title: Closing the gap on causal processes of infection risk from cross-sectional data: structural equation models to understand infection and co-infection.
abstract: BACKGROUND
  Epidemiological studies of disease exposure risk are frequently based on observational, cross-sectional data, and use statistical approaches as crucial tools for formalising causal processes and making predictions of exposure risks. However, an acknowledged limitation of traditional models is that the inferred relationships are correlational, cannot easily distinguish direct from indirect determinants of disease risk, and are often considerable simplifications of complex interrelationships. This may be particularly important when attempting to infer causality in patterns of co-infection through pathogen-facilitation.
  
  
  METHODS
  We describe analyses of cross-sectional data using structural equation models (SEMs), a contemporary advancement on traditional regression approaches, based on our study system of feline gammaherpesvirus (FcaGHV1) in domestic cats.
  
  
  RESULTS
  SEMs strongly supported a latent (host phenotype) variable associated with FcaGHV1 exposure and co-infection risk, suggesting these individuals are simply more likely to become infected with multiple pathogens. However, indications of pathogen-covariance (potential facilitation) were also variably detected: potentially among FcaGHV1, Bartonella spp and Mycoplasma spp.
  
  
  CONCLUSIONS
  Our models suggest multiple exposures are primarily driven by host phenotypic traits, such as aggressive male phenotypes, and secondarily by pathogen-pathogen interactions. The results of this study demonstrate the application of SEMs to understanding epidemiological processes using observational data, and could be used more widely as a complementary tool to understand complex cross-sectional information in a wide variety of disciplines.
authors.affiliation: School of Biological Sciences, University of Tasmania, Hobart, TAS, Australia. scott.carver@utas.edu.au.
authors.forename: Scott
authors.initials: S
authors.lastname: Carver
authors.affiliation: Faculty of Veterinary Science, University of Sydney, Sydney, NSW, Australia. julia.beatty@sydney.edu.au.
authors.forename: Julia A
authors.initials: JA
authors.lastname: Beatty
authors.affiliation: Department of Biomedical Sciences, Oregon State University, Corvallis, OR, USA. ryan.troyer@oregonstate.edu.
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Troyer
authors.affiliation: School of Biological Sciences, University of Tasmania, Hobart, TAS, Australia. rachel.harris@utas.edu.au.
authors.forename: Rachel L
authors.initials: RL
authors.lastname: Harris
authors.affiliation: Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO, USA. kathrynroses@gmail.com.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Stutzman-Rodriguez
authors.affiliation: Faculty of Veterinary Science, University of Sydney, Sydney, NSW, Australia. vanessa.barrs@sydney.edu.au.
authors.forename: Vanessa R
authors.initials: VR
authors.lastname: Barrs
authors.affiliation: The Animal Doctors Pte Ltd., Singapore, Singapore. tsuey312@hotmail.com.
authors.forename: Cathy C
authors.initials: CC
authors.lastname: Chan
authors.affiliation: School of Veterinary Sciences, University of Bristol, Langford, Bristol, UK. S.Tasker@bristol.ac.uk.
authors.forename: Séverine
authors.initials: S
authors.lastname: Tasker
authors.affiliation: Department of Clinical Sciences, Colorado State University, Fort Collins, CO, USA. michael.lappin@colostate.edu.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Lappin
authors.affiliation: Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO, USA. sue.vandewoude@colostate.edu.
authors.forename: Sue
authors.initials: S
authors.lastname: VandeWoude
mesh_terms: D000818:Animals; D001424:Bacterial Infections / Q000453:epidemiology / Q000635:transmission / Q000662:veterinary*; D001473:Bartonella / Q000302:isolation & purification; D056808:Biostatistics; D002371:Cat Diseases / Q000453:epidemiology* / Q000635:transmission*; D002415:Cats; D060085:Coinfection / Q000453:epidemiology*; D003430:Cross-Sectional Studies; D018562:Disease Transmission, Infectious; D004812:Epidemiologic Methods; D018142:Gammaherpesvirinae / Q000302:isolation & purification; D009174:Mycoplasma / Q000302:isolation & purification; D018570:Risk Assessment; D014777:Virus Diseases / Q000453:epidemiology / Q000635:transmission / Q000662:veterinary*