Abstract
The scientific community identified non stool-based biomarkers as the way forward to support soil-transmitted helminth (STH; Ascaris lumbricoides, Trichuris trichiura and the hookworms Ancylostoma duodenale and Necator americanus) and schistosome (S. mansoni and S. haematobium) deworming programs. This support is needed in making the decision of whether or not to stop preventive chemotherapy intervention efforts and to ultimately transition towards a post-intervention surveillance phase. We applied a two-step micro-array approach to identify antigenic linear epitopes in the STH and S. mansoni proteomes. In a first experiment, we identified antigenic peptides by applying sera from 24 STH and/or S. mansoni infected Ethiopian children on a high-density peptide microarray containing 3.3 million peptides derived from the complete STH and S. mansoni proteomes. A second array experiment with 170,185 peptides that were recognized in the first array was designed to identify non-specific antibody reactivity by applying sera from 24 healthy individuals from Belgium (a non-endemic country). From this array testing cascade, several peptides were identified for STH but none of them appeared to be unique for one species. We therefore concluded that for STH, none of the peptides revealed to be sufficiently sensitive or species specific. For S. mansoni, some promising peptides were identified prompting future investigation. Based on these results, it is unlikely that linear epitopes would be highly useful in detecting species-specific antibody responses to STH in endemic communities. For S. mansoni, one particular peptide of the micro-exon gene 12 (MEG-12) protein deserves further research. In addition, this study emphasizes the need of well-characterized biobanks for biomarker discovery, particularly when the integration of multiple disease programs is envisioned.
Highlights
Two decades ago, during the 54th World Health Assembly, resolution WHA54.19 was approved
We produced an array that contained 2,832,723 peptides representing a total of 110,208 protein sequences across the six different helminth species (Table 1) (A. lumbricoides, A. suum, T. trichiura, A. duodenale, N. americanus, and S. mansoni)
Even though there was some variability between sample reactivity to the negative scramble peptide, none of the samples showed an outlying signal above the threshold (5,000 RLU)
Summary
Two decades ago, during the 54th World Health Assembly, resolution WHA54.19 was approved This resolution urged member states to increase efforts to control two of the most impactful neglected tropical diseases (NTDs), namely soil-transmitted helminthiasis (caused by Ascaris lumbricoides, Trichuris trichiura and the hookworms Ancylostoma duodenale and Necator americanus) and schistosomiasis (predominantly caused by Schistosoma mansoni and S. haematobium) by ensuring access to essential drugs. Combining their burden of disease, they affect an estimated 1 billion individuals worldwide, resulting in a health toll of over 3.3 million daily adjusted life years [1,2]. In order to monitor whether programs have reached these ambitious targets, the development and availability of sensitive and specific diagnostics is critical
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