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Gas gangrene in mammals: a review

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VDIXXX10.1177/1040638720905830Gas gangrene in mammalsOliveira Junior et al.

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Journal of Veterinary Diagnostic Investigation

Gas gangrene in mammals: a review 1­–9

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DOI: 10.1177/1040638720905830
https://doi.org/10.1177/1040638720905830
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Carlos A. Oliveira Junior, Rodrigo O. S. Silva, Francisco C. F. Lobato,

Mauricio A. Navarro, Francisco A. Uzal1

Abstract. Gas gangrene is a necrotizing infection of subcutaneous tissue and muscle that affects mainly ruminants and
horses, but also other domestic and wild mammals. Clostridium chauvoei, C. septicum, C. novyi type A, C. perfringens type A,
and C. sordellii are the etiologic agents of this disease, acting singly or in combination. Although a presumptive diagnosis of
gas gangrene can be established based on clinical history, clinical signs, and gross and microscopic changes, identification of
the clostridia involved is required for confirmatory diagnosis. Gross and microscopic lesions are, however, highly suggestive
of the disease. Although the disease has a worldwide distribution and can cause significant economic losses, the literature is
limited mostly to case reports. Thus, we have reviewed the current knowledge of gas gangrene in mammals.

Key words: cattle; clostridia; gas gangrene; horses; sheep.

Introduction their presence should be interpreted with caution in carcasses

because invasion of tissues from the intestine begins shortly
Several bacteria of the genus Clostridium are known in human after death or during the last minutes of life.52 These 5 clos-
and veterinary medicine because of their ability to cause dis- tridial species exert their effect via the production of power-
eases through the production of powerful exotoxins.30 Among ful toxins (Table 1).57,58
these diseases, gas gangrene (previously referred to as malig-
nant edema) is a highly lethal histotoxic disease that affects
several animal species with worldwide distribution.65,70,78 Clostridium septicum
Although gas gangrene is most frequently observed in The involvement of C. septicum in gas gangrene was con-
sheep, cattle (Figs. 1, 2), and horses (Fig. 3),20,53,65,70 it has firmed in 1881 by Robert Koch.31,67 C. septicum produces 4
also been described in other domestic mammals, including major toxins, (i.e., alpha, beta, delta, and gamma), but alpha-
goats,27,30 pigs (Fig. 4),54 dogs, and cats.53,56,62 Individual toxin, a lethal and necrotizing pore-forming cytolysin, is rec-
cases of gas gangrene have also been described in several ognized as the factor that is essential for the virulence of this
wild animal species including an Indian elephant (Elephas microorganism.35 This toxin uses glycosyl-phosphatidylino-
maximus),59 a guanaco (Lama pacos),78 a lynx (Lynx sitol–anchored proteins on the membrane of target cells as
canadensis),33 and a brown bear (Ursus arctos).10 Cases the receptor.34,57 After proteolytic activation, many activated
have also been described in a marmoset (Callithrix jac- monomers form a transmembrane pore that has lytic and
chus)84 and a rhesus macaque (Macaca mulatta).42 No age vacuolating properties.28,34 Gamma-toxin, a hyaluronidase,
predisposition has been described in any animal species, might play a role in the spreading of bacteria or their toxins
except for cases of omphalophlebitis, which occur in neo- through tissues.34 If this is the case, this toxin would be at
natal animals.44,51 least partially responsible for the hallmark lesions of gas
Despite the undeniable importance of gas gangrene in gangrene, which are edema and hemorrhage.57 The roles of
mammals, information regarding this disease is dispersed and the other toxins of C. septicum in the virulence of this micro-
mostly in the form of case reports. We review and discuss organism are largely unknown.
herein the most relevant aspects of gas gangrene in mammals. C. septicum is widespread in the environment, and it is
considered by some authors as the main cause of gas gan-
Etiology grene in ruminants,52,70 probably because it is frequently
Gas gangrene can be caused by one or more of the following
Veterinary School, Federal University of Minas Gerais, Brazil
clostridial species: Clostridium septicum, C. chauvoei, C. (Oliveira Junior, Silva, Lobato); California Animal Health and Food Safety
novyi type A, C. perfringens type A, and C. sordellii.19,53,70 Laboratory, University of California, Davis, CA (Navarro, Uzal).
These agents are widespread in the environment, and some 1
Corresponding author: Francisco A. Uzal, California Animal Health
of them are frequently found as part of the intestinal micro- and Food Safety Laboratory, San Bernardino Branch, University of
biota of many animal species.29,68,74,80,81 All of these clostrid- California–Davis, 105 W Central Avenue, San Bernardino, CA 92408.
ial species can also be frequent postmortem invaders,74 and fuzal@cahfs.ucdavis.edu
2 Oliveira Junior et al.

Figures 1-4. Gas gangrene in cattle, horse, and pig. Figures 1, 2. Gas gangrene caused by Clostridium septicum in a heifer. Figure
1. Severe subcutaneous hemorrhage and edema. Figure 2. Severe subcutaneous edema expanding the subcutis. Figure 3. Gas gangrene
caused by Clostridium sordellii in a horse, with severe subcutaneous and interstitial muscle edema. Reproduced with permission.65
Figure 4. Chronic gas gangrene caused by Clostridium septicum, Clostridium chauvoei, and Clostridium sordellii in a pig. The portal of
entry in this case was not determined. Courtesy of J. M. Benoit.

Table 1. Gene location, molecular weight, and mode of action of the main clostridial toxins responsible for gas gangrene in animals.

Molecular
Agent Toxin Location weight (kDa) Mode of action Reference
25
C. septicum Alpha Plasmid or chromosome 48 Pore formation
25
C. chauvoei Toxin A (CctA) Chromosome 33 Pore formation
80
C. perfringens type A Alpha (CPA) Chromosome 42 Phospholipase C/
sphingomyelinase
21
C. sordellii Lethal toxin (TcsL) Chromosome 300 GTPase inactivation
21
Hemorrhagic toxin (TcsH) Chromosome 260 GTPase inactivation
22,58
C. novyi type A Alpha Phage 250 GTPase inactivation
GTPase = guanosine triphosphatase.

isolated in pure culture from tissues of animals with this dis- 6- to 24-mo-old.2,12,76 However, this microorganism is also com-
ease. This, however, may just represent the capacity of this monly associated with gas gangrene of ruminants, usually act-
organism to overgrow other histotoxic clostridia when they ing in combination with other histotoxic clostridia.6,38,70
act together, given that C. septicum grows very quic C. chauvoei produces several potent exotoxins, but toxin
kly.11,12,29,44,68 Nevertheless, several cases of gas gangrene in A (CctA), a pore-forming toxin of the leucocidin toxin super-
which only C. septicum was detected by fluorescent antibody family, is the main virulence factor.25 Other toxins, such as
(FA) testing or immunohistochemistry (IHC) seem to contra- the neuraminidase of C. chauvoei, are thought to play an
dict the above statement.61,62,78,81 FA testing and IHC provide important role in spreading C. chauvoei in the tissues of
a snapshot of the relative proportion of different clostridial infected animals.77 C. chauvoei is able to survive in bovine
species present in animal tissues and are not affected by the macrophages, a fact that is considered critical for the patho-
presence of other microorganisms.8 genesis of blackleg, which is thought to involve activation of
spores dormant in macrophages when conditions of reduced
redox potential occur.55 However, in most cases of gas gan-
Clostridium chauvoei
grene associated with C. chauvoei, the pathogenesis of the
C. chauvoei is commonly recognized as the cause of blackleg, a disease is believed to be exogenous; that is, the microorgan-
so-called “endogenous” myonecrosis that affects mainly cattle ism or its spores gain entry into the tissues via cutaneous or
 Gas gangrene in mammals 3

mucosal wounds.6,46 Although it is possible that an endoge- virulence, namely lethal toxin (TcsL) and hemorrhagic toxin
nous mechanism also exists for other clostridia, particularly (TcsH).21,83 These 2 toxins are closely related to Clostridium
in cases of gas gangrene in non-human primates,84 this has difficile toxins A (TcdA) and B (TcdB), respectively.7,30 TcsL
not been confirmed. and TcsH have glucosylation (UDP-glucose) activity, and
their main targets are endothelial cells.58 Both toxins bind to
as-yet uncharacterized receptors on endothelial cells, where
Clostridium perfringens type A
they are internalized and cause disruption of the cytoskeleton.
C. perfringens, previously known as Clostridium plagarum The result is loss of cell adhesion, which leads to hemorrhage
and Clostridium welchii,47,72 is commonly found in soil and and edema with a drop in blood pressure.7 This effect at the
microbiota of many healthy mammals; its role as an entero- cellular level explains, at least in part, the severe edema and
pathogen has not been clarified fully.71,81 C. perfringens is hemorrhage in most cases of C. sordellii–associated disease.65
classified into 7 types according to the production of 6 so- C. sordellii can cause gas gangrene in several domestic and
called major typing toxins, namely alpha, beta, epsilon, wild mammals.10,20,24,39,43,51,65
iota, enterotoxin, and necrotic enteritis–like beta.63 Of
these, C. perfringens type A produces only alpha-toxin
Clostridium novyi type A
(CPA), which has been proven to be essential for the patho-
genesis of gas gangrene in humans.9 Although there is C. novyi type A, originally named Bacillus oedematis num-
ample evidence of the significant role of CPA in human gas ber 2,72 was isolated in 1894 by Frederick Novy, from lesions
gangrene, the same does not hold true for gas gangrene of of guinea pigs that had died after injections of casein.30 This
other mammals, and the role of CPA in animal gas gangrene microorganism is commonly found in soil and rarely in the
remains speculative. CPA is a phospholipase C with sphin- microbiome of healthy animals.11,29,41,48 C. novyi type A pro-
gomyelinase activity that affects host signaling, contribut- duces alpha-toxin, a large glucosylating toxin with necrotiz-
ing to tissue necrosis, thrombosis, and reduction or absence ing and lethal activity, which is considered the main virulence
of leukocyte influx into the infection site.49,80 Because these factor of this microorganism.9 Similar to TcsL and TcsH of C.
changes are seen in cases of animal gas gangrene associated sordellii, the alpha-toxin of C. novyi type A acts on endothe-
with C. perfringens type A, it is likely that, in those cases, lial cells, causing loss of cell-to-cell contact, which leads to
CPA is an important virulence factor for animal gas gan- edema, followed by a drop in blood pressure, multi-organ
grene. Perfringolysin O (PFO), a pore-forming toxin, is not failure, and death.7,58 C. novyi type A also produces novyly-
essential for gas gangrene in humans, but in mice inocu- sin, a cytolysin that damages cell membranes.7,58
lated experimentally with C. perfringens type A, it acts syn- Cases of gas gangrene caused by C. novyi type A in
ergistically with CPA, causing macrophage cytotoxicity at humans linked to the use of injectable drugs are common.41,64
the beginning of the infection, coupled with thrombosis and In domestic mammals, reports of gas gangrene caused by C.
a decrease in inflammatory cell influx at later stages of the novyi type A are scarce, with a few reports in horses, cattle,
infection.82 Although there is no information available on and sheep.23,43 An intra-abdominal abscess caused by this
the role of this toxin in spontaneous cases of animal gas agent in a horse has been reported.5 In this case, it was spec-
gangrene, it is possible that PFO also plays a role in some ulated but never proven, that the horse picked up C. novyi
of these cases. from a pasture in which cattle had been grazing.5 However,
C. perfringens type A seems to be more prevalent in the presence of C. novyi in those cattle was not investigated,
human than in animal cases of gas gangrene.37 Among and the suggestion that they could have been the origin of the
domestic mammals, C. perfringens type A gas gangrene has equine infection is purely speculative.
been described in goats, sheep, cattle, pigs, and horses.70
This microorganism was the most common cause of gas gan-
Epidemiology
grene in 1 study of 37 horses.53 The pathogenesis of C. per-
fringens type A in gas gangrene of ruminants has not been All of the etiologic agents of gas gangrene described above
thoroughly studied, although in most cases in which this are widespread; most of them can be found, albeit with dif-
microorganism produces gas gangrene, other histotoxic clos- ferent prevalences, in the intestinal content of animals and in
tridia, including C. septicum, C. chauvoei, and others, are the environment, including fresh water and soil.29,81 The
involved.70 spores are found more often in wet soils rich in organic mat-
ter, and regions where the soils are seasonally flooded are
more prone to be contaminated by some of these microor-
Clostridium sordellii
ganisms than are dry soils.52 The use of treated wastewater
C. sordellii was first isolated in 1922 by Alfredo Sordelli from for irrigation of pastures is a factor that can increase environ-
an acute edematous wound infection of a human patient and mental contamination because most spores are not destroyed
was initially named Bacillus oedematis sporogenes.4,73 C. during the treatment of contaminated water.32 Because sev-
sordellii produces at least 5 toxins, 2 of which are essential for eral clostridial species responsible for gas gangrene are
4 Oliveira Junior et al.

present in the intestines of wild and domestic animals,4,70 the similar to that of blackleg. In blackleg cases, spores of C.
presence of these animals on pastures is likely to also increase chauvoei are ingested and, after one or more cycles of repro-
soil contamination. In addition, earth movement associated duction in the intestine, are absorbed into the systemic circu-
with construction or other human activities may also increase lation through which they reach several tissues, including
the risk of infection by some of the clostridial species respon- cardiac and skeletal muscle, where they stay dormant for
sible for gas gangrene.11,45 variable periods of time, sometimes years. When blunt
The occurrence of gas gangrene is dependent on close trauma or other injuries that do not produce skin or mucosal
contact between the clostridial species involved and animals, wounds occur and produce a reduction of the redox potential,
typically contamination of wounds after vaccination, parturi- the spores germinate, proliferate, and produce the toxins that
tion, shearing, marking, neutering, docking, bleeding, and are responsible for the disease.2,3 A similar pathogenesis,
other traumatic interventions.20,43,50,68 A lack of, or a subopti- although suggested,1,16,53,84 has not been proven for other
mal, vaccination program, idiopathic individual lack of clostridial species.
immune response, or high challenge doses can also contrib- Most clostridial toxins involved in cases of gas gangrene
ute to the occurrence of gas gangrene.20,45 The disease gener- act first on endothelial cells, producing circulatory alterations
ally occurs sporadically, but outbreaks have been reported in and, consequently, edema, hemorrhage, ischemia, and local
association with the injection of contaminated products or necrosis.4,65 This environment provides the ideal conditions
the use of contaminated needles.14,18,20 for survival and multiplication of these microorganisms and
In cattle and sheep, cases of gas gangrene are more com- the production of more toxins.7 In addition, several enzymes
mon in extensive production systems, and C. septicum is the produced by histotoxic clostridia, including collagenases,
most common etiologic agent.45,50 In both host species, out- DNases, hyaluronidases, and neuraminidases also contribute
breaks involving several animals are not unusual, and the to initial evasion of host defenses, tissue damage, and nutrient
main risk factor in these cases is vaccination without proper acquisition, allowing the spread of the infection.7,30,58 When
asepsis, although cases associated with other veterinary the toxins gain access to the blood circulation, toxemia
interventions43,52 and parturition50 are also common. ensues, followed by shock and death.7,58 Bacteremia is also
In horses, C. perfringens type A and C. septicum are the common, with the agents of gas gangrene being found in
most common causes of gas gangrene.14,53 C. sordellii, which blood and several organs.52 In cases in which C. perfringens
was previously associated with multiple cases of omphalitis type A is involved, intravascular hemolysis may also occur as
in foals,51 has recently been identified as a significant cause a result of the highly hemolytic nature of CPA and PFO.80
of gas gangrene in horses (Fig. 2).65 Although C. sordellii–
associated omphalitis was described in male and female
Clinical signs
newborn foals,51 no association between other forms of gas
gangrene and age or sex of horses has been identified. How- Depression, tachycardia, respiratory distress, muscle trem-
ever, in a study of 37 cases of equine gas gangrene, 43% of ors, anorexia, and fever are clinical signs often seen in cases
cases occurred in Quarter Horses,53 a heavily muscled breed of gas gangrene.6,19,56 Within a few hours after infection, the
that is predisposed to several muscle diseases.69 Based on inoculation site and adjacent tissues are swollen, erythema-
this, it was suggested that Quarter Horse individuals may be tous, painful, and hot. As the infection progresses, there is
more predisposed to gas gangrene than other breeds.53 This, increased swelling because of subcutaneous edema and emphy-
however, is speculative and has not been proved. Intramus- sema, the latter becoming evident as crepitation during palpa-
cular injections seem to be the most common antecedent of tion. If the lesions are in the limbs, this usually leads to reluctance
gas gangrene in these horses.14,23,53,65 to move, lameness, and eventually recumbency.18,20,23 The skin
is usually taut and diffusely red or black as dermal necrosis
ensues.19 In later stages of the disease, the affected areas become
Pathogenesis cold.52 In most cases, death occurs as a consequence of toxemia
Contamination of wounds with spores or vegetative forms of and shock between a few hours to 3 d after the onset of clinical
histotoxic clostridia represents the starting point of most signs. Rare cases can have a clinical course of 30 d or more.18,23,43
cases of gas gangrene.20,43,78 Low redox potential, metabo- Occasionally, animals die without showing any clinical
lites of decomposing protein, and acid pH promote germina- signs.52
tion of spores and stimulate proliferation of vegetative forms In post-parturient gas gangrene, a form of necrotizing vul-
of clostridia.73 This is followed by the production of toxins vovaginitis and metritis after parturition in heifers, vulvar
(Table 1), which are ultimately responsible for the lesions swelling is the most common clinical sign. It starts 1–3 d
and clinical signs characteristic of gas gangrene. after calving, accompanied by fever, depression, recum-
Cases have been described in which no evidence of bency, discharge of red-brown fluid and, finally, death.50 In
wounds was found, which lend credence to the suggestion these cases, it has been postulated that trauma associated
that some cases of gas gangrene, notably in non-human with parturition produces wounds in the birth canal, which
primates84 and rarely in horses,16,53 may have a pathogenesis are the portal of entry for C. septicum.50
 Gas gangrene in mammals 5

All affected tissues may have minimal-to-severe leukocyte

infiltration composed mostly by neutrophils, many of them
degenerate (Fig. 7). Abundant gram-positive bacilli with
mostly sub-terminal spores, single or in clusters, are present
within areas of edema or hemorrhage and rarely within
degenerate muscle fibers (Fig. 6).4,43,61 Congestion and hem-
orrhage of liver and lungs, and medullary hemorrhage and
necrosis of thymus and regional lymph nodes, may also be
seen.18,36,43
In post-parturient gas gangrene, multifocal necrosis and
ulcers are observed in vulvar, vaginal, and uterine mucosae.
Perivulvar and systemic tissues have lesions similar to those
described above for other cases of gas gangrene.36,50
Figure 5. Postpartum gas gangrene in a heifer. Note mucosal In cases of clostridial omphalophlebitis, arteritis is
tears covered by inflammatory exudate in vulva and vagina. observed in umbilical arteries, and the urachus has transmu-
Reproduced with permission.50
ral edema, hemorrhage, and mixed inflammatory cell infil-
trates. Diffuse hemorrhagic and gelatinous edema and
Gross changes congestion are seen in all tissues around the navel.44,51
Absence of significant inflammatory response is a charac-
The main gross changes associated with gas gangrene are teristic of cases of human C. perfringens–associated gas
diffuse, blood-stained, and gelatinous subcutaneous edema gangrene.15 This is the result, in part, of impaired neutrophil
and emphysema (Figs. 1–3).19,23,56 Underlying muscles fre- mobility caused by the action of alpha-toxin of C. perfringens.15
quently have petechiae, ecchymoses, and/or multifocal-to- A similar lack of inflammatory infiltrate has been described in
coalescing dark-red, gray, or blue discoloration indicating some, but not all, cases of animal gangrene, produced by sev-
areas of necrosis with or without edema and gas bubbles eral clostridial species,44,50 and it is possible that other clos-
(Figs. 2, 3).6,19,43 Serosal and subendocardial hemorrhages, tridial toxins have a similar leukocytoclastic effect to that seen
and congested and edematous regional lymph nodes, spleen, with C. perfringens alpha-toxin, but this has not been
lungs, and liver can be observed as a consequence of the proved.
severe toxemia.18,19,53,65 Gross findings are similar regardless
of the clostridial species involved.52,70
In post-parturient gas gangrene of cattle, diffuse, gelati- Diagnosis
nous, and hemorrhagic perineal and perivaginal edema is A presumptive antemortem diagnosis is based on history and
common, which sometimes extends to adjacent musculature clinical signs. Confirmation of the diagnosis in the live ani-
(Fig. 5). Multifocal necrosis and ulceration are observed in mal may be achieved by extraction of subcutaneous exudate,
vulvar, vaginal, and uterine mucosae, which may be covered which can be examined by Gram, FA test (Fig. 7), or when
by a fibrinous pseudomembrane; systemic lesions are similar the course of the disease allows it, bacterial culture, and/or
to those described above.50 PCR.26,52 When outbreaks occur, the diagnosis is usually
In cases of clostridial omphalophlebitis in foals, yellow based on postmortem examination and diagnostic workup on
gelatinous edema is usually found in the parietal peritoneum, one or more affected animals.52,70
subcutaneous tissue, and abdominal muscles around the A presumptive postmortem diagnosis of gas gangrene can
internal umbilical remnant, which is swollen and hemor- be established based on clinical history, including clinical
rhagic. An excess of blood-stained and odoriferous perito- signs, and gross and microscopic changes (Figs. 6, 7).70 Lab-
neal fluid is also common. Petechiae and ecchymoses are oratory tests are, however, essential for confirmatory diagno-
observed in abdominal serosae.51 sis, which should be based on identification of the clostridia
involved. Muscle, subcutaneous tissue, and/or fluid from
grossly affected areas of recently dead animals should be
Microscopic changes
submitted to the laboratory. These samples should be col-
The subcutaneous tissue has severe proteinaceous edema and lected in sterile containers and submitted fresh, refrigerated,
hemorrhage (Fig. 6). Vasculitis with fibrinoid necrosis and or frozen (Table 2), for anaerobic culture and/or
thrombosis is a very frequent finding.10,18 The skin has dif- PCR.17,23,26,62,65,66 Rapid identification of several clostridia
fuse congestion, hemorrhage, and emphysema, and in later involved in gas gangrene may be achieved by targeting the
stages, may show coagulative necrosis.61 Skeletal myofibers flagellin gene (fliC) of C. novyi type A, C. septicum, and C.
are swollen, hypereosinophilic, and have a loss of striations, chauvoei by direct PCR on clostridial isolates or DNA
vacuolation, and hypercontraction bands (Fig. 7).23,44,61,65 extracted from affected tissues.66 However, failure to amplify
Severe interstitial hemorrhage and edema can be observed.56 certain virulence genes should be interpreted with caution
6 Oliveira Junior et al.

Figures 6–9. Gas gangrene produced by Clostridium septicum in a heifer. Figure 6. Severe subcutaneous edema with sparse leukocytic
infiltrate and myriad intralesional rods. H&E. Reproduced with permission.70 Figure 7. Interstitial muscle edema and mild neutrophilic
infiltrate. H&E. Figure 8. Subcutaneous tissue smear stained with fluorescent antibody for C. septicum. Inset: higher magnification. Figure
9. Immunohistochemistry for C. septicum.

Table 2. Main detection techniques for gas gangrene in mammals.

Detection test

Bacteriology PCR FA IHC

Storage conditions Fresh, refrigerated, or Fresh, refrigerated, Fresh or refrigerated Formalin-fixed
of tissues frozen frozen, or formalin-
fixed
Sensitivity Moderate High Moderate Moderate
Specificity High Medium High High
Advantages Simple and cheap Fast; can be performed Fast; can be performed Can be done on formalin-fixed
on isolates or on tissues on smears tissues; allows association of
organisms with lesions
Disadvantages Time-consuming; need for May detect May detect Time-consuming
a next step to identify nonpathogenic nonpathogenic
the isolates (PCR, FA, clostridia clostridia
MALDI-TOF MS).
FA = fluorescent antibody; IHC = immunohistochemistry; MALDI-TOF MS = matrix-assisted laser desorption/ionization time-of-flight mass spectrometry; PCR = polymerase
chain reaction.

because some of these genes are encoded in plasmids that fixed (FF) tissues.79 The low sensitivity for FF tissue is a
may be lost upon subculture (e.g., tcsL and tcsH genes of C. result of the fact that the routinely used indirect fluorescent
sordellii).21,83 Matrix-assisted laser desorption/ionization technique provides minimal amplification of the signal on
time-of-flight mass spectrometry is also useful in identifica- tissues.75 IHC is also useful in the identification of several
tion of isolated clostridia.40 Air-dried smears of grossly clostridial species in FF tissues. This technique has the
affected tissues should be submitted for a FA test (Fig. 8).70 advantage of correlating the presence of the microorganisms
Fluorescent antibodies have been used, albeit with variable with microscopic lesions (Fig. 9), and, because most modern
efficacy, to identify several clostridial species in formalin- IHC systems amplify the signal significantly, the sensitivity
 Gas gangrene in mammals 7

of these tests is usually much higher than that of the FA test Declaration of conflicting interests
routinely used for clostridial disease diagnosis.8,60 The authors declared no potential conflicts of interest with respect
The collection of samples for microbial analysis must be to the research, authorship, and/or publication of this article.
performed as soon as possible after death because several
clostridial species that are normally present in the intestine Funding
invade tissues soon before or after death, which can generate The authors received no financial support for the research, author-
false-positive results.12 ship, and/or publication of this article.

Control and prophylaxis ORCID iDs

Mauricio A. Navarro https://orcid.org/0000-0002-7744-8052
Gas gangrene is usually an acute disease and therefore there
Francisco A. Uzal https://orcid.org/0000-0003-0681-1878
is usually no time for treatment.38 This is particularly true for
livestock under extensive rearing conditions and in other References
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