Measles infections often produce severe illness in children, associated with high fever, widespread rash, and transient immunosuppression. This condition remains a major cause of mortality among children in developing countries.
The highest attack rates have been in children, usually sparing infants less than 6 months of age because of passively acquired antibody; however, a shift in age-specific attack rates to greater involvement of adolescents and young adults was observed in the United States in the 1980s. A marked decline in measles in the United States during the early 1990s may reflect decreased transmission as increased immunization coverage takes ef-fect. However, in developing countries an estimated 1 million children still die from this disease each year.
Epidemics tend to occur during the winter and spring and increasingly are limited to one dose vaccine failures or groups who do not accept immunizations. The infection rate among exposed susceptible subjects in a classroom or household setting is estimated at 85%, and more than 95% of those infected become ill. The period of communicability is estimated to be 3 to 5 days before appearance of the rash to 4 days afterward.
After implantation in the upper respiratory tract, viral replication proceeds in the respira-tory mucosal epithelium. The effect within individual respiratory cells is profound. Even though measles does not directly restrict host cell metabolism, susceptible cells are dam-aged or destroyed by virtue of the intense viral replicative activity and the promotion of cell fusion with formation of syncytia. This results in disruption of the cellular cytoskele-ton, chromosomal disorganization, and the appearance of inclusion bodies within the nu-cleus and cytoplasm. Replication is followed by viremic and lymphatic dissemination throughout the host to distant sites, including lymphoid tissues, bone marrow, abdominal viscera, and skin. Virus can be demonstrated in the blood during the first week after ill-ness onset, and viruria persists for up to 4 days after the appearance of rash.
During the viremic phase, measles virus infects T and B lymphocytes, circulating monocytes, and polymorphonuclear leukocytes without producing cytolysis. Profound depression of cell-mediated immunity occurs during the acute phase of illness and persists for several weeks thereafter. This is believed to be a result of virus-induced downregulation of interleukin-12 production by monocytes and macrophages. The effect on B lymphocytes has been shown to suppress immunoglobulin synthesis; in addition, generation of natural killer cell activity appears to be impaired. There is also evidence that the capability of polymorphonuclear leukocytes to generate oxygen radicals is diminished, perhaps directly by the virus or by activated suppressor T cells. This may further explain the enhanced susceptibility to bacterial superinfections. Virion components can be detected in biopsy specimens of Koplik’s spots and vascular endothelial cells in the areas of skin rash.
In addition to necrosis and inflammatory changes in the respiratory tract epithelium, sev-eral other features of measles virus infection are noteworthy. The skin lesions show vasculitis characterized by vascular dilation, edema, and perivascular mononuclear cell infiltrates. The lymphoid tissues show hyperplastic changes, and large multinucleated reticuloendothelial gi-ant cells are often observed (Warthin–Finkeldey cells). Some of the giant cells contain intra-cytoplasmic and intranuclear inclusions. Similarly involved giant epithelial cells can be found in a variety of mucosal sites, the respiratory tract, skin, and urinary sediment.
The major findings in measles encephalitis include areas of edema, scattered petechial hemorrhages, perivascular mononuclear cell infiltrates, and necrosis of neurons. In most cases, perivenous demyelination in the CNS is also observed. The pathogenesis is thought to be related to infiltration by cytotoxic (CD8+) T cells, which react with myelin-forming or virus-infected brain cells.
Cell-mediated immune responses to other antigens may be acutely depressed during measles infection and persist for several months. There is evidence that measles virus-specific cell mediated immunity developing early in infection plays a role in mediating some of thefeatures of disease, such as the rash, and is necessary to promote recovery from the illness. Antibodies to the virus appear in the first few days of illness, peak in 2 to 3 weeks, and then persist at low levels. Immunity to reinfection is lifelong and is associated with the presence of neutralizing antibody. In patients with defects in cell-mediated immunity, including those with severe protein–calorie malnutrition, infection is prolonged, tissue involvement is more severe, and complications such as progressive viral pneumonia are common.