Complications after vaccinations: how often do they occur?

Complications after vaccinations are interpreted by both specialists and a large number of people without special (and sometimes even medical) knowledge, so the frequency of more rare events can be reliably established only through post-licensing surveillance. Modern vaccines at pre-registration check are estimated on target groups of 20-60 thousand, which allows to identify complications arising with a frequency of 1:10 000 and more often. 

There are groups around the world that oppose vaccination. Their arguments recently concern the possible connection of vaccination with the development of rare chronic diseases, usually unknown etiology. As a rule, all such accusations are checked in large population studies, which, unfortunately, are rarely covered in our press.

Obviously, most complications are related to BCG vaccination; hardly a serious complication on other vaccines would not have been reported and investigated.

Complications after vaccinations are extremely rare: most children have either predictable reactions, or intercurrent diseases - most often SARS. Afebra cramps have a frequency of 1: 70,000 doses of DTP and 1: 200,000 doses of HCV, allergic rashes and / or Quincke's edema -1: 120,000 vaccinations. Similar results are given by most other authors.

In a study in the US (680,000 children received DTP and 137,500-MMR), no fever convulsions were observed at all, and the frequency of febrile seizures was 4-9% after DTP and 2.5-3.5% after MMR. Thrombocytopenic purpura is observed with a frequency of 1:22 300 doses of MMR. Meningitis with the use of mumps vaccine from the Jeryl Lynn strain is practically not observed (1: 1 000 000), from strain LZ - in isolated cases.

Statistics of deaths in the post-vaccination period in the USSR until 1992 and later in Russia show that only 22% of them are associated with vaccination, in half of cases with generalized BCG-it in children with immunodeficiencies. Out of 16 deaths from post-vaccination complications of children, anaphylactic shock occurred in 3 cases, related to preventable causes of death. Obviously, some of the children who died from other causes could be saved if properly diagnosed; this applies, above all, to meningitis and pneumonia.

[1], [2], [3], [4], [5],

Complications, the connection of which with the vaccination is not confirmed

The development of severe disease in the post-vaccination period, especially the unknown etiology, often serves as an excuse for charging him with vaccination. And although this connection is only temporary, it is very difficult to prove the absence of a cause-and-effect relationship. Nevertheless, in recent years there have been works showing the possibilities to prove the absence of such a connection.

Since the charges most often relate to autoimmune diseases, knowledge of the background incidence of them allows us to calculate the risk of their development in the post-vaccination period. Such work was carried out in the United States in connection with the introduction of the Gardasil vaccine in the Calendar.

The number of autoimmune diseases (per 100,000), expected as an accidental coincidence with the mass vaccination (0-1-6 months) of adolescent girls and young women

The time after the expected introduction of the vaccine	1 day	1ned.	6 weeks
Consultations in the emergency room - adolescent girls
Asthma	2.7.	18.8	81.3
Allergy	1.5	10.6	45.8
Diabetes	0.4	2.9	12.8
Hospitalization - teenage girls
Inflammatory bowel disease	0.2	1.0	4,5
Thyroiditis	0.1	0.9	4.0
Systemic lupus erythematosus	0.1	0.5	2.0
Multiple sclerosis, neuritis of the auditory nerve	0.0	0.2	1.0
Advice in the emergency room - young women
Asthma	3.0	21.2	91.5
Allergy	2.5	17.4	75.3
Diabetes	0.6	3.9	17.0
Hospitalization - young women
Inflammatory bowel disease	0.3	2.0	8.8
Thyroiditis	2.4	16.6	71.8
Systemic lupus erythematosus	0.3	1.8	7.8
Multiple sclerosis, neuritis of the auditory nerve	0.1	0.7	3.0

It was shown that in 2005 - before the vaccination began - the appeal of adolescent girls about immunocompromised diseases was 10.3% of all calls, more often about asthma. Treatment for non-atopic diseases reached 86 per 100 000, primarily, for diabetes. Concerning autoimmune diseases, 53 girls and 389 young women were hospitalized (per 100,000); the most frequent diagnosis was autoimmune thyroiditis; in girls, the frequency of hospitalization for polyneuropathy was 0.45, multiple sclerosis and optic neuritis - 3.7, in young women, respectively, 1.81 and 11.75.

It is estimated that in the case of mass vaccination according to the scheme 0-1-6 months. With an 80% coverage, a significant number of vaccinated people would seek help for these diseases as a result of simple coincidence in time. Since in a number of diseases the risk of hospitalization of young women is much higher than that of adolescent girls, preference should be given to vaccination (in particular against papillomovirus infection) in adolescence.

[6], [7], [8], [9], [10],

Encephalitis and pertussis vaccination

The panic wave of fear of encephalitis in the 1970s reduced the coverage of pertussis vaccination, which led to an epidemic in a number of countries with a large number of serious complications. A British study of encephalopathy in 1979 (taking into account all cases within 1 month after DTP vaccination) gave vague, statistically insignificant results; in the next 10 years, there was no difference in the incidence of serious residual changes in vaccinated children and in control. These and other facts raise doubts about the possibility of the connection of encephalitis with the vaccination against whooping cough. From 1965 to 1987, we observed only 7 cases of encephalitis, regarded as a consequence of DTP; a part of these children were retrospectively diagnosed with viral or degenerative CNS damage. In subsequent years, the investigation of all suspicious encephalitis-related illnesses with their DTP vaccination revealed no specific pathology.

In the United States, the issue of the relationship between vaccinations and persistent changes in the CNS was re-examined (case-control method) in a contingent of 2 million children aged 0-6 years for 15 years (1981-1995). There was no association between vaccinations (within 90 days after DTP or CPC) and CNS pathology. With the exclusion of children with CNS diseases of known etiology, the relative risk of developing CNS lesion within 7 days after DTP was 1.22 (CI 0.45-3.1), and within 90 days after PDA - 1.23 (CI 0.51 -2.98), which indicates the absence of a causal relationship. Apparently, the discussion on this topic should be considered closed.

[11], [12], [13], [14], [15], [16], [17],

Encephalopathy in the post-vaccination period

The nature of encephalopathy was recently deciphered: genetic analysis was performed by 14 patients with encephalopathy within 72 hours after vaccination with a pertussis vaccine (convulsions, half of the cases lasting more than 30 minutes, mostly clonic, in half of the cases at a temperature below 38 ° C) . Subsequently, 8 children were diagnosed with severe myoclonic epilepsy in infants (TMKE), 4 had a borderline form, and 2 had Lennox-Gastaut syndrome.

For TMKE, the al mutation in the subunit of the gene of the sodium channel of neurons (SCN1A) is characteristic. The mutation was detected in 11 of 14 patients with encephalopathy (in all children with TMKE and in 3 of 4 children with its borderline form), and a genetic analysis of the parents showed that these mutations were new in most cases. This work shows the importance of such studies, as they allow us to see the true cause of the developed pathology; the introduction of the vaccine and / or the associated temperature response may be a trigger for the development of encephalopathy in a child with a genetic predisposition to severe epilepsy.

[18], [19], [20], [21], [22], [23],

Syndrome of sudden death of children and vaccination

The reason to talk about the connection of the syndrome of sudden death of children, as complications after vaccinations, gave rise to cases of the syndrome of sudden death of children - "death in a crib", at the age of 2-4 months, which coincides with the time of vaccination. The fact that this is a coincidence in time and has no cause-effect relationship was clearly demonstrated in the field of research, mainly the day of DTP.

As the emergence of new vaccines continues to bother the public, research on this issue continues. One of the latest works on this topic has analyzed the possible connection of the syndrome of sudden death of children with the introduction of a 6-valent vaccine (diphtheria, tetanus, whooping cough, IPV, Hib, HBV). A comparison of 307 cases of sudden death syndrome of children and 921 controls did not reveal any association with vaccination, conducted 0-14 days earlier.

The widespread use of influenza vaccine in the elderly is accompanied by isolated cases of sudden cardiac death of the elderly after vaccination. So. In October 2006, four cases of death of elderly people (all over 65 years old) who received influenza vaccine were recorded in 2 outpatient clinics in Israel. This led to a temporary cessation of vaccination, which was resumed after 2 weeks - after proving the lack of connection with her deaths. This evidence was based on a comparison of the mortality of elderly (over 55 years) individuals, taking into account age and pathology. It turned out that mortality in the period up to 14 days after influenza vaccination is 3 times less than in its absence.

A report from Israel caused a number of countries in Europe to postpone the onset of influenza vaccination, but it was resumed after the European Center for Disease Control (ECDC) reported that there was no connection between sudden death and vaccination.

In November 2006, four cases of sudden death following influenza vaccination in persons aged 53, 58, 80 and 88 years were also reported in the Netherlands. The connection with vaccination on the basis of medical data was considered extremely unlikely, and this conclusion was statistically substantiated: it was shown that the probability of death of at least one person in each of these age categories on the day of vaccination is 0.016, which is 330 times greater, than the probability that no one on the day of vaccination will die. These and similar studies were the basis for the continued vaccination against influenza, which is annually received by more than 300 million people worldwide.

Otosclerosis and measles vaccinations

In macrophages and chondroblasts from the inflammatory exudate of the middle ear of individuals with otosclerosis, the proteins of the measles virus were repeatedly found, which raised the question of a possible rhodium and a vaccine virus in the development of the disease. Studies in the FRG showed, however, that increasing measles vaccination coverage is accompanied by a significant decrease in the frequency of otosclerosis - this can confirm the association of its development with measles, but in no way with vaccination.

Vaccination against hepatitis B and multiple sclerosis

The accusation of the association of multiple sclerosis with vaccination against hepatitis B was raised in 1997 by a neurologist working in a well-known French clinic whose wife developed this disease a few weeks after vaccination. Replication of this statement led to a decrease in immunization coverage, very popular in France: by the end of 1998, more than 70 million doses of vaccine had been introduced, it was received by more than 1/3 of France's population and more than 80% of 16-20-year-olds.

The question of the possible relationship of this vaccine with multiple sclerosis was investigated by the Commission for monitoring the side effects of drugs. Already in 1997, a case-control study in Paris and Bordeaux showed that the increased risk of the first episode of multiple sclerosis (or another demyelinating disease) after vaccination against hepatitis B, if any, is insignificant in magnitude, unreliable and does not differ from such after another inoculation. In the population receiving the hepatitis B vaccine, the incidence of multiple sclerosis was the same as among the non-vaccinated (1: 300 000 in adults and 1: 1 000 000 in children). These data were confirmed in studies that covered 18 neurological clinics in France, as well as in England. The reports on the development of neurological disease after vaccination are entirely explained by the increase in the number of vaccinated (from 240,000 in 1984 to 8,400,000 in 1997).

Opponents of vaccinations were exaggerating the fact that the Ministry of Health of France suspended the vaccination against hepatitis B in schools in the fall of 1998 due to the difficulties in providing necessary explanations for parents of vaccinated schoolchildren. The Ministry of Health at the same time recommended to continue this type of vaccination of children, adolescents and adults in medical institutions and doctors' offices.

The question of the safety of hepatitis B vaccination was discussed at the WHO Consultative Meeting in September 1998. Along with the data from France and England, the results of studies from the USA, Canada, and Italy were reviewed. The meeting, after examining three hypotheses, recommended continuing vaccination against hepatitis B.

The hypothesis that the debut of multiple sclerosis and vaccination coincided in time was recognized as the most probable, since the age-sex characteristics of cases of multiple sclerosis, which developed shortly after vaccination, corresponds to that of patients not vaccinated against hepatitis B.

In favor of the hypothesis about the role of vaccination as a triggering factor in genetically predisposed individuals, there might be some increase in the relative risk of developing multiple sclerosis after the administration of both hepatitis and other vaccines (RR 1.3-1.8). However, in none of the studies, this increase did not reach the level of reliability (95% confidence interval 0.4-6.0), and in a number of them the increase in OR was not found at all.

The third hypothesis - the causal link between hepatitis vaccination and multiple sclerosis - was rejected, since there was never any connection between hepatitis B and demyelinating diseases.

Since opponents of vaccination have accused that vaccination may contribute to the development of multiple sclerosis and at a later date, the vaccine status of 143 patients with multiple sclerosis with a debut under the age of 16 with a control group of 1122 children of the same age and place of residence was compared. It was shown that there is no link between hepatitis B vaccination and the onset of the disease 3 years after vaccination (RR 1.03, 95% CI 0.62-1.69), as well as for 1, 2, 4, 5 and 6 years .

Guyana-Barre polyradiculoneuropathy and vaccination

Interest in this problem arose after the USA was informed of the relationship of this syndrome (frequency 1: 100,000 doses) using the influenza A / New Jersey swine vaccine. AT1976-1977 For other influenza vaccines, this connection was not detected, the incidence of vaccine was 1: 1 million. Differed little from the background. Nevertheless, this issue was not closed.

This issue was re-examined in the UK in a group of medical practices with 1.8 million registered patients. For the years 1992-2000. There were 228 cases of polyadiculoneuropathy Guillain-Barre with a standardized incidence rate of 1.22 per 100 000 person-years (95% CI 0.98-1.46) in women and 1.45 (95% CI 1.19-1.72) in men. Only 7 cases (3.1%) of Guyenne-Barr's polyradiculoneuropathy occurred in the first 42 days after vaccination: in 3 out of 7 cases-influenza. Thus, the relative risk of developing Guillain-Barre polyradiculoneuropathy in the first 6 weeks after immunization was only 1.03 (95% CI 0.48-2.18), indicating a complete lack of communication.

The opinion of the Guillain-Barre polyradiculoneuropathy association with mass vaccination of OPV (based on a report from Finland) was refuted after careful analysis. It is not confirmed by our observations of acute flaccid paralysis.

Monitoring the safety of Menacinth Meningococcal Vaccine in adolescents in the US showed no significant difference in the incidence of PI syndrome between vaccinated and non-vaccinated.

Vaccination and heterologous immunity

An unfavorable impact on vaccine coverage is also provided by the idea of their possible negative impact on the overall infectious morbidity. This issue is particularly exaggerated due to the increased use of combination vaccines, contrary to published data from the 1990s, for example, on reducing the incidence of invasive bacterial infections in children who received DTP. Clear data are also obtained on the reduction in the overall incidence of children during the first month after vaccination.

However, in 2002, a review of the US Institute of Medicine indicated the existence of biological mechanisms by which combination vaccines could increase the risk of developing "non-targeted" infections. This opinion, however, was not confirmed in the study, which included all children of Denmark (more than 805 thousand) during 1990-2002. (2,900,000 person-years of observation). Considered all cases of hospitalization for ARI, viral and bacterial pneumonia, OCI, sepsis, bacterial meningitis, viral CNS lesions. The results obtained showed that the introduction of vaccines, incl. Combined (ADS-polio, AACDS-popio, MMK) not only does not increase the relative risk of hospitalization of the child for "untargeted" infection, but also for some of them reduces this risk. For living vaccines (BCG, HCV), heterologous immunity was stimulated in several studies (including blind and twin) in developing countries. In groups vaccinated with live vaccines, the death rate was 2.1-5.0 times lower than in the control group where placebo or inactivated vaccines were administered.

These observations remove the problem of "reducing nonspecific reactivity" and increasing the infectious disease caused by vaccines, which frightens parents and many doctors.

Now you are convinced that complications after vaccinations are very rare?