title: Survival of Mycobacterium tuberculosis during experimental aerosolization and implications for aerosol challenge models.
abstract: OBJECTIVE
  We undertook a series of experiments to investigate factors that contribute to variation in Mycobacterium tuberculosis viability and infectivity, during experimental aerosolization, with an aim to optimize a strategy to enable a more reproducible delivered dose within animal models of tuberculosis.
  
  
  RESULTS
  The viability and infectivity of the challenge suspension was determined in relation to aerosolization time, concentration, method of preparation and M. tuberculosis strain. Challenge stocks generated from frozen aliquots of M. tuberculosis were shown to undergo a 1 log(10) CFU ml(-1) decrease in viability during the first 10 min of aerosolization. This correlated with a decrease in surface lung lesions developing in guinea pigs challenged during this time. The phenomenon of decreased viability in vitro was not observed when using freshly grown, nonfrozen cells of M. tuberculosis. The viability of aerosolized bacilli at the point of inhalation relative to the point of aerosolization always remained constant.
  
  
  CONCLUSIONS
  Based on these findings, we have developed an improved strategy by which to reproducibly deliver aerosol infection doses to individually challenged animals and separately challenged groups of animals.
  
  
  CONCLUSIONS
  Study of the aerobiological characteristics of micro-organisms is a critical step in the validation of methodology for aerosol infection animal models, particularly where large numbers of animals and nonhuman primates are used.
authors.affiliation: Health Protection Agency - Porton Down, Porton Down, Salisbury, UK. simon.clark@hpa.org.uk
authors.forename: S O
authors.initials: SO
authors.lastname: Clark
authors.forename: Y
authors.initials: Y
authors.lastname: Hall
authors.forename: D L F
authors.initials: DL
authors.lastname: Kelly
authors.forename: G J
authors.initials: GJ
authors.lastname: Hatch
authors.forename: A
authors.initials: A
authors.lastname: Williams
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D004195:Disease Models, Animal; D006168:Guinea Pigs; D008168:Lung / Q000382:microbiology / Q000473:pathology; D050296:Microbial Viability; D009169:Mycobacterium tuberculosis / Q000472:pathogenicity*; D009330:Nebulizers and Vaporizers / Q000382:microbiology*; D013997:Time Factors; D014376:Tuberculosis / Q000382:microbiology* / Q000473:pathology
chemical_list: D000336:Aerosols