TY - JOUR
T1 - Association of acute toxic encephalopathy with litchi consumption in an outbreak in Muzaffarpur, India, 2014
T2 - a case-control study
AU - Shrivastava, Aakash
AU - Kumar, Anil
AU - Thomas, Jerry D.
AU - Laserson, Kayla F.
AU - Bhushan, Gyan
AU - Carter, Melissa D.
AU - Chhabra, Mala
AU - Mittal, Veena
AU - Khare, Shashi
AU - Sejvar, James J.
AU - Dwivedi, Mayank
AU - Isenberg, Samantha L.
AU - Johnson, Rudolph
AU - Pirkle, James L.
AU - Sharer, Jon D.
AU - Hall, Patricia L.
AU - Yadav, Rajesh
AU - Velayudhan, Anoop
AU - Papanna, Mohan
AU - Singh, Pankaj
AU - Somashekar, D.
AU - Pradhan, Arghya
AU - Goel, Kapil
AU - Pandey, Rajesh
AU - Kumar, Mohan
AU - Kumar, Satish
AU - Chakrabarti, Amit
AU - Sivaperumal, P.
AU - Kumar, A. Ramesh
AU - Schier, Joshua G.
AU - Chang, Arthur
AU - Graham, Leigh Ann
AU - Mathews, Thomas P.
AU - Johnson, Darryl
AU - Valentin, Liza
AU - Caldwell, Kathleen L.
AU - Jarrett, Jeffery M.
AU - Harden, Leslie A.
AU - Takeoka, Gary R.
AU - Tong, Suxiang
AU - Queen, Krista
AU - Paden, Clinton
AU - Whitney, Anne
AU - Haberling, Dana L.
AU - Singh, Ram
AU - Singh, Ravi Shankar
AU - Earhart, Kenneth C.
AU - Dhariwal, A. C.
AU - Chauhan, L. S.
AU - Venkatesh, S.
AU - Srikantiah, Padmini
N1 - Publisher Copyright:
© 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND license
PY - 2017/4/1
Y1 - 2017/4/1
N2 - Background Outbreaks of unexplained illness frequently remain under-investigated. In India, outbreaks of an acute neurological illness with high mortality among children occur annually in Muzaffarpur, the country's largest litchi cultivation region. In 2014, we aimed to investigate the cause and risk factors for this illness. Methods In this hospital-based surveillance and nested age-matched case-control study, we did laboratory investigations to assess potential infectious and non-infectious causes of this acute neurological illness. Cases were children aged 15 years or younger who were admitted to two hospitals in Muzaffarpur with new-onset seizures or altered sensorium. Age-matched controls were residents of Muzaffarpur who were admitted to the same two hospitals for a non-neurologic illness within seven days of the date of admission of the case. Clinical specimens (blood, cerebrospinal fluid, and urine) and environmental specimens (litchis) were tested for evidence of infectious pathogens, pesticides, toxic metals, and other non-infectious causes, including presence of hypoglycin A or methylenecyclopropylglycine (MCPG), naturally-occurring fruit-based toxins that cause hypoglycaemia and metabolic derangement. Matched and unmatched (controlling for age) bivariate analyses were done and risk factors for illness were expressed as matched odds ratios and odds ratios (unmatched analyses). Findings Between May 26, and July 17, 2014, 390 patients meeting the case definition were admitted to the two referral hospitals in Muzaffarpur, of whom 122 (31%) died. On admission, 204 (62%) of 327 had blood glucose concentration of 70 mg/dL or less. 104 cases were compared with 104 age-matched hospital controls. Litchi consumption (matched odds ratio [mOR] 9·6 [95% CI 3·6 – 24]) and absence of an evening meal (2·2 [1·2–4·3]) in the 24 h preceding illness onset were associated with illness. The absence of an evening meal significantly modified the effect of eating litchis on illness (odds ratio [OR] 7·8 [95% CI 3·3–18·8], without evening meal; OR 3·6 [1·1–11·1] with an evening meal). Tests for infectious agents and pesticides were negative. Metabolites of hypoglycin A, MCPG, or both were detected in 48 [66%] of 73 urine specimens from case-patients and none from 15 controls; 72 (90%) of 80 case-patient specimens had abnormal plasma acylcarnitine profiles, consistent with severe disruption of fatty acid metabolism. In 36 litchi arils tested from Muzaffarpur, hypoglycin A concentrations ranged from 12·4 μg/g to 152·0 μg/g and MCPG ranged from 44·9 μg/g to 220·0 μg/g. Interpretation Our investigation suggests an outbreak of acute encephalopathy in Muzaffarpur associated with both hypoglycin A and MCPG toxicity. To prevent illness and reduce mortality in the region, we recommended minimising litchi consumption, ensuring receipt of an evening meal and implementing rapid glucose correction for suspected illness. A comprehensive investigative approach in Muzaffarpur led to timely public health recommendations, underscoring the importance of using systematic methods in other unexplained illness outbreaks. Funding US Centers for Disease Control and Prevention.
AB - Background Outbreaks of unexplained illness frequently remain under-investigated. In India, outbreaks of an acute neurological illness with high mortality among children occur annually in Muzaffarpur, the country's largest litchi cultivation region. In 2014, we aimed to investigate the cause and risk factors for this illness. Methods In this hospital-based surveillance and nested age-matched case-control study, we did laboratory investigations to assess potential infectious and non-infectious causes of this acute neurological illness. Cases were children aged 15 years or younger who were admitted to two hospitals in Muzaffarpur with new-onset seizures or altered sensorium. Age-matched controls were residents of Muzaffarpur who were admitted to the same two hospitals for a non-neurologic illness within seven days of the date of admission of the case. Clinical specimens (blood, cerebrospinal fluid, and urine) and environmental specimens (litchis) were tested for evidence of infectious pathogens, pesticides, toxic metals, and other non-infectious causes, including presence of hypoglycin A or methylenecyclopropylglycine (MCPG), naturally-occurring fruit-based toxins that cause hypoglycaemia and metabolic derangement. Matched and unmatched (controlling for age) bivariate analyses were done and risk factors for illness were expressed as matched odds ratios and odds ratios (unmatched analyses). Findings Between May 26, and July 17, 2014, 390 patients meeting the case definition were admitted to the two referral hospitals in Muzaffarpur, of whom 122 (31%) died. On admission, 204 (62%) of 327 had blood glucose concentration of 70 mg/dL or less. 104 cases were compared with 104 age-matched hospital controls. Litchi consumption (matched odds ratio [mOR] 9·6 [95% CI 3·6 – 24]) and absence of an evening meal (2·2 [1·2–4·3]) in the 24 h preceding illness onset were associated with illness. The absence of an evening meal significantly modified the effect of eating litchis on illness (odds ratio [OR] 7·8 [95% CI 3·3–18·8], without evening meal; OR 3·6 [1·1–11·1] with an evening meal). Tests for infectious agents and pesticides were negative. Metabolites of hypoglycin A, MCPG, or both were detected in 48 [66%] of 73 urine specimens from case-patients and none from 15 controls; 72 (90%) of 80 case-patient specimens had abnormal plasma acylcarnitine profiles, consistent with severe disruption of fatty acid metabolism. In 36 litchi arils tested from Muzaffarpur, hypoglycin A concentrations ranged from 12·4 μg/g to 152·0 μg/g and MCPG ranged from 44·9 μg/g to 220·0 μg/g. Interpretation Our investigation suggests an outbreak of acute encephalopathy in Muzaffarpur associated with both hypoglycin A and MCPG toxicity. To prevent illness and reduce mortality in the region, we recommended minimising litchi consumption, ensuring receipt of an evening meal and implementing rapid glucose correction for suspected illness. A comprehensive investigative approach in Muzaffarpur led to timely public health recommendations, underscoring the importance of using systematic methods in other unexplained illness outbreaks. Funding US Centers for Disease Control and Prevention.
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U2 - 10.1016/S2214-109X(17)30035-9
DO - 10.1016/S2214-109X(17)30035-9
M3 - Article
C2 - 28153514
AN - SCOPUS:85014808535
SN - 2214-109X
VL - 5
SP - e458-e466
JO - The Lancet Global Health
JF - The Lancet Global Health
IS - 4
ER -