Malicious Measles Myths: Memory-Holing a Monster
Measles is already having a great 2024. We ought to put a stop to that.
Headlines today are awash (for very good reason) in concerning announcements of measles outbreaks, with massive rises being seen particularly in Europe as gaps in vaccination coverage during the COVID-19 pandemic coupled with a return to more-or-less pre-pandemic life are coming home to roost. As this occurs, you will see well-organized efforts by the anti-vaccine lobby to discourage vaccination. In this post, I discuss the problems in common claims that they have made in the past that you will doubtlessly see again as these events unfold. In particular, claims deal with the seriousness of measles as a disease, the ease with which measles can be treated, the effectiveness of measles vaccines, and the belief that people should be entitled to all of the benefits of living in a society while not having to make any contributions to those benefits. I implore everyone to ensure they are up to date on measles vaccination. The consequences of measles are grave and avoidable.
Myth: Measles is just a fever and a rash
It is key to believe that measles is a mild, self-limiting illness to be able to justify the refusal of measles vaccines. It is true that most cases of measles are not themselves acutely fatal and most people do recover, but measles is very far from being a mild, self-limiting illness.
Historically, there have been measles outbreaks that have produced deaths in numbers comparable to those of smallpox, to the extent that it can be hard to tell in historical accounts which disease struck. In the early 20th century, it was first noted that people’s tuberculin skin tests (a marker of immune memory to tuberculosis) that were previously positive suddenly turned negative after an encounter with measles. This was perhaps the first hint that measles infection had alarming consequences on the immune system. It is only in recent years that the extent of the harm of measles’s effects on the immune system was fully appreciated with loss of antibodies to as much as 73% (but on average about 20%) of all antigens we had antibodies to before the infection. In contrast to something like HIV, measles does not generally cause chronic infections (although the antigens from the virus are surprisingly persistent in the body- seemingly a key contributor to the durable immunity the virus elicits), which means that the immune repertoire has a chance to bounce back once the infection is brought under control- but even so, this recovery is not complete. Measles also infects T cells, preferentially memory T cells because they express higher levels of the measles receptor CD150, though the damage to the T cell compartment is not as pronounced as it is for B cells. Together these consequences serve to render people who are infected with measles at markedly higher risk for infections. In fact, most measles deaths are actually because of secondary infections brought on by measles weakening the immune system. This means that measles outbreaks threaten herd immunity to other pathogens as well. It’s been shown that the effects of measles on the immune system can render people more susceptible to infectious diseases for 2 to 3 years, which is thought to account for the substantial increases in all-cause mortality that followed measles outbreaks, and which disappear upon measles vaccination.
Still, the direct consequences of measles infections themselves are far from trivial. In a recent outbreak in the Netherlands in which 77 cases were documented among children, parents of 43 of the cases described their children’s illness as severe. It is estimated that 1 in 4 measles cases are sick enough to require hospitalization and about 1 in 1000 people will die directly from the infection. In lower income countries, 10% of measles cases are fatal, but in populations lacking immunity altogether that number can be as high as 25%. It is honestly hard to think of a part of the body that isn’t harmed by measles. The virus enters the blood and can access every part of the body. Measles infections have been known to cause myocarditis, appendicitis, pneumonia, croup (laryngotracheobronchitis), thrombocytopenia (low platelets), vasculitis, middle ear infections, arthritis, kidney damage, blindness, hearing loss (including deafness), and more. Complications with measles are common: 30% of cases from 1987 to 2000 in the US were documented to have at least one and 6% of measles cases evolve into pneumonia.
The encephalitides (plural of encephalitis, i.e., brain inflammation, usually because of infection in this case) caused by measles deserve special mention:
Primary measles encephalitis occurs in 1-3 people per 1000 measles infections, being fatal in 10-15% of them, with another 25% having permanent neurological damage which can result in intellectual disability or seizures. This onset of this form of encephalitis commonly overlaps with the rash caused by measles.
Acute post-measles encephalitis (APME) occurs in the days to weeks after measles infection has seemingly resolved in about 1-2 per 1000 measles cases. APME occurs after the measles virus has already been cleared from the body, thought to arise because of a similarity in the structure of measles proteins and proteins found in neurons, which causes the immune system to attack myelin (the fatty sheath covering neurons). 1 in 3 of patients may have a recurrence. This condition is thought to increase the risk of developing multiple sclerosis. 20% of cases are fatal.
Measles inclusion body encephalitis (MIBE) is a condition occurring mainly in immunocompromised people who become infected with measles and cannot clear the virus. The condition results in seizures, typically not responsive to anticonvulsive medication, and is fatal in about 75% of cases.
The cruelest condition caused by measles however has to be subacute sclerosing panencephalitis, or SSPE. This condition was once thought to be exceedingly rare, but it appears to occur as often as 1 in 609 cases if measles is contracted in infancy and 1 in 1367 cases if contracted under the age of 5. SSPE usually occurs 6 to 15 years after the initial infection with measles and causes progressive neurological decline, beginning subtly with personality changes or underperformance in school, before eventually more pronounced intellectual issues begin to become apparent and movement issues develop. Eventually, seizures start occurring, which then progresses into coma and death. SSPE is irreversible and fatal in nearly all cases over a period of 1-3 years1. There is no effective treatment.
Measles is higher risk in girls, those without access to care, those of lower socioeconomic status, pregnant individuals, malnourished individuals, people living with HIV, and in secondary household contacts. In the pre-vaccine era, it is estimated that 2-4 million people died of measles or the consequences of its infection (i.e., susceptibility to other infections) every year. It was the leading killer of children globally, and it is responsible for more children’s death than any other vaccine-preventable disease globally even today, with 100,000 deaths globally as recently as 2016. The existence of our exceptionally effective measles vaccines means that this calamitous devastation to public health is a conscious choice we make every time we refuse to vaccinate.
Myth: Measles infection is a better way to get immunity to measles
The kernel of truth here is that measles infection does seem to induce more robust immunity than measles vaccination. That’s not all that surprising as the vaccine uses an attenuated virus, so it won’t be able to trigger as potent inflammation as the infection, meaning it is less stimulating to the immune system2. Authentic measles infection also replicates to a far greater extent than the vaccine strain virus, which allows it to seed virtually every lymph node in the body to induce immune responses, a factor proposed to contribute to the incredible longevity of immunity and protection. Interestingly, a remarkably high proportion of the plasma antibody response to measles infection (but not vaccination) is driven by IgG4. Nonetheless, the risks of measles are drastically higher than those of the MMR vaccine. Critically, whereas we can see a substantial decline in antibody responses following measles infection, no such decrease is seen after vaccination (in fact, there is a significant increase in antibody diversity after MMR vaccination):
Still, on practical level, the difference in the immune response elicited by measles vaccines vs infection is mostly academic. One dose of measles vaccine is 95% effective in preventing measles. 2 doses of measles vaccine confer likely lifelong protection and ensure an immune response in nearly everyone who takes them:
Furthermore, almost everyone who does not respond to the first dose will respond to the second (although the age at vaccination does seem to be a factor). It has also been demonstrated that measles vaccination induces antibodies that cover all variants (genotypes) of the virus, and that the evolution of the H and F proteins that allow measles virus to enter cells is very restricted (i.e., there is very little room for the proteins to mutate while retaining the ability to cause infections and spread person-to-person). In short, measles vaccines check all the boxes for gold standard vaccine effectiveness3.
Still, there are a few important caveats. During the pre-vaccine era, as population turned over (people immune to measles died, people not immune to measles were born and then aged out of the protection from maternal antibodies), there was a constantly replenished pool of people susceptible to infections. Because of this, there would be measles outbreaks every 2-5 years, and people would be constantly re-exposed to measles throughout their lifetime, providing substantial opportunities for boosting the immune response against it, even without getting sick. As vaccines succeed in eliminating measles, exposures to the virus will decline, meaning these boosting events will not occur. Note that this epidemiological reality also confounds estimates on the durability of protection from measles infection, biasing it upwards. Modeling suggest that in the absence of these exposures, measles vaccination can retain protective levels of immunity for a period of on average 25 years, but this is based on a single dose of vaccine, whereas the standard is now (and has long been) 2 doses; the picture is likely more optimistic than this would suggest. Still, it is therefore not impossible that as generations of people residing in measles-eliminated regions get older, boosters of measles vaccines may be needed to retain protection and herd immunity so long as the virus remains around. In particular, circulation of the B3 and D8 genotypes of measles is a concern as these are less effectively neutralized by the antibodies elicited by measles vaccines. We could, however, avoid this whole rigamarole by simply eradicating measles. All we need is a very aggressive global vaccination campaign.
Myth: Hygiene will prevent measles
This one is pretty simple: measles is airborne. It is so airborne that even under outdated frameworks of infectious disease transmission that dichotomize spread into droplet and airborne, measles was considered the prototype of airborne. You are considered to have been exposed to measles if you so much as use an elevator that someone with measles has used even 2 hours earlier. If someone in your household has measles and you aren’t immune, there is a >90% chance that you will get measles. In a susceptible population, each case of measles results in 12-18 more cases. Unless you have a hygiene strategy that gets around the biological imperative of breathing, it will not prevent measles.
Admittedly, some have expanded hygiene to cover things like the wearing of masks and respirators (in the older conception of this canard, the presumption was that only you just needed to wash your hands to avoid measles- I do wish I were joking). Negative pressure isolation rooms are fundamentally required to prevent the spread of measles, and while guidance exists regarding the use of respirators (N95s or equivalent) in the care of measles patients, measles infection of the eye is well characterized; some guidance suggests eye protection for some actions. Nonetheless, data on how well these measures work to combat the spread of measles are largely lacking. Unfortunately, the only definitive routes to protection from measles are through (1) recovery from measles infection (which is by far the most dangerous option), (2) measles vaccination, or (3) passive immunity such as through maternal antibodies (but obviously this one comes with a very real time limit).
Myth: Vitamin A means that we don’t need a measles vaccine
With these myths there is usually a kernel of truth, and here the kernel is fairly rich. There is undeniable evidence that vitamin A deficiency worsens measles in children and the WHO has long recommended that all children with severe measles, regardless of vitamin A status, receive supplemental vitamin A. Despite this, evidence that this helps in those who are themselves not deficient in vitamin A is of low quality and subject to significant confounding, which raises questions about whether the intervention is actually useful in these individuals. Data on what role vitamin A status has on measles in adults are also very limited, as infections occur overwhelmingly in childhood. Despite this, supplemental vitamin A, in the appropriate doses, is a very low-risk intervention, hence the broad WHO guidance. Importantly, a single dose of vitamin A is not shown to prevent mortality from measles- only 2 doses given on consecutive days are (dosing depends on the age and weight of the child). The effect of vitamin A seems to be fairly specific to measles, as vitamin A supplementation is not shown to prevent mortality in pneumonia due to other causes. Measles infection has also been reported to acutely cause a drop in vitamin A levels by 30% or more, with larger effects in malnourished children.
So: why isn’t it enough? We can actually see the answer in Samoa. In 2019, in Samoa, there was a tragic incident in which a measles vaccine was inappropriately diluted with a muscle relaxant by two nurses and administered to two infants, ultimately resulting in the children’s death. Importantly, this occurred because of the diluent, the muscle relaxant, and had nothing to do with the measles vaccine itself. This error was then capitalized upon by anti-vaccine activists, including Robert F. Kennedy Jr., who managed to get measles vaccine uptake down to 40% for the first dose and 28% of the second dose among those under 5 years of age. This set the stage for an explosion of measles cases: about 5700 cases were documented and 83 deaths were observed, overwhelmingly in unvaccinated children younger than age 5. Despite the distortions that have since been applied to attempt to maintain good PR for the measles virus, there is no evidence to support either malnutrition or vitamin A deficiency as a contributor to this horrible event, nor any obvious immunological deficiencies. Vitamin A was used as per WHO guidelines to manage these cases- 83 people still died. Furthermore there is the rather obvious piece that while vitamin A may improve survival of measles cases, it does nothing to deter their transmission. It also isn’t shown to prevent many of the concerning complications of measles, such as subacute sclerosing panencephalitis or the destruction of immune memory that renders people susceptible to infections they have already recovered from. Vaccination is the only tool we have that accomplishes all of these things.
It should also be noted that while vitamin A deficiency can be very serious and its prevention remains key for proper health in general, overconsumption of vitamin A can also cause toxic effects. Young children are particularly susceptible to vitamin A toxicity. Of particular concern are the consequences of vitamin A overconsumption in pregnancy, which can cause devastating neurological, cardiovascular, immunological, and even skeletal effects on the fetus. These risks principally apply to vitamin A consumed through pharmacological means (particularly in its more active forms like isotretinoin) as there are feedback mechanisms to limit its toxicity when taken in through diet (at least, from plant sources, as the vitamin A here is initially inactive). However, polar bear and seal liver have both been known to cause vitamin A toxicity (Inuits described that consuming large amounts of these resulted in an illness causing headaches and prostration in the 16th century).
Incidentally, there were actually some data from investigators in Indonesia who showed that administration of vitamin A could reduce the immune response to measles when the supplement was given at the same time as the vaccine; however, this finding has not been replicated in other lower income countries. Thus it is still recommended by WHO that a dose of vitamin A be given with each dose of measles in places where deficiency is common4.
Myth: It’s worth it to get measles for a reduced risk of cancer
There are some isolated case reports of people developing measles and then their tumors shrinking in the historical literature. This is a far cry from the idea that having measles reduces your risk of cancer (in fact, given what measles infection does to your immune system, one would expect the exact opposite effect, as the immune system is key to eliminating cancerous cells- although because people tend to get measles in childhood it would be hard to see an epidemiological effect as cancer in young children is relatively rare). Ironically, measles virus has actually been used with some success for the treatment of cancers because it can infect and kill tumor cells… but this is specifically the vaccine strain of the virus. This is because the tumors in question express high levels of the protein CD46, which measles virus uses to enter and infect cells- but only the vaccine strain viruses can use CD46. Wild measles virus does not have the ability to use this receptor. Of note, therapeutic applications of vaccine-strain measles virus use doses equivalent to about 10 million times more than what is found in a dose of vaccine:
Myth: The measles vaccine causes measles outbreaks
This is rooted in the deeply misunderstood idea of vaccine shedding. There has never been a well-documented case of an individual transmitting vaccine strain measles virus to another person, full stop. In fact, in virtually all cases, encounter with a vaccinated person marks a dead end for transmission chains of the virus, whereas refusal of vaccination markedly increases the risk of contracting measles. In particular, I recall how this headline from 2014 was misused specifically to claim that measles can be spread from vaccinated people ignoring the fact that this is about a vaccinated person who was infected after an encounter with wild measles and the word “first” in the title to denote the extraordinary nature of the event. Importantly, even though this case had over 200 contacts, only 4 developed measles, and there were no additional cases of the disease from these 4, showing again that vaccines markedly reduce the chances of transmission upon infection. The case does highlight concerns that in an era where there is essentially no chance for asymptomatic boosting against measles, immunity to the virus might wane more quickly, which becomes important when someone infected with measles visits a travel hub for example. This one incident has not been enough to make recommendations that people receive a third dose of MMR however, although that has been considered in light of the more rapid waning of immunity seen against mumps and outbreaks on college campuses. One interesting note is that the index patient in this outbreak received MMR vaccines at age 3 and age 4, whereas in the US, the interval between first and second doses is typically longer as the first is given at 12-15 months and the second between 4-6 years; it is possible that had she received the first dose earlier and there were a longer interval between the two doses, the immune response may have been better, and she may have had higher levels of neutralizing antibodies against measles (although technically the second dose of MMR is not a booster but rather intended to elicit protection in nonresponders). It is also possible that the vaccines she had received were not properly stored, which may have reduced their effectiveness.
Myth: Alexander Langmuir said measles wasn’t a big deal
Alexander Langmuir was an American epidemiologist who created the Epidemic Intelligence Service (EIS) of the CDC. Undeniably he is an authority in the arena of infectious diseases, and the quote that is attributed to him reads:
[Measles is a] self-limiting infection of short duration, moderate severity, and low fatality has maintained a remarkably stable biological balance over the centuries.
What people leave out is… the part that comes immediately after it (emphasis mine).
Those epidemiologists, and there are many, who tend to revere the biological balance have long argued that the ecological equilibrium of measles is solidly based, that it cannot readily be disrupted, and that therefore we must learn to live with this parasite rather than hope to eradicate it.
This speaker, not so long ago, was counted among this group and waxed eloquent on this subject in print.
Happily, this era is ending. New and potent tools that promise effective control of measles are at hand. If properly developed and wisely used, it should be possible to disrupt the biological balance of measles. Its eradication from large continental land masses such as North America and many other parts of the world can be anticipated soon.
The importance of any disease as a public health problem must be gauged from many angles. For example, using mortality as a criterion heart disease becomes most important. Short-term morbidity makes the common cold rank high. For chronic disability arthritis and mental disease dominate. For public interest and parental concern, in spite of relatively low incidence, nothing has equaled poliomyelitis. According to these criteria, the importance of measles cannot be compared with any of the diseases mentioned so far, but it should still be classed as an important health problem on two main counts. First, any parent who has seen his small child suffer even for a few days with persistent fever of 105°, with hacking cough and delirium wants to see this prevented, if it can be done safely. Second, at last there is promise that something can be accomplished by organized health action.
In other words, Langmuir initially did believe that measles was a mild and self-limiting illness until he saw what it actually did to children afflicted with it and the means to prevent measles with a safe and effective vaccine arose. He then reconsidered his misguided views.
Nonetheless, this myth is instructive not simply because it showcases the wanton dishonesty of the anti-vaccine lobby who will literally clip quotes to show the exact opposite meaning of what their speaker intended, but because it highlights a fallacy: the appeal to authority. Langmuir, for all his undeniable accolades, could have sincerely believed that measles was not a big deal (and in fact, he did believe it for a time), and none of those accolades would have shielded him from the harsh and immutable truth that he was wrong. The data simply do not support that position and there is no degree or honor that can be awarded to undo that. Incidentally, Langmuir is the originator of the 5-micron false dichotomy between airborne and droplet transmission that is thought to have greatly hindered effective public health responses against COVID-19 in the beginning by not allowing for appropriate precautions against spread.
Myth: You don’t need to care about my vaccination status if you’re vaccinated
As an immunocompetent person who has had 2 doses of MMR vaccine, I do not find myself particularly worried for my own well-being at the prospect of some arrant measles virus particles finding their way into my body. Nonetheless, there are good reasons to care about others’ vaccination status even if one doesn’t consider oneself at risk. For one thing, the herd immunity threshold for measles is extremely high- about 95%. Between people who cannot get vaccinated with measles vaccines (such as those undergoing chemotherapy, those who are pregnant, those who are immunocompromised, and those too young to be vaccinated) there is hardly any wiggle room for people to refuse vaccination for nonmedical reasons and also maintain protection of the vulnerable. Nonetheless, I recognize that some people are accustomed to a certain solipsism when it comes to matters of public health so aside from the fact that measles is devastating to those vulnerable populations who cannot get vaccinated, people should be aware of what measles infections actually mean. For one thing, the immunological damage caused by measles is well recognized. If outbreaks get large enough, they will erode herd immunity to other infectious diseases wherein protection might not be nearly as achievable. This also necessarily means significantly more pressure on the healthcare system and economic strain. As it is and has been demonstrated painfully by the COVID-19 pandemic, the surge capacity of the medical system is very much finite. If you get into a car accident in a world where measles has shepherded in a new renaissance for infectious diseases, be prepared to receive substandard care. Also such occurrences will invariably come with public health efforts to control transmission that will have disruptive effects on your daily life. It would be much preferable to avoid having to deal with all of this by simply ensuring that everyone who can be vaccinated against measles is vaccinated against measles.
There are some sources that suggest some people have survived SSPE but other authoritative sources report that all cases are fatal. In any case, spontaneous remission with SSPE is extremely rare, and therapy is not curative. I did manage to locate a single report of a case of SSPE treated with long-term interferon alpha administered intraventricularly (i.e., directly into the brain) via an Ommaya reservoir for years which seemed to help for a period without causing ill effects (which I personally found very unusual given the known neurotoxic effects observed in type I interferonopathies- although it is possible that these manifestations are hard to detect in SSPE). However, the relief was not preserved and the patient remained in stage III of SSPE at the time of publication, so at best the therapy offered a temporary remission (though the fact that measles IgM in the CSF turned negative is surprising and impressive). This is not nothing; in fact, I think the loved ones of those experiencing SSPE would be profoundly grateful for even this much, but this doesn’t change the fact that this is a horrible disease that is avoidable. Furthermore, this kind of response to intraventricular interferon is essentially a best-case scenario.
Kind of a nerdy point but I’ll make it because I think people who read my work lean on the nerdy side: the factors that make vaccine-strain measles attenuated are not fully understood. Diane Griffin reviewed the possible factors thoroughly here. It is commonly argued that the basis is related to the fact that the attenuated strains of measles virus have a mutation in their hemagglutinin (N481Y) can use the protein CD46 to enter cells instead of CD150 (SLAMF1) and nectin-4 (poliovirus receptor-like protein 4, PVRL4). At face value though, this is hard to rationalize. CD46 is expressed by every nucleated cell in the body whereas CD150 is expressed predominantly on T cells, activated B cells, macrophages, and dendritic cells; nectin-4 is found on epithelial cells and abundant on the placenta. The ability to enter by CD46 would endow measles virus with more susceptible (though not necessarily permissive) cells to infect. Thus as a mechanism of attenuation, this could only make sense if the newly susceptible but nonpermissive cells act like a sink to lower viral load, but it seems strange that these random nucleated cells might be more resistant to infection than the cells of the immune system. Furthermore, when macaques are infected with measles virus that has had its hemagglutinin protein replaced to the vaccine strain, the virus still infects the same cell types- suggesting that the ability to use CD46 in vitro does not necessarily allow its use in vivo (perhaps a factor in the need to use shockingly high doses of vaccine strains of measles virus for oncolytic virotherapy). There was however reduced replication overall in viruses with the vaccine strain virus in this study, suggesting that the H protein does indeed contribute. Another factor here might be the presence of defective interfering particles in the measles vaccine which enable an early induction of interferon that suppresses replication of vaccine-strain virus.
People often describe measles vaccines as inducing sterilizing immunity- that is, immunity so great that it completely stops infections from occurring. This is not true and it leads people to unrealistic expectations of what vaccination can accomplish. Infections of measles vaccinees upon exposure are not uncommon, but are overwhelmingly asymptomatic or minimally symptomatic (sometimes described as modified measles) and virtually never lead to onward transmission of the virus.
It is an interesting question whether or not vitamin A should be supplemented in places where vitamin A is apparently not deficient when given alongside MMR and there isn’t much data to inform either way. Vitamin A has been shown to have an antiviral effect against measles through its effects on cellular gene transcription. On this basis, giving vitamin A to someone who does not have vitamin A deficiency can likely reduce the ability of the measles vaccine virus to replicate inside the body (which, to begin with, has very limited ability to replicate in immunologically competent people). This is consistent with the finding that infants who received vitamin A with the measles vaccine in Indonesia were less likely to develop a rash- and this is the study that found a markedly reduced response to the vaccine in the vitamin A recipients. The ability of the vaccine strain virus to replicate within the body is key to ensuring an effective immune response. Therefore, it is likely that in the absence of vitamin A deficiency, or at high doses, administering vitamin A with measles vaccination may actually reduce the effectiveness of the vaccine.
A powerful comprehensive take down of antivaxx myths regarding measles vaccination and outcomes by Edward N.!
Including a tour-de-force in-depth review of the measles virus history, highlighting its impact on public health. Big Kudos Edward!!
Cheers! Shannon
THANKS for your work. Excellent review with appropriate levels of virology, immunology and cell biology weaved into the narrative . Great for an old practicing primary doc such as myself .