ADVERSE EFFECTS OF RABIES VACCINE OBSERVED IN

THE PEOPLE OF DIFFERENT AGE GROUPS IN SUKRARAJ

TROPICAL AND INFECTIOUS DISEASE HOSPITAL

Research Report Submitted in Partial Fulfillment of the Requirements of

the Degree of Bachelor of Pharmacy from JF Institute of Health
Sciences Hattiban, Lalitpur Affiliated Tribhuwan University

Institute of Medicine

Submitted by:

Krishna Neupane

TU Regd.No:4-2-940-15-2014
APPROVAL SHEET

The research report entitled “Adverse effect of rabies vaccine observed in the people of different
age group in Sukraraj Tropical and Infectious Hospital ” of animal bitten people in Sukraraj
Tropical and Infectious Hospital, Teku ,Kathmandu and the report being submitted to JF Institute
of Health Sciences affiliated to Tribhuwan University, to fulfill the partial requirement of
Bachelor Degree in Pharmacy.

Student ………………………….................

Krishna Neupane

Research Approved by

Research Supervisor …………………………………….

Anju Bajracharya

Pharmacy Coordinator .……………………………………

Nirajan Bhusal

External Examiner ……………………………………

……………………………………

Date: …………………………………

ii
ACKNOWLEDGEMENT

I have high regards to Sukraraj Tropical And Infectious Disease Hospital for facilitating the data
collection required to conduct this study for the partial fulfillment of degree of Bachelor of
Pharmacy . I would also extend my sincere gratitude to the Principal, Professor Mrs. Radha
Ranabhat for guidance , and advice and absolute support.

I would like to extend my immense gratitude to my research supervisor Mrs. Anju Maharjan for
her guidance , supervision and cooperation throughout the study . I owe my gratitude to program
co-ordinator Mr. Nirajan Bhusal for motivating, suggesting, guiding and cooperation with me
from the very beginning of proposal to the completion of the final report .

I am thankful to Mr. Anup Bastola , Senior Dr. of Sukraraj Hospital , and all the faculty members
of JF Institute of Health Science for their enthusiastic guidance, supervision and advice during
my theisis work.

I owe my grateful to my colleagues Mr. Rabindra Paudel , Mr. Kamal Kunwar , Sangam K.C as
well as all my classmates who helped from their side during my research work. I would also like
to thank to all my teachers, seniors , juniors, friends and well wisher who helped me directly or
indirectly to accomplish the task.

iii
ABSTRACT

Objectives: This research was conducted to find out the adverse effect seen in the people of
different age groups after vaccination of rabies vaccine . In this research 176 people of different
age groups and genders are taken . Data was collected two from 22 August to 5 September in
Sukraraj Tropical and Infectious Disease Hospital Teku.

Results: From our data we found most of the effect last for short period of time and cured itself
without further medication . Among collected data 61.3% people suffered from pain , 54.4%
people suffered from Swelling , 66.3% suffered from redness , 53.8% people suffered from
itching , 13.1% people suffered from dizziness , 43.1% people suffered from skin rashes/
allergy , 45.6% people suffered from muscle pain , 15% people suffered from restlessness ,
32.5% people suffered from weakness , 24.4% people suffered from fever and 4.4% people were
seen other effect.

Methodology:

Conclusion: Among the adverse effect seen the age group of 5 to 15 and above 55 are seen more
adverse effect than others age group while the age group of 25 to 35 are seen less adverse effect .
. Similarly , adverse effect is seen more in female than in male.

iv
ACRONYMS

ARV Anti-rabies Vaccine

HRIG Human Rabies Immune globin

RIG Rabies Immune globin

WHO World Health Organization

IM Intra-muscular

ID Intra-dermal

IU International Unit

ADR Adverse Drug Reaction

v
Contents
APPROVAL SHEET...................................................................................................................................ii
ACKNOWLEDGEMENT..........................................................................................................................iii
ABSTRACT...............................................................................................................................................iv
ACRONYMS..............................................................................................................................................v
LIST OF TABLES....................................................................................................................................viii
LIST OF FIGURES..................................................................................................................................viii
CHAPTER ONE: INTRODUCTION..........................................................................................................1
1.1 Background...........................................................................................................................................1
1.2 History of rabies Vaccine......................................................................................................................2
1.3 Present scenario in Nepal.......................................................................................................................2
1.3 Rabies vaccine used in Nepal................................................................................................................2
1.4 Working Mechanism of Rabies Vaccine................................................................................................3
1.5 Route of vaccine administration............................................................................................................3
1.6 Vaccination time and course of total vaccination..................................................................................4
1.7 Adverse effect seen in the people after vaccination...............................................................................4
1.8 Rational of the study..............................................................................................................................5
1.9 Objectives Of Study...............................................................................................................................7
1.9.1 General Objectives.............................................................................................................................7
1.9.2 Specific Objectives.............................................................................................................................7
CHAPTER TWO : LITERATURE REVIEW.............................................................................................8
CHAPTER THREE: METHODOLOGY..................................................................................................10
3.1 Study area............................................................................................................................................10
3.2 Study type:...........................................................................................................................................10
3.3 Sample technique and sample size:......................................................................................................10
3.4 Patient inclusion and exclusion criteria:..............................................................................................11
3.5 Data collection technique and study duration......................................................................................11
3.6 Validity and Reliability.......................................................................................................................11
CHAPTER FOUR : DATA ANALYSIS AND ITS INTERPRETATION................................................12
4.1 Demography of the patients:................................................................................................................12

vi
4.2 Gender of the patients..........................................................................................................................12
4.3 Patients regarding categorization of age groups:.................................................................................13
4.4 Susceptible animal:..............................................................................................................................14
4.5 Adverse reaction from ARV as reported by interview:........................................................................16
4.6 Adverse reaction in different age groups:............................................................................................18
CHAPTER FIVE : DISCUSSION.............................................................................................................24
CHAPTER SIX : CONCLUSION.............................................................................................................26
REFERENCE............................................................................................................................................27
ANNEX.....................................................................................................................................................31

vii
LIST OF TABLES

Table 1: Gender of the patients......................................................................................................10

Table 2: Adverse reaction from ARV as reported by interview....................................................14

LIST OF FIGURES

Figure 1: Gender of the patients....................................................................................................11

Figure 2: Age group of the patients...............................................................................................12
Figure 3: Suceptible animal...........................................................................................................13
Figure 4 : Prevalence of ADRs due to ARV at STAIDH Teku, Kathmandu................................15
Figure 5: Adverse reaction in Age group (5-15):..........................................................................16
Figure 6: Adverse reaction in Age group (16-25):........................................................................17
Figure 7: Adverse reaction in Age group (26-35).........................................................................18
Figure 8 : Adverse reaction in Age group (35-45)........................................................................19
Figure 9 : Adverse reaction in Age group (46-55)........................................................................20
Figure 10: Adverse reaction in Age group (55+)...........................................................................21

viii
CHAPTER ONE: INTRODUCTION

1.1 Background

Rabies is an acute viral zoonotic disease that causes fatal encephalomyelitis in human and many
other mammals (Tulek N., 2008) . Although highly effective prophylaxis is available , this viral
infection remains a cause of death in almost all the countries , with the exception of Antarctica
and some island nations. (Bleck TP et al., 2010)

According to the World Health Organization (WHO); over 10 million people per year, mostly
from Asia are Vaccinated following contact with the disease. Rabies post exposure prophylaxis
is almost 100% successful when it is applied using vaccines prepared in modern tissue culture
concomitantly with rabies immunoglobulin (WHO) at the correct dose and time.

Rabies vaccine is a vaccine used to prevent rabies. There are a number of vaccines available that
are safe and effective . They used to prevent rabies before and for a period of time after exposure
to the virus such as by a dog or cat bite. The immunity that develops is long lasting after a full
course . Doses are usually given by the injection in muscle or skin . After exposure vaccination is
typically used along with rabies immunoglobulin . It is recommended that those who are at the
high risk of exposure be vaccinated before potential exposure. Vaccines are effective in human
and other animal. Vaccination dogs is very effective in preventing the spread of rabies of
human . (Rabies vaccine :WHO position paper, 2010 )

Primarily cell culture of embryonated egg based rabies vaccine are also used worldwide . Two
types of RIG preparations are in use: RIG of human (HRIG) , at a recommended at dose of 20
IU/kg, and RIG of equinie (ERIG) origin, at a recommended 40 IU/kg for ERIG . According to
recent WHO and CDC recommendations , full RIG dosage should be administered around the
would, if anatomically appropriate .(Wilde H., 2002 )

Rabies vaccine may be safely used in all age group . About 35 to 45 percent of people a brief
period of redness and pain at the injection site. About 5 to 15 percent of people may have fever,
headaches or nausea . After exposure to rabies there is no contraindication to its use.

1
Most vaccines do not contain thimerosal . Vaccines made from nerve tissue are used in a few
countries , mainly in Asia and Latin America, but are less effective and have greater side effects .
Their use is thus not recommended by the World Health Organization . (Rabies vaccines: WHO
position paper , 2010 )

1.2 History of rabies Vaccine

The first rabies vaccine was introduced in 1885 and was followed by an improved version in
1908 . The credit of invention of rabies vaccine goes to Luis Pasteur. Rabies vaccine is the
World Health Organization list of essential medicine . Millions of people globally has been
vaccinated and it is estimated more than 2 million people a year .

1.3 Present scenario in Nepal

In the context of Nepal more than 500 people are bitten by various animal each day . Out of 500
only half of people are known about the vaccination . Other people ingnored as they are unkown
about the rabies vaccine . Vaccination against rabies vaccine is available in every district
headquarter of Nepal . In the context of Kathmandu more than 200 people are bitten by animal
daily . Out them more than 100 people come for vaccination in Sukraraj Tropical Center which is
located in Teku. Vaccination of rabies vaccine is expensive in private clinic as it cost more than
Rs 600 but in government hospital it cost only 100 because of funding from Nepal government in
rabies vaccine. According to data given by Sukraraj Hospital More than 20 people die per year
because of Rabies in their hospital .

1.3 Rabies vaccine used in Nepal

In Nepal the vaccine of Brand name Abhayrab is used for vaccination . It is manufactured by
Human Biological Institute ( A division of Indian immunological limited )

Compostion:

2
Purified lyophilized Rabies Antigen derived from Rabies virus (L. Pasteur 2061/Vero strain
propogated in Vero cells ) Inactivated .

Potency : 2.5 I.U per vial

Stabilizers: Maltose and and human albumin

Preservative : Thiormesal 0.015% w/v

Reconstitution:

Reconstitute the freeze dried vaccine with 0.5ml dilutent (0.9% Sodium Choride Inj I.P)
provided along with pack

Storage Temperature: It should be stored within 2 degree to 8 degree Celsius .

1.4 Working Mechanism of Rabies Vaccine

Rabies vaccine contains inactivated rabies virus. It works by provoking the body immune
response to this virus , without actually causing the disease. When body is exposed to foreign
organism such as bacteria and virus , the immune system produce antibody towards them. These,
antibodies kill such foreign organism . The rabies vaccine stimulates against the rabies virus and
is given to prevent the diseases.

1.5 Route of vaccine administration

Rabies vaccine is administered in skin and muscle . It is mainly given by Intradermal and
Intramuscular route. In most of the countries rabies vaccine is given by Intramuscular route . But
in South Asia it is mainly given by Intradermal route. If the vaccine is given by Intramuscular
route one additional dose is required so intramuscular route is expensive and it is very difficult to
complete the full dose in the country like Nepal where people are unaware about the requirement
of full vaccination course. Intradermal route is painful in comparison to the Intramuscular route
so Intradermal route is mainly given in 2 arms diving equal dose in each arms.

3
 1.6 Vaccination time and course of total vaccination

The total dose of rabies vaccine is 0.5ml at a time from the age group after one years. The
maximum dose required for full vaccination is 5 dose . It is divided according to the days bitten
by animals. The dosing time is classified as:

1) Day 0 is the day of first vaccination after bitten by animal within 24 hours.
2) Day 3 is the second vaccination day
3) Day 7 is the third vaccination day
4) Day 14 is the fourth vaccination day
5) Day 27 is the fifth vaccination day

One individual may require different dosing course which depends on the pre vaccination of dog
with rabies vaccine , death or alive of the animal .The people which require different dosing
course is categorized as:

A) If a person is bitten by animal or dogs which is pre vaccinated with rabies vaccine for that person
3 dose of rabies vaccine is sufficient.
B) If a person is bitten by the street dog and the drug did not die within 14 days then that person
require four dose of rabies vaccine.
C) If a person is bitten by the street dog and the dog died within 14 days then the person require five
dose of rabies vaccine.

1.7 Adverse effect seen in the people after vaccination

Adverse effect: Adverse effect is defined as the undesirable and harmful effect seen in the
people after the medication or surgery . Adverse effect can hinder the treatment and lead to more
complications .

After rabies vaccine severe adverse effect not seen generally . The adverse effect seen are cured
itself without further medication . Generally people with rabies vaccine are mostly seen with the
effects likes swelling , muscle pain , injection site pain , itching , allergies etc. Some people may
also suffer from fever , headache , dizziness , weakness and others adverse effects .

4
 Generally seen adverse effects after rabies vaccine is listed as:

a) Injection site Pain

b) Swelling
c) Skin Itching
d) Skin redness
e) Dizziness
f) Skin rashes
g) Nausea
h) Vomiting
i) Muscle pain
j) Restlessness
k) Weakness
l) Fever
m) Headache
n) Abdominal pain

All people may not have adverse effect . In context of some people no any such effects also can
be seen whereas in case of some people multiple adverse effects also can be seen .

1.8 Rational of the study

Rabies is probably the oldest recorded infection of mankind. The development of the first rabies
vaccine by Pasteur surely had been hoped to eliminate or at least drastically reduce its incidence.
However, this goal has not been achieved because rabies is maintained in many animal
reservoirs, including both domestic and wild. There are still many aspects of the pathogenicity of
rabies that are unknown. For example, we have no explanation for the long incubation period (up
to 6 years). Furthermore, new patterns of rabies infection present a problem for epidemiologists
and virologists alike. There are several cases of human rabies in which there was no history of a
bite. Despite these continuing problems, there has been tremendous progress in the control of
rabies. Cheap and safe vaccines for animals as well as humans have been developed. Oral

5
vaccination of wildlife with recombinant rabies virus vaccines is beginning to reduce the
incidence of rabies among foxes and raccoons. Vaccination of stray dogs could lead to the
eradication of rabies in countries where dog rabies is the sole source of human exposure.( Zhen
FangFu , 1997)

Rabies continues to be an important public health problem and many other developing countries.
Rabies vaccine is presumed to be cheap, although the actual cost of production may not be low.
However, it is not a safe vaccine as it causes demyelinating central or peripheral nervous system
side-effects in 1/3000–7000 persons vaccinated; this adverse reaction is occasionally fatal. Cell
culture rabies vaccines are also available in India; unlike the Sample vaccine they are safe and
can be used for pre-exposure vaccination, but they are more expensive. The dilemma is whether
it is ethically acceptable to continue to use the Sample vaccine in humans while safer products
are available. What is urgently needed is a decision tree which would enable economical use of
cell culture vaccines together with the backing of professional bodies in medical practice, who
will declare that cost is not the only factor in choosing a rabies vaccine — safety is also of
paramount importance. ( T.Jacob John,1997 ) Thus, it is necessary to do more research
regarding the clinician to evaluate a patient’s response to treatment to determine the efficacy of
the treatment and to identify any adverse reaction.

In this study, we investigated the side effects that developed in patients following administration
of anti rabies vaccine . We aimed to determine the differences in the side effects of vaccines
according to trade marks and to different vaccination schedules.

6
 1.9 Objectives Of Study

1.9.1 General Objectives

 To access of the adverse effect of ARV used in Nepal.

1.9.2 Specific Objectives

 To find out the adverse effects of ARVS.

 To find out demographic pattern of patient vaccinated from ARV.
 To find out adverse effect of ARV in different age group.

7
CHAPTER TWO : LITERATURE REVIEW

Bonito RF, de Oliveira NM and Nishioka Sde A conducted a research article named “ Adverse
reactions associated with a Fuenzalida-Palacios rabies vaccine: a quasi-experimental study” in 2004.In
this article Fuenzalida-Palacios rabies vaccine has been used in South America for rabies post-exposure
prophylaxis. To determine the frequency of adverse reactions associated with this vaccine compared to a
control group a quasi-experimental study was carried out in Uberlândia, Brazil, from May 1997 to April
1998. Victims of bites or other injuries by dogs or other mammals and who received or not post-exposure
prophylaxis with Fuenzalida-Palacios rabies vaccine were compared as to the occurrence of a list of signs
and symptoms. Out of 2,440 victims of bites and other injuries from dogs and other mammals 2,114
participated in the study; 1,004 of them provided follow-up information within 10 to 15 days. Headache
and pain at the injection sites were the most commonly found symptoms (125/1,000). No neuroparalytic
event was detected. Patients who were given Fuenzalida-Palacios rabies vaccine and those who were not
had similar incidences of symptoms (risk ratios close to 1). Regarding the occurrence of adverse
reactions, Fuenzalida-Palacios rabies vaccine is a valid alternative for rabies post-exposure prophylaxis.

Zhang XR, Wu ZG, and Zhang WS on their article “ Adverse reaction caused by rabies
vaccine in China: a Meta-analysis “ in 2017 searched electronically databases including CNKI,
VIP information resource integration service platform, WanFang Data, CBM, PubMed and The
Cochrane Library, to collect studies on Chinese people who had received full rabies vaccination
and recording all the adverse reactions, from January 2000 to July 2016. Inclusion and exclusion
criteria were strictly followed. Meta-analysis for the adverse reaction rate was performed using
the R software. Results: A total of 29 related papers had met the inclusion criteria, with no
publication bias noticed. A total number of 11 020 cases had adverse reactions, among all the 94
222 respondents, with an incidence of adverse reactions as 1.04%-47.78%. The overall incidence
rate of adverse reaction was 9.82% (95%CI: 7.58%-12.72%). A combined local adverse reaction
rate appeared as 12.05% (95% CI: 9.26%-15.69%). The systemic adverse reaction rate was
9.06% (95%CI: 7.07%-11.61%). The overall adverse reaction rate on aqueous vaccine was

8
32.39% (95%CI: 21.88%-47.94%). Combined adverse reaction rate of freeze
dried vaccine appeared as 8.65% (95%CI: 4.54%-16.51%). Significant differences were seen
between both groups (P<0.05). The local adverse reaction rate caused by rabies vaccination was
higher than the systemic adverse reaction rate. The adverse reaction rate of aqueous rabies
vaccine was higher than that of freeze dried rabies vaccine. Our results suggested that the
aqueous vaccineshould gradually be eliminated.

Sari T, Tulek N, Bulut C, Oral B, and Tuncer Ertem in their article named “Adverse events
following rabies post-exposure prophylaxis: a comparative study of two different schedules and
two vaccines ” A total of 1685 patients were vaccinated. 265 patients (15.7%) administered the
Essen regimen with equine rabies immunoglobulin and 1420 patients (84.2%) administered
Zagreb regimen. 761 (45.2%) patients were vaccinated with a verocell vaccine; Verorab and 924
patients (54.8%) were vaccinated with Abhayrab. All side effects were higher in female patients
than those of males. The patients with chronic illness also had significantly, increased side
effects; headache (12.4%), pain at site of administration (11.3%), and arthralgia (10.5%)
compared to the patients without chronic illness. They grouped the patients in three as; 0-15
years, 15-60 years, and 60 years and above. In the first group; fever (21.2%), vomiting (2.4%)
and coughing (2.1%); in the second group (15-60 years), headache (8.8%), arthralgia (6.7%)
were significantly increased compared to the other groups. Side effects are significantly higher
with schema of 2-1-1 and Abhayrab trade mark vaccine, particularly following the first doses.

9
CHAPTER THREE: METHODOLOGY

I will interviewee and inform each patient who underwent prophylaxis with regard to possible
side effects. I will administer questionnaires addressing possible side effects listed on the form to
each patient visit during prophylaxis; in addition, I will asked the patients to inform us of any
unexpected conditions in the following month. The side effects that recorded as being related to
the vaccine were as follows: Local side effects; pain, swelling, redness, itching, paraesthesia at
site of vaccine administration, and systemic side effects; headache, dizziness, fever, itching,
weakness, abdominal pain, lymphadenopathy (LAP), nausea, vomiting, myalgia, cough,
insomnia, numbness, irregular menstruation, decreased libido, rash, sore throat, arthralgia,
encephalopathy and other (with explanation). Finally I will evaluate the side effects of the
vaccine with regard to age, gender, chronic disease, each dose of vaccine, different vaccine
schedules, with administration of RIG and trade name of vaccine used.

3.1 Study area

The study area was done in Sukraraj Tropical centre, Teku.

3.2 Study type:

The study type retrospective, cross sectional descriptive type.

3.3 Sample technique and sample size:

Simple random sampling used around 200 patients.

10
 3.4 Patient inclusion and exclusion criteria:

3.4.1 Inclusion criteria:

 Patients above 5 years.

3.4.2 Exclusion criteria:

 Patients below 5 years.

 Patient who is mentally disabled and incomplete clinical information.

3.5 Data collection technique and study duration

 A formal request will be made from the concerned authority to the hospital and verbal contest
will be obtain from exponents the study.
 The respondents were assured of confidentiality and privacy of the information and encouraged
to be sincere and truthful to the responses.
 The data was collected through face to face interview with semi-structure type of questionnaire

A predesigned questionnaire (ANNEX 1 ) will ask to patient and a written or verbal consent will
obtain from patient before starting interview as well as laboratory reports .

3.6 Validity and Reliability

The content validity will be maintained by consulting guide teacher, subject teacher and
colleague. The methods for research will be modified according to their suggestion and
guidance.

11
CHAPTER FOUR : DATA ANALYSIS AND ITS INTERPRETATION

All the collected data from Sukraraj Tropical and Infections diseases hospital, teku from 22
Augist to 5th September, were entered in Microsoft Excel 2010 version and analyzed by using
IBM SPSS Statistics version 24 software. Data were analyzed interms of frequency, distribution
and percentage.

4.1 Demography of the patients:

Total number of the patients participated in this study were 176 in which male patients were
53.4% and female patients were 46.6%.

4.2 Gender of the patients

Table 1: Gender of the patients

Frequency Percent
Valid Male 94 53.4 53.4
Female 82 46.6 46.6
Total 176 100.0 100.0

12
Figure 1: Gender of the patients

4.3 Patients regarding categorization of age groups:

The patients among 176 interviewed victims 31 were from age group 5-15,36 from age group 16-
25, 36 from age group 26-35, 26 from age group 36-45 , 22 from age group 46-55 and remaining
25 were patients age ranged above 55.

13
Figure 2: Age group of the patients

4.4 Susceptible animal:

Among the 176 patients interviewed, majority of the patients treated with ARV came after the
bitten by the dog and minority of the patients came after the bitten by cat. No other animal bitten
cases are not included in this study.

14
Figure 3: Suceptible animal

15
4.5 Adverse reaction from ARV as reported by interview:

Percentage of
No. of patients the cases
Pain 98 61.3%
Swelling 87 54.4%
Redness 106 66.3%
Itching 86 53.8%
Dizziness 21 13.1%
Skin rash/Allergy 69 43.1%
Nausea 10 6.3%
Muscle Pain 73 45.6%
Restlessness 24 15.0%
Weakness 52 32.5%
Fever 39 24.4%
Others 7 4.4%

Table 2: Adverse reaction from ARV as reported by interview

Most frequently occurring side effect of Anti Rabies Vaccine is Redness at site of injection
(66.3%) followed by the Pain at site (61.3%), Itching (53.8%),Muscle pain( 45.6%) , Skin rash/
Allergy (43.1%), Weakness( 32.5%) and so on.

16
Prevalence of ADRs due to ARV at STAIDH Teku, Kathmandu
(for all age groups)

70.00%

60.00%

50.00%

40.00%

30.00%

20.00%

10.00%

0.00%
) ) ) ) ) ) ) ) ss ) ) )
5% 5% 8% 5% 3% 3% 0% 8% ne 0% 5% 8%
.2 .2 .3 .7 .6 .1 .5 .3 s .0 .2 .3
66 61 54 53 46 43 32 24 l es 15 (6 (4
s( n( g( ( n( y( ss
( r( st s( a rs
s i
lin ng i rg ve Re es us
e
he
ne Pa el hi Pa le ne Fe Ot
ed Itc
cle Al ak z zin Na
R Sw us h/ W
e Di
M s
Ra
in
Sk

Figure 4 : Prevalence of ADRs due to ARV at STAIDH Teku, Kathmandu

17
4.6 Adverse reaction in different age groups:

Adverse reaction in Age group (5-15):

Total number of participant were 31, in which 17 were male and 14 were female patients.
Adverse reaction in age group 5-15 must commonly shows Redness (83.9%), Fever (80.6%)
followed by Pain at site (71.0%). Restlessness, vomiting and others reaction were not shown in
this group.

Prevalence of ADR due to ARV for age group 5-15

90.00%
80.00%
70.00%
60.00%
50.00%
40.00%
30.00%
20.00%
10.00%
0.00%
Redness Fever Pain Skin Rash/ Swelling Itching Muscle Weakness Dizziness Nausea
Allergy Pain

Figure 5: Adverse reaction in Age group (5-15):

18
Adverse reaction in Age group (16-25):

Total number of participant were 36, in which 19 were male and 17 were female patients
Adverse reaction in age group 16-25 must commonly shows Redness (52.8%) and Pain at site
(52.8%) followed by Swelling (47.2%).

Figure 6: Adverse reaction in Age group (16-25):

19
Adverse reaction in Age group (26-35):

Total number of participant were 36, in which 19 were male and 17 were female patients
Adverse reaction in age group 16-25 must commonly shows Pain at site (52.8%), Muscle pain
(52.8%) followed by Rednss(50%). Fever adverse reaction was not shown in this group.

Figure 7: Adverse reaction in Age group (26-35)

20
Adverse reaction in Age group (36-45):

Total number of participant were 26, in which 14 were male and 12 were female patients.
Adverse reaction in age group 16-25 must commonly shows Redness (50%), Itching (50.0%)
followed by Pain at site (46.2%). Dizziness, Nausea and fever adverse reaction were not shown
in this group.

Figure 8 : Adverse reaction in Age group (35-45)

21
Adverse reaction in Age group (46-55):
Total number of participant were 22, in which 13 were male and 9 were female patients. Adverse
reaction in age group 16-25 must commonly shows Redness (68.2%), Muscle pain (63.6%)
followed by Pain, Swelling and itching. Fever and others adverse reaction were not shown in this
group.

Prevalence of ADR due to ARV in age group 46-55

80.00%
70.00%
60.00%
50.00%
40.00%
30.00%
20.00%
10.00%
0.00%
s i n ng i n g s y ss s a
es Pa hi Pa lin es rg ne es us
e
dn Itc el kn l le s in
R e cle Sw e a
/A l es Di
z z Na
us W sh st
M Ra Re
in
Sk

Figure 9 : Adverse reaction in Age group (46-55)

22
Adverse reaction in Age group (55+):

Total number of participant were 25, in which 12 were male and 13were female patients.
Adverse reaction in age group 16-25 must commonly shows weakness (60.0%), Redness
(60.0%) followed by Pain, Restlessness, Muscle pain and fever.

Prevalence of ADR due to ARV at age group 55+

70.00%
60.00%
50.00%
40.00%
30.00%
20.00%
10.00%
0.00%
s s i n ss i n r ng g y s a rs
es ne
s
Pa ne Pa ve hi lin rg es us
e
he
kn d s Fe Itc el Al
le in Ot
e a R e l es cle Sw / Di
z z Na
W st us sh
Re M Ra
in
Sk

Figure 10: Adverse reaction in Age group (55+)

23
CHAPTER FIVE : DISCUSSION

Dog and other animal bites leading to risk of developing rabies will continue to occur in most
developing countries and there will be ever increasing demand for safe and potent rabies
vaccines. The rabies virus is transmitted through exposure to saliva from an infected animal bite,
such as dogs, bats, skunks, raccoons, and cats. Rabies is endemic in dogs in most South-East
Asian countries and is most commonly transmitted to humans via rabid dog bites. It can also be
transmitted from inhalation of aerosolized rabies virus, tissue and organ transplants, or where
broken skin or mucous membranes come into contact with any infected body fluid, whether
humans or mammals.

In our study, 176 people exposed to rabies through dog and other animal bites were recruited for
the study at four different centers. All subjects had single bites belonging to WHO category II or
III. None had multiple bites or bites on head and neck. The rabid status of the biting animal was
not confirmed in any case as all were street dogs and were not traceable after the incident.

In our study , total number of the patients participated in this study were 176 in which male
patients were 53.4% and female patients were 46.6%. The number of male and female patients
was almost the same. Similar study conducted in India by D.H Ashwathnaryana et al in 2010
have 73% were male patients and 27% were female patients.

The patients among 176 interviewed victims 31 were from age group 5-15,36 from age group 16-
25, 36 from age group 26-35, 26 from age group 36-45 , 22 from age group 46-55 and remaining
25 were patients age ranged above 55.

In our study, majority of the patients treated with ARV came after the bitten by the dog and
minority of the patients came after the bitten by cat. No other animal bitten cases are not
included in this study similar study conducted in India by D.H Ashwathnaryana et al in 2010,
where 88.0% patients were visited the hospital after bitten by Dog, 8.0% patients were visited the
hospital after bitten by Monkey and 4.0% of patients visited after bitten by the cat.

24
In our study, most frequently occurring side effect of Anti Rabies Vaccine is Redness at site of
injection (66.3%) followed by the Pain at site (61.3%), Itching (53.8%), Muscle pain ( 45.6%) ,
Skin rash/ Allergy (43.1%), Weakness ( 32.5%) and so on. Similar study carried out by Kimie J
kagawa et al in 1992, most adverse reactions were mild and limited to the injection site , as
63.5% of the students that experienced adverse reactions reported pain and 48% ,redness 40% ,
reported pruritus and 16% swelling at the injection site. None reported extended or general
pruritus. Some students reported nausea (6.3%), dizziness (3.2%), malaise (11%) and headache
(14.3 %). Fever (19.1%) and muscle aches (16%) were more frequently reported, and 4 subjects
(6.3%) reported lymphadenopathy. Overall, local adverse reactions occurred in no more than
12.3% of the vaccinated persons and systemic reactions as fever, myalgia, dizziness or malaise
were reported in < 4% of the students.

Possible reasons behind the adverse effect of ARV observed in people of different age group:

1. People of different age group have different immunity power.

2. Elder people and children are not sufficient enough to produce required antibody to
combat antigen.
3. Amount of antigen is higher than antibody produced by the body.
4. Proper storage facility is not available while transportation and distribution.
5. Inappropriate mixing of dry ARV with its diluents.
6. Patients with other associated medical illness.

25
CHAPTER SIX : CONCLUSION

The main reservoir of rabies is the dog, which is responsible for almost 99% of fatal rabies cases
in humans. Although the rabies vaccines available for animals are safe, immunogenic, and
efficacious when administered as recommended, vaccines that do not contain proper
immunogenic antigens should be identified and discarded. Lack of efficacy is also considered an
adverse outcome of vaccination. Although no vaccine can claim 100% efficacy, true lack of
efficacy is uncommon and failure to immunize is more likely to result from inappropriate
administration, pre-existing disease, immunosuppression, or genetic non-responsiveness than to a
problem with the vaccine itself.

Physician should be watchful of adverse effects in prescribing rabies vaccination especially in

patients with a history of allergic conditions. In a people with suspected adverse reactions
following rabies vaccine, a thorough clinical assessment should be made to weigh benefits versus
risks of proceeding with rabies vaccination, bearing in mind that the disease is deadly.

Although it is impossible to completely prevent adverse reactions to vaccines, the data presented
here support the view that the benefits of core vaccination against infectious diseases outweigh
the low risk of an adverse reaction.

26
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trial with human diploid cell rabies vaccine in children. Clin Infect Dis 1999;29:141e9.
 Anderson LJ, Sikes RK, Langkop CW, Mann JM, Smith JS, Winkler WG, et al. Postexposure
trial of a human diploid cell strain rabies vaccine. J Infect Dis 1980;142:133e8.
 Ajjan N, Pilet C. Comparative study of the safety and protective value. In pre-exposure use. Of
rabies vaccine cultivated on human diploid cells (HDCV) and of the new vaccine grown on Vero
cells. Vaccine 1989;7:125e8.
 Wilde H, Chomckey P, Prakongsri S, Punyaratabandhy P, Chutivongse S. Adverse effects of
equine rabies immune gobulin. Vaccine 1989;7:10e1.
 Shohat T, Green MS, Nakar O, Ballin A, Duvdevani P, Cohen A, et al. Gender differences in the
reactogenicity of measlesmumps-rubella vaccine. Isr Med Assoc J 2000;2:192e5.
 Ash LR. Preferential susceptibility of male jirds (Meriones uniculatus) to infection with Brugia
pahangi. J Parasitol 1971; 57:777e80.
 Leitner G, Heller ED, Friedman A. Sex-related differences in immune response and survival rate
of broiler chicken. Vet Immunol Immunopathol 1989;21:249e60.
 Gomes E, Cardoso MF, Praca F, Gomes L, Marino E, Demoly P. Self reported drug allergy in a
general adult Portuguese population. Clin Exp Allergy 2004;34:1597e601.
 Dundee JW, McDonald JR, Clark RS. Frequency of atopy and allergy in an anesthetic patient
population. Br J Anaesth 1978; 50:793e8.
 "Rabies vaccines: WHO position paper" (PDF). Weekly epidemiological record. 32(85): 309–
320. Aug 6, 2010. Archived (PDF) from the original on 2015-02-27

30
ANNEX

QUESTIONNAIRES

Name: Address:
Gender: Male/Female Age:

Possible adverse effect that may be seen in the patients after vaccination

a) Injection site reactions Yes No

(pain, swelling, itching, or
redness)
b) Dizziness Yes No
c) Skin rash/ allergy Yes No
d) Nausea Yes No
e) Vomiting Yes No
f) Muscle pain Yes No
g) Restlessness Yes No
h) Weakness Yes No
i) Fever Yes No
j) Others: Specify:

31
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