1 EPIDEMIOLOGY 200B Methods II – Prediction and Validity Scott P. Layne, MD.
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Transcript of 1 EPIDEMIOLOGY 200B Methods II – Prediction and Validity Scott P. Layne, MD.
1
EPIDEMIOLOGY 200BMethods II – Prediction and
Validity
Scott P. Layne, MD
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PART 2
Staphylococcus aureus
March 2010
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Infectious Disease AgentsBacteria
Gram Positive --> Staphylococcus sp.Gram NegativeZoonoticVector BourneAnaerobicAcid FastSpirochetesChlymidiaMycoplasma / Ureaplasma
VirusesPrionsFungiParasites
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Colonizationvs
Infection
Host Microbe
External
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Microbe
Cell wall constituents
Enzymes
Toxins
Direct destruction of tissue
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Host
Adhesion
Invasion
Chemotaxis (cell movement)
Opsonization (C3b, IgG)
Intracellular killing
Genetics (HLA makeup)
Integument
Trauma, Foreign Bodies
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External
Contamination
Exposure
Traffic
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Staphylococcus aureus
Transmission & Ecology
Carried in nasal membranes and skin of warn-blooded animals
Colonizes one-third of humans at any one time
Spread by close contacts
Spread by contaminated hands and surfaces
Spread enhanced by sneezing
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Staph Related Diseases
Staphylococcus aureusSkin InfectionsFood PoisoningToxic Shock SyndromeOsteomyelitisInfective ArthritisAcute EndocarditisPneumoniaSepsisParotitis
High probability of blood borne spread leading to multiple sites of infection
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Staph Related Diseases
Staphylococcus epidermidisAdult bacteremiaSub-acute endocarditisNeonatal bactermia
Staphylococcus saprophyticusUrinary Tract Infections
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Skin InfectionsFolliculitis
Boils
Carbuncles
Cellulitis
Scalded skin syndrome
Burn infections
Wound infections
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Food PoisoningEnterotoxin A effects
Fever and Myalgias
Respiratory symptoms
Headache
Gastrointestinal symptoms, vomiting, diarrhea
Short incubation periods (2 - 6 hours)
Epidemic outbreaks
#2 cause (20%) of food borne outbreaks
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Bioterrorism Potential ?
Source: Textbook of Military Medicine
Effects of inhaled Staph Enterotoxin B in lung
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Toxic Shock SyndromeMenstrual vs Non-menstrual cases
Hyperabsobable tampons
CriteriaT > 38.9BP < 90Rash with desquamation
Rule out RMSF, Leptospirosis, Measles
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Toxic Shock Syndrome
Involvement of three or more of the following organsGut: vomiting, diarrheaMuscle: myalgias, elevated CPKKidney: pyuria, elevated creatinineLiver: hepatitisBlood: thrombocytopeniaCNS: disorientation
Overall ~5% case fatality
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Osteomyelitis#1 causative organismcaused by trauma or blood borne spread
Infective Arthritis#1 causative organism
Acute Endocarditis #1 causative organismInfects normal, abnormal, prosthetic valves
Post Viral Lobar PneumoniaEspecially after influenza
Bacteremia and Sepsis #1 causative organism
Other Infections
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Domains
Diseases
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Diseases
Antibiotics Toxins
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Antibiotic Testing
Minimum Inhibitory Concentration (MIC)Minimum Bactericidal Concentration (MBC)
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Antibiotic BiotypesMethicillin Sensitive Staph aureus (MSSA)
Rx: OxacillinCephalexinClindamycinVancomycin
Methicillin Resistant Staph aureus (MRSA)Rx: Vancomycin
Vancomycin Intermediate Staph aureus (VISA)Vancomycin Resistant Staph aureus (VRSA)
Rx: TeichoplaninFusidic acidQuinupristin-dalfopristin (Synercid)Linezolid (Zyvox)RifampinBactrimMinocyclineDaptomycin (Cubicin)
Lowerresistance
Higherresistance
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ToxinsHemolysins (RBC)
Alpha toxin
Beta toxin
Delta toxin
Gamma toxin
Panton-Valentine Leukocidin (WBC)
Enterotoxins (food poisoning)Toxin A
Toxin F
Toxic Shock Syndrome Toxin (superantigen)
Exfoliatin (intraepidermal separation)
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Toxins
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Strain Typing
Electrophoresis of proteins
Multilocus enzyme electrophoresis
Plasmid analysis
Restriction endonuclease analysis of chromosomal DNA
Restriction fragment length polymorphisms
Ribotyping
Nucleotide sequence analysis
Whole genome sequencing
2,872,769 bp & 2,560 genes (USA300)
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Hospital Community
Connection / Mystery ?
More resistantto antibiotics
More virulentfrom toxins
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Two Overall Patterns
Hospital-acquired MRSA (h-MRSA)
Community-acquired MRSA (c-MRSA)
h-MRSA has more antibiotic resistance genes than c-MRSA
c-MRSA has more virulence genes than h-MRSA
c-MRSA is causing serious and fatal infections in healthy people
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Hospital-acquired MRSAIn 1960s, MRSA began to appear in hospitalized patients
In 1970s, MRSA became the main cause of nosocomial infections worldwide
In 1996, VISA was first isolated with 8 cases to date
In 1997, VRSA was first isolated with 4 cases to date
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ICU: High Risk for MRSA
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Risk Factors for Nosocomial Infection
Severity of illness
Previous exposure to antimicrobial agents
Underlying diseases or conditions
Chronic renal disease
Insulin-dependent diabetes mellitus
Peripheral vascular disease
Dermatitis
Skin lesions
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Risk Factors (cont.)
Invasive procedures
Surgery
Dialysis
Presence of invasive devices
Urinary catheterization
Repeated contact with healthcare system
Colonization by multidrug-resistant organism
Advanced age
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Infection Control StrategiesBacterial surveillance (laboratory)
Antibiotic use pattern (pharmacy)Antibiotic use intervention (alter Rx)
Hand washingGlovesGownsFace masksPatient isolation, cohortingTraffic control
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Hospital Community
Connection ?
More resistantto antibiotics
More virulentfrom toxins
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Community-acquired MRSA
Reproduction, Mutation, Selection
In 1999, MSRA associated with 4 fatal cases in infants, with all carrying the gene for Panton-Valentine (PVL) toxin
Today, there are multiple clones and/or strains
USA300
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C-MRSA Case DefinitionPositive culture, sensitivity testing
Outpatient setting or within 48 hours after hospitalization
Person no medical history of MRSA infection or colonization
Person has no medical history in the past year of
Hospitalization
Nursing home, skilled facility, hospice
Dialysis
Surgery
Person has no permanent indwelling catheters or medical devices that pass through the skin into the body
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Outbreak Reports
Correctional facilities
Athletic teams
Men who have sex with men (MSM)
Fire stations
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Infectious Disease NewsDecember 2004
Football Team
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LA County JailOutbreak 2002 - 2003
928 inmates with MRSA infections
66 inmates hospitalized
10 inmates had invasive disease
bacteremia, endocarditis, osteomyelitis
Predominant strain identified (PFGE)
Largest jail worldwide165,000 persons per year
20,000 per day
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Transmission Factors
CrowdingMany outbreaks occur in settings where people are in close proximity.
Frequent contactsFootball linemen often have skin infections in sites where they have skin abrasions
Compromised skinBroken skin is more likely to be an infection site than intact skin
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Transmission Factors
Contaminated surfaces, shared itemsIncludes towels, razors, toothbrushes
Lack of cleanlinessTransmission is more likely in places where people cannot achieve appropriate hand and body hygiene
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Intervention Program
2003, Fencers, ColoradoIncreased hand hygiene
Showering with soap after every practice or tournament
Covering cuts and abrasions with a bandage until healed
Laundering personal items such as towels and supporters after each use
Cleaning or laundering shared athletic equipment such as pads or helmets at least once a week but ideally after each use
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Intervention Program
2003, Fencers, ColoradoEstablishing a routine cleaning schedule for the sensor
wires
Consulting a health-care provider for wounds that do not heal or appear infected.
No further infections have been reported.
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Community SurveillanceIn 2000, CDC began working closely with four states, with a combined population of about 12 million persons, to study the epidemiology of CA-MRSA infections. The information from these studies is helping CDC understand the nature of the disease, why people get infected, and to develop future studies designed to improve our ability to prevent these infections. These data are being collected in Connecticut, Minnesota, Georgia, and Maryland as part of CDC's Emerging Infections Program, Active Bacterial Core surveillance (ABCs). This program is being expanded to six states in 2004.
http://www.cdc.gov/ncidod/hip/ARESIST/mrsa_comm_faq_print.htm
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At nine Emerging Infections Program sites (EIPs), surveillance is conducted for invasive bacterial diseases due to pathogens of public health importance. For each case of invasive disease in the study population, a case report with basic demographic information is filed and, in most cases, bacterial isolates from a normally sterile site from patients are sent to CDC for laboratory study.
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% Staph aureus Isolates Resistant to Methicillin
Sources: National Nosocomial Infections Surveillance System. Am J Infect Control. 1999;27:520-532; Am J Infect Control. 2000;28:429-448; Am J Infect Control. 2001;29:404-421.
0
20
40
60
80
100
1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000
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Proportion of Staph aureus Nosocomial Infections Resistant to Oxacillin (MRSA) In
Intensive Care Unit Patients, 1989-2003
Source: NNIS System (2003 data are incomplete)
0
10
20
30
40
50
60
70
1989 1991 1993 1995 1997 1999 2001 2003
Year
Percent Resistance
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Staphylococcus aureus(MRSA)
Examples of questions that can be addressed
Risk factors associated with transmission
Optimal schedules for utilizing antibiotics
Impacts of hand washing or other control measures
Are there super-spreaders
What governs spread of virulent clones
What determines ecological fitness
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ReadingEmily Kajita, Justin Okano, Erin N. Bodine, Scott P. Layne, Sally Blower. 2007. Modeling an outbreak of an emerging pathogen. Nature Reviews Microbiology 5, 1 – 10.