Abstract
Cryptosporidium is a major cause of severe diarrhea-related disease in children in developing countries, but currently no vaccine or effective treatment exists for those who are most at risk of serious illness. This is partly due to the lack of in vitro culturing methods that are able to support the entire Cryptosporidium life cycle, which has led to research in Cryptosporidium biology lagging behind other protozoan parasites. In vivo models such as gnotobiotic piglets are complex, and standard in vitro culturing methods in transformed cell lines, such as HCT-8 cells, have not been able to fully support fertilization occurring in vitro. Additionally, the Cryptosporidium life cycle has also been reported to occur in the absence of host cells. Recently developed bioengineered intestinal models, however, have shown more promising results and are able to reproduce a whole cycle of infectivity in one model system. This review evaluates the recent advances in Cryptosporidium culturing techniques and proposes future directions for research that may build upon these successes.
Highlights
Parasites of the Cryptosporidium genus are among the main pathogens causing severe diarrheal disease and death in young children in developing countries [1]
The type I interferon pathway was upregulated in both lung and small intestine organoids 72 h post-infection with C. parvum, mirroring the host defenses observed in human cryptosporidiosis
This study found that secretory cell expression was not required for robust C. parvum growth in vitro after a cell monolayer derived from an Atoh1 knockout mouse supported C. parvum infection [57,63]
Summary
Parasites of the Cryptosporidium genus are among the main pathogens causing severe diarrheal disease and death in young children in developing countries [1]. In Australasia, high-income North America, and high-income Asia-Pacific, there were no Cryptosporidium-related deaths in children under five years of age reported in 2016, whereas in the same year and age bracket, approximately 42,000 Cryptosporidium-related deaths occurred in sub-Saharan Africa. This highlights the reality that low-income countries bear a disproportionate burden globally for cryptosporidiosis, and sub-Saharan. The drug nitazoxanide is the only pharmaceutical intervention approved by the US Food and Drug Administration to treat Cryptosporidium infection It is only efficacious in immunocompetent patients, leaving those in most urgent need with no effective treatment [10]. Out of the four pathogens identified as causing the majority of moderate-to-severe diarrhea in children under five years of age (rotavirus, Cryptosporidium, Shigella, and enterotoxigenic Escherichia coli producing heat stable toxin) [1], Cryptosporidium is the only pathogen without either an effective vaccine or treatment [13,14,15]
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