Measles is no longer an endemic disease in the USA. However, measles often arrives via infected travelers by airplane from other areas of the world, often spreading to susceptible persons before the classic symptoms become apparent. Due to its high transmissibility by aerosol, it is frequently transmitted in emergency rooms and medical offices from people who are seeking care during the early manifestations of measles infection.
Despite an effective live virus vaccine that was licensed in 1963, measles remains one of the leading causes of death in children younger than 5 years of age and kills approximately 400 children per day worldwide. Measles is a serious disease, which spreads rapidly to others in respiratory droplets from sneezing and coughing. It is one of the most contagious diseases known.
The global measles initiative to reduce measles mortality worldwide has had remarkable success at reducing deaths from measles from 733,000 in 2000 to 164,000 in 2008. Measles in the developing world has a much higher mortality rate than in developed countries because of complex interactions between malnutrition, age at infection, type and outcome of complications, crowding or intensity of exposure, and the availability of care.
Measles in the USA prior to the measles vaccine was estimated to cause 4,000,000 cases per year (equivalent to the entire birth cohort in the USA); virtually every person had measles virus infection by age 20. There were 150,000 cases with lower respiratory complications (such as bacterial or viral pneumonia, bronchitis, and croup); 150,000 cases of otitis media; 48,000 hospitalizations; and 4000 cases of encephalitis annually. Between 1989 and 1991, when the USA experienced renewed measles activity—prior to introducing a second dose of measles vaccine—there were 55,000 cases and more than 130 deaths.
Uncomplicated measles in developed countries begins 1 to 2 weeks after exposure. The illness begins with fever followed by cough, coryza (runny nose), and conjunctivitis, similar to many other respiratory infections; the infection is very contagious at this stage.
After several days the fever increases and the pathognomonic enanthem, Koplik spots appear (a rash on the inside of the cheek, which is often not observed). One to 2 days later (usually about day 14 after exposure) the characteristic erythematous maculopapular rash appears first on the face and then spreads down the body. Early on, the rash usually blanches on pressure, but as it begins to fade 3–5 days later it becomes brownish, also clearing first on the face and spreading down.
Infections of the middle ears, pneumonia, croup, and diarrhea are common complications of measles. Approximately 5% of children (500 out of 10,000) with measles will develop pneumonia. Measles encephalitis occurs in 1 per 1,000 cases of natural measles, and when it occurs it has a mortality of almost 50%; many of the survivors have permanent brain damage. This translates to 1 to 3 of every 1,000 children who get measles in the USA will die from the disease. Death occurs more commonly in infants, especially malnourished children, and among immunocompromised persons, including those with HIV infection and leukemia. These latter persons—who often cannot be immunized—can be protected by herd immunity if those around them are immune.
Subacute sclerosing panencephalitis (SSPE) is a rare fatal illness caused by ongoing measles virus infection of the brain. Symptoms of brain damage usually begin 7 to 10 years after infection. Death occurs 1 to 3 years after the onset of symptoms. Risk factors for develop- ing SSPE include developing measles infection at a young age. The incidence of SSPE is estimated to be between 7 and 11 cases per 100,000 cases of measles. The measles vaccine virus has not been associated with SSPE.
The measles virus was first isolated in tissue culture in 1954, just as the polioviruses in the laboratory of John Enders. Vaccine development followed rapidly with licensure in the USA in 1963. The virus was passaged multiple times, first in human kidney cells and then in human amnion cells. It was then adapted to chick embryos and finally passaged in chick embryo cells. The initial live virus vaccine that was licensed prevented measles complications but was associated with high rates of fever and rash, leading to further attenuation of the vaccine.
The vaccine virus was found to be both temperature and light unstable, and required the addition of stabilizers. Even in the lyophilized form with the addition of stabilizers, it must be stored in the dark at 2–8°C. After reconstitution, the virus loses about 50% of its potency in 1 hour at room temperature.
The further attenuated live virus vaccine was combined in 1971 with mumps and rubella live virus vaccines into a single injection, the measles, mumps, and rubella vaccine (abbreviated MMR), and subsequently with varicella vaccine (MMRV) in 2005. Two doses of vaccine are recommended for all the vaccine compo- nents to ensure that more than 95% of the population be immune to measles, which is the threshold for maintaining community (herd) immunity.
A formalin-inactivated vaccine was also developed and licensed at the same time as the live virus vaccine but is no longer utilized because those who received that vaccine developed a new disease called “atypical measles,” which resembled Rocky Mountain Spotted Fever (a tick-borne disease caused the bacterium Rickettsia rickettsia), when they encountered live measles virus (either wild type or vaccine virus).
Following licensure of measles vaccine, rates of the disease in the USA fell dramatically. However, 95% or more of individuals must be immune to measles to prevent its transmission in communities. Because of this, most states in the 1970s instituted mandatory immunization of children as a condition of school entry. In 1991 a two-dose immunization strategy was instituted. This has resulted in elimination of endemic measles in the USA.
Because of misinformation about measles vaccine safety in the United Kingdom, beginning in 1998, MMR vaccine coverage declined across Europe, result- ing in outbreaks of measles and mumps in Europe, the USA, and Canada.
There were 140 cases of measles in the USA in 2008; more than three quarters of these cases were linked to imported measles from another country, and most of the imported cases occurred among unimmunized American travelers.