Issue Brief Food Policy Research Center
Pigs and MRSA: What Are the Human Health Risks and to Whom?
- MRSA (methicillin resistant Staphylococcus aureus) has been a major cause of human infections for over 50 years, particularly in hospitals. MRSA is among the foremost bacteria of concern regarding antimicrobial resistance.
- From the mid 1990s, MRSA epidemiology changed globally as new MRSA variants caused infections in otherwise healthy people having no exposure to hospitals.
- Since 2004, the discovery of novel MRSA variants in livestock has raised concerns about potential public health impacts of animal reservoirs of MRSA.
- A specific MRSA lineage (ST398) is the focus of concern in livestock. ST398 was unknown before being found in patients in the Netherlands who had exposure to pig farms. ST398 MRSA is now known to occur in many countries and species (cattle, poultry, and horses).
- Exposure to MRSA from livestock is a concern for people working with live animals (farmers, veterinarians). Risk to the general public via other routes appears minimal.
- MRSA of livestock origin are less likely to persist and spread in people than MRSA of human origin. No community outbreak of ST398 MRSA infection has been reported anywhere, nor has a single case of clinical infection been reported in the United States of America (USA).
- The impact of ST398 MRSA on human illness has been very low. Policy strategies to reduce ST398 should be assessed with respect to feasibility and cost prior to implementation.
How prevalent are MRSA in pig populations and farmers?
S. aureus are normal inhabitants of pigs, and occur in all herds.1 The prevalence of MRSA in pig herds varies widely (0 to 50%) among European countries.2 The pig herd prevalence of MRSA in North America is uncertain, but appears lower than in many European countries.3,4 MRSA prevalence is high (>50%) in pigs in positive herds, but has minimal effect on swine health. S. aureus is found in dust and air on pig farms,5 and healthy people working in barns often harbor the swineS. aureus variants in their noses.1,3,6,7 MRSA can be detected in 20 – 80% of healthy workers on MRSA positive herds, much more than in the general public (1.5% in the USA; <0.11% in the Netherlands). 8,9 The risk of exposure to MRSA from livestock is mostly limited to people with direct animal contact and their immediate families.10-12
Do people get permanently colonized by MRSA acquired from livestock?
The capacity of S. aureus/MRSA strains of livestock origin to colonize, spread, and cause disease in humans remains uncertain. It appears that ST398 persist only briefly (hours to days) in most people, but some may be colonized for months to years and not necessarily develop an infection.13-17 Studies in Dutch hospitals found ST398 spread between people was some fourfold less likely than for human MRSA strains.18,19 No community outbreak of ST398 MRSA infection has been reported to date. Other MRSA lineages also occur in pigs (e.g., ST9 in Asia, ST5 in North America), but their public health implications are not known.
Do MRSA acquired from livestock cause significant disease in humans?
A study of a pig dense region of Denmark concluded there is ‘an infectious occupational exposure of huge quantitative dimensions but of unknown clinical importance’.20 ST398 MRSA have been found in both superficial and systemic infections of humans, confirming a non-zero risk. The common statement that ST398 cause a large proportion of MRSA cases in countries like the Netherlands is misleading as it is based on studies that include people who are colonized (e.g., positive nasal swabs), but not infected.21 Analyses of actual infections show ST398 MRSA are much less prevalent, particularly among serious MRSA infections such as bacteremia.22,23
Globally, there has been only one ST398 MRSA fatality reported over 9 years (compared to an estimated 18,000 annual MRSA fatalities in the USA alone).24 Population-based estimates (cases per 100,000 people per year) of the incidence of ST398 MRSA infections in pig dense areas where ST398 MRSA are prevalent are: 2 clinical infections, 0.38 invasive infections, and 0.04 bacteremia cases in the Netherlands;22,23 and 0.25 clinical infections in Denmark (none invasive).21In contrast, the CDC estimates 31.8 invasive cases and 6.3 fatalities from MRSA per 100,000 people per year in the USA.25 Although ST398 MRSA have been found in nasal swabs of USA livestock, farmers, and veterinarians,6 there has yet to be a case of infection with ST398 MRSA reported in the USA. Future reports of ST398 MRSA infections, particularly minor skin infections, are certain to occur and will need to be assessed in the context of the substantial burden of MRSA infections due to human adapted strains in the USA.
How are livestock-associated MRSA different from MRSA that cause infections in hospitals?
Reports of medically significant ST398 MRSA infections in healthy livestock workers are few despite high exposure to MRSA. Overall, S. aureus are remarkably versatile and virulent bacteria that can survive and multiply in many environments. However, ST398 MRSA from pigs appear to contain few of the known S. aureus virulence factors (genetic components that enable them to cause severe infection),27,28 which may explain the rarity of serious clinical infections.22,27 Recently, ST398 variants were found in urban populations in the USA, China, and Europe without livestock contact. These strains are genetically distinct from animal variants, indicating that not all ST398 infections can be attributed to livestock.29,30
How or why did livestock-associated MRSA come to be?
The reasons for the emergence of ST398 in pigs are not understood and are likely complex. Although use of antimicrobials for growth promotion has been suggested, this simplistic hypothesis conflicts with the emergence of ST398 MRSA after growth promotion use was phased out in Europe. More plausible candidates are increased feeding of zinc to pigs consequent to removal of growth promotion antimicrobials,31 and use of long-acting injectable cephalosporins for livestock. Ongoing research indicates that pigs harbor diverse populations of methicillin-susceptible S. aureus (MSSA). In the USA, the predominant lineages of MSSA in pigs correspond with MRSA variants found in pigs around the world (ST398, ST9, ST5).32 This suggests that preexisting variants of S. aureus that are normal inhabitants of pigs have acquired resistance to methicillin, rather than the recent emergence of novel organisms in livestock.
What policy options should be considered?
Other than increasing surveillance, only the Netherlands (where people carrying MRSA are isolated and treated before admission to hospitals), has changed health policy in response to ST398 MRSA. Hospitals now screen all livestock workers (who are commonly positive for ST398 MRSA) and this policy markedly increased health care costs. However, due to the rarity of severe ST398 MRSA infections and lower transmissibility, it is argued that less stringent containment measures are warranted in hospitals for ST398 than human MRSA to reduce costs.33 The theoretical case for reducing MRSA in livestock is self-evident,34 but no strategies to do so have been defined yet alone assessed with respect to feasibility or cost.
- Armand-Lefevre L, Ruimy R, Andremont A. Clonal comparison of Staphylococcus aureus isolates from healthy pig farmers, human controls, and pigs. Emerg Infect Dis. 2005;11(5):711-714.
- Anon. Analysis of the baseline survey on the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in holdings with breeding pigs, in the EU, 2008  - Part A: MRSA prevalence estimates. EFSA Journal2009;7(11):1376
- Smith TA, Gebreyes WA, Abley MJ, Bayleyegn M, Harper-Maples A, Forshey BM, Male MJ, Martin HW, Sreevatsan S, Thakur S, Thiruvengadam M, Davies PR. Methicillin-resistant Staphylococcus aureus in pigs and farm workers on conventional and antibiotic-free swine farms in the USA. PLoS ONE 2013;8(5): e63704.
- Weese JS, Rousseau J, Deckert A, Gow S, Reid-Smith RJ. Clostridium difficile and methicillin-resistantStaphylococcus aureus shedding by slaughter-age pigs. BMC Vet Res. 2011 Jul 26;7:41. doi: 10.1186/1746-6148-7-41.
- Gibbs SG, Green CF, Tarwater PM, Mota LC, Mena KD, Scarpino PV. Isolation of antibiotic-resistant bacteria from the air plume downwind of a swine confined or concentrated animal feeding operation. Environ Health Perspect 2006; 114: 1032-1037.
- Voss A, Loeffen F, Bakker J, Wulf MW. Methicillin-resistant Staphylococcus aureus in pig farming. Emerg Infect Dis2005;11(12):1965-1966.
- Khanna T, Friendship R, Dewey C, Weese JS.Methicillin resistant Staphylococcus aureus colonization in pigs and pig farmers. Vet Microbiol 2008; 128: 298-303.
- Gorwitz RJ, Kruszon-Moran D, McAllister SK, McQuillan G, McDougal LK, Fosheim GE, Jensen BJ, Killgore G, Tenover FC, Kuehnert MJ. Changes in the prevalence of nasal colonization with Staphylococcus aureus in the United States, 2001-2004. J Infect Dis 2008;197(9):1226-1234.
- Bode LG, Wertheim HF, Kluytmans JA, Bogaers-Hofman D, Vandenbroucke-Grauls CM et al. (2011) Sustained low prevalence of meticillin-resistant Staphylococcus aureus upon admission to hospital in The Netherlands. J Hosp Infect 79: 198-201.
- van Cleef BA, Verkade EJ, Wulf MW, Buiting AG, Voss A, Huijsdens XW, et al. Prevalence of livestock-associated MRSA in communities with high pig-densities in The Netherlands. PLoS ONE. 2010;5:e9385. http://dx.doi.org/10.1371/journal.pone.0009385
- Cuny C, Nathaus R, Layer F, Strommenger B, Altmann D, Witte W. Nasal colonization of humans with methicillin-resistant Staphylococcus aureus (MRSA) CC398 with and without exposure to pigs. PLoS ONE. 2009;4(8): e6800.doi:10.1371/journal.pone.0006800
- Bisdorff B, Scholhölter JL, Claussen K, Pulz M, Nowak D, Radon K. MRSA-ST398 in livestock farmers and neighbouring residents in a rural area in Germany. Epidemiol Infect. 2012;140(10):1800-8.
- Graveland H Wagenaar JA, Bergs K, Heesterbeek H, Heederik D, Persistence of livestock associated MRSA CC398 in humans is dependent on intensity of animal contact. PLoS One 2011; 6: e16830.
- van Cleef BA, Graveland H, Haenen AP, van de Giessen AW, Heederik D, Wagenaar JA, Kluytmans JA. Persistence of livestock-associated methicillin-resistant Staphylococcus aureus in field workers after short-term occupational exposure to pigs and veal calves. J Clin Microbiol 2011; 49: 1030-1033.
- Verkade E, van Benthem B, den Bergh MK, van Cleef B, van Rijen M, Bosch T, Kluytmans Dynamics and determinants of Staphylococcus aureus carriage in livestock veterinarians: a prospective cohort study. J.Clin Infect Dis. 2013 Jul;57(2):e11-7.
- Frana TS, Beahm AR, Hanson BM, Kinyon JM, Layman LL, Karriker LA, Ramirez A, Smith TC. Isolation and characterization of methicillin-resistant Staphylococcus aureus from pork farms and visiting veterinary students. PLoS One. 2013;8(1):e53738.
- Sun J, Linhares L, Yang M, Sreevatsan S, Davies P (2013). Longitudinal study of Staphylococcus aureus and MRSA colonization of US swine veterinarians. Proceedings, 10th International Conference on the Epidemiology and Control of Foodborne Pathogens in Pork (SafePork), Portland ME, Sept 10-12 2013.
- Wassenberg MW, Bootsma MC, Troelstra A, Kluytmans JA, Bonten MJ.. Transmissibility of livestock-associated methicillin-resistant Staphylococcus aureus (ST398) in Dutch hospitals. Clin Microbiol Infect 2011; 17: 316-319
- Bootsma MC, Wassenberg MW, Trapman P, Bonten MJ.. The nosocomial transmission rate of animal-associated ST398 meticillin-resistant Staphylococcus aureus. J R Soc Interface 2011; 8: 578-584.
- Omland O, Hoffmann L. Occupational acquisition of methicillin-resistant Staphylococcus aureus in humans--a description of MRSA carrier and infected cases from the region of north Jutland in Denmark. Ann Agric Environ Med. 2012;19(4):637-640.
- Huijsdens XW, Bosch T, van Santen-Verheuvel MG, Spalburg E, Pluister GN, van Luit M, Heck ME, Haenen A, de Neeling AJ. Molecular characterisation of PFGE non-typable methicillin-resistant Staphylococcus aureus in The Netherlands, 2007. Euro Surveill 2009;14:19335.
- Wulf MW, Verduin CM, van Nes A, Huijsdens X, Voss A. Infection and colonization with methicillin resistantStaphylococcus aureus ST398 versus other MRSA in an area with a high density of pig farms. Eur J Clin Microbiol Infect Dis 2012 Jan;31(1):61-5.
- van Cleef BA, van Benthem BH, Haenen AP, Bosch T, Monen J, Kluytmans JA. Low incidence of livestock-associated methicillin-resistant Staphylococcus aureus bacteraemia in The Netherlands in 2009. PLoS One. 2013 Aug 29;8(8):e73096
- Lozano C, Aspiroz C, Ezpeleta AI, Gómez-Sanz E, Zarazaga M, Torres C. Empyema caused by MRSA ST398 with atypical resistance profile, Spain. Emerg Infect Dis 2011; 17: 138-140
- Klevens RM, Morrison MA, Nadle J, Petit S, Gershman K, Ray S, Harrison LH, Lynfield R, Dumyati G, Townes JM, Craig AS, Zell ER, Fosheim GE, McDougal LK, Carey RB, Fridkin SK. Invasive methicillin-resistant Staphylococcus aureus infections in the United States. JAMA. 2007;298(15):1763-1771.
- Schijffelen MJ, Boel CH, van Strijp JA, Fluit AC. Whole genome analysis of a livestock-associated methicillin-resistantStaphylococcus aureus ST398 isolate from a case of human endocarditis. BMC Genomics 2010; 11: 376.
- Hallin M, De Mendonça R, Denis O, Lefort A, El Garch F, Butaye P, Hermans K, Struelens MJ. Diversity of accessory genome of human and livestock-associated ST398 methicillin resistant Staphylococcus aureus strains. Infect Genet Evol 2011; 11: 290-299.
- McCarthy AJ, van Wamel W, Vandendriessche S, Larsen J, Denis O, Garcia-Graells C, Uhlemann AC, Lowy FD, Skov R, Lindsay JA. Staphylococcus aureus CC398 clade associated with human-to-human transmission. Appl Environ Microbiol. 2012;78(24):8845-8848.
- Uhlemann AC, Porcella SF, Trivedi S, Sullivan SB, Hafer C, Kennedy AD, Barbian KD, McCarthy AJ, Street C, Hirschberg DL, Lipkin WI, Lindsay JA, DeLeo FR, Lowy FD Identification of a highly transmissible animal-independent Staphylococcus aureus ST398 clone with distinct genomic and cell adhesion properties.MBio.2012;3(2):10.1128/mBio.00027-12.
- Cavaco LM, Hasman H, Aarestrup FM. Zinc resistance of Staphylococcus aureus of animal origin is strongly associated with methicillin resistance. Vet Microbiol. 2011 Jun 2;150(3-4):344-8
- Davies PR, Sun J, Linhares L, Sreevatsan S, Yang M. MSSA spa types in US pigs and swine veterinarians correspond with MRSA spa types reported globally in swine. Proceedings, 3rd ASM-ESCMID Conference on Methicillin-resistant Staphylococci in Animals: Veterinary and Public Health Implications, Copenhagen, Denmark, November 4-7, 2013, 47A
- van Meurs ML, Schellekens JJ, de Neeling AJ, Duim B, Schneeberger PM, Hermans MH. Real-time PCR to distinguish livestock-associated (ST398) from non-livestock-associated (methicillin-resistant) Staphylococcus aureus. Infection. 2013 Apr;41(2):339-46. doi:10.1007/s15010-012-0319-5.
- Porphyre T, Giotis ES, Lloyd DH, Stärk KD. A metapopulation model to assess the capacity of spread of meticillin-resistant Staphylococcus aureus ST398 in humans. PLoS One. 2012;7(10):e47504. doi: 10.1371/journal.pone.0047504.