Translating from Egg- to Antigen-Based Indicators for <i>Schistosoma Mansoni</i> Elimination Targets: A Bayesian Latent Class Analysis Study

Abstract

Background: Schistosomiasis is a parasitic disease infecting over 240-million people. World Health Organization (WHO) targets for Schistosoma mansoni elimination are based on faecal egg counts (FEC), without translation to the widely-used, urine-based, point-of-care circulating cathodic antigen diagnostic (POC-CCA). We aimed to standardise POC-CCA score interpretation and translate them to FEC-based standards, broadening diagnostic utility in progress towards elimination. Methods: A Bayesian latent-class model was fit to data from 210 school-aged-children over four timepoints pre- to six-months-post-treatment. We used 1) FEC and established POC-CCA scoring (Negative, Trace, +, ++ and +++), and 2) FEC and G-Scores (a new, alternative scoring (G1 to G10)). We established the relationship between FECs and POC-CCA scores, and the score-associated probability of true infection. A simulation parametrised with model estimates established antigen-based elimination targets. Findings: True infection was associated with POC-CCA scores of ≥ + or ≥G3. POC-CCA scores cannot predict FECs because low FECs saturate POC-CCA cassettes. Post-treatment POC-CCA sensitivity/specificity fluctuations indicate a changing relationship between egg excretion and antigen levels (living worms). Elimination targets can be identified by the POC-CCA score distribution in a population. A population with ≤2% ++ and above, or ≤1% G7 and above indicates achieving current FEC-based elimination targets. Interpretation: Population-level POC-CCA scores (either scoring method) can be used to access WHO elimination targets prior to treatment. Caution should be excersied on an individual level and following treatment as POC-CCAs lack resolution to discern between WHO FEC-based moderate- and high-intensity infection categories with limited use in certain settings and evaluations. Funding: This work was supported by the European Research Council (ERC) [ERC Starting Grant number SCHISTO_PERSIST_680088 to PHLL]; Wellcome Trust [grant number 204820/Z/16/Z to PHLL]; Engineering and Physical Sciences Research Council (EPSRC) [grant number EP/T003618/1 to JMP and PHLL and grant number EP/R01437X/1 to PI J. Cooper and PHLL, University of Glasgow ]; Medical Research Council [grant number MR/P025447/1 to PHLL] Declaration of Interest: None to declare. Ethical Approval: Ethical Approval was granted from the Vector Control Division Research Ethics Committee (VCDREC/062), Uganda National Council of Science and Technology (UNCST-HS 2193) and University of Glasgow Medical, Veterinary and Life Sciences Research Ethics Committee (200160068).