|Year : 2013 | Volume
| Issue : 1 | Page : 22-30
Effect of individualized homoeopathic treatment in influenza like illness: A multicenter, single blind, randomized, placebo controlled study
PS Chakraborty1, CD Lamba1, D Nayak1, MD John2, DB Sarkar3, Amitava Poddar4, JS Arya5, K Raju6, Kumar Vivekanand7, H Binod Kumar Singh8, H Baig9, AK Prusty10, Vikram Singh1, C Nayak1
1 Central Council for Research in Homoeopathy, New Delhi, India
2 Clinical Research Unit (H), Port Blair, India
3 Dr. Anjali Chatterji Regional Research Institute (H), Kolkata, West Bengal, India
4 Clinical Research Unit (H), Siliguri, West Bengal, India
5 Regional Research Institute (H), Guwahati, Assam, India
6 Clinical Research Unit (H), Chennai, Tamil Nadu, India
7 Central Research Institute (H), Noida, Uttar Pradesh, India
8 Regional Research Institute (H), Imphal, Manipur, India
9 Drug Standardization Unit, Hyderabad, Andhra Pradesh, India
10 Regional Research Institute (H), Puri, Odisha, India
|Date of Submission||01-Feb-2013|
|Date of Acceptance||28-Mar-2013|
|Date of Web Publication||29-Jun-2013|
C D Lamba
Research Officer (H), Scientist 1, Central Council for Research in Homoeopathy, 61-65, Institutional Area, Janak Puri, New Delhi - 110 058
Source of Support: None, Conflict of Interest: None
Background: In the past decade the upsurge of influenza throughout the globe was significant and in recent years this has resurfaced showing failures of all the preventive and therapeutic measures against it. Thus, this study was undertaken to evaluate the effect of homoeopathic medicines in the treatment of Influenza like illness (primary objective) and to compare the complication rate among patients receiving homoeopathic medication as compared to the patients receiving placebo and also to compare the efficacy of LM potency vis-ΰ-vis Centesimal potency (secondary objective). Material and Methods: This was a multicenter, prospective, randomized, triple arm placebo controlled trial conducted at nine Institutes and Units of Central Council for Research in Homoeopathy (CCRH) from June 2009 to December 2010. The patients fulfilling the inclusion criteria were randomized to LM, Centesimal and Placebo groups. Homoeopathic interventions were given as per the principles of homoeopathy. Symptoms of Influenza like illness (ILI) were assessed as per validated scales. Data analysis was done using statistical package of SPSS 20.0 version. Each symptom was compared for 10 days among the allocated groups by using Kruskal wallis test and bonferroni correction for the multiple comparisons. Results: Out of 739 screened cases, 447 cases were eligible for enrolment comprising of LM (n=152), (n=147) and placebo (n=148) cases. There was a significant difference in temperature from 2 nd day onwards in LM and Centesimal groups. The significant improvement was observed in headache and myalgia on 1 st day in both the treatment groups. Likewise, significant improvement was noted in malaise on 2 nd day in both the groups; sore throat on 1 st day in LM and 2 nd day in Centesimal; fatigue on 2 nd day in LM and on 3 rd day in Centesimal group; nasal complaints on 2 nd day in LM and 1 st day in Centesimal group; chill on 3 rd day in LM group and 1 st day in Centesimal group and in sweat on 1 st day in the treatment groups. Cough improved significantly from 3 rd day in both the groups. Conclusion: The study revealed the significant effect of individualized homoeopathic treatment in the patients suffering from ILI with no significant difference between LM and Centesimal groups. The complication/sequel rate was also significantly less in the intervention groups.
Keywords: Centesimal potency, Homoeopathy, Influenza like illness, LM potency, Placebo, Randomized trial
|How to cite this article:|
Chakraborty P S, Lamba C D, Nayak D, John M D, Sarkar D B, Poddar A, Arya J S, Raju K, Vivekanand K, Singh H B, Baig H, Prusty A K, Singh V, Nayak C. Effect of individualized homoeopathic treatment in influenza like illness: A multicenter, single blind, randomized, placebo controlled study. Indian J Res Homoeopathy 2013;7:22-30
|How to cite this URL:|
Chakraborty P S, Lamba C D, Nayak D, John M D, Sarkar D B, Poddar A, Arya J S, Raju K, Vivekanand K, Singh H B, Baig H, Prusty A K, Singh V, Nayak C. Effect of individualized homoeopathic treatment in influenza like illness: A multicenter, single blind, randomized, placebo controlled study. Indian J Res Homoeopathy [serial online] 2013 [cited 2017 Aug 20];7:22-30. Available from: http://www.ijrh.org/text.asp?2013/7/1/22/114268
| Introduction|| |
Globally, influenza is considered as one of the most important infectious diseases.  The World Health Organization (WHO) estimates that the average global burden of interpandemic influenza is approximately 1 billion cases of influenza, 3-5 million cases of severe illness and 300,000-500,000 deaths annually.  Complicating the global influenza burden is the recent recognition of a novel quad-reassortment swine-origin influenza A virus which is the agent associated with the WHO declared influenza pandemic. 
The first case of P-09-H1N1 (which causes influenza) positive in India was reported on 16 th May 2009. In Eastern India, testing for influenza was initiated in June, 2009 and continued through July, 2010 to determine the prevalence and epidemiological character of circulating pandemic H1N1 (pH1N1) strain. Real time Polymerase Chain Reaction (PCR) was carried out on nasal and throat swab samples of patients with influenza like symptoms of those who sought medical care in local government hospitals. Of 2971 patients tested, 382 (12.86%) were positive for influenza A and 103 (3.47%) for influenza B. Of 382 influenza positives, 284 (74.35%) and 98 (25.65%) were subtyped as pH1N1 and seasonal H1N1, and H3N2, respectively.  Coincidently, the Council had initiated this study during that time.
Influenza viruses are transmitted through the respiratory route and infections vary from asymptomatic to severe and life threatening.  Influenza is also a significant cause of work absenteeism, lost productivity and the resultant cost to employers and employees may be considerable. ,
Two major pharmaceutical interventions for influenza control and prevention are currently in use: Vaccination and antiviral treatment and neither is perfect. Influenza vaccines, which have been in use for a long time, are safe but need to be administered annually and their immunogenicity in high-risk groups, such as very young children, the elderly and severely immunocompromised patients, is lower than in the rest of the population.  According to the intervention review of vaccinations, influenza vaccines have a modest effect in reducing influenza symptoms and working days lost. There is no evidence that they affect complications, such as pneumonia, or transmission.  Antiviral drugs are in very limited supply and the choices are few, a clear disadvantage if drug resistance develops. Furthermore, their effectiveness when initiated late in severely ill patients has not been clearly established. 
In a systematic review and meta-analysis of observational studies for benefits and harms of oseltamivir, zanamivir, amantadine or rimantadine in the treatment of influenza, it was concluded that the therapy with oral oseltamivir and inhaled zanamivir may provide a net benefit over no treatment of influenza. However, as with the randomized trials, the confidence in the estimates of the effects for decision making is low to very low.  Strong et al., also conducted a study in the context of a school outbreak of 2009 pandemic influenza, in which mass treatment and prophylaxis with oseltamivir was associated with adverse effects in a considerable proportion of pupils and staff. 
According to Cooley et al., Influenza like illness (ILI) epidemic curves coexist with corresponding past influenza epidemics; consequently, the influenza epidemic curve and the ILI epidemic curve will have the same footprint and shape. Moreover, when epidemic occurs there is resource constraint to diagnose a case of influenza with the laboratory methods, rather most of the cases will be diagnosed clinically (ILI).  Canuti M. et al., found that among clinically presented cases of ILI 39% were positive to influenza virus. 
Homoeopaths had claimed a better success in the previous pandemics especially, pandemic during 1918.  A few clinical trials in ILI with homoeopathic intervention were conducted in the past with a positive result. , However, nowhere individualized homoeopathic treatment was put under a systematic trial (Randomized Controlled Trial). Though certain medicines emerged as most useful during the past pandemics, but as we know the influenza virus has the ability to mutate, so also the severity and clinical presentations. Although, ILI as a disease entity is commonly used for surveillance of influenza cases, but this study was undertaken to see the effect of individualized homoeopathic treatment in ILI, keeping in view the epidemic/pandemic nature of the disease.
| Objectives|| |
Primary objective of the study was to evaluate the effect of homoeopathic medicines in the treatment of ILI and the secondary objectives were to compare the complication rate among patients receiving homoeopathic medication as compared to the complication rate in patients receiving placebo and to compare the efficacy of LM potency vis-ΰ-vis Centesimal potency.
| Material and Methods|| |
The study was a multicenter, prospective, randomized, triple arm placebo controlled trial conducted at nine Institutes and Units of Central Council for Research in Homoeopathy (CCRH): Central Research Institute (CRI) (H), Noida; Regional Research Institute (RRI) (H), Puri; Regional Research Institute (H), Imphal; Regional Research Institute (H), Guwahati; Clinical Research Unit (CRU) (H), Chennai; Clinical Research Unit (H), Port Blair; Clinical Research Unit (H), Siliguri, Drug Standardization Unit (DSU), Hyderabad and Dr. Anjali Chatterji Regional Research Institute (DACRRI) (H), Kolkata, India from June 2009 to December 2010. The study was conducted in accordance with the Declaration of Helinsinki's on Human Experimentation.  The ethical clearance was obtained from Ethical Committee of CCRH to conduct the study. The trial was registered with Clinical Trial Registry-India (CTRI) retrospectively, registration number being CTRI/2012/04/002590.  Patients fulfilling the inclusion criteria were enrolled in the study only after getting the written informed consent. In case of minors, written informed consent was obtained from the parents/guardian before inclusion in the study. A standardized patient case record form (CRF) was used for case taking. The patients were randomly allocated to LM potency (Group I), Centesimal potency (Group II) or placebo (Group III) groups as per the computer generated randomization chart.
Symptoms of ILI viz. fever, headache, myalgias, malaise, sore throat, fatigue, nasal complaints (nasal discharge, obstruction), chill, sweat, and cough were identified. The severity of these were assessed on visual analog scale (VAS) in which the patient or parent/guardian in case of a minor rated each symptom between 0 and 10 depending on the severity. Moreover, 0 indicated no complaint and 10 indicated worse possible complaint. Higher score indicated more severe symptoms.
Oral temperature was recorded in degrees Fahrenheit at 4 hours interval. Cough was assessed with cough score scale adapted from Hsu et al. 
Randomization was carried out by a computer generated random number list to receive from verum (Centesimal or LM potency) or placebo group.  Enrolment number of the patient was used for the purpose for randomization and initial randomization was maintained for all follow-up visits. Both intervention groups were assessed on the same parameters.
Inclusion and Exclusion Criteria
Patients of either sex, in the age group 12-60 years, who presented to the investigator within 36 hours of onset of ILI characterized by abrupt onset of fever (≥100.4°F or 38°C body temperature) with at least one respiratory symptom (cough, sore throat, or nasal symptom [discharge, obstruction]) and at least one constitutional symptom (headache, malaise, myalgia, sweats, chills, or fatigue) were included in the study.
The patients who had received any other medication (particularly anti-viral) within the previous 36 hours of his/her presentation, immunization against influenza or ILI for that season, patients suffering from psychiatric, cardiac, pulmonary, renal diseases, hemoglobinopathies, immune compromised or with any other clinically active illness were not included in the study. Similarly, pregnant women, lactating mother, and those with history of drug or alcohol abuse were also excluded from the study.
For arriving at the similimum, investigator made an in-depth interview with the patient or parent/guardian in case of a minor, as per the guidelines laid down by Hahnemann in the 5 th and 6 th edition of Organon of Medicine. , After a thorough case taking in the CRF, investigator framed the totality of symptoms and repertorized the symptoms using appropriate repertory, as per the presentation of patients' symptoms, either manually or using a computer-based homoeopathic software. Final selection of medicine was done in consultation with Materia Medica.
Group I: LM potency
The treatment of each patient was initiated with 0/1 potency to be followed-by next higher potency, serially, as per need of the case. One globule (poppy seed size, comprising milk sugar lactose and the homoeopathic medicine prepared as per Homoeopathic Pharmacopoeia of India) of the desired potency was dissolved in 120 mL of distilled water, containing 2.4 mL (2% v/v) of dispensing ethyl alcohol, premixed in it, followed by ten uniformly forceful downward strokes given against the bottom of the phial as per standard guideline of preparation of homoeopathic medicines. This was given to the respective patient. The patient or parent/guardian (in case of a minor) was also instructed to give ten uniformly forceful downward strokes to the phial with the hand on a firm surface, before taking each dose. Then three tea-spoonfuls (15 mL) of this solution were mixed in eight tea-spoonfuls (40 mL) of water in a clean glass and the solution was stirred well. One tea spoonful (5 mL) of this solution constituted one dose and this was to be taken as advised by the investigator. The liquid remaining in the glass after taking the dose was to be discarded. All the homoeopathic medicines were procured from a licensed homoeopathic pharmacy.
Group II: Centesimal potency
The indicated medicine was given in 30C potency. Each dose of the indicated medicine in the Centesimal potency (treatment group) consisted of four homoeopathic globules (size no. 20) in a case of adults and two globules (size no. 20) in the case of children. All medicines of the Centesimal potency were also procured from a licensed homoeopathic pharmacy.
Repetition of doses for both LM and Centesimal scales
The indicated medicines were repeated every few minutes to hours depending upon the requirement of the enrolled cases.
Group III: Placebo group
The patients of the placebo group were given globules impregnated with non-succussed dispensing alcohol.
In the verum group (Group I and II), if the temperature of the patients exceeded 102°F, then at first the patients were treated with homoeopathic medicines as outlined above and observed for 1 hour. If the temperature decreased or remained constant, then he/she was continued with homoeopathic intervention according to the investigation protocol and if temperature showed a tendency to rise further then Paracetamol was given in a similar way as in the placebo group, where Paracetamol was given as and when required.
Daily follow-up and assessment was carried out for successive 9 days using the assessment form and the VAS. Subsequent follow-ups were done on 17 th , 24 th , 30 th day of illness for any complication/sequel related to ILI.
Outcome Assessment and Statistical Analysis
The patients were assessed for fever, headache, myalgia, malaise, sore throat, fatigue, nasal complaints (nasal discharge, obstruction), chill, sweat, and cough daily at fixed time for 9 days following the baseline assessment as per the study protocol. Thereafter, weekly follow-ups were carried out on 17 th , 24 th , 30 th day of illness for any complication/sequel related to ILI. The data was expressed in terms of Median/inter quartile range (IQR). The demographic details and other relevant results are depicted in Tables and Graphs. Data analysis was carried out using the statistical package of SPSS 20.0 version. Analysis was carried out by using Intention to treat method; missing data of patients withdrawn due to non-reporting, referral and protocol deviation were replaced on the last observation carried forward principle. Each symptom (exact value of temperature for fever and VAS value for other symptoms) was compared for 10 days of the group (LM, Centesimal and placebo) by using the Kruskal wallis test and bonferroni correction was used for the multiple comparisons.
| Results|| |
Out of 739 screened cases, 447 cases (Male 217 and Female 230) who fulfilled the eligibility criteria constituting LM (n = 152), Centesimal (n = 147), and placebo (n = 148) groups were enrolled in the study. Flow chart depicting inflow of patients is given in [Figure 1]. Mean age of the patients was 30.6 years. Mean duration of illness was 20.5 hours with nearly 50% patients reporting within 12-24 hours of onset of complaints [Table 1].
The Median/IQR of fever, headache, myalgia, malaise, sore throat, fatigue, nasal complaints, chill, sweat and cough was similar in LM, Centesimal and placebo groups. P values also showed that all the three groups were symptomatically similar at baseline [Table 2].
The three groups were compared as LM versus Centesimal, LM versus placebo and Centesimal versus placebo using the Kruskal wallis test. Significant differences were observed between verum and placebo groups for all the symptoms compared. However, there was no statistically significant difference of treatment outcome between LM and Centesimal treatment groups.
Temperature showed a significant difference from 2 nd day onward in LM and Centesimal groups and temperature became normal by 5 th day of treatment while it became normal on 7 th day in the placebo group. Similarly, statistically significant improvement was observed in headache and myalgia on 1 st day (follow-up) in both the treatment groups. Likewise, significant improvement was noted in malaise on 2 nd day in both the groups; sore throat on 1 st day in LM and 2 nd day in Centesimal group; fatigue on 2 nd day in LM and on 3 rd day in Centesimal group; nasal complaints on 2 nd day in LM and 1 st day in Centesimal group; chill on 3 rd day in LM group and 1 st day in Centesimal group and the sweat on 1 st day in the treatment groups. Cough improved significantly from 3 rd day in both the groups [Table 3]. During the treatment period, the Paracetamol was required by 33 (22%) patients in the LM group, 30 (20%) patients in Centesimal and 89 (60%) cases in the placebo group at varying time periods.
|Table 3: Comparison between treatment group (LM and Centesimal) with placebo|
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The most commonly indicated medicines were Arsenic album (n = 75), followed by Bryonia (n = 33) and Rhus toxicodendron (n = 32) [Table 4].
Complications were observed only in 23 cases (5%) of the total enrolled cases, out of which placebo group had 16 (70%) cases, LM group had 1 (4%) case and Centesimal group had 6 (26%) cases. The complications noticed were bronchitis (n = 14), sinusitis (n = 5), bronchial asthma (n = 2) and tracheobronchitis (n = 2).
| Discussion|| |
The current definition of ILI is a sudden onset of fever, a temperature >38°C and cough or sore throat in the absence of another diagnosis. The sensitivity of the definition is generally about 60%; the specificity is lower, ranging from about 5% when influenza is not prevalent (that is, 5% of people who meet the case definition do actually have influenza) to 60-70% during the influenza season. The usefulness of specific influenza signs and symptoms for detecting influenza has been evaluated in a number of studies.  The most important are cough, fever, and myalgia or fatigue. Notably, sore throat has been found in several studies to be a negative indicator of influenza, meaning that people with a sore throat are more likely to have an illness other than influenza.  Based on these observations, the new definition proposed is 'An acute respiratory illness with a measured temperature of ≥38°C and cough, with the onset within the past 7 days.' In this study all cases at baseline had fever, 64.6% cases had cough, 59.9% cases had a sore throat, 81.2% cases had myalgia and 56.5% cases had fatigue and 80.5% cases had nasal complaints. Although, the findings corroborate with the proposed definition of ILI, but nasal complaints were present in higher frequency than expected in the study population.
Although, few clinical trials in ILI with homoeopathic intervention had a positive result, , but none had systematically (RCT) evaluated the individualized homoeopathic treatment in ILI. This trial evaluated the effect of individualized homoeopathic intervention in ILI. The results indicate that the medicinal group (LM and Centesimal) had significant improvement in most of complaints from 2 nd day of follow-up, which was significantly earlier than the improvement of symptoms in the placebo group, which showed improvement from 5 th day onward in most of the complaints. Temperature showed a significant difference from 2 nd day onward in the interventional groups and became normal by 5 th day of treatment although it became normal on 7 th day in the placebo group. Similarly, statistically significant improvement was observed in headache and myalgia on 1 st day (follow-up) in both the treatment groups although these improved on 6 th and 5 th day respectively in the placebo group. Likewise, significant improvement was noted in malaise on 2 nd day in both groups and on 6 th day in the placebo group; sore throat on 1 st day in LM, 2 nd day in Centesimal group and 5 th day in the placebo group; fatigue on 2 nd day in LM, 3 rd day in Centesimal group and 7 th day in the placebo group; nasal complaints on 2 nd day in LM, 1 st day in Centesimal group and 5 th day in the placebo group; chill on 3 rd day in LM group, 1 st day in Centesimal group and 4 th day in the placebo group and the sweat on 1 st day in the treatment groups and 3 rd day in the placebo group. Cough improved significantly from 3 rd day in both groups and on 5 th day in the placebo group. The incidence of ILI was higher in younger age group - 37.8% in the age group 12-24 years, 33.8% in the age group 25-36 years, 18.3% in the age group 37-48 years and 10.1% aged 49-60 years. It was also observed that number of drop outs were more in the placebo group. 16 cases were referred due to persistent high fever, the maximum cases being from the placebo group. Overall 5% cases reported complications/sequels, out of which 70% were in the placebo group. Complications/sequels of influenza include pneumonia and exacerbations of underlying pulmonary and cardiac disease.  The complications noticed in the study population were bronchitis, sinusitis, bronchial asthma, and tracheobronchitis.
In a recent observational study to determine the characteristics and management of patients in France visiting the allopathic and homoeopathic general practitioners for ILI, it was observed that Belladonna, Eupatorium perfoliatum, Gelsemium and Bryonia were prescribed and found useful, which is notably in consensus with this study. 
There was no significant differences in both the treatment groups viz. LM and Centesimal. Thus, medicines in both the scales are equally useful in treating ILI. Overall, the medicinal group had a quick recovery, required lesser number of Paracetamol tablets and had minimal complications as compared with the placebo group. Thus, the individualized homoeopathic intervention is effective in the management of ILI.
It is evident from the study that the individualized homoeopathic intervention could control the disease activity thereby bringing down the temperature to normal on 5 th day in the verum group as compared to 7 th day in the placebo group along with alleviation of other symptoms of ILI. However, this study had some of the weaknesses e.g., quality of life parameters like sleep disturbances or time to return to normal activities were not recorded. Furthermore, the Paracetamol tablets was used in the verum group if the temperature did not come down with the indicated medicine for the safety of patients. Therefore, it cannot be clearly stated that there was a pure effect of homoeopathic treatment on reducing the temperature in ILI. Regarding the complications/sequelae, it also cannot be clearly stated that whether it was developed after ILI or had exacerbated after ILI as the past history of the patients was not recorded.
| Conclusion|| |
The study revealed the significant effect of individualized homoeopathic treatment in the verum group as compared to placebo group on the symptom complex of ILI. There was no significant difference in both the treatment groups viz., LM and Centesimal. Furthermore, it was observed that the complications/sequel rate was significantly less in the treatment group as compared to the placebo group. Therefore, further studies can be taken up on the laboratory confirmed cases of Influenza with the viral load/viral shedding as one of the outcome parameters to validate the results. However, based on the findings, preventive and interventional trials can be taken up on the clinically diagnosed cases of influenza during the outbreak of an epidemic.
| Acknowledgment|| |
The authors are thankful to Dr. R. K. Manchanda, Director General, Central Council for Research in Homoeopathy, New Delhi, for giving valuable suggestions in the construction of this article.
Suggestions given by Dr. Anil Khurana, Scientist-4, Assistant Director (H), CCRH, New Delhi, while critically reviewing the contents of the article, are sincerely acknowledged.
The statistical support for the data verification and analysis was obtained from Mrs. Maya Padmanabhan, Statistical Assistant, CCRH, New Delhi. The authors deeply acknowledge her active contribution.
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[Table 1], [Table 2], [Table 3], [Table 4]