Translating From Egg- to Antigen-Based Indicators for Schistosoma mansoni Elimination Targets: A Bayesian Latent Class Analysis Study

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.

Schistosomiasis solution is not as simple as mass drug administration: Lamberton Lab takes a holistic approach to break the cycle of infection

“…In Clark et al (2022), we established a functional relationship between Kato-Katz counts, POC-CCA scores and the score-associated probability of true infection. A model was used to quantify sensitivity and specificity measures, producing an area under the curve value that can be used to determine how well a diagnostic is working and, in turn, the optimal POC-CCA scoring system and positivity threshold.…”

Reproducibility matters: intra- and inter-sample variation of the point-of-care circulating cathodic antigen test in two Schistosoma mansoni endemic areas in Uganda

“…A descriptive analysis was initially carried out, with the prevalence and mean infection intensities and standard errors estimated using the raw Kato-Katz data. Prevalences were also estimated using the raw POC-CCA data, employing a range of positivity thresholds of the average G-score of G2, G2.5, G3 and G4 or above [29]. When multiple G-scores were available for the same sample, the average (arithmetic mean) G-score was calculated taking the G-scores for their numeric value (e.g.…”

“…To quantify the intra- and inter-sample variation, we extended a Bayesian latent class analysis framework recently developed [29,33,38]. Briefly, a latent (hidden) variable captures the true infection status of an individual (status = 0 for uninfected individuals or with undetectable levels of infection, status = 1 for infected individuals).…”

“…The G-score system improves on this, using 10 pre-printed test lines of increasing intensities, ranging from G1 to G10, enabling a wider range of semi-quantitative results and lower inter-reader variation [32]. Recent latent class analyses have further elucidated ‘trace’ results [29,33], with the probability of G3 being a true positive being much higher than for G2, resulting in a recommendation that G3 and above be classified as positive [29], improving population-level predictions, as well as individual-level diagnoses. In the absence of a perfect schistosomiasis diagnostic test (gold standard), a composite reference standard (CRS) can be built using different imperfect test results.…”

Understanding perceptions of schistosomiasis and its control among highly endemic lakeshore communities in Mayuge, Uganda

“…The WHO recommend a minimum coverage of MDA of 75% to reduce morbidity and transmission [ 24 , 33 , 35 ]; this is far higher than the achieved in this high endemicity community [ 15 ] and many others [ 28 , 36 ]. Despite continued high endemicity in Mayuge [ 37 , 38 ], across Uganda [ 39 ] and sub-Saharan Africa [ 40 , 41 ] our understanding of why some individuals and groups are not taking MDA, or understanding how to, or manage to, change their high-risk behaviour, is still lacking.…”