Friday, August 5, 2011

Measles Part 2: The Vaccine and the Control of a Killer


This week at Infection Landscapes I will conclude the 2 part series on measles by examining the measles vaccine, as well as efforts in various areas across the world to control and eliminate the disease. We will take a solid look at good clinical and epidemiologic data showing measles vaccine to be safe and effective in preventiing measles. We will also examine the fraudulent Wakefield study to show how the results and conclusions do not represent good science. I will conclude with a discussion of the potential for measles eradication. As we will see, the nature of the infection has some elements that make it a good candidate for eradication, while other features that present significant, and perhaps, insurmountable obstacles. We inhabit a moment in time demanding sober consideration of measles, because we are, unfortunately, on the brink of widespread epidemic.

The Vaccine.  It is beyond the scope of this publication to present a complete introduction to vaccinology. Nevertheless, I think it will be instructive to give some general background on vaccines so that the reader can be grounded in a basic understanding of how they work. Vaccines can be said to fit within 2 broad categories of infection resistance: First, there are those that confer resistance by engaging passive immunity, and second, there are those that confer resistance by engaging active immunity. Vaccines that utilize passive immunity involve the direct injection of non-host antibodies into the host. These vaccines do not involve the host mounting an immune response to antigen. As such, the protection conferred from these kinds of vaccines are typically very short lived. Incidentally, passive immunity is also engaged when maternal antibodies are passed from mother to fetus in utero, and from mother to infant during breastfeeding.

Active immunity, on the other hand, results in protection that is a product of the host's own immune system. Active immunity follows the host's own immune response following exposure to an antigen. Immunogenic antigens are foreign particles, commonly protein or polysaccharide components of organisms, that are recognized by the host's immune system and subsequently elicit a response. Ultimately, the goal of active immunization is to stimulate an immune response to one or more of these antigens, which then confers protective immunity to natural infection by the pathogenic organism without causing serious clinical illness.

Depending on what aspects of a vaccine you are trying to classify, or research, there are four broad categories of vaccines that stimulate active immunity: live attenuated vaccines, inactivated vaccines, recombinant vaccines, and DNA vaccines. The first two are mutually exclusive, since the first involves a living organism and the second does not, but not all four categories are necessarily exclusive of each other. For the sake of simplicity I am going to limit this brief introduction to a description of the first two categories: live attenuated vaccines and inactivated vaccines.

Live attenuated vaccines are vaccines wherein the pathogenic organism has been rendered non-pathogenic, but remains viable. I say "viable" rather than "alive" because viruses cannot be said to be truly alive (to be fair, this is the source of some considerable debate). The essential function of such a vaccine is to inoculate the host with the viable organism, in non-pathogenic form, so that it can replicate or multiply in the host and thereby induce an immune response. The ability of the organism to make more of itself is the critical step, which, of course, requires that the organism remains "alive" even though it is no longer pathogenic. Live vaccines typically generate a strong immune response, stimulating both humoral and cell-mediated immunity, both of which also involve the production of memory B and T cells, respectively. As such, the active immunity gained from live vaccines tends to be long-term, often life-long, if the correct dosing schedule is followed. While these vaccines are very good at stimulating powerful immune responses and conferring long-term immune memmory, their widespread distribution can often be hampered by one important factor: they require a cold chain. Because the organisms in the vaccines are viable "living" organisms, they require a regulated microclimate during the course of their transportation from one geographical area to the next. In other words, they have to be kept at a constant temperature, which is typically much cooler than the outdoor temperature in tropical locations. Thus, the geographic distribution of live vaccines requires that they be kept "cold" at each point along the transport "chain" as they move by air, road, waterway, or cross-country, through the landscape. Thus, the cold chain. In tropical or sub-tropical resource-poor areas this can be a daunting logistical task, which often foils attempts at widespread distribution of vaccine.

Inactivated vaccines consist of either 1) whole microbes that have been "killed", using heat or chemicals, for example, or 2) extracted or purified components of the organisms, which serve as immunogenic antigens to stimulate the host's immune response. Inactivated vaccines typically stimulate short-lived immunity that is more humoral than cell-mediated, and which is much poorer at generating immunologic memory. This is because the organisms are no longer viable and so do not replicate in the host. These vaccines will often require several doses to boost the specific antibody level, and since the immunologic memory produced is not good, the protective immunity conferred usually wanes with time, which necessitates booster doses to reestablish immunity. One of the great benefits of inactivated vaccines, however, is their robustness to the environment. Because they do not incorporate viable organisms, these vaccines typically do not require a cold chain. As such, they are much more amenable to widespread distribution in geographic locations that would otherwise present logistical difficulties in dissemination.

This very brief introduction just scratches the surface of vaccines. In the infectious disease course that I teach, I usually spend 2 lectures on general vaccinology. Nevertheless, the current description should provide a basic understanding of the nature of vaccines so that we can proceed to discuss the measles vaccine specifically.

Measles vaccine is a live attenuated vaccine. It can be administered as a single-antigen vaccine for measles virus alone, or it can be combined with other antigen innoculations for combination vaccination programs. Examples of the latter include the measles-rubella (MR) vaccine, the measles-mumps-rubella (MMR) vaccine, or the measles-mumps-rubella-varicella (MMRV) vaccine. The vaccine, in each of these forms, is remarkably effective at conferring individual protection and herd immunity, when administration is optimized. Optimal administration of measles vaccine is determined by three critical factors: First, the age at which the first dose of vaccine is given; Second, the scheduling of second, follow-up inoculations in routine vaccine schedules; Third, the level of vaccine coverage across the whole population.

Let's consider each in turn.

The age at which children received their first vaccination is directly associated with the success of the vaccine. Administering the vaccine at 9 months of age, which is the age of routine vaccination in many countries where measles is endemic, will typically result in approximately 85% of the children developing protective antibody titers. However, when the vaccine is administered at 12 months of age, between 90% and 95% of children develop protective antibody titers. The difference is due to the cross-reaction of the vaccine with maternal antibodies, which may still be circulating in large enough quantities in some children to prevent the immune system from mounting a complete immune response to the attenuated measles virus. As such, the vaccine can lose its efficacy in up to 10% of children. However, as we discussed in detail in Measles Part 1, in countries where measles is endemic, the administration of vaccine at an earlier age may be a public health necessity in order to prevent maximal morbidity and mortality in the most vulnerable population, i.e. young children and infants. Therefore, it will often be the case, that a large-scale measles control campaign will first have to prioritize a shift in the burden of disease from the youngest children to the older children, so the age-dynamics of measles transmission will also shift. Such a shift will eventually lead to less risk in the youngest age group, and thus the ability to vaccinate at 12 months instead of 9 months, with the resulting improved efficacy and increased generalized herd immunity soon to follow. See Measles Part 1 for an explanation of measles transmission dynamics.

The scheduling of second inoculations as part of routine vaccination schedules is very important because the duration of protection conferred by measles vaccine will not be life-long for everyone inoculated. In fact, secondary vaccine failure occurs in approximately 5% of children between 10 and 15 years after the initial vaccination. This may not sound like much, but in most populations it will be enough to compromise herd immunity and in any population it will always be enough to interrupt the potential for virus elimination. This is due to the extreme infectivity of measles virus as discussed last time in Measles Part 1.

The level of vaccine coverage across a given population is an important contributor to the endemicity of disease and the transmission dynamics, which, again, where described in detail in Measles Part 1. A minimum of 95% consistent vaccine coverage in a population is required to both maintain complete herd immunity and create the potential for measles elimination in that population. This high level of vaccine coverage is, again, due to the highly infectious nature of the measles virus.

Are there adverse events associated with this vaccine? Let's consider the reality: To begin, this vaccine, as I have already stated above, is very safe. This is not my opinion, nor is it the opinion of the public health or medical community. Instead, this is a conclusion drawn from extensive and exhaustive study conducted over 50 years, from the early 1960s (the vaccine was introduced in 1963) until the present day. In March 1968, a study was published in the British Medical Journal comparing the administration of live measles vaccine, live plus killed measles vaccine, and no vaccine among 36, 211 British children randomized to one of the three arms. This publication constituted the Second Report to the Medical Research Council by the Measles Vaccines Committee of the UK. The study was initiated in 1964 and reported on two years of follow-up in this population sample. The live vaccine alone showed 94%, and the live plus killed vaccine showed 88% efficacy, and neither demonstrated any complications. This study represents some of the earliest population-based, randomized controlled trial data we have with very large numbers of participants. It is a very good early argument for the efficacy and safety of measles vaccine. Many subsequent studies followed reaffirming these findings.

Today, however, the trivalent measles, mumps, rubella (MMR) vaccine is the form common to most vaccine schedules. In 1975, the Bullentin of the World Health Organization reported the results from a population-based randomized controlled trial in the Dominican Republic. Immunogenicity was achieved in 99% of the 926 participants. Furthermore, there was no difference in side effects between the trivalent vaccinees and those receiving either the monovalent measles vaccine, or no vaccine at all. Similarly, this report represents some of the earliest population-based randomized controlled trial data demonstrating the safety and efficacy of the MMR vaccine.

These early studies have been followed by decades of similar studies affirming the safety and efficacy of measles vaccination. An exhaustive systematic review was conducted by the European Research Program for Improved Vaccine Safety Surveillance. This review, which was published in the journal Vaccine in September of 2003, examined 22 high-quality prospective and retrospective studies conducted to assess potential adverse events associated with MMR. Synthesizing all of these studies, the report concluded that the MMR is not associated with Crohn's disease, autism, asceptic meningitis, or other major adverse events when comparing vaccinees to placebo.

In February of 1998, the Lancet published a study by Andrew Wakefield and colleagues entitled, Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children. This paper, which has now been retracted by the Lancet because the methods, data and conduct of the study have been thoroughly discredited, posited an assoication between reciept of the MMR vaccine and the development of autism. This claim was based on 12 gastrointestinal patients of the author. The authors purported that the MMR vaccine components caused inflammation in the epithelium of the gut tract in these children, which subsequently led to neurologic sequelae consistent with autism. This study had no control group, and no biologic plausibility defined by a pathway from MMR inoculation to gut disease to autism. No such relationships had previously be reported, nor was there any biologic model in which they fit. In addition, the temporal association between MMR vaccine and gut and neurologic symptoms was based on retrospective assessment of vaccine history by the parents. Thus, there is great potential for recall bias. So the conclusions based on the data, as they were, were not scientifically sound. Moreover, it has since been revealed, largely due to the outstanding investigation conducted by Brian Deer for the the Times of London, that, aside from the scientifically unsound conclusions drawn from the paper's results, Wakefield falsified the actual laboratory findings, which found no MMR DNA sequences in 99% of the samples tested. Those that were positive were not different among the autistic and non-autistic children. Furthermore, Deer's investigations revealed several conflicts of interest, including a patent for a new monovalent measles vaccine and over half a million pounds in funding from a legal firm to aid in identifying a link between MMR and autism.

During the initial press conference convened to adress Wakefield's 1998 Lancet paper, he stated that he did not think it safe to continue with trivalent vaccination against measles, mumps and rubella until the link between MMR and autism could be more clearly elucidated. This media coverage, as well as the explosive media coverage that followed for several years, is likely responsible for the dramatic decline in MMR vaccination in the beginning of the 21st century and the subsequent rise in measles incidence in many countries that had previously attained very good levels of measles control. Many thousands of cases and hundreds of deaths have followed in geographic regions where measles had been eliminated.

Andrew Wakefield's unethical and fraudulent scientific conduct notwithstanding, there have been a plethora of well conducted epidemiologc studies examining the potential association between autism and MMR, autism and thimerosal, and autism and multiple vaccine administration. All have shown that no association exists between autism and vaccination. In February of 2009, the journal Vaccine published another a review of 27 studies examining each of these possible links, all of which were clearly shown to demonstrate no association with autism.

In summary, across decades of rigorous study we know the following: approximately 5-15% of vaccine recipients will develop fever following vaccination. Also, approximately 5% of vaccine recipients will develop a transient rash that resolves in a few days. There is NO association, causal or otherwise, between measles vaccine and autism.

In addition to decades of scientific research that has unequivocally established the safety and effectiveness of measles vaccine, In the United States there are 2 very important surveillance programs in place, which are responsible for collecting data on all adverse events associated with all vaccine administration across the country on an annual basis. And these programs will continue to do so for as long as we administer vaccines. The first program is the Vaccine Safety Datalink (VSD), which was established in 1991 as a partnership between the Centers for Disease Control and Prevention (CDC) and health management organizations (HMOs). This program has effectively established large age cohorts over the last 20 years for the observation of any potential adverse events associated with any vaccine administered in the HMO setting, which constitutes the majority of personal interface with clinical services in the United States. While initially established for children, this vaccine surveillance program has subsequently been expanded to include adolescents and adults as well.

The other major program is the National Vaccine Adverse Events Reporting System (VAERS). This is a passive surveillance system so it is dependent upon the accurate reporting of clinical personnel and local health departments for the collection of case-series data. Unlike the VSD, the VAERS results are based on case-series so there is no denominator and, thus, this surveillance system cannot be used to estimate rates. As such, VAERS is primarily an early warning system for identifying adverse or rare events associated with vaccines, whereas the VSD is used for estimating rates.

The combination of decades of sound, peer-reviewed scientific research with long-term national surveillance programs have provided overwhelming evidence that measles vaccine is remarkably safe and effective. As I said before, this is not an opinion but rather a scientifically drawn conclusion based on long-term and substantive data. Even still, broad surveillance systems are in place and are well established so that all vaccines are meticulously monitored in the actual human populations in which they are administered. Measles vaccination is safe. We are protected, if we vaccinate.

History and Successes of Vaccination Campaigns. We have discussed how vaccines work, in general, and the nature of measles vaccine, in particular. We have discussed the evidence of measles vaccine safety and efficacy. Now, let us examine the history of measles vaccine intervention and explore the population-based effectiveness of vaccine program implementation, and the great strides that have been made toward control and elimination of this deadly disease.

The measles vaccine was introduced in the United States in 1963 as a single antigen, single dose vaccine. The combination MMR vaccine replaced the single antigen vaccine in 1971, and the two dose schedule was implemented in 1989. Before widespread implementation of the measles vaccine in 1963, there were approximately 500,000 cases of measles per year in the United States. The initial, single dose program reduced measles incidence to approximately 20,000 cases per year by 1968, an already impressive 25-fold reduction in disease. Nevertheless, it was quickly recognized that a single dose across the life course would still leave roughly 5% of the population without immunity due to the 5% vaccine failure after the first inoculation. A second inoculation was shown to be efficacious in 95% of the 5% who had secondary vaccine failure following the first inoculation. A such, the suggested vaccine schedule was expanded to the following in 1989: first dose at 12 to 15 months of age, followed by the second dose at 4 to 6 years of age (corresponding to the time when children enter school). Following the widespread adoption of the expanded schedule, measles incidence was reduced to less than 150 cases per year from 1997 through 2005. The national low was 37 cases in 2004. Here is an informative graph from the CDC demonstrating the change in measles incidence from 1944 to 2007 and how this trajectory is coincident with the introduction of the single and two dose vaccine schedules:


Success has not been limited to the United States, however. Indeed, effective control has been far more widespread throughout the western hemisphere largely due to extraordinary efforts by the Pan American Health Organization (PAHO). By 2002, autochthonous measles was declared eliminated in the western hemisphere. Measles was gone from the Americas with only minor isolated loci of endemicity in the far northern provinces of arctic Canada. While the United States had the benefit of large-scale resources in terms of vaccine production and administration infrastructure, most of the rest of the Americas did not. PAHO's massive mobilization of vaccination campaigns across many diverse local populations throughout the Americas represents one of the most successful public health accomplishments in human history. The PAHO campaign was (and is) comprised of four essential components of vaccination implementation that proceed in distinct phases: Catch-up, Keep-up, Follow-up, and Mop-up.

Catch-up: This is the first phase of the program utilizing a brute force, all-out approach to begin the process of measles elimination. It is a one-time, population-wide comprehensive vaccination of all children between the ages of 1 to 14 years regardless of previous vaccination or disease history.

Keep-up: Although this is the second phase, it also begins at the inception of the overall program. This phase is focused on improving the ongoing regular vaccination program that follows a specific schedule for every individual in a population, beginning in infancy. For example, in the United States, the regular vaccination schedule requires immunization for all children at 12-15 months of age, and then again at 4-6 years of age. This is part of the regular public health infrastructure. So, the object of this phase of the PAHO program was simply to improve the public health infrastructure such that all new children born into a population receive vaccination once they reach the appropriate vaccination age. The specific PAHO goal for this phase has been to achieve 90% regular vaccination coverage in each successive birth cohort.

Follow-up: This phase consists of subsequent, intermittent, population-wide mass vaccination campaigns every 3 to 5 years that now target all children between the ages of 1 to 5 years, but again regardless of previous vaccine or disease history.

Mop-up: This final phases consists of regular ongoing targeting of special, particularly difficult to reach, subpopulations within the wider community. An example of uniquely targeted groups in the Mop-up phase are the homeless, displaced communities, and migratory peoples in difficult to reach geographies.

In addition to these four phases of the broader campaign, measles surveillance with laboratory confirmation of all reported cases has been implemented in every country in the western hemisphere.

The results of this extraordinary campaign are dramatic. Measles incidence has been reduced across the whole of the Americas by greater than 99%, from greater than 250,000 cases per year in 1990 to only 85 cases in 2005. Below is a report from the CDC's Morbidity and Mortality Weekly Report on the early success of the PAHO campaign (published here):


This PAHO campaign is now the global model for regional elimination of measles across the greatly varied geographic landscapes wherein endemic measles remains a credible threat to child health.

In the broader global arena, however, the scope will not necessarily be the same in all geographic regions. This is primarily due to the availability of resources.

Here is the global distribution of vaccine coverage according to the World Health Organization in 2007:




There clearly remains a deficit in coverage for much of Africa and Southeast Asia. There are two factors that conspire to make measles elimination in these regions especially difficult. The first is the nature of the virus, itself, and its extremely high infectivity as we discussed in Measles Part 1. The infectious quality of the virus requires that approximately 95% vaccine coverage is attained in order to hold realistic prospects for regional elimination of measles. The nature of the vaccine is the second important factor that, along with the highly infectious pathogen, undermines efforts to achieve high vaccine coverage: it is a live-attenuated vaccine. Thus it requires a cold chain. The logistics of cold chain transport can be quite challenging in many of the rural areas in the countries represented in the map above. Logistical difficulties are compounded by poverty. Poor countries often lack the resources to obtain enough vaccine for distribution to the whole population, as well as maintaining a cold chain across the large network of transport required to administer the vaccine to all children in the population.

As such, attempts at measles control, especially in resource poor areas, with geographically semi-isolated communities, may begin with goals of mortality reduction rather than regional elimination. The Global Immunization Vision and Strategy (GIVS), which was conceptualized by the a joint effort of the WHO and UNICEF. This strategy calls on UN member states to reduce measles mortality by 90% from that which was experienced in 2000. Mortality reduction campaigns typically employ a one-time, population-wide mass vaccination campaign targeting all children around the age of 9 months. Reducing mortality first may be the most viable first step for measles control in those parts of the world where the disease endemicity remains high.

In addition, some areas where measles elimination had been realized are now threatened with resurgent disease due to waning adherence to vaccine schedules. Much of this lack of adherence stems from public misunderstanding due to the reporting of the flawed study described above. Tens of thousands of cases of measles now occur annually in the UK and France alone. While less in the United States, we nevertheless experienced three times the normal incidence of measles here by the first half of 2011.

The irony is that measles virus is a good candidate for complete eradication, as was achieved with smallpox. Here's why: 1) it has no reservoir other than humans, thus preventing the virus' survival in any sylvan disease cycle, 2) despite being an RNA virus, the RNA genome of measles virus has a fairly low rate of mutation over time, which means we do not have to worry about constantly creating new vaccines in response to antigenic drift, and 3) the vaccine confers a high level of immunogenicity in the host.

However, there is one factor, as described above, that may forever undermine attempts at eradication: the measles virus is so infectious that it requires vaccination of 95% of a given population to effect elimination in that population. Given the difficulty of vaccine transport in those areas where endemicity remains greatest, we find ourselves so close...and, yet, so far.


23 comments:

  1. When you discuss the damaging Wakefield study, you place the blame on the media for propagation of the story. I think that at least part of the blame belongs with the celebrity attention that the study received. Anti-vaccine movements, like other movements, need to have fame and/or money to be able to present their side to others and convince others of their side.
    You also mention toward the end there is a low mutation rate, despite the fact that it is an RNA virus. Is it possible, with its small genome that only codes for 8 proteins, that each protein is so specific to measles infection that a mutation will negatively affect the virus's ability to infect?

    ReplyDelete
    Replies
    1. I believe that that is correct: that the genome of measles is quite parsimonious, so what you expect to happen with an RNA virus--mutations accumulating without a proofreading function--doesn't create a virus with new antigenic markers because the mutations lead to loss of function.

      The other reason, is that the measles virus is not segmented, so it cannot undergo genetic reassortment in the way that, say, influenza virus does.

      It's possible that the blame belongs with celebrity attention, but it seams as though we're also losing our collective memory. I've never met anyone with the measles, or any of the potentially awful sequelae (like irreversible encephalopathy). I think it may be the case that, where vaccines are concerned, and especially effective vaccines, it might be our challenge to remember that we are actively preventing disease, especially when that disease's marks on society aren't seen.

      Delete
  2. Christopher DonnellySeptember 29, 2011 at 5:02 PM

    I agree with this idea of needing financial support for attention, but I also believe that a lot of anti-vaccine movements have to do with a general distrust for government or medicine in general. As we saw this week with the ebola outbreak case study, there was a strong distrust for the health care workers in Gabon investigating the outbreak; I realize that an outbreak is different then a vaccine, but the idea is the same. The media and celebrity influences will get the word out there, but I belief that a distrust in authority is also a main driving factor. Like the Swine Flu outbreak of 2009, it seems as though people are just waiting for a reason to support these anti-vaccine movements

    ReplyDelete
    Replies
    1. I agree with the notion that distrust or doubt in medicine, or sometimes worse – the confusion by “scientific knowledge” as published in Wakefield’s study, leads to refusal of vaccination and anti-vaccine movements in the general public. The safety, effectiveness and adverse effects of a vaccine are certainly important factors the public is most concerned about. In addition, these information will not be confirmed until years of study, just like MMR vaccine. It is the public health and medical professionals’ obligation to clarify the misunderstanding and to disseminate the correct information to the public. More importantly, a strict and on-going surveillance system should be maintained to help eliminate the disease – not just continuing on the current vaccination protocol, but also focusing on the program that targets on the generation who has missed the best opportunity for vaccination due to false information, as importations of measles from other countries that have low adherence to the vaccination have posed the greatest risk for outbreaks in U.S.

      Delete
  3. Andriane MelanthiouOctober 7, 2011 at 1:52 PM

    Immunizations have been a great way of protecting the public from a variety of diseases and associated outbreaks. I know that besides the anti-vaccine movements we have seen in the past, a lot of religious groups do not believe in vaccinations or even regularly visiting a physician. This is a bit scary to say the least because such beliefs really place the general public at high risk. This is something for public health professionals to look into because we should be able to get important health messages across to everyone. Future outbreaks will therefore be reduced if not prevented altogether.

    ReplyDelete
    Replies
    1. @ Andriane Melanthiou you raise a very valid point that public health professionals should investigate how religions can sometime impede individuals from participating in vaccination programs, and how these actions possibly put the general public at risk. I found online that unicef in 2004 started an international intervention program specifically focusing on building trust in immunization by partnering with different religious leaders and groups throughout the world (However, I am not sure if it is still being conducted). The main objectives of this intervention were: forging alliances, building trust, learning from each other, and providing resources. All in hopes that these partnerships would lead to an increase in vaccinations in areas of the world that need them the most.
      Here is the link if you are interested:www.unicef.org/ceecis/building_trust_immunization.pdf

      Delete
    2. I also looked into this issue of religious exemptions for immunizations. It seems that all 50 states require some form of vaccination before a child begins at a public school. However, 48 states have allowed religious exemptions and 18 states have allowed exemptions by "personal belief," by which they mean religious denominations not recognized by the State, such as Pastafarianism, or the Church of the Flying Spaghetti Monster
      (http://www.vaccinesafety.edu/cc-exem.htm).

      This allows the population the option to forego vaccinating their child (in NY, only 0.45% had claimed such a religious exemption in 2011). However, in a recent ruling in NY, a federal judge upheld the City's barring of unvaccinated children from school even though 2 of the children had exemptions, writing in his opinion that he doubted the constitutionality of religious objections to vaccination
      (http://www.nytimes.com/2014/06/23/nyregion/judge-upholds-policy-barring-unvaccinated-students-during-illnesses.html).

      A new challenge for public health officials in trying to gain the trust of the community is the rising prices of vaccinations. As Dr. Walsh pointed out in the article, a cold chain is required for the MMR vaccine and it can apparently get quite expensive. Just this week, I saw an article in the NYT where some poor doctor had to remortgage her house to afford the spiking costs of vaccines and secure fridges for these vaccines. The MMR shot apparently costs her patients over $50, and there are two shots. Many patients may not be able to afford the $100 and with insurance companies reimbursing doctors insufficiently for these expensive shots, many private primary care physicians may soon stop offering vaccines. This could spell disaster for many communities, especially poor communities which see an influx of immigrants and/or travelers. Poor communities that either don't have enough information about the benefits of vaccines, don't have enough money to afford the vaccines, or don't have enough doctors offering vaccinations will be at a higher risk for an epidemic if (or should I say when, with the speed of travel being what it is) a malignant organism is introduced. Public health officials must focus on all these issues if measles is to be eradicated. Here's the article:
      http://www.nytimes.com/2014/07/03/health/Vaccine-Costs-Soaring-Paying-Till-It-Hurts.html.

      Delete
    3. Racquel BreretonJuly 18, 2014 at 6:09 PM

      I agree. A lot of these theories and anti-vaccination belief arise from misinformation. People of such communities and groups are not ultimately uninformed. Trust and effective communication are crucial to relay the importance of immunization.

      Delete
  4. In recent times, Measles has gained more coverage due to its now reemergence with now 477 confirmed cases from Jan 1 to June 13th as reported by the CDC
    http://www.cdc.gov/measles/cases-outbreaks.html. Alarming is that this is the highest amount of cases since measles elimination was documented in 2000 with one of the largest clusters in Ohio (138 confirmed cases), California (60) and NY (26) http://www.washingtonpost.com/news/to-your-health/wp/2014/05/29/u-s-measles-outbreak-sets-record-for-post-elimination-era/. Majority of these cases were from travelers and those who weren't vaccinated highlighting an important aspect of public health efforts in trying to combat measles and how fear and lack of awareness following the Wakefield study has now created an atmosphere of doubt and long-term consequences. Herd immunity is now more jeopardized in this sense and that efforts need to be revived to further make sure measles doesn't become more widespread.

    ReplyDelete
    Replies
    1. An excellent point was brought up about how many of the outbreaks have been from travelers who were not vaccinated. The CDC provided useful information on how travelers can take the necessary precautions in order to avoid infection, such as what age and the dose amount needed for protection. (http://www.cdc.gov/measles/travelers.html)

      Delete
  5. I do agree with your view of being in the brink of a widespread epidemic, many individuals are opting out of vaccinating there children as a result of speculation that it leads to autism. The fact that these assumptions are gaining much support is pretty worrisome, especially with such a highly infectious disease. Individuals are using the flawed study as well as celebrities who have decided to not vaccinate their children as reasons to also opt out. Public health and CDC campaign should focus on these individuals as well as provide more education on the vaccinations.

    ReplyDelete
    Replies
    1. Yes education is very important. It is not only the study that connects vaccines to autism, which gives "anti-vacciners" leverage, there are more reasons why people refuse to vaccine their children. these other ideas must be addressed rationally in order that those people can feel their perspective has been taken into account and considered.

      Delete
  6. While I wish the section on the safety of the measles vaccine was not necessary, it has indeed become a growing issue in the United States. Through the efforts of certain bad actors on the national stage, we have seen the reemergence of measles in 17 outbreaks in the first 6 months (until June 27th) alone. There have been 539 cases in the first half of 2014, keeping us on pace for a record number of cases in the 21st century so far, the highest number of cases per year since measles elimination was achieved here in 2000 (http://www.cdc.gov/measles/cases-outbreaks.html). One of the reasons for the resurgence this year is because the Philippines is experiencing a large outbreak, and a number of cases where imported into the US from that area. This is another factor, in addition to the one presented in the article, that undermines attempts at eradication of the disease: increasingly fast travel and laxer public health regulations of travel can influence the spread of disease.

    Also, I’d like to bring up the hard numbers on vaccination rates. As was mentioned in this article, measles is so infectious that a 95% vaccination rate of a population is required to affect elimination of measles. The CDC in 2013 found that 20 states reported less than 95% coverage of the 2 doses of MMR vaccine among kindergarten children in the 2012-2013 school year (http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6230a3.htm; Table 1). It is hardly a surprise that 8 of these 20 states have had cases of measles so far this year.

    ReplyDelete
  7. One of the reason many individuals do not get vaccinated is because they depend on herd immunity. People are depending heavily on herd immunity when it is currently declining due to the lack of vaccinations occurring. 

    What are the current herd immunity percentage?

    I am curious to understand why some kids can enter school when they are not vaccinated. If herd immunity is declining, shouldn’t there be a stronger enforcement of children vaccinating? 

    ReplyDelete
  8. Nicole MastrogiovanniJuly 11, 2014 at 8:03 AM

    Difaa, I completely agree that many people are now depending on herd immunity for measles versus becoming protected and vaccinated themselves however this leads now to a greater percentage of people that are unvaccinated thus lowering the herd immunity rate, increasing the potential for spread of disease higher than we have experience in some years. I believe some children were excused from having the vaccine before entering school due to religious/culture beliefs and backgrounds but now many parents are not having their children vaccinated for fear that the vaccine is potentially harmful due to not enough knowledge, since the disease hasn’t been around for a few decades now, as well as media rumors endorsed by also uninformed celebrities. In other countries that are still developing, knowledge of measles and the vaccine are probably low as well as reaching populations in various types of outskirts and regions can be difficult.

    ReplyDelete
  9. It's a shame that so many believe what they hear on television such as he link of Autism and the MMR vaccine. I myself know people who have children and don't want them vaccinated because hearing about the bogus report. There has to be more awareness and education with medications and vaccinations because up to this day many people still do not know why they have to finish antibiotics that they have started.

    ReplyDelete
    Replies
    1. David, I'm so glad you mentioned this in your post. In some ways, I feel like one of the biggest problems measles presents us with these days is the obstacle to vaccination. I've read somewhere, unfortunately I can't remember where, that parts of Brooklyn--Park Slope sounds familiar--have some of the lowest vaccination rates in the country. It's paradoxical and very frustrating to know that prevention is out there but resisted due to debunked science. Just goes to show how important our positions can be in educating the public about true interpretations of jargon-heavy, complex, and exclusive science articles. There's a lot of value to make science, especially health science, more accessible.

      Delete
  10. In a word, we are facing the 2015 outbreak of measles that originated in Disneyland due to fears of Autism. Parental reservations about vaccinating their children with the Measles vaccine stems from anxiety about the preservative thimerisol, which despite evidence that it does not cause autism, was removed from the MMR vaccine since 2001 as a precaution. Thimerosal breaks down into ethylmercury, but unlike methylmercury which is found in some fish, it does not accumulate in the body as a neurotoxin. American’s reliance on herd immunity is no longer a safe bet in this global community. In a global perspective, it is unacceptable that there are still 200,000 measles deaths per year, mostly in India and many sub-Saharan African cultures, where vaccines are not widely available. WHO’s efforts to make this the Decade of Vaccines (DoV) by increasing Universal Access to all vaccines is a 2 sided coin. First, there needs to be a strong public health campaign communicating a clear message about the safety of the measles vaccine. More should be done to discredit Wakefield's unethical and fraudulent scientific misconduct, which has now become urban legend. Most people don’t know the facts on which they decide not to vaccinate. Second, universal access to the measles vaccines must be established for all children internationally, a project that the US should also be invested in; it’s a small world after all!

    ReplyDelete
    Replies
    1. This is a great review of vaccines and it is interesting to think of measles as a good candidate for eradication. It was eliminated in the U.S. but the vaccination rates are frustratingly just not high enough. During the recent Disney land outbreak I looked up some of the anti-vaccine webpages to try to understand why there is such a movement and I realized there are a lot of adverts on these pages for very expensive food supplements and alternative meds (i.e. not meds) that promise to counter the effects of autism and other disorders. So people are making money out of the distress that parents have over having a child with serious problems and the result is a measles outbreak. I believe a few states tightened the exemptions after this outbreak so only kids with valid health reasons for not being vaccinated are exempt.
      It is interesting to see how the dose recommended was refined over time. Safety and efficacy are part of clinical trials but it is interesting to see how the efficacy and safety was monitored after introduction, over years in large populations.

      Delete
  11. With the increase in outbreaks in recent years in the United States, I think that public health initiatives should be made to widely discredit the false claims against measles vaccines. The argument that many people make seem to be the link with autism, but I think that maybe advertisements should be widely publicized on TV. Especially because there is so much scientific evidence proving otherwise, and the doctor that published those findings initially has had his medical license revoked. It seems that most Americans would not think of measles being a severe disease, but that is because it has been mostly eliminated in the US so they do not know how serious it can be. I think that the most effective way to get people to vaccinate children would be to educate the public on how damaging a measles infection can be.

    ReplyDelete
    Replies
    1. I also agree that we need a renewed public health effort to discredit the false claims against vaccines. Additionally, it would be beneficial to remind Americans (and likely those in other developed countries who have forgotten about the health burden caused by measles and consequently have seen waning vaccine rates) about the complications that measles can cause. As I mentioned via Facebook I was led to an anti-vaccination page and through the comments saw that many people believe measles is harmless. As we learned in class this is not the case but if this is the thinking of anti-vacciners it is understandable why people would feel vaccinations are unnecessary. Thus, it seems we are at a critical point where false claims must be dismantled via research and then research must be widely publicized in a way that all Americans can understand. Communication is paramount in public health initiatives. Similarly, all of the research in the world discrediting false claims is useless if it is not shared with the general public in an effective manner.

      Delete
  12. Recently on FB I saw a post about the link between autism and vaccinations. Quite honestly I am baffled (and horrified) that people still hold this belief despite multiple studies showing no association (as mentioned in the posting). At this point because the anti-vaccination campaigns seem to be gathering a larger uninformed mass, the media should take up the task of explaining both the importance of vaccines and discrediting the negative associations that people believe. Obviously, public health has a role to play. However, unfortunately the media (and social media) seem to more easily reach a larger mass than PH campaigns. Thus, they should increase awareness about vaccine importance while discrediting misinformation rather than just tell people they NEED to vaccinate their children. Although not every anti-vacciner can be reasoned with, many are probably just ill-informed and providing evidence to back-up any statement may help change their mind. As a side bar, The Lancet should also take a role in publishing one of the systematic reviews or meta-analyses on MMR vaccine efficacy and safety as they were the one that published the fraudulent article in the first place. Additionally, as the Lancet is a scientific magazine with a broader reader base they have the ability to reach more of the population. Either way, the anti-vaccination movement seems to be growing and social media allows these ideas to spread quickly...some sort of public health awareness initiative/ media collaboration should happen sometime in the very near future!

    ReplyDelete
  13. I found it interesting that measles has not changed its genomic makeup throughout the changes. Are there other diseases where the virus or genomic species remains unchanged? what is unique about Measles that it does not have mutations.
    ALthough the genetic formula for the vaccine an remain the same as it was when it was first inveted, has there been improvements on the vaccine since its first use?

    ReplyDelete

Note: Only a member of this blog may post a comment.