Adverse consequences of vaccination

Adverse consequences of vaccination

Vaccination is the only safe, reliable, and effective way of protecting animals against the major infectious diseases. Society does not remember the devastating toll taken by infectious diseases before the development of modern vaccines. Exaggerated fear of negative side effects has discouraged owners from having their pets (and themselves) from being vaccinated. The rise of the Internet and the development of social media have enabled those who oppose vaccination to spread their opinions. Those who resist vaccination for themselves or their children are unlikely to be enthusiastic about vaccinating their pets. Much of this resistance is a result of adverse events and controversy regarding effectiveness associated with the earliest vaccines. In spite of the fact that these problems have long been solved, it takes a considerable time before confidence is restored. There is a lack of awareness of the rigorous safety tests that modern vaccines must undergo before they are marketed. Good manufacturing practices and the quality control procedures used by the biologics industry, together with rigorous regulatory controls, serve to minimize the occurrence of these events. Past issues have been corrected and vaccine safety has steadily improved. Modern vaccines are safe to use and overwhelmingly beneficial. Adverse events associated with vaccination that might compromise the health of an animal are usually rare, mild, and transient. Hypothetical, speculative, or historical adverse effects sometimes dominate perceptions. Nevertheless, it has been truly said, “The most dangerous vaccine is the one not given.” In reading this chapter the reader should be aware that the events described here are rare, somewhat historical, and relatively unimportant when compared with the benefits of vaccination.

Drivers of vaccine usage differ significantly between companion animals and commercial livestock. Owners of companion animals are concerned for the health and well-being of their pets and are intolerant of any adverse events that cause discomfort, pain, or sickness. Livestock producers in contrast vaccinate to maintain livestock health, prevent disease spread, maximize economic return, and to minimize zoonotic disease risks. Vaccines that cause a drop in milk production, decreased feed conversion, increased time to market, or a decline in carcass quality may have significant economic consequences and will not be used.

Adverse effect principles

In determining whether a vaccine causes an adverse effect, the following three principles should apply. First, is the effect consistent? The clinical responses should be the same if the vaccine is given to a different group of animals, by different investigators, and irrespective of the method of investigation. Second, is the effect specific? The association should be distinctive and the adverse event linked specifically to the vaccine concerned. It is important to remember that an adverse event may be caused by vaccine adjuvants and components other than the major antigens. Finally, there must be a temporal relationship. Administration of the vaccine should precede the earliest manifestations of the event or a clear exacerbation of a continuing condition.

The US Centers for Disease Control and Prevention (CDC) has classified adverse events as follows:

Adverse events

The use of vaccines is not free of risk, and an owner has reason to be upset if their healthy animal is sickened by the administration of a vaccine. Residual virulence and toxicity, allergic responses, disease in immunodeficient hosts, neurological complications, and harmful effects on the fetus are potential risks associated with the use of vaccines (Table 10.1). Veterinarians should use only licensed vaccines, and the manufacturer’s recommendations must be carefully followed. Before using a vaccine, the veterinarian should consider the likelihood that an adverse event will happen, and also the possible consequences or severity of this event. These factors must be weighed against the benefits to the animal. A common but mild complication requires a very different consideration than a rare, severe complication (Table 10.2).

TABLE 10.1 ■

The Classification of Adverse Events

Classification Features
Certain Event with appropriate time course
No other explanation
Consistent definitive signs
Probable Reasonable time relationship
Unlikely to be caused by something else
Possible No other reasonable explanation
Reasonable time relationship
Unlikely No reasonable time relationship
Other plausible explanations
Unknown Insufficient data
Cannot be verified

TABLE 10.2 ■

Frequency of Adverse Reactions as Defined by the European Medicines Agency

Very common More than 1 in 10 animals showing adverse reactions (>10%)
Common Greater than 1 but less than 10 animals per 100 animals vaccinated (1%–10%)
Uncommon More than 1 but less than 10 animals per 1000 animals vaccinated (0.1%–1%)
Rare More than 1 but less than 10 animals per 10,000 animals vaccinated (0.01%–0.1%)
Very rare Less than 1 animal in 10,000 reported (<0.01%)

The issue of the risk associated with vaccination remains in large part a philosophical one because the advantages of vaccination are well documented and extensive, whereas the risk for adverse effects is poorly documented, and in many cases, largely speculative. Nevertheless, established facts should be recognized, unsubstantiated allegations rebutted by sound data, and uncertainties acknowledged. For example, there is absolutely no evidence that vaccination itself leads to ill health. Although difficult to prove, a negative, competent statistical analysis has consistently failed to demonstrate any general adverse effect of vaccination.

Identification of an adverse event is based on the clinical judgment of the attending veterinarian and is therefore subject to bias. Standard case definitions of a vaccine-associated adverse event are not yet available. It still is often difficult to distinguish association from causality (Box 10.1).

BOX 10.1 ■

Canine Autism and Vaccination

Autism spectrum disorder is a chronic developmental disorder in children. Its causes are largely unknown. It usually becomes apparent in young children over one year of age at around the same time they receive their initial vaccinations. In a paper published in 1998, a physician studied 12 children with autism. He asked the parents if the children had been vaccinated, with the measles, mumps, and rubella vaccine, within the previous two weeks. Eight said yes, so the author went on to assert in his paper that this vaccine caused autism. He postulated that autism resulted from measles infection. The paper was eventually retracted and the author lost his medical license. Subsequent population-based studies have failed to demonstrate any link between vaccination and autism. Thousands of children are vaccinated every year and large amounts of data are available for analysis. All these show the same thing. There is no link between vaccination and autism risk. However, the word was out. The Internet and Twitter spread the word. Additionally, pet owners began to claim that their dog’s behavior had changed after vaccination—canine autism. The British Veterinary Association felt obliged to issue a statement regarding these claims.

“There is currently no reliable scientific evidence to indicate autism in dogs or a link between vaccination and autism. Vaccinations save lives and are an important tool in keeping our pets healthy. All medicines have potential side-effects but in the case of vaccines, these are rare and the benefits of vaccination in protecting against disease far outweigh the potential for an adverse reaction.”

Traditionally, adverse events resulting from vaccine administration have been reported by veterinarians to manufacturers or government agencies. The resulting numbers have been difficult to analyze satisfactorily for two major reasons. First, reporting is voluntary, so significant underreporting occurs. Adverse events are often regarded as insignificant, or it may be inconvenient to report them. Second, very little data has been available on the number of animals vaccinated. Although manufacturers know the number of doses of vaccine sold, they are unable to measure the number of animals vaccinated.

It has, however, proved possible by examining the electronic medical records of a very large small animal general practice, to determine the prevalence of vaccine-associated adverse events in over a million dogs. The use of a standardized reporting system within a very large population has permitted objective analysis of the prevalence of adverse events occurring within three days of vaccine administration. Out of 1,226,159 dogs receiving 3,439,576 vaccine doses, 4678 adverse events were recorded (38.2/10,000 dogs); 72.8% of these events occurred on the same day the vaccine was administered, 31.7% were considered to be allergic reactions, 1.7% were classified as anaphylaxis, and 65.8% were considered “vaccine reactions” and were likely caused by innate immune responses. Three dogs died. The lowest rate of such events was associated with Bordetella vaccination and the highest rate with Lyme disease vaccine. Additional analysis indicated that the risk of adverse events was significantly greater for small dogs than for large dogs (Fig. 10.1); for neutered than for sexually intact dogs; and for dogs that received multiple vaccines on one occasion. Each additional vaccine dose administered increased the risk of an adverse event occurring by 27% in dogs under 10 kg and by 12% in dogs heavier than 12 kg (Fig. 10.2). High-risk breeds included dachshunds, pugs, Boston terriers, miniature pinschers, and Chihuahuas. Overall, the increased prevalence of adverse events in young adult, small-breed, neutered dogs and their relationship to multiple dosing suggests that veterinarians should look carefully at the practice of giving the same vaccine dose to all dogs irrespective of their size.

In another report, from Japan 351 dogs showed an adverse event out of 57,300 vaccinated (62.7/10,000 doses). (Vaccines used included canine parvovirus, canine distemper, canine adenovirus 2, canine coronavirus, and leptospirosis.) Of these 351 dogs, 1 died, 41 had anaphylaxis, 244 developed dermatological signs, and 160 showed gastrointestinal signs. About half the anaphylaxis events occurred within 5 minutes of vaccination. Additional analysis of these anaphylaxis cases reported 87% collapse, 77% cyanosis, and both collapse and cyanosis in 71% of affected dogs. Breeds affected included miniature dachshunds (50%; these accounted for about 30% of all the anaphylaxis cases), Chihuahuas (10%), mixed breeds (5%), and toy poodles (5%). Miniature Schnauzers also appeared to be unusually prone to anaphylaxis. The highest frequency of adverse reactions occurred in dogs under 5 kg. Most adverse events were observed within 12 hours after vaccination. The adverse event rate in Japan as reported here (62.7/10,000 doses) is much higher than in the United Kingdom (0.093/10,000 doses), or in the United States (38.2/10,000 dogs).

Innate immune reactions

Vaccines may elicit mild transient injection site reactions as a result of inflammation. These inflammatory responses may manifest themselves within two to three days. As pointed out in Chapter 2, some degree of inflammation is required for the efficient induction of protection. This may cause pain or pruritus. The sting produced by some vaccines may present problems, not only to the animal being vaccinated, but also to the vaccinator, if the animal reacts violently. Lethargy, anorexia, soreness, minor behavioral changes, and tenderness at the vaccine site are normal postvaccinal responses and should resolve within 12 to 24 hours. Swellings may develop at the reaction site less commonly. These may be firm or edematous and may be warm to the touch. They appear within 24 hours and can last for about a week. Unless an injection-site abscess develops, these swellings leave little trace.

Vaccines containing killed gram-negative bacteria may be intrinsically toxic owing to the presence of pathogen-associated molecular patterns such as endotoxins, lipids, muramyl peptides, and porins that can bind to pattern recognition receptors and provoke cytokine release. In extreme cases this may lead to anorexia, and fever. Although such reactions are usually only a temporary inconvenience to male animals, they may be sufficient to provoke early embryonic deaths in pregnant females. It may be prudent to avoid vaccinating pregnant animals unless the risks of not giving the vaccine are considered to be too great. Vaccination with either immune-stimulating complex (ISCOM) vaccines or live recombinant vectored vaccines against influenza and tetanus may induce an acute-phase response in horses.

Innate immune responses may reduce an animal’s growth rate and diminish its feed efficiency. This growth suppression can be mimicked by injection of interleukin (IL)-1 and tumor necrosis factor (TNF)-α. These cytokines act on the brain to reduce appetite while at the same time, causing degradation of skeletal muscle.

Intranasal vaccines such as those containing Bordetella bronchiseptica and some viruses may cause transient cough or sneezing. This simply reflects the mild innate response triggered as the vaccine organisms invade the upper respiratory tract.

Hypersensitivity responses

Type I hypersensitivities

Vaccines have the potential to cause rare but serious allergic reactions (type I hypersensitivity). For example, allergic responses may occur when an animal produces immunoglobulin (Ig)E in response, not only to the immunizing antigen, but also to other components in vaccines. The most significant allergens are often vaccine excipients. For example, reactions are most likely to occur after injection of vaccines that contain trace amounts of fetal calf serum (specifically bovine serum albumin), egg proteins (ovalbumin), or gelatin. (Gelatin and serum albumin are added to vaccines as stabilizers to protect the vaccine antigens during the freeze-drying process.) Some vaccines may also contain antibiotics such as neomycin to which an animal may be sensitized. Severe allergic responses have been associated with the use of killed foot-and-mouth disease, rabies, and contagious bovine pleuropneumonia vaccines in cattle. Signs include angioedema, affecting mainly the head and ears, urticaria, pruritus, acute-onset diarrhea, vomiting, dyspnea, and collapse. All forms of hypersensitivity are more commonly associated with multiple injections of antigens and therefore tend to be associated with the use of killed vaccines.

It is important to emphasize that a type I hypersensitivity reaction is an immediate response to an antigen and occurs within a few minutes after exposure to an antigen (Fig. 10.3). It is good practice to keep an animal in the clinic for 15 to 25 minutes after vaccination to ensure that any immediate problems can be promptly recognized and treated (Box 10.2). Reactions occurring more than two or three hours after administration of a vaccine are likely not type I hypersensitivity reactions.

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Jan 21, 2021 | Posted by in GENERAL | Comments Off on Adverse consequences of vaccination

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