Accelerate Development of New Therapies for Childhood Cryptosporidium Infection (Round 18)
Funds for NGOs Last date 9 Nov 2016
THE OPPORTUNITY:Diarrhea caused by infection with Cryptosporidium species (primarily Cryptosporidium hominis or C. parvum) is becoming increasingly appreciated as a major contributor to diarrhea morbidity and mortality in children in the developing world. This has been supported by data generated from the Global Enterics Multisite Study (GEMS)1 and Mal-ED2 epidemiological studies. These data suggest that Cryptosporidium may be responsible for a significant fraction of all cases of moderate-to-severe diarrhea in children under two living in these regions. Currently, no vaccine exists and the only approved drug for the treatment of diarrhea caused by Cryptosporidium infection is nitazoxanide (NTZ). Of particular importance, the efficacy of NTZ in those most at-risk for morbidity and mortality associated with Cryptosporidium and diarrhea (malnourished children and the immunocompromised) appears modest. Current tools for investigation of Cryptosporidium biology and development of new interventions are lacking. In order to make progress in addressing the burden of cryptosporidial diarrhea in children living in the developing world, more sophisticated tools are needed.
THE CHALLENGE: Due to a historical lack of funding for both basic and applied research in Cryptosporidium, particularly for pediatric disease, this area lags behind many others in available knowledge and tools for research. Currently, methods to allow cultivation in the laboratory are nascent and not well-established, there are no methods for cryopreservation of the parasites, and tools for manipulation of the parasite genome are very limited and have only very recently been described. Due to these constraints, access to standardized and well-characterized research strains remains limited and moderate- to large-scale drug screening campaigns have been challenging or impossible to contemplate. These technical challenges are compounded by a lack of well-validated drug targets as well as a poor understanding of the optimal pharmacology for treatment of this infection. While significant progress has been made in the past two years, there remains room to improve the overall arsenal of tools and techniques that would allow a robust program in discovery and development of new drug treatments for pediatric cryptosporidiosis. Additionally, as new therapeutics are developed, there remain outstanding questions about how best to ensure that these agents are maximally effective and safe in our target population, children less than 2 years old with diarrhea who also likely suffer from enteric dysfunction due to repeated exposure to diarrheal pathogens and poor nutrition. The safety and efficacy of therapeutics must take into account these additional factors, and methods to assess their impact on drug metabolism, pharmacology, and efficacy prior to entering the clinic are needed.
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