Measles outbreaks and how far should we go in requiring vaccination? [Respectful Insolence]


Whenever we discuss vaccines and vaccine hesitancy, thanks to Andrew Wakefield the one vaccine that almost always comes up is the MMR, which is the combined measles-mumps-rubella vaccine. In 1998, Wakefield published a case series of cherry-picked patients in which he strongly inferred that the MMR vaccine was associated with autism and “autistic enterocolitis.” Of course, even the way Wakefield spun it, this wasn’t enough evidence to link the MMR vaccine to autism, which is no doubt why Wakefield never explicitly said that it did in the paper describing his case series. My guess has always been that the peer reviewers wouldn’t let him. However, outside of the scientific literature, unconstrained by peer reviewers, Wakefield was not nearly so shy about explicitly linking the MMR to autism. As a result, MMR uptake plummeted in the UK, and measles returned to become endemic again, after having been declared eliminated before. We now know Wakefield is a fraud, thanks to Brian Deer’s excellent investigative work, but the damage was done, and MMR uptake still hasn’t returned to pre-scare levels.

Unfortunately, measles is still in the news, even in the US, where the predominant mode of antivaccine fear mongering has not been about MMR, at least not the way it was in the UK in the wake of Wakefield’s case series. Most recently, there was what has become known as the Disneyland measles outbreak, in which an outbreak centered at Disneyland resulted in mini-outbreaks throughout the country. And, yes, the unvaccinated played a major role.

Not as well known are some previous measles outbreaks. One of these occurred in Ohio in 2014 and was traced to unvaccinated Amish men who traveled to the Phillippines, where measles is endemic. In fact, it’s bad there. with the World Health Organization having confirmed 21,403 cases of measles and 110 measles-associated deaths. This brings us to a study that appeared today in The New England Journal of Medicine (NEJM) that examined this particular outbreak, A Measles Outbreak in an Underimmunized Amish Community in Ohio. It’s more of a narrative than a study in that it’s a descriptive study of what happened, including the efforts used to contain the outbreak once it was identified, noting in the introduction:

When measles outbreaks occur in a region in which measles has been eliminated, they occur in clusters of unvaccinated persons, including those in religious communities. The Amish, a Christian sect descended from the Swiss Anabaptists, practice group solidarity and rejection of modern conveniences. Although the Amish Church does not specifically prohibit vaccination, the personal and cultural beliefs of the Amish limit participation in preventive health care, which results in low immunization rates16-19 and an increased risk of vaccine-preventable diseases. During measles outbreaks, the infection can spread unchecked among community members, which subsequently places susceptible persons in the general population at risk. Such outbreaks afford a unique opportunity to measure the ways in which high baseline immunity in a population and targeted public health responses contribute to the prevention of measles epidemics.

During the outbreak, which lasted from March to July 2014, there were 573 suspected cases of measles investigated, of which 190 (33%) were ruled out, which resulted in 383 confirmed cases. The authors note that this outbreak occurred in one of the largest Amish settlements in the US, with over 32,000 people. It was centered in Holmes County but quickly spread to neighboring counties. The overall age distribution showed that 26% of the cases occurred among children from 5-17 years of age and 48% among young adults 18-39 years of age—at least until the halfway point of the outbreak. After that, the rates changed to 52% and 25%, respectively. Early on in the outbreak, the transmission setting for 38% of the cases was church, and for 48% was home; later in the outbreak, these rates changed to 5% and 90%, respectively. Public places where lots of people gather are fantastic incubators to get an outbreak started.

Here’s where vaccination status comes in:

Before the outbreak, 340 case patients (89%) were unvaccinated As part of the public health response, 106 case patients (28%) received the MMR vaccine; of these, 16 (15%) received the vaccine before assumed exposure. No case patients received immune globulin as prophylaxis after exposure.

In 2014 in the general population in Ohio, vaccination coverage with at least one dose or at least two doses of MMR among young children and adolescents was 95.6% and 88.2%, respectively, and coverage with at least two doses of MMR among children in kindergarten was 91.9%.33 On the basis of data collected from the affected households, coverage with at least a single dose of MMR vaccine in this community was estimated to be at least 14% before the outbreak.

And there’s why the outbreak was able to spread so fast. MMR uptake among this Amish community was far below what was required to provide herd immunity. The exact percentage vaccinated necessary to maintain herd immunity depends on several factors. It’s not necessary to go into them here, but suffice to say that for a disease as highly contagious as measles in general vaccine uptake greater than 90% of the population is needed. Thus, this outbreak demonstrates how, in a state where vaccine uptake is very high there can still be a large outbreak. All it takes is a pocket of people with low vaccine uptake, like the Amish in Ohio. This is illustrated in a video that accompanies the article that’s well worth watching.

The article also details the public health response. This included containment interventions conducted according to CDC guidelines. These included enhanced surveillance, meetings with bishops and local health department personnel to encourage reporting, to emphasize the importance of vaccination, and to inform patients about the availability of testing. News of the outbreak spread rapidly through word-of-mouth, as well as by stories in the local Amish newspapers. Alerts were sent to health care providers. The jack-booted thugs from the CDC public health advisors from the CDC (sorry, dealing with antivaccine loons for so long sometimes causes me to lapse into their jargon) assisted local health officials in their investigation, and door-to-door case finding was conducted in areas where underreporting was suspected.

There there was a mass vaccination campaign:

During 120 free vaccination clinic sessions, 12,229 doses of MMR vaccine were administered to 10,644 persons; 6461 of the persons who received at least one dose (61%) were 5 to 39 years of age (Table 3 and Figure 3FIGURE 3). Case patients were isolated until they were no longer infectious (4 days after the onset of rash), and nonimmune persons who were exposed to measles were voluntarily quarantined at home and followed for the development of symptoms until beyond the maximum incubation period (21 days). The church-related entity that organized the charitable work in the Philippines adopted pretravel immunization measures for subsequent volunteers.

These are the sorts of things public health officials have to do once an outbreak starts. Preventing an outbreak is, obviously, far more desirable. One notes that persuading the population to vaccinate, even in the case of an outbreak. Fortunately, this time around the community involved was less resistant to vaccination than during past outbreaks and was very cooperative:

A few notable features of the outbreak revealed important characteristics of the affected community. First, the degree of opposition to immunization was less strenuous than it was in previous outbreaks among the Amish, in which vaccination was refused. In addition, infectious and exposed persons were willing to limit attendance at church gatherings, weddings, and other events, which may explain the changes in age distribution and exposure setting during the outbreak; initial transmission seemed to occur more often among adults, whereas subsequent transmission occurred more often among younger age groups once measles was introduced into households. Second, the rate of hospitalization due to measles was lower among the Amish (approximately 3%) than in the general U.S. population (approximately 20%), which may reflect differences in health-seeking behavior and the cost of medical care, because the Amish tend to be uninsured. Third, measles attack rates were 1.5 to 1.9 times as high among persons younger than 40 years of age as among those 40 to 54 years of age, which suggests that older age groups had previous natural immunity; this finding is consistent with reported measles outbreaks in Ohio in the late 1980s. The fact that no case patients were 55 years of age or older supports the statement in official recommendations that persons born before 1957 have presumptive evidence of measles immunity. Fourth, although we had expected lower attack rates among children younger than 1 year of age because of transfer of maternal antibodies, unvaccinated mothers had a high probability of remaining susceptible through early adulthood because of the low background incidence of measles in an area in which measles has been eliminated, which therefore diminished any potential transfer of protective antibodies to their neonates.

In other words, when measles isn’t around in the population, you can’t count on maternal antibodies transferred to the baby protecting against measles. All of this brings us to the conclusion:

This evaluation illustrates the way in which a clustering of persons who do not routinely vaccinate against measles can result in an accumulation of susceptible persons and can subsequently create a niche of sustained measles transmission. Since the outbreak, local health departments have continued to promote and offer vaccination. Although acceptance of vaccination among some of the Amish has generally improved, the demand for immunization has varied by county, and efforts to ascertain and to improve coverage in this and other Amish communities are needed. We highlight the importance of early recognition of measles and suggest that prompt initiation of control measures ahead of the epidemic curve may be key to limiting the spread of measles. Effective strategies rely on community commitment through engagement of local leaders, isolation of infectious persons, quarantine of those exposed, and vaccination of susceptible persons. The single best means of containment of measles, however, is maintenance of high initial levels of measles immunity in the population.

Let’s repeat that again: The best means of containment of measles is the maintenance of high initial levels of measles immunity in the population—through vaccination.

The question then becomes: How to maintain that high level of vaccination. To this end, there was also a Perspective article by James Colgrove, PhD, MPH entitled Vaccine Refusal Revisited — The Limits of Public Health Persuasion and Coercion. This is an article that explicitly addresses the difficult issues around how far the government should go to require vaccination. Colgrove starts his article that coercion as a strategy in public health goes way back, citing examples from the 19th century of compulsory smallpox vaccination laws that covered both children and adults. These laws included penalties that ranged from exclusion from school for unvaccinated children and fines or quarantine for adults who refused vaccination. These laws worked, too, and, contrary to what you will hear from antivaccinationists, their constitutionality was consistently upheld in numerous court challenges that ultimately made it to the Supreme Court, where the 1905 Supreme Court case of Jacobson v. Massachusetts also affirmed their constitutionality.

As time went on, persuasion became as important, if not more so, than coercion:

The use of coercion has always raised concerns about state intrusions on individual liberty and the scope of parental control over child-rearing. Compulsory vaccination laws in the 19th century typically contained no explicit opt-out provisions. Today, all states offer medical exemptions, and almost all offer religious or philosophical exemptions. Nevertheless, even a law with an opt-out provision may exert a coercive effect, to the extent that the availability of the exemption may be limited and conditional and the consequence of the law is to make the choice to withhold vaccination more difficult (if only marginally so) for the parent. These laws continue to be the target of antivaccination activism.

That’s an understatement. Fast forward 110 years, to when SB 277 was passed in California. Passed in the wake of the Disneyland measles outbreak, it’s a law that fully took effect this school year and eliminated non-medical exemptions to school vaccine requirements. Given how easy nonmedical exemptions were to obtain in California, it was a not unreasonable measure to take. Unfortunately, although other states have tried to pass similar laws since, no other state has succeeded. In any case, resistance to SB 277 has been fierce, with demonstrations, but also disturbingly lots of Nazi imagery comparing the law to the Holocaust and the unvaccinated to Jews, complete with some even making badges patterned after the yellow Star of David badges Jews were forced to wear to identify themselves in the Third Reich and conquered territories.

Colgrove points out that today public health officials are working on both persuasion and coercive approaches, but mostly persuasion. He notes that social scientists are working to develop a much more nuanced understanding of the phenomenon of vaccine hesitancy, which actually encompasses a wide range of behaviors that range from reluctance to vaccinate to suspicion of some vaccines but not others to wanting to delay vaccines to full-out antivaccine wingnuts like the crew at Age of Autism or The Drinking Thinking Moms’ Revolution. Of course, one thing that I tend to think that social scientists do too much of is trying to craft strategies to reach antivaccinationists. Don’t get me wrong. Reaching the vaccine-hesitant is important. Many, if not most, of them can be reached with the right message. Trying to reach the hard core antivaccine wingnuts is what I like to call a long run for a short slide, a lot of effort for not much chance of a return.

Where I do agree with Colgrove is that neither coercion nor persuasion is sufficient. Noting that even the best-crafted persuasive appeals can’t achieve the near-universal vaccine uptake needed to protect the population against a disease as contagious as measles, he concludes:

Both persuasion and coercion are necessary, and neither is sufficient. Laws serve as a critical safety net as well as a powerful symbolic statement of proimmunization social norms. Education and persuasion are needed to maintain public understanding of the value of vaccines and trust in health professionals, both of which are essential to securing compliance with laws. The melding of the two approaches — along with ensuring a stable, accessible, and affordable supply of vaccines for everyone who needs them — is the central challenge for vaccine policymakers. As has been the case since the 19th century, effectiveness, efficiency, ethics, and political acceptability all need to be balanced in a careful calculus.

Figuring out what the proper balance is and how to achieve that calculus is more difficult now than it was in the 19th century or even the 20th century. Thanks to the Internet and social media, antivaccine forces, which were relegated to using pamphlets and speeches, can reach millions or billions. They can forge like-minded virtual communities of individuals imbibing the same self-reinforcing misinformation, immune to correction. That is the unique challenge of the 21st century in maintaining high vaccine uptake.



from ScienceBlogs http://ift.tt/2dGKEzs

Whenever we discuss vaccines and vaccine hesitancy, thanks to Andrew Wakefield the one vaccine that almost always comes up is the MMR, which is the combined measles-mumps-rubella vaccine. In 1998, Wakefield published a case series of cherry-picked patients in which he strongly inferred that the MMR vaccine was associated with autism and “autistic enterocolitis.” Of course, even the way Wakefield spun it, this wasn’t enough evidence to link the MMR vaccine to autism, which is no doubt why Wakefield never explicitly said that it did in the paper describing his case series. My guess has always been that the peer reviewers wouldn’t let him. However, outside of the scientific literature, unconstrained by peer reviewers, Wakefield was not nearly so shy about explicitly linking the MMR to autism. As a result, MMR uptake plummeted in the UK, and measles returned to become endemic again, after having been declared eliminated before. We now know Wakefield is a fraud, thanks to Brian Deer’s excellent investigative work, but the damage was done, and MMR uptake still hasn’t returned to pre-scare levels.

Unfortunately, measles is still in the news, even in the US, where the predominant mode of antivaccine fear mongering has not been about MMR, at least not the way it was in the UK in the wake of Wakefield’s case series. Most recently, there was what has become known as the Disneyland measles outbreak, in which an outbreak centered at Disneyland resulted in mini-outbreaks throughout the country. And, yes, the unvaccinated played a major role.

Not as well known are some previous measles outbreaks. One of these occurred in Ohio in 2014 and was traced to unvaccinated Amish men who traveled to the Phillippines, where measles is endemic. In fact, it’s bad there. with the World Health Organization having confirmed 21,403 cases of measles and 110 measles-associated deaths. This brings us to a study that appeared today in The New England Journal of Medicine (NEJM) that examined this particular outbreak, A Measles Outbreak in an Underimmunized Amish Community in Ohio. It’s more of a narrative than a study in that it’s a descriptive study of what happened, including the efforts used to contain the outbreak once it was identified, noting in the introduction:

When measles outbreaks occur in a region in which measles has been eliminated, they occur in clusters of unvaccinated persons, including those in religious communities. The Amish, a Christian sect descended from the Swiss Anabaptists, practice group solidarity and rejection of modern conveniences. Although the Amish Church does not specifically prohibit vaccination, the personal and cultural beliefs of the Amish limit participation in preventive health care, which results in low immunization rates16-19 and an increased risk of vaccine-preventable diseases. During measles outbreaks, the infection can spread unchecked among community members, which subsequently places susceptible persons in the general population at risk. Such outbreaks afford a unique opportunity to measure the ways in which high baseline immunity in a population and targeted public health responses contribute to the prevention of measles epidemics.

During the outbreak, which lasted from March to July 2014, there were 573 suspected cases of measles investigated, of which 190 (33%) were ruled out, which resulted in 383 confirmed cases. The authors note that this outbreak occurred in one of the largest Amish settlements in the US, with over 32,000 people. It was centered in Holmes County but quickly spread to neighboring counties. The overall age distribution showed that 26% of the cases occurred among children from 5-17 years of age and 48% among young adults 18-39 years of age—at least until the halfway point of the outbreak. After that, the rates changed to 52% and 25%, respectively. Early on in the outbreak, the transmission setting for 38% of the cases was church, and for 48% was home; later in the outbreak, these rates changed to 5% and 90%, respectively. Public places where lots of people gather are fantastic incubators to get an outbreak started.

Here’s where vaccination status comes in:

Before the outbreak, 340 case patients (89%) were unvaccinated As part of the public health response, 106 case patients (28%) received the MMR vaccine; of these, 16 (15%) received the vaccine before assumed exposure. No case patients received immune globulin as prophylaxis after exposure.

In 2014 in the general population in Ohio, vaccination coverage with at least one dose or at least two doses of MMR among young children and adolescents was 95.6% and 88.2%, respectively, and coverage with at least two doses of MMR among children in kindergarten was 91.9%.33 On the basis of data collected from the affected households, coverage with at least a single dose of MMR vaccine in this community was estimated to be at least 14% before the outbreak.

And there’s why the outbreak was able to spread so fast. MMR uptake among this Amish community was far below what was required to provide herd immunity. The exact percentage vaccinated necessary to maintain herd immunity depends on several factors. It’s not necessary to go into them here, but suffice to say that for a disease as highly contagious as measles in general vaccine uptake greater than 90% of the population is needed. Thus, this outbreak demonstrates how, in a state where vaccine uptake is very high there can still be a large outbreak. All it takes is a pocket of people with low vaccine uptake, like the Amish in Ohio. This is illustrated in a video that accompanies the article that’s well worth watching.

The article also details the public health response. This included containment interventions conducted according to CDC guidelines. These included enhanced surveillance, meetings with bishops and local health department personnel to encourage reporting, to emphasize the importance of vaccination, and to inform patients about the availability of testing. News of the outbreak spread rapidly through word-of-mouth, as well as by stories in the local Amish newspapers. Alerts were sent to health care providers. The jack-booted thugs from the CDC public health advisors from the CDC (sorry, dealing with antivaccine loons for so long sometimes causes me to lapse into their jargon) assisted local health officials in their investigation, and door-to-door case finding was conducted in areas where underreporting was suspected.

There there was a mass vaccination campaign:

During 120 free vaccination clinic sessions, 12,229 doses of MMR vaccine were administered to 10,644 persons; 6461 of the persons who received at least one dose (61%) were 5 to 39 years of age (Table 3 and Figure 3FIGURE 3). Case patients were isolated until they were no longer infectious (4 days after the onset of rash), and nonimmune persons who were exposed to measles were voluntarily quarantined at home and followed for the development of symptoms until beyond the maximum incubation period (21 days). The church-related entity that organized the charitable work in the Philippines adopted pretravel immunization measures for subsequent volunteers.

These are the sorts of things public health officials have to do once an outbreak starts. Preventing an outbreak is, obviously, far more desirable. One notes that persuading the population to vaccinate, even in the case of an outbreak. Fortunately, this time around the community involved was less resistant to vaccination than during past outbreaks and was very cooperative:

A few notable features of the outbreak revealed important characteristics of the affected community. First, the degree of opposition to immunization was less strenuous than it was in previous outbreaks among the Amish, in which vaccination was refused. In addition, infectious and exposed persons were willing to limit attendance at church gatherings, weddings, and other events, which may explain the changes in age distribution and exposure setting during the outbreak; initial transmission seemed to occur more often among adults, whereas subsequent transmission occurred more often among younger age groups once measles was introduced into households. Second, the rate of hospitalization due to measles was lower among the Amish (approximately 3%) than in the general U.S. population (approximately 20%), which may reflect differences in health-seeking behavior and the cost of medical care, because the Amish tend to be uninsured. Third, measles attack rates were 1.5 to 1.9 times as high among persons younger than 40 years of age as among those 40 to 54 years of age, which suggests that older age groups had previous natural immunity; this finding is consistent with reported measles outbreaks in Ohio in the late 1980s. The fact that no case patients were 55 years of age or older supports the statement in official recommendations that persons born before 1957 have presumptive evidence of measles immunity. Fourth, although we had expected lower attack rates among children younger than 1 year of age because of transfer of maternal antibodies, unvaccinated mothers had a high probability of remaining susceptible through early adulthood because of the low background incidence of measles in an area in which measles has been eliminated, which therefore diminished any potential transfer of protective antibodies to their neonates.

In other words, when measles isn’t around in the population, you can’t count on maternal antibodies transferred to the baby protecting against measles. All of this brings us to the conclusion:

This evaluation illustrates the way in which a clustering of persons who do not routinely vaccinate against measles can result in an accumulation of susceptible persons and can subsequently create a niche of sustained measles transmission. Since the outbreak, local health departments have continued to promote and offer vaccination. Although acceptance of vaccination among some of the Amish has generally improved, the demand for immunization has varied by county, and efforts to ascertain and to improve coverage in this and other Amish communities are needed. We highlight the importance of early recognition of measles and suggest that prompt initiation of control measures ahead of the epidemic curve may be key to limiting the spread of measles. Effective strategies rely on community commitment through engagement of local leaders, isolation of infectious persons, quarantine of those exposed, and vaccination of susceptible persons. The single best means of containment of measles, however, is maintenance of high initial levels of measles immunity in the population.

Let’s repeat that again: The best means of containment of measles is the maintenance of high initial levels of measles immunity in the population—through vaccination.

The question then becomes: How to maintain that high level of vaccination. To this end, there was also a Perspective article by James Colgrove, PhD, MPH entitled Vaccine Refusal Revisited — The Limits of Public Health Persuasion and Coercion. This is an article that explicitly addresses the difficult issues around how far the government should go to require vaccination. Colgrove starts his article that coercion as a strategy in public health goes way back, citing examples from the 19th century of compulsory smallpox vaccination laws that covered both children and adults. These laws included penalties that ranged from exclusion from school for unvaccinated children and fines or quarantine for adults who refused vaccination. These laws worked, too, and, contrary to what you will hear from antivaccinationists, their constitutionality was consistently upheld in numerous court challenges that ultimately made it to the Supreme Court, where the 1905 Supreme Court case of Jacobson v. Massachusetts also affirmed their constitutionality.

As time went on, persuasion became as important, if not more so, than coercion:

The use of coercion has always raised concerns about state intrusions on individual liberty and the scope of parental control over child-rearing. Compulsory vaccination laws in the 19th century typically contained no explicit opt-out provisions. Today, all states offer medical exemptions, and almost all offer religious or philosophical exemptions. Nevertheless, even a law with an opt-out provision may exert a coercive effect, to the extent that the availability of the exemption may be limited and conditional and the consequence of the law is to make the choice to withhold vaccination more difficult (if only marginally so) for the parent. These laws continue to be the target of antivaccination activism.

That’s an understatement. Fast forward 110 years, to when SB 277 was passed in California. Passed in the wake of the Disneyland measles outbreak, it’s a law that fully took effect this school year and eliminated non-medical exemptions to school vaccine requirements. Given how easy nonmedical exemptions were to obtain in California, it was a not unreasonable measure to take. Unfortunately, although other states have tried to pass similar laws since, no other state has succeeded. In any case, resistance to SB 277 has been fierce, with demonstrations, but also disturbingly lots of Nazi imagery comparing the law to the Holocaust and the unvaccinated to Jews, complete with some even making badges patterned after the yellow Star of David badges Jews were forced to wear to identify themselves in the Third Reich and conquered territories.

Colgrove points out that today public health officials are working on both persuasion and coercive approaches, but mostly persuasion. He notes that social scientists are working to develop a much more nuanced understanding of the phenomenon of vaccine hesitancy, which actually encompasses a wide range of behaviors that range from reluctance to vaccinate to suspicion of some vaccines but not others to wanting to delay vaccines to full-out antivaccine wingnuts like the crew at Age of Autism or The Drinking Thinking Moms’ Revolution. Of course, one thing that I tend to think that social scientists do too much of is trying to craft strategies to reach antivaccinationists. Don’t get me wrong. Reaching the vaccine-hesitant is important. Many, if not most, of them can be reached with the right message. Trying to reach the hard core antivaccine wingnuts is what I like to call a long run for a short slide, a lot of effort for not much chance of a return.

Where I do agree with Colgrove is that neither coercion nor persuasion is sufficient. Noting that even the best-crafted persuasive appeals can’t achieve the near-universal vaccine uptake needed to protect the population against a disease as contagious as measles, he concludes:

Both persuasion and coercion are necessary, and neither is sufficient. Laws serve as a critical safety net as well as a powerful symbolic statement of proimmunization social norms. Education and persuasion are needed to maintain public understanding of the value of vaccines and trust in health professionals, both of which are essential to securing compliance with laws. The melding of the two approaches — along with ensuring a stable, accessible, and affordable supply of vaccines for everyone who needs them — is the central challenge for vaccine policymakers. As has been the case since the 19th century, effectiveness, efficiency, ethics, and political acceptability all need to be balanced in a careful calculus.

Figuring out what the proper balance is and how to achieve that calculus is more difficult now than it was in the 19th century or even the 20th century. Thanks to the Internet and social media, antivaccine forces, which were relegated to using pamphlets and speeches, can reach millions or billions. They can forge like-minded virtual communities of individuals imbibing the same self-reinforcing misinformation, immune to correction. That is the unique challenge of the 21st century in maintaining high vaccine uptake.



from ScienceBlogs http://ift.tt/2dGKEzs

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