Abstract
.Primary Mycobacterium tuberculosis transmission is an important driver of the global epidemic of resistance to tuberculosis drugs. A few studies have compared tuberculosis infection in contacts of index cases with different drug-resistant profiles, suggesting that contacts of multidrug-resistant (MDR) tuberculosis cases are at higher risk. Repeated tuberculosis exposure in contacts of MDR tuberculosis patients through recurrent tuberculosis may modify this relationship. We compared tuberculosis infection in household contacts of MDR and drug-susceptible (DS) tuberculosis patients from six cities in southeastern China and investigated whether repeated tuberculosis exposure was a mediating factor. Tuberculosis infection was defined as a tuberculin skin test induration ≥ 10 mm. In all, 111 (28.0%) of 397 household contacts of MDR tuberculosis patients and 165 (24.7%) of 667 contacts of DS tuberculosis index cases were infected with tuberculosis. In a multivariate model not including the previous tuberculosis exposure, contacts of MDR tuberculosis patients had a higher likelihood of tuberculosis infection (adjusted odds ratio [AOR] = 1.37; 95% confidence interval [CI] = 1.01–1.84; P = 0.041). In a separate multivariate model adjusted for the previous tuberculosis exposure, the odds ratio of tuberculosis infection flipped and contacts of MDR cases were now at lower risk for tuberculosis infection (AOR = 0.55; 95% CI = 0.38–0.81; P = 0.003). These findings suggest prior tuberculosis exposure in contacts strongly mediates the relationship between tuberculosis infection and the index drug resistance profile. Prior studies showing lower risk of developing tuberculosis among contacts of MDR tuberculosis patients may be partially explained by a lower rate of tuberculosis infection at baseline.
Highlights
Drug-resistant tuberculosis has the potential to substantially impede current and future efforts to control the global tuberculosis epidemic
– 0.567 between contact Bacillus Calmette-Guerin (BCG) vaccination status, the number of bedrooms in the household, and contact age or sex (Table 3). In this large household survey with over 1,000 exposed contacts and almost 500 index cases, we found that contacts of MDR tuberculosis patients were repeatedly exposed to tuberculosis and this strongly mediated the relationship between tuberculosis infection and a source case’s drugresistance profile
Some studies have shown that exposed contacts of MDR tuberculosis patients are at lower risk for primary progressive disease and our results suggest that they may be at lower risk for tuberculosis infection after considering recurrent and continuous exposure
Summary
Drug-resistant tuberculosis has the potential to substantially impede current and future efforts to control the global tuberculosis epidemic. The comparative transmission potential of MDR and DS tuberculosis patients is controversial.[4] Several studies argue that MDR tuberculosis patients are less likely to transmit to their social network compared with DS tuberculosis patients because of potential fitness costs through genetic mutations linked to resistance.[5,6,7,8,9] Tuberculosis infection in household contacts is used to compare the fitness of mycobacteria tuberculosis.[10,11,12] Few studies have compared rates of tuberculosis infection in household contacts of MDR and DS tuberculosis patients and these suggest contacts of MDR patients have higher levels of tuberculosis infection.[9,10,11,12,13] Two of these studies[10,11] found higher levels of tuberculosis infection among contacts of MDR tuberculosis patients but this difference did not reach statistical significance. Three other studies[9,12,13] found a statistical higher rate of tuberculosis infection among contacts of MDR patients
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