Rubella (German Measles) is an acute, benign,contagious disease of children and young adults. The cardinal manifestations of the illness are a pale pink rash and posterior cervical lymphatics. Paradoxically, this mild disease is one of the few viral infections convincingly associated with the genesis of fetal abnormalities. When infection is acquired in outer, it often results in generalized disease of the infant and protracted excretion of virus after birth.. Accordingly, recognition and prevention of the disease are matters of far reaching consequence.
Rubella virus is a small, spherical RNA virus with a mean diameter of 550 to 600 A The particle is ether sensitive —an attribute of lipid-containing enveloped viruses. The vim’s develops by budding from marginal and intra- cytoplasmic membranes. Classification of the virus is uncertain at present, but similarities of structure and development to certain group A arboviruses have been noted. (’There is no evidence of arthropod transmission.)
The virus agglutinates the erythrocytes of newly hatched chicks—a characteristic that permits measurement of both virus and antibody. Rubella virus replicates with the production of cytopathic effects in a number of commonly employed cell culture systems, including African green monkey and human diploid cells. Virus replication and production of embryopathic effects similar to those in humans have been experimentally induced in rats.
Incidence and Epidemiology.
Accurate information on the incidence of rubella is not available. The mildness and brevity of its clinical signs may confound the diagnosis and reporting of many instances of infection. Studies of the experimental disease lend support to prior clinical evidence that infection may occur without rash, and indicate a further diagnostic pitfall. It can be said, however, that the disease is seen on every continent, may occur in epidemic form, and has its highest incidence in the early spring. The disease is less frequently acquired in childhood than measles, as is attested by seismologic studies and by the fact that rubella is more common than measles in young adults.
The higher incidence of infection in younger age groups in institutional outbreaks, argues against a greater .susceptibility of the adult. It is probable that rubella is spread by the respiratory route by close and sustained personal contact.. The infection is contagious during the period of prodromal symptoms and the first day of rash. Only recently it has been recognized that the infant with congenitally acquired infection may excrete virus for months after birth and is contagious during this time. The epidemiologic implications of this fact —first established in the large epidemic, of 1963-1964- are yet to be determined. There is evidence that the newborn may be unusually contagious, and that although he may have no obvious stigmata of infection, yet he may be shedding virus.
Immunity is lasting. Authenticated second attacks are rare, and are virtually unprovable because of the nebulous nature of the clinical syndrome. Passive immunity of variable efficacy may be conferred by the injection of gamma globulin from the serum of patients convales-cent from the disease (see Prevention). Rubella has no immunologic relationship to measles.
Pathology of Rubella.
Death from uncomplicated post- natally acquired rubella is unknown. Histologic changes characteristic of the disease have not been demonstrated. The onset of disease is attended by leukemia resulting from a decrease in both lymphocytes and necrophiliacs. After five days, absolute lymphocytes is manifest. The total leukocyte count is normal at the tenth day.
Necropolises of fetal and infantile victims of maternal infection have shown a variety of embryonal defects related to developmental arrest involving all three germ layers. Those defects most consistently associated with maternal rubella are microscopically, cataract, patency of the ductus arteriosus, and defects of the interventricular septum. However, recent studies have revealed a wide spectrum of tissue damage in association with virologically proved disease of varying severity.
In some infants hepatic and renal degeneration and myocardial necrosis without inflammation have been noted, whereas in others thrombocytopenia and purpura may be the sole abnormality. It has been proposed that the generalized visceral involvement and characteristic residua of the disease may result from a sequence of platelet damage, intramuscular coagulation, and thrombosis Bayer. Another theory holds that the smaller size of the rubella- infected infant and some abnormalities may reflect inhibition of multiplication of embryonic cells by the virus.
Clinical Manifestations of Rubella.
Postnatal Acquired Rubella.
Fourteen to twenty-one days after exposure to the infection, the onset of rubella is evidenced by symptoms variable in their occurrence and severity. Cough, sore throat, and coryza may initiate the illness, but are often absent; headache, malaise, and myalgia may precede the eruption, especially in young adults. Commonly, fever and obvious enlargement of posterior cervical nodes antedate the appearance of the rash. Fever, when present, rarely exceeds 101° F.. and seldom persists beyond 48 hours. Injection of the bulbar conjunctivae may be noted. Palpable, tender, and occasionally visible lymphadenopathy involves postauricular and suboccipital nodes with sufficient frequency to be an important diagnostic sign. Generalized peripheral lymphadenitis, and, more rarely, splenomegaly, may occur.
The exanthema of rubella is usually apparent within 24 hours of the first symptoms as a faint macular erythema that first involves the face and neck. Characterized by its brevity and evanescence, it spreads rapidly to the trunk and extremities, sometimes leaving one site even as it appears at the next. The pink macules that constitute the rash.blanch with pressure and rarely stain the skin. Diffuse erythema on the second day of rash may closely simulate Scarlet fever. The eruption has vanished by the third day. Rubella may occur without rash. An enanthem has been described that is inconstant in form and occurrence, and lacks the premonitory significance of the Koplik spots of measles. The lesions consist of red macules that usually involve the soft palate.
Recovery is- almost always prompt and uneventful, although relapse occurs with greater frequency than with most viral diseases (5 to 8 per cent). Secondary bacterial infections rarely occur. Rare complications are arthralgia, neuritis, gingivitis, thrombocytopenic purpura, and increased capillary fragility. Heart block has been described. A meningoencephalitis of short duration may occur one to six days after the appearance of rash. Its incidence is estimated at 1 in 6000 cases, and it is fatal in approximately 20 per cent of those afflicted. Rubella encephalopathy is not associated with demyelinization (in contrast to other postviral encephalitides). Survivors may have electroencephalographic abnormalities, but intellectual function seems to be preserved.
The fortuitous coincidence of the development •’Of cell culture systems for the isolation of rubella virus and the occurrence of a global epidemic of rubella (in 1963-1964) has demonstrated that the classic ocular and cardiac “teratogenic” effects of rubella are but isolated manifestations of a continuing and persisting fetal infection. It is now clear that congenital transcendental infection of the fetus occurs as a consequence of maternal infection (which may or may not be clinically evident) usually in the first trimester of pregnancy. Virus is demonstrable in placental and fetal tissues obtained by therapeutic abortion at that time. If pregnancy is not interrupted (and spontaneous abortion is uncommon’1, fetal infection persists, and upon delivery of the infant, virus is recoverable from the throat, urine, feces, conjunctivae, bone marrow, and cerebrospinal fluid of the living infant and from most organs at autopsy.
About 10 to 15 per cent of infants bom to mothers infected in the first trimester of pregnancy have stigmata of infection readily recognizable in the first year of life. These include cardiac lesions, cataracts, glaucoma, microphthalmia, and esophageal atresia.
Other signs include needed clouding, fullness of the fontanels, lessemm long bones, and electroencephalogrtspkie formalities has been shown that the character of the antibody changes during the first year from IgG (presumably maternal) to IgM, indicating a primary response of the infant to the persisting viral antigen. Studies of older infants and children with stigmata of congenital rubella show them to be free of demonstrable virus and to possess the IgG immunoglobulins that characteristically persist after other viral infections.
Diagnosis of Rubella.
Rubella may be diagnosed clinically with assurance only during an epidemic. It may be difficult to distinguish from mild or modified measles, infectious mononucleosis, or scarlet fever. Distinction from measles may be made on the basis of the pinker, nonstaining rash, the milder course, and the lesser catarrh of rubella. Sore throat is a more prominent complaint in scarlet fever; the course of infectious mononucleosis is often more protracted, and splenomegaly is more frequent than in rubella.
Specific diagnosis of rubella may now be made by isolation of the virus in any of several cell culture systems, or by demonstration of neutralizing hemagglutination-inhibiting or complement-fixing antibody response during infection. The high incidence of dermatoglyphic abnormalities (50 per cent) and increased percentage of chromosome breaks described in patients following congenital rubella may prove to have diagnostic value when studied further.
Prognosis of Rubella.
Complete recovery from postnatally acquired rubella is almost invariable. The rare deaths attributable to rubella follow the infrequent complication of meningoencephalitis. Infection in pregnancy constitutes a hazard to the fetus but not to the mother.
There is no specific treatment for the disease. Few patients suffer. discomfort severe enough to warrant symptomatic medication. Headache and myalgia may be controlled by aspirin; bed rest is advisable for the duration of the fever.
Prevention of German Measles.
Passive Immunization. In contrast to measles, current evidence is conflicting with regard to the prophylaxis of rubella with convalescent serum and gamma globulin. Various lots of gamma globulin appear to vary in prophylactic potency, some being completely ineffective. However, the virus has been neutralized in vitro in human volunteer experiments by human gamma globulin or convalescent serum (Krugman and Ward, 1953). Administrdtion. of gamma globulin to the pregnant woman may only mask her symptoms of infection yet not protect the fetus from viral invasion. Its use may thus only ofoscure the picture and confound decision about the need for therapeutic abortion. Hence the practice seems inadvisable.
Rubella may be prevented in children and adults by the parenteral administration of an attenuated derived from passage of virus in African green monkey kidney cells. Seroconversion rates after immunization are approximately 95 per cent. As with other live virus vaccines, serum antibody titers are lower than those following natural infection
However, antibody persists for at least three years following vaccination, but the permanence of vaccine-induced immunity still must be established by further observation. In children, vaccination is attended by little, if any. reaction; but in women, rash, malaise, arthralgia, and mild, acute arthritis occur frequently, the incidence being directly related to age. For this reason, it is currently recommended that immunization be carried out principally in childhood. However, since the epidemic threshold —at least in semiclosed populations — is low (between 4.7 and 8.4 per cent), containment of the disease by mass immunization may prove difficult. Therefore, despite the higher reaction rates in adults, it seems advisable to immunize women of childbearing age for whose , unborn children rubella may have tragic consequences.