Although accurate assessment of the prevalence of Schistosoma mansoni is important for the design and evaluation of control programs, the most widely used tools for diagnosis are limited by suboptimal sensitivity, slow turn-around-time, or inability to distinguish current from former infections. Recently, two tests that detect circulating cathodic antigen (CCA) in urine of patients with schistosomiasis became commercially available. As part of a larger study on schistosomiasis prevalence in young children, we evaluated the performance and diagnostic accuracy of these tests—the carbon test strip designed for use in the laboratory and the cassette format test intended for field use. In comparison to 6 Kato-Katz exams, the carbon and cassette CCA tests had sensitivities of 88.4% and 94.2% and specificities of 70.9% and 59.4%, respectively. However, because of the known limitations of the Kato-Katz assay, we also utilized latent class analysis (LCA) incorporating the CCA, Kato-Katz, and schistosome-specific antibody results to determine their sensitivities and specificities. The laboratory-based CCA test had a sensitivity of 91.7% and a specificity of 89.4% by LCA while the cassette test had a sensitivity of 96.3% and a specificity of 74.7%. The intensity of the reaction in both urine CCA tests reflected stool egg burden and their performance was not affected by the presence of soil transmitted helminth infections. Our results suggest that urine-based assays for CCA may be valuable in screening for S. mansoni infections.
References
[1]
Fenwick A, Webster JP, Bosque-Oliva E, Blair L, Fleming FM, et al. (2009) The Schistosomiasis Control Initiative (SCI): rationale, development and implementation from 2002–2008. Parasitology 136: 1719–1730. doi: 10.1017/S0031182009990400
[2]
Knopp S, Rinaldi L, Khamis IS, Stothard JR, Rollinson D, et al. (2009) A single FLOTAC is more sensitive than triplicate Kato-Katz for the diagnosis of low-intensity soil-transmitted helminth infections. Trans R Soc Trop Med Hyg 103: 347–354. doi: 10.1016/j.trstmh.2008.11.013
[3]
Barreto ML, Silva JT, Mott KE, Lehman JS Jr (1978) Stability of faecal egg excretion in Schistosoma mansoni infection. Trans R Soc Trop Med Hyg 72: 181–187. doi: 10.1016/0035-9203(78)90056-1
[4]
Teesdale CH, Fahringer K, Chitsulo L (1985) Egg count variability and sensitivity of a thin smear technique for the diagnosis of Schistosoma mansoni. Trans R Soc Trop Med Hyg 79: 369–373. doi: 10.1016/0035-9203(85)90384-0
[5]
Kongs A, Marks G, Verle P, Van der Stuyft P (2001) The unreliability of the Kato-Katz technique limits its usefulness for evaluating S. mansoni infections. Trop Med Int Health 6: 163–169. doi: 10.1046/j.1365-3156.2001.00687.x
[6]
Cesari IM, Ballen DE, Mendoza L, Matos C (2005) Detection of Schistosoma mansoni membrane antigens by immunoblot analysis of sera of patients from low-transmission areas. Clin Diagn Lab Immunol 12: 280–286. doi: 10.1128/CDLI.12.2.280-286.2005
[7]
Deelder AM, Qian ZL, Kremsner PG, Acosta L, Rabello AL, et al. (1994) Quantitative diagnosis of Schistosoma infections by measurement of circulating antigens in serum and urine. Trop Geogr Med 46: 233–238.
[8]
Barsoum IS, Colley DG, Kamal KA (1990) Schistosoma mansoni: detection of circulating antigens in murine schistosomiasis by antigen-capture sandwich ELISA using a monoclonal antibody. Exp Parasitol 71: 107–113. doi: 10.1016/0014-4894(90)90013-3
[9]
Agnew A, Fulford AJ, De Jonge N, Krijger FW, Rodriguez-Chacon M, et al. (1995) The relationship between worm burden and levels of a circulating antigen (CAA) of five species of Schistosoma in mice. Parasitology 111(Pt 1): 67–76. doi: 10.1017/S0031182000064611
[10]
Polman K, Stelma FF, Gryseels B, Van Dam GJ, Talla I, et al. (1995) Epidemiologic application of circulating antigen detection in a recent Schistosoma mansoni focus in northern Senegal. Am J Trop Med Hyg 53: 152–157.
[11]
van Dam GJ, Wichers JH, Ferreira TM, Ghati D, van Amerongen A, et al. (2004) Diagnosis of schistosomiasis by reagent strip test for detection of circulating cathodic antigen. J Clin Microbiol 42: 5458–5461. doi: 10.1128/JCM.42.12.5458-5461.2004
[12]
Odogwu SE, Ramamurthy NK, Kabatereine NB, Kazibwe F, Tukahebwa E, et al. (2006) Schistosoma mansoni in infants (aged<3 years) along the Ugandan shoreline of Lake Victoria. Ann Trop Med Parasitol 100: 315–326. doi: 10.1179/136485906X105552
[13]
Stothard JR, Kabatereine NB, Tukahebwa EM, Kazibwe F, Rollinson D, et al. (2006) Use of circulating cathodic antigen (CCA) dipsticks for detection of intestinal and urinary schistosomiasis. Acta Tropica 97: 219–228. doi: 10.1016/j.actatropica.2005.11.004
[14]
Karanja DM, Colley DG, Nahlen BL, Ouma JH, Secor WE (1997) Studies on schistosomiasis in western Kenya: I. Evidence for immune-facilitated excretion of schistosome eggs from patients with Schistosoma mansoni and human immunodeficiency virus coinfections. Am J Trop Med Hyg 56: 515–521.
[15]
Black CL, Steinauer ML, Mwinzi PN, Evan Secor W, Karanja DM, et al. (2009) Impact of intense, longitudinal retreatment with praziquantel on cure rates of schistosomiasis mansoni in a cohort of occupationally exposed adults in western Kenya. Trop Med Int Health 14: 450–457. doi: 10.1111/j.1365-3156.2009.02234.x
[16]
Walter SD, Irwig LM (1988) Estimation of test error rates, disease prevalence and relative risk from misclassified data: a review. J Clin Epidemiol 41: 923–937. doi: 10.1016/0895-4356(88)90110-2
[17]
Dawid AP, Skene AM (1979) Maximum Likelihood estimation of observer error-rates using the EM algorithm. Applied Statistics 28: 20–28. doi: 10.2307/2346806
[18]
Rindskopf D, Rindskopf W (1986) The value of latent class analysis in medical diagnosis. Stat Med 5: 21–27. doi: 10.1002/sim.4780050105
[19]
Qu Y, Tan M, Kutner M (1996) Random effects models in latent class analysis for evaluating accuracy of diagnostic tests. Biometrics 52: 797–810. doi: 10.2307/2533043
[20]
Menten J, Boelaert M, Lesaffre E (2008) Bayesian latent class models with conditionally dependent diagnostic tests: a case study. Stat Med 27: 4469–88. doi: 10.1002/sim.3317
[21]
Dendukuri N, Hadgu A, Wang L (2009) Modeling conditional dependence between diagnostic tests: a multiple latent variable model. Stat Med 28: 441–461. doi: 10.1002/sim.3470
[22]
Vacek PM (1985) The effect of conditional dependence on the evaluation of diagnostic tests. Biometrics 41: 959–968. doi: 10.2307/2530967
[23]
Pepe MS, Janes H (2007) Insights into latent class analysis of diagnostic test performance. Biostatistics 8: 474–484. doi: 10.1093/biostatistics/kxl038
[24]
Torrance-Rynard VL, Walter SD (1997) Effects of dependent errors in the assessment of diagnostic test performance. Stat Med 16: 2157–2175. doi: 10.1002/(SICI)1097-0258(19971015)16:19<2157::AID-SIM653>3.0.CO;2-X
[25]
Koukounari A, Webster JP, Donnelly CA, Bray BC, Naples J, et al. (2009) Sensitivities and specificities of diagnostic tests and infection prevalence of Schistosoma haematobium estimated from data on adults in villages northwest of Accra, Ghana. Am J Trop Med Hyg 80: 435–441.
[26]
Carabin H, Balolong E, Joseph L, McGarvey ST, Johansen MV, et al. (2005) Estimating sensitivity and specificity of a faecal examination method for Schistosoma japonicum infection in cats, dogs, water buffaloes, pigs, and rats in Western Samar and Sorsogon Provinces, The Philippines. Int J Parasitol 35: 1517–1524. doi: 10.1016/j.ijpara.2005.06.010
[27]
Booth M, Vounatsou P, N'Goran EK, Tanner M, Utzinger J (2003) The influence of sampling effort and the performance of the Kato-Katz technique in diagnosing Schistosoma mansoni and hookworm co-infections in rural Cote d'Ivoire. Parasitology 127: 525–531. doi: 10.1017/S0031182003004128
[28]
Nandini Dendukuri PBaLJ (2008) BayesLatentClassModels: A program for estimating diagnostic test properties and disease prevalence. 1.3 ed.
[29]
de Vlas SJ, Gryseels B (1992) Underestimation of Schistosoma mansoni prevalences. Parasitol Today 8: 274–277. doi: 10.1016/0169-4758(92)90144-Q
[30]
Hanelt B, Mwangi IN, Kinuthia JM, Maina GM, Agola LE, et al. (2010) Schistosomes of small mammals from the Lake Victoria Basin, Kenya: new species, familiar, and the implications for schistosomiasis control. Parasitology 137: 1109–1118. doi: 10.1017/S0031182010000041
[31]
Stothard JR (2009) Improving control of African schistosomiasis: towards effective use of rapid diagnostic tests within and appropriate disease surveillance model. Trans R Soc Trop Med Hyg 103: 325–332. doi: 10.1016/j.trstmh.2008.12.012
[32]
Standley CJ, Lwambo NJS, Lange CN, Kariuki HC, Adriko M, et al. (2010) Performance of circulating cathodic antigen (CCA) urine-dipsticks for rapid detection of intestinal schistosomiasis in schoolchildren from shoreline communities of Lake Victoria. Parasit Vectors 3: 7. doi: 10.1186/1756-3305-3-7
[33]
van Lieshout L, De Jonge N, Mansour MM, Bassily S, Krijger FW, et al. (1993) Circulating cathodic antigen levels in serum and urine of schistosomiasis patients before and after chemotherapy with praziquantel. Trans R Soc Trop Med Hyg 87: 311–312. doi: 10.1016/0035-9203(93)90142-D
[34]
Standley CJ, Adriko M, Arinaitwe M, Atuhaire A, Kazibwe F, et al. (2010) Epidemiology and control of intestinal schistosomiasis on the Sesse Islands, Uganda: integrating malacology and parasitology to tailor local treatment recommendations. Parasit Vectors 3: 64. doi: 10.1186/1756-3305-3-64
