A new antigen detection ELISA for the diagnosis of Strongyloides infection

Balachandra, Dinesh; Rahumatullah, Anizah; Lim, Theam Soon; Mustafa, Fatin Hamimi; Ahmad, Hussain; Anuar, Nor Suhada; Noordin, Rahmah

doi:10.1016/j.actatropica.2021.105986

Cited by 10 publications

(9 citation statements)

References 25 publications

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“…It is worth noting that galectins have already been reported to be involved in host-pathogen interaction and to display immuno-regulatory properties in S. ratti [49]. Also, several commercial and in-house assays already use the recombinant Ss-NIE for S. stercoralis serodiagnosis [9,[50][51][52][53]. Ss-NIE is also included in a commercial research use only (RUO) serological test, together with Ss-IR, which was not identified in our dataset [9].…”

Section: Resultsmentioning

confidence: 99%

Novel insights into the somatic proteome of Strongyloides stercoralis infective third-stage larvae

et al. 2023

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Background Strongyloidiasis is a neglected tropical disease affecting an estimated 600 million people, particularly in resource-limited settings. The infection can persist lifelong due to unusual auto-infective cycle of Strongyloides stercoralis. The lack of a diagnostic gold standard and limited knowledge of the mechanisms underpinning this chronic infection are key issues in disease management. To date, only a few proteomics studies have been conducted to elucidate the molecular mechanisms associated with Strongyloides parasitism or to highlight novel immunological markers, with the result that our knowledge of S. stercoralis proteome remains limited. This study aims at expanding the characterization of S. stercoralis infective larvae (iL3) in order to further explore the mechanisms of parasitism and to highlight possible novel targets for serodiagnosis. Methods iL3 obtained from an infected subject were analysed by high-throughput tandem mass spectrometry. To achieve a more comprehensive characterization of the iL3 proteome we analysed the experimental dataset using an automatic search strategy combined with manual annotation, which included gene ontology (GO) analysis, InterPro annotation, assessment of the homology with Homo sapiens and other pathogens of clinical importance and B-cell epitope prediction. Results Our pipeline identified 430 S. stercoralis proteins, 187 (43%) of which were uncharacterized. Oxidoreductases and peptidases were amongst the most represented protein categories, as highlighted by molecular function GO analyses, while membrane and mitochondrial proteins were the most represented cellular component GO categories. A high proportion of proteins bearing the CAP, SCP or thioredoxin domain or belonging to cysteine-rich secretory, transthyretin-like or peptidase protein families were also identified. Additionally, we highlighted nine proteins displaying low homology with H. sapiens or other related pathogens and bearing amino acid sequences with immunogenic properties. Conclusions Our comprehensive description and annotation of the S. stercoralis iL3 proteome contribute to expanding the ‘omics characterization of this parasite and provide experimental evidence on the most represented proteins associated with S. stercoralis parasitism, as inferred from genomic and transcriptomic data. Moreover, novel candidate immunogenic proteins to be evaluated as novel serological diagnostic markers are highlighted. Graphical Abstract

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Section: Resultsmentioning

confidence: 99%

Novel insights into the somatic proteome of Strongyloides stercoralis infective third-stage larvae

et al. 2023

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“…Vaccine candidates for S . stercoralis : sodium potassium ATPase (SsEAT), tropomyosin, and a galectin (LEC-5) [ 103 , 104 ] may also generate effective antibodies for antigen capture, if the relevant antigens are detectable in stool, as could serological antigens SsIR [ 105 ] and NIE [ 106 ], the latter of which has been detected in serum [ 107 ].…”

Section: Discussionmentioning

confidence: 99%

“…Somatic protein datasets would include tegument antigens as might be present in stool if whole or parts of larvae were present, or if the proteins were secreted via non-classical pathways, as proposed for some S. venezuelensis proteins [102]. Vaccine candidates for S. stercoralis: sodium potassium ATPase (SsEAT), tropomyosin, and a galectin (LEC-5) [103,104] may also generate effective antibodies for antigen capture, if the relevant antigens are detectable in stool, as could serological antigens SsIR [105] and NIE [106], the latter of which has been detected in serum [107].…”

Section: Limitations and Future Workmentioning

confidence: 99%

A comparative ‘omics’ approach for prediction of candidate Strongyloides stercoralis diagnostic coproantigens

et al. 2023

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Human infection with the intestinal nematode Strongyloides stercoralis is persistent unless effectively treated, and potentially fatal in immunosuppressed individuals. Epidemiological data are lacking, partially due to inadequate diagnosis. A rapid antigen detection test is a priority for population surveillance, validating cure after treatment, and for screening prior to immunosuppression. We used a targeted analysis of open access ‘omics’ data sets and used online predictors to identify S. stercoralis proteins that are predicted to be present in infected stool, Strongyloides-specific, and antigenic. Transcriptomic data from gut and non-gut dwelling life cycle stages of S. stercoralis revealed 328 proteins that are differentially expressed. Strongyloides ratti proteomic data for excreted and secreted (E/S) proteins were matched to S. stercoralis, giving 1,057 orthologues. Five parasitism-associated protein families (SCP/TAPS, prolyl oligopeptidase, transthyretin-like, aspartic peptidase, acetylcholinesterase) were compared phylogenetically between S. stercoralis and outgroups, and proteins with least homology to the outgroups were selected. Proteins that overlapped between the transcriptomic and proteomic datasets were analysed by multiple sequence alignment, epitope prediction and 3D structure modelling to reveal S. stercoralis candidate peptide/protein coproantigens. We describe 22 candidates from seven genes, across all five protein families for further investigation as potential S. stercoralis diagnostic coproantigens, identified using open access data and freely-available protein analysis tools. This powerful approach can be applied to many parasitic infections with ‘omic’ data to accelerate development of specific diagnostic assays for laboratory or point-of-care field application.

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“…On the other hand, continuous infection or autoinfection may have contributed to the persistence of antibodies in adults. As serological diagnosis by IgG-ELISA may not be very useful in differentiating active and past infections [ 57 ], infection of adult indigenous evaluated herein could be either acute or chronic strongyloidiasis.…”

Section: Discussionmentioning

confidence: 99%

Seroprevalence and associated risk factors of strongyloidiasis in indigenous communities and healthcare professionals from Brazil

et al. 2023

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Strongyloides stercoralis, a pathogenic roundworm, is considered endemic in several tropical and subtropical areas worldwide. Indigenous populations have the highest soil-transmitted helminthiases-related mortality rates, but the prevalence and risk factors associated with S. stercoralis in Brazilian indigenous populations have not been established. Thus, the present study aimed to assess the seroprevalence and associated risk factors for S. stercoralis in indigenous communities and the healthcare professionals serving them in Brazil. Indigenous populations living in nine communities and healthcare professionals were tested for anti- S. stercoralis antibodies by ELISA. A questionnaire was used to assess socio-epidemiological information. Associated risk factors for seropositivity were tested by chi-square or Fisher’s exact tests, using bivariate analyses and multivariate logistic regression. Overall, 174/463 (37.6%; CI 95%: 33.3–42.1) indigenous persons and 77/147 (52.4%; 95% CI: 44.3–60.3) healthcare professionals were seropositive for anti- S. stercoralis antibodies. Seropositivity among the two groups was statistically significant (p = 0.0016; OR = 0.547; 95% CI: 0.376–0.796) and revealed that healthcare professionals were 1.83 times more likely to be seropositive. The multivariate analysis showed that being male or being adult were also risk factors, while having a septic tank as a sanitary facility represented a protective factor for S. stercoralis exposure in indigenous persons. None of the variables evaluated were associated with S. stercoralis exposure in the professional group. The study herein has reported a high seroprevalence to Strongyloides stercoralis in indigenous communities of Brazil and healthcare professionals, warning for potential public health concerns of strongyloidiasis in such populations.

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A new antigen detection ELISA for the diagnosis of Strongyloides infection

Cited by 10 publications

References 25 publications

Novel insights into the somatic proteome of Strongyloides stercoralis infective third-stage larvae

Novel insights into the somatic proteome of Strongyloides stercoralis infective third-stage larvae

A comparative ‘omics’ approach for prediction of candidate Strongyloides stercoralis diagnostic coproantigens

Seroprevalence and associated risk factors of strongyloidiasis in indigenous communities and healthcare professionals from Brazil

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