Unexplained illness in children aged 15 years and younger in Muzaffarpur, Bihar, India, which claims many lives during an outbreak that occurs in May-June, has been solved. Scientists from the U.S. and India have found that consumption of litchi fruit and skipping evening meal can result in very low blood glucose level (less than 70 mg/dL) and acute encephalopathy including seizures and coma, and causes death in many cases. The results were published in the journal Lancet Global Health.
Children in Muzaffarpur frequently spend the day eating litchis and some skip the evening meal. Skipping evening meal, by itself results in low blood sugar levels during the night. This is particularly so in the case of young children as they have limited hepatic glycogen reserves. Hypoglycin A and methylenecyclopropylglycine (MCPG), which are naturally present in litchi fruit, make the condition worse. The toxins block enzymes involved in normal glucose metabolism and this results in an inability to synthesis glucose leading to acutely low level of blood sugar. The build-up of other metabolic by-products could also have an adverse effect (encephalopathy) on the child. These two cause death in many children.
The study shows the modifying effect of skipping the evening meal on the impact of these toxins.
In 2013, scientists from Delhi’s National Centre for Disease Control, India (NCDC) and the U.S. Centers for Disease Control and Prevention (CDC) started an investigation. The first focus of the team was to evaluate if the mysterious condition was due to an infectious cause or not. “Most of the children did not have fever. And on testing the spinal fluid we did not find elevated white blood cell count. These two indicated that it was less likely to be to an infectious cause. It gave us a clue that we should look at non-infectious causes,” recalls Dr. Padmini Srikantiah, Global Disease Detection Program – India, CDC, Atlanta and the corresponding author of the paper.
With infectious causes ruled out and most sick children presenting with low blood glucose levels the team started investigating the role of toxins — exposure to pesticide, insecticide and heavy metals to name a few.
“In late 2013, CDC colleagues in Atlanta brought to our attention the well reported case of toxic hypoglycaemic syndrome in West Indies caused by hypoglycin A, a toxin found in ackee fruit, which is in the same family as litchi,” she says. “MCPG, which is a homologue had been detected in the seed of litchis, and was reported to cause low blood glucose in rats. So we started with a hypothesis.”
The 2014 outbreak allowed the scientists to investigate the role of pesticides, herbicides, heavy metals, besides hypoglycin A and MCPG in litchi fruits. “We heard over and over again from parents that their children were healthy and running around the day before, but presented with seizures and loss of consciousness in the early morning. Some people also said their children had skipped the evening meal the previous day [to illness],” says Dr. Srikantiah.
Over 62% sick children had blood glucose level less than 70 mg/dL. The median was 48 mg/dL and it was as low as 8 mg/dL.
Researchers compared 104 children with illness with similar number of controls. They found metabolites of hypoglycin A and MCPG in 66% (48 of 73 cases) of urine samples but none from the 15 controls. About 90% of children with illness showed severe disruption of fatty acid metabolism. In 36 litchi samples tested, hypoglycin A ranged from 12.4-152 microgram per gram and MCPG ranged from 45-220 microgram per gram. The level of hypoglycin A and MCPG was twice in unripe compared with ripe fruits.
“After our field investigation in July 2013, we didn’t know the cause but we recommended dextrose therapy to children who were sick. Mortality fell from 44% in 2013 to 31% in 2014. So administration of dextrose to sick children is very important,” she says. Whether malnourishment and other factors also play a role merits further investigation.
“Our data supports a public health recommendation — minimising litchi consumption, eating evening meal throughout the outbreak period and implementing rapid glucose correction for suspected illness. These recommendations are specific to children in Muzaffarpur. ” she says.