Actionable sequence data on infectious diseases in the clinical workplace.

Abstract

Among the wide variety of diagnostic and therapeutic challenges in the clinical workplace, infectious diseases pose unusually difficult problems. First, the diversity of disease-causing agents is prodigious, and infectious agents may disseminate to and invade almost any host anatomic compartment. Second, these agents, because of their short generation times and, in some cases, high mutation rates, evolve quickly, resulting in evasion of host defenses, inter- and intrahost diversification in real time, and acquired resistance to antimicrobial drugs. Third, some infectious diseases progress quickly, i.e., within hours or days, and offer only a fleeting, narrow window of opportunity for successful therapeutic intervention early in the course of disease. Thus, to be actionable, diagnostic tests must be broad in their range, specific, sensitive, and rapid. These needs have not been adequately met by current, routine approaches, such as cultivation, serology, and specific PCR assays. As a result, inappropriately broad or mistargeted antimicrobial agents are used, resulting in drug resistance and other adverse effects, and important diseases are untreated or treated too late. A recently published case report by Wilson et al. (1) highlights the potential impact of DNA sequencing technology on infectious disease diagnosis, and illustrates in a best-case scenario how this technology may address these needs. The report describes a 14-year-old boy with severe combined immunodeficiency, who had undergone bone marrow transplantation and was maintained on monthly intravenous infusions of immune globulin and antibiotic prophylaxis against Pneumocystis pneumonia. Approximately 1 month after a trip to Puerto Rico, he experienced 10 days of unexplained fever, headache, and conjunctivitis. Over the course of the following 12 months, he suffered from uveitis, thrombocytopenia, and 2 more acute episodes of fever, headache, and photophobia and developed a lymphocyte-predominant cerebrospinal fluid (CSF) pleocytosis, as well as biopsy-proven granulomatous leptomeningitis. All routine tests for infectious disease agents …