title: Fitness of drug resistant Mycobacterium tuberculosis and the impact on the transmission among household contacts.
abstract: There has been an on-going debate on whether the development of drug resistance in Mycobacterium tuberculosis reduces its relative fitness and its ability to cause disease. The aim of this study was to explore this relationship. For this purpose, we evaluated the in vitro growth of clinical isolates and the transmission of the strains within the patients' households. Clinical and epidemiological data from patients in households, drug-susceptibility and genetic patterns of the isolates were collected. BACTEC MGIT 960™ system with the Epicenter™ software was used to perform fitness experiments and calculate the relative fitness (RF) comparing with the H73Rv reference strain. From 39 households, 124 patients and 388 contacts were included. Concerning transmission, 20 Multi drug-resistant (MDR) and 16 drug sensitive (DS) index cases generated 23 and 28 secondary cases, respectively. An average RF drop of 16.7% was found for MDR strains, but only mutations in rpoB codons 531 were associated with reduced fitness. When the strains were transmitted, their RF tended to decrease, and strains with low RF were less frequently transmitted. Within the limitations of this study, the results showed that the decrease in RF was associated to a limited transmission among the households' contacts.
authors.affiliation: Reference Laboratory of Tuberculosis Control Program of Buenos Aires Province, Dr. Cetrangolo Hospital, Vicente López, Buenos Aires Province, Argentina.
authors.forename: Nora S
authors.initials: NS
authors.lastname: Morcillo
authors.affiliation: Reference Laboratory of Tuberculosis Control Program of Buenos Aires Province, Dr. Cetrangolo Hospital, Vicente López, Buenos Aires Province, Argentina.
authors.forename: Belén R
authors.initials: BR
authors.lastname: Imperiale
authors.affiliation: Mycobacteria Laboratory, Petrona V. de Cordero Hospital, San Fernando, Buenos Aires Province, Argentina.
authors.forename: Ángela
authors.initials: Á
authors.lastname: Di Giulio
authors.affiliation: Biotechnology Institute, National Institute of Agricultural Technology (INTA), Hurlingham, Buenos Aires Province, Argentina.
authors.forename: Martín J
authors.initials: MJ
authors.lastname: Zumárraga
authors.affiliation: Instituto Venezolano de Investigaciones Científicas, Caracas, Venezuela.
authors.forename: Howard
authors.initials: H
authors.lastname: Takiff
authors.affiliation: Biotechnology Institute, National Institute of Agricultural Technology (INTA), Hurlingham, Buenos Aires Province, Argentina. Electronic address: cataldi.angeladrian@inta.gob.ar.
authors.forename: Ángel A
authors.initials: ÁA
authors.lastname: Cataldi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000995:Antitubercular Agents / Q000494:pharmacology; D002648:Child; D002675:Child, Preschool; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics; D005192:Family Health / Q000706:statistics & numerical data*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008826:Microbial Sensitivity Tests / Q000379:methods; D008875:Middle Aged; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development / Q000472:pathogenicity; D018088:Tuberculosis, Multidrug-Resistant / Q000382:microbiology* / Q000635:transmission; D014774:Virulence / Q000235:genetics; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents
keywords: Drug-resistance; Family transmission; Fitness; Household contacts; Tuberculosis