With most diseases, a spectrum of responses may be seen in infected humans, such that a person may develop antibody from a subclinical infection or after colonization by an agent without actually having symptoms of the disease. In these cases, the presence of antibody in a single serum specimen or a similar titer of antibody in paired sera may merely indicate past contact with the agent and cannot be used to accurately diagnose recent disease. Therefore, in the vast majority of serologic procedures for diagnosis of recent infection, testing of both acute and convalescent sera is the method of choice. Except for detecting the presence of IgM, testing of a single serum may be recommended in certain cases. Mycoplasma pneumoniae and viral influenza B infections are examples in which high titers may indicate recent infection. IgM levels may be diagnostic if the infecting or disease-causing agent is extremely rare, such as rabies or exposure to botulism toxin, and people without disease or prior immunization would have no chance of developing an immune response.
The prevalence of antibody to an etiologic agent of disease in the population correlates with the number of people who have come into contact with the agent, not the number who actually develop disease. For most dis eases, only a small proportion of infected individuals actually develop symptoms; others develop protective antibodies without experiencing signs and symptoms of the disease. In a number of circumstances, serum is tested to determine whether a patient is immune; that is, whether the patient has antibody to a particular agent either in response to a past infection or to immunization. These tests can be performed with a single serum sample. The results of the tests must be correlated with the actual immune status of individual patients to determine the level of detectable antibody present, in order to deter mine whether the individual has developed a true immunity to infection or a secondary reinfection. For example, sensitive tests can detect the presence of very tiny amounts of antibody to the rubella virus. Certain people, however, may still be susceptible to infection with the rubella virus with such small amounts of circulating antibody, and a higher level of antibody may be required to ensure protection from disease.
Alternatively, depending on the etiologic agent, even low levels of antibody may protect a patient from pathologic effects of disease and not prevent a second reinfection. For example, a person previously immunized with killed poliovirus vaccine who becomes infected with pathogenic poliovirus experiences multiplication of the virus in the gut and virus entry into the circulation. Damage to the central nervous system is blocked by humoral antibody in the circulation. As more sensitive testing methods are developed and these types of problems become more common, microbiologists must work closely with clinicians to develop guidelines for interpreting serologic test results in relation to the immune status of individual patients. Moreover, patients may respond to an antigenic stimulus by producing cross-reacting anti bodies. These antibodies are nonspecific and may cause misinterpretation of serologic tests.
Table 1 provides a brief list of representative serologic tests available for immunodiagnosis of infectious diseases, the specimen required, interpretation of positive and negative test results, and examples of applications of each technique. Because serologic assays are rapidly evolving, this table is not intended to be all-inclusive.
Table1. Noninclusive Overview of Tests Available for Serodiagnosis of Infectious Diseases
