Death to polio. Long live vaccines!

In the 17th century 12% of children in the UK died before their first birthday.³ Babies and children died of tetanus, whooping cough, diphtheria, dysentery, tuberculosis, typhus, typhoid fever, rickets, chicken pox, measles, scarletfever, smallpox and plague. Babies in the UK are now routinely vaccinated against 13 potentially life threatening diseases and consequently the infant mortality rate is 0.36%.⁴

Vaccines have played an enormous role in this huge reduction in infant mortality but have also had an impact on the general reduction of morbidity. The table below shows the substantial reduction in the average annual number of cases for various vaccine-preventable diseases in the US during the twentieth century and in 2010.⁵

The first vaccination

Back in the 17th and 18th centuries, smallpox was a virulent disease and massive killer claiming an estimated 400,000 lives a year within Europe.⁶ Smallpox victims experienced fever and a distinctive skin rash which progressed to sores, pustules and scabs. 30% of people who contracted smallpox died. Those who survived had permanent scars over large areas of their body and some were left blind. Smallpox (which is caused by the contagious variola virus) was spread through coughs and sneezes as well as contact with the fluid that oozed from the patient’s sores.

Doctors used variolation to help protect patients from smallpox. This technique involved either blowing dried smallpox scabs into a patient’s nose or inserting them under the skin. This resulted in patients contracting of a mild form of smallpox where the associated mortality was 1-2% compared to 30% if the disease was contracted naturally. Edward Jenner, a country doctor in the UK, was aware of folklore that said milkmaids didn’t get smallpox and instead only caught a weakened, non-life threatening version called cowpox (also known as vaccinia). He believed that the pus within with cowpox blisters offered protection against smallpox.

In May 1796 (long before the days of research ethics committees) he put his theory to the test. Jenner first took pus from cowpox lesions collected from the hand of a milkmaid, which contained live virus. He then made a few scratches on the arm of an 8 year old boy and inoculated him by applying the pus from the milkmaid into the scratches. The boy developed cowpox and recovered after a few days. A month or so later, Jenner exposed the boy to smallpox. As predicted (and presumably to Jenner’s relief) the boy did not go on to develop smallpox, on this or any subsequent occasion. Jenner had identified treatment to prevent smallpox which did not have the mortality rates associated with variolation.

Eradication of smallpox

The public were initially uncertain about Jenner’s smallpox vaccination, particularly being treated with material originating from cows. In a time before clean working practises were understood, cowpox samples became contaminated and patients were
sometimes accidentally inoculated with smallpox, compounding public uncertainty! Variolation was forbidden in 1840 and compulsory inoculation with cowpox followed in 1853.

The smallpox vaccination process continued and remained virtually unchanged for the next 150 years. The game changer for the vaccination process occurred in the 1950s with the development of a vaccinia virus suspension. This permitted freeze-drying into ampules which allowed long term storage without refrigeration.

In 1967 the WHO launched the “Intensified Smallpox Eradication Programme”. This was a massive undertaking and involved vaccinating at least 80% of the population in each country which proved particularly challenging in developing countries. This comprehensive vaccination programme worked. The last naturally occurring case of smallpox was in 1977 and in 1980 the WHO declared smallpox had been eradicated.

It is primarily due to Jenner’s work that information on this deadly disease is now written in the past tense. It has been claimed that the work carried out by Jenner has saved more lives than any other person.

Development of further vaccines

Attempts to emulate Jenner’s vaccination process by inoculating with live organisms from the sores of similar diseases failed. It wasn’t until the late 1800s that Louis Pasteur discovered that microorganisms could be attenuated (modified) in the laboratory so that they were weakened but would still produce an immune response in the body.

The rabies virus was collected from spinal cords of infected rabbits and then weakened by drying the tissue out.

The first example of this type of vaccine for humans was against rabies. The rabies virus was collected from spinal cords of infected rabbits and then weakened by drying the tissue out. By 1900, five vaccines had been developed, against smallpox, rabies, typhoid, cholera and plague.

There are 4 main classes of vaccines. They all act by exposing the immune system to part or all of the pathogen but without causing the full blown disease. The immune system is then able to react if the pathogen reappears.

Live Attenuated Vaccines (LAV)
These vaccines contain a live pathogen which has been weakened (attenuated). When administered, the weakened pathogen will only cause a very mild form of the disease, if any. Examples are vaccines for rabies, typhoid, tuberculosis, polio (Sabin vaccine), measles, mumps and rubella.

Inactivated Vaccine
These vaccines contain intact pathogens which have been killed. They tend to elicit a weaker immune response and therefore require several doses, or boosters. Examples are vaccines for influenza, cholera, polio (Salk vaccine) and hepatitis A vaccines.

Subunit (purified antigen)
For some viral diseases, an immune response can be generated following exposure to a fragment rather than the whole virus itself. Vaccines for hepatitis B, human papillomavirus and plague are subunit vaccines.

Toxoid (inactivated toxins)
Some pathogens cause harm by releasing toxins (usually peptides or proteins). In these instances a vaccine can be created using modified toxins which allows the immune system to recognise and eliminate the toxins before they can cause any ill effects. Tetanus and diphtheria are both prevented with toxoid vaccines.

Vaccine side effects and controversy

The holy grail of vaccine preparation is to develop durable, long-term immunity against the target disease in the minimal number of doses, whilst avoiding adverse events. Moreover the vaccine needs to be suitable for mass production, stable for prolonged periods at extreme storage conditions and affordable.

The WHO says that vaccines used in national immunisation programmes are considered safe and effective when used correctly.⁷ It is accepted that vaccines are not risk free, therefore in order to have a successful vaccination programme, the public’s trust is a necessity to ensure adequate and sustained vaccine uptake which is critical to obtain herd immunity.

Ironically, the more successful a vaccination campaign and the less visible the disease becomes, the more the public focuses on the vaccine’s adverse events which can lead to decreased acceptance of the vaccine.

In the 1970s, 36 children in the UK suffered severe neurological damage following immunisation with a combined vaccine for diphtheria, tetanus and whooping cough. The whooping cough portion of the triple vaccine used inactivated whole cells and it was found this could result in an excessive immunological response, which was associated with the reported adverse events. However, the risks were very low – serious neurological illness was rare (0 to 10.5 per million vaccinations) and the risk of permanent brain damage even lower. But as a result, whooping cough vaccination rates reduced from 77% to 33%, and as low as 9% in some areas. Consequently, there were 3 major epidemics of whooping cough, 200,000 additional cases where at least 100 children died. In response, an acellular version of the vaccine (using cellular material rather than whole cells) was developed in the 1980s and is now used in combined childhood vaccinations.

Number of worldwide vaccine preventable disease cases 2008-2017, Council on Foreign Relations

A more recent controversy surrounded the combined measles, mumps and rubella (MMR) vaccine. In 1998, the Lancet published (although later retracted) a now widely discredited and “fatally flawed” paper by Andrew Wakefield. The paper studied 12 children and claimed to have found a causal link between the MMR vaccine and autism. However, Wakefield had employed dubious research methods and had undeclared conflicts of interest. He received over £400,000 to try and disprove vaccine safety and had also filed a patent relating to treatments for bowel conditions (which that vaccine apparently caused). Following skewed media coverage, public mistrust increased which led to a 10% fall in vaccine uptake rates and a sharp rise in cases of measles. While numerous studies have shown the MMR vaccine does not increase the risk of autism (the largest of which was over 95,000 children), vaccination rates have yet to recover to pre-scare levels.

Childhood vaccination programmes differ from country to country depending on government policy. For example, the chickenpox vaccine is part of the immunisation schedule in the USA, Japan and Germany but not in the UK. The NHS is concerned that vaccinating children against chickenpox could increase the risk of chickenpox and shingles in adults. Chickenpox is more severe in adults with risks of severe infection and secondary complication with increasing age. Additionally, if you have chickenpox as a child, further exposure to the disease as an adult boosts your immunity to shingles. However, there is unease that the chickenpox vaccine is not included in the programme due to public mistrust linked to the MMR scandal. Perhaps the MMR battle needs to be fought and won before the chickenpox vaccine is included in the vaccination programme?

The vaccination scares which have occurred tend to reflect political and social concerns rather than critical appraisal of the real risks.

The vaccination scares which have occurred tend to reflect political and social concerns rather than critical appraisal of the real risks. Celebrities and newspapers have used vaccines to peddle their own attacks on governments and pharmaceutical companies. The public often follows medical advice given by celebrities, who can use their influence for good. However, in recent years the media has given inappropriate level of coverage to celebrity opinion of public health matters; and social media allows celebrities to directly communicate to their thousands or millions of followers. Worryingly, the public appears to mistake celebrity status for medical authority, and this extends to the anti-vaccination movement. In February 2017, the New York Times published an article⁹ suggesting that the “anti-vaccination movement was gaining ascendancy in the US”. There is genuine concern that the high number of non-medical exceptions for school vaccinations will result in the loss of herd immunity, consequently outbreaks of diseases like measles are inevitable.

Conclusion

Medicine has advanced beyond all recognition in the 220 years since Jenner inoculated a little boy with pus from a cowpox lesion. The impact of vaccines on human health rivals any of the advances of modern medicine, from antibiotics through to genetics, biologic therapies and tissue engineering.

Vaccines allow science to turn the malevolent face of nature against itself. Pathogens that previously caused untold death and disease have now virtually disappeared from living memory in developed countries. Vaccination programmes are a true public health triumph, saving many millions of lives.

Significant progress in vaccine development is now being made for many diseases previously thought to be incurable, such as HIV, ebola and malaria. However the challenges are not simply scientific. We also face ongoing challenges in education, communication and compliance. As we have seen, when immunisation rates drop, we can quickly find ourselves battling against diseases we thought had been consigned to history.