Burden of transmitted multidrug resistance in epidemics of XXXX : a transmission modelling analysis.

@entity1 @entity378 @entity6371
BACKGROUND: Multidrug-resistant (MDR) @entity378 can be acquired through de-novo mutation during @entity378 treatment or through transmission from other individuals with @entity6371 . Understanding the balance between these two mechanisms is essential when allocating resources for @entity6371 . We aimed to create a dynamic transmission model of an @entity6371 epidemic to estimate the contributions of treatment-related acquisition and @entity1 -to- @entity1 transmission of resistance to incident @entity6371 cases. METHODS: In this modelling analysis, we constructed a dynamic transmission model of an @entity6371 epidemic, allowing for both treatment-related acquisition and @entity1 -to- @entity1 transmission of resistance. We used national @entity378 notification data to inform Bayesian estimates of the proportion of each country's 2013 @entity6371 incidence that resulted from MDR transmission rather than treatment-related MDR acquisition. FINDINGS: Global estimates of 3  5% @entity6371 prevalence among new @entity378 notifications and 20  5% among re-treatment notifications translate into an estimate that resistance transmission rather than acquisition accounts for a median 95  9% (95% uncertainty range [UR] 68  0-99  6) of all incident @entity6371 , and 61  3% (16  5-95  2) of incident @entity6371 in previously treated individuals. The estimated proportion of @entity6371 resulting from transmission varied substantially with different countries' notification data-ranging from 48% (95% UR 30-75) in Bangladesh to 99% (91-100) in Uzbekistan. Estimates were most sensitive to estimates of the transmissibility of MDR strains, the probability of acquiring MDR during @entity378 treatment, and the responsiveness of @entity6371 to first-line treatment. INTERPRETATION: Notifications of MDR prevalence from most high-burden settings are consistent with most incident @entity6371 resulting from transmission rather than new treatment-related acquisition of resistance. Merely improving the treatment of drug-susceptible @entity378 is unlikely to greatly reduce future @entity6371 incidence. Improved diagnosis and treatment of @entity6371 -including new tests and drug regimens-should be highly prioritised. FUNDING: National Institutes of Health and the Bill _ Melinda Gates Foundation.
