DEFINITION: According to clinical case definition by WHO, AES is defined as acute onset of fever and a change in mental status including symptoms such as confusion, disorientation, or inability to talk and/ or new onset of seizures excluding febrile convulsions in a person of any age at any time of year.1
CAUSATIVE AGENTS: Viruses have been mainly attributed to be the cause of AES in India although other sources such as bacteria, fungus, parasites, spirochetes, chemicals, and toxins have been reported over the past few decades.2 Apart from viral encephalitis, a severe form of leptospirosis and toxoplasmosis can cause AES. The causative agent of AES varies with season and geographical location, and predominantly affects population below 15 years.2 Japanese encephalitis (JE), a vector-borne viral disease, caused by a group B arbovirus (Flavivirus) and transmitted by Culicine mosquito. Acute Encephalitis Syndrome (AES) is most widely caused by the Japanese Encephalitis (JE) virus. Bihar stands third in the reporting of JE cases in India.3
HISTORY OF AES IN INDIA: The history of AES in India has paralleled with that of the Japanese encephalitis virus (JEV) since the first report in 1955 from Vellore, Tamil Nadu. The first outbreak of JEV was reported in Bankura district, West Bengal in 1973. Thereafter, sporadic cases of AES and outbreaks have been the leading cause of premature deaths due to the disease in India.
After 2012, AES cases in India have shifted towards the JE etiology. Based on the reports, Indian states of Uttar Pradesh (UP), Bihar, Assam, West Bengal, and Tamil Nadu were identified as JE endemic zones. In the year 2013, starting from the monsoon months till the end of November, 2,205 people were reported to be affected by JE, and the death toll due to JE rose up to 590 (Indian Express, November 26, 2013). Many cases of AES were reported in 2014 from the states of UP (3,329 cases, 627 deaths), Assam (2,194 cases, 360 deaths), West Bengal (2,381 cases, 169 deaths), and Bihar (1,385 cases, 355 deaths) (Indian Express, September 22, 2015). JE was the major cause of these deaths, albeit virologists identified another causal agent in the form of ‘toxin-mediated illnesses. Investigators hypothesized the causal agent as a toxin prevalent in the litchi fruit (Indian Express, October 14, 2014). In these cases, although encephalitis was not confirmed, pathogenesis leads to encephalopathy with hypoglycemia. Sixty-three percent of 390 patients suffered from hypoglycemia with a low blood glucose level of 70 mg/dl, and it was observed that only treatment for hypoglycemia reduced the number of deaths from 44% in 2013 to 26% in 2014. The toxin was identified as methylene cyclopropyl glycine and was found to rise in litchi seed. Later, though not confirmed, the rise in the toxin in litchi seeds was implied to the use of alpha-cypermethrin above the minimum safety levels (Indian Express, July 23, 2014).4
During 2016, a major outbreak of JE and acute encephalitis syndrome (AES) occurred in the Malkangiri district of Odisha, causing 103 deaths in children, of which 37 were caused by JE and 66 by AES.5
As per data with the state government of Bihar, 720 patients suffering from AES were admitted in hospitals, of which 586 were cured and 154 died till June 28, 2019.6
DIAGNOSTIC SCHEMES FOR PATHOGEN-ASSOCIATED AES
In clinical practices, most cases are diagnosed based on clinical manifestation, lab reports, neuroimaging, and electrophysiologic findings. Suspected cases of pathogen-associated AES may be defined as a patient with neurological symptoms ranging from headache to meningitis or encephalitis with fever of variable severity. Symptoms may include fever, headache, stupor, meningeal signs, coma, disorientation, tremors, hypertonia, paralysis (generalized) and loss of coordination. Patients with fever or altered sensorium for more than 6 h with no skin rash may be included in the suspected cases of pathogen-associated AES. A probable case of pathogen-associated AES may be described as a suspected case with plausible laboratory results showing detection of pathogen-specific IgM antibody from serum taken during the acute phase of illness or higher and stable titers of pathogen-specific antibody determined by ELISA/HI/neutralizing assay. A confirmed case of pathogen-associated AES is through the detection of pathogen-specific IgM antibody in cerebrospinal fluid or indication of rise in paired sera from the acute and convalescent phases of illness through IgM/IgG, HI, ELISA, neutralization test or detection of pathogenic (virus, bacteria, parasite, spirochetes, and fungi) genome or antigens in the blood or other body fluids including tissues through PCR, immunofluorescence or immunochemistry.7
Acute encephalopathy and acute meningitis – pyogenic, tubercular, fungal or viral – are other examples of acute central nervous system (CNS) diseases due to infectious or non-infectious aetiologies that can and must be differentiated from acute encephalitis.
In acute encephalopathy, brain pathology is noninflammatory, often biochemical; hence, CSF shows no pleocytosis. Onset is often without prodromal phase and tends to be in the morning hours, the child having been well the previous evening. Changes in sensorium, seizures and upper motor neuron-type muscle tone abnormalities and abnormal movements point to cerebral dysfunction. Encephalopathy occurring in clusters is often conflated with acute encephalitis outbreak.
Acute meningitis is diagnosed when the clinical presentation points to meningeal inflammation – with fever, headache, neck rigidity, positive Kernig, and Brudzinski signs and high pleocytosis in CSF. In pyogenic meningitis, CSF cells are predominantly polymorphonuclear leucocytes, while in most others, these are predominantly lymphocytes. While viral meningitis is often self-limited, bacterial and fungal meningitis will progress to severe brain dysfunction and death, if left untreated. When features of encephalitis and meningitis co-exist, the disease is called meningoencephalitis.8
Factors which might have increased IR of AES –
1. Overcrowding with the resultant worsening of environmental sanitation and difficulty in getting protected water supply might have resulted in infections spreading rapidly.
2. Some cases of AES with specific treatment might have died before a diagnosis was made and so were not removed from the AESn study group. Lack of facilities for urgently required advanced investigations (e.g., magnetic resonance imaging scan in a case of Acute disseminated encephalomyelitis [ADEM]) might have played a role in such cases.
3. Malnutrition is an important factor contributing to illness and is the most common cause of immune deficiency worldwide.9
- Increase access to safe drinking water and proper sanitation facilities.
- Improve nutritional status of children at risk of JE/AES.
- Vector control
- National programme for preventive and control of Japanese encephalitis / Acute encephalitis syndrome.
Several government initiatives have been undertaken to educate and improve the hygiene of people living in the JE endemic zones. Government and non-government organizations have been instrumental in providing proper nutrition to the AES-affected population as most of the affected people belong to the lower economic strata of society. There have been initiatives to help the people residing in the endemic zones for alternative professions such as giving up pig-rearing since pigs are the primary host for JE viruses. Special schools have been set up to help children challenged by clinical sequelae of JE infection.10
STUDY DONE ON ACUTE ENCEPHALITIS SYNDROME:
A study conducted on AES in eastern India where 98 children are treated and the most common presenting features are vomiting, convulsions and altered sensorium. In the Study bacterial meningoencephalitis was the most common etiology followed by viral encephalitis.11
- Acute encephalitis syndrome (AES) secondary to scrub typhus infection is rarely seen clinically. A 50-year-old man was a real-time polymerase chain reaction test was positive for tsutsugamushi. Finally, he recovered. Scrub typhus is an acute mite-borne febrile illness caused by Orientia tsutsugamushi.12
- A case series study was undertaken at the department of paediatrics, VIMS, Bellary. 136 Children aged 0- 15 years with fever or h/o fever (>380c), altered level of consciousness persisting for >24hrs, convulsions, change in behaviour were included as study subjects. The predominant presenting feature was fever, followed by convulsions 102 (75%) and vomiting 85 (62.5%). A higher proportion of cases were reported during post-monsoon period 62 (45.1%) followed by monsoon 41(30.1%). Higher proportion of them had viral etiology on CSF analysis, among which five of them were positive for J.E & four of them had Dengue encephalitis, which was confirmed by laboratory profile.13
TREATMENT WITH HOMOEOPATHY
Homoeopathy, a system of medicine, which follows holistic approach to the patient. In clinical practice, however, practitioners frequently treat patients with chronic conditions that conventional medicine cannot adequately address, including arthritis, allergies, autoimmune diseases, or non-life-threatening acute conditions such as viral infections. In epidemic/endemic diseases also homoeopathy can play a vital role to prevent and treat diseases such as dengue, acute encephalitis, chikungunya, etc.
Central Council for Research in Homoeopathy (CCRH), an apex body, for undertaking research in Homoeopathy under Ministry of AYUSH, Govt. of India, has been taking steps for exploring the usefulness of Homoeopathy in preventing/treating epidemic/endemic diseases including AES/JE. Continuous efforts are being made to document the treatment and preventive effects of homoeopathic medicines in AES/JE. The excerpts of the research finding of different studies undertaken in this area are as follows:
CCRH had already completed one preclinical study (2007-10) to assess the effectiveness of Homoeopathic medicine Belladonna as preventive for on in vitro and in vivo model in collaboration with School of Tropical Medicine, Kolkata. It was found that Belladonna significantly protected the suckling mice from JE infection.
Further, it has undertaken a study in collaboration with King George’s Medical University, Lucknow, Uttar Pradesh to understand the action of Belladonna – Calcarea carb – Tuberculinum as combined regimen on JE. The study is being initiated in March 2015 and is ongoing.
PROPHYLACTIC (PREVENTIVE) STUDIES
CCRH had carried out research studies for prevention and treatment of JE during its epidemics in eastern parts of U.P. in 1989, 1991 and 1993. Belladonna 200, single dose was distributed as preventive to 3,22,812 persons in 96 villages in three districts of U.P. (Gorakhpur, Deoria, Maharajganj) during the period 29th Oct. to 16th Nov. 1991 in the wake of reoccurrence of JE epidemic in Uttar Pradesh (India) by a team of research workers of CCRH, New Delhi. Follow up of 39,250 persons was done and it was found that none of them reported any signs and symptoms of JE.
Apart from this, the Government of Andhra Pradesh had published about the effectiveness of homeopathic medicine Belladonna, Calcarea carbonica, and Tuberculinum as prophylactic in combating Japanese encephalitis. As prophylactic drugs, Belladonna 200 on 1, 2, 3 days one dose each, Calcarea carbonica 200 on 10th day and Tuberculinum 10 M on 25th day were administered in a phased manner to all children in the age group of 0-15 years in the month of August every year for three consecutive years. This project was named B.C.T. After its commencement in 1999 the mortality and morbidity rates of J.E. fell drastically. 343 cases were reported in 2000 with 72 deaths, in 2001 only 30 cases with 4 deaths, in 2002 only 18 cases but no deaths, in 2003 and 2004 no cases were recorded.
A research unit is being set up by CCRH on the premises of BRD medical college, Gorakhpur in the year 2012 for exploring the role of homoeopathic medicines in managing AES. Because of various challenges in treating this condition and less documentation and experience in this area, an exploratory observational comparative study was conducted in the year 2012. A total of 151 children diagnosed with AES were enrolled. Out of them, 121 children were given standard care along with homoeopathic medicine and 30 children were kept under standard care alone. The result showed 12 (9.9%) death homoeopathy added group whereas it was 13 (43%) death in standard care group. There was 33% reduction in death and disability in group were homoeopathy was added compared to standard care alone. The results were statistically significant.
The encouraging results of above study lead to undertake a randomized controlled trial with a total of 612 patients. Three hundred six children were given standard care along with homoeopathy and 306 were given standard care along with placebo. There was 16% reduction in death and disability in homeopathy added to standard care group (12.7%) in comparison to placebo added to standard care group (28.4%) which was statistically significant.
The homoeopathic medicines found effective for prescribing to children suffering from AES are Belladonna, Stramonium, Arsenicum album, Helleborus niger, Bryonia alba, Sulphur, Cuprum metallicum, Opium and Nux vomica.14
Now-a-days, AES and JE is an endemic problem in Bihar, Assam state of our country. To prevent the infection and reduce the death due to JE and AES should take a step from the village level, malnutrition, hygiene should be corrected, health facilities should be available and early diagnosis and early treatment very important.
1.Solomon T, Thao TT, Lewthwaite P et al. A cohort study to assess the new WHO Japanese Encephalitis surveillance standards. Bulletin of the World Health Organization 2008; 86:178-86
2.Joshi R, Kalantri SP, Reingold A, Colford JM Jr: Changing landscape of acute encephalitis syndrome in India: a systematic review. Natl Med J India 2012; 25: 212–220.
3.kumar P, Pisudde PM, Sarthi PP, Sharma MP, Keshri VR: Acute encephalitis syndrome and Japanese Encephalitis, status and trends in Bihar State, India. April 2016 vol 45, supplement 1, pages306-307.
4.Ghosh S, Basu A: Acute Encephalitis Syndrome in India: The Changing Scenario. National Brain Research Centre, Manesar, Haryana, India. September 9, 2016; 23:131–133.
5.Sahu SS, Sonia T, Dash S, Gunasekaran K, Jambulingam P. Insecticide resistance status of three vectors of Japanese encephalitis in east central India. Med Vet Entomol. 2019 Jun;33(2):213-219.
6. India Today Web Desk Muzaffarpur July 3, 2019UPDATED: July 3, 2019 11:55 IST
7. Saxena S K, Kumar S, Maurya V K. Pathogen- associated acute encephalitis syndrome: therapeutics and management. Future microbiology, vol.14, no.4 Editorial.
8.JohnT J, Verghese V P, Arunkumar G, Gupta N, and Swaminathan S. The syndrome of acute encephalitis in children in India: Need for new thinking. Indian J Med Res. 2017 Aug; 146(2): 158–161.
9. Potharaju N R. Incidence rate of acute encephalitis syndrome without specific treatment in India and Nepal. Indian Journal of community medicine. Year: 2012 | Volume: 37 | Issue: 4 | Page: 240-251
10.Acute encephalitis syndrome. Wikipedia.
11.Biswas R, Bhattacharya T, Mondal T, Banerjee S, Bandyopadhyay S K. A study on clinical features, aetiology, outcomes and predictors of mortality and morbidity in children with acute encephalitis syndrome in eastern India. Journal of Evolution of Medical and Dental Sciences.October 2018, vol.7. Issue 41, page 4462-4466.
12. Wang C Y, Chang W H, Su Y J. Acute encephalitis syndrome caused by Orientia tsutsugamushi. May 2019 (http://ht.amegroups.com/issue/view/344) /
13. Kamble S, Raghvendra B. A clinico-epidemiological profile of acute encephalitis syndrome in children of Bellary, Karnataka, India. International Journal of Community Medicine and Public Health Kamble S et al. Int J Community Med Public Health. 2016 Nov;3(11):2997-3002
14. Manchanda R K, Khurana A, OberaiP, NayakD, Roja V. acute encephalitis syndrome/je, homoeopathic perspective, healthy India chronicle.