Emerging Disease and zoonoses #11--Streptococcus suis

Okay, so I lied. I was planning to wrap up the emerging diseases and zoonoses series with the post on monkeypox, but I think I'll just continue it as a sporadic event, since a new paper fits into the series perfectly.

I talk a lot here about streptococcus. As regular readers know, there's a good reason for that. Though my main research right now is on Streptococcus agalactiae (group B streptococcus, GBS), I also have a project working on a related organism, Streptococcus suis. As the "suis" name suggests, this is mainly a pathogen of swine. Indeed, it's kind of the pig equivalent of GBS: generally transmitted from the asymptomatic mother to newborn, it causes a rapidly fatal disease in neonatal piglets, manifesting as sepsis, meningitis, and occasionally pneumonia. It has also caused sporadic disease in humans, where meningitis is again the most common serious manifestation. Human fatality rate is generally around 5-10%.

Though S. suis is present in swine worldwide, there has never been a human case of the disease reported in the United States, and only two reported in Canada. The vast majority of human disease has been reported in Asia, especially Thailand, China, and Hong Kong. Indeed, in Hong Kong S. suis is the third most common cause of bacterial meningitis. Almost all of these cases have been in people in close contact with swine: farmers, butchers, veterinarians--hence, another zoonotic disease. And last year in China, the largest outbreak of S. suis ever recorded took place, sickening at least 204 and killing 38 (a 19% mortality rate). The new paper I mentioned in the first paragraph, published in PLoS Medicine describes the outbreak.

The outbreak in China began in June of 2005, in the Sichuan Province. The cause, initially unknown, was rapidly identified as S. suis, due partly to similarities with a previous (but smaller) outbreak of the bacterium in the same area in 1998. Both outbreaks were due to serotype 2 isolates of the bacterium. Of the 35 known serotypes of the bacterium, serotype 2 is the most common worldwide, and by far the most common one to cause disease in humans. During the human outbreak, there was a concurrent epidemic in pigs, and all of the human cases were reported to have contact with infected pigs prior to developing symptoms. Of the fatal cases, all but one developed STSS: streptococcal toxic shock-like syndrome. (The other fatal case died of meningitis).

Though the group A streptococcus (Streptococcus pyogenes) is usually associated with STSS disease in humans, other types of strep--including types B, C, and G--can also cause STSS, though much less frequently. This syndrome is generally caused by the production of bacterial superantigens. These are bacterial proteins that activate the immune system by binding to both MHC (Major Histocompatibility Complex) molecules on an antigen-presenting cell, and T cell receptors on the T cell. Normally, foreign proteins are chopped up into peptides, which are then captured by the MHC molecules. The MHC is on the surface of your body's antigen-presenting cells, which are recognized by T cell receptors: surface molecules on your T cells. When they come into contact and the T cell recognizes the peptide in the MHC molecule as foreign, the immune response is stimulated: T cells are activated, cytokines are released, etc. When this cascade is triggered via a superantigen instead of a "regular" antigen, however, cytokines are over-produced and a far greater proportion of T cells are activated--this leads to the symptoms of STSS: fever, chills, and malaise initially, followed by rash, possible peeling of the skin, and can eventually lead to reduced blood pressure followed by organ failure and death.

Because STSS caused by S. suis was a novel finding, the authors tested the S. suis isolates recovered from patients for the production of superantigens. They came back negative. However, the assay used is a tissue culture assay--perhaps the antigens simply aren't produced under those conditions, so the jury's still out on the issue of superantigen production by S. suis.

Limited genetic analysis was also performed. Not surprisingly, the isolates from the outbreak were closely related, and also grouped with isolates recovered during the 1998 outbreak. Thus, it appears that a unique, highly virulent lineage of S. suis is endemic in this region of China.

Again, there are cultural differences that make it unlikely that a disease outbreak of this nature would happen in the U.S. Some previous cases of invasive S. suis disease in humans have been attributed to eating meat from diseased animals, which is unlikely in the U.S. Additionally, humans and animals are generally in closer contact in Asia, and again, sterile practices may not always be followed. However, as mentioned, S. suis is present worldwide, and there are some indications that even when it does cause disease in humans, it is misdiagnosed.

Eradication of the bacterium from the swine population, additionally, seems unlikely. Like Strep pyogenes, S. suis remains susceptible to penicillin, but also like S. pyogenes, S. suis can hide out in the tonsils, making it difficult to clear from the animal. A vaccine would improve the situation, but is not forthcoming. Once again, the emergence of this bacterium underscores the need for better collaboration between those involved in human health, and those whose job it is to deal with the health of animals.

Reference
Tang, J et al. 2006. Streptococcal Toxic Shock Syndrome Caused by Streptococcus suis Serotype 2. PLoS Medicine. 3(5):e151.

Images from http://www.museums.norfolk.gov.uk/img/Piglets.jpg and http://www.whfreeman.com/immunology/CH04/figure04-14a.jpg