MRSA ST398 PRESENT IN MIDWESTERN US SWINE AND SWINE WORKERS

[PORKER]

Flounder dug this up!

Staphylococcus aureus is one of the most common and devastating human pathogens [1]. Though approximately a third of the population is colonized with S. aureus [2,3], colonization by strains of S. aureus that are resistant to methicillin (methicillin-resistant S. aureus, MRSA) is less common. A recent publication estimated that 1.5% of the United States (U.S.) population (,4.1 million persons) is colonized with MRSA [4]. Klevens et al. recently showed that deaths from MRSA infections in the U.S. have eclipsed those from many other infectious diseases, including HIV/AIDS. On the basis of data from several major metropolitan areas in the U.S., these investigators estimated that MRSA caused 94,000 infections and over 18,000 deaths in the U.S. in 2005 [5].

Moreover, MRSA has been found in a variety of animals, including horses [6,7], cattle [8], dogs, cats [9], and swine [10,11,12]. Voss et al. reported that the prevalence of MRSA among pig farmers was >760 times higher than that among patients admitted to Dutch hospitals [13]. Multi locus sequence typing (MLST) suggested that these MRSA isolates belonged to sequence type 398 (ST398), and had been transmitted from pigs to pig farmers, among pig farmers and their family members, and from the colonized son of a swine veterinarian to a hospital nurse. A subsequent study found that 4.6% of veterinarians and veterinary students were colonized with MRSA compared with a population-based estimate of 1% [14].
Additional studies in swine have shown that isolates obtained from swine and their human caretakers are frequently indistinguishable, suggesting transmission between the two animal species [11,12]. Indeed, investigations in the Netherlands demonstrated that ST398 now accounts for 20% of all MRSA detected in that country, documenting the importance of considering livestock and PLoS ONE | www.plosone.org 1 January 2009 | Volume 4 | Issue 1 | e4258 other animals when examining the epidemiology of MRSA [15]. However, despite research examining swine-associated MRSA in the Netherlands and Canada [10,12], currently the prevalence of MRSA in swine or their caretakers is unknown in the U.S. In a rural state such as Iowa, which produces 25% of the swine raised in the U.S., transmission of MRSA on swine farms or in veterinary facilities could complicate efforts to reduce MRSA transmission statewide and beyond. Therefore, we conducted a pilot culture survey to examine the prevalence of MRSA in swine and swine workers in two swine farming production systems in Iowa and Illinois.

[flounder]

DOI: 10.3201/eid1604.091435

Suggested citation for this article: Golding GR, Bryden L, Levett PN, McDonald RR, Wong A, Wylie J, et al.

Livestock-associated methicillin-resistant Staphylococcus aureus sequence type 398 in humans, Canada.

Emerg Infect Dis; [Epub ahead of print]


Livestock-associated Methicillin-Resistant Staphylococcus aureus Sequence Type 398 in Humans, Canada

George R. Golding, Louis Bryden, Paul N. Levett, Ryan R. McDonald, Alice Wong, John Wylie, Morag R. Graham, Shaun Tyler, Gary Van Domselaar, Andrew E. Simor, Denise Gravel, and Michael R. Mulvey
Author affiliations: National Microbiology Laboratory, Winnipeg, Manitoba, Canada (G.R. Golding, L. Bryden, M.R. Graham, S. Tyler, G. Van Domselaar, M.R. Mulvey); Saskatchewan Disease Control Laboratory, Regina, Saskatchewan, Canada (P.N. Levett, R.R. McDonald); Royal University Hospital, Saskatoon, Saskatchewan, Canada (A. Wong); Cadham Provincial Laboratories, Winnipeg (J. Wylie); Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada (A.E. Simor); and Public Health Agency of Canada, Ottawa, Ontario, Canada (D. Gravel)

Rates of colonization with livestock-associated methicillin-resistant Staphylococcus aureus (MRSA) sequence type 398 have been high for pigs and pig farmers in Canada, but prevalence rates for the general human population are unknown. In this study, 5 LA-MRSA isolates, 4 of which were obtained from skin and soft tissue infections, were identified from 3,687 tested MRSA isolates from persons in Manitoba and Saskatchewan, Canada. Further molecular characterization determined that these isolates all contained staphylococcal cassette chromosome (SCC) mecV, were negative for Panton-Valentine leukocidin, and were closely related by macrorestriction analysis with the restriction enzyme Cfr91. The complete DNA sequence of the SCCmec region from the isolate showed a novel subtype of SCCmecV harboring clustered regularly interspaced short palindromic repeats and associated genes. Although prevalence of livestock-associated MRSA seems to be low for the general population in Canada, recent emergence of infections resulting from this strain is of public health concern.

High prevalence of colonization with livestock-associated (LA) methicillin-resistant Staphylococcus aureus (MRSA) sequence type (ST) 398 among pigs and pig farmers was first

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reported in the Netherlands (1) and has since been identified in Canada (2) and the United States (3). In Canada, this LA-MRSA strain was identified in pigs and pig farmers in southwestern Ontario, where prevalence of MRSA colonization was 24.9% (71/285) and 20% (5/25), respectively (2). In the United States, nasal samples from 20 production system workers and 299 swine from 2 farms in Illinois and Iowa showed that 45% (9/20) and 49% (147/299), respectively, were colonized with LA-MRSA (3). Despite such high prevalence of MRSA colonization on these tested farms, to our knowledge, no human or animal infections resulting from LA-MRSA strains have been reported in North America.
To determine whether LA-MRSA has recently emerged in the general population of Canada, we identified human infections and colonizations associated with the LA-MRSA strain in Canada and molecularly characterized the isolates. We also identified a novel staphylococcal cassette chromosome (SCC) mecV subtype harboring clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated genes (cas).

SNIP...


Discussion

The high prevalence of LA-MRSA colonization of pigs and pig farmers in Canada (2) and the United States (3) and this report of human infections suggest that this LA-MRSA strain from Canada poses potential public and occupational health concern in North America. This strain has been associated with various types of infections in pigs (17,1 and humans (19,20) and is transmissible from animal patients to veterinary workers (21), healthcare workers (22), and family members (1). Evidence also suggests that this strain might be spreading from animals to the environment, which may facilitate the colonization or infection of persons who are not involved in animal husbandry (23). Whereas in 2006 in the Netherlands LA-MRSA accounted for >20% of all MRSA isolated (24), carriage of this strain in the general population of 2 provinces in Canada (Manitoba and Saskatchewan) appears rare (0.14%). This difference could be attributed to the substantially higher density of pigs in the Netherlands (1,244 pigs/km2) than in Manitoba (55 pigs/km2), Saskatchewan (6 pigs/km2), and Ontario (91 pigs/km2) (www.agriculture.gov.sk.ca/Pig_Densities). It is also plausible that the much lower proportions of LA-MRSA in Canada, relative to a country with low MRSA endemicity such as the Netherlands, is attributable to competition with other highly successful human epidemic MRSA clones circulating in Canada, including CMRSA2 (USA200/800), CMRSA7 (USA400), and CMRSA10 (USA300) (25,26).
The tested LA-MRSA isolates were highly susceptible to most classes of antimicrobial drugs, except β-lactams and tetracyclines, the latter of which has been attributed to its high usage in animal husbandry (27). The complete sequence of the SCCmec region showed a novel SCCmecV subtype sharing sequence identity in its J1 and J3 regions with chromosomal genes in the S. epidermidis RP62A chromosome (GenBank accession no. CP000029), including a

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CRISPR system. CRISPRs and associated cas genes are present in many other bacterial (≈40%) and archaeal (≈90%) genomes (28,29) and have been shown to be involved in sequence-directed immunity against phages (30,31) and plasmids (32). The resistance to plasmids and phages encoded by this system could explain why many of these ST398-MRSA-V strains contain fewer antimicrobial drug resistance genes and phage-encoded virulence factors than do other epidemic MRSA strains (33,34). The origin of this CRISPR system is unknown, but the propagation of CRISPR loci throughout prokaryote genomes has been proposed to occur through horizontal gene transfer by conjugation of megaplasmids >40 kb (35). Because the CRISPR system identified in this study is encoded within a putative mobile genetic element, we propose that an additional mechanism of mobilization to other methicillin-susceptible Staphylococcus spp. is plausible.

This novel subtype of SCCmecV was found in only 4 of the 6 LA-MRSA isolates identified in this study. One isolate not containing this novel SCCmec subtype (08 BA 08100) could also be distinguished by a different but closely related spa type (t1250) (Table 1) and variant PFGE fingerprint (Figure 2) when compared with the other LA-MRSA isolates, which suggests that at least 2 epidemiologically different strains of LA-MRSA circulate in Saskatchewan. The other LA-MRSA isolate that did not contain this novel SCCmec element was obtained in Ontario. However, this isolate was the same spa type (t034) and was closely related, according to PFGE, to the LA-MRSA isolates identified in Saskatchewan. Therefore, in addition to PFGE and spa typing, SCCmec subtyping could provide a useful epidemiologic tool for surveillance, outbreak investigations, or traceability studies of this emerging strain. For detection of this SCCmecV subtype (tentatively designated V.2.1.2; Vb), we propose using primer set 1 (spanning orfX into Sk02 in the J3 region) and primer set 7 (spanning Sk20 into cas1 in the J1 region) (Table 4).

Visual comparison of PFGE fingerprints from this study with those reported from patients from the Dominican Republic and the United States (northern Manhattan, New York, NY) (36), showed substantial variations in fingerprint patterns, as well as related but different spa types. These variations suggest further molecular and geographic diversity of these LA-MRSA strains on a global scale.

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Because cases of LA-MRSA infections have only recently been identified in Canada, additional surveillance efforts are required to monitor the emergence and clinical relevance of this MRSA strain in Canada, including communities, the environment, livestock, farmers, and production facility workers. Whether these strains pose a major threat to human health in light of the low livestock density and continued spread of epidemic hospital and community strains of MRSA in Canada remains unknown.

http://www.cdc.gov/eid/content/16/4/pdfs/09-1435.pdf


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