PATHOGENS                              iNPeter Davies BVSc,PhDUniversity of Minnesota
Emerging diseases in intensive livestock    production   Media       Shoot first – ask questions later (maybe)   Blogos...
Diseases in the twilight zone   BSE       Model prediction up to 50,000 human deaths from        variant CJD       Lowe...
Discovery vs. emergence   Conventional microbiology reveals the tip of the    iceberg   Today have very powerful diagnos...
Diseases in the twilight zone   Influenza viruses   MRSA   Clostridium difficile   Noroviruses   Sapoviruses   Intes...
Recent Emerging Disease Issues in SwineWhat                                 Where        When*   Swine Health*   Human    ...
Recent Emerging Disease Issues in SwineW                                    Where        When*   Swine Health*   Human    ...
S. aureus and C. difficile   Common commensals found in healthy people and animals   Opportunistic pathogens increasing ...
MRSA in animals – publication rate 12       Cattle 10                                                       Pig, Sheep    ...
PFGE with the SmaI enzymeSoge et al. J. Antimicrob. Chemother. 2009;64:1148-1155           MRSA isolated from   US West Co...
Holland – an issue emerges!   Very low MRSA prevalence       ‘Search and destroy’ policy       Intensive screening and ...
S. aureus subtyping                               ‘Livestock associated’   PFGE                         Sma1 Untypable  ...
MRSA in market hogs (de Neeling et al,    2006)   National survey of slaughter pigs in Holland        39% of 540 pigs po...
Colonization of farm workers   ST398 also isolated from pig farmers           (Voss et al 2005)       23% of farmers pos...
EFSA farm prevalence study (dust samples)
MRSA spa types in swine barn dust      (EFSA, 2010)        Predominant in North America*
ST398 MRSA              Not just a pig problem!   Pigs – widespread (but not China, UK, Ireland, Japan)       ST9   Cal...
MRSA in pigs in Ontario                     (Khanna et al, 2007)   Convenience sample of 20 Ontario herds       25% (71/...
Livestock associated MRSA in USA   Two farms in Iowa                                  (Smith 2007)       One positive – ...
Prevalence and characterization of MRSA in     pigs and farm workers on conventional and     antibiotic free swine farms i...
MRSA on conventional and ABF swine farms   MRSA detected in pigs on 4 farms       All 4 conventional farms in IA-IL    ...
MRSA on conventional and ABF swine farms         32 spa type 539/t034         2 spa type 2/NT         2 other ‘LA’ (t011; ...
MRSA in farm workers on conventional andABF swine farms    17 spa type 539/t034    5 spa type 2/NT        Not LA type   53...
MSSA isolates in MN   98 isolates of MSSA characterized in MN       92 from pigs, 6 from people       Pig samples clust...
Summary   MRSA detected in market hogs and    occupationally exposed people   Spa type 539/t034 predominant   Spa type ...
Exposure assessment – ST398   High risk of exposure in groups with direct    livestock contact       Major concerns abou...
Risk assessment   Consequences of occupational exposure       Colonization vs. Infection   What is the burden of diseas...
Questions?             28
Current and future studies   Epidemiology of S. aureus in multiple site pig    farms (NPB)   MRSA colonization and infec...
Occupational exposure   Consistent observations that people with    occupational exposure to animal species more likely  ...
45                                          40                   Clinical cases = 122                                     ...
Lethal pneumonia caused by an ST398         S. aureus strain      Rasigade et al (2010)   Observations       Fatal necro...
No pigsNo MRSA           33
“One Health” means            more than one inference   ‘.. concern because strains ST398 strains were    able to acquire...
The rest of the story                     Davies et al, EID June 2011   t571 ST398 MSSA detected in 9 families from the D...
Emergence of unusual bloodstream infections associated      with pig-borne-like Staphylococcus aureus ST398 in      France...
The rest of the story……   Understanding LA-MRSA is embryonic   Naïve perceptions of complex epidemiology       All MRSA...
Community dissemination of MRSA ST398                                            Cuny et al (2009)   Study of German farm...
Nasal colonization with ST 398                                     Cuny et al (2009)Group                         N       ...
Communities in pig dense areas in Holland                                                        (van Cleef 2010)   Maili...
Exposure assessment – ST398   High risk of exposure in groups with direct    livestock contact       Major concerns abou...
Risk assessment   Consequences of occupational exposure       Colonization vs. Infection   What is the burden of diseas...
Transmission of ST398 MRSA among people   Studies of transmission in Dutch hospitals        (Bootsma, 2010)       ST398 ...
Distribution of LA MRSA and other MRSA clinicalisolates in Europe             (van Cleef et al., 2011)                    ...
Diversity of genome of human and LA ST398    MRSA strains                  (Hallin et al., 2011)   ‘LA-MRSA strains repre...
Duration of colonization   Research workers (short term exposure)               van Cleef et al (2011)       33 of 199 e...
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Dr. Peter Davies - Pathogens in the Twilight Zone: Update on emerging disease issues with implications for the pork industry

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Pathogens in the Twilight Zone: Update on emerging disease issues with implications for the pork industry - Dr. Peter Davies, University of Minnesota, from the 2011 The Allen D. Leman Swine Conference, September 17-20, 2011, St Paul, MN, USA.

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  • PFGE with the SmaI enzyme of MRSA and MSSA. PFGE pattern A: lane 1, MRSA 10-55; and lane 2, MSSA 10-51. PFGE type B: lane 3, MRSA 9-48. PFGE type C: lane 4, MRSA 10-579; and lane 5, MSSA 10-578. PFGE type D: lane 6, MRSA OSS143-7; lane 7, MSSA OSS143-6; and lane 8, MSSA 11-31. Lane 9, MW standards.
  • Dr. Peter Davies - Pathogens in the Twilight Zone: Update on emerging disease issues with implications for the pork industry

    1. 1. PATHOGENS iNPeter Davies BVSc,PhDUniversity of Minnesota
    2. 2. Emerging diseases in intensive livestock production Media  Shoot first – ask questions later (maybe) Blogosphere  Just shoot and ask no questions  Move on to next ‘crisis’ Guilty until proven innocent Habitual overstatement of public health risks 2
    3. 3. Diseases in the twilight zone BSE  Model prediction up to 50,000 human deaths from variant CJD  Lower limit of 5,000  Global tally after 15 years is around 200. H5N1 avian influenza  Guesstimates up to 150 million circulated  564 Laboratory confirmed cases (August 9, 2011)  330 fatalities. 3
    4. 4. Discovery vs. emergence Conventional microbiology reveals the tip of the iceberg Today have very powerful diagnostic tools Closely related hosts (mammals, homeotherms) likely to be colonized by ‘closely related’ organisms Discovery involves much uncertainty  Interspecies transmission  Virulence in various species 4
    5. 5. Diseases in the twilight zone Influenza viruses MRSA Clostridium difficile Noroviruses Sapoviruses Intestinal spirochetes …. 5
    6. 6. Recent Emerging Disease Issues in SwineWhat Where When* Swine Health* Human Media Health* hype*Clostridium difficile (pigs) Global 1986 +/- ++(?) ++PRRS Global 1987 +++++ - -Salmonella typhimurium DT104 Global 1993 +/- ++ ++++PCV2 Global 1996 +++++ - -Hepatitis E infection USA/global 1995 - +/- +/-Menangle virus Australia 1997 + +/- -Nipah virus Malaysia 1998 ++ ++ ++Bungowannah virus Australia 2003 + - -MRSA ST398 EU/global 2004 - +/- +++++virulent Streptococcus suis type 2 China 2005 ? ++ ++H1N1 pandemic influenza Global 2009 + ++++(?) +++++
    7. 7. Recent Emerging Disease Issues in SwineW Where When* Swine Health* Human Media Health* hype*Clostridium difficile (pigs) Global 1986 +/- ++(?) ++PRRS Global 1987 +++++ - -Salmonella typhimurium DT104 Global 1993 +/- ++ ++++PCV2 Global 1996 +++++ - -Hepatitis E infection USA/global 1995 - +/- +/-Menangle virus Australia 1997 + +/- -Nipah virus Malaysia 1998 ++ ++ ++Bungowannah virus Australia 2003 + - -MRSA ST398 EU/global 2004 - +/- +++++virulent Streptococcus suis type 2 China 2005 ? ++ ++H1N1 pandemic influenza Global 2009 + ++++(?) +++++
    8. 8. S. aureus and C. difficile Common commensals found in healthy people and animals Opportunistic pathogens increasing in incidence and clinical severity Recognized human pathogens long before animal reservoirs thought of epidemiological significance. Important nosocomial agents - hospital infections principal concern Community acquired infections more important in recent years. Animal colonization raises risk of livestock as sources of community acquired infections. Both isolated from pork
    9. 9. MRSA in animals – publication rate 12 Cattle 10 Pig, Sheep Cat, Dog 8 HorseN 6 4 2 0 70s 80s 90- 96 97 98 99 00 01 02 03 04 05 06 07 95 2010: > 50 papers Years 9
    10. 10. PFGE with the SmaI enzymeSoge et al. J. Antimicrob. Chemother. 2009;64:1148-1155 MRSA isolated from US West Coast public marine beaches
    11. 11. Holland – an issue emerges! Very low MRSA prevalence  ‘Search and destroy’ policy  Intensive screening and typing with sma1 PFGE 2004: 6mo girl screened before for surgery for a congenital heart defect  MRSA isolate not typable with Sma1 PFGE 2 other screening isolates not typable by Sma1 PFGE All 3 ‘cases’ epidemiologically linked to pigs Studies of MRSA prevalence in pigs, farmers and pork 11
    12. 12. S. aureus subtyping ‘Livestock associated’ PFGE Sma1 Untypable MLST ST398 (CC398) SCCmec typing (I – VIII) III, IV, V Spa typing  Ridom t034, t011, t108……...  egenomics 539, ………………..….. 12
    13. 13. MRSA in market hogs (de Neeling et al, 2006) National survey of slaughter pigs in Holland  39% of 540 pigs positive (nasal swabs)  44 of 54 (81%) of farms positive All isolates a ‘single clonal group’  Nontypable (NT) by sma1 PFGE  MLST: ST 398  3 closely related spa types predominant (t011, t108, t1254,…) Panton-Valentine Leucocidin (PVL) toxin negative Uniformly resistant to tetracycline  Use of tetracyclines may be selecting for MRSA? 13
    14. 14. Colonization of farm workers ST398 also isolated from pig farmers (Voss et al 2005)  23% of farmers positive on nasal swab  760x general population prevalence Dutch health authorities changed MRSA screening procedures  People exposed to pigs and calves considered high risk  Isolated and screened before hospital admission ST398 MRSA isolated from pork (van Loo et al., 2007) 14
    15. 15. EFSA farm prevalence study (dust samples)
    16. 16. MRSA spa types in swine barn dust (EFSA, 2010) Predominant in North America*
    17. 17. ST398 MRSA Not just a pig problem! Pigs – widespread (but not China, UK, Ireland, Japan)  ST9 Calves – Holland Horses – Austria, Belgium, France, Germany, Holland, Canada Chickens – Belgium Dogs – Austria, Canada Lack of host specifity may indicate zoonotic risk! 17
    18. 18. MRSA in pigs in Ontario (Khanna et al, 2007) Convenience sample of 20 Ontario herds  25% (71/285) of pigs positive  20% (5 of 25) farmers positive Predominant (75%) spa types similar to ST398 Dutch isolates  Spa type t034 predominant 18
    19. 19. Livestock associated MRSA in USA Two farms in Iowa (Smith 2007)  One positive – 70% of pigs (ST398) Slaughter pigs (Davies et al, 2009)  539 pigs from 45 farms  25% of pigs MRSA positive  Diverse spa types - t034 predominant 19
    20. 20. Prevalence and characterization of MRSA in pigs and farm workers on conventional and antibiotic free swine farms in the USA Collaborative Study – National Pork Board  54 farms across 3 centers (MN, IA-IL, OH_NC)  18 farms per state  9 conventional, 9 antibiotic free  24 pigs per farm; any human volunteers Difficulties in finding farms  45 farms enrolled (24 conv., 21 ABF)  1084 pigs; 154 people 20
    21. 21. MRSA on conventional and ABF swine farms MRSA detected in pigs on 4 farms  All 4 conventional farms in IA-IL  All pigs negative in ABF farms 45 (4.2%) of 1084 pigs positive 29 (18.8%) of 154 people positive  24 of 40 (60%) people positive on two farms with highest pig prevalence 21
    22. 22. MRSA on conventional and ABF swine farms 32 spa type 539/t034 2 spa type 2/NT 2 other ‘LA’ (t011; t571
    23. 23. MRSA in farm workers on conventional andABF swine farms 17 spa type 539/t034 5 spa type 2/NT Not LA type 539/t034 1 other 23
    24. 24. MSSA isolates in MN 98 isolates of MSSA characterized in MN  92 from pigs, 6 from people  Pig samples clustered on 4 farms (3 conv., 1 ABF) 65 (71%) of pigs isolates were spa type 539/t034  1 isolate from human 24
    25. 25. Summary MRSA detected in market hogs and occupationally exposed people Spa type 539/t034 predominant Spa type 2/tunknown also detected in all studies  Similar to Canada Lack of knowledge of S. aureus epidemiology in pigs  Spa type 539/t034 in MN 25
    26. 26. Exposure assessment – ST398 High risk of exposure in groups with direct livestock contact  Major concerns about occupational risk  Some exposure risk to direct family members Currently no indication of significant community exposure 26
    27. 27. Risk assessment Consequences of occupational exposure  Colonization vs. Infection What is the burden of disease?  Virulence  Transmission Diversity within ST398 lineage  Animal vs. human isolates 27
    28. 28. Questions? 28
    29. 29. Current and future studies Epidemiology of S. aureus in multiple site pig farms (NPB) MRSA colonization and infection in swine veterinarians (NIOSH)  70 ‘volunteers’  Study duration of colonization over 18 months  Prospective study of infection risk 29
    30. 30. Occupational exposure Consistent observations that people with occupational exposure to animal species more likely to be colonized with MRSA  As yet minimal data indicating increased risk of infection Interspecies transmission of S. aureus  Frequency, Quantity, Duration Burden of disease  Primarily occupational? 30
    31. 31. 45 40 Clinical cases = 122 35 Invasive = 27 30 25 Burden of disease 20 15 from ST398 MRSA 10 5 0 Ca m De la nd Be ina Sc ong nd n ng da G a rk Au y ria en Sw ly ai an iu Ita Ho na la ed st Ch Sp nm lg K m l ot Ho er Many reports don’t distinguish infection from colonization Small number of serious infections Retrospective study of human isolates in Canada  5 ST398 out of 3,687 (4 skin/soft tissue infections) CDC has examined >12,000 isolates  ST398 had not identified in a human clinical case Current evidence suggests low pathogenicity? 31
    32. 32. 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” 32
    33. 33. No pigsNo MRSA 33
    34. 34. “One Health” means more than one inference ‘.. concern because strains ST398 strains were able to acquire PVL genes’ 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 34
    35. 35. The rest 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 independent 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) 35
    36. 36. 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 36
    37. 37. 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. 37
    38. 38. Community dissemination of MRSA ST398 Cuny et al (2009) Study of German farming community where MRSA ST398 prevalent on pig farms Nasal swabs from  Pig farmers and family members  Swine vets and family members  462 pupils (10 to 16 yo) in villages in the high density pig farming area 38
    39. 39. Nasal colonization with ST 398 Cuny et al (2009)Group N Pct PosPig farmers 113 86% Prevalence Ratio= 20Farmer family members 116 4.3%Swine Veterinarians 18 45% Prevalence Ratio= 5Vet family members 44 9%Schoolchildren* 462 0.007% (3) *All 3 positive children lived on pig farms 39
    40. 40. Communities in pig dense areas in Holland (van Cleef 2010) Mailing in 3 selected municipalities in the Netherlands where livestock MRSA prevalent Adults complete questionnaire and nose swab (n = 583)  One of 534 persons without livestock-contact positive (0.2%)  13 of 49 of farm residents/workers positive (26.5%) Conclusions:  High prevalence of livestock-associated MRSA in people with direct contact with farm animals.  Not spread into the wider community 40
    41. 41. Exposure assessment – ST398 High risk of exposure in groups with direct livestock contact  Major concerns about occupational risk  Some exposure risk to direct family members Currently no indication of significant community exposure 41
    42. 42. Risk assessment Consequences of occupational exposure  Colonization vs. Infection What is the burden of disease?  Virulence  Transmission 42
    43. 43. 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) 43
    44. 44. Distribution of LA MRSA and other MRSA clinicalisolates in Europe (van Cleef et al., 2011) 44
    45. 45. Diversity of genome of human and LA ST398 MRSA strains (Hallin et al., 2011) ‘LA-MRSA strains represent a homogenous lineage distinct from co-local HA- and CA-MRSA strains  characterized by a lack of human-associated virulence and adhesion determinants Absence of detectable enterotoxin gene among ST398 LA-MRSA strains from a wide host range is reassuring regarding their foodborne pathogenic potential.’ 45
    46. 46. Duration of colonization Research workers (short term exposure) van Cleef et al (2011)  33 of 199 exposures led to positive culture on farm  Only 3 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. 46

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