bacterial infections of intestine in animals
TRANSCRIPT
Bacterial Infections of Intestine
Bacterial survival, persistence, and proliferation are controlled by virulence genes Bacterial virulence can be resolved into five
components: attachment colonization or entry into the host evasion of host defense multiplication and/or spread within the host, and
damage to the host, by direct virulence attributes, or by stimulation of an immunoinflammatory response
transmission to other susceptible animals.
Escherichia coli E.coli has several virulence factors which promote
colonization or adhesion to the mucosa they cause metabolic dysfunction or death of
enterocytes they affect the local or systemic vasculature or they promote invasion and septicemia.
"Enterotoxigenic" E. coli (ETEC) cause secretory small-bowel diarrhea
stimulated by enterotoxins Common cause of neonatal diarrhea in
many spp.
"Enteropathogenic" E. coli (EPEC) In humans may colonize the mucosa of the
intestine by a mechanism involving adhesion-effacement
Also called as "enteroadherent" E. coli- EAEC, or "attachingeffacing“ E. coli – AEEC
Uncommon in animals Some don’t produce toxins but cause villus atrophy Some secrete cytotoxins with local and systemic
effects e.g. shiga, verotoxins "Enteroinvasive" E. coli (EIEC) can be internalized
by surface enterocytes and subsequently septicemia develop
Enterotoxigenic colibacillosis Major forms of diarrhea in neonatal pigs,
calves, and lambs, as well as in humans. Mucosal colonization and toxin production are
important virulence attributes Toxins can stimulate electrolyte and water
secretion from the intestinal cells Colonization and enterotoxin production must
occur together for disease to ensue. Associated with minor microscopic
inflammation or limited or no architectural changes
Bacteria adhere to mucosa in small intestine and proliferate
Fimbriae, or pili (polymers of protein pilin) are colonization factors
Attach to specific glycoconjugate receptors on the surface of enterocytes
Age related ETEC produces two classes of plasmid encoded proteins-
heat-labile toxin (LT) and heat-stable toxin (ST) Heat-labile toxin cause chloride secretion by
enterocytes, sodium, and water following osmotically from the mucosa
Effects on the cell are irreversible
Heat-stable toxin (STa, STb) STa causes an increase in cyclic guanosine
monophosphate, which inhibits Na/C1 co-transpor and therefore water absorption by surface enterocytes,
while in crypt epithelium it promotes C1- and water secretion.
STb (in pigs mostly)may cause secretion by stimulation of prostaglandin E2 and 5-hydroxytryptamine production.
Exfoliation and atrophy of villi
At Necropsy : difficult to differentiate from other causes of diarrhea
Characteristic fluid content in the flaccid small and large bowel, usually with clotted milk still in the stomach
No other remarkable finding In contrast to the viruses and Isospora, ETEC
usually does not cause significant villus atrophy
Small clumps of bacteria may be found on surface of enterocytes especially in ileum
Some neutrophils in propria
Enterotoxic colibacillosis in a piglet. Villi are tall andcrypts are short, as is expected in a 2-3-day-old animal
Bacteria on the surface of enterocytes (arrow)
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Enterotoxic colibacillosis in a calf. Mild neutrophil infiltratein lamina propria and between base of villi, Atrophy of villi not
evident,surface epithelium normal. (Courtesy ofJJ Hadad, CL Gyles.)
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Enteropathogenic colibacillosis cause direct damage to the mucosa a characteristic mechanism of attachment to, and
effacement of epithelium More common in humans In animals rabbit, pigs, dogs Initial attachment by fimbriae Attachment causes secretion of bacterial proteins e.g. intimin Translocated intimin receptor, a bacterial protein is
transported into the cytoplasm of enterocytes This is then expressed as a receptor for intimin Reorganization of cellular cytoskeleton It results in formation of cupped pedestal-like structures
beneath the attached bacteria, and the subsequent loss of microvilli
Mild to severe atrophy of villi Attenuation of surface cells, or microerosions, in
the large intestine Fusion of villi may occur in small intestine, and
goblet-cell numbers are depleted in both large and small bowel.
Moderate mucosal congestion, and local infiltration by neutrophils.
A distinct subset of EPEC is the Shiga toxin-producing E. coli (STEC), also known as enterohemorrhagic E. coli (EHEC).
Inhibition of protein synthesis in target cells and induce apoptosis, some produce hemolysin
Animals may carry EHEC serotype O157:H7, a major pathogen in humans,
In calves under 4 weeks of age strains of EHEC have been associated with a syndrome of erosive fibrinohemorrhagic
enterocolitis and deysentery At necropsy, gross lesions are usually confined to the
spiral colon and rectum, Ileum and cecum are occasionally involved with mild
fibrinous or fibrinohemorrhagic enteritis/typhlitis In the colon, mild patchy congestion of the mucosa to
marked mucosal reddening, with adherent mucus, necrotic debris, and blood
colonic contents are fluid and frequently bloodtinged
Congestion of the margins of mucosal folds in the rectum, or overt fibrinohemorrhagic proctitis.
Mesenteric lymph nodes are often enlarged Microscopically, in affected small intestine the profile
of villi is ragged or markedly scalloped, and they are blunted, moderately atrophic, or fused.
Epithelial cells in colon and small bowel are short, rounded up, and in some cases exfoliating singly or in small clumps, causing focal microerosions
Coccobacilli Glands in the large bowel may be dilated, lined by
flattened epithelium, and filled with sloughed epithelium and leukocytes
TEM: Colon of a calf infected with enterohemorrhagic E.coli
Septicemic cotibacillosis commonly in calves results from reduced transfer or absorption of
maternal colostral immunoglobulin, or from intercurrent disease or debilitation.
Aerobactin produced by plasmid colV help in bacterial survival in low iron extracellular envoirnment
Endotoxin released by dying bacteria causes the vascular damage and shock
mildly congested or blue-red, slightly rubbery lungs, and
a firm spleen, evidence of omphalitis Serosal hemorrhage in severe acute cases with
hydropericardiaum, congestion of intestine
Subacute cases may develop localized infection on serous surfaces,in the joints and meninges.
Fibrinous peritonitis, pleuritis, and pericarditis, fibrinopurulent arthritis and meningitis, and
hypopyon
Salmonellosis S. bongori and S.enterica. six subspecies of S. enterica (enterica, salamae,
arizonae, diarizonae, indica, and houtenae) S. enterica enterica common in humans and animals S. enterica Typhimurium (new terminology writing
pattern, serotype capitalized not italicized ) S. Typhi (humans), S. Dublin (cattle), and S.
Choleraesuis (swine) S. Typhimurium,causes enterocolitis in young
animals in most species Asymptomatic Salmonella carriage may be common
Pathogenesis stages: entry of the bacteria into the host attainment of the primary site of infection,
usually the enterocyte attachment to the surface (colonization) invasion of enterocytes. minimal infective oral dose of 107-109 Must overcome the non specific resistance like
salivary enzymes, acid pH of the gastric environment. Mucus and lysozymes in the glycocalyx, peristalsis, and constant sloughing of enterocytes
Invading salmonella in some spp enter the mucosa through M cells in payer’s patches
In salmonellosis characterized by enterocolitis organism remains spread mesenteric lymph nodes
For bacteremia organism must survive in macrophages and disseminated including motility, pili, or fimbriae, effector proteins
Invasion of enterocytes, especially those in the ileum, occurs within 12 hours of oral infection with the help of type 3 protein
LPS containing serotypes can more efficiently survive in the pahgolysosomes
Diarrhea in salmonellosis is not mediated by enterotoxins
Effector proteins associated with SPI-1 induce secretory diarrhea by blocking chloride channel closure
Proteins encoded in SPI-5 also promote neutrophil recruitment and electrolyte secretion
Inflammation induced PG E2 which can cause chloride hypersecretion
Cellular death reduces absorptive surface area Thus diarrhea is an outcome of active secretion of
electrolyte, malabsorption due to reduced mucosal surface area and enterocyte competence, and inflammatory exudation
Pseudomembrane formation can occur Thrombosis of mucosal venules is common in
Salmonella enteritis Enteritis in salmonellosis is characterized
by fibrinous or fibrinohemorrhagic exudates Some salmonella strain may survive in
macrophages by inhibiting NADPH oxidase-mediated oxidative killing
These strains may cause septicemia The carrier state is important in the
epidemiology of the disease.
Salmonellosis in horses S. Typhimurium prevalence is increasing, especially that of
multidrug-resistant definitive phage type 104 Many horses are Salmonella carriers, and when
they are stressed, diarrhea follows. Abortion of pregnant mares has been associated
with S. Abortusequi Peracute, acute, chronic, asymptomatic carrier Septicemic form occur in 1-6 week age Diarrhea, often with characteristic green
color,blood, casts may be present Febrile , rapid death in 2-3 days
Acute septicemic cases show small hemorrhages on the serous or mucosal membranes
visceral lymph nodes are enlarged, juicy and hemorrhagic
Marked pulmonary congestion and edema, and renal cortical pallor and medullary congestion
Peracute lesions: intense hyperemia of the gastric mucosa, probably venous infarction, with some edema, hemorrahage
In acute cases, there is diffuse and intense fibrinohemorrhagic inflammation of the cecum and colon
gray-red pseudomembrane
In chronic salmonellosis extensive or patchy fibrinous or
ulcerative lesions of the cecum and colon Histologically, acute ileocecocolic
lymphadenitis, hemorrhage, necrosis, or diphtheresis intestine, fibrin thromobsis, mononuclear infiltration
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Salmonellosis in cattle S. Typhimurium and S. Dublin In calves, salmonellosis is a febrile disease typified by
dejection, dehydration, and usually diarrhea Feces are yellow or gray, may contain blood or mucous
foul odour Enlargement of mesenteric lymph nodes and gross
enteric lesions moderately severe gastrointestinal inflammation, acute
swelling, and hemorrhage of the visceral lymph nodes Enteritis may be catarrhal, but sometimes it is
hemorrhagic or more commonly causes exudation of yellow fibrin
mucosa overlying the lymphoid tissues may become necrotic and slough
In fibrinous enteritis,ground glass appearance of mucosa
Intestinal lesions are usually most severe in the ileum Microscopic lesions in intestine thin layer of
fibrinocellular exudate on the surface of short and blunt villi
Extensive necrosis and ulceration of the mucosa, with fibrin and neutrophils exuding from the ulcerated areas into the lumen
Mononuclear cells in lamina propria Fibrin thrombi are often evident in proprial capillaries
and venuels Centers of lymphoid follicles in the Peyer's patches are
completely involuted.
The liver is often pale with many minute paratyphoid nodules.
spleen, macrophage reaction is sometimes diffuse
diffuse. "Paratyphoid" granulomas may also be found
microscopically in the kidney, lymph nodes, and bone marrow.
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In subacute salmonellosis of calves, there may be cranial bronchopneumonia, usually with adhesions and abscessation.
Purulent exudate is in synovial cavities Salmonellosis in adult cattle may occur in
outbreaks Associated with chronic diarrhea and loss of
condition Carrier status for years, shed in milk
Yersiniosis Yersinia enterocolitica and Y. pseudotuberculosis are gram-
negative organisms. Enterocolitis, mesenteric lymphadenitis, and, less commonly,
septicemia in sheep, cattle, goats, deer, and pigs organisms invade through the intestinal epithelium or M cells Enormous recruitment of neutrophils and ensuing destruction of
cytoarchitecture of payer’s patches and overlying epithelium Mild gross lesions in subacute and chronic cases Abnormally fluid intestinal content, with congestion, edema,
roughening, and perhaps small loci of pallor, focal hemorrhages, erosion, or mild ulceration and fibrin effusion.
Raised nodules up to 5 mm in diameter, with depressed centers, may be evident in affected large bowel.
histologically by masses of gramnegative coccobacilliforming microcolonies, in the lamina propria of villi and around the necks of crypts
Microabscesses, moderate atrophy of villi and hyperplasia of crypts
In fulminant Yersinia infection in all species, there is fibrinous orfibrinohemorrhagic enterocolitis, caseous necrotic debris
Caseous mesenteric lymphadenitis, with mature pyogranulomas containing microcolonies of bacteria, surrounded by neutrophils and giant cells
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Enteritis associated with Campylobacter spp. Campylobacter jejuni and C. coli (important in
humans) C.jejuni, can cause enteritis in animals Many human infections are acquired by drinking
raw milk, or from other animal foodstuff, especially poultry products.
C. jejuni has been associated with bloody mucoid diarrhea in dogs
May cause Lymphoplasmacytic inflammation centered on ileum and colon
"Weaner colitis" is a diarrhea in sheep with high morbidity, southeastern Australia due to unidentified Campylobacter spp
Enteric clostridial infections Clostridium perfringens, five toxigenic spp C. difficile fibrinous enteritis, especially in
horses, neonatal pigs, and dogs C.piliforme (formerly Bacillus pilformis) causes
Tyzzer's disease, characterized by enteritis and colitis, usually with multifocal necrotic
hepatitis and myocarditis, C. chauvoei causing blackleg-like myositis C. septicum causes clostridial abomasitis
(braxy) in sheep, calves C. botulinum causes toxicoinfectious botulism
in horses, cattle
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Toxins alpha toxin is a lecithinase that acts on cell
membranes, producing hemolysis or necrosis of cells beta toxin is a poreforming toxin that
induces a variety of neurologic effects epsilon toxin is a protoxin iota toxin increases capillary permeability. Kappa toxin is a collagenase, and lambda a
nonspecific proteinase.
C. perfringens and C. difficile requires a change in the enteric microenvironment like change in feed, abnormally nutrient-rich
digesta, antibiotic therapy altered pancreatic exocrine function or trypsin inhibitors, reduced motility, and primary infections with agents such as
Canine parvovirus, or coccidia
Mechanism of disease production local necrotizing effects of toxin on the
mucosa, causing hemorrhagic, fibrinous, or necrotic enteritis
secretory effects of locally acting enterotoxin, causing diarrhea and minor mucosal lesions; or
systemic absorption of (entero) toxin, with effects at sites distant from the gut
Clostridium perfringens type A Most common of the five types microflora of both soil and intestinal tract major toxin is the alpha toxin, collagenase and
hyaluronidase minor toxins enteritis in foals; enterocolitis in horses; necrotizing enterocolitis in neonatal piglets; hemorrhagic enteritis in lambs and neonatal calves; diarrhea, and hemorrhagic enteritis in dogs; as well as necrotic enteritis in chickens. produce gas gangrene in humans and animals Foals: lesions localized to small intestine, the mucosa
of which was dark purple. Histologically: marked diffuse necrosis of the mucosa
white scours in suckling pigs and diarrhea in feeder pigs
necrotizing enterocolitis, villus atrophy, and serositis Hemorrhagic canine gastroenteritis:often found dead lying in a pool of bloody excreta; sometimes
hemorrhagic diarrhea is noted prior to death. Autopsy reveals hemorrhagic enteritis and colitis Hemorrhagic bowel syndrome has been
described in mainly dairy cattle in the USA. Acute illness, with bloating, gut stasis, and melena. Necrohemorrhagic enteritis with extensive
intraluminal hemorrhage
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Clostridium perfringens type B lamb and calf dysentery,usually in lambs up to
10-14 days Lambs may die without signs, Abdominal pain semifluid dark feces mixed or coated with blood abdomen is often tympanitic The characteristic lesion is extensive hemorrhagic
enteritis serous or blood-stained fluid in peritoneal cavity Penetrating ulcers and peritonitis in sever cases wall of the intestine is hemorrhagic, and the areas
of necrosis extend deeply into the mucous membrane,
liver is usually pale and friable, spleen is normal or slightly enlarged and
pulpy. kidneys may be enlarged, edematous, pale,
and soft from toxic degeneration pericardial sac contains abundant clear
gelatinous fluid, the myocardium is pale and soft, and hemorrhagic
Similar disease in calves
Clostridium perfringens type C Adult sheep and goats, feeder cattle, and in neonatal
lambs, calves, foals, and pigs. In adult sheep, C. pefringens type C causes "struck"a
disease of pastured animals, mortality rate of 5-15% Sometimes sudden death, sometime abdominal pain,
straining At necropsy,: the peritoneal cavity contains up to 3
liters of clear, pale-yellow fluid that clots on exposure to air
Becomes stained with hemoglobin if necropsy is delayed
small intestine is intensely hyperemic, either in patches or along most of its length with ulceration
primary intestinal lesion is superficial mucosal necrosis that advances more deeply, with a peripheral leukocytic reaction, congestion, and hemorrhage
disease in feedlot cattle is similar to "struck.“ jejunal and ileal content are bloody with fibrin
clots and necrotic debris. Excessive straw-colored pleural and
pericardial fluid and petechiation of epicardium and endocardium are
Clostridium perfringens type D Enterotoxemia ("pulpy kidney" disease, "overeating"
disease) sheep and goats Focal symmetrical encephalomalacia (FSE) of sheep is
caused by the epsilon toxin of type D. Toxin binds to receptors on endothelial cells, especially
in the brain and renal tubular epithelial cells Mostly course is peracute and the animal is found dead survivers show drooling,rapid breathing, hyperesthesia,
straining, opisthotonos, and terminal coma or convulsions.
In adult sheep, in which the clinical course may be several days, diarrhea with the passage of dark semifluid feces is common.
neurological signs may develop except in goats large amounts of grain or concentrate predisposes Starch helps in bacterial proliferation and toxins
production Toxin is absorbed through the mucosa Necropsy: Putrefactive changes occur rapidly. excessive straw-colored pericardial fluid congestion and edema of the lungs hemorrhage beneath the endocaMium of the left
ventricle Blotchy hemorrhages beneath the parietal peritoneum are characteristic
Liver congested, spleen enlarged pulpy Short lengths of the small intestine are
distended with gas, and are hyperemic. medullary congestion, hemorrhage, and
tubular degeneration but rapid autolysis or delayed necropsy can cause pulpy kidney
Hyperglycemia and glucosuria associated with the toxemia,
Brain lesions occur in lambs with subacute enterotoxemia
focal symmetrical encephalomalacia.
Pattern of brain lesion 1. basal ganglia, internal capsule, dorsolateral
thalamus,and substantia nigra are involved commonly
2. white matter of the frontal gyri, sparing only the communicating U fibers.
lesion begins with edema, leaking of plasma and RBC
Calves: Splenic swelling is more common in calves than in
lambs, and rapid autolysis of the kidney is not a prominent finding,
Histologically mild degeneration and necrosis of the epithelium of
the proximal convoluted tubules with edema, congestion,
and interstitial hemorrhage in the renal cortex, and congestion of the medulla (these are autolytic changes but are useful diagnostically); superficial desquamation in the intestine with
congestion, and numerous typical bacilli in the contents; congestion and hemorrhage of the spleen with
disruption ofreticulum; subepicardial hemorrhage and degeneration in the
Purkinje network; and proteinaceous edema fluid in the lungs
In goats peracute, acute, chronic, and subclinical. mild to severe hyperemia of the mucosa, especially
of the distal small intestine, cecum, and spiral colon The affected areas may be covered by a thin layer
of fibrin. The intestinal contents are olive-green to red and
mucoid. The mesenteric lymph nodes are enlarged and
edematous. Hydropericardium, pulmonary edema, and "pulpy"
kidneys may be seen, but are inconsistent, and brain lesions
are absent.
In natural cases, the microscopic lesions in the small intestine vary from a mild pleocellular leukocytic reaction in the lamina propria to a mild fibrinous, or, rarely, hemorrhagic enteritis.
the tips of the villi are necrotic, eroded, and covered by fibrinocellular exudates or blood.Villus atrophy may follow.
Clostridium perfringens type E cause intestinal disease in calves. Congested abomasum, hemorrhagic enteritis Acute death
Paratuberculosis (Johne's disease)
Mycobacterium avium subsp, paratuberculosis resistance to killing in macrophages marked loss of muscle mass and serous atrophy of fat
depots, intermandibular edema, and fluid effusion in the body cavities
Plaques of intimal fibrosis and mineralization may be evident in the thoracic aorta
The mesenteric nodes, particularly the ileocecat, are always enlarged, pale, and edematous, especially in the medulla.
Lymphangitis is common, diffuse thickening of the mucosa, which is folded into
transverse rugae, the crests of which may be congested.
transmural granulomatous enteritis Granulomatous lymphadenitis