title: Human dose response relation for airborne exposure to Coxiella burnetii.
abstract: BACKGROUND
  The recent outbreak of Q fever in the Netherlands between 2007 and 2009 is the largest recorded Q fever outbreak. Exposure to Coxiella burnetii may cause Q fever but the size of the population exposed during the outbreak remained uncertain as little is known of the infectivity of this pathogen. The quantification of the infectiousness and the corresponding response is necessary for assessing the risk to the population.
  
  
  METHODS
  A human challenge study was published in the 1950s but this study quantified the dose of C. burnetii in relative units. Data from a concurrent guinea pig challenge study were combined with a recent study in which guinea pigs were challenged with a similar aerosol route to quantify human exposure. Concentration estimates for C. burnetii are made jointly with estimates of the dose response parameters in a hierarchical Bayesian framework.
  
  
  RESULTS
  The dose for 50% infection (InfD50%) in human subjects is 1.18 bacteria (95% credible interval (CI) 0.76-40.2). The dose for 50% illness (IllD50) in challenged humans is 5.58 (95%CI 0.89-89.0) bacteria. The probability of a single viable C. burnetii causing infection in humans is 0.44 (95%CI 0.044-0.59) and for illness 0.12 (95%CI 0.0006-0.55).
  
  
  CONCLUSIONS
  To our knowledge this is the first human dose-response model for C. burnetii. The estimated dose response relation demonstrates high infectivity in humans. In many published papers the proportion of infected individuals developing illness is reported to be 40%. Our model shows that the proportion of symptomatic infections may vary with the exposure dose. This implies that presence of these bacteria in the environment, even in small numbers, poses a serious health risk to the population.
authors.affiliation: Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. J.Brooke@umcutrecht.nl.
authors.forename: Russell John
authors.initials: RJ
authors.lastname: Brooke
authors.forename: Mirjam E E
authors.initials: ME
authors.lastname: Kretzschmar
authors.forename: Nico T
authors.initials: NT
authors.lastname: Mutters
authors.forename: Peter F
authors.initials: PF
authors.lastname: Teunis
mesh_terms: D000391:Air Microbiology; D000818:Animals; D016997:Coxiella burnetii / Q000302:isolation & purification*; D004196:Disease Outbreaks; D006168:Guinea Pigs; D006801:Humans; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D016012:Poisson Distribution; D011778:Q Fever / Q000453:epidemiology / Q000382:microbiology* / Q000635:transmission; D018570:Risk Assessment