Evaluatıon of adverse events following immunization reported during national immunization programs (Between 2017-2019 in Ankara Province)

ABSTRACT

Vaccination services are important in primary health-care service. The Expanded Programme on Immunization (EPI) began in 1981 in Turkey. Vaccines are generally safe products; although rare, undesirable effects may be observed after vaccination. In order to increase vaccination rates, vaccine acceptability and service quality; the Vaccine Adverse Event Reporting System (VAERS) and performing necessary interventions are indispensable parts of vaccination programs. This study aimed to evaluate Adverse Events Following Immunization (AEFI) cases during 2017–2019 in Ankara. A total of ~1.7 million doses of vaccine were administered, and only 71 adverse events following immunization (AEFI) were reported (0.41 cases/million doses of risk). AEFI forms were examined, and of these 71 cases, 17 (24%) were hospitalized and 54 (76%) were followed-up.

KEYWORDS:

• Expanded program on immunization
• vaccine adverse events
• vaccine

Introduction and purpose

The purpose of immunization is to protect people and society against vaccine-preventable diseases. Vaccination services protect babies, children and adults against serious and life-threatening infectious diseases.¹

The Expanded Programme on Immunization (EPI), which began in 1981 in Turkey, includes pertussis, diphtheria, tetanus, measles, rubella, mumps, tuberculosis, poliomyelitis, hepatitis B, Haemophilus influenzae type b and Streptococcus pneumoniae vaccines. Vaccination services should reach vulnerable age groups to vaccinate them before they get infection by reducing morbidity and mortality of diseases to control these diseases and even eliminate them completely. Thanks to vaccination studies that have been carried out successfully in Turkey for many years, vaccine-preventable diseases and related deaths have been largely prevented.

Vaccines used in Turkey are those used in many developed countries and thus are highly reliable vaccines, with United States Food and Drug Administration (FDA) and/or European Medicines Agency’s (EMA) certification. Vaccines will be offered services in Turkey, passed through an approval process by the Ministry of Health. This process includes the pyrogenicity tests and reliability tests of the vaccine. Although rare, undesirable effects may be observed after vaccination. To increase vaccination rates, vaccine acceptability and service quality, monitoring systems and performing necessary interventions are indispensable parts of vaccination programs.¹

Adverse Events Following Immunization (AEFI)

Such events in a vaccinee are known vaccine side effects or undesirable medical event that is thought to be related to the vaccination. The undesirable effect after vaccination may cause parents to hesitate to have their child vaccinated or even to reject vaccination. Hesitation also can be encountered due to causes besides vaccine-related side effects.^2–4 In some cases, AEFI may be due to the vaccine itself, in others to errors during the administration of the vaccine, or it may be irrelevant to the vaccine or administration.

Vccine side effects, program application errors (that may occur during production, distribution and administration of the vaccine), injection reaction, random effects, and unknown effects are collected in these five groups.

Adverse events following vaccinations monitoring system

Vaccination programs are indispensable and very important for maintaining the trust of the society in vaccines.²

Strategies to be applied in achieving this goal

• Regularly monitoring, analyzing and interpreting AEFI that occur.

• To reveal whether AEFI is due to vaccination when serious adverse effects are seen.

• Interfering with problems that cause program implementation errors.

• If the increase in vaccine side effects is higher than expected, to intervene.

• Interventions and appropriate communication channels have been shown to assure the public’s trust in the vaccination program.²

AEFI reports and related research are carried out with the standard Post-Vaccine Adverse Event Report and Review Form prepared by the Ministry of Health. Then the Provincial Adverse Events After Vaccination Advisory Board meets and classifies the event according to the reason after examining the Adverse Events After Vaccination Notification and Examination Form and Case Research Report. The report is sent to the Ministry of Health, General Directorate of Public Health, Department of Vaccine Preventable Diseases.

Evaluating the data of this monitoring system and creating solutions for problems contribute to this process. This study aimed to evaluate AEFI cases during 2017–2019 in Ankara.

Materials and methods

This descriptive study occurred during 2017–2019 in the Adverse Events After Vaccination Advisory Board. Serious cases such as local reaction, acute allergic reaction, convulsion, encephalitis, arthritis, BCGitis, lymphadenitis, injection reaction, bacterial abscess, paralysis, notification and examination forms, case research reports and board decisions were reviewed retrospectively. The data were collected using the Post-Vaccınatıon Undesırable Effect Report And Revıew Form created by the Ministry of Health. Relevant clinical data were expressed without the use of personal identification information in accordance with local rules. To use the data in the study, permission was obtained from the Ankara Provincial Health Directorate Public Health Services Presidency Provincial Research Demands Evaluation Commission with the decision of the meeting dated 03/03/2020, and approval was obtained on 07/05/2020 from the Ankara Provincial Health Directorate for the publication of this article. Descriptive analyses were presented using numbers and percentages.

Results

Between 2017 and 2018, 13 kinds of vaccines were administered in 10 sessions in a total of 21 individual vaccinations. From January 2019, Pneumococcal Conjugate Vaccine (PCV) was reduced from 3 doses plus 1 booster to 2 doses plus booster (Table 1). In Ankara Province, in the 0–11 months, 12–24 months, 1st and 8th grade age groups, 275–282 K children were vaccinated per year (Table 2).

Table 1. Turkish Ministry of Health childhood vaccination calendar, 2019

Vaccines	Birth	End of 1 month	End of 2 months	End of 4 months	End of 6 months	End of 12 months	End of 18 months	End of 24 months	Elementary 1 degree	Elementary 8 degree
HepB	I	II			III
BCG			I
PCV			I	II		B
DaPT-IPV-Hib			I	II	III		B
OPV					I		II
VAR						I
MMR						I			II
HepA							I	II
DaPT-IPV									B
Td										B

Hepatitis B: Hepatitis B Vaccine.

BCG: Bacille Calmette-Guérin (Tuberculosis) Vaccine.

PCV: Pneumococcal Conjugate Vaccination.

OPV: Oral Polio Vaccine.

VAR: Varicella vaccine.

MMR: Measles, Mumps & Rubella Vaccine.

HepA: HepatitisA Vaccine.

DaPT-IPV: Diphtheria and tetanus toxoids and acellular pertussis adsorbed and inactivated poliovirus vaccine (P).

Td: Tetanus and diphtheria toxoids adsorbed (A).

B: Booster.

Table 2. In Ankara Province, according to Turkish Ministry of Health childhood vaccination schedule, number of vaccination practices in 2017–2019

	2017	2018	2019
Month 0–11*	73,238	71,419	70,746
Month 12–24 Ay**	74,896	73,718	71,023
1.Degree^	63,193	68,171	69,142
8. Degree^^	70,575	63,288	64,094
Total implemented vaccination	281,902	276,596	275,005
Vaccination implementation***	5,919,942	5,808,516	5,775,105

* DaPT-IPV-Hib3; **DaPT-IPV-Hib-B; ***Calculated as 21 applications.

^DaPT-IPV-B; ^^Td-B.

In this study, 71 cases (0.41 cases/million doses of risk) were included in the AEFI Notification and Examination Forms and Case Research Reports with the 1.7 M vaccine administrations examined for 2017–2019: local reaction in 27 (35%), acute allergic reaction in 16 (23%), convulsion in 9 (13%), bacterial abscesses in 5 (7%), encephalitis in 1 (1%), arthritis in 1 (1%), BCGitis in 1 (1%), lymphadenitis in 1 (1%), injection reaction in 1 (1%), paralysis in 1 (1%) (Table 3). From these cases, 17 (24%) were hospitalized and 54 (76.%) were followed-up.

Table 3. Distribution of cases with ASIE according to childhood vaccine application times (2017–2019)

	2 months	4 months	6 months	12 months	18 months	24 months	Elemantary School 1 Degree	Elemantary School 8 Degree
	(n = 10)	(n = 5)	(n = 5)	(n = 8)	(n = 7)	(n = 2)	(n = 23)	(n = 3)
Local reaction	1	1	2	2	4	0	15	2
Acute allergic reaction	3	1	0	3	1	1	7	0
Convulsion	3	3	1	1	1	0	0	0
Encephalitis	0	0	1	0	0	0	0	1
Artritis	0	0	0	1	0	0	0	0
BCGitis	1	0	0	0	0	0	0	0
Lymphadenitis	1	0	0	0	0	0	0	0
Injection Reaction	0	0	0	0	0	1	0	0
Bacterial abscess	1	0	1	1	1	0	1	0
Paralysis	0	0	0	0	1	0	0	0

Discussion

In our study, the rate of AEFI was determined as “0.41 case/million dose risk”.

Turnbull et al. reported that after Bacille Calmette-Guérin (Tuberculosis) Vaccine (BCG), severe local reactions including lymphadenitis occurred in 1% of the study group, and pain, redness or swelling in 1.5% after BCG vaccination. Although our data is 3 years old, a lower AEFI was observed.⁵

In a study during 1982–1986, 561 aged between 14–18 months and 6 years vaccinated with the Measles, Mumps & Rubella Vaccine (MMR) vaccine containing Enders-Edmonston measles virus strain, Jeryl Lynn mumps virus strain and Wistar RA 27/3 rubella virus strain. Five hundred and sixty-one thousand children were enrolled in a surveillance study by the National Institute of Public Health, and in their follow-up, it was found that 9 children with encephalitis and 10 with meningitis developed the disease within 3 months after vaccination. This was not seen after our vaccination practices.⁶

In a study during1990-2003, after inactivated influenza vaccination for children under 2 years of age, according to case reports, the four most common AEFI coding terms were fever, unspecified or urticarial rash and injection site reaction.⁷

Although similar side effects are observed in our study, these side effects cannot be directly linked to influenza since this vaccine is given simultaneously with other vaccines.

In a study of the risk of anaphylaxis of children and adolescents after administration of 7.6 M vaccine doses including MMR, – Hepatitis B Vaccine (HepB), Tetanus and diphtheria toxoids adsorbed (Td), d Diphtheria and tetanus toxoids and acellular pertussis adsorbed, inactivated poliovirus and Haemophilus influenzae type b conjugate vaccine (DTaP-IPV/Hib) and oral polio vaccine (OPV), 0.65 cases/million doses were reported, including vaccine-related anaphylaxis (95% CI: 0.21–1.53), none of which resulted in death. They reported that they observed an anaphylaxis case only after 653 thousand MMR vaccine doses and reviewed additional allergic conditions as “1.53 cases/million dose risk” (95% CI: 0.04–8.52).⁸

In the study of Kondolot et al., families were followed up in the child neurology clinic after agreeing to participate in the follow-up of their children from January 2013 to January 2015. A questionnaire was applied to investigate the age, diagnosis age, gender, maternal age and maternal education levels of children, whether their vaccinations are complete, the reasons for incomplete vaccination, whether there were emergency applications due to AEFI, and seasonal influenza vaccination and vaccination status. Seventeen percent of these patients had been vaccinated due to neurological diseases, 11% were still vaccinated. Among these patients, the rate of admission to the emergency service was higher in the group whose vaccine was interrupted than in the group that was fully vaccinated (p < .001).⁹

In another study, the first dose of hepatitis B vaccine was applied in the second day post-birth, and an abscess was described as a case report.¹⁰

According to Communicable Disease Control and Prevention (CDC) Adverse Events Following Immunization January 2019 report; Immunizations may very rarely lead to acute encephalitis, particularly in the setting of live-attenuated viral vaccines. The risk of encephalitic complications from viral infections (1/1000 cases of measles; 1/6000 cases of rubella) is greater than the risk following vaccination (1/1,000,000 following MMR). Similarly, in our study, there was no encephalitis case after MMR, only one encephalitis case was detected after the 6th month vaccination.¹¹

According to CDC Vaccine Adverse Event Reporting System; 10 seizure, 5 generalized tonic clonic seizure, 3 partial seizures; 3 clonic convulsion,11 febril convulsion, 3 status epilepticus, 1 lymphadenopaty reported between 2017 and 2019. The convulsion in our study was detected higher than in US. It was thought that this difference might be related to the limitations in reporting systems. As CDC states; reports may include incomplete, inaccurate, coincidental and unverified information.¹²

Conclusion and recommendations

Between 2017 and 2019, over 17 M vaccine doses were administered, and AEFI were reported in only 71cases; of these, 17 (24%) were hospitalized and 54 (76%) were followed-up. The rate of serious side effects was found to be very low. Thus, vaccine practices were very safe in Ankara province. Vaccine is the main practice of preventive medicine that should be given to children.