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Tuesday, February 7, 2017

Lychee fruit poisoning causing death in Up, Bihar. Ref: 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; Online First.

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 [Bihar], the country's largest litchi [lychee] cultivation region. In 2014, we aimed to investigate the cause and risk factors for this illness.

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 2 hospitals in Muzaffarpur with new-onset seizures or altered sensorium. Age-matched controls were residents of Muzaffarpur who were admitted to the same 2 hospitals for a non-neurologic illness within 7 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).

Between 26 May and 17 Jul 2014, 390 patients meeting the case definition were admitted to the 2 referral hospitals in Muzaffarpur, of whom 122 (31 percent) died. On admission, 204 (62 percent) 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 percent CI 3.6-24]) and absence of an evening meal (2.2 [1.2-4.3]) in the 24 hours 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 percent 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 percent] of 73 urine specimens from case-patients and none from 15 controls; 72 (90 percent) 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 microg/g to 152.0 microg/g and MCPG ranged from 44.9 microg/g to 220.0 microg/g.

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.

Communicated by:
Dr Irene Lai MBBS (Sydney) FFTM RCPS (Glasg)
Global Medical Director, Medical Information & Analysis
Level 3, 45 Clarence St, Sydney NSW 2000

[The etiologies of seasonal encephalitis (or encephalopathies) in northeastern India have not been well defined. Many have been attributed to Japanese encephalitis (JE). However, JE virus infections have been excluded in many cases, with the undiagnosed cases termed acute encephalitis syndrome (AES). Previous ProMED-mail posts have implicated Reye syndrome, consumption of lychees, and heat stroke, as well as JE virus infections, as responsible for AES (see ProMED-mail archive no. 20161111.4621162).

Dr Jacob John has asserted that many of these are hypoglycemic Reye syndrome cases. He noted that in the pre-monsoon period, particularly in May and June, outbreaks of Reye-like acute hypoglycemic encephalopathy occur in the north western region of Bihar state and that is also popularly, but unfortunately, called AES. Many doctors, the media, and the public consider these encephalopathy cases as encephalitis because of the term AES. This has been now clarified and in June 2014 children were treated by 10 per cent dextrose infusion and many lives were saved. Other etiologies have been proposed by clinicians. A published article in a pediatric journal proposed that some cases are due to heat stroke.

It has been proposed previously that consumption of lychees is responsible for some encephalitis cases. Encephalopathy and hypoglycemia have been associated with consumption of lychee fruit containing phytotoxins, specifically alpha-(methylenecyclopropyl)glycine (see ProMED-mail archive no. 20150201.3132842). Several reports have associated AES with contaminated water, suggesting enterovirus etiology. A recent report indicates that the scrub typhus bacterium may be causing many encephalitis deaths in the nearby northeastern state of Assam.

The report above makes a convincing case for lychee consumption as the etiology of many of these cases in areas of lychee production in Bihar state. Public education will be essential to prevent these lychee intoxications. Japanese encephalitis virus is also endemic in this area, but is preventable by vaccination and should not be ignored.

ProMED thanks Dr Irene Lai for sending in this report, along with a press release from the US Embassy in India: US and Indian Governments identification of a cause of unexplained illness in Bihar state (https://in.usembassy.gov/u-s-indian-governments-identify-cause-unexplained-illness-bihar/).

Maps of India can be seen at http://www.mapsofindia.com/maps/india/india-political-map.htm and http://healthmap.org/promed/p/11360. - Mod.TY]

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