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Vaccination strategies in the context of antibiotic reduction

14 March 2018


Prof. Paolo Martelli, DVM, Diplomate ECPHM, President of the ECPHM, Full Professor of Veterinary Clinical Medicine, Parma University, Italy, outlines how to achieve swine herd immunity based on recent scientific findings. Adapted from remarks given at BIOMIN Antibiotic-free Days in November 2017.

Tools for the reduction or substitution of antibiotics in animal feed diets are already available. However, vaccination remains the most important tool for disease prevention. A different antibiotic strategy now needs to be applied, one that incorporates their prudent use.

One Health

Although ‘One Health’ is a new concept in terms of animal disease prevention, there are already some university lecturers sharing their knowledge about it, highlighting its importance. Although the terminology is new, there is nothing new about the interaction of the three main areas involved in disease prevention: the animal, humans, and the environment. These three areas overlap as seen in the figure at [01:50]. Ecology is the relationship between animals and their environment, and translational medicine allows knowledge sharing between human medicine and animal veterinary medicine.

Traditionally seen as public health, the new concept is One Health. This is due to the increasing amount of interaction between human medicine, animal medicine and the environment. One Health encourages the prudent use of antibiotics rather than avoiding them completely.

One Health and responsible use of antibiotics

The concept of responsible or prudent use of antimicrobials is not new. The discussion around reducing the use of antibiotics started twenty-five years ago. At that time, it was not urgent. Today, it has become an emergency. Predictions show that by 2050, people will be dying as a result of antibiotic resistance. Mortality due to infection with antibiotic-resistant microorganisms will be higher than the mortality due to cancer unless action is taken.

Reduction, replacement and rationality need to be applied in order to use antibiotics responsibly. From an ethical perspective, antibiotics cannot simply be eliminated from use because sick animals and sick humans must be treated. That treatment currently involves the administration of antibiotics. Being prudent with antibiotic use means adopting a therapeutic strategy, and only prescribing such medication after correct diagnosis of the problem.

Antibiotics cannot be used as an umbrella

Antimicrobials cannot be used to cover up mistakes in management, environment, biosecurity or welfare. For a long time, antibiotics have been used to counterbalance areas that were lacking [03:00] but this cannot continue. Improvements in any area can have a huge positive impact on the efficiency and the health of animals, reducing the role of antibiotics as the umbrella. Such improvements involve a long-term change of mindset, but any implementation of a strategy for disease prevention is a step in the right direction.

Special attention should be paid to genetics as the new frontier of animal health. Further investigation into the role played by genetics, searching for specific genera responsible for disease susceptibility, could revolutionize animal health. The answers will not be delivered in the short term, but in the next ten to 20 years there should be huge advances in this area. There are already whole congresses based on the role of genetics in disease prevention with full days of discussion on this topic alone.

Immune response mode of action

The development of the immune system starts at a very early stage, soon after conception [09:44]. By the final trimester of gestation, the immune system is competent. Fetuses show an immune response because their innate immunity and adaptive immunity are active. From birth until weaning, both components of the immune system mature and develop.

Animals have a competent immune system when they are vaccinated in the first weeks of life. Their immune system is different to that of an adult, but it is already functioning very well. What do we expect from the immune system, and what do we expect from a vaccination? Everything identified by the animal as ‘non-self’ is treated by the immune system. The immune response means the animal has clinical and immunological protection. This is also expected from a vaccination; when an animal is vaccinated, we expect it to be protected.

If an animal is not vaccinated, the likelihood that it will die increases. However, this depends on the situation the animal is in, its environment, exposure to infectious agents, and the status of the animal including its age. The lifespan of a pig reared for meat is only six months. The immune response in a young animal is very different compared to that of a sow or boar. As the animal ages, the efficiency of the immune system reduces.

Clinical protection

The figure at [18:27] illustrates the meaning of clinical protection. The right hand column shows the severity of disease in a non-vaccinated animal whereas the centre column shows the greatly reduced severity in a vaccinated animal. The curve is completely different for vaccinated animals compared to non-vaccinated animals. Body temperature is one parameter to be measured in clinical protection, but one of the most important parameters is average daily weight gain (ADWG).

Daily gain as clinical parameter

The effect of infection on ADWG is shown at [18:55]. The red bar represents the ADWG in an infected, non-vaccinated animal. The blue bar represents an infected, vaccinated animal and the green bar shows the ADWG of a non-infected animal.

Vaccination and mortality

Fever and mortality are other measures of clinical protection. In a trial conducted by Martelli et al. (2011), the probability of a pig vaccinated with a single dose of porcine circovirus type 2 vaccine at three weeks of age suffering from porcine circovirus disease (PCVD) was twelve times less than that of an unvaccinated pig. The same study showed that unvaccinated pigs required 30% more injections with antibiotics than vaccinated pigs when faced with a PCVD challenge. Even though PCVD is a viral infection and therefore not treated with antibiotics, the number of injections went up due to co-infections. In the vaccinated population, fewer injections were administered due to the lower rate of co-infection. One infection can open the door to other infections.

Vaccination efficacy perception

The efficacy of a vaccination is a matter of perception; it is not possible to measure efficacy in the field. Experimental conditions can be measured, as can experiment outputs such as ADWG, mortality and morbidity. There are some very efficacious vaccines available against Aujeszky’s disease and PCV2. Recent experiences of porcine parvovirus (swine flu) have demonstrated the efficacy of the PCV2 vaccine. The swine fever vaccine is efficacious in Asian countries but less so in America and Europe. Swine producers face difficult challenges from Actinobacillus pleuropneumoniae, mycoplasma hyopneumoniae, Glasser’s disease and streptococcus suis, contributing to the generally low perception of vaccine efficacy. Despite using vaccinations against these diseases for over 20 years, the realization that their efficacy is low is becoming more apparent.

One potential reason could be the inability to trigger a response from the immune system at the site of the infection. Vaccines are typically injected intramuscularly or intradermally which creates very good systemic immunity. However, especially in cases of mycoplasma hyopneumoniae, local immunity is needed which is not stimulated when the vaccine is injected intramuscularly. This highlights that eliciting an immune response from an animal when the vaccine has been administered via a different route is not possible. The next generation of vaccines should address this problem.

E. coli presents a very interesting case as some intramuscular vaccines show good results, and others fail. Some recently available E. coli vaccines have the fimbriae as the antigen. This is why they induce a specific immunity to the parts of the microorganism that play a very important role in the pathogenesis of the infection.

Herd immunity

Herd immunity means creating resistance to infection and to the spread of infection in a herd due to the immunity of a large percentage of the population. Herd immunity is a common term, also used in human medicine to describe the whole population having the same immune status at the same time. The level of herd immunity is altered when a susceptible animal is introduced to the population.

One of the most important tools for the eradication of Aujeszky’s disease is vaccination. However, this strategy fails when we have a sub-population of animals that are not properly vaccinated against the disease. This is a clear example of the importance of herd immunity. Other factors such as pathogen changes, antigenic variability and the genetic setting of the virus should all be considered in terms of herd immunity.

Vaccination and virus transmission in herds

Herd populations with varying levels of vaccination and infection rates are shown at [31:07]. The higher the vaccination rate in a population, the lower the infection rate. This infers that infections can spread more easily through a population that is not vaccinated. When a high percentage of the population is vaccinated, the rate of transmission of an infection is very low because vaccinated animals have a reduced capacity for transmitting the virus. This transmission capacity is known as the reproduction ratio or ‘R’ value.

The ‘R’ value can be greater than one, less than one or one. An ‘R’ value of 0.3 means that when one infected animal comes into contact with other animals, the infection will only spread to 0.3 of them. An ‘R’ value of more than five means that when one infected animal comes into contact with other animals, the infection will spread to at least five of them.

When a population of animals is vaccinated, there is always a proportion that do not respond. This is true of all animal species and humans due to physiology. For some vaccinations, seroconversion only occurs in a small proportion of the population. With other vaccinations, 100% seroconversion is expected. In some cases, seroconversion has occurred but there is no protection. Laboratory analysis methods used to demonstrate seroconversion are not able to measure the level of protection.

Immune response

Infections can play a role in reducing the immune response, but it is very difficult to identify immune suppression. The PRRS virus determines regulation of the immune system. PCV2 infections determine immune tolerance. Neither is able to cause immune suppression, which is something entirely different.

Stress and nutritional factors can also influence the immune system. The immune system is a very complex set of interactions. Many hundreds of chemical substances interact when the immune system is stimulated.

When an infection is detected, the first line of defence is the animal’s innate immunity. The beginning of this process is inflammation. Inflammation is a very, very important part of the immune reaction. An efficient immune reaction is not possible without some degree of inflammation. A lesser-known part of the immune response is the neuroendocrine response. Hormones work to control and shut down the defence and clearance of the microorganisms. These hormones include cortisol and also the growth hormone.

When animals are infected and sick, and those animals have very poor performance, it is not only because of reduced feed intake, but also because the growth hormone is being used in the neuroendocrine response of the immune system.

Effects of mycotoxins on vaccination

There is no question that mycotoxins have an effect on the immune system, but their mode of action continues to be discussed. The literature contains numerous references supporting the fact that mycotoxins have an effect on the efficiency of the immune response. Aflatoxins interact with the cytokines, a part of the immune system that is not measurable. They also influence the important inflammatory response. Zearalenone also effects the efficacy of vaccinations. Therefore, it is very important to consider mycotoxin contamination of feed when developing herd management programs, to ensure maximum efficacy of vaccinations.


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