Our last posting, Andrew Wakefield and the Measles Vaccine Controversy (February 9, 2015), discussed how the British journal, The Lancet, published a study by former British surgeon, Andrew Wakefield, which claimed to find a link between autism and the trivalent measles, mumps, and rubella (MMR) vaccine. Despite Wakefield’s paper being totally discredited and, consequently, being retracted by the The Lancet, as well as by ten of Wakefield’s twelve coauthors, Wakefield has stood by his claims, and is regarded as a hero by large segments of the American and British publics. What’s more, the increase in vaccine noncompliance resulting from Wakefield’s paper largely underlies the current measles outbreak in the United States (1).
Thus far, virtually all of the coverage in the media concerning Wakefield’s paper and vaccine noncompliance has been with regard to measles. But the trivalent MMR vaccine also protects against two additional well known and potentially serious viral diseases; mumps and rubella. Here are some key facts about these other two illnesses.
In pre-vaccine days, mumps was most commonly a non-life-threatening childhood infection, characterized by a painful swelling of the salivary glands and fever. Yet children still suffered from rare, but severe complications, including deafness and permanently disabling or even fatal encephalitis.
Mumps occurred mainly in children in those pre-vaccine days because mumps, like measles, is highly contagious. Consequently, an individual was unlikely to pass through childhood without having been infected.
Non-compliant parents should now be aware that one upshot of mumps vaccination regimens is that if their unvaccinated children were to be infected, it would very likely be in adolescence or adulthood. Importantly, the risk of serious mumps complications is far higher in adolescents and adults than in young children. For instance, a particularly painful orchitis (inflammation of the testis) is rare in prepubescent boys with mumps, but it occurs in more than a third of cases involving adolescents and adult men, in whom it can lead to atrophy of the affected testicle. Other glands that may be affected by mumps include the pancreas (often), ovaries, thyroid, and breast.
The introduction of a mumps vaccine in the United States in 1968 reduced the number of reported mumps cases from over 150,000 per year (there were many more unreported cases) to a few hundred cases per year. However, mumps outbreaks still occurred in the U.S., most recently in 2011-2013, when several small mumps outbreaks happened on college campuses in California, Virginia, and Maryland. A series of outbreaks also occurred in the United States in 2005-2006.
To appreciate why mumps outbreaks still occur, even in highly vaccinated populations, and why vaccine noncompliance can facilitate those outbreaks, consider the following points. First, although the mumps vaccine is highly effective, it does not prevent infection in 100% of vaccine recipients. Instead, it is estimated to protect 80% to 90% of vaccinated individuals.
Second, we need to consider again the concept of herd immunity; the immunity in the whole population that results when a sufficient percentage of individuals in the population has been vaccinated. When herd immunity is attained, there are not enough susceptible individuals in the population to sustain the chain of transmission.
What then is the percentage of individuals in a population that needs to be immune to attain herd immunity; the herd immunity threshold. It varies from one pathogen to another, depending on the virulence of the disease, the efficacy of the vaccine, and the infectiousness of the pathogen. For mumps, the herd immunity threshold is estimated to be 75%-86%. Consequently, the 10% to 20% of people who received the MMR vaccine, but who are still susceptible to mumps, may leave enough wiggle room for occasional outbreaks to still happen. Additionally, and importantly, unvaccinated individuals in the population can account for a sufficient enough discrepancy between the percentage of immune individuals in the population and the herd immunity threshold to enable outbreaks to occur. And, it is an indisputable fact that when outbreaks do occur, the vast majority of clinical cases involve unvaccinated individuals.
Particular circumstances may also facilitate an outbreak. For example, the close-contact settings of college campuses may have enabled the 2011-2013 incidents to happen. And, since routine vaccination against mumps only began in 1977, more than one-third of the mumps cases reported between1985 and 1987 occurred in adolescents, who, as a group, were inadequately vaccinated during the 1070s. And, since some of those individuals, and the ones affected in the 2011-2013 outbreaks, were post-pubescent, they were more prone to developing more serious mumps complications. Another point to note about mumps before moving on is that an individual infected with mumps can unknowingly transmit the virus for several days before the emergence of symptoms.
Rubella, also known as German measles, makes for a different, and perhaps more compelling state of affairs. Rubella, like measles and mumps, was generally known as a mild childhood illness, with most rubella cases occurring in children between 5 to 9 years of age. Clinical cases were characterized by a rash and swollen glands. However, about half of all serologically confirmed childhood rubella infections were subclinical, and many adults were unsure of whether or not they ever had that illness.
The reason most rubella infections occurred in children is because rubella, like measles and mumps, is so highly contagious. And, since rubella epidemics occurred every few years in pre-vaccine days, over 80% of individuals were immune to the virus by the time they reached adulthood.
As in the case of mumps, the advent of vaccination against rubella in 1969 brought about a change in the age distribution of rubella cases, such that outbreaks now mostly affect adolescents and young adults. Importantly, the vast majority of these cases occur in unvaccinated individuals, validating that reappearances of rubella are mainly due to vaccine noncompliance, rather than to vaccine failure.
But, since rubella is usually such an innocuous illness, why is vaccination against rubella needed at all? The key reason is that rubella poses an especially severe danger to the fetus of a susceptible pregnant woman. That is so because the rubella virus is one of only a handful of viruses able to cross the human placenta (2). Consequently, a susceptible woman, who is infected during pregnancy, runs a substantial risk that her baby will be infected in utero and, as a result, be born with severe rubella-associated birth defects (congenital rubella syndrome), which include deafness, blindness, heart disease, mental retardation, and impaired growth. One study reported that 85% of all infants born to unvaccinated women, who were infected during the first eight weeks of pregnancy, had congenital rubella syndrome! [The risks to the fetus go up dramatically if the mother is infected during the first or last trimesters of pregnancy.] Rubella infection during pregnancy can also cause a premature delivery or a still birth.
Babies born with congenital rubella syndrome are also a potential source for further rubella transmission since they shed substantial amounts of rubella virus for several months after birth. What’s more, these babies pose a particular threat to pregnant woman, either directly, or via infecting staff members in maternity wards, prenatal clinics, or doctors’ offices.
Unvaccinated women, who are already pregnant, are advised against receiving the rubella vaccine because there is a slight (1.6%) theoretical chance that the live vaccine might cause congenital rubella syndrome. Thus, any unvaccinated woman planning to become pregnant is very strongly urged to be vaccinated before conceiving. She then needs to wait at least four weeks for the vaccine to take. If a woman is not sure of her immune status, a blood test for anti-rubella antibodies can tell her whether or not she is already immune. [Accurate information on all aspects of rubella and the rubella vaccine can be found at the U.S. Centers for Disease Control website.]
Some pregnant women, for one reason or another, will remain unvaccinated. Also, since the clinical efficacy of the rubella vaccine is about 90%, an additional small percentage of women who have been vaccinated are nonetheless susceptible to rubella. However, virtually all susceptible women, and their babies, can yet be protected if enough parents comply with vaccine regimens and have their children vaccinated on schedule.
No vaccine is 100% effective. Nonetheless, the case for vaccination against rubella is compelling. Before the introduction of rubella vaccination in 1969, rubella-associated birth defects were strikingly common. Indeed, a world-wide rubella epidemic from 1964 to 1965 resulted in approximately 12.5 million rubella cases in the United States alone, including 20,000 infants who were born here with congenital rubella syndrome!
The 1964 rubella outbreak was the last such one to occur in the United States. Now, approximately 10 cases of rubella are reported each year, and congenital rubella syndrome is very rare.
The remaining few cases of rubella that still occur in the United States usually originate from infected individuals visiting from regions of the world where rubella is still endemic, or from unvaccinated U.S. residents who traveled to one of those regions and then unknowingly brought the disease back home. Importantly, rubella cases in the U.S. almost always occur in unvaccinated individuals.
A few other points to note: First, recalling that more than half of all rubella infections are clinically unapparent, individuals with asymptomatic infections nevertheless are infectious and can transmit the disease to others. What’s more, infected individuals, who will develop clinical disease, can unknowingly transmit the infection for seven days before the onset of their symptoms. [The incubation period between the time of infection and the onset of symptoms is usually 16 to 18 days.] Second, susceptible children are the major source of rubella infection. That is so because they are readily exposed to the virus in the crowded conditions existing in schools and day care centers. Third, for reasons just noted, children are the major targets for vaccination against rubella. Fourth, the herd immunity threshold for rubella is 83-85%.
Bearing in mind the crucial principle of herd immunity, and that newborns, and some children (e.g. those receiving chemotherapy or who have certain immune disorders), and pregnant women as well, cannot receive the MMR vaccine, one might presume, rightly perhaps, that receiving the vaccine is to some extent altruistic. Yet the trivalent MMR vaccine does directly protect the vaccine recipient from measles and mumps, both of which are potentially serious viral illnesses.
The MMR vaccine also protects against, rubella. But, since a major concern in that instance is to prevent infection of susceptible pregnant women, immunization against rubella may appear somewhat more altruistic. Still, vaccinated young females will be protected later in life, when they might be expectant mothers themselves. And, vaccinated young boys, as well as girls, may have the knowledge one day that they were not the cause of someone else’s tragedy. Moreover, the public at large pays the price for vaccine noncompliance, as previously eradicated diseases make their way back into the population.
In The Selfish Gene, Richard Dawkins invents a model population of birds to help explain the evolution of altruistic behaviors. Dawkins’ views in The Selfish Gene are somewhat controversial. Nonetheless, his bird model reminds me of the principle of herd immunity, and the case for human compliance with vaccine regimens. The birds are endangered by a deadly disease spread by ticks. They try cope with their situation by grooming themselves to remove their ticks. However, there is one spot they cannot reach—the tops of their heads. Evolution solves their dilemma by selecting for a behavior in which the birds work together to remove each others ticks. Importantly, some critical percentage of the birds must express this altruistic adaptation if it is to be effective. If too many of the birds were to “cheat” by having other birds remove their ticks, while not reciprocating, at least some of the population would suffer. And, if there were enough cheaters, the population would be overrun with the disease.
References:
(1) Andrew Wakefield and the Measles Vaccine Controversy, Posted on the blog February 9, 2015.
(2) Norkin, Leonard C., Virology: Molecular Biology and Pathogenesis, ASM Press, 2010. See Chapter 3 for a discussion of the placenta as a barrier to infection of the fetus.
Leonard Norkin Virology Site 