Putting Ourselves Out of the Schistosomiasis Business

Posted 10:07 AM, January 14, 2013, by Michael Harrison Hsieh

Scientists studying any given disease have an ideal goal, that, if achieved, would be paradoxical: finding a cure and effectively driving themselves out of working on the disease. This superficially seems to apply to schistosomiasis, chronic infection with parasitic Schistosoma worms. A recent article in Acta Tropica, "Time to set the agenda for schistosomiasis elimination", highlights that global eradication of schistosomiasis may someday soon be on the horizon.

Mass drug administration campaigns, wherein entire villages and towns are treated with the anti-schistosomal agent known as praziquantel, are being conducted worldwide to treat Schistosoma-infected individuals. Is it true that no more schistosomiasis research would be needed if schistosomiasis was cured worldwide in a magical, instantaneous "global" dose of praziquantel? Indeed, the answer is "no". As outlined in the Acta Tropica article, transmission of schistosomiasis would not necessarily be interrupted in some settings, given the aquatic and intermediate host-based life stages of schistosomes. For example, Schistosoma japonicum is known to have at least 40 different mammalian hosts, and thus eradication of this schistosome may require treatment of infected livestock as well as humans and public health measures. We are still learning about the non-human host-based life cycle of schistosomes, and research in these areas remains critical.

Let's take the theoretical exercise one step further. If we could not only cure every human of schistosomiasis, but also eliminate all aquatic and animal reservoirs, would we be out of business? Again, the answer is "no". Although praziquantel can reverse schistosomal liver and bladder fibrosis early in infection, it does not alleviate advanced cases (Richter, Acta Tropica 2000). Indeed, we understand very little about fibrosis in general, despite this pathologic process being implicated in 45% of all deaths in the developed world (reviewed by Wynn). Praziquantel also cannot treat schistosomiasis-induced bladder cancer or HIV contracted as a result of genital lesions associated with female genital schistosomiasis. Understanding how schistosomiasis leads to these lethal sequelae will remain to be a crucial endeavor long after the disease is eradicated.

The limitations of praziquantel and our inadequate knowledge of schistosomiasis underscore the importance of models of urogenital schistosomiasis (Fu et al. and Ray et al.). These models have identified potential mediators of fibrosis, immunomodulation, and carcinogenesis. Given that urogenital schistosomiasis-induced bladder cancer is felt to be an inflammatory process, studying this disease, even if eradicated, may reveal new links between inflammation and carcinogenesis that are suitable as therapeutic targets in non-schistosomal cancers.

I sincerely hope that schistosomiasis is eradicated soon. A valuable analogy and lesson may lie in the vaccinia-smallpox story. Vaccinia, a pox virus, was used as the vaccine that led to smallpox's eradication. However, vaccinia continues to be used as a scientific tool to introduce genes into tissues, and has returned to the limelight due to concerns regarding smallpox being revived as a bioterrorism weapon. Fortunately no one is interested in "weaponizing" schistosomes. Nevertheless, we can and should continue to use schistosomes as research weapons against many diseases, including schistosomiasis itself.

Rollinson, D., Knopp, S., Levitz, S., Stothard, J., Tchuenté, L., Garba, A., Mohammed, K., Schur, N., Person, B., Colley, D., & Utzinger, J. (2012). Time to set the agenda for schistosomiasis elimination Acta Tropica DOI: 10.1016/j.actatropica.2012.04.013

Richter J (2000). Evolution of schistosomiasis-induced pathology after therapy and interruption of exposure to schistosomes: a review of ultrasonographic studies. Acta tropica, 77 (1), 111-31 PMID: 10996127

Wynn, T. (2008). Cellular and molecular mechanisms of fibrosis The Journal of Pathology, 214 (2), 199-210 DOI: 10.1002/path.2277

Fu CL, Odegaard JI, Herbert DR, & Hsieh MH (2012). A novel mouse model of Schistosoma haematobium egg-induced immunopathology. PLoS pathogens, 8 (3) PMID: 22479181

Ray D, Nelson TA, Fu CL, Patel S, Gong DN, Odegaard JI, & Hsieh MH (2012). Transcriptional profiling of the bladder in urogenital schistosomiasis reveals pathways of inflammatory fibrosis and urothelial compromise. PLoS neglected tropical diseases, 6 (11) PMID: 23209855

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