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      Update on Cryptosporidium spp.: highlights from the Seventh International Giardia and Cryptosporidium Conference Translated title: Mise à jour sur Cryptosporidium spp.: Faits saillants de la Septième Conférence Internationale sur Giardia et Cryptosporidium

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          Abstract

          While cryptosporidiosis is recognized as being among the most common causes of human parasitic diarrhea in the world, there is currently limited knowledge on Cryptosporidium infection mechanisms, incomplete codification of diagnostic methods, and a need for additional therapeutic options. In response, the Seventh International Giardia and Cryptosporidium Conference (IGCC 2019) was hosted from 23 to 26 June 2019, at the Rouen Normandy University, France. This trusted event brought together an international delegation of researchers to synthesize recent advances and identify key research questions and knowledge gaps. The program of the interdisciplinary conference included all aspects of host-parasite relationships from basic research to applications to human and veterinary medicine, and environmental issues associated with waterborne parasites and their epidemiological consequences. In relation to Cryptosporidium and cryptosporidiosis, the primary research areas for which novel findings and the most impressive communications were presented and discussed included: Cryptosporidium in environmental waters, seafood, and fresh produce; Animal epidemiology; Human cryptosporidiosis and epidemiology; Genomes and genomic evolution encompassing: Comparative genomics of Cryptosporidium spp., Genomic insights into biology, Acquiring and utilizing genome sequences, Genetic manipulation; Host-parasite interaction (immunology, microbiome); and Diagnosis and treatment. High quality presentations discussed at the conference reflected decisive progress and identified new opportunities that will engage investigators and funding agencies to spur future research in a “one health” approach to improve basic knowledge and the clinical and public health management of zoonotic cryptosporidiosis.

          Translated abstract

          Bien que la cryptosporidiose soit reconnue comme l’une des premières causes de diarrhée parasitaire humaine dans le monde, la connaissance des mécanismes de l’infection par Cryptosporidium est limitée, la codification des méthodes diagnostiques est incomplète et des options thérapeutiques supplémentaires sont requises. En réponse à cette situation, la Septième Conférence Internationale sur Giardia and Cryptosporidium (IGCC 2019) s’est tenue du 23 au 26 juin 2019, à l’Université de Rouen-Normandie, France. Cet événement renommé a rassemblé une délégation internationale de chercheurs pour faire la synthèse des avancées récentes et identifier les principaux thèmes de recherche et les lacunes dans les connaissances. Le programme de cette conférence interdisciplinaire comprenait tous les aspects des relations hôte-parasite, de la recherche fondamentale aux applications à la médecine humaine et vétérinaire, ainsi que les questions environnementales liées aux parasites d’origine hydrique et leurs conséquences épidémiologiques. En ce qui concerne Cryptosporidium et la cryptosporidiose, les principaux domaines de recherche pour lesquels de nouvelles découvertes et les communications les plus impressionnantes ont été présentées et discutées comprenaient : Cryptosporidium dans les eaux environnementales, les fruits de mer et les produits frais ; Épidémiologie animale ; Cryptosporidiose et épidémiologie humaine ; Génomes et évolution génomique englobant : Génomique comparative des Cryptosporidium spp., Perspectives génomiques en biologie, Acquisition et utilisation des séquences du génome, Manipulation génétique ; Interaction hôte-parasite (immunologie, microbiome) ; Diagnostic et traitement. Les présentations de grande qualité discutées à la conférence ont fait état de progrès décisifs et ont permis de cerner de nouvelles possibilités qui inciteront les chercheurs et les organismes de financement à stimuler la recherche future dans une approche « une seule santé » afin d’améliorer les connaissances de base et la gestion clinique et de santé publique de la cryptosporidiose zoonotique.

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          Most cited references 37

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          The genome of Cryptosporidium hominis.

          Cryptosporidium species cause acute gastroenteritis and diarrhoea worldwide. They are members of the Apicomplexa--protozoan pathogens that invade host cells by using a specialized apical complex and are usually transmitted by an invertebrate vector or intermediate host. In contrast to other Apicomplexans, Cryptosporidium is transmitted by ingestion of oocysts and completes its life cycle in a single host. No therapy is available, and control focuses on eliminating oocysts in water supplies. Two species, C. hominis and C. parvum, which differ in host range, genotype and pathogenicity, are most relevant to humans. C. hominis is restricted to humans, whereas C. parvum also infects other mammals. Here we describe the eight-chromosome approximately 9.2-million-base genome of C. hominis. The complement of C. hominis protein-coding genes shows a striking concordance with the requirements imposed by the environmental niches the parasite inhabits. Energy metabolism is largely from glycolysis. Both aerobic and anaerobic metabolisms are available, the former requiring an alternative electron transport system in a simplified mitochondrion. Biosynthesis capabilities are limited, explaining an extensive array of transporters. Evidence of an apicoplast is absent, but genes associated with apical complex organelles are present. C. hominis and C. parvum exhibit very similar gene complements, and phenotypic differences between these parasites must be due to subtle sequence divergence.
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            Genetic modification of the diarrheal pathogen Cryptosporidium parvum

            Recent studies into the global causes of severe diarrhea in young children have identified the protozoan parasite Cryptosporidium as the second most important diarrheal pathogen after rotavirus 1–3 . Diarrheal disease is estimated to be responsible for 10.5% of overall child mortality 4 . Cryptosporidium is also an opportunistic pathogen in the context of HIV-AIDS and organ transplantation 5,6 . There is no vaccine and only a single approved drug that provides no benefit for those in gravest danger, malnourished children and immunocompromised patients 7,8 . Cryptosporidiosis drug and vaccine development is limited by the poor tractability of the parasite, which includes lack of continuous culture, facile animal models, and molecular genetic tools 3,9 . Here we describe an experimental framework to genetically modify this important human pathogen. We establish and optimize transfection of C. parvum sporozoites in tissue culture. To isolate stable transgenics we develop a mouse model that delivers sporozoites directly into the intestine, a Cryptosporidium CRISPR/Cas9 system, and in vivo selection for aminoglycoside resistance. We derive reporter parasites suitable for in vitro and in vivo drug screening, and we evaluate the basis of drug susceptibility by gene knock out. We anticipate the ability to genetically engineer the parasite will be transformative for Cryptosporidium research. Genetic reporters will provide quantitative correlates for disease, cure and protection and the role of parasite genes in these processes is now open to rigorous investigation.
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              Foodborne cryptosporidiosis.

              Foodborne illness, the majority of which is caused by enteric infectious agents, costs global economies billions of dollars each year. The protozoan parasite Cryptosporidium is particularly suited to foodborne transmission and is responsible for >8 million cases of foodborne illness annually. Procedures have been developed for sensitive detection of Cryptosporidium oocysts on fresh produce and molecular diagnostic assays have been widely used in case linkages and infection source tracking, especially during outbreak investigations. The integrated use of advanced diagnostic techniques with conventional epidemiological studies is essential to improve our understanding of the occurrence, source and epidemiology of foodborne cryptosporidiosis. The implementation of food safety management tools such as Good Hygienic Practices (GHP), Hazard Analysis and Critical Control Points (HACCP), and Quantitative Microbial Risk Assessment (QMRA) in industrialised nations and Water, Sanitation, and Hygiene (WASH) in developing countries is central for prevention and control and foodborne cryptosporidiosis in the future.
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                Author and article information

                Journal
                Parasite
                Parasite
                parasite
                Parasite
                EDP Sciences
                1252-607X
                1776-1042
                2020
                13 March 2020
                : 27
                : ( publisher-idID: parasite/2020/01 )
                Affiliations
                [1 ] Department of Infectious Disease & Global Health, Cummings School of Veterinary Medicine at Tufts University North Grafton 01536 MA USA
                [2 ] Spanish National Centre for Microbiology 28220 Majadahonda Spain
                [3 ] Institute of Parasitology, Biology Centre CAS 370 05 České Budějovice Czech Republic
                [4 ] Faculty of Agriculture, University of South Bohemia in České Budějovice 370 05 České Budějovice Czech Republic
                [5 ] Cryptosporidium Reference Unit, Public Health Wales SA2 8QA Swansea UK
                [6 ] Swansea Medical School, Swansea University SA2 8PP Swansea UK
                [7 ] Center for Tropical and Emerging Global Diseases, Institute of Bioinformatics and Department of Genetics, University of Georgia Athens 30602 GA USA
                [8 ] College of Veterinary Medicine, South China Agricultural University Guangzhou 510642 Guangdong PR China
                [9 ] Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania 380 South University Avenue Philadelphia 19104 PA USA
                [10 ] INRAE, Université François Rabelais de Tours, Centre Val de Loire, ISP, Laboratoire Apicomplexes et Immunité Mucosale 37380 Nouzilly France
                [11 ] French National Cryptosporidiosis Reference Center, Rouen University Hospital 1 Rue de Germont 76031 Rouen Cedex France
                [12 ] EA 7510, UFR Santé, University of Rouen Normandy, Normandy University 22 Bd. Gambetta 76183 Rouen Cedex France
                Author notes
                [* ]Corresponding author: loic.favennec@ 123456univ-rouen.fr
                Article
                parasite200029 10.1051/parasite/2020011
                10.1051/parasite/2020011
                7069357
                32167464
                © G. Widmer et al., published by EDP Sciences, 2020

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                Page count
                Figures: 0, Tables: 0, Equations: 2, References: 44, Pages: 10
                Categories
                Review Article

                cryptosporidium, cryptosporidiosis, epidemiology, genomics

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