88 Measles

Measles (rubeola; hard measles; red measles; 9-day measles; morbilli) is a common, acute, viral infec­tious disease, principally of children, with world­wide distribution, that is clinically characterized by fever and a typical red, blotchy rash combined with cough, coryza, or conjunctivitis.

Etiology and Epidemiology

Measles is caused by a virus, which is in the genus Morbillivirus of the family Paramyxoviridae. Al­though the virus does not survive drying on a sur­face, it can survive drying in microdroplets in the air.

Measles is one of the most highly communicable diseases, transmitted by contact of susceptible indi­viduals with the nose and throat secretions of in­fected persons, primarily by droplet spread. Infec­tion also occurs by direct contact, and by indirect contact through freshly soiled articles and airborne transmission. There is no reservoir for measles other than human beings, which means that a continuous chain of susceptible contacts is necessary to sustain transmission. The period of communicability is from slightly before the beginning of the prodromal phase of the disease to 4 days after the start of the rash. There is no carrier state. Measles has an incubation period from time of exposure to onset of fever of about 10 days with a range from 8 to 13 days. The incubation period from time of exposure to rash on­set is about 14 days.

In populated areas with no or low vaccination cov-

erage, measles is primarily an endemic disease of children, with epidemics occurring every 2 to 5 years. In such areas, the greatest incidence is in children under 2 years of age. Epidemic measles has a winter-spring seasonality in temperate climates and a less marked hot-dry seasonality in equatorial regions.

Measles mortality is highest in the very young and the very old. In malnourished children in the developing world, the case fatality rate may be as high as 5 to 10 percent or more. Some studies have indicated that multiple cases within a family group may lead to higher mortality rates.

Distribution and Incidence

Measles has a worldwide distribution, and the Ex­panded Programme on Immunization of the World Health Organization maintains an information sys­tem on reported cases and vaccination coverage in member countries. Because of underreporting, world­wide reported measles incidence represents only a small fraction of an estimated 50 million cases and 1.5 million deaths caused annually by measles in developing countries. It should be emphasized that reported incidence is subject to completeness of re­porting and also to a general trend of improving disease Stuveillance. Measles vaccination as part of the Expanded Programme on Immunization, with global coverage estimated at 55 percent for children under 1 year of age (52 percent in developing coun­tries), is currently averting over 40 million cases and over 1 million deaths resulting from the disease each year in Third World countries.

In populated areas where measles is both endemic and epidemic, over 90 percent of the adult popula­tion will show serologic evidence of prior infection. In remote or island populations where measles is not endemic, a significant proportion of the population can be susceptible, which may produce large out­breaks when the measles virus is introduced from the outside.

Immunology

Infants usually have a passive immunity to measles as a result of maternal antibodies acquired transpla- centally from immune mothers. This passive immu­nity protects the infant from measles infection for 6 to 9 months, depending on the amount of maternal antibody acquired.

Measles infection induces a lifelong immunity. Several methods for confirming infection and immu­nity have been developed, including the following: serologic tests, fluorescent antibody techniques, and isolation of the virus from patients during the acute phase of the disease.

A single dose of live attenuated measles virus vaccine confers long-term, probably lifelong, immu­nity in over 95 percent of susceptible individuals. The optimal age for vaccination is related to the persistence of passive immunity from maternal anti­bodies and patterns of disease transmission. For de­veloped countries with low incidence, such as the United States, vaccination at 15 months of age is recommended, whereas in developing countries the Expanded Programme on Immunization recom­mends vaccination at 9 months of age.

Measles vaccine may confer immunity if given within 72 hours of exposure; and immune globulin (IG), if given within 6 days of exposure, may provide a limited-duration protection from measles, owing to passively acquired antibodies from the immune globulin.

Clinical Manifestations and Pathology

The prodromal phase of measles disease typically includes symptoms and signs of fever, cough, coryza, and conjunctivitis. During this stage, small whitish specks on reddened areas of the mucosal lining of the mouth called Koplik’s spots are diagnostic of mea­sles. The prodromal period continues for 3 to 7 days until the characteristic blotchy reddish rash ap­pears. This rash usually appears first on the head and then spreads down the body and outward to the limbs, lasting about 4 to 7 days.

Complications due to viral replication or secon­dary bacterial infection may occur, however, and result in middle-ear infections and pneumonia. Diar­rhea may also complicate measles and, in the devel­oping world, is one of the most important causes of measles-associated mortality. Neurological involve­ment may also occur, resulting in encephalitis dur­ing or soon after the acute illness or in the rare subacute sclerosing panencephalitis (SSPE) after a lengthy incubation period. Measles is uncommon during pregnancy, and the limited data available do not appear to demonstrate clearly any increased risk of fetal mortality or congenital malformations.

History and Geography

Ancient Times Through the Eighteenth Century

The origin of measles is unknown. Francis Black (1976) has noted that populations of a sufficient size to allow for a continuous chain of susceptibles re­quired to sustain measles transmission would not have developed until sometime after 2500 B.C. He has suggested that measles may have arisen as an adaptation of one of the other viruses of the same genus (which includes rinderpest and canine distem­per). It is interesting to note that Hippocrates, writ­ing in the fourth century B.C., did not describe a rash illness that would be consistent with measles, even though his recorded case histories document the existence of many other infections in ancient Greece.

The history of measles is confused with that of smallpox in much of the early literature. Although records are scanty, major unidentified epidemics with high mortality rates spread through the Roman Empire in A.D. 165-80 and again in 251-66. Wil­liam McNeill (1976) has noted that there are some suggestive circumstances that make it tempting to believe that these two “demographic disasters” sig­naled the arrival of measles and smallpox. In China, two major epidemics with high mortality were re­corded in A.D.

During medieval times, measles was referred to by the Latin term morbilli, the diminutive of morbus, meaning the “little disease.” August Hirsch (1883-6) notes that measles was also called rubeola, rossalia, rosagia, as well as the colloquial names fersa or sofersa (Milanese), mesles and later measles (English), maal and masern (German), and the masura or spots (Sanskrit). The derivation of the English name “measles” is in some doubt. One sug­gestion is that it may have come from the Latin term miscellus or misella, a diminutive of the Latin miser, meaning “miserable” - a term given to those suffer­ing from leprosy. The sores on the legs of leprosy patients were known as mesles, and John of Gaddes- den in the early fourteenth century unjustifiably coupled these mesles with the disease morbilli of medical authors. Eventually the term “measles” lost its connection with leprosy.

Measles, smallpox, and other rash illnesses contin­ued to be confused in Europe during the Middle Ages. The seventeenth-century physician and epide­miologist Thomas Sydenham studied measles epi­demics in 1670 and 1674 and made observations on the clinical features of the illness and its complica­tions.

Nineteenth Century

The most famous epidemiological study of measles was conducted by Peter Panum and reported in his classic Observations Made During the Epidemic of Measles on the Faroe Islands in the Year 1846 (1940). Measles attacked about 6,100 islanders during 1846 and was associated with the deaths of 102 of the 7,864 inhabitants, who had been completely free of the disease for 65 years. Panum confirmed the respi­ratory route of transmission, the incubation period, and the lifelong immunity acquired from previous infection. Hirsch (1883-6) built on Panum’s work and recorded the universal geographic distribution of measles by noting accounts of epidemics that had occurred in most parts of the world. He noted that measles reached the Western Hemisphere soon after the arrival of the first European colonists and fol­lowed the westward movement of the settlers. He suggested that introduction of the disease into the Australian continent occurred in 1854 after first ap­pearing in the Hawaiian Islands in 1848.

A particularly vivid account of the dramatic 1876 measles epidemic in Fiji quoted by Hirsch illustrates the conditions that accounted for the relatively high mortality:

Later in the epidemic, when it is said to be like plague,... the people, seized with fear, had abandoned their sick.... The people chose swampy sites for their dwellings, and whether they kept close shut up in huts without ventila­tion, or rushed into the streams and remained in the water during the height of the illness, the consequences were equally fatal. The excessive mortality resulted from terror at the mysterious seizure, and [from] the want of the commonest aids during illness.... Thousands were car­ried off by want of nourishment and care, as well as by dysentery and congestion of the lungs....

It was especially dramatic when measles struck a “virgin soil” population that had no prior or recent exposure to measles disease or measles vaccine, and thus the outbreak affected most persons. With re­gard to the introduction of measles by the Spaniards from the Old World into the Amerindian populations of the New World, McNeill (1976) noted that “mea­sles followed hard upon the heels of smallpox, spread­ing through Mexico and Peru in 1530—1. Deaths were frequent, as is to be expected when such a disease encounters a virgin population dense enough to keep the chain of infection going.” High mortality was also reported in measles epidemics that oc­curred in virgin soil island populations in the Pacific Ocean in the nineteenth century: 40,000 deaths out of a population of 150,000 in Hawaii in 1848, 20,000 deaths comprising 20 to 25 percent of the population of Fiji in 1874, and 645 deaths out of 8,845 cases in Samoa in 1911. High mortality in these settings was likely due to some of the same factors that result in high mortality rates among unvaccinated individu­als in many areas of the developing world today, including lack of supportive care, lack of treatment for complications, and malnutrition. In virgin soil settings where populations were well nourished and where better medical care was available, the mortal­ity rate was much lower, as noted in the outbreak of measles in southern Greenland in 1951 where, in one district, 4,257 persons out of a population of about 4,400 contracted measles and 77 deaths oc­curred (Christensen et al. 1953).

Not until 1896 did Henry Koplik publish a descrip­tion of Koplik’s spots, although apparently their sig­nificance was independently recognized about a cen­tury earlier by John Quier in Jamaica and Richard Hazeltine in Maine.

Prevention and Control

Research leading to the development of current mea­sles vaccines began around the beginning of this century. John Anderson and Joseph Goldberger (1911) demonstrated that the illness was caused by a virus, by injecting filtered material from patients with acute diseases into monkeys. Harry Plotz (1938) and Geoffrey Rake and Morris Shaffer (1940) reported the cultivation of measles virus in tissue culture. In 1954, with the advent of reliable tissue culture techniques, J. F. Enders and T. C. Peebles were able to isolate the measles virus. Subsequent research by S. L. Katz, M. J. Milanovic, and J. F. Enders (1958) resulted in the development of an attenuated strain of measles vaccine which was pro­duced in 1958. In 1963, after field trials, the attenu­ated (“live”) measles vaccine was licensed for gen­eral use in the United States. An inactivated (“killed”) measles vaccine was also developed, but was shown to be inferior and is no longer available.

With the establishment of the World Health Orga­nization Expanded Programme on Immunization in 1974, measles vaccine has been introduced into the national immunization programs of most countries. The current levels of immunization coverage for mea­sles vaccine show wide geographic variation. Except for more remote isolated populations where the oc­currence of measles disease is not endemic and is subject to infrequent introduction of virus, the geo­graphic occurrence in the world today is related to the immunization coverage with measles vaccine. In countries with sustained, large-scale immunization programs and reliable disease surveillance, the im­pact of control efforts has been documented through decreasing numbers of reported cases. Global mea­sles eradication is considered to be technically possi­ble, but it is increasingly recognized that extremely high immunization coverage levels will be necessary to achieve such a goal.

Robert J. Kim-Farley

This chapter was written in the author’s private capacity. No official support or endorsement by the Centers for Disease Con­trol is intended or should be inferred.

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