Description

The Problem

Schistosomiasis is a neglected tropical disease that the WHO reports affects over 200 million patients globally, is a danger for over 700 million, and kills three hundred thousand yearly—mostly in developing countries (Verjee 19). Those affected suffer symptoms including severe abdominal pain and swelling, various intestinal malfunctions such as diarrhea, and fatal organ damage. Long term effects in children include stunted growth and limited cognitive development (Gurarie et al 11). The disease has also earned infamy as a "poor man's disease" because the incapacitation of its victims punishes their work and livelihood.



Worldwide spread of schistosomiasis, 2012. Image adapted from Map: Distribution of schistosomiasis, worldwide, 2012, WHO, © 2012 (McManus, D.P., Dunne, D.W., Sacko, M. et al.)

How Schistosoma Works

Various strains of the parasite infect human beings. Though they vary in geographical range, all Schistosoma follow the same life cycle; upon hatching from eggs, miracidia immediately swim through the water in search of Biomphalaria glabrata: freshwater ramshorn snails. They enter the snail's bloodstream and grow into larvae until maturity—at which point they exit the snail as flatworms and penetrate human hosts.



Though they manage to do so through various methods of contact, the most common is penetration of any breaks in skin. Schistosomes sexually reproduce and lay eggs in the intestines and other organs of patients, who excrete the eggs via bodily waste and the cycle renews itself. The process of the eggs being laid and maturing is what leads to the detrimental effects of schistosomiasis. Schistosoma can survive for years and even decades in patients' bodies, causing prolonged pain and symptoms within the host (Verjee 19).

Failure of Current Solutions

The main treatment administered to patients is a drug known as Praziquantel (PZQ). Though PZQ has remained the mainstay drug for over 40 years, several issues have festered during the decades of its use. Pharmaceutical companies refuse to provide significant amounts, as developing nations often do not have the means to fund the production; thus, the vast majority of Schistosomiasis cases who are in lower socioeconomic standing are left with little to no access to PZQ.

Those who do manage to purchase PZQ are met with further challenges. Following WHO guidelines, correct application of PZQ requires a strict regimen of 40 mg per kg body weight per day, orally, divided in two doses the first day, and further dosage 2-4 weeks later if patient immune response is weak. Correct application of the drug is subsequently hard to follow and misuse can lead to parasite survival. Furthermore, initial symptoms of the disease are strikingly similar to common cold, or non-existent, making diagnosis and application of treatment even more difficult. To add on to the situation, certain strains of the parasite have begun to develop resistance to PZQ, raising concern and need for a more feasible solution. In fact, it is widely unknown exactly how the structure of PZQ leads to schistosoma death. A 2012 study highlighted a concerning reduction in S. mansoni susceptibility to PZQ in endemic foci such as Egypt and Senegal (Vale et al 12).

The SchistoGONE Solution

Rather than struggling against distribution, cost, detection, and application issues by treating already-infected patients, SchistoGONE aims at the root of the problem: eradicating Schistosoma. By targeting freshwater snails, known as Biomphalaria glabrata—the sole intermediary hosts of the Schistosoma—SchistoGONE intercepts the life cycle of the worms before they are able to reach sexual maturity and reproduce, killing the parasite inside the snail.

We have decided to use engineered W303 Saccharomyces cerevisiae yeast and e.coli to produce the anti-parasitic compound sanguinarine, an anti-schistosomal we have researched and tested to confirm as the best balance of environmentally safe while also effective in killing the sporocysts phase of schistosoma. S. cerevisiae naturally attracts molluscs like B. glabrata, which then voluntarily consume the yeast and sanguinarine at no harm to their survival (Chan et al 14). Sanguinarine is presented to B. glabrata in easily accessible and specially designed eco-plates situated on river shores. Application of SchistoGONE eco-plates is simple via a distinguished bioreactor refueling apparatus. SchistoGONE thus intercepts schistosoma at the sporocyst phase within the snail guts and bloodstream, breaking the parasite life cycle.

References

Chan, G. F., Othman, F., Zulkiffli, M. H., Yousif, R. H., Yusof, A. M., & Rashid, N. A. A. (2014). Yeasts as the Novel Attractant of Pomacea canaliculata. International Journal of Sciences: Basic and Applied Research, 18, 51-60.

Gurarie, D., Wang, X., Bustinduy, A. L., & King, C. H. (2011). Modeling the effect of chronic schistosomiasis on childhood development and the potential for catch-up growth with different drug treatment strategies promoted for control of endemic schistosomiasis. The American journal of tropical medicine and hygiene, 84(5), 773.

McManus, D. P., Gordon, C., & Weerakoon, K. G. (2018). Testing of water samples for environmental DNA as a surveillance tool to assess the risk of schistosome infection in a locality. International Journal of Infectious Diseases, 76, 128-129.

Vale, N., Gouveia, M. J., Rinaldi, G., Brindley, P. J., Gärtner, F., & Correia da Costa, J. M. (2017). Praziquantel for schistosomiasis: single-drug metabolism revisited, mode of action, and resistance. Antimicrobial agents and chemotherapy, 61(5), e02582-16.

Verjee, M. A. (2019). Schistosomiasis: still a cause of significant morbidity and mortality. Research and reports in tropical medicine, 10, 153.