Diagnostic Performance and Discordance of Kato–Katz Method, POC-CCA Test, and PCR in Detecting Schistosoma mansoni in a Low-Prevalence South African Setting

Background/Objectives: Intestinal schistosomiasis caused by Schistosoma mansoni is often underestimated in low-transmission settings due to the limited sensitivity of traditional stool microscopy. More sensitive approaches, including antigen detection and molecular diagnostics, are required to detect infections where egg excretion is low or intermittent. This study aimed to determine the prevalence of S. mansoni infection among school-going children in Nelson Mandela Bay (NMB) using a multi-modal diagnostic approach. Methods: This cross-sectional study included 759 schoolchildren aged 5–14 years from 15 primary schools in NMB. Stool samples were analyzed using the Kato–Katz technique to detect S. mansoni eggs, while urine samples were tested using the point-of-care circulating cathodic antigen (POC-CCA) assay for antigen detection. A subset of stool samples from POC-CCA-positive participants (n = 28) was further analyzed using conventional PCR (cPCR), targeting the S. mansoni cox1 gene, for molecular confirmation. Only a single stool specimen was collected per participant. Results: Among the 759 participants (58% male, 42% female), no egg-positive cases were detected. However, POC-CCA testing identified S. mansoni antigen in 3.2% of participants. Of the 28 POC-CCA-positive samples analyzed by cPCR, 9 (32.1%) were PCR-positive, representing molecular confirmation within the antigen-positive subset rather than overall prevalence. Conclusions: Traditional microscopy underestimated S. mansoni prevalence in this low-prevalence setting. Antigen detection combined with molecular diagnostics improved case identification and highlighted ongoing transmission. These findings support the integration of sensitive diagnostic tools into schistosomiasis surveillance and control strategies in South Africa.