Measles Vaccination and Infection: Questions and Misconceptions
Measles is experiencing a historic resurgence in the United States, largely as a result of declining vaccination rates in certain regions of the country. Measles epidemics are nothing new: the measles virus, also known as rubeola, has been plaguing humankind for centuries. The current outbreak, however, is different from those that occurred regularly in the pre-vaccine area, because it is taking place within a highly vaccinated population. This results in potential confusion for the public and in complications for physicians, epidemiologists and clinical microbiology labs working to identify infected patients and to track and control the outbreak. In a recent post, we discussed the laboratory diagnosis of measles in the post-elimination era; here we will explore some common sources of confusion and misconceptions about the current measles outbreak in the U.S. and similar epidemics in populations where most people have been vaccinated.
Can You Get Measles if You've been Vaccinated?
It is possible to get measles after being vaccinated, but it's extremely rare.
The measles vaccine (which in the U.S. is always given as part of the combined measles-mumps-rubella (MMR) vaccine) is highly effective, with the standard 2-dose schedule providing protective immunity to approximately 99% of individuals who receive it. Routine vaccination of children, with doses usually given at 12 months and 4 years of age, ultimately resulted in successful elimination of measles in the U.S in the year 2000.
Elimination, however, is not the same as eradication: elimination is defined as zero incidence of a disease in a defined geographical area, whereas eradication refers to zero incidence of the disease worldwide (measles possesses qualities that make it a candidate for eradication: an effective vaccine is available, the clinical syndrome it causes is readily recognizable and no non-human reservoirs exist). At present, measles is still highly prevalent throughout the world, with an estimated annual 7 million cases and more than 100,000 deaths worldwide. As a result, the ~1% of people who fail to develop protective immunity after receiving 2 MMR vaccines can contract measles if they travel to areas where the disease remains endemic or have contact with an infected person from a measles-endemic area.
Why Do Some People Who Receive the Measles Vaccine Get Measles During Outbreaks?
There are 2 types of vaccine failure that can make people susceptible to infection after vaccination, and both are extremely rare events:
- Primary vaccine failure. About 1 of every 100 vaccinated individuals do not develop a protective antibody response after receiving 2 measles vaccinations; these people are said to have primary vaccine failure. When measles vaccination was introduced in 1963, it was given as a single dose, but elimination was only achieved after a second dose was added to the schedule in 1989 to reduce the number of people with primary vaccine failure.
- Secondary vaccine failure. Secondary vaccine failure occurs when the antibody response to vaccination fades over time. Secondary vaccine failure appears to be even rarer than primary vaccine failure and in most people measles vaccination appears to confer life-long protection.
In an elimination setting, people with primary or secondary vaccine failure (as well as other people vulnerable to measles, including children too young to be vaccinated and certain immunocompromised individuals) are extremely unlikely to acquire measles, simply because they aren't exposed to it. The presence of more measles-infected people, however, increases the risk of an infected person contacting someone with primary or secondary vaccine failure. Now that rates of immunization are falling and the U.S. is at risk of losing elimination status, individuals who are not immune to measles are ever more likely to encounter people infected with measles and thus to become infected themselves.
The distribution of cases in the United States' ongoing measles outbreaks (Figure 1) provides a good example of how measles epidemics affect people with different vaccination statuses. Of the 704 cases reported between January 1 and April 29, 2019, the majority (71%) occurred in unvaccinated individuals, while 11% of infected people had received at least one dose of MMR vaccine; the vaccination status of 18% of the cases was unknown (Figure 2). When you consider that fewer than 10% of children in the U.S. overall are not vaccinated against measles, the fact that at least 71% of cases occurred in unvaccinated individuals gives a sense of how much more vulnerable this population is to infection with measles, which is one of the most contagious infections known – as many as 90% of non-immune people exposed to a person with measles will become infected!
The number of vaccinated individuals (or adults born before 1957, who nearly all acquired immunity from natural infection in the pre-vaccine area) is so much larger than that of unvaccinated people that there will inevitably be far more of them exposed to measles. As a result, even if only a tiny fraction of vaccinated individuals become infected, this will still account for a substantial number of cases.
Can You Get Measles from the Measles Vaccine?
Unless you are significantly immunocompromised (in which case you should generally not receive the vaccine), the answer is no.
The measles vaccine is a live attenuated virus vaccine, which means that it contains live but significantly weakened (“attenuated”) measles virus. Replication of the attenuated virus in immune cells is essential to develop an effective immune response. The beauty of vaccination with a live vaccine is this “play-acting” of natural infection, in which a safe, limited version of infection induces a full, robust and lasting immune response, which is essentially equivalent to the immune response induced by natural infection. Some children do develop a fever and mild rash 5-12 days after measles vaccination; these symptoms, which usually last for only 1-2 days, are believed to result from replication of the attenuated virus as the immune response develops. Although these symptoms resemble a very mild version of some of the symptoms of measles, it's important to remember that these symptoms do not represent a case of measles. Here are a few essential ways in which vaccine-associated symptoms differ from actual measles:
|Measles infection||Measles vaccine-associated symptoms|
|Symptoms||High fever, rash, cough, nasal congestion and conjunctivitis that may last a week or more||Mild and short-lived fever and rash|
|Transmission||Extraordinarily contagious||Cannot be spread from person to person|
|Complications||Include pneumonia and ear infections as well as encephalitis and a fatal, untreatable late-onset condition (subacute sclerosing panencephalopathy, SSPE)||Not associated with these types of complications|
|Mortality||Killed an average of 400-500 people in the U.S. and 2.6 million worldwide every year in the pre-vaccine era, and remains a major cause of death in the developing world||No confirmed deaths from measles vaccination except rare cases in severely immunocompromised individuals (in whom vaccination is not recommended)|
Severely immunocompromised people can acquire measles from vaccination; for this reason measles vaccination (and vaccination with other live vaccines) is generally not recommended in people with immunocompromising conditions. This is another reason why it is so important to vaccinate everyone who can safely receive the vaccine: people who cannot be vaccinated depend on the herd immunity conferred by consistent high rates of vaccination in the community for protection. Another group that relies on herd immunity is children who are too young to be vaccinated. In the U.S., the first dose of MMR vaccine is routinely given at 12 months of age, but an additional dose can be given as early as 6 months if deemed appropriate by a pediatrician, typically during an outbreak setting or prior to international travel.
What Does it Mean When Vaccine-Strain Measles is Identified from a Patient?
Vaccine-strain measles virus can be recovered from a nasopharyngeal (i.e. deep nose) swab from a person who has recently received the MMR vaccine, but this does not mean that this person has measles.
When there is no measles circulating in the community, a recently vaccinated child who develops fever and rash can generally be assumed to be experiencing either a vaccine response or one of the many common and usually self-limited childhood viral infections that cause similar symptoms, which the child may have coincidentally contracted around the time of vaccination. In either case, it isn't usually necessary to figure out the cause of the symptoms, as no specific treatments or interventions are needed. However, when measles is present in the community, a post-measles rash could actually represent a true measles infection acquired either shortly before or just after vaccination (that is, before vaccine-induced immunity has had time to develop). This might seem like an unlikely coincidence, but it can happen in the setting of an outbreak in a community with low vaccination rates when parents decide to get their previously unimmunized children up to date on measles vaccination after seeing the disease affect other children.
Determining whether a fever and rash are due to vaccine-associated symptoms or wild-type measles is extremely important from a public health perspective. Measles cases are tracked closely by epidemiologists and other public health officials. Children with measles must be kept isolated from others, and people they have been in contact with require additional isolation and post-exposure prophylaxis if they are not immune to measles. As discussed above, because the measles vaccine is a live virus vaccine, the attenuated vaccine strain does replicate within a subset of immune cells after vaccination, and as a result it can be detected in nasopharyngeal samples, just like wild-type measles. Again, though, it is important to note that vaccine-strain measles is not transmitted from person-to-person and does not cause the complications that frequently result from wild-type measles infection. Real-time PCR-based techniques that can rapidly distinguish vaccine-strain measles from wild-type measles can be extremely helpful in quickly identifying infected children in an outbreak setting without needlessly quarantining uninfected children. This type of testing is not routinely available in reference laboratories, however, so physicians who having difficulty distinguishing between vaccine-associated symptoms and wild type measles infection should contact their local public health department for information on testing options.
Vaccination is an incredibly effective tool in the prevention of infectious diseases and infection-related deaths, and it confers numerous additional economic and social benefits. The capacity of vaccines to induce highly specific, effective, and long-lasting responses from the immune system without the dangers of infection is astounding, but confusion and misunderstanding among the public about the way vaccines work can have profound implications for vaccine uptake and disease control and elimination. The immune response to live vaccines like MMR is complex, but the bottom line is simple: these vaccines are safe, they are effective, and they have saved—and continue to save—countless lives.