Astrovirus Encephalitis | CDC EID

EID Journal Home > Volume 16, Number 6–June 2010

Volume 16, Number 6–June 2010
Research
Astrovirus Encephalitis in Boy with X-linked Agammaglobulinemia
Phenix-Lan Quan, Thor A. Wagner, Thomas Briese, Troy R. Torgerson, Mady Hornig, Alla Tashmukhamedova, Cadhla Firth, Gustavo Palacios, Ada Baisre-De-Leon, Christopher D. Paddock, Stephen K. Hutchison, Michael Egholm, Sherif R. Zaki, James E. Goldman, Hans D. Ochs, and W. Ian Lipkin
Author affiliations: Columbia University, New York, New York, USA (P.-L. Quan, T. Briese, M. Hornig, A. Tashmukhamedova, G. Palacios, A. Baisre-De-Leon, J.E. Goldman, W.I. Lipkin); University of Washington, Seattle, Washington, USA (T.A. Wagner, T.R. Torgerson, H.D. Ochs); Seattle Children's Hospital, Seattle (T.A. Wagner, T.R. Torgerson, H.D. Ochs); Pennsylvania State University, Pittsburgh, Pennsylvania, USA (C. Firth); Centers for Disease Control and Prevention, Atlanta, Georgia, USA (C.D. Paddock, S.R. Zaki); and 454 Life Sciences, Branford, Connecticut, USA (S.K. Hutchison, M. Egholm)

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Abstract
Encephalitis is a major cause of death worldwide. Although >100 pathogens have been identified as causative agents, the pathogen is not determined for up to 75% of cases. This diagnostic failure impedes effective treatment and underscores the need for better tools and new approaches for detecting novel pathogens or determining new manifestations of known pathogens. Although astroviruses are commonly associated with gastroenteritis, they have not been associated with central nervous system disease. Using unbiased pyrosequencing, we detected an astrovirus as the causative agent for encephalitis in a 15-year-old boy with agammaglobulinemia; several laboratories had failed to identify the agent. Our findings expand the spectrum of causative agents associated with encephalitis and highlight unbiased molecular technology as a valuable tool for differential diagnosis of unexplained disease.
The economic cost of encephalitis is profound. Among the general population of western industrialized countries, the annual incidence of acute encephalitis is 7.3 cases per 100,000 persons (1). Although some persons recover from encephalitis without apparent sequelae, up to 71.0% experience lasting sequelae and up to 7.4% die (1,2). Khetsuriani et al. reported that each year in the United States alone, encephalitis is associated with ≈19,000 hospitalizations (average hospital stay 12 days), 1,400 deaths, and a cost of ≈$650 million for encephalitis-associated hospitalization (1).

Encephalitis is associated with a wide spectrum of infectious agents, including viruses, bacteria, fungi, and parasites (3). The most commonly implicated viruses are herpes simplex, varicella-zoster, Epstein-Barr, mumps, measles, and enteroviruses (4). Despite the use of various diagnostic methods (culture, molecular, immunohistochemical, or serologic), a causative agent is not identified for a high proportion of encephalitis cases (up to 75%) (5). This diagnostic failure may reflect the absence of a known agent or its molecular footprint at time of sampling, suboptimal specimen handling, lack of assay sensitivity, or presence of an unexpected or novel agent not considered in conventional assays. A better understanding of emerging and reemerging pathogens implicated in outbreaks of encephalitis (e.g., West Nile virus, Hendra virus, Nipah virus, Australian bat lyssavirus, and enterovirus 71) indicates an urgent need for novel tools for rapid differential diagnostic testing and surveillance (6,7).

The advent of unbiased molecular discovery technologies offers new opportunities to identify novel pathogens without the constraints imposed by assays selective for known or expected agents. We used unbiased high-throughput pyrosequencing to detect an astrovirus in a patient who died with unexplained encephalitis.

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Astrovirus Encephalitis | CDC EID