consider a hypothetical STI (sexually transmitted infection) clinic in which the rapid plasma reagin (RPR) test, a screening test for syphilis, is being evaluated in 1,000 patients with genital ulcer disease who are suspected of having primary syphilis:
| PRIMARY SYPHILIS | ||||
| PRESENT | ABSENT | |||
| RPR TEST RESULT | POSITIVE | 420 | 60 | Positive predictive value = 420/(420 + 60) = 0.88Positive predictive value = 88% |
| NEGATIVE | 220 | 300 | Negative predictive value = 300/(300 + 220) = 0.58Negative predictive value = 58% | |
| Sensitivity = 420/(420 + 240) = 0.66Sensitivity = 66% | Specificity = 300/(300 + 60) = 0.83Specificity = 83% | |||
On the basis of these data, the sensitivity of this test (the true-positive rate, calculated as true-positive results divided by the number of patients with disease) in primary syphilis is 66%. The specificity (1 minus the false-positive rate) is 83%. Note that in this high-prevalence population (the prevalence here is the total number of cases in which primary syphilis is present—640 divided by the total number of individuals, 1,000—and is thus 0.64 or 64%), the predictive value of a positive test is fairly good, at 88%. The positive predictive value of an assay varies with the prevalence of the disease in the population. This is a key point. An example of this in our syphilis serology example in a low-prevalence population will serve to illustrate the point.
The same RPR serologic assay is being used in a hypothetical population of octogenarian nuns, none of whom are or have been sexually active in at least 6 decades.
| SYPHILIS | ||||
| PRESENT | ABSENT | |||
| RPR TEST RESULT | POSITIVE | 1 | 169 | Positive predictive value = 1/170 = 0.006Positive predictive value = 0.6% |
| NEGATIVE | 0 | 830 | Negative predictive value = 830/830 = 1.00Negative predictive value = 100% | |
| Specificity = 830/999 = 0.83Specificity = 83% | ||||
In this patient population, there is only one true case of syphilis, presumably acquired many years previously. The specificity of the test in this patient population is the same as it is in the individuals attending the STI clinic (in reality, it is likely to be different in different populations and also in different stages of syphilis). Because there is one case of syphilis, and 169 of the positive RPR results are false-positive test results, the positive predictive value in this patient population is only 0.6%. Clearly, this is a patient population in which the decision to test for syphilis using the RPR assay is not cost-effective.
In making a decision to order a specific test, the physician should know what he or she will do with the test results—essentially, how the results will alter the care of the patient. In a patient who the physician is certain does not have a specific disease, if the test for that disease has an appreciable rate of false-positive results, a positive test result is likely to be false positive and should not alter clinical care. Conversely, if the physician is certain that a patient has a disease, there is no good reason to order a test with a low sensitivity, as a negative result will likely be false negative. Tests are best used when there is uncertainty and when the results will alter the posttest probability and, therefore, the management of the patient.
SPECIMEN SELECTION, COLLECTION, AND TRANSPORT
Each laboratory test has three stages.
1 1. The preanalytical stage: The caregiver selects the test to be done, determines the type of specimen to be collected for analysis, ensures that it is properly labeled with the patient’s name, and facilitates rapid and proper transport of this specimen to the laboratory.
2 2. The analytical stage: The specimen is analyzed by the laboratory for the presence of specific microbial pathogens. The remaining sections of this chapter describe various analytic approaches to the detection of pathogens.
3 3. The postanalytical stage: The caregiver uses the laboratory results to determine what therapies, if any, to use in the care of the patient.
The preanalytical stage is the most important stage in laboratory testing! If the wrong test is ordered, if the wrong specimen is collected, if the specimen is labeled with the wrong patient’s name, or if the correct specimen is collected but is improperly transported, the microbe causing the patient’s illness may not be detected in the analytical stage. As a result, at the postanalytical stage, the caregiver may not have the appropriate information to make the correct therapeutic decision. The maxim frequently used in laboratory medicine is “garbage in, garbage out.”
Specimen selection is important. A patient with a fever, chills, and malaise may have an infection in any one of several organ systems. If a patient has a urinary tract infection and if urine is not selected for culture, the etiology and source of the infection will be missed. Careful history taking and physical examination play an important role in selecting the correct specimen.
Continuing with the example of a patient with a fever due to a urinary tract infection, the next phase in the diagnosis of infection is the collection of a urine specimen. Because the urethra has resident microbiota, urine specimens typically are not sterile. A properly collected urine specimen is one in which the external genitalia are cleansed and midstream urine is collected. Collection of midstream urine is important because the initial portion of the stream washes out much of the urethral microbiota. Even with careful attention to detail, clean-catch urine can be contaminated with urethral microbiota, rendering the specimen uninterpretable at the postanalytical stage.
An important concept when considering
