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Mycotoxins in myelopathies of man
THE LANCET
meat contaminated with VRE. In clinical settings the spread of VRE should be limited as much as possible.2 One of the VRE genotypes shared among dogs and cats was recently found in a human carrier (unpublished data). This raises the question, which dog poses a greater risk to the postman: the one that barks or the one that wags its tail? Alex van Belkum, Nicole van den Braak, *Ronald Thomassen, Henri Verbrugh, Hubert Endtz University Hospital Rotterdam, Department of Bacteriology, Rotterdam; and *Kliniek voor Gezelschapsdieren, 3086 JM Rotterdam, Netherlands
1
2
Wall PG, Threlfall EJ, Ward LR, Rowe B. Multiresistant Salmonella typhimurium DT104 in cats: a public health risk. Lancet 1996; 348: 471. The Hospital Infection Control Practices Advisory Committee HICPAC. Recommendations for preventing the spread of vancomycin resistance: recommendations of the Hospital Infection Control Practices Advisory Committee. Am J Infect Control 1995; 23: 87–94.
Mycotoxins in myelopathies of man SIR—Environmental cofactors have been thought to have a role in chronic idiopathic spastic paraparesis (CHISPA), either infected with human T-cell lymphotropic virus type 1 (HTLV-1) (CHISPA +) or not (CHISPA ⫺).1,2 These patients are usually found in hot and humid regions, most of which have heavy rains, and these conditions allow foods to be polluted by fungi some of which become toxigenic.1,2 Our chance finding of deoxynivalenol in a patient with CHISPA +2 led us to investigate the presence of mycotoxins in patients with CHISPA in southwestern Colombia, an HTLV-1 endemic area.1,2 12 patients (seven men) aged between 34 and 70 years (mean 45 years) with CHISPA + and in three male patients aged between 34 and 55 years (mean 48·6 year) with CHISPA ⫺ were investigated. The mean illness duration in these groups was 9·2 and 6·3 years, respectively. We obtained at least 25 mL urine from each of these patients and transported the frozen samples by aeroplane to Bogota, Colombia, for subsequent mycotoxin analysis. Urine specimens obtained from four healthy individuals and from two patients with other neurological disorders, who also lived in the endemic area, were used as controls. Concentrations of aflatoxins (B1, B2, G1, and G2), ochratoxin A, nivalenol, deoxynivalenol, and fumosinin B1 metabolites were investigated by high performance liquid chromatography with detection of fluorescence in all samples, and high performance thin liquid chromatography was randomly done in a third of the samples to confirm the results with techniques described elsewhere.2 Mycotoxins were detected in 11 of 12 patients with CHISPA + and in all three patients with CHISPA ⫺. Deoxynivalenol, fumosinin B1, and nivalenol were detected in 13 patients (0·3–12·4 µg per 100 mL), eight patients (9·35–222·6 µg per 100 mL), and seven patients (0·22–1·3 µg per 100 mL), respectively. Overall 14 of the 15 patients with CHISPA were positive for at least one fusarium metabolite. None had toxic metabolites belonging to genera Aspergillus or Penicillium. We did not detect mycotoxins in any of the control urine specimens tested (2 test, p=0·0003, Fisher’s exact test p=0·0001). To the best of our knowledge this is the first report of mycotoxins in patients harbouring HTLV-1 infection, but more interesting was the finding of these toxins in patients with CHISPA ⫺. Mycotoxins are carcinogens as well as immunosuppressors allowing different pathogens, including retroviruses, to act opportunistically.2,3 They could also interfere with some metabolic pathways involving
Vol 348 • October 12, 1996
sphingolipids (eg, fumosinins), blocking the Nacetyltransferase enzyme, producing apoptosis and spastic paraparesis in animals.2,4 These mechanisms may be involved in the development of similar but seronegative clinical pictures frequently found simultaneously in these endemic areas for CHISPA +,1,2 resembling those in other diseases associated with viral infections and carcinogens, and described in places with similar environments to those described above such as hepatocellular and oesophageal carcinoma.5 It is interesting to note that deoxynivalenol and nivalenol have consistently been found in staple food from other places, such as Kyushu Island, Japan,3 also considered an endemic area for CHISPA +, suggesting that our findings in Colombian patients may be related to the pathogenesis of these retroviral infections.2 Our results indicate that the investigation of these toxins in other populations affected by these germs, including past mycotoxin exposure, is needed. We thank Nila del Castillo for field work and Alonso Gomez, ex-Minister of Health of Colombia, for collaboration. FEL-S was supported by a grant from the Ministry of Health of Colombia.
*Fidias E León-S, Marta Carpintero, Nicholas Gaffga, Leonidas Ocampo, Jaime Bayona Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama, USA; Unit of Neurology, UIS; *University Hospital, Bucaramanga, Colombia; LAQMA, Environmental Monitoring Chemical Laboratory, Santa Fe de Bogota, Colombia; International Research Laboratory, School of Public Health, University of Alabama at Birmingham, Alabama; Chicamocha Clinic, Bucaramanga; and Manuela Beltran University, Bucaramanga
1
2
3 4
5
Zaninovic V, León-S FE. Fifteen years of follow-up in HTLV-1 positive and HTLV-1 negative spastic paraparesis at Southwestern Colombia, South America. J Neurovirol (in press). León-S FE, Carpintero M, Bayona J, et al. Un coctel neuropatologico de micotoxinas, retrovirus y paraparesia espastica tropical. UIS-Salud (in press). León-S FE, Ariza Deleón A, Ariza-CA, León ME. Peopling of Americas. Science 1996; 273: 723–24. Wang H, Jones C, Ciacci-Zanella J, Holt T, Gilchrist DG, Dickman MB. Fumonisins and alternaria alternata lucopersici toxins: sphinganine analog mycotoxins induce apoptosis in monkey kydney cells. Proc Natl Acad Sci USA 1996; 93: 3461–65. Chang F, Syrjanen S, Tervahauta A, Kurvinen K, Wang L, Syrjanen K. Frequent mutations of p53 gene in oesophageal squamous cell carcinomas with and without human papillomavirus (HPV) involvement suggest the dominant role of environmental carcinogens in oesophageal carcinogenesis. Br J Cancer 1994; 70: 346–51.
Sheffield risk and treatment table for primary prevention of coronary heart disease SIR—The Sheffield strategy for primary prevention of heart disease (Ramsay and colleagues, Aug 10, p 387)1 is much improved from its first version in that it partly recognises genetic hyperlipidaemias2 and incorporates some of Megnien and co-workers’3 suggestions. However, Ramsay and colleagues’ quantitative approach to cholesterol is not matched by similar attention to the quantitative risk associated with systolic blood pressure and the age-variable definitions of hypertension. This is in striking contrast with the joint European guidelines (EAS/ESH/ESC) in which this issue is addressed and which remain a far better method of assessment, being analogous to the Farmingham cohort data.2 However, even these guidelines minimise the risks associated with hypertriglyceridaemia or low high-density lipoprotein (HDL) in the search for simplicity of use. We disagree that the West of Scotland Coronary Prevention Study risk of 1·86% per year is not desirable or treatable.3,4 The west of Scotland is one of the highest-risk areas for coronary heart disease in the world, and the Sheffield guidelines imply that the majority of cases should not be treated, even there.4 The cost of £20 000 per life year gained does not differ significantly from that for treating mild
1039
meat contaminated with VRE. In clinical settings the spread of VRE should be limited as much as possible.2 One of the VRE genotypes shared among dogs and cats was recently found in a human carrier (unpublished data). This raises the question, which dog poses a greater risk to the postman: the one that barks or the one that wags its tail? Alex van Belkum, Nicole van den Braak, *Ronald Thomassen, Henri Verbrugh, Hubert Endtz University Hospital Rotterdam, Department of Bacteriology, Rotterdam; and *Kliniek voor Gezelschapsdieren, 3086 JM Rotterdam, Netherlands
1
2
Wall PG, Threlfall EJ, Ward LR, Rowe B. Multiresistant Salmonella typhimurium DT104 in cats: a public health risk. Lancet 1996; 348: 471. The Hospital Infection Control Practices Advisory Committee HICPAC. Recommendations for preventing the spread of vancomycin resistance: recommendations of the Hospital Infection Control Practices Advisory Committee. Am J Infect Control 1995; 23: 87–94.
Mycotoxins in myelopathies of man SIR—Environmental cofactors have been thought to have a role in chronic idiopathic spastic paraparesis (CHISPA), either infected with human T-cell lymphotropic virus type 1 (HTLV-1) (CHISPA +) or not (CHISPA ⫺).1,2 These patients are usually found in hot and humid regions, most of which have heavy rains, and these conditions allow foods to be polluted by fungi some of which become toxigenic.1,2 Our chance finding of deoxynivalenol in a patient with CHISPA +2 led us to investigate the presence of mycotoxins in patients with CHISPA in southwestern Colombia, an HTLV-1 endemic area.1,2 12 patients (seven men) aged between 34 and 70 years (mean 45 years) with CHISPA + and in three male patients aged between 34 and 55 years (mean 48·6 year) with CHISPA ⫺ were investigated. The mean illness duration in these groups was 9·2 and 6·3 years, respectively. We obtained at least 25 mL urine from each of these patients and transported the frozen samples by aeroplane to Bogota, Colombia, for subsequent mycotoxin analysis. Urine specimens obtained from four healthy individuals and from two patients with other neurological disorders, who also lived in the endemic area, were used as controls. Concentrations of aflatoxins (B1, B2, G1, and G2), ochratoxin A, nivalenol, deoxynivalenol, and fumosinin B1 metabolites were investigated by high performance liquid chromatography with detection of fluorescence in all samples, and high performance thin liquid chromatography was randomly done in a third of the samples to confirm the results with techniques described elsewhere.2 Mycotoxins were detected in 11 of 12 patients with CHISPA + and in all three patients with CHISPA ⫺. Deoxynivalenol, fumosinin B1, and nivalenol were detected in 13 patients (0·3–12·4 µg per 100 mL), eight patients (9·35–222·6 µg per 100 mL), and seven patients (0·22–1·3 µg per 100 mL), respectively. Overall 14 of the 15 patients with CHISPA were positive for at least one fusarium metabolite. None had toxic metabolites belonging to genera Aspergillus or Penicillium. We did not detect mycotoxins in any of the control urine specimens tested (2 test, p=0·0003, Fisher’s exact test p=0·0001). To the best of our knowledge this is the first report of mycotoxins in patients harbouring HTLV-1 infection, but more interesting was the finding of these toxins in patients with CHISPA ⫺. Mycotoxins are carcinogens as well as immunosuppressors allowing different pathogens, including retroviruses, to act opportunistically.2,3 They could also interfere with some metabolic pathways involving
Vol 348 • October 12, 1996
sphingolipids (eg, fumosinins), blocking the Nacetyltransferase enzyme, producing apoptosis and spastic paraparesis in animals.2,4 These mechanisms may be involved in the development of similar but seronegative clinical pictures frequently found simultaneously in these endemic areas for CHISPA +,1,2 resembling those in other diseases associated with viral infections and carcinogens, and described in places with similar environments to those described above such as hepatocellular and oesophageal carcinoma.5 It is interesting to note that deoxynivalenol and nivalenol have consistently been found in staple food from other places, such as Kyushu Island, Japan,3 also considered an endemic area for CHISPA +, suggesting that our findings in Colombian patients may be related to the pathogenesis of these retroviral infections.2 Our results indicate that the investigation of these toxins in other populations affected by these germs, including past mycotoxin exposure, is needed. We thank Nila del Castillo for field work and Alonso Gomez, ex-Minister of Health of Colombia, for collaboration. FEL-S was supported by a grant from the Ministry of Health of Colombia.
*Fidias E León-S, Marta Carpintero, Nicholas Gaffga, Leonidas Ocampo, Jaime Bayona Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama, USA; Unit of Neurology, UIS; *University Hospital, Bucaramanga, Colombia; LAQMA, Environmental Monitoring Chemical Laboratory, Santa Fe de Bogota, Colombia; International Research Laboratory, School of Public Health, University of Alabama at Birmingham, Alabama; Chicamocha Clinic, Bucaramanga; and Manuela Beltran University, Bucaramanga
1
2
3 4
5
Zaninovic V, León-S FE. Fifteen years of follow-up in HTLV-1 positive and HTLV-1 negative spastic paraparesis at Southwestern Colombia, South America. J Neurovirol (in press). León-S FE, Carpintero M, Bayona J, et al. Un coctel neuropatologico de micotoxinas, retrovirus y paraparesia espastica tropical. UIS-Salud (in press). León-S FE, Ariza Deleón A, Ariza-CA, León ME. Peopling of Americas. Science 1996; 273: 723–24. Wang H, Jones C, Ciacci-Zanella J, Holt T, Gilchrist DG, Dickman MB. Fumonisins and alternaria alternata lucopersici toxins: sphinganine analog mycotoxins induce apoptosis in monkey kydney cells. Proc Natl Acad Sci USA 1996; 93: 3461–65. Chang F, Syrjanen S, Tervahauta A, Kurvinen K, Wang L, Syrjanen K. Frequent mutations of p53 gene in oesophageal squamous cell carcinomas with and without human papillomavirus (HPV) involvement suggest the dominant role of environmental carcinogens in oesophageal carcinogenesis. Br J Cancer 1994; 70: 346–51.
Sheffield risk and treatment table for primary prevention of coronary heart disease SIR—The Sheffield strategy for primary prevention of heart disease (Ramsay and colleagues, Aug 10, p 387)1 is much improved from its first version in that it partly recognises genetic hyperlipidaemias2 and incorporates some of Megnien and co-workers’3 suggestions. However, Ramsay and colleagues’ quantitative approach to cholesterol is not matched by similar attention to the quantitative risk associated with systolic blood pressure and the age-variable definitions of hypertension. This is in striking contrast with the joint European guidelines (EAS/ESH/ESC) in which this issue is addressed and which remain a far better method of assessment, being analogous to the Farmingham cohort data.2 However, even these guidelines minimise the risks associated with hypertriglyceridaemia or low high-density lipoprotein (HDL) in the search for simplicity of use. We disagree that the West of Scotland Coronary Prevention Study risk of 1·86% per year is not desirable or treatable.3,4 The west of Scotland is one of the highest-risk areas for coronary heart disease in the world, and the Sheffield guidelines imply that the majority of cases should not be treated, even there.4 The cost of £20 000 per life year gained does not differ significantly from that for treating mild
1039