The Road to Elimination: Current State of Schistosomiasis Research and Progress Towards the End Game

Abstract

The new WHO Roadmap for Neglected Tropical Diseases targets the global elimination of schistosomiasis as a public health problem. To date, control strategies have focused on effective diagnostics, mass drug administration, complementary and integrative public health interventions. Non-mammalian intermediate hosts and other vertebrates promote transmission of schistosomiasis and have been utilized as experimental model systems. Experimental animal models that recapitulate schistosomiasis immunology, disease progression, and pathology observed in humans are important in testing and validation of control interventions. We discuss the pivotal value of these models in contributing to elimination of schistosomiasis. Treatment of schistosomiasis relies heavily on mass drug administration of praziquantel whose efficacy is comprised due to re-infections and experimental systems have revealed the inability to kill juvenile schistosomes. In terms of diagnosis, nonhuman primate models have demonstrated the low sensitivity of the gold standard Kato Katz smear technique. Antibody assays are valuable tools for evaluating efficacy of candidate vaccines, and sera from graded infection experiments are useful for evaluating diagnostic sensitivity of different targets. Lastly, the presence of Schistosomes can compromise the efficacy of vaccines to other infectious diseases and its elimination will benefit control programs of the other diseases. As the focus moves towards schistosomiasis elimination, it will be critical to integrate treatment, diagnostics, novel research tools such as sequencing, improved understanding of disease pathogenesis and utilization of experimental models to assist with evaluating performance of new approaches.

Keywords: diagnosis; elimination; research; schistosomiasis; vaccines.

Figure 1

A framework for the development of new diagnostic tagrets for schistosomiasis. Schistosome protein sequences are investigated to identify those that are present in host circulation. By computational approaches suitable peptides are selected based on prediction algorithms (step 1), the best hit candidates (depicted as orange in the figure) are commericially synthesised either as multiple antigenic peptides (MAPs) or conjugated to a carrier protein like ovalbumin (step 2). In step 3, mice/rats/rabbits are immunized with the synthetic peptides to raise antibodies according to the desired protocol. Serum samples are collected serially including pre-vaccination, during vaccination timepoints and after the final dose. In step 4, antibodies in serum can be tested directly (polyclonal antibodies) or can be enriched for a preferred isotype, first against the synthetic peptide or native target like worm vomitus for proteins from the schistomose gut in an ELISA format. For surface proteins, the nataive target can be schistosome tissue sections by immunohistochemistry. Step 5: Promising candidates are validated for sensitivity in larger animals (preferably the baboon model) where graded infections are possible to determine the limit of detection by comparing reactivity of serum to recovered worm burden. Step 6: Candidates are tested against serum and/or urine samples from individuals with confirmed schistosome infection. Finally, additional development steps are carried out to design the validated targets as rapid point-of-care diagnostic kits.