The Cause of the Measles Outbreak: It’s Not Vaccine Failure—It’s a Failure to Vaccinate
In the pre-vaccine era, virtually every child developed measles. The U.S. birth rate in the immediate pre-vaccine era was more than 4 million per year, so on average, more than 10,000 new cases of measles occurred every day.
Since that time, the widespread availability and use of the measles vaccine in the United States has been immensely successful and has resulted in a greater than 99% reduction in reported measles cases compared with the pre-vaccine era.
In 2000, measles was declared as having been “eliminated” from the United States, which is defined as the absence of continuous disease transmission for at least 12 months.1
Measles is no longer endemic in this country. In 2004, only 37 measles cases were reported here, and in the past decade most cases either have originated outside of the United States or have been linked to a case originating outside this country.
Against this backdrop, then, it may have come as a bit of a surprise that measles has been very much in the news recently. Nevertheless, measles is still common around the world—an estimated 20 million cases worldwide lead to more than 100,000 measles-related deaths each year—and the threat of measles importation remains great. In 2014, 644 U.S. measles cases were reported, the highest number in 20 years. Many of these cases were linked to travelers who had contracted measles in the Philippines, the site of a large outbreak with more than 50,000 reported cases.2
The U.S. measles situation seems to be intensifying: From January 1 to February 20, 2015, 154 people from 17 states and Washington, DC, were reported as having contracted measles, and the case count has risen every week since.3 The great majority of these cases are part of an ongoing outbreak that began in late December 2014 and has been linked to an amusement park in California. Specimens from many of the patients contracting measles during this outbreak have shown measles genotype B3, which has caused many cases of illness in the Philippines and elsewhere over the past 6 months. The Centers for Disease Control and Prevention (CDC) is working with state and local health departments to control this outbreak, but measles is extremely contagious, making control measures difficult and costly.
Is the Measles Vaccine Working?
Perhaps naturally, a resurgence of measles can provoke questions about whether the vaccine somehow has been failing. Indeed, some of the recent U.S. measles cases have occurred in children who previously had been vaccinated. For example, in the most recent multistate outbreak that began in California, among persons whose vaccination history had been documented, most measles cases (82%) occurred among those who had not been vaccinated, but several (18%) occurred in those who had been vaccinated.3
At first glance, this information may worry parents that the measles vaccine is not effective, and it may deter some parents from having their children vaccinated. However, such cases among vaccinated persons are not unexpected and are not evidence that the vaccine is not working well.
The causes of vaccine failure are divided into 2 categories: primary failure resulting from a lack of initial seroconversion, and secondary failure resulting from a loss of immunity after initial seroconversion.4
When the measles vaccine is administered after 12 months of age, primary failure is unusual but can occur in up to 5% of children who receive a single dose of the vaccine. The causes of primary failure might include inactive vaccine (such as could occur if the vaccine has not been stored and handled appropriately) and inadequate host response (such as could occur if an infant is vaccinated before 12 months of age, and transplacentally acquired maternal antibodies to measles interfere with viral replication and the normal vaccine “take”).
Because measles is highly contagious and has the potential to spread even in highly vaccinated groups, a second dose of the measles vaccine has been recommended at age 4 to 6 years. This second dose of vaccine really is not a “booster,” but it should result in seroconversion for most of the children who had failed to respond to the first dose.
Primary failure after 2 doses of measles vaccine is very unusual, but it may occur in as many as 1% of vaccinated persons. Immunity after measles illness typically is lifelong. Similarly, secondary failures following administration of the measles vaccine are very uncommon.
An infant with measles in Manila, the Philippines, in early 2014 during a widespread measles outbreak in that country.
Why Some Vaccinated Children Get Measles
Since the rate of seroconversion after receiving the measles vaccine is not 100%, even after 2 doses, it can be expected that some who are vaccinated will remain susceptible to measles, and that some cases of measles will occur among children who have been vaccinated.
In order to demonstrate more precisely how often this might happen, we created a hypothetical cohort of 18,000 children from birth to 18 years of age, with 1,000 children in each year of age. Using data from the CDC’s 2013 National Immunization Survey5 and from CDC data about children entering kindergarten,6 we estimated the percentage of children in each birth year having received 1 or 2 doses of the measles vaccine. For example, the estimated rates of having received 1 dose of measles vaccine are 55% at age 13 months, 87% at age 19 months, and 90% at age 24 months.
For the first 2 years of life, we estimated the susceptibility and vaccination rates for our hypothetical cohort in half-year increments. In the first 5 months of life, we estimated that all of the infants were protected by maternal antibodies and therefore were immune to measles. From 6 to 11 months, maternal antibodies wane, so we estimated that only 25% of infants still were protected but that the remainder had become susceptible, having not yet received the measles vaccine.
We estimated the vaccination rate for the first dose of the measles, mumps, and rubella (MMR) vaccine from age 12 to 17 months to be 71% (55% + 87%/2) and from age 18 to 23 months to be 89% (87% + 90%/2). From age 2 to 3 years and from age 3 to 4 years, our estimated first-dose vaccination rates were 93% and 94%, respectively. From age 4 to 5 years, we again divided the year in half and assumed that during the first half of this year, 47% of the population would have received 1 dose of vaccine and 47% would have received 2 doses. During the second half of the year, the rate for having received 2 doses increased to 75%, and the rate for having received 1 dose decreased to 22%.
For the 2011-2012 school year, 95% of 5-year-olds entering kindergarten in the United States had received 2 doses of the MMR vaccine.6 For the remaining children aged 5 to 18 years, our 2-dose vaccination rate remained constant at 95%, with a 1-dose rate of 2%, and 3% of children unvaccinated. We assumed a 95% rate of seroconversion after the first vaccine dose and a 99% rate of seroconversion after 2 doses. We assumed that the vaccine-induced protection lasted throughout the 18 years with no secondary vaccine failures.
For each half-year and 1-year increment, we calculated the number (and percentage) of children in 2 groups: those who are immune to measles and those who are susceptible. The immune group includes children younger than 1 year old who are protected by transplacentally acquired maternal antibodies, and includes children at least 1 year old who are immune because of having received 1 or 2 doses of measles vaccine. The susceptible group includes children who have not been vaccinated and those who remain susceptible despite having been vaccinated.
U.S. immunization rates are generally high, so the overall rate of immunity to measles in our hypothetical cohort was correspondingly high (16,559 of 18,000, or 92%). Presumably, this is why relatively few cases of measles now occur in this county. On the other hand, 1,441 children, or 8% of the cohort, remained susceptible to measles. Of these 1,441 children, the great majority (1,155, or 80%) had not been vaccinated. Of the unvaccinated children, 375 (32%) were too young to have received the vaccine, but 780 (68%) were old enough and simply had not been vaccinated. The rest of the susceptible children (286, or 20%) had received the vaccine but were nonresponders and therefore had remained susceptible to the virus. This last group represents 1.6% of the population.
If we assume that exposures to measles occur randomly among the population, and we make no allowance for the localized pockets of unimmunized children in various communities, then approximately 20% of measles cases would be expected to have occurred in children who had been vaccinated. This rate is, in fact, very similar to the rate that has been observed in the recent outbreak beginning in California.
Key Findings
Here are the 2 primary take-home messages about measles from this exercise:
First, the overall rate of immunity to measles in this hypothetical cohort is more than 90%. This explains why so relatively few cases of measles now occur in the United States. Measles is highly contagious, but the measles vaccine is highly efficacious. The elimination of endemic measles in this country by means of widespread vaccination has been a remarkable public health accomplishment.
Second, because the vaccine does not protect 100% of children who are vaccinated, some cases of measles will occur among children who have been vaccinated, even with high rates of immunization coverage. The vaccine might be considered to have “failed” these very few children, but this in no way detracts from the high level of protection that the vaccine provides to the great majority of those who receive it. The great majority of children in our cohort who are susceptible to measles are the children who have not been vaccinated.
In short, the primary cause of the current measles outbreak is not vaccine failure, it is failure to vaccinate.
Amy L. Wrentmore, MD, and Gregory F. Hayden, MD, are in the Division of General Pediatrics, Department of Pediatrics, at the University of Virginia School of Medicine in Charlottesville, Virginia.
References
1. Centers for Disease Control and Prevention (CDC). Measles – United States, 2011. MMWR Morb Mortal Wkly Rep. 2012 Apr 20;61(15):253-257.
2. Centers for Disease Control and Prevention (CDC). Measles cases in the United States reach 20-year high [press release]. May 29, 2014.
http://www.cdc.gov/media/releases/2014/p0529-measles.html. Accessed March 4, 2015.
3. Centers for Disease Control and Prevention (CDC). Measles cases and outbreaks. http://www.cdc.gov/measles/cases-outbreaks.html. Updated March 2, 2015. Accessed March 4, 2015.
4. Hayden GF. Measles vaccine failure: a survey of causes and means of prevention. Clin Pediatr (Phila). 1979;18(3):155-167.
5. Centers for Disease Control and Prevention (CDC). National Immunization Survey (NIS) - children (19-35 months): U.S. vaccination coverage reported via NIS. http://www.cdc.gov/vaccines/imz-managers/coverage/nis/child/. Updated September 2, 2014. Accessed March 4, 2015.
6. Centers for Disease Control and Prevention (CDC). Vaccination coverage among children in kindergarten — United States, 2011-12 school year. MMWR Morb Mortal Wkly Rep. 2012;61(33):647-652.
Acknowledgement
The authors thank Paul A. Gastanaduy, MD, at the Centers for Disease Control and Prevention in Atlanta, Georgia, who reviewed this manuscript and made several helpful suggestions.