The cause of the mysterious outbreak of an unexplained neurological illness in Bihar's Muzaffarpur district, which had claimed nearly 100 lives each year till 2014, has been traced to the succulent litchi fruit.
Scientists from the US and India, after a joint investigation, have concluded that consuming litchi - a tropical fruit Muzaffarpur is famous for - on an empty stomach triggers the illness and death.
Seasonal outbreak of the mysterious illness, characterised by acute seizures and changed mental status, has been plaguing Muzaffarpur for nearly two decades. Some similar cases have been reported from Malda in West Bengal.
According to researchers, skipping an evening meal results in night-time hypoglycaemia, or low-blood sugar, particularly in children with limited reserve of glycogen-glucose stored in liver and muscles. This triggers oxidation of fatty acids for energy production and generation of glucose.
Naturally-occurring toxins that are found in litchis - hypoglycin A and methylenecyclopropylglycine (MPCG) - disrupt the fatty acid metabolism, leading to acutely low levels of blood sugar. This affects brain function, leading to acute seizures and stroke.
The reserach findings have been published in the latest issue of the medical journal The Lancet.
For years, many theories were proposed for the seasonal outbreak, including the possibility of pesticide exposure and infectious encephalitis, but no one could find confirmation.
In 2013, the National Centre for Disease Control (NCDC) in India and US Center for Disease Control initiated a joint investigation into the matter. The hospital-based surveillance involved laboratory investigations to assess potential infectious and non-infectious causes in 390 children less than 15 years old, who were admitted to Shri Krishna Medical College hospital and Krishnadevi Deviprasad Kejriwal maternity hospital - the chief referral medical centres in Muzaffarpur - with sudden neurological illness. Of them, 122 (31 per cent) died.
On admission, 204 (62 per cent) had low blood glucose level. Most of them had consumed litchis and parents said they had missed the evening meal the previous day . Parents in affected villages reported that during May and June, children frequently spent their day eating litchis in orchards and many of them returned home in the evening and did not have a meal.
"This study, to the best of our knowledge, is the largest investigation of the Muzaffarpur outbreak and the first comprehensive confirmation that this recurring outbreak illness is associated with litchi consumption and toxicity from both hypoglycin A and MPCG. We confirm the presence of MPCG and hypoglycin in litchis, and for the first time, our data shows the metabolites of these toxins in human biological specimens, the biological impact of these toxins on human metabolism, and the modifying effect of the lack of an evening meal of the impact of these toxins," scientists report in the Lancet.