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

Abstract

The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) was funded in 2008 to conduct research that would support country schistosomiasis control programs. As schistosomiasis prevalence decreases in many places and elimination is increasingly within reach, a sensitive and specific test to detect infection with Schistosoma mansoni and Schistosoma haematobium has become a pressing need. After obtaining broad input, SCORE supported Leiden University Medical Center (LUMC) to modify the serum-based antigen assay for use with urine, simplify the assay, and improve its sensitivity. The urine assay eventually contributed to several of the larger SCORE studies. For example, in Zanzibar, we demonstrated that urine filtration, the standard parasite egg detection diagnostic test for S. haematobium, greatly underestimated prevalence in low-prevalence settings. In Burundi and Rwanda, the circulating anodic antigen (CAA) assay provided critical information about the limitations of the stool-based Kato-Katz parasite egg-detection assay for S. mansoni in low-prevalence settings. Other SCORE-supported CAA work demonstrated that frozen, banked urine specimens yielded similar results to fresh ones; pooling of specimens may be a useful, cost-effective approach for surveillance in some settings; and the assay can be performed in local laboratories equipped with adequate centrifuge capacity. These improvements in the assay continue to be of use to researchers around the world. However, additional work will be needed if widespread dissemination of the CAA assay is to occur, for example, by building capacity in places besides LUMC and commercialization of the assay. Here, we review the evolution of the CAA assay format during the SCORE period with emphasis on urine-based applications.

Figure 1.

Circulating anodic antigen (CAA) levels detectable in urine specimens collected at baseline, 1, 3, 8, and 9 weeks after infection from baboons infected with Schistosoma mansoni cercariae and perfused at week 9 to determine worm burdens. CAA levels, shown on the y axis on a logarithmic scale, were measured in urine with the UCAA250 assay and demonstrate detectable levels (above the UCAA cutoff threshold, gray area) by week 3.

Figure 2.

Prevalence of Schistosoma haematobium was determined by the standard filtration of 10 mL urine (dark bars) and the UCAA2000 (light gray bars) applied to the same urine samples collected from children attending 16 schools on Pemba island. Figure redrawn, based on Knopp et al.

Figure 3.

Comparative prevalence levels shown on the y axis on a logarithmic scale in five different countries based on egg counts (urine or stool) and the UCAA2000 assay for antigen detection. Areas with different endemicity settings: low endemicity settings in Brazil (n = 258), Cambodia (n = 196), and China (n = 317); medium- through high-endemicity settings in Lao PDR (n = 181) and Tanzania (n = 44). Solid bars indicate prevalence based on egg microscopy in urine or stool (species depending). Hatched bars indicate prevalence by CAA as determined in urine with the UCAA2000 assay.