Friday, June 21, 2019

AES outbreaks in Muzaffarpur: Lessons to be learnt

Dr KK Aggarwal

In 2015, in a letter to the Principal Secretary (Health), Government of Bihar, Dr Jagdish Prasad, the then Director General 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 the year 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.

Hypoglycemia came up as a distinctive finding of the study and it was observed that its management improved prognosis. Hence, it was advised to monitor blood sugar in these patients. This necessitates availability of glucometer with all Asha workers and primary health care centers.

Another fruit similar to litchi is Ackee fruit (Blighia sapida) a common food source in West Africa and the Caribbean, especially among impoverished and malnourished children. 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, hypoglycemia, seizures, and coma occurring between 2 and 48 hours after ingestion of unripe ackee fruit. Without rapid correction of hypoglycemia, the death rate approaches 100%. Pathologic findings on liver biopsy include cholestasis and centrilobular necrosis.

Symptoms of hypoglycemia include neurogenic (autonomic) and neuroglycopenic symptoms. Severity of symptoms may or may not predict the severity of the hypoglycemia.

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

Autonomic symptoms of hypoglycemia 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, behavior that is out of character, and hypothermia. In extreme hypoglycemia, seizure and coma may occur.

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

When hypoglycemia 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 etiology of the hypoglycemia 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 hypoglycemia can result in permanent central nervous system damage, and occasionally in death.

Treatment of hypoglycemia is IV dextrose; till it is given, 1 tsf sugar with one drop of water should be given sublingually every 20 minutes.

The letter further says 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 a 'evening day meal’, to rural children on the lines of mid-day meal in these months.
Metabolites of certain compounds (hypoglycin A and methylenecyclopropylglycine or MCPG), which are naturally present in litchi fruits, were found in the urine of the patients. These compounds cause hypoglycemia. Children, especially in rural areas of Muzarffarpur 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 diagnostic and critical care capacity at all levels of health care was also emphasized upon to facilitate timely diagnosis and management of such cases.

Following were a few of the recommendations:

Recommendations to reduce mortality


Rapid assessment and correction of hypoglycaemia

          Through IEC and sensitisation workshops - Increase awareness among community, field level health workers (ASHAs, Balwadi/Anganwadi workers, Auxiliary Nurse Midwives, Multipurpose workers, School health staff etc.) and health staff at PHCs/CHCs/referral treatment centres on - symptoms of this illness for early detection, - about availability of free ambulatory services for early transportation, - about availability of facilities for rapid assessment and correction of glucose at nearest government health facility as well as - about availability of specialised treatment facilities at identified referral centres for early life saving interventions.
          Provision of adequate numbers of glucometers to all PHCs/CHCs/referral treatment centres for timely detection of low blood glucose
          Train PHCs/CHCs/referral treatment centres staff on assessment of glucose using glucometer in children presenting with history of seizures and/or altered sensorium
          Provide and train staff of PHCs/CHCs/referral treatment centres on protocol for correction of hypoglycaemia in children with suspected outbreak illness/ altered sensorium
Strengthen diagnostic and critical care capacity at all levels of health care

          As characteristically most cases report sickness in early morning hours, availability of a trained medical doctor during night in the outbreak season months of May to July at all PHCs/CHCs in the district is essential for early detection and management of cases.
          Provide and train staff of PHCs and CHCs on protocol for first line of life saving health care
          Strengthen diagnostic facilities at all identified referral treatment centres for timely and appropriate diagnosis
o     Strengthen laboratory facilities for electrolytes, liver function tests, CSF cytology/biochemistry and bacteriology tests
o     Post adequate number trained pathologists/laboratory technicians for round the clock specimen collection, testing and reporting
o     Provide adequate numbers of pulse oximeters
o     Provide facilities of EEG and post EEG trained technicians
o     Provide facilities of CT Scans and MRI brain and post trained Radiologists/Technicians
o     Encourage collecting biopsy specimens and histopathology testing to confirm a tissue diagnosis of encephalopathy
          Strengthen specialised manpower for assessment and treatment of cases
o     Post adequate number of paediatricians at each of the identified referral treatment centres to handle increased case load during outbreak season
o     Short term deputation of a neurologist and a critical care specialist during outbreak season
o     Provide treatment guidelines and train paediatricians of the identified referral treatment centres on this treatment protocol
o     Provide training in critical care to paediatricians of the identified referral treatment centres

Purpose: Reduce illness


Through IEC - Increase awareness among community on providing at night-time a full meal of home-made complex and low glycemic index carbohydrate (whole intact grains - such as barley (Jav) and oats (Jai); this would help maintain a stable postprandial blood glucose and possibly minimise risk of early morning fasting hypoglycemia.

Improve general nutritional status
- Undertake projects to reduce malnutrition among young children, especially the rural children of low socioeconomic status

Considering the finding of detection of hypoglycin and MCPG (natural hypoglycemic compounds known to be present in fruits of litchi family) metabolites in urine specimens of a large proportion of case-patients, it would be advisable to make efforts by IEC to minimise consumption of litchi fruits among young children in rural areas of affected district, pending further investigations in this regards.

It is difficult to understand why these recommendations did not get implemented.

Dr KK Aggarwal
Padma Shri Awardee
President Elect Confederation of Medical Associations in Asia and Oceania   (CMAAO)
Group Editor-in-Chief IJCP Publications
President Heart Care Foundation of India
Past National President IMA

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