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Title: Cryptosporidiosis: Global burden, novel diagnostics, therapeutics and vaccine targets

Author
item CHECKLEY, W - Johns Hopkins University
item WHITE, A. - University Of Texas
item JAGANATH, D. - Johns Hopkins University
item ARROWOOD, M. - Centers For Disease Control And Prevention (CDC) - United States
item CHALMERS, R. - Public Health England (PHE)
item Fayer, Ronald

Submitted to: Lancet Infectious Diseases
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/28/2014
Publication Date: 1/1/2015
Citation: Checkley, W., White, A.C., Jaganath, D., Arrowood, M., Chalmers, R., Fayer, R. 2015. Cryptosporidiosis: Global burden, novel diagnostics, therapeutics and vaccine targets. Lancet Infectious Diseases. 15:85-94.

Interpretive Summary: The Bill and Melinda Gates Foundation recently convened a group of experts in cryptosporidiosis to discuss the global burden, diagnostics, therapeutics, and preventive strategies. The goal was to better understand the epidemiology, detect, manage and prevent Cryptosporidium infections. Cryptosporidiosis has been identified as an important cause of morbidity and mortality worldwide, especially among children in resource-limited settings. For example, in a study of over 20,000 children in Africa and Asia Cryptosporidium was second to rotavirus as a cause of diarrhea morbidity in children aged <2 years, and was associated with a 2.3 times greater hazard of death among children aged 12 to 23 months. In contrast, Cryptosporidium infections in high-income countries like the US and UK are relatively rare. Current diagnostic tests for cryptosporidiosis are suboptimal, requiring specialized tests that are insensitive at best. Alternatives to microscopy, including antigen-detection and polymerase chain reaction, improve sensitivity. Serologic assays provide additional information for epidemiologic studies. Current therapy is suboptimal with limited activity in normal hosts and no proven efficacy in controlled trials of AIDS patients. The availability of Cryptosporidium genomes has helped identify promising therapeutic targets, and drugs are in development for several targets. Partial immunity following exposure suggests the potential for successful vaccination, and several vaccines are in development. Research in these areas could significantly improve global public health. This information will be of interest to public health professionals.

Technical Abstract: The Global Enteric Multicenter Study (GEMS) evaluated clinical syndromes of moderate-to-severe diarrhea in >20,000 children across seven sites in sub-Saharan Africa and South Asia and identified Cryptosporidium amongst the four highest contributors to diarrhea worldwide in children <5 years of age while contributing to longer duration of diarrhea, and greater childhood morbidity and mortality. While human infections have been noted with over 15 species, the majority of childhood infections worldwide have been attributed to C. hominis and C. parvum. Malnutrition in early childhood also increases the risk of diarrhea with and exacerbates effects of cryptosporidiosis on growth. Tools for detecting Cryptosporidium in stool include microscopy, antigen detection, PCR, and serodiagnostics. Microscopy is inexpensive but demands good staining and visual skills. In developed countries, clinical laboratories employ antigen detection as the diagnostic method of choice. PCR is widely used for detection in research laboratories and affords excellent sensitivity. Anti-parasitic treatment for cryptosporidiosis remains suboptimal. Drug and vaccine development is compromised by the inability to propagate the organism in vitro, but sequencing of the parasite genome has helped identify multiple unique pathways that are being targeted for development of chemotherapeutic agents.