Chapter 243. MeaslesWilbert H. Mason
Measles is highly contagious and was once an inevitable experience during childhood. Due towidespread vaccination, endemic transmission has been interrupted in the United States;however, indigenous or imported cases have occasionally resulted in epidemics in the UnitedStates. In some areas of the world, measles remains a serious threat to children.
ETIOLOGY.
Measles virus is a single-stranded lipid enveloped RNA virus in the family Paramyxoviridae andgenus Morbillivirus. Other members of this genus are rinderpest virus of cattle and distemper virus of dogs, but humans are the only host of measles virus. Of the 6 major structural proteinsof measles virus, the 2 most important in terms of induction of immunity are the hemagglutinin(H) protein and the fusion (F) protein. The neutralizing antibodies are directed against the Hprotein, and antibodies to the F protein limit proliferation of the virus during infection. Smallvariations in genetic composition have also been identified that result in no effect on protectiveimmunity but provide molecular markers that can distinguish between viral types. These markershave been useful in the evaluation of endemic spread of measles.
EPIDEMIOLOGY.
The measles vaccine has changed the epidemiology of measles dramatically. Once worldwide indistribution, endemic transmission of measles has been interrupted in many countries wherethere is widespread vaccine coverage. Historically, in the United States it caused universalinfection in childhood with 90% of children acquiring the infection before 15 yr of age. Morbidityand mortality associated with measles decreased prior to the introduction of the vaccine due toimproved health care and nutrition. However, the incidence declined dramatically following theintroduction of the measles vaccine 1963. The attack rate fell from 313 cases/100,000population in 1956-60 to 1.3 cases/100,000 in 1982-88. It is most common in the winter andspring.A nationwide indigenous measles outbreak occurred in 1989-1991 resulting in >55,000 cases,11,000 hospitalizations, and 123 deaths, demonstrating that the infection had not yet beenconquered. The resurgence was attributed to vaccine failure in a small number of school-agedchildren and low coverage of preschool-aged children and because of more rapid waning of maternal antibodies in infants born to mothers who never experienced wild-type measlesinfection. Implementation of the 2 dose vaccine policy and more intensive immunizationstrategies resulted in interruption of endemic transmission in the United States in 1993. Thecurrent rate is <1 case/1,000,000 population.Measles continues to be imported into the United States from abroad; therefore, continuedmaintenance of >90% immunity through vaccination is necessary to prevent widespreadoutbreaks from occurring ( Fig. 243-1 ).
TRANSMISSION.
The portal of entry of measles virus is through the respiratory tract or conjunctivae followingcontact with large droplets or small droplet aerosols in which the virus is suspended. Patientsare infectious from 3 days before the rash up to 4-6 days after its onset. Approximately 90% of the exposed susceptible individuals develop measles. Face-to-face contact is not necessarybecause viable virus may be suspended in air up to 1 hr after a source case leaves a room.Secondary cases have been reported in physicians' offices and in hospitals by spread of aerosolized virus.
PATHOLOGY.
Measles infection causes necrosis of the respiratory tract epithelium and an accompanyinglymphocytic infiltrate. Measles produces a small vessel vasculitis on the skin and on the oralmucous membranes. Histology of the rash and exanthem reveals intracellular edema anddyskeratosis associated with formation of epidermal syncytial giant cells with up to 26 nuclei.Viral particles have been identified within these giant cells. In lymphoreticular tissue, lymphoidhyperplasia is prominent. Fusion of infected cells results in multinucleated giant cells,theWarthin-Finkeldey giant cells that are pathognomonic for measles, with up to 100 nuclei andintracytoplasmic and intranuclear inclusions ( Fig. 243-2 )
PATHOGENESIS
.Measles consists of 4 phases: incubation period, prodromal illness, exanthematous phase, andrecovery. During incubation, measles virus migrates to regional lymph nodes. A primary viremiaensues that disseminates the virus to the reticuloendothelial system. A secondary viremiaspreads virus to body surfaces. The prodromal illness begins following the secondary viremiaand is associated with epithelial necrosis and giant cell formation in body tissues. Cells are killedby cell-to-cell plasma membrane fusion associated with viral replication that occurs in manybody tissues, including cells of the central nervous system (CNS). Virus shedding begins in theprodromal phase. With onset of the rash, antibody production begins and viral replication andsymptoms begin to subside. Measles virus also infects CD4+ T cells, resulting in suppression of the Th1 immune response and a multitude of other immunosuppressive effects.
CLINICAL MANIFESTATIONS.
Measles is a serious infection characterized by high fever, an enanthem, cough, coryza,conjunctivitis, and a prominent exanthem. After an incubation period of 8-12 days, the prodromalphase begins with a mild fever followed by the onset of conjunctivitis with photophobia, coryza, aprominent cough and increasing fever. The enanthem, Koplik spots, is the pathognomonic signof measles and appears 1 to 4 days prior to the onset of the rash ( Fig. 243-3 ). They first appear as discrete red lesions with bluish white spots in the center on the inner aspects of the cheeks atthe level of the premolars. They may spread to involve the lips, hard palate, and gingiva. Theyalso may occur in conjunctival folds and in the vaginal mucosa. Koplik spots have been reportedin 50-70% of measles cases but probably occur in the great majority.Symptoms increase in intensity for 2-4 days until the 1st day of the rash. The rash begins aroundthe forehead (around the hairline), behind the ears, and on the upper neck as a redmaculopapular eruption. It then spreads downward to the torso and extremities, reaching thepalms and soles in up to 50% of cases. The exanthem frequently becomes confluent on the faceand upper trunk (Figs. 243-4 and 243-5 [4] [5]).With the onset of the rash, symptoms begin to subside and the rash fades over about 7 days inthe same progression as it evolved, often leaving a fine desquamation of skin in its wake. Of themajor symptoms of measles, the cough lasts the longest, often up to 10 days. In more severecases, generalized lymphadenopathy may be present, with cervical and occipital lymph nodesespecially prominent.
INAPPARENT MEASLES INFECTION.
In individuals with passively acquired antibody, such as infants or recipients of blood products, asubclinical form of measles may occur. The rash may be indistinct, brief, or, rarely, entirelyabsent. Likewise, some individuals who have received vaccine when exposed to measles maydevelop a rash but few other symptoms. Persons with inapparent or subclinical measles do notshed measles virus and do not transmit infection to household contacts.Children who had received the original formalin-inactivated measles vaccine at times developeda more severe form of disease called atypical measles. Patients had onset of high fever andheadache followed by the appearance of a maculopapular rash on the extremities that becomepetechial and purpuric and progressed in a centripetal direction. The illness was frequentlycomplicated by pneumonia and pleural effusions. It is thought that atypical measles was causedby development of circulating immune complexes that formed due to an abnormal immuneresponse to the vaccine.
LABORATORY FINDINGS.
The diagnosis of measles is almost always based on clinical and epidemiologic findings.Laboratory findings in the acute phase include reduction in the total white blood cell count, withlymphocytes decreased more than neutrophils. Absolute neutropenia has been known to occur,however. In measles not complicated by bacterial infection, the erythrocyte sedimentation rateand C-reactive protein levels are normal.
DIAGNOSIS.
In the absence of a recognized measles outbreak, confirmation of the clinical diagnosis is oftenrecommended. Serologic confirmation is most conveniently made by identification of immunoglobulin M (IgM) antibody in serum. IgM antibody appears 1-2 days after the onset of therash and remains detectable for about 1 mo. If a serum specimen is collected <72 hoursfollowing onset of rash and is negative for measles antibody, a repeat specimen should beobtained. Serologic confirmation may also be made by demonstration of a 4-fold rise in IgGantibodies in acute and convalescent specimens taken 2-4 wk later. Viral isolation from blood,urine, or respiratory secretions can be accomplished by culture at the Centers for DiseaseControl and Prevention (CDC) or local or state laboratories. Molecular detection by polymerasechain reaction is possible but is a research tool.
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