Streptococcus suis Infection in 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 alpha-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, serotypes 20, 22, 26 are now considered as S parasuis, serotypes 32 and 34 as S orisratti and serotype 33 as S ruminantium. The latter has been defined as a ruminant-associated pathogen. In summary, there are presently 29 serotypes of S suis recognized. 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 are highly virulent and belong mainly to the clonal complex or CC1, as characterized by multilocus sequence typing. . Within this CC, sequence type or ST1 is the one most commonly isolated from clinical cases. Most serotype 2 strains from North America belong to CC28, with ST28 and ST25 being the most prevalent, and presenting lower virulence capacities, which may explain the importance of other serotypes in this continent, such as serotypes 1/2 and 3.

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. A still unconfirmed hypothesis suggests that S suis can also reach the bloodstream through the intestinal route. 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. This pathogen has become highly prevalent in countries where prophylactic and metaphylactic use of antimicrobials are not allowed.

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 weeks after weaning), rarely in suckling and growing pigs, and almost never in 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 pigs. However, some herds with animals harboring virulent strains but not showing illness may suddenly develop serious clinical disease in the presence of predisposing factors such as:

Disease outbreaks due to S suis infection have been frequently reported with co-infections of porcine reproductive and respiratory syndrome Porcine Reproductive and Respiratory Syndrome virus and, less frequently, with swine influenza Influenza A Virus in Swine Swine influenza is a highly contagious respiratory disease that results from infection with influenza A virus (IAV). IAV causes respiratory disease characterized by anorexia, depression, fever... read more virus. 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 highly common in North America. Endocarditis is also a frequent finding but mostly in growing pigs, with affected animals 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 to be proved.

Presumptive diagnosis is generally based on history, clinical signs, age of animals, and gross lesions. Isolation and serotyping of the infectious agent and, if possible, evaluation of microscopic lesions in affected tissues confirm the diagnosis. After isolation, biochemical identification of S suis isolates is routinely carried out by MALDI-TOF. Serotyping is important to confirm and implement preventive measures, because isolation of a predominant serotype should be observed. When S suis is a secondary agent, several different serotypes will be recovered from different animals of the same herd. Multiplex PCR tests are available to easily serotype S suis strains. 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, mainly for serotype 2. 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. Whole genome sequencing can also be used to compare isolates.

Detection of virulent strains of S suis from tonsils or nasal cavities should not be done, because S suis is a normal inhabitant of these sites, and universal virulence factors are unknown. In addition, 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. There is only one PCR test that specifically identifies "true" S suis and is based on the gene recN.

Differential diagnoses include:

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.

Low resistance of isolates to penicillin has been reported and varies among countries, but extended spectrum beta-lactams such as ampicillin and amoxicillin appear to retain good effectiveness. Treatment can also be administrated via the drinking water or in amoxicillin-medicated feed in countries where this practice is allowed. 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 (mainly in cases of meningitis) and improve the overall condition of pigs. Animals should be watered carefully to avoid dehydration, because they are sometimes unable to drink.

Vaccines available in the field are autogenous 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 6–9 weeks old, early piglet vaccination should be implemented, and 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 to passively protect piglets is commonly used in the field, being less costly, but offers poor results, probably due to a decline of maternal antibodies before 5 weeks of age.

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:

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 southeast 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.