Abstract
Schistosomiasis is a parasitic disease affecting over 240-million people. World Health Organization (WHO) targets for Schistosoma mansoni elimination are based on Kato-Katz egg counts, without translation to the widely used, urine-based, point-of-care circulating cathodic antigen diagnostic (POC-CCA). We aimed to standardize POC-CCA score interpretation and translate them to Kato-Katz-based standards, broadening diagnostic utility in progress towards elimination. 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) Kato-Katz and established POC-CCA scoring (Negative, Trace, +, ++ and +++), and 2) Kato-Katz and G-Scores (a new, alternative POC-CCA scoring (G1 to G10)). We established the functional relationship between Kato-Katz counts and POC-CCA scores, and the score-associated probability of true infection. This was combined with measures of sensitivity, specificity, and the area under the curve to determine the optimal POC-CCA scoring system and positivity threshold. A simulation parametrized with model estimates established antigen-based elimination targets. True infection was associated with POC-CCA scores of ≥ + or ≥G3. POC-CCA scores cannot predict Kato-Katz counts because low infection intensities saturate the 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% ++/+++, or ≤0.5% G7 and above, indicates achieving current WHO Kato-Katz-based elimination targets. Population-level POC-CCA scores can be used to access WHO elimination targets prior to treatment. Caution should be exercised on an individual level and following treatment, as POC-CCAs lack resolution to discern between WHO Kato-Katz-based moderate- and high-intensity-infection categories, with limited use in certain settings and evaluations.
Highlights
Schistosomiasis, caused by a parasitic helminth, is endemic in 54 countries, infecting over 240 million people and has the second greatest socio-economic impact of any parasitic disease after malaria [1] with several million people experiencing severe morbidity despite nearly two decades of interventions [2]
Whilst heavy intensity infections aggregate largely between G7-G10 or +++, zero epg by Kato-Katz and low intensity infections (1–99 epg) are distributed across all point-of-care circulating cathodic antigen diagnostic (POC-CCA)+ and G-Scores, at all timepoints, such that in the field there would be no indication of infection intensity from just the POC-CCA scores
We show the probability of infection associated with each POC-CCA score (Figure 3)
Summary
Schistosomiasis, caused by a parasitic helminth, is endemic in 54 countries, infecting over 240 million people and has the second greatest socio-economic impact of any parasitic disease after malaria [1] with several million people experiencing severe morbidity despite nearly two decades of interventions [2]. For S. mansoni, “heavy” is ≥400 eggs per gram of stool (epg), when measured by Kato-Katz from stool samples [4] These thresholds are problematic because they assume that the egg count is linearly related to the unobservable infection intensity (adult worm density) and morbidity, and because Kato-Katz lack sensitivity and show significant within- and between-sample and -day variation [5, 6]. This categorization is unlikely to be static in time, and underappreciates the contribution of light or moderate intensity infections to morbidity and transmission. These guidelines are in contrast to community risk categories, which are given in terms of infection prevalence, not intensity [7]
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