- Author: Elias Ezike, MD; Chief Editor: Russell W Steele, MD more...
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. See the images below.
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.
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.
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 the images below).
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.
From 2000 to 2012, rising numbers of WHO member states began using rubella-containing vaccines (RCVs) in their immunization program and began reporting rubella and congenital rubella syndrome (CRS) surveillance data. As of December 2012, 132 (68%) WHO member states had introduced RCV, a 33% increase from 99 member states in 2000. Some 43% of infants had received a RCV dose in 2012, a 96% increase from the 22% of infants who had been vaccinated against rubella in 2000. A total of 94,030 rubella cases were reported to WHO in 2012 from 174 member states, an 86% decrease from the 670,894 cases reported in 2000 from 102 member states.[1, 2]
Rubella occurs worldwide. 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.
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 the image below).
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.
|Year||Number of Cases||Number of Deaths||Cases of Congenital Rubella Syndrome|
No ethnic difference in incidence has been clearly demonstrated, although the characteristic rash is more difficult to diagnose in persons with dark skin.
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.
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.
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- Table 1. Reported Cases of Rubella, Deaths From Rubella, and Number of Cases of Congenital Rubella Syndrome in the United States From 1969-2007[4, 5, 6, 7]
- Table 2. Clinicopathologic Abnormalities in Congenital Rubella
- Table 3. Age-Specific CD4+ T-lymphocyte Count and Percentage of Total Lymphocytes as a Criteria for Severe Immunosuppression in Persons with HIV
|Year||Number of Cases||Number of Deaths||Cases of Congenital Rubella Syndrome|
|Intrauterine growth retardation||Common||Early||...|
|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||...|
|Ventricular septal defect||Uncommon||Early||...|
|Atrial septal defect||Uncommon||Early||...|
|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|
|Hearing loss||Common||Early/Delayed||Usually bilateral; mostly sensorineural; may be central in origin; rare when maternal rubella occurs >4 months' gestation; sometimes progressive|
|Microcephaly||Uncommon||Early||May be associated with normal intelligence|
|Encephalographic abnormalities||Common||Early||Usually disappear by age 1 y|
|Behavioral disorders||Common||Delayed||Frequently related to deafness|
|Chronic progressive panencephalitis||Uncommon||Delayed||Manifest in second decade of life|
|Speech defects||Common||Delayed||Uncommon in absence of hearing loss|
|Blueberry muffin spots||Uncommon||Early||Represents dermal erythropoiesis|
|Chronic rubelliform rash||Uncommon||Early||Usually generalized; lasts several weeks|
|Interstitial pneumonia||Uncommon||Delayed||Generalized; probably immunologically mediated|
|Jaundice||Uncommon||Early||Usually appears in the first day of life|
|Hepatitis||Uncommon||Early||May not be associated with jaundice|
|Thrombocytopenia||Common||Early||Transient; no response to steroid therapy|
|Altered blood group expression||Uncommon||Early||...|
|Radiographic lucencies||Common||Early||Transient; most common in distal femur and proximal tibia|
|Large anterior fontanel||Uncommon||Early||...|
|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||...|
|< 12 mo||1-5 y||6-12 y||≥13 y|
|Total CD4+ T-lymphocytes||< 750/mcl||< 500/mcl||< 200/mcl||< 200/mcl|
|CD4+ T-lymphocytes (as % of total lymphocytes)||< 15%||< 15%||< 15%||< 14%|