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J. R. Harris, S. R. Lockhart, T. Chiller, Letter re: Marr editorial, Clinical Infectious Diseases, Volume 54, Issue 7, 1 April 2012, Pages 1038–1039, https://doi.org/10.1093/cid/cir1019
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TO THE EDITOR—We appreciate the thoughtful review provided by Dr Marr [1] in response to our paper [2]. Marr raises several important issues, and we support her conclusion that we have uncovered the tip of the iceberg with respect to C. gattii infections in the United States. Future data may provide additional insight into seemingly counterintuitive findings, such as the association between central nervous system symptoms and patient survival. We also agree that there are likely as-yet-unrecognized areas of C. gattii endemicity outside the Pacific Northwest, which are associated with infections elsewhere.
We would, however, like to clarify points regarding our definition of the outbreak and outbreak strains. Outbreaks, as Marr correctly notes, are defined by a greater-than-expected number of cases of a disease within a given time period and geography. Case definitions differ for each outbreak, but genetic typing increasingly plays a role in that definition. A Salmonella outbreak today, for example, would not be defined as all Salmonella isolates identified in the United States during a specific time period, but rather all Salmonella typhimurium isolates with 1 or a few specific pulsed-field gel electrophoresis pattern(s) and epidemiologic links between case patients during that time period. In our article, we defined outbreak strains based not on exposure, as Marr states, but on genotyping results for C. gattii isolates. Three clonal groups of isolates (VGIIa, VGIIb, and VGIIc) represented 81% of all human isolates identified at the Centers for Disease Control and Infection (CDC) since 2004. That no VGIIa/b/c strain infections were found in persons without Pacific Northwest exposure is the factor that delineated these strains as belonging to a localized outbreak. Most non-VGIIa/b/c isolates were from patients outside the Pacific Northwest without a single common exposure history and were genetically dissimilar to each other. The small number of patients from the Pacific Northwest with non-VGIIa/b/c infections likely represents a low level of endemic, nonoutbreak-associated C. gattii disease, which was detected by enhanced surveillance.
