19e Other bacterial diseasesStreptococcosis

Many pyogenic (β-haemolytic) streptococci of clinical significance have animal connections. In the last edition of this book two species of streptococci were considered of major zoonotic interest, namely Streptococcus suis and S. zooepidemicus. Since then, numerous sporadic zoonoses due to other streptococci have been reported, and a newly recognized fish pathogen with zoonotic potential termed S. iniae has emerged. Changes in nomenclature make the terminology confusing. For example, the organism known as S. zooepidemicus—now termed S. dysgalactiae subsp. zooepidemicus—still causes pharyngitis in humans, complicated rarely by glomerulonephritis after ingestion of unpasteurized milk. Pigs remain the primary hosts of S. suis with human disease mainly affecting those who have contact with pigs or handle pork.

Once a sporadic disease, several major epidemics associated with high mortality have been reported in China. The major change in reports of zoonotic streptococcal infections has been the emergence of severe skin and soft tissue infections, and an increasing prevalence of toxic shock, especially due to S. suis (Tang et al. 2006), group C (Keiser 1992) and group G β-haemolytic streptococci (Barnham et al. 2002). Penicillin remains the mainstay of treatment for most infections, although some strains of group C and G streptococci are tolerant (minimum bactericidal concentration difficult or impossible to achieve in vivo) (Portnoy et al. 1981; Rolston and LeFrock 1984) and occasionally strains with increased minimum inhibitory concentrations (MIC) for penicillin are reported.

Agents preventing exotoxin formation, such as clindamycin and occasionally human intravenous immunoglobulin, may be used in overwhelming infection where circulating exotoxins need to be neutralized in order to damp down the massive release of cytokines generated by their production (Darenberg et al. 2003). Prevention of human disease focuses on maintaining good hygienic practice when dealing with live animals or handling raw meat or fish products, covering skin lesions, thorough cooking of meats and pasteurization of milk.

Streptococci are Gram-positive (i.e. blue-staining) spheres arranged in chains. The name is derived from strepto (Greek for twisted chain or pliant) and kokkos (Greek for berry/kernel); the most pathogenic streptococci are termed ‘pyogenic’ (pus-forming). Most are β-haemolytic, i.e. colonies surrounded by a zone of β-haemolysis (complete) when cultured on agar containing blood, the haemolytic activity occasionally affected by the nature of the animal blood used. As part of the lacto-bacteria group, streptococci produce lactic acid from the fermentation of carbohydrates, being incapable of respiratory metabolism. Since streptococci are facultative anaerobes, they grow well in anaerobic conditions. Streptococcal growth is inhibited by acid conditions so growth may be optimized by buffering broth cultures, as in Todd Hewitt medium.

Streptococci were first described by Billroth in 1874, and five years later Pasteur isolated streptococci from the blood of a woman with puerperal sepsis. Streptococcus pyogenes, the type species, was first described in 1884 by Rosenbach. Throughout history S. pyogenes has been responsible for tonsillitis, sepsis in childbirth (puerperal sepsis), cellulitis (inflammation of skin and superficial soft tissues) and deeper soft tissue infections such as necrotizing fasciitis and myositis. In the last 20 years, S. pyogenes has increasingly been recognized as causing streptococcal toxic shock syndrome (STSS).

Although other β-haemolytic streptococci can produce similar illnesses, including tonsillitis, soft tissue infections and more rarely, toxic shock in animals and man, streptococcal zoonoses are comparatively unusual because of host and tissue specificity. Most streptococci exist happily as part of the normal flora of animals and man, often in the oropharynx or gut.

Serological differentiation of the β-haemolytic streptococci depends on the nature of the carbohydrate components of the cell wall. The Lancefield typing scheme, first described in 1933, is based on the capillary precipitin reaction between the group specific carbohydrate cell wall antigens (extracted by hot acids) and hyperimmune rabbit antisera (Lancefield and Hare 1935). Nowadays commercial kits are available for ‘grouping’ of streptococci, using various methodologies. The most predominant method utilizes agglutination of antibody-coated particles, the defining group-specific antigens denoted by letters. There are now 20 serogroups of β-haemolytic streptococci, divided according to the original Lancefield typing scheme: A to V (excluding I and J). The most common human infections are generally caused by groups A–F.

In older reports the streptococcal species was rarely identified beyond the serogroup, and some were probably misidentified. Due to advances in molecular methodology, streptococcal taxonomy has changed in recent years making the comparative evaluation and interpretation of older reports of streptococcal zoonoses difficult.

Lancefield groups may contain one or more species, but confusion in differentiation easily arises when some species possess more than one group antigen, technically having features in common with other streptococci and so may be misidentified. One classic and confusing example of overlapping group antigens is S. dysgalactiae subsp. equisimilis, which may possess Lancefield group A, C, G or L carbohydrate antigens, and is one of the so-called ‘large colony’ types of streptococci. Equally, many of the so-called ‘small colony’ strains of the S. anginosus group possess similar antigens but, as they are rarely associated with zoonoses, they will not be considered further in this chapter.

Biochemical tests are used in addition to ‘grouping’ and helps further differentiate the various strains. Finally, modern molecular techniques have enabled a much better understanding of the diversity and genetic relationship of the streptococci.

In order to simplify this complex taxonomy for better understanding, Table 19e.1 may be helpful, referring to the streptococci by their old names and modern equivalents.

The type species for the haemolytic streptococci is Streptococcus pyogenes, the classical ‘group A β-haemolytic streptococcus.’ S. pyogenes is not, however, alone in carrying the group A antigen, as some strains of Group C streptococci such as S. equisimilis may also possess it.

Historically, S. pyogenes mastitis followed contamination by the hands of human milkers. Although companion animals have long been recognized as the source of many childhood zoonoses, including tonsillitis (Copperman 1982), S. pyogenes is rarely isolated from asymptomatic animals (Wilson et al. 1995). Whilst the prevalence of S. pyogenes in dogs and cats is reported as 2.8% (Crowder et al. 1978), simultaneous Group A streptococcus (GAS) infection in animal and owner is apparently exceedingly rare (Falck 1997). Furthermore, those GAS strains colonizing companion animals are probably acquired from close contact with their owners; for example, licking or sharing sleeping areas and is effectively a ‘humanosis’ rather than a zoonoses. GAS infections tend to manifest clinically as conjunctivitis, the animals then acting as reservoirs for secondary human infection.

S. pyogenes colonizes the throat of 25–30% of otherwise asymptomatic, healthy humans, especially children, in whom the major manifestation of infection is tonsillitis. Cellulitis and the more severe skin and soft tissue infections such as necrotizing fasciitis and myositis, when associated with toxic shock syndrome, have an associated mortality as high as 80%.

Cows occasionally suffer mastitis with S. pyogenes. Among many historical outbreaks due to contaminated milk, Gollege (1932) reported an outbreak in a farming family where two cows were infected, but infections were confined only to the family as a result of pasteurization of the milk before sale. Infected cows may excrete S. pyogenes for up to 13 months (Bendixen and Minett 1937). Outbreaks may occur in meat processing (Barnham and Neilson 1987) as minor skin wounds, with contamination of knives and work surfaces facilitating horizontal spread between workers.

S. pyogenes infection may occasionally recur inexplicably within families despite control measures and companion animals may be a hidden reservoir. Extensive swabbing of 61 dogs, cats, rabbits and guinea pigs from 46 households suffering with recurrent infections found two families who owned a dog and a cat each of which were suffering with conjunctivitis (Falck 1997). After simultaneous pe

nicillin therapy of all the family members and their pets no further infections were noted in either humans or animals (Falck 1997). Recurrent S. pyogenes pharyngitis was finally cleared only when the family and the dog were treated concomitantly with penicillin (Mayer and van Ore 1983). Another report implicated the family cat as the reservoir (Roos et al. 1988). Hence, an animal reservoir should be considered in otherwise unexplained recurrent human infection.

Six β-haemolytic species or subspecies possess the group C antigen (Facklam 2002). Most are β-haemolytic on sheep blood agar. Commonly found in domestic animals, guinea pigs, and birds, the four most common are S. dysgalactiae, S. equi, S. equisimilis, and S. equi subsp. zooepidemicus (formerly S. zooepidemicus), of which the latter currently has the most zoonotic potential.

Since S. equi and S. zooepidemicus are so similar, they are now referred to as S. equi subsp. equi and S. equi subsp. zooepidemicus respectively. Since S. dysgalactiae and S. equisimilis are closely related they are now termed S. dysgalactiae subsp. dysgalactiae and S. dysgalactiae subsp. equisimilis respectively.

S. equi subsp. equi is a β-haemolytic streptococcus expressing a group C antigen, and found mainly in horses.

S. equi subsp. equi causes a suppurative lymphadenitis and nasal discharge of horses which is highly contagious. Swelling of the lymph nodes occasionally compromises the airway, hence the common name ‘strangles.’ Once thought exclusive to horses, a case of canine strangles has been reported in a British dog (Ladlaw et al. 2006).

Many authorities have stated firmly that S. equi subsp. equi is not a zoonoses, although there is one report of ‘human strangles’ occurring in a 56 year old horse handler presenting with massive facial swelling and a cheek abscess from which S. equi subsp. equi and Bacteroides spp. were isolated. The suspected portal of entry was carious teeth (Breiman and Silverblatt 1986). A recent hospital outbreak of S. dysgalactiae subsp. equisimilis in Brazil was suggested to arise from horses grazing nearby, but despite identical strains being carried in their faeces, the link remained unproven (Torres et al. 2007).

S. equi subsp. zooepidemicus (S. zooepidemicus in earlier papers) is the commonest zoonotic pathogen amongst the group C streptococci and commensal in many animals, especially in the equine upper respiratory tract.

S. equi subsp. zooepidemicus is a common commensal and opportunistic pathogen. Previously known as S. zooepidemicus and a cause of bovine mastitis, equine respiratory infection, poultry infection, S. equi subsp. zooepidemicus causes abortions and wound infections in younger horses, and endemic cervical lymphadenopathy with draining abscesses in guinea pigs.

Transmission of S. equi subsp. zooepidemicus to man is mainly associated with contact with horses or consumption of contaminated dairy products. It causes acute pharyngitis, and may spread to the lungs causing pneumonia, and via the bloodstream causing meningitis, endocarditis, and septic arthritis. S. equi subsp. zooepidemicus was not isolated from any human throat swabs in studies by Lewis and Balfour (1999), Turner et al. (1997), and Duca et al. (1969). In an outbreak of S. equi subsp. zooepidemicus in Helsinki in 2003 following the consumption of unpasteurized fresh goat cheese, six people developed septicaemia with a further case of purulent septic arthritis. The median age of the patients was 70 years and none died. Strains indistinguishable by pulsed field gel electrophoresis and ribotyping were isolated from the human throat swabs, goat cheese samples, milk tank and vaginal samples of one goat (Kuusi et al. 2006).

Several outbreaks of acute glomerulonephritis have occurred after consumption of unpasteurized milk. The first outbreak affected 85 people in Romania (Duca et al. 1969) and the second began with mild upper respiratory tract infections affecting five of six members of a dairy farming family in Yorkshire (Barnham et al. 1983). In the latter, the farmer and two of the three children developed malaise, oedema, abdominal pain, haematuria, and hypertension—all signs and symptoms of acute glomerulonephritis. A recent outbreak of human nephritis in Brazil attributed to S. equi subsp. zooepidemicus, 3 of 133 confirmed cases died, 7 required haemodialysis and 96 were hospitalized (Balter et al. 2000). Rare disease presentations include septicaemia as the first manifestation of Hairy Cell Leukaemia (Oever et al. 2009).

Unlike other group C streptococci, S. dysgalactiae subsp. dysgalactiae is α-haemolytic, showing partial haemolysis and greenish discoloration on agar containing horse blood. Almost exclusively an animal pathogen, it is a well-recognized cause of bovine mastitis. The first report of isolation in dogs was from newborn Great Dane puppies which died of septicaemia within 72 hours (Vela et al. 2006).

Human infections due to S. dysgalactiae subsp. dysgalactiae are very rare, although a case of bacteraemia in a 48 year old female Chinese chef with a history of mastectomy developed two days after a puncture wound acquired whilst cleaning raw tilapia and shrimps (Koh et al. 2009).

Group G β-hemolytic streptococci (GGS) may be easily overlooked or misdiagnosed as S. pyogenes since up to 67% are sensitive to bacitracin. There are two types of GGS, S. equisimilis subsp. equisimilis, the GGS most commonly affecting humans, and S. canis (usually found in cattle and dogs). Similarities between GGS and S. pyogenes extend to the production of a streptolysin antigenically similar to that of S. pyogenes. Named streptolysin S (SL-S), this is one of the most potent cytotoxins known and probably responsible for much of the tissue destruction observed in animal and human infections (Humar et al. 2002).

S. equisimilis subsp. equisimilis may possess Lancefield group A, C, G or L carbohydrate antigens. S. equisimilis subsp. equisimilis produces streptokinase and streptolysin O, and infection produces an increase in the antistreptolysin O titre (ASOT), a serological test used commonly to diagnose recent S. pyogenes infection.

S. equisimilis subsp. equisimilis is a commensal of the mucous membranes of horses and swine. Occasionally isolated from aborted equine placentas, the organisms may be responsible for a strangles-like illness in horses (Preziusio et al. 2010). Suppurative erosive arthritis in swine, and pharyngitis in humans and horses has been reported (Turner et al. 1997).

Despite commonly colonizing humans in throat, nose and genital swabs, actual infections with S. equisimilis subsp. equisimilis are rare. Cases of endocarditis, pneumonia and cellulitis (Carmeli et al. 1995) have been reported with a recent recognition of its importance as a cause of vertebral osteomyelitis (Kumar et al. 2005).

S. equisimilis subsp. equisimilis commonly cause skin and soft tissue infections (SSTI) and increasingly streptococcal toxic shock syndrome (STSS).

GGS human infection is usually associated with other co-morbidities, including malignancy and defective lymphatic circulation. During a two year survey of Atlanta and San Franciscan residents with invasive group G streptococcal isolates, 87% had underlying disease (Broyles et al. 2009).

Lancefield group G streptococcus S. canis (Devriese et al. 1986), is a β-haemolytic opportunistic pathogen colonizing wounds or bites and carried by dogs, foxes, cattle, rodents, mink and rabbits. Despite apparent penicillin sensitivity on plate sensitivity testing, both group C and group G streptococci may exhibit ‘tolerance’, i.e. the MIC is far lower than the bactericidal concentration achievable in vivo (Rolston and LeFrock 1984).

S. canis colonizes dogs and cats and can cause neonatal septicaemia in puppies. GGS mastitis in cattle is rare, with an anecdotal report of a dog licking cows’ teats as a source of the infection (Tikofsky and Zadoks 2005). However, an outbreak in a New York herd in 1999 involved 46/90 (51%) cows infected with S. canis. The outbreak was finally brought under control after culling many infected cows, amoxicillin treatment, and the introduction of scrupulous hand hygiene. The infection was believed to originate from a farm cat that was afflicted with chronic S. canis sinusitis and enjoyed free access to the milking quarters. Milk from affected cattle and nasal secretions from the cat produced identical isolates (Tikofsky and Zadoks 2005). On the basis of ribotyping the authors conclude that S. canis was spread by secretions from the cat with sinusitis to one of the cows, and then horizontally through the herd because of poor milking hygiene.

The true prevalence of human disease is unknown because of lack of full identification in many laboratories. A cluster of S. canis ulcer infections occurred in three dog owners. The first, a 53 year old male with diabetic neuropathy suffered S. canis infection on a non-healing foot ulcer which needed extensive debridement. The second patient, an 80 year old female, had a gangrenous toe infected with S. canis and Pasteurella canis. The third patient, a 75 year old male had recurrent S. canis septicaemia from a pressure sore (Lam et al. 2007). Recurrent septicaemia is not uncommon in GGS infections. A 75 year old female was treated apparently successfully with penicillin for fever and swelling of the right thigh following a dog bite. She was readmitted with recurrent septicaemia three weeks later. Transoesophageal echocardiogram excluded endocarditis and after another prolonged course of antibiotics she returned home. Isolates from her and her dog were identical (Takeda et al. 2001).

Whether the apparent susceptibility of patients with rheumatoid arthritis to streptococcal infection is due to concomitant steroid or other immunosuppressive therapy is unclear. A 65 year old Japanese female with rheumatoid arthritis was handling raw fish, making tempura. Small burns on her fingers acquired during deep frying the fish were thought to be the entry site for the streptococci that produced a toxic shock syndrome. Post mortem examination revealed a necrotizing arteritis, septic pulmonary emboli, splenic abscesses, intestinal arteritis and abscesses in the kidneys and muscle (Hirose et al. 1997).

S. iniae is a fish pathogen with newly recognized zoonotic potential having already caused several outbreaks. S. iniae is β-haemolytic on sheep blood agar, but is not groupable with Lancefield antigens. Isolates are non-motile and sensitive to vancomycin. Most strains grow at 10°C but not 45°C and few grow in 6.5% sodium chloride.

Of two highly related clones only one has caused invasive disease, suggesting that an as yet unidentified virulence factor exists (Weinstein et al. 1997).

S. iniae causes subcutaneous abscesses in freshwater dolphins in aquaria and necrotic infection of the caudal peduncle of farmed fish. Outbreaks of invasive disease in aquaculture affect fish farms in countries worldwide, including Japan, Taiwan, Israel and North America (Weinstein et al. 1997).

Four cases of bacteraemia were identified in Toronto in 1995, three of whom suffered severe cellulitis, with one case of meningitis, endocarditis and septic arthritis. Three patients had prepared tilapias prior to infection and all had broken skin. During one year, nine further cases were found, all of whom had handled live or freshly killed tilapia imported from the USA (Weinstein et al. 1997). The most likely mode of entry to the body was via trauma to the hands from residual fins or scales (Koh et al. 2009) with 8/9 bacteraemic patients reporting having injured their hands whilst processing the fish within 24 hours prior to infection. Numerous other reports of S. iniae infection have emerged (Weinstein et al. 1997; Lau et al. 2003). Common risk factors are old age, and pre-existing co-morbidities such as diabetes mellitus.

Some authors have speculated that many of these infections are overlooked or misidentified, especially since six clinical isolates in the Canadian surveillance had initially been identified as S. uberis (non-pathogenic for man) (Weinstein et al. 1997).

Since its discovery in piglets nearly fifty years ago (de Moor 1963), S. suis has caused only sporadic cases of zoonotic infection, but latterly has been responsible for major epidemics in humans. Facultatively anaerobic and α- or non-haemolytic, not all isolates are pathogenic. Virulence varies with the serotype of S. suis. Initially designated as Lancefield group R streptococci, S. suis now belongs to the Lancefield S, R and T groups.

In many ways S. suis is the porcine equivalent of S. agalactiae, the β-haemolytic streptococcus of Group B (GBS) that affects human babies. Adult sows are asymptomatic carriers, with ∼80% carriage rate in some pig herds and, like human GBS infections, mothers can infect their infant offspring by vertical transmission. Transmission to humans is via damaged skin or the consumption of undercooked pork.

S. suis colonies are small, 0.5–1.0mm in diameter, and often slightly mucoid. S. suis is a facultative anaerobe, unable to grow in 6.5% sodium chloride, and may be α-haemolytic on sheep blood agar and β-haemolytic on horse blood agar and may therefore be misidentified (Tramontana et al. 2008). Phenotypically, S. suis can resemble S. gordoniae, S. sanguinis and S. parasanguinis (Facklam et al. 2002).

S. suis comprises 35 serotypes based on capsular polysaccharides. Serotypes are of variable virulence, some causing severe infections such as meningitis and septicaemia. S. suis types 1 and 2 are the predominant causes of infection. Serotypes 32 and 34 have now been recognized as distant from other serotypes and are termed S. orisratti.

S. suis type 2, the most pathogenic, is a hardy organism, resistant to many environmental conditions and survives 10 minutes at 60°C, or 2 hours at 50°C. The organism may survive six weeks on carcasses held at 10°C, one month in dust and three months in faeces at 0°C (Lun et al. 2007).

A surprising feature of the recent S. suis outbreak in China has been the high incidence of toxic shock syndrome (Chan et al. 2007). Whereas streptococcal toxic shock syndrome due to S. pyogenes is due mainly to superantigens inducing an intense inflammatory response by massively activating T-cells and releasing cytokines, S. suis type 2 is thought to produce toxic shock due to the presence of a unique 89kb fragment in the genome. This encodes a two-component signal transduction system (SalK-SalR) necessary for full virulence. Other potential virulence factors identified include muraminidase-released precursor, extracellular factor and ‘suilysin’—a thiol-activated haemolysin originally derived from a Netherlands strain.

Multilocus sequence typing of S. suis showed the 2005 epidemic Chinese strains are grouped into a sequence type (ST) termed ST7 on the basis of the presence of seven housekeeping genes. Whole genome sequencing of the representative strain of the 2005 epidemic identified a potential pathogenicity island (PAI) named 89K. This may function as a new specific virulence marker for the Chinese S. suis-2 clones (Chen et al. 2007) since the virulent strains carrying 89K are ST7.

S. suis type 2 is a pathogen for man and pigs. The domestic pig (Sus scrofa domestica) is a major reservoir although there are three reports of infections from wild boar, including a case of a poacher who contracted meningitis (Halaby et al. 2000).

The major site of carriage in swine is the palatine tonsils. Infection produces polyarthritis, meningitis and septicaemia in suckling pigs. Piglets are the most susceptible to infection, especially if bred in poor housing with poor ventilation.

Meningitis is common in older, weaned pigs, who present with depression, anorexia, trembling, incoordination, and with other features of nervous system dysfunction such as opisthotonous, fits, blindness, ear infections, deafness and vestibular dysfunction. Pneumonia, endocarditis and abortions have been reported and occasionally other animals may be affected. The most pathogenic type is S. suis type 2 (Gottschalk et al. 2007) and about 10% of infected pigs at slaughter have evidence of endocarditis with subacute bacteraemia in many more (Robertson and Blackmore 1989).

The first human infections were reported in 1968 in Denmark (Arends and Zanen 1988). Apart from the 1996 and 2005 Chinese outbreaks, most human cases are sporadic and relatively uncommon. Although the majority of reported cases have occurred in China (69%) and Thailand (11%), there have been sporadic human cases in other countries, with 8% occurring in the Netherlands (Yang et al. 2009). No person to person spread has been reported (Lun et al. 2007). In one survey in New Zealand some 21% of New Zealand pig farmers had antibodies to S. suis type 2, and it has been estimated that the incidence of subclinical infections could be as high as 30% annually (Robertson and Blackmore 1989). 10% of meat inspectors and 9% of dairy farmers, most of them also kept pigs, were also seropositive (Robertson and Blackmore 1989).

Breton et al. (1986) reported S. suis 2 in 8.1% (28/347) of pig herds destined for slaughter in Ontario. A carriage rate of 9.4% was found in slaughtermen. They concluded that the eviscerators removing the larynx and lungs from carcasses were at significantly higher risk (p<0.05) of exposure to S. suis than other abattoir workers.

Furthermore, 80% of S. suis isolated from hands and knives of workers were from the lung evisceration station (Breton et al. 1986).

The most serious outbreaks have occurred in China. In Jiangsu province (1998 and 1999), and more recently in Sichuan province (2005), serious epidemics with a particularly high mortality were reported. Serotype 2 strains responsible for the Chinese Jiangsu outbreak (1998) killed 14/25 people affected. During June–Aug 2005 an outbreak of S. suis serotype 2 occurred during which 204 cases occurred and 38 died (Tang et al. 2006).

The classical presentation of meningitis or septicaemia in humans mirror the presentations of illness in pigs. S. suis meningitis is associated with a high incidence of hearing loss on recovery, together with ataxia, which very occasionally persists. The prevalence of deafness in human survivors of S. suis infection may be due to a special affinity of S. suis for the meninges, especially the cochlear division of the eighth cranial nerve. In a large series of cases, 72.5% had meningitis (Jiang et al. 2006), often accompanied by ataxia, coma, petechiae, articular pain, ecchymoses, rashes and rhabdomyolysis. One percent had endocarditis, 0.8% pneumonia and 0.3% peritonitis. More than 80% of those with septicaemia and shock died, 42% having diarrhoea, 77% vomiting, and 93% cutaneous haemorrhages. In the largest Chinese outbreak involving 215 cases, 62% with toxic shock syndrome died (Yu et al. 2006). Toxic shock syndrome is now emerging as a common presentation of S. suis infection, associated with a high mortality.

Of 204 cases in another study, 198 were farmers, 5 were butchers and one was a veterinary surgeon (Tang et al. 2006); some had broken skin, with cuts on their hands and feet, and all had had direct contact with ill or dead pigs. More than 25% (59 of those affected) suffered with toxic shock, 104 with meningitis and 41 others were mainly suffering with septicaemia. Fatal cases all began acutely with malaise, fever, headache, diarrhoea, hyperpyrexia, hypotension, an erythematous blanching rash affecting the extremities and usually a leucocytosis. Of those with toxic shock, 83% developed acute respiratory distress syndrome (ARDS), and 50% became comatose (Tang et al. 2006).

The first reported case of S. suis meningitis in Hawaii affected a 34 year old Tongan coconut tree trimmer. Despite having slaughtered pigs by hand in readiness for a celebration, he had no skin lesions likely to be entry sites. Despite treatment with ceftriaxone, he needed readmission twice after discharge because of hearing loss, nystagmus and dizziness, all of which eventually resolved completely with steroid therapy (Fittipaldi et al. 2009).

Penicillin resistance is uncommon. Intravenous gentamicin and penicillin was successful in a series of eight patients with septicaemia (Tramontana et al. 2008), in which the isolates were phenotypically similar to S. parasanguis, and were initially misidentified by conventional methodology but later confirmed by 16s rRNA sequencing. The patients recovered after two weeks of intravenous therapy followed by two weeks of oral amoxycillin.

In severe cases, high dose ceftriaxone has been ineffective, and combination therapy, such as amoxicillin plus ceftriaxone and gentamicin. Once septic shock has developed, there appears to be a limited effect of any antimicrobial (Lun et al. 2007). Several authors recommend prolonged therapy since relapse after 2 and 4 weeks of therapy (Gottschalk et al. 2007).

S. pyogenes, S. iniae, S. suis and S. canis can all enter the skin via traumatic scratches or breaks. Measures, such as wearing protective clothing when dealing with pig carcasses, and ensuring maximal hygiene when butchering or gutting fish are essential. Avoiding consumption of raw milk products would prevent S. equi subsp. zooepidemicus acquisition and thorough cooking of pork may prevent some infections. The World Health Organization recommend that pork should reach 70°C internal temperature or until juices run clear (Lun et al. 2007). Pasteurization of milk probably prevents many infections that would otherwise occur.

Despite research attempts, there are no vaccines yet available to prevent acquisition of infection. Good animal husbandry and hygiene remain the major methods of protection against infection.