A two-year-long investigation into the “mystery” disease termed Acute Encephalitis Syndrome (AES) that kills tens of young children in Muzaffarpur, Bihar, every year has found no evidence of infectious microbes in the victims.
Instead, the investigators have said, their findings suggest “toxin mediated illness”, with a hypothesis of a toxin in the prevalent litchi fruit in the area.
The joint report, by the Centers for Disease Control (CDC), Atlanta, and National Centre for Disease Control (NCDC), under the Union Health Ministry, compares the outbreak to ackee fruit poisoning reported in the Carribean islands and West Africa.
Correction of hypoglycemia, or low blood glucose, in patients as per their recommendations, adds the report, has helped reduce mortality from 44 per cent last year to 26 per cent in 2014.
In an article in the latest internal newsletter of the NCDC, Dr Padmini Srikantiah of the CDC’s India wing and Dr Aakash Shrivastava of the NCDC’s epidemiology division say, “Based on the 2013 findings, we concluded that the outbreak appeared to be more consistent with a non-inflammatory encephalopathy rather than infectious encephalitis.”
Encephalopathy is a general term used to describe neurological symptoms while encephalitis indicates infection as a cause for the same. Explained a scientist, “We are saying the presentation indicates a generalised cause rather than an infection.”
Comparing the annual disease to ackee fruit poisoning, the authors have suggested the “potential presence of a toxin, Methylene Cyclopropyl Glycine (MCPG), with hypoglycemic activity that is found in the litchi seed”.
The CDC-NCDC team points out that hypoglycemia, not identified as a common symptom till now, was present in a majority of the cases, which the authors have said could be sparking the neurological symptoms.
In 2013, of the 303 children tested, including the control group, “hypoglycemia in 94 per cent of the children trended towards an increased risk of death”, according to the findings.
This year, 63 per cent of the 390 patients between May 26 and July 17 showed blood glucose less than 70 mg/dL.
However, various studies, including by the National Research Centre for Litchi (NRCL) in Muzaffarpur, have discounted any toxins in the litchi fruit pulp, root of the crop, seeds and skin as causing the symptoms. Litchi is a common fruit in the area.
According to the CDC-NCDC authors, “It is possible that exposure or ingestion of this toxin (MCPG) may have the potential to lead to acute hypoglycemia and precipitate the seizures that seem to be the clinical hallmark of this illness… Animal studies suggest that ingestion of MCPG may have the potential to cause acute hypoglycemia and encephalopathy, similar to ackee food poisoning described in the Carribean and West Africa.”
The investigators have advised the Bihar government to supply glucometers to hospitals to monitor sugar levels of affected children, ensure rapid treatment of hypoglycemia, and conduct a “detailed field study” to evaluate potential toxins.
The joint NCDC investigation team is, meanwhile, conducting a field study to identify toxins in pesticides, heavy metals, naturally occurring plant or fruit-based agents in Muzaffarpur area. Laboratory samples from patients are also being tested for toxin metabolites and residues.
AES affects young children between the ages of one and five, resulting in fever, sudden seizures and altered mental status. It was earlier characterised by over 90 per cent mortality.
This year, a team of the National Vector Borne Disease Control Programme had found a pesticide, Alphacyphermethrin, to be above minimum safe limits in a chemical analysis of litchi samples in Malda in West Bengal, but said it was too early to “confirm its toxicity in humans”.
Researchers, however, continue to deny the presence of any toxins in litchis. According to Dr Vishal Nath, director of the National Centre for Litchi under the Indian Council of Agricultural Research, based in Muzaffarpur, “We have been working on investigating a corelation between litchi and AES cases for years, and have performed hundreds of toxicology studies. We have established no association between the two.”
He adds that every year AES cases start surfacing in June, by when 90 per cent of the litchi crop in Muzaffarpur has already been “picked, sold and disposed of”.
Comment: We see a large number of patients from poor socio-economic status coming to PGI Chandigarh as well. Many of them die, while others are left paralysed. If we can find the root cause of these symptoms, this may help in avoiding these fatalities. Trying to find the pieces of this fascinating medical jig saw puzzle is also a great challenge. I am hopeful that Indian scientists will be able to rise above their egos, and together find the reasons for these cases of 'brain fever'