New Approaches with Different Types of Circulating Cathodic Antigen for the Diagnosis of Patients with Low Schistosoma mansoni Load

Grenfell, Rafaella Fortini Queiroz; Harn, Donald A.; Tundup, Smanla; Da’dara, Akram A.; Siqueira, Liliane Maria Vidal; Coelho, Paulo Marcos Zech

doi:10.1371/journal.pntd.0002054

Cited by 24 publications

(29 citation statements)

References 43 publications

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“…Furthermore, in a study performed in an endemic area in the State of Minas Gerais, 100% of the individuals evaluated 30 days after schistosomiasis treatment resulted negative for serum CCA (10) . This indicates that levels of serum and urine CCA and CAA decrease significantly some weeks after treatment, constituting a biomarker for schistosomiasis cure.…”

Section: Introductionmentioning

confidence: 99%

Performance of POC-CCA® in diagnosis of schistosomiasis mansoni in individuals with low parasite burden

Siqueira

Couto

Taboada

et al. 2016

Rev. Soc. Bras. Med. Trop.

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Introduction: Schistosomiasis, caused by Schistosoma mansoni, is a public health concern in Brazil. However, the most popular diagnostic method, the Kato-Katz technique, exhibits low sensitivity in low-endemicity areas. We aimed to compare the performance of an immunological assay, the point-of-care circulating cathodic antigen (POC-CCA®) test, with that of two parasitological techniques in a low-endemicity population. Methods: Our study included 141 individuals living in Estreito de Miralta, Minas Gerais, Brazil. Fecal samples were obtained from all participants and analyzed for schistosomiasis using two parasitological techniques: the Kato-Katz technique and the saline gradient technique. Additionally, POC-CCA® strips were utilized for testing urine samples. The results obtained by the different techniques were compared. Results: Analysis of two or 24 slides using the Kato-Katz technique resulted in a positivity rate of 10.6% (15/141) or 19.1% (27/141), respectively. The saline gradient technique yielded a positivity rate of 17.0% (24/141). The prevalence according to both parasitological techniques was 24.1% (34/141). The POC-CCA® test yielded a positivity rate of 22.7% (32/141); however, the positivity rate was merely 2.1% if trace results were considered negative. The agreements observed between POC-CCA® and the parasitological techniques were good (Kappa indexes > 0.64). The POC-CCA® test was more sensitive than the two-slide Kato-Katz technique (p < 0.05) in detecting cases of S. mansoni infection when trace results were considered positive. Conclusions: These findings reinforce the importance of using multiple diagnostic techniques in low-endemicity areas for effective control of disease.

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Section: Introductionmentioning

confidence: 99%

Performance of POC-CCA® in diagnosis of schistosomiasis mansoni in individuals with low parasite burden

Siqueira

Couto

Taboada

et al. 2016

Rev. Soc. Bras. Med. Trop.

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“…Our ROC curve analyses showed highly accurate power of discrimination indicating almost perfect test. Using a similar set of samples, Sarhan et al (2014) showed AUC of 0.99 and 0.87 using SEA and SWAP antigens [78], and Grenfell et al (2013) showed 0.94 using recombinant CCA [79]. Even crude extracts of worm antigens can be used for ELISA, such assays would require infrastructure to maintain the parasite cycle and the complexity of large-scale production and standardization.…”

Section: Discussionmentioning

confidence: 99%

“…Additional studies utilizing other S.mansoni recombinant proteins also showed better results than K-K performed by 2 slides in low-endemic areas. The recombinant CCA showed 100% sensitivity and 96% specificity by IgG detection in chronic individuals using magnetic microspheres [79]. The IgG-ELISA using recombinant 200-kDa tegumental protein demonstrated 90% sensitivity and 93.3% specificity with a strong correlation with egg burden in the same set of individuals [75].…”

Section: Discussionmentioning

confidence: 99%

Serological proteomic screening and evaluation of a recombinant egg antigen for the diagnosis of low-intensity infections in endemic area in Brazil Antigen target in schistosomiasis diagnosis

Moraes¹,

Shollenberger

Castro-Borges

et al. 2018

Preprint

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52Background: Despite decades of employment of control programs, schistosomiasis 53 remains a global public health problem. To further reduce prevalence and intensity of 54 infection, or to achieve the goal of elimination in low-endemic areas, there need to be 55 better diagnostic tools to detect low intensity infections in low-endemic areas as Brazil. 56The rationale for development of new diagnostic tools is because in low-endemic 57 settings, the standard Kato-Katz diagnostic method loses its sensitivity and misses low 58 intensity infections. To develop new diagnostic tools, we employed a proteomics 59 approach search for biomarkers associated with schistosome-specific immune responses 60 to develop sensitive and specific new methods for immunodiagnosis. 61 62 Methods and findings: Immunoproteomic analysis was performed on an egg extract of 63 Schistosoma mansoni using pooled sera from infected or non-infected individuals from 64 a low-endemic area of Brazil. Cross reactivity with other helminth parasites was 65 determined using pooled sera from individuals infected with different parasitic 66helminths. Using this approach we identified 23 spots recognized by schistosome acute 67 and chronic sera samples. To identify immunoreactive spots that are likely glycan 68 epitopes, we compared immunoreactivity of spots treated by sodium metaperiodate 69 oxidation of egg extract. This treatment yielded 12/23 spots maintaining 70 immunoreactivity, suggesting they are protein epitopes. From these 12 spots, 11 spots 71 cross-reacted with sera from infection with other helminths and 10 spots cross-reacted 72 with the negative control group. Spot number 5 was exclusively immunoreactive with 73 sera from schistosome-infected groups in native and deglycosylated conditions and 74 corresponds to a Major Egg Antigen. We expressed the Major egg antigen as a 75 recombinant protein and showed by western blot a similar recognition pattern of that of 4 76 the native protein. IgG-ELISA gave a sensitivity of 87.10% and specificity of 89.09% 77 represented by area under ROC curve of 0.95. IgG-ELISA performed better than the 78 conventional K-K (2 slides) identifying 56/64 cases harboring 1-10 egg per gram of 79 feces that were undiagnosed by K-K parasitological technique.80 81 Conclusions: The serological proteome approach was able to identify a new diagnostic 82 candidate. The recombinant egg antigen provided good performance in IgG-ELISA to 83 detect individuals with extreme low-intensity infections (1 egg per gram of feces). 84 Therefore, the IgG-ELISA using this newly identified recombinant major egg antigen 85 can be a useful tool to be combined with other techniques in low-endemic areas to 86 determine the true prevalence of schistosome infection that is underestimated by Kato-87 Katz method. Further, to overcome the complexity of ELISA in the field, a second-88 generation of antibody-based rapid diagnostic tests (RDT) can be developed. 89 90 Recombinant Protein, Endemic Areas. 92 93 94 95 96 97 98 99 5 100 Author Summary 101 102 ...

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“…Native CCA glycoprotein contains 0-linked poly ( Lewis X ) carbohydrate chains with approximately 25 repeating units. Carbohydrate chains containing multiple Lewis X determinants have been identified on several glycolipids not only from schistosomes but also from other parasites, from human adenocarcinomas and also, circulating granulocytes carry relatively high abundance of branched N-linked polysaccharides having Lewis X repeating units, as previously discussed [17]. Another alternative is the detection of Schistosoma sp.…”

Section: Introductionmentioning

confidence: 93%

Newly Established Monoclonal Antibody Diagnostic Assays for Schistosoma mansoni Direct Detection in Areas of Low Endemicity

et al. 2014

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BackgroundCurrent available methods for diagnosis of schistosomiasis mansoni lack sufficient sensitivity, which results in underreporting of infectious in areas of low endemicity.Methodology/Principal FindingsWe developed three novel diagnostic methodologies for the direct detection of schistosome infection in serum samples. These three new methods were evaluated with positive patients from a low endemicity area in southeast Brazil. The basis of the assay was the production of monoclonal antibodies against the protein backbone of heavily glycosylated Circulating Cathodic Antigen (CCA). The antibodies were also selected for having no specificity to repeating poly-Lewis x units. Assays based on the detection CCA-protein should not encounter a limitation in sensitivity due to a biological background of this particular epitope. Three diagnostic methodologies were developed and validated, (i) Immunomagnetic Separation based on improved incubation steps of non-diluted serum, (ii) Direct Enzyme-linked Immunosorbent Assay and (iii) Fluorescent Microscopy Analysis as a qualitative assay. The two quantitative assays presented high sensitivity (94% and 92%, respectively) and specificity (100%), equivalent to the analysis of 3 stool samples and 16 slides by Kato-Katz, showing promising results on the determination of cure.Conclusions/SignificanceThe Immunomagnetic Separation technique showed excellent correlation with parasite burden by Cohen coefficient. The qualitative method detected 47 positive individuals out of 50 with the analysis of 3 slides. This easy-to-do method was capable of discriminating positive from negative cases, even for patients with low parasite burden.

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New Approaches with Different Types of Circulating Cathodic Antigen for the Diagnosis of Patients with Low Schistosoma mansoni Load

Cited by 24 publications

References 43 publications

Performance of POC-CCA® in diagnosis of schistosomiasis mansoni in individuals with low parasite burden

Performance of POC-CCA® in diagnosis of schistosomiasis mansoni in individuals with low parasite burden

Serological proteomic screening and evaluation of a recombinant egg antigen for the diagnosis of low-intensity infections in endemic area in Brazil Antigen target in schistosomiasis diagnosis

Newly Established Monoclonal Antibody Diagnostic Assays for Schistosoma mansoni Direct Detection in Areas of Low Endemicity

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