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 eggdetection 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.

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

“…These efforts are described elsewhere in this supplement. 44 In addition, because of the extreme need, SCORE also supported initial efforts to use CAA in the development of a rapid diagnostic 44 that would be suitable for mapping both S. mansoni and S. haematobium.…”

SCORE Operational Research on Moving toward Interruption of Schistosomiasis Transmission

“…In areas on Pemba with an apparent prevalence of < 10% by urine filtration, the prevalence determined with the UCP-LF CAA assay was almost three times higher. 3,41 Other limitations of the Zanzibar elimination study are described in a recent article on the 5-year study results. 16 The SCORE studies provide lessons learned for future research, such as the difficulty conducting randomized control trials (RCTs) to assess strategies to interrupt transmission of schistosomiasis.…”

“…SCORE's work on developing and evaluating mapping and diagnostic tools is described in other articles in this supplement. 2,3 In 2012, the World Health Assembly (WHA) issued resolution WHA 65.21, which called for the expansion of schistosomiasis control programs and to "initiate elimination campaigns where appropriate." 4 Following this, in 2013, SCORE received supplemental funding from the BMGF to build on data and experiences obtained by SCORE thus far and expand operational research on elimination of schistosomiasis.…”

Contributions of the Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) to Schistosomiasis Control and Elimination: Key Findings and Messages for Future Goals, Thresholds, and Operational Research

“…SCORE also invested substantially into the development of the highly sensitive and genus-specific UCP-LF CAA assay. 38 This tool should play an important role as a highly sensitive and specific diagnostic test and for verification of elimination of schistosomiasis. This assay has now been used many times, including in the SCORE studies within the ZEST program on Zanzibar, where it demonstrated much higher levels of S. haematobium than measured by the widely used urine filtration method.…”

“…25 The UCP-LF CAA assay was also used in Burundi 24 and Rwanda, where it contributed to our understanding of the strengths and limitations of the POC-CCA, and in numerous other studies. 38 SCORE's role in refocusing attention on the importance of snails in transmission. SCORE has contributed substantially to a rejuvenation of interest in the control of the vector snails and the potential of monitoring snails in determining the force of infection.…”