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

Grenfell, Rafaella Fortini Queiroz; Martins, Watson; Enk, Martin Johannes; Almeida, Áureo; Siqueira, Liliane Maria Vidal; Silva-Moraes, Vanessa; Oliveira, Edward; Carneiro, Nídia Francisca de Figueiredo; Coelho, Paulo Marcos Zech

doi:10.1590/s0074-02762013000300011

Cited by 30 publications

(30 citation statements)

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“…S. mansoni ‐endemic areas with low parasite burden are representative of most parasite transmission areas in Brazil and other regions of the world subjected to frequent schistosomiasis treatment as the main strategy of disease control. Diagnosis and treatment of schistosomiasis cases in these areas is often challenging because of the small number of eggs eliminated in the host's faeces, favouring parasite transmission and frequent re‐infection of individuals . Although there was an expressive reduction in number of severe S. mansoni ‐induced hepatosplenic disease and deaths in these endemic areas, abdominal US scans identified liver and circulatory damage, such as periportal fibrosis, in Schistosoma ‐infected individuals harbouring low parasite load, a finding that should be further investigated.…”

Section: Discussionmentioning

confidence: 99%

Plasma levels of innate immune mediators are associated with liver fibrosis in low parasite burden Schistosoma mansoni‐infected individuals

et al. 2018

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In the murine model, it was demonstrated that pro-inflammatory cytokines and chemokines are essential to the formation and modulation of Schistosoma-induced granulomatous inflammation. However, the relationship of these immune mediators and disease severity is hard to be established in naturally infected individuals. The current study evaluates the association between plasma concentrations of MIF, sTNF-R1, CCL3, CCL7 and CCL24 and schistosomiasis morbidity in Schistosoma mansoni-infected patients with a low parasite burden. For this propose, 97 S. mansoni-infected individuals were subjected to abdominal ultrasound analysis and clinical examination. Among them, 88 had plasma concentration of immune mediators estimated by ELISA assay. Multivariate linear regression models were used to evaluate the relationship between the plasma concentration of immune mediators and the variables investigated. Although most individuals presented low parasite burden, over 30% of them showed signs of fibrosis defined by ultrasound measurements and 2 patients had a severe form of schistosomiasis. No association between parasite burden and the plasma levels of chemokine/cytokines or disease severity was observed. There was a positive association between plasma concentration of CCL4, sTNF-R1, CCL3 and MIF with gall bladder thickness and/or with portal vein thickness that are liver fibrosis markers. In contrast, no association was found between CCL7 plasma concentrations with any of the schistosomiasis morbidity parameters evaluated. The data showed that CCL24, sTNFR1, MIF and CCL3 can be detected in plasma of S. mansoni-infected individuals and their concentration would be used as prognostic makers of Schistosoma-induced liver fibrosis, even in individuals with low parasite burden.

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Section: Discussionmentioning

confidence: 99%

Plasma levels of innate immune mediators are associated with liver fibrosis in low parasite burden Schistosoma mansoni‐infected individuals

et al. 2018

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“…Other studies have used other tests as reference for the diagnosis of schistosomiasis mansoni. 18,57,58 Parasitological techniques, mainly, the KK technique, have brought a substantial benefit to helminthiasis control. 7 The presence of LEAs can be considered an indicator of positive outcomes of the schistosomiasis control programs.…”

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confidence: 99%

Detection of Schistosoma mansoni Antibodies in a Low-Endemicity Area Using Indirect Immunofluorescence and Circumoval Precipitin Test

Espírito-Santo

Pintó

Gargioni

et al. 2014

The American Journal of Tropical Medicine and Hygiene

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Abstract. Parasitological diagnostic methods for schistosomiasis lack sensitivity, especially in regions of low endemicity. The objective of this study was to determine the prevalence of Schistosoma mansoni infections by antibody detection using the indirect immunofluorescence assay (IFA-IgM) and circumoval precipitin test (COPT). Serum samples of 572 individuals were randomly selected. The IFA-IgM and COPT were used to detect anti-S. mansoni antibodies. Of the patients studied, 15.9% (N = 91) were IFA-IgM positive and 5.1% (N = 29) had COPT reactions (P 0.001 by McNemar's test). Immunodiagnostic techniques showed higher infection prevalence than had been previously estimated. This study suggests that combined use of these diagnostic tools could be useful for the diagnosis of schistosomiasis in epidemiological studies in areas of low endemicity.

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“…Parasitological examination was performed by K-K and GS as described. Serological reactivity to SEA and SWAP was performed by IgG-ELISA in the Reference Center for Schistosomiasis as previously described [35]. Patients with eggs in the feces and reactive for both IgG-ELISA assays were removed from the healthy group.…”

Section: Methodsmentioning

confidence: 99%

“…We used different sets of pooled sera from acute and chronically infected patients, as well as from helminth positive, but schistosome-negative individuals, to select highly specific schistosome antigens. Antibodies against schistosome eggs have been considered useful antigens for the diagnosis of schistosomiasis [35, 42, 53]. Therefore, we screened soluble egg extracts (SEE) by two-dimensional western blotting (2D-WB).…”

Section: Introductionmentioning

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

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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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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

Abstract: Schistosomiasis diagnosis is based on the detection of eggs in the faeces

Cited by 30 publications

References 29 publications

Plasma levels of innate immune mediators are associated with liver fibrosis in low parasite burden Schistosoma mansoni‐infected individuals

Plasma levels of innate immune mediators are associated with liver fibrosis in low parasite burden Schistosoma mansoni‐infected individuals

Detection of Schistosoma mansoni Antibodies in a Low-Endemicity Area Using Indirect Immunofluorescence and Circumoval Precipitin Test

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

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