Analysis Of Common Vaccines and Associated Adverse Events in Immunized Pediatric Population in India: A Review

Immunization is essential for safeguarding children against vaccine-preventable infectious disease and providing them with lifelong immunity. As the pediatric population is more vulnerable of developing an adverse reaction due to compromised immunity, the monitoring, prevention and treatment of any suspected adverse event following immunization (AEFI) is of utmost importance. According to United nation international children emergency fund (UNICEF) 2023 report; every year vaccine saves 4.4 million lives globally and if the goals of immunization are met then it could rise to 5.8 million by 2030⁽¹⁾. In India immunization program was introduced in 1978; it gained momentum in 1985 and was renamed as universal immunization program. The aim of universal immunization program is to protect every individual primarily focusing on infants, children, and pregnant women from vaccine preventable diseases; by ensuring that every individual must receive vaccines at appropriate age ⁽²⁾. According to the vaccine confidence project at the London school of hygiene and tropical medicine, India is one of the three countries where the perception of the importance of vaccines has improved by upto 98%. India’s Universal immunization program, one of the largest public health intervention, globally targets approximately 27 million newborns and 30 million pregnant women each year. The national immunization schedule provides age-appropriate immunizations free of cost against 12 vaccine-preventable infectious diseases ⁽³⁾. Unlike other drugs vaccines also have adverse effects, and these adverse events were infrequently observed among children’s following immunization which decreases confidence and perception about the importance of vaccine in children among the parents. Vaccine pharmacovigilance is essential for detection, monitoring, prevention and treatment of AEFI’s. It plays a crucial role in improving surveillance and safety. Due to the rising population, climatic change and the increased burden of infectious diseases, various challenges have emerged, in response; India is experiencing a surge in demand for vaccines, prompting heightened healthcare awareness and government initiatives to improve immunization coverage⁽⁴⁾. According to 2023 UNICEF report, India has successfully reduced the number of zero dose children from 2.7 million in 2021 to 1.1 million in 2022. This rapidly increasing immunization coverage and the addition of new vaccines to the immunization schedule have also heightened concerns about their safety ⁽⁵⁾. To ensure safe and effective immunization services; post-marketing survelliance of adverse event following immunization was initiated in 1988 by the immunization division ministry of health and family welfare. This survelliance programme was aimed to report, investigate and assess the potential causes reported as adverse event following immunization across the country ⁽⁶⁾. Although many studies have documented the safety and efficacy of vaccines, concerns regarding adverse events following immunization (AEFIs) persist among parents and healthcare providers. This apprehension can lead to vaccine hesitancy, ultimately impacting immunization coverage rates and the collective immunity of the population. These results prompt us to conduct a systematic review or meta-analysis of existing observational studies to evaluate the association between the most common vaccines and adverse events following immunization in the Pediatric population.

METHODOLOGY

We searched the publication in the electronic database like Google scholar, PubMed and Indian journals publishing article in the field of immunization and or vaccination. Only English language original research article published in past 10 years from 2014 onwards until 31^st March 2024 were obtain based on the following key terms used for Google scholar and PubMed search was-: “adverse event following immunization” OR “vaccine adverse event” OR “Pediatric age group” OR “Indian population”. A total of 20 full text article were screened and based on the given below inclusion and exclusion criteria finally 12 article were taken into consideration for detailed review and analysis.

Prisma Flowchart (studies were included as per the following criteria)

A study conducted by Mittal et al. at the Government Medical College in Nainital, Uttarakhand, aimed to determine adverse events (AEFI) following immunization for children under two years old. The study found that 48.8% of adverse events occurred after administering pentavalent + oral polio vaccine at 10 weeks, followed by DPT + Measles rubella vaccines at 16-24 months. Males were more prone to adverse events, with 58.12% of AEFI occurring in children under one year. The most common clinical manifestation was fever (47.6%), followed by swelling at the injection site (25%). The study suggests that raising awareness among healthcare professionals and the public about reporting adverse events can optimize vaccine safety and boost public confidence in child immunization [7]. [Table-: 1, 2] [Figure-: 1, 2, 3]

A Prospective observational study conducted by Aherkar et al. at B.J. Medical College and Sassoon General Hospital in Pune from 2013 to 2014 found an overall incidence rate of 8.62% of adverse events following immunization (AEFI) among 1206 children aged 0-6 years. The most common AEFIs were fever and swelling at the injection site, followed by diarrhea, excessive crying, and running nose. The first dose of the DPT vaccine had the highest AEFI incidence (37.8%), decreasing with subsequent doses. All reported events were classified as mild to moderate, with a sudden onset in 70.07% of cases. According to the Naranjo scale, 98.18% of AEFIs were considered probable adverse reactions to the vaccines, underscoring the need for rigorous pharmacovigilance in India's immunization program. The study emphasizes the importance of continuous monitoring and robust reporting systems to enhance vaccine safety and public trust in immunization efforts [8]. [Table-: 1, 2] [Figure-: 1, 2, 3] A 3 year prospective observational study was conducted by J Sebastian, P Gurumurthy et al. over 3 years among age group 0-4 years at JSS hospital, Mysuru. A total of 3322 adverse event following immunization was reported among 2628 vaccinated subject. The incidence of adverse events with pentavalent vaccines was 84.4%, with fever being the most common clinical manifestation. The study found a consistent causal relationship in 93.4% of reported adverse events, with inconsistent in 5.3%, indeterminate in 0.9%, and unclassifiable in 0.4%. Improper administration technique and vaccine adjuvants increased local site reactions, with neonates and toddlers at higher risk. Active monitoring of adverse events is needed in this age group [9]. [Table-: 1, 2] [Figure-: 1, 2, 3] Deoja et al. conducted a 2 month prospective observational study at Mahatma Gandhi Medical College and Research Institute in Puducherry aimed to assess rare reactions and known adverse events following immunization in children. Out of 331 children who received 480 doses of different vaccines, 19% reported suspected adverse events. The pentavalent vaccine was associated with the highest adverse event (46%), followed by the combination of DPT + OPV (21.5%). Fever was the most common clinical manifestation (44.6%), followed by swelling at the injection site (22%). The study found that 87% of reactions were indeterminate and 13% had a consistent causal relationship [10]. [Table-: 1,2] [Figure-: 1, 2, 3]  A cross-sectional study was conducted in Rohtak district of Haryana, India, to detect adverse effects following immunization (AEFI) in 209 children under two years old. The study involved contacting mothers of the vaccinated children on the 8^th and 30^th day after vaccination in first centre. Six children could not be contacted and were excluded from the study. The study found that AEFI incidence rates per 1000 doses were higher following the 1^st dose the pentavalent vaccine [312.05], henceforth by 2^nd dose [290.78] and 3^rd dose [271.42]. The most significant adverse effects following 1^st, 2^nd and 3^rd doses of the pentavalent vaccine were fever [31.3%] [29.1%], [27.1%] subsequently followed by irritability, swelling at the injection site, anorexia, pain, redness, and nodule. The study highlights the importance of addressing AEFI in immunization programs [11]. [Table-: 1, 2] [Figure-: 1, 2, 3]  To identify the factors associated with reported adverse event following immunization, a cross-sectional observational study was conducted at the metropolitan city from July 2012 to July 2013. A total of 118 cases of adverse event following immunization were reported. Males were more prone to adverse event following immunization than female; and the age group between 0-3 months constitutes 39% of all reported cases. Combination of OPV + DPT + HBV constitute 69.94% (83) AEFI with most common clinical manifestation of convulsion 68.84% then followed by fever 58.47% and local swelling at site of injection 11.86%. The study concludes that correct immunization technique is extremely important in reducing the negative impact of immunization on health. Effective reporting, analysis and treatment of AEFI improve the quality of vaccinated subjects [12]. [Table-: 1, 2] [Figure-: 1, 2, 3]   Poornima et al. conducted a six-month observational prospective study at Guwahati Medical College and Hospital, involving 1378 children aged 0-12 years. The study included subjects with informed consent and followed up through a two-phase telephonic survey. Found that Out of the 3361 doses administered, 244 adverse events (AEFI) were reported, with an incidence of 17.7%. The most common AEFI was fever, followed by swelling at the injection site, excessive crying, diarrhoea, nodule at the injection site, rash, and the least common was convulsions. The study highlights the importance of reporting and surveillance of AEFI for the proper evaluation of the safety and effectiveness of the vaccination program [13]. [Table-: 1, 2] [Figure-: 1, 2, 3]  Another prospective observational study was conducted at G.S.V.M. medical college in Kanpur, Uttar Pradesh, to examine vaccine adverse events in Pediatric patients, 36 vaccine-induced reactions were found, with females being more prone to adverse reactions. The age group 0-6 months had the highest adverse reactions (79.41%), followed by 6 months to 1 year (11.78%). DPT was the most common vaccine, followed by hepatitis B vaccine (14.70%). The most common clinical manifestations were fever (14.70%) and convulsion (11.77%). The study concluded that vaccines are essential for preventable diseases under immunization programs, and accurate monitoring and management of vaccine-induced adverse reactions can reduce morbidity and mortality rates related to immunization [14]. [Table-: 1, 2] [Figure-: 1, 2, 3] Nisarg Joshi et al. conducted a prospective observational study at Gujarat, aimed to study the pattern of adverse events following vaccination in the Pediatric population. Out of 4320 children who received 10110 vaccine doses, 899 experienced 1003 adverse events. The incidence rate was 20.8%. The most common clinical manifestations were fever (34.33%), excessive crying (31.24%), and swelling at the injection site (11.96%). The majority of adverse events reported in children aged 1-12 months were 623 (62.1%) and 327 (32.6%) in the 0-1 month age group. The study concluded that effective implementation of a vaccine adverse event reporting system helps to make assure the benefits of vaccine continue to be far greater than risk. [15]. [Table-: 1, 2] [figure-: 1, 2, 3] A study conducted in Srinagar, Jammu and Kashmir from May 2018 to October 2019 found that 23% of infants experienced adverse events following immunization. The most common adverse events were reported with the first dose of OPV-1, LPV-1, f-IPV-1 (32.3%) then followed by second dose of OPV-2, LPV-2 (26.18%). Pentavalent vaccines were seems to be most implicated in causing fever (54.90%) then followed by diarrhoea (8.30%), and vomiting (8.14%). The study concluded that close monitoring, regular reporting, and analysis of adverse events can reduce adverse reactions and improve parental child participation in immunization programs [16]. [Table-: 1, 2] [Figure-: 1, 2, 3] Varun Paramkushman et al. conducted a 6 month prospective observational at tertiary care hospital and primary healthcare centre of Warangal district  from April to September 2016 to assess the adverse event occurring post vaccination among Pediatric population found that vaccines can cause rare adverse events, which are rare in less studied populations like India. The study involved 826 vaccinated subjects who received 1882 vaccine doses. Incidence of adverse event following the administration of pentavalent vaccine (62.04%) were found to be highest then followed by BCG vaccines (22.9%). The most common clinical manifestations were mild fever (59.41%), pain at the injection site (12.94%), and swelling at the injection site (13.72%). The study suggests that vaccine vigilance and or survelliance of adverse events occurring post-vaccination are crucial in developing countries like India. Clinical pharmacists and other healthcare professionals can increase reporting rates, reduce the frequency and severity of adverse events, and improve public participation in immunization programs [17]. [Table-: 1, 2] [figure-: 1, 2, 3]  For evaluating the adverse event following immunization; a 1-year prospective observational study was performed at department of pediatric Sri Venkateswara medical college, Andhra Pradesh. A total of 20414 children were received 60548 doses of vaccines, out of them 8246 adverse event were recorded. Neonates of less than 1 week experienced 40.4% (3331) adverse events. Males 56.7% (4675) were more prone to adverse events as compared to female child 43.3% (3570). Combination of pentavalent + OPV + IPV contribute maximum 38.1% (3147) adverse event with fever 58% (1826) being the most common clinical manifestation. The study concludes that effective reporting of adverse event following immunization to CDSCO can helps in identifying and preventing the vaccine responsible for adverse events [18]. [Table-: 1, 2] [Figure-: 1, 2, 3]

Tables and figures-:

Table 1-: General characteristics of study

CONCLUSION