Guidelines addressing latent TB infection (LTBI) treatment in MDR-TB contacts are vague and somewhat contradictory [24, 27, 28]. The WHO, citing the unknown efficacy of tailored preventative regimens, recommends observing contacts with careful clinical follow-up over two years . The American Thoracic Society recommends observation or treatment with one of two regimens for 6-12 months . These recommendations reflect the lack of high quality evidence required to direct decisions. Indeed, a recent Cochrane review failed to identify randomized control trials on MDR-TB contact tracing, while a 2006 systematic review found only two comparative studies suitable for analysis [23, 29].
Given our results, combined with the discouraging completion rates of susceptibility-profile tailored regimens [30–32], IPT could be seen as a potential option in close contacts of MDR-TB patients in low incidence settings. This strategy, however, is not without risk . MDR-TB transmission does occur in low incidence settings . Moreover, in high incidence settings, the majority of patients with TB disease in MDR-TB contact populations develop MDR-TB [16, 18, 19]. Such contacts will not likely benefit from IPT. More importantly, however, this strategy could propagate drug-resistant disease by selectively killing drug sensitive organisms [34–37]. Thus, the risk of IPT appears to outweigh its benefit in MDR-TB contacts.
Our results demonstrate that MDR-TB contacts have higher rates of TST positivity compared with DS-TB contacts. This may reflect the increased transmissibility of MDR-TB strains. Alternatively, the high rates of TST positivity in MDR-TB and HMR-TB contacts may reflect differential distribution of unmeasured determinants for LTBI, such as source time-to-diagnosis, source cavitary disease or contact environmental and socioeconomic determinants. Indeed the development of DS-TB in all close contacts of MDR-TB with incident TB disease supports the notion that close contacts of drug-resistant source cases may be at higher risk for LTBI and TB disease independent of transmission from an identified MDR-TB source case.
There are several limitations in our study, the most significant being the lack of molecular typing data, which could help determine whether the discrepant drug susceptibility profiles were from strains with the same genotype. A second limitation is the small population of drug-resistant cases and contacts available for analysis. Previous studies examining traditional contact tracing in MDR-TB patients have demonstrated disease rates ranging from 0-8% in close contacts, consistent with our data [10–19]. However, in studies examining drug-susceptibility profiles, 62-92% of contacts that subsequently developed active disease had MDR-TB [13–16, 18–20]. These rates are consistent with data demonstrating that 70% of secondary cases have the same genotype as their source case .
Finally, data on several determinants for TB infection are absent from analysis, including time-to-diagnosis, socioeconomic status and medical co-morbidities. Differential rates of TST positivity may be, in part, related to the differential distribution of these determinants. Nonetheless, our data suggests that risk for M. tuberculosis infection is higher in the contacts of drug resistant cases, and that thorough contact tracing should be performed in this population.