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Clostridium perfringens enteritis and enterotoxaemia

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Datasheet

Clostridium perfringens enteritis and enterotoxaemia

Summary

  • Last modified
  • 13 July 2017
  • Datasheet Type(s)
  • Animal Disease
  • Preferred Scientific Name
  • Clostridium perfringens enteritis and enterotoxaemia
  • Overview
  • Clostridium perfringens is an important cause of clostridial enteric disease in domestic animals, and a frequent cause of myonecrosis in both humans and domestic animals. C. perfringens type A is consi...

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PictureTitleCaptionCopyright
Cholangiohepatitis caused by Clostridium perfringens in broilers of 8 weeks of age.
TitlePathology. Clostridium perfringens infections in poultry.
CaptionCholangiohepatitis caused by Clostridium perfringens in broilers of 8 weeks of age.
CopyrightSri Poernomo
Cholangiohepatitis caused by Clostridium perfringens in broilers of 8 weeks of age.
Pathology. Clostridium perfringens infections in poultry.Cholangiohepatitis caused by Clostridium perfringens in broilers of 8 weeks of age.Sri Poernomo
Ulcerative enteritis caused by Clostridium perfringens in broilers of more than 1 year old.
TitlePathology. Clostridium perfringens infections in poultry.
CaptionUlcerative enteritis caused by Clostridium perfringens in broilers of more than 1 year old.
CopyrightSri Poernomo
Ulcerative enteritis caused by Clostridium perfringens in broilers of more than 1 year old.
Pathology. Clostridium perfringens infections in poultry.Ulcerative enteritis caused by Clostridium perfringens in broilers of more than 1 year old.Sri Poernomo

Identity

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Preferred Scientific Name

  • Clostridium perfringens enteritis and enterotoxaemia

International Common Names

  • English: clostridial enteritis, Clostridium perfringens types C, A, in suckling pigs; clostridial myositis in large animals; clostridial myositis, myonecrosis, malignant edema synonymous with gas gangrene, in large animals; clostridiosis; Clostridium perfringens associated diarrhea in pigs; Clostridium perfringens mastitis; Clostridium perfringens type A; enteritis; enterotoxaemia; enterotoxemia, Clostridium perfringens in cattle; enterotoxemia, Clostridium perfringens type D in sheep and goats; focal symmetrical encephalomalacia in sheep and goats; gangrene; gas gangrene; haemorrhagic enteritis; hemorrhagic enterotoxemia, Clostridium perfringens type C in sheep; lamb dysentery, Clostridium perfringens type B; myonecrosis; necrotic enteritis; necrotic enteritis in poultry, NetB, Clostridium perfringens type A; necrotic, ulcerative enteritis, Clostridium sp., in birds; necrotizing abomasitis, calves, Clostridium perfringens type A; necrotizing enteritis in foals, NetF, Clostridium perfringens type A; overeating disease; pulpy kidney disease; pulpy-kidney disease; struck, Clostridium perfringens type C in sheep; yellow lamb, Clostridium perfringens type A

Local Common Names

  • UK: struck

Overview

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Clostridium perfringens is an important cause of clostridial enteric disease in domestic animals, and a frequent cause of myonecrosis in both humans and domestic animals. C. perfringens type A is consistently recovered from both the intestinal tracts of animals and from the environment. Other types (B, C, D, and E) usually found in the intestinal tracts of normal animals, are less common, but can sometimes also be found in the environment in areas where disease produced by these organisms is endemic. Recovery of C. perfringens from tissues of dead animals must be viewed with caution, since this organism can sometimes be an invader from the gut after death.

Hosts/Species Affected

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For further information on hosts, see the text on Disease Course.

Different types of Clostridium perfringens

C. perfringens is traditionally divided into 5 types, A-E, based on the variable production of different mouse-lethal toxins (alpha toxin, CPA; beta toxin, CPB; epsilon toxin, ETX; iota toxin, ITX). This typing system is used globally but current understanding of C. perfringens as an enteric pathogen of animals shows that it is becoming archaic. In particular, the discovery in some type A strains of the critical role of the pore-forming toxin NetB in necrotic enteritis of poultry (Keyburn et al., 2008), of the pore-forming toxin NetF in necrotizing enteritis of foals and canine haemorrhagic gastroenteritis (Mehdizadeh Gohari et al., 2016), and of the association of the enterotoxin CPE in type A isolates from humans with food poisoning (Lindström et al., 2011; Xiao et al., 2102) or with antibiotic-associated diarrhoea (Sparks et al., 2001), have all revealed that there are distinct pathogenic subtypes of type A C. perfringens beyond those included in the 5 “traditional” types. There may be other pathogenic types but further work is required to show this as understanding of the role of C. perfringens in enteric disease of animals continues to evolve.

Recent molecular typing and genome sequencing studies have shown that these enteric subtypes of C. perfringens are characterised by the following features: (i) Their membership of clonal lineages, so that they represent expansion of particular strains; (ii) The presence of toxin genes (cpb, sometimes cpe, etx, itx, netB, netF), often present as part of a large pathogenicity locus and present on members of the large tcp family of C. perfringens conjugative plasmids. The tcp plasmid family possess regions (tcp) of genes for conjugative transfer functions that are common to members of this plasmid family. C. perfringens strains may carry several different large tcp plasmids, each encoding distinct toxin genes as well as larger regions (pathogenicity loci) associated with these toxins and also important for disease production (Li et al., 2013; Freedman et al., 2015). The basis of the unusual persistence in the bacterial host of several distinct toxin-bearing plasmids that have common tcp genetic regions has recently been clarified (Parreira et al., 2012; Lepp et al., 2013; Freedman et al., 2015).

Acquisition of one or more tcp-based virulence or toxin-bearing plasmids through conjugation is thought to be the critical event in the evolution of virulence in enteric pathogenic C. perfringens.  This is followed by clonal expansion of the strain that has acquired this virulence plasmid, in some cases combined with acquisition of additional different tcp-based virulence plasmids. Speculatively, this may also be followed by evolution of chromosomal genes in the host C. perfringens as part of increasing fitness as a pathogen (Lepp et al., 2013). Investigation of lineage differences in C. perfringens is the subject of active research largely based on genome sequencing (Hassan et al., 2015).

Besides the acquisition of toxin-bearing virulence plasmids and further host bacterial strain evolution, it is increasingly apparent that enteric C. perfringens can and have adapted to particular hosts such as chickens or swine, likely through evolution of genetic regions for specific adhesion systems that allow the bacterium to colonize specifically a specific animal species (Jost et al., 2006; Hibberd et al., 2011; Lepp et al., 2013; Mehdizadeh Gohari et al., 2015). The ability of enteric C. perfringens to adapt to particular hosts and to acquire animal host specific virulence plasmids is comparable to the evolution of the different enteric pathovars of Escherichia coli, another versatile and dynamic enteric pathogen of humans and animals.

Enteritis caused by type B, type C, and by selected type A strains usually involves the small intestine and is commonly seen in neonatal animals. The predilection for disease in neonatal farm animals occurs because of the inhibition of pancreatic trypsin in the small intestine by trypsin-inhibitory factors in colostrum. In older animals, such as chickens with avian necrotic enteritis, trypsin inhibition by feed components such as soy beans may also predispose to disease. The small intestine is usually protected from the action of clostridial toxins by their breakdown by trypsin once they have been secreted from the bacterium. Protease production by commensals in the large intestine also seems to destroy toxins secreted by C. perfringens. By contrast, type D C. perfringens disease is an enterotoxaemia that follows the systemic absorption of epsilon toxin from the small intestine after activation of the prototoxin by the action of trypsin.

There is a tendency to describe sudden death associated with large numbers of C. perfringens and small intestinal haemorrhage as “enterotoxaemia”. Many of these cases are associated with inflammation and marked intestinal haemorrhage and necrosis. They are thus best described as an enteritis; however toxins absorbed through damaged intestinal epithelium may lead to toxaemia and death. There is usually no enteritis and no intestinal inflammation present in cases of type D C. perfringens enterotoxaemia.

Current understanding of the different types of enteric C. perfringens is summarized in Table 1.

Table 1: Current understanding of the different types of Clostridium perfringens and their known or possible association with enteric disease in animals.

 

Type

Critical toxin

Animal species affected

Disease

A

NetB

Avian

Poultry necrotic enteritis, notably broiler chickens

NetF

Horses, dogs

Foal necrotizing enteritis; canine haemorrhagic gastroenteritis.

Unknown (CPA?)

Cattle, sheep

Clostridial abomasitis; may be caused by several pathogenic enteric clostridial species; details of the pathogenesis are still obscure. 

Unknown  (CPA?)

Cattle

Haemorrhagic enteritis (“enterotoxaemia”) of calves, especially Belgian Blue; pathogenesis is still obscure. 

Unknown, if any

Pigs

Suggested but unproven role in neonatal mild necrotizing enterocolitis of piglets.

Unknown (CPA?)

Sheep

“Yellow lamb disease”. Not well characterized, but possible “type A enterotoxaemia” characterized by generalized jaundice, haemoglobinuria and death.

B

CPB, ETX

Sheep

Lamb dysentery; chronic enteritis (“pine”) in older lambs.

C

CPB

Cows, goats, horses, humans, pigs, sheep

Haemorrhagic and/or necrotizing enteritis neonatal farm animals (calves, foals, goat kids, lambs, piglets), and others; humans (“pigbel”, “darmbrand”).

D

ETX

Goats, sheep, cows

Enterotoxaemia (“pulpy kidney disease”) of sheep and goats; enteritis adult goats; rarely enterotoxaemia in adult cattle.

E

ITX

Cows, rabbits, sheep

Haemorrhagic enteritis in calves and possibly lambs; possible enteritis in rabbits but may be a misdiagnosis for C. spiroforme enterocolitis; host range, disease and pathogenesis not clear.

 

Distribution

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Disease caused by C. perfringens is distributed worldwide. Myonecrosis (malignant oedema, gas gangrene) is primarily an endogenous infection mainly associated with type A strains and is globally distributed. It occurs wherever there are people and animals and wherever there is tissue trauma with contamination by faeces or soil. The enteritis strains (selected subtypes of type A, types B, and E) and enterotoxaemia strains (type D) are less universally distributed, but are nonetheless widely detected as causes of disease in domestic animals and, occasionally, in humans (type C). There are regional differences in prevalence, for example, type B strains are rare in North America, but regional differences are not well characterized.

Distribution Table

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The distribution in this summary table is based on all the information available. When several references are cited, they may give conflicting information on the status. Further details may be available for individual references in the Distribution Table Details section which can be selected by going to Generate Report.

Continent/Country/RegionDistributionLast ReportedOriginFirst ReportedInvasiveReferenceNotes

Asia

AzerbaijanReported present or known to be presentOIE Handistatus, 2005
BahrainCAB Abstracts data miningOIE Handistatus, 2005
BhutanNo information availableOIE Handistatus, 2005
Brunei DarussalamNo information availableOIE Handistatus, 2005
ChinaWidespreadWang HN et al., 1996
-Hong KongNo information availableOIE Handistatus, 2005
Georgia (Republic of)Last reported1995OIE Handistatus, 2005
IndiaOIE Handistatus, 2005
IndonesiaReported present or known to be presentOIE Handistatus, 2005
IranNo information availableOIE Handistatus, 2005
IraqReported present or known to be presentOIE Handistatus, 2005
IsraelReported present or known to be presentOIE Handistatus, 2005
JapanNo information availableOIE Handistatus, 2005
JordanReported present or known to be presentOIE Handistatus, 2005
KazakhstanDisease not reportedOIE Handistatus, 2005
Korea, DPRDisease not reportedOIE Handistatus, 2005
Korea, Republic ofReported present or known to be presentPark et al., 1994; OIE Handistatus, 2005
KuwaitDisease not reportedOIE Handistatus, 2005
LebanonNo information availableOIE Handistatus, 2005
Malaysia
-Peninsular MalaysiaDisease not reportedOIE Handistatus, 2005
-SabahDisease never reportedOIE Handistatus, 2005
-SarawakCAB Abstracts data miningOIE Handistatus, 2005
MongoliaReported present or known to be presentOIE Handistatus, 2005
MyanmarNo information availableOIE Handistatus, 2005
NepalNo information availableOIE Handistatus, 2005
OmanReported present or known to be presentOIE Handistatus, 2005
PhilippinesDisease not reportedOIE Handistatus, 2005
QatarDisease not reportedOIE Handistatus, 2005
Saudi ArabiaReported present or known to be presentOIE Handistatus, 2005
SingaporeDisease never reportedOIE Handistatus, 2005
Sri LankaDisease not reportedOIE Handistatus, 2005
SyriaReported present or known to be presentOIE Handistatus, 2005
TaiwanLast reported1998OIE Handistatus, 2005
TajikistanNo information availableOIE Handistatus, 2005
ThailandDisease not reportedOIE Handistatus, 2005
TurkeyLast reported1996Gozun and Kiran, 1999; OIE Handistatus, 2005
TurkmenistanNo information availableOIE Handistatus, 2005
United Arab EmiratesReported present or known to be presentWernery et al., 1996; OIE Handistatus, 2005
UzbekistanReported present or known to be presentOIE Handistatus, 2005
VietnamDisease never reportedOIE Handistatus, 2005
YemenNo information availableOIE Handistatus, 2005

Africa

AlgeriaReported present or known to be presentOIE Handistatus, 2005
AngolaReported present or known to be presentOIE Handistatus, 2005
BeninNo information availableOIE Handistatus, 2005
BotswanaReported present or known to be presentOIE Handistatus, 2005
Burkina FasoNo information availableOIE Handistatus, 2005
BurundiNo information availableOIE Handistatus, 2005
CameroonReported present or known to be presentOIE Handistatus, 2005
Cape VerdeNo information availableOIE Handistatus, 2005
Central African RepublicDisease not reportedOIE Handistatus, 2005
ChadNo information availableOIE Handistatus, 2005
Congo Democratic RepublicDisease not reportedOIE Handistatus, 2005
Côte d'IvoireLast reported1996OIE Handistatus, 2005
DjiboutiDisease not reportedOIE Handistatus, 2005
EgyptLast reported1996Hussein and Mustfa, 1999; OIE Handistatus, 2005
EritreaDisease not reportedOIE Handistatus, 2005
EthiopiaReported present or known to be presentOIE Handistatus, 2005
GhanaNo information availableOIE Handistatus, 2005
GuineaDisease never reportedOIE Handistatus, 2005
Guinea-BissauNo information availableOIE Handistatus, 2005
KenyaReported present or known to be presentOIE Handistatus, 2005
LibyaReported present or known to be presentOIE Handistatus, 2005
MadagascarDisease never reportedOIE Handistatus, 2005
MalawiNo information availableOIE Handistatus, 2005
MaliNo information availableOIE Handistatus, 2005
MauritiusDisease not reportedOIE Handistatus, 2005
MoroccoReported present or known to be presentOIE Handistatus, 2005
MozambiqueNo information availableOIE Handistatus, 2005
NamibiaReported present or known to be presentOIE Handistatus, 2005
NigeriaNo information availableAyoade et al., 1999; OIE Handistatus, 2005
RéunionNo information availableOIE Handistatus, 2005
RwandaNo information availableOIE Handistatus, 2005
Sao Tome and PrincipeCAB Abstracts data miningOIE Handistatus, 2005
SenegalNo information availableOIE Handistatus, 2005
SeychellesNo information availableOIE Handistatus, 2005
SomaliaNo information availableOIE Handistatus, 2005
South AfricaReported present or known to be presentOIE Handistatus, 2005
SudanDisease not reportedOIE Handistatus, 2005
SwazilandNo information availableOIE Handistatus, 2005
TanzaniaNo information availableOIE Handistatus, 2005
TogoNo information availableOIE Handistatus, 2005
TunisiaReported present or known to be presentOIE Handistatus, 2005
UgandaDisease not reportedOIE Handistatus, 2005
ZambiaNo information availableMunang'andu et al., 1996; OIE Handistatus, 2005
ZimbabweNo information availableOIE Handistatus, 2005

North America

BermudaDisease not reportedOIE Handistatus, 2005
CanadaReported present or known to be presentOIE Handistatus, 2005
MexicoDisease not reportedOIE Handistatus, 2005
USAReported present or known to be presentMadsen, 1995; Songer and Glock, 1998; OIE Handistatus, 2005

Central America and Caribbean

BarbadosOIE Handistatus, 2005
BelizeNo information availableOIE Handistatus, 2005
British Virgin IslandsDisease not reportedOIE Handistatus, 2005
Cayman IslandsLast reported1998OIE Handistatus, 2005
Costa RicaDisease never reportedOIE Handistatus, 2005
CubaLast reported1996OIE Handistatus, 2005
CuraçaoDisease not reportedOIE Handistatus, 2005
DominicaReported present or known to be presentOIE Handistatus, 2005
Dominican RepublicNo information availableOIE Handistatus, 2005
El SalvadorNo information availableOIE Handistatus, 2005
GuadeloupeNo information availableOIE Handistatus, 2005
GuatemalaDisease never reportedBuergelt et al., 1999; OIE Handistatus, 2005
HaitiDisease never reportedOIE Handistatus, 2005
HondurasDisease never reportedOIE Handistatus, 2005
JamaicaReported present or known to be presentOIE Handistatus, 2005
MartiniqueReported present or known to be presentOIE Handistatus, 2005
NicaraguaDisease never reportedOIE Handistatus, 2005
PanamaDisease not reportedOIE Handistatus, 2005
Saint Kitts and NevisNo information availableOIE Handistatus, 2005
Saint Vincent and the GrenadinesNo information availableOIE Handistatus, 2005
Trinidad and TobagoDisease never reportedOIE Handistatus, 2005

South America

ArgentinaReported present or known to be presentUzal et al., 1999; OIE Handistatus, 2005
BoliviaOIE Handistatus, 2005
BrazilReported present or known to be presentAzevado et al., 1998; OIE Handistatus, 2005
ChileReported present or known to be presentOIE Handistatus, 2005
ColombiaDisease not reportedOIE Handistatus, 2005
EcuadorNo information availableOIE Handistatus, 2005
Falkland IslandsDisease not reportedOIE Handistatus, 2005
French GuianaNo information availableOIE Handistatus, 2005
GuyanaDisease not reportedOIE Handistatus, 2005
ParaguayNo information availableOIE Handistatus, 2005
PeruOIE Handistatus, 2005
UruguayReported present or known to be presentOIE Handistatus, 2005
VenezuelaDisease not reportedOIE Handistatus, 2005

Europe

AndorraReported present or known to be presentOIE Handistatus, 2005
AustriaNo information availableOIE Handistatus, 2005
BelarusReported present or known to be presentOIE Handistatus, 2005
BelgiumNo information availableDaube et al., 1994a; Daube et al., 1994b; OIE Handistatus, 2005
Bosnia-HercegovinaNo information availableOIE Handistatus, 2005
BulgariaLast reported2001OIE Handistatus, 2005
CroatiaReported present or known to be presentOIE Handistatus, 2005
CyprusReported present or known to be presentOIE Handistatus, 2005
Czech RepublicNo information availableOIE Handistatus, 2005
DenmarkNo information availableOIE Handistatus, 2005
EstoniaOIE Handistatus, 2005
FinlandLast reported2000OIE Handistatus, 2005
FranceReported present or known to be presentOIE Handistatus, 2005
GermanyReported present or known to be presentJohannsen et al., 2000; OIE Handistatus, 2005
GreeceReported present or known to be presentKritas et al., 2000; OIE Handistatus, 2005
HungaryReported present or known to be presentOIE Handistatus, 2005
IcelandReported present or known to be presentOIE Handistatus, 2005
IrelandReported present or known to be presentOIE Handistatus, 2005
Isle of Man (UK)No information availableOIE Handistatus, 2005
ItalyNo information availableTerreni, 1999; OIE Handistatus, 2005
JerseyNo information availableOIE Handistatus, 2005
LatviaDisease never reportedOIE Handistatus, 2005
LiechtensteinDisease not reportedOIE Handistatus, 2005
LithuaniaCAB Abstracts data miningOIE Handistatus, 2005
LuxembourgDisease not reportedOIE Handistatus, 2005
MacedoniaReported present or known to be presentOIE Handistatus, 2005
MaltaLast reported2001OIE Handistatus, 2005
MoldovaReported present or known to be presentOIE Handistatus, 2005
NetherlandsReported present or known to be presentKlaasen et al., 1999; OIE Handistatus, 2005
NorwayReported present or known to be presentOIE Handistatus, 2005
PolandNo information availableOIE Handistatus, 2005
PortugalReported present or known to be presentOIE Handistatus, 2005
RomaniaMocanu, 1989; OIE Handistatus, 2005
Russian FederationReported present or known to be presentAndrosik and Moskalyova, 1999; OIE Handistatus, 2005
SlovakiaDisease not reportedOIE Handistatus, 2005
SloveniaDisease not reportedOIE Handistatus, 2005
SpainOIE Handistatus, 2005
SwedenReported present or known to be presentOIE Handistatus, 2005
SwitzerlandNo information availableKlaasen et al., 1999; OIE Handistatus, 2005
UKReported present or known to be presentChanter N et al., 1999; OIE Handistatus, 2005
-Northern IrelandReported present or known to be presentOIE Handistatus, 2005
UkraineOIE Handistatus, 2005
Yugoslavia (former)No information availableOIE Handistatus, 2005
Yugoslavia (Serbia and Montenegro)Reported present or known to be presentOIE Handistatus, 2005

Oceania

AustraliaReported present or known to be presentOIE Handistatus, 2005
French PolynesiaNo information availableOIE Handistatus, 2005
New CaledoniaReported present or known to be presentOIE Handistatus, 2005
New ZealandReported present or known to be presentOIE Handistatus, 2005
SamoaNo information availableOIE Handistatus, 2005
VanuatuDisease not reportedOIE Handistatus, 2005
Wallis and Futuna IslandsNo information availableOIE Handistatus, 2005

Pathology

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For information on pathology, see the text on Disease Course.

Diagnosis

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Clinical Diagnosis

Determining a role of C. perfringens in enteric disease depends on the clinical or pathological changes present, the demonstration of the presence of critical toxins or toxin genes (Table 1) and the exclusion of other pathogens.

C. perfringens is a common intestinal inhabitant of animals and humans. It is similar to Escherichia coli in that it rapidly colonizes the intestine following birth, to temporarily reach large numbers in both the small and large intestines, before settling down to maintain in the large bowel at numbers up to about 105 per gram of content. The prevalence of colonization decreases with age. Isolation of C. perfringens is therefore, on its own, inadequate for a diagnosis of C. perfringens enteric disease. It is necessary either to demonstrate the presence of the toxin or of toxin gene relevant to the particular infection and disease process


Lesions

These are briefly described in the text under Disease Course.


Differential Diagnosis


Confirmation of C. perfringens as the aetiological agent, by means of bacteriological culture and determination of toxin genotype or phenotype, is essential since disease caused by other agents or events may mimic infection by clostridia. In addition, C. perfringens is commonly normally present in the intestine or faeces. In particular sudden death, as can occur in enterotoxaemia, can have many causes, infectious and non-infectious. Haemorrhagic and necrotizing enteritis has a more limited array of potential causes, but processing of appropriate specimens will allow identification of the infecting type. The more mild forms of enteritis (mild necrotic enteritis in chickens) can be confused with other bacterial infections, as well as viral infections (such as rotavirus).


Laboratory Diagnosis


Key components of definitive diagnosis are bacteriological culture of appropriate specimens and toxin-typing or genotyping (PCR) of isolates, the demonstration in the intestine or faeces of specific toxins relevant to the particular disease, or the demonstration of toxin DNA in the intestine by real time-PCR, or combinations of these approaches.

Demonstration of major toxins by in vivo (mouse) assays is now widely regarded as inhumane and is now rarely or never used. The use of animals for diagnosis has been largely replaced by PCR for specific genes on C. perfringens isolates recovered in large numbers from the affected intestine or faeces, or by quantitative (real time, RT) PCR on faeces or intestinal content. Immunoassays (ELISA) for intestinal toxin such as ETX are sometimes also used. Caution is needed with the use of direct faecal RT-PCR since some laboratories incorrectly regard the presence of the cpa gene above certain numbers as evidence of type A-associated disease. Since C. perfringens often normally colonizes the intestine, the detection of the cpa gene alone (and likely also the CPA protein) as a diagnostic marker may be highly misleading. The sensitivity and specificity of ELISA detection of the CPE enterotoxin in diagnosis of enterotoxin-associated enteric disease in animals has not been characterized but false-positives have been identified in dogs and in horses, so that cautious interpretation of this approach to diagnosis of CPE-associated disease is also required.

With the exception of enterotoxaemia associated with ETX-producing C. perfringens, histopathology of intestine tissue will often reveal characteristic necrotizing changes as well as the characteristic presence of large numbers of C. perfringens lining the necrotic epithelial surface. Histopathological changes of microangiopathy with perivascular proteinaceous oedema in the brain are pathognomic in type D infection in sheep and are present in about 90% of cases (Uzal and Songer, 2008). The detection of urinary glucose is supportive of the diagnosis. There are rare reports of “type A enterotoxaemia” in lambs characterised by generalised jaundice, haemoglobinuria and periacinar necrosis of the liver, among other necropsy findings (McGowan et al., 1958; Uzal and Songer, 2008); in one of the reports epsilon toxin was also detected (Uzal and Songer, 2008). The current method of diagnosis of type A enteritis in neonatal piglets is based on isolation of large numbers of C. perfringens type A possessing the consensus cpb2 gene detected by polymerase chain reaction (PCR) from the faeces or intestinal contents, and the exclusion of other known causes of neonatal diarrhoea (Songer and Uzal, 2005). This diagnostic approach is not however specific since cpb2-positive C. perfringens are usually present in large numbers in the small bowel of young piglets (Chan et al., 2013; Farzan et al., 2013).

List of Symptoms/Signs

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SignLife StagesType
Cardiovascular Signs / Prolonged capillary refill time Sign
Cardiovascular Signs / Tachycardia, rapid pulse, high heart rate Sign
Cardiovascular Signs / Tachycardia, rapid pulse, high heart rate Sign
Cardiovascular Signs / Tachycardia, rapid pulse, high heart rate Sign
Cardiovascular Signs / Tachycardia, rapid pulse, high heart rate Sign
Digestive Signs / Abdominal distention Sign
Digestive Signs / Abdominal distention Sign
Digestive Signs / Anorexia, loss or decreased appetite, not nursing, off feed Sign
Digestive Signs / Anorexia, loss or decreased appetite, not nursing, off feed Sign
Digestive Signs / Anorexia, loss or decreased appetite, not nursing, off feed Sign
Digestive Signs / Anorexia, loss or decreased appetite, not nursing, off feed Sign
Digestive Signs / Anorexia, loss or decreased appetite, not nursing, off feed Sign
Digestive Signs / Anorexia, loss or decreased appetite, not nursing, off feed Sign
Digestive Signs / Anorexia, loss or decreased appetite, not nursing, off feed Sign
Digestive Signs / Anorexia, loss or decreased appetite, not nursing, off feed Sign
Digestive Signs / Anorexia, loss or decreased appetite, not nursing, off feed Sign
Digestive Signs / Anorexia, loss or decreased appetite, not nursing, off feed Sign
Digestive Signs / Bloat in ruminants, tympany Sign
Digestive Signs / Bloat in ruminants, tympany Sign
Digestive Signs / Bloody stools, faeces, haematochezia Cattle & Buffaloes:Calf,Pigs:Piglet,Sheep & Goats:Lamb Sign
Digestive Signs / Congestion oral mucous membranes, erythema, redness oral mucosa Sign
Digestive Signs / Congestion oral mucous membranes, erythema, redness oral mucosa Sign
Digestive Signs / Diarrhoea Cattle & Buffaloes:Calf,Poultry:Young poultry,Pigs:Piglet,Sheep & Goats:All Stages Sign
Digestive Signs / Dysphagia, difficulty swallowing Sign
Digestive Signs / Dysphagia, difficulty swallowing Sign
Digestive Signs / Excessive salivation, frothing at the mouth, ptyalism Sign
Digestive Signs / Grinding teeth, bruxism, odontoprisis Sign
Digestive Signs / Inability to open (trismus) and / or close jaw, mouth Sign
Digestive Signs / Mucous, mucoid stools, faeces Sign
Digestive Signs / Mucous, mucoid stools, faeces Sign
Digestive Signs / Mucous, mucoid stools, faeces Sign
Digestive Signs / Mucous, mucoid stools, faeces Sign
Digestive Signs / Rumen hypomotility or atony, decreased rate, motility, strength Sign
Digestive Signs / Rumen hypomotility or atony, decreased rate, motility, strength Sign
Digestive Signs / Steatorrhea, fatty stools, faeces Sign
Digestive Signs / Unusual or foul odor, stools, faeces Sign
General Signs / Abnormal proprioceptive positioning, knuckling Sign
General Signs / Ataxia, incoordination, staggering, falling Sheep & Goats:All Stages Sign
General Signs / Back swelling, mass back region Sign
General Signs / Cyanosis, blue skin or membranes Sign
General Signs / Cyanosis, blue skin or membranes Sign
General Signs / Cyanosis, blue skin or membranes Sign
General Signs / Dehydration Sign
General Signs / Dehydration Sign
General Signs / Dehydration Sign
General Signs / Dehydration Sign
General Signs / Dehydration Sign
General Signs / Dysmetria, hypermetria, hypometria Sign
General Signs / Dysmetria, hypermetria, hypometria Sign
General Signs / Dysmetria, hypermetria, hypometria Sign
General Signs / Dysmetria, hypermetria, hypometria Sign
General Signs / Exercise intolerance, tires easily Sign
General Signs / Fever, pyrexia, hyperthermia Sign
General Signs / Fever, pyrexia, hyperthermia Sign
General Signs / Fever, pyrexia, hyperthermia Sign
General Signs / Fever, pyrexia, hyperthermia Sign
General Signs / Fever, pyrexia, hyperthermia Sign
General Signs / Forelimb lameness, stiffness, limping fore leg Sign
General Signs / Forelimb swelling, mass in fore leg joint and / or non-joint area Sign
General Signs / Generalized lameness or stiffness, limping Sign
General Signs / Generalized weakness, paresis, paralysis Sign
General Signs / Generalized weakness, paresis, paralysis Sign
General Signs / Generalized weakness, paresis, paralysis Sign
General Signs / Generalized weakness, paresis, paralysis Sign
General Signs / Generalized weakness, paresis, paralysis Sign
General Signs / Generalized weakness, paresis, paralysis Sign
General Signs / Head, face, ears, jaw, nose, nasal, swelling, mass Sign
General Signs / Hindlimb lameness, stiffness, limping hind leg Sign
General Signs / Hindlimb swelling, mass in hind leg joint and / or non-joint area Sign
General Signs / Hypothermia, low temperature Sign
General Signs / Hypothermia, low temperature Sign
General Signs / Hypothermia, low temperature Sign
General Signs / Icterus, jaundice Sign
General Signs / Icterus, jaundice Sign
General Signs / Inability to stand, downer, prostration Sign
General Signs / Inability to stand, downer, prostration Sign
General Signs / Inability to stand, downer, prostration Sign
General Signs / Inability to stand, downer, prostration Sign
General Signs / Inability to stand, downer, prostration Sign
General Signs / Increased mortality in flocks of birds Poultry:Young poultry Sign
General Signs / Lack of growth or weight gain, retarded, stunted growth Sign
General Signs / Mammary gland swelling, mass, hypertrophy udder, gynecomastia Sign
General Signs / Mammary gland swelling, mass, hypertrophy udder, gynecomastia Sign
General Signs / Neck swelling, mass cervical region Sign
General Signs / Opisthotonus Sheep & Goats:All Stages Sign
General Signs / Orbital, periorbital, periocular, conjunctival swelling, eyeball mass Sign
General Signs / Pale mucous membranes or skin, anemia Sign
General Signs / Pale mucous membranes or skin, anemia Sign
General Signs / Paraparesis, weakness, paralysis both hind limbs Sign
General Signs / Pelvic or perineal swelling, mass Sign
General Signs / Petechiae or ecchymoses, bruises, ecchymosis Sign
General Signs / Reluctant to move, refusal to move Sign
General Signs / Reluctant to move, refusal to move Sign
General Signs / Sudden death, found dead Cattle & Buffaloes:Calf,Poultry:Young poultry,Sheep & Goats:All Stages Sign
General Signs / Sweating excessively, hyperhidrosis Sign
General Signs / Swelling mass anus rectum Sign
General Signs / Swelling mass penis, prepuce, testes, scrotum Sign
General Signs / Swelling mass, vulva, clitoris Sign
General Signs / Swelling mass, vulva, clitoris Sign
General Signs / Swelling, mass external abdomen Sign
General Signs / Tenesmus, straining, dyschezia Sign
General Signs / Tenesmus, straining, dyschezia Sign
General Signs / Thoracic swelling, mass, thorax, chest, ribs, sternum Sign
General Signs / Trembling, shivering, fasciculations, chilling Sign
General Signs / Trembling, shivering, fasciculations, chilling Sign
General Signs / Trembling, shivering, fasciculations, chilling Sign
General Signs / Trembling, shivering, fasciculations, chilling Sign
General Signs / Trembling, shivering, fasciculations, chilling Sign
General Signs / Underweight, poor condition, thin, emaciated, unthriftiness, ill thrift Sign
General Signs / Underweight, poor condition, thin, emaciated, unthriftiness, ill thrift Sign
General Signs / Underweight, poor condition, thin, emaciated, unthriftiness, ill thrift Sign
General Signs / Weight loss Sign
General Signs / Weight loss Sign
Musculoskeletal Signs / Back or thoracic crepitation, crepitus chest, ribs Sign
Musculoskeletal Signs / Forelimb crepitation, crepitus front leg Sign
Musculoskeletal Signs / Head or neck crepitation, crepitus Sign
Musculoskeletal Signs / Hindlimb or pelvic crepitation, crepitus rear leg, pelvis Sign
Nervous Signs / Abnormal behavior, aggression, changing habits Sign
Nervous Signs / Circling Sign
Nervous Signs / Coma, stupor Cattle & Buffaloes:Calf,Sheep & Goats:All Stages Sign
Nervous Signs / Constant or increased vocalization Sign
Nervous Signs / Constant or increased vocalization Sign
Nervous Signs / Dullness, depression, lethargy, depressed, lethargic, listless Sign
Nervous Signs / Dullness, depression, lethargy, depressed, lethargic, listless Sign
Nervous Signs / Dullness, depression, lethargy, depressed, lethargic, listless Sign
Nervous Signs / Dullness, depression, lethargy, depressed, lethargic, listless Sign
Nervous Signs / Dullness, depression, lethargy, depressed, lethargic, listless Sign
Nervous Signs / Dullness, depression, lethargy, depressed, lethargic, listless Sign
Nervous Signs / Dullness, depression, lethargy, depressed, lethargic, listless Sign
Nervous Signs / Dullness, depression, lethargy, depressed, lethargic, listless Sign
Nervous Signs / Dullness, depression, lethargy, depressed, lethargic, listless Sign
Nervous Signs / Dullness, depression, lethargy, depressed, lethargic, listless Sign
Nervous Signs / Dullness, depression, lethargy, depressed, lethargic, listless Sign
Nervous Signs / Excitement, delirium, mania Sign
Nervous Signs / Head pressing Sign
Nervous Signs / Head pressing Sign
Nervous Signs / Hyperesthesia, irritable, hyperactive Sign
Nervous Signs / Propulsion, aimless wandering Sign
Nervous Signs / Propulsion, aimless wandering Sign
Nervous Signs / Propulsion, aimless wandering Sign
Nervous Signs / Seizures or syncope, convulsions, fits, collapse Sign
Nervous Signs / Seizures or syncope, convulsions, fits, collapse Sign
Nervous Signs / Seizures or syncope, convulsions, fits, collapse Sign
Nervous Signs / Seizures or syncope, convulsions, fits, collapse Sign
Nervous Signs / Seizures or syncope, convulsions, fits, collapse Sign
Nervous Signs / Tremor Sign
Nervous Signs / Tremor Sign
Nervous Signs / Tremor Sign
Ophthalmology Signs / Blindness Sign
Ophthalmology Signs / Blindness Sign
Ophthalmology Signs / Nystagmus Sign
Ophthalmology Signs / Nystagmus Sign
Ophthalmology Signs / Strabismus Sign
Pain / Discomfort Signs / Colic, abdominal pain Cattle & Buffaloes:Calf,Sheep & Goats:All Stages Sign
Pain / Discomfort Signs / Pain mammary gland, udder Sign
Pain / Discomfort Signs / Pain mammary gland, udder Sign
Pain / Discomfort Signs / Pain on external abdominal pressure Sign
Pain / Discomfort Signs / Pain, neck, cervical, throat Sign
Pain / Discomfort Signs / Skin pain Sign
Reproductive Signs / Agalactia, decreased, absent milk production Sign
Reproductive Signs / Agalactia, decreased, absent milk production Sign
Reproductive Signs / Agalactia, decreased, absent milk production Sign
Reproductive Signs / Bloody milk, red, pink, brown milk Sign
Reproductive Signs / Cold mammary gland, cool udder Sign
Reproductive Signs / Edema of mammary gland, udder Sign
Reproductive Signs / Firm mammary gland, hard udder Sign
Reproductive Signs / Mastitis, abnormal milk Sign
Reproductive Signs / Mastitis, abnormal milk Sign
Reproductive Signs / Slough of mammary gland, udder Sign
Reproductive Signs / Warm mammary gland, hot, heat, udder Sign
Reproductive Signs / Warm mammary gland, hot, heat, udder Sign
Respiratory Signs / Abnormal breathing sounds of the upper airway, airflow obstruction, stertor, snoring Sign
Respiratory Signs / Dyspnea, difficult, open mouth breathing, grunt, gasping Sign
Respiratory Signs / Dyspnea, difficult, open mouth breathing, grunt, gasping Sign
Respiratory Signs / Increased respiratory rate, polypnea, tachypnea, hyperpnea Sign
Respiratory Signs / Increased respiratory rate, polypnea, tachypnea, hyperpnea Sign
Skin / Integumentary Signs / Cold skin, cool ears, extremities Sign
Skin / Integumentary Signs / Cold skin, cool ears, extremities Sign
Skin / Integumentary Signs / Cold skin, cool ears, extremities Sign
Skin / Integumentary Signs / Cold skin, cool ears, extremities Sign
Skin / Integumentary Signs / Cracked skin, fissure Sign
Skin / Integumentary Signs / Foul odor skin, smell Sign
Skin / Integumentary Signs / Moist skin, hair or feathers Sign
Skin / Integumentary Signs / Ruffled, ruffling of the feathers Sign
Skin / Integumentary Signs / Skin edema Sign
Skin / Integumentary Signs / Skin erythema, inflammation, redness Sign
Skin / Integumentary Signs / Skin erythema, inflammation, redness Sign
Skin / Integumentary Signs / Skin necrosis, sloughing, gangrene Sign
Skin / Integumentary Signs / Skin necrosis, sloughing, gangrene Sign
Skin / Integumentary Signs / Skin ulcer, erosion, excoriation Sign
Skin / Integumentary Signs / Subcutaneous crepitation, skin emphysema Sign
Skin / Integumentary Signs / Subcutaneous crepitation, skin emphysema Sign
Skin / Integumentary Signs / Warm skin, hot, heat Sign
Urinary Signs / Glucosuria Sign
Urinary Signs / Haemoglobinuria or myoglobinuria Sign
Urinary Signs / Haemoglobinuria or myoglobinuria Sign
Urinary Signs / Red or brown urine, pink Sign
Urinary Signs / Red or brown urine, pink Sign

Disease Course

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Type A

Type A C. perfringens is the most widespread type found in the intestines or faeces of animals, in the environment, and as causes of histotoxic infection (including wound contamination, anaerobic cellulitis, gangrenous mastitis, and gas gangrene/malignant oedema). The different enteric diseases associated or possibly associated with type A strains have been outlined in Table 1.

Necrotic enteritis of domestic poultry is almost invariably caused by netB-positive strains of type A C. perfringens, although type C strains have been rarely described as a cause of this disease. Diarrhoea may occur, but usually no signs are observed and birds are simply found dead. Patches of or focal necrosis is common in the small intestine (jejunum, ileum) but the caecal or colonic intestinal mucosa is often free of necrosis. The affected area of intestine often contains foul-smelling gas, and is commonly thin-walled and friable. The mucosal surface may have irregular areas of ulceration surrounded by fibrin and necrosis, or be characterised by a thick “Turkish towel” appearance of necrotic cells and debris in a fibrinous consolidated exudate. Microscopic lesions are those of extensive necrosis that can extend into the submucosa. A clear demarcation between necrotic and viable tissue is often marked by the presence of tightly adhering C. perfringens. “Subclinical” necrotic enteritis is associated with generalized mild superficial necrosis in the small intestine, sometimes with focal ulcerative necrosis, but without mortality. Concurrent infection with coccidia can predispose birds to necrotic enteritis.

Necrotizing enteritis of neonatal foals has been shown to be caused by netF-positive strains of type A C. perfringens (Mehdizadeh Gohari et al., 2015). Most foals with NetF-positive type A C. perfringens-associated enterocolitis are younger than six days of age, with no breed or gender predisposition. The disease may start as early as 12-24 hours of age, and foals may die within 24 hours of onset of disease. Foals are usually diarrhoeic, dull and depressed, colicky, and dehydrated. Intestinal pain can be intense. Metabolic acidosis and other electrolyte disturbances are common. The gross pathology of fatal cases of netF-positive foal necrotizing enterocolitis is characterized by fibrinonecrotic enterocolitis, in some cases with intestinal mural emphysema. Disease may develop into a severe chronic localized region of necrosis in the small intestine. The villus epithelium in the small intestine shows acute coagulative necrosis, separated from the underlying more viable tissue by a band of mostly neutrophilic infiltration. Large numbers of Gram-positive rods adhering to the necrotic intestinal mucosa are a prominent characteristic.

Type A C. perfringens has been described as the cause of mild necrotizing enterocolitis and villous atrophy in neonatal pigs, with primary lesions in the jejunum and ileum. This disease has not been well characterized and experimental reproduction of the disease in piglets has not been well controlled and convincing.  Diagnosis of neonatal piglet diarrhoea apparently due to C. perfringens type A has increased, and has been associated with increased pre-weaning mortality. Disease can develop in suckling pigs in the first week of life, and typical clinical signs include non-haemorrhagic, mucoid diarrhoea seen within 48 h of birth, and lasting for 5 days (Songer and Uzal, 2005; Schwartz, 2009). Further research is required to demonstrate that type A C. perfringens is a cause of neonatal enteritis in swine (Chan et al., 2013).

Acute clostridial abomasitis occurs sporadically in pre-ruminant calves, ranging in age from two days to about three weeks.  The condition may present as acute diffuse abomasitis, the most widely recognized presentation, but also as severe abomasal bloat or deep to perforating abomasal ulcers (Van Kruiningen et al., 2009). Histologically, coagulation necrosis of the mucosal surface and emphysema of the mucosa and submucosa with oedema of the lamina propria and submucosa are prominent features. Severe clostridial enteritis may occur with or without abomasitis in the same outbreak. C. perfringens type A is commonly isolated in large numbers from the abomasum in fatal cases of abomasitis in young calves. Calves affected may be of beef breeds suckling on their mother on pasture, or dairy calves reared without their mother and being fed pooled stored colostrum or milk replacer. The disease is usually peracute. Clostridial abomasitis has also been observed in three- to four-month-old beef calves, in which the disease was attributed to ingestion of coarse roughage as the amount of milk ingested decreased. In the single experimental study that has reproduced the disease, inoculation of C. perfringens type A into the rumen of healthy calves resulted in anorexia, bloat, depression, diarrhoea and, in some cases, death (Roeder et al., 1988). Necropsy showed variable degrees of abomasitis that included petechial and/or ecchymotic haemorrhages and ulcers of variable size and depth, including those that were almost perforating. The generally sporadic nature of clostridial abomasitis complicates understanding of the disease and consequently its effective diagnosis, treatment and control. Genome analysis failed to identify type A C. perfringens strains uniquely associated with abomasitis (Nowell et al., 2012; Schegel et al., 2012).

Haemorrhagic enteritis, sometimes described as “enterotoxaemia”, occurs in young calves fed cows’ milk or milk replacer and is characterized by sudden death with diffuse small intestinal haemorrhage and bloody intestinal content (Muylaert et al., 2010). Small intestinal microscopic lesions are those of haemorrhage and necrosis from the villi to the crypts. It is seen especially in Belgian Blue calves, a breed that because of its size and conformation is always born by Caesarian section. Large numbers of type A C. perfringens are isolated from the intestine. Despite extensive investigation, the basis of this disease is still not well characterized (Valgaeren et al., 2013) but, like clostridial abomasitis with which the disease presentation overlaps, may be associated with the alpha-toxin (CPA) production in the intestine.

Strains of type A are also implicated in enteric diseases, including lamb enterotoxaemia (yellow lamb disease). This occurs sporadically and in apparently weather-related cycles in the Pacific Northwest of the USA (Fleming, 1985; McGowan et al., 1958). Affected animals have icterus and haemoglobinuria, and usually die rapidly. Large numbers of C. perfringens (up to 107 per gram of content) are often found in small intestinal contents. A recent study of yellow lamb disease was associated with a type D C. perfringens (Giannitti et al., 2014).

The role of CPE-producing type A strains in diarrhoeal disease of animals is totally unclear. False-positive enterotoxin ELISA data have led to misleading suggestions of a role in diarrhoeal illness in horses and dogs. In humans, CPE-producing type A have, however, been associated with antibiotic-associated and sporadic diarrhoeal illness (Collie et al., 1998). Further investigation of this area is required. As an important generalization, the relative infrequency of cpe-positive type A C. perfringens in farm animals suggests that these strains are not involved in enteric disease in farm animals.

Type B

Type B causes lamb dysentery, in which the infection is acquired from the dam or the environment and is potentiated by heavy lactation and aggressive feeding. Inappetance and abdominal pain are followed by bloody diarrhoea, recumbency, coma and death after 24 h or less. Haemorrhage and ulceration of the small intestine are typical. Case fatality rates are near 100%. Disease in older lambs manifests as chronic abdominal pain without diarrhoea. Type B infection is uncommon, perhaps because of the efficacy of vaccination of ewes with toxoid vaccines. Lesions are most prominent in the jejunum and are similar to those described in type C enteritis below.

Type C

Type C infections occur in pigs, cattle, sheep, horses, chickens, and humans worldwide. Neonatal animals are most susceptible.

Peracute disease characterized by rapidly fatal haemorrhagic diarrhoea affects piglets of 1 to 2 days of age, with case fatality rates of 50 to 100%. The intestinal surface is often dark red, with gas bubbles in tissue and haemorrhagic exudate in the lumen (Jäggi et al., 2009). There is also extensive haemorrhagic necrosis of the mucosa, submucosa, and even muscularis mucosa. Older piglets (1 to 2 weeks of age) have a longer clinical course, with yellowish diarrhoea and necrosis of the jejunal mucosa. Sows or the faecally-contaminated environment are thought to be the source of the infection for newborn pigs. Microscopic lesions are those of severe necrotizing and haemorrhagic enteritis or colitis with mucosal and submucosal thromobosis.

A similarly presenting disease is seen in neonatal calves, lambs, and goats. Calves (usually <10 days of age) develop haemorrhagic and necrotizing enteritis, often accompanied by evidence of abdominal pain; in lambs, the disease resembles dysentery. Tetany and opisthotonus may be observed. Case fatality rates approach 100%.

Adult sheep can be affected by an enteritis named ‘struck’ due to the rapidity of death of affected animals. Damage to the gastrointestinal mucosa encourages multiplication of type C, which results in mucosal necrosis and toxaemia, usually without dysentery or diarrhoea.

Type D

Type D strains cause enterotoxaemia (“overeating disease”), most prevalent in lambs aged three to ten weeks born to heavily-lactating ewes. Enterotoxaemia also affects weaned animals fed rich rations in feedlots or may occur when young lambs are moved to lush pasture. Disease often follows an upset in the intestinal flora precipitated by a sudden dietary change. Rapid multiplication of type D strains and production of epsilon toxin are favoured by excess dietary starch in the small intestine. The resulting toxaemia affects the central nervous system and other tissues, leading to sudden death with little or no evidence of enteritis. One feature that sets type D infections apart from those caused by netB- or netF-associated type A infections or by type B or C infections is the absence of haemorrhage or necrosis in the small bowel. Type D infections are genuine enterotoxaemias rather than cases of enteritis. The common name ‘pulpy kidney’ derives from a characteristic lesion, which results from rapid post mortem autolysis of toxin-damaged tissue. Gross lesions in lambs include sometimes mild congestion and increased fluid content of the small intestine, often with pulmonary oedema. Peritoneal and pericardial effusions are common, as are sub-endocardial and sub-epicardial haemorrhages. Hyperglycaemia and glycosuria are pathognomonic for type D enterotoxaemia. Older lambs and sheep will show cerebellar coning. Focal encephalomalacia is a chronic neurological manifestation of enterotoxaemia. The most consistent microscopic lesion is of microangiopathy (perivascular proteinaceous oedema) in the brain.

Enterotoxaemia in adult goats is distinct from the disease in sheep or goat kids in that fibrinous or haemorrhagic enterocolitis are a consistent presentation. Although the disease may present as sudden death, more commonly it presents as a bloody diarrhoea with intense abdominal pain (colic) that may last for several days before animals succumb or respond to treatment. Disease is seen in milking goats that are on production rations.

Type E

Type E causes haemorrhagic enteritis and sudden death of lambs and calves. It has been the subject of only about a dozen reports since the initial observation in the late 1940s, and has been thought to be quite rare. However, genotyping has revealed that it may be responsible for as much as 10% of cases of clostridial haemorrhagic enteritis in neonatal calves in the USA. Disease in young calves occurs in animals at 1 to 3 weeks of age, and is characterised by diarrhoea and death (Songer 1996; Songer and Miskimmins, 2004). Grossly, lesions are those of acute haemorrhage in the small bowel, which may include the abomasum, with microscopic lesions mucosal haemorrhagic, necrosis and inflammation.

Epidemiology

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In myonecrosis or cellulitis, infections by C. perfringens typically begin with acquisition of the infecting agent from the faecally-contaminated environment. Vegetative cells multiply in debilitated tissue, sometimes after germination of spores, leading to anaerobic cellulitis or, more seriously, to gas gangrene. Although toxin-typing of isolates from myonecrosis cases is rarely performed, these organisms are almost certain to be type A since this is the predominant type found in nature. The host is a dead-end in myonecrosis cases, in that transmission does not occur because the host usually dies.

Enteric infections in neonates usually follow acquisition of C. perfringens from the mother, either directly (through perineal or udder contamination by faeces) or indirectly (from faecal contamination of the environment). Although there is little direct evidence for animal-to-animal transmission (e.g., among pigs in a litter) this is to be expected, based on their shedding of large numbers of C. perfringens and the shape of the epidemic curve, which suggests the occurrence of secondary cases. The rapid multiplication of C. perfringens to large numbers in the small and large intestine of neonatal animals is well recognized and is one reason for the predominance of disease in neonates; the multiplication is transient and the numbers that remain to colonize the large bowel drop over time as the developing large bowel microflora becomes more complex and the competition for nutrients more intense. Clostridium perfringens is as much part of the large bowel and faecal flora as is Escherichia coli.

In other cases (such as catastrophic and rapidly-fatal infections of more mature animals, such as type D enterotoxaemia), the causative agent lives in the digestive tract and, given appropriate conditions, can multiply and produce clinical and pathological effects. In these cases, transmission from host-to-host through the faecal-oral route is possible. However, the organism entering the digestive tract must find the same appropriate conditions or the disease will not occur. In any case, shedding of the organism by infected animals probably stocks the environment for such time as allows other animals to become colonized.

Zoonoses and Food Safety

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Although Clostridium perfringens enterotoxin (CPE) seems to be of limited importance in animal disease, carriage of CPE-producing strains by domestic animals may have health implications for humans. Most and possibly all cpe-positive C. perfringens associated with human food poisoning represent a clonal lineage that is however thought to be environmental rather than animal in origin (Lindström et al., 2011; Lahti et al., 2012), even though the actual vehicle for human food poisoning is usually rich in animal protein (e.g., a warm beef stew). If a carcass is contaminated at slaughter, routine cooking will not kill any spores present. This is not a problem unless the cooked product is allowed to cool slowly, allowing not only germination of spores but substantial multiplication of vegetative cells. When ingested, these cells are induced to sporulate by the environment of the gastrointestinal tract and this is accompanied by CPE production and clostridial food poisoning. There is no evidence of effective control measures to prevent shedding of enterotoxigenic strains, but most food animal origin type A C. perfringens do not carry the cpe gene. Novel enterotoxins (binary enterotoxin, BEC; iota-like enterotoxin) have been described in C. perfringens in recent years (Yonogi et al., 2014; Irikura et al., 2015), but whether animals are a source of these strains for human food poisoning has not been investigated.

Prevention and Control

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C. perfringens is usually susceptible to a wide variety of antimicrobials, including bacitracin, cephalosporins including first-generation drugs, chloramphenicol lincosamides such as lincomycin and clindamycin, macrolides such as erythromycin, penicillins including penicillin G, tetracyclines, and virginiamycin, but is resistant to aminoglycosides. Acquired resistance to bacitracin, macrolides, lincosamides, tetracyclines, and virginiamycin, all antibiotics used for growth promotion and disease prophylaxis, has been reported in strains isolated from pigs and poultry. Treatment is by parenteral or oral administration of antibiotics, especially with penicillin G or macrolides.

Prophylaxis in swine or chickens by use of bacitracin has been effective; in chickens, ampicillin, bacitracin, nitrovin, penicillin G, tylosin, and virginiamycin are useful in preventing necrotic enteritis. Increasingly, use of antibiotics to prevent C. perfringens enteric infections, such as avian necrotic enteritis, is no longer permitted, for example in the European Union. These antibiotics are therefore used only for treatment of disease. In the pre-antibiotic era, therapy with equine hyperimmune antiserum was used although death often occurred too rapidly for it to be applied. Such antiserum is now largely unavailable. Passive immunization protects for two to three weeks but is now almost exclusively replaced by prophylactic use of antibiotics.

The acute course of C. perfringens-associated enteric diseases dictates that immunoprophylaxis must be practised. Commercial clostridial bacterin-toxoid vaccines are usually multivalent, and consist of inactivated cells, toxins, or both. These vaccines are usually administered annually and, where available, are highly effective. Immunization of ewes is widely practiced to provide maternal lactogenic immunity to lambs; the lambs in turn are immunized at 8-10 weeks of age once their colostrally-derived antibodies have declined. The response of adult dairy milking goats to epsilon toxoid vaccines is variable, so these animals are often vaccinated 3 times annually. Sows may also be vaccinated with type C based vaccines to provide effective protection of piglets from clostridial enteritis. Vaccines are not currently available for avian necrotic enteritis.

References

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Garcia JP; Li J; Shrestha A; Freedman JC; Beingesser J; McClane BA; Uzzal FA, 2014. Clostridium perfringens type A enterotoxin damages the rabbit colon. Infection and Immunity, 82:2211-2218.

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Gozun H; Kiran MM, 1999. Pathological studies of hepatic lesions in sheep slaughtered at Konya abattoirs. Veterinarium, 10:1-19.

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01/03/16 Updated by:

John F. Prescott, University Professor Emeritus, Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada

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