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INTRODUCTION

The diagnosis of a microbial infection begins with an assessment of the clinical and epidemiologic features and formulation of a diagnostic hypothesis. Anatomic localization of the infection depends on physical and radiologic findings (eg, right lower lobe pneumonia, subphrenic abscess). This clinical diagnosis suggests a number of possible etiologic agents based on knowledge of infectious syndromes and their courses. The specific cause or etiologic diagnosis is then established by the application of methods described in this chapter. A combination of science and art on the part of both the clinician and laboratory worker is required: The clinician must select the appropriate tests and specimens to be processed and, where appropriate, suggest the suspected etiologic agents to the laboratory. The laboratory scientist must use the methods that will demonstrate the probable agents and be prepared to explore other possibilities suggested by the clinical situation or by the findings of the laboratory examinations. The best results are obtained when communication between the clinician and laboratory is optimal.

❋ Clinical diagnosis guides approach to etiologic diagnosis

Behind every clinical specimen submitted to the diagnostic laboratory should be a question. Does my patient have, can I exclude, does the result confirm the disease? Answers to such questions depend on understanding, whether articulated specifically or not, the characteristics of the tests ordered and performed. These characteristics are sensitivity (the test’s ability to rule out [snout] a disease because there are few false-negative results and thus fewer cases missed) and specificity (the test’s ability to rule in [spin] or confirm an etiology because there are few false-positive results). Ideally, a test would have both excellent sensitivity and specificity, but traditional methods often involved a trade-off between the two, which only emphasizes the need to know the clinical question or reason for ordering a test. Molecular methods, however, tend to have improved sensitivity as well as specificity, which is dramatically so for viral etiologic diagnoses.

❋ Sensitivity is capacity of test to rule OUT a diagnosis

❋ Specificity is ability of test to rule IN or confirm diagnosis

Predictive value of a test is determined by its sensitivity and specificity and the prevalence of disease in a population or the likelihood thereof in a patient based on the history, clinical findings, and epidemiology of the infectious disease agent being considered. The more sensitive a test, the greater its negative predictive value (NPV), thus a patient with a negative test is very unlikely to have the disease. A positive result with a more specific test makes a diagnosis more likely or has a higher positive predictive value (PPV) and basically confirms an etiologic diagnosis. When the prevalence of a disease is exceedingly low or the likelihood is virtually nil based on the history, clinical findings, and epidemiology, even tests with high sensitivity and specificity may have a low PPV. This reality highlights the ...

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