eMedicine Specialties > Pediatrics: General Medicine > Infectious Disease
Rubella
Updated: Apr 22, 2009
Introduction
Background
The name rubella is derived from a Latin term meaning "little red." Rubella is generally a benign communicable exanthematous disease. It is caused by rubella virus, which is a member of the Rubivirus genus of the family Togaviridae. Nearly one half of individuals infected with this virus are asymptomatic. Clinical manifestations and severity of illness vary with age. For instance, infection in younger children is characterized by mild constitutional symptoms, rash, and suboccipital adenopathy; conversely, in older children, adolescents, and adults, rubella may be complicated by arthralgia, arthritis, and thrombocytopenic purpura. Rare cases of rubella encephalitis have also been described in children.
The major complication of rubella is its teratogenic effects when pregnant women contract the disease, especially in the early weeks of gestation. The virus can be transmitted to the fetus through the placenta and is capable of causing serious congenital defects, abortions, and stillbirths. Fortunately, because of the successful immunization program initiated in the United States in 1969, rubella infection and congenital rubella syndrome rarely are seen today.
Number of rubella cases per year.
Number of congenital rubella syndrome cases per year.
Deaths from rubella per year.
The few cases of rubella recorded in recent years involve susceptible individuals who have not been immunized with rubella vaccine and do not have a history of previous rubella infection.
An independent panel convened by the Centers for Disease Control and Prevention (CDC) in 2004 found that about 91% of the US population is immune to rubella. This explains the decreased number of outbreaks of rubella and congenital rubella syndrome reported in the recent years.
Pathophysiology
Postnatal rubella
The usual portal of entry of rubella virus is the respiratory epithelium of the nasopharynx. The virus is transmitted via the aerosolized particles from the respiratory tract secretions of infected individuals. The virus attaches to and invades the respiratory epithelium. It then spreads hematogenously (primary viremia) to regional and distant lymphatics and replicates in the reticuloendothelial system. This is followed by a secondary viremia that occurs 6-20 days after infection. During this viremic phase, rubella virus can be recovered from different body sites including lymph nodes, urine, cerebrospinal fluid (CSF), conjunctival sac, breast milk, synovial fluid, and lungs. Viremia peaks just before the onset of rash and disappears shortly thereafter. An infected person begins to shed the virus from the nasopharynx 3-8 days after exposure for 6-14 days after onset of the rash.
Congenital rubella syndrome
Fetal infection occurs transplacentally during the maternal viremic phase, but the mechanisms by which rubella virus causes fetal damage are poorly understood. The fetal defects observed in congenital rubella syndrome are likely secondary to vasculitis resulting in tissue necrosis without inflammation. Another possible mechanism is direct viral damage of infected cells. Studies have demonstrated that cells infected with rubella in the early fetal period have reduced mitotic activity. This may be the result of chromosomal breakage or due to production of a protein that inhibits mitosis. Regardless of the mechanism, any injury affecting the fetus in the first trimester (during the phase of organogenesis) results in congenital organ defects.
Frequency
United States
During the 1962-1965 worldwide epidemic, an estimated 12.5 million rubella cases occurred in the United States, resulting in 20,000 cases of congenital rubella syndrome. Since the licensing of the live attenuated rubella vaccine in the United States in 1969, a substantial increase has been noted in the vaccination coverage among school-aged children and the population immunity. In 2004, the estimated vaccination coverage among school-aged children was about 95%, and the population immunity was about 91%.
As a result of the progress made in vaccination against rubella, a remarkable drop has occurred in the number of cases of rubella and congenital rubella syndrome. For instance, in 1969, a total of 57,686 cases of rubella and 31 cases of congenital rubella syndrome were recorded. Subsequently, from 1993-2000, the number of cases of rubella recorded annually decreased to a range of 128-364, and cases of congenital rubella syndrome also dropped to 4-9 cases per year. Since 2001, the annual number of rubella cases ranged from a record low of 7 in 2003 to 23 in 2001, and congenital rubella syndrome cases between 0-3 per year (see Table 1, Media files 1-2).
Number of rubella cases per year.
Number of congenital rubella syndrome cases per year.
An independent panel convened by the CDC in 2004 to assess progress towards elimination of rubella and congenital rubella syndrome in the United States concluded unanimously that rubella is no longer endemic in the United States. In fact, the pattern of virus genotypes isolated in recent years was consistent with virus originating in other parts of the world.
Following the near record-low levels in rubella incidence in the United States, the occurrence of isolated outbreaks among susceptible adults has also become rare. In fact no outbreak of rubella was reported from 2000-2005, in contrast to the preceding year interval, 1996-1999, when 16 outbreaks were reported. The median number of cases per outbreak was 21. The most recent cases occurred in New York during 1997-1998, Kansas in 1998, Nebraska in 1999, and Arkansas in 1999. Most of these outbreaks were reported in college campuses, military installations, prisons, and workplaces, including health care environments. In most instances, the individuals involved in these outbreaks have no history of rubella immunization. In addition, most of the outbreaks have been reported among persons who emigrated from countries where rubella is not included in the routine immunization schedule.
International
Rubella occurs worldwide.1 The number of reported cases is high in countries where routine rubella immunization is either not available or was recently introduced. For instance, in Mexico in 1990, a total of 65,591 cases of rubella were reported. After the introduction of rubella vaccine into the childhood immunization schedule in 1998, the number of reported cases declined 68% to 21,173. In Europe, the incidence of rubella remains high. For instance, in 2003, a total of 304,320 cases were reported; 41% of these were from the Russian Federation, and 40% were from Romania.
Although the burden of congenital rubella syndrome is not well characterized in all countries, more than 100,000 cases are estimated to occur each year in developing countries alone. In Europe, a total of 47 cases of congenital rubella syndrome were reported from 2001-2003; 32% were from the Russian Federation, and 36% were from Romania.
Mortality/Morbidity
The morbidity and mortality rates of rubella disease dropped remarkably since the licensing of live attenuated rubella vaccine in 1969. In fact, in 1969, complicated rubella infection caused 29 fatalities in the United States, whereas from 1992-2001, only 0-2 deaths per year were recorded (see Table 1 and Media file 3).
Deaths from rubella per year.
In contrast to postnatal rubella, which is not a debilitating disease, congenital rubella infection may result in growth delay, learning disability, mental retardation, hearing loss, congenital heart disease, and eye, endocrinologic, and neurologic abnormalities.
Table 1. Reported Cases of Rubella, Deaths From Rubella, and Number of Cases of Congenital Rubella Syndrome in the United States From 1969-20072,3,4,5
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Table
| Year | Number of Cases | Number of Deaths | Cases of Congenital Rubella Syndrome |
| 1969 | 57,686 | 29 | 31 |
| 1970 | 56,552 | 31 | 77 |
| 1971 | 45,086 | 20 | 68 |
| 1972 | 25,507 | 14 | 42 |
| 1973 | 27,804 | 16 | 35 |
| 1974 | 11,917 | 15 | 45 |
| 1975 | 16,652 | 21 | 30 |
| 1976 | 12,491 | 12 | 30 |
| 1977 | 20,395 | 17 | 23 |
| 1978 | 18,269 | 10 | 30 |
| 1979 | 11,795 | 1 | 62 |
| 1980 | 3,904 | 1 | 50 |
| 1981 | 2,077 | 5 | 19 |
| 1982 | 2,325 | 4 | 7 |
| 1983 | 970 | 3 | 22 |
| 1984 | 752 | 1 | 5 |
| 1985 | 630 | 1 | 0 |
| 1986 | 551 | 1 | 5 |
| 1987 | 306 | 0 | 5 |
| 1988 | 225 | 1 | 6 |
| 1989 | 396 | 4 | 3 |
| 1990 | 1,125 | 8 | 11 |
| 1991 | 1,401 | 1 | 47 |
| 1992 | 160 | 1 | 11 |
| 1993 | 192 | 0 | 5 |
| 1994 | 227 | 0 | 7 |
| 1995 | 128 | 1 | 6 |
| 1996 | 238 | 0 | 4 |
| 1997 | 181 | 0 | 5 |
| 1998 | 364 | 0 | 7 |
| 1999 | 267 | 0 | 9 |
| 2000 | 176 | 0 | 9 |
| 2001 | 23 | 2 | 3 |
| 2002 | 18 | N/A* | 1 |
| 2003 | 7 | N/A | 1 |
| 2004 | 10 | N/A | 0 |
| 2005 | 11 | N/A | 1 |
| 2006 | 11 | N/A | 1 |
| 2007 | 12 | N/A | 0 |
| Year | Number of Cases | Number of Deaths | Cases of Congenital Rubella Syndrome |
| 1969 | 57,686 | 29 | 31 |
| 1970 | 56,552 | 31 | 77 |
| 1971 | 45,086 | 20 | 68 |
| 1972 | 25,507 | 14 | 42 |
| 1973 | 27,804 | 16 | 35 |
| 1974 | 11,917 | 15 | 45 |
| 1975 | 16,652 | 21 | 30 |
| 1976 | 12,491 | 12 | 30 |
| 1977 | 20,395 | 17 | 23 |
| 1978 | 18,269 | 10 | 30 |
| 1979 | 11,795 | 1 | 62 |
| 1980 | 3,904 | 1 | 50 |
| 1981 | 2,077 | 5 | 19 |
| 1982 | 2,325 | 4 | 7 |
| 1983 | 970 | 3 | 22 |
| 1984 | 752 | 1 | 5 |
| 1985 | 630 | 1 | 0 |
| 1986 | 551 | 1 | 5 |
| 1987 | 306 | 0 | 5 |
| 1988 | 225 | 1 | 6 |
| 1989 | 396 | 4 | 3 |
| 1990 | 1,125 | 8 | 11 |
| 1991 | 1,401 | 1 | 47 |
| 1992 | 160 | 1 | 11 |
| 1993 | 192 | 0 | 5 |
| 1994 | 227 | 0 | 7 |
| 1995 | 128 | 1 | 6 |
| 1996 | 238 | 0 | 4 |
| 1997 | 181 | 0 | 5 |
| 1998 | 364 | 0 | 7 |
| 1999 | 267 | 0 | 9 |
| 2000 | 176 | 0 | 9 |
| 2001 | 23 | 2 | 3 |
| 2002 | 18 | N/A* | 1 |
| 2003 | 7 | N/A | 1 |
| 2004 | 10 | N/A | 0 |
| 2005 | 11 | N/A | 1 |
| 2006 | 11 | N/A | 1 |
| 2007 | 12 | N/A | 0 |
*N/A indicates that data are not available.
Race
No ethnic difference in incidence has been clearly demonstrated, although the characteristic rash is more difficult to diagnose in persons with dark skin.
Sex
No appreciable differences in infection rates by sex are apparent in children, but in adults, more cases are reported in women than in men. Rubella arthralgia and arthritis are more frequent in women than in men.
Age
Before licensing of the live attenuated vaccine in 1969, rubella in the United States was primarily a disease of school-aged children, with a peak incidence in children aged 5-9 years. Following widespread use of rubella vaccine in children, peak incidence has shifted to persons older than 20 years, who comprise 62% of cases of rubella reported in the United States.
Clinical
History
- Postnatal rubella
- Exposure: Rubella virus is transmitted from person to person via the aerosolized particles from the respiratory tract. A history of exposure may not be present. Individuals may acquire the infection from a completely asymptomatic patient or from an individual shedding the virus during the incubation period.
- Incubation period: The incubation is usually 14-21 days after exposure to a person with rubella.
- Prodromal phase: Prodromal symptoms are unusual in young children but are common in adolescents and adults.
- The following signs and symptoms usually appear 1-5 days before the onset of rash:
- Eye pain on lateral and upward eye movement (a particularly troublesome complaint)
- Conjunctivitis
- Sore throat
- Headache
- General body aches
- Low-grade fever
- Chills
- Anorexia
- Nausea
- Tender lymphadenopathy (particularly posterior auricular and suboccipital lymph nodes)
- Forchheimer sign (an enanthem observed in 20% of patients with rubella during the prodromal period; can be present in some patients during the initial phase of the exanthem; consists of pinpoint or larger petechiae that usually occur on the soft palate)
- Congenital rubella history focuses on the following:
- The number of weeks of pregnancy when maternal exposure to rubella occurred (The risk of congenital rubella syndrome is higher if maternal exposure occurs during the first trimester.)
- Maternal history of immunization or medical history of rubella
- Evidence of intrauterine growth retardation during pregnancy
- Manifestations suggestive of congenital rubella syndrome in a child
Physical
- Postnatal rubella
- Rash
- The exanthem of rubella consists of a discrete rose-pink maculopapular rash ranging from 1-4 mm.
Image in a 4-year-old girl with a 4-day history of low-grade fever, symptoms of an upper respiratory tract infection, and rash. Courtesy of Pamela L. Dyne, MD.
- Rash in adults may be quite pruritic.
- The synonym "3-day measles" derives from the typical course of rubella exanthem that starts initially on the face and neck and spreads centrifugally to the trunk and extremities within 24 hours. It then begins to fade on the face on the second day and disappears throughout the body by the end of the third day.
- The exanthem of rubella consists of a discrete rose-pink maculopapular rash ranging from 1-4 mm.
- Temperature: Fever is usually not higher than 38.5°C (101.5°F).
- Lymph nodes: Enlarged posterior auricular and suboccipital lymph nodes are usually found on physical examination.
- Mouth: The Forchheimer sign may still be present on the soft palate.
- Rash
- Congenital rubella syndrome (see Table 2)
- The classic triad presentation of congenital rubella syndrome consists of the following:
- Sensorineural hearing loss is the most common manifestation of congenital rubella syndrome. It occurs in approximately 58% of patients. Studies have demonstrated that approximately 40% of patients with congenital rubella syndrome may present with deafness as the only abnormality without other manifestations. Hearing impairment may be bilateral or unilateral and may not be apparent until the second year of life.
- Ocular abnormalities including cataract, infantile glaucoma, and pigmentary retinopathy occur in approximately 43% of children with congenital rubella syndrome. Both eyes are affected in 80% of patients, and the most frequent findings are cataract and rubella retinopathy. Rubella retinopathy consists of a salt-and-pepper pigmentary change or a mottled, blotchy, irregular pigmentation, usually with the greatest density in the macula. The retinopathy is benign and nonprogressive and does not interfere with vision (in contrast to the cataract) unless choroid neovascularization develops in the macula.
- Congenital heart disease including patent ductus arteriosus (PDA) and pulmonary artery stenosis is present in 50% of infants infected in the first 2 months' gestation. Cardiac defects and deafness occur in all infants infected during the first 10 weeks of pregnancy and deafness alone is noted in one third of those infected at 13-16 weeks of gestation.
- Other findings in congenital rubella syndrome include the following:
- Intrauterine growth retardation, prematurity, stillbirth, and abortion
- CNS abnormalities, including mental retardation, behavioral disorders, encephalographic abnormalities, hypotonia, meningoencephalitis, and microcephaly
- Hepatosplenomegaly
- Jaundice
- Hepatitis
- Skin manifestations, including blueberry muffin spots that represent dermal erythropoiesis and dermatoglyphic abnormalities
- Bone lesions, such as radiographic lucencies
- Endocrine disorders, including late manifestations in congenital rubella syndrome usually occurring in the second or third decade of life (eg, thyroid abnormalities, diabetes mellitus)
- Hematologic disorders, such as anemia and thrombocytopenic purpura
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[ CLOSE WINDOW ]Table
Abnormality Common/Uncommon Early/Delayed Comment General Intrauterine growth retardation Common Early ... Prematurity Uncommon Early ... Stillbirth Uncommon Early ... Abortion Uncommon Early ... Cardiovascular system Patent ductus arteriosus Common Early May occur with pulmonary artery stenosis Pulmonary artery stenosis Common Early Caused by intimal proliferation Coarctation of the aorta Uncommon Early ... Myocarditis Uncommon Early ... Ventricular septal defect Uncommon Early ... Atrial septal defect Uncommon Early ... Eye Cataract Common Early Unilateral or bilateral Retinopathy Common Early Salt-and-pepper appearance; visual acuity unaffected; frequently unilateral Cloudy cornea Uncommon Early Spontaneous resolution Glaucoma Uncommon Early/Delayed May be bilateral Microphthalmia Common Early Common in patients with unilateral cataract Subretinal neovascularization Uncommon Delayed Retinopathy with macular scarring and loss of vision Ear Hearing loss Common Early/Delayed Usually bilateral; mostly sensorineural; may be central in origin; rare when maternal rubella occurs >4 months' gestation; sometimes progressive CNS Meningoencephalitis Uncommon Early Transient Microcephaly Uncommon Early May be associated with normal intelligence Intracranial calcifications Uncommon Early ... Encephalographic abnormalities Common Early Usually disappear by age 1 y Mental retardation Common Delayed ... Behavioral disorders Common Delayed Frequently related to deafness Autism Uncommon Delayed ... Chronic progressive panencephalitis Uncommon Delayed Manifest in second decade of life Hypotonia Uncommon Early Transitory defect Speech defects Common Delayed Uncommon in absence of hearing loss Skin Blueberry muffin spots Uncommon Early Represents dermal erythropoiesis Chronic rubelliform rash Uncommon Early Usually generalized; lasts several weeks Dermatoglyphic abnormalities Common Early ... Lungs Interstitial pneumonia Uncommon Delayed Generalized; probably immunologically mediated Liver Hepatosplenomegaly Common Early Transient Jaundice Uncommon Early Usually appears in the first day of life Hepatitis Uncommon Early May not be associated with jaundice Blood Thrombocytopenia Common Early Transient; no response to steroid therapy Anemia Uncommon Early Transient Hemolytic anemia Uncommon Early Transient Altered blood group expression Uncommon Early ... Immune system Hypogammaglobulinemia Uncommon Delayed Transient Lymphadenopathy Uncommon Early Transient Thymic hypoplasia Uncommon Early Fatal Bone Radiographic lucencies Common Early Transient; most common in distal femur and proximal tibia Large anterior fontanel Uncommon Early ... Micrognathia Uncommon Early ... Endocrine glands Diabetes mellitus Common Delayed Usually becomes apparent in second or third decade of life Thyroid disease Uncommon Delayed Hypothyroidism, hyperthyroidism, and thyroiditis Growth hormone deficiency Uncommon Delayed ... Genitourinary system Cryptorchidism Uncommon Early ... Polycystic kidney Uncommon Early ... Abnormality Common/Uncommon Early/Delayed Comment General Intrauterine growth retardation Common Early ... Prematurity Uncommon Early ... Stillbirth Uncommon Early ... Abortion Uncommon Early ... Cardiovascular system Patent ductus arteriosus Common Early May occur with pulmonary artery stenosis Pulmonary artery stenosis Common Early Caused by intimal proliferation Coarctation of the aorta Uncommon Early ... Myocarditis Uncommon Early ... Ventricular septal defect Uncommon Early ... Atrial septal defect Uncommon Early ... Eye Cataract Common Early Unilateral or bilateral Retinopathy Common Early Salt-and-pepper appearance; visual acuity unaffected; frequently unilateral Cloudy cornea Uncommon Early Spontaneous resolution Glaucoma Uncommon Early/Delayed May be bilateral Microphthalmia Common Early Common in patients with unilateral cataract Subretinal neovascularization Uncommon Delayed Retinopathy with macular scarring and loss of vision Ear Hearing loss Common Early/Delayed Usually bilateral; mostly sensorineural; may be central in origin; rare when maternal rubella occurs >4 months' gestation; sometimes progressive CNS Meningoencephalitis Uncommon Early Transient Microcephaly Uncommon Early May be associated with normal intelligence Intracranial calcifications Uncommon Early ... Encephalographic abnormalities Common Early Usually disappear by age 1 y Mental retardation Common Delayed ... Behavioral disorders Common Delayed Frequently related to deafness Autism Uncommon Delayed ... Chronic progressive panencephalitis Uncommon Delayed Manifest in second decade of life Hypotonia Uncommon Early Transitory defect Speech defects Common Delayed Uncommon in absence of hearing loss Skin Blueberry muffin spots Uncommon Early Represents dermal erythropoiesis Chronic rubelliform rash Uncommon Early Usually generalized; lasts several weeks Dermatoglyphic abnormalities Common Early ... Lungs Interstitial pneumonia Uncommon Delayed Generalized; probably immunologically mediated Liver Hepatosplenomegaly Common Early Transient Jaundice Uncommon Early Usually appears in the first day of life Hepatitis Uncommon Early May not be associated with jaundice Blood Thrombocytopenia Common Early Transient; no response to steroid therapy Anemia Uncommon Early Transient Hemolytic anemia Uncommon Early Transient Altered blood group expression Uncommon Early ... Immune system Hypogammaglobulinemia Uncommon Delayed Transient Lymphadenopathy Uncommon Early Transient Thymic hypoplasia Uncommon Early Fatal Bone Radiographic lucencies Common Early Transient; most common in distal femur and proximal tibia Large anterior fontanel Uncommon Early ... Micrognathia Uncommon Early ... Endocrine glands Diabetes mellitus Common Delayed Usually becomes apparent in second or third decade of life Thyroid disease Uncommon Delayed Hypothyroidism, hyperthyroidism, and thyroiditis Growth hormone deficiency Uncommon Delayed ... Genitourinary system Cryptorchidism Uncommon Early ... Polycystic kidney Uncommon Early ...
- The classic triad presentation of congenital rubella syndrome consists of the following:
Causes
- Rubella and congenital rubella syndrome are caused by rubella virus. Only one antigenic type of rubella virus is available, and humans are the only natural hosts. The virus is spherical with a diameter of 50-70 nm, has a central core (ie, nucleocapsid), and is covered externally by a lipid-containing envelope. The nucleocapsid is composed of polypeptide (C protein) and a single-stranded RNA.
- Its outer envelope is made up of glycosylated lipoprotein, which contains 2 virus-specific polypeptides (E1, E2) and a host-cell–derived lipid. These 2 envelope proteins comprise the spiked 5-nm to 6-nm surface projections that are observed on the outer membrane of rubella virus and are important for the virulence of the virus.
- Monoclonal antibodies directed against epitopes of E1 and E2 have neutralizing activity. Protein E1 is the viral hemagglutinin that binds both hemagglutination-inhibiting and hemolysis-inhibiting antibodies.
- Rubella virus is rapidly inactivated by 70% alcohol, ethylene oxide, formalin, ether, acetone, chloroform, free chlorine, deoxycholate, beta-propiolactone, ultraviolet light, extreme pH (<6.8 or >8.1), heat (>56°C), and cold (from -10°C to -20°C). It is resistant to thimerosal and is stable at temperatures of -60°C or less.
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Further Reading
Keywords
rubella, German measles, 3-day measles, roseola, röteln, roetheln, third disease, congenital rubella syndrome, CRS, rubella virus, rash, skin rash, adenopathy, arthralgia, arthritis, thrombocytopenic purpura, rubella encephalitis, postnatal rubella, vasculitis, hearing loss, learning disability, treatment, diagnosis, congenital heart disease, conjunctivitis, sore throat, Forchheimer sign, 3-day measles, sensorineural hearing loss, infantile glaucoma, pigmentary retinopathy, patent ductus arteriosus, pulmonary artery stenosis, deafness, intrauterine growth retardation, prematurity, stillbirth, hypotonia, meningoencephalitis, microcephaly, hepatosplenomegaly, jaundice, hepatitis, blueberry muffin spots, bone lesions, endocrine disorders
