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. 2001 Jul;109(7):663–668. doi: 10.1289/ehp.01109663

Human fatalities from cyanobacteria: chemical and biological evidence for cyanotoxins.

W W Carmichael 1, S M Azevedo 1, J S An 1, R J Molica 1, E M Jochimsen 1, S Lau 1, K L Rinehart 1, G R Shaw 1, G K Eaglesham 1
PMCID: PMC1240368  PMID: 11485863

Abstract

An outbreak of acute liver failure occurred at a dialysis center in Caruaru, Brazil (8 degrees 17' S, 35 degrees 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 microg/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.

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Selected References

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  1. An J., Carmichael W. W. Use of a colorimetric protein phosphatase inhibition assay and enzyme linked immunosorbent assay for the study of microcystins and nodularins. Toxicon. 1994 Dec;32(12):1495–1507. doi: 10.1016/0041-0101(94)90308-5. [DOI] [PubMed] [Google Scholar]
  2. Chu F. S., Huang X., Wei R. D. Enzyme-linked immunosorbent assay for microcystins in blue-green algal blooms. J Assoc Off Anal Chem. 1990 May-Jun;73(3):451–456. [PubMed] [Google Scholar]
  3. Dabholkar A. S., Carmichael W. W. Ultrastructural changes in the mouse liver induced by hepatotoxin from the freshwater cyanobacterium Microcystis aeruginosa strain 7820. Toxicon. 1987;25(3):285–292. doi: 10.1016/0041-0101(87)90257-1. [DOI] [PubMed] [Google Scholar]
  4. Hillenkamp F., Karas M., Beavis R. C., Chait B. T. Matrix-assisted laser desorption/ionization mass spectrometry of biopolymers. Anal Chem. 1991 Dec 15;63(24):1193A–1203A. doi: 10.1021/ac00024a002. [DOI] [PubMed] [Google Scholar]
  5. Hirooka E. Y., Pinotti M. H., Tsutsumi T., Yoshida F., Ueno Y. Survey of microcystins in water between 1995 and 1996 in Paraná, Brazil using ELISA. Nat Toxins. 1999;7(3):103–109. doi: 10.1002/(sici)1522-7189(199905/06)7:3<103::aid-nt47>3.0.co;2-d. [DOI] [PubMed] [Google Scholar]
  6. Ismail N., Becker B. N., Hakim R. M. Water treatment for hemodialysis. Am J Nephrol. 1996;16(1):60–72. doi: 10.1159/000168972. [DOI] [PubMed] [Google Scholar]
  7. Jochimsen E. M., Carmichael W. W., An J. S., Cardo D. M., Cookson S. T., Holmes C. E., Antunes M. B., de Melo Filho D. A., Lyra T. M., Barreto V. S. Liver failure and death after exposure to microcystins at a hemodialysis center in Brazil. N Engl J Med. 1998 Mar 26;338(13):873–878. doi: 10.1056/NEJM199803263381304. [DOI] [PubMed] [Google Scholar]
  8. MacKintosh C., Beattie K. A., Klumpp S., Cohen P., Codd G. A. Cyanobacterial microcystin-LR is a potent and specific inhibitor of protein phosphatases 1 and 2A from both mammals and higher plants. FEBS Lett. 1990 May 21;264(2):187–192. doi: 10.1016/0014-5793(90)80245-e. [DOI] [PubMed] [Google Scholar]
  9. Matsushima R., Yoshizawa S., Watanabe M. F., Harada K., Furusawa M., Carmichael W. W., Fujiki H. In vitro and in vivo effects of protein phosphatase inhibitors, microcystins and nodularin, on mouse skin and fibroblasts. Biochem Biophys Res Commun. 1990 Sep 14;171(2):867–874. doi: 10.1016/0006-291x(90)91226-i. [DOI] [PubMed] [Google Scholar]
  10. Nishiwaki-Matsushima R., Ohta T., Nishiwaki S., Suganuma M., Kohyama K., Ishikawa T., Carmichael W. W., Fujiki H. Liver tumor promotion by the cyanobacterial cyclic peptide toxin microcystin-LR. J Cancer Res Clin Oncol. 1992;118(6):420–424. doi: 10.1007/BF01629424. [DOI] [PubMed] [Google Scholar]
  11. Pouria S., de Andrade A., Barbosa J., Cavalcanti R. L., Barreto V. T., Ward C. J., Preiser W., Poon G. K., Neild G. H., Codd G. A. Fatal microcystin intoxication in haemodialysis unit in Caruaru, Brazil. Lancet. 1998 Jul 4;352(9121):21–26. doi: 10.1016/s0140-6736(97)12285-1. [DOI] [PubMed] [Google Scholar]
  12. Press F. Science and technology in the white house, 1977 to 1980: part 2. Science. 1981 Jan 16;211(4479):249–256. doi: 10.1126/science.211.4479.249. [DOI] [PubMed] [Google Scholar]
  13. Robinson N. A., Miura G. A., Matson C. F., Dinterman R. E., Pace J. G. Characterization of chemically tritiated microcystin-LR and its distribution in mice. Toxicon. 1989;27(9):1035–1042. doi: 10.1016/0041-0101(89)90154-2. [DOI] [PubMed] [Google Scholar]
  14. Robinson N. A., Pace J. G., Matson C. F., Miura G. A., Lawrence W. B. Tissue distribution, excretion and hepatic biotransformation of microcystin-LR in mice. J Pharmacol Exp Ther. 1991 Jan;256(1):176–182. [PubMed] [Google Scholar]
  15. Runnegar M. T., Andrews J., Gerdes R. G., Falconer I. R. Injury to hepatocytes induced by a peptide toxin from the cyanobacterium Microcystis aeruginosa. Toxicon. 1987;25(11):1235–1239. doi: 10.1016/0041-0101(87)90142-5. [DOI] [PubMed] [Google Scholar]
  16. Runnegar M. T., Falconer I. R. Effect of toxin from the cyanobacterium Microcystis aeruginosa on ultrastructural morphology and actin polymerization in isolated hepatocytes. Toxicon. 1986;24(2):109–115. doi: 10.1016/0041-0101(86)90112-1. [DOI] [PubMed] [Google Scholar]
  17. Theiss W. C., Carmichael W. W., Wyman J., Bruner R. Blood pressure and hepatocellular effects of the cyclic heptapeptide toxin produced by the freshwater cyanobacterium (blue-green alga) Microcystis aeruginosa strain PCC-7820. Toxicon. 1988;26(7):603–613. doi: 10.1016/0041-0101(88)90243-7. [DOI] [PubMed] [Google Scholar]
  18. Williams D. E., Craig M., Dawe S. C., Kent M. L., Andersen R. J., Holmes C. F. 14C-labeled microcystin-LR administered to Atlantic salmon via intraperitoneal injection provides in vivo evidence for covalent binding of microcystin-LR in salmon livers. Toxicon. 1997 Jun;35(6):985–989. doi: 10.1016/s0041-0101(96)00196-1. [DOI] [PubMed] [Google Scholar]

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