Cryptosporidium parvum Jennifer E. Dumaine,1 Jayesh Tandel,1 and Boris Striepen1, * 1 Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, 380 South University Avenue, Philadelphia, PA 19104, USA TrendsTrendsininParasitologyParasitology Cryptosporidium is a leading cause of diarrheal disease in young children and untreated AIDS patients in resourcelimited countries worldwide. Transmission occurs via the fecal–oral route, and sources of Cryptosporidium infection include contaminated water or food, or contact with infected people or animals. Upon ingestion of the infective parasite oocysts, motile sporozoites emerge and invade epithelial cells of the small intestine where they develop in an intracellular but extracytoplasmic niche. Cryptosporidium completes its complex life cycle in a single host, with both asexual and sexual stages present in the intestine. Replication of the parasite, and the resulting immune response contribute to the development of severe, watery diarrhea in infected individuals. Currently, there is no vaccine, and only one drug (nitazoxanide), which has limited efficacy in those most susceptible. TrendsTrendsininParasitologyParasitology KEY FACTS: Human infections are caused by C. parvum and Cryptosporidium hominis but transmission of multiple additional species occurs locally. Zoonotic C. parvum strains appear genetically distinct from anthroponotic strains. C. parvum invasive stages resemble those of other apicomplexans, but invasion and intracellular development show important differences. C. parvum has a minute genome (9.1 Mbp encoding 4020 genes), lacks an apicoplast and mitochondrial DNA, has greatly reduced metabolic capabilities, and relies on host metabolism. Recent advances: genetic engineering, cryopreservation, culture in organoids, tractable life cycle, phenotypic screens delivered potent drug leads, a natural mouse model to study protective immunity. DISEASE FACTS: Cryptosporidiosis is a major cause of global child mortality, particularly under the age of two. With advanced water treatment, outbreaks are still frequent due to oocyst resistance to water chlorination. The main disease symptoms are severe watery diarrhea, nausea, vomiting, and wasting. Chronic infection causes villus blunting, nutrient malabsorption, and stunted growth. Infection results in protective immunity, albeit not sterile and not in a single infection. T cells are required to clear the infection, and interferon-γ is a key mediator of parasite restriction. TAXONOMY AND CLASSIFICATION: SUPERPHYLUM: Alveolata PHYLUM: Apicomplexa CLASS: Conoidasida ORDER: Cryptogregarinorida FAMILY: Cryptosporidiidae GENUS: Cryptosporidium SPECIES: C. parvum *Correspondence: striepen@upenn.edu (B. Striepen). Trends in Parasitology, May 2020, Vol. 36, No. 5 © 2019 Elsevier Ltd. All rights reserved. https://doi.org/10.1016/j.pt.2019.11.003 485 Trends in Parasitology | Parasite of the Month Acknowledgment Our work on Cryptosporidium is supported by grants from the National Institutes of Health and the Bill and Melinda Gates Foundation to B.S. and a National Institute of Allergy and Infectious Diseases (NIAID) T32 fellowship to J.E.D. Resources www.cdc.gov/parasites/crypto/index.html https://cryptodb.org/cryptodb/ Literature 1. Kotloff, K.L. et al. (2013) Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): a prospective, case-control study. Lancet 382, 209–222 2. 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(2013) Drug repurposing screen reveals FDA-approved inhibitors of human HMG-CoA reductase and isoprenoid synthesis that block Cryptosporidium parvum growth. Antimicrob. Agents Chemother. 57, 1804–1814 8. Vinayak, S. et al. (2015) Genetic modification of the diarrhoeal pathogen Cryptosporidium parvum. Nature 523, 477–480 9. Wilke, G. et al. (2019) A stem-cell-derived platform enables complete Cryptosporidium development in vitro and genetic tractability. Cell Host Microbe 26, 123–134 10. Tandel, J. et al. (2019) Life cycle progression and sexual development of the apicomplexan parasite Cryptosporidium parvum. Nat. Microbiol. 4, 2226–2236 11. Nader, J.L. et al. (2019) Evolutionary genomics of anthroponosis in Cryptosporidium. Nat. Microbiol. 4, 826–836 Trends in Parasitology | Parasite of the Month 486 Trends in Parasitology, May 2020, Vol. 36, No. 5 © 2019 Elsevier Ltd. All rights reserved. https://doi.org/10.1016/j.pt.2019.11.003