Camille's Bites of Life

Introduction:

Since its first reported occurrence around the 11th and 12th centuries, measles has become one of the most notable viruses in epidemiological and human history [1]. Before its vaccine development, measles was regarded as a “classic example of successful parasitism” [2, p. 1]. Since then, vaccination has played a central role in eliminating the risk of contracting measles in most parts of the world; nonetheless, cases still appear in almost every country in unvaccinated individuals [3]. The fatality rates associated with measles infection seem to decrease in many countries based on higher socioeconomic status, however, many developing countries maintain high case-fatality rates regardless of this. Around 770,000 people of the 30 million that contracted measles died in 2000; this number demands attention to be brought to countries where vaccination is low, fatality rates are high, and complications may rise [3]. This begs the question of what factors contribute to the number of cases of measles we observe today as well as public opinion of the virus, especially in light of global vaccination efforts. Though it does not have the case numbers as it once did (most noticeably in developed countries), the study of the history, virology and socioeconomic impacts that surround the measles virus has been and will continue to be a significant aspect of understanding and maintaining the remission of highly infectious diseases in society today.

History:

 The history and epidemiology of the measles virus (MeV) show the timeline of how the virus has emerged over the past centuries and the primary causes of the virus’s prevalence. This section will go over the history of measles and the immune responses that occur once the virus has been spread. The measles virus originated from non-human species and caused emerging infectious diseases in the 11th and 12th centuries [1]. It is considered an ancient disease and its first clinical presentation of the disease was written in the seventh century by a Persian doctor named Rhazes [4]. His findings attempted to distinguish measles from smallpox, indicating that measles had more severe side effects than smallpox. 

The first written record of measles was in the United States in 1657 by a citizen in Boston, Massachusetts. Twenty years later, an English doctor named Thomas Sydenham, published Medical Observations on the History and Cure of Acute Diseases and was able to differentiate the differences between measles from scarlet fever, and smallpox [4]. It was not until 1757 when a Scottish physician named Francis Home found out that the virus was detectable in the blood and that there is a chance for lifelong immunity after recovery from the disease. He was able to prove that MeV was a bloodborne disease as he produced this disease in healthy people by injecting those without the disease with blood samples from infected people [4]. Measles came to be known as “the most widely distributed and most commonly recognized of all acute diseases to which a man is subject” marked by a fever that will lead to a rash [5, p. 34]. Before the current vaccine, the United States incidence was at least 12,000 measles deaths each year and around 4 million people were infected annually [4]. The vaccine was created from blood samples of sick students in Boston, Massachusetts in 1954. With the vaccine, most children were able to recover without any problems. The vaccine was finally licensed in 1963 as it first showed safety in monkeys and then in humans [4]. It was renamed in 1968 as Attenuvax and did not require any additional injections to reduce inflammatory reactions. In 1967, the United States federal government declared a goal of eliminating MeV by vaccinating approximately 10 million children [6]. With this in mind, the Attenuvax vaccine merged with mumps and rubella vaccines to produce the MMR vaccine in 1971 [4]. In the year 2000, the Centers for Disease Control (CDC) finally declared measles eliminated due to no more new cases reported within the last twelve months [7]. However, the declaration of measles being eliminated was reversed in 2010 due to recent outbreaks and lack of child immunization.  

Epidemiology: 

Measles is characterized by the respiratory mode of transmission, high contagiousness, and the lifelong immunity that follows the infection. It is driven by the contact patterns of susceptible and infectious individuals that are affected by birth rates and human mobility. It can be often transmitted by respiratory droplets over short distances and by small particle aerosols that remain up in the air for two hours [8]. The incubation period for measles is for about 10 days and 14 days for the virus to onset the rash. The measles virus RNA can be traced in the blood and urine after the rash onset [8]. The endemic virus transmission has a typical temporal pattern characterized by annual seasonal epidemics, resulting from the accumulation of susceptible people over successive birth cohorts and a decline in the number of susceptible individuals following an outbreak. Measles was the first immunosuppressive infection to be described. Transient lymphopenia occurs in the blood during measles likely due to the redistribution of lymphocytes from peripheral blood to lymphatic tissues [8]. The clinical diagnosis of measles is more challenging to clinicians unfamiliar with the disease in undernourished and immunocompromised children in whom rash might be absent. It is also well aware that latent immunization is an important factor regarding the spatial distribution of measles [9]. An explanation of the phenomenon of measles was provided by the concept of an active plus the latent immunization of the child population and the changes in the transmission of the virus through droplet infection from the carriers to other people who come in contact with them [9].

Symptoms of measles include high fever, respiratory issues, runny nose, watery eyes, Koplik spots, and a rash that appears a few days later [10] The primary cause of death of those who contracted measles was reported to involve respiratory complications, neurologic complications, or both [11]. Uncommon complications of measles, particularly in children, can include but are not limited to, “encephalitis, myocarditis, pericarditis, nephritis, thrombocytopenic purpura, appendicitis, and pneumothorax” [11, p. 248]. Some of the more common complications observed with measles infection are “pneumonia, diarrhea, malnutrition, otitis media, mouth ulcers, corneal epithelial keratitis, corneal ulceration, and blindness” [11, p. 243]. 

Before the introduction of the measles vaccine, measles primarily affected young children and there were over 1 million cases reported annually [12]. An estimate of around 255,000 measles cases and 90,000 deaths occur annually in Nigeria [13]. It is a highly infectious disease that will infect about 90% of individuals under 10 years of age who are unvaccinated [13]. Africa and Southeast Asia contributed around 70% of the measles cases in the year 2000 and 84% of the measles-related deaths [13]. The Sub-Saharan African region has the highest mortality rate associated with the disease. For example in Nigeria, measles exhibits a seasonal pattern as more cases occur in the drier seasons.  During the 1980s, the measles vaccination was established in all African countries through the World Health Organization in Immunization. The measles vaccine has been widely used throughout Africa and the incidence rate was at its historic low [13]. Therefore, it has been advised that vaccination with at least two doses is the most effective measure to combat the spread of measles. 

With all the information provided about measles, one must be able to adapt to the preventative measures that measles has provided. Developing nations in continents such as Africa and Southeast Asia will be able to see a decline in measles cases by providing precautions to their citizens. For example in China, the first measles vaccine is given to infants greater than eight months old and the second one is taken between ages 4-6 [14]. Taking the vaccination is important because it has been scientifically proven that it can provide safety amongst human populations and combat the spread of the virus. 

Virology:

The historical emergence of the measles virus (MeV) highlights its high adaptability to new environments and susceptibility to both humans and non-human primates. This section will discuss the virology of measles, what makes it a highly contagious virus, and how certain strains emerge in new areas. 

The measles virus belongs to the family Paramyxoviridae, the genus Morbillivirus, and, according to Moss et al., are closely related to canine distemper virus and rinderpest virus [8]. It is transmitted mainly through respiratory routes, affecting organ systems that can eventually lead to worsening conditions such as pneumonia [8]. In terms of hosts and reservoirs for the virus, humans and primates are the only natural hosts, but MeV can be isolated in vitro successfully during the prodromal phase from respiratory secretions and blood [15]. As Bellini et al. note, MeV cultures successfully grew in primary cell cultures but were capable of growth in human kidney, intestine, skin, muscle, foreskin, and uterus cells [15]. This suggests that the virus can grow and persist in a diverse range of cells associated with their hosts’ bodies. 

When it comes to MeV’s shape and size, measles virions are approximately 120-125 nm in diameter, taking on a spherical, pleomorphic shape with a lipid envelope [16]. This demonstrates the adaptability of the measles virions, indicating that despite its large size for a virion, its flexible shape allows for more transmissibility to susceptible host cells. 

Furthermore, MeV contains two important viral transmembrane envelope glycoproteins: F (fusion) proteins and H (hemagglutinin) proteins. F proteins are dumb-bell-shaped glycoproteins anchored in the external membrane located near the carboxyl-terminus [17]. H Proteins, on the other hand, are conical-shaped glycoproteins that lack neuraminidase activity, meaning it is not associated with viral particle release from the host cell [17]. Rather, H proteins mediate the attachment to host cells, which is required for virus-host cell membrane fusion [15]. This is important because the mediation of attaching the virion to the host cell permits entry of the virus. MeV contains coding for six significant structural proteins: N protein, P protein, M protein, F glycoprotein, H glycoprotein, and the large polymerase component [15]. These proteins are important for the virus’ function as the diverse range of proteins are being used to create and replicate nucleocapsid structures, package the virus, enter the host cell, and mediate interaction within the infected cell [18]. All of these components are necessary for viral function as they aim to regulate the entry and replication of MeV within the host cell.

One of the major measles virus receptors is known as the CD46 molecule, which, according to Bellini et al., is absent in human enterocytes but has a widespread distribution in human tissue [15]. This highlights the susceptibility of human individuals as natural hosts to MeV as this receptor is important for the processes of entering host cells. In a study by Dörig et al., testing human-rodent somatic cells and their abilities to bind to the measles virus, they found that the hamster cell lines expressing the human CD46 molecule could bind to the virus [19]. Not only that but the CD46+ cells were proven to produce syncytia and viral proteins, indicating that the molecule can both bind to the measles virus and reinforce infection [19]. Similar to the CD46 molecule, the BST2 transmembrane protein has also been shown to affect MeV replication in the brain [20]. Both the BST2 protein and the human CD46 molecule are important when understanding the virology of MeV as it demonstrates that several molecules and proteins can directly affect how the virus can persist on a molecular level. 

Because MeV is an anti-genetically stable monotypic virus, one can achieve lifetime immunity from a natural recovery from the virus [18]. However, antibodies to H and F proteins are required for protection against infection as one would have to modify predicted gene sequences of the glycoproteins for protection and vaccination against the virus [16]. This demonstrates how many vaccination strategies in preventing the measles virus contain the modification of the existing genes within their significant glycoproteins. Because of this, many methodical approaches to creating vaccines have resulted in differences between antigenic variation and wild-type viruses [15]. This is important as it influences many strategies of worldwide control, elimination, and eradication.

It is important to study the virology of MeV as these forms and functions come together in different variations, producing multiple strains that have affected different parts of the world. For instance, a 2013 study observing the molecular characterization of the measles virus in Cameroon between 2010 and 2011, identified one of the many subtypes of the virus, genotype B3, as an endemic genotype prominent in the African continent [21]. This is important as it shows the genetic variation between the different proteins and how, depending on the location, could impact the type of strains a host population is susceptible to. Observing this incidence shows the importance of measles virology as it demonstrates how the virus’ adaptability and variety in the form of new strains allows the virus to persist in new environments within its host population. 

Impact on Scientific Community: 

As previously noted, researching the measles virus was important for uncovering the virology of the disease and how it can continue affecting humans. However, this was also important for the scientific community as it allowed researchers to identify new methods for approaching infectious diseases.

One of the many ways MeV was able to impact the scientific community was through its efforts of improving the field of epidemiological research. According to Langmuir et al., the ecological approach was the disease concept most used within the field of epidemiology. Within this framework, information was very limited on how to eradicate MeV, arguing that the “ecological equilibrium of measles is solidly based” [2, p. 1]. In other words, populations would have to live with the disease if it were to be eradicated. Therefore, to combat these limitations, research done during MeV outbreaks considered perspective on mortality and how it can serve as a criterion in the process of eradicating a disease. This was important as it allowed further research to find direct correlations between factors such as age and risk of transmission, making the epidemiological approaches more useful in viewing diseases with high mortality and morbidity such as MeV.

Similarly, MeV research has enabled the creation of new frameworks, which has helped to consider wider populations at risk for certain diseases. This was important for the scientific community as it allowed researchers to not only view MeV from a biological standpoint but from a socioeconomic standpoint as well. As Menkir et al. state, the new framework helped to understand the impact factors such as income had on transmission rates of MeV, which was a revolutionary perspective to consider for its time [22]. The model highlights comparisons between poor and stable income groups and how measles has affected morbidity and mortality among those groups [22]. Likewise, the model demonstrates public health access to resources such as vaccines and how it impacts susceptibility and transmission rates. Models that consider factors such as socioeconomic status are important as it accounts for MeV infection among groups of people and how status and income can affect the susceptibility of a population to a virus such as measles. 

Additionally, virological surveillance has also improved due to MeV research. As demonstrated in a study regarding MeV elimination in Italy, it emphasizes the importance of accurate laboratory diagnosis and displaying the genotypes associated with sporadic cases and endemics in Italy. Due to these improvements, researchers were able to identify D4 and D8, strains associated with endemic circulation, and D9 and H1, which were strains associated with sporadic cases due to importation from Asian countries [23]. Due to advanced research on MeV, many countries were able to identify new strains using improved methods of virological surveillance, which has provided researchers with many opportunities for preventative and public health care. 

With all this considered, it is important to emphasize the impact MeV has had on the scientific community, whether it was due to the improvement of epidemiological research, virological surveillance, or new socio-economic frameworks. MeV has allowed researchers to consider many factors on one’s health and how location can play a role in determining susceptibility. Therefore, MeV research was important because of how it extended those perspectives, providing researchers with new methods of how to improve preventative care and resource distribution. 

Economic Impact of Measles:

Prior to the invention and dispersal of the MMR vaccine, measles devastated the United States with over 4 million total cases and about 400 deaths per year [24]. Beyond cutting case numbers and saving thousands of people from death, the MMR vaccine also had striking economic benefits. From 1966 to 1968 alone, net economic savings from the development and implementation of the MMR vaccine totalled to over $403 million USD [24]. The cost of immunizations when compared to the economic benefits of immunization came out to be 13%, a substantially large return on the investment in vaccination protocols and technology [24]. 

Still, even in 2002, long after the MMR vaccine’s development and popularization, cases still arose. Between 2002 and 2003, Italy experienced a measles outbreak that brought about €8.8 million in hospital charges alone [25]. As hospitalization costs only made up about 40-50% of the total costs associated with the outbreak, the total costs that resulted from 5,154 cases were estimated to be €17.6 – 22.0 million [25]. This large sum spent on reactionary protocols, when applied to vaccination costs, would be equivalent to the cost of 1.5–1.9 million children’s vaccinations with one dose of the MMR vaccine [25]. After an even more thorough economic analysis of the costs and benefits of vaccination, it can be said that “Under even the most conservative assumptions,the national 2-dose MMR vaccination program is highly cost-beneficial and results in substantial cost savings” [26, p. 131]. 

Though vaccination is widely available in most developed countries, it is mostly developing countries in which we observe the highest case numbers today. Across the world, measles continues to kill more than any other vaccine-preventable disease [27].
Elimination of the virus from populations in developing countries is still a work in progress due to a lacking coverage of vaccination, the measles virus being endemic to certain areas, and overcrowding [11][27]. Vaccination campaigns appear to be lacking despite the measles vaccine itself being relatively inexpensive [27]. However, by 2000 improved nutrition was noticed to cause a decrease in measles fatality rate [11]. Socioeconomic conditions as well as vaccination efforts appear to work in tandem to lower measles case numbers; thus better diet, housing, and access to vaccination may be able to improve the measles statistics observed in developing countries [11]. 

Social Impact of Measles:

However, for all the good that the MMR vaccine has brought to the world, it has not been without controversy. Central to the controversy is a debate on whether or not the vaccine may cause autism in children who receive it [28]. Although there is a strong stigma surrounding the MMR vaccine in certain circles due to claims that it may cause autism, no scientific evidence has produced conclusive evidence supporting these claims [28]. The stigma surrounding autism itself is a large factor in this issue, as many desire to eliminate the condition outright. Assumptions made about the condition play into damaging stereotypes and ignore the lived experiences of those with autism [28]. This social issue is a phenomenon observed in more developed countries, such as the United States; it is not as prevalent in low income countries where access to vaccination is limited in the first place.

The hostility from certain mothers, and even some doctors, towards the vaccine seems to outweigh the societal responsibility that is unofficially assigned to citizens [28]. Most people acknowledge and accept that vaccination is a societal responsibility, as it is for the public good; yet some fail to realize that it not only protects other children, but their own as well [29]. Others argue that vaccination against viruses like measles are “out of the realm of individual or parental discretion, and situates it in the realm of societal obligation,” saying that under vaccination ethics, children are owed vaccination by society [30, p. 611]. Even slightly lower vaccination rates create pockets of measles susceptibility that have caused a reemergence of measles spread in the United Kingdom [30]. Studies have suggested that policy makers should consider utilizing herd immunity potential in campaigns to promote vaccination, as it may appeal to larger demographics and increase vaccination rates [29]. 

Discussion: 

All in all, the measles virus has become a significant event that allowed the world to change in terms of history, scientific research, and the economy. Measles has been going around for centuries and now resides at a point of almost complete elimination in developed countries. With the readily available MMR vaccination, the CDC was able to declare the virus eradicated. The main work that needs to be done to ensure its true elimination though, is in lower income countries where vaccination efforts are lacking and measles is endemic. By taking the right precautions and being aware of the implications that measles can have on one’s body, we know to make sure that measles does not negatively impact our community’s health in the long term. Similarly, based on scientific research, many characteristics were uncovered in regards to the measles virus and how their virology can impact fields such as epidemiological research and infection prevention. By widening their perspectives and constructing new frameworks, researchers were able to obtain more information regarding measles and apply methods for infection control and prevention policies. Finally, though most individuals in the states are now vaccinated against measles, a strong stigma exists within certain groups of people. Despite this observed vaccine hesitance, most people view vaccines as a necessary part of healthcare and are willing to fulfill their societal role of keeping their neighbors safe. From an economic standpoint, additionally, vaccines provide a much more cost-effective solution to measles occurrence as treatments for the virus are often far more expensive and demand more from the healthcare infrastructure. 

Based on all the literature presented, the measles virus has had a significant impact on history, science, and the economy. The knowledge obtained from history can aid in the protective and public health efforts used to control diseases today. Scientific discoveries helped to expand the field of epidemiology by considering new perspectives through socioeconomic frameworks. Lastly, MeV has helped to identify problems economically, highlighting cost and public health effective strategies for both a manageable society and economy. All three of these points are significant as it shows how the strategies and challenges faced by measles outbreaks could be applied to how disease research and management are implemented today and will be in the future. 

Works Cited

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