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This virus causes measles, a disease characterized by a maculopapular rash. It occurs primarily in childhood.
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The genome of measles virus consists of single-stranded RNA with a negative polarity (Table 39–1). It is an enveloped virus with a helical nucleocapsid. The virus has a single serotype. Humans are the natural host.
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Summary of Replicative Cycle
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After adsorption to the cell surface via its hemagglutinin, the virus penetrates and uncoats and the virion RNA polymerase transcribes the negative-strand genome into mRNA. Multiple mRNAs are synthesized, each of which is translated into the specific viral proteins; no polyprotein analogous to that synthesized by poliovirus is made. The helical nucleocapsid is assembled, the matrix protein mediates the interaction with the envelope, and the virus is released by budding from the cell membrane.
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Transmission & Epidemiology
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Measles virus is transmitted via respiratory droplets produced by coughing and sneezing both during the prodromal period and for a few days after the rash appears. Measles occurs worldwide, usually in outbreaks every 2 to 3 years, when the number of susceptible children reaches a high level. The World Health Organization (WHO) estimates there are 7 million cases of measles each year worldwide.
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In the year 2000, the Centers for Disease Control and Prevention (CDC) declared that measles is eliminated from the United States. Elimination meant that sustained transmission within the United States no longer occurred. However, cases acquired abroad (imported cases) followed by small outbreaks continue to occur. In 2016, measles was declared eradicated from the Western Hemisphere.
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In 2019, a widespread outbreak of measles occurred in the United States. As of this writing, more than 700 cases have occurred in 22 states. It is believed to have originated from an imported case in an unimmunized child.
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The attack rate is one of the highest of viral diseases; most children contract the clinical disease on exposure. When this virus is introduced into a population that has not experienced measles, such as the inhabitants of the Hawaiian Islands in the 1800s, devastating epidemics occur. In malnourished children, especially those in developing countries, measles is a much more serious disease than in well-nourished children. Vitamin A deficiency is especially important in this regard, and supplementation of this vitamin greatly reduces the severity of measles. Patients with deficient cell-mediated immunity (e.g., acquired immunodeficiency syndrome [AIDS] patients) have a severe, life-threatening disease when they contract measles.
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Pathogenesis & Immunity
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After infecting the cells lining the upper respiratory tract, the virus enters the blood and infects reticuloendothelial cells, where it replicates again. It then spreads via the blood to the skin. The rash is caused primarily by cytotoxic T cells attacking the measles virus-infected vascular endothelial cells in the skin. Antibody-mediated vasculitis may also play a role. Shortly after the rash appears, the virus can no longer be recovered and the patient can no longer spread the virus to others. Multinucleated giant cells, which form as a result of the fusion protein in the spikes, are characteristic of the lesions.
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Lifelong immunity occurs in individuals who have had the disease. The hemagglutinin on the surface of the virion is the antigen against which neutralizing antibody is directed. Although IgG antibody may play a role in neutralizing the virus during the viremic stage, cell-mediated immunity is more important. The importance of cell-mediated immunity is illustrated by the fact that agammaglobulinemic children have a normal course of disease, are subsequently immune, and are protected by immunization. Maternal antibody passes the placenta, and infants are protected during the first 6 months of life.
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Infection with measles virus can transiently depress cell-mediated immunity against other intracellular microorganisms, such as Mycobacterium tuberculosis, leading to a loss of purified protein derivative (PPD) skin test reactivity, reactivation of dormant organisms, and clinical disease. The proposed mechanism for this unusual finding is that when measles virus binds to its receptor (called CD46) on the surface of human macrophages, the production of interleukin-12 (IL-12), which is necessary for cell-mediated immunity to occur, is suppressed. In 2019, it was reported that measles virus infection can cause the loss of preexisting antibodies, perhaps by affecting memory B cells.
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After an incubation period of 10 to 14 days, a prodromal phase characterized by fever, conjunctivitis (causing photophobia), running nose, and coughing occurs. Koplik’s spots appear several days before the rash and are virtually diagnostic. They are bright red lesions with a white, central dot that are located on the buccal mucosa (Figure 39–1). A few days later, a maculopapular rash appears on the face and proceeds gradually down the body to the lower extremities, including the palms and soles (Figure 39–2 and Table 39–2). The rash develops a brownish hue several days later.
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The complications of measles can be quite severe. Encephalitis occurs at a rate of 1 per 1000 cases of measles. The mortality rate of encephalitis is 10%, and there are permanent sequelae, such as deafness and mental retardation, in 40% of cases. In addition, both primary measles (giant cell) pneumonia and secondary bacterial pneumonia occur. Bacterial otitis media are quite common. Subacute sclerosing panencephalitis (SSPE) is a rare, fatal disease of the central nervous system that occurs several years after measles (see Chapter 44).
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Measles in a pregnant woman leads to an increased risk of stillbirth rather than congenital abnormalities. Measles virus infection of the fetus is more severe than rubella virus infection, so the former typically causes fetal death, whereas the latter causes congenital abnormalities.
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Atypical measles occurs in some people who were given the killed vaccine and were subsequently infected with measles virus. It is characterized by an atypical rash without Koplik’s spots. Because the killed vaccine has not been used for many years, atypical measles occurs only in adults and is infrequent.
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Most diagnoses are made on clinical grounds, but a polymerase chain reaction (PCR) assay for measles virus RNA can be performed in cases that are difficult to diagnose. A greater than fourfold rise in antibody titer to measles virus can also be used.
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There is no antiviral therapy available.
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Prevention rests on immunization with the live, attenuated vaccine. The vaccine is effective and causes few side effects. Two doses are recommended. The first dose should be given between 12 and 15 months of age and the second dose at 4 to 6 years of age. It is usually given in combination with rubella and mumps vaccines (MMR vaccine). The vaccine should not be given to children prior to 12 months of age, because maternal antibody in the child can neutralize the virus and reduce the immune response. Because immunity can wane, a booster dose at 4 to 6 years is recommended.
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The vaccine contains live virus, so it should not be given to immunocompromised persons or pregnant women. The vaccine has decreased the number of cases of measles greatly in the United States; there were only 138 reported cases of measles in 1997. However, outbreaks still occur among unimmunized individuals (e.g., children in inner cities and in developing countries).
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The killed vaccine should not be used. Immune globulin can be used to modify the disease if given to unimmunized individuals early in the incubation period. This is especially necessary if the unimmunized individuals are immunocompromised.