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FIGURE 3.1 The relationship between case detection and outbreak detection. After the severe acute respiratory syndrome (SARS) 2003 outbreak, the Beijing center for disease prevention developed a biosurveillance system that comprised 61 "fever clinics'' to which city residents were instructed to report if they developed fever (or were referred by emergency departments and physicians). Clinic staff entered the data from each clinic daily into a Web-based interface for central analysis. (Figure courtesy of Fu-Chiang Tsui.)

FIGURE 3.2 Rules for classifying a patient as probable or confirmed severe acute respiratory syndrome (SARS). For expositional clarity, we split the Centers for Disease Control and Prevention (CDC) SARS case definition into two figures. Figure 3.3 contains definitions of the clinical, epidemiological, and laboratory criteria. The complete CDC SARS case definition is in Appendix C, which includes four additional rules for classifying patients as SARS Reports under Investigation. SARS-CoV refers to the coronavirus that causes the disease SARS. (From http://www.cdc.gov/ncidod/sars/guidance/b/app1.htm.)

SARS-CoV disease classification

Probable case of SARS-CoV disease; in a person who meets the clinical criteria for severe respiratory illness and the epidemiologic criteria for likely exposure to SARS-CoV

Confirmed case of SARS-CoV disease: in a person who has a clinically compatible illness (i.e. early, mild-to-moderate, or severe) that ts laboratory confirmed

Some limitations are that not every sick individual sees a clinician, clinicians may not correctly diagnose every individual they see, and clinicians may forget to report cases or fail to report cases in the time frame required by law (Ewert et al., 1994,1995). Even when a clinician reports a case, the reporting occurs relatively late in the disease process. With some exceptions (e.g., suspected meningococcal meningitis, suspected measles, suspected anthrax) clinicians report cases only after they are certain about the diagnosis.

2.2. Case Detection by Laboratories

Case detection by laboratories is also a by-product of routine laboratory operation. Laboratories perform diagnostic tests. From the results of these tests, they often become aware of cases of notifiable diseases either before or at the same time as the clinician that ordered the test.

Laboratories play an increasing role in the detection of cases (including hepatitis A, cases of foodborne illness and influenza) as rapid, reliable, and specific laboratory tests are increasingly available. (Laboratories did not play a central role in the detection of outbreaks described in Chapter 2 because most of these outbreaks were caused by novel agents with no existing laboratory test.) The strength of laboratories as case detectors is that they are process oriented; therefore, they may report cases more reliably than can busy clinicians. A weakness is that there is not a definitive diagnostic test for every disease. A laboratory cannot detect a case unless a sick individual sees a clinician, who must suspect the disease and order a definitive test. Furthermore, not every individual for whom a test is ordered will comply and have the test done, and for some individuals with an illness, the test can be negative. Lag times for the completion of laboratory work can be substantial.

We further discuss the case detection role (and other roles) of laboratories in biosurveillance in Chapter 8.

2.3. Case Definitions

We next discuss several approaches to case detection that use case definitions. A case definition is a Boolean (logical) combination of patient findings, such as the patient must have fever AND either cough OR pneumonia. A case definition contains findings that are both necessary and sufficient for an investigator

(or a clinician or research epidemiologist) to conclude that a patient has a disease.

Readers with backgrounds in public health should be quite familiar with case definitions.

Figure 3.2, for example, is the Centers for Disease Control and Prevention (CDC) case definition for both confirmed and probable cases of severe acute respiratory syndrome (SARS). Figure 3.3 contains definitions of the clinical, epidemiological, and laboratory criteria used in the case definitions. You can find additional examples of case definitions at Web sites operated by World Health Organization (WHO), CDC, and state and local departments of health (WHO, 2003; CDC, 2005).

2.4. Case Detection by Sentinel Clinicians

Health departments worldwide organize networks of sentinel clinicians to assist in monitoring influenza (Snacken et al., 1995,1998; Fleming and Cohen, 1996; Zambon, 1998; Aymard et al.,1999;Manuguerra and Mosnier,2000;Schoub et al.,2002). A sentinel clinician reports the number of individuals she sees per week who match a case definition for influenza-like illness (ILI). The California Department of Health Services provides school nurses with the following case definition for ILI: fever (greater than 100.0°F) AND cough and/or sore throat. The Global Influenza Surveillance Program of the Department of Defense uses a slightly different case definition: fever (greater than 100.5°F) and either cough or sore throat or clinical radiographic evidence of acute nonbacterial pneumonia. In some jurisdictions, the health department supplies the sentinel clinicians with rapid diagnostic tests for influenza, the results of which the clinicians also report.

The motivation for the sentinel clinician ILI system is earlier and more complete case finding of influenza to enable health departments to better control this common yet dangerous epidemic disease. Sentinel systems are not limited to influenza.The International Society of Travel Medicine and the CDC track diseases in patients who present to travel clinics (GeoSentinel, 2005).

2.5. Case Detection by Drop-In Surveillance

In the 1990s, the threat of bioterrorism led to the development of sentinel clinician-like capability for other diseases.This need

FIGURE 3.3 Definitions of criteria used in severe acute respiratory syndrome (SARS) classification rules in Figure 3.2. (From http://www.cdc.gov/ ncidod/sars/guidance/b/app1.htm.)

A. Clinical Criteria

Early illness: Presence of two or more of the following features: fever (might be subjective), chills, rigors, myalgia, headache, diarrhea, sore throat, rhiuorrhea Mild-to-moderate respiratory illness

One or more clinical findings of lower respiratory illness (e g., cough, shortness of breath, difficulty breathing) Severe respiratory illness

Meets clinical criteria of mild-to-moderate respiratory illness, and One or more of the following findings: Radiographic evidence of pneumonia, or Acute respiratory distress syndrome, or

Autopsy findings consistent with pneumonia or acute respirator,' distress syndrome without an identifiable cause 11. Epidemiologic Criteria

Possible exposure to SARS-assoclated coronavirus (SARS-CoV)

One or more of the following exposures in the 10 days before onset of symptoms:

Travel to a foreign or domestic location with documented or suspected recent transmission of SARS-CoV or Close contact with a person with mi Id-to-moderate or severe respiratory illness and with history of travel in the 10 days before onset of symptoms to a foreign or domestic location with documented or suspected recent transmission of SARS-CoV

Likely exposure to SARS-CoV

One or more of the following exposures in the 10 days before onset of symptoms: Close contact with a confirmed case of SARS-CoV disease or

Close contact with a person with mild-moderate or severe respiratory illness for whom a chain of transmission can be linked to a confirmed case of SARS-CoV disease in the 10 days before onset of symptoms f. I j a ho rat «l'y Criteria

Tests to detect SARS-CoV are being refined, and their performance characteristics assessed; therefore, criteria for laboratory diagnosis of SARS-CoV are changing. The following are the general criteria for laboratory confirmation of SARS-CoV:

Detection of serum antibody to SARS-CoV by a test validated by CDC (e.g., enzyme immunoassay [EIA]), or Isolation in cell culture of SARS-CoV from a clinical specimen, or

Detection of SARS-CoV RNA by a re verse-transcription-polymerase chain reaction (RT-PCR) test validated by CDC and with subsequent confirmation in a reference laboratory (e.g., CDC)

Information regarding the current criteria for laboratory diagnosis of SARS-CoV is available at www-cdc.qov/ncidQd/sais/labdtaqnosis-hcm-

was most acute in cities that were hosting prominent events, such as the Olympic Games.

Drop-in surveillance refers to the practice of asking physicians in emergency departments to complete a form for each patient seen during the two- to six-week period surrounding a special event (County of Los Angeles, 2000; Arizona Department of Health Services, 2002; CDC, 2002b; Das et al., 2003; Moran and Talan, 2003). The clinicians record whether the patient meets the case definition for one or more syndromes of interest (Figure 3.4). Hospital staff, an epidemiologist, or an assistant then transcribes the data from the form into a database.

Sydney, Salt Lake City, and Athens used a surveillance variant during their Olympic Games that eliminated the need for physicians to fill out a form for each patient (Meehan et al., 1998; Dafni et al., 2004; Mundorff et al., 2004). Health department personnel visited each emergency department on a daily or more frequent basis and reviewed patient logs (and in some cases charts) to extract the required information.

The strength of drop-in surveillance (and sentinel clinician surveillance) is that it detects sick individuals on the day they first present for medical care; however, it is labor intensive.

Drop-in surveillance is a method of both case detection and outbreak detection. The drop-in surveillance team for the special event analyzes information from many emergency departments in the city on a daily basis for increased numbers of patients suggestive of an outbreak. Drop-in surveillance is initiated at least a week in advance of an event, if possible, so that a baseline rate of patients presenting with respiratory or diarrheal illness can be established.

2.6. Case Detection by Screening

Screening involves interviewing and testing people during a known outbreak to identify additional cases (or carriers of the disease). Screening is most often used for contagious diseases, for which it is important to find infected individuals to prevent further infections. A biosurveillance organization may use

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