Nationwide Remapping of Schistosoma mansoni Infection in Rwanda Using Circulating Cathodic Antigen Rapid Test: Taking Steps toward Elimination

Abstract

. The field standard for the detection of Schistosoma mansoni infection is Kato–Katz (KK), although it misses many active infections, especially light infections. In 2014, a reassessment of S. mansoni prevalence was conducted in Rwanda using the more sensitive point-of-care circulating cathodic antigen (POC-CCA) rapid assay. A total of 19,371 children from 399 schools were selected for testing for single urine CCA. Of these, 8,697 children from 175 schools were also tested with single stool double-slide KK. Samples from eight of these 175 schools were tested again with CCA and additionally with the highly specific and sensitive up-converting phosphor-lateral flow circulating anodic antigen (UCP-LF CAA) assay. Latent class analysis was applied to all four test results to assess sensitivity and specificity of POC-CCA and estimate the proportion of trace results from Rwanda likely to be true infections. The overall prevalence of S. mansoni infection in Rwanda when CCA trace results were considered negative was 7.4% (school interquartile range [IQR] 0–8%) and 36.1% (school IQR 20–47%) when trace was considered positive. Prevalence by KK was 2.0% with a mean intensity of infection of 1.66 eggs per gram. The proportion of active infections among children diagnosed with CCA trace was estimated by statistical analysis at 61% (Bayesian credibility interval: 50–72%). These results indicate that S. mansoni infection is still widespread in Rwanda and prevalence is much underestimated by KK testing. Circulating cathodic antigen is an affordable alternative to KK and more suitable for measuring S. mansoni prevalence in low-intensity regions.

Circulating Anodic Antigen (CAA): A Highly Sensitive Diagnostic Biomarker to Detect Active Schistosoma Infections—Improvement and Use during SCORE

“…Latent class analysis indicated that the POC-CCA assay has much higher sensitivity and specificity than does the Kato-Katz assay. 36 Based on the UCAA2000 results and comparing all assays using LCA, approximately 50% of POC-CCA trace positives were estimated to be true positives.…”

Evaluation, Validation, and Recognition of the Point-of-Care Circulating Cathodic Antigen, Urine-Based Assay for Mapping Schistosoma mansoni Infections

“…In Rwanda, testing similar numbers of children in the same ways yielded remarkably similar KK and POC-CCA data and analyses, with POC-CCA results indicating S. mansoni infections, albeit most of low intensity, in all 31 mapping units. 20 A subset of urine specimens (398) from Burundi was selected from eight sentinel site schools to include a spectrum of prevalence levels, spanning 0-20% by the KK assay and 12-90% by the POC-CCA assay. These urine samples were sent to Leiden University Medical Center (LUMC) to be further tested by the very sensitive and schistosome-specific upconverting phosphor lateral flow circulating anodic antigen (UCP-LF CAA) assay.…”

“…Again, the Rwanda data and LCA analyses provide conclusions very similar to those from the Burundi mapping. 20 It is clear based on the mapping studies in Burundi and Rwanda that even when prevalence is very low by KK, it is much higher by POC-CCA. It is also clear that most of those who are KK negative and POC-CCA positive have trace readings.…”

“…What should an NTD program manager do when confronted with a person who is egg negative/POC-CCA positive, particularly when there are few individuals with POC-CCA readings greater than 1+ and an overall prevalence by the KK assay that is very low? This issue arose in the Burundi 19 and Rwanda studies, 20 where prevalence in some villages was very low or zero by KK, but many children were POC-CCA positive, albeit with a preponderance of trace readings (see in the following text). If these children had worms that were excreting eggs, albeit at low levels, they still could be at risk for morbidity or pose a risk for transmission.…”

“…At that point, confirmatory assays and surveillance schemes will be needed to monitor for sporadic, resurgent transmission. 28 Mapping dataset from St. Lucia 24 Mapping dataset from Rwanda 20 Ortu et al 19 KK…”