Association of acute toxic encephalopathy with litchi consumption in an outbreak in Muzaffarpur, India, 2014: a case-control study

Shrivastava, Aakash and Kumar, Anil and D Thomas, Jerry and F Laserson, Kayla and Bhushan, Gyan and D Carter, Melissa and Chhabra, Mala and Mittal, Veena and Khare, Shashi and J Sejvar, James and Dwivedi, Mayank and L Isenberg, Samantha and Johnson, Rudolph and L Pirkle, James and D Sharer, Jon and L Hall, Patricia and Yadav, Rajesh and Velayudhan, Anoop and Papanna, Mohan and Singh, Pankaj and Somashekar, D and Pradhan, Arghya and Goel, Kapil and Pandey, Rajesh and Kumar, Mohan and Kumar, Satish and Chakrabarti, Amit and Sivaperumal, P and Kumar, A Ramesh and G Schier, Joshua and Chang, Arthur and Ann Graham, Leigh and P Mathews, Thomas and Johnson, Darryl and Valentin, Liza and L Caldwell, Kathleen and M Jarrett, Jeffery and A Harden, Leslie and R Takeoka, Gary and Tong, Suxiang and Queen, Krista and Paden, Clinton and Whitney, Anne and L Haberling, Dana and Singh, Ram and Shankar Singh, Ravi and C Earhart, Kenneth and C Dhariwal, A and S Chauhan, L and Venkatesh, S and Srikantiah, Padmini (2017) Association of acute toxic encephalopathy with litchi consumption in an outbreak in Muzaffarpur, India, 2014: a case-control study. The Lancet Global Health, 5 (4). e458-e466. ISSN 0140-6736

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Abstract

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.

Item Type: Article
Subjects: WA Public Health
Divisions: Faculty of Medicin
Depositing User: Touba Derakhshande
Date Deposited: 11 Sep 2017 06:24
Last Modified: 11 Sep 2017 06:24
URI: http://eprints.bpums.ac.ir/id/eprint/5871

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