The Clinical Significance of Measles: A Review

SUPPLEMENT ARTICLE The Clinical Significance of Measles: A Review Robert T. Perry1 and Neal A. Halsey2 1 National Immunization Program, Centers for Disease Control and Prevention, Atlanta, Georgia; 2Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland Before the introduction of measles vaccines, measles virus infected 95%–98% of children by age 18 years [1–4], and measles was considered an inevitable rite of passage. Exposure was often actively sought for children in early school years because of the greater severity of measles in adults. CHARACTERISTIC ILLNESS After an incubation period of 8–12 days, measles begins with increasing fever (to 39C–40.5C) and cough, coryza, and conjunctivitis [5, 6]. Symptoms intensify over the 2–4 days before the onset of rash and peak on the first day of rash [7]. The rash is usually first noted on the face and neck, appearing as discrete erythematous patches 3–8 mm in diameter. The lesions increase in number for 2 or 3 days, especially on the trunk and the face, where they frequently become confluent (figure 1). Discrete lesions are usually seen on the distal extremities, and with careful observation, small num- N.H. has research grants from Glaxo SmithKline (a manufacturer of measles vaccine) for studies of Haemophilus influenzae type b and Lyme disease vaccines. Financial support: CDC cooperative agreement for the Clinical Immunization Safety Assessment (CISA) Network. Reprints or correspondence: Dr. Neal Halsey, Dept. of International Health, Johns Hopkins Bloomberg School of Public Health, w5515, 615 N. Wolfe St., Baltimore, MD 21205 (). The Journal of Infectious Diseases 2004; 189(Suppl 1):S4–16  2004 by the Infectious Diseases Society of America. All rights reserved. 0022-1899/2004/18909S1-0002$15.00 S4 • JID 2004:189 (Suppl 1) • Perry and Halsey bers of lesions can be found on the palms of 25%–50% of those infected. The rash lasts for 3–7 days and then fades in the same manner as it appeared, sometimes ending with a fine desquamation that may go unnoticed in children who are bathed daily. An exaggerated desquamation is commonly seen in malnourished children [6, 9, 10]. Fever usually persists for 2 or 3 days after the onset of the rash, and the cough may persist for as many as 10 days. Koplik’s spots usually appear 1 day before the onset of rash and persist for 2 or 3 days. These bluish-white, slightly raised, 2- to 3-mm-diameter lesions on an erythematous base appear on the buccal mucosa, usually opposite the first molar, and occasionally on the soft palate, conjunctiva, and vaginal mucosa [11, 12]. Koplik’s spots have been reported in 60%–70% of persons with measles but are probably present in most persons who develop measles [13]. An irregular blotchy enanthem may be present in other areas of the buccal mucosa. Photophobia from iridocyclitis, sore throat, headache, abdominal pain, and generalized mild lymphadenopathy are also common. Measles is transmitted by the respiratory route and is highly infectious. Infectivity is greatest in the 3 days before the onset of rash, and 75%–90% of susceptible household contacts develop the disease [14–16]. The early prerash symptoms are similar to those of other common respiratory illnesses, and affected persons often participate in routine social activities, facilitating Forty years after effective vaccines were licensed, measles continues to cause death and severe disease in children worldwide. Complications from measles can occur in almost every organ system. Pneumonia, croup, and encephalitis are common causes of death; encephalitis is the most common cause of long-term sequelae. Measles remains a common cause of blindness in developing countries. Complication rates are higher in those !5 and 120 years old, although croup and otitis media are more common in those !2 years old and encephalitis in older children and adults. Complication rates are increased by immune deficiency disorders, malnutrition, vitamin A deficiency, intense exposures to measles, and lack of previous measles vaccination. Case-fatality rates have decreased with improvements in socioeconomic status in many countries but remain high in developing countries. infections are not known to transmit measles virus to household contacts [33]. Atypical measles occurred in children who received formalininactivated (killed) measles vaccine that was in use in the United States from 1963 to 1968 [34]. These children developed high fever, a rash that was most prominent on the extremities and often included petechiae, and a high rate of pneumonitis [34– 36]. Recent studies in monkeys indicate that this illness was caused by antigen-antibody immune complexes resulting from incomplete maturation of the antibody response to the vaccine [37, 38]. COMPLICATIONS transmission. Numerous outbreaks of disease in highly vaccinated populations occur when children in the first few days of illness attend sporting events as participants or spectators, especially indoor events such as basketball and wrestling tournaments [17–21]. Outbreaks also occur when ill children are brought to a doctor’s office or emergency room for evaluation for fever, irritability, or rash [22, 23]. MILD, MODIFIED, AND ATYPICAL MEASLES Milder forms of measles occur in children and adults with preexisting partial immunity. Infants who have low levels of passively acquired maternal antibody and persons who receive blood products that contain antibody often have subclinical infections or minimal symptoms that may not be diagnosed as measles [24– 26]. Vaccination protects 190% of recipients against disease, but after exposure to natural measles, some vaccinees develop boosts in antibody associated with mild symptoms and may have rash with little or no fever or nonspecific respiratory symptoms [27–32]. People with inapparent subclinical measles virus RESPIRATORY COMPLICATIONS Otitis media. Otitis media is the most common complication of measles reported in the United States and occurs in 14% of children !5 years old (table 2). Presumably, inflammation of the epithelial surface of the eustachian tube causes obstruction and secondary bacterial infection. Lower rates of otitis media are noted with increasing age, most likely a function of the increasing diameter of the eustachian tube and the decreasing risk of obstruction. Laryngotracheobronchitis. Laryngotracheobronchitis or“measles croup” was noted in 9%–32% of US children hospitalized with measles [73–78]. The majority of affected children were !2 years old. In one-third to one-half of such cases, culture of samples from the trachea yields positive results for bacterial pathogens, with a purulent exudate and evidence of secondary bacterial tracheitis, pneumonia, or both. The most commonly cultured organism is Staphylococcus aureus, although StreptoClinical Significance of Measles • JID 2004:189 (Suppl 1) • S5 Figure 1. Development and distribution of meas (...truncated)