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Acute Encephalitis Syndrome (AES): Introduction, Reason & Details Theories

112 child losses their lives in Bihar’s Muzaffarpur, unfortunately, the death toll is not stopping. Bihar Chief Minister Nitish Kumar along with his deputy Sushil Kumar Modi had visited the SK Medical College and Hospital on Tuesday. State Chief Secretary Deepak Kumar told reporters in Patna that the CM was satisfied with medical facilities at SKMCH. Nitish also ordered 24-hour availability of doctors to deal with an emergency situation, the chief secretary added.

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AES is a broad term involving several infections and affects young children. The syndrome can be caused by viruses, bacteria or fungi. In India, the most common cause is the virus that causes Japanese encephalitis (JE). Health Ministry estimates attribute 5-35% of AES cases to the JE virus. In the latest outbreak in Muzaffarpur, the cause is yet to be clinically identified in most of the children.


What is Acute Encephalitis Syndrome – AES?

It wasn’t until 2008 that the WHO (World Health Organization) defined acute encephalitis syndrome. A case of AES is defined as a person of any age, at any time of the year, who has an acute onset of fever and a change in mental status – with symptoms ranging from confusion, disorientation, coma or the inability to talk.

The AES has traditionally been attributed to viruses, although research has indicated that other sources ranging from bacteria to parasites can also be causative agents. Japanese Encephalitis (JE) is the most common form of the disease worldwide, with an estimated 15,000 deaths annually.


What Does it Mean for Doctors on Ground?

In India, Japanese Encephalitis has traditionally been the most important cause of AES. But this has resulted in an overemphasis on parallel AES and JE surveillance. But take 2014 for instance: the total number of AES cases and deaths from India were 10,853 and 1,717 respectively. However, for JE, the figures were 1,657 and 293.

A 2015 study by the King George’s Medical University (KGMU) in Lucknow described AES as a “mixed pot” and said that the 2014 data “implies that other undiscovered or neglected etymology of AES, which accounts for about 85%, also exists and should also be looked for.”

The wide range of causal agents, combined with the rapid neurological impairment, mean that for doctors on the ground, the implications are fatal. A doctor at the Baba Raghav Das (BRD) Medical College in Gorakhpur told News18, “There is a very small window at tertiary centers. But even at primary healthcare centers, the problem boils down to the lack of knowledge about the cause. What caused it, families will ask us. And we just don’t know.”

In Bihar, the Directorate of Health Services (DHS) has said that the JE virus has caused only two of the total AES cases this year (this was when the total cases were 342). AES, doctors suspect, could be caused by infections ranging from scrub typhus, dengue, mumps, measles or even Nipah or Zika virus. The cause for the outbreak in Muzaffarpur is so far unidentified.


When did India First Report the Virus?

Since the first report of the JE virus in Vellore, Tamil Nadu, in 1955, the study of AES and JE have paralleled each other. In fact, the first outbreak of JEV reported in Bankura, West Bengal in 1973 also saw sporadic cases of AES and outbreaks leading to deaths. Before 1975, very few cases of JE were identified in India, while from 1975 to 1999, more cases of JE were reported with frequent outbreaks that led to the development and identification of areas where JE was endemic: the Gangetic plains, parts of the Deccan and Tamil Nadu.


Disease Changed Over Years

It was after 2000 that there came a dramatic change in the understanding of AES: with a sharp rise in AES cases, which were not caused by the JE virus. In 2012, AES cases shifted towards the JE etymology – or simply, the emphasis shifted towards cases where the JE virus was the cause. On the basis of reported cases, the government identified Uttar Pradesh, Bihar, Assam, West Bengal and Tamil Nadu as JE endemic zones.


Is AES Transmitted by Mosquitoes?

As more cases were reported, varying research also threw up new questions that needed to be answered. In 2012, the National Institute of Virology (NIV) was collected 1,000 samples of cerebrospinal fluid (CSF) from children admitted at BRD Medical College and was able to identify 100 isolates of organisms called enteroviruses (EV) – particularly the EV 89 and EV 76 types.

This was something that scientists in NIV had been warning off since 2005, but this made it clear that these enteroviruses spread through contaminated water and triggered symptoms similar to JE. Essentially, implying that it wasn’t just mosquito bites that made children sick, but also drinking contaminated water.

The same year saw another study, this time by scientists from the US Center for Disease Control and Prevention arguing for classifying ‘encephalitis’ outbreaks as Acute Neurological Syndrome (ANS) based on the hypothesis that the causal agent was a toxin prevalent in litchi fruit.

The joint report with the National Centre for Disease Control (NCDC), under the Union Health Ministry, compared the outbreak to Ackee fruit poisoning reported in the Caribbean islands and Western Africa. It also added that the correction of low blood glucose in patients had helped reduced mortality from 44 percent in 2013 to 26 percent the next year.

The toxin was identified as methylene cyclopropyl glycine that was found to rise in litchi seeds – although this was discounted almost immediately by the National Research Centre for Litchi (NRCL) in Muzaffarpur, who said numerous studies had not been able to detect any toxin in the fruit pulp, root, seeds or skins.


Can AES be Transmitted Through Mites?

In August last year, researchers from the Indian Council of Medical Research and the BRD Medical College presented new findings as to the cause of AES: a mite, too small to be seen by the naked eye, which causes a bacteria leading to scrub typhus. The study said, “Hospital-based surveillance studies indicated that about one-fifth of the patients with acute febrile illness were due to scrub typhus. Further studies are required to identify the etymology of about a third of AES cases that test negative for scrub typhus, JEV, or dengue.”

In other words, the majority of AES cases were actually scrub typhus cases – a finding, they argued was key, since the disease can be treated easily if detected early. This wasn’t the first time such a claim had been made, with studies published as early as 2014 linking scrub typhus to AES.


Link Between AES and Hypoglycaemia

The intersection of AES and hypoglycemia has been studied at Muzaffarpur in Bihar, Vietnam, and Bangladesh. Doctors explain that hypoglycemia isn’t a symptom of AES, but a sign. In Bihar, convulsions are found in a combination of hypoglycemia which is caused due to malnutrition. 2014, a research paper, ‘Epidemiology of Acute Encephalitis Syndrome in India: Changing Paradigm and Implication for Control’ pointed out that both Bihar’s Muzaffarpur and Vietnam’s Bac Giang province have litchi orchards in the neighborhood.

“The possible association with some toxin in litchi or in the environment needs to be documented. Methylene cyclopropyl glycine (MCPG) which has been known to be a content of litchi fruit has been shown to cause hypoglycemia in experimental animals,” the study said.

But while the litchi connection remains a contentious issue, often debated by doctors and researchers – what can’t be denied is that malnutrition makes the area particularly vulnerable. At both eastern UP and Bihar, where AES cases dominate, National Family Health Survey-4 data show that in 2015-16, 48 % of children aged less than five in Bihar were stunted – the highest in India.


Data & Information collected from News18

Written by Ashutosh Kumar

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