Bovine cryptosporidiosis: impact, host-parasite interaction and control strategies

Thomson et al. Vet Res (2017) 48:42 DOI 10.1186/s13567-017-0447-0 Open Access REVIEW Bovine cryptosporidiosis: impact, host‑parasite interaction and control strategies Sarah Thomson1 , Carly A. Hamilton2, Jayne C. Hope2, Frank Katzer1, Neil A. Mabbott2, Liam J. Morrison2 and Elisabeth A. Innes1* Abstract Gastrointestinal disease caused by the apicomplexan parasite Cryptosporidium parvum is one of the most important diseases of young ruminant livestock, particularly neonatal calves. Infected animals may suffer from profuse watery diarrhoea, dehydration and in severe cases death can occur. At present, effective therapeutic and preventative measures are not available and a better understanding of the host–pathogen interactions is required. Cryptosporidium parvum is also an important zoonotic pathogen causing severe disease in people, with young children being particularly vulnerable. Our knowledge of the immune responses induced by Cryptosporidium parasites in clinically relevant hosts is very limited. This review discusses the impact of bovine cryptosporidiosis and describes how a thorough understanding of the host–pathogen interactions may help to identify novel prevention and control strategies. Table of contents 1 Introduction 1.1 Parasite life cycle 2 Bovine cryptosporidiosis 2.1 Prevalence 2.2 Economic and production impact 2.3 Zoonotic implications 2.4 Environmental impacts 3 Current control measures for bovine cryptosporidiosis 3.1 Farm management practices 3.2 Therapeutics 3.2.1 Livestock 3.2.2 Vaccines 4 Immunology of cryptosporidiosis 4.1 Innate immune response 4.1.1 Epithelial cells 4.1.2 Natural killer (NK) cells 4.1.3 γδ T cells 4.1.4 Dendritic cells (DCs) 4.1.5 Macrophages 4.2 Adaptive immune response 4.2.1 CD4+ T cells 4.2.2 Th1 immune responses 4.2.3 Th2 immune responses 4.2.4 Th17 immune responses 4.2.5 CD8+ T cells 4.2.6 B cells 4.2.7  Models to study the interaction between Cryptosporidium and the host 5 Concluding remarks *Correspondence: † Sarah Thomson and Carly A. Hamilton are joint first authors 1 Moredun Research Institute, Pentlands Science Park, Bush Loan, Edinburgh EH26 0PZ, Scotland, UK Full list of author information is available at the end of the article © The Author(s) 2017. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/ publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Thomson et al. Vet Res (2017) 48:42 1 Introduction Cryptosporidium parvum was first described in 1907 by Edward Ernst Tyzzer in the small intestine of mice [1]. Since then, over 30 species of Cryptosporidium have been described that infect a wide range of host species [2]. Several species infect cattle and have a significant impact upon animal health and production, especially in young calves. Unfortunately, relatively few tools are available to combat bovine cryptosporidiosis (no vaccine and one drug of limited utility), and our knowledge of host–pathogen interactions in the bovine host is also very limited. Addressing these important gaps in our understanding of bovine cryptosporidiosis will aid the development of interventions going forward. This review summarises our current understanding of bovine cryptosporidiosis, with a particular focus on what is currently known about the bovine immune response to this pathogen, and discusses avenues for new research to further our understanding of host-parasite interactions in bovine cryptosporidiosis. Cryptosporidiosis was first reported in cattle in the early 1970s [3], but the observed clinical disease could not be solely attributed to Cryptosporidium as there was Page 2 of 16 evidence of co-infection with other viral and bacterial pathogens. In 1983, neonatal diarrhoea in experimentally infected calves was reported with Cryptosporidium species as the single infective agent [4]. Cryptosporidiosis is now recognised as endemic in cattle worldwide and is one of the most important causes of neonatal enteritis in calves globally [5–7]. Veterinary surveillance reports show cryptosporidiosis has been the main diagnosed cause of enteritis in calves in the UK between 2007 and 2011 (Figure 1) [8]. 1.1 Parasite life cycle Cryptosporidium oocysts are transmitted between hosts via the faecal-oral route, either directly via contact with faeces from infected hosts, or indirectly through environmental contamination or ingestion of contaminated food or water. Following ingestion of infective Cryptosporidium oocysts by the host, the conditions in the gastrointestinal tract (low pH and body temperature) trigger oocyst excystation and four sporozoites are released (Figure 2A). Cryptosporidium parvum sporozoites adhere to epithelial cells (Figure 2B) of the ileum, specifically at the Figure 1 Pathogens causing diarrhoea in young calves. Cryptosporidium is the most commonly detected pathogen causing diarrhoea in calves less than 1 month of age as a proportion of diagnosable submissions 2007–2011 (veterinary investigation diagnosis analysis [VIDA]). Thomson et al. Vet Res (2017) 48:42 ileocaecal junction in the case of C. parvum. Following attachment, the sporozoites become incorporated within a parasitophorous vacuole formed by the host cell membrane yet remain extracytoplasmic. A feeder organelle, unique to Cryptosporidium and present in all intracellular stages, acts as the interface between the parasite and the host cell. The feeder organelle enables the parasite to obtain all necessary nutrients from the host while still being protected from the host immune response and hostile gut conditions (Figure 3). After the development of the feeder organelle the sporozoite itself becomes more spherical in shape and forms a trophozoite (Figure 2C). The parasite begins asexual reproduction (Figure 2D) and develops into a type I meront (Figure 2E) which releases merozoites. The merozoites that are formed within the type I meront can immediately re-infect the host, by invading neighbouring epithelial cells and beginning asexual reproduction again, or develop into a type II meront. Page 3 of 16 Type II meronts release four merozoites that initiate the sexual reproductive cycle. The released merozoites invade host cells and differentiate into either macrogamonts (Figure 2H) or microgamonts (Figure 2G). Microgamonts develop multiple nuclei and release free microgametes that penetrate and fertilise the macrogamete, producing a zygote (Figure 2I). Meiosis occurs and the zygote differentiates into four sporozoites as the oocyst develops and is rele (...truncated)