PM2ch32.pdf

Outbreak Investigation

Chapter 32

OUTBREAK INVESTIGATION

JENICE N. LONGFIELD, MD, MPH

INTRODUCTION

VERIFY THE DIAGNOSIS OR DEFINE THE PROBLEM

Establish a Case Definition

Ascertain Cases

VERIFY THE EXISTENCE OF AN EPIDEMIC

ORGANIZE A MULTIDISCIPLINARY TEAM

Composition of the Team

Logistical Plans and Management

IDENTIFY DISEASE CONTROL MEASURES

DESCRIBE THE OUTBREAK BY PERSON, TIME, AND PLACE

Orient the Outbreak to Person

Orient the Outbreak in Time

Orient the Outbreak to Place

IDENTIFY RISK FACTORS AND MECHANISMS

Frequency Measures and Severity Assessment

Epidemiologic Measures of Risk

DEVELOP TENTATIVE HYPOTHESES AND A PLAN

Determine Type of Outbreak and Critical Exposure

Hypothesize About Mechanism of Transmission

Develop Survey Instruments

Plan for Administrative and Logistical Considerations

Identify Medical Treatment Resources

Reevaluate Control Measures in Place

TEST THE HYPOTHESIS

Collect Data and Specimens

Determine the Need for Additional Studies and Analysis

Evaluate the Adequacy of the Case Definition

Establish Criteria for Deciding the Outbreak is Under Control

COMPARE RESULTS WITH THOSE OF THE PUBLISHED LITERATURE

FINALIZE A REPORT WITH RECOMMENDATIONS TO CONTROL FURTHER

SPREAD

Write an Executive Summary and Prepare a Complete Report

Evaluate the Effectiveness of Recommendations

SUMMARY

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Military Preventive Medicine: Mobilization and Deployment, Volume 2

J.N. Longfield ; Colonel, Medical Corps, US Army; Chief, Department of Clinical Investigation, Brooke Army Medical Center, San

Antonio, TX 78234-6200

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Outbreak Investigation

INTRODUCTION

The use of the epidemiologic method to identify

and control an acute disease problem in a popula-

tion represents the most dramatic application of the

science of epidemiology. Knowledge gained from a

well-conducted outbreak investigation can enable

the investigator to intervene and control an epidemic.

The relatively quick tempo of this scientific endeavor

also contributes to its unique place in research. The

literature is replete with classic examples of outbreaks

occurring in military populations. 1–3 Carrying out

the military mission is associated with living, work-

ing, eating, and playing in a group environment

under harsh conditions. This togetherness, coupled

with potentially unique occupational and environ-

mental exposures, can result in outbreaks in de-

ployed service members. Vaccines or effective

chemoprophylaxis do not exist for many endemic

diseases. Recognition of new pathogens and the

reemergence of known pathogens with new drug

resistance patterns have contributed to a resurgence

of infectious diseases as a threat to the military force

in the field. 4–9

The Epidemic Intelligence Service program for

public health officers at the Centers for Disease

Control and Prevention (CDC) grew out of the fear

of biological warfare during the Korean War. 10 As

the 21st century opens, the potential for govern-

ments or individual terrorists to use biological or

chemical agents against a population has not less-

ened and may indeed be greater than it was in the

1950s. The 1995 terrorist attack on a Japanese sub-

way train using the nerve gas sarin resulted in more

than 5,000 people injured and 11 deaths. 11 Biological

warfare and biological terrorist events by definition

seek to create epidemics and so the need remains

for a cadre of capable epidemiologists to respond

to domestic or military public health emergencies

of this nature. 12

This chapter is intended to provide a practical,

detailed discussion of the specific steps to use in

conducting the investigation of an outbreak in the

field (Exhibit 32-1). The initial purpose of the in-

vestigation is to determine the population at risk

and identify the specific cause or exposure risk fac-

tors of disease. As the description of the outbreak

becomes clearer, explicit objectives can be formu-

lated for the planned field work to develop and test

hypotheses proposed to explain the outbreak. This

permits effective intervention, which in turn will

end the crisis.

EXHIBIT 32-1

OUTBREAK INVESTIGATION METHODOLOGY

Verify the diagnosis or define the problem

Establish a case definition

Ascertain cases

Verify the existence of an epidemic

Test hypotheses

Collect data and specimens

Determine the need for additional studies and

analysis

Evaluate the adequacy of the case definition

Establish criteria for deciding outbreak is under

control

Organize a multidisciplinary team

Identify disease control measures

Describe the outbreak by person, time, and place

Compare results to those of the published literature

Finalize report with control recommendations

Write an executive summary and prepare a

complete report

Evaluate effectiveness of control recommenda-

tions

Identify risk factors and mechanisms

Develop tentative hypotheses and a plan

Determine type of outbreak and critical exposure

Hypothesize about mechanism of transmission

Develop survey instruments

Plan for administrative and logistical consider-

ations

Identify medical treatment resources

Reevaluate control measures in place

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Military Preventive Medicine: Mobilization and Deployment, Volume 2

VERIFY THE DIAGNOSIS OR DEFINE THE PROBLEM

An outbreak investigation is an iterative process

that passes through distinct phases. An outbreak

investigation begins with the recognition of a problem,

usually cases with similar symptoms clustered in space

and time. An alert observer must then call on the

services of the public health system. The appointed

investigator needs to obtain as much detailed in-

formation as possible from the initial report. Cases

of clinical illness should be fully described, to in-

clude the type of symptoms, frequency of symp-

toms, onset time, and duration of the illness. In

some instances, the actual diagnosis is already

known. On other occasions, only a collection of

signs and symptoms is apparent. When the etiology

is unclear, the differential diagnosis for the clinical

presentation of symptoms and physical exam find-

ings must be considered. Clinical clues and timing

of onset can help narrow the possibilities. For example,

the presence of blood and fecal leukocytes in diarrheal

stools indicates an inflammatory process and limits

the number of pathogens to be considered. The pres-

ence of paresthesias or other neurological symptoms

immediately suggests the possibility of a chemical

intoxication from ciguatoxin, scombrotoxin, para-

lytic shellfish poisoning, or mushroom poisoning.

It is very important at this early stage to determine

the type of studies (eg, smears, cultures, serologies,

radiographs) necessary to verify the diagnosis. Ap-

propriate laboratories should be made aware of the

possible organisms, toxins, or other agents being

considered because some will require special me-

dia or special testing.

Following this initial notification of a problem,

two equally important determinations must take

place: (1) verification of the diagnosis or at least

definition of the problem and (2) verification of the

existence of an epidemic. Often these two funda-

mental steps will occur simultaneously. The order

in which these two steps are listed in the investiga-

tion process will vary, depending on the leader’s

preferences. Part of the complexity of launching and

conducting an investigation of this type is the ne-

cessity to organize and take action in multiple di-

rections simultaneously. Delay in taking action

could result in loss of important data.

be quantified. Categorization of cases as possible,

probable, or confirmed using type and number of

symptoms, culture results, and other pertinent infor-

mation will sometimes be useful in further refining

the case definition. Case definitions for known diag-

noses have been published by the CDC, 13 and the use

of standard definitions allows for better comparisons

between outbreaks. The case definition criteria must

be applied consistently to all persons studied. A broad

case definition may be refined later but a very nar-

row initial definition may miss cases. Consider the

clinical spectrum of apparent illnesses being seen and

whether this is a disease or condition in which a large

number of asymptomatic cases are likely. Arriving at

a clear case definition may sometimes be extremely

problematic, as is best exemplified by the attempts to

establish a case definition of “Gulf War syndrome.” 14

An accurate and sensitive case definition is essential

to reduce misclassification and confounding when

investigating potential exposure risk factors. 15 Epide-

miologic investigation of outbreaks usually begins

with identification of a distinct disease syndrome and

proceeds to evaluation of risk factors using epidemio-

logic methods. This is successful even with newly rec-

ognized diseases such as toxic shock syndrome. 16

Studies of Persian Gulf War veterans have been com-

plicated because neither a distinct clinical picture nor

distinct exposure risks are clear. 17

Ascertain Cases

Case finding efforts begin using the case defini-

tion or definitions established. Investigators must

start and maintain a line listing or log of all presumed

cases. This log should include name, social security

number, unit, sex, age, and other relevant informa-

tion (eg, pending culture results). It is important to

include a phone number or contact location for each

presumed case on the list. Other possible sources

of information for finding cases with the condition

of interest should be considered. These sources

might include medical records, emergency room

logs, specific clinic logs, or laboratory records. A

check on relevant quality control or quality assur-

ance procedures in the laboratory, clinic, or other

facilities should be done to rule out artifactual in-

creases in numbers. On military installations, the

surrounding civilian community should be checked

for additional cases through queries to local physi-

cians, clinics, or public health departments. Because

of the mobility of the military population, cases may

have been exposed in one location and have trav-

eled elsewhere, even across continents, during the

Establish a Case Definition

After gathering the initial impressions, the inves-

tigators must develop a workable case definition

and begin case finding efforts. Simple, objective

criteria are best. The type, magnitude, and fre-

quency of symptoms, as well as their duration, must

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Outbreak Investigation

incubation period. Cases of coccidioidomycosis, in

a classic example, occurred as the result of expo-

sure on military bases in endemic areas in Califor-

nia but did not present until personnel traveled else-

where. 18 In situations such as these, distant locations

may need to be contacted. The need for a thorough

travel history and an elevated level of diagnostic

suspicion is key to case recognition. The case find-

ing efforts may need to be broadened to the Offices

of the Surgeons General in the Department of De-

fense and to the CDC. Patients may even self refer

once news of the outbreak and the investigation

becomes known. The media can assist health au-

thorities in informing the public and in directing

the referral of possible cases for evaluation through

its public service announcements. In military set-

tings, cases may sometimes be found by using ques-

tionnaires to screen units. Follow-up interviews and

evaluations may be required to determine actual

case status. For communicable diseases, finding the

contacts of known cases may identify additional cases

and provide other relevant information. Unrecognized

cases, those with mild illness or who are asymptom-

atic, may provide additional clues or supporting data

concerning the presumed disease or hypothesized

etiology.

VERIFY THE EXISTENCE OF AN EPIDEMIC

After describing, defining, and finding cases, then

the question is whether the number of cases found

constitutes an epidemic. Last defines an epidemic as

the “occurrence in a community or region of cases of

an illness… [or] health-related behavior or…event

clearly in excess of normal expectancy. 19p54 A single

case of an extremely rare or exotic disease, such as

botulism poisoning, pulmonary anthrax, or Ebola in-

fection, also constitutes an epidemic (and may indi-

cate a biological terrorist event). To determine the

usual level of disease occurrence, investigators must

examine available historical data, such as medical

records, clinic logs, and laboratory logs. Personally

visiting sites such as the records department or the

laboratory may lead to other useful data sources (eg,

culture logs by body site of specimen source). Site vis-

its will also provide a better understanding of the type

and quality of the data available. To conclude that the

current level of disease is excessive, investigators must

first define the event and then compare the current

rate with that of the past. Comparing the routine

surveillance rates for skin disorder consultations for

British troops in Bosnia disproved media reports of a

serious outbreak. 20 The significance of possible

differences can be depicted graphically and assessed

statistically by testing differences of proportions or

calculating confidence intervals.

The limitations of the data or the data source af-

fect the interpretation of the data. The ideal or pre-

ferred morbidity measures for disease ascertain-

ment should also be identified. The profound

changes in the practice of medicine precipitated by

the managed care movement make comparisons

with historical rates problematic. Changes in access

to care, referral patterns, test-ordering practices,

hospitalization decisions, utilization management

mandates, and other health management proce-

dures can all affect the apparent incidence of dis-

ease. 21 These changes in practice patterns decrease

the utility of historical data, such as hospitalization

rates, for assessing secular trends and identifying

outbreaks. Investigators must judiciously determine

if the epidemic is real or artifactual after assessing

the situation, data sources, and practice patterns.

Pseudoepidemics can also occur because of false-

positive results of laboratory tests or from changes

in personnel or administrative processes affecting

the sensitivity of diagnosis. In the 1980s, an appar-

ent outbreak of skin cancer occurred at Letterman

Army Medical Center, as determined by inpatient

admission statistics. However, it was an adminis-

trative policy change directing that all patients with

skin cancer be admitted for biopsy and excision that

led to this artifactual epidemic (Kadlec RK. Walter

Reed Army Institute of Research, 1989. Unpublished

data). Specimen contamination in the microbiology

laboratory has also been implicated in a number of

“clusters” of multidrug-resistant tuberculosis.

Newer techniques of molecular biology, such as

pulsed-field gel electrophoresis (PFGE), may be

used to detect these pseudo-outbreaks and document

their extent and resolution. 22,23 The risk also exists

of cross contamination in the molecular laboratory

from contamination of polymerase chain reaction

assays. The most serious dangers are contamination

of specimens with postamplification products from

previous analyses or contamination of negative spec-

imens with controls or positive specimens. 24 Empha-

sis on new and expanded surveillance programs for

emerging infectious diseases has already been dem-

onstrated to increase the potential for identifying

pseudo-outbreaks, as occurred with cyclosporiasis

in Florida and cryptosporidiosis in New York. 25 It

is advisable to get confirmation by an appropriate

reference laboratory early in any investigation of

apparent clusters of emerging pathogens (see chap-

ter 34, Laboratory Support for Infectious Disease

Investigations in the Field).

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