title: Defining the relationship between Plasmodium vivax parasite rate and clinical disease.
abstract: BACKGROUND
  Though essential to the development and evaluation of national malaria control programmes, precise enumeration of the clinical illness burden of malaria in endemic countries remains challenging where local surveillance systems are incomplete. Strategies to infer annual incidence rates from parasite prevalence survey compilations have proven effective in the specific case of Plasmodium falciparum, but have yet to be developed for Plasmodium vivax. Moreover, defining the relationship between P. vivax prevalence and clinical incidence may also allow levels of endemicity to be inferred for areas where the information balance is reversed, that is, incident case numbers are more widely gathered than parasite surveys; both applications ultimately facilitating cartographic estimates of P. vivax transmission intensity and its ensuring disease burden.
  
  
  METHODS
  A search for active case detection surveys was conducted and the recorded incidence values were matched to local, contemporary parasite rate measures and classified to geographic zones of differing relapse phenotypes. A hierarchical Bayesian model was fitted to these data to quantify the relationship between prevalence and incidence while accounting for variation among relapse zones.
  
  
  RESULTS
  The model, fitted with 176 concurrently measured P. vivax incidence and prevalence records, was a linear regression of the logarithm of incidence against the logarithm of age-standardized prevalence. Specific relationships for the six relapse zones where data were available were drawn, as well as a pooled overall relationship. The slope of the curves varied among relapse zones; zones with short predicted time to relapse had steeper slopes than those observed to contain long-latency relapse phenotypes.
  
  
  CONCLUSIONS
  The fitted relationships, along with appropriate uncertainty metrics, allow for estimates of clinical incidence of known confidence to be made from wherever P. vivax prevalence data are available. This is a prerequisite for cartographic-based inferences about the global burden of morbidity due to P. vivax, which will be used to inform control efforts.
authors.affiliation: Spatial Ecology and Epidemiology Group, Tinbergen Building, Department of Zoology, University of Oxford, South Parks Road, Oxford, UK. katherine.battle@zoo.ox.ac.uk.
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Battle
authors.affiliation: Spatial Ecology and Epidemiology Group, Tinbergen Building, Department of Zoology, University of Oxford, South Parks Road, Oxford, UK. ewan.cameron@zoo.ox.ac.uk.
authors.forename: Ewan
authors.initials: E
authors.lastname: Cameron
authors.affiliation: Sanaria Institute for Global Health and Tropical Medicine, Rockville, MD, USA. carlos.guerraloaiza@gmail.com.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Guerra
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, UK. nick.golding@zoo.ox.ac.uk.
authors.forename: Nick
authors.initials: N
authors.lastname: Golding
authors.affiliation: Spatial Ecology and Epidemiology Group, Tinbergen Building, Department of Zoology, University of Oxford, South Parks Road, Oxford, UK. kirsten.duda@zoo.ox.ac.uk.
authors.forename: Kirsten A
authors.initials: KA
authors.lastname: Duda
authors.affiliation: Spatial Ecology and Epidemiology Group, Tinbergen Building, Department of Zoology, University of Oxford, South Parks Road, Oxford, UK. rosalind.howes@zoo.ox.ac.uk.
authors.forename: Rosalind E
authors.initials: RE
authors.lastname: Howes
authors.affiliation: Eijkman-Oxford Clinical Research Unit, Jalan Diponegoro No 69, Jakarta, Indonesia. iqbal.elyazar@gmail.com.
authors.forename: Iqbal R F
authors.initials: IR
authors.lastname: Elyazar
authors.affiliation: Global and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, NT, Australia. rprice@menzies.edu.au.|Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK. rprice@menzies.edu.au.
authors.forename: Ric N
authors.initials: RN
authors.lastname: Price
authors.affiliation: Eijkman-Oxford Clinical Research Unit, Jalan Diponegoro No 69, Jakarta, Indonesia. kevin.baird@ndm.ox.ac.uk.|Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK. kevin.baird@ndm.ox.ac.uk.
authors.forename: J Kevin
authors.initials: JK
authors.lastname: Baird
authors.affiliation: Indiana University School of Public Health, Bloomington, IN, USA. rcreiner@indiana.edu.|Fogarty International Center, National Institutes of Health, Bethesda, MD, USA. rcreiner@indiana.edu.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Reiner
authors.affiliation: Spatial Ecology and Epidemiology Group, Tinbergen Building, Department of Zoology, University of Oxford, South Parks Road, Oxford, UK. smitdave@gmail.com.|Sanaria Institute for Global Health and Tropical Medicine, Rockville, MD, USA. smitdave@gmail.com.|Fogarty International Center, National Institutes of Health, Bethesda, MD, USA. smitdave@gmail.com.
authors.forename: David L
authors.initials: DL
authors.lastname: Smith
authors.affiliation: Spatial Ecology and Epidemiology Group, Tinbergen Building, Department of Zoology, University of Oxford, South Parks Road, Oxford, UK. peter.gething@zoo.ox.ac.uk.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Gething
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, UK. simon.hay@well.ox.ac.uk.|Fogarty International Center, National Institutes of Health, Bethesda, MD, USA. simon.hay@well.ox.ac.uk.|Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, 98121, USA. simon.hay@well.ox.ac.uk.
authors.forename: Simon I
authors.initials: SI
authors.lastname: Hay
mesh_terms: D001499:Bayes Theorem; D019353:Endemic Diseases; D006801:Humans; D015994:Incidence; D016780:Malaria, Vivax / Q000453:epidemiology* / Q000469:parasitology; D008962:Models, Theoretical; D018512:Parasitemia / Q000453:epidemiology* / Q000469:parasitology; D010966:Plasmodium vivax / Q000502:physiology*; D015995:Prevalence; D012008:Recurrence