Sustained fecal-oral human-to-human transmission following a zoonotic event Miranda de Graaf, Relja Beck, Simone Caccio, Birgitta Duim, Pieter Fraaij, Françoise Le Guyader, Marc Lecuit, Jacques Le Pendu, Emmie de Wit, Constance Schultsz To cite this version: Miranda de Graaf, Relja Beck, Simone Caccio, Birgitta Duim, Pieter Fraaij, et al.. Sustained fecal- oral human-to-human transmission following a zoonotic event. Current Opinion in Virology, Elsevier, 2016, 22, pp.1 - 6. 10.1016/j.coviro.2016.11.001. inserm-01445250 HAL Id: inserm-01445250 https://www.hal.inserm.fr/inserm-01445250 Submitted on 24 Jan 2017 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Available online at www.sciencedirect.com ScienceDirect Sustained fecal-oral human-to-human transmission following a zoonotic event 1 2 3 Miranda de Graaf , Relja Beck , Simone M Caccio , 4,5 1,6 7 Birgitta Duim , Pieter LA Fraaij , Franc¸oise S Le Guyader , 8,9 10 11 Marc Lecuit , Jacques Le Pendu , Emmie de Wit and 12 Constance Schultsz Bacterial, viral and parasitic zoonotic pathogens that transmit Problem setting via the fecal-oral route have a major impact on global health. In recent years there have been many examples of patho- However, the mechanisms underlying the emergence of such gens crossing the species barrier and infecting humans, pathogens from the animal reservoir and their persistence in the although the vast majority of these zoonotic events did human population are poorly understood. Here, we present a not result in sustained human-to-human transmission [1– framework of human-to-human transmission of zoonotic 3]. Nevertheless, the continuing emergence of zoonotic pathogens that considers the factors relevant for fecal-oral pathogens is a cause of concern globally, especially due to human-to-human transmission route at the levels of host, the high morbidity and mortality of pathogens like pathogen, and environment. We discuss current data gaps and MERS-CoV and A/H5N1 influenza virus [4,5]. Human- propose future research directions. to-human transmission of microorganisms generally Addresses occurs via one or multiple transmission routes, including 1 Department of Viroscience, Erasmus Medical Center, Rotterdam, The the fecal-oral, airborne, direct contact, or vector-borne Netherlands 2 route. Whilst pathogens including bacteria, parasites and Department for Bacteriology and Parasitology, Croatian Veterinary viruses have very different biological properties, they can Institute, Zagreb, Croatia 3 Department of Infectious Diseases, Istituto Superiore di Sanita` , Rome, Italy employ similar routes of transmission and emergence. 4 Department of Infectious Diseases and Immunology, Faculty of Identification of the mechanisms underlying the effective Veterinary Medicine, Utrecht University, Utrecht, The Netherlands human-to-human transmission of emerging zoonotic 5 WHO Collaborating Center for Campylobacter/OIE Reference pathogens and their commonalities across different Laboratory for Campylobacteriosis, Utrecht, The Netherlands 6 pathogens, may help design of interventions aimed at Department of Pediatrics, Erasmus Medical Center-Sophia, Rotterdam, The Netherlands reducing the risk of sustained human-to-human transmis- 7 Ifremer, Laboratoire de Microbiologie, Nantes, France sion after a zoonotic event. 8 Institut Pasteur, Inserm U1117, Biology of Infection Unit, Paris, France 9 Paris Descartes University, Sorbonne Paris Cite´ , Necker-Pasteur Expert opinion meeting Centre for Infectiology, Necker-Enfants Malades University Hospital, Institut Imagine, Assistance Publique-Hoˆ pitaux de Paris, Paris, France As part of the activities of the ANTIGONE consortium 10 Inserm, CNRS, University of Nantes, Nantes, France on the emergence of zoonotic pathogens, an expert opin- 11 Laboratory of Virology, National Institute of Allergy and Infectious ion meeting was organized. Using a comparative approach Diseases, National Institutes of Health, Hamilton, MT, United States 12 including parasites, bacteria and viruses that transmit via Department of Global Health and Department of Medical the fecal-oral route, the meeting aimed at identifying the Microbiology, Academic Medical Center, Amsterdam, The Netherlands key drivers of sustained human-to-human transmission Corresponding author: Schultsz, Constance ([email protected]) after a zoonotic event, taking into account the host, the pathogen and the interface (transmission amplifiers). In addition, major knowledge gaps were identified that Current Opinion in Virology 2017, 22:1–6 require future research in order to better control emerging This review comes from a themed issue on Emerging viruses: zoonotic pathogens that potentially are transmitted intraspecies transmission through a fecal-oral route. The main conclusions of this Edited by Linfa and Ron meeting are presented in this perspective. A framework of fecal-oral transmission http://dx.doi.org/10.1016/j.coviro.2016.11.001 Enteric pathogens can be transmitted between humans by the fecal-oral route via direct contact or indirect 1879-6257/# 2016 The Authors. Published by Elsevier B.V. This is an contact via contaminated fluids, including surface water, open access article under the CC BY-NC-ND license (http://creative- commons.org/licenses/by-nc-nd/4.0/). food, and carriers such as fomites (Figure 1). The risk of a zoonotic pathogen becoming human-to-human transmis- sible depends on its adaptation to the human host and the environment. To analyze this process, we considered fecal-oral transmission of a zoonotic pathogen between www.sciencedirect.com Current Opinion in Virology 2017, 22:1–6 2 Emerging viruses: intraspecies transmission Figure 1 Flies Fields/floors Feces of infected person Foods Fluids New Host Fingers Current Opinion in Virology Fecal-oral transmission between humans. After shedding from the host enteric pathogens can be transmitted between humans by the fecal-oral route via direct contact between humans, or via indirect contact via contaminated fluids, including surface water, food, and carriers such as fomites. two human hosts as follows; the human host that is Transmission amplifiers specific for fecal-oral infected with a zoonotic pathogen after a zoonotic event transmission is defined as the donor while the susceptible human host Several key transmission amplifiers are specific for fecal- that is subsequently infected by the first human host is oral transmission (Figure 2), such as the intestinal micro- considered the recipient. The transmission interface is biomes of the donor and recipient hosts. Individuals with the environment that the pathogen encounters after a healthy intestine are less likely to become infected or release from the donor and before infecting the recipient. colonized by opportunistic pathogens, although the resis- For sustained fecal-oral human-to-human transmission tance provided by a healthy colonization (microbiome) certain elements in this transmission cycle, which we will can, in principle, be disrupted by a pathogenic species refer to as transmission amplifiers, appear essential depending on its pathogenic potential (virulence) [6,7]. whereas other elements are not an absolute requirement, The composition of the human intestinal microbiome is, but increase the likelihood of transmission. Transmission amongst others dependent on the presence of a functional amplifiers may interact and their presence may or may not immune system [8–10]. Changes in microbiome compo- depend on conditions under which transmission occurs, sition, in addition to the impaired immunity itself, may including for example socio-economic conditions and impact the outcome of infection and subsequent trans- cultural and behavioral variation. We designed a frame- mission. work of human-to-human transmission that includes the transmission amplifiers relevant for the fecal-oral trans- Clinical symptoms such as diarrhea and vomiting can mission route at the levels of host, pathogen, and envi- increase the likelihood of fecal-oral transmission as ronment (Figure 2). they can facilitate the spread of a pathogen into the Current Opinion in Virology 2017, 22:1–6 www.sciencedirect.com Human-to-human transmission following a zoonotic event de Graaf et al. 3 Figure 2 Pathogen 1. Donor 2. Transmission Amplifiers 3. Recipient Host • Gut microbiome • Environmental microbiome • Gut microbiome Environment • Pathogenicity (ability to • Stability in the environment • Intestinal niche adaptations Specific for fecal-oral cause diarrhea) • Environment (climate) (low oxygen, acid) transmission route • Intestinal tract niche • Human behavior (hygiene, • Receptor expression in adaptation (persistence) agriculture, food processing) intestinal tract • Shedding in stool • Replication • Preexisting immunity • Immune function • Immune evasion • Immune evasion (pathogen) • Immune functions • Replication • Infectious dose • Pathogen genome plasticity • Receptor usage Current Opinion in Virology Framework for human-to-human transmission after a zoonotic event showing the key transmission amplifiers from the