Vaccines - Part I - Origins & Risk-Benefit Analysis

Vaccines are one of the biggest improvements to health that science has provided us. They are right up there with hygiene (soap) and antibiotics. At the same time, vaccines are one of the most maligned.

This will be the first of many posts on the topic, so let's start by defining what we're talking about.

What is a vaccine?

Vaccines are preventative medicine. A vaccine contains a piece of the virus or bacterium. When introduced into the body, the immune system mounts a defence and the body learns to recognize the actual virus or bacterium. This way, if the body actually encounters it in the real world, the immune system can quickly clear the body of the organism. 

Vaccines were brought to us by an English country physician named Edward Jenner. At the time in the late 1700's, the world was ravaged by smallpox. Dr. Jenner heard that milkmaids (people who milked cows) did not contract at all or did not contract as severe a form of smallpox. He thought that clearing cowpox (a mild disease in humans) conferred some benefit when fighting off smallpox (a much deadlier disease). To test his hypothesis, Dr. Jenner injected pus he had taken from the hand of a milkmaid infected with cowpox, into an eight-year-old boy (the son of his gardener). He later observed that this child did not contract smallpox when smallpox-material was given to him (ground scabs from smallpox-infected people).

The immense ethical issues of this experiment notwithstanding, Dr. Jenner did successfully develop the first virus and also showed that it is not necessary to use the exact same organism to develop immunity. Indeed today, many vaccines are developed from analogues (look-alike proteins) that mimic those commonly found in deadly diseases. Finally, though we sometimes use the term immunization, vaccine and vaccination are still commonly used: it comes from Variolae vaccinae (Latin for "smallpox of the cow"), the term devised by Dr. Jenner.

In perhaps the World Health Organizations's greatest contributions to health, smallpox was eradicated in 1980 after a successful worldwide vaccination campaign.

Modern vaccines and the resistance to them

These days, some people eschew vaccines. There is a concern that the costs, or potential costs, outweigh the benefits. Some believe that vaccines benefit the public at large, but not the individual. Others believe that they can trade off of the herd-immunity effect, which says that, in general, if 95% of the population is immunized against a specific disease, the organism will not have enough people to infect to spread widely. Herd immunity is important and it is being eroded by fewer and fewer people getting vaccinated. In 2014, in my hometown, the Toronto Star reported that the vaccination rate for some schools is down to 60%. 

It is important to remember that herd immunity protects people that cannot be vaccinated, especially children that are too young to be immunized (partially or fully) and people who are immunocompromised (e.g. people undergoing chemotherapy for cancer treatment).

One problem with the now well-recognized herd immunity effect is that as hysteria seems to grow with vaccines, some people believe that physicians are recommending vaccines to protect the general public but do so by placing the individual at risk. This would be a violation medical ethics. The physician is bound by fiduciary duty to treat the patient in front of them - to do what is in their best interests and no one else's.

Adverse effects

So what adverse effects are there? To start, it is important to note that all medical interventions carry some risk of side-effects.

Here is one example:

ADVERSE REACTIONS 

[...]

General: Hypersensitivity reactions including the following: skin eruptions (maculopapular to

exfoliative dermatitis), erythema, cellulitis, paresthesia, urticaria, laryngeal edema, fever,

eosinophilia; other serum sickness-like reactions (including chills, fever, edema, arthralgia and

prostration); and anaphylaxis including shock and death. 

Note: Urticaria, other skin rashes and serum sickness-like reactions may be controlled with

antihistamines and, if necessary, systemic corticosteroids. Whenever such reactions occur,

penicillin G should be discontinued unless, in the opinion of the physician, the condition being

treated is life-threatening and amenable only to treatment with penicillin G. Serious anaphylactic

reactions require immediate emergency treatment with epinephrine. Oxygen, intravenous

steroids, and airway management, including intubation, should also be administered, as

indicated.

Gastrointestinal: Pseudomembranous colitis. Onset of pseudomembranous colitis symptoms

may occur during or after antibacterial treatment. 

Hematologic: Hemolytic anemia, leukopenia, thrombocytopenia. There has been one report of

pancytopenia in an elderly patient, who received concomitant methotrexate and flucloxacillin. 

Neurologic: Neuropathy 

Urogenital: Nephropathy 

The following adverse events have been temporally associated with parenteral administration of

penicillin G benzathine, although a causal relationship has not necessarily been established. 

Body as a Whole: Hypersensitivity reactions including allergic vasculitis, pruritus, fatigue,

asthenia and pain; aggravation of existing disorder; headache. 

Cardiovascular: Cardiac arrest; hypotension; tachycardia; ventricular arrhythmia, palpitations;

pulmonary hypertension; pulmonary embolism; vasodilation; vasovagal reactions;

cerebrovascular accident; syncope. 

Gastrointestinal: Nausea, vomiting; blood in stool; intestinal necrosis 

Hemic and lymphatic: Lymphadenopathy 

Injection site: Injection site reactions including pain, inflammation, lump, abscess, cellulitis,

necrosis, edema, hemorrhage, cellulites, hypersensitivity, atrophy, ecchymosis, and skin ulcer.

Neurovascular reactions including warmth, vasospasm, pallor, mottling, gangrene, numbness of

the extremities, cyanosis of the extremities, and neurovascular damage. 

Metabolic: Elevated BUN, creatinine and SGOT 

Musculoskeletal: Joint disorder, periostitis, exacerbation of arthritis, myoglobinuria,

rhabdomyolysis.

Nervous system: nervousness, tremors, dizziness, somnolence; confusion, memory impairment;

anxiety; euphoria; transverse myelitis, seizures; coma. 

A syndrome manifested by a variety of CNS symptoms, such as severe agitation with confusion,

visual and auditory hallucinations, and a fear of impending death (Hoigne’s syndrome), has

been reported after administration of penicillin G procaine and less commonly, after injection of

the combination of penicillin G benzathine and penicillin G procaine. Other symptoms

associated with this syndrome, such as psychosis, seizures, dizziness, tinnitus, cyanosis,

palpitations, tachycardia and/or abnormal perception in taste, also may occur.

Respiratory: Hypoxia, apnea, dyspnea 

Skin: Diaphoresis 

Special Senses: Blurred vision, blindness 

Urogenital: Neurogenic bladder; hematuria; proteinuria; renal failure; impotence; priapism [emphasis added]

This is for penicillin. A drug that is commonly requested by patients, yet it has the potential to cause:

• Priapism (sustained, unwanted, erection lasting longer than four hours);
• Blindness;
• Cardiac arrest; and
• Death.

Yet the world seems to have a love-affair with antibiotics and we routinely request antibiotics when they will likely not help us and may harm us.

The HPV Vaccine

Now let's turn to vaccines. Since the side effects in question depend upon the specific vaccine, let's look at the HPV vaccine, because it's a vaccine that has received a lot of media attention recently. Here is some HPV vaccine information given by the Centers for Disease Control in the US:

The HPV vaccine is very safe, and it is effective at preventing HPV. Vaccines, like any medicine, can have side effects. Many people who get the HPV vaccine have no side effects at all. Some people report having very mild side effects, like a sore arm from the shot. The most common side effects are usually mild.

Common Side Effects of HPV Vaccine:

• Pain, redness, or swelling in the arm where the shot was given
• Fever
• Headache or feeling tired
• Nausea
• Muscle or joint pain

Brief fainting spells and related symptoms (such as jerking movements) can happen after any medical procedure, including vaccination. Sitting or lying down for about 15 minutes after a vaccination can help prevent fainting and injuries caused by falls.

On very rare occasions, severe (anaphylactic) allergic reactions may occur after vaccination. People with severe allergies to any component of a vaccine should not receive that vaccine.

These data were gathered after a decade of use of the vaccine. During that time, nearly 90 million doses of the vaccine were given in the US. There are actually three HPV vaccines, but if we use the CDC numbers for Gardisil, which accounts for approximately 87% of the HPV vaccinations in the US, they reported 79,000,000 doses of vaccines and 33,945 adverse events reported over a ten year period. That's an adverse events rate of 0.0424% (and remember that not all reported adverse events are attributable to the vaccine). Of those:

In the VAERS reports, the most frequently reported symptoms overall were: fainting; dizziness; headache; nausea; fever; and pain, redness, and swelling in the arm where the shot was given. Of the reports to VAERS, 7% were classified as “serious.”  About 14% of the VAERS reports were not related to health problems, but were reported for reasons such as improper vaccine storage or the vaccine being given to someone for whom it was not recommended.

The risk-benefit ratio
The question then becomes: given the severity (relatively minor) of the side effects and frequency (minuscule), what benefit is conferred upon the person receiving it.

HPV is not one virus, but a group of approximately 200. Some are high risk for causing cancer and some are not. Some people say that since the vaccines do not cover every single strain, it's not worth getting vaccinated. However, there may never be one vaccine that covers them all, so what matters is the overall risk reduction for causing cancer balanced with the risk of adverse effects. While regular pap smears and protection against STI's is still important, it is not the case that these will prevent cervical cancer, nor do they ensure that cervical cancer will be caught early.

From cancer.gov:

All three vaccines prevent infections with HPV types 16 and 18, two high-risk HPVs that cause about 70% of cervical cancers and an even higher percentage of some of the other HPV-associated cancers. Gardasil also prevents infection with HPV types 6 and 11, which cause 90% of genital warts. Gardasil 9 prevents infection with the same four HPV types plus five additional high-risk HPV types. 

In addition to providing protection against the HPV types included in these vaccines, the vaccines have been found to provide partial protection against a few additional HPV types that can cause cancer, a phenomenon called cross-protection.

Finally, Ontario only recently started providing the HPV vaccine to both boys and girls. It was a misconceived policy to restrict HPV vaccination to girls for nearly a decade, as described well by this University of Toronto Medical Journal article:

The nearly decade-long delay in including boys has been partly fueled by flawed theoretical assumptions inherent to the concept of herd immunity, which relies on immunizing high rates of females to provide passive immunity to non-immunized males. This model gives rise to several health inequity concerns, and relies on the false premise that sexual contact only occurs between men and women, and only occurs between Canadians while inside Canada.

... 

[P]erhaps the most overlooked health inequity inherent to the female-only herd immunity HPV vaccination model is that it entirely excludes gay, bisexual, and other men who have sex with men (GBMSM) in addition to persons living with HIV. This is particularly concerning given the signicantly higher rates of HPV infection, subsequent cancers, as well as associated psychosocial burden in these vulnerable populations relative to the general population. Even if immunization rates in women reached 100%, the HPV chain of transmission would still be maintained through GBMSM and thus these populations have been disproportionately left at risk by female-only vaccination programs. [citations omitted]

Bottom-line
If people were told that there was a pill they could give their kids that would almost guarantee that they would not get certain types of cancer, people would be clamoring for it (think antibiotics). But tell people that the same medicine comes in the form of a vaccine and people are fearful, despite the risk-benefit ratio being similar.