Detecting two Schistosoma circulating antigens - CCA and CAA - in urine and serum to improve diagnosis of human schistosomiasis

Pytsje T Hoekstra; Claudia J de Dood; Theresia Abdoel; Stan Hilt; Angela van Diepen; Katja Polman; Peter Kremsner; Lisette van Lieshout; Andrea Kreidenweiss; Ayola Akim Adegnika; Daniela Fusco; Tahinamandranto Rasomoelina; Mala Rakoto Andrianarivelo; Raphaël Rakotozandrindrainy; Rivo Andry Rakotoarivelo; Elisa Sicuri; Govert J van Dam; Paul L A M Corstjens

doi:10.3389/fpara.2024.1460331

Detecting two Schistosoma circulating antigens - CCA and CAA - in urine and serum to improve diagnosis of human schistosomiasis

Front Parasitol. 2024 Oct 4:3:1460331. doi: 10.3389/fpara.2024.1460331. eCollection 2024.

Authors

Pytsje T Hoekstra¹, Claudia J de Dood², Theresia Abdoel³, Stan Hilt¹, Angela van Diepen¹, Katja Polman⁴, Peter Kremsner^{5

6

7}, Lisette van Lieshout¹, Andrea Kreidenweiss^{5

6}, Ayola Akim Adegnika^{1

5

6

7}, Daniela Fusco⁸, Tahinamandranto Rasomoelina⁹, Mala Rakoto Andrianarivelo⁹, Raphaël Rakotozandrindrainy¹⁰, Rivo Andry Rakotoarivelo¹¹, Elisa Sicuri¹², Govert J van Dam¹, Paul L A M Corstjens²

Affiliations

¹ Leiden University Center for Infectious Diseases (LUCID), Leiden University Medical Center, Leiden, Netherlands.
² Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, Netherlands.
³ Mondial Diagnostics, Amsterdam, Netherlands.
⁴ Department of Public Health, Institute of Tropical Medicine, Antwerp, Belgium.
⁵ Institute of Tropical Medicine, University Hospital Tübingen, Tübingen, Germany.
⁶ German Center for Infection Research (DZIF), partner site Tübingen, Tübingen, Germany.
⁷ Centre de Recherches Médicales de Lambaréné, Lambaréné, Gabon.
⁸ Department of Infectious Disease Epidemiology, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
⁹ Centre d'Infectiologie Charles Mérieux, Antananarivo, Madagascar.
¹⁰ University of Antananarivo, Antananarivo, Madagascar.
¹¹ University of Fianarantsoa, Fianarantsoa, Madagascar.
¹² ISGlobal, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain.

Abstract

Background: Schistosomiasis is caused by infection with parasitic Schistosoma worms and affects more than 250 million people globally. The detection of schistosome derived circulating cathodic and anodic antigens (CCA and CAA) has proven highly valuable for detecting active Schistosoma infections, causing both intestinal and urinary schistosomiasis.

Aim: The combined detection of CCA and CAA was explored to improve accuracy in detecting Schistosoma infections.

Methods: Parallel detection of CCA and CAA was performed on two banked sample sets with matching serum and urine samples from Schistosoma mansoni (Sm) and S. haematobium (Sh) infected individuals using the non-concentration based lateral flow (LF) test comprising the sensitive luminescent up-converting reporter particle (UCP) technology.

Results: Parallel detection of CCA and CAA increased the positivity rate for detecting both Sm and Sh infections compared to the detection of either antigen separately, demonstrating the added value of detecting both antigens in a single sample to confirm diagnosis, independent from the Schistosoma species. Significantly higher CCA concentrations in urine were observed in Sm infected individuals compared to Sh infected individuals, while serum CCA-concentrations were similar between species. CAA concentrations were higher in serum compared to those in urine, irrespective of species. When exploring the relationship of CCA and CAA in urine, the CCA/CAA ratio in Sm infected individuals was significantly higher than in Sh infected individuals, while no differences were observed in serum.

Discussion and conclusion: Parallel detection of CCA and CAA via the UCP-LF platform showed added diagnostic value through an increased positivity rate for the detection of Sm and Sh infections, compared to only detecting either of the antigens. The combined and quantitative detection of CCA and CAA is indicative for identifying the infecting species, but needs further exploration.

Keywords: circulating anodic antigen (CAA); circulating cathodic antigen (CCA); diagnostics; duplex test; schistosomiasis.

Copyright © 2024 Hoekstra, de Dood, Abdoel, Hilt, van Diepen, Polman, Kremsner, van Lieshout, Kreidenweiss, Adegnika, Fusco, Rasomoelina, Rakoto Andrianarivelo, Rakotozandrindrainy, Rakotoarivelo, Sicuri, van Dam and Corstjens.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This publication was produced by freeBILy which is part of the EDCTP2 programme supported by the European Union (grant number RIA2016MC-1626-FREEBILY). The funding body had no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.