Fig 1.
Theoretical relationship between time since symptom onset and titers in one infected (red) and three uninfected (blue) individuals.
These titers are mapped onto a two-dimensional representation of acute and convalescent titers. Ellipsoids represent the expected distribution of acute and convalescent titers for infected and uninfected individuals while the underlying marginal distribution of these acute titers is presented at the top. Opacity of each pair of points represents titers at each acute sample. For the infected individual (red) the lightest point represents how titers compare when sampling close to the date of symptom onset while the darkest red point represents how titers compare when sampling more than a week from symptom onset, often defined as a “recent” infection. The marginal distribution of acute titers colored by infected and uninfected individuals is presented above the acute and convalescent titer plot to demonstrate how these recent infections can present.
Fig 2.
Simulated serological data using serosim and subsequent results using the full mixture model on (a) HAI, (b) IgG and (c) IgM data with additional observational noise.
For each we present the predicted infection status using the mixture model approach along with the true underlying infection status. Parameters chosen for forward simulation are presented in S1 Table and resulting metrics of accuracy are presented in S4 Table.
Table 1.
Characteristics for Kamphaeng Phet cohort studies split by source (KPS1 and KFCS) as well as across the entire dataset. Information on age, hospitalization as well as serological assay results for RT-PCR, haemagglutination inhibition assay (HAI), and enzyme immunoassay (EIA) are presented.
Table 2.
Comparison of each accuracy metric (sensitivity, specificity, F1, and area under the curve for reporter operator curve (AUC ROC)) on each model. Models are defined by which assays were incorporated (i.e., HAI, IgG, and/or IgM). Bolded values represent the best performing model for the infection definition and metric of interest.
Fig 3.
Acute and convalescent serological data from Thai cohorts used in this analyses, colored by true infections status and prediction of infection during model testing.
a) Geometric mean titers of a haemagglutination inhibition assay (GM HAI) for all four serotypes of dengue virus. b) Immunoglobulin M (IgM) c) Immunoglobulin G (IgG) d) Ratio of IgM to IgG at both acute and convalescent sera samples.