|Year : 2015 | Volume
| Issue : 1 | Page : 34-41
Evaluation of homoeopathic medicines as add-on to institutional management protocol in Acute Encephalitis Syndrome: An exploratory observational comparative study
Raj K Manchanda1, Praveen Oberai2, Varanasi Roja3, Supriya Singh4, Neha Singh4, Tariq Khan4, Ramesh Prasad5, JR Singh6
1 Director General, Central Council for Research in Homoeopathy, New Delhi, India
2 Research Officer/Scientist-4, Central Council for Research in Homoeopathy, New Delhi, India
3 Research Officer/Scientist-1, Central Council for Research in Homoeopathy, New Delhi, India
4 Senior Research Fellow (H), Clinical Trial Unit (Homoeopathy), Gorakhpur, Uttar Pradesh, India
5 Research Officer/Scientist-1, Clinical Trial Unit (Homoeopathy), Gorakhpur, Uttar Pradesh, India
6 Research Officer/Scientist-4, Clinical Trial Unit (Homoeopathy), Gorakhpur, Uttar Pradesh, India
|Date of Submission||03-Nov-2014|
|Date of Acceptance||11-Mar-2015|
|Date of Web Publication||31-Mar-2015|
Raj K Manchanda
Central Council for Research in Homoeopathy, New Delhi
Source of Support: None, Conflict of Interest: None
Background: Acute Encephalitis Syndrome (AES) treated according to Institutional Management Protocol (IMP) has considerable mortality and morbidity. The study was undertaken to evaluate the effect of homoeopathic treatment (H) as an add-on to IMP (IMP + H) for children affected with AES.
Materials and Methods: This was an exploratory observational study carried out in the IPD setting (epidemic ward) of Baba Rhaghav Das Medical College and Nehru Hospital, Uttar Pradesh (July to November 2012) using convenience sampling. Children whose guardians gave consent were treated with IMP + H and rest remained on IMP only. Glasgow outcome scale was used at discharge for the final outcome.
Results: 151 children (121 in IMP + H and 30 in only IMP) diagnosed with AES (aged 6 months to 18 years) were enrolled. The results showed 12 (9.9%) death out of 121 children administered IMP + H whereas it was 13 (43%) out of 30 children on IMP alone. Proportional odds analysis with covariate adjustment showed added benefit of Homoeopathy in children with AES as compared to IMP alone (adjusted odds ratio, 0.17, 95% confidence interval 0·06-0.45, P = 0·0001). The most useful medicines are Belladonna, Stramonium, Arsenicum album, Helleborus, Bryonia alba, Sulphur, and Cuprum metallicum.
Conclusion: This exploratory observational study suggests reduction of mortality and morbidity with add-on homoeopathic medicine. Further randomized controlled trial study with comparable groups is desirable. If findings are confirmed by subsequent research, add-on Homoeopathy might have relevant implication for its management.
Keywords: Acute Encephalitis Syndrome, Homoeopathy, India, Institutional management protocol, Morbidity, Mortality, Observational study
|How to cite this article:|
Manchanda RK, Oberai P, Roja V, Singh S, Singh N, Khan T, Prasad R, Singh J R. 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
|How to cite this URL:|
Manchanda RK, Oberai P, Roja V, Singh S, Singh N, Khan T, Prasad R, Singh J R. Evaluation of homoeopathic medicines as add-on to institutional management protocol in Acute Encephalitis Syndrome: An exploratory observational comparative study. Indian J Res Homoeopathy [serial online] 2015 [cited 2020 May 29];9:34-41. Available from: http://www.ijrh.org/text.asp?2015/9/1/34/154347
| Introduction|| |
Acute Encephalitis Syndrome (AES) is defined as acute onset of fever and changes in mental status (including symptoms such as confusion, disorientation, coma, or inability to talk) and/or new onset of seizures (excluding simple febrile seizures) in a person of any age, at any time of year (World Health Organization).  More than 100 different pathogens can cause AES: Viruses, bacteria, mycobacteria, rickettsia, and rarely toxoplasma. Substantial cases are viral in origin; however, exact etiology still remains obscure in 68-75%. ,,,
In the most robust, prospective studies conducted in western industrialized countries, a minimum incidence of 10.5/100,000 AES cases was reported for children and 2.2/100,000 for adult. The minimum incidence for all ages was 6.34/100,000 in a tropical setting.  The National Vector Borne Disease Control Programme Report (2008-13)  describes the incidence of AES in 17 regions of India. A total of 36,120 cases were notified in those areas, of which 5,521 died; the highest mortality being from Uttar Pradesh (UP), followed by Assam and Bihar. In UP, the disease affects mainly children; >2000 cases of AES are reported each year since 2006. 
The spectrum of brain involvement and the outcome of the disease are dependent on the specific pathogen, the immunological state of the host and a range of environmental factors. Although specific therapy is limited to only several viral agents, correct diagnosis, and supportive and symptomatic treatment (when no specific therapy is available)  . The supportive and symptomatic management/Institutional Management Protocol (IMP) includes intravenous (I/V) fluids, correction of blood sugar, suction oxygen, I/V anticonvulsant, use of ambubag if necessary, catheterization, use of mannitol, injection paracetamol, input/output charting, pulse, respiratory rate, temperature and blood pressure monitoring. 
A double-blind placebo controlled trial of administration of interferon-α-2a to Vietnamese children indicated no benefit.  Similar results were also found with oral Ribavirin for Japanese encephalitis (JE) in children in UP  and Dexamethasone in Bangkok.  Researchers from the School of Tropical Medicine, Kolkata, in collaboration with the Central Council for Research in Homoeopathy (CCRH) found that homoeopathic medicine Belladonna is able to prevent pock formation on the chorioallantoic membrane due to the JE virus.  Again, the same investigators tested the preventive role of Belladonna in an (in vivo) mouse model.  Single case reports of managing encephalitis with Homoeopathy suggest beneficial effects. ,
Some studies investigated the effect of adjunctive Homoeopathy in critically ill patients on conditions like severe sepsis  and tracheal secretions of critically ill patients.  Kent's repertory lists 28 medicines under rubric "inflammation of the brain"  but no clinical study has yet been conducted to establish their actual usefulness. Homoeopathy might be used as an adjunct to IMPs in the treatment of children with AES. Keeping this in view, the Council conducted the present study to evaluate homoeopathic treatment (H) as an add-on to IMP in reducing the mortality and disability associated with AES and to detect useful medicines to be included in a future randomized controlled study.
| Materials and methods|| |
The study was conducted by means of convenience sampling. It was a preliminary exploratory observational study, wherein homoeopathic intervention was given as an add-on to IMP to children with AES whose parents/guardians were willing to administer homoeopathic medicines; the children whose parents/guardians who did not give consent were subjected to IMP alone.
Clinical Trial Unit (Homoeopathy) at Baba Rhaghav Das (BRD) Medical College and Nehru Hospital, Gorakhpur, UP. The patients admitted in the epidemic ward were approached by the investigators to seek consent. Laboratory investigations were undertaken by the institutional state-of-art reference laboratory. Ethical clearance was obtained from the Ethical Committee of the Council. The investigators were given training on the study protocol before the initiation of the study.
- Children above 6 months and less than 18 years of age at any time of year with the acute onset of fever of ≤15 days and
- a change in mental status (including symptoms such as confusion, disorientation, coma, or inability to talk)
- and/or new onset of seizures
- Written informed consent
- Single generalized convulsion lasting <15 minutes, and who recovers consciousness within 60 minutes of the seizure.
During the period from July to November 2012 (monsoon or postmonsoon), the children admitted in the epidemic ward of BRD Medical College and Nehru Hospital and diagnosed with AES were screened for the enrolment. The children were assessed for severity at admission using the Modified Glasgow Coma Scale (MGCS), low scores indicating reduced level of consciousness. ,,
Institutional Management Protocol
All the children were given IMP for managing their symptoms and signs as per presentation, such as fever, focal neurological deficit, cerebral and/or pulmonary edema, anaemia, gastrointestinal haemorrhage, feeding problems, dysnoea, circulatory problems, seizures, renal insufficiency, myocarditis and heart failure, thrombocytopaenia, etc. ,
The medicines were procured from Good Manufacturing Practices certified companies in Centesimal potencies Hahmnemannian (CH), which include 6 CH, 30 CH and 200 CH. The investigators themselves administered the first dose of indicated medicine to the children and took care for its compliance for administration of subsequent doses which were given by their guardians. Indicated medicine customized to each patient as per symptoms/signs was given in 30 CH potency in one drop (=0.050 mL) orally. Any clinical change observed after administration (improvement/deterioration) lead to change of potency/repetition/medicine.
Outcome Measures and Follow-up
The Glasgow Outcome Scale (GOS)  was to interpret the outcome at discharge from the Hospital. The scale has five levels: Good recovery (normal life), moderate disability (patient independent in daily life), severe disability (patient dependent for daily support), neuro-vegetative stage (patient unresponsive and speechless for weeks or months) and death. The children were assessed at least twice per day or more frequently as per need until discharge.
Note was used also made of the time to resumption of oral feeding and Length Of hospital Stay (LOS). As a rule, the children were discharged from the hospital as soon as they could be fed by mouth and were afebrile. Children whose parents chose to take them home irrespective of the response to treatment were categorized as "Discharge On Patient's/guardians Request" (DOPR). However, some patients did not wait for discharge, but just left the hospital without informing the staff; this condition was referred as "Leaving Against Medical Advice" (LAMA). The patients' functional status at the time of discharge was recorded in terms of ability to comprehend speech, feed orally, speak, and walk.
Being an exploratory study first of its bind in AES, in the IPD settings using homoeopathic intervention in one arm, convenience sampling was performed to enroll the children.
All the descriptive statistical analyses were performed using SPSS version 20. Mean and standard deviation were used to express continuous variables. Median, interquartile range and percentages were used to present ordinal variables and proportions. GOS was dichotomized as "good" (i.e., recovery with normal functioning, recovery with disability) or "bad" (death and neuro-vegetative state). The cases of LAMA and DOPR were not considered for analysis. Odds Ratio (OR), Relative Risk (RR), and absolute benefit increase were also calculated. Logistic regression was used to estimate adjusted OR and 95% confidence interval (CI). OR estimate was adjusted for MGCS collected which has baseline differences. P < 0.05 was considered significant.
| Results|| |
A total of 1,898 children with AES were admitted to BRD Medical College and Nehru Hospital during the study period, however, only 165 were screened for eligibility of inclusion. From these, 14 children were excluded, and 151 children who met the inclusion criteria were enrolled and analyzed. Of these, 121 children were administered IMP + H and 30 IMP alone. The flow chart of patients in the study is depicted in [Figure 1]. The baseline characteristics of the children are described in [Table 1]. Although there was difference in the total number of patients between the groups, their baseline characteristics were comparable, except for mean MGCS score (IMP + H: 8 ± 2.8; IMP = 6.6 ± 2.3; P < 0.05), disorientation (IMP + H = 68%; IMP = 90%, P < 0.05) and speech difficulties (IMP + H = 73%; IMP = 63%, P < 0.05).
Overall analysis showed 12 (9.9%) deaths in H + IMP group and 13 (43%) in IMP group (adjusted OR for mGCS score: 0.17, 95% CI = 0·06-0.45, P = 0·0001). At discharge, IMP + H group demonstrated a trend toward lower death rate compared to IMP (RR, 0.2; 95% CI: 0.1-0.4; P = 0.0001) [Table 2]. Eight children either left against medical advice or were discharged on guardian's request.
|Table 2: Outcome of the adjunctive homoeopathic treatment in children suffering from AES |
Click here to view
The outcomes of patients admitted to Intensive Care Unit (ICU) and epidemic ward, were also analyzed separately; the results are described in [Table 2]. In ICU subgroup, the death rate was 10/15 (66.7%) and 5/22 (22.7%) for IMP and IMP + H, respectively (OR = 0.12, 95% CI: 0·02-0.6, P = 0·007). At discharge, group IMP + H demonstrated a trend toward lower death rate relative to IMP. Similarly, among the children who remained in the epidemic ward, 3/15 (20%) and 7/99 (7%) of 99 in IMP and IMP + H groups died, respectively (OR = 0.2, 95% CI: 0·05-1, P = 0·06). The response as per mGCS score at admission for the ICU group described in [Table 3], which shows no deaths among the children with scores 3-5 in IMP + H group.
There was statistically significant difference (P = 0.0001) in resumption of oral feeding. However, no difference was observed in LOS (P > 0.05). No adverse events were noted in association with the homoeopathic treatment. The probable causes of death were: Respiratory failure (n = 4), aspiration pneumonia (n = 8), multi-organ failure (n = 1), cardiorespiratory failure (n = 4), and others (n = 8).
A total of 162 prescriptions were made to 121 children along the study period. The frequency of medicines prescribed is given in [Table 4]. The most useful medicines were Belladonna, Stramonium, Arsenicum album, Helleborus, Bryonia alba, Sulphur and Cuprum metallicum. Homoeopathic medicines were prescribed with a median of 2 doses (range: 1-12 doses) in a median interval of 12 h (1-24 h). The indications of the most frequently prescribed medicines are described in [Table 5].
The patients (n = 10) suffered from minor disabilities, including: Loss of speech and hearing (H + IMP: 1; IMP: 1), loss of speech only (H + IMP: 1; IMP: 1), loss of vision (H + IMP: 1; IMP: 1), standing, walking, speech and memory problems (H + IMP: 1; IMP: 1), behavioral problem (H + IMP: 1; IMP: 0), and squint (H + IMP: 0; IMP: 1).
| Discussion|| |
In India, approximately 70% of the disease burden corresponds to the state of UP, an epicenter for this killer disease. Although the incidence of JE is decreasing, the annual incidence of JE-negative AES remained relatively stable along the period from 2008 to 2012.  In 2013 alone, 3,008 patients suffering from AES were admitted to different government hospitals at eastern UP, 640 of whom died.  Jain et al.  conducted a study in North India (UP) including 1578 patients, out of whom 59.4% died from viral AES, including JE, dengue, mumps, measles, varicella-zoster, etc., while 5.9% deaths were due to AES of unknown etiology. Residual neuropsychiatric disability at discharge due to AES of viral and unknown etiology was found in 47.4% and 3.2%, respectively. 
In our study, the death rate in IMP group was 43% (out of 30) whereas it was 9.9% (out of 121) in H + IMP group, which points to the benefits of adjunctive homoeopathic treatment in the survival of children. The OR for reduced mortality and morbidity also showed some effect in favor of add-on Homoeopathy. The large availability of patients, appropriate coordination between administrative staff, doctors, and nursing staff at BRD Medical College and Nehru Hospital enabled us to conduct the study. The lack of adverse effects and the administration of homoeopathic medicines via the oral route being easy and possible even in ventilated/intubated patients are relevant advantages, which add further strength to the study.
However, as the groups were non-comparable and nonrandomized, definite conclusion cannot be drawn. Bias cannot be ignored, due to the difference in the number of patients in each group and MGCS scores at baseline. These shortcomings might be overcome in a Randomized Controlled Trial (RCT).
The medicines fetching highest prescriptions are given in data label. Whereas the medicines in blue, yellow, rust and light green colors have been prescribed in 1, 2, 3, and 4 patients each, respectively.
| Conclusion|| |
The present exploratory observational study suggests reduction of mortality and morbidity with add-on homoeopathic medicines. Further RCT studies with comparable groups are desirable. If findings are confirmed by subsequent research, add-on homoeopathy might have relevant implications for the management of AES in children.
| Acknowledgments|| |
The authors are thankful to the former Director General Dr. Alok Kumar and Prof. (Dr.) C. Nayak for providing technical co-operation and administrative support for conducting the study. Contributions of Dr. R. K. Singh, Former Principal, BRD Medical College and Nehru Hospital, for providing permission to treat the patients in the paediatric ward and accommodations for our unit in the premises; Dr. K. P. Khushwaha, Principal, BRD Medical College and Nehru Hospital and former HOD, Paediatric ward, for providing technical support in the preparation and implementation of the study; Dr. D. K. Srivastava, Professor, HOD, Community Medicine, BRD Medical College and Nehru Hospital, Gorakhpur and Dr. Milind Gore, Scientist G, National Institute of Virology, Field Station, Gorakhpur, for providing technical support in preparing the protocols and conducting investigations; Dr. R. M. Pandey, HOD, Department of Biostatistics, All India Institute of Medical Sciences, New Delhi, and Mrs. Maya Padmanabhan for helping with statistical analysis and Miss. Vandana Sharma for typographical assistance are acknowledged. Parents of children enrolled in the study are also acknowledged.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]