Homeopathy
DOI: 10.1055/s-0044-1788663
Original Research Article

Effectiveness of Eupatorium Perfoliatum 30C in Preventing Dengue Fever—A Prospective, Community-Based, Open Label, Parallel Cohort Study in Delhi, India

1   Department of Epidemic Cell, Central Council for Research in Homoeopathy, New Delhi, India
,
Lovepreet Kaur
1   Department of Epidemic Cell, Central Council for Research in Homoeopathy, New Delhi, India
,
Rupali Bhalerao
2   Ayurswasthya Yojana, Central Sector Scheme, Ministry of Ayush, New Delhi, India
,
Karanpreet Nahar
3   Department of Clinical Research, Dr. D.P Rastogi Central Research Institute of Homoeopathy, Noida, Uttar Pradesh, India
,
Hanuman Ram
4   Department of Clinical Research, Clinical Research Unit for Homoeopathy, Goa, India
,
Pawan Sharma
5   Department of Health and Family Welfare, State Homoeopathic Dispensary, Bagdogra, under Ayush Branch, West Bengal, India
,
Ankit Gupta
6   Delhi Government Homoeopathic Unit, Acharya Shree Bhikhshu Hospital, New Delhi, India
,
Smita Singh
1   Department of Epidemic Cell, Central Council for Research in Homoeopathy, New Delhi, India
,
Anil Khurana
7   National Commission for Homoeopathy, New Delhi, India
,
Raj Kumar Manchanda
8   Directorate of AYUSH, Government of National Capital Territory of Delhi, Ayurvedic and Unani Tibbia College Campus, New Delhi, India
› Author Affiliations
Funding This study was funded by the Central Council for Research in Homoeopathy, New Delhi, India.
 

Abstract

Objective The study was undertaken to evaluate the protective effect of Eupatorium perfoliatum (EP) 30C on the incidence of dengue fever.

Design This study was designed as a prospective, open label, parallel cohort study.

Interventions Participants were enrolled in two medicine cohort (MC) communities and one control cohort (CC) community. Participants in MC who were more than 5 years of age received four medicated globules and those aged between 1 and 5 years received two medicated globules of EP 30C once a week for 10 weeks. Participants in CC received no medical intervention. Both cohorts received information and educational material regarding dengue.

Outcome Measures The primary outcome was incidence of dengue cases based on laboratory confirmation or the clinical definition of dengue as per the case definition notified by the National Vector-Borne Disease Control Program, Government of India, during the 14 weeks of intervention and observation.

Results The analysis included 20,607 participants residing in three slums of Delhi, of which MC and CC included 15,298 and 5,309 participants respectively. The overall protective effect of EP 30C in MC against probable/laboratory-confirmed dengue was 59.59% (95% confidence interval [CI], 50.74 to 66.85, p = 0.0001). The overall protective effect of EP 30C against laboratory-confirmed dengue was 72.78% (95% CI, 54.45 to 83.74, p = 0.0001): 26 cases per 15,298 (0.13 per 1,000 person-weeks) in MC versus 33 cases per 5,309 (0.46 per 1,000 person-weeks) in CC.

Conclusion The use of EP 30C was associated with some protection against probable and laboratory-confirmed dengue.


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Introduction

The rise in dengue incidence and endemicity has become a reason for concern worldwide.[1] [2] [3] [4] Understanding the full impact of dengue on economic and health infrastructure, especially in highly populous nations such as India, is challenging due to the presence of many sub-clinical or asymptomatic cases that are often mis- or under-reported.[5] [6] [7] Between 2015 and 2017, India reported 417,480 cases of dengue in the country, with 790 deaths.[8] These cyclic outbreaks of dengue were the leading cause of hospitalisations and deaths among children in the country.[9] Moreover, the financial burden associated with dengue fever in India during 2016 was estimated to be 5.71 billion U.S. dollars, reflecting a considerable increase from previous estimates.[10]

Increased migration, population growth and inadequate infrastructure all lead to an increase in human waste, thereby fostering mosquito breeding and increasing the spread of dengue vector.[11] [12] Adding to the burden is the emergence and co-existence of new genotypes of the dengue virus,[13] as well as the overlapping of co-infections depicting similar clinical profiles.[14] [15] [16]

The World Health Organization (WHO) had set a goal to cut dengue-related death and morbidity by at least 25% and 50% respectively by 2020.[17] However, the lack of targeted anti-viral treatments for dengue,[18] [19] as well as serious safety and ethical issues about dengue vaccines, particularly Dengvaxia,[20] [21] have worsened the problem. In India, a few potential dengue vaccines are undergoing trials and should soon be accessible.[22] Prophylactic measures and vector control are currently crucial to the prevention of disease.

Delhi has India's highest population density, accommodating approximately one-third of its residents in sub-standard housing, including 675 slums and Jhuggi-Jhopri clusters (inadequately built settlements located on public land).[23] The lack of adequate housing and the limited access to basic amenities in these regions significantly increases the vulnerability of their inhabitants to infections.[24] In 2018, 7,136 cases of dengue were reported from Delhi,[8] though the precise incidence of dengue in slums was never estimated. A survey conducted in 2013 indicated that 8% of households in Delhi's slums reported at least one diagnosed dengue case.[25] Another study, conducted by Kusuma & Babu,[26] revealed that dengue was the primary illness necessitating hospitalisation among the urban poor in Delhi. These findings highlight the disproportionate burden of dengue on marginalised communities within the city, emphasising the pressing need to address this issue effectively.

The apparent success of homeopathy in managing past epidemics,[27] [28] [29] along with promising outcomes observed in clinical trials conducted during dengue outbreaks in India,[30] [31] Pakistan,[32] Malaysia,[33] Brazil,[34] [35] Thailand[36] and Cuba,[37] underlines the potential of homeopathy as a prophylactic and treatment modality.

According to Sinha et al, Eupatorium perfoliatum (EP) extract significantly inhibited dengue virus infection in a pre-treated HepG2 cell line; the extract also significantly decreased dengue virus-induced autophagy.[38] A study previously conducted in Delhi's slums, whilst establishing protection of 65.7% against laboratory-confirmed dengue using EP 30C as prophylactic, overlooked cases that came under the definition of ‘suspected/probable’ dengue.[39] Considering the burden of probable cases of dengue, the current study was undertaken to determine any protective effect of EP 30C against dengue in the vulnerable population of urban slums of Delhi.


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Methods

Study Design and Setting

This was a prospective, community-based, open-label, parallel cohort study, conducted in apparently healthy individuals in three urban slums (Mayapuri, Peeragarhi and Zakhira) in the west zone of Delhi, capital city of India. The study was conducted from July to October 2018. The study was registered with the Clinical Trials Registry India (CTRI Number: CTRI/2018/08/015328).


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Ethical Approval

Ethical clearance was obtained from the Institutional Ethics Committee of the Central Council for Research in Homoeopathy, New Delhi, before initiation of the study (Ref No. 1-3/2015-16/CCRH/Tech./EC/6-2; May 7th, 2018).


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Participants

Participants were enrolled in two cohorts: medicine cohort (MC) and control cohort (CC). MC included individuals residing in the urban areas of Mayapuri and Peeragarhi and who received EP 30C as below. CC included residents of the urban area of Zakhira and received no medical intervention. All three areas are labeled urban slums by the Government of the National Capital Territory of Delhi, having sub-standard housing, severe overcrowding, unhygienic living conditions, and low socio-economic incomes.

Apparently healthy residents, of either sex, aged 1 year or above, with no history of febrile or dengue-like illness in the previous 7 days, were included. Pregnant women, lactating mothers, children aged less than 1 year and persons with end-stage disease or who were immuno-compromised were excluded. Individuals taking any preventive medicine for dengue were also excluded. A signed informed consent form was obtained from the head of the family during a baseline survey in which the family was briefed on the potential benefits and risks of participating in the study and provided with an information sheet. Families not providing written consent were excluded.


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Prophylactic Intervention

Participants in MC who were over 5 years of age received four medicated globules of EP 30C once a week for 10 weeks by virtue of home visits from trained health workers (HWs). Children aged between 1 and 5 years received two pills of EP 30C from HWs once a week for 10 weeks. The homeopathic medicine EP is a standard pharmacopeial preparation[40] and was procured from a good manufacturing practice-compliant homeopathic pharmacy. The participants in both cohorts were provided with information and educational material regarding dengue awareness and general preventive measures.


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Outcome Measures

The primary outcome was the incidence of dengue, based on the case definition notified by the National Vector-Borne Disease Control Program, Government of India.[41]

Clinical Features of Dengue Fever

An acute febrile illness of 2 to 7 days' duration whose clinical presentation includes two or more of the following:

Headache, retro-orbital pain, myalgia, arthralgia, rash, and haemorrhagic manifestations.


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Probable Dengue Fever/Dengue Haemorrhagic Fever

A case compatible with the clinical description of dengue fever during outbreak OR positive results from the non-enzyme-linked immunosorbent assay (ELISA)-based non-structural glycoprotein (NS1) antigen and immunoglobulin (IgM) antibody tests.


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Confirmed Dengue Fever

A case compatible with the clinical description of dengue fever, with at least one of the following.

  • Isolation of dengue virus culture from serum, plasma and leucocytes.

  • Demonstration of IgM antibody titer by positive ELISA test on single serum sample.

  • Demonstration of dengue virus antigen in serum sample by NS1-ELISA.

  • IgG seroconversion in paired sera after 2 weeks with four-fold increase of IgG titer.

  • Detection of viral nucleic acid by polymerase chain reaction.

The secondary outcome measure was the duration of dengue fever. The duration of dengue fever (time to fever clearance) was defined as the time from the first appearance of fever until the temperature dropped to ≤ 37.5°C and remained below this temperature for at least 48 hours.


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Data Collection

Active surveillance was established, consisting of a team of HWs and supervisors residing in the same community, to provide medicine and monitor the compliance of participants. The HWs were trained by the investigators about the study protocol and data collection before the initiation of the study. Socio-demographic data, including basic demographic information, co-morbidities, habits and occupation, were collected during the first visit in a pre-designed case recording form (CRF). Households were visited on a weekly basis by the HWs; however, if any house was found locked during the weekly visits, the HW visited the same house within 48 hours or would contact through telephone to monitor the compliance. Participants who had moved to a new location during the study period were also noted.


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Follow-up

The study population was actively followed for 14 weeks. During follow-up visits, all episodes of febrile illness (undifferentiated or dengue-like) reported by the participants were recorded on the CRF. Participants were also advised to inform telephonically in case they developed any febrile illness. Those individuals who presented with febrile illness or symptoms consistent with dengue were advised to undergo a serological test for dengue. The diagnosis was based on detection of NS1 Ag and/or IgM Ab and/or IgG Ab against dengue virus. Persons who suffered from febrile illness were advised to undertake treatment of their own choice; however, the clinical progression of these persons was observed until their symptoms subsided. The study staff and physicians consistently monitored all sites to ensure meticulous adherence to the study protocol.


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Sample Size

Recruitment was done at the cluster level by convenience sampling.


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Statistical Analysis

Continuous data were presented as mean ± standard deviation (SD) and analyzed using the t-test. Categorical data were expressed as percentages and analyzed using the chi-square test. Incidence rates were calculated as person-weeks, considering the numerator as the number of events, and the denominator as the sum of person-time contributed by each cohort member during the study period. The protective effect was estimated as [100% ×  (1–odds ratio)] of the probable/laboratory-confirmed dengue cases in MC compared to CC. Dengue cases were further assessed in stratified groups based on age and sex to understand the effect of these confounders on the protective effect of EP.

Binary logistic regression was performed for probable/laboratory-confirmed cases of dengue, taking into consideration confounding factors, and an adjusted odds ratio was calculated for dengue infections for the population that consumed EP 30C (MC). In a sensitivity analysis, we restricted the estimated protective effect of EP to the cases of laboratory-confirmed infections only. A Kaplan–Meier curve was used to estimate the time to fever clearance, and the statistical significance of any difference between the groups was assessed by the log-rank test.

All results are expressed with 95% confidence interval (CI). Statistical significance was set at p < 0.05 (two-tailed) and an odds ratio of less than 1.0 indicated a protective association. The analyses were performed using IBM SPSS Statistics for Windows, version 20 (IBM Corp., Armonk, New York, United States).


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Results

Demography

Out of the population of 20,814 screened, a total of 20,607 participants (MC, n = 15,298; CC, n = 5,309) were enrolled prospectively, with 0.98% (n = 206) participants excluded at the beginning as they matched the exclusion criteria. Twenty-five participants were found to be absent for three consecutive visits by the HWs: that missed follow-up was nevertheless incorporated in the analysis as the data for that period were collected upon these 25 individuals' subsequent return. The overall flow of study enrolment is illustrated in [Fig. 1].

Zoom Image
Fig. 1 Participant recruitment and flow.

The mean age (±SD) in MC was 26.34 (±16.1) years and in CC 23.85 (±15.5) years. Of the enrolled population, 57.79% (11,909) were males and 42.21% (8,698) were females. The description of the baseline characteristics of the enrolled study population is given in [Table 1].

Table 1

Baseline demographic characteristics of enrolled participants

Variable

MC

n = 15,298

CC

n = 5,309

p-Value

Age (years)

(mean ± SD)

26.34 ± 16.1

23.85 ± 15.5

0.0001

Age group

 1–19 y

5,829 (38.10)

2,304 (43.40)

0.0001

 20–39 y

6,141 (40.14)

2,042 (38.46)

 40 y and above

3,328 (21.76)

963 (18.14)

Sex

 Male

8,828 (57.71)

3,081 (58.03)

0.678

 Female

6,470 (42.29)

2,228 (41.97)

Educational qualification

 Primary

9,345 (61.09)

2,608 (49.12)

0.0001

 Secondary

2,327 (15.21)

786 (14.81)

 Graduate

683 (4.46)

104 (1.96)

 Postgraduate

60 (0.39)

5 (0.09)

 Illiterate

2,598 (16.98)

1,206 (22.72)

 Child <5 y

285 (1.86)

600 (11.30)

Abbreviations: CC, control cohort; MC, medicine cohort; SD, standard deviation.


Note: Data presented as n (%).


In total, 1,495 episodes of febrile illnesses were reported by the participants, of which 6.79% (n = 1,039) of illnesses were recorded in MC and 8.59% (n = 456) in CC. Of the 1,495 reported illnesses, 1,090 cases (72.91%) of febrile illnesses (819 in MC and 271 in CC) were excluded from the analysis as they did not meet the dengue case definition criteria. 405 (27.09%) cases of febrile illnesses were included in the analysis for the estimation of protective effect.


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Prevention of Dengue

Overall Prevention of Probable and Laboratory-Confirmed Dengue

Of the total of 276,901 person-weeks of active surveillance from enrolment to 14 weeks, MC and CC were observed for 205,736 and 71,165 person-weeks respectively. Of the 405 febrile illnesses that came under the case definition of dengue, 220 (54.32%) illnesses were reported from MC and 185 (45.68%) in CC.

The incidence of dengue in MC was 1.07 (95% CI, 0.93 to 1.22) per 1,000 person-weeks, as compared with 2.60 (95% CI, 2.24 to 2.99) per 1,000 person-weeks in CC, indicating a reduction of 58.84% in the incidence of dengue. The overall unadjusted protective effect of EP in MC against dengue was 59.59% (95% CI, 50.74 to 66.85, p = 0.0001).

Sub-group analysis was done by stratifying the risk factors age and sex ([Table 2]). A statistically significant protective effect was seen in both sexes and across all age groups except in the age group of 40+ years (protective effect, 33.45%; 95% CI, −6.96 to 58.59; p = 0.0926). The greatest protective effect was observed in the age group of 1 to 19 years (66.92%; 95% CI, 55.21 to 75.56; p = 0.0001). A protective effect of 60.11% was seen in the age group of 20 to 39 years. Significant protection was observed in both sexes, though greater in females (protective effect, 62.79%; 95% CI, 52.4 to 70.91; p = 0.0001) than in males (protective effect, 53.96%; 95% CI, 33.49 to 67.14, p = 0.0001). A comparison of trend of dengue cases between the cohorts is given in [Fig. 2].

Table 2

Protective effect of Eupatorium perfoliatum 30C against probable/laboratory confirmed dengue

Variable

MC

n = 15,298

CC

n = 5,309

Protective effect

% (95% CI)

p-Value

No./Total (%)

Cases of dengue/1,000 person week

No./Total (%)

Cases of dengue/1,000 person week

Probable/laboratory-confirmed dengue

220/15,298 (1.44)

1.07

185/5,309 (3.48)

2.60

59.59 (50.74–66.85)

0.0001

1–19 y

80/5,829 (1.37)

1.03

93/2,304 (4.04)

3.05

66.92 (55.21–75.56)

0.0001

20–39 y

82/6,141 (1.34)

0.99

67/2,042 (3.28)

2.43

60.11 (44.69–71.23)

0.0001

40 y and above

58/3,328 (1.74)

1.29

25/963 (2.60)

1.91

33.45 (-6.96–58.59)

0.0926

Male

80/8,828 (0.91)

0.67

60/3,081 (1.95)

1.43

53.96 (35.49–67.14)

0.0001

Female

140/6,470 (2.16)

1.63

125/2,228 (5.61)

4.29

62.79 (52.4–70.91)

0.0001

Abbreviations: 95% CI, 95% confidence interval; CC, control cohort; MC, medicine cohort.


Zoom Image
Fig. 2 Trend of the weekly distribution of dengue in each cohort.

Binary logistic regression was performed for the dengue cases to assess the impact of age and sex on the likelihood of reporting dengue. After adjusting for confounders, the protective effect of EP against dengue was found to be 60% (95% CI, 0.33 to 0.49, p = 0.0001).


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Prevention of Laboratory-confirmed Dengue Only

During the observation period, 827 individuals (MC, n = 515 [62.27%]; CC, n = 312 [37.73%]) were tested for dengue. Fifty-nine individuals (in MC, n = 26 [5.04%] and in CC, n = 33 [10.03%]) tested positive for dengue.

The incidence of laboratory-confirmed dengue in MC (0.13 per 1,000 person-week) was found to be lower in comparison with CC (0.46 per 1,000 person-week), which is statistically significant (p = 0.0001). The overall unadjusted protective effect of EP against laboratory-confirmed dengue was 72.78% (95% CI, 54.45 to 83.74, p = 0.0001) ([Table 3]).

Table 3

Protective effect of Eupatorium perfoliatum 30C against laboratory confirmed dengue

Variable

MC

n = 15,298

CC

n = 5,309

Protective effect

% (95% CI)

p-Value

No./Total (%)

Cases of dengue/1,000 person week

No./Total (%)

Cases of dengue/1,000 person week

Laboratory-confirmed dengue

26/15,298 (0.17)

0.13

33/5,309 (0.62)

0.46

72.78 (54.45–83.74)

0.0001

1–19 y

8/5,829 (0.14)

0.10

16/2,304 (0.69)

0.53

80.35 (54.02–91.6)

0.0002

20–39 y

12/6,141 (0.2)

0.14

16/2,042 (0.78)

0.58

75.21 (47.51–88.29)

0.0003

40 y and above

6/3,328 (0.18)

0.13

1/963 (0.10)

0.08

−73.75 (−1345.02–79.11)

0.6092

Male

15/8,828 (0.17)

0.13

17/3,081 (0.55)

0.40

69.32 (38.5–84.7)

0.0009

Female

11/6,470 (0.17)

0.13

16/2,228 (0.72)

0.55

76.46 (49.19–89.09)

0.0002

Abbreviations: 95% CI, 95% confidence interval; CC, control cohort; MC, medicine cohort.


Sub-group analysis was done by stratifying the risk factors age and sex: a significant protective effect was seen in all ages and both sexes, as shown in [Table 3]. Females and persons in age group 1 to 19 years were those most protected, with a protective effect of 76.46% (49.19 to 89.09, p = 0.0002) and 80.35% (54.02 to 91.60, p = 0.0002) respectively. In the MC, the age group 40+ years presented an incidence of 0.13 per 1,000 person-week, whereas in the CC the same age group reported an incidence of just 0.08 per 1,000 person-week.

Binary logistic regression was performed to assess the impact of age and sex on the likelihood of reporting of laboratory-confirmed dengue. After adjusting for the effect of confounders, the protective effect of EP against laboratory-confirmed dengue was 72% (95% CI, 0.16 to 0.46, p = 0.0001).


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Time to Fever Clearance

A Kaplan–Meier curve was drawn to compare the time taken for the resolution of fever ([Fig. 3]) of dengue cases. We observed that in MC the resolution of fever was 0.91 day earlier than in CC (MC: 4.18 ± SE 0.09 days, 95% CI: 4.00 to 4.375; CC: 5.09 ± SE 0.22 days, 95% CI: 4.65 to 5.52).

Zoom Image
Fig. 3 Kaplan–Meier estimates of time required (hours) for clearance of fever.

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Prevalence of Symptoms in Dengue Cases

Apart from fever, the frequently observed symptoms in both cohorts were body ache (69.14%), fatigue (74.07%), nausea (18.27%), abdominal pain/tenderness (28.89%), restlessness (9.14%), rash/itching (3.21%) and inappetence (50.62%).

Apart from fever, the frequently observed symptoms in the dengue cases in MC were body ache (60.5%), fatigue (64.55%), headache (63.18%), inappetence (52.27%) and abdominal pain/tenderness (22.27%); whereas in dengue cases in CC, symptoms observed frequently were fatigue (85.41%), body ache (79.46%), headache (77.30%) and inappetence (48.65%). A marked decreasing prevalence of symptoms was observed in MC as compared with CC ([Fig. 4]).

Zoom Image
Fig. 4 Comparison of symptoms of dengue between cohorts. Abbreviations: MC, medicine cohort; CC, control cohort.

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Other Acute Febrile Illnesses

Of the 819 acute febrile illnesses in MC not considered as dengue, 5.25% (n = 43) were diagnosed as typhoid, 0.37% (n = 3) malaria, and 94.38% (n = 773) as undifferentiated acute fever. Of 271 acute febrile cases of CC not considered as dengue, 5.54% (n = 15) were diagnosed as typhoid, 0.74% (n = 2) malaria, and 93.73% (n = 254) undifferentiated acute fever.


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Safety and Hospitalisation

In the 26 cases of laboratory-confirmed dengue in MC, no hospitalisation was required, and the individuals recovered at home, whereas 9.09% (n = 3) persons in CC were hospitalised. No deaths due to dengue were reported in either cohort. No related adverse events were recorded from either cohort.


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Discussion

In our study, we found that the protective effect of EP was 72% against laboratory-confirmed dengue over a period of 14 weeks. The result was statistically significant in both sexes and in all age groups except persons aged 40 years and above. While the global strategy for dengue prevention and control formulated by the WHO had aimed to reduce dengue morbidity by 25% by 2020,[17] in our study a reduction of 58.84% in dengue incidence was observed with the administration of EP 30C. The vulnerable age group,[42] [43] specifically those aged 1 to 19 years, was maximally protected. The low incidence of dengue and the notably non-significant inter-group findings in those with laboratory-confirmed disease who were aged 40 years and above might be attributable to the presence of neutralising antibodies in their blood from prior exposure to dengue, providing age-related protection against re-infection.[22]

Slum dwellers are exposed to multiple risk factors that converge to significantly increase the burden of morbidity and mortality.[44] According to Adiga et al,[45] the slum population is more vulnerable to infectious diseases such as cholera, malaria, dengue and human immunodeficiency virus. During the 2017 dengue outbreak in Delhi slums, a study observed a protective effect of 65.77% against laboratory-confirmed dengue, with the maximum effect seen in the 1 to 19 years age group.[39] While these findings are consistent with our study, the 2017 work did not account for the undiagnosed cases that met the criteria for probable dengue. Additionally, our study documented the duration of the febrile stage, highlighting EP's potential impact on the post-infection progression of the disease.

In a retrospective study conducted between 2014 and 2016, Keawmuneewong et al[36] observed that EP 200C possessed 89.9% effectiveness in preventing dengue fever. Marino et al[35] observed a decrease in the incidence of dengue in Brazil in May 2001 after administering a single dose of EP 30C. However, despite some methodological deficiencies, such as the lack of active surveillance for probable dengue and the absence of a concurrent control group for comparison, a prophylactic impact of EP was perceived.

Exploring the potential of EP on human immunity might further reveal its role in the prevention and treatment of dengue. Studies using EP in in-vivo and in-vitro models have been conducted with encouraging outcomes, implicating its anti-inflammatory,[46] anti-plasmodial[47] and anti-viral properties, primarily by inhibiting viral attachment and multiplication.[38] [48]

Our study, like any other clinical trial, has its limitations. Not all study participants underwent dengue testing, which limits our ability to estimate the preventive impact of EP on dengue infection rates. Nevertheless, the observed reduction in dengue symptom prevalence validates the effectiveness of EP. It will be intriguing to ascertain if EP can inhibit the infection in future studies. Our study falls short of determining the asymptomatic burden of the disease, particularly in evaluating EP's effectiveness among asymptomatic populations, as dengue testing in such individuals was not undertaken. Vikram et al[49] reported that approximately 65% of dengue infections in Delhi go unaccounted for, due to people being either asymptomatic or having very mild symptoms aside from fever. Such cases would have been missed in our study if not reported by the individuals concerned.

Homeopathic medicines, unlike vaccines, do not stimulate the production of antibodies against pathogens. Though homeopathy's protective effects have been observed against different diseases, the underlying mechanism of action remains unexplored. Further scientific evaluation is necessary to understand whether protection arises from reduced infection rates, decreased transmission, or lowered individual susceptibility.[50]

Incorporation of a placebo control group and blinding of participants could have further strengthened the study results; however, due to the study's large sample size, its intrinsic nature as a public health trial, and with ethical and administrative constraints related to placebo controls, implementing blinding was not feasible. To minimise bias in outcome evaluation, forthcoming trials should aim to adopt a double-blind, placebo-controlled design. Nonetheless, for evaluating the effectiveness of interventions, recommendations also endorse the inclusion of observational studies, including those employing a parallel cohort design.[51] [52]

The effectiveness of targeted homeopathic interventions against specific infectious diseases has been validated through several studies. Whilst individual studies may have their imperfections, the results cumulatively indicate that homeopathy as a prophylactic measure in various infectious diseases is promising.[53] Our community-based prophylaxis study involved individuals of all age groups and weekly surveillance to assess the incidence of dengue. However, the findings of our study might not be completely generalisable across India due to the diversity of populations in different parts of the country. Replication of our study in other geographical regions would contribute important evidence for or against the prophylactic potential of EP.

With dengue vaccines in India still under trial,[22] the results of our study suggest a prophylactic and potentially cost-effective solution against dengue. This could be valuable in addressing the rising threat of the disease. EP might serve as a beneficial prophylactic choice during dengue outbreaks or, in the future, as a concurrent intervention with vaccines.


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Conclusion

The use of EP 30C in Delhi was associated with some protection against probable and laboratory-confirmed dengue. Further research is required to confirm or refute the findings.


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Highlights

  • The study estimated the protective effect of Eupatorium perfoliatum 30C on the incidence of dengue fever during the outbreak of 2018 in three urban slums of Delhi.

  • The analysis included 20,607 participants, where the overall unadjusted protective effect of Eupatorium perfoliatum 30C against probable/laboratory-confirmed dengue was found to be 59.59%.

  • The unadjusted protective effect against laboratory-confirmed dengue was 72.78%, significant in both sexes and in all age groups except persons aged 40 years and above.

  • A potential prophylactic measure against dengue is suggested by the findings of this study.


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Conflict of Interest

None declared.

Acknowledgements

The authors acknowledge the onsite assistance of the supervisors and health care workers at different study locations. Data entry operators (Ms. Rajni, Ms. Sarita, Ms. Tarannum and Mr. Deepak) and multi-task workers are acknowledged for their secretarial assistance. A word of sincere thanks goes to Dr. Satvinder Singh, Research Officer (Biochem.), and Mr. Arun Kumar from Dr. D.P. Rastogi Central Research Institute for Homoeopathy, Noida, for the collection of blood samples and timely delivery of reports. The authors are thankful to Dr. Ruchika Bhalla, Research Associate (Hom.), for input in the drafting of the manuscript. We extend our gratitude to the support of the local administration at the different study sites for permission to conduct the work. We also acknowledge the cooperation of all study participants, without which the project could not successfully have taken place.


Address for correspondence

Dr. Debadatta Nayak, MD
Central Council for Research in Homoeopathy
61-65, Institutional Area, Opposite D Block, Janakpuri, New Delhi—110058
India   

Publication History

Received: 07 December 2023

Accepted: 03 June 2024

Article published online:
24 October 2024

© 2024. Faculty of Homeopathy. This article is published by Thieme.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany


Zoom Image
Fig. 1 Participant recruitment and flow.
Zoom Image
Fig. 2 Trend of the weekly distribution of dengue in each cohort.
Zoom Image
Fig. 3 Kaplan–Meier estimates of time required (hours) for clearance of fever.
Zoom Image
Fig. 4 Comparison of symptoms of dengue between cohorts. Abbreviations: MC, medicine cohort; CC, control cohort.