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Wayne W. Carmichael,¹ Sandra M.F.O. Azevedo,² Ji Si An,¹ Renato J. R. Molica,³ Elise M. Jochimsen,⁴ Sharon Lau,⁵ Kenneth L. Rinehart,⁵ Glen R. Shaw,⁶ and Geoff K. Eaglesham⁷

¹Department of Biological Sciences, Wright State University, Dayton, Ohio, USA; ²Instituto de Biofisica Carlos Chagas Filho, Universidade do Brasil, Rio de Janeiro, Brasil; ³Instituto Technologico de Pernambuco, Recife, Brasil; ⁴Hospital Infections Program, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA; ⁵Roger Adams Laboratory, School of Chemical Sciences, University of Illinois, Urbana, Illinois, USA; ⁶National Research Center for Environmental Toxicology, Coopers Plains, Queensland, Australia; ⁷Queensland Health Scientific Services, Coopers Plains, Queensland, Australia

Abstract

An outbreak of acute liver failure occurred at a dialysis center in Caruaru, Brazil (8°17^' S, 35°58^' W) , 134 km from Recife, the state capital of Pernambuco. At the clinic, 116 (89%) of 131 patients experienced visual disturbances, nausea, and vomiting after routine hemodialysis treatment on 13-20 February 1996. Subsequently, 100 patients developed acute liver failure, and of these 76 died. As of December 1996, 52 of the deaths could be attributed to a common syndrome now called Caruaru syndrome. Examination of phytoplankton from the dialysis clinic's water source, analyses of the clinic's water treatment system, plus serum and liver tissue of clinic patients led to the identification of two groups of cyanobacterial toxins, the hepatotoxic cyclic peptide microcystins and the hepatotoxic alkaloid cylindrospermopsin. Comparison of victims' symptoms and pathology using animal studies of these two cyanotoxins leads us to conclude that the major contributing factor to death of the dialyses patients was intravenous exposure to microcystins, specifically microcystin-YR, -LR, and -AR. From liver concentrations and exposure volumes, it was estimated that 19.5 µg/L microcystin was in the water used for dialysis treatments. This is 19.5 times the level set as a guideline for safe drinking water supplies by the World Health Organization. Key words: cyanobacteria, cyanotoxins, cylindrospermopsins, microcystins, toxins. Environ Health Perspect 109:663-668 (2001) . [Online 20 June 2001]

http://ehpnet1.niehs.nih.gov/docs/2001/109p663-668carmichael/ abstract.html

Address correspondence to W.W. Carmichael, Department of Biological Sciences, Wright State University, 3640 Colonel Glen Highway, Wright State University, Dayton, OH 45435 USA. Telephone: (937) 775-3173. Fax: (937) 775-3320. E-mail: wayne.carmichael@wright.edu

We thank F.S. Chu for helping to confirm ELISA analysis of serum. We also thank C. Holmes, D.M. Cardo, L.A. Carmichael, S.T. Cookson, W.R. Jarvis, M.B. de C. Antunes, D.A. de M. Filho, and T.M. Lyra for assistance with epidemiology, database management, specimen collection, and shipment.

Partial support for specimen analysis was provided to W.W.C. by the Centers for Disease Control and Prevention. MALDI mass spectra were obtained on instruments supported by grants from the National Institute of General Medical Sciences (GM 27029) , the National Institutes of Health (RR 01575) , and the National Science Foundation (PCM 8121494) to K.L.R.

Received 16 August 2000 ; accepted 30 January 2001.