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Muzaffarpur Encephalopathy: A multi-ministry coordination and comprehensive action plan is the answer – by Dr K K Aggarwal

The outbreak of acute encephalitis syndrome (AES) in Muzaffarpur has claimed 114 lives so far. AES has been occurring every year for the past so many years with no solution in sight.

A visit by the Chief Minister of the state, or the state or central health minister is alone not the answer.

Since this is a local outbreak in Muzaffarpur and adjoining districts, the state should declare a public health emergency and invoke the Essential Commodities Act. This would bring the entire state health services, both government and private sectors, under the gambit of the Essential Commodities Act and the Essential Services Maintenance Act as ‘essential medical services’.

A multi-ministry coordination and comprehensive action plan should be drawn up and acted upon.

  • The Health Ministry should arrange for 24×7 ICU, ventilators, ambulances. Asha workers should be provided with glucometres and thermometers so that they can monitor the temperature and blood sugar levels. They should be taught how to prevent deaths due to hypoglycaemia in children. They should be advised to give 1 teaspoon of sugar sublingually (not as a drink) every 20 minutes in children less than 15 years of age. It should be made sure that the child does not clinch teeth or swallow the sugar. All healthcare providers should do home to home survey.
  • ICMR, DST and medical colleges should spearhead research in the illness to understand its cause and to prevent its future outbreaks.
  • The Agriculture Ministry should act on rotten litchis, should advise farmers to destroy the rotten fruits, and should also create awareness on the harms of eating only litchis by malnourished children.
  • The Ayush Ministry should find out if the traditional medicine systems have some alternative treatment to offer.
  • The Women & Child Development Ministry should look after the nutrition of the children in the area. An Evening Day Meal Scheme for the children can be started in addition to the Mid Day Meal Scheme already in place.
  • The Transport Ministry and the Civil Aviation Ministry should arrange for airlifting of patients and shift them to other states for management of the disease, as and when required.
  • The Law Ministry should ensure that no law and order problem arises in such situations and the action plan is implemented smoothly.
  • The Environment Ministry should take all measures to prevent heat stroke in the area by providing makeshift shelter homes.
  • The Military can be called in for house to house visits to identify probable cases. When Zika virus threatened Brazil in 2015-16, when it was preparing to host the 2016 Olympic Games, the army was called into action and asked to join the efforts to control the virus, which was made into a public movement.

It’s time some concrete steps are taken to prevent recurrence of this illness.


Lychee Hypoglycaemia and Lychee Encephalopathy

Hungary malnourished children with poor glycogen reserve in liver eat whatever they find in Lychee orchards leading to hypoglycaemia triggered by MCPG in fruit followed by failure of neoglucogenesis leading to fatty acid metabolism with production of by-products responsible for encephalopathic changes.

The consumption of Lychee fruit (especially unripe) followed by fasting, consumption of Lychee fruit in the morning after overnight fasting, and doing only Lychee fast by malnourished children are associated with the outbreaks of hypoglycaemia and encephalopathy with high mortality. About 10% deaths in the affected patients are seen in severe hypoglycaemia.

Metabolites of hypoglycin A and methylene-cyclo-propyl-glycine MCPG are found in two-thirds of urine specimens from the victims.

Another similar fruit is Ackee fruit (Blighia sapida) a common food source in West Africa and the Caribbean, especially among impoverished and malnourished children.

Edible when ripe and properly prepared, the unripe fruit contains high concentration of the toxin, hypoglycin A, which, when metabolized, inhibits long chain fatty acid breakdown and transport into the mitochondria.

Toxicity manifests as a Reye-like syndrome with vomiting, hypoglycaemia, seizures, and coma occurring between 2 and 48 hours after ingestion of unripe ackee fruit. Without rapid correction of hypoglycaemia, the death rate approaches 100 percent.

Pathologic findings on liver biopsy include cholestasis and centrilobular necrosis.

Symptoms of Hypoglycaemia

  • Neurogenic (autonomic) symptoms
  • Neuroglycopenic symptoms

The severity of symptoms may or may not predict the severity of the hypoglycaemia.

Neuroglycopenic symptoms typically occur at lower plasma glucose levels than autonomic symptoms. However, with repeated episodes of hypoglycaemia, the threshold glucose concentration for adrenergic symptoms decreases, such that they may not appear before the onset of neuroglycopenic symptoms.

Autonomic symptoms of hypoglycaemia in children and adults are due to increased adrenergic activity, and include sweating, weakness, tachycardia, tremor, and feelings of nervousness, and/or hunger.

Neuroglycopenic symptoms include lethargy, irritability, confusion, behaviour that is out of character, and hypothermia. In extreme hypoglycaemia, seizure and coma may occur.

In infants, symptoms of hypoglycaemia are nonspecific and include jitteriness, irritability, feeding problems, lethargy, cyanosis, and tachypnoea.

When hypoglycaemia is suspected, a rapid (bedside) plasma glucose determination should be performed.

If it is low (≤50 mg/dL for this initial bedside measurement), critical samples should be obtained before treatment, if this can be done without delaying treatment. Obtaining critical samples before the initiation of therapy, and collecting the first voided urine sample, can dramatically improve the ability to diagnose the aetiology of the hypoglycaemia and simplify the subsequent diagnostic evaluation.

These symptoms and signs occur at plasma glucose concentrations between 10 and 50 mg/dL. Severe and repeated episodes of hypoglycaemia can result in permanent central nervous system damage, and occasionally in death.


  • IV dextrose
  • Till it is given give one TSF sugar with one drop of water sublingual every twenty minutes.

The Ministry of Health Findings

In 2015, in a letter to the Principal Secretary (Health), Government of Bihar, Dr Jagdish Prasad, the then Director General of Health Services, had shared the findings of a study carried out in 2013 on the outbreaks of AES in Muzaffarpur, including the plan and implementation of the study in 2014, with an aim to reduce the associated mortality and morbidity. This study was carried out jointly by NCDC, NVBDCP and ICMR. The US CDC provided technical support for the study.

Hypoglycaemia came up as a distinctive finding of the study and its management improved prognosis. It necessitates availability of glucometre with all Asha workers and primary healthcare centres.

Hence, it was advised to monitor blood sugar in the patients. The letter further said that “the morbidity may further be averted if the parents are sensitized to provide children a good quantity of complex carbohydrate meals before bed time such as to maintain normal levels of glucose throughout the night hours.” Malnutrition in the rural low socioeconomic group children needs to be prevented or reduced.

In the last few days, I have also been talking about starting an ‘evening day meal, to rural children on the lines of mid-day meal in these months (May, June, July).

Metabolites of certain compounds [hypoglycin A and methylenecyclopropylglycine (MCPG)], which are naturally present in litchi fruits, were found in the urine of the patients. These compounds cause hypoglycaemia. Children, especially in rural areas of Muzaffarpur, should avoid eating litchi fruits.

These cases mostly present in early morning hours; hence, a trained doctor or a nurse should be posted from May to July, especially during the night.

The need to strengthen the diagnostic and critical care capacity at all levels of healthcare was also emphasized upon. This would facilitate timely diagnosis and management of such cases.

Public Health Answer: Regulate Lychee production and consumption so that the rotten unripe Lychee is not consumed by children.

Update: Are we missing re-feeding syndrome?

We know Lychee has been involved in Muzaffarpur children death.

  • Mostly children
  • Mostly malnourished
  • Present with convulsions
  • High mortality in spite of replacing sugar levels
  • Toxins hypoglycin A in lychee and their components in patient’s urine
  • Mostly absence of fever

What might be happening?

In significantly malnourished children, who have not eaten food for more than three days, if they are given oral (lychee in this case), enteral, or parenteral nutritional replenishment, it can cause electrolyte and fluid shifts that may precipitate disabling or fatal medical complications.

The refeeding syndrome is marked by Hypophosphataemia, Hypokalaemia, congestive heart failure, peripheral edema, Rhabdomyolysis, seizures, fever and Hemolysis. Hypophosphataemia is the hallmark of the syndrome and predominant cause of the refeeding syndrome.

Rapidly treating hypoglycaemia with IV or oral sugar will harm without managing the electrolyte imbalance. The best food in these situations is sugarcane juice and not lychee.

The risk of hypophosphataemia during refeeding appears to be greater in patients who are more severely malnourished and at lower percent of ideal body weight. People may have higher haemoglobin levels due to dehydration and intravascular volume depletion.

The pathogenesis of hypophosphataemia begins when stores of phosphate are depleted during episodes of starvation. When nutritional replenishment starts and patients are fed carbohydrates, glucose causes release of insulin, which triggers cellular uptake of phosphate (and potassium and magnesium) and a decrease in serum phosphorous levels. Insulin also causes cells to produce a variety of depleted molecules that require phosphate (adenosine triphosphate and 2,3-diphosphoglycerate), which further depletes the body’s stores of phosphate.

The subsequent lack of phosphorylated intermediates causes tissue hypoxia, myocardial dysfunction, and respiratory failure due to an inability of the diaphragm to contract, haemolysis, rhabdomyolysis and seizures.

Risk factors for the re-feeding syndrome include low baseline levels of phosphate, potassium, or magnesium prior to re-feeding the patient and little or no nutritional intake for the previous 5 to 10 days. Patients are at the highest risk for the re-feeding syndrome in the first one to two weeks of nutritional replenishment and weight gain.

Generally, the risk progressively dissipates over the next few weeks if there has been consistent forced intake and weight gain.


Treat these patients as re-feeding syndrome and not as simple hypoglycaemia. Hypophosphataemia or hypokalaemia can be treated orally with sodium phosphate or potassium phosphate in two divided doses to correct deficits.

The author Dr K K Aggarwal is President of Heart Care Foundation of India.


More Suggestions

Dr R N Gupta

  • It is clear that there is a dearth of expert doctors in the hospital and an absence of proper system for tackling such a situation. That’s why the death is increasing day by day.
  • Hope the govt will act accordingly.
  • In addition to it, I would like to suggest to constitute an expert committee of specialists, including a microbiologist and a pharmacy expert (PhD in Pharmacy).

Dr K K Kalra

  • The disease should be made notifiable.
  • Post mortem should be done.
  • Documentation of clinical profile should be standardised and an expert group should do the audit of these cases to find the root cause.

Dr O P Sharma

  • It is not the first episode in the area. Hence the answer is mass vaccination.

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