Streptococcus suis a Cause of Human Meningitis: Another Emerging Pig Pathogen

By Ellen Jo Baron, Ph.D., D(ABMM), Professor Emerita, Stanford University School of Medicine, Director of Medical Affairs, Cepheid, is Associate Editor for Infectious Disease Alert.

Dr. Baron is Secretary-Treasurer of the NGO Diagnostic Microbiology Development Program (www.dmdp.org)

Synopsis: The number of cases of pig-associated meningitis and sepsis caused by Streptococcus suis has been increasing dramatically in Southeast Asia, with recent increases seen also in Spain and UK. The initial diagnosis is often incorrectly determined to be Streptococcus pneumoniae. One particular clone, Sequence Type 1, is responsible for much of this recent expansion. In contrast to S. pneumoniae, ceftriaxone resistance is not uncommon with this species. Several cases have been reported in the U.S. and new reports of first cases (Korea; Cambodia) highlight the growing recognition of this syndrome.

Sources: Sekizaki, T. Streptococcus suis: An Emerging Biothreat. Jrl Disaster Research 2012;7:303-312.

Choi, S.M. et al. Meningitis Caused by Streptococcus suis: Case Report and Review of the Literature. Jrl Clin Neurol 2012; 8:79-82.

In addition to increasing the risk of acquiring swine flu, kissing pigs could now be associated with another serious disease. Streptococcus suis meningitis is considered an emerging infectious disease, although cases of systemic infection have been described since 1954 in veterinarians. The first human meningitis cases other than in veterinarians were reported in Denmark in 1968, and a 2009 review noted that published cases worldwide increased from slightly more than 400 in 2007 to >700 cases in just 2 years.1 Perhaps it is still considered emerging because we in the U.S. are just discovering it. The first case report in a U.S. patient was in 2006 and a second case from a California hospital was described in 2008.2-3 Only one additional case has been reported in the U.S.4 In fact, it is possible that microbiology laboratories may be failing to identify S. suis, calling it "viridans streptococcus," which may suggest that it is a contaminant rather than a pathogen in the cerebral spinal fluid or the blood. To confuse unfamiliar microbiologists even more, the isolate may be positive for Lancefield type D, a hallmark of both enterococci and viridans streptococcal strains in the S. bovis family.

My first encounter with the organism was when the rural hospital microbiology laboratory for which I consult (and which is supported by the NGO Diagnostic Microbiology Development Project) in Kampong Cham, Cambodia, reported a viridans streptococcus from a woman patient with meningitis. I read the microbiology report: "Gram positive cocci in pairs and short chains, catalase negative, alpha-hemolytic colonies on sheep blood agar, bile soluble, and optochin resistant" and told the laboratory technician that she must have made a mistake. I said, "Viridans streptococci do not cause meningitis, so this must be S. pneumoniae and your optochin disk must have expired and lost potency."

Readers may remember from medical school training that the antimicrobial compound optochin should inhibit S. pneumoniae and thus display a rather large zone of inhibition. S. pneumoniae are soluble in sodium deoxycholate (bile), a usually fail-safe rapid test. In addition, because the isolate was intermediate for ceftriaxone, another anomalous result, it was sent to the Naval Medical Research Unit (NAMRU-2) in Phnom Penh for confirmatory testing.

To my surprise, an API 20 Strep strip (abbreviated biochemical test panel) and, eventually, molecular sequencing identified the strain as Streptococcus suis. Based on the Gram stain result, the patient's regimen was changed from the original anti-malarial empiric therapy to penicillin, and 5 days later she left the hospital in relatively good condition. This was the first identification of this species in Cambodia, although nearby Vietnam had been experiencing outbreaks for years.5 In fact, S. suis is the most common cause of meningitis in Vietnam. Virtually all cases subsequently seen in Cambodia (our laboratories are up to around 20) and those in Southeast Asia, Europe, and the few reported in the U.S. are associated with exposure to pigs. Patients have eaten pork, handled sick pigs or worked with pork meat. The first case from Korea was reported this year although the patient had no known pig exposure.6 An unusual risk factor is a practice seen only among a few young Chinese men, eating raw pig liver and kidney as a proof of manliness. This reminds me of a recent report about 2 young men from Wyoming who acquired Campylobacter enteritis after castrating lambs with their teeth.7 A few of the lambs were said to have diarrhea. Don't ask.

In the U.S. S. suis disease is most likely to be seen in patients who have recently visited Asia and had close contact with pigs or eaten undercooked pork. S. suis is an important cause of infection in pigs and piglets, but it is usually carried asymptomatically in the oropharynx. Although rates of colonization among pigs may reach 80% (50% in Japan), only a small proportion of pigs and piglets become ill.8 Pigs carry many serotypes but almost all human infections worldwide are caused by serotype 2. In addition to pigs, other animals including cattle, deer, horses, cats, and dogs, can carry the organism asymptomatically.

A virulence factor associated with this serotype and apparently less common in pig strains than in human strains is the polysaccharide capsule of serotype 2. Drug resistance is carried on integrative conjugative elements (ICEs). It is postulated that massive use of antibiotics in the livestock industry contributes to the acquisition and spread of the ICEs.9 Similarly, S. suis — with its easily mobile genetic elements — may be the source of resistance genes in more common human streptococcal pathogens, another illustration of unintended consequences of the animal husbandry industry in the U.S. Multilocus sequence typing (MLST) is the major tool used to track the epidemiology of S. suis. Among human isolates, MLST sequence type 1 (ST1) is most common. Independent of the sequence type, the serotype 2 capsule seems to be the major virulence factor; mutations in the gene for the capsule are avirulent.

Human disease may present with fever, headache, dizziness, nausea, vomiting, nuchal rigidity, and a unique symptom — hearing loss. As many as 66% of patients may exhibit this finding, many of whom do not ever recover full hearing capacity. CSF has all the signs of meningitis, and organisms are often seen on direct Gram stain. Organisms are usually susceptible to penicillin, but they variable susceptibilities for tetracycline (many are resistant), macrolides, clindamycin, and now a few are intermediate to third generation cephalosporins. Strains resistant to other beta-lactams, trimethoprim-sulfa, aminoglycosides, chloramphenicol, and fluoroquinolones have been reported. A large outbreak in China that occurred in 2005 heralded the new finding of a toxic shock-like syndrome associated with S. suis rather than the regular presentation of meningitis. All cases were due to a single ribotype which was the ST7 MLST type. This outbreak, with a total of 215 cases and 39 deaths (within a median of 25 hours), started with goat exposure, not pigs, although pig-associated cases occurred later.10

S. suis meningitis and potentially toxic shock syndrome may increase in the U.S. with the increasing globalization of our food sources and our human population. Clinicians and microbiologists should be aware that patients with meningitis — especially associated with hearing loss — seem to yield only "viridans streptococci" from their CSF cultures.

References

  1. Wertheim, H. F., et al.Streptococcus suis: An emerging human pathogen. Clin Infect Dis 2009;48:617-625.
  2. Lee, G. T., et al. Streptococcus suis meningitis, United States. Emerg Infect Dis 2008;14:183-185.
  3. Willenburg, K. S., et al. Human Streptococcus suis meningitis in the United States. N Engl J Med 2006;354:1325.
  4. Fittipaldi, N., et al. Streptococcus suis meningitis, Hawaii. Emerg Infect Dis 2009;15:2067-2069.
  5. Horby, P., et al. Stimulating the development of national Streptococcus suis guidelines in Viet Nam through a strategic research partnership. Bull WHO 2010; 88:458-461.
  6. Choi, S. M., et al. Meningitis caused by Streptococcus suis: case report and review of the literature. J Clin Neurol 2012; 8:79-82.
  7. Centers for Disease Control and Prevention. Campylobacter jejuni Infections Associated with Sheep Castration — Wyoming, 2011. MMWR 2011; 60:1654.
  8. Sekizaki, T. Streptococcus suis: An Emerging Biothreat. Jrl Disaster Res 2012;7:303-312.
  9. Palmieri, C., et al. Streptococcus suis, an Emerging Drug-Resistant Animal and Human Pathogen. Front Microbiol 2011;2:235.
  10. Yu, H., et al Human Streptococcus suis outbreak, Sichuan, China. Emerg Infect Dis 2006;12:914-920.