Vaccination Exploration: The Case of Measles, Mumps and Rubella
Getting sick with these childhood diseases could mean much more than a fever and a rash.
A brief history of vaccination
Infectious diseases have existed alongside (and within) humans throughout history. Efforts to prevent contagion have been attempted since before the discovery of our immune system and the pathogens that try to invade it.
The practice of immunization is based on the idea of exposing the body to a weakened or dead infectious agent (or part of it) to induce a mild version of the disease that the host is able to fight off, remaining protected at the next encounter.
Variolation—injecting material from a smallpox patient’s sore into a healthy person’s arm to protect against smallpox—was common practice starting in the 17th century in China, the Middle East and Africa, and well before Edward Jenner created the first modern vaccine in 1798.
Jenner observed that milkmaids who had been infected with vaccinia virus (the cause of cowpox in cows) did not get sick with smallpox. He was able to achieve immunization against smallpox by inoculating people with the vaccinia virus—hence the terms “vaccination” and “vaccine.”
This first empiric vaccine laid the foundation for the development of many other vaccines over the course of the 19th century. Scientists fine-tuned the technology to make vaccines safer and more effective. In the 20th century, isolation of many infectious agents together with progress in immunology, cell culture and molecular biology, allowed for the advent of more vaccines that have saved millions of lives and changed the course of human history.
Spotlight on the mumps, measles and rubella vaccine (MMR)
The Wistar Institute developed the rubella vaccine that is currently given to children in the U.S. and many other countries as part of the MMR trivalent vaccine, which provides protection against mumps, measles and rubella.
Licensed by Merck in 1971, this vaccine combined the three existing vaccines into one and dramatically curbed three childhood infections that affected millions in the pre-vaccine era and were associated with severe complications and death. The Wistar rubella vaccine is also contained in the MMRV vaccine ProQuad licensed by Merck and approved in the U.S. in 2005, which also protects against varicella virus (chickenpox).
Measles is a highly contagious disease that causes fever, respiratory symptoms and a rash. In a small percentage of cases, it can result in serious complications and death, especially in young children, pregnant women and immunocompromised individuals. Complications include pneumonia, which is the most common cause of death from measles in young children and occurs in one out of every 20 infected children; encephalitis, or swelling of the brain, that can lead to convulsions, deafness or intellectual disability and affects one child out of every 1,000 infected; and premature or low-birth-weight babies in pregnant women.
The rubeola virus that causes the measles was isolated in 1954, after which several generations of vaccines were developed. In 1968, the final (and current) version of the attenuated vaccine was created and since then has contributed to measles cases plummeting in the U.S. In 2000, endemic measles was declared eliminated. Yet in recent years measles has returned with several outbreaks happening in the U.S. and beyond, linked to falling immunization rates in certain groups.
Mumps is a very contagious viral infection that manifests with swelling and pain in the salivary glands, fever, headache, muscle aches, and fatigue. In the vast majority of cases mumps causes very mild symptoms, but in rare cases it can lead to serious complications. These include meningitis, an inflammation of the brain and spinal cord membranes; hearing loss; encephalitis; and orchitis, or the inflammation of testicles, which occurs in one third of boys infected with mumps.
In 1963, the mumps virus was isolated, and a vaccine was licensed in 1967 that has contributed to a more than 99% decrease in mumps cases in the U.S.
Rubella, or German measles, usually manifests with mild symptoms and a red rash but is associated with severe complications in pregnant women, known as congenital rubella syndrome (CRS). CRS can cause miscarriage, stillbirth and birth defects such as heart problems, loss of hearing and eyesight and intellectual disability.
In 1964, a major rubella outbreak started in Europe, crossed the Atlantic Ocean and swept into the U.S., infecting 12.5 million, killing 2,000, causing 20,000 cases of CRS, and leading to thousands of miscarriages and children born with birth defects.
The first rubella vaccines used in the U.S. were licensed in 1969/1970. At the same time, another vaccine developed at Wistar in the laboratory of Stanley A. Plotkin, M.D., was licensed in Europe. The Wistar-developed vaccine proved to be more effective and have a better safety record than the others, leading the U.S. to switch in 1979. Plotkin’s vaccine is still used today and is the only rubella vaccine currently licensed in U.S.
With critical support from the Bill & Melinda Gates Foundation, Wistar is now working with external collaborators to expand and archive the research-grade rubella virus seed stock in order to provide companies with GMP materials to produce new vaccines, increasing distribution around the world and bolstering supply security.
The MMR vaccine is very effective against measles: two doses are about 97% effective while one dose is about 93% effective. Yet, measles has been on the rise globally, leading to a public health alert. The World Health Organization reported that there were more cases of measles in the first half of 2019 than in any year since 2006. In the first half of 2019 in the U.S. alone, there have been 1,182 measles cases across 30 states—a high in the last 25 years.
There are many reasons for this resurgence. Because measles is highly contagious, it is estimated that 95% of people need to be vaccinated in order to protect the population from outbreaks—a concept called herd immunity. Current U.S. vaccination rates are holding around 91% and more children in Europe are being vaccinated than ever before, but these rates are still under the required threshold, therefore the population is still vulnerable to outbreaks.
Vaccination rates and measles outbreaks
But why is the measles resurgence happening now if the vaccination coverage has been stable or improved in recent years? This could be partly due to the nature of highly contagious diseases that tend to spread in wave-like cyclic patterns.
On the other hand, statistical and epidemiological analysis indicate a correlation between a decrease in vaccination coverage and measles outbreaks. In fact, several outbreaks have been reported in close-knit communities with particularly low vaccination rates due to vaccine skepticism or refusal for religious or philosophical reasons. In those cases, travelers brought measles back from other regions where large outbreaks were occurring, and infection spread fast among unvaccinated people.
Healthcare inequality also puts children in medically underserved families at higher risk of infection.
Therefore, while measles has a tendency to resurge in populations with a lower than 95% vaccine coverage, pockets where vaccination rates are lower than the nation’s average offer breeding ground for the virus to spread undisturbed.
Rigorous studies have confirmed that the MMR vaccine is very safe and overwhelmingly debunked reports of any association with autism in children.
As with all medicines, vaccines may have side effects. The MMR vaccine has been associated with mild and temporary side effects including rash, fever and headache. More serious adverse events, including seizures, are very rare and not associated with long-term effects. Allergic reactions are also rare. The risk to benefit ratio is such that getting the MMR vaccine is much safer than getting measles, mumps or rubella.