What can we offer to 3 million MDRTB household contacts in 2016?

Abstract

The diagnosis of multidrug resistant tuberculosis (MDR-TB) in any individual is the beginning of a prolonged and difficult therapeutic journey. It also marks the moment from which to begin consideration of how to manage close contacts. Preventive therapy for drug-susceptible latent tuberculosis infection has been demonstrated to be effective at reducing the risk of future disease; the stakes are higher when considering prevention of MDR-TB because treatment of active disease is more prolonged and toxic and much less effective. This has encouraged exploration of the potential utility of preventive therapy, with second-line agents, in reducing future incident drug-resistant TB. Three clinical trials of preventive therapy for contacts of patients with MDR-TB are starting in 2015/16; results will not be available until at least 2020, so what should be offered to exposed contacts in the interim? A recent policy brief, arising from a global consultation meeting of international experts, recommended preventive therapy based upon very limited available observational data. However the many known unknowns associated with this approach, include the high proportion of index-contact pairs with discordant drug susceptibility profiles and (even if susceptibilities are shared) the lack of data supporting the use of the selected agents in the treatment of latent infection (rather than active disease). It is important to acknowledge that the alternative to offering preventive therapy is not doing nothing. On the contrary, identified contacts should be maintained under close, active surveillance for 24 months, enabling early detection of active disease in the small proportion amongst whom this may occur. Such patients should benefit from less extensive disease at diagnosis and early access to individualized therapeutic regimens with improved treatment outcomes. Moreover the vast majority of contacts that do not develop disease will benefit from avoidance of potentially toxic, unnecessary therapy. Whether preventive therapy or close observation are implemented, national programmes should maintain a register of all contacts, interventions and 24 month outcomes; these will provide important performance metrics for programmatic management of MDRTB. If harmonized and standardized internationally, such a register could rapidly yield a wealth of observational data, to complement the trial results of the future.