The introduction of a whole cell pertussis vaccine is associated with an increased risk of developing febrile seizures, however, how this trend persists when used with a cell-free (acellular) vaccine remains unknown. Because of the possibility of developing serious adverse events (including epilepsy) associated with the administration of the pertussis vaccine, many parents fear that this type of danger could threaten their children. This situation in the 80s of the 20th century was the main reason for refusal of vaccination, which, according to experts in the field of public health, led to an increase in the incidence of pertussis in adolescents and children less than 6 months old. This trend has been identified by the United States Centers for Disease Control and Prevention (CDC).

A group of researchers led by Dr Yuelian Sun (Department of Public Health, University of Aarhus, Denmark) conducted a study, the results of which were published on February 22 in the journal JAMA.

Representatives of health authorities in most countries have started the transition from whole cell pertussis vaccine to cell-free vaccine, since after the introduction of the latter, side effects are recorded much less frequently. However, the question of the risk of developing febrile seizures, which often accompany immunization with the whole cell vaccine, after vaccination with the use of the acellular pertussis vaccine has not yet been fully resolved.

The aim of a Danish study was to assess the probability of developing febrile seizures and epilepsy after a series of immunizations with a combined vaccine containing diphtheria, tetanus toxoid, the acellular pertussis component, the virus inactivated poliomyelitis and Haemophilus influenzae polysaccharide b (HT) IPV-Hib) at 3, 5 and 12 months. The study analyzed the side effects caused by vaccination with the combined DTaP-IPV-Hib vaccine, which has started to be used actively in Denmark since 1997. Since September 2002, the vaccine acellular pertussis is an integral part of the DTaP- vaccine. IPV-Hib.

According to the Danish Civil Registry, around 98% of Danish citizens visit a general practitioner who, among other responsibilities, takes care of vaccination issues. Vaccines are provided free of charge and the GP is financially responsible. Vaccination is carried out three times: at 3, 5 and 12 months, the introduction of a booster dose is carried out at 5 years.

The study used data from the Danish National Hospital Register the Danish National Hospital Register, which contains information on the incidence of febrile seizures and epilepsy based on the Danish version of the ICD 10 revised international statistical classification of diseases. The researchers performed 2 analyzes: a cohort analysis and an analysis of self-reported cases of febrile seizures.

A population cohort study of 378,834 children born in Denmark for the period from January 1, 2003 to December 31, 2008 was followed until December 31, 2009 inclusive.

The main parameters evaluated during the study were the relative risk of developing febrile attacks within 7 days (0, 1-3 days and 4-7 days) after each vaccination and the relative risk of epilepsy after the first vaccination. in a cohort study, as well as the relative frequency of febrile seizures that occurred within 7 days (0, 1-3 days and 4-7 days) after each vaccination according to independent reports.

During the observation period, from 3 months and ending with 18 months, out of 378,834 children, 329,521 (87.0%) received a dose of the DTaP-IPV-Hib at 3 months, 339288 (90.0%)) at 5 months and 320049 (84.5%) at 12 months. 6854 children (1.8%) did not receive the DTaP-IPV-Hib vaccine. The number of children diagnosed with febrile seizures was 7,811 (2.1%).

7,811 children under 18 months of age were diagnosed with febrile seizures, of which 17 children had febrile seizures within 7 days of first administration (incidence rate 0.8 per 100,000 person-days), 32 after the second administration (1.3 per 100,000 person-days) and 201 after the introduction of the third dose of the vaccine (8.5 per 100,000 person-days).

In general, there was no increased risk of developing febrile attacks within 7 days after administration of each dose of vaccine, however, an increased risk of febrile attacks compared to the control group was observed on the first day (relative risk 6.02; 95% CI 2.86-12.65) and on the day of the second vaccination (relative risk 3.94; 95% CI 2.18-7.10). No similar trend was observed on the day of the third vaccination (relative risk 1.07; 95% CI, 0.73-1.57). Febrile seizures were detected in 9 children after the first dose (5.5 per 100,000 person-days), in 12 children after the second dose (5.7 per 100,000 person-days) and in 27 children after the third dose of vaccine (13.1 per 100,000 person-days).

During the 7 years of follow-up, 131 unvaccinated children and 2117 vaccinated children were diagnosed with epilepsy, in 813, she was diagnosed between 3 and 15 months of life (2.4 per 1000 person-years), and in 1304 at a more advanced age (1.3 per 1000 person-years). After vaccination, children had a lower risk of developing epilepsy between 3 and 15 months (relative risk 0.63; 95% CI 0.50-0.79), at older ages, the probability of developing epilepsy coincided with that of unvaccinated children (relative risk 1.01; 95% CI 0.66-1.56). The relative incidence of febrile seizures in the analysis of self-reported cases was comparable to that of the cohort analysis and the results remained unchanged even after additional analysis in certain categories: girls, boys, children vaccinated according to the vaccination schedule , children vaccinated after being put into practice pneumococcal vaccine. Children vaccinated with pneumococcal vaccine and DTaP-IPV-Hib had an increased risk of developing febrile seizures in the first three days after vaccination at 5 months and on the day of the third vaccination at 12 month.

Among 250 children whose first episode of febrile seizure was recorded 7 days after vaccination, 80 children (32.0%) had repeated episodes of febrile seizure and 8 (3.2%) subsequently developed epilepsy.

Among the 7,561 study participants in whom the first episode of febrile seizures developed 7 days after vaccination, 2,207 (29.2%) reported a relapse of febrile seizures and 208 (2.8%) reported subsequently developed epilepsy.

In children with a first episode of febrile seizure within one week of receiving the vaccine, there was a similar risk of recurrent febrile seizure (risk ratio 1.09; 95% confidence interval, 0.86- 1.38) and epilepsy (risk ratio 0.61; 95% confidence interval 0.27-1.40), comparable to that of children with a first episode of febrile seizures beyond the interval 7 days.

Compared to a group of unvaccinated children, vaccinated patients had a lower risk of developing epilepsy in the first 15 months of life (risk ratio 0.63; 95% confidence interval 0.50- 0.79), at an older age, the risk of developing epilepsy between the two groups was not significantly different (risk ratio 1.01; 95% confidence interval 0.66-1.56).

The researchers were able to establish that the relative risk of developing febrile attacks increased on the day of the first and second vaccinations, but the absolute risk remained low (less than 4 per 100,000 vaccinations), while in the 7 days following the introduction of the DTaP-IPV-Hib vaccine the number of cases of febrile seizures has not increased significantly. In the presence of the first episode of febrile seizures within 7 days of vaccination, the likelihood of relapse of febrile seizures and epilepsy did not increase. The incidence of epilepsy between the two groups (vaccinated and unvaccinated children) did not differ significantly.

Immunization with the DTaP-IPV-Hib vaccine was associated with an increased risk of developing febrile seizures after vaccination at 3 and 5 months, while the absolute risk of developing febrile seizures has not increased significantly. The likelihood of developing epilepsy was independent of the administration of the DTaP-IPV-Hib vaccine.