121 Rubella

Rubella (German measles; 3-day measles) is a com­mon, acute, viral infectious disease, principally of children and young adults, with worldwide distribu­tion frequently characterized clinically as a mild rash illness.

Etiology and Epidemiology

Rubella is caused by the rubella virus, which is in the genus Rubivirus of the family Togaviridae. Ru­bella virus is 50 to 60 nanometers in diameter and contains a single-stranded RNA genome.

Rubella is a highly contagious disease 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, by indirect contact through freshly soiled articles, and by airborne transmission. There is no reservoir for rubella other than human beings, which means that a continuous chain of susceptible contacts is necessary to sustain transmission. The period of communicability is from about 1 week be­fore rash onset to at least 4 days after. There is no carrier state except for infants with congenital ru­bella, who may shed virus for many months after birth. Rubella’s incubation period from time of expo­sure to onset of rash is 16 to 18 days, with a range of 14 to 23 days.

In populated areas with no or low vaccination cov­erage, rubella is primarily an endemic disease of children with periodic epidemics. However, a signifi­cant proportion of adults remain susceptible, and thus congenital rubella may result if a pregnant woman contracts rubella.

The risk of congenital rubella is related to gesta­tional age at the time of maternal infection. Fetal or placental infection has been shown to accompany 85 percent of maternal infections that occur during the first 8 weeks of pregnancy. Data from the last major epidemic in the United States, which occurred from 1964 to 1965 and resulted in 20,000 infants bom with congenital rubella syndrome, showed that the risk of developmental defects was about 50 percent in infants whose mothers were infected during the first month of pregnancy, 22 percent during the sec­ond, 6 percent during the third, and about 1 percent during the fourth month of pregnancy. Other investi­gators have shown that infection in the first 8 weeks of pregnancy also leads to high rates of abortion or stillbirth.

Distribution and Incidence

Rubella has a global distribution. Although it is not a reportable disease in most countries, is under­reported in countries where it is a notifiable dis­ease, and may be clinically inapparent in as many as 50 percent of infections, serologic surveillance demonstrates its existence throughout the world. In populated areas where rubella is both endemic and epidemic, between 80 and 90 percent of the adult population will show serologic evidence of prior in­fection. In remote or island populations where ru­bella is not endemic, a significant proportion of the population can be susceptible, which may lead to large outbreaks when the virus is introduced from the outside.

In some countries with extensive use of rubella vaccine and where rubella is a reportable disease, such as the United States and the United Kingdom, there have been impressive declines in reported cases of rubella and congenital rubella syndrome.

Immunology

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

Rubella infection in both clinically apparent and inapparent cases induces a lifelong immunity. Be­cause a significant percentage of rubella infections are clinically inapparent, persons may develop im­munity without recognizing that they have been in­fected. Several serologic tests for confirming infec­tion or immunity have been developed, and it is also possible to isolate the virus from patients during the acute phase of the disease.

A single dose of live attenuated rubella virus vaccine confers long-term, probably lifelong, im­munity in approximately 95 percent of susceptible individuals.

Clinical Manifestations and Pathology

The prodromal phase of postnatally acquired rubella usually occurs from 1 to 5 days prior to rash onset, but may be completely lacking, especially in children. Prodromal symptoms may include headache, low- grade fever, malaise, conjunctivitis, mild rhinitis, and Iymphadenopathy (most commonly tender swell­ing of the lymph nodes behind the ears and at the base of the skull). The rash phase of illness begins with a reddish, discrete rash, sometimes itchy, usually ap­pearing first on the face and then spreading to the hands and feet. Although the progression, duration, and extent of the rash vary greatly, it typically covers the whole body within 24 hours and has disappeared completely by the end of the third day - hence the name 3-day measles. It is important to note that the variability and sometimes the absence of prodromal symptoms as well as rash make a clinical diagnosis uncertain, and laboratory serologic tests are neces­sary for confirmation of the diagnosis.

Complications in postnatally acquired illness may include arthritis and arthralgia, which are more common in adults and women than in prepubertal children and men.

In congenitally acquired rubella, the fetal infec­tion may result in abortion, stillbirth, congenital malformations, or growth retardation. The congeni­tal rubella syndrome is the result of inhibition of cell multiplication in the developing fetus and a chronic infective state that may persist for many months after birth. Some consequences of fetal infection may not become apparent until years after birth. Com­mon congenital abnormalities and active infective processes at birth include cataracts, deafness, cen­tral nervous system defects leading to mental retar­dation, structural defects of the heart and myocardi­tis, bone lesions, pneumonitis, and hepatitis.

History and Geography

The early history of rubella is confused with that of other illnesses that produce a rash such as measles and smallpox. Although it has been suggested that the early Arabian physicians differentiated rubella as a form of measles known as Hhamikah, the disease appears to have been first described in 1619 by Daniel Sennert, who used the term Rotheln (rδtelri) and at­tributed the name, which seems to have been a popu­lar term, to the red color of the rash. Two German physicians are generally credited with clinically de­scribing rubella as a separate entity during the 1750s, and it continued to be called Rotheln by Ger­man investigators from the mid-eighteenth to the mid-nineteenth century. The early interest in the dis­ease by German physicians apparently led to the use of the term “German measles” in other countries. It has, however, also been suggested that the word may have actually been “germane” rather than “Ger­man,” with derivations meaning “closely akin to.” In other words, “germane measles” was intended to indi­cate a disease similiar to measles.

In 1866 Henry Veale, a Scottish physician serving in India, published a description of 30 cases of rubella and proposed the name “rubella” as being “short for the sake of convenience in writing, and euphonious for ease in pronunciation.” At the International Con­gress OfMedicine in London in 1881, a general consen­sus was reached that rubella was an independent en­tity.

Then, in 1941, Norman McAlister Gregg, an Aus­tralian ophthalmologic surgeon, published a land­mark work on his observations of an epidemic of congenital cataracts and other ocular and cardiac abnormalities in infants of mothers who had con­tracted rubella in the first trimester of their preg­nancy. Although skepticism at first prevailed in the medical community, his observations were con­firmed by other investigators in Australia, the United States, and the United Kingdom who also described other congenital abnormalities associated with rubella in pregnancy. The comprehensive paper on rubella published by Conrad Wesselhoeft in 1947 helped to draw world attention to the importance of Gregg’s findings, and in 1953, Saul Krugman, Rob­ert Ward, and their colleagues were able to docu­ment, through volunteer studies, that rubella infec­tion can occur without rash.

The rubella virus was isolated and propagated in tissue culture in 1962 simultaneously by T H. Weller and F. A. Neva at the Harvard School of Public Health in Boston and by P. D. Parkman, E. L. Buescher, and M. S. Artenstein at the Walter Reed Army Institute of Research in Washington, D.C. In addition to provid­ing the tools needed to further understanding of the epidemiology of the disease, including the hemagglu­tination-inhibition test introduced in 1967, this isola­tion also led to subsequent research and development of vaccines.

The World Health Organization (WHO) has coordi­nated collaborative Seroepidemiological studies of ru­bella documenting geographic patterns. In countries without any sustained, large-scale immunization programs, it has been shown that rubella infection is widespread. It was also possible to show through serial Seroepidemiological studies that rubella epi­demics may occur even when clinical records do not document an outbreak of overt rubella. Urban areas demonstrate sustained circulation of virus, whereas rural areas may show patterns of lower immunity rates. In island or remote communities, many per­sons may be susceptible. In countries with sus­tained, large-scale immunization programs, the im­pact of control efforts has been demonstrated by a decrease in the numbers of cases of reported rubella and congenital rubella syndrome and of Susceptibles in the population.

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.

Bibliography

Amstey, Marvin S., ed. 1984. Virus infection in pregnancy. New York.

Assaad₁ F., and K. Ljungars-Esteves. 1985. Rubella - world impact. Reviews of Infectious Diseases 7 (Supplement 1): S29-36.

Benenson, Abram S., ed. 1985. Control of communicable diseases in man. Washington, D.C.

Bett, Walter R., ed. 1954. The history and conquest of common diseases. Norman, Okla.

Cockburn, Charles W. 1969. World aspects of the epidemiol­ogy of rubella. American Journal of Diseases of Chil­dren 118: 112-22.

Cooper, Louis Z. 1985. The history and medical conse­quences of rubella. Reviews of Infectious Diseases 7 (Suppl. 1): S2-9.

Emminghaus, H. 1870. Ueber Rubeolen. Jahrbuch fiir Kinderheilkunde und physische Erziehung 4: 47—59.

Feigin₁ Ralph D., and James D. Cherry, eds. 1981. Text­book Ofpediatric infectious diseases. Philadelphia.

Forbes, John A. 1969. Rubella: Historical aspects. Ameri­can Journal OfDiseases of Children 118: 5—11.

Goodall, E. W 1934. A short history of the epidemic infec­tious diseases. London.

Gregg, Norman McA. 1941. Congenital cataract following German measles in the mother. Transactions of Oph­thalmological Society of Australia 3: 35-46.

Hiro, Y., and S. Tasaka. 1938. Die Roteln sind eine Vi- ruskrankheit. Monatschrift fiir Kinderheilkunde 76: 328-32.

Krugman, S., et al. 1953. Studies on rubella immuniza­tion. I. Demonstration of rubella without rash. Jour­nal of the American Medical Association 151: 285—8.

Parkman, P. D., et al. 1962. Recovery of rubella virus from Army recruits. Proceedings of the Society for Experi­mental Biology and Medicine 111: 225-30.

Squire, William. 1881. On rubella: Rubeola sine catarrho: Rotheln, or German measles. Transactions OftheInter- national Congress of Medicine 4: 27-31.

U.S. Public Health Service. Centers for Disease Control. 1987. Rubella and congenital rubella - United States, 1984-1986. Morbidity and Mortality Weekly Reports 36: 664-6, 671-5.

Veale, Henry. 1866. History of an epidemic of Rotheln, with observations on its pathology. Edinburgh Medi­cal Journal 12: 404—14.

Weller, T. H., and F. A. Neva. 1962. Propagation in tissue cul­ture of cytopathic agents from patients with rubella­like illnesses. Proceedings of the Society for Experimen­tal Biology and Medicine 111: 215-25.

Wesselhoeft₁ Conrad. 1947. Rubella (German measles). New England Journal OfMedicine 236: 943-50.

Withering, William. 1779. An account of the scarlet fever and sore throat, or scarlatina anginosa; particularly as it appeared at Birmingham in the year 1778. London.