MEASLES : CLINICAL ASPECTS
Common synonyms for measles include rubeola, 5-day measles, and hard measles. The incubation period ranges from 7 to 18 days. A typical illness usually begins 9 to 11 days after exposure, with cough, coryza, conjunctivitis, and fever. One to three days after on-set, pinpoint gray–white spots surrounded by erythema (grains-of-salt appearance) appear on mucous membranes. This sign, called Koplik’s spots, is usually most noticeable over the buccal mucosa opposite the molar teeth and persists for 1 to 2 days. Within a day of the appearance of Koplik’s spots, the typical measles rash begins, first on the head, then on the trunk and extremities. The rash is maculopapular and semiconfluent; it persists for 3 to 5 days before fading. Fever and severe systemic symptoms gradually diminish as the rash progresses to the extremities. Lymphadenopathy is also common, with particularly noticeable involvement of the cervical nodes.
Measles can be very severe, especially in immunocompromised or malnourished patients. Death can result from overwhelming viral infection of the host, with extensive involvement of the respiratory tract and other viscera. In some developing countries, mor-tality rates of 15 to 25% have been recorded.
Bacterial superinfection, the most common complication, occurs in 5 to 15% of all cases. Such infections include acute otitis media, mastoiditis, sinusitis, pneumonia, and sepsis. Clinical signs of encephalitis develop in 1 of 500 to 1000 cases. This condition usually occurs 3 to 14 days after onset of illness and can be extremely severe. The mortality in measles encephalitis is approximately 15%, and permanent neurologic damage among survivors is estimated at 25%. Acute thrombocytopenic purpura may also develop during the acute phase of measles, leading to bleeding episodes. Abdominal pain and acute ap-pendicitis can occur secondary to inflammation and swelling of lymphoid tissue.
Subacute sclerosing panencephalitis is a rare, progressive neurologic disease of children, which usually begins 2 to 10 years after a measles infection. It is characterized by insidious onset of personality change, poor school performance, progressive intellectual deterioration, development of myoclonic jerks (periodic muscle spasms), and motor dysfunctions such as spasticity, tremors, loss of coordination, and ocular abnormalities, including blindness. Neu-rologic and intellectual deterioration generally progress over 6 to 12 months, with children eventually becoming bedridden and stuporous. Dysfunctions of the autonomic nervous sys-tem, such as difficulty with temperature regulation, may develop. Progressive inanition, superinfection, and metabolic imbalances eventually lead to death. Most of the pathologic features of the disease are localized to the CNS and retina. Both the gray and the white mat-ter of the brain are involved, the most noteworthy feature being the presence of intranuclear and intracytoplasmic inclusions in oligodendroglial and neuronal cells.
The disease is a result of chronic wild measles virus infection of the CNS. Studies have shown that patients have a variety of patterns of missing measles virus structural proteins in brain tissue. Thus, any of several defects in viral gene expression may prevent normal viral assembly, allowing persistence of defective virus at an intracellular site with failure of immune eradication.
Rarely, a similar progressive, degenerative neurologic disorder may be related to per-sistent rubella virus infection of the CNS. This condition is seen most often in adoles-cents who have had congenital rubella syndrome. Rubella virus has been isolated from brain tissue in these patients, again using cocultivation techniques. The incidence of subacute sclerosing panencephalitis is approximately one per 100,000 measles cases. Its occurrence in the United States has decreased markedly over the past 25 years with the widespread use of live measles vaccine. At present, there is no accepted effective therapy for subacute sclerosing panencephalitis.
The typical measles infection can often be diagnosed on the basis of clinical findings, but laboratory confirmation is necessary. Virus isolation from the oropharynx or urine is usually most productive in the first 5 days of illness. Measles grows on a variety of cell cultures, producing multinucleated giant cells similar to those observed in infected host tissues. If rapid diagnosis is desired, measles antigen may be identified in urinary sediment or pharyn-geal cells by direct fluorescent antibody methods. Serologic diagnosis may involve comple-ment fixation, hemagglutination inhibition, EIA, or indirect fluorescent antibody methods.
No specific therapy is available other than supportive measures and close observation for the development of complications such as bacterial superinfection. Intravenous ribavirin has been suggested for patients with severe measles pneumonia, but no controlled studies have been performed.
Live, attenuated measles vaccine is available and highly immunogenic, most commonly administered as MMR. To ensure effective immunization, the vaccine should be adminis-tered to infants at 12 to 15 months of age with a second dose at 4 to 6 or 11 to 12 years of age. Immunity induced by the vaccine may be lifelong. Because the vaccine consists of live virus, it should not be administered to immunocompromised patients and it is not rec-ommended for pregnant women. Exceptions to these guidelines include susceptible human immunodeficiency virus–infected persons. Exposed susceptible patients who are immunologically compromised (including small infants) may be given immune serum globulin intramuscularly. This treatment can modify or prevent disease if given within 6 days of exposure, but protection is transient.