Encephalitis may not be real cause of children's deaths in Muzaffarpur; investigation necessary into possible toxins in lychees

Any instance of Acute Encephalitis Syndrome (which is, in itself, a misnomer), anywhere in the country, is seen as yet another instance of acute viral encephalitis, supposedly caused by the Japanese encephalitis virus, and is seen as yet another opportunity to order mass vaccination against it.

Authorities appear to think that vaccination against Japanese encephalitis is the panacea for all such outbreaks. Hardly any thought is given to first confirm the exact etiology. As a result, the move fails to contain the recurrent outbreaks that lead to deaths of hundreds of children every year in different parts of the country.

The case of Bihar is very peculiar. Recurrent outbreaks have been occurring in Muzaffarpur and other adjoining districts for the past several years with a very distinct seasonality. All the known features of the outbreak — victims being poor, young rural children of a narrow age group, involvement of only malnourished children, failure to identify an etiological agent, including the Japanese encephalitis virus, despite intensive investigations year after year, absence of the infection in vector mosquitoes — point toward non-infectious pathology.

Involvement of Japanese encephalitis as a probable etiology behind these outbreaks was also ruled out by a recent entomo-virological study from Muzaffarpur. A few researchers have identified these outbreaks as being caused due to heat stroke, and others have indicated the possibility of methylenecyclopropyl-glycine (MCPG) as a toxin responsible for a hypoglycemic encephalopathy. All the available pointers lead toward a non-infectious, probably a toxin-mediated etiology, where lychee-cultivation is to be blamed. It is not a mere coincidence that outbreaks with similar features are reported from yet another litchi-producing region of the country, Malda, and from other countries like Vietnam and Bangladesh. Whether the culprit is a biological toxin contained in the fruit itself, or any pesticide employed in the cultivation, or some other toxin involved, needs to be determined.

‘Environmental toxins’ may be a possibility 

All outbreaks need not have been due to one specific disease or syndrome. Cases may even be occurring sporadically, but whether sporadic and epidemic cases represent one syndrome needs clarification.

Currently, there seem to be two sets of these outbreaks dominating the entire scenario. The first one caused by viruses like Japanese encephalitis, Chandipura, influenza, enteroviruses, etc, or bacteria such as Orientia tsutsugamushi (e.g. scrub typhus in Gorakhpur). Another group of these outbreaks is caused by environmental toxins like cassia occidentalis, toxins in lychee fruits like MCPG and MCPA (hypogycins), etc. While the former group constitutes a true encephalitic illness, the latter is not actually encephalitis but a multi-system disease in which the brain is involved secondarily. However, this key difference is often not appreciated owing to faulty case definition that leads to unnecessary investigations.

Four health professionals, including this author, investigated fatal, recurring outbreaks of acute brain illness in many districts of western Uttar Pradesh, Uttarakhand and Haryana during late 1990s and early 2000s. It was found that the cases were not of encephalitis but a Reye-like encephalopathy that presented in the form of an outbreak every year during winter months. Later, we found it was caused by the consumption of the beans of a ubiquitous weed, c_assia occidentalis,_ that lead to the genesis of Acute HME syndrome.  The anthroqimones present in the beans were responsible for this syndrome. This was a landmark study that presented a new paradigm in outbreak investigations in India and some neighbouring countries. It also brought the role of environmental toxins to the forefront.

When we retrospectively analysed some of the unexplained outbreaks in the past, like in Bengaluru, Haryana, Punjab and Chandigarh, they all pointed towards HME syndrome secondary to cassia consumption. All these illnesses were confused with encephalitis or with Reye syndrome. In fact, we can now claim that any Reye-like illness presenting in an epidemic form must be investigated for the possibility of some environmental toxin as a putative etiologic agent.

In a similar instance in western Uttar Pradesh, where recurrent outbreaks of an unknown brain disease were responsible for the deaths of hundreds of young poor children year after year, the Union government instituted massive campaigns of Japanese encephalitis vaccination in many districts. But they failed to have any impact. Later, it was discovered that the consumption of a local weed, cassia occidentalis and a multisystem illness, “acute hepatomyoencephalopathy syndrome" (erroneously referred as to “Saharanpur Encephalitis") was responsible for the recurring outbreaks, not viral encephalitis. Massive health education measures led to the disappearance of the disease in just a few years.

Coordinated approach necessary

Currently, the investigation of the outbreak in India looks like five blind people describing an elephant. So, what India needs is a well-coordinated, systematic outbreak investigation approach with an appropriate methodology to investigate all these recurring outbreaks of an unknown etiology, rather than clubbing them under one head of viral encephalitis and resorting to empiric preventive measures like mass Japanese encephalitis vaccination. A thorough approach would entail first defining the clinical entity, histopathological investigations including autopsies, if required, and detailed epidemiological and toxicological investigations in a coordinated manner.

A precise case definition is necessary for any outbreak investigation. Strict case definitions were applied in only a few investigations, and in all of them, the disease was clinically not encephalitis. Outbreak investigations in India have been lacking on this front, right from the days of the “Jamshedpur fever” described by the late Dr Najeeb Khan in 1954. Similarly, the enigma of the so-called ‘Nagpur encephalitis’, which was earlier attributed to the Japanese encephalitis virus and later to heat hyperpyrexia, still persists.

Coming to the Muzaffarpur illness, these recurrent outbreaks are caused by some toxins involved in either the litchi fruit itself, like PCPG or MCPA, or some hitherto undiagnosed compound used in the litchi cultivation. The disease is not actually encephalitis but an encephalopathy that needs further elucidation. Rapid correction of hypoglycemia may prevent death in a few cases.

The author is a former national convener of the Indian Academy of Pediatrics Committee on Immunisation and is a pediatric generalist and neonatologist at the Mangla Hospital and Research Centre in Bijnor.