Mem Inst Oswaldo Cruz, Rio de Janeiro, VOLUME 114 | FEB 2019

Diagnosis of Schistosoma mansoni infections: what are the choices in Brazilian low-endemic areas?

Vanessa Silva-Moraes1,4/+, Lisa M Shollenberger1,5, Liliane Maria Vidal Siqueira1, William Castro-Borges3, Donald A Harn4, Rafaella Fortini Queiroz e Grenfell1,4, Ana Lucia Teles Rabello2, Paulo Marcos Zech Coelho1

1Fundação Oswaldo Cruz-Fiocruz, Instituto René Rachou, Biologia do Schistosoma mansoni e sua interação com o hospedeiro, Belo Horizonte, MG, Brasil
2Fundação Oswaldo Cruz-Fiocruz, Instituto René Rachou, Grupo de Pesquisas Clínicas e Políticas Públicas em Doenças Infecciosas e Parasitárias, Belo Horizonte, MG, Brasil
3Universidade Federal de Ouro Preto, Laboratório de Enzimologia e Proteômica, Ouro Preto, MG, Brasil
4University of Georgia, College of Veterinary Medicine, Department of Infectious Diseases, Athens, GA, United States of America
5Old Dominion University, Department of Biological Sciences, Norfolk, VA, United States of America

DOI: 10.1590/0074-02760180478
169 views 97 downloads

The population of Brazil is currently characterised by many individuals harbouring low-intensity Schistosoma mansoni infections. The Kato-Katz technique is the diagnostic method recommended by the World Health Organization (WHO) to assess these infections, but this method is not sensitive enough in the context of low egg excretion. In this regard, potential alternatives are being employed to overcome the limits of the Kato-Katz technique. In the present review, we evaluated the performance of parasitological and immunological approaches adopted in Brazilian areas. Currently, the diagnostic choices involve a combination of strategies, including the utilisation of antibody methods to screen individuals and then subsequent confirmation of positive cases by intensive parasitological investigations.

Schistosomiasis is one of seventeen neglected tropical diseases (NTDs) listed by the World Health Organization (WHO), and this disease presents a substantial public health and economic burden and is considered a disease of poverty. An estimated 779 million people are at risk of infection, and approximately 252 million people are currently infected.(1, 2) The Global Health Estimates of 2015 attributed 3.51 million disability-adjusted life years (DALYs) and 10.1 million deaths in 2016 to schistosomiasis, which is a mortality figure that has been challenged as a gross underestimate.(3, 4) In the Americas, the only known species of parasite that is associated with intestinal schistosomiasis and continues to be endemic in parts of Brazil, Venezuela, and the Caribbean is Schistosoma mansoni.(5)

Schistosomiasis induces acute, severe, and chronic morbidity among those who are infected. If untreated, it can result in anaemia, splenomegaly, and fibrosis that can cause portal hypertension, esophageal varices, and upper gastrointestinal bleeding; in serious cases, it triggers kidney and neurological complications and death.(6) Three major control strategies have been adopted to combat schistosomiasis, and these include chemotherapy, diagnostics, and improvements in sanitation and hygiene.(7) Since the mid-1980s, the main global strategy to fight schistosomiasis has been treatment with praziquantel (PZQ).(8) PZQ treatment in general has reduced the high levels of prevalence and intensity of infection so that control programs are able to manage morbidity. After decades of extensive PZQ use, however, low-intensity infections exhibiting high re-infection rates remain and transmission persists.(9, 10)

The failure of PZQ to eliminate schistosomiasis has placed new emphasis on the role of diagnostics in the control of schistosomiasis. The plan for 2020 that focuses on “elimination of disease as a public health problem” also now emphasises attainable strategies for accurately diagnosing low-intensity infections.(11, 12, 13) As a result of intensive control strategies, many previously high-endemic areas are now considered low-endemic areas. They are characterised by < 10% prevalence, and the majority of infected individuals harbour low-intensity infections (number of eggs per gram of faeces (EPG) is < 100).(9, 14, 15) Detection of schistosome eggs in stools by microscopic examination using the Kato-Katz technique (K-K) is the recommended method by the WHO for diagnosing an active infection. K-K, however, possesses poor sensitivity for low-intensity infections and therefore cannot be currently considered the gold standard.(16, 17) Improvements in the diagnostic field are strongly supported by control programs in Brazil, which is a low-endemic country where PZQ mass drug administration (MDA) is only indicated in localities with egg-positivity above 25% and the main control strategy focuses on strengthening diagnoses and treatment of infected individuals at the primary care level.(5, 18, 19, 20)

Over the past 40 years, Brazil has developed an extensive history regarding the fight against schistosomiasis. Integrated control measures, such as investments in basic sanitation and hygiene, improvement in the population’s income levels and quality of life, and chemotherapy have yielded considerable success in terms of reducing the prevalence, transmission, and morbidity.(15) The number of severe clinical cases and deaths has decreased significantly.(21) Currently, Brazil has chronic patients living in endemic areas, as well as acute cases derived from migration of populations due to urbanisation and rural tourism.(18, 22, 23, 24, 25, 26, 27, 28, 29) Low parasite loads are persistent among most individuals from endemic areas as a result of consecutive rounds of treatment and frequent exposure to the infective agent.(18, 30) Further, low-intensity infections may occur upon a single exposure to the infective agent, such as exposure during tourism to transmission areas and movement of residents from endemic areas to urban centres.(27, 28, 29)

The prevalence in Brazil was estimated at 1% by the National Schistosomiasis and Soil-transmitted Helminth Infection Survey (INPEG) conducted between 2010 and 2015.(15) When comparing the two last surveys, a large reduction in prevalence was observed, (10.09% between 1949 and 1953 and 9.24% between 1975 and 1979);(15) however, infection persists, and the lack of a diagnostic method that is compatible with the epidemiological scenario presents a concern.(13, 15, 17) Although K-K is affordable and suitable for low-income areas, its sensitivity decreases dramatically in the current conditions of low egg excretion, and it is not as efficient for determining disease prevalence as it was in the past when medium and high parasite loads (> 100 EPG) were predominant.(26) Infected individuals who are not diagnosed correctly and do not receive the proper treatment remain infected and contribute to the maintenance of transmission and the establishment of a new focus.(18, 31, 32)

The INPEG was the major survey that covered all states within the federation of Brazil. A total of 197,564 school-age individuals (7-17 years old) were evaluated in 27 states by an analysis of parasitological method (two K-K slides). Studies in Brazilian areas, however, have recently demonstrated that disease prevalence has been underestimated by a factor of between two and four, likely due to the inability of the K-K to detect low-intensity infections.(18, 32, 33) This failure to determine the accurate disease prevalence led to shortcomings in decisions made during national control programs, and this elevated prevalence remains a major challenge for disease elimination.(26) Given this, the question arises as to whether the low prevalence rate observed indicates that Brazil is moving toward elimination, or whether Brazil is simply underestimating prevalence because of the use of a method that is not sensitive enough to detect low-intensity infections. If the goal of elimination is a priority for the WHO, new and more sensitive methods must be utilised to achieve this purpose.

Significant progress has been made in regard to development of more sensitive tests. Diagnoses using antibodies,(24) antigens,(34) and DNA(18, 35) have been evaluated. These techniques have exhibited high sensitivity, however, their reduced specificity in comparison to microscopy-based methods make them inadequate as single-use tests.(33, 36) Because of the high specificity of egg-based techniques for detecting active infections, new sensitive parasitological methods have been developed, including the saline gradient (SG)(37) and Helmintex (HX).(38) Improvements have also been made to the conventional protocol of K-K, and these include increasing the number of samples and the number of slides to be evaluated.(18, 31, 39)

As an alternative to time-consuming parasitological methods, a rapid diagnostic test (RDT) based on the detection of active parasite-secreted antigen in urine was also developed. The point-of-care circulating cathodic antigen test (POC-CCA®) has been commercially available since 2008, and owing to its higher sensitivity than K-K, it has been suggested as a suitable substitute for K-K in S. mansoni prevalence mapping.(40, 41, 42, 43, 44, 45) The majority of studies validating POC-CCA®, however, were conducted in Africa using K-K as a reference method.(45) As K-K is not sensitive enough to detect low-intensity infections and cannot be considered the gold standard for evaluation of new methods, POC-CCA® performance in low-endemic areas remains to be validated before it is released for general use.(46) Only 10 studies were conducted in Brazil, which has a significantly different prevalence and morbidity profile, and these tests yielded controversial results regarding sensitivity and specificity.(25, 26, 33, 36, 39, 47, 48, 49, 50, 51)

As human schistosomiasis is becoming more of a low-endemic area disease, and the WHO-recommended method K-K has low efficiency for accurately detecting low-intensity infections, certain strategies have been adopted to overcome the current limitations. We review here some strategies that are applied in Brazil, which is a low-endemic country with hard-to-detect individuals targeted to achieve elimination. Our approach focuses on laboratory and field-based parasitological and immunological assays that can be summarised in three steps. The first is improvement of parasitological methods (increased number of samples or K-K slides and addition of other more sensitive egg-based assays), the second is antibody-based detection as an auxiliary tool to parasitological investigations (acute diagnostic and preliminary screening in endemic areas), and the third is antigen-based RDT POC-CCA® as a possible candidate to be part of the control. These methods have been used alone or in combination and have been accepted because of their easy application and accessible costs.

It is important to emphasise that molecular techniques have also been applied in addition to parasitological and immunological methods in Brazilian endemic areas with significant performance.(18, 35, 52, 53, 54, 55) They have been described as a complementary tool for parasitological methods for detecting low burden individuals and during assessment of cure after treatment.(18, 52, 56) Polymerase chain reaction (PCR)-based detection of parasite DNA in stools or urine is more sensitive than parasitological methods and has been employed increasingly for diagnosis in high-resource settings;(57) however, the infrastructure needed and the costs of reagents and equipment remain relatively high, which limits its use in low-resource settings such as Brazil. Some authors have estimated the costs as US $6 and US $8 for conventional and real-time PCR, respectively,(14) and US $17 for PCR-enzyme-linked immunosorbent assay (PCR-ELISA).(53)





01. Disease GBD, Injury I, Prevalence C. Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet. 2016; 388(10053): 1545-602.
02. Hotez PJ, Alvarado M, Basanez MG, Bolliger I, Bourne R, Boussinesq M, et al. The global burden of disease study 2010: interpretation and implications for the neglected tropical diseases. PLoS Negl Trop Dis. 2014; 8(7): e2865.
03. WHO - World Health Organization. Global health estimates 2015: disease burden by cause, age, sex, by country and by region, 2000-2015. 2016. Available from:
04. GBD 2016 Causes of Death Collaborators. Global, regional, and national age-sex specific mortality for 264 causes of death, 1980-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet. 2017; 390(10100): 1151-210.
05. WHO/PAHO - World Health Organization/Pan American Health Organization. Neglected infectious diseases in the Americas: success stories and innovation to reach the neediest. 2016. Available from:
06. Colley DG, Bustinduy AL, Secor WE, King CH. Human schistosomiasis. Lancet. 2014; 383(9936): 2253-64.
07. Savioli L, Fenwick A, Rollinson D, Albonico M, Ame SM. An achievable goal: control and elimination of schistosomiasis. Lancet. 2015; 386(9995): 739.
08. WHO - World Health Organization. Schistosomiasis: number of people treated worldwide in 2016. Wkly Epidemiol Rec. 2017; 92: 749-60.
09. Knopp S, Becker SL, Ingram KJ, Keiser J, Utzinger J. Diagnosis and treatment of schistosomiasis in children in the era of intensified control. Expert Rev Anti Infect Ther. 2013; 11(11): 1237-58.
10. Webster JP, Molyneux DH, Hotez PJ, Fenwick A. The contribution of mass drug administration to global health: past, present and future. Philos Trans R Soc Lond B Biol Sci. 2014; 369(1645): 20130434.
11. WHO - World Health Organization. Accelerating work to overcome the global impact of neglected tropical diseases. A roadmap for implementation. 2012. Available from:
12. NTDs UtC. London declaration on neglected tropical diseases. 2012. Available from:
13. WHO - World Health Organization. WHA65.21. Elimination of schistosomiasis. Sixty-fifth World Health Assembly; 21-26 May, 2012; Geneva: WHO; 2012. p. 36-7.
14. Cavalcanti MG, Silva LF, Peralta RH, Barreto MG, Peralta JM. Schistosomiasis in areas of low endemicity: a new era in diagnosis. Trends Parasitol. 2013; 29(2): 75-82.
15. Katz N. Inquérito nacional de prevalência da esquistossomose mansoni e geo-helmintoses (2010-2015). Belo Horizonte: Instituto René Rachou (Fiocruz); 2018 March, 2018. Contract No.: k197.
16. Katz N, Chaves A, Pellegrino J. A simple device for quantitative stool thick-smear technique in schistosomiasis mansoni. Rev Inst Med Trop Sao Paulo. 1972; 14(6): 397-400.
17. WHO/PAHO - World Health Organization/Pan American Health Organization. Schistosomiasis regional meeting. Defining a road map toward verification of elimination of schistosomiasis transmission in Latin America and the Caribbean by 2020. 2014. Available from:
18. Siqueira LMV, Gomes LI, Oliveira E, de Oliveira ER, de Oliveira AA, Enk MJ, et al. Evaluation of parasitological and molecular techniques for the diagnosis and assessment of cure of schistosomiasis mansoni in a low transmission area. Mem Inst Oswaldo Cruz. 2015; 110(2): 209-14.
19. Favre TC, Pereira AP, Beck LC, Galvao AF, Pieri OS. School-based and community-based actions for scaling-up diagnosis and treatment of schistosomiasis toward its elimination in an endemic area of Brazil. Acta Trop. 2015; 149: 155-62.
20. Favre TC. Directives for schistosomiasis control in endemic areas of Brazil. 2012. Available from:
21. Sarvel AK, Oliveira AA, Silva AR, Lima AC, Katz N. Evaluation of a 25-year-program for the control of schistosomiasis mansoni in an endemic area in Brazil. PLoS Negl Trop Dis. 2011; 5(3): e990.
22. Enk MJ, Lima ACL, Barros HS, Massara CL, Coelho PMZ, Schall VT. Factors related to transmission of and infection with Schistosoma mansoni in a village in the South-eastern Region of Brazil. Mem Inst Oswaldo Cruz. 2010; 105(4): 570-7.
23. Grenfell RF, Martins W, Drummond SC, Antunes CM, Voieta I, Otoni A, et al. Acute schistosomiasis diagnosis: a new tool for the diagnosis of schistosomiasis in a group of travelers recently infected in a new focus of Schistosoma mansoni. Rev Soc Bras Med Trop. 2013; 46(2): 208-13.
24. Grenfell RFQ, Martins W, Enk M, Almeida A, Siqueira L, Silva-Moraes V, et al. Schistosoma mansoni in a low-prevalence area in Brazil: the importance of additional methods for the diagnosis of hard-to-detect individual carriers by low-cost immunological assays. Mem Inst Oswaldo Cruz. 2013; 108(3): 328-34.
25. Coelho PM, Siqueira LM, Grenfell RF, Almeida NB, Katz N, Almeida A, et al. Improvement of POC-CCA interpretation by using lyophilization of urine from patients with Schistosoma mansoni low worm burden: towards an elimination of doubts about the concept of trace. PLoS Negl Trop Dis. 2016; 10(6): e0004778.
26. Grenfell RFQ, Taboada D, Coutinho LA, Pedrosa MLC, Assis JV, Oliveira MSP, et al. Innovative methodology for point-of-care circulating cathodic antigen with rapid urine concentration for use in the field for detecting low Schistosoma mansoni infection and for control of cure with high accuracy. Trans R Soc Trop Med Hyg. 2018; 112(1): 1-7.
27. Enk MJ, Amaral GL, Costa e Silva MF, Silveira-Lemos D, Teixeira-Carvalho A, Martins-Filho OA, et al. Rural tourism: a risk factor for schistosomiasis transmission in Brazil. Mem Inst Oswaldo Cruz. 2010; 105(4): 537-40.
28. Blanton RE, Barbosa LM, Reis EA, Carmo TM, dos Santos CR, Costa JM, et al. The relative contribution of immigration or local increase for persistence of urban schistosomiasis in Salvador, Bahia, Brazil. PLoS Negl Trop Dis. 2015; 9(3): e0003521.
29. Lambertucci JR, Drummond SC, Voieta I, de Queiroz LC, Pereira PP, Chaves BA, et al. An outbreak of acute Schistosoma mansoni schistosomiasis in a nonendemic area of Brazil: a report on 50 cases, including 5 with severe clinical manifestations. Clin Infect Dis. 2013; 57(1): e1-6.
30. Gazzinelli G, Viana IR, Bahia-Oliveira LM, Silveira AM, Queiroz CC, Carvalho OS, et al. Immunological profiles of patients from endemic areas infected with Schistosoma mansoni. Mem Inst Oswaldo Cruz. 1992; 87(Suppl. 4): 139-42.
31. Siqueira LMV, Coelho PMZ, de Oliveira AA, Massara CL, Carneiro NFF, Lima ACL, et al. Evaluation of two coproscopic techniques for the diagnosis of schistosomiasis in a low-transmission area in the state of Minas Gerais, Brazil. Mem Inst Oswaldo Cruz. 2011; 106(7): 844-50.
32. Enk MJ, Lima AC, Drummond SC, Schall VT, Coelho PM. The effect of the number of stool samples on the observed prevalence and the infection intensity with Schistosoma mansoni among a population in an area of low transmission. Acta Trop. 2008; 108(2-3): 222-8.
33. Oliveira WJ, Magalhaes FDC, Elias AMS, de Castro VN, Favero V, Lindholz CG, et al. Evaluation of diagnostic methods for the detection of intestinal schistosomiasis in endemic areas with low parasite loads: saline gradient, Helmintex, Kato-Katz and rapid urine test. PLoS Negl Trop Dis. 2018; 12(2): e0006232.
34. Grenfell RF, Coelho PM, Taboada D, de Mattos AC, Davis R, Harn DA. Newly established monoclonal antibody diagnostic assays for Schistosoma mansoni direct detection in areas of low endemicity. PLoS One. 2014; 9(1): e87777.
35. Espirito-Santo MC, Alvarado-Mora MV, Pinto PL, Sanchez MC, Dias-Neto E, Castilho VL, et al. Comparative study of the accuracy of different techniques for the laboratory diagnosis of schistosomiasis mansoni in areas of low endemicity in Barra Mansa city, Rio de Janeiro state, Brazil. Biomed Res Int. 2015; 2015: 135689.
36. Lindholz CG, Favero V, Verissimo CM, Candido RRF, de Souza RP, dos Santos RR, et al. Study of diagnostic accuracy of Helmintex, Kato-Katz, and POC-CCA methods for diagnosing intestinal schistosomiasis in Candeal, a low intensity transmission area in northeastern Brazil. PLoS Negl Trop Dis. 2018; 12(3): e0006274.
37. Coelho PMZ, Jurberg AD, Oliveira AA, Katz N. Use of a saline gradient for the diagnosis of schistosomiasis. Mem Inst Oswaldo Cruz. 2009; 104(5): 720-3.
38. Teixeira CF, Neuhauss E, Ben R, Romanzini J, Graeff-Teixeira C. Detection of Schistosoma mansoni eggs in feces through their interaction with paramagnetic beads in a magnetic field. PLoS Negl Trop Dis. 2007; 1(2): e73.
39. Siqueira LM, Couto FF, Taboada D, Oliveira AA, Carneiro NF, Oliveira E, et al. Performance of POC-CCA (R) in diagnosis of schistosomiasis mansoni in individuals with low parasite burden. Rev Soc Bras Med Trop. 2016; 49(3): 341-7.
40. van Dam GJ, Wichers JH, Ferreira TM, Ghati D, van Amerongen A, Deelder AM. Diagnosis of schistosomiasis by reagent strip test for detection of circulating cathodic antigen. J Clin Microbiol. 2004; 42(12): 5458-61.
41. Colley DG, Binder S, Campbell C, King CH, Tchuente LAT, N’Goran EK, et al. A five-country evaluation of a point-of-care circulating cathodic antigen urine assay for the prevalence of Schistosoma mansoni. Am J Trop Med Hyg. 2013; 88(3): 426-32.
42. Tchuente LAT, Fouodo CJK, Ngassam RIK, Sumo L, Noumedem CD, Kenfack CM, et al. Evaluation of circulating cathodic antigen (CCA) urine-tests for diagnosis of Schistosoma mansoni infection in Cameroon. PLoS Negl Trop Dis. 2012; 6(7): e1758.
43. Shane HL, Verani JR, Abudho B, Montgomery SP, Blackstock AJ, Mwinzi PN, et al. Evaluation of urine CCA assays for detection of Schistosoma mansoni infection in Western Kenya. PLoS Negl Trop Dis. 2011; 5(1): e951.
44. Coulibaly JT, Knopp S, N’Guessan NA, Silue KD, Furst T, Lohourignon LK, et al. Accuracy of urine circulating cathodic antigen (CCA) test for Schistosoma mansoni diagnosis in different settings of Cote d’Ivoire. PLoS Negl Trop Dis. 2011; 5(11): e1384.
45. Kittur N, Castleman JD, Campbell Jr CH, King CH, Colley DG. Comparison of Schistosoma mansoni Prevalence and intensity of infection, as determined by the circulating cathodic antigen urine assay or by the Kato-Katz fecal assay: a systematic Review. Am J Trop Med Hyg. 2016; 94(3): 605-10.
46. Peralta JM, Cavalcanti MG. Is POC-CCA a truly reliable test for schistosomiasis diagnosis in low endemic areas? The trace results controversy. PLoS Negl Trop Dis. 2018; 12(11): e0006813.
47. Silveira AM, Costa EG, Ray D, Suzuki BM, Hsieh MH, Fraga LA, et al. Evaluation of the CCA immuno-chromatographic test to diagnose Schistosoma mansoni in Minas Gerais state, Brazil. PLoS Negl Trop Dis. 2016; 10(1): e0004357.
48. Ferreira FT, Fidelis TA, Pereira TA, Otoni A, Queiroz LC, Amancio FF, et al. Sensitivity and specificity of the circulating cathodic antigen rapid urine test in the diagnosis of schistosomiasis mansoni infection and evaluation of morbidity in a low- endemic area in Brazil. Rev Soc Bras Med Trop. 2017; 50(3): 358-64.
49. Bezerra FSM, Leal JKF, Sousa MS, Pinheiro MCC, Ramos Jr AN, Silva-Moraes V, et al. Evaluating a point-of-care circulating cathodic antigen test (POC-CCA) to detect Schistosoma mansoni infections in a low endemic area in north-eastern Brazil. Acta Trop. 2018; 182: 264-70.
50. Silva JDDF, Pinheiro MCC, Sousa MS, Gomes VDS, Castro IMN, Ramos ANJ, et al. Detection of schistosomiasis in an area directly affected by the Sao Francisco River large-scale water transposition project in the northeast of Brazil. Rev Soc Bras Med Trop. 2017; 50(5): 658-65.
51. Marinho CC, Groberio AC, Silva C, Lima TLF, Santos RCD, Araujo LG, et al. Morbidity of schistosomiasis mansoni in a low endemic setting in Ouro Preto, Minas Gerais, Brazil. Rev Soc Bras Med Trop. 2017; 50(6): 805-11.
52. Enk MJ, Oliveira e Silva G, Rodrigues NB. Diagnostic accuracy and applicability of a PCR system for the detection of Schistosoma mansoni DNA in human urine samples from an endemic area. PLoS One. 2012; 7(6): e38947.
53. Gomes LI, Marques LHS, Enk MJ, de Oliveira MC, Coelho PM, Rabello A. Development and evaluation of a sensitive PCR-ELISA system for detection of schistosoma infection in feces. PLoS Negl Trop Dis. 2010; 4(4): e664.
54. Carneiro TR, Peralta RHS, Pinheiro MCC, de Oliveira SM, Peralta JM, Bezerra FSM. A conventional polymerase chain reaction-based method for the diagnosis of human schistosomiasis in stool samples from individuals in a low-endemicity area. Mem Inst Oswaldo Cruz. 2013; 108(8): 1037-44.
55. Oliveira LM, Santos HL, Goncalves MM, Barreto MG, Peralta JM. Evaluation of polymerase chain reaction as an additional tool for the diagnosis of low-intensity Schistosoma mansoni infection. Diagn Microbiol Infect Dis. 2010; 68(4): 416-21.
56. Senra C, Gomes LI, Siqueira LMV, Coelho PMZ, Rabello A, Oliveira E. Development of a laboratorial platform for diagnosis of schistosomiasis mansoni by PCR-ELISA. BMC Res Notes. 2018; 11(1): 455.
57. Meurs L, Brienen E, Mbow M, Ochola EA, Mboup S, Karanja DM, et al. Is PCR the next reference standard for the diagnosis of Schistosoma in stool? A comparison with microscopy in Senegal and Kenya. PLoS Negl Trop Dis. 2015; 9(7): e0003959.
58. Solomon AW, Engels D, Bailey RL, Blake IM, Brooker S, Chen JX, et al. A diagnostics platform for the integrated mapping, monitoring, and surveillance of neglected tropical diseases: rationale and target product profiles. PLoS Negl Trop Dis. 2012; 6(7): e1746.
59. Lim MD, Brooker SJ, Belizario Jr VY, Gay-Andrieu F, Gilleard J, Levecke B, et al. Diagnostic tools for soil-transmitted helminths control and elimination programs: a pathway for diagnostic product development. PLoS Negl Trop Dis. 2018; 12(3): e0006213.
60. Rabello AL, Rocha RS, de Oliveira JP, Katz N, Lambertucci JR. Stool examination and rectal biopsy in the diagnosis and evaluation of therapy of schistosomiasis mansoni. Rev Inst Med Trop Sao Paulo. 1992; 34(6): 601-8.
61. Pinheiro MCC, Carneiro TR, Hanemann ALP, de Oliveira SM, Bezerra FSM. The combination of three faecal parasitological methods to improve the diagnosis of schistosomiasis mansoni in a low endemic setting in the state of Ceará, Brazil. Mem Inst Oswaldo Cruz. 2012; 107(7): 873-6.
62. Gomes JF, Hoshino-Shimizu S, Dias LC, Araujo AJ, Castilho VL, Neves FA. Evaluation of a novel kit (TF-Test) for the diagnosis of intestinal parasitic infections. J Clin Lab Anal. 2004; 18(2): 132-8.
63. Carvalho JB, Santos BM, Gomes JF, Suzuki CT, Shimizu SH, Falcao AX, et al. TF-test modified: new diagnostic tool for human enteroparasitosis. J Clin Lab Anal. 2016; 30(4): 293-300.
64. Nacife M, Siqueira LMV, Martins R, Vianna VN, Barbosa KF, Masioli CZ, et al. Prevalence of schistosomiasis mansoni in indigenous Maxakali villages, Minas Gerais, Brazil. Rev Inst Med Trop Sao Paulo. 2018; 60: e26.
65. Caldeira K, Teixeira CF, da Silveira MB, de Fries LCC, Romanzini J, Bittencourt HR, et al. Comparison of the Kato-Katz and Helmintex methods for the diagnosis of schistosomiasis in a low-intensity transmission focus in Bandeirantes, Paraná, southern Brazil. Mem Inst Oswaldo Cruz. 2012; 107(5): 690-2.
66. Favero V, Candido RRF, De Marco Verissimo C, Jones MK, St Pierre TG, Lindholz CG, et al. Optimization of the Helmintex method for schistosomiasis diagnosis. Exp Parasitol. 2017; 177: 28-34.
67. Collaborators GS. Measuring the health-related sustainable development goals in 188 countries: a baseline analysis from the Global Burden of Disease Study 2015. Lancet. 2016; 388(10053): 1813-50.
68. Grenfell R, Harn DA, Tundup S, Da’dara A, Siqueira L, Coelho PM. New approaches with different types of circulating cathodic antigen for the diagnosis of patients with low Schistosoma mansoni load. PLoS Negl Trop Dis. 2013; 7(2): e2054.
69. Colley DG. Morbidity control of schistosomiasis by mass drug administration: how can we do it best and what will it take to move on to elimination? Trop Med Health. 2014; 42(Suppl. 2): 25-32.
70. Doenhoff MJ, Chiodini PL, Hamilton JV. Specific and sensitive diagnosis of schistosome infection: can it be done with antibodies? Trends Parasitol. 2004; 20(1): 35-9.
71. Grenfell RF, Silva-Moraes V, Taboada D, de Mattos AC, de Castro AK, Coelho PM. Immunodiagnostic methods: what is their role in areas of low endemicity? ScientificWorldJournal. 2012; 2012: 593947.
72. Gomes LI, Enk MJ, Rabello A. Diagnosing schistosomiasis: where are we? Rev Soc Bras Med Trop. 2014; 47(1): 3-11.
73. Carneiro TR, Pinheiro MC, de Oliveira SM, Hanemann AL, Queiroz JA, Bezerra FS. Increased detection of schistosomiasis with Kato-Katz and SWAP-IgG-ELISA in a northeastern Brazil low-intensity transmission area. Rev Soc Bras Med Trop. 2012; 45(4): 510-3.
74. Lambertucci JR. Acute schistosomiasis mansoni: revisited and reconsidered. Mem Inst Oswaldo Cruz. 2010; 105(4): 422-35.
75. Enk MJ, Katz N, Coelho PMZ. A case of Schistosoma mansoni infection treated during the prepatent period. Nat Clin Pract Gastroenterol Hepatol. 2008; 5(2): 112-5.
76. Murta FLG, Massara CL, Nogueira JFC, Carvalho OS, de Mendonça CLF, Pinheiro VAO, et al. Ecotourism as a source of infection with Schistosoma mansoni in Minas Gerais, Brazil. Trop Dis Travel Med Vaccines. 2016; 2: 3.
77. Rabello A. Acute human schistosomiasis mansoni. Mem Inst Oswaldo Cruz. 1995; 90(2): 277-80.
78. Beck L, Van-Lume DS, Souza JR, Domingues AL, Favre T, Abath FG, et al. Discriminating acute from chronic human schistosomiasis mansoni. Acta Trop. 2008; 108(2-3): 229-33.
79. Valli LC, Kanamura HY, da Silva RM, Silva MI, Vellosa SA, Garcia ET. Efficacy of an enzyme-linked immunosorbent assay in the diagnosis of and serologic distinction between acute and chronic Schistosoma mansoni infection. Am J Trop Med Hyg. 1997; 57(3): 358-62.
80. Vendrame CM, Carvalho MD, Yamamoto CR, Nakhle MC, Carvalho SA, Chieffi PP. Evaluation of anti-Schistosoma mansoni IgG antibodies in patients with chronic schistosomiasis mansoni before and after specific treatment. Rev Inst Med Trop Sao Paulo. 2001; 43(3): 153-9.
81. Bergquist NR. Schistosomiasis: from risk assessment to control. Trends Parasitol. 2002; 18(7): 309-14.
82. Oliveira RR, Figueiredo JP, Cardoso LS, Jabar RL, Souza RP, Wells MT, et al. Factors associated with resistance to Schistosoma mansoni infection in an endemic area of Bahia, Brazil. Am J Trop Med Hyg. 2012; 86(2): 296-305.
83. de Oliveira EJ, Kanamura HY, Takei K, Hirata RDC, Nguyen NY, Hirata MH. Application of synthetic peptides in development of a serologic method for laboratory diagnosis of schistosomiasis mansoni. Mem Inst Oswaldo Cruz. 2006; 101(Suppl. 1): 355-7.
84. de Oliveira EJ, Kanamura HY, Takei K, Hirata RD, Valli LC, Nguyen NY, et al. Synthetic peptides as an antigenic base in an ELISA for laboratory diagnosis of schistosomiasis mansoni. Trans R Soc Trop Med Hyg. 2008; 102(4): 360-6.
85. Carvalho GBF, Resende DM, Siqueira LMV, Lopes MD, Lopes DO, Coelho PMZ, et al. Selecting targets for the diagnosis of Schistosoma mansoni infection: an integrative approach using multi-omic and immunoinformatics data. PLoS One. 2017; 12(8): e0182299.
86. Carvalho GB, Pacifico LG, Pimenta DL, Siqueira LM, Teixeira-Carvalho A, Coelho PM, et al. Evaluation of the use of C-terminal part of the Schistosoma mansoni 200kDa tegumental protein in schistosomiasis diagnosis and vaccine formulation. Exp Parasitol. 2014; 139: 24-32.
87. Goncalves MM, Barreto MG, Peralta RH, Gargioni C, Goncalves T, Igreja RP, et al. Immunoassays as an auxiliary tool for the serodiagnosis of Schistosoma mansoni infection in individuals with low intensity of egg elimination. Acta Trop. 2006; 100(1-2): 24-30.
88. Igreja RP, Matos JA, Goncalves MM, Barreto MM, Peralta JM. Schistosoma mansoni-related morbidity in a low-prevalence area of Brazil: a comparison between egg excretors and seropositive non-excretors. Ann Trop Med Parasitol. 2007; 101(7): 575-84.
89. da Frota SM, Carneiro TR, Queiroz JA, Alencar LM, Heukelbach J, Bezerra FS. Combination of Kato-Katz faecal examinations and ELISA to improve accuracy of diagnosis of intestinal schistosomiasis in a low-endemic setting in Brazil. Acta Trop. 2011; 120(Suppl. 1): S138-41.
90. de Oliveira EJ, Kanamura HY, Lima DMC. Efficacy of an enzyme-linked immunosorbent assay as a diagnostic tool for schistosomiasis mansoni in individuals with low worm burden. Mem Inst Oswaldo Cruz. 2005; 100(4): 421-5.
91. Hinz R, Schwarz NG, Hahn A, Frickmann H. Serological approaches for the diagnosis of schistosomiasis - A review. Mol Cell Probes. 2017; 31: 2-21.
92. Makarova E, Goes TS, Marcatto AL, Leite MF, Goes AM. Serological differentiation of acute and chronic schistosomiasis using Schistosoma mansoni recombinant protein RP26. Parasitol Int. 2003; 52(4): 269-79.
93. Clements MN, Corstjens P, Binder S, Campbell Jr CH, de Dood CJ, Fenwick A, et al. Latent class analysis to evaluate performance of point-of-care CCA for low-intensity Schistosoma mansoni infections in Burundi. Parasit Vectors. 2018; 11(1): 111.
94. Bergquist R, Johansen MV, Utzinger J. Diagnostic dilemmas in helminthology: what tools to use and when? Trends Parasitol. 2009; 25(4): 151-6.
95. Utzinger J, Becker SL, van Lieshout L, van Dam GJ, Knopp S. New diagnostic tools in schistosomiasis. Clin Microbiol Infect. 2015; 21(6): 529-42.
96. Corstjens PL, De Dood CJ, Kornelis D, Fat EM, Wilson RA, Kariuki TM, et al. Tools for diagnosis, monitoring and screening of Schistosoma infections utilizing lateral-flow based assays and upconverting phosphor labels. Parasitology. 2014; 141(14): 1841-55.
97. van Dam GJ, Bogitsh BJ, van Zeyl RJ, Rotmans JP, Deelder AM. Schistosoma mansoni: in vitro and in vivo excretion of CAA and CCA by developing schistosomula and adult worms. J Parasitol. 1996; 82(4): 557-64.
98. van Lieshout L, De Jonge N, Mansour MM, Bassily S, Krijger FW, Deelder AM. Circulating cathodic antigen levels in serum and urine of schistosomiasis patients before and after chemotherapy with praziquantel. Trans R Soc Trop Med Hyg. 1993; 87(3): 311-2.
99. Deelder AM, Qian ZL, Kremsner PG, Acosta L, Rabello AL, Enyong P, et al. Quantitative diagnosis of Schistosoma infections by measurement of circulating antigens in serum and urine. Trop Geogr Med. 1994; 46(4 Spec No): 233-8.
100. Corstjens PL, van Lieshout L, Zuiderwijk M, Kornelis D, Tanke HJ, Deelder AM, et al. Up-converting phosphor technology-based lateral flow assay for detection of Schistosoma circulating anodic antigen in serum. J Clin Microbiol. 2008; 46(1): 171-6.
101. Corstjens P, Hoekstra PT, de Dood CJ, van Dam GJ. Utilizing the ultrasensitive Schistosoma up-converting phosphor lateral flow circulating anodic antigen (UCP-LF CAA) assay for sample pooling-strategies. Infect Dis Poverty. 2017; 6(1): 155.
102. Sousa MS. Up-converting phosphor-lateral flow, Kato-Katz e POC-CCA: uma análise comparativa no diagnóstico da infecção por Schistosoma mansoni em uma área de baixa endemicidade Ceará, Brazil. Fortaleza: Universidade Federal do Ceará; 2015.
103. Corstjens PL, Nyakundi RK, de Dood CJ, Kariuki TM, Ochola EA, Karanja DM, et al. Improved sensitivity of the urine CAA lateral-flow assay for diagnosing active Schistosoma infections by using larger sample volumes. Parasit Vectors. 2015; 8: 241.
104. van Grootveld R, van Dam GJ, de Dood C, de Vries JJC, Visser LG, Corstjens P, et al. Improved diagnosis of active Schistosoma infection in travellers and migrants using the ultra-sensitive in-house lateral flow test for detection of circulating anodic antigen (CAA) in serum. Eur J Clin Microbiol Infect Dis. 2018; 37(9): 1709-16.
105. Colley DG, Andros TS, Campbell Jr CH. Schistosomiasis is more prevalent than previously thought: what does it mean for public health goals, policies, strategies, guidelines and intervention programs? Infect Dis Poverty. 2017; 6(1): 63.
106. Mwinzi PN, Kittur N, Ochola E, Cooper PJ, Campbell Jr CH, King CH, et al. Additional evaluation of the point-of-contact circulating cathodic antigen assay for Schistosoma mansoni infection. Front Public Health. 2015; 3: 48.
107. Lamberton PH, Kabatereine NB, Oguttu DW, Fenwick A, Webster JP. Sensitivity and specificity of multiple Kato-Katz thick smears and a circulating cathodic antigen test for Schistosoma mansoni diagnosis pre- and post-repeated-praziquantel treatment. PLoS Negl Trop Dis. 2014; 8(9): e3139.
108. Adriko M, Standley CJ, Tinkitina B, Tukahebwa EM, Fenwick A, Fleming FM, et al. Evaluation of circulating cathodic antigen (CCA) urine-cassette assay as a survey tool for Schistosoma mansoni in different transmission settings within Bugiri District, Uganda. Acta Trop. 2014; 136: 50-7.
109. Ortu G, Ndayishimiye O, Clements M, Kayugi D, Campbell CH, Lamine MS, et al. Countrywide reassessment of Schistosoma mansoni infection in Burundi using a urine-circulating cathodic antigen rapid test: informing the National Control Program. Am J Trop Med Hyg. 2017; 96(3): 664-73.
110. Sousa-Figueiredo JC, Stanton MC, Katokele S, Arinaitwe M, Adriko M, Balfour L, et al. Mapping of schistosomiasis and soil-transmitted helminths in Namibia: the first large-scale protocol to formally include rapid diagnostic tests. PLoS Negl Trop Dis. 2015; 9(7): e0003831.
111. Coelho P, Caldeira RL. Critical analysis of molluscicide application in schistosomiasis control programs in Brazil. Infect Dis Poverty. 2016; 5(1): 57.
112. WHO - World Health Organization. Helminth control in school-age children: a guide for managers of control programmes [Guide]. 2011. [updated September/2011]. Second: [xii; 75 pp.]. Available from:

+ Corresponding author:,
Received 12 October 2018
Accepted 21 February 2019

Citation: Silva-Moraes V, Shollenberger LM, Siqueira LMV, Castro-Borges W, Harn DA, Queiroz e Grenfell RF, et al. Diagnosis of Schistosoma mansoni infections: what are the choices in Brazilian low-endemic areas? Mem Inst Oswaldo Cruz. 2019; 114: e180478.

Our Location

Memórias do Instituto Oswaldo Cruz

Av. Brasil 4365, Castelo Mourisco 
sala 201, Manguinhos, 21040-900 
Rio de Janeiro, RJ, Brazil

Tel.: +55-21-2562-1222

This email address is being protected from spambots. You need JavaScript enabled to view it.

Support Program

logo fiocruz logo governo
logo faperj logo cnpq marca capes