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Lychee Fruit Identified As Culprit In Mysterious Illness Plaguing Indian Children

A frightening and mysterious outbreak that has plagued Muzaffarpur, India for over 20 years has been attributed to lychee consumption according to a recent article in Lancet Global Health. Each year between May and July, hundreds of children who went to bed seemingly healthy would awake with acute neurological symptoms. Forty percent of them would die. The illness was unique in that a single child in a village could be struck leaving siblings spared. Going back to 1995, the mysterious illness has been attributed to everything from heat stroke to infection to pesticides. “They were in a kind of panic,” said Dr. Rajesh Yadav, an investigator with the India Epidemic Intelligence Service, speaking to the New York Times. “Their children were dying, and it was an unknown thing.”

Who was on the Case?
A joint investigation by India’s National Center for Disease Control and the India office of the Centers for Disease Control and Prevention in Atlanta set out to crack the case. The results of the investigation that carefully tracked the outbreak in the year 2014 were published last month. Investigators identified consumption of the lychee, also known as litchi, fruit as the culprit - particularly consumption of the underripe fruit on an empty stomach. According to the New York Times, “The Lancet article walks through a two-year medical detective story, as epidemiologists like Dr. Yadav closely examined the lives of hundreds of afflicted children, trying to understand everything they had eaten, drunk and breathed.” Below are key findings that helped unravel the mystery.

No signs of Infection
The first puzzling result was that these children showed no evidence of infection. Many outbreaks of this nature are immediately assumed to be caused by infection. Yet, the sick children were not febrile nor did they have elevated white blood cell counts, both common indicators of infection.

Abnormally Low Blood Glucose Levels
Next, investigators assayed for a large number of markers, casting a wide net for hints. They found one in the form of strikingly low blood glucose levels, and they found further that children with the lowest levels were twice as likely to die.

Similarities to a Previous Outbreak
The final piece of the puzzle fell into place when investigators recognized similarities to a previous outbreak in the West Indies. In that case, the outbreak had been tied to a toxin found in the ackee fruit. This toxin, hypoglycin, as well as a similar toxin, methylenecyclopropyl glycine, are both found in the lychee fruit. The toxins in the fruit can cause acute hypoglycemia through inhibition of glucose synthesis. Following the development of a urinalysis test for hypoglycin, remarkable abnormalities were found in the affected children, strongly implicating consumption of lychee fruit on an empty stomach as the cause of extreme hypoglycemia.

Limitations of the Findings
According to the study, “Parents in affected villages report that during May and June, young children frequently spend their day eating litchis in the surrounding orchards; many return home in the evening uninterested in eating a meal.” This common behavioral pattern coupled with the finding that only a single child from a village might be affected suggests that more factors than simply lychee consumption and a missed meal might contribute to susceptibility, including as yet unidentified genetic differences. The authors also concede that, “causality is considerably more difficult to establish,” but they believe their, “findings reflect a plausible, but not necessarily  sufficient, causal pathway between lychee consumption and illness.

Further Implications of the Study
The authors of the study also reference similar outbreaks in other lychee cultivation regions of India as well as Bangladesh and Vietnam that have yet to be investigated as exhaustively as the outbreak in Muzaffarpur. They suggest their findings may shed light on these similar illnesses. In general, the Muzaffarpur outbreak truly highlights the need for thorough investigation of unexplained illnesses in resource-limited settings. The application of similar systematic approaches has the potential to dramatically improve public health outcomes.

Lancet Global Health Article

New York Times Coverage    ■

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