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Emerging pathogens 2007

Emerging pathogens 2007. Peter H. Gilligan PhD Clinical Microbiology-Immunology Labs UNC Hospitals. How I became a clinical microbiologist. Obtained doctoral degree in microbiology at the University of Kansas

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Emerging pathogens 2007

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  1. Emerging pathogens 2007 • Peter H. Gilligan PhD • Clinical Microbiology-Immunology Labs • UNC Hospitals

  2. How I became a clinical microbiologist • Obtained doctoral degree in microbiology at the University of Kansas • Did post-doctoral training (2 years) in medical and public health microbiology at UNC Hospitals • Director of Microbiology Labs at St Christopher’s Hospital for Children (Philadelphia) for 4 years • Past 20+ years, Associate Director then Director of the Clinical Microbiology-Immunology Labs at UNC Hospitals • Have served on medical school admission committee for approximately 15 years and the MD/PhD advisory (admissions) committee for the past 10 years

  3. What do clinical microbiologists do? • We serve: • our patients • our health care-providing colleagues, physicians, nurses, physician assistants, pharmacy colleagues • hospital administrators • We make money for the institution • general public by insuring the public health • Involved in studying outbreaks of several emerging infectious diseases

  4. How do we serve? • central role in the diagnosis and management of infectious diseases • central role in infection control and antimicrobial use • recognize emerging disease threats and outbreaks including bioterrorism events • we educate & train health care providers • we create new knowledge (research) to deal with practical problems

  5. Best things about my job • Direct impact on patient care and public health of the community • Intellectually challenging job requiring a broad fund of knowledge-need to know a little about a lot of things –I am never bored!!!!!!! • Work with highly motivated and intelligent individuals • Get to be at the cutting edge of infectious disease diagnosis

  6. Worst things about my job • Incredible amounts of governmental oversight • Increasing emphasis on financial aspects of the job • Declining talent pool of technologists • Need to be responsible for an organization that run 24/7/365-we never close. Personally have worked through ice storms, blizzards, and hurricanes.

  7. How you can become a clinical microbiologist • CLS programs available here, ECU, WCU, WSSU, Wake Forest, UNC-CH • Education is also available on line • 2 more years of school to get a BS in CLS • Take ASCP certification exam to become certified as a MT. • Starting salary is 38,000 and up • Career options are amazingly diverse; many former UNC students work in leadership positions in the pharmaceutical and biotech industries

  8. HIV* Avian influenza SARS* Cryptosporidium* E. coli O157:H7* Nipah virus nv Creutzfeldt-Jakob disease Sin Nombre Virus West Nile Virus Clostridium difficle* Bacillus anthracis(BT agent) Cyclospora CA-MRSA* Rapidly growing mycobacterium* Rotavirus* BK virus* Chlamydia pneumoniae Pencillinum marneffei Legionella* MDR- TB and pneumococcus* Burkholderia cepacia complex* VRE/VRSA* Helicobacter pylori* Invasive Group A streptococcal disease* HHV-6* HPV* HCV* Emerging/Re-emerging Infectious Diseases in the past 25 years

  9. How do new pathogens emerge • Organisms that jump species barriers • Changing ecosystems • Changes in food production techniques • Evolution of medical devices and care • Long term survival of immunosuppressed • Pathogens that are detected because of new technology • Misuse of micro-organisms • Biocrime/bioterrorism • Organism evolution as a result of human intervention • Antibiotic pressure

  10. How do microbes change? • Bacteria, because they evolve very quickly, can readily adapt to hostile environments • Assume a generation time for a bacteria of 50 minutes • 30 generations/day; or 220,000 bacterial generations for each human generation (assume generation is 20 years) • Bacteria have a huge evolutionary advantage over humans

  11. How emerging pathogens develop? • Mutation drives evolution • constantly occurring • usually silent or lethal • environmental pressure such as antibiotics may select “resistance” mutation • Key feature of success of antibiotic resistant strains is their genetic fitness I.e. their ability to compete in a complex microbial environment • Recognition that certain bacteria may be hypermutators because of mutation in DNA repair genes • These strains may not be as “fit” as wild-types but may predominant in certain chronic infections such as P. aeruginosa causing chronic pulmonary infections in CF patients

  12. How do emerging pathogens develop? • Recombination • Resistance genes from antibiotic producing organisms • genetic exchange of resistant genes can occur among organisms which are genetically diverse • Think Cholera toxin genes to E. coli • transfer of resistance/virulence genes can be mediated by plasmids/phage/transposons/ integrons

  13. Organisms that jump species barriers • HIV, SARS, Avian flu • HIV likely jumped from primates to humans • SARS from pigs(?) • Avian flu-hasn’t yet made the jump from birds to humans because human to human spread is rare, if it occurs at all. However mutation may result in that occurring. • Technology allows us to quickly develop diagnostics for new pathogens • Took years to develop HIV diagnostics • Took weeks to develop SARS diagnostics

  14. Changing ecosystems • Lyme disease • A perfect storm • Farmland in New England returned to forest • Natural predators for deer were eliminated • Deer populations and the ticks they carried increased because of ecosystem changes • People built homes and spent increasing amounts of time in the woods • This resulted in increased exposure to deer ticks that carried Borrelia • Ticks were pencil point in size and often difficult to see

  15. Changes in food production techniques • Increased use of factory farming • Feedlots bring together large numbers of animals who produce large amounts of waste • Waste can lead to run-off of EHEC that can contaminant adjacent fields as was seen in recent spinach outbreaks • Large meat packing operations can result in 50 ton lots of ground meat containing 100s of animals • Meat can be distributed throughout the US • Contaminated lots can then lead to large scale outbreaks

  16. Changes in medical care • Immunosuppression either as a result of HIV or medically therapy (ex. transplants) results in emerging infections • Pneumocystis, MAC, toxoplasma and CMV in HIV patients • CMV, adenovirus and HHV-6 in transplant patients • The use of indwelling artificial materials such as catheters, shunts, artificial joints present new ecosystems and new organisms • Examples-coagulase negative staphylococci growing as a biofilm on artificial joints/catheters/shunts • Rapidly growing mycobacteria causing keratitis following LASIK surgery

  17. Pathogens detected with new technology • Prime example is HCV • Viral genome elucidated using molecular cloning techniques • Broad range 16S RNA primers are used to detect non-cultivable bacteria • Next big thing- application of molecular tools to understand how mixed microbial populations cause disease • Likely diseases caused by mixed microbial populations are bacterial vaginosis, peridontal disease, inflammatory bowel disease, CF lung disease

  18. How does bacterial resistance develop? • Bacterial resistance develops in response to antimicrobial pressure • It is estimated that 3 million lbs of antimicrobials are used each year in the US • Much of it is used in children to treat viral respiratory illness • Estimated that 3/4 of children in US younger than two receive antimicrobials • Children then may serve as a key role for the emergence of antimicrobial resistance • 10x that amount are used in animals • End result- tremendous selective pressure that results in the emergence of bacterial resistance

  19. UNC-ED • 6% of wounds from ED in 1st quarter of 2005 grew MRSA • 45% of wounds from ED in 2nd quarter of 2005 grew MRSA • ? Due to proliferation of CA-MRSA? • GOAL • To characterize and determine the prevalence of CA-MRSA isolates at UNC hospitals

  20. Molecular analysis: CA- vs. HA-MRSA Adapted from Weber, CID, 2005:41S

  21. Virulence of CA-MRSA • Panton-Valentine leukocidin (PVL) • Hemolysin first reported in 1932 by Panton and Valentine • Located on mobile phage • 2 co-transcribed genes, lukS-PV and lukF-PV • The two subunits form a hexameric pore-forming cytolytic toxin with a high affinity for PMNs and macrophages • PVL producing strains associated with skin and soft tissue infections and necrotizing pneumonia • Rarely associated with osteomyelitis, septicemia, or endocarditis • Rare HA-MRSA strains with PVL have similar clinical syndrome • Usually only 2% of all S. aureus isolates produce PVL but found in the majority of epidemic CA-MRSA strains

  22. SCCmec types (Staphylococcal chromosome cassette) 21-24 Adapted from Diederen and Kluytmans, JID, 2005

  23. Susceptibility Patterns tmp-smz ery vanc gent pen clinda cefox ery vanc doxy doxy gent clinda cefox tmp-smz pen CA-MRSA HA-MRSA 93% are erythromycin resistant 16% clindamycin resistant

  24. CA-MRSA Timeline Children without identifiable risk factors Prison and jail populations 2003 Late 1990s 1980 Mid 1990s 2000 Necrotizing pneumonia, United States and Europe Outbreak in Detroit 2/3 of patients were IVDU 1998 - Athletes/sports teams 1999 - Native Americans IVDU=intravenous drug users Naimi TS et al. JAMA. 2003;290:2976-2984. Zetola N et al. Lancet Infect Dis. 2005;5:275-286. Levine DP et al. Ann Intern Med. 1982;97:330-338. CDC. Morb Mortal Wkly Rep. 2003;52:793-795. Groom AV et al. JAMA. 2001;286:1201-1205. Herold BC et al. JAMA. 1998;279:593-598. CDC. Morb Mortal Wkly Rep. 2001;50:919-922. Gillet Y et al. Lancet. 2002;359:753-759. CDC. Morb Mortal Wkly Rep. 1999;48:707-710.

  25. Clinical presentation CA-MRSA • CA-MRSA • SSTIs (abscesses, cellulitis, folliculitis, impetigo, furunculosis*) • Typically treated with excision and drainage; +/- oral antibiotics • Occasionally require IV antibiotics, hospitalization and surgical intervention • Necrotizing pneumonia especially in young people secondary to influenza was reported this flu season • Mortality was over 50%- median time to death 3.5 days • Median age was 17.5 years • 5 isolates from Louisiana were CA-MRSA genotype of the same PFGE type • Both levofloxacin and inducible clindamycin resistance seen in these isolates

  26. Case 5 • The patient is a 16 yo who presents with shoulder and left chest wall pain • An MRI is ordered because of concerns about a abscess • The patient becomes hypotensive, SOB, is intubated and admitted to the MICU. • Prior to admission, he denied fever, chills, cough and night sweats • He lives on a farm in rural central NC with exposures to dogs cats and horses • In the past year a horse had been put done due to “strangles.” Strangles is a respiratory infection caused by Streptococcus equi

  27. Case 5 • No contributory travel or sexual history. Does not use drugs or alcohol • Two months previously he had a right-sided preauricular abscess incised and drained • Treated with Augmentin and infection resolved • On PE, afebrile, pulse was 103 bpm, RR 30 and BP 99/62 • Skin examination was significant for a small violaceous lesion at the site of the prior abscess • Had several pustules on his leg and a hyperpigmented macules on his left great toe • LDH was highly elevated, he was anemic and had a sed rate of 60

  28. Gram stain of sputum

  29. Culture from blood bottle

  30. Study Design I. Outpatient wound cultures (SSTIs) with MRSA (6/05 to 3/06), n=233 • Nosocomial MRSA isolates (blood) (6/05 to 4/06), n=76 • Wound cultures with MRSA regardless of location (6/06-7/06), n=100 • Respiratory cultures with MRSA from Cystic Fibrosis (CF) patients • (10/05 to 4/07), n=339 V. Child care centers VI. All isolates recovered at Lilongwe Medical Center (6-06-2-07) n>100 • Definition of CA-MRSA Panton-Valentine leukocidin positive SCCmec type IV

  31. IV II 500 I. PVL and SCCmec Characterizationof outpatient wound isolates SCCmec typing** 72% 0.5% 0.5% 11% 9% 6% n=233 (n= 42) (n= 191) ** Oliveira and Lencastre (2002) Antimicrob Agents Chemother46, 2155-61.

  32. Study Design I. Outpatient wound cultures (SSTIs) with MRSA (6/05 to 3/06), n=233 • Nosocomial MRSA isolates (blood) (6/05 to 4/06), n=76 • Wound cultures with MRSA regardless of location (6/06-7/06), n=100 • Respiratory cultures with MRSA from Cystic Fibrosis (CF) patients • (10/05 to 4/07), n=339 V. Child care centers VI. All isolates recovered at Lilongwe Medical center (in June 07) • Definition of CA-MRSA Panton-Valentine leukocidin positive SCCmec type IV

  33. SCCmec typing IV II 500 II. PVL and SCCmec Characterizationnosocomial blood isolates # of isolates 55% 21% 15% 9% n=76 (n= 16) (n= 60)

  34. Clinical Characterization CA HA I CA Molecular Characterization 1 14 1 16 HA 0 41 1 42 I 0 1 17 18 2 72 2 II. Clinical and Molecular Analysisnosocomial blood isolates N=76

  35. Study Design I. Outpatient wound cultures (SSTIs) with MRSA (6/05 to 3/06), n=233 • Nosocomial MRSA isolates (blood) (6/05 to 4/06), n=76 • Wound cultures with MRSA regardless of location (6/06-7/06), n=100 • Respiratory cultures with MRSA from Cystic Fibrosis (CF) patients • (10/05 to 4/07), n=339 V. Child care centers VI. All isolates recovered at Lilongwe Medical center (in June 07) • Definition of CA-MRSA Panton-Valentine leukocidin positive SCCmec type IV

  36. IV II 500 III. PVL and SCCmec Characterizationof 2006 wound isolates SCCmec typing 72% # of isolates 9% 10% 8% n=100 (n= 81) (n= 19)

  37. Thanks to: • Melissa Miller • Jennifer Goodrich • Joel Wedd • Mwai Makoka and the UNC project Lilongwe • Tameaka Sutton-Shields • Kyle Rodino • All the CMIL technologists who identify, save and freeze isolates so we can do this research

  38. As Brian the scientist would say, “Any Questions?”

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