Epid 600 Class 13 Outbreaks

EPID 600; Class 13 Outbreak! Concepts in infectious disease epidemiology University of Michigan School of Public Health

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Infectious disease “An illness due to a specific infectious agent or its toxic products that arises through transmission of that agent or its products from an infected person, animal or inanimate reservoir to a susceptible host; either directly or indirectly through an intermediate plant or animal host, vector or the inanimate environment”

Benensen AS, editor. Control of Communicable Diseases Manual. Sixteenth Edition, 1995.

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Dynamics of disease transmission HOST Epidemiologic Triad VECTOR AGENT

ENVIRONMENT

Human disease results from interaction between the host, agent and the environment. A vector may be involved in transmission. Host susceptibility to the agent is determined by a variety of factors, including genetic background, nutritional status, vaccination, prior exposure, context

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Factors associated with increased risk of human disease Host Characteristics

Agent

Environmental Factors

Age

Biologic (Bacteria, viruses)

Temperature

Sex

Chemical (Poison, smoke)

Humidity

Race

Physical (Trauma, radiation)

Altitude

Occupation

Nutritional (Lack, excess)

Crowding

Marital Status

Housing

Genetics

Neighborhood

Previous Diseases

Water

Immune Status

Food Air Pollution

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Modes of disease transmission The potential for a given agent to cause an outbreak depends on the characteristics of the agent, including the mode of transmission of the agent Two basic modes of transmission Direct Indirect Certain diseases can be transmitted directly or indirectly

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Direct mode of disease transmission In an infectious setting, immediate and direct transfer of an agent to a host by an infected person or animal Touching, biting, or sexual intercourse are classic examples Measles virus: airborne by droplet spread or direct contact with nasal/throat secretions of infected persons In a noninfectious setting, the host may have direct contact with the agent in the environment Children ingesting lead paint from playground equipment

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Indirect mode of disease transmission Vehicle-borne Transmission through contaminated inanimate objects (toys, food, water, surgical utensils, or biological products such as blood, tissues or organs) Vector-borne Transmission through simple contamination by animal or arthropod vectors or their actual penetration of the skin or mucous membranes Airborne Transmission occurs when microbial, particulate, or chemical agents are aerosolized and remain suspended in air for long periods of time 7

Incubation period Interval from receipt of infection to the time of onset of clinical illness (signs and symptoms) Different diseases have different incubation periods No precise incubation period but a range is characteristic for a disease What accounts for this delay? Time needed for the pathogen to replicate to the “critical mass” necessary for clinical disease Site in the body at which the pathogen replicates Dose of the infectious agent received at time of infection 8

Outcomes of exposure to an agent The spectrum of severity varies by disease: 1. 

Exposure, No infection

2. 

Carrier - Individual harbors the pathogen but does not show evidence of clinical illness; a potential source of infection (can transmit the agent)

3. 

Subclinical Infection - Disease that is not clinically apparent; leads to immunity, carrier, or non-immunity

4. 

Clinical Infection - Apparent disease characterized by signs and symptoms; results in immunity, carrier, non-immunity, or severe consequences such as death

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Endemic, epidemic, pandemic Endemic - The habitual presence (or usual occurrence) of a disease within a given geographic area Epidemic - The occurrence of an infectious disease clearly in excess of normal expectancy, and generated from a common or propagated source Pandemic - A worldwide epidemic affecting an exceptionally high proportion of the global population Number of Cases of Disease

“Endemic” “Epidemic” Time

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Deaths in Greater London; December 1 – 15, 1952

Period of Dense Fog

Number of Deaths

1.000 800 600 400 200 0 1

2

3

4

5

6

7

8

9

December

10 11 12 13 14 15 11

Disease Outbreaks Typically, sudden and rapid increase in the number of cases of a disease in a population Common Source Cases are limited to those who share a common exposure Food-borne, water Propagated Disease often passed from one individual to another Measles, STDs

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Essential Steps in an Outbreak Investigation

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Steps of an Outbreak Investigation 1. 

Establish the existence of an outbreak

2. 

Verify the diagnosis

3. 

Define and identify cases

4. 

Describe and orient the data in terms of person, place and time

5. 

Develop hypotheses

6. 

Evaluate hypotheses

7. 

Refine hypotheses and carry out additional studies

8. 

Implement control and prevention measures

9. 

Communicate findings 14

Step 1: Establish the existence of an outbreak Before you decide whether an outbreak exists, you must first determine the expected or usual number of cases for the given area and time

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Step 1: Establish the existence of an outbreak Data sources Health department surveillance records for a notifiable disease Sources such as hospital discharge records, mortality records and cancer or birth defect registries for other diseases and conditions If local data is not available, make estimates using data from neighboring states or national data

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Step 1: Establish the existence of an outbreak Whether or not an outbreak is investigated or control measures are implemented is not strictly tied to verifying that an epidemic exists… Other factors may come into play, including: Severity of the illness Potential for spread Political considerations Public concern and pressure from community Availability of resources

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How do we know when we have an excess over what is expected? Public Health Surveillance “The ongoing and systematic collection, analysis, and interpretation of outcome-specific data for use in the planning, implementation, and evaluation of public health practice”.

Thacker, Berkleman. Epidemiologic Reviews 1988;10:164-90

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Notifiable disease

Disease for which regular, frequent, and timely information regarding individual cases is considered necessary for the prevention and control of disease

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Step 2: Verify the diagnosis Two goals in verifying a diagnosis Ensure that the problem has been properly diagnosed Ensure that the outbreak really is what it has been reported to be Review clinical findings and laboratory results for affected people Visit or talk to several of the people who became ill For outbreaks involving infectious or toxic chemical agents, be certain that the increase in diagnosed cases is not the result of a mistake in the laboratory.

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Step 3: Define and identify cases Establish a case definition - a standard set of criteria for deciding whether a person should be classified as having the disease under study In many outbreaks, a working definition of the disease syndrome must be drawn up that will permit the identification and reporting of cases As the investigation proceeds and the source, mode of transmission and/or etiologic agent becomes better known, you can modify the working definition

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Step 3: Define and identify cases A case definition includes four components Clinical information about the disease 2.  Characteristics about the people who are affected (person) 3.  Information about the location (place) 4.  A specification of time during which the outbreak occurred (time) 1. 

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Step 3: Define and identify cases To increase sensitivity & specificity of reporting, we use three classifications of cases that reflect the degree of certainty regarding diagnosis: 1. Confirmed 2. Probable 3. Possible

The case definition is used to actively search for more cases beyond the early cases and the ones that presented themselves.

Confirmed Case Laboratory Verification

+

Clinical Features

+

Probable Case

++

Possible Case

+ 23

Step 3: Define and identify cases The following information should be collected from every affected person in an outbreak: 1. Identifying information - name, address, phone 2. Demographic information - e.g., age, sex, race, occupation 3. Risk factor information 4. Clinical information Verify the case definition has been met for every case Date of onset of clinical symptoms to create an epidemic curve

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Step 3: Define and identify cases The first cases to be recognized are usually only a small proportion of the total number To identify other cases, use as many sources possible Passive Surveillance - Relies on routine notifications by healthcare personnel (recall Notifiable Diseases) Active Surveillance - Involves regular outreach to potential reporters to stimulate reporting of specific conditions; investigators are sent to the afflicted area to collect more information Contact physician offices, hospitals, schools to find persons with similar symptoms or illnesses Send out a letter, telephone or visit the facilities to collect information 25

Step 4: Describe and orient the data in terms of time, place and person Characterizing an outbreak by time, place and person is called descriptive epidemiology Descriptive epidemiology is important because You can learn what information is reliable and informative (e.g., similar exposures) And what may not be as reliable (e.g., many missing responses to a particular question) Provides a comprehensive description of an outbreak by showing its trend over time, its geographic extent (place) and the populations (people) affected by the disease 26

Step 4: Describe and orient the data in terms of time The time course of an epidemic is shown by the distribution of the times of onset of the disease, called the Epidemic Curve Graph of the number of cases of the health event by their date of onset Provides a simple visual display of the magnitude and time trend of the outbreak May stratify epidemic curves by place (residence, work, school, etc.) or by personal traits (age, gender, race, etc.) to assess whether time of onset varies in relation to place or person characteristics

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Step 4: Describe and orient the data in terms of place Assessment of the outbreak by place provides Information on the geographic extent of the problem A “spot map” indicating place of occurrence of cases may show clusters or patterns that provide clues to the nature and source of the outbreak Patterns reflecting water supply, wind currents, or proximity to a restaurant, swimming pool, school room or workplace If the size of overall population varies between comparison areas, a “spot map” of the area may be misleading because it only shows number of cases 28

Step 4: Describe and orient the data in terms of person Examine risks in subgroups of the affected population according to personal characteristics, as well as interaction between characteristics Age, race, sex, occupation, social group, medical status Characterizing an outbreak by person helps to determine which subgroups of the population are at risk

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Examples of epidemic curves

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Step 5: Develop hypotheses Though we generate hypotheses from the beginning of the outbreak, at this point, the hypotheses are sharpened and more accurately focused. Use existing knowledge (if any) on the disease, or find analogies to diseases of known etiology Hypotheses should address Source of the agent Mode of transmission Exposures associated with disease and should be proposed in a way that can be tested

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Step 6: Evaluate hypotheses Generally, after a hypothesis is formulated, one should be able to show that All additional cases, lab data, and epidemiologic evidence are consistent with the initial hypothesis; and No other hypothesis fits the data as well Observations that add weight to validity The greater the degree of exposure (or higher dosage of the pathogen), the higher the incidence of disease Higher incidence of disease in the presence of one risk factor relative to another factor

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Reminder....attack rate An attack rate is the proportion of a well-defined population that develops illness over a limited period of time, such as during an epidemic or outbreak Useful for comparing the risk of disease in groups with different exposures Remember..an attack rate is an incidence proportion (even though it is called a “rate”) Often expressed as a percent

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Attack rate Attack Rate = Number of new cases occurring in a given time period Population at risk at the start of the time period = Number of people at risk who develop a certain illness Total number of people at risk

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Calculating an Attack Rate in a food-borne outbreak In a foodborne outbreak occurring among people attending a social function or common geographical site Calculate an attack rate for people who ate a particular item (exposed) and an attack rate for those who did not eat the item (unexposed) The attack rate is calculated by dividing the number who became ill and consumed the item by the total number of people who consumed that item

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Identifying the source of an outbreak Look for an item with A high attack rate among those exposed AND A low attack rate among those not exposed (so the ratio of attack rates for the two groups is high) Ideally, most of the people who became ill should have been exposed to the proposed agent so that the exposure could explain most, if not all, of the cases.

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Step 7: Refine hypotheses and carry out additional studies Additional epidemiologic studies What questions remain unanswered about the disease? What kind of study used in a particular setting would answer these questions? When analytic studies do not confirm the hypotheses reconsider the original hypotheses orlook for new vehicles or modes of transmission

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Step 7: Refine hypotheses and carry out additional studies Laboratory and environmental studies Epidemiologic studies can implicate the source of infection, and guide appropriate public health action But sometimes laboratory evidence can “clinch” the findings Environmental studies often help explain why an outbreak occurred and may be very important in certain settings

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Case control methods applied to a food-borne outbreak The usual approach is to apply the case-control methodology to determine what exposures ill people had that well people did not have List all of the relevant items on the menu Determine the proportions of ill and of non-ill persons who ate each of the items by questionnaire Identify the food item with the largest difference in attack rates between cases (ill) and controls (non-ill)

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Step 8: Implementing control and prevention measures The practical objectives of an epidemic investigation are to stop the current epidemic and establish measures that would prevent similar outbreaks in the future Preliminary control measures should be implemented as soon as possible

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Ro = βcD

R o = Reproductive Rate (number of secondary infections/infected case) β = average probability susceptible partner will be infected over duration of relationship c = average rate of acquiring new partners D = average duration of infectiousness

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To sustain an epidemic

Ro > 1

but also

β > 0 (transmission must be possible) can block with barriers c>0

(new susceptibles) can reduce contacts

D>0

(maintain infectiousness) can treat infection 42

Therefore, elements of epidemic control The elements of epidemic control include: Controlling the source of the pathogen (if known) e.g., Remove or inactivate the pathogen Interrupting the transmission e.g., Sterilize environmental source of spread; vector control Controlling or modifying the host response to exposure e.g., Immunize the susceptibles; use prophylactic chemotherapy

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Step 9: Communicate findings At the end of the investigation, communicate findings to others who need to know Prepare a final report Provide information on the nature, spread, and control measures employed The report can take several forms: 1. An

oral briefing for local health authorities

2. A written 3.  Formal

report to a journal [note: MMWR]

presentation of recommendations

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Diarrhea at a high school dinner In November 2006, between 200-300 students and teachers reported gastroenteritis after attending a school function in Denmark The cause was determined to be primarily enterotoxigenic E. coli. Enterotoxigenic E. coli is transmitted through fecally contaminated food or water, and mainly diagnosed as travelers’ diarrhea in industrialized countries So how did this happen at a dinner in Denmark?

45 2006. Pakalniskiene et al. A foodborne outbreak of enterotoxigenic E. coli and Salmonella Anatum infection after a high-school dinner in Denmark, November Epidemiol Infect. 2008; 1-6

Diarrhea at a high school dinner

Pasta salad with pesto has the highest number of exposed cases (98%), and a high attack rate; bread rolls come in at a close second: exposure=96% 46 2006. Pakalniskiene et al. A foodborne outbreak of enterotoxigenic E. coli and Salmonella Anatum infection after a high-school dinner in Denmark, November Epidemiol Infect. 2008; 1-6

Diarrhea at a high school dinner So which is it? Bread rolls or pesto?

Eating more portions of pasta had a dose response effect on the risk ratio; this was not true of the bread rolls 47 2006. Pakalniskiene et al. A foodborne outbreak of enterotoxigenic E. coli and Salmonella Anatum infection after a high-school dinner in Denmark, November Epidemiol Infect. 2008; 1-6

Diarrhea at a high school dinner None of the food preparers had a history of recent illness or foreign travel; nor did their stool samples test positive for E coli Investigators concluded that basil in the pesto was the likely culprit The basil had been imported from a country that uses surface and run-off water for irrigation Basil from that same country has been linked to various other outbreaks as well [aside: the purported producer of the basil denies having grown basil in the four years prior to the investigation]

48 2006. Pakalniskiene et al. A foodborne outbreak of enterotoxigenic E. coli and Salmonella Anatum infection after a high-school dinner in Denmark, November Epidemiol Infect. 2008; 1-6