to isolate a microorganism by culture, visualize it microscopically, or detect it by antigenic or molecular detection techniques. In those situations, an alternative approach is to determine if the patient has mounted an immune response against a specific agent as evidence that he or she has been infected with that agent. The immune response is generally measured by detecting antibodies in the serum of patients—thus the name serology.
Serology has both advantages and disadvantages. As advantages, (i) specimens for testing are readily available; (ii) antibodies are relatively stable molecules, so transport is not a major concern as it is with culture; and (iii) tests have been designed that can detect most known agents, such as HIV and HCV, which are difficult to detect by other means. Depending on the target antigen against which the immune response is measured, the test can show both high sensitivity and high specificity. Compared with other techniques, these tests are relatively inexpensive and easy to perform, in part because they have been automated. As a result, they can be used to screen large numbers of specimens for selected infectious agents. For example, this approach is used to screen blood products used for transfusions to ensure that the transfused patient does not receive blood contaminated with hepatitis B and C viruses, HIV, or T. pallidum, the agent of syphilis.
Serologic tests also have several disadvantages and should be interpreted with some caution. To have a positive test, the patient must have mounted an immune response. Serum obtained from an acutely ill patient may have been taken during the window period in an infection before the patient had time to mount an immune response. Therefore, to get the most accurate result, acute and convalescent specimens should be obtained. The convalescent specimen should show a significant increase (or, in some cases, decrease) from the antibody level of an acute specimen. This is usually a 4-fold change in the titer. Because the convalescent specimen should be obtained a minimum of 2 weeks after the acute specimen, serologic diagnosis is often retrospective. Because obtaining a convalescent specimen is often difficult logistically, the only value that may be available is that from the acute specimen. Patients may have relatively high antibody levels because of previous infection with the test organism and, as a result, may have a false-positive result. Antigenic cross-reactions between the test organism and other antigens may also lead to false-positive results. Some immunocompromised patients are unable to mount a response and may never have a positive serologic test.
Serologic tests can be done in combination using a screening test followed by a confirmatory test. This approach is used most commonly in the diagnosis of syphilis, HIV infection, and Lyme disease. The screening test should be highly sensitive so that all true-positive results will be detected. This test may not be highly specific, meaning that some results may be false positives. It should also be easily performed, so that large numbers of specimens can be tested fairly inexpensively. The confirmatory test needs to be highly specific so that the correct diagnosis can be applied to the patient who screens positive for the infectious agent. It tends to be much more expensive and technically complex than the screening test. Western blotting or an equivalent technique is used in the confirmatory tests for Lyme disease, HIV infection, and HCV infection. In this technique, a patient is considered to be positive for the agent only if the patient has antibodies to multiple specific antigens.
REFERENCES
1. Alby K, Gilligan PH. 2013. Identification of pathogens by classical clinical tests, p 1–45. In Rosenberg E, DeLong EF, Lory S, Stackebrandt E, Thompson T (ed), The Prokaryotes, 4th ed, vol 5, Human Microbiology. Springer-Verlag, Berlin, Germany.
2. Boone DJ. 2007. How can we make laboratory testing safer? Clin Chem Lab Med 45:708–711.
3. Miller MB, Gilligan PH. 2012. Mechanisms and detection of antibiotic resistance, p 1421–1433. In Long SS, Pickering LK, Prober CG (ed), Principles and Practice of Pediatric Infectious Diseases, 4th ed. Churchill-Livingstone, New York, NY.
4. Plebani M. 2006. Errors in clinical laboratories or errors in laboratory medicine? Clin Chem Lab Med 44:750–759.
SECTION ONE
UROGENITAL TRACT INFECTIONS
INTRODUCTION TO SECTION I
We begin this text with a discussion of infections of the genitourinary tract for two reasons. First, the number of microorganisms that frequently cause infection in these organs is somewhat limited. Second, urinary tract infections (UTIs) and sexually transmitted infections (STIs) are two of the most common reasons why young adults, particularly women, consult a physician. UTIs are examples of endogenous infections, i.e., infections that arise from the patient’s own microbiota. In the case of UTIs, the microbes generally originate in the gastrointestinal tract and colonize the periurethral region before ascending the urethra to the bladder. STIs are exogenous infections; i.e., the infectious agent is acquired from a source outside the body. In the case of STIs, these agents are acquired by sexual contact.
UTIs are much more common in women than in men for a number of reasons. The urethra is shorter in women than in men, and straight rather than curved as in men, making it easier for microbes to ascend to the bladder. Prostatic secretions have antibacterial properties, which further protects the male. The periurethral epithelium in women, especially women with recurrent UTIs, is more frequently colonized with microorganisms that cause UTIs. It should also be noted that the incidence of UTIs is higher in sexually active women, as coitus can introduce organisms colonizing the periurethral region into the urethra. The incidence of nosocomial UTIs, however, is similar in women and men. In these infections, catheterization is the major predisposing factor.
The incidence of STIs is similar in both heterosexual men and women; however, the morbidity associated with these infections tends to be much greater in women. In particular, irreversible damage to reproductive organs, caused by both Chlamydia trachomatis and Neisseria gonorrhoeae, is all too common. Infections with these two organisms are almost always symptomatic in males, though the few men who do not have symptoms can be responsible for infecting many partners. By contrast, a significant number of women may be infected asymptomatically at first. They may manifest signs and symptoms of infection only when they develop pelvic inflammatory disease, which can result in sterility. Fetal loss or severe perinatal infection may be caused by two other STI agents, herpes simplex virus and Treponema pallidum, the etiologic agent of syphilis.
Important agents of genitourinary tract infections are listed in Table 1. Only organisms in this table should be considered in your differential diagnosis for the cases in this section. You should note that not all organisms that can be spread sexually, such as hepatitis B virus and Entamoeba histolytica, are listed. This is because these infections do not have genitourinary tract manifestations.
TABLE I SELECTED GENITOURINARY TRACT PATHOGENS
| ORGANISM | GENERAL CHARACTERISTICS | SOURCE OF INFECTION | DISEASE MANIFESTATION |
| Bacteria | |||
|
|
