Research Article: Mediating Effect of Repeated Tuberculosis Exposure on the Risk of Transmission to Household Contacts of Multidrug-Resistant Tuberculosis Patients

Date Published: February 04, 2018

Publisher: The American Society of Tropical Medicine and Hygiene

Author(s): Peng Lu, Xiaoyan Ding, Qiao Liu, Wei Lu, Leonardo Martinez, Jiansheng Sun, Feng Lu, Chongqiao Zhong, Hui Jiang, Changdong Miao, Limei Zhu, Haitao Yang.


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.

Partial Text

Drug-resistant tuberculosis has the potential to substantially impede current and future efforts to control the global tuberculosis epidemic. Resistance to tuberculosis drugs leads to reduced treatment effectiveness and overall elevated costs in tuberculosis treatment and, due to this, multidrug-resistant (MDR) tuberculosis patients are more likely to have catastrophic costs, adverse health outcomes, and mortality compared with drug-susceptible (DS) tuberculosis patients.1 China has the most MDR patients globally and primary transmission is largely responsible for increasing rates of drug resistance in recent years.2,3 A further understanding of the transmission dynamics of drug-resistant tuberculosis patients to susceptible contacts in their social network is necessary to implement effective policy that can assist in blunting the spread of the epidemic.

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 drug-resistance profile. After adjusting for repeated exposures, contacts of DS tuberculosis were at almost two times more likely to have tuberculosis infection. 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 also be at lower risk for tuberculosis infection after considering recurrent and continuous exposure.




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