Re: India Encephalitis 2014 - 184 fatalities
Re: India Encephalitis 2014 - 184 fatalities
Published Date: 2014-06-13 02:21:14
Subject: PRO/AH/EDR> Japanese encephalitis & other - India (04): (BR)
Archive Number: 20140613.2536936
JAPANESE ENCEPHALITIS AND OTHER - INDIA (04): (BIHAR)
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[1] Comment
Date: Wed 11 Jun 2014
From: T Jacob John <tjacobjohn@yahoo.co.in> [edited]
This is regarding the posting of 9 Jun 2014: Japanese encephalitis & other - India (02): (BR), archive number 20140609.2527999.
The Muzaffarpur [district, Bihar state] outbreaks, annually recurrent, are quite different from many other outbreaks of Japanese encephalitis [JE] in various parts of India, including some parts of Bihar [state].
(1). The season: JE has a post-monsoon seasonality, obviously due to increase in _Culex_ mosquitoes -- Muzaffarpur outbreaks are during May-June (with some in April and some in July), and with onset of monsoon rains the outbreak stops.
(2). The clinical illness: The clinical and laboratory parameters are not like encephalitis (ICD 10 A 86), but typical of encephalopathy. Onset is sudden, without any prodromal phase, typically in the early morning hours. Till previous evening the child [has been] well. Cerebrospinal fluid [CSF] is clear with no increase in cell count. Low CSF sugar and low blood sugar are documented in some 40 per cent of children. Thus, the diagnosis is acute encephalopathy (ICD 10 G 92 and 93). The cause is non-infectious.
The reason, I believe, why earlier investigators (and there were several teams of experts, including from CDC, who had investigated this problem over a few or even many years) missed this clear distinction was that Japanese encephalitis occurs typically in recurrent seasonal outbreaks, and any acute brain disease occurring in annual seasonal outbreaks are taken for granted as some encephalitis. Once you diagnose encephalitis, the direction of investigation is to take clinical samples and look for viruses.
Those who have not kept up with the literature over the decades may not be aware of the many reports of outbreaks of acute encephalopathy in India (Jamshedpur fever; Nagpur encephalopathy; Reye syndrome outbreak, hepatomyoencephalopathy) and in Thailand (Udorn encephalopathy). So, acute encephalopathy can occur in outbreaks; when outbreaks occur in annual seasonal recurrent fashion, there has to be some factor(s) with repetitive behavior, triggering or actually causing the disease in clusters. Epidemiological puritans can argue if non-infectious encephalopathy outbreaks are truly outbreaks or merely clusters.
(3). Muzaffarpur is famous for lychee [litchi] orchards. May and June are lychee harvest season. The strong spatial and temporal association of the outbreaks with lychee harvesting have been noticed by all previous investigators, but they did not pursue the association in depth. Similar lychee-harvest-associated acute encephalopathy outbreaks have been recently reported in Bangladesh and Viet Nam. In Bangladesh the diagnosis was encephalopathy -- hence pesticides were considered the noxious agent. In Viet Nam, lychee-associated viruses were explored. Even in Muzaffarpur, fruit-eating bats have been noted, and some investigators proposed some bat viruses.
Malda in West Bengal is another lychee cultivating region in India, and this year [2014], a similar outbreak has been reported in the media (
http://timesofindia.indiatimes.com/...ills-8-kids-in-Malda/articleshow/36225598.cms).
(4). The Jamaican vomiting disease (acute hypoglycemic encephalopathy) is triggered by eating unripe ackee fruit [_Blighia sapida_], which contains a toxin called hypoglycin A (Methylenecyclopropylalanine, MCPA). Ackee and lychee belong to one family, namely soapberry (_Sapindaceae_). Lychee seeds have been shown to have a lower analogue of MCPA, namely methylenecyclopropylglycine (MCPG). In animal experiments, both MCPA and MCPG interfere with fatty acid oxidation, in mitochondria, thus causing acute encephalopathy like in Jamaican vomiting disease.
We all know lychee is a safe and enjoyably edible fruit, very popular. Eating lychee cannot simply be blamed for the Muzaffarpur (or the Bangladesh and Viet Nam) outbreaks. Yet, the presence of MCPG in lychee seeds must be pursued -- my investigation this year [2014] was aimed at investigating cases for "metabolic fatty acid derangement" and lychee seeds and fruits for MCPG or associated substances. Unfortunately, I was given some colleagues who interfered with funding for the studies, and thus I lost the opportunity to complete the investigations this season. Just 4 days ago, I received word that funding may be back on track, but that is too late for this year.
The pathogenesis appears to be blocked gluconeogenesis -- why children go into gluconeogenesis has to be investigated -- most victims are undernourished, and probably liver glycogen-depleted. So perhaps their glycogenolysis is inadequate to supply brain cells with energy source, namely glucose. Therefore, gluconeogenesis is necessary, but some toxin blocks the pathway -- like in any fatty acid metabolic derangement syndrome (usually of genetic origin). These are all hypothetical, to explain what we have observed. Organic acidemia and aciduria would have confirmed the diagnosis, but this year I did not have funds to pursue this.
In summary, the Muzaffarpur (and Malda in India, Bangladesh and Viet Nam) seasonal brain disease outbreaks in children are a peculiar acute encephalopathy, non-infectious in origin, probably predisposed by undernutrition and somehow associated with either lychee seed swallowing, or some such unknown link, to be investigated next year. Please be sure I am not giving lychee a bad name; please eat lychee to your hearts' content, for lychee is a great and safe fruit.
I am attaching a recent hypothesis note published in: John TJ, Das M. Acute encephalitis syndrome in children in Muzaffarpur: hypothesis of toxic origin. Current Science, 2014; 106: 1184-1185 (10 May 2014).
--
T Jacob John
<tjacobjohn@yahoo.co.in>
...
http://www.promedmail.org/direct.php?id=2536936
