226 had MDR-TB exposure. 107 children with DS-TB exposure had TB infection (34.3%) vs. 101 (44.7%) of children with MDR-TB exposure (adjusted Odds Ratio [aOR]: 2.05; 95% confidence interval [CI]: 1.34–3.12). A total of 15 (6.6%) MDR-TB vs. 27 (8.7%) DS-TB child contacts had TB disease at enrolment (aOR: 0.43; 95% CI: 0.19–0.97).ConclusionsOur results suggest a higher risk of TB infection in child contacts with household MDR-TB vs. DS-TB exposure, but a lower risk of TB disease. Although potentially affected by residual confounding or selection bias, our results are consistent with the hypothesis of impaired virulence in MDR-TB strains in this setting.
Highlights
The relative fitness of organisms causing drug-susceptible (DS) and multidrug-resistant (MDR) tuberculosis (TB) is unclear
We evaluated the impact of drug resistance on the infectivity and virulence of M. tuberculosis by determining the risk of TB infection and TB disease in young child household contacts of DR-TB and drug-susceptible (DS)-TB source cases soon after the diagnosis of TB in the identified source case
Data were obtained from children with household TB exposure to a case of infectious pulmonary DS-TB or MDR-TB, who were routinely diagnosed and treated at the local TB facility, and were enrolled in two contact investigation studies implemented between August 2008 and June 2011
Summary
The relative fitness of organisms causing drug-susceptible (DS) and multidrug-resistant (MDR) tuberculosis (TB) is unclear. In 1953, Middlebrook and Cohn demonstrated that mycobacteria resistant to isoniazid were less able to cause disease in guinea pigs than susceptible organisms [1]. In the laboratory, rifampicin-resistant organisms have been demonstrated to be less able to grow in competition assays than rifampicin-susceptible organisms [2]. With time, the rifampicin-resistant organisms frequently develop compensatory mutations that restore fitness [3]. For TB source cases with disease caused by drug-
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