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Tools for diagnosis, monitoring and screening of Schistosoma infections utilizing lateral-flow based assays and upconverting phosphor labels



The potential of various quantitative lateral flow (LF) based assays utilizing up-converting phosphor (UCP) reporters for the diagnosis of schistosomiasis is reviewed including recent developments. Active infections are demonstrated by screening for the presence of regurgitated worm antigens (genus specific polysaccharides), whereas anti-Schistosoma antibodies may indicate ongoing as well as past infections. The circulating anodic antigen (CAA) in serum or urine (and potentially also saliva) is identified as the marker that may allow detection of single-worm infections. Quantitation of antigen levels is a reliable method to study effects of drug administration, worm burden and anti-fecundity mechanisms. Moreover, the ratio of CAA and circulating cathodic antigen (CCA) is postulated to facilitate identification of either Schistosoma mansoni or Schistosoma haematobium infections. The UCP-LF assays allow simultaneous detection of multiple targets on a single strip, a valuable feature for antibody detection assays. Although antibody detection in endemic regions is not a useful tool to diagnose active infections, it gains potential when the ratio of different classes of antibody specific for the parasite/disease can be determined. The UCP-LF antibody assay format allows this type of multiplexing, including testing a linear array of up to 20 different targets. Multiple test spots would allow detection of specific antibodies, e.g. against different Schistosoma species or other pathogens as soil-transmitted helminths. Concluding, the different UCP-LF based assays for diagnosis of schistosomiasis provide a collection of tests with relatively low complexity and high sensitivity, covering the full range of diagnostics needed in control programmes for mapping, screening and monitoring.


Corresponding author

*Corresponding author: Department of Molecular Cell Biology, Leiden University Medical Center, Einthovenweg 20, P.O. Box 9600, 2300 RC, Leiden, the Netherlands. E-mail:


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Agnew, A., Fulford, A. J. C., de Jonge, N., Krijger, F. W., Rodriguezchacon, M., Gutsmann, V. and Deelder, A. M. (1995). The relationship between worm burden and levels of a circulating antigen (CAA) of 5 species of Schistosoma in mice. Parasitology 111, 6776.
Ayele, B., Erko, B., Legesse, M., Hailu, A. and Medhin, G. (2008). Evaluation of circulating cathodic antigen (CCA) strip for diagnosis of urinary schistosomiasis in Hassoba school children, Afar, Ethiopia. Parasite – Journal de la Societe Francaise de Parasitologie 15, 6975.
Bergquist, N. R. (1992). Schistosomiasis research funding – the TDR contribution. Memorias do Instituto Oswaldo Cruz 87, 153161.
Bergquist, R., Johansen, M. V. and Utzinger, J. (2009). Diagnostic dilemmas in helminthology: what tools to use and when? Trends in Parasitology 25, 151156.
Bergwerff, A. A., van Dam, G. J., Rotmans, J. P., Deelder, A. M., Kamerling, J. P. and Vliegenthart, J. F. (1994). The immunologically reactive part of immunopurified circulating anodic antigen from Schistosoma mansoni is a threonine-linked polysaccharide consisting of → 6)-(beta-D-GlcpA-(1→3))-beta-D-GalpNAc-(1→repeating units. Journal of Biological Chemistry 269, 3151031517.
Chen, Z., Abrams, W. R., Geva, E., de Dood, C. J., Gonzalez, J. M., Tanke, H. J., Niedbala, R. S., Zhou, P., Malamud, D. and Corstjens, P. L. (2013). Development of a generic microfluidic device for simultaneous detection of antibodies and nucleic acids in oral fluids. BioMed Research International 2013, 543294.
Colley, D. G., Binder, S., Campbell, C., King, C. H., Tchuem Tchuente, L. A., N'Goran, E. K., Erko, B., Karanja, D. M., Kabatereine, N. B., van Lieshout, L. and Rathbun, S. (2013). A five-country evaluation of a point-of-care circulating cathodic antigen urine assay for the prevalence of Schistosoma mansoni. American Journal of Tropical Medicine Hygiene 88, 426432.
Corstjens, P. L. A. M. and Malamud, D. (2008). Point-of-care diagnostics for infectious diseases. In Salivary Diagnostics (ed. Wong, D. T.), pp. 136149. Wiley-Blackwell, Hoboken, NY, USA.
Corstjens, P., Zuiderwijk, M., Brink, A., Li, S., Feindt, H., Neidbala, R. S. and Tanke, H. (2001). Use of up-converting phosphor reporters in lateral-flow assays to detect specific nucleic acid sequences: a rapid, sensitive DNA test to identify human papillomavirus type 16 infection. Clinical Chemistry 47, 18851893.
Corstjens, P. L., Li, S., Zuiderwijk, M., Kardos, K., Abrams, W. R., Niedbala, R. S. and Tanke, H. J. (2005). Infrared up-converting phosphors for bioassays. IEE Proceedings Nanobiotechnology 152, 6472.
Corstjens, P. L., Chen, Z., Zuiderwijk, M., Bau, H. H., Abrams, W. R., Malamud, D., Niedbala, R. S. and Tanke, H. J. (2007). Rapid assay format for multiplex detection of humoral immune responses to infectious disease pathogens (HIV, HCV, and TB). Annals of the New York Academy of Sciences 1098, 437445.
Corstjens, P. L. A. M., van Lieshout, L., Zuiderwijk, M., Kornelis, D., Tanke, H. J., Deelder, A. M. and van Dam, G. J. (2008). Up-converting phosphor technology-based lateral flow assay for detection of Schistosoma circulating anodic antigen in serum. Journal of Clinical Microbiology 46, 171176.
Corstjens, P. L., Kardos, K., Niedbala, R. S., Tanke, H. J., Zuiderwijk, M., Feindt, H. H., Mokkapati, V. K. and Kimball, J. A. (2010). Lateral flow assay device with multiple equidistant capture zones. United States Patent 7,858,396.
Corstjens, P. L. A. M., de Dood, C. J., van der Ploeg-van Schip, J. J., Wiesmeijer, K. C., Riuttamaki, T., van Meijgaarden, K. E., Spencer, J. S., Tanke, H. J., Ottenhoff, T. H. M. and Geluk, A. (2011). Lateral flow assay for simultaneous detection of cellular- and humoral immune responses. Clinical Biochemistry 44, 12411246.
Coulibaly, J. T., N'Goran, E. K., Utzinger, J., Doenhoff, M. J. and Dawson, E. M. (2013 a). A new rapid diagnostic test for detection of anti-Schistosoma mansoni and anti-Schistosoma haematobium antibodies. Parasites and Vectors 6, 29.
Coulibaly, J. T., N'Gbesso, Y. K., Knopp, S., N'Guessan, N. A., Silue, K. D., van Dam, G. J., N'Goran, E. K. and Utzinger, J. (2013 b). Accuracy of urine circulating cathodic antigen test for the diagnosis of Schistosoma mansoni in preschool-aged children before and after treatment. PLOS Neglected Tropical Diseases 7, e2109.
Dawson, E. M., Sousa-Figueiredo, J. C., Kabatereine, N. B., Doenhoff, M. J. and Stothard, J. R. (2013). Intestinal schistosomiasis in pre school-aged children of Lake Albert, Uganda: diagnostic accuracy of a rapid test for detection of anti-schistosome antibodies. Transactions of the Royal Society of Tropical Medicine and Hygiene 107, 639647.
de Bont, J., van Lieshout, L., Deelder, A. M., Ysebaert, M. T. and Vercruysse, J. (1996). Circulating antigen levels in serum of cattle naturally infected with Schistosoma mattheei. Parasitology 113, 465471.
de Jonge, N., Fillie, Y. E. and Deelder, A. M. (1987). A simple and rapid treatment (trichloroacetic-acid precipitation) of serum samples to prevent nonspecific reactions in the immunoassay of a proteoglycan. Journal of Immunological Methods 99, 195197.
de Jonge, N., Fillie, Y. E., Hilberath, G. W., Krijger, F. W., Lengeler, C., de Savigny, D. H., van Vliet, N. G. and Deelder, A. M. (1989). Presence of the schistosome circulating anodic antigen (CAA) in urine of patients with Schistosoma mansoni or S. haematobium infections. American Journal of Tropical Medicine and Hygiene 41, 563569.
de Jonge, N., Rabello, A. L. T., Krijger, F. W., Kremsner, P. G., Rocha, R. S., Katz, N. and Deelder, A. M. (1991). Levels of the schistosome circulating anodic and cathodic antigens in serum of schistosomiasis patients from Brazil. Transactions of the Royal Society of Tropical Medicine and Hygiene 85, 756759.
Deelder, A. M. and Kornelis, D. (1981). Immunodiagnosis of recently acquired Schistosoma mansoni infection – a comparison of various immunological techniques. Tropical and Geographical Medicine 33, 3641.
Deelder, A. M., Kornelis, D., Makbin, M., Noordpool, H. N., Codfried, R. M., Rotmans, J. P. and Oostburg, B. F. J. (1980). Applicability of different antigen preparations in the enzyme-linked immunosorbent-assay for schistosomiasis mansoni. American Journal of Tropical Medicine and Hygiene 29, 401410.
Deelder, A. M., Qian, Z. L., Kremsner, P. G., Acosta, L., Rabello, A. L. T., Enyong, P., Simarro, P. P., Vanetten, E. C. M., Krijger, F. W., Rotmans, J. P., Fillie, Y. E., de Jonge, N., Agnew, A. M. and van Lieshout, L. (1994). Quantitative diagnosis of Schistosoma infections by measurement of circulating antigens in serum and urine. Tropical and Geographical Medicine 46, 233238.
Deelder, A. M., van Dam, G. J., Kornelis, D., Fillie, Y. E. and van Zeyl, R. J. M. (1996). Schistosoma: analysis of monoclonal antibodies reactive with the circulating antigens CAA and CCA. Parasitology 112, 2135.
Deelder, A. M., van Dam, G. J. and van Lieshout, L. (2012). Response to: Accuracy of circulating cathodic antigen tests for rapid mapping of Schistosoma mansoni and S. haematobium infections in Southern Sudan by RA Ashton et al. (2011) Tropical Medicine & International Health 16, pp. 1099–1103. Tropical Medicine & International Health 17, 402403.
Elhag, S. M., Abdelkareem, E. A., Yousif, A. S., Frah, E. A. and Mohamed, A. B. (2011). Detection of schistosomiasis antibodies in urine patients as a promising diagnostic maker. Asian Pacific Journal of Tropical Medicine 4, 773777.
Erko, B., Medhin, G., Teklehaymanot, T., Degarege, A. and Legesse, M. (2013). Evaluation of urine-circulating cathodic antigen (urine-CCA) cassette test for the detection of Schistosoma mansoni infection in areas of moderate prevalence in Ethiopia. Tropical Medicine & International Health 18, 10291035.
Flowers, J. R., Hammerberg, B., Wood, S. L., Malarkey, D. E., van Dam, G. J., Levy, M. G. and McLawhorn, L. D. (2002). Heterobilharzia americana infection in a dog. Journal of the American Veterinary Medical Association 220, 193196.
Gabriel, S., de Bont, J., Phiri, I. K., Masuku, M., Riveau, G., Schacht, A. M., Deelder, A. M., van Dam, G. J. and Vercruysse, J. (2002). Transplacental transfer of schistosomal circulating anodic antigens in cows. Parasite Immunology 24, 521525.
Grenfell, R., Harn, D. A., Tundup, S., Da'dara, A., Siqueira, L. and Coelho, P. M. Z. (2013). New approaches with different types of circulating cathodic antigen for the diagnosis of patients with low Schistosoma mansoni load. PLOS Neglected Tropical Diseases 7, e2054.
Gutman, J., Fagbemi, A., Alphonsus, K., Eigege, A., Miri, E. S. and Richards, F. O. (2008). Missed treatment opportunities for schistosomiasis mansoni, in an active programme for the treatment of urinary schistosomiasis in Plateau and Nasarawa states, Nigeria. Annals of Tropical Medicine and Parasitology 102, 335346.
Huyse, T., Webster, B. L., Geldof, S., Stothard, J. R., Diaw, O. T., Polman, K. and Rollinson, D. (2009). Bidirectional introgressive hybridization between a cattle and human schistosome species. PLOS Pathogens 5, e1000571.
Kahama, A. I., Kremsner, P. G., van Dam, G. J. and Deelder, A. M. (1998). The dynamics of a soluble egg antigen of Schistosoma haematobium in relation to egg counts, circulating anodic and cathodic antigens and pathology markers before and after chemotherapy. Transactions of the Royal Society of Tropical Medicine and Hygiene 92, 629633.
Kariuki, T. M., Farah, I. O., Yole, D. S., Mwenda, J. M., van Dam, G. J., Deelder, A. M., Wilson, R. A. and Coulson, P. S. (2004). Parameters of the attenuated schistosome vaccine evaluated in the olive baboon. Infection and Immunity 72, 55265529.
Kariuki, T. M., van Dam, G. J., Deelder, A. M., Farah, I. O., Yole, D. S., Wilson, R. A. and Coulson, P. S. (2006). Previous or ongoing schistosome infections do not compromise the efficacy of the attenuated cercaria vaccine. Infection and Immunity 74, 39793986.
Kariuki, T. M., Farah, I. O., Wilson, R. A. and Coulson, P. S. (2008). Antibodies elicited by the secretions from schistosome cercariae and eggs are predominantly against glycan epitopes. Parasite Immunology 30, 554562.
King, C. H., Dickman, K. and Tisch, D. J. (2005). Reassessment of the cost of chronic helmintic infection: a meta-analysis of disability-related outcomes in endemic schistosomiasis. Lancet 365, 15611569.
Knopp, S., Becker, S. L., Ingram, K. J., Keiser, J. and Utzinger, J. (2013). Diagnosis and treatment of schistosomiasis in children in the era of intensified control. Expert Review of Anti-Infective Therapy 11, 12371258.
Kremsner, P. G., De, J. N., Simarro, P. P., Muhlschlegel, F., Mir, M., Sima, F. O., Feldmeier, H., Bienzle, U. and Deelder, A. M. (1993). Quantitative determination of circulating anodic and cathodic antigens in serum and urine of individuals infected with Schistosoma intercalatum. Transactions of the Royal Society of Tropical Medicine and Hygiene 87, 167169.
Krijger, F. W., van Lieshout, L. and Deelder, A. M. (1994). A simple technique to pretreat urine and serum samples for quantitation of schistosome circulating anodic and cathodic antigen. Acta Tropica 56, 5563.
Leutscher, P. D., van Dam, G. T., Reimert, C. M., Ramarakoto, C. E., Deelder, A. M. and Ornbjerg, N. (2008). Eosinophil cationic protein, soluble egg antigen, circulating anodic antigen, and egg excretion in male urogenital schistosomiasis. American Journal of Tropical Medicine and Hygiene 79, 422426.
Malamud, D., Bau, H., Niedbala, S. and Corstjens, P. (2005). Point detection of pathogens in oral samples. Advances in Dental Research 18, 1216.
Midzi, N., Butterworth, A. E., Mduluza, T., Munyati, S., Deelder, A. M. and van Dam, G. J. (2009). Use of circulating cathodic antigen strips for the diagnosis of urinary schistosomiasis. Transactions of the Royal Society of Tropical Medicine and Hygiene 103, 4551.
Mokkapati, V. K., Sam, N. R., Kardos, K., Perez, R. J., Guo, M., Tanke, H. J. and Corstjens, P. L. (2007). Evaluation of UPlink-RSV: prototype rapid antigen test for detection of respiratory syncytial virus infection. Annals of the New York Academy of Sciences 1098, 476485.
Niedbala, R. S., Feindt, H., Kardos, K., Vail, T., Burton, J., Bielska, B., Li, S., Milunic, D., Bourdelle, P. and Vallejo, R. (2001). Detection of analytes by immunoassay using up-converting phosphor technology. Analytical Biochemistry 293, 2230.
Obeng, B. B., Aryeetey, Y. A., de Dood, C. J., Amoah, A. S., Larbi, I. A., Deelder, A. M., Yazdanbakhsh, M., Hartgers, F. C., Boakye, D. A., Verweij, J. J., van Dam, G. J. and van Lieshout, L. (2008). Application of a circulating-cathodic-antigen (CCA) strip test and real-time PCR, in comparison with microscopy, for the detection of Schistosoma haematobium in urine samples from Ghana. Annals of Tropical Medicine and Parasitology 102, 625633.
Polman, K., Diakhate, M. M., Engels, D., Nahimana, S., van Dam, G. J., Ferreira, S. T. M. F., Deelder, A. M. and Gryseels, B. (2000). Specificity of circulating antigen detection for schistosomiasis mansoni in Senegal and Burundi. Tropical Medicine and International Health 5, 534537.
Santos, M. M. A. G., Garcia, T. C., Orsini, M., Disch, J., Katz, N. and Rabello, A. (2000). Oral fluids for the immunodiagnosis of Schistosoma mansoni infection. Transactions of the Royal Society of Tropical Medicine and Hygiene 94, 289292.
Shane, H. L., Verani, J. R., Abudho, B., Montgomery, S. P., Blackstock, A. J., Mwinzi, P. N., Butler, S. E., Karanja, D. M. and Secor, W. E. (2011). Evaluation of urine CCA assays for detection of Schistosoma mansoni infection in Western Kenya. PLOS Neglected Tropical Diseases 5, e951.
Smith, H., Doenhoff, M., Aitken, C., Bailey, W., Ji, M. J., Dawson, E., Gilis, H., Spence, G., Alexander, C. and van Gool, T. (2012). Comparison of Schistosoma mansoni soluble cercarial antigens and soluble egg antigens for serodiagnosing schistosome infections. PLOS Neglected Tropical Diseases 6, e1815.
Standley, C., Lwambo, N., Lange, C., Kariuki, H., Adriko, M. and Stothard, J. (2010). Performance of circulating cathodic antigen (CCA) urine-dipsticks for rapid detection of intestinal schistosomiasis in schoolchildren from shoreline communities of Lake Victoria. Parasites and Vectors 3, 7.
Stothard, J. R., Kabatereine, N. B., Tukahebwa, E. M., Kazibwe, F., Rollinson, D., Mathieson, W., Webster, J. P. and Fenwick, A. (2006). Use of circulating cathodic antigen (CCA) dipsticks for detection of intestinal and urinary schistosomiasis. Acta Tropica 97, 219228.
Tchuem Tchuenté, L. A., Momo, S. C., Stothard, J. R. and Rollinson, D. (2013). Efficacy of praziquantel and reinfection patterns in single and mixed infection foci for intestinal and urogenital schistosomiasis in Cameroon. Acta Tropica 128, 275283.
Tjon Kon Fat, E. M., Abrams, W. R., Niedbala, R. S. and Corstjens, P. L. A. M. (2012). Lateral flow sandwich assay utilizing upconverting phosphor (UCP) reporters. In Laboratory Methods in Cell Biology: Biochemistry and Cell Culture, Vol. 112 (ed. Conn, P. M.), pp. 203234. Methods in Cell Biology. Elsevier, New York, NY, USA.
van Dam, G. J., Bergwerff, A. A., Thomas-Oates, J. E., Rotmans, J. P., Kamerling, J. P., Vliegenthart, J. F. and Deelder, A. M. (1994). The immunologically reactive O-linked polysaccharide chains derived from circulating cathodic antigen isolated from the human blood fluke Schistosoma mansoni have Lewis x as repeating unit. European Journal of Biochemistry 225, 467482.
van Dam, G. J., Bogitsh, B. J., van Zeyl, R. J. M., Rotmans, J. P. and Deelder, A. M. (1996 a). Schistosoma mansoni: in vitro and in vivo excretion of CAA and CCA by developing schistosomula and adult worms. Journal of Parasitology 82, 557564.
van Dam, G. J., Claas, F. H., Yazdanbakhsh, M., Kruize, Y. C., van Keulen, A. C., Ferreira, S. T., Rotmans, J. P. and Deelder, A. M. (1996 b). Schistosoma mansoni excretory circulating cathodic antigen shares Lewis-x epitopes with a human granulocyte surface antigen and evokes host antibodies mediating complement-dependent lysis of granulocytes. Blood 88, 42464251.
van Dam, G. J., Stelma, F. F., Gryseels, B., Falcao Ferreira, S. T., Talla, I., Niang, M., Rotmans, J. P. and Deelder, A. M. (1996 c). Antibody response patterns against Schistosoma mansoni in a recently exposed community in Senegal. Journal of Infectious Diseases 173, 12321241.
van Dam, G. J., Wichers, J. H., Ferreira, T. M. F., Ghati, D., van Amerongen, A. and Deelder, A. M. (2004). Diagnosis of schistosomiasis by reagent strip test for detection of circulating cathodic antigen. Journal of Clinical Microbiology 42, 54585461.
van Dam, G. J., de Dood, C. J., Lewis, M., Deelder, A. M., van Lieshout, L., Tanke, H. J., van Rooyen, L. H. and Corstjens, P. L. (2013). A robust dry reagent lateral flow assay for diagnosis of active schistosomiasis by detection of Schistosoma circulating anodic antigen. Experimental Parasitology 135, 274282.
van Lieshout, L., de Jonge, N., Elmasry, N., Mansour, M. M., Bassily, S., Krijger, F. W. and Deelder, A. M. (1994). Monitoring the efficacy of different doses of praziquantel by quantification of circulating antigens in serum and urine of schistosomiasis patients. Parasitology 108, 519526.
van Lieshout, L., Polderman, A. M., de Vlas, S. J., de Caluwe, P., Krijger, F. W., Gryseels, B. and Deelder, A. M. (1995). Analysis of worm burden variation in human Schistosoma mansoni infections by determination of serum levels of circulating anodic antigen and circulating cathodic antigen. Journal of Infectious Diseases 172, 13361342.
Wang, Z. J., Xue, C. L., Lou, W. X., Zhang, X. Y., Zhang, E. Y., Wu, W. D. and Shen, G. J. (2002). Non-invasive immunodiagnosis of Schistosomiasis japonica: the detection of specific antibodies in saliva. Chinese Medical Journal 115, 14601464.
Webster, B. L., Diaw, O. T., Seye, M. M., Webster, J. P. and Rollinson, D. (2013). Introgressive hybridization of Schistosoma haematobium group species in Senegal: species barrier break down between ruminant and human schistosomes. PLOS Neglected Tropical Diseases 7, e2110.
Whitty, C. J. M., Mabey, D. C., Armstrong, M., Wright, S. G. and Chiodini, P. L. (2000). Presentation and outcome of 1107 cases of schistosomiasis from Africa diagnosed in a non-endemic country. Transactions of the Royal Society of Tropical Medicine and Hygiene 94, 531534.
Wilson, R. A., van Dam, G. J., Kariuki, T. M., Farah, I. O., Deelder, A. M. and Coulson, P. S. (2006). The detection limits for estimates of infection intensity in Schistosomiasis mansoni established by a study in non-human primates. International Journal for Parasitology 36, 12411244.
World Health Organization (2012). Elimination of Schistosomiasis. 65th World Health Assembly, resolution WHA65.21, agenda item 13.11, WHO, Geneva, Switzerland.
Xu, J., Feng, T., Lin, D. D., Wang, Q. Z., Tang, L., Wu, X. H., Guo, J. G., Peeling, R. W. and Zhou, X. N. (2011). Performance of a dipstick dye immunoassay for rapid screening of Schistosoma japonicum infection in areas of low endemicity. Parasites and Vectors 4, 87.
Zarling, D. A., Rossi, M. J., Peppers, N. A., Kane, J., Faris, G. W., Dyer, M. J., Ng, S. Y. and Schneider, L. V. (1997). Up-converting reporters for biological and other assays using laser excitation techniques. United States Patent 5,674,698.
Zijlmans, H. J., Bonnet, J., Burton, J., Kardos, K., Vail, T., Niedbala, R. S. and Tanke, H. J. (1999). Detection of cell and tissue surface antigens using up-converting phosphors: a new reporter technology. Analytical Biochemistry 267, 3036.



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