Vaccines: Disease, Eradication, Misinformation, and Reemergence

No one really likes vaccinations. Children view the procedure with the trepidation of a victim being pursued by a madman with a butcher’s knife, while parents make soothing, inane comments to their terrified offspring, such as “the sharp, pointy weapon is nothing to be afraid of!” as they are forced to pry their children from underneath the doctor’s table (my sister was particularly prone to this type of needle-avoidance). Personally, I view my own shots with a perverse fascination, but that probably comes from being, as my parents say, ‘an unusual child.’ In general, vaccinations are viewed by both parents and patients with resigned acceptance, although in the past decade there has been an upsurge of media attention toward possible side effects. Some individuals have become leery of the procedure, choosing to keep their children unvaccinated. Just how much of these concerns are based on truth, and how much stems from misinformation?

It is important to understand the science behind vaccinations, and the process of development, before jumping to conclusions. Vaccines have provided relief from decimating diseases, even eradicating mass killers such as smallpox. They are an unparalleled scientific miracle, which utilizes the wonders of our own immune system to provide protection from deadly diseases.

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Infection and Our Immune System

When a pathogen, such as a virus or bacterium, enters your body it can cause an infection by its mere presence or by directly attacking the body in some way. The immune system is our natural defense against such invaders. We have both an innate immune response and an active immune response.

The innate immune system is our first line of defense. It is non-specific, and includes barriers such as your skin, digestive tract lining and mucus, saliva, and tears. It also includes inflammation, which is initiated by signals released by injured or infected cells. The body then increases the movement of blood plasma and leukocytes (white blood cells) to the injured area in order to eradicate the infectious agent and heal the tissues, presenting with some pain, redness, and swelling. Other components of the innate immune system include the complement system (a collection of plasma proteins that help recruit inflammatory cells to the injured tissue, mark pathogens for destruction, kill the pathogens, and then remove the foreign matter) and the following types of white blood cells. Mast cells aid in pathogen defense and healing, but are most associated with an allergic response. Phagocytes are the famous Pac-Man cells that actually engulf pathogens and various particles and destroy them. Within phagocytes, you have macrophages, neutrophils, and dendritic cells.  There are also Natural Killer Cells, aptly named cells that target infected cells in your body and destroys them.

We also have an adaptive immune system, which plays a larger role in the vaccination process. This system provides a stronger, more specific, and longer lasting response to pathogens. It utilizes antigens in order to acquire specificity. An antigen is any alien substance (e.g., bacterial, chemical, pollen) that our immune system can recognize as foreign and produce a protein that binds specifically to it (i.e., antibody). Lymphocytes are a type of white blood cell which are essential to this system, mainly B cells and T cells. B cells create and secrete antibodies (immunoglobulins) which block the antigens/infectious agents from binding to our cells, as well as marks them for destruction. T cells recognize specific antigens and send instructions to the immune system to initiate a response, recognize and kill infected cells, and also help make antibodies. This is all great news for us, but the really neat part is that after reacting to a specific invader, some of these B and T cells become memory cells. They persist for years, sometimes the entire lifespan of their host, and remain specific to that antigen. This means that if the pathogen/antigen is encountered again, it is immediately recognized and rapidly dealt with, preventing the disease. This is immunity.

There are two types of immunity. Passive immunity is when a person is given antibodies, rather than producing them. This occurs naturally in newborns, as babies receive their mothers’ antibodies through the placenta. Scientists have also adapted it, giving patients antibody-containing blood products (immunoglobulin) from people who have an active immunity (we’ll get to that next). This is used to provide immediate protection from a specific disease or toxin, but it only lasts for several weeks or months.

On the other hand, active immunity can last a lifetime. This occurs, as previously described, by exposure to a pathogen resulting in the immune system producing antibodies. If it happens through suffering through the disease, it is called natural immunity. Herein lies a problem; most of us would prefer to avoid the disease–especially when it is a nasty piece of work with high morbidity and mortality, like smallpox. This is where vaccinations come in. The immune system can be trained by introducing either killed or weakened forms of the pathogen. This is what vaccinations do, and it results in the immune system building a defense system and memory of that specific pathogen.

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Vaccines

Vaccines contain specific pathogens in a non-active state. This means that the body is exposed to the antigen of the pathogen, without the pathogen having the means to actually cause the disease. Consequently, the body manufactures antibodies and memory cells. This allows immunity to form without the body being subjected to the disease; a type of preventative medicine. Each vaccine must undergo extensive testing before they reach FDA approval for use, involving numerous clinical trials to verify the efficacy and risks. There are several types of vaccines based on the type of pathogen involved.

Live, attenuated vaccines contain living viruses that are either weakened or altered so that they cannot cause the disease in people with functioning immune systems. As this is the closest form to natural infection, it is very efficient in training the immune system. While attenuated viruses are too weak to prove a problem for most of us, these vaccinations are not given to anyone with weakened immune systems, such as chemotherapy patients. The MMR and chickenpox vaccinations are examples of attenuated vaccines.

Inactivated vaccines are also for viruses, but in this case the virus is killed before injection. While this form does cause an immune response as desired, it often requires several doses to either build up or maintain the immunity. The polio vaccine is an inactivated vaccine.

Toxoid vaccines are vaccinations providing immunity against bacteria that produce toxins. These contain weakened forms of the toxin so that they do not cause the illness. This trains the immune system to respond and eliminate the natural toxin. Our routine tetanus shots are an example of this (remember this post on tetanus?) as well as diphtheria.

Subunit vaccines are used for both viruses and bacteria. These innovative vaccines only contain certain components of the pathogen. An incredible amount of time and effort has yielded the identification of the components containing the essential antigen for some pathogens, allowing only that part to be injected without the rest of the organism/virus. This allows for the disease-causing components to be completely absent. The whooping cough component of the DTaP vaccine is an example of this type.

Conjugate vaccines are bacterial vaccinations for bacteria that disguise their antigens with a polysaccharide coating. The vaccine can connect the polysaccharides to the antigens that trigger an immune response, such as the haemophilus influenza type B vaccines.

(all previous material sourced from the CDC and [9])

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Source: Vaccines.gov

Risks and Misconceptions

While the biology behind vaccinations is a beautiful example of scientific innovation, people receiving vaccines are more concerned with the benefit and cost ratio. First of all, it is important to realize that rigorous, stringent requirements and standards are in place today. Only the safest and most effective medicines are accepted for final testing. Furthermore, adverse effects are constantly monitored and reviewed.

Any medicine can have adverse effects due to individual, unique physiology. Unfortunately, vaccines are no exception. Given that millions of vaccines are given per year, we would expect to see cases of very rare adverse effects not seen in clinical trials, as they rarely include such large numbers of participants. The vast majority of vaccine recipients have no reaction to vaccinations. If a reaction does occur, it is often very minor and clears up within days: soreness, a slight rash, a mild fever. In a few instances, vaccinations can cause higher fevers, chills, and aches. The most extreme reactions are exceedingly rare: in one out of 100,000 to 1,000,000 children, encephalopathy (often an inflammation of the brain) or severe allergic reactions can occur [4].

These systemic reactions, the more serious fevers and allergic reactions, tend to occur within minutes of vaccine administration. All providers of vaccinations are required to be certified with the necessary equipment and treatment needed for such reactions, so most cases are caught and treated [5].

The Institute of Medicine (IoM) has gathered a great deal of data and studies concerning vaccine safety. While they found many rumored connections to be false (such as Autism, which I will cover shortly), they did acknowledge the rare risks. Vaccines made from live viruses tend to have the most risks associated with them, and understandably so. The MMR vaccine can cause fever-related seizures, albeit extremely rarely and usually with no long-term effects. The chickenpox vaccination and the MMR both have possible side-effects in people with immune system problems. These include brain inflammation, hepatitis, shingles, and pneumonia, and are why patients with compromised immune systems are generally not given live, attenuated vaccinations. The Institute of Medicine lists six vaccinations that can cause anaphylaxis, a severe allergic reaction (MMR, chickenpox/varicella, influenza, hepatitis B, meningococcal, and tetanus). As this reaction occurs very shortly after the injection, the risk is largely negated by lingering at the doctor’s for half an hour [4, 10,  IoM].

Understanding the risks of vaccinations is further complicated by the vast array of vaccines and the rarity of the reported effects. When there are only 1/100,000 or less cases of an adverse effect, it can be difficult to tie it directly to the vaccine or disprove the connection. The effects of vaccinations are constantly being studied, and rumors are always breaking out. Most of these are found to be false; studies have shown no association between Guillain-Barré Syndrome and vaccinations, no statistically significant association between the hepatitis B vaccine and rheumatoid arthritis, nor with the influenza vaccine and rheumatoid arthritis [1,2,5,8]. Some of the connections are too rare to understand fully, or may be confirmed (such as the allergic reactions). One of the most persistent risk-rumors is that of the connection between Autism and vaccinations.

The Autism Myth

Despite being disproved time and time again, the misconception that Autism can be caused by vaccinations is incredibly widespread. Perhaps it is due to the complexity and lack of understanding of Autism, a condition whose exact causes and scope remain mostly a mystery. As Autism screening improves, the known cases skyrocket, encouraging attempts to explain the disorder based on widely spread modern practices, such as vaccination.

A pivotal player in the Autism-vaccine connection is Andrew Wakefield, a medical researcher who published a paper concerning Autism in The Lancet, 1998. He went on to publish a second paper in 2000, claiming that the MMR (measles, mumps, and rubella) vaccine had not undergone adequate safety testing. The papers remained relatively obscure until he discussed them in a press conference, launching a public health crisis. The media (yellow journalism at its best) soaked up the story, and it spread across the internet like wildfire. Parents began refusing to have their children vaccinated, fearing inadvertently causing Autism. The vaccination rate dropped below 80% in England, with less than 50% of children immunized in London in the first decade of 2000. Measles, which had previously been eradicated in England, re-emerged with cases rising to 1,370 in 2008. Concurrently, scientists attempted to clarify this connection but dozens of studies yielded no association. By 2004, the scientific community was near-unanimous in the belief that there was no association between MMR and Autism [3].

Unfortunately, the media and internet love a sensational and scary story. The idea was firmly planted and repeated, so that by 2009 one in five parents believed that Autism was related to the MMR vaccination. Meanwhile, the medical and scientific community, suffering a backlash of mistrust, examined Wakefield more closely. Two years before he published the 1998 paper, he received $670,000 in compensation as a consultant to attorneys representing the parents of children who had allegedly suffered due to the MMR vaccine, a conflict of interest that scientists are required to disclose. The situation resulted in the British General Medical Council starting a formal investigation of Wakefield that found him guilty of failure to disclose conflicts of interest and scientific misconduct. He was listed as an inventor on a patent for a new vaccine eliminating measles and involved in the company that would be producing it. Furthermore, his study had not been approved by a bioethics committee and he had altered his patients’ medical histories (several children whom he claimed had Autism in his study did not, in fact, have any such diagnosis!). Wakefield’s medical license was revoked, and his claims thoroughly disproven [3,7].

Dozens of studies have found no correlation between MMR vaccinations and children with Autism. The research evidence is overwhelming, yet the myth still persists. The consequences of parents’ loss of confidence in vaccinations for their children can already be seen in the re-emergence and outbreaks of measles [3,6,7].

A Final Thought

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All decisions in life are gambles weighted on benefit and cost ratios. Very few things, if any, come without associated risks. There are inarguably some rare risks associated with vaccinations, just as there are risks in leaving yourself or your children unvaccinated. To paraphrase the CDC, by choosing to vaccinate, you are betting that you or your child could be exposed to the pathogen in question, accepting the small risk of a vaccine reaction to protect against the possibility and consequences of acquiring the disease. By choosing not to vaccinate, you are betting that you or your child will not be exposed to the disease, or that the disease will not be serious, and consequently accepting the risk of illness to avoid the possibility of a vaccine reaction. These odds of encountering pathogens vary from disease to disease; we are more frequently exposed to the tetanus toxin, for example, and less to more exotic diseases [11, CDC].

When we vaccinate we are not only protecting ourselves, but our community and posterity. When the majority of a population is immune to a disease the probability of outbreaks are low; the disease cannot spread easily if one person becomes infected because it cannot infect others who are immune. This is known as herd immunity. When fewer people are immune, it is much easier for a disease to become an outbreak since it has an ample supply of hosts that it can infect. With herd immunity comes disease eradication, which we have achieved with smallpox, for example. This protects not only ourselves, but future generations from diseases.

Personally, I choose to side with the very low risks associated with vaccinations (especially in an era of rising antibiotic resistance). However, there are undeniable risks, even if they are low. If you are a concerned patient or parent, take the time to reach out to your doctor, or another medical professional, and ask them about the risks and benefits of vaccinations.

References

[1] Baxter, R. et al. “Lack of Association of Guillain-Barré Syndrome With Vaccinations.” Clin Infect Dis. 2013. 57(2):197-204.

[2] Brewer, T. “Preventing tuberculosis with bacillus Calmette-Guerin vaccine: a meta-analysis of the literature.” CID. 2003. 31(S3).

[3] Flaherty, D. “The vaccine-Autism connection: a public health crisis caused by unethical medical practices and fraudulent science.” The Annals of Pharmacotherapy. 2011. 45:1302-1304.

[4] “General Recommendations on Immunizations: Recommendations of the advisory committee on immunization practices (ACIP).” Centers for Disease Control and Prevention: MMWR. Recommendations and reports. 2011. 60(2).

[5] Heijstek, M. et al. “Vaccination in paediatric patients with auto-immune rheumatic diseases: a systemic literature review for the European League against Rheumatism evidence-based recommendations.” Autoimmun Rev. 2011. 11(2):112-122.

[6] Loring, D. et al. “Time trends in Autism and in MMR immunization coverage in California.” JAMA. 2001. 285(9):1183-1186.

[7] McMurray, R. et al. “Managing controversy through consultation: a qualitative study of communication and trust around MMR vaccination decisions.” The British Journal of General Practice. 2004.

[8] Ray, P. et al. “Risk of rheumatoid arthritis following vaccination with tetanus, influenza, and hepatitis B vaccines among persons 15-59 years of age.” Vaccine. 2011. 29:6592-6597.

[9] Rueckert, C. and Guzman, C. “Vaccines: from empirical development to rational design.” Plos Pathogens. 2012. 8(11).

[10] Trunz, B. et al. “Effect of BCG vaccination on childhood tuberculous meningitis and miliary tuberculosis worldwide: a meta-analysis and assessment of cost-effectiveness.” The Lancet. 2006. 367(9517):1173-1180.

[11] Weinstein, N. et al. “Risk Perceptions: Assessment and Relationship to Influenza Vaccination.” Health Psychology. 2007. 26(2):146-151.

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