A Dangerous Piggyback Ride: The Emergence of Swine-associated MRSA

1. A Dangerous Piggyback Ride: The Emergence of Swine-associated MRSA John M. Balbus, MD MPH American Public Health Association San Diego, October 25-29, 2008

3. Some numbers… Pounds of antibiotics fed to US pigs, 1997 Number of US deaths from MRSA, 2005 Year MRSA first cultured Pounds of bacon consumed per capita US, 1998 10.4 million 18,650 1961 3.2 BG: Can you get a more up-to-date number on bacon/pork consumption? Also, part of me says you could omit this “fun” slide, since two of the stats appear elsewhere – but I also think you need it or another slide to introduce the extent of use of abx in US pigs.BG: Can you get a more up-to-date number on bacon/pork consumption? Also, part of me says you could omit this “fun” slide, since two of the stats appear elsewhere – but I also think you need it or another slide to introduce the extent of use of abx in US pigs.

5. What is MRSA? Methicillin-resistant Staphylococcus aureus, a pathogenic bacteria Methicillin resistance signifies resistance to other clinically important ß-lactam antibiotics

6. History of resistant S. aureus 1940s: > 50% S. aureus resistant to penicillins 1960: methicillin introduced 1961: first MRSA strains identified 1967: multi-drug resistant MRSA seen 1993: community-acquired (CA-) MRSA identified 2005: MRSA reported widespread on pig farms in Europe

7. Clinical significance of MRSA MRSA carriage common Frequently causes skin/soft tissue infections (93%) Invasive infections less frequent but serious

8. Public Health Significance of MRSA 94,360 invasive infections and 18,650 deaths in US in 2005 Invasive infections: 32/100,000 persons 2x greater than S. pneumoniae (14); and 30x more than H. influenzae (<1) Longer hospitalizations, increased costs, and higher mortality

9. The Netherlands:the beginnings of an ST398 epidemic Historically low MRSA carriage (~1%) Aggressive “search and destroy” policy 2004 and 2005: screening found several ST398 cases in vets/pig farmers Same strain in pigs First suggestion of pig—human transmission

10. Dutch case-control study Elevated Odds Ratio for NT-MRSA (ST398) pig farmers: 12.2 (95% CI 3.1-48.6) cattle farmers 19.7 (95% CI 2.3-169.5) Map A: overlap of ST398 cases on pig density demonstrating spatial relationship; Map B: overlap of typable MRSA cases on pop density showing spatial relationship Maybe type out “odds ratio (OR)” – I assume that’s the meaning for OR – since this is the first time you use the abbreviation??Map A: overlap of ST398 cases on pig density demonstrating spatial relationship; Map B: overlap of typable MRSA cases on pop density showing spatial relationship Maybe type out “odds ratio (OR)” – I assume that’s the meaning for OR – since this is the first time you use the abbreviation??

11. MRSA carriage--Netherlands 32% (23/95) of cases NT (non-typable) NT-MRSA related to exposure to pigs or calves OR: 327; 95% CI, 38-2514

12. Prevalence of ST398 in pigs Dutch abattoirs: 39% (209/540) of pigs ST398 colonized All slaughterhouses (n=9), 81% of farms ST398(+) All tested isolates (n=44) resistant to tetracycline “…reflecting the high and predominant use of tetracyclines in pig husbandry”

13. Pig MRSA and antibiotic use 23% (7/31) Dutch farms with ST398 colonized pigs OR = 30.0 for ST398 on farms regularly using antibiotics (95% CI: 2.8 to 322)

14. Belgian Study 44% (663/1500) pigs MRSA (+)—all ST398 38% (48/127) pig farmers MRSA (+)—all ST398 2 X 2 Table of MRSA carriage in pigs and humans by farm: MRSA colonization of pig farmers 23-fold higher (37.8% vs 1.6%) than control population Large Ministry of Health commissioned study with 3 arms: 1) MRSA prevalence in general population ascertained by screening emergency department attendees, 1.6% carriage rate; 2) 50 pig farms, 30 pigs each for MRSA, samples typed and antibiotic resistance determined; 3) Pig farmers and family members on farms tested in (2)Large Ministry of Health commissioned study with 3 arms: 1) MRSA prevalence in general population ascertained by screening emergency department attendees, 1.6% carriage rate; 2) 50 pig farms, 30 pigs each for MRSA, samples typed and antibiotic resistance determined; 3) Pig farmers and family members on farms tested in (2)

16. Risk factors: Human MRSA carriage on Belgian pig farms (III) BG: This slide is hard to read. Could omit, since the presentation is long?BG: This slide is hard to read. Could omit, since the presentation is long?

17. Contaminated Dutch Meat Samples by MRSA Strain A total of 1293 samples of unheated meat were taken in the retail trade (supermarkets, butchers, poulterers, etc.), throughout the country. Sampling took place from June to December 2007. MRSA isolated from 138 samples, 22 different Spa-types were found and 116 (84%) isolates proved to be MLST type 398. MRSA was present in around 11% of the samples. The highest prevalences were found in turkey, chicken and veal. BG: I would definitely mention the prospect that consumer handling of contaminated meat can lead to MRSA carriage or skin infections – which potentially makes MRSA different than other foodborne pathogens which must be ingested. Also -- Could mention that a Seattle TV station (the ABC affiliate) had a lab test 98 Seattle are pork samples, ½ of them ground pork – and detected MRSA in 3. The story hasn’t run yet, but should by the time of APHA. A total of 1293 samples of unheated meat were taken in the retail trade (supermarkets, butchers, poulterers, etc.), throughout the country. Sampling took place from June to December 2007. MRSA isolated from 138 samples, 22 different Spa-types were found and 116 (84%) isolates proved to be MLST type 398. MRSA was present in around 11% of the samples. The highest prevalences were found in turkey, chicken and veal. BG: I would definitely mention the prospect that consumer handling of contaminated meat can lead to MRSA carriage or skin infections – which potentially makes MRSA different than other foodborne pathogens which must be ingested. Also -- Could mention that a Seattle TV station (the ABC affiliate) had a lab test 98 Seattle are pork samples, ½ of them ground pork – and detected MRSA in 3. The story hasn’t run yet, but should by the time of APHA.

18. Livestock – Human MRSA transmission: A conceptual model BG: I am not sure I understand the connection to abattoirs.BG: I am not sure I understand the connection to abattoirs.

19. Worldwide Detection of ST398

20. Clinical disease and ST398 Bacteremia (Hong Kong) Pneumonia, PVL gene seen (China) Endocarditis (Netherlands) Ventilator-Associated Pneumonia (Germany) Osteomyelitis (Scotland) Soft tissue infections (multiple countries) Panton–Valentine leukocidin (PVL) gene is a virulence factor frequently found in CA-MRSA; majority of ST398 studies tested for the presence of this gene, which has only been reported as present in the 5 MRSA ST398 samples in the China study. PVL, a bicomponent cytotoxin, causes leukocyte destruction and tissue necrosis. This cytotoxin is produced by <5% of S. aureus isolates and has been associated with necrotic lesions involving the skin and with severe necrotizing pneumonia.Panton–Valentine leukocidin (PVL) gene is a virulence factor frequently found in CA-MRSA; majority of ST398 studies tested for the presence of this gene, which has only been reported as present in the 5 MRSA ST398 samples in the China study. PVL, a bicomponent cytotoxin, causes leukocyte destruction and tissue necrosis. This cytotoxin is produced by <5% of S. aureus isolates and has been associated with necrotic lesions involving the skin and with severe necrotizing pneumonia.

21. Closer to home Ontario: MRSA carriage prevalence: 45% (9/20) of farms, 25% (71/285) of pigs, and 20% (5/25) of pig farmers 59% of MRSA was ST398 Iowa, Illinois 2008: 70% of 209 swine carried ST398 45% of workers in second study of IA farms Spearman correlation coefficient: farms with MRSA + pigs and humans = 0.63 (p = 0.0025) BG: Didn’t Tara Smith look at Iowa and Illinois? Do you want me to find the abstract? (My files are currently stored, since I don’t have a laptop this week.) Spearman correlation coefficient: farms with MRSA + pigs and humans = 0.63 (p = 0.0025) BG: Didn’t Tara Smith look at Iowa and Illinois? Do you want me to find the abstract? (My files are currently stored, since I don’t have a laptop this week.)

22. Surveillance : Is anyone looking? Europe: Well-developed (EARSS) US: No national MRSA surveillance—USDA does not test livestock FY09 funding for FDA-USDA to conduct MRSA testing NARMS (National Antimicrobial Resistance Monitoring) follows other foodborne pathogens NARMS (National Antimicrobial Resistance Monitoring) follows other foodborne pathogens

23. Addressing the problem Establish baseline and scope Conduct studies on US farms Food surveillance in US Include MRSA in FDA risk assessments Eliminate non-essential uses of antibiotics in farm animals Preservation of Antibiotics for Medical Treatment Act (PAMTA) A recent report from the Pew Commission on Industrial Farm Animal Production suggested 12 measures: Restrict antibiotic (abx) use in animals; Clarify antimicrobial use definitions; Improve monitoring/reporting of abx use; Improve monitoring of resistant organisms in animals/food/humans; Increase vet oversight of abx use in animals; Enable 48 hour traceback of food animals; Enforce environmental monitoring laws, increase surveillance in animal production workers; Increase public health (PH) research on animal production workers; Increase collaboration between MDs, PH, and vets; Create an integrated food safety administration; Improve meat production risk assessment system; and Mitigate animal production diseases to reduce abx use A recent report from the Pew Commission on Industrial Farm Animal Production suggested 12 measures: Restrict antibiotic (abx) use in animals; Clarify antimicrobial use definitions; Improve monitoring/reporting of abx use; Improve monitoring of resistant organisms in animals/food/humans; Increase vet oversight of abx use in animals; Enable 48 hour traceback of food animals; Enforce environmental monitoring laws, increase surveillance in animal production workers; Increase public health (PH) research on animal production workers; Increase collaboration between MDs, PH, and vets; Create an integrated food safety administration; Improve meat production risk assessment system; and Mitigate animal production diseases to reduce abx use