POC-CCA3: Reducing batch-to-batch variation in the WHO-endorsed POC-CCA for Schistosoma mansoni and improving test interpretation

BackgroundWorld Health Organization (WHO) schistosomiasis control programmes typically rely on Kato-Katz microscopy (KK) to detect Schistosoma mansoni eggs, although KK has limited sensitivity, especially in low-intensity infections. The WHO-endorsed point-of-care circulating cathodic antigen test (POC-CCA) is more sensitive but lacks the complete specificity of KK and has suffered significant batch-to-batch variability, compromising reliability. We evaluated an updated version, POC-CCA3, with the aim of addressing this batch-to-batch variation. MethodsThe POC-CCA3 employs recombinant monoclonal antibodies for Schistosoma CCA detection. School-aged children (n=870) in moderate (Tororo) and high endemicity (Mayuge) settings in Uganda were tested using KK, POC-CCA, and POC-CCA3 tests over three consecutive days. Data were analysed using descriptive statistics and Bayesian Latent Class Analysis, estimating diagnostic performance including sensitivity, specificity, receiver operating characteristic curves, and batch-specific variation and day-to-day variation. ResultsModel median prevalence estimates were 91.4% (Mayuge) and 31.2% (Tororo). A single POC-CCA3 test at G-score threshold 4 achieved estimated sensitivity and specificity, respectively, 86.3% and 92.9% in moderate and 88.1% and 95.5% in high endemicity settings. POC-CCA3 has a small increase in the probability of meeting the WHO TPP for monitoring and evaluation compared to the original POC-CCA. Overall diagnostic performance (AUC >94.2%) was higher compared to POC-CCA, with markedly lower batch-to-batch variation. Conclusions/Next stepsThe POC-CCA3 demonstrates superior performance and greater consistency compared to POC-CCA. A G-score threshold of 4 maximises performance towards WHO target product profile (TPP) requirements. However, neither test consistently meets WHO specificity requirements from a single sample, suggesting the need for continued refinement.