News and Views: Measles — the Virus, the Disease, the Vaccine
Published on in Vaccine Update for Healthcare Providers
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Published on in Vaccine Update for Healthcare Providers
Did you know that in some parts of Africa, people don’t name their children until the threat of measles has passed? In the United States, and many other parts of the world, this might seem odd, particularly as some parents have come to fear the MMR vaccine more than the three diseases it prevents. In light of the ongoing measles outbreaks caused in part by the decisions of some to forgo vaccination, we thought it might be useful to review information about measles.
Read on to find answers to the following questions:
Measles is an RNA virus of about 100 to 300 nm in size. In the scheme of viral size, measles is on the larger side. Related most closely to rinderpest virus (cow measles), measles is believed to have evolved in an environment in which cattle and people were in close proximity. The eradication of rinderpest, the only virus other than smallpox to be eradicated, increases hope that someday measles can be eradicated as well. Although we hear more about polio eradication, measles virus is a good candidate because it meets three important criteria. First, it only infects humans. Second, it is genetically stable. Third, a safe and effective vaccine is available.
Measles virus can infect several different kinds of cells, including epithelial, endothelial, and immune system cells. Immune cells infected by measles virus include immature lymphocytes, T and B cells, activated monocytes, macrophages, and mature dendritic cells. Because measles virus buds from, rather than lyses, infected cells, it typically spreads through the body inside of infected cells. After infecting the lower respiratory tract and local lymph nodes, viral-infected cells travel through the blood to the spleen and lymph nodes, lungs, thymus, liver, skin, conjunctivae, kidneys, gastrointestinal tract, and genital mucosa. It is rare for cells of the central nervous system to be infected, so the mechanism for complications that include involvement of the central nervous system has been studied. Working theories include altered presentation of myelin antigens, molecular mimicry, genetic susceptibility, or dysregulation of the immune response. This latter theory currently seems to be the most likely.
Cells infected with measles can be identified microscopically by their large size, altered shape, which may include spindles, multi-nucleated appearance, and the presence of inclusion bodies in the cytoplasm or nuclei of the cells. Infected cells will start to appear in the blood around 4 to 7 days after the infection begins. The immune response is characterized by a CD8+ T cell response; however, CD4+ T cells also respond. Individuals who experience the most severe disease have been found to have low levels of CD4+ T cells.
Measles was the first infection to be recognized as an immune suppressive agent. In addition to decreased levels of CD4+ cells, a decreased CD4/CD8 ratio can be found during the acute phase of infection, and lymphocytopenia is also evident, albeit the latter is more often seen in infected females and malnourished individuals. The immune suppression lasts for weeks after measles infection and can cause reactivation of chronic infections that were previously controlled, such as tuberculosis, or result in a period of remission from immune-mediated conditions, such as juvenile rheumatoid arthritis, nephrotic syndrome, or idiopathic thrombocytopenic purpura.
The time from infection to start of symptoms is about 10 to 14 days. The earliest symptoms, lasting about two to four days, include:
The body rash typically begins on the head and then spreads to the trunk before reaching the limbs. And while the body rash is a tell-tale sign of infection, clinically it offers information that may not be as quickly recognized. Specifically, the appearance of the body rash means:
Early on, the body rash will blanch with pressure. It will begin to fade in the order it appeared — typically about three to four days later, and its color will change from red to brown, The disappearance of the rash may be accompanied by flaking or sloughing of skin, particularly in malnourished individuals.
Atypical measles presents with:
This version of the disease is most often associated with a group of individuals who received an inactivated version of the measles vaccine available in the 1960s (see “Measles — The vaccine” section of story for more information).
Complications can occur based on which body systems are involved, whether the infection persists, or as a result of secondary infections taking advantage of the coincident immune suppression caused by infection. While most deaths that occur from measles are the result of other infections, the importance of preventing measles as a means of preventing the coincident immune suppression cannot be understated. In industrialized settings, about 60 percent of deaths are due to pneumonia, but the causal agents can be viral or bacterial in nature. The bacteria that most likely are associated with pneumonia include staph, pneumococcus, or Haemophilus influenzae type b.
The likelihood for, and type of, complications is dependent on economic and individual factors, such as immune status. For example,
Neurologic involvement can result in a series of severe conditions:
Although only about 500,000 cases of measles were reported in the U.S. annually before a vaccine became available, it was likely that the entire birth cohort was infected (about 4 million cases). Each year, measles infections caused:
Measles virus is spread by respiratory droplets — directly by coughing and sneezing and indirectly by small-particle aerosols that remain in the air after an infected person has left the area. The coughing and sneezing that results from infection is due to the sloughing of infected epithelial cells lining the upper respiratory tract. Because it takes time for the rash to appear, people are contagious for about four days before the rash develops, and remain infectious for about another four days after its appearance.
One of the most infectious diseases known, measles has an R0 of about 12 to 18, meaning that every infected individual is likely to infect 12 to 18 more susceptible people a day. In a home with more than one susceptible individual, the susceptible individuals have a 76 to 90 percent likelihood of being infected.
In temperate climates, measles tends to be a disease of the winter and early spring. Further, because the virus requires a supply of susceptible people and spreads easily in close quarters, it has been shown to spread most often from cities to suburbs to rural areas.
The earliest attempts to protect against measles infection occurred in 1749 when passing measles from one infected person to another was tried, such as was done for smallpox. The process, called morbillization, did not work.
Between 1920 and 1940, attempts to create inactivated or attenuated vaccines in chick embryos met with only limited success.
The breakthrough that paved the way for modern measles vaccine success was tissue culture. By 1963, the first measles vaccine in the U.S., derived using tissue culture, was licensed. Unfortunately, it had a troublesome side effect portfolio, often causing fever and rash. If immunoglobulin was given simultaneously, side effect rates improved, but scientists realized that the strain, called the Edmonston strain, needed further attenuation to improve its safety. In 1965, a further weakened version became available, but the strain used in today’s measles vaccine, Moraten which stands for “more attenuated,” was not introduced until 1968. While most other countries also use strains developed from the Edmonston strain, they do not necessarily use Moraten. A few notable exceptions use vaccines developed from strains that did not derive from Edmonston, including Russia, Japan and China, among others.
In addition to different versions of measles vaccine throughout the world, vaccination schedules also vary. Public health officials from different regions of the world work to balance the average age of exposure with the disappearance of maternal antibodies, which interfere with vaccine effectiveness. In areas where the likelihood for exposure in infancy is greater, the vaccine tends to be recommended around 9 months of age; whereas in areas, such as the U.S., where early exposure is (typically) of less concern, the first dose is delayed until 12 to 15 months of age. The trade-off for the three to six month window is an increase in effectiveness from about 85 percent to more than 95 percent. In the U.S., the second dose, recommended between 4 and 6 years of age, is primarily meant to increase the number of protected individuals to closer to 100 percent.
“Adults born in 1957 or later should receive at least one dose of MMR vaccine unless they have other acceptable evidence of immunity to these three diseases (Table 3). However, persons who received measles vaccine of unknown type, inactivated measles vaccine, or further attenuated measles vaccine accompanied by IG or high-titer measles immune globulin (no longer available in the United States) should be considered unvaccinated and should be revaccinated with one or two doses of MMR vaccine.” (Refer to section of recommendations, “Recommendations for Vaccination for Measles, Rubella, and Mumps, Vaccination of Adults (Aged >18 Years)”).
World Health Organization. Let every child have a name: The road to a world without measles. 26 Sept. 2012. Accessed: https://www.who.int/immunization/newsroom/let_every_child_have_a_name/en/
Griffin DE. “Measles Virus” in Fields Virology, Sixth Edition. Knipe DM and Howley PM, eds. 2013. Wolters Kluwer, Philadelphia, PA, pp.1042-1069.
Strebel PM, Papania MJ, Gastañaduy PA, and Goodson JL. “Measles Vaccines” in Plotkin’s Vaccines, Seventh Edition. Plotkin SA, Orenstein WA, Offit PA, and Edwards KM, eds. 2018. Elsevier, Philadelphia, PA, pp.579-618.
Contributed by: Charlotte A. Moser, MS, Paul A. Offit, MD
Categories: Vaccine Update March 2019, News and Views About Vaccines
Materials in this section are updated as new information and vaccines become available. The Vaccine Education Center staff regularly reviews materials for accuracy.
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