amenable microorganisms is currently suboptimal. When traditional diagnostic methods are rigorously applied to syndromes of suspected infectious etiology, such as pneumonia, encephalitis, lymphocyte-predominant meningitis, pericarditis, acute diarrhea, and sepsis, only a minority of cases can be explained microbiologically. In addition, a long list of chronic inflammatory diseases with features of infection remain poorly understood and inadequately explained from a microbiological perspective.
Newer technologies can succeed where methods for pathogen identification through serology or cultivation have failed in the past because of the absence of specific reagents or fastidious requirements for agent replication. The newly available technologies include methods based on the analysis of microbial nucleic acid sequences (e.g., DNA microarrays, PCR), analysis of microbial protein sequences (e.g., mass spectrophotometry), immunological systems for microbe detection (e.g., expression libraries), and host response profiling. Over the past decade, the use of molecular pathogen discovery methods has resulted in the identification of several novel agents, including Borna disease virus, hepatitis C virus, Sin Nombre virus, HHV-6, HHV-8, Bartonella henselae, and Tropheryma whippelii. The advent of molecular pathology has heightened the power of diagnostic pathology. Despite these achievements, however, sensitive and specific rapid diagnostic tools that can be used to diagnose common diseases in the office, clinic, and emergency room simply are not being used or are unavailable.
For example, although many different microbe-specific PCR assays have been described, only a small proportion has actually entered into routine clinical practice. Examples include assays for N. gonorrheae, C. trachomatis, herpes simplex virus, and HIV. A modest number of recent studies have confirmed that the use of these molecular diagnostic tests can reduce patient-care costs and favorably impact patient management (Dumler and Valsamakis, 1999; Ramers et al., 2000). In particular, the development of rapid, real-time (semiquantitative) PCR with point-of-care microbial detection within 30 minutes (Belgrader et al., 1998, 1999b) could potentially alter the use of antibiotics on a widespread scale and reduce antibiotic resistance (Bergeron and Ouellette, 1998). Some of the factors that may have limited more widespread use of these theoretically appealing molecular approaches include difficulty in obtaining specimens and transporting them to the laboratory, a paucity of studies that address clinical validation, and the need for specialized expertise.
CDC and NIH should work with FDA, other government agencies (e.g., DOD, USDA, the national laboratories), and industry on the development, assessment, and validation of rapid, inexpensive and cost-effective, sensitive, and specific etiologic diagnostic tests for microbial threats of public health importance.