To evaluate safety of measles and rubella combined vaccine. Subjects and methods: Randomized, controlled and single-blind clinical trial study was conducted on 756 people aged 1 to 45 years old in Hanam and Hoabinh provinces. Results: Incidence of adverse events within the 30-minute and the 28-day follow-up in the two study groups were 5.6% and 9.5%; 7.5% and 7.5%. Conclusions: Measles and rubella combined vaccine was safely used on volunteers and not significantly different from the control group.
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SAFETY OF MEASLES AND RUBELLA COMBINED VACCINE
MANUFACTERING BY POLYVAC IN VIETNAMESE VOLUNTEERS
Nguyen Xuan Dong 1 ; Dinh Hong Duong 2 ; Nguyen Thuy Huong 3
Ha The Tan 2 ; Vu Tung Son 2 ; Vu Ngoc Hoan 2
SUMMARY
Objectives: To evaluate safety of measles and rubella combined vaccine Subjects and
methods: Randomized, controlled and single-blind clinical trial study was conducted on 756
people aged 1 to 45 years old in Hanam and Hoabinh provinces Results: Incidence of adverse
events within the 30-minute and the 28-day follow-up in the two study groups were 5.6% and
9.5%; 7.5% and 7.5% Conclusions: Measles and rubella combined vaccine was safely used on
volunteers and not significantly different from the control group
* Keywords: Measles and rubella combined vaccine; Safety
INTRODUCTION
In our country, the epidemic situation
of measles and rubella has changed
positively with the trend of substantially
decline morbidity and mortality after
implementing vaccines in the expanded
immunization programe However, measles
is still circulating with a 3 - 5 year period
of epidemic, rubella has an outbreak time,
especially the congenital rubella syndrome
in children increases the medical, economic
and social burden every year [1, 2, 3]
The goal of eliminating these two
diseases in our country is still difficult due
to the lack of vaccines The vaccine against
rubella and rubella used previously was
imported from India In fulfillment of a cost
decrease in the expanded immunization
programe and actively control, prevent
has successfully produced measles and rubella combined vaccine (MRVAC) according to technology transfer from Japan Before applying in community, we conducted this study to assess the safety
of MRVAC
SUBJECTS AND METHODS
1 Subjects
* Volunteers:
A total of 756 people in Hanam and Hoabinh provinces participated in the study, including 420 children from 1 to 2, 168 people over 2 to under 18 and 168 people from 18 to 45 years old There were 504 subjects vaccinated MRVAC and 252 subjects immunized control vaccine
Research time: from April 8, 2016 to July
27, 2016
1 Military Institute of Medicine Preventive
2 Vietnam Military Medical Univerity
3 Center for Research and Production of Vaccines and Biologicals
Corresponding author: Nguyen Xuan Dong (Nguyen.Xuan.Dong81@gmail.com)
Date received: 25/06/2019
Date accepted: 05/08/2019
Trang 2* Vaccines:
Study vaccine: MRVAC vaccine produced
by POLYVAC
- Ingredients: Each bottle 10 doses of
measles vaccine is reconstituted with 5.5
mL solvent Each dose 0.5 mL includes:
Live, further attenuated AIK-C measles
Live, further attenuated Takahashi rubella
strain ≥ 1,000 PFU
Stabilizers: Lactose 2%; D-sorbitol
0.72%; L-sodium glutamate 0.4%; hydrolized
gelatin 0.36%
Antibiotics: erythromycin ≤ 12.5 µg;
anamycin ≤ 12.5 µg
- Lot number: MR-0115; production date: November 4, 2015; expiry date: November
4, 2017
Control vaccine: measles-rebella (MR)
vaccine produced by India Lot number: 012N4072; production date: July 2014; expiry date: August 1, 2016
2 Methods
* Research design: A randomized,
controlled and single-blind clinical trial study was conducted
Local, systemic and serious adverse events within the 30-minute and the 28-day follow-up were supervised, evaluated
to collect data by questionnaires The safety of vaccines were assessed by the incidence of such events
Vaccination
0 AE, SAE supervision 28 follow-up day
within the 30-minute Last check, questionnaires
Figure 1: Vaccination and adverse events supervision diagram
RESULTS AND DISCUSSION
1 Adverse events occur within 30 minutes after vaccination
Table 1: Adverse events within 30 minutes after vaccination in two study groups
MRVAC (n = 504)
Control vaccine (n = 252) Adverse events within 30 minutes after
vaccination
p
Events
Within 30 minutes after vaccination, the incidence of adverse events occurred in MRVAC group significantly lower than the control group, respectively: 5.6% and 9.5%
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(p < 0.05, Chi-square test) In particular, mainly local events with redness at the injection site (p < 0.05, Chi-square test), pain at the injection site and swelling at the injection site No systemic events recorded The local events were mild and resolved after 1 - 2 days
2 Adverse events occur within 28 day after vaccination
Table 2: Adverse events within 28 day after vaccination in two study groups
MRVAC (n = 504)
Control vaccine (n = 252) Adverse events within 28 day after
vaccination
p
Events
Within 28 days after vaccination, the
incidence of adverse events occurred in
both MRVAC and control groups was
7.5% In particular, mainly fever (6.5%
and 5.2%), cough (2.6% and 2.0%) Other
events appeared at low rates Noted other
events such as sore throat, VA inflammation,
rash, predominantly occurs in children
aged 1 - 2 years The incidence of events
in the two study groups was not different
(p > 0.05, Chi-square test) Except for two
cases with severe and serious events, the
rest were mild and self-resolved after 1 - 3
days Local events prevailed within 30 minutes but within 28 days after vaccination, systemic events had a higher occurrence rate
The incidence of adverse events in our study was higher than single and lower vaccine had the same formula produced
in Japan and equivalent to some other
MR combination vaccines The study by Doan Huy Hau et al with AIK-C measles strain did not record the rate of local events, fever rate was 3.1%, cough was 6.2% and diarrhea was 0.7% Yamane et
Trang 4al’s research with rubella Takahashi did
not found adverse events The study by
Takeuchi Y et al showed that the
prevalence of local events was 2.2%,
fever was 25.1%, rash was 21.4% and
lymphadenopathy was 3.0% The study
by Kumagai T had only 2 cases of mild erythema, 1 case of diarrhea and 1 case
of headache, the study by Ozaki T et al only recorded 1 case of mild fever, however the sample size of those studies were small [4, 5, 6, 7, 8]
Table 3: Distribution of adverse events occurred within 28 days after MRVAC
vaccination by province
Hanam (n = 267)
Hoabinh (n = 237)
Adverse events within 28 day after
vaccination
p
Events
The rate of events in Hanam province
was 12.7%, which was significantly higher
than Hoabinh province (1.7%), of which
the majority of children were in the form of
fever, cough, sore throat occupying high
rate The cause of this difference may be
due to the time of deployment in Hoabinh
was from May to June, while in Hanam
was from April to May, coinciding with the
period of humid, hot-cold erratic in the
North, and as a result, young children was
susceptible with respiratory diseases, contributing to making a difference
3 Serious adverse event
- The first case: Male, 3 years old, MRVAC group He had sudden abnormal symptom from 6th day after vaccination with toxic infection syndrome (a fever
of 390C, leukocytes were 17.4 x 109/l), gastrointestinal disorder, abdominal wall reaction (±), McBurney’ point (±)
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Preliminary and postoperative diagnosis:
Acute appendicitis After surgery, subject
recuperate well and was collected M1
blood sample according to the research
schedule
- The second case: Female, 27 years
old, MRVAC group Subjects had variety
manifestation from 3rd day after vaccination
with moderate fever, severe and prolonged
time swelling, redness, pain at the injection
site Conclusion: Injection site abscess
After taking antibiotics, anti-inflammatory
and antipyretic drugs, subjects recuperated
and completely cured after 1 month
Some serious adverse events associated
with MRVAC have been recorded such
as hypersensitivity reactions, acute and
chronic arthritis, encephalitis, subacute
meningitis, Guillain-Barré syndrome,
seizures, thrombocytopenia and autism
These serious adverse event cases could
not relate to vaccines Immunization errors
might be culprit of injection site abscess
case [9, 10]
CONCLUSION
Measles and rubella combined vaccine
achieved safety requirements with adverse
events occurring within 30 minutes, 28 days
after vaccination rate was 5.6% and 7.5%,
equivalent to MR vaccine manufactured
by India Two serious adverse events
cases did not associate with vaccines
REFERENCES
1 Dang Thi Thanh Huyen, Duong Thi Hong
Several epidemiological and clinical characteristics
of measles in Vietnam, 2013 - 2014 Vietnam
Journal of Preventive Medicine 2016, Vol
XXVI, 4 (177), pp.98-106
2 Dang Thi Thanh Huyen, Duong Thi Hong
et al Epidemiology of rubella in Vietnam,
2008 - 2012 Vietnam Journal of Preventive Medicine 2015, Vol XXV, 8 (168), pp.216-224
3 Tran Nhu Duong, Vu Hai Ha et al
Epidemiological characteristics of cases of congenital rubella syndrome surveyed at Vietnam National Hospital of Pediatrics, 2011
- 2016 Vietnam Journal of Preventive Medicine
2016, Vol XXVI, 10 (183), pp.35-42
4 Doan Huy Hau, Dao Xuan Vinh, Dinh Hong Duong et al Evaluation of safety and
immunogenicity of the MVVAC manufactering
by POLYVAC (phase 1 and 3) Vietnam
Vol XXI, 4, pp.110-117
5 Yamane Y, Nagashima T, Asahara T et
al Studies on the live attenuated rubella virus
vaccine III Clinical trials with rubella virus (Takahashi strain) vaccine in children and women Kitasato Arch Exp Med 1974, 47, pp.89-100
6 Takeuchi Y, Togashi T, Sunakawa K et
al Field trial of combined measles and rubella
live attenuated vaccine Infectious Disease Magazine 2002, 76 (1), pp.56-62
7 Kumagai T, Ihara T, Nakayama T et al
measles-rubella combined vaccine in school-entry-aged subjects with naturally acquired measles immunity Pediatr 2015, 57 (4), pp.597-602
8 Ozaki T, Nishimura N, Gotoh K et al
Phases 3 and 4 immunization immunogenicity with combined measles-rubella vaccine
Kansenshogaku Zasshi 2011, 85 (3), pp.250-255
9 WHO Supplementary information on
vaccine safety Part 2: Background rates of adverse events following immunization 2000
10 WHO Global Manual on Surveillance
of Adverse Events Following Immunization
2014.