Effectiveness of Homeopathic Medicines as Add-on to Institutional Management Protocol for Acute Encephalitis Syndrome in Children: An Open-Label Randomized Placebo-Controlled Trial
19 December 2017
17 April 2018
05 June 2018 (eFirst)
Background Acute encephalitis syndrome (AES) is endemic to certain parts of India, with limited treatment options. In our initial exploratory comparative observational study of 151 patients with AES, there was significantly reduced mortality with adjunctive homeopathy compared to institutional management protocol (IMP). The present randomized placebo-controlled trial brings more statistical rigor to this research program.
Methods This study was conducted at a pediatric unit from 2013 to 2015. Children aged > 6 months and ≤ 18 years and receiving IMP were randomized to receive adjunctive homeopathy (n = 325) or placebo as control (n = 323). The primary effectiveness analysis was based on Glasgow Outcome Scale (GOS). Morbidity was assessed using the Liverpool Outcome Score for Assessing Children at Follow-up. Analysis was by intention to treat.
Results A total of 612 children were analyzed (Homeopathy [H] = 304; Control [C] = 308). The primary outcome, GOS, differed significantly between H and C groups. There was 14.8% death/neuro-vegetative state in the H group compared to 29.8% in the C group. Relative risk was 0.49 (95% confidence interval [CI]: 0.36 to 0.68), with absolute risk reduction of 15.0% (95% CI: 8.6 to 21.6%). Number needed to treat to prevent one additional death/neuro-vegetative state was 6.6 (95% CI: 4.6 to 11.6). Proportional-odds analysis also revealed a greater effect in the H group: odds ratio, 0.40 (95% CI: 0.27 to 0.60). The most frequently used medicines were Belladonna (n = 116), Stramonium (n = 33), Arsenicum album (n = 25), Sulfur (n = 18), Opium (n = 17), and Nux vomica (n = 10).
Conclusion Adjunctive homeopathic medicines may improve clinical outcomes associated with AES. Further randomized and controlled studies, using double-blinded trial design, are recommended to discover if the current findings may be corroborated.
• Children aged 6 months to 18 years were randomized to receive adjunctive homeopathy (n = 325) or adjunctive placebo (n = 323).
• A total of 612 children were analyzed (Homeopathy: 304; Placebo: 308) on ITT basis.
• The primary effectiveness analysis was based on the Glasgow Outcome Scale (GOS).
• GOS differed significantly between the Homoeopathy and Placebo groups: there was 14.8% death/neuro-vegetative state in the former group compared to 29.8% in the latter.
- 1 World Health Organization. Japanese encephalitis surveillance standards. *From WHO-recommended standards for surveillance of selected vaccine-preventable diseases WHO/V&B/03.01. January 2006. Available at http://www.path.org/files/WHO_surveillance_standards_JE.pdf . Accessed May 23, 2017
- 2 Govt. of India. National Vector Borne Disease Control Program. Available at: http://nvbdcp.gov.in/Doc/je-aes.pdf . Accessed July, 2017
- 3 Joshi R, Kalantri SP, Reingold A, Colford Jr JM. Changing landscape of acute encephalitis syndrome in India: a systematic review. Natl Med J India 2012; 25: 212-220
- 4 Govt. of India. Guidelines Clinical Management of Acute Encephalitis Syndrome Including Japanese Encephalitis Directorate of National Vector Borne Disease Control Programme 2009. Available at : http://nvbdcp.gov.in/Doc/Revised%20guidelines%20on%20AES_JE.pdf . Accessed May 24, 2017
- 5 Solomon T, Dung NM, Wills B. , et al. Interferon alfa-2a in Japanese encephalitis: a randomised double-blind placebo-controlled trial. Lancet 2003; 361 (9360): 821-826
- 6 AYUSH INDIA. 2016. Ministry of AYUSH. Available at: http://ayush.gov.in/sites/default/files/Medical%20Manpower%20Table.pdf . Accessed May 24, 2017
- 7 Mohan GR. Management of a Case of Encephalitis with Homoeopathy. Available at: http://homoeocuredrmohan.blogspot.in/2013/03/management-of-case-of-encephalitis-with.html . Accessed Mar 19, 2017
- 8 Natarajan KV. Encephalitis cured with Gelsemium. Available at : http://www.interhomeopathy.org/encephalitis_cured_with_gelsemium . Accessed March 19, 2017
- 9 Schroyens F. Synthesis Repertorium Homeopathicum Syntheticum. 9.1 ed. New Delhi: B Jain Publishers; 2008
- 10 Manchanda RK, Oberai P, Roja V. , et al. Evaluation of homoeopathic medicines as add-on to institutional management protocol in acute encephalitis syndrome: an exploratory observational comparative study. Indian J Res Homoeopathy 2015; 9: 34-41
- 11 Central Drugs Standard Control Organization. Good Clinical Practices. Dte.GHS, Ministry of Health and Family Welfare, Government of India. Available at: http://www.cdsco.nic.in/html/GCP1.html . Accessed May 29, 2017
- 12 Dean ME, Coulter MK, Fisher P, Jobst K, Walach H. Reporting data on homeopathic treatments (RedHot): a supplement to CONSORT. Homeopathy 2007; 96: 42-45
- 13 Kirkham FJ, Newton CRJC, Whitehouse W. Paediatric coma scales. Dev Med Child Neurol 2008; 50: 267-274
- 14 Sharma S, Mishra D, Aneja S, Kumar R, Jain A, Vashishtha VM. ; Expert Group on Encephalitis, Indian Academy of Pediatrics. Consensus guidelines on evaluation and management of suspected acute viral encephalitis in children in India. Indian Pediatr 2012; 49: 897-910
- 15 Mittal M, Kushwaha KP. AES: Clinical presentation and dilemmas in critical care management. J Commun Dis 2014; 46: 50-65
- 16 Schroyens F. Synthesis Repertory. 9th ed. New Delhi: B Jain Publishers (P) Ltd; 2007
- 17 Boericke W. Pocket Manual of Homeopathic Materia Medica & Repertory. Third revised and Augmented edition based on 9th ed. New Delhi: B Jain Publishers (P) Ltd; 2007
- 18 University of Liverpool Brain Infections Group. Liverpool Outcome Score for Assessing Children at Follow-up. 2006 ; Available at: https://vaccineresources.org/details.php?i=677 . Accessed Nov. 14, 2017
- 19 Jennett B, Bond M. Assessment of outcome after severe brain damage. Lancet 1975; i (7905): 480-484
- 20 Agarwal A, Gutch M, Kumar S, Agrawal S. State of the globe: acute febrile encephalopathy. J Glob Infect Dis 2016; 8: 127-128
- 21 Sen PK, Dhariwal AC, Jaiswal RK, Lal S, Raina VK, Rastogi A. Epidemiology of acute encephalitis syndrome in India: changing paradigm and implication for control. J Commun Dis 2014; 46: 4-11
- 22 Ghosh S, Basu A. Acute encephalitis syndrome in India: the changing scenario. Ann Neurosci 2016; 23: 131-133
- 23 Kumar S, Pandey AK, Gutch M. , et al. Acute viral encephalitis clinical features and outcome: experience from a tertiary center of North India. Ann Trop Med Public Health 2015; 8: 262-266
- 24 Kumar R, Basu A, Sinha S. , et al. Role of oral Minocycline in acute encephalitis syndrome in India - a randomized controlled trial. BMC Infect Dis 2016; 16: 67
- 25 Goel S, Chakravarti A, Mantan M, Kumar S, Ashraf MA. Diagnostic approach to viral acute encephalitis syndrome (AES) in paediatric age group: a study from New Delhi. J Clin Diagn Res 2017; 11: DC25-DC29
- 26 Misra UK, Mani VE, Kalita J. A cost-effective approach to the diagnosis and management of acute infectious encephalitis. Eur Neurol 2017; 77: 66-74