Monthly Archives: February 2015

Andrew Wakefield and the MMR Vaccine Controversy: What about Mumps and Rubella?

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.

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Andrew Wakefield and the Measles Vaccine Controversy

Controversy over the measles vaccine, and the spate of vaccine noncompliance that underlies the current measles outbreak in the United States, stem mostly from a totally debunked 1998 study by former British surgeon, Andrew Wakefield. In Wakefield’s now infamous report, he and co-authors claimed to find a link between the measles vaccine and autism. Here are some essential facts concerning measles, the measles vaccine, and Wakefield’s paper.

We begin with the crucial concept of herd immunity. People who cannot get vaccinated (e.g., young infants, pregnant women, children suffering from leukemia or other immune deficiencies) are nonetheless protected from measles by herd immunity; the immunity in the whole population that results when a high enough 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.

But, if enough parents opt out of having their children vaccinated, then herd immunity is lost, and outbreaks might then occur, as is happening now. Herd immunity against measles requires vaccination rates as high as 95 percent. That is so because measles is one of the most contagious of all viruses. Yet, all too many parents are now opting out of vaccinating their children; in many cases for fear that the measles vaccine might cause autism.

The measles incubation period is another important issue. The elapsed time, between initial infection and onset of illness, averages 10–12 days (rash may not appear until 18 days). Moreover, infected individuals can transmit the virus for several days before becoming ill. These points, together with the exceptionally high rate of measles transmission, mean that keeping sick children home from school or play group, is not an effective means for containing spread of the disease.

Next, consider the severity of measles, which all too many people, including some medical professionals, do not appreciate. [I heard one medical doctor on TV say measles is like the common cold.] Before the introduction of the first measles vaccine in 1963, and the WHO-sponsored global eradication program, death rates from measles ran as high as 7 to 8 million children, worldwide, annually. And, despite the current availability of effective measles vaccines, there still are more than 30 million measles cases per year worldwide, of which more than 1 million are fatal. As you might expect, the vast majority of fatal measles cases occur in unvaccinated populations in the developing world. In fact, in some unprotected groups, measles is the major cause of death in children less than five-years-old. [Reliable information on all aspects of measles can be found on line at “Measles – Centers for Disease Control and Prevention,” http://www.cdc.gov/…/meas.]

The above data unmistakably support the case for vaccination against measles. Ever since the first measles vaccine was introduced in 1963, the incidence of measles has been dramatically reduced in all regions of the world where vaccination programs were put in place. In the United States, the number of measles cases declined from about 500,000 per year before 1963, to no endemic cases whatsoever in 2000!

But, since measles persisted elsewhere in the world, and, since the measles virus is so highly contagious, it returned to the United States in the years between 1989 and 1991, when vaccination rates fell below the critical level needed to maintain herd immunity. In that earlier 1989 outbreak, poor compliance with vaccine programs was, ironically, due to the success of the vaccine program. Because measles was no longer existent in the United States, it was not in the public’s consciousness, resulting in public complacency towards vaccination.

At present, segments of the public are opting out of vaccinating their children largely because of Wakefield’s discredited 1998 paper in The Lancet, which asserted that the trivalent measles, mumps, and rubella (MMR) vaccine might cause autism. Here is the story of how and why Wakefield’s 1998 paper fell into disrepute.

The validity of Wakefield’s 1998 findings first came under question in 2004 when an article in the Sunday Times of London reported that Wakefield had not disclosed a conflict of interest that might have compromised his objectivity. The newspaper revealed that Wakefield accepted £55,000 ($103,000) to support his study, from lawyers representing parents of autistic children. The purpose of the financial support was to validate the parents’ legal claims against the vaccine manufacturer. Astonishingly, some of the families in Wakefield’s study actually were selected by these lawyers. Next, in 2006, the Sunday Times reported that the lawyers had paid Wakefield personally more than £400,000, none of which was ever reported.

The Sunday Times report that exposed Andrew Wakefield
The Sunday Times report that exposed Andrew Wakefield

Irrespective of Wakefield’s conflict of interest, the 1998 study was exceptionally weak on several counts. First, its conclusions were based on a sample size of only twelve children. What’s more (and virtually unbelievably), the association between the vaccine and autism was concluded merely from interviewing the children’s parents; people who were not likely to be the most objective of observers, since at least some were looking for someone or something to blame for their children’s condition.

The credibility of Wakefield’s already weak paper took a major hit when it was revealed in 2009 that he had manipulated patients’ data. Wakefield’s paper claimed that the families of eight of the twelve children attributed their children’s autism to the MMR vaccine and that the children’s problems emerged within days after their vaccinations. The Wakefield paper also reported the discovery of a new inflammatory bowel disease it associated with the vaccine, and it proposed that the new disease also might be connected to autism. However, an investigation by the British Medical Council (BMC) found that in most cases the data in The Lancet was not in accord with the children’s medical records. In only one case was there any suggestion that there was any problem within days of the vaccination. In fact, in many of the cases, the parents expressed concerns about autism before their children’s’ vaccinations. And, a November 2011 paper in the British Medical Journal reported that an investigation of Wakefield’s raw data revealed that none of the twelve children in his study had signs of inflammatory bowel disease.

The BMC’s investigating panel ruled that Wakefield had “failed in his duties as a responsible consultant”, acted both against the interests of his patients, and “dishonestly and irresponsibly” in his published research. What’s more, the British Medical Journal took the extraordinary step of publishing a report in which it concluded that Wakefield’s study was not simply bad science, but a deliberate and elaborate fraud. Shortly afterwards, Wakefield was removed from the United Kingdom’s Medical Register and barred from practicing medicine in the UK.

In a large scale study, involving more than a half million children, the U.S. Institute of Medicine (IOM), a respected independent arbiter, found no evidence whatsoever of any connection between vaccines and autism. Other large and well designed studies likewise found no such connection.

In 2010, The Lancet responded to the above revelations by retracting Wakefield’s 1998 paper. Moreover, ten of Wakefield’s twelve co-authors issued a retraction, which included the following: “We wish to make it clear that in this paper no causal link was established between (the) vaccine and autism, as the data were insufficient. However the possibility of such a link was raised and consequent events have had major implications for public health. In view of this, we consider now is the appropriate time that we should together formally retract the interpretation placed upon these findings in the paper…”

The Lancet retracts Wakefield’s paper
The Lancet retracts Wakefield’s paper

Despite these developments, Wakefield has stood by his claims, and many still regard him as a hero. What’s more, Wakefield’s claims continue to influence many parents, and they are a major reason for the sharp decline in vaccination rates in the United Kingdom and in the United States.

Why might The Lancet have published Wakefield’s 1998 paper in the first place? As explained by Richard Horton, Editor-in-Chief of The Lancet, the journal was interested in the new gastrointestinal disorder described in the paper, rather than in the parents’ testimony regarding a possible link between the MMR vaccine and autism. Horton states: “The central thrust of the paper was this new syndrome. This is not an uncommon kind of report. If you read any text book of epidemiology, the very first description of any new syndrome often comes with either a case report or a case series.” [Note the rather inconspicuous title of Wakefield’s highly flawed but influential paper: “Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children”]

Horton also noted that the journal was well aware that the Wakefield paper might have an adverse public health impact, which it sought to avoid by including in the paper the disclaimer that there was no proof of causation or association between the MMR vaccine and autism, and also by identifying the paper as an “early” report. But the media and the public could hardly be expected to disregard the sensational story behind the disclaimers.

We conclude with a few related items.

Doubts about Wakefield’s scientific credibility might have been raised before he ever turned his attention to the measles vaccine and autism. In 1993 he published reports concluding that the measles virus might cause Crohn’s disease, and two years after that he published a paper (in The Lancet) suggesting a link between the measles vaccine and Crohn’s disease. Neither of these claims could be verified by a number of subsequent peer-reviewed studies.

Some individuals believe that thimerosal (a mercury compound once added to some vaccines as a preservative) is the link between vaccines and autism. Regarding the possibility that thimerosal in the MMR vaccine might be responsible for autism, the MMR vaccine is a live vaccine, and thimerosol was added only to killed vaccines (e.g., the vaccines against diphtheria, whooping cough, and tetanus). What’s more, all routine vaccinations in the United States have been thimerosol-free since 2001.

One might presume that the way to convince vaccine skeptics of the safety of vaccines, and of their importance for the good of all, is for public health experts and medical practitioners to confront the deniers with the data and the facts. Yet the result of those efforts is usually quite the opposite of what is intended. When confronted with the facts, the deniers dig their heels in even deeper to hold on to their anti-vaccine position. And, we scientists don’t reassure the public by always qualifying our pronouncements with statements such as “to the best of our knowledge” or “as far as we know.” [I am by no means suggesting that we ought to abandon our inclination to not speak in absolutes.]

The state of affairs was not helped when some 2016 presidential aspirants (one of whom is a medical doctor) not only equivocated over the pubic health aspects of the vaccine controversy, but also framed it as an issue of government infringement on the peoples’ liberties. As expected, the latter position has more political potency among conservative voters. However, the debate does not break cleanly between liberals and conservatives, or along income or education demographics. In fact, the movement to forgo vaccinations has become popular in some more liberal and affluent communities; the organic grocery demographic. [Somehow it is better to expose a child to a dangerous disease, so that the child might have “natural” immunity to the disease, rather than have the child receive a safe vaccine that prevents the dangerous disease in the first place.] Even veterinarians are running up against the anti-vaccine movement, as more and more pet owners are foregoing vaccines against distemper and other pet ailments.

Because government enforcement of vaccine regimens might be viewed by many as an intrusion on individual liberty, all but two states (Mississippi and West Virginia) allow exemptions based on religious beliefs. In addition, nineteen states allow exemptions based on personal (whatever that may mean) beliefs. All states do allow medical exemptions, since some children (e.g. those receiving chemotherapy or who have certain immune disorders) cannot receive vaccines. Nevertheless, despite the fact that states in which it is easier to obtain non-medical exemptions have higher rates of vaccine-preventable disease, moves are afoot in several states (including Mississippi and West Virginia) to make it easier still to obtain personal belief exemptions.

Reference: Wakefield, A. J., S. H. Murch, A. Anthony, J. Linnell, D. M. Casson, M. Malik, M. Berelowitz, A. P. Dhillon, M. A. Thomson, P. Harvey, A. Valentine, S. E. Davies, and J. A. Walker-Smith. 1998. Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children. The Lancet 351:637–641.