RESUMO
Microcystins are among the most commonly detected toxins associated with cyanobacteria blooms worldwide. Two episodes of intravenous microcystin exposures occurred among kidney dialysis patients during 1996 and 2001. Analysis of serum samples collected during these episodes suggests that microcystins are detectable as free and bound forms in human serum. Our goal was to characterize the biochemical evidence for human exposure to microcystins, to identify uncertainties associated with interpretation of these observed results, and to identify research needs. We analyzed serum samples using enzyme-linked immunosorbent assay (ELISA) methods to detect free microcystins, and gas chromatography/mass spectrometry (GC/MS) to detect 2-methyl-3-methoxy-4-phenylbutyric acid (MMPB). MMPB is derived from both free and protein-bound microcystins by chemical oxidation, and it appears to represent total microcystins present in serum. We found evidence of free microcystins in patient serum for more than 50 days after the last documented exposure. Serum concentrations of free microcystins were consistently lower than MMPB quantification of total microcystins: free microcystins as measured by ELISA were only 8-51% of total microcystin concentrations as detected by the GC/MS method. After intravenous exposure episodes, we found evidence of microcystins in human serum in free and protein-bound forms, though the nature of the protein-bound forms is uncertain. Free microcystins appear to be a small but variable subset of total microcystins present in human serum. Research is needed to elucidate the human toxicokinetics of microcystins, in part to determine how observed serum concentrations can be used to estimate previous microcystin exposure.
Assuntos
Toxinas Bacterianas/sangue , Exposição Ambiental/análise , Microcistinas/sangue , Diálise Renal , Toxinas Bacterianas/intoxicação , Brasil , Humanos , Microcistinas/intoxicação , Toxemia/sangue , Toxemia/etiologiaRESUMO
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.
Assuntos
Carcinógenos/efeitos adversos , Cianobactérias/isolamento & purificação , Surtos de Doenças , Falência Hepática Aguda/microbiologia , Peptídeos Cíclicos/efeitos adversos , Instituições de Assistência Ambulatorial , Brasil/epidemiologia , Carcinógenos/análise , Cianobactérias/química , Diálise , Ensaio de Imunoadsorção Enzimática , Humanos , Fígado/química , Fígado/patologia , Falência Hepática Aguda/etiologia , Microcistinas , Peptídeos Cíclicos/análise , Abastecimento de ÁguaRESUMO
BACKGROUND: Hemodialysis is a common but potentially hazardous procedure. From February 17 to 20, 1996, 116 of 130 patients (89 percent) at a dialysis center (dialysis center A) in Caruaru, Brazil, had visual disturbances, nausea, and vomiting associated with hemodialysis. By March 24, 26 of the patients had died of acute liver failure. METHODS: A case patient was defined as any patient undergoing dialysis at dialysis center A or Caruaru's other dialysis center (dialysis center B) during February 1996 who had acute liver failure. To determine the risk factors for and the source of the outbreak, we conducted a cohort study of the 130 patients at dialysis center A and the 47 patients at dialysis center B, reviewed the centers' water supplies, and collected water, patients' serum, and postmortem liver tissue for microcystin assays. RESULTS: One hundred one patients (all at dialysis center A) met the case definition, and 50 died. Affected patients who died were older than those who survived (median age, 47 vs. 35 years, P<0.001). Furthermore, all 17 patients undergoing dialysis on the Tuesday-, Thursday-, and Saturday-night schedule became ill, and 13 of them (76 percent) died. Both centers received water from a nearby reservoir. However, the water supplied to dialysis center B was treated, filtered, and chlorinated, whereas the water supplied to dialysis center A was not. Microcystins produced by cyanobacteria were detected in water from the reservoir and from dialysis center A and in serum and liver tissue of case patients. CONCLUSIONS: Water used for hemodialysis can contain toxic materials, and its quality should therefore be carefully monitored.