Keywords
Eupatorium perfoliatum
- dengue fever - homeopathy - prevention
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.
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).
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).
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.
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.
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.
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.
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.
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.
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.
Sample Size
Recruitment was done at the cluster level by convenience sampling.
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).
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 ].
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.
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.
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).
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).
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).
Fig. 3 Kaplan–Meier estimates of time required (hours) for clearance of fever.
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 ]).
Fig. 4 Comparison of symptoms of dengue between cohorts. Abbreviations: MC, medicine cohort;
CC, control cohort.
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.
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.
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.
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.
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.