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
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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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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