PRESENTATION
BROCHURE ESSENTIAL GUIDES ON SWIN
HEALTH AND PRODUCTION
N onatal Diarrhoea Ana Carvajal Urueña Pedro Rubio Nistal Héctor Argüello Rodríguez Jaime Gómez Laguna Rubén Miranda Hevia
ESSENTIAL GUIDES ON SWINE HEALTH AND PRODUCTION
Neonatal Diarrhoea
ESSENTIAL GUIDES ON SWIN
HEALTH AND PRODUCTION
N onatal Diarrhoea Ana Carvajal Urueña Pedro Rubio Nistal Héctor Argüello Rodríguez Jaime Gómez Laguna Rubén Miranda Hevia
AUTHORS: Ana Carvajal Urueña, Pedro Rubio Nistal,
Héctor Argüello Rodríguez, Jaime Gómez Laguna and Rubén Miranda Hevia
FORMAT: 17 × 11 cm NUMBER OF PAGES: 90 NUMBER OF IMAGES: to be determined BINDING: softcover, wire-o
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This handbook aims to be a useful and practical tool for pig production companies and vets who have to tackle digestive diseases in piglets in their first few days of life. It includes chapters on the physiology and immunity of the piglet gastrointestinal tract, and the causes, diagnosis, and control strategies – those that are currently available and alternatives that will soon be developed – for the main agents that cause neonatal diarrhoea in pigs. The contents are the result of the joint work of renowned specialists with many years’ experience in enteric diseases in pigs.
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Neonatal Diarrhoea
Presentation of the book Newborn piglets are immature animals whose gastrointestinal tract is not fully developed. Their protection against pathogens depends on the passive immunity provided by sow colostrum and milk. Neonatal diarrhoea of infectious aetiology is one of the leading problems in swine production. To the pressure of intensive systems, the persistence of pathogens on pig farms, and the re-emergence of old known agents, such as the porcine epidemic diarrhoea virus, new factors are added that challenge piglet health. The most relevant of them are the generalisation of hyperprolific lines, with fewer energy and immune resources per piglet, and the increasing limitations on the use of antibiotics, due to both legislative restrictions and the lack of efficacy associated with the development of antibiotic resistance. The above are then compounded with an ethical component: the consumers’, breeders’, and veterinary practitioners’ concern for the wellbeing of the animals, which are very vulnerable in these early stages of life. A comprehensive understanding of the aetiological agents, of their pathogenic mechanisms, and of the epidemiology of the diseases they cause is therefore essential to implement adequate control measures. This manual aims to provide a clear and practical view of the enteric processes that affect piglets in the first days of life, and includes chapters on the physiology and immunity of the digestive tract, the aetiology of these processes, their diagnosis, and the principal control strategies currently available as well as the alternatives in the near future. This work is the result of the joint efforts of renowned specialists with years of experience in enteric diseases in swine, and aims to provide information of interest to veterinary practitioners faced with these problems in their daily work on farms, as well as to pig production companies. The authors
The authors Ana Carvajal Urueña Degree in veterinary medicine from the University of León (Spain) in 1990 and PhD in veterinary medicine from the same university in 1994. During her pre- and postdoctoral training, she completed various research fellowships at the Faculty of Veterinary Medicine of the University of Zurich (Switzerland). Since 2001 she has been a lecturer at the Department of Animal Health at the University of León, and has taught in the fields of infectious diseases, preventive medicine and epidemiology. She also teaches postgraduate students on different masters programmes related to research and pig production and health. She is a member of the DIGESPORC research group dedicated to the study of infectious enteric diseases in pigs. Within this group, she has participated in research related to diseases of viral origin, porcine epidemic diarrhoea, as well as conditions caused by bacteria, such as intestinal spirochaete infections, Lawsonia intracellularis infections, and porcine salmonellosis infections, among others. In 2005, she earned a diploma from the European College of Veterinary Public Health (ECHPV) in the speciality of population medicine.
Neonatal Diarrhoea
Pedro Rubio Nistal Degree in veterinary medicine from the University of Leรณn in 1981, having earned an extraordinary degree award, and PhD in veterinary medicine from the same university in 1988. During his postdoctoral training, he completed research fellowships at the Faculty of Veterinary Medicine of the University of Ghent (Belgium). He first held the position of assistant lecturer, and, in 1989, he was named a permanent lecturer of infectious diseases and epidemiology in the Department of Animal Health of the University of Leรณn. Since 2000 he has been the chair of the aforementioned department. He also teaches postgraduate students on different masters programmes related to research and pig production and health. He has been a diplomate of the European College of Porcine Health Management (ECPHM) since 2007. He was also a member of several expert committees in the European Union. He directs the DIGESPORC research group dedicated to the study of gastrointestinal infections in pigs. He has supervised 13 doctoral theses and directed and participated in government-funded and privately funded research projects on porcine gastrointestinal diseases of both viral aetiology (porcine epidemic diarrhoea, transmissible gastroenteritis) and bacterial aetiology (dysentery and spirochaetosis, salmonellosis, proliferative enteropathy, etc.). The DIGESPORC group is also currently conducting on research on gut microbiota and alternatives to antibiotic use. Coauthor of a patent for a swine dysentery vaccine and of another patent for a probiotic specific to piglets with the spin-off Aquilรณn CyL S.L., of which he is a founding partner and scientific director.
Héctor Argüello Rodríguez Degree in veterinary medicine from the University of León in 2007 and PhD in veterinary medicine from the same university in 2013. After earning his PhD, he moved on to work at the TEAGASC Agriculture and Food Development Authority (Ireland) as a postdoctoral researcher until early 2016. He is currently a “Juan de la Cierva” postdoctoral researcher in the Department of Genetics at the University of Córdoba (Spain). His research career has focused on the study of enteric diseases in pigs, with a special interest in porcine salmonellosis. His research focuses on the diagnosis and study of the pathogenesis of enteric diseases, the pig’s local and systemic immune response, and the treatment and control of these diseases. He is currently studying the influence of microbiota on enteric processes in pigs, alternatives to antibiotic therapy, and the host’s immune response. He has published 14 papers in international scientific journals, more than 20 papers in national and international congresses, and over 20 research articles in pig sector journals. He also lectures on microbiology, preventive medicine, infectious diseases, molecular microbiology, and veterinary biotechnology at the Faculties of Veterinary Medicine of the universities of León and Córdoba (Spain) and University College Dublin, and works as an advisor for undergraduate and postgraduate students. He has received several awards for his doctoral thesis and has been a member of the FAO expert committee in charge of preparing an opinion document on the control of Salmonella in pork and beef.
Neonatal Diarrhoea
Jaime Gómez Laguna Degree in veterinary medicine from the University of Córdoba in 2004, PhD in veterinary medicineand recipient of a doctoral award from the University of Córdoba in 2009. He has completed predoctoral and postdoctoral fellowships at different prestigious national and international institutions. He currently works at the University of Córdoba, as part as of the AGR-137 research group “Animal Pathology. Pathogenic Mechanisms”. Previously, he worked in the R&D Department of CICAP (Valle de los Pedroches agriculture and food quality and research centre) (2010–2015), and coordinated projects in the Primary Production Unit as the head of the AGR-263 research group “Agri-Food Research”. He teaches in the Department of Comparative Anatomy and Pathology of the University of Córdoba, as well as in different master’s degree programmes of the universities of Córdoba and Murcia on topics related to pig health and immunology. He is a member of the Spanish Society of Veterinary Pathology (SEAPV) and the European Society of Veterinary Pathology (ESVP).
Rubén Miranda Hevia Degree in veterinary medicine from the University of León in 2012. He is currently completing his doctoral thesis in the field of porcine gut microbiota. He has lectured in the fields of infectious diseases, preventive medicine, and epidemiology. He has given training courses on molecular techniques, written various papers for national and international congresses, and published articles in magazines specialised in pig production. He is a member of the DIGESPORC research group dedicated to the study of infectious enteric diseases in pigs. Within this group, he has actively participated in research on alternatives to the use of antibiotics, mainly probiotics and phytobiotics, evaluating their antimicrobial activity and mechanisms of action.
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His research focuses on the study of immunopathogenesis against viruses of interest for pigs, as well as on the diagnosis and impact of zoonotic pathogens, such as Salmonella and Mycobacterium tuberculosis complex. He has participated in numerous national and international research projects, with an emphasis on the pig health and management, which have led him to co-direct five doctoral theses, all on pig health. He is an editor and scientific reviewer for different scientific journals, as well as for international research projects (National Pork Board [USA], Alberta Livestock and Meat Agency [Canada], European Commission H2020, NSC [Poland]).
ESSENTIAL GUIDES ON SWIN
HEALTH AND PRODUCTION
N onatal Diarrhoea Ana Carvajal Urueña Pedro Rubio Nistal Héctor Argüello Rodríguez Jaime Gómez Laguna Rubén Miranda Hevia
Table of contents 1. Digestive tract structure and function Digestive tract structure Digestive tract function
2. Immunity in the piglet Intestinal defence mechanisms Maternal immunity
3. Main aetiological agents Bacterial diarrhoea Viral diarrhoea Parasitic diarrhoea (Cystoisospora suis) Novel agents involved in neonatal diarrhoea
4. Main diagnostic tools Clinical and pathological diagnosis Sample collection Laboratory diagnosis
5. Control Symptomatic treatment Aetiological treatment Immune prophylaxis Management during gestation, farrowing and lactation New control options Housing sows in groups during lactation
1
Digestive tract structure and function
Neonatal Diarrhoea
Digestive tract structure
6
Figure 1. Digestive tract of a newborn piglet, showing the oesophagus, stomach, small intestine, and large intestine.
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DIGESTIVE TRACT STRUCTURE AND FUNCTION
Stomach: ◗ Significant increase in stomach size in the first 3–4 days of life. ◗ Its secretory capacity (hydrochloric acid and pepsinogen) increases fivefold in the first week of life. Small intestine: ◗ Significant development in the last weeks of gestation, and even more so in the first 10 days of life. ◗ At the end of the foetal period, enterocyte digestive enzyme activity and glucose absorption capacity increase, preparing the piglet for a milk diet.
7
Large intestine: ◗ A little later, the incorporation of new foods and colonisation with diverse microbiota, particularly anaerobes, promotes development of the large intestine. ◗ Its limited development in newborn pigs prevents it from compensating for insufficient small intestine absorption.
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1
Digestive tract structure and function
Neonatal Diarrhoea
Structure of the intestine ◗ Mucosa: simple columnar epithelium (enterocytes and goblet cells), lamina propria and lamina muscularis mucosae. ◗ Submucosa: includes immune system cells (gut-associated lymphoid tissue).
Mucosa
◗ Muscular layer: two layers of smooth muscle arranged longitudinally and transversely. ◗ Serosa: connective tissue covered by a simple epithelium.
Submucosa Muscular layer
8
Serosa 1 mm
Figure 2. Cross-section of the small intestine of a piglet.
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DIGESTIVE TRACT STRUCTURE AND FUNCTION
Lumen
Mucosa
Intestinal villus
Microvilli or brush border
9
Submucosa Serosa
Muscular layer
Crypt of Lieberkühn
Tight junction
Enterocyte
Figure 3. The structure of the small intestine follows the four tunics characteristic of the digestive tract. From the outside in: serosa, muscular layer, submucosa and mucosa.
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1
Digestive tract structure and function
Neonatal Diarrhoea
The mucosa is the barrier between the external environment of the intestinal lumen, and the internal environment.
Microvilli
10
25 µm
Villi
1 mm
Figure 4. Given its tremendous functional importance, the mucosal surface area is maximised by microvilli in the apical border of enterocytes, the brush border (solid lines); intestinal villi, finger-like projections of the intestinal epithelium (dotted lines), and gross circular or transverse folds of the submucosa and mucosa (arrows).
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DIGESTIVE TRACT STRUCTURE AND FUNCTION
Intestinal villi These are the functional unit of this organ.
a 11
b 100 µm
Figure 5. At the base of the villi (a) are the crypts of Lieberkühn (b), which are glandular depressions with important secretory functions where the precursor cells of the mature cells forming the epithelium of the villi are located.
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1
Digestive tract structure and function
Neonatal Diarrhoea
◗ At birth, villi have an elongated, thin, finger-like shape. ◗ The villi undergo considerable development in the first days of the piglet’s life, with an increase in their height and width, together with a deepening of their crypts. ◗ In newborn piglets, a shortened cell renewal cycle of only 2–3 days is ensured by a high mitotic activity of stem cells in the crypts. Table 1. The principle cells in the mucosa of the small intestine and their function. Enterocytes (main cells) Goblet cells Enteroendocrine cells M cells Stem cells (crypts) Immature cells
12
Absorption and digestion Mucus production Production of different intestinal hormones and, thus, participation in regulatory processes Antigen uptake in intestinal mucosa Epithelial cell replacement Primarily a secretory function at the intermediate stage between the precursor cells in the crypts and the resultant mature cells
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DIGESTIVE TRACT STRUCTURE AND FUNCTION
Digestive tract function In the first weeks of life, the piglet receives a milk diet, which is perfectly adapted to the conditions of its digestive tract, reaching true digestibility coefficient values close to 100 %. In contrast, the intestine is not completely functional as a protective barrier in the first weeks of life, and a certain amount of time is required to complete its maturation.
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Digestion:
breakdown of complex molecules
Absorption:
transport of simple molecules 13
Barrier:
protection against pathogenic microorganisms
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1
Digestive tract structure and function
Neonatal Diarrhoea
Digestion: ◗ Carbohydrate digestion begins in the mouth with the incorporation of α-amylase from saliva. ◗ Protein digestion starts in the stomach through the action of pepsin generated from pepsinogen secreted in this organ and transformed into its active form at an acidic pH (production of HCl). ◗ Two types of digestion take place in the small intestine, the primary organ involved in digestion: luminal phase digestion, mediated by pancreatic enzymes (lipase, trypsin, and chymotrypsin) and by the bile, which permits the emulsification of fats; and secondly, membranous digestion mediated by enzymes produced by enterocytes (disaccharidase and peptidase).
14
Absorption: ◗ Absorption (simple diffusion, facilitated diffusion, and active transport) occurs mainly in the small intestine. ◗ The large intestine participates in the absorption of water, minerals, vitamins and other metabolites.
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DIGESTIVE TRACT STRUCTURE AND FUNCTION
Ion and water exchange The exchange of ions and water throughout the digestive tract plays a major role in the osmotic regulation of the body and is key in the mechanisms involved in neonatal diarrhoea. To better understand this process, it should be remembered that: ◗ Water exchange throughout the intestine is passive, as it follows the osmotic transport of electrolytes and nutrients.
15
◗ The mucosa of the small intestine is highly permeable to the passive exchange of water and small ions, which ensures that the contents of the small intestine are approximately isosmotic with the fluid in the interstitial spaces of the intestine. ◗ The absorption of sodium (Na+) takes place in the small intestine through a series of active transcellular mechanisms, which primarily depend on the ATP-driven Na+ pump located in the basement membrane of the enterocytes. Na+ ions are transported from inside the cell to the lateral intercellular space, causing water to enter from the intestinal lumen.
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1
Digestive tract structure and function Paracellular permeability
Tight junctions
Figure 6. The ATP-driven Na+ pump moves Na+ ions depending on the concentration gradient from inside the cell to the lateral intercellular space, causing water to enter from the intestinal lumen. Since cell membranes and tight junctions are highly permeable to water, the exchange is rapid through transcellular and paracellular pathways, allowing the differences in osmotic pressure between the intestinal lumen and the lateral intercellular spaces to be minimal.
Neonatal Diarrhoea
Na+
H2O
Microvilli
16
K+ Transcellular permeability
Na+
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DIGESTIVE TRACT STRUCTURE AND FUNCTION
Feeding the piglet The piglet’s first food is colostrum. The transition between colostrum and milk occurs between day two and three of lactation, with an increase in the concentration of fat (primary source of energy) and lactose and a decrease in protein. It should be noted that sow’s milk is deficient in iron and copper. Table 2. Composition
Colostrum (3 hours postpartum)
of sow’s milk and colostrum.
Crude protein:
Milk (day 7 of lactation)
g/kg
% energy
g/kg
% energy
175
56.5
56
21.5
Immunoglobulins
96
20
Albumin
47
13
Casein
32
23
Fat
67
36.1
101
65.0
Lactose
32
7.4
49
13.5
Lactoferrin
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1.1–1.3
17
0.3
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