title: Construction of a mathematical model for tuberculosis transmission in highly endemic regions of the Asia-Pacific.
abstract: We present a mathematical model to simulate tuberculosis (TB) transmission in highly endemic regions of the Asia-Pacific, where epidemiology does not appear to be primarily driven by HIV-coinfection. The ten-compartment deterministic model captures many of the observed phenomena important to disease dynamics, including partial and temporary vaccine efficacy, declining risk of active disease following infection, the possibility of reinfection both during the infection latent period and after treatment, multidrug resistant TB (MDR-TB) and de novo resistance during treatment. We found that the model could not be calibrated to the estimated incidence rate without allowing for reinfection during latency, and that even in the presence of a moderate fitness cost and a lower value of R0, MDR-TB becomes the dominant strain at equilibrium. Of the modifiable programmatic parameters, the rate of detection and treatment commencement was the most important determinant of disease rates with each respective strain, while vaccination rates were less important. Improved treatment of drug-susceptible TB did not result in decreased rates of MDR-TB through prevention of de novo resistance, but rather resulted in a modest increase in MDR-TB through strain replacement. This was due to the considerably greater relative contribution of community transmission to MDR-TB incidence, by comparison to de novo amplification of resistance in previously susceptible strains.
authors.affiliation: Burnet Institute, 89 Commercial Road, Melbourne 3004, Australia; Victorian Infectious Diseases Service at the Peter Doherty Institute for Infection and Immunity, Victoria 3010, Australia; Department of Medicine (Royal Melbourne Hospital/Western Hospital), University of Melbourne, Victoria 3010, Australia. Electronic address: jtrauer@burnet.edu.au.
authors.forename: James M
authors.initials: JM
authors.lastname: Trauer
authors.affiliation: Victorian Infectious Diseases Service at the Peter Doherty Institute for Infection and Immunity, Victoria 3010, Australia; Department of Microbiology and Immunology, University of Melbourne, Victoria 3010, Australia. Electronic address: justin.denholm@mh.org.au.
authors.forename: Justin T
authors.initials: JT
authors.lastname: Denholm
authors.affiliation: Burnet Institute, 89 Commercial Road, Melbourne 3004, Australia; Victorian Infectious Diseases Service at the Peter Doherty Institute for Infection and Immunity, Victoria 3010, Australia; Department of Medicine (Royal Melbourne Hospital/Western Hospital), University of Melbourne, Victoria 3010, Australia. Electronic address: emma.mcbryde@mh.org.au.
authors.forename: Emma S
authors.initials: ES
authors.lastname: McBryde
mesh_terms: D000995:Antitubercular Agents / Q000627:therapeutic use; D001208:Asia / Q000453:epidemiology; D006801:Humans; D008962:Models, Theoretical; D010139:Pacific Islands / Q000453:epidemiology; D014376:Tuberculosis / Q000188:drug therapy / Q000453:epidemiology*
chemical_list: D000995:Antitubercular Agents
keywords: BCG vaccine; Disease Transmission—Infectious; Latent tuberculosis; Models—Theoretical; Tuberculosis—Multidrug Resistant