Rubella

Rubella is a trivial exanthema of childhood. However, in 1941 an Australian ophthalmologist, Gregg, noticed an unusual concentration of cases of congenital cataract among newborn babies in his practice—an epidemic of blindness. A diligent search of his records revealed that most of the mothers had contracted rubella in the first trimester of pregnancy. Further investigations revealed that these unfortunate children had also suffered a range of other congenital defects including deafness, mental retardation, and cardiac abnormalities (see Chapter 14).

Clinical Features

In childhood rubella is such a mild disease that most adults are subsequently uncertain whether they have ever contracted it. The fine, pink, discrete macules of the erythematous rash appear first on the face, then spread to the trunk and limbs, and fade after 48 hours or less. In nearly half of all infections there is no rash at all. Fever is usually inconspicuous, but a characteristic feature is that postauricular, suboccipital, and posterior cervical lymph nodes are enlarged and tender from very early in the illness. Mild polyarthritis, usually involving the hands, is a fairly frequent feature of the disease in adult females; it is usually fleeting but rarely may persist for up to several years. Thrombocytopenic purpura and postinfectious encephalopathy are rare complications. Progressive rubella panencephalitis is an even rarer and inevitably fatal complication, developing insidiously in the second decade of life, usually in children with congenital rubella.

Congenital Rubella

At least 20% of all infants infected in utcro during the first trimester of pregnancy are born with severe congenital abnormalities, usually multiple (Fig. 25-5); most of the remainder have milder defects. The commonest con-

Flg. 25-5 Congenital rubella syndrome, with severe bilateral deafness and severe bilateral visual defects (microphthalmia, cataract, corneal opacity, and strabismus) (Courtesy Dr. K. Hayes.)

genital abnormalities are neurosensory deafness (total or partial, due to cochlear degeneration, becoming progressively apparent in the early years after birth), blindness (total or partial, especially cataracts, but sometimes glaucoma, microphthalmia, or retinopathy), congenital heart disease (especially patent ductus arteriosus, sometimes accompanied by pulmonary artery stenosis or septal defects), and microcephaly with mental retardation. Other common manifestations of the so-called congenital rubella syndrome (CRS) include bone translucency and retardation of growth, hepatosplenomegaly, and thrombocytopenic purpura. Despite the diversity and severity of this pathology, the congenital rubella syndrome is sometimes missed at birth. About 10-20% of babies with CRS die during the first year, and up to 80% develop some evidence of disease within the early years of life. Up to 20% of children with CRS develop insulin-dependent diabetes mellitus as young adults.

Pathogenesis and Immunity

The virus enters the body by inhalation to multiply asymptomically in the upper respiratory tract and then spread via local lymph nodes to the bloodstream. Not a great deal is known about the events that occupy the 18-day (range 2-3 weeks) incubation period which precedes the appearance of the rash. Virus has been found in lymphocytes and in synovial cells of joints of adults with rubella arthritis. Naturally acquired immunity to rubella lasts for many years; second infections occur occasionally but are usually subclinical and boost immunity further.

When rubella virus infects a woman during the first trimester of pregnancy there is a high probability that the baby will suffer congenital abnormalities. Severe damage (deafness, blindness, heart or brain defects) occurs in 15-30%; of all infections during the first trimester, and in about 5% of those in the fourth month (usually deafness), but rarely thereafter. Minor abnor malities are even more frequent, and following spontaneous abortion or stillbirth virus can be found in practically every organ.

What makes rubella virus teratogenic, when numerous nonteratogenic viruses are so much more pathogenic postnatally and so much more cytocidal lor cultured cells? Paradoxically, this relative lack of pathogenicity may hold the clue to its teratogenicity. More cytocidal viruses may destroy cells and kill the fetus, leading to spontaneous abortion (as does rubella occasionally). Rubella virus may merely slow down the rate of cell division, as has been demonstrated in cultured human fetal cells, leading to a decrease in overall cell numbers and accounting for the small size of rubella babies. Moreover, death of a small number of cells or slowing of their mitotic rate at critical stages in ontogeny might interfere with the development of key organs which are being formed during the first trimester.

Neither the mother's nor the baby's immune response is able to clear the virus from the fetus. Although maternal IgG crosses the placenta and the infected fetus manufactures its own IgM antibodies (Fig. 25-6), cell-mediated immune responses are defective and remain so postnatally. Clones of infected cells may escape immune cytolysis even though maternal IgG might restrict systemic spread of virus. Whatever the explanation, the rubella syndrome in the fetus is a true persistent infection of the chronic type. Throughout the pregnancy and for several months after birth the baby continues to shed virus in any or all of its secretions.

Laboratory Diagnosis

Rubella virus can be cultured in certain cell lines, such as RK-13 and Vero cells, but grows slowly without conspicuous cytopathic effects. Because of its lack of sensitivity, isolation in cell culture is used only as a supplementary method of diagnosing rubella from adult throat swabs, but it does have a

Fig. 25-6 Pattern of viral excretion {+) and the infant's antibody response in congenital rubella (From S. Krugmnn and R. Ward, "Infectious Diseases of Children and Adults," 5th Ed, Mosby, St Louis, 1973 )

place in the diagnosis of CRS; virus can be isolated from the throat, urine, cerebrospinal fluid, or leukocytes of a newborn infant with CRS.

Serology constitutes the standard approach to the laboratory diagnosis of rubella. There are three common situations in which the clinician requires help from the laboratory: (1) A woman considering vaccination wishes to know whether she has ever had rubella and is now immune; (2) An unim-munized woman develops a rash in the first trimester of pregnancy, or comes into contact with someone with rubella, and wishes to know whether she has contracted the disease and whether she should have an abortion; (3) A baby is born with signs suggestive of the rubella syndrome, or its mother is now believed to have possibly contracted rubella during the first trimester.

As there is only one serotype of rubella virus, and specific IgG continues to be demonstrable in serum for many years after clinical or subclinical infection, detection of antibody is evidence of immunity. Diagnosis of rubella in a pregnant woman requires the demonstration of either a rising titer of rubella antibody in paired sera, or rubella IgM antibody in a single specimen. If paired sera are used, the first bleed must to taken during the first week after the onset of the rash; otherwise, a fourfold rise in antibody titer may not be delected in fhe convalescent specimen taken 10 or more days later. On the other hand, if a pregnant women is concerned about recent exposure to a known case of rubella, the first sample should be taken as soon as possible, but the second should be delayed for at least a month to allow for the 2 to 3-week incubation period of her putative infection. Rubella IgM antibody is generally demonstrable by 1 week after the appearance of the rash and persists for at least 1 month (occasionally 3 months). IgM serology may be the only method of diagnosis in the case of a woman who first consults her doctor weeks after the rash has gone.

Diagnosis of the rubella syndrome in a newborn baby is also made by demonstrating rubella IgM in a single specimen of serum, this time the baby's. Many babies will have rubella IgG antibodies, acquired transplacental^ from the mother who may have been vaccinated or infected with the virus years earlier. As IgM antibodies do not cross the placenta, rubella IgM detected in umbilical cord blood must have been synthesized by the baby itself m utero and is diagnostic of congenital rubella. It continues to be made in detectable amounts for 3-6 months after birth.

Traditionally, hemagglutination inhibition (HI) has been the preferred procedure for identifying and quantifying rubella antibodies in serum, but the need to first remove nonspecific inhibitors from the serum makes it technically tricky. Accordingly, Hi is being supplanted by a range of simpler techniques, notably EIA and latex particle agglutination, both of which are available as disposable kits. EIA is also the procedure of choice for IgM capture assays.

Epidemiology

Rubella virus is shed in oropharyngeal secretions and is presumed fo be spread by the respiratory route. It is highly transmissible, usually being acquired by school-age children, and spreads readily within the family. The disease is endemic worldwide.

Prior to the introduction of vaccines, spring epidemics occurred every few years in temperate climates, and over 80% of women had acquired immunity by the time they reached the child-bearing years. Widespread vaccination of infants in the United States commencing in 1969 reduced the incidence of rubella in that country in 1988 to less than 1% of the level 20 years earlier. Since 1988 there have been a number of outbreaks in certain unvaccinated religious communities, as well as among young adults in institutions such as prisons and colleges. Analysis of the reasons for this slight resurgence points to failure to vaccinate rather than vaccine failure, and underlines the importance of intensifying rather than relaxing the drive to eliminate CRS when the battle seems to be almost won.

Control

Live attenuated rubella vaccines, now generally based on the RA27/3 strain grown in a human fibroblast line, have been in use since 1969. A combined measles-mumps-rubella (MMR) vaccine was introduced in 1972. Either vaccine induces durable immunity in at least 95% of recipients, and over 90% have been shown to be protected for at least 15 years, not only against disease but also against the establishment of viremia, even though antibody titers are significantly lower than following natural infection. Although substantially attenuated, rubella vaccines quite commonly induce Iymphadenopathy, a fleeting rash, or low-grade fever. Arthralgia is rare in children but occurs in 25% of nonimmune postpubertal females; it begins 1-3 weeks after vaccination and is usually confined to the small peripheral joints, rarely persisting for more than a few weeks. After vaccination, attenuated rubella virus is shed in small amounts from the throat but is incapable of spreading to contacts, so immunization of children is not contraindicated if the mother is pregnant.

There is no evidence that the vaccine virus is teratogenic, and hence accidental immunization during pregnancy is not an indication for termination. Nevertheless, prudence suggests that women not be deliberately immunized during the first trimester and that nonpregnant vaccinees should be advised to avoid conception for the next 2-3 months, and/or be immunized immediately postpartum.

Since 1972 the United States has practiced universal vaccination of all infants with MMR at 15 months of age. From 1991 it has been recommended also that a booster dose of MMR vaccine be routinely administered to all children, either on entering kindergarten or on entering junior high school. In addition, every effort must be made to identify and immunize those women of child-bearing age who may have missed out on the vaccine altogether; about 10% of this age group in the United States are currently seronegative. Suitable opportunities are at premarital screening (but pregnancy should be avoided for the next 3 months) or immediately postpartum (when further pregnancy is unlikely). Although initially a number of European countries selectively immunized schoolgirls at 12-13 years of age (and nonimmune older women of child-bearing age), most have now changed to the U.S. regime.

There remains the difficult problem of what to do with the woman who does in fact contract a laboratory-confirmed rubella infection during the first

3-4 months of pregnancy. There is general agreement that the risk of serious permanent damage to the baby is so substantial that the attending physician should recommend an abortion.

Babies with congenital rubella shed substantial amounts of virus from their throats for up to several months after birth and constitute a considerable risk to pregnant women, directly or via infected nursing staff in maternity hospitals or postnatal clinics. Such babies should be nursed in isolation, preferably by vaccinated or naturally immune personnel.

Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

Get My Free Ebook


Post a comment