The risk of global epidemic replacement with drug-resistant Mycobacterium tuberculosis strains.
OBJECTIVE
Multidrug-resistant tuberculosis (MDR-TB) is a threat to tuberculosis (TB) control. To guide TB control, it is essential to understand the extent to which and the circumstances in which MDR-TB will replace drug-susceptible TB (DS-TB) as the dominant phenotype. The issue was examined by assessing evidence from genomics, pharmacokinetics, and epidemiology studies. This evidence was then synthesized into a mathematical model.


METHODS
This model considers two TB strains, one with and one without an MDR phenotype. It was considered that intrinsic transmissibility may be different between the two strains, as may the control response including the detection, treatment failure, and default rates. The outcomes were explored in terms of the incidence of MDR-TB and time until MDR-TB surpasses DS-TB as the dominant strain.


CONCLUSIONS
The ability of MDR-TB to dominate DS-TB was highly sensitive to the relative transmissibility of the resistant strain; however, MDR-TB could dominate even when its transmissibility was modestly reduced (to between 50% and 100% as transmissible as the DS-TB strain). This model suggests that it may take decades or more for strain replacement to occur. It was also found that while the amplification of resistance is the early cause of MDR-TB, this will rapidly give way to person-to-person transmission.
Australian Institute of Tropical Health and Medicine, James Cook University, 1 James Cook Drive, Townsville, QLD 4811, Australia. Electronic address: emma.mcbryde@jcu.edu.au.
Emma S
ES
McBryde
Australian Institute of Tropical Health and Medicine, James Cook University, 1 James Cook Drive, Townsville, QLD 4811, Australia.
Michael T
MT
Meehan
Australian Institute of Tropical Health and Medicine, James Cook University, 1 James Cook Drive, Townsville, QLD 4811, Australia; Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Melbourne, Victoria, Australia.
Tan N
TN
Doan
Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Melbourne, Victoria, Australia; Centre for Population Health, the Burnet Institute, Melbourne, Victoria, Australia.
Romain
R
Ragonnet
The Children's Hospital at Westmead and the Marie Bashir Institute for Infectious Diseases and Biosecurity (MBI), University of Sydney, Sydney, New South Wales, Australia.
Ben J
BJ
Marais
Australian Institute of Tropical Health and Medicine, James Cook University, 1 James Cook Drive, Townsville, QLD 4811, Australia.
Vanina
V
Guernier
School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia; Victorian Tuberculosis Program at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
James M
JM
Trauer
D000995:Antitubercular Agents / Q000627:therapeutic use; D058872:Epidemics; D014943:Global Health; D006801:Humans; D015994:Incidence; D008954:Models, Biological; D009169:Mycobacterium tuberculosis / Q000235:genetics; D018570:Risk Assessment; D018088:Tuberculosis, Multidrug-Resistant / Q000453:epidemiology* / Q000382:microbiology; D014397:Tuberculosis, Pulmonary / Q000453:epidemiology* / Q000382:microbiology
D000995:Antitubercular Agents
Antibiotic resistance; Communicable disease control; Mathematical modelling; Tuberculosis