School of Public Health and Community Medicine

Acute Encephalitis Syndrome Outbreaks in India – an ongoing puzzle.

image - India AES Cases

By Ronan Kelly. 

October 1 2014

Ronan Kelly (USA) is a Senior Moderator at www.FluTrackers.com, with an interest in outbreaks in India.

Past history of AES in India

Acute Encephalitis Syndrome (AES) is a growing problem in India. The first major outbreak was in West Bengal in 1973 involving 700 cases and over 300 deaths. Subsequent serological studies identified the Japanese Encephalitis (JE) virus as the cause. (1,2) Between 1978 and 2007, over 100,000 cases of AES with a case fatality rate (CFR) of almost 33% were reported from 13 different states. It was widely presumed that JE was the predominant aetiological agent in these outbreaks. (3,4) However, a study of patients admitted between 1985-1988 at King George’s Medical College (now Shahuji Maharaj Medical University) in Lucknow revealed bacterial meningitis as a diagnosis in 18% of apparent AES patients with JE indicated in only 12% of cases. Measles, Mumps, Malaria also played a part to some smaller degree, but 50% of the cases remained undiagnosed. Reye’s Syndrome was not found in any case.(5) An investigation of repeated AES outbreaks in Saharanpur in the early 2000s found that children were eating beans of the Cassia occidentalis plant which was causing acute hepatomyoencephalopathy. These patients were being misdiagnosed as AES cases. Local government organized removal of the plants and provided information programs for residents. As a result, fatalities in the district dropped from around 100 per year to zero in 2010. (6,7)

Current epidemiology (2008- 2014)

Between Jan 1, 2008 and Aug 27, 2014; 44,097 cases and 5,728 deaths were reported due to AES in India. This figure represents a significant increase in the recent annual number of reported cases even as the CFR has dropped to around 13%. An average of 8,139 cases per year have been reported for 2011-2013 an increase of 220% over the period 2003-2007.(8,9) This is likely an underestimate. Government statistics do not generally include cases that never make it to hospital, and AES outbreaks predominantly affect rural communities with poor access to healthcare who are less likely to be notified as AES cases. Much of the recent increase is accounted for by a surge in reported cases in Assam (cases tripled in 2011 and stayed at that level ever since) and West Bengal (cases jumped sevenfold in 2011 and doubled again since then). Nationally, since 2008, only 6,825 (15.5%) patients tested positive for JE. In many cases, the causative agent remains elusive. 

The State of Uttar Pradesh has experienced periodic AES outbreaks since 1978, but following a major outbreak in 2006, the annual case load has exceeded 3,000 patients, three times the level prior to that year.(10) The State has accounted for almost half (over 20,000) of cases and 3,560 deaths since 2008. Only 8.1% of the cases have been confirmed for JE and the State has annually hosted a variety of investigative teams. In recent years, various enteroviruses such as EV-76, EV-89 as well as coxsackievirus B5 and echovirus 19 have been found associated with AES cases.(11,12)  It has been suggested that shallow wells pumping up contaminated drinking water are a major problem. However, making any conclusions about what is causing AES outbreaks in Uttar Pradesh is hampered by poor patient record systems. A study from Kushinagar in 2011-2012 found that record keeping, test results and vaccination history were so poor that “inferences about the epidemiology and etiology of AES could not be made”.(13)

One of the conclusions that can be drawn from the various studies in Uttar Pradesh is that the cause of AES outbreaks can vary from location to location. This is also true for the country at large. For example while outbreaks in Assam have consistently tested >35% positive for JE since 2008, Chandipura Virus has been implicated in outbreaks in Gujarat. West Nile Virus (WNV), as in Kerala in 2011, may also be playing a part.(14) But some outbreaks remain a mystery. One intriguing outbreak has drawn much attention. The State of Bihar has seen periodic outbreaks for over twenty years. Recent recurrent outbreaks centered on Muzaffarpur appear unusual. One such outbreak of unknown aetiology occurred in 2012. Rather than peaking in September as is usual for JE, on this occasion the peak happened in June. None of the 334 patients tested positive for JE and at least 118 (35.3%) of them died.(15) This year (2014), the outbreak lasted through June and early July and resulted in around 200 deaths. None tested positive for JE, Chandipura, Nipah or WNV. The victims were mostly children, mostly poor, mostly malnourished. The outbreak coincided with the litchi (lychee) picking season. One hypothesis is that a toxin in unripe litchis leads to hypoglycaemic syndrome in under nourished children causing symptoms that are being diagnosed as AES. (16) Others suggest that the outbreak is really a form of encephalopathy brought about by heatstroke. (17) In parallel with Uttar Pradesh, most cases got their drinking water from shallow hand pumps, but I am not aware of any enteroviruses being identified.(18) Investigations over the past two years have resulted in local treatment recommendations such as rapid assessment for and correction of hypoglycaemia. Preliminary study suggests that this may have reduced the mortality rate in Muzaffarpur this year down to 26%.(19,20)

India’s AES outbreaks are complicated. Without any rapid diagnosis in outbreak situations, patients are treated symptomatically. Prevention would be a much better strategy, but to ensure that scarce resources are being well utilized, each individual outbreak must be investigated. Areas where JE is prevalent should receive timely vaccination prior to the next transmission season. JE vaccination should be considered in scheduled childhood immunizations in endemic areas. Use of JE vaccine must be weighed up between disease incidence and vaccine side effects, but is warranted in highly endemic areas. Improvements in infrastructure, healthcare, nutrition, access to clean water and proper sanitation will have to be made, probably at considerable cost. (This would also help to reduce the 100,000 diarrhoea deaths each year, but that’s another story). Local environmental factors like the Cassia in Saharanpur, litchis in Muzaffarpur and water quality in Gorakhpur must be examined and proven or discarded.

There is still much to be done. Images of children crowded 3 to a bed at BRD hospital in Gorakhpur, while their parents hold up the IV bags need to be relegated to history. The value of epidemiological investigation is unquestionable, particularly for outbreaks of unknown aetiology such as in Bihar.

References:

(1)   Bandyopadhyay, B et al. Incidence of Japanese Encephalitis among Acute Encephalitis Syndrome Cases in West Bengal, India, BioMed Research International Volume 2013 (2013), Article ID 896749, 5 pages http://dx.doi.org/10.1155/2013/896749

(2)   Rodrigues, FM A post epidemic serological survey of humans in Bankura District, West Bengal, following the epidemic of Japanese encephalitis in 1973, abs. Indian Journal of Medical Research Volume 63, Issue 10, 1975, Pages 1478-1485.

(3)   Dhillon, GP & Raina, VK. Epidemiology of Japanese encephalitis in context with Indian scenario. (abs.) J Indian Med Assoc. 2008 Oct;106(10):660-3. http://www.ncbi.nlm.nih.gov/pubmed/19552100

(4)   Tiwari, S et al. Japanese encephalitis: a review of the Indian perspective, Braz J Infect Dis. 2012;16(6):564–573 http://ac.els-cdn.com/S1413867012002073/1-s2.0-S1413867012002073-main.pdf?_tid=bc1909f4-475e-11e4-a10d-00000aacb361&acdnat=1411943473_4bfe8ac0a4c10fd0de3e521be1cd22da Kumar, R et al. Virological investigations of acute encephalopathy in India, Archives of Disease in Childhood 1990; 65: 1227-1230 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1792621/pdf/archdisch00656-0043.pdf

(5)   Kumar, R et al. Virological investigations of acute encephalopathy in India, Archives of Disease in Childhood 1990; 65: 1227-1230 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1792621/pdf/archdisch00656-0043.pdf

(6)   Panwar, RS & Kumar, N. Cassia occidentalis toxicity causes recurrent outbreaks of brain disease in children in Saharanpur,  Indian J Med Res 127, April 2008, pp 413-414 http://medind.nic.in/iby/t08/i4/ibyt08i4p413.pdf

(7)   Panwar, RS. Disappearance of a deadly disease acute hepatomyoencephalopathy syndrome from Saharanpur, Indian J Med Res Jan 2012; 135(1): 131–132. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3307174/

(8)   Operational Guide for Japanese Encephalitis Vaccination in India, MoHFW, September 2010, Immunization Division, Department of Family Welfare, Ministry of Health and Family Welfare, Government of India.

(9)   Details of AES/JE Cases and Deaths from 2008-2014 - Directorate of National Vector Borne Disease Control Programme- Delhi http://nvbdcp.gov.in/Doc/je-aes-cd-Aug14.pdf

(10) Kumari, R & Joshi, PL A review of Japanese encephalitis in Uttar Pradesh, India WHO South-East Asia Journal of Public Health 2012;1(4):374-395 http://www.searo.who.int/publications/journals/seajph/whoseajphv1n4p374.pdf?ua=1

(11) Sapka, GN et al. Enteroviruses in Patients with Acute Encephalitis, Uttar Pradesh, India,  Emerg Infect Dis Volume 15, Number 2—February 2009 http://wwwnc.cdc.gov/eid/article/15/2/08-0865_article

(12) Kumar, A. An epidemic of encephalitis associated with human enterovirus B in Uttar Pradesh, India, 2008. J Clin Virol. 2011 Jun;51(2):142-5. doi: 10.1016/j.jcv.2011.02.011. Epub 2011 Mar 27. http://www.ncbi.nlm.nih.gov/pubmed/21444241

(13) Manish, K. Acute Encephalitis Syndrome Surveillance, Kushinagar District, Uttar Pradesh, India, 2011–2012 , Emerg Infect Dis. Volume 19, Number 9—September 2013http://wwwnc.cdc.gov/eid/article/19/9/12-1855_article

(14) Anukumar, B. et al. West Nile encephalitis outbreak in Kerala, India, 2011. J Clin Virol. 2014 Sep;61(1):152-5. doi: 10.1016/j.jcv.2014.06.003. Epub 2014 Jun 7. (abs) http://www.ncbi.nlm.nih.gov/pubmed/24985196

(15) AES Report Bihar Year: 2011 & 2012, State Health Society, Patna, IDSP http://www.statehealthsocietybihar.org/idsp/AES_report_2011_2012.pdf

(16) John, TJ & Das, M. Acute encephalitis syndrome in children in Muzaffarpur: hypothesis of toxic origin, Current Science, Vol. 106, No. 9, 10 May 2014 http://www.currentscience.ac.in/Volumes/106/09/1184.pdf

(17) Sahni, GS. Recurring Epidemics of Acute Encephalopathy in Children in Muzaffarpur, Bihar, , Indian Pediatr 2012;49: 502-503 http://www.indianpediatrics.net/june2012/june-502-503.htm

(18) Dinesh, DS et al. Possible factors causing Acute Encephalitis Syndrome outbreak in Bihar, India. Int.J.Curr.Microbil.App.Sci. (2013): 2(12):531-538 http://www.ijcmas.com/vol-2-12/D.S.Dinesh,%20et%20al.pdf

(19) Srikantiah, P & Shrivastava, A. NCDC-CDC Muzaffarpur Encephalopathy Outbreak Investigations, 2013–2014, NCDC Newsletter, July–September 2014 Volume 3, Issue 3 http://nicd.nic.in/writereaddata/linkimages/newsltr_0709149594874338.pdf

(20) Shah, A & John, TJ. Recurrent outbreaks of hypoglycaemic encephalopathy in Muzaffarpur, Bihar. Current Science, Vol. 107, No. 4, 25 August 2014. http://www.currentscience.ac.in/Volumes/107/04/0570.pdf

 

Comments

As a consultant of ICMR, iNDIA THIS ARTICLE WILL BE OF GREAT HELP TO TRY WORK ON THIS ASPECT SOON

It's fine that Kelly has talked about AES in Bihar. But this year also many children are dying due to AES of unknown cause. We should try to confirm the cases whether the death is due to toxin or neurological heat shock or bacterial or viral cause. Let's try to save the future Muzaffarpur Scientist RMRI(ICMR) Patna-800007 Mobile:09472508523 e-mail: ganeshiitkgp@gmail.com

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