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 rarer events can be reliably established only with the help of post-licensing epidemiological surveillance. Modern vaccines are evaluated in pre-registration testing on target groups of 20-60 thousand, which allows us to identify complications that occur with a frequency of 1:10,000 and more often.

There are anti-vaccination groups all over the world. Their arguments recently concern the possible connection between vaccination and the development of rare chronic diseases, usually of unknown etiology. As a rule, all such accusations are tested in large population studies, which, unfortunately, are rarely covered in our press.

It is clear that the majority of complications are associated with BCG vaccination; it is unlikely that a serious complication to other vaccines would not be reported and investigated.

Complications after vaccinations are extremely rare: most children have either predictable reactions or intercurrent diseases - most often acute respiratory viral infections. Afebrile seizures have a frequency of 1:70,000 doses of DPT and 1:200,000 doses of gastrointestinal tract vaccine, allergic rashes and/or Quincke's edema - 1:120,000 vaccinations. Similar data are provided by most other authors.

In a US study (680,000 children received DPT and 137,500 MMR), afebrile seizures were not observed at all, and the frequency of febrile seizures was 4-9% after DPT and 2.5-3.5% after MMR. Thrombocytopenic purpura is observed with a frequency of 1:22,300 doses of MMR. Meningitis is practically not observed when using the mumps vaccine from the Jeryl Lynn strain (1:1,000,000), from the LZ strain - in isolated cases.

Statistics of deaths in the post-vaccination period in the USSR before 1992 and later in Russia show that only 22% of them are related to vaccination, in half of the cases - to generalized BCG-itis in children with immunodeficiencies. Of the 16 children who died from post-vaccination complications, 3 had anaphylactic shock, which is a preventable cause of death. Obviously, some of the children who died from other causes could have been saved with proper diagnosis; this applies primarily to meningitis and pneumonia.

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Complications that are not confirmed to be related to the vaccine

The development of a severe disease in the post-vaccination period, especially of unknown etiology, often serves as a reason to blame vaccination. And although such a connection is only temporary, it can be very difficult to prove the absence of a cause-and-effect relationship. However, in recent years, studies have appeared that show the possibility of proving the absence of such a connection.

Since the accusations most often relate to autoimmune diseases, knowledge of the background incidence of them allows calculating 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 into the Calendar.

Number of autoimmune diseases (per 100,000) expected to occur by chance in association with mass vaccination (0-1-6 months) of adolescent girls and young women

Time after expected administration of the vaccine	1 day	1 week	6 weeks
Emergency Department Consultations - 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, auditory neuritis	0,0	0.2	1.0
Emergency Department Consultations - 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, auditory neuritis	0.1	0.7	3.0

It was shown that in 2005, before the start of vaccination, the number of visits from adolescent girls for immune-related diseases was 10.3% of all visits, most often for asthma. Visits for non-atopic diseases reached 86 per 100,000, primarily for diabetes. Fifty-three girls and 389 young women were hospitalized for autoimmune diseases (per 100,000); the most common diagnosis was autoimmune thyroiditis; among girls, the frequency of hospitalization for polyneuropathy was 0.45, multiple sclerosis and optic neuritis - 3.7, among young women, 1.81 and 11.75, respectively.

It is estimated that if mass vaccination according to the 0-1-6 month schedule with 80% coverage was carried out, a significant number of those vaccinated would seek help for these diseases as a result of a simple coincidence in timing. Since the risk of hospitalization for a number of diseases is much higher for young women than for adolescent girls, preference should be given to vaccination (in particular against HPV infection) in adolescence.

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Encephalitis and whooping cough vaccination

The panic wave of fear of encephalitis in the 1970s reduced the coverage of pertussis vaccination, which led to epidemics in several countries with a large number of serious complications. The British study of encephalopathy (accounting for all cases within 1 month after DPT vaccination) conducted in 1979 gave uncertain, statistically insignificant results; in the following 10 years, it did not reveal differences in the frequency of serious residual changes in vaccinated children and in controls. These and other facts cast doubt on the possibility of a connection between encephalitis and pertussis vaccination. From 1965 to 1987, we observed only 7 cases of encephalitis assessed as a consequence of DPT; some of these children were retrospectively diagnosed with viral or degenerative CNS damage. In subsequent years, the investigation of all diseases suspected of encephalitis did not reveal any connection with DPT vaccination, but a specific pathology was identified.

In the USA, the question of the association of vaccinations with persistent CNS changes was re-examined (by the case-control method) on a contingent of 2 million children aged 0-6 years for 15 years (1981-1995). No association was found between vaccinations (within 90 days after DPT or MMR) and CNS pathology. When excluding children with CNS diseases of known etiology, the relative risk of developing CNS damage within 7 days after DPT was 1.22 (CI 0.45-3.1), and within 90 days after MMR - 1.23 (CI 0.51-2.98), indicating the absence of a causal relationship. Apparently, the discussion on this topic should be considered closed.

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Encephalopathy in the post-vaccination period

The nature of encephalopathy has recently been deciphered: genetic analysis was performed on 14 patients with encephalopathy within 72 hours after vaccination with a vaccine with a pertussis component (convulsions, in half of the cases lasting more than 30 minutes, mainly clonic, in half of the cases against the background of a temperature below 38°). Subsequently, severe myoclonic epilepsy of infancy (SME) was diagnosed in 8 children, its borderline form in 4, and Lennox-Gastaut syndrome in 2.

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

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Sudden Infant Death Syndrome and Vaccination

The reason to talk about the existence of a connection between sudden infant death syndrome as a complication after vaccinations was the increase in cases of sudden infant death syndrome - "death in the crib" - at the age of 2-4 months, which coincides in time with the beginning of vaccinations. The fact that this coincidence in time and has no cause-and-effect relationship was clearly demonstrated in a number of studies, mainly on DPT.

As the emergence of new vaccines continues to worry the public, research into this issue continues. One of the most recent studies on this topic analyzed the possible association of sudden infant death syndrome with the introduction of a 6-valent vaccine (diphtheria, tetanus, pertussis, IPV, Hib, HBV). A comparison of 307 cases of sudden infant death syndrome and 921 controls did not reveal any association with vaccination administered 0-14 days earlier.

Widespread use of the flu vaccine in elderly people is accompanied by individual cases of sudden - cardiac - death of elderly people after vaccination. Thus. In October 2006, in Israel, 4 cases of death of elderly people (all over 65 years old) who received the flu vaccine were recorded in 2 outpatient clinics. This led to a temporary cessation of vaccination, which was resumed 2 weeks later - after proof of the absence of a connection with it of fatal outcomes. This proof was based on a comparison of the mortality of elderly (over 55 years old) people taking into account age and the presence of pathology. It turned out that mortality in the period up to 14 days after the flu vaccination is 3 times less than in its absence.

The report from Israel forced several European countries to postpone the start of flu vaccinations, but they were resumed after the European Centre for Disease Control (ECDC) reported that there was no link between the sudden deaths and the vaccination.

In November 2006, four cases of sudden death following influenza vaccination were also reported in the Netherlands, in individuals aged 53, 58, 80 and 88 years. A link to vaccination was considered extremely unlikely based on medical data, and this conclusion was statistically supported by showing that the probability of at least one person in each of these age groups dying on the day of vaccination was 0.016, which is 330 times greater than the probability of no one dying on the day of vaccination. These and similar studies have provided the basis for continuing influenza vaccination, which is given to more than 300 million people worldwide each year.

Otosclerosis and measles vaccinations

Measles virus proteins were repeatedly found in macrophages and chondroblasts from the inflammatory exudate of the middle ear of individuals with otosclerosis, which raised the question of the possible role of the vaccine virus in the development of the disease. Research in Germany has shown, however, that increased measles vaccination coverage is accompanied by a significant decrease in the incidence of otosclerosis - this may confirm the connection between its development and measles, but not with vaccination.

Hepatitis B Vaccination and Multiple Sclerosis

The allegation of a link between multiple sclerosis and the hepatitis B vaccine was made in 1997 by a neurologist working at a well-known French clinic, whose wife developed the disease a few weeks after the vaccination. The spread of this claim led to a decline in the coverage of the vaccine, which is very popular in France: by the end of 1998, more than 70 million doses of the vaccine had been administered, reaching more than one-third of the population of France and more than 80% of people aged 16-20.

The question of a possible link between this vaccine and multiple sclerosis was studied by the Monitoring Commission on Adverse Drug Reactions. As early as 1997, a case-control study in Paris and Bordeaux showed that the increased risk of a first episode of multiple sclerosis (or another demyelinating disease) after vaccination against hepatitis B, if any, was insignificant in magnitude, unreliable, and no different from that after another vaccination. In the group of the population that received the hepatitis B vaccine, the frequency of multiple sclerosis was the same as among those not vaccinated (1:300,000 in adults and 1:1,000,000 in children). These data were confirmed in studies covering 18 neurological clinics in France, as well as in England. The reports of neurological disease developing after vaccination are entirely explained by the increase in the number of people vaccinated (from 240,000 in 1984 to 8,400,000 in 1997).

Vaccine opponents have been harping on the fact that the French Ministry of Health suspended vaccinations against hepatitis B in schools in the fall of 1998, due to difficulties in providing the necessary explanations to parents of vaccinated schoolchildren. At the same time, the Ministry of Health recommended continuing this type of vaccination of children, adolescents, and adults in medical institutions and doctors' offices.

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

The hypothesis about the coincidence in time of the debut of multiple sclerosis and vaccination was considered the most probable, since the age and sex characteristics of cases of multiple sclerosis that developed soon after vaccination correspond to those of patients not vaccinated against hepatitis B.

The hypothesis about the role of vaccination as a trigger factor in genetically predisposed individuals could be supported by a slight increase in the relative risk of developing multiple sclerosis after the administration of both hepatitis and other vaccines (OR = 1.3-1.8). However, in none of the studies did this increase reach the level of reliability (95% confidence interval 0.4-6.0), and in a number of them no increase in OR was found at all.

The third hypothesis, that of a causal relationship between hepatitis B vaccination and multiple sclerosis, was rejected because no association between hepatitis B and demyelinating diseases has ever been observed.

Since opponents of vaccination have made accusations that vaccination can contribute to the development of multiple sclerosis at later stages, the vaccination status of 143 patients with multiple sclerosis with onset before the age of 16 was compared with a control group of 1122 children of the same age and place of residence. It was shown that there was no association between vaccination against hepatitis B and the onset of the disease 3 years after vaccination (OR 1.03, 95% CI 0.62-1.69), as well as for intervals of 1, 2, 4, 5 and 6 years.

Guillain-Barré polyradiculoneuropathy and vaccination

Interest in this problem arose after a link was reported in the United States (frequency 1:100,000 doses) with the use of the A/New Jersey influenza "swine vaccine".1976-1977. No such connection was found for other influenza vaccines, the frequency in vaccinated people was 1:1 million, i.e., it differed little from the background. Nevertheless, this question was not closed.

This issue was re-examined in the UK in a cohort of practices with 1.8 million registered patients. During 1992–2000 there were a total of 228 cases of Guillain–Barré polyradiculoneuropathy with a standardised 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%) had onset of Guillain–Barré polyradiculoneuropathy within 42 days of vaccination: 3 of the 7 cases were with influenza vaccination. Thus, the relative risk of developing Guillain–Barré polyradiculoneuropathy in the first 6 weeks after immunisation was only 1.03 (95% CI 0.48–2.18), indicating no association at all.

The association of Guillain-Barré polyradiculoneuropathy with mass OPV vaccination (based on a report from Finland) has been refuted after careful analysis. It is not supported by our observations of acute flaccid paralysis.

A safety study of the meningococcal vaccine Menactra in adolescents in the United States found no significant differences in the incidence of PE between vaccinated and unvaccinated individuals.

Vaccination and heterologous immunity

The idea that vaccination coverage may have a negative impact on overall infectious morbidity also has an adverse effect. This issue is particularly discussed in connection with the expansion of the use of combination vaccines, despite published data from the 1990s, for example, on the reduction in the incidence of invasive bacterial infections in children who received DPT. Clear data have also been obtained on the reduction in overall morbidity in children during the first month after vaccination.

However, in 2002, a review by the US Institute of Medicine indicated the presence of biological mechanisms by which combination vaccines can increase the risk of developing "non-target" infections. This opinion, however, was not confirmed in a study that included all Danish children (more than 805 thousand) during 1990-2002 (2,900,000 person-years of observation). All cases of hospitalization for acute respiratory infections, viral and bacterial pneumonia, acute intestinal infections, sepsis, bacterial meningitis, and viral CNS infections were taken into account. The results showed that the introduction of vaccines, including combination ones (ADS-polio, DTP-popio, MMK) not only does not increase the relative risk of a child's hospitalization for a "non-target" infection, but also reduces this risk for some of them. With regard to live vaccines (BCG, HCV), stimulation of heterologous immunity has been demonstrated in several studies (including blind and twin studies) conducted in developing countries. In groups of children vaccinated with live vaccines, mortality 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 “reduced non-specific reactivity” and increased infectious morbidity under the influence of vaccines, which frightens parents and many doctors.

Are you now convinced that complications from vaccinations are very rare?