The Anatomy of an Epidemic: The Anatomy of an Epidemic: A Rational Approach to A Rational Approach to

Understanding, Preventing and Understanding, Preventing and Combating Infectious DiseasesCombating Infectious Diseases

Stephen Weber, MD, MSStephen Weber, MD, MS

Assistant ProfessorAssistant ProfessorSection of Infectious DiseasesSection of Infectious Diseases

Hospital EpidemiologistHospital EpidemiologistDirector, Infection Control ProgramDirector, Infection Control Program

University of Chicago HospitalsUniversity of Chicago Hospitals

OverviewOverview

1.1. IntroductionIntroduction2.2. Modeling and the Anatomy of Modeling and the Anatomy of

EpidemicsEpidemics3.3. Preventing and Controlling EpidemicsPreventing and Controlling Epidemics4.4. Epidemics and LuckEpidemics and Luck

SmallpoxSmallpox SARSSARS AnthraxAnthrax MonkeypoxMonkeypox MumpsMumps Antibiotic-resistant Antibiotic-resistant

AcinetobacterAcinetobacter Community-Community-

associated MRSAassociated MRSA

Supertoxigenic Supertoxigenic Clostridium difficileClostridium difficile

Avian influenzaAvian influenza Bordatella pertussisBordatella pertussis MeaslesMeasles West Nile VirusWest Nile Virus Highly-resistant Highly-resistant

Pseudomonas Pseudomonas aeruginosaaeruginosa

Defining an epidemicDefining an epidemic

1.1. An outbreak of a contagious disease that An outbreak of a contagious disease that spreads rapidly and widely.spreads rapidly and widely.

2.2. An increased frequency of infection above the An increased frequency of infection above the normal or usual levelnormal or usual level

0

25

50

75

100

No. o

f cas

es

2004 2005 2006 2007

Smallpox

0

25

50

75

100

No. o

f cas

es

2004 2005 2006 2007

Seasonal viruses

Epidemic SurveillanceEpidemic Surveillance

World Health Organization (WHO)World Health Organization (WHO)

Centers for Disease Control and Prevention Centers for Disease Control and Prevention

Illinois Department of Public HealthIllinois Department of Public Health

Chicago Department of Public HealthChicago Department of Public Health

UCH Infection Control ProgramUCH Infection Control Program

Individual CliniciansIndividual Clinicians

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Modeling and the Anatomy of Modeling and the Anatomy of EpidemicsEpidemics

Modeling MeaslesModeling Measles

Keeling, et al. Keeling, et al. Proc R Soc LondProc R Soc Lond. 2002. 2002

Modeling MalariaModeling Malaria

McKenzie and Samba, et al. McKenzie and Samba, et al. Am J Trop Med HygAm J Trop Med Hyg. 2004. 2004

dX/dt = A B Y (N - X) - r X

dY/dt = A C X (M - Y) - m Y

R0 = 1

Progression of an EpidemicProgression of an Epidemic

R0 = 2

R0 = 3

Basic reproductive number (RBasic reproductive number (R00)) Expected number of secondary Expected number of secondary

cases on the introduction of one cases on the introduction of one infected individual in a infected individual in a susceptible populationsusceptible population

RR00 > 1 Epidemic disease > 1 Epidemic disease

RR00 = 1 Endemic disease = 1 Endemic disease

RR00 < 1 Disease dies out < 1 Disease dies out

Generation #R0 1 2 3 …10

2 1 2 4 512

1 1 1 1 1

0.5 4 2 1 0

Basic Reproductive NumbersBasic Reproductive Numbers

SARS in general population: 0.49SARS in general population: 0.49 SARS (hospital transmission): 2.6SARS (hospital transmission): 2.6 Smallpox in a vulnerable population: 3.0-5.2Smallpox in a vulnerable population: 3.0-5.2 Measles (pre-vaccine): 10-15Measles (pre-vaccine): 10-15 Measles in Belgian schools (1996): 6.2-7.7Measles in Belgian schools (1996): 6.2-7.7 1918 pandemic influenza: 1.8-2.01918 pandemic influenza: 1.8-2.0 Influenza on a commercial airliner: 10.4Influenza on a commercial airliner: 10.4

Liao, et al. Liao, et al. Risk AnalRisk Anal. 2005; Chowell, et al. . 2005; Chowell, et al. Emerg Inf Dis. Emerg Inf Dis. 2004; Mossong, et al. 2004; Mossong, et al. Epidemiol InfectEpidemiol Infect. 2005; Meltzer, et al. . 2005; Meltzer, et al. Emerg Inf DisEmerg Inf Dis. 2001.. 2001.

RR00 = p = p xx k k xx d d

p = transmissibilityp = transmissibilityk = contactsk = contactsd = duration of d = duration of

contagiousnesscontagiousness

Transmissibility (p)Transmissibility (p)

1.1. Quantity of pathogen releasedQuantity of pathogen released2.2. Mechanism of disseminationMechanism of dissemination3.3. Inherent infectiousness of the Inherent infectiousness of the

pathogenpathogen

RR00 = = pp x k x d x k x d

Quantity of pathogen releasedQuantity of pathogen released

Varies with state of Varies with state of diseasedisease Early chickenpoxEarly chickenpox Herpes simplexHerpes simplex Cattarhal phase of Cattarhal phase of

viral infectionsviral infections Varies with activityVaries with activity

Coughing vs. sneezing Coughing vs. sneezing vs. talkingvs. talking

RR00 = = pp x k x d x k x d

Mechanism of disseminationMechanism of dissemination RespiratoryRespiratory

Influenza, tuberculosisInfluenza, tuberculosis ContactContact

Seasonal virusesSeasonal viruses Antibiotic-resistant bacteriaAntibiotic-resistant bacteria

Fecal-oralFecal-oral Salmonella, shigella, hepatitis ASalmonella, shigella, hepatitis A

Blood and body fluidBlood and body fluid HIV, Hepatitis B and CHIV, Hepatitis B and C

RR00 = = pp x k x d x k x d

Respiratory disseminationRespiratory disseminationDropletDroplet Droplet nucleiDroplet nuclei

PathogenPathogen BacteriaBacteria TBTB

SizeSize ≥≥ 5 5µµ < 5< 5µµ

DistanceDistance < 3 feet< 3 feet ??

PersistencePersistence < 10 min.< 10 min. > 1 hr.> 1 hr.

DestinationDestination Upper airwaysUpper airways AlveoliAlveoli

RR00 = = pp x k x d x k x d

Inherent infectiousnessInherent infectiousness

RR00 = = pp x k x d x k x d

E. coli E. coli infecting bladder infecting bladder epitheliumepithelium

Biological differences Biological differences between organismsbetween organisms Adhesions, proteinasesAdhesions, proteinases

Variation in host Variation in host responseresponse

Expressed as the Expressed as the minimal infectious doseminimal infectious dose

ContactsContacts Number of contactsNumber of contacts

May be facilitated by May be facilitated by environmental factorsenvironmental factors

Intensity of contactsIntensity of contacts

RR00 = p x = p x kk x d x d

RR00 = p x = p x kk x d x d

Duration of Contagiousness (d)Duration of Contagiousness (d)

Assuming a constant frequency of Assuming a constant frequency of contacts and an unchanging degree of contacts and an unchanging degree of transmissibility, the longer the period of transmissibility, the longer the period of time that a patient is contagious the more time that a patient is contagious the more likely he/she is to transmit the pathogen.likely he/she is to transmit the pathogen.

For some infections, the period of For some infections, the period of contagiousness may not always be contagiousness may not always be associated with symptoms of illness. associated with symptoms of illness. RR00 = p x k x = p x k x dd

Duration of Contagiousness (d)Duration of Contagiousness (d)

The Ebola paradoxThe Ebola paradox Rapid mortality Rapid mortality

reduces period of reduces period of contagiousnesscontagiousness

RR00 = p x k x = p x k x dd

Preventing and Controlling Preventing and Controlling EpidemicsEpidemics

Childbed fever: Vienna, 1847Childbed fever: Vienna, 1847

Robert A. Thom (1966)Robert A. Thom (1966)

Cholera: London 1854Cholera: London 1854

RR00 = p = p xx k k xx d d

Interventions to prevent the spread of Interventions to prevent the spread of epidemics target transmissibility (p), epidemics target transmissibility (p),

contacts (k) or duration of contacts (k) or duration of contagiousness (d).contagiousness (d).

Modeling and Infection Modeling and Infection ControlControl

Limiting transmissibility (p)Limiting transmissibility (p) Reduce the quantity of Reduce the quantity of

pathogen releasedpathogen released Symptom controlSymptom control

Anti-tussivesAnti-tussives Barrier precautionsBarrier precautions

Masks for patientsMasks for patients

Limiting transmissibilityLimiting transmissibility Act on the Act on the

mechanism of mechanism of disseminationdissemination Environmental Environmental

controlscontrols Reduce inherent Reduce inherent

infectiousnessinfectiousness Difficult to reduce, Difficult to reduce,

but possible to but possible to increaseincrease

Overall, 63% of VRE (+) patient rooms are Overall, 63% of VRE (+) patient rooms are contaminatedcontaminated

Sheets: 40%Sheets: 40%

Bedside Tables: Bedside Tables: 20%20%

Bed rails: 26%Bed rails: 26%

Blood pressure Blood pressure cuffs: 14%cuffs: 14%

Preventing ContactPreventing Contact

Quarantine and IsolationQuarantine and Isolation

““une quarantaine une quarantaine de joursde jours (a period (a period

of forty days)”of forty days)”

SS MM TT WW RR FF SSExposed Symptom

s BeginContagioContagiousus

QuarantineQuarantine

IsolationIsolation

Social ControlsSocial Controls

Restriction on Restriction on public events and public events and gatheringsgatherings

Travel limitationsTravel limitations Building Building

quarantinesquarantines Import/Export Import/Export

controlscontrols

Reducing duration of Reducing duration of contagiousnesscontagiousness

Antimicrobial therapyAntimicrobial therapy Influenza controlInfluenza control Anti-HIV therapyAnti-HIV therapy

Enhanced case Enhanced case recognitionrecognition Syndromic surveillanceSyndromic surveillance Limit contactsLimit contacts

Ebola revisitedEbola revisited

00

Period of infectivityPeriod of infectivity DeathDeath

11 22

Days of illnessDays of illness

Ebola: Natural HistoryEbola: Natural History

33

Ebola revisitedEbola revisited

00

DeathDeath

11 22

Days of illnessDays of illness

333 44

Traditional Traditional funeral funeral

practicespractices

Period of infectivityPeriod of infectivity

Ebola: Current PracticeEbola: Current Practice

33

Ebola revisitedEbola revisited

00

DeathDeath

11 22

Days of illnessDays of illness

Period of infectivityPeriod of infectivity

333 44

ICU SupportICU Support

Ebola: USAEbola: USA

33

Epidemics and LuckEpidemics and Luck

Epidemic MisfortuneEpidemic Misfortune Epidemics do not conform Epidemics do not conform

to the predictions of to the predictions of deterministic models. deterministic models. Stochastic phenomena Stochastic phenomena prevail.prevail. Monkeypox: Co-transport of Ghanan giant rat with Monkeypox: Co-transport of Ghanan giant rat with

prairie dogsprairie dogs West Nile Virus: Survival of carrier mosquito through West Nile Virus: Survival of carrier mosquito through

transatlantic flighttransatlantic flight SARS: Co-mixing of viruses between humans, fowl SARS: Co-mixing of viruses between humans, fowl

and civetsand civets HIV: Single African ancestral eventHIV: Single African ancestral event

Improving the OddsImproving the Odds Understanding the role of Understanding the role of

chance in epidemics chance in epidemics permits the deployment of permits the deployment of manageable strategies to manageable strategies to prevent spread.prevent spread.

Improved performance of Improved performance of day to day practices may day to day practices may be more important than an be more important than an elaborate emergency elaborate emergency response system.response system.

ConclusionsConclusions

1.1. Epidemics are driven by a relatively Epidemics are driven by a relatively understandable interplay of pathogens, understandable interplay of pathogens, infected and susceptible hosts.infected and susceptible hosts.

2.2. Understanding the mathematical as well as Understanding the mathematical as well as the biological underpinnings of epidemics is the biological underpinnings of epidemics is critical to prevention and control.critical to prevention and control.

3.3. Sometimes, it really is better to be lucky Sometimes, it really is better to be lucky than to be good.than to be good.