Abstract
The intestinal apicomplexan parasite Cryptosporidium is a major cause of diarrheal disease in humans worldwide. However, treatment options are severely limited. The search for novel interventions is imperative, yet there are several challenges to drug development, including intractability of the parasite and limited technical tools to study it. This review addresses recent, exciting breakthroughs in this field, including novel cell culture models, strategies for genetic manipulation, transcriptomics, and promising new drug candidates. These advances will stimulate the ongoing quest to understand Cryptosporidium and the pathogenesis of cryptosporidiosis and to develop new approaches to combat this disease.
Highlights
The intestinal apicomplexan parasite Cryptosporidium is responsible for waterborne outbreaks of diarrheal disease worldwide and continues to cause opportunistic infection in immunocompromised hosts, including patients with untreated HIV/AIDS1
Despite the global burden of cryptosporidiosis, treatment options are limited to supportive therapy and a single US Food and Drug Administration-approved drug, nitazoxanide, which has limited efficacy in malnourished children and is ineffective in immunocompromised individuals[8,9,10,11]
This study identified genes involved in ribosome biogenesis and translation as being upregulated in C. parvum during infection in vitro compared with oocysts
Summary
The intestinal apicomplexan parasite Cryptosporidium is responsible for waterborne outbreaks of diarrheal disease worldwide and continues to cause opportunistic infection in immunocompromised hosts, including patients with untreated HIV/AIDS1. Novel cell culture models enable propagation of Cryptosporidium parvum in vitro There are several constraints to drug development for cryptosporidiosis[4,12]. Enteroids are stem cell-derived 3D structures that can be generated from crypts derived from human intestinal biopsies, can be passaged indefinitely, and are a more physiological alternative to transformed cell lines[28,29] This 3D ex vivo model supports robust C. parvum infection and results in the production of oocysts[30]. Some of these candidates do not eliminate oocyst shedding, lead to only modest reduction in diarrhea severity or duration (or both), or have been neither rigorously tested for toxicity nor evaluated in pre-clinical trials Many of these compounds are modifiable, and it might be possible to develop new analogs with enhanced efficacy and decreased toxicity to human cells. Grant information The author(s) declared that no grants were involved in supporting this work
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