Livestock associated MRSA: What are the risks to human health? - Dr. Peter Davies, from the 2012 Allen D. Leman Swine Conference, September 15-18, St. Paul, Minnesota, USA. More presentations at http://www.swinecast.com/2012-leman-swine-conference-material

1. Livestock Associated MRSA
What are the risks
to human health?
Peter Davies BVSc, PhD
University of Minnesota

2. Questions: LA-MRSA
 Background of MRSA in human health and
Livestock Associated MRSA
 NPB funded “white paper” on human health
implications of LA-MRSA
 Preliminary data on NIOSH study of US swine
veterinarians
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3. Staphylococcus
aureus
 Common inhabitant of warm-blooded animals
 ‘Normal flora’ (20-30% of people)
 Opportunistic pathogen
 Important pathogen of humans
 Mild to severe infections
 Skin/soft tissue infections
 Invasive: pneumonia, septicemia and death

4. Methicillin resistant S. aureus
(MRSA)
‘Truth’ prior to 1995
 First detected in 1961
 Emerged as a major problem of chronically ill in
institutions
 Resistance linked to antimicrobial use in hospitals
 Not a concern for broader community
 No epidemiologic role of animal reservoirs
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5. ‘Quantum shifts’ in MRSA epidemiology
 Emergence of ‘Community Acquired’ MRSA
 Global phenomenon since mid 1990s
 Different ‘clones’ distinct from ‘hospital’ strains
 Detection of MRSA in animals
 Food animals
 Companion animals
 Horses
 “Exotic” animals
 Zoonotic risk - realities and perceptions??
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6. What are LA-MRSA?
 Distinct ‘family’ of closely related MRSA first
found in Holland in 3 people linked to pigs (2004)
 Distinct ‘subtyping’ profile
 PFGE (standard CDC method):
 Untypable
 MLST (DNA sequencing of 7 genes)
 Novel sequence type (ST)398
 ‘Spa’ typing of protein A gene (DNA sequence
patterns)
 ~ 30 ‘spa types’ within ST398 family (t034, t011..) 6

7. What are the
risks?
H
 To whom?
 How?
Y T
 How often?
How severe?
M
S

M -
R
FO
IN O N
I S TI
M A

8. Livestock Associated MRSA
Knowns, unknowns, and uncertainties
 Generally accepted facts
 Common occurrence of LA-MRSA in livestock

Pigs, cattle, avian, horse, ..?
 Many countries
 High prevalence of MRSA in livestock farmers,
veterinarians, slaughter plant workers
 20-40% in farmers (vs. ~ 0.5 - 2% in population)

Mainly LA-MRSA
 Very low risk of exposure in other groups
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9. Occupational exposure!
 Consistent observation: occupational exposure to
animals increases risk of MRSA positive culture
 Farmers, veterinarians, abattoir workers
 Colonization vs. contamination
 Duration of ‘colonization’
 Role of regular animal contact
 Consequences of colonization
 Infection risk
 Transmission risk
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10. Duration of colonization
 Research workers (short term exposure) van Cleef et al (2011)
 33 of 199 exposures led to positive culture on farm
 Only 1 of 33 retested positive after 24 hours
 Evidence suggests most short term exposure leads to short
term ‘colonization’
 Veal farmers in Holland Graveland et al (2011)
 Rapid decline in prevalence during absence of animal contact
 LA-MRSA poor persistent colonizers in most humans.
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11. Transmission of ST398 MRSA among people
 Studies of transmission in Dutch hospitals (Bootsma, 2010)
 ST398 is 5.9 times less transmissible than non-ST398 MRSA
in Dutch hospitals’
 ‘Spreading capacity per admission insufficient to lead to an
epidemic’
 ‘Nosocomial transmission of ST398 MRSA is 72% less
likely than non-ST398 MRSA strains’
Wassenberg (2011)
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12. Burden of disease from ST398 MRSA
 National Pork Board white paper
 Studies of ST398 S. aureus were compiled in a Refworks database
 Focus on reports of human clinical disease
 Did not assess studies reporting colonization alone
 Attempt to identify all published information related to
clinical infections with ST398 organisms
 Both MRSA and MSSA
 Quantify burden of disease due to LA-MRSA
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13. Burden of disease from ST398 MRSA
 Many reports don’t distinguish infection from colonization
 Small number of serious infections
 Often no livestock association
 One reported fatality with ST398 MSSA without livestock contact
 Retrospective study of human isolates in Canada
 5 ST398 out of 3,687 MRSA isolates
 4 skin/soft tissue infections (Golding et al 2010)
 CDC has examined >12,000 isolates in USA
 ST398 not identified in a human clinical case (June 2011)
 MN DOH – no ST398 among 7,000 isolates tested
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14. Burden of disease from ST398 MRSA
 83 papers/reports of ST398 associated clinical cases
 Some where most isolates were from screening samples
 Data recorded
 Country
 Numbers of isolates from screening swabs
 Numbers of isolates from clinical infections
 Clinical presentations

bacteremia; pneumonia; skin or soft tissue infection, etc.
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15. Burden of disease from ST398 MRSA
 Data recorded
 History of animal contact
 Number of fatalities.
 Number of cases with invasive infections ( not SSTI)
 Invasive if reported as bacteremia or pneumonia, or if
isolates obtained from sites other than SSTI (e.g.,
urine, sputum isolates)
 Conservative
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16. Burden of disease from ST398 MRSA
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17. Self reported disease in US swine farmers
Leedom Larson et al (2010)
 Mail survey
 135 (17.2%) surveys received from 783 pork producers
actively farming hogs
 Five (3.7%) respondents reported a history of
physician-diagnosed MRSA SSTI
 Time period unclear (ever?)
 No bacteriological information or control group
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18. Distribution of LA-MRSA and other MRSA clinical
isolates in Europe (van Cleef et al., 2011)
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19. Geographic distribution of S. aureus
causing invasive infections in
Europe
Grundmann et al 2010
 357 laboratories serving 450 hospitals in 26
countries (2006-2007)
 2,890 MSSA and MRSA isolates from invasive infections
 ST 398 spa types (t011, t034, t571, t1255, and
t2383) identified on 12 occasions (1.3%)
 None harbored the mecA gene.
 No cases of ST398 MRSA invasive disease

20. Public health risk of ST398 MRSA
 Current evidence suggests low transmissibliity
 No reports of outbreaks
 Current evidence suggests low virulence?
 Significantly less invasive disease in Europe
 Serious infections uncommon
 General lack of virulence determinants
 Elevated infection risk in farm workers yet to be
documented
 What about the fatalities?
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21. Fatal ST398 infections
 5 fatal cases reported
 4 MSSA not MRSA
 Spa type t571 (not common in swine)
 No significant livestock contact
 One MRSA with livestock contact
 t011 (common in swine)
 85yo man with lung carcinoma and COPD
 Higher burden from MSSA than MRSA
 Were livestock involved?
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22. Lethal pneumonia caused by an ST398
S. aureus strain Rasigade et al (2010)
 Observations
 Fatal necrotizing pneumonia in a previously healthy 14yo girl
 ST 398 - spa type t571
 PVL positive
 Tetracycline susceptible
 Methicillin susceptible (MSSA)
 No livestock contact
 Inference
 “spread of S. aureus ST398 among livestock is a matter of
increasing concern because strains of this sequence type were
able to acquire PVL genes”
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23. “One Health” means
more than one inference
 ‘.. concern because strains ST398 strains were able to
acquire PVL genes’ Rasigade et al (2010)
 But….
 Livestock strains almost uniformly tetracycline resistant and PVL
negative
 Spa type t571 uncommon in animal isolates
 Could adaptation of ST398 to livestock hosts include loss
of human virulence factors?
 Could some ST398 variants persist in people without any
role of livestock?
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24. More of the story
Davies et al, EID June 2011
 t571 ST398 MSSA detected in 9 families from the Dominican
Republic living in Manhattan
 with no apparent contact with livestock (Bhat et al., 2007)
 t571 the sole MSSA spa type in Dutch study of ST398 clinical
isolates, including 3 cases of nosocomial bacteremia
 with no apparent livestock contact (van Belkum et al., 2008)
 t571 the predominant (11%) MSSA type at a Beijing hospital
 Livestock contact unlikely (Chen et al 2010)
 Recent case report of t571 MSSA from Colombia
 With no apparent livestock contact (Jimenez et al 2011)

25. Emergence of unusual bloodstream infections associated
with pig-borne-like Staphylococcus aureus ST398 in
France. (van de Marquet et al., 2011)
 Study of t571 MSSA strains from cases of bloodstream
infections in France
 The 30 isolates differed from pig-borne strains
 Isolates shared similarities with strains from humans in
China and virulent USA300 strains
 Epidemiologic diversity in ST398 lineage
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26. LA-MRSA: Implications
 Not good news for swine/livestock industries
 Priority to understand occupational risks
 Preventive measures in industry
 Personal hygiene
 Showers (soaps, towels)
 Clothing
 Wound treatment, covering
 Awareness and medical treatment
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27. The rest of the story……
 Understanding LA-MRSA is embryonic
 Naïve perceptions of complex epidemiology
 All MRSA found in livestock are ST398
 Livestock are the only reservoirs of ST398
 ST398 isolates of diverse genotype and geographic origin
may also be epidemiologically distinct
 Requires systematic investigation of S. aureus
epidemiology in animals and humans.
 Occupational health and public relations concerns
 Not yet a public health concern!
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28. Current studies
 Ecology of S. aureus in multiple site production
systems (NPB)
 Longitudinal study of S. aureus and MRSA
colonization and infection in swine veterinarians
 NIOSH (UMASH center)
 Team Nostril – 66 AASV members
 Survey of occupational health and safety in US
swine veterinarians
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29. Team Nostril – preliminary results
 High prevalence of colonization relative to general
population
 MSSA (72%, 52%)
 MRSA (12%, 8%)
 Mix of spa types
 Livestock associated spa types in MSSA and MRSA
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30. Survey of US swine veterinarians
2 MRSA cases: 117 vets - >3000 vet-years – 1 day lost work 30

31. Survey of occupational health and safety
in US swine veterinarians
 Survey monkey
 400 target population
 132 respondents (ongoing)
 If you are a US swine vet - Help us out!
 Respond to regular reminders

One time only (15 – 20 mins)
 Contact us if you have not received an email request to
complete the survey
 Leticia Linhares (linh0009@umn.edu)
 Peter Davies (davie001@umn.edu)
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