INTRODUCTION:

Immunity is capability of an organism to resist harmful or infectious diseases. One cannot be infected by a specific disease if he/she is immune to that disease. Immunization is a process which is essential for a person to be protected against any infectious disease through vaccination. Vaccine is a medicinal product which offers necessary immunity to protect the person against a specific disease for which the vaccine is administered. It can be administered by injections, by mouth or through nose.¹Vaccines are administered to infants, young children, preteens, teens and adults. Some people like health care provider, military members and people with health conditions may require additional vaccination considering their risk for specific disease.²

Every component in vaccine serves a specific purpose. Antigens and adjuvants are two ingredients which offer immune response to specific disease. Preservatives like thimerosal and stabilizers like sugar and gelatin are components which ensure safety and long term efficiency of a vaccine. Some components like cell cultures, inactivating (germ-killing) materials and antibiotics which are needed to produce vaccine, are not needed in vaccine to work in a person and thus get removed before production of final product.³Vaccines being immunogenic, are not devoid of adverse events. Any untoward medical occurrence which follows immunization and which does not necessarily have a causal relationship with vaccine is termed as "Adverse event following immunization (AEFI)".⁴AEFIs can possibly occur due to vaccine interactions, programme errors, coincidence (I.e., event occurred after immunization but not related to vaccine) or injection reactions.⁵

AEFIs are classified in to five categories according to World Health Organization (WHO) and Council for International Organizations of Medical Sciences (CIOMS). They are

Vaccine product related reaction;

Vaccine quality related reaction;

Immunization error related reaction;

Immunization anxiety related reaction;

Coincidental event;

Any AEFI which results in death, is life threatening, requires hospitalization, caused significant disability or requires intervention to prevent damage is considered as "Serious AEFI".⁶ In 1974, for the development and expansion of immunization programs, to prevent spread infectious diseases and to enable availability of immunization to every child in the world, the "Expanded programme of Immunization (EPI)" has been established.⁷ Advisory Committee on Immunization Practices (ACIP) is a board of public health experts which is responsible for vaccine recommendations.⁸

Universal immunization programme (UIP) was established in 1985 which is an integral part of National Health Mission (NHM) and one of the largest public health programs. It monitors all the immunization programmes.⁹ Surveillance of all AEFIs is carried out by UIP and Pharmaco-vigilance programme of India (PvPI). Problems encountered by the programme are lack of awareness among public and health care providers regarding seriousness of target disease, inadequate programme management and equipment, lack of skills for vaccine handling and monitoring. All reported AEFIs undergo systematic causality assessment as per WHO algorithm. Considering the vast network of AEFI reporting committees or ADR Monitoring Centers (AMC) at district and state levels, significant number of AEFIs is still underreported.¹⁰

Although there exists a huge literature regarding AEFI and assessment for causality of AEFI globally and also nationally, there are very less/almost no studies conducted on AEFI. In our state there are very few studies conducted to know incidence rates of obtained AEFIs following vaccine administration. These reasons led a foundation to our study. The present study was aimed to identify, report, assess the causality, severity, predictability, preventability of AEFIs and to know the reasons behind them, check the incidence rates of AEFIs for Pentavalent dose-I.

METHODS AND MATERIALS:

Study design:

The current study is a prospective observational and was conducted over a period of 9 months from July 2019 to march 2020. Ethical clearance was obtained from the institutional ethical committee of ChebroluHanumaiah Institute of Pharmaceutical Sciences, Guntur before beginning the study.

Study site:

The study was conducted at immunization center at pediatrics department, NRI general and multispecialty hospital, mangalagiri, India. All the vaccines supplied were administered on all the 3 working days.

Inclusion criteria:

Children aged from day 1 of both the genders and those who were receiving only DPT- I/HIB- I/IPV- I/OPV- II/HBV- II/Rota virus vaccines were included in the study.

Exclusion criteria:

Children with congenital anomalies and were administering any of the vaccines and those who were not willing to give consent were excluded from the study.

Study procedure:

After statistical analysis, a sample of 500 was assessed for the criteria, some of them were excluded due to obvious reasons like not giving the consent, not accepting the phone call, not visiting our immunization center for subsequent vaccination dosage. Finally 348 subjects were recruited in to the study after obtaining the verbal informed consent from the subjects’ guardian. The guardians were provided with a patient information leaflet in which the vaccines and possible AEFI data, precautions were included. Subjects were watched for 30 minutes to check any serious AEFIs post vaccination at the immunization center. After the child was administered with the Pentavalent-I dose of vaccination, they were followed up for a telephonic interview and were made to know about thepossible AEFIs observed after 1 week. All the AEFIs were noted in the patient data collection form. The patient data collection form was designed in such a way that it includes all the data regarding subject, vaccine and AEFI. It includes the personal information of subject like guardians name, age, sex, weight, registration number of the subject. Further it includes the vaccine details and the date of administration for all the doses. It was followed by the symptoms of adverse events, date and time of events started.

Assessment of AEFIs:

AEFIs were assessed by using WHO Vaccine AEFI causality assessment scale, schumock and thornton severity assessment scale and preventability scales. The assessments were carried out by the AEFI assessment team which was composed of one professor from pediatrics department, three clinical pharmacists and a Pharmacovigilance specialist. All the observed AEFIs were reported at the pediatrics department of NRI general and multi-specialty hospital from where all the reported AEFIs were reported to local ADR Monitoring Center (AMC). In case of any queries raised regarding demographics/vaccination details, we collected the information from registration center and made a call to the guardians for further confirmation.

RESULTS:

The total number of subjects enrolled in to the study was about 500. Subjects who were followed till the end of the study were about 348 of which 197(54.9%) are male and 157(45.1%) are female participants. The response rate of the subjects was found to be 69.6%, leaving a percentage of 30.4% as dropouts. The mains reasons for dropouts was found to be not giving the consent (4.2%), not answering the phone call (8.2%), vaccinating subsequently at some other immunization centers (18%).

After vaccinating the children with Pentavalent-I dose about 1138 AEFIs (Adverse Events Following Immunization) were recorded out of 348 children. The details of Distribution of AEFI at different weeks with different vaccines were furnished in the Table 1.

Table 1: Distribution of adverse event reports at different weeks

S. No	Adverse Events Following Immunization	Number of infants
1	Fever+ swelling+ erythema+ crying for 24 hrs	203
2	Fever+ swelling+ erythema+ crying for 48 hrs	52
3	Fever+ swelling + crying for 24 hrs	30
4	Fever + erythema+ crying for 24 hrs	22
5	Fever+ swelling+ Erythema	9
6	Swelling + erythema+ crying for 24 hrs	6
7	Swelling + crying for 24 hrs	6
8	Fever+ Swelling + crying for48 hrs	2
9	Fever+ Crying for 24 hrs	2
10	Fever+ Erythema	1
11	Crying for 24 hrs	1
12	Crying for 48 hrs	1
13	No events	13
14	Total	348
15	Children with AEFI	335

The AEFIs were most frequently observed with Pentavac ® which consists of [Diphtheria+ Tetanus+ whole cell pertussis (DTwP) + Hepatitis B (Hep B) + Hemophilus Influenza B (HiB)] and was followed by Zero dose which consists of Bacillus Calmitte Guerin (BCG), Hepatitis B (Hep B) + Oral polio virus (OPV) vaccine. Fever was the major reaction noted with pentavalent doses administration. It accounts for 26.62 %(303) of total AEFIs (1138) observed with pentavalent dose.

The incidence rate of AEFIs for Pentavalent-I dose was reported to be 96.264%,. Fever was the most frequently observed AEFI and it accounts for 26.62% of total reactions followed by erythema which accounts for 26.01% of AEFIs followed by swelling, crying for 24 hours and crying for 48 hours with an incidence rate of 25.21%, 19.33%, 3.33% respectively. The frequencies of AEFIs are detailed in Figure 1.

Fig. 1: Severity profile of AEFIs.

Causality assessment of AEFI:

“WHO causality assessment scale” was used to perform the causality assessment of observed AEFIs. The scale divided into consistent, indeterminate and inconsistent type of AEFIs. All the reactionsin the current study are consistent more specifically vaccine product related reactions. There was neither vaccine quality, immunization error related nor immunization anxiety related reactions in our study.

Severity assessment of AEFI:

Hartwig-seigal scale was used to perform the severity assessment of observed AEFIs in the study. Out of 1138AEFIs51.23% (583) of AEFI were mild in nature followed by 48.77% (555) of AEFIs which were moderate. There exist neither severe nor serious AEFIs in our study. Figure 2 details about the severity profile of observed AEFI.

Fig. 2: Severity profile of AEFIs.

Predictability assessment of AEFI:

As there is a strong literature regarding the adverse events following immunization and according to the predictability scale, all the AEFIs in our study are 100% predictable.

Preventability assessment of AEFI:

Out of 1138 AEFIs only 303(26.62%) were definitely preventable. All the other 835(73.38%) AEFIs were not preventable AEFIs. The percentage of probably preventable AEFIs in the sample was zero (0%). The details were furnished in Figure 3.

Fig. 3: Preventability profile of AEFIs.

There observed no death or hospitalization due to AEFIs in our study and in all the cases the AEFIs were self limiting after a 2-3 days.

DISCUSSION:

Immunization safety has got an equal concern as the efficacy of vaccines in the national vaccine preventable disease (VPD) programs. Expectations from vaccinations are much higher, and problems arising from the vaccine or vaccination are less acceptable to the general public. The incidence of observed AEFIs after Pentavalent-I dose was found to be 92.264%. A couple of studies done previously by Joshi ND et al, (2013) Adherkar RY et al, (2016) were found to have the incidence rates of AEFI as 20.85 and 11.9% respectively.^11,12 Two similar studies conducted by the researchers in countries Spain and Iran were found to have incidence rates of 22.7%, 19.0% respectively (2016, 2004).^13,14

The most common AEFI in thePentavalent dose of our study was fever (26.62%) which was consistent with the results of two individual studies Joshi et al(2013) in India (34.6%) and Zhou et al (2003) in US (25.8%).^11,15

A study by Carrasco-Garrido et al in Spain and by Mansoor et al in New Zealand mentions swelling at the site of injection as the most common AEFI. In our study it was about 25.21% and is the third most common AEFI following erythema, while it contributes about 10.8% in a study by zhou et al (2003) in US.¹⁵

Most AEFIs in our study were reported with DPT-containing vaccines (Pentavac® and Quadravac®), as seen in studies of Mansoor et al 2014, Adherkar RY et al, 2016, Mahajan D et al 2019, J Sebastian, P Gurumurthy et al, (2019).

It is evident that the vaccines after the 6-8 weeks dose, adverse events reporting were maximum which supports the results of a north Indian study. The major AEFI being the fever followed by swelling and erythema, crying for 24hrs and 48hrs in Pentavalent dose-I. This does not comply with the study of Kar et al. (2017) where the highest being the compliant of fever, inconsolable crying followed by swelling and redness at the injection site.¹⁶

Causality Assessment:

AEFIs categorized under consistent causal association to vaccination were 100% in the present study. Whereas in a couple of studies in India by J Sebastian et al, (2019) and Singh et al (2018) were 93.4% and 53% respectively.^17,18

The rate of programmatic error/immunization error-related reactions in our study was zero. But the previous studies suggesting that the rate of immunization error related reactions were about 12.7% and 14.9%.¹⁹

In our study we observed no cases of programmatic/ immunization error related reaction. The major reason for the lack of immunization error related-reactions in our study may be due to the experience of the immunization center staff, and strict adherence to vaccine handling procedures. Lack of experience of immunization center staff can be a major contributing factor to these kinds of reactions, and can easily be overcome by proper training of the staff involved in the vaccine handling process.^{18, 20}There was no evidence of vaccine quality defect related reactions in the present study which is consistent with the results of an Indian study.¹⁸

We did not observe any AEFIs which were related to Immunization anxiety since the subjects in our study were of age group of 0-3 months only. It is evident that the immunization anxiety related reactions are mainly observed in the adolescent/adult population. In a study it was reported a higher rate of immunization anxiety-related reaction (22.0%) since it included both the adolescent, children of younger age.¹⁸

There were no indeterminate cases of AEFI in our study. Two previous studies by J Sebastian et al(2019) and Singh et al(2018) reported that there exists 0.9% and 29% of indeterminate cases respectively. In the current study there exists no AEFI which are having inconsistent causal association with the vaccination which is contrary to a south Indian study with a rate of (5.3%). Zero cases were reported in our study with unclassifiable events but previous studies were reported about 0.4%, 11.4%.^17,18

Severity Assessment:

The total 1138 AEFIs were classified according to their severity by using WHO severity assessment scale. Out of 1138 AEFIs, 51.23% (583) of AEFIs were classified as Mild, 48.77% (555) of AEFIs were classified as Moderate and there observed no severe AEFIs. A previous study conducted by Nisarg Joshi et al majority of AEFI were mild in nature, only 0.7% (n=1003) were febrile convulsions which were serious.¹¹In the current study there exists no AEFI which are having inconsistent causal association with the vaccination which is contrary to a south Indian study with a rate of (5.3%).¹

LIMITATIONS:

1. Since we cannot rule out the exaggeration and untrue answers regarding the adverse events from guardians of children, there may be a possibility of social-desirability bias in the current study.

2. The incidence rates of the AEFI in the study are high; this might be due to the smaller simple size of our study.

CONCLUSION:

All the AEFIs were appeared to be consistent following causality assessment. Majority of predictable AEFIs were non preventable, albeit few of them were preventable. Greater percentage of AEFIs was non-serious and mild. Conducting more similar studies across the countryeases knowing the relation between AEFI and pharmacoepidemiological data. A national vaccine safety database is an immediate need of hour to predict severity of AEFIs and to prevent the serious ones.

ACKNOWLEDGEMENT:

The author would like to thank Department of Pediatrics, NRI General Hospital, Guntur, Andhra Pradesh, India for supporting the study. The author also would like to thank the logistic and technical support given by Pharmacovigilance Programme of India, Indian Pharmacopoeia Commission, Ghaziabad, India and Department of Pharmacy Practice, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Ooty, Nilgiris, Tamil Nadu, India for supporting the study.

CONFLICT OF INTEREST:

The authors declare that there is no conflict of interest.

ABBREVATIONS:

AEFI: Adverse Event Following Immunization;

WHO: World Health Organization;

CIOMS: Council for International Organizations of Medical Sciences;

EPI: Expanded Programme of Immunization;

ACIP: Advisory Committee on Immunization Practices;

UIP: Universal Immunization Programme;

NHM: National Health Mission;

PvPI: Pharmacovigilance programme of India;

AMC: ADR Monitoring Centers;

VPD: Vaccine Preventable Disease.

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Received on 30.09.2023 Modified on 18.12.2023

Research J. Pharm. and Tech 2024; 17(7):3409-3414.

DOI: 10.52711/0974-360X.2024.00533