Livestock Associated MRSAWhat are the risksto human health?Peter Davies BVSc, PhDUniversity of Minnesota
Questions: LA-MRSA   Background of MRSA in human health and    Livestock Associated MRSA   NPB funded “white paper” on h...
Staphylococcus                          aureus   Common inhabitant of warm-blooded animals       ‘Normal flora’ (20-30% ...
Methicillin resistant S. aureus                      (MRSA)                   ‘Truth’ prior to 1995   First detected in 1...
‘Quantum shifts’ in MRSA epidemiology   Emergence of ‘Community Acquired’ MRSA       Global phenomenon since mid 1990s  ...
What are LA-MRSA?   Distinct ‘family’ of closely related MRSA first    found in Holland in 3 people linked to pigs (2004)...
What are the       risks?                                 H   To whom?   How?                           Y   T   How oft...
Livestock Associated MRSA    Knowns, unknowns, and uncertainties   Generally accepted facts       Common occurrence of L...
Occupational exposure!   Consistent observation: occupational exposure to    animals increases risk of MRSA positive cult...
Duration of colonization   Research workers (short term exposure)               van Cleef et al (2011)       33 of 199 e...
Transmission of ST398 MRSA among people   Studies of transmission in Dutch hospitals        (Bootsma, 2010)       ST398 ...
Burden of disease from ST398 MRSA   National Pork Board white paper       Studies of ST398 S. aureus were compiled in a ...
Burden of disease from ST398 MRSA   Many reports don’t distinguish infection from colonization   Small number of serious...
Burden of disease from ST398 MRSA   83 papers/reports of ST398 associated clinical cases       Some where most isolates ...
Burden of disease from ST398 MRSA   Data recorded       History of animal contact       Number of fatalities.       Nu...
Burden of disease from ST398 MRSA                                    16
Self reported disease in US swine farmers                      Leedom Larson et al (2010)   Mail survey       135 (17.2%...
Distribution of LA-MRSA and other MRSA clinicalisolates in Europe             (van Cleef et al., 2011)                    ...
Geographic distribution of S. aureuscausing invasive infections inEuropeGrundmann et al 2010      357 laboratories servin...
Public health risk of ST398 MRSA   Current evidence suggests low transmissibliity       No reports of outbreaks   Curre...
Fatal ST398 infections   5 fatal cases reported   4 MSSA not MRSA       Spa type t571 (not common in swine)       No s...
Lethal pneumonia caused by an ST398         S. aureus strain      Rasigade et al (2010)   Observations       Fatal necro...
“One Health” means            more than one inference   ‘.. concern because strains ST398 strains were able to    acquire...
More of the story                    Davies et al, EID June 2011   t571 ST398 MSSA detected in 9 families from the Domini...
Emergence of unusual bloodstream infections associated      with pig-borne-like Staphylococcus aureus ST398 in      France...
LA-MRSA: Implications   Not good news for swine/livestock industries   Priority to understand occupational risks   Prev...
The rest of the story……   Understanding LA-MRSA is embryonic   Naïve perceptions of complex epidemiology       All MRSA...
Current studies   Ecology of S. aureus in multiple site production    systems (NPB)   Longitudinal study of S. aureus an...
Team Nostril – preliminary results   High prevalence of colonization relative to general    population       MSSA (72%, ...
Survey of US swine veterinarians2 MRSA cases: 117 vets - >3000 vet-years – 1 day lost work 30
Survey of occupational health and safety    in US swine veterinarians   Survey monkey       400 target population      ...
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Dr. Peter Davies - Livestock associated MRSA: What are the risks to human health?

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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

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Dr. Peter Davies - Livestock associated MRSA: What are the risks to human health?

  1. 1. Livestock Associated MRSAWhat are the risksto human health?Peter Davies BVSc, PhDUniversity of Minnesota
  2. 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 2
  3. 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. 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 4
  5. 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?? 5
  6. 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. 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. 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 8
  9. 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 9
  10. 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. 10
  11. 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) 11
  12. 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 12
  13. 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 13
  14. 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. 14
  15. 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 15
  16. 16. Burden of disease from ST398 MRSA 16
  17. 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 17
  18. 18. Distribution of LA-MRSA and other MRSA clinicalisolates in Europe (van Cleef et al., 2011) 18
  19. 19. Geographic distribution of S. aureuscausing invasive infections inEuropeGrundmann 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. 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? 20
  21. 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? 21
  22. 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” 22
  23. 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? 23
  24. 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. 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 25
  26. 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 26
  27. 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! 27
  28. 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 28
  29. 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 29
  30. 30. Survey of US swine veterinarians2 MRSA cases: 117 vets - >3000 vet-years – 1 day lost work 30
  31. 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) 31

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