Biodefense

ElaineL
lettertotheeditor.pdf

Sverdlovsk Revisited: Pulmonary Pathology of Inhalational Anthrax Versus Anthraxlike Bacillus cereus Pneumonia

To the Editor.—The case report of rapidly progressive, fatal pneumonia caused by Bacillus cereus producing anthrax lethal toxin and edema toxin represents a landmark achievement in pathology.1 The investigators’ de- cisiveness and speed in applying a contemporary genome sequencing approach were remarkably effective in establishing a diagnosis and deter- mining the absence of a public health emergency. The designation of the case as anthraxlike led me to compare it with the 41 documented cases in the 1979 Sverdlovsk (now Yekaterin- burg), Russia, outbreak of inhalation- al anthrax associated with accidental release of Bacillus anthracis spores from a biologic weapons facility.2

Respiratory failure in inhalational anthrax is caused mainly by massive bilateral pleural effusions and com- pressive atelectasis and was the major cause of death in 39% (16 of 41) of the cases in Sverdlovsk, Russia. Indeed, the importance of draining these pleural effusions has received insuf- ficient attention as a crucial, support- ive therapeutic measure that increas- es the survival time for specific antimicrobial and antitoxin treatment to reverse the disease progression.

The pathogenesis of inhalational anthrax involves phagocytosis of B anthracis spores by pulmonary den- dritic cells, transport of the spores within them to the tracheobronchial lymph nodes where the spores germi- nate, and replication of vegetative bacilli that secrete edema toxin and lethal toxin.3 There, the toxins cause extensive tissue injury, hemorrhage, and extension of the process through the mediastinum, resulting in the characteristic radiographic mediasti- nal widening and chest pain. Invasion of the blood stream with hematoge- nous dissemination of the bacteria resulted in hemorrhagic meningitis as the major cause of death in 34% (14 of 41) of the Sverdlovsk cases.

The highly probable basis for the pulmonary parenchymal hemorrhag- es was multifocal vascular lesions. Anthrax vasculitis was identified as a key pathologic lesion in the Sver- dlovsk cases and was characterized by fibrinoid necrosis of the vessel wall with mild neurotrophic and moderate macrophage infiltration.2 Those le- sions were also the apparent basis for hemorrhagic lesions in the meninges, gastrointestinal submucosa, and me- diastinum. Another, less-critical pul- monary lesion was extension of the mediastinal hemorrhage and edema from the hilum of the lungs into the pulmonary parenchyma along the bronchovascular bundles.

The recent case of pneumonia caused by B cereus producing anthrax toxins occurred in a welder, which has been reported previously in other cases in Texas and Louisiana.4,5 The Sverdlovsk series of inhalational an- thrax cases included patients who had arc welder’s pulmonary hemosidero- sis or silicosis. Cases with pneumoco- niosis were more likely to have hem- orrhagic pulmonary consolidation (75%, 6 of 8 patients) than were patients without pneumoconiosis (29%, 2 of 7 patients).

The Sverdlovsk autopsy series is particularly instructive for its indi- cation of the pathogenesis, particu- larly hemorrhage from vasculitic lesions, and its indication of required supportive therapy, namely effective drainage of pleural effusions. The Sverdlovsk cases differed from the recent Texas case, which lacked the severe tracheobronchial and medias- tinal hemorrhages and had abundant bacteria in the alveolar spaces, rather than predominantly in the pulmo- nary microcirculation.

DAVID WALKER, MD Department of Pathology University of Texas Medical

Branch Galveston, TX 77555-0609

References

1. Wright AM, Beres SB, Consamus EN, et al. Rapidly progressive, fatal, inhalation anthrax-like infection in a human: case report, pathogen genome sequencing, pathology, and coordinated response. Arch Pathol Lab Med. 2011;135(11):1447–1459.

2. Grinberg LM, Abramova FA, Yampolskaya OV, Walker DH, Smith JH. Quantitative pathology of inhalational anthrax 1: quantitative microscopic findings. Mod Pathol. 2001;14(5):482–495.

3. Cleret A, Quesnel-Hellmann A, Vallon-Eberhard A, et al. Lung dendritic cells rapidly mediate anthrax spore entry through the pulmonary route. J Immunol. 2007;178(12):7994–8001.

4. Miller JM, Hair JG, Hebert M, Hebert L, Roberts Jr. FJ. Fulminating bacteremia and pneumonia due to Bacillus cereus. J Clin Microbiol. 1997;35(2):504–507.

5. Avashia SB, Riggins WS, Lindley C, et al. Fatal pneumonia among metalworkers due to inhalation exposure to Bacillus cereus containing Bacillus anthra- cis toxin genes. Clin Inf Dis. 2007;44(3):414–416.

doi: 10.5858/arpa.2011-0542-LE

Letters to the Editor

Arch Pathol Lab Med—Vol 136, March 2012 Letters to the Editor 235

<< /ASCII85EncodePages false /AllowTransparency false /AutoPositionEPSFiles true /AutoRotatePages /None /Binding /Left /CalGrayProfile (Dot Gain 30%) /CalRGBProfile (None) /CalCMYKProfile (U.S. Sheetfed Coated v2) /sRGBProfile (sRGB IEC61966-2.1) /CannotEmbedFontPolicy /Error /CompatibilityLevel 1.4 /CompressObjects /Off /CompressPages true /ConvertImagesToIndexed false /PassThroughJPEGImages true /CreateJobTicket false /DefaultRenderingIntent /Default /DetectBlends true /DetectCurves 0.1000 /ColorConversionStrategy /LeaveColorUnchanged /DoThumbnails false /EmbedAllFonts true /EmbedOpenType false /ParseICCProfilesInComments true /EmbedJobOptions true /DSCReportingLevel 0 /EmitDSCWarnings false /EndPage -1 /ImageMemory 1048576 /LockDistillerParams false /MaxSubsetPct 100 /Optimize false /OPM 1 /ParseDSCComments false /ParseDSCCommentsForDocInfo true /PreserveCopyPage true /PreserveDICMYKValues true /PreserveEPSInfo true /PreserveFlatness true /PreserveHalftoneInfo false /PreserveOPIComments false /PreserveOverprintSettings true /StartPage 1 /SubsetFonts true /TransferFunctionInfo /Apply /UCRandBGInfo /Remove /UsePrologue false /ColorSettingsFile () /AlwaysEmbed [ true ] /NeverEmbed [ true ] /AntiAliasColorImages false /CropColorImages true /ColorImageMinResolution 150 /ColorImageMinResolutionPolicy /OK /DownsampleColorImages true /ColorImageDownsampleType /Bicubic /ColorImageResolution 600 /ColorImageDepth 8 /ColorImageMinDownsampleDepth 1 /ColorImageDownsampleThreshold 1.50000 /EncodeColorImages true /ColorImageFilter /FlateEncode /AutoFilterColorImages false /ColorImageAutoFilterStrategy /JPEG /ColorACSImageDict << /QFactor 0.15 /HSamples [1 1 1 1] /VSamples [1 1 1 1] >> /ColorImageDict << /QFactor 0.40 /HSamples [1 1 1 1] /VSamples [1 1 1 1] >> /JPEG2000ColorACSImageDict << /TileWidth 256 /TileHeight 256 /Quality 30 >> /JPEG2000ColorImageDict << /TileWidth 256 /TileHeight 256 /Quality 30 >> /AntiAliasGrayImages false /CropGrayImages true /GrayImageMinResolution 150 /GrayImageMinResolutionPolicy /OK /DownsampleGrayImages true /GrayImageDownsampleType /Bicubic /GrayImageResolution 600 /GrayImageDepth 8 /GrayImageMinDownsampleDepth 2 /GrayImageDownsampleThreshold 1.50000 /EncodeGrayImages true /GrayImageFilter /FlateEncode /AutoFilterGrayImages false /GrayImageAutoFilterStrategy /JPEG /GrayACSImageDict << /QFactor 0.15 /HSamples [1 1 1 1] /VSamples [1 1 1 1] >> /GrayImageDict << /QFactor 0.40 /HSamples [1 1 1 1] /VSamples [1 1 1 1] >> /JPEG2000GrayACSImageDict << /TileWidth 256 /TileHeight 256 /Quality 30 >> /JPEG2000GrayImageDict << /TileWidth 256 /TileHeight 256 /Quality 30 >> /AntiAliasMonoImages false /CropMonoImages true /MonoImageMinResolution 1200 /MonoImageMinResolutionPolicy /OK /DownsampleMonoImages true /MonoImageDownsampleType /Bicubic /MonoImageResolution 1200 /MonoImageDepth -1 /MonoImageDownsampleThreshold 1.50000 /EncodeMonoImages true /MonoImageFilter /CCITTFaxEncode /MonoImageDict << /K -1 >> /AllowPSXObjects false /CheckCompliance [ /None ] /PDFX1aCheck false /PDFX3Check false /PDFXCompliantPDFOnly true /PDFXNoTrimBoxError false /PDFXTrimBoxToMediaBoxOffset [ 0.00000 0.00000 0.00000 0.00000 ] /PDFXSetBleedBoxToMediaBox false /PDFXBleedBoxToTrimBoxOffset [ 0.00000 0.00000 0.00000 0.00000 ] /PDFXOutputIntentProfile (Euroscale Coated v2) /PDFXOutputConditionIdentifier (FOGRA1) /PDFXOutputCondition () /PDFXRegistryName (http://www.color.org) /PDFXTrapped /False /CreateJDFFile false /SyntheticBoldness 1.000000 /Description << /DEU <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> /FRA <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> /JPN <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> /PTB <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> /DAN <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> /NLD <FEFF004700650062007200750069006b002000640065007a006500200069006e007300740065006c006c0069006e00670065006e0020006f006d00200064006500200063006f006d007000610074006900620069006c006900740065006900740020006d006500740020005000440046002f0058002d003300200074006500200063006f006e00740072006f006c006500720065006e00200065006e00200061006c006c00650065006e0020005000440046002d0064006f00630075006d0065006e00740065006e002000740065002000700072006f006400750063006500720065006e002000640069006500200063006f006d007000610074006900620065006c0020007a0069006a006e002e0020005000440046002f0058002000690073002000650065006e002000490053004f002d007300740061006e0064006100610072006400200076006f006f00720020006800650074002000750069007400770069007300730065006c0065006e002000760061006e002000670072006100660069007300630068006500200069006e0068006f00750064002e002000520061006100640070006c0065006500670020006400650020006700650062007200750069006b00650072007300680061006e0064006c0065006900640069006e0067002000760061006e0020004100630072006f00620061007400200076006f006f00720020006d00650065007200200069006e0066006f0072006d00610074006900650020006f00760065007200200068006500740020006d0061006b0065006e002000760061006e0020005000440046002d0064006f00630075006d0065006e00740065006e002000640069006500200063006f006d007000610074006900620065006c0020007a0069006a006e0020006d006500740020005000440046002f0058002d0033002e0020004400650020005000440046002d0064006f00630075006d0065006e00740065006e0020006b0075006e006e0065006e00200077006f007200640065006e002000670065006f00700065006e00640020006d006500740020004100630072006f00620061007400200065006e002000520065006100640065007200200034002e003000200065006e00200068006f006700650072002e> /ESP <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> /SUO <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> /ITA <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> /NOR <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> /SVE <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> /ENU (Settings for the Rampage workflow.) >> >> setdistillerparams << /HWResolution [2400 2400] /PageSize [612.000 792.000] >> setpagedevice