Streptococcus suis Infection
S suis is a significant pathogen of swine and one of the most important causes of bacterial mortality in piglets after weaning. It is considered a normal inhabitant of the upper respiratory tract (especially nonvirulent strains) and can be easily found in tonsils, which are considered a natural niche. It can also be isolated from the reproductive and GI tracts of clinically healthy pigs.
S suis possesses antigens somehow related to Lancefield group D streptococcus , but it is taxonomically far from other members of this group. It is considered a facultatively anaerobic, gram-positive, nonmotile coccus, oriented in chains of varying lengths. S suis produces α-hemolysis (incomplete hemolysis) on blood agar and is catalase negative. It has a worldwide distribution, and originally 35 serotypes based on capsular antigens had been described (serotypes 1 to 34 and serotype 1/2). However, there is still some controversy, because serotypes 20, 22, 26, 32, 33, and 34 have been suggested as not being part of the S suis species. Nonetheless, the number of serotypes considered as highly virulent is relatively small and depends mainly on geographic location.
Most studies on virulence factors of S suis have been performed with serotype 2 only. Type 2 virulent and nonvirulent strains exist, but characterization of virulence factors is still incomplete. Capsular polysaccharide is so far the most important critical virulence factor. However, well encapsulated nonvirulent serotype 2 strains do exist. Some proteins, such as the muramidase-released protein, the extracellular factor, and the hemolysin (suilysin), constitute virulence-related proteins for serotype 2 strains isolated in Europe and Asia but not for North American strains. So far, there is no single true predictor of pathogenicity. In fact, serotype 2 strains from different continents are phenotypically and genotypically very different. Most strains from Asia and Europe belong mainly to the sequence type or ST1, as characterized by multilocus sequence typing, and are highly virulent. Serotype 2 strains from North America belong to ST25 and ST28, presenting lower virulence capacities, which may explain the importance of other serotypes in this continent, such as serotypes 3 and 1/2.
The mechanisms that enable S suis to disseminate throughout the animal are not well understood. The bacterium is able to spread systemically from the nasopharynx, occasionally resulting in septicemia and death. The palatine and pharyngeal tonsils are both potential portals of entry for S suis, leading to subsequent hematogenous or lymphogenous dissemination. Survival of the organism once in the bloodstream may be facilitated by the capsular polysaccharide as well as cell wall components, which efficiently hamper phagocytosis. If S suis does not cause acute fatal septicemia, bacteria are able to reach the CNS via mechanisms that are only partially elucidated, such as invasion of brain microvascular endothelial cells or through the choroid plexus epithelial cells. In both septicemic and CNS cases, excessive host inflammation seems to play an important role in the pathogenesis of infection.
S suis is present in all parts of the world in swine intensive areas. Serotypes 1–9 (including serotype 1/2 that shares antigens with serotypes 1 and 2) represent >70% of S suis isolates recovered from diseased pigs, mainly in North America where most studies have been done. Serotype 2 is, in general, the most prevalent worldwide, but its importance is lower in North America and higher in Asia and some countries in Europe, such as France. Serotype 9 is the most frequently isolated type in other European countries, such as Spain, Germany, and the Netherlands.
Most clinically healthy pigs are carriers of multiple serotypes of S suis, although a few are colonized by virulent strains. Piglets become colonized with S suis from vaginal secretions during parturition and while nursing. Asymptomatic carriers serve as a source of infection for their pen mates after they are mixed and commingled in the nursery, when maternal antibodies are no longer present. Clinical infections are seen mainly in weaned pigs (2–5 wk after weaning), growing pigs, and less frequently, suckling piglets and adult animals. Transmission between herds occurs by the movement and mixing of healthy carrier pigs. The introduction of a highly virulent strain into a naive herd may result in subsequent onset of disease in weaned and/or growing pigs. However, some herds with animals harboring virulent strains but not showing illness may suddenly develop serious clinical disease in the presence of other predisposing factors such as overcrowding, poor ventilation, excessive temperature fluctuations, mixing of pigs with an age spread of >2 wk, and coinfections with other pathogens. Disease outbreaks due to S suis infection have been frequently reported with coinfections of porcine reproductive and respiratory syndrome virus (see Porcine Reproductive and Respiratory Syndrome). S suis might also be transmitted via fomites and flies, although probabilities are low. Although S suis has been isolated from different mammal species and birds, the importance of such reservoirs is unknown.
Even when the carrier rate in pigs is near 100%, the incidence of the disease varies from period to period and is usually <5%. However, in the absence of treatment, mortality rates can reach 20%. The earliest sign is usually fever, which may occur initially without other obvious signs. It is accompanied by a pronounced septicemia that may persist for several days if untreated. During this period, there is usually a fluctuating fever and variable degrees of inappetence, depression, and shifting lameness. In peracute cases, pigs may be found dead with no premonitory signs. Meningitis is the most striking feature and the one on which a presumptive diagnosis is usually based. Pigs in the early stages of meningitis may hold their ears back and squint their eyes. Other early nervous signs include depression, incoordination, and adoption of unusual stances (eg, dog-sitting), which soon progress to inability to stand, paddling, opisthotonos, convulsions, and nystagmus. Swollen joints and lameness are indicative of polyarthritis, which is common in North America. Endocarditis is also a frequent finding in older piglets, with affected pigs dying suddenly or showing signs of dyspnea, cyanosis, and wasting. Signs of respiratory disease may be seen in some outbreaks, although the role of S suis as a primary agent of pneumonia, in the absence of other pathogens, remains controversial.
Lesions are mainly seen in weaned and growing pigs and are associated with lymphadenopathy, meningitis, arthritis, and endocarditis. Polyserositis similar to that seen in Glässer's disease is sometimes seen. Lesions may include fibrinopurulent exudates in the brain, swollen joints, fibrinous serositis, and cardiac valvular vegetations. Splenomegaly and petechial hemorrhages indicating septicemia are common. Significant microscopic lesions are usually limited to the brain, heart, and joints. The predominant lesions are neutrophilic meningitis and chorioiditis, with hyperemic meningeal blood vessels, and fibrinopurulent or suppurative epicarditis. Evidence of encephalitis, edema, and congestion of the brain may be present. The choroid plexus may have disruption of the plexus brush border, and fibrin and inflammatory cell exudates may be present in the ventricles. Microscopic lesions do not seem to be associated with a given serotype.
Presumptive diagnosis is generally based on history, clinical signs, age of animals, and gross lesions. Isolation and serotyping of the infectious agent and evaluation of microscopic lesions in affected tissues confirm the diagnosis. After isolation, biochemical identification of S suis isolates recovered from diseased animals is possible with a minimum of biochemical tests. Serotyping is important to confirm and implement preventive measures, and several multiplex PCR tests to easily serotype S suis strains have been reported (and can be used by any laboratory). Validated and specific serologic tests to detect antibodies are not available for S suis. Genetic characterization, including multilocus sequence typing, is done in some laboratories and is particularly useful for epidemiologic studies. For European and Asian strains of serotype 2, detection of the muramidase-released protein, the extracellular factor, and the hemolysin (suilysin) by PCR as an indication of virulence can also be done.
Detection of virulent strains of S suis from tonsils or nasal cavities cannot be done, because universal virulence factors are unknown. These sites are highly contaminated, and traditional bacterial isolation has a low sensitivity. Strains isolated from tonsils must be confirmed by PCR as being S suis, because biochemical tests are not able to correctly differentiate this bacterial species from other streptococci normally present in the upper respiratory tract of swine.
Differential diagnoses include polyserositis caused by Haemophilus parasuis or Mycoplasma hyorhinis; meningitis caused by H parasuis; endocarditis caused by Erysipelothrix rhusiopathiae; septicemia caused by H parasuis, Actinobacillus suis, Escherichia coli, Erysipelothrix rhusiopathiae, or Salmonella Choleraesuis; and polyarthritis caused by other streptococci, staphylococci, E coli, or A suis.
Prompt recognition of the early clinical signs of streptococcal meningitis, followed by immediate parenteral treatment of affected pigs with an appropriate antibiotic, is currently the best method to maximize survival. The early stages of meningitis may be difficult to detect, so weaned pigs should be observed 2–3 times daily on farms where S suis infections are a problem. Resistance of isolates to penicillin has been reported and varies among countries, but extended spectrum β-lactams such as ampicillin and amoxicillin appear to retain some good effectiveness. Treatment can also be administrated via the drinking water or in amoxicillin-medicated feed. However, because of the method of spread of the disease, treatment needs to be started quickly. Whichever method of medication is used, treatment should be continued for at least 5 days. Administration of an anti-inflammatory preparation is sometimes recommended to reduce inflammation of affected tissues and improve the overall condition of pigs with S suis meningitis. Treatment of sows with antibiotics before farrowing may reduce pathogen transmission to piglets, although results are controversial.
Vaccines available in the field are bacterins (inactivated whole cells), and they have proved to be relatively ineffective in preventing outbreaks. If somehow useful, the protection would be serotype-specific. Because affected animals are in general 6–10 wk old, interference with maternal antibodies should be considered. In addition, the adjuvant used seems to play an important role; a bacterin with a water-in-oil emulsion as an adjuvant provided better results than the same bacterin with an aluminum hydroxide–based adjuvant. Sow vaccination also had poor results.
One main problem is that S suis is one of several bacterial pathogens that have been able to defeat eradication efforts in nursing or early weaned pigs, because animals are already colonized immediately after or even during farrowing.
Streptococci are susceptible to the action of aldehyde, biguanide, hypochlorite, iodine, and quaternary ammonium disinfectants.
Human infections with S suis can result in septicemia, meningitis, permanent hearing loss, endocarditis, and arthritis. In Western countries, mortality has been reported to approach 7%, and most cases are related to employment in the swine industry (ie, pig farmers, abattoir workers, persons transporting pork, meat inspectors, butchers, and veterinarians). In Asia, the general population is at risk, and mortality rates can be >20%. S suis is considered one of the most common causes of adult meningitis in Thailand, Vietnam, and Hong Kong. Serotype 2 and, to a lesser extent, serotype 14 are mainly involved in human cases. Transmission to people occurs via contamination of skin wounds or mucous membranes by blood or secretions from infected pigs or by consuming raw meat or blood (as is the case in Asia). The disease is considered to be underdiagnosed and underreported in several countries.