Measles, vaccines, and the herd

The first confirmed measles death in the US since 2003 was recorded in Washington State recently, where a woman died from measles-associated pneumonia. According to a health department news release, she had an underlying condition and was taking medications that suppressed her immune system. People undergoing immunosuppressive therapy are at high risk of contracting infections and, if they develop infection, often do not exhibit the signs immunocompetent persons show. This woman is thought to have become infected at a medical clinic during a local outbreak; the etiology of her pneumonia wasn't recognized as measles until autopsy.

Measles is highly contagious (R₀, the basic reproduction ratio of the pathogen, can be as high as 18) and there are hundreds of thousands, if not millions, of immunocompromised persons in the US who depend upon the immunity of those around them for protection. When a large fraction the community possesses immunity to a pathogen, circulation of the pathogen becomes less intense. When the prevalence of immunity becomes high enough, it ceases to circulate. In this simple picture, if the fraction 1–1/R₀ of a population can be made immune, and that fraction is maintained over time over time, then a pathogen can be eradicated.

In reality, herd immunity is more complex than this. Many complications arise from imperfect vaccine immunity, population heterogeneity (including network effects), uneven vaccination, and those who opt not to receive vaccines. These complexities make it challenging, from a public health practice perspective, to protect populations with vaccines. Nonetheless, this woman's death illustrates how important it is to immunize as many people as possible: Doing so heightens protection of those vulnerable to vaccine preventable infections.

This case has been reported within the context of anti-vaccination notions, or as I prefer to think of it, vaccine skepticism. Regardless of the terminology, there is one simple truth to the incident: She developed what proved to be a fatal infection because someone in her community was not immune to the measles virus. That seems needless when a safe and effective vaccine that conveys long-lived immunity is available. Hopefully laws like those enacted in California and Vermont recently will spread to other states and help to increase the prevalence of vaccine-associated immunity in communities throughout the US.

(image source: Wikipedia)

MERS as (another) messenger of prevention

It's hard for me to know how to interpret the MERS situation in South Korea. At a high level, a recently recognized viral respiratory pathogen has traveled halfway around the world and is causing morbidity and mortality in a small section of an immunologically naive population. It appears to be associated with hospitals. What do we take away from this? Lessons will be learned when the event subsides and people study what happened, but to me, MERS reminds us that outbreaks of pathogens for which there are no vaccines or drug therapies underscore the importance of prevention.

When possible, preventing pathogens from physically reaching or entering a host by respiratory, percutaneous, alimentary, blood et al pathways is preferable to relying on pharmaceutics. Drugs tend to be complex and costly to develop, can take a long time to enter the marketplace, and -- especially in the case of antibiotics and antivirals -- they can become obsolete over time. Moreover, drugs are often toxic to the patient. Prevention is applicable in situations when appropriate drugs don't exist (e.g., for newly emerged pathogens), when it isn't possible to administer drugs in a timely manner, or when patients cannot tolerate them. 

Consider two anecdotes related to the spread of MERS virus in South Korean hospitals. As described by Choe Sang-Hun, it appears that the index patient in the South Korean event had "coughed and wheezed his way through four hospitals before officials figured out, nine days later, that he had something far more serious and contagious." Furthermore, ED wait times in Korea can be extraordinarily long by US standards. Another patient, who waited two-and-a-half days in the emergency department before a hospital bed became available, infected 55 additional individuals during their wait. Apparently, 2.5 days isn't an unusually long waiting time in some Seoul hospitals. 

Applying effective prevention measures to patients suspected of infection is the only way of stopping the chain of transmission in such environments. Unfortunately, it is unclear how to achieve good infection control for MERS and a range of other pathogens. Eli Perencevich described the issue clearly, as usual, in the Controversies in Hospital Infection Prevention blog recently: 

. . . we don't actually know how to achieve good infection control for MERS and the other diseases he [Tom Frieden] mentioned [measles, DR-TB, SARS, Ebola]. If only we invested in studies to understand how to best implement PPE in these [hospital] settings. One could imagine improved PPE technology, refined PPE donning and doffing algorithms and enhanced environmental cleaning as potential targets for future studies examining optimal protection from MERS. Not coincidentally, many of these are the same targets that Mike, Dan and I mentioned in our Ebola+PPE editorial several months ago. If we invest in infection prevention technology and implementation research, our health care system will be safer regardless of the pathogen du jour.

And that's the point that MERS makes me think about. Yes we need antimicrobials and vaccines that work against specific pathogens, of course we do, but developing such drugs is a major effort. Biochemical pathways must be understood, pathogen life histories and survival strategies must be elucidated, and the host response must be characterized among many, many other things. Doesn't it make sense that research on pathogen-agnostic approaches to prevention, which don't require such specific and complex information, might be simpler and broadly applicable? 

Investing in research on infection prevention approaches, and how to implement them sustainably in realistic clinical environments, would pay benefits far beyond helping to thwart the spread of exotic and newly emerged pathogens. We may learn how to better control and prevent the usual suspects of hospital associated infection, which, afterall, are responsible for a tremendous burden of disease day in and day out.

(image source: Wikipedia)

Vaccines: What do we think?

CNN published a poll on Monday of this week that contains some interesting statistics. A story announcing the poll began

A new CNN/ORC poll shows nearly 8 of 10 Americans believe parents should be required to vaccinate their healthy children against preventable diseases such as measles, mumps, rubella and polio. If the children are not vaccinated, most agree the child should not be allowed to attend public school or day care . . . 

The basic methodology and results are described here. Overall, 78% of respondents believed parents should be required to vaccinate children against preventable diseases if they are healthy. The age stratified results depict an interesting trend: Older Americans are most supportive of required vaccinations (84% of those 50+ versus 72% of those under 50) and those at the younger end of the spectrum -- and in particular, those of common childbearing ages -- are much less supportive (only 67% of those 18-34 years of age).

Pondering these statistics might lead one to muse that it would have been useful if the poll, rather than asking if parents should be required to vaccinate, had instead asked simply if parents should vaccinate. On Tuesday another poll appeared, this time by Reuters/Ipsos, that asked just that. Information on that poll can be found here. A Reuters news story summarized this poll:

Seventy-eight percent of respondents in the online survey said all children should be vaccinated unless there is a direct health risk to them from vaccination. Only 13 percent opposed vaccinations. . . 

The story went on to note that the "numbers are absolutely overwhelming in favor of vaccinations with a consistent minority in opposition." That's good, but probably not good enough. Herd immunity likely needs to be over 90% in order to eliminate measles. If the poll was representative of the larger US population, then the 78% statistic suggests that we have some work to do.

Of course, polls are not compete studies, and it's hard to know what to make of such results. However, I don't think they're entirely reassuring.

(image source: CDC)

Elimination, not eradication

In discussions of past and present measles activity in the United States, one sometimes reads that measles was once eradicated here.

It wasn't, though in 2000 it was declared eliminated.

Measles elimination is defined as interruption of continuous (i.e., endemic) transmission lasting ≥12 months. Eradication, on the other hand, implies global elimination. Smallpox was declared eradicated in 1980 and we're trying hard to eradicate polio and others at present. Measles has not been eradicated.

Eradication of measles may be possible, though there significant challenges. Sadly, despite the availability of a safe and effective vaccine, the disease continues to maintain a strong foothold in many regions of the globe. This persistence poses a threat to non-immune persons in our mobile world, as we are currently seeing in the US.

If you hear someone confuse elimination for eradication, you might gently correct them. It's important that people understand the threats to their health and wellbeing. 

(image source: CDC)

Your belief does not trump his right to recover

One story connected to the California measles episode in particular speaks to me. It concerns a dad speaking out, in defense of his son's fragile health, against the decisions of many not to vaccinate their children. The man's son is recovering from leukemia and cannot yet be vaccinated against measles. He is justifiably concerned about unvaccinated classmates posing a potentially mortal infection risk to his son and has requested that such children be barred from school.

The question of why some don't vaccinate their children (or themselves) is complex and multifaceted, but it seems to have one thing in common with other major public health issues of recent times: the idea that "it's my right to". In addition to it's my right to not vaccinate my children, we often hear that it's my right to possess assault rifles and it's my right to have raw milk on the market.

Should these be individual rights? From a public health perspective I would argue no, and point out that there's another fundamental question to be answered: Do we want to live in a society where someone's "rights" endanger the health and wellbeing of others? We've answered that question before for other major public health issues: there are mandatory seat belt laws in many states; it's not legal to drive under the influence of alcohol; and it's not legal to smoke in public areas in many parts of the nation. Such laws attempt to limit the ability of an individual to place others at risk. The dad in California has the right -- in fact, the obligation -- to protect his son's health and wellbeing. Could enacting legislation mandating vaccination except in specific medical circumstances be a solution?

I resonated with the man's concern for his son partially because cancer has touched the lives of close friends of mine. Those at risk from infection due to therapy-related immunocompromise and chronic disease are thought to number in the millions in the US. They have rights and deserve to be protected. Legislation on this issue, if possible, won't happen quickly. Pragmatically, I think we need to understand why some people believe that vaccines are dangerous when there's no evidence to support that claim and much evidence demonstrating that measles -- and other vaccine-preventable preventable diseases -- are lethally dangerous. Why are the likes of Jenny McCarthy more credible to some than the US Institute of Medicine? Understanding such issues may provide a basis for a conversation and, ultimately, change.

(image source: CDC)

When it comes to measles, it is a small world after all

Dan Diamond wrote an essay recently in Forbes in which he notes the asymmetry of public reaction to Ebola versus measles. He describes how on the one hand, even though Ebola was unlikely to cause an epidemic in the US the public went nuts with Fearbola, while on the other hand measles represents a much more realistic threat of spread but people are somewhat apathetic about it. It seems a valid observation.

It may be difficult to understand public perception of threat when it comes to infectious disease, but, epidemiologically speaking, there are some important differences between the two, as partially summarized in the table below.

	Measles	Ebola
R0	~7-18	~2
Serial interval	8-12 days	5-15 days
Incubation period	10-12 days	2-12 days
CFR	3%	25-90%
Infectious period	~ 4 days before rash to several days after onset of rash	At onset of symptoms
Vaccine preventable	Yes	No

Importantly, persons infected with measles virus are infectious before they begin to feel ill, so they are able to spread the virus in the course of their normal activities. Fearbola -- the epidemic of hyped and often unfounded messages surrounding the threat of Ebola to the US -- struck in part because of the high case fatality rate (CFR) and the lack of a vaccine conveying immunity to the Ebola virus. That contrasts strongly with measles. Even though the measles outbreak that started at Disneyland Resort Theme Parks in California is expanding, I doubt there will be a Fearmeasles epidemic, even though measles can be fatal and cause long term sequelae.

That said, this is a fascinating event due partially to people's attitudes regarding vaccines. Recently, the ramifications of such attitudes, in terms of implications for public health agencies, has been expressed very clearly by Lisa Aliferis (writing for NPR):

Local health officers in counties [in California] affected are busy tracing those who infected patients have been in contact with. Dr. Erica Pan, deputy health officer of Alameda County, says the county has shifted resources from Ebola preparedness to contact tracing for measles. Last year there were four cases of measles in Alameda County, she said, "but we had 400 contacts to investigate."

This is remarkable. On 23 January, the California Department of Health reported that in LA and Orange counties alone there were 31 confirmed cases. A simple back-of-the-envelope calculation suggests that if 4 cases required 400 contacts to be investigated (100 contacts per case on average), then 31 cases could require 3100 contacts to be investigated. No wonder health departments are refocusing resources away from Ebola and onto measles.

People who do not vaccinate their children, or catch up on missed vaccines as adults, do not only place themselves in danger of infection, they place the community in danger. Moreover, they cause scarce public health resources to be spent on controlling a vaccine preventable disease. It's ironic that the lyrics to It's a small world -- the theme song of a ride at Disneyland of the same name -- read

It's a world of laughter, a world of tears.
It's a world of hopes and a world of fears.
There's so much that we share,
That it's time we're aware
It's a small world after all. 

Indeed.

(image source: Wikipedia)

Recall bias, or how I learned to stop worrying about measles and love my vaccination beliefs

The multi-state outbreak of measles in the US, which originated at Disneyland theme parks in California, has received much attention in the press recently. Sadly, the event isn't terribly surprising: many people, including children, lack immunity. The reasons for this are varied, and include the MMR vaccine being recommended for children over 12 months of age; persons not completing the recommended vaccination sequence; waning immunity in older persons; and lack of vaccination.

This latter issue is related to the anti-vaccination movement and this dimension is receiving attention in the media. Some of the discourse is revealing. One example appeared in the New York Times recently, which quoted a Santa Monica pediatrician who has cautioned against the way vaccines are used in the past (but does administer the vaccine in his practice):

“I think whatever risk there is -- and I can’t prove a risk -- is, I think, caused by the timing,” he said, referring to when the shot is administered. “It’s given at a time when kids are more susceptible to environmental impact. Don’t get me wrong; I have no proof that this vaccine causes harm. I just have anecdotal reports from parents who are convinced that their children were harmed by the vaccine.”

Perhaps such comments could be rephrased more bluntly: I believe that the vaccine could be dangerous to kids because people who know less about medicine and epidemiology than I do tell me, with great conviction, that they think it's dangerous. Even blunter still might be: The idea that vaccines can be dangerous has a high truthiness, so count me in. Or even, After talking to some patients I've decided to stop worrying about measles and love my unfounded beliefs about vaccination.

I've written before about the importance of understanding those who subscribe to anti-vaccination notions. Statements like this from a physician illustrate how much work has to be done. Several years ago Delgado-Rodríguez and Llorca wrote a very nice continuing professional education paper on bias in epidemiology, which physicians with similar beliefs should read. The following passage is especially important:

Recall bias: if the presence of disease influences the perception of its causes (rumination bias) or the search for exposure to the putative cause (exposure suspicion bias), or in a trial if the patient knows what they receive may influence their answers (participant expectation bias). This bias is more common in case-control studies, in which participants know their diseases, although it can occur in cohort studies (for example, workers who known their exposure to hazardous substances may show a trend to report more the effects related to them), and trials without participants’ blinding.

If someone wants to find a cause for a medical event, they will. The plural of "anecdote" is not "data", no matter how convincing the anecdotes may seem.

(image source: Wikipedia)

Measles, right here in River City

Measles used to be a major childhood disease, affecting virtually all children in dramatic periodic outbreaks. The measles virus causes high fever, rash, runny nose, conjunctivitis, and malaise. It can also result in death. In the 1960s a vaccine was developed, and it was ultimately merged into what became the currently-used MMR vaccine. That vaccine helped reduce the incidence of measles to virtually non-existent levels in the US. A recent MMWR depicts the dramatic decrease of disease after vaccine introduction:

Sadly, a 1998 report finding an association between the MMR vaccine and autism led to decrease in the incidence of vaccination and attendant increase in measles disease (inset of the graphic). That study was retracted in 2010 after investigators failed to confirm its findings. Nonetheless, a large number of consumers continue to believe the bogus result that the MMR and other vaccines cause autism and thus forgo vaccinating their children. (There are additional reasons people do not vaccinate their children besides fear of autism; just google "why I'm not vaccinating my child" and you'll get a good sampling of those reasons.)

Recent months have seen continued transmission of measles in susceptible populations across the US, including California and New York City. Why is measles a problem when an effective vaccine is so commonly available? Often, travelers become infected overseas in areas where the prevalence of the measles virus is higher than in the US, and transmit the virus to susceptible individuals (often children) when they return. In NYC, a substantial proportion of the cases appear to be in children too young for the vaccine.

The simple fact is that if people do not have immunity to measles, they are overwhelmingly likely to develop infection and disease following an exposure. This is a highly transmissible virus; estimates of the basic reproduction number, R0, are as high as 18. The high degree of herd immunity in the US limits the size of outbreaks, but, as we see in the current situations in New York and California, transmission occurs due to the presence of unvaccinated persons.

In the US, all states require children to be vaccinated before starting school. However, depending on the state, children can be exempted from the requirement for medical (notably in transplant patients and those with allergies to vaccine components), religious, or personal belief reasons. Figure 3 (shown here) of a recent MMWR on measles transmission in the US depicts the current reasons for not receiving measles vaccination. Between January and August 2013, most measles cases (82%) were in persons who were unvaccinated. Of those, 79% cited philosophical/religious objections to vaccination as the reason for not receiving the vaccine. Outbreaks related to religious communities are well documented in the news; recent examples include measles in Washington State and British Columbia, measles in New York City, and measles in Texas.

Though this post has focused measles, there are similar issues with other vaccine preventable diseases, including mumps, pertussis, meningitis, and others. Vaccine coverage, both in the US and overseas, must be increased if we are to decrease the incidence of such diseases. We must learn how to more effectively communicate the benefits and risks to those who decide against vaccination.

(image source: first graphic, Wikipedia; second & third graphics, CDC)