Tuesday, August 9, 2011

From Jim Musser and colleagues: Rapidly Progressive, Fatal, Inhalation Anthraxlike Infection in a Human

http://www.archivesofpathology.org/doi/pdf/10.1043/2011-0362-SAIR.1

Rapidly Progressive, Fatal, Inhalation Anthraxlike Infection in a Human Case Report, Pathogen Genome Sequencing, Pathology, and Coordinated Response
Angela M. Wright, MD; Stephen B. Beres, PhD; Erin N. Consamus, MD; S. Wesley Long, MD, PhD; Anthony R. Flores, MD, PhD; Roberto Barrios, MD; G. Stefan Richter, PhD; So-Young Oh, PhD; Gabriella Garufi, PhD; Hannah Maier, BS; Ashley L. Drews, MD; Kathryn E. Stockbauer, PhD; Patricia Cernoch, MT; Olaf Schneewind, MD, PhD; Randall J. Olsen, MD, PhD; James M. Musser, MD, PhD

Context.—Ten years ago, a bioterrorism event involving Bacillus anthracis spores captured the nation’s interest, stimulated extensive new research on this pathogen, and heightened concern about illegitimate release of infectious agents. Sporadic reports have described rare, fulminant, and sometimes fatal cases of pneumonia in humans and nonhuman primates caused by strains of Bacillus cereus, a species closely related to Bacillus anthracis.

Objectives.—To describe and investigate a case of rapidly progressive, fatal, anthraxlike pneumonia and the overwhelming infection caused by a Bacillus species of uncertain provenance in a patient residing in rural Texas.

Design.—We characterized the genome of the causative strain within days of its recovery from antemortem cultures using next-generation sequencing and performed immunohistochemistry on tissues obtained at autopsy with antibodies directed against virulence proteins of B anthracis and B cereus

Results.—We discovered that the infection was caused by a previously unknown strain of B cereus that was closely related to, but genetically distinct from, B anthracis. The strain contains a plasmid similar to pXO1, a genetic element encoding anthrax toxin and other known virulence
factors. Immunohistochemistry demonstrated that several homologs of B anthracis virulence proteins were made in infected tissues, likely contributing to the patient’s death.
Conclusions.—Rapid genome sequence analysis permitted us to genetically define this strain, rule out the likelihood of bioterrorism, and contribute effectively to the institutional response to this event. Our experience strongly reinforced the critical value of deploying a wellintegrated, anatomic, clinical, and genomic strategy to respond rapidly to a potential emerging, infectious threat to public health.

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