TY - JOUR
T1 - The relative fitness of drug-resistant Mycobacterium tuberculosis
T2 - A modelling study of household transmission in Peru
AU - Knight, Gwenan M.
AU - Zimic, Mirko
AU - Funk, Sebastian
AU - Gilman, Robert H.
AU - Friedland, Jon S.
AU - Grandjean, Louis
N1 - Funding Information:
This work was funded by the TB Modelling and Analysis Consortium (TBMAC, Bill and Melinda Gates Foundation, OPP1084276). L.G. is also funded by a Wellcome Trust Grant 201470/Z/16/Z.
Funding Information:
1National Institute of Health Research Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, and 2Infectious Diseases and Immunity, Imperial College London, Commonwealth Building, Hammersmith Campus, Du Cane Road, London W12 0NN, UK 3Centre for the Mathematical Modelling of Infectious Diseases, Infectious Disease Epidemiology, and 4TB Centre, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK 5Laboratorio de Bioinformática y Biología Molecular, Facultad de Ciencias, Universidad Peruana Cayetano Heredia, 31 Avenue Honorio Delgado 430, Distrito de Lima, Peru 6Johns Hopkins Bloomberg School of Public Health, 615 N Wolfe Street, Baltimore, MD 21205, USA 7Wellcome Trust Imperial College Centre for Global Health, St Mary’s Hospital Campus, Imperial College London, Praed Street, London, W2 1NY, UK
Publisher Copyright:
© 2018 The Authors.
PY - 2018
Y1 - 2018
N2 - The relative fitness of drug-resistant versus susceptible bacteria in an environment dictates resistance prevalence. Estimates for the relative fitness of resistant Mycobacterium tuberculosis (Mtb) strains are highly heterogeneous and mostly derived from in vitro experiments. Measuring fitness in the field allows us to determine how the environment influences the spread of resistance. We designed a household structured, stochastic mathematical model to estimate the fitness costs associated with multidrug resistance (MDR) carriage in Mtb in Lima, Peru during 2010 - 2013. By fitting the model to data from a large prospective cohort study of TB disease in household contacts, we estimated the fitness, relative to susceptible strains with a fitness of 1, of MDR-Mtb to be 0.32 (95% credible interval: 0.15 - 0.62) or 0.38 (0.24 - 0.61), if only transmission or progression to disease, respectively, was affected. The relative fitness of MDR-Mtb increased to 0.56 (0.42 - 0.72) when the fitness cost influenced both transmission and progression to disease equally. We found the average relative fitness of MDR-Mtb circulating within households in Lima, Peru during 2010 - 2013 to be significantly lower than concurrent susceptible Mtb. If these fitness levels do not change, then existing TB control programmes are likely to keep MDR-TB prevalence at current levels in Lima, Peru.
AB - The relative fitness of drug-resistant versus susceptible bacteria in an environment dictates resistance prevalence. Estimates for the relative fitness of resistant Mycobacterium tuberculosis (Mtb) strains are highly heterogeneous and mostly derived from in vitro experiments. Measuring fitness in the field allows us to determine how the environment influences the spread of resistance. We designed a household structured, stochastic mathematical model to estimate the fitness costs associated with multidrug resistance (MDR) carriage in Mtb in Lima, Peru during 2010 - 2013. By fitting the model to data from a large prospective cohort study of TB disease in household contacts, we estimated the fitness, relative to susceptible strains with a fitness of 1, of MDR-Mtb to be 0.32 (95% credible interval: 0.15 - 0.62) or 0.38 (0.24 - 0.61), if only transmission or progression to disease, respectively, was affected. The relative fitness of MDR-Mtb increased to 0.56 (0.42 - 0.72) when the fitness cost influenced both transmission and progression to disease equally. We found the average relative fitness of MDR-Mtb circulating within households in Lima, Peru during 2010 - 2013 to be significantly lower than concurrent susceptible Mtb. If these fitness levels do not change, then existing TB control programmes are likely to keep MDR-TB prevalence at current levels in Lima, Peru.
KW - Drug-resistance
KW - Fitness
KW - Mathematical modelling
KW - Tuberculosis
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U2 - 10.1098/rsif.2018.0025
DO - 10.1098/rsif.2018.0025
M3 - Article
C2 - 29950511
AN - SCOPUS:85049639019
VL - 15
JO - Journal of the Royal Society Interface
JF - Journal of the Royal Society Interface
SN - 1742-5689
IS - 143
M1 - 20180025
ER -