T cell peptides derived from invasive stages of Schistosoma mansoni as potential schistosomiasis vaccine

Schistosomiasis is a parasitic disease that affects 143 million people in endemic countries. This work analyzed overexpressed sequences from the cercaria phase to the early schistosomulum phase using bioinformatics tools to predict host interaction and selected proteins for predicting T cell epitopes. The final peptides were chemically synthesized, and their toxicity was evaluated in vitro. Peptides were formulated in the Adjuvant Adaptation (ADAD) vaccination system and injected into BALB/c mice that were challenged with S. mansoni cercariae to assess protection and immunogenicity. A total of 39 highly expressed S.mansoni proteins were identified as being of potential interest. Three T cell peptides predicted to bind MHC mouse and human class II were synthesized and formulated for vaccination. SmGSP and SmIKE reduced the number of eggs trapped in the liver by more than 50% in challenged BALB/c mice. The liver of mice vaccinated with either SmGSP or SmTNP had a significantly reduced affected liver surface. Transcriptome-based T cell peptides elicit partial protection and could be candidates for a multiantigen vaccine

Reproducibility matters: intra- and inter-sample variation of the point-of-care circulating cathodic antigen test (POC-CCA) in two Schistosoma mansoni endemic areas in Uganda

Over 240 million people are infected with schistosomiasis. Detecting Schistosoma mansoni eggs in stool using Kato–Katz thick smears (Kato-Katzs) is highly specific but lacks sensitivity. The urine-based point-of-care circulating cathodic antigen test (POC-CCA) has higher sensitivity, but issues include specificity, discrepancy between batches and interpretation of trace results. A semi-quantitative G-score and latent class analyses making no assumptions about trace readings have helped address some of these issues. However, intra-sample and inter-sample variation remains unknown for POC-CCAs. We collected 3 days of stool and urine from 349 and 621 participants, from high- and moderate-endemicity areas, respectively. We performed duplicate Kato-Katzs and one POC-CCA per sample. In the high-endemicity community, we also performed three POC-CCA technical replicates on one urine sample per participant. Latent class analysis was performed to estimate the relative contribution of intra- (test technical reproducibility) and inter-sample (day-to-day) variation on sensitivity and specificity. Within-sample variation for Kato-Katzs was higher than between-sample, with the opposite true for POC-CCAs. A POC-CCA G3 threshold most accurately assesses individual infections. However, to reach the WHO target product profile of the required 95% specificity for prevalence and monitoring and evaluation, a threshold of G4 is needed, but at the cost of reducing sensitivity. This article is part of the theme issue ‘Challenges and opportunities in the fight against neglected tropical diseases: a decade from the London Declaration on NTDs’

Improving non-invasive diagnostics for schistosomiasis using antigen detection: rapid test development and interpretation

Abstract not currently available