Serological proteomic screening and evaluation of a recombinant egg antigen for the diagnosis of low-intensity Schistosoma mansoni infections in endemic area in Brazil.
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2019
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Background
Despite decades of use of control programs, schistosomiasis remains a global public health
problem. To further reduce prevalence and intensity of infection, or to achieve the goal of
elimination in low-endemic areas, there needs to be better diagnostic tools to detect low-
intensity infections in low-endemic areas in Brazil. The rationale for development of new
diagnostic tools is that the current standard test Kato-Katz (KK) is not sensitive enough to
detect low-intensity infections in low-endemic areas. In order to develop new diagnostic
tools, we employed a proteomics approach to identify biomarkers associated with schisto-
some-specific immune responses in hopes of developing sensitive and specific new meth-
ods for immunodiagnosis.
Methods and findings
Immunoproteomic analyses were performed on egg extracts of Schistosoma mansoni using
pooled sera from infected or non-infected individuals from a low-endemic area of Brazil. Cross reactivity with other soil-transmitted helminths (STH) was determined using pooled
sera from individuals uniquely infected with different helminths. Using this approach, we
identified 23 targets recognized by schistosome acute and chronic sera samples. To identify
immunoreactive targets that were likely glycan epitopes, we compared these targets to the
immunoreactivity of spots treated with sodium metaperiodate oxidation of egg extract. This
treatment yielded 12/23 spots maintaining immunoreactivity, suggesting that they were
protein epitopes. From these 12 spots, 11 spots cross-reacted with sera from individuals
infected with other STH and 10 spots cross-reacted with the negative control group. Spot
number 5 was exclusively immunoreactive with sera from S. mansoni-infected groups in
native and deglycosylated conditions and corresponds to Major Egg Antigen (MEA). We
expressed MEA as a recombinant protein and showed a similar recognition pattern to that
of the native protein via western blot. IgG-ELISA gave a sensitivity of 87.10% and specificity
of 89.09% represented by area under the ROC curve of 0.95. IgG-ELISA performed better
than the conventional KK (2 slides), identifying 56/64 cases harboring 1–10 eggs per gram
of feces that were undiagnosed by KK parasitological technique.
Conclusions
The serological proteome approach was able to identify a new diagnostic candidate. The
recombinant egg antigen provided good performance in IgG-ELISA to detect individuals
with extreme low-intensity infections (1 egg per gram of feces). Therefore, the IgG-ELISA
using this newly identified recombinant MEA can be a useful tool combined with other
techniques in low-endemic areas to determine the true prevalence of schistosome infection
that is underestimated by the KK method. Further, to overcome the complexity of ELISA
in the field, a second generation of antibody-based rapid diagnostic tests (RDT) can be
developed.
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MORAES, V. S. et al. Serological proteomic screening and evaluation of a recombinant egg antigen for the diagnosis of low-intensity Schistosoma mansoni infections in endemic area in Brazil. PLOS Neglected Tropical Diseases, v. 14, mar. 2019. Disponível em: <https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0006974>. Acesso em: 11 out. 2022.