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Routine fruit washing to prevent acute toxic encephalopathy – Authors' reply
Correspondence
Routine fruit washing to prevent acute toxic encephalopathy Authors’ reply
P A Desingu points out our investi gation finding that routinely washing vegetables and fruits could be protective against acute toxic encephalopathy1 and suggests that this indicates that an exogenous toxin or agent in unwashed fruits or vegetables, rather than the naturally occurring toxins hypoglycin A and methylenecyclopropylglycine (MCPG) found in lychees, might be associated with the recurring epidemic toxic encephalopathy in Muzaffarpur. We considered this possibility, and tested extensively for evidence of exogenous agents, such as pesticides and herbicides, in the biological specimens of affected children as well as in fruits, vegetables, and grains collected from affected villages; these results were all consistently negative.1 Additionally, an exogenous toxin that can be eliminated by washing a fruit or vegetable would probably be associated with rapid onset of symptoms shortly after exposure, such as that seen with a typical organophosphate or carbamate pesticide. 2 By contrast, children affected with the toxic encephalopathy in Muzaffarpur overwhelmingly presented in the early morning (0400– 0800) with profound hypoglycaemia and seizures, hours after any potential exposure to a toxic agent. This observed clinical presentation is more consistent with the impaired glucose and fatty acid metabolism that results from hypoglycin A or MCPG toxicity. Furthermore, a toxin associated with this illness would also have to explain the profound derangement in urinary amino acids observed in affected children; this rarely observed metabolic abnormality suggests a mitochondrial toxin as would be expected with hypoglycin A and MCPG, and is not known to be associated with any www.thelancet.com/lancetgh Vol 5 September 2017
exogenous substance or pesticide. This pattern of metabolic derangement is what has been reported and accepted as evidence of hypoglycin A toxicity from ackee fruit poisoning, even without direct evidence of hypoglycin A toxicity.3,4 Our investigation further showed the presence of metabolites of hypoglycin A in the urine of affected children.1 Based on these findings, and as we report in our Article,1 the absence of clinical, epidemiological, or laboratory findings to support causes of illness related to infectious pathogens, pesticides, or heavy metals suggest the observed protective association of routinely washing fruit or vegetables was not directly related to an exogenous toxin or infectious agent.
4
Meda HA, Diallo B, Buchet JP, et al. Epidemic of fatal encephalopathy in preschool children in Burkina Faso and consumption of unripe ackee (Blighia sapida) fruit. Lancet 1999; 353: 536–40.
We declare no competing interests. The findings and conclusions in this Correspondence are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention. Copyright © The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND 4.0 license.
Akshay C Dhariwal, Srinivas Venkatesh, *Aakash Shrivastava, Amit Chakrabarti, Jerry D Thomas, Melissa D Carter, Rudolph Johnson, Kayla F Laserson, Padmini Srikantiah [email protected] National Centre for Disease Control, India, Directorate General of Health Services (ACD, SV, AS) and National AIDS Control Organization (SV), Ministry of Health and Family Welfare, Government of India, New Delhi, 110054, India; National Institute of Occupational Health, Indian Council of Medical Research, Ministry of Health and Family Welfare, Government of India, Ahmedabad, Gujarat, India (AC); National Center for Environmental Health (JDT, MDC, RJ) and Center for Global Health (KFL, PS), US Centers for Disease Control and Prevention, Atlanta, GA, USA; and Global Disease Detection Program - India, US Centers for Disease Control and Prevention, New Delhi, India (KFL, PS) 1
2 3
Shrivastava A, Kumar A, Thomas JD, et al. Association of acute toxic encephalopathy with litchi consumption in an outbreak in Muzaffarpur, India, 2014: a case-control study. Lancet Glob Health 2017; 5: e458–66. King AM, Aaron CK. Organophosphate and carbamate poisoning. Emerg Med Clin North Am 2015; 33: 133–51. Joskow R, Belson M, Vesper H, Backer L, Rubin C. Ackee fruit poisoning: an outbreak investigation in Haiti 2000-2001, and review of the literature. Clin Toxicol 2006; 44: 267–73.
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Routine fruit washing to prevent acute toxic encephalopathy Authors’ reply
P A Desingu points out our investi gation finding that routinely washing vegetables and fruits could be protective against acute toxic encephalopathy1 and suggests that this indicates that an exogenous toxin or agent in unwashed fruits or vegetables, rather than the naturally occurring toxins hypoglycin A and methylenecyclopropylglycine (MCPG) found in lychees, might be associated with the recurring epidemic toxic encephalopathy in Muzaffarpur. We considered this possibility, and tested extensively for evidence of exogenous agents, such as pesticides and herbicides, in the biological specimens of affected children as well as in fruits, vegetables, and grains collected from affected villages; these results were all consistently negative.1 Additionally, an exogenous toxin that can be eliminated by washing a fruit or vegetable would probably be associated with rapid onset of symptoms shortly after exposure, such as that seen with a typical organophosphate or carbamate pesticide. 2 By contrast, children affected with the toxic encephalopathy in Muzaffarpur overwhelmingly presented in the early morning (0400– 0800) with profound hypoglycaemia and seizures, hours after any potential exposure to a toxic agent. This observed clinical presentation is more consistent with the impaired glucose and fatty acid metabolism that results from hypoglycin A or MCPG toxicity. Furthermore, a toxin associated with this illness would also have to explain the profound derangement in urinary amino acids observed in affected children; this rarely observed metabolic abnormality suggests a mitochondrial toxin as would be expected with hypoglycin A and MCPG, and is not known to be associated with any www.thelancet.com/lancetgh Vol 5 September 2017
exogenous substance or pesticide. This pattern of metabolic derangement is what has been reported and accepted as evidence of hypoglycin A toxicity from ackee fruit poisoning, even without direct evidence of hypoglycin A toxicity.3,4 Our investigation further showed the presence of metabolites of hypoglycin A in the urine of affected children.1 Based on these findings, and as we report in our Article,1 the absence of clinical, epidemiological, or laboratory findings to support causes of illness related to infectious pathogens, pesticides, or heavy metals suggest the observed protective association of routinely washing fruit or vegetables was not directly related to an exogenous toxin or infectious agent.
4
Meda HA, Diallo B, Buchet JP, et al. Epidemic of fatal encephalopathy in preschool children in Burkina Faso and consumption of unripe ackee (Blighia sapida) fruit. Lancet 1999; 353: 536–40.
We declare no competing interests. The findings and conclusions in this Correspondence are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention. Copyright © The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND 4.0 license.
Akshay C Dhariwal, Srinivas Venkatesh, *Aakash Shrivastava, Amit Chakrabarti, Jerry D Thomas, Melissa D Carter, Rudolph Johnson, Kayla F Laserson, Padmini Srikantiah [email protected] National Centre for Disease Control, India, Directorate General of Health Services (ACD, SV, AS) and National AIDS Control Organization (SV), Ministry of Health and Family Welfare, Government of India, New Delhi, 110054, India; National Institute of Occupational Health, Indian Council of Medical Research, Ministry of Health and Family Welfare, Government of India, Ahmedabad, Gujarat, India (AC); National Center for Environmental Health (JDT, MDC, RJ) and Center for Global Health (KFL, PS), US Centers for Disease Control and Prevention, Atlanta, GA, USA; and Global Disease Detection Program - India, US Centers for Disease Control and Prevention, New Delhi, India (KFL, PS) 1
2 3
Shrivastava A, Kumar A, Thomas JD, et al. Association of acute toxic encephalopathy with litchi consumption in an outbreak in Muzaffarpur, India, 2014: a case-control study. Lancet Glob Health 2017; 5: e458–66. King AM, Aaron CK. Organophosphate and carbamate poisoning. Emerg Med Clin North Am 2015; 33: 133–51. Joskow R, Belson M, Vesper H, Backer L, Rubin C. Ackee fruit poisoning: an outbreak investigation in Haiti 2000-2001, and review of the literature. Clin Toxicol 2006; 44: 267–73.
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