Vet. World, 2012, Vol.5(5):311-319 REVIEW

Canine Toxic Shock Syndrome (CSTSS) is a serious often fatal disease syndrome seen in dogs caused as a result of an infection caused by gram positive cocci of the family Streptococci. The main bacterium involved in the etiology of Canine Streptococcal Toxic Shock Syndrome is Streptoccoccus canis, which was discovered by Deveriese in 1986 and implicated as a cause of this disease syndrome in 1996 by Miller and Prescott. The clinical findings in this syndrome are very much similar to those seen in the infamous 'Toxic Shock 'caused by staphylococcal toxins in humans, especially females. Like in humans, the reason for emergence/reemergence of Canine Streptococcal Toxic Shock Syndrome (CSTSS) is unclear and very little is known about its transmission and prevention. The disease is characterized by multi systemic organ failure and a shock like condition in seemingly healthy dog often following an injury. In absence of proper and prompt diagnosis and subsequent treatment by injectable antibiotics and aggressive shock therapy, dog often succumbs to the disease within a few hours. The dog may have some rigidity and muscle spasms or convulsions and a deep unproductive cough followed by haemorrhage 
from nasal and mouth along with melena. On necropsy, these dogs show severe edema of the gastrointestinal tract, congestion of multiple organs, severe pulmonary congestion and evidence of thrombo embolism. Necrotizing fasciitis is a localized form of streptococcal infection seen as extensive soft tissue sloughing and necrosis along the fascial planes. No vaccination is available so avoidance of the probable causal factors mainly participation in community events, estrus, change of environment and shipping is the only way to keep pet dogs away from this disease.


Introduction
canis also causes various infections in cats, including arthritis, wound infections, septicaemia and streptococcal Streptococci are a family of heterogenous group toxic shock syndrome, and it can cause mastitis in of gram positive bacteria which have been implicated cows (Iglauer et al., 1991;Hassan et al., 2005).Very in causing either localized or systemic infections in few human infections with S. canis have been both humans and animals.Some strains rarely cause documented; However, human infections with this disease and are often found as commensal inhabitants species may be underestimated because many clinical of the skin and mucosal surfaces (oral, nasal, and isolates are reported to only as "group G Streptococcus" intestine), while other strains are capable of causing or GGS.Syndromes that have been associated specifically serious or even life threatening infections.
with S. canis include septicaemia, meningitis and In dogs, S. canis is an opportunistic pathogen, peritonitis (Bert and Lambert-Zechovsky, 1997; inhabiting vagina and anal mucosa and has been Takeda et al., 2001; Whatmore et al., 2001).isolated from a variety of diseases including skin infections, infections of urogenital and respiratory tracts, otitis externa, septicemia, necrotizing fasciitis In the early 1990's, Streptococci (Group A, âand streptococcal toxic shock syndrome (Bornand, hemolytic Strept) emerged as the cause of a previously 1992 ;Miller et al., 1996;DeWinter et al., 1999).S. unrecognized disease in humans and the disease came to be known as Streptococcal Toxic shock Syndrome (Lyskova et al., 2007).They fail to ferment sorbitol because it closely resembled the spectrum of toxic and are negative for hippurate, fibrinolysin, tyrosine, shock caused by the better known "Toxic Shock" in starch hydrolysis, Voges-Prauskauer and pyrrolidowomen caused by a Staphylococcal toxin.
nnylarylamidase reactions (Devriese et al., 1986).The bacterium, Streptococcus canis was CAMP) like described for the first time by Devriese in 1986 and it's reactions are present in around 60% strains.Since role in causing a toxic shock like disease syndrome in clonal expansion is thought to be partially responsible for the spread of invasive strains of S.pyogenes in dogs was described in 1996 by Miller and Prescott humans, attempts were made to study the relatedness who reported on a series of seven dogs from southern of S. canis isolates from CSTSS and NF using pulse Ontario, Canada that had severe systemic disease and field gel electrophoresis and biotyping, it was found shock associated with infection with â-hemolytic that S. canis isolated from cases of CSTSS and/or NF Streptococcus canis (Lance field Group G).Out of in dogs were not clonally related (De Winter and these seven dogs, four had associated necrotizing Prescott, 1999).In contrast to this, pulsed field gel fasciitis.Since then, the disease has been reported in electrophoresis (PFGE) profile in feline isolates other dog breeds and is increasingly becoming a cause suggested a clonal origin (Kruger et al., 2010).S. canis of concern for dog owners.Like in humans, the reason has also been implicated in a case of fatal necrotizing for the emergence/re-emergence of canine STSS/NF is fasciitis and myositis in a cat (Sura et al., 2008) Sher pei, racing greyhounds, Great Dane etc seem to Most biotypes produce phosphatase, leucine be particularly susceptible to CSTSS but cases have arylamidase, arginine dihydrolase, alpha-D-and betabeen increasingly reported in other breeds and the D-galactosidase and fermented lactose and ribose

Host Susceptibility
Christine Atkinson Munch Peterson ( disease has become a concern for owners of dogs etc.The reproductive tract of bitches in season is an housed in large groups or those participating in shows open invitation to bacteria as licking of genitalia of or performance events.bitch in season by infected male is a important risk factor.Dogs licking the face of humans with a streptococcal throat or cellulites or of a child with impetigo are definitely at risk.Crowded conditions Canine Streptococcal Toxic Shock Syndrome and dog shows especially indoors and in fall and resembles a severe invasive group A streptococcal winter months increase the risk of disease disease in humans also known as Streptococcal Toxic S. pyogenes transmission.Also handlers and judges may transmit Shock caused by which is also transferable to dogs although rarely.In people, S. canis has been the infection by examining , handling multiple dogs isolated from cases of septicemia, localized soft tissue sequentially without washing their hands .Stress infections, UTIs and osteomyelitis (Galperine et al., factors as traveling long distances, confinement, 2007).Both S.canis and S.equi subsp.zooepidemicus exposure to stressful conditions, estrus may reduce a are opportunistic pathogens that are zoonotic in dog's resistance to the disease.Healthy adult dogs are not as susceptible to streptococcal infections as nature, capable of causing severe invasive disease in younger or older dogs are.This may be because a domestic animals and humans.A SCM (S.canis Myoung dog's immune system may be less effective than like) protein has been identified that binds human that of a healthy adult.plasminogen and facilitates bacterial transmigration mediating the fibrinolytic activity of S. canis in humans (Fulde et al.

, 2011) Transmission of S.canis
Streptococcal infection is a rapidly progressing, to humans seems to require a close contact and most highly invasive process leading to STSS, a shock like cases, to date, were probably acquired by syndrome, multiorgan failure and necrotizing fasciitis.contamination of open wounds or dog bites.Practice Not much is known about its pathogenesis and of identifying streptococci only by the Lancefield protective immune mechanism.Pyrogenic exotoxins serological group or biochemical tests may result in cause fever in humans and animals and also help to underestimation of the presence of S. canis in the induce shock by lowering the threshold to exogenous human population as published biochemical description are inconsistent (Whatmore et al., 2001; endotoxins (Dillon, 1968).Streptococcal pyrogenic Lam et al., 2007) .Also many clinical isolates are exotoxins A and B induce the production of Tumor reported to only as 'Group G streptococcus' and are no necrosis factor-á (TNF á) (Fast et al., 1989) and further investigated.One case each of septicemia in interleukin-1â (IL-1 â) and interleukin- is a potent producer of women and 77 year old man caused by exotoxin which may be responsible for the rapid presumably after a dog bite and vicinity with a pet dog progression of sepsis, shock and multiorgan failure in respectively.In another study, Group G streptococci case of CSTSS.were found in 16.67% of cases of human otitis externa In people, the clonal expansion of invasive by microbiological examination (Cristina and Degi., strains of S.pyogenes is thought to promote the 2009 ).Three cases of ulcers in dog owners caused by S.canis et al development of toxic shock syndrome but this does have been described by Lam ., 2007.Out not appear to be the case in the dogs.Furthermore, of 92 patients with group G streptococcal bacterimia, one patient was identified with S.canis but with no proteins from the S. canis isolates from the cases of history of dog bite (Liao et al., 2008).
NF have homology with only 2 proteins (M protein and Streptolysin O) of the 10 known virulence factors of invasive S.pyogenes (DeWinter et al., 1999).This finding suggests that yet another unknown factors are involved in the pathogenesis of S.canis toxic shock-The portal of entry in dogs usually seems to be like syndrome in dogs.M proteins contribute to invasi-the throat and lungs.Close physical contact with an veness through its ability to impede phagocytosis of infected but asymptomatic dog is reasonably safe but streptococci by polymorphonuclear leukocytes jaw-wrestling and play-fighting can transmit the (Lancefield, 1962).Data suggest that the streptococcal infection.Sharing a run with an infected dog is an exotoxin and a number of staphylococcal toxins can important risk factor, as well as water bowls, bedding

Mode of Transmission and Risk Factors involved
stimulate T-cell responses through their ability bind to both Class II major histocompatibility complex of Canine streptococcal toxic shock syndrome has antigen presenting cells and the V region of the T-cell â generated a great deal of concern among dog owners.receptor (Mollick and Rich, 1991).The net effect Severe symptoms typical of CSTSS seem to result would be to induce T-cell stimulation with the when the bacteria invade the blood stream, inducing production of cytokines capable of mediating shock septicemia and toxemia with a cascade of toxins.and tissue injury.Peptidoglycan, lipoteichioc acid Dogs that develop Canine streptococcal toxic (Stevens et al., 1992), and killed organisms (Hackett et  ).Whatever the mechanisms, induction of depressed and too weak to move, experience rigidity cytokines in vivo is likely the causes of shock and and spasms of muscle coupled with a high fever (105º exotoxins, cell wall components, and the like, are F -107ºF).As the disease progresses, a deep, non potent inducers of TNF and IL-1.
productive cough develops, followed by a rapid onset Some investigations have attributed the virulence of spontaneous hemorrhaging like hemoptysis, of the bacteria and more specifically fasciitis to epistaxis, hematuria, melena and ecchymoses of expression of bacterial enzymes such as hyaluronidase skeletal muscles.There are evidences of hypotensive which degrades the fascia (Stevens et al., 1995).shock with involvement of atleast one other organ or Development of TSS is dependent on the presence of system (Prescott et al., 1997).In generalized systemic superantigens (Sags) in Streptococci.In humans, form, there is much more rapid onset with shock like STSS and NF associated with S. pyogenes isolates condition like hypotension, severe weakness, rapid possessing lysogenic bacteriophage-encoded heart rate, pale mucous membrane, extreme pain, superantigen genes, are thought to be crucial in the collapse, coma and acute death.Many dogs develop development of the disease (Cunningham, 2000

(MODS).
There is severe edema of the gastrointestinal 1991).These superantigens are powerful inducers of tract (GIT), congestion of multiple organs, including T-cell proliferation and cause the release of massive lungs and evidence of thromboembolism, all pointing amounts of host cytokines with sometimes lethal to shock due to sepsis or toxemia.effects (Fleischer, 1995;Kotb, 1995).Investigators attempting to identify superantigen genes in S. canis by DNA hybridization analysis using various Necrotizing fasciitis, a deep seated infection of S.pyogenes superantigen genes found that S.canis the subcutaneous tissue that progressively destroys lacked genes with significant homology to the probes fascia and fat.A diagnosis of NF is made if there is (De Winter et al., 1999).Recently the presence of Sag either histopathologic or surgical evidence of superficial gene smeZ was detected in a human S.canis isolate fascial oedema and necrosis.Most dogs with NF also although examination of isolates from dogs with TSS showed serious systemic disease including hypotension or NF has failed to detect the presence of Sag genes and sepsis.(DeWinter et al, 1999;Igwe, 2003 andMiller et al., Prescott et al., (1997) reported 14 cases of canine 1996).A complete understanding of how S.canis STSS and NF in 1992 from Ontario, Canada having causes invasive disease would include analysis of the typical signs of STSS although one dog also had signs genetic diversity among these isolated species of spinal cord involvement.Out of 14, 8 dogs had (Pesavanto et al., 2007).It is assumed that S.canis associated NF.A consistent sign in all cases of NF was contains many virulence characteristics of Group A intense pain.Localized heat and swelling were Streptococcus (GAS) including an M type protein identified within 48 hours of presentation.All dogs (Collins et al., 1992), hemolysins and erythrogenic with NF had extensive accumulation of exudate along toxins, but lacks some of the other recognized the fascial planes.virulence genes with significant homology to those in Necrotizing fasciitis is the localized form of S.pyogenes (DeWinter et al., 1999).

Necrotizing Fasciitis
infection.Dogs with NF have high rectal S.canis is a beta haemolytic streptococci which usually produce phosphatase, leucine amidopeptidase, temperature and tend to develop extensive soft tissue arginine dihydrolase, alpha-D-and beta-D-galacto-sloughing of the underlying fatty tissue; hence it has been called 'flesh eating bacteria'.Areas most sidase and ferment lactose and ribose.It also produces commonly involved are hock joints, flanks and the a CAMP like reaction on sheep blood agar after 24 abdominal skin.There is pus discharge from affected hour incubation (Lyskova et al., 2007; DeWinter and areas which is very painful to touch.Prescott, 1999).Genetic methods like DNA-DNA reassociation procedures, Pulse Field Gel Electrophoresis and 16 s r RNA gene sequencing can also be used Mortality rate normally exceeds 70-80% as the for diagnosis.Serologic tests include Anti Streptolysin course of disease is so rapid that a dog may succumb to O (ASO) titer, anti-hyaluronidase titer and anti DNAseB.it in as little as 1to 4 hours from the appearance of the Veterinarians should consider possible CSTSS first signs, so that some dogs are simply found dead in when the clinical signs, including pain are out of their runs, houses or yards.
proportion to the injury sustained or a predisposing medical problem.Rapid deterioration, marked pain and/or discomfort, with or without severe tissue Canine Toxic shock syndrome and/or necrotizing swelling are consistent findings in these dogs.A fasciitis resemble the toxic shock syndrome in people diagnosis of STSS should be made if a dog has infected with S.pyogenes.On postmortem, affected hypotensive shock and shows involvement of at least 1 dogs typically have deep dermal or subcutaneous other organ or system along with isolation of a lesions along the limbs or trunk.Involvement of Lancefield Group G streptococcus, usually in pure multiple organ system suggests a period of septicemia culture from infected site.A diagnosis of NF is made if before the development of this syndrome (Prescott and there is either histopathologic evidence of necrosis of De Winter, 1997).Most dogs die without developing the fascial planes and tissues, and if a Group G any significant postmortem lesions.In a finding, most streptococcus in pure culture is isolated from this site significant pathologic lesion was a suppurative and as well.haemorrhagic broncho-pneumonia with focal areas of bronchiolar epithelial ulceration, superimposed on Treatment needs to be started as early as possible lesions of chronic bronchiectesis along with widespread vascular congestion affecting all solid organs (Prescott in order to have any chance of saving the affected dog. The prognosis for systemic STSS must be considered et al., 1995).Dogs with NF have extensive accumulation very poor and dogs often succumb even after a heroic of exudates along with necrotic fascial planes.
effort at the treatment.Those dogs who survive have been treated with intravenous antibiotics to which streptococci are susceptible, particularly to penicillin Diagnosis is based on the history of previous G and Clindamycin and shock therapy may include trauma, typical clinical signs, bacterial culture and volume resuscitation, vasopressors, extensive surgical sensitivity of discharges of the affected tissue samples.debridement of fascial planes and open wound In most cases, there is history of sudden development management with daily irrigation of antibiotics (Prescott of clinical signs like intense pain, fever with lateral et al., 1995).One important point to be considered is recumbancy, rapid spontaneous hemorrhages associated that organism is often resistant to enrofloxacin and with hemoptysis, epistaxis, severe bruising of skin and aminoglycosides therefore multiple antibiotic therapies in some cases, bloody diarrhea.There may be hypotension, with agents such as cephalexin, clindamycin, lincomycin, multiorgan failure and quick death especially without erythromycin and potentiated sulfas should be proper treatment.Isolation and identification of Gram considered.The best approach is based on sensitivity positive cocci in pairs or chains from clinically information from a culture but that will take some time relevant, normally sterile sites (infected smears, to generate.tissues or aspirates), usually in pure culture gives a In a study, the antimicrobial sensitivity tests definite diagnosis.Bacteria may also be found in showed that all isolates of S.canis were sensitive to wounds, blood, secretions, pus or other sites.
penicillin G and ampicillin and the least effective Streptococcus can be identified by their antimicrobial agent was tetracycline (only 33.8% of haemolytic pattern on blood agar, colony morphology, susceptible strains).The respective rates of resistance biochemical reactions and serology.to vancomycin, chloramphenicol, erythromycin and muscle fascia, and timely Gram staininig of clindamycin were 10.5%, 7%, 3.5% and 2.3% respectively surgically obtained material may provide an early and (Lyskova et al., 2007).
definite etiologic diagnosis in order to initiate correct Early recognition, a correct diagnosis and treatment procedure.prompt treatment is essential.Dogs treated with the Alongside this allopathic line of treatment, altercorrect injectible antibiotics at the early stages of the native therapeutic approaches including homeopathic condition are more likely to recover.Treatment of medicines like CARBO VEG.IM at 10-15 minutes cases with NF will improve with debridement or intervals and ARNICA can be given to the dogs clearing away of the dead tissue, but healing is identified with CSTSS.prolonged and skin grafts are often necessary.Long term management is intense with frequent bandage changes, cleaning of the wounds, antibiotic therapy The threat of canine streptococcal toxic shock syndrome and NF has been increasingly becoming a and the need for multiple anesthetic procedures to serious threat to dogs and dog owners as well as repair and reconstruct the damaged areas most often veterinarians.Reported cases of canine CSTSS and hock joints, the flanks and the abdominal skin.
S. NF have increased since 1995 in Northern America In a mouse model of myositis caused by pyogenes especially Canada though not much data is available , penicillin was ineffective when treatment from Indian subcontinent regarding the status of this was delayed > 2 hrs after initiation of infection et al., syndrome.(Stevens 1988).Survival of erythromycintreated mice was greater than that of both penicillin-For effective control of CSTSS and NF, factors treated mice and untreated controls, but only if contributing to its spread must be understood as an treatment was begun within 2hours.Mice receiving important pathogen causing fatal diseases.Popularity Clindamycin, however, had survival rates of 100%, of fluroquinolones especially enrofloxacin for use in 100%, 80% and 70% even if treatment was delayed dogs has been associated with the emergence of CSTSS by S.canis (Miller et al., 1996).Enrofloxacin 0,2,6 and 16.5 hours, respectively (Stevens et  There are no commercial vaccines.Stress factors, group C and group G streptococci isolated from such as travelling long distances, confinement, exposure patients with invasive infections.These authors have to stressful situations; estrus etc may decrease a dog's also suggested that among high risk patients with resistance to disease.Dog equipments should be kept invasive GCS and GGS infections who can't be treated clean and not shared by multiple dogs.The reprowith penicillin, tolerance of other antibiotics, ductive tract of bitches in season is an open invitation including vancomycin, should be closely monitored to bacteria as well so it is advisable to spay or neuter and a combination therapy for synergy (Aminoglycocompanion animals.Wounds should be kept clean and sides and a cell wall active agent) in the initial good hygiene should be practiced.Biting, fighting, treatment of these patients should be adopted.
taking part in dog shows and other community Though antibiotic selection is critically important, activities increase the risk of illness.Also overgrown other measures, such as prompt and aggressive explonails and teeth pose a threat.ration and debridement of suspected deep-seated S.canis or S.equi subsp zooepidemicus are a part wounds are mandatory.Fever is the most frequent of the normal flora in some species so it is very finding along with excruciating pain.Later systemic difficult to control the infections caused by them.Only toxicity develops, and evidence of necrotizing fasciitis factors leading to development of the disease condition and myositis may appear.Surgical debridement may can be understood and avoided.Dogs should be made be too late at this point.Neutralization of circulating to avoid high risk condition.toxins should be the main consideration.Two reports describe successful use of intravenous gamma globulins in treating streptococcal TSS in humans (Barry et al., A new streptococcal protective antigen SPA of 1992; Yong, 1994).
S.canis (SPASc) has been recognized and this might Prompt surgical incision with visualization of

Control and Prevention
Future Prospects shock syndrome are healthy only hours prior to al., 1991; Muller et al., 1994.) are capable of inducing becoming very sick.Pain is the most common initial TNFá production by mononuclear cells in vitro symptom and is abrupt in onset and severe, and usually (Wannamaker et al., 1951; Muller et al., 1994; Hackett precedes tenderness or physical findings.Without a et al., 1994).Exotoxins such as streptolysin O (SLO) prompt therapy, the dog's condition deteriorates very are also potent inducers of TNFá and pre-Interleukin rapidly with death occurring within eight to twelve (IL)-1 â to release preformed IL-1 â (Kappur et al., hours.Typically, dogs that develop CSTSS are 1993 . unclear and very little is known about transmission or prevention.Streptococcal Toxic shock Syndrome is a severe The emergence of streptococcal toxic shock and often fatal disease characterized by shock and syndrome and necrotizing fasciitis caused by S.canis multiorgan failure.Both S.canis and S.equi subsp. was reported by DeWinter & Prescott in 1999 from zooepidemicus have been isolated from dogs with Canada and USA after a series of seven dogs suffering cases of Streptococcal Toxic shock Syndrome with S. with systemic infections caused by S.canis was canis being the major bacterium involved.reported by Miller and Prescott in 1996 from Southern Necrotizing fasciitis ("flesh eating Strep") is a Ontario, Canada.Since then, new more invasive strains localized form of streptococcal infection characterized of S.canis have emerged, resulting in frightening new by rapidly advancing infection of subcutaneous diseases in dogs as well as humans and various other tissues including muscle, fat and skin with extensive animal species.The disease syndrome is now ; disseminated intravascular coagulation (DIC) which Goshorn and Schlievert, 1989; Kaul et al., 1997; rapidly leads to multiple organ dysfunction syndrome McShan, 2000; Stevens et al., 1989; Yu and Ferati, al., causes a bacteriophage induced lysis of S.canis and 1995; Stevens et al., 1994).superantigen expression which might result in the Beta-Lactum failure has been reported in spread of virulent gene into other bacteria thereby treating pharyngitis caused by Group G streptococcus contributing to emergence of the pathogen ((Ingrey et (Savini et al., 2008).Evidence of invitro vancomycin al., 2003).tolerance was also reported by Zoutis et al., (1999) by