Wednesday 11 June 2003
Definition: Measles virus is a leading cause of vaccine-preventable death and illness worldwide.
In 2001, there were an estimated 30 million cases of measles, including 777,000 deaths, most of which occurred in developing countries. Because of poor nutrition, children in developing countries are 10 to 1000 times more likely to die of measles pneumonia than are Western children.
Epidemics of measles occur among unvaccinated individuals. Measles can produce severe disease in people with defects in cellular immunity (such as HIV-infected patients or patients with hematologic malignancy). In the United States, the incidence of measles has decreased dramatically since 1963, when a measles vaccine was licensed.45
Measles virus is a single-stranded RNA virus of the paramyxovirus family that includes mumps, respiratory syncytial virus (the major cause of lower respiratory infections in infants), parainfluenza virus (a cause of croup), and human metapneumovirus. There is only one strain of measles virus.
Two cell-surface receptors have been identified for measles virus: CD46, a complement regulatory protein that inactivates C3 convertases, and signaling lymphocytic activation molecule (SLAM), a molecule involved in T-cell activation.
CD46 is expressed on all nucleated cells, while SLAM is expressed on cells of the immune system. Both these receptors bind the viral hemagglutinin protein.
Measles virus is spread by respiratory droplets, initially multiplies within upper respiratory epithelial cells, and then spreads to lymphoid tissues, where it can replicate in mononuclear cells, including T lymphocytes, macrophages, and dendritic cells.
Virus then spreads by the blood throughout the body. Most children develop T cell-mediated immunity to measles virus that controls the viral infection and produces the measles rash, a hypersensitivity reaction to viral antigens in the skin.
Measles may cause croup, pneumonia, diarrhea with protein-losing enteropathy, keratitis with scarring and blindness, encephalitis, and hemorrhagic rashes ("black measles") in malnourished children with poor medical care.
The rash does not occur in patients with deficiencies in cell-mediated immunity but does occur in agammaglobulinemic patients. Antibody-mediated immunity to measles virus protects against reinfection. Measles also can cause immunosuppression, and measles virus interactions with SLAM on T cells or dendritic cells may explain some of these immunosuppressive effects.
The subacute sclerosing panencephalitis (SSPE) and the measles inclusion body encephalitis (in immunocompromised individuals) are rare late complications of measles. The pathogenesis of SSPE is not well understood, but a replication-defective variant of measles may be involved in this persistent viral infection.
The blotchy, reddish brown rash of measles virus infection on the face, trunk, and proximal extremities is produced by dilated skin vessels, edema, and a moderate, nonspecific, mononuclear perivascular infiltrate.
Ulcerated mucosal lesions in the oral cavity near the opening of Stensen ducts (the pathognomonic Koplik spots) are marked by necrosis, neutrophilic exudate, and neovascularization.
The lymphoid organs typically have marked follicular hyperplasia, large germinal centers, and randomly distributed multinucleate giant cells, called Warthin-Finkeldey cells, which have eosinophilic nuclear and cytoplasmic inclusion bodies.
These are pathognomonic of measles and are also found in the lung and sputum. The milder forms of measles pneumonia show the same peribronchial and interstitial mononuclear cell infiltration that is seen in other nonlethal viral infections. In severe or neglected cases, bacterial superinfection may be a cause of death.
Measles pneumonia by Washington Deceit
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Patterson JB, Manchester M, Oldstone MB. Disease model: dissecting the pathogenesis of the measles virus. Trends Mol Med. 2001 Feb;7(2):85-8. PMID: 11286761