title: A latent Markov modelling approach to the evaluation of circulating cathodic antigen strips for schistosomiasis diagnosis pre- and post-praziquantel treatment in Uganda.
abstract: Regular treatment with praziquantel (PZQ) is the strategy for human schistosomiasis control aiming to prevent morbidity in later life. With the recent resolution on schistosomiasis elimination by the 65th World Health Assembly, appropriate diagnostic tools to inform interventions are keys to their success. We present a discrete Markov chains modelling framework that deals with the longitudinal study design and the measurement error in the diagnostic methods under study. A longitudinal detailed dataset from Uganda, in which one or two doses of PZQ treatment were provided, was analyzed through Latent Markov Models (LMMs). The aim was to evaluate the diagnostic accuracy of Circulating Cathodic Antigen (CCA) and of double Kato-Katz (KK) faecal slides over three consecutive days for Schistosoma mansoni infection simultaneously by age group at baseline and at two follow-up times post treatment. Diagnostic test sensitivities and specificities and the true underlying infection prevalence over time as well as the probabilities of transitions between infected and uninfected states are provided. The estimated transition probability matrices provide parsimonious yet important insights into the re-infection and cure rates in the two age groups. We show that the CCA diagnostic performance remained constant after PZQ treatment and that this test was overall more sensitive but less specific than single-day double KK for the diagnosis of S. mansoni infection. The probability of clearing infection from baseline to 9 weeks was higher among those who received two PZQ doses compared to one PZQ dose for both age groups, with much higher re-infection rates among children compared to adolescents and adults. We recommend LMMs as a useful methodology for monitoring and evaluation and treatment decision research as well as CCA for mapping surveys of S. mansoni infection, although additional diagnostic tools should be incorporated in schistosomiasis elimination programs.
authors.affiliation: MRC Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom ; Department of Statistics, London School of Economics and Political Science, London, United Kingdom.
authors.forename: Artemis
authors.initials: A
authors.lastname: Koukounari
authors.affiliation: MRC Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom.
authors.forename: Christl A
authors.initials: CA
authors.lastname: Donnelly
authors.affiliation: Department of Statistics, London School of Economics and Political Science, London, United Kingdom.
authors.forename: Irini
authors.initials: I
authors.lastname: Moustaki
authors.affiliation: Schistosomiasis Control Initiative at Vector Control Division - Ministry of Health, Kampala, Uganda.
authors.forename: Edridah M
authors.initials: EM
authors.lastname: Tukahebwa
authors.affiliation: Schistosomiasis Control Initiative at Vector Control Division - Ministry of Health, Kampala, Uganda.
authors.forename: Narcis B
authors.initials: NB
authors.lastname: Kabatereine
authors.affiliation: Department of Pathology, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Shona
authors.initials: S
authors.lastname: Wilson
authors.affiliation: Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom.
authors.forename: Joanne P
authors.initials: JP
authors.lastname: Webster
authors.affiliation: Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: André M
authors.initials: AM
authors.lastname: Deelder
authors.affiliation: Section for Parasitology and Aquatic Diseases, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Birgitte J
authors.initials: BJ
authors.lastname: Vennervald
authors.affiliation: Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Govert J
authors.initials: GJ
authors.lastname: van Dam
mesh_terms: D000871:Anthelmintics / Q000627:therapeutic use*; D000953:Antigens, Protozoan / Q000097:blood*; D006801:Humans; D008390:Markov Chains; D011223:Praziquantel / Q000627:therapeutic use*; D012552:Schistosomiasis / Q000175:diagnosis* / Q000188:drug therapy*; D012680:Sensitivity and Specificity; D014454:Uganda
chemical_list: D000871:Anthelmintics; D000953:Antigens, Protozoan; D011223:Praziquantel