1900s. Disease Eradication

The impact of vaccination on the health of the world’s people is hard to exaggerate. With the exception of safe water, no other modality, not even antibiotics, has had such a major effect on mortality reduction and population growth.

–Stanley Plotkin, M.D.

1900s: Disease Eradication

1980s: Paradigm Shift

2000: Measles Elimination

2014: Disneyland Outbreak

2015: California SB 277

2015: Current Climate

 

Turning a Prognosis of Death into Prevention and Eradication: Vaccine Development

As we navigate the current measles epidemic and evaluate the need for mandatory vaccinations, it is vital to understand the origination of vaccines and the successful eradication of several infectious diseases. The deliberate effort to protect humans against diseases, plaques, and pestilences has an early origination date in the 7th century. Indian Buddhists drank snake venom in efforts to become immune to its effects and in the 18th century the first documentation of Chinese variolation against smallpox was discovered (6). As the concept of disease changed throughout the 19th century, the development of novel ways to prevent deadly diseases spurred alongside it. In the eighteenth century, society viewed the environment, such as weather, seasons, diet, and occupation, as the incubator of infectious diseases. Practitioners made use of patient histories to diagnose imbalances in a person’s health and devise a course of treatment. Over time doctors came to believe infectious microorganisms introduced into the body, vectors carrying pathogens, or deficiencies of certain substances caused diseases as opposed to the previous miasmatic theory. Diseases such as small pox, cholera, polio, and influenza were rampant across the country necessitating the urgency to develop prevention measures. With this, the evolution of the modern vaccine began.

At the start of the 19th century, small pox vaccine became the first introduced vaccine. Small pox is a severe infectious disease-causing rash and fever which can result in death. Throughout the 18th century, small pox was one of the most deadly diseases that killed people of all ages, genders, and socioeconomic status. Its case fatality rate ranged between 20 to 60%. Individuals that survived the disease were frequently left with disfiguring scars (7). As early as 900 AD, people in China and India had been using the practice of variolation, which exposes a healthy subject to smallpox scabs in order to develop immunity against the disease by initiating a mild, immunological response to the exposure. By 1721, the practice of variolation was introduced into the United Kingdom with the procedure performed on Lady Mary Wortley Montagu’s daughter. However with the announcement of his small pox vaccine in 1796, British physician Edward Jenner is credited with the development of the first modern understanding of vaccine. He demonstrated that an infection of cowpox conferred immunity to the virulent smallpox and could be passively transferred between peoples (7). Correlating with an increase in public acceptance of vaccinations, incidences of small pox decreased from 1802 to 1840 (4). By 1979, the World Health Assembly had declared the once widely feared and deadly small pox disease to be eradicated.

Announcement of Polio Vaccine and mass production of Salk's vaccine.
Announcement of Polio Vaccine and mass production of Salk’s vaccine.

Another success story attributing to the power of vaccines is polio and the development of the vaccine to prevent it. Polio is a viral disease caused by an entero virus that can lead to paralysis and death. The first outbreaks began in rural areas with prosperous populations. This disease gained increased public attention and hysteria when United States President Franklin D. Roosevelt was diagnosed with infantile paralysis, also known as polio, and was confined to a wheelchair during his time in office (6). In the 1950’s, there was a rush to develop the first polio vaccine. Upon a deeper epidemiological understanding of polio by learning it had three different strains, scientists were able to better comprehend the disease mechanism. In 1955, John Salk made an announcement that decreased fear across the world. He had developed a vaccine that would be effective against all three strains through the use of an inactivated virus. With a heightened public attention to the development of the vaccine, many researchers continued their quest for improving the vaccine. In 1960 a live, attenuated virus developed by Albert Sabin was discovered. By 1964, Sabin’s live virus replaced Salk’s killed virus to become the accepted vaccination method. In 1988, the World Health Organization initiated a Global Polio Eradication Initiative. Through the use of vaccinations, the WHO targeted polio to be the second disease after small pox to be effaced from the world (6).

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Reported measles cases and deaths, United States, 1912–2001.

Paralleling the fear and highly contagious global outbreaks of small pox and polio, measles became a national public health concern in 1912, requiring all diagnosed cases to be reported. On average over 6,000 deaths were reported each year in the United States in the first decade of disease reporting. Measles is a highly contagious virus that can cause fever, rash, cold, and conjunctivitis. Severe
complications include pneumonia, encephalitis, and death (2). Highlighting the severity of the contagious diseases, the Center for Disease Control reports that in the decade before the measles vaccine was discovered nearly all children got measles before they were fifteen. Approximately 400 to 500 people died each year, 48,000 had to be hospitalized, and 4,000 had evidence of encephalitis. With the effort to prevent the highly contagious disease, researchers John Enders and colleagues isolated the measles virus from a blood sample and derived from it a vaccine in 1963. The widespread use of vaccinations resulted in a decrease of annual cases from approximately 530,00 between 1953 and 1962 to 204, 136 in 1966 (5). In 2000 the WHO declared measles to be eradicated from the world, however there have been numerous outbreaks of measles and the spread of the contagious disease is widening. This preventable disease previously declared eliminated is a public health concern once again. Through the journey of the history of measles vaccinations and immunization requirements, the understanding of why measles has returned and public health initiatives to reach herd immunity will be uncovered.

Power of Prevention: Science of Vaccine

With the knowledge of the concept and causes of diseases, the scientific community was able to invent the concept of public health. By the middle of the 19th century, smallpox vaccination became a regular part of the doctor’s visit agenda. Then in 1955, the polio vaccine was implemented into the United States followed by the measles vaccine in 1963. These vaccines carried with them the possibility to eradicate the targeted infectious diseases if there was compliance and enough of the population got vaccinated.

Uncovering the immunology of vaccines led researchers to develop the most efficacious prevention measures. Vaccines, such as the measles vaccine, will activate the immune system when injected into the body by the introduction of antigen specific antibodies. The immune system has B-lymphocytes that produce antibodies that will bind to a specific disease-causing pathogen. CD8-T lymphocytes also recognize and terminate the spread of infectious pathogens or can secrete antiviral cytokines that can aid in pathogen protection. CD4+ T helper cells control the maintenance of B- and CD8-T lymphocytes to uphold resistance. Upon introduction of a measles pathogen, B and T cells will initiate responses. In order to maintain immunity over the course of a lifetime, there must be persistence of the vaccine antibodies and memory cell regeneration that can be quickly reactivated in the presence of pathogen exposure (7). For further information about vaccine immunological responses click here.

There are multiple types of vaccines that can confer immunity to the subject. For small pox, Jenner used a related organism rather than a weakened form of the virus to establish a vaccine. This virus also shows immunity against moneypox by having cross-protected T cell mediated responses. The polio vaccine that Salk developed was a killed virus in contrast to the attenuated virus that Sabin discovered. Similarly to Sabin’s polio vaccine, the current measles vaccine is a live attenuated virus. In addition to having multiple types of vaccines, there can also be multiple doses of vaccines. For measles, the vaccine is administered in two doses. One dose will be given between 12 and 15 months and the second dose between four to six years. The reason for two doses is that some people may not develop enough antibodies after just one dose (6).

Explanation of Immune Response and Vaccines.

The measles vaccine has improved since it was first introduced. In 1975, the original killed vaccine known as the Edmonston B strain was withdrawn because it had evidence of a high frequency of fever and rash. Concurrently with the development of Edmonston B strain in 1965, another live vaccine was introduced, known as the Schwarz strain. However, this vaccine strain was also withdrawn. In 1968, the Edmonston-Enders strain was licensed which has caused less adverse reactions than the original vaccine. The vaccine is prepared in a chick embryo fibroblast tissue culture. The vaccine is supplied as a freeze-dried powder and is then reconstituted with sterile, preservative-free water (2). Over the last half century the measles vaccine has been greatly improved to the current attenuated strain vaccine that has drastically reduced side effects.

 

Government Takes Charge: Immunization Requirements

Paralleling the first vaccine developed in the United States, the small pox vaccine was the first documented case of immunization requirements. In 1809, Massachusetts enforced the requirement of small pox vaccination to control the frequency of outbreaks across the state. So began the spiraling effort to increase public safety and decrease the threat of preventable disease contagion (4). In the 1850’s, opposition to vaccine requirements sparked a decrease in vaccine use mirrored with an increase of small pox outbreaks in 1870’s. More states inaugurated mandatory vaccine requirements and furthered their enforcement mechanisms. However, this was often met with resilience leading states such as California, Indiana, Illinois, Utah, West Virginia, Wisconsin, and Minnesota to repeal vaccination laws.

Responding to the dissidence in vaccination requirements, the Supreme Court ruled in Jacobson vs. Massachusetts that the United States government gives states the power to pass and enforce mandatory vaccination requirements. This ruling in accordance with the development of new vaccines prompted states to require additional vaccination requirements, such as measles vaccination requirement for school aged children in the 1960’s and 1970’s (7). By 1969, 17 states required children to be vaccinated by the time the entered school. In efforts to combat the disease, public health officials often excluded non-vaccinated children from school during measles outbreaks. Eventually in the beginning of 1980’s, all 50 states had measles vaccination requirements (7). Read more about the paradigm shift of vaccination and requirements in the following pages.

 

Medical Barriers to Vaccinations: Who is Exempt?

Vaccines such as small pox, polio, and measles have proven effective at combating the spread of preventable diseases. In the case of measles, two vaccines at the recommendation dose will produce antibodies conferring protection against the disease. However, there are subgroups of people that are medically exempt from obtaining the vaccine:

  • Infants under 12 months of age
  • People with a suppressed immune system ex. cancer patients
  • People with allergies to the vaccine components
  • Pregnant women

Infants under twelve months of age lack a mature immune system due to limited B cell response and underdeveloped antigen and T cell mechanism. However, infants acquire their mother’s inhibitory antibodies to protect them from pathogens until six to nine months of age (3). Since the measles virus is a live virus, immunosuppressed patients cannot combat the weakened virus and produce antibodies against it. According to the CDC, the vaccine is contraindicated in people with congenial disease, severe HIV infection, serious malignant disease, leukemia, undergoing radiation immunosuppressive therapeutic treatment, or undergoing treatment with high-dose steroids, antimetabolites, or alkylating agents (1). The vaccine contains small amounts of human albumin, neomycin, sorbtiol, and gelatin (2). For individuals that cannot receive the vaccine for medical reasons, the presence of unvaccinated individuals in their community increases their susceptibility to the disease. The medical exempt patients are a heightened risk group for contracting measles.

Move on in time to the next period: 1980’s Paradigm Shift. Click Here.

References:

1. “Measles Vaccines: WHO Position Paper.” Weekly Epidemiological Record. World Health Organization, 28 Aug. 2009. Web. 15 May 2015. <http%3A%2F%2Fwww.who.int%2Fwer%2F2009%2Fwer8435.pdf%3Fua%3D1>.

2. “MMR (Measles, Mumps, & Rubella) VIS.” Centers for Disease Control and Prevention. Centers for Disease Control and Prevention, 18 June 2013. Web. 17 Apr. 2015. <http://www.cdc.gov/vaccines/hcp/vis/vis-statements/mmr.html>.

3. Moss WJ. Measles control and the prospect of eradication. Curr Top Microbiol Immunol.2009;330:173–189.

4. Omer, Saad B., Daniel A. Salmon, Walter A. Orenstein, M. Patricia deHart, and Neal Halsey. “Vaccine Refusal, Mandatory Immunization, and the Risks of Vaccine-Preventable Diseases.” New England Journal of Medicine 360, no. 19 (May 7, 2009): 1981–88. doi:10.1056/NEJMsa0806477.

5. Oreinstein, Walter. “Evolution of Measles Elimination Strategies in the United States.” The Journal of Infectious Diseases, 2004. Web. 16 May 2015. <http://jid.oxfordjournals.org/content/189/Supplement_1/S17.long>.

6. Plotkin, Stanley A., and Walter A. Orenstein. Vaccines. Philadelphia: W.B. Saunders, 1999. Print.

7. Riedel, Stefan. “Edward Jenner and the History of Smallpox and Vaccination.” National Center for Biotechnology Information. U.S. National Library of Medicine, 18 Jan. 2005. Web. 16 May 2015. <http://www.ncbi.nlm.nih.gov/pubmed/16200144>.

 

 

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