| disease | Rubella |
| alias | Rubella, German Measles, German Measles |
Rubella (rubella, German measles) is a common acute infectious disease caused by the rubella virus. It is characterized by fever and a full-body rash, often accompanied by swollen lymph nodes behind the ears and at the back of the head. Since the systemic symptoms are generally mild and the course of the disease is short, it is often considered insignificant. However, in recent years, severe cases have been frequently reported during rubella outbreaks. If a pregnant woman is infected with rubella, it can cause serious harm to the fetus. Both children and adults can contract the disease.
bubble_chart Epidemiology
(1) Source of pestilence The patient is the only source of pestilence, including subclinical or latent infections, whose actual numbers are higher than those of symptomatic cases, making them an important yet easily overlooked source of pestilence. The pestilence period occurs 5–7 days before onset and 3–5 days after onset, with the day of onset and the day before being the most contagious. Viruses can be isolated from the patient's oral, nasal, and pharyngeal secretions, as well as from blood, urine, and feces.
(2) Transmission routes Generally, rubella in children and adults is primarily spread through respiratory droplets. Close contact between people can also transmit pestilence. Newborns infected in utero, particularly those with viral shedding in the throat for weeks, months, or even over a year, can infect healthcare workers or family members lacking antibodies through contaminated bottles, nipples, bedding, diapers, or direct contact, leading to transmission in nurseries. Fetal infection can result in late abortion, stillbirth, premature labor, or congenital rubella with multiple congenital malformations.
(3) Susceptible population The disease is most common in children aged 5–9. During the rubella outbreak in Shanghai in the spring and summer of 1993, the incidence rate reached 451.57 per 100,000, with the highest rate in the 10–14 age group, followed by 5–9-year-olds. Outbreaks among adolescents, adults, and the elderly are not uncommon. Since the late 1980s [third stage], multiple regions in China have experienced epidemics. Recent hemagglutination inhibition antibody tests for rubella antibodies in Hangzhou showed a positivity rate of 98% in children and adults, with 100% in women over 21. In Shanghai, 97.5% of women of childbearing age were positive, and in Beijing, 99.28%. Antibody levels vary worldwide. Infants under six months are rarely affected due to passive immunity from their mothers. Most cases result in long-lasting immunity after infection. Rubella is more common in winter and spring, though recent outbreaks have occurred in summer, spreading in kindergartens, schools, and military units. Since the 1980s, major outbreaks have been reported in Japan, the U.S., India, Mexico, and Australia. In the UK, during the 1978–1979 peak outbreak, late abortions in pregnant women were most frequent. Long-term follow-up of infants born during this outbreak revealed that some symptoms only manifested 2–3 years after birth.Rubella virus is an RNA virus belonging to the Togaviridae family and is a human-specific virus. Under electron microscopy, it mostly appears spherical, with a core diameter of 50–70 nm. The antigenic structure of the rubella virus is highly stable, and only one antigenic type is currently known. The rubella virus can survive and proliferate in the placenta or fetus (as well as for several months or even years after birth), causing a long-term, multisystem chronic progressive infection. This virus can grow in cell cultures such as rabbit kidney, baby hamster kidney, African green monkey kidney, and rabbit cornea, and can agglutinate red blood cells from chickens, pigeons, geese, and human type O. The virus has weak viability outside the body and is sensitive to ultraviolet light, ether, cesium chloride, deoxycholic acid, etc. It can be inactivated at pH <3.0. The virus is not heat-resistant; it can be killed at 56°C for 30 minutes or 37°C for 1.5 hours. It is unstable when stored at 4°C and is best preserved at -60 to -70°C, where it can remain viable for 3 months. Under dry freezing conditions, it can be stored for up to 9 months.
The pathogenesis of congenital rubella is not yet fully understood. It is known that after a pregnant woman is infected with rubella, the virus can spread via the bloodstream during viremia, infecting the placenta and ultimately the fetus. Infection of the placental chorionic membrane leads to prolonged and widespread involvement of small blood vessels and capillary walls. The earlier the mother is infected during pregnancy, the higher the chance of fetal infection: 10–30% in the first month, 5–20% in the third month, 1–5% in the fourth month, and a small number of cases may still occur later. Due to the fetus's underdeveloped cellular immune function and inability to produce interferon—especially when infected with rubella—the virus persists extensively in the body. As fetal cells divide, the virus invades new generations of cells, continuously proliferating and spreading. This results in persistent, multi-organ systemic infection, leading to diverse congenital defects, collectively termed congenital rubella syndrome (CRS). The most common symptoms include cataracts, sensorineural deafness, congenital heart disease, meningoencephalitis, myocardial necrosis, interstitial pneumonia, giant cell hepatitis, nephritis, hypospadias, and others. Such newborns may continue to shed the virus for months or even years after birth. Many show no obvious symptoms at birth, but serological tests confirm intrauterine rubella infection. Recent studies repeatedly indicate that children with congenital rubella often exhibit progressive abnormal immune responses.
Depending on the mode of infection, it can be divided into naturally acquired rubella and congenital rubella, which present differently.
Naturally acquired rubella is often subclinical, with rash being either present or absent. Common complications include arthralgia, arthritis, encephalitis, and thrombocytopenic purpura.
Congenital rubella syndrome includes: (1) Cardiovascular diseases (patent ductus arteriosus, ventricular septal defect, pulmonary artery stenosis); (2) Ocular defects (cataracts, retinopathy, microphthalmia, glaucoma); (3) Deafness; (4) Growth retardation; (5) Thrombocytopenic purpura; (6) Hepatosplenomegaly; (7) Jaundice; (8) Hepatitis; (9) Central nervous system lesions (psychomotor retardation, encephalitis, microcephaly, aseptic meningitis); (10) Bone disorders (osteoporosis of long bones, bone deformities); (11) Genitourinary system abnormalities (cryptorchidism, nephritis).
(1) Acquired rubella (or naturally acquired rubella) has an average incubation period of 18 days (14–21 days).
1. Prodromal stage: Relatively brief, lasting about 1–2 days, with mild symptoms. Low-grade or grade II fever, headache, loss of appetite, fatigue, lack of strength, and mild upper respiratory tract inflammation such as cough, sneezing, runny nose, sore throat, and conjunctival congestion. Occasionally accompanied by vomiting, diarrhea, epistaxis, and gum swelling. Some patients may exhibit rose-colored or hemorrhagic macules and papules on the soft palate and pharynx, but the buccal mucosa remains smooth, without congestion or mucosal spots.
Generally, prodromal symptoms in infants and young children are often mild or absent, whereas they are more pronounced in older children and adults and may persist for 5–6 days.
2. Stage of full eruption: The rash typically appears 1–2 days after fever, initially on the face and neck, and rapidly spreads downward to cover the trunk and limbs within a day, though the palms and soles usually remain unaffected. The rash begins as fine, pale red macules and papules, or papules, 2–3 mm in diameter. The rash is sparser on the face and distal limbs, with some merging to resemble measles. On the trunk, especially the back, the rash is dense and confluent, resembling scarlet fever. The rash usually lasts for 3 days (1–4 days) before fading, earning it the nickname "three-day measles." Facial rash is characteristic of rubella. In rare cases, the eruption may be hemorrhagic, accompanied by systemic bleeding tendencies. During the stage of full eruption, low-grade fever, grade I upper respiratory tract inflammation, splenomegaly, and generalized superficial lymphadenopathy are common, with particularly noticeable enlargement of the posterior auricular, occipital, and posterior cervical lymph nodes. The enlarged lymph nodes are grade I tender, non-confluent, and non-suppurative. In some cases, splenomegaly and lymphadenopathy may precede the eruption by 4–10 days, and lymph nodes gradually return to normal, though complete recovery may take several weeks. Post-rash, there is usually no pigmentation or desquamation, though a few severe cases may exhibit fine bran-like scaling, with large-scale peeling being extremely rare.
Non-rash rubella: Rubella patients may present only with fever, upper respiratory tract inflammation, and lymphadenopathy without a rash. Others may show no symptoms or signs after rubella virus infection, with serological tests confirming rubella antibody positivity—these are termed subclinical or asymptomatic cases. Epidemiological surveys in different regions have found the ratio of symptomatic patients to non-rash or subclinical cases to be 1:6–9.
(2) Congenital rubella syndrome. After the fetus is infected, severe cases can lead to dead fetus, late abortion, or premature labor. Mild cases may result in fetal growth retardation, with birth weight, length, head circumference, and chest circumference all lower than those of normal newborns. These differences often remain uncorrected by the age of one. Such infants are prone to multiple malformations, and it is estimated that over 5% of neonatal congenital malformations are caused by congenital rubella. Common congenital malformations or diseases include internal visual obstruction, retinal disease, glaucoma, iridocyclitis, neural deafness, vestibular injury, otitis media, congenital heart disease, myocardial necrosis, hypertension, interstitial pneumonia, giant cell hepatitis, hepatosplenomegaly, lymphadenopathy, glomerulosclerosis, thrombocytopenic purpura, hemolytic anemia, aplastic anemia, encephalitis, meningitis, microcephaly, and intellectual disabilities. Rubella virus can be isolated from the pharynx, blood, urine, or cerebrospinal fluid of congenital rubella patients, with higher positive rates in infants under one year old. There are also reports of rubella virus persisting in brain tissue for up to 12 years after congenital infection, leading to progressive rubella panencephalitis. Most congenital rubella infants exhibit clinical symptoms at birth, but progressive symptoms and new malformations may also appear months or years after birth. Malformations appearing after one year of age include deafness, psychomotor abnormalities, language disorders, and skeletal deformities. Therefore, children at risk of congenital rubella should be followed up until 2–3 or 4–5 years of age. In the U.S., it was reported that during a major rubella epidemic, among 4,005 newborns, over 2% were confirmed by viral isolation or serological testing to have congenital rubella (compared to the usual local rate of 0.1%). Among these 4,005 cases, 68% were subclinical, showing no malformations or defects during the neonatal period. However, 71% of these cases developed various congenital rubella symptoms during follow-up in the first five years of life. This demonstrates that congenital rubella syndrome is a severe consequence of rubella virus infection. Recent reports in China also indicate that among 835 pregnant women in early gestation, 1.44% tested positive for rubella IgM antibodies, and fetal blood rubella IgM positivity accounted for 62.5% of maternal infections.
bubble_chart Auxiliary Examination
(1) Peripheral Blood Picture: The total white blood cell count decreases, lymphocytes increase, and atypical lymphocytes and plasma cells appear.
(2) Rapid Diagnosis: Recently, the direct immunofluorescence method has been used to detect rubella virus antigens in exfoliated cells from throat swabs. The diagnostic value of this method still requires further observation.
(3) Virus Isolation: For general rubella patients, nasopharyngeal secretions are collected. For congenital rubella patients, urine, cerebrospinal fluid, blood, or bone marrow is cultured in continuous cell lines such as RK-13, Vero, or SIRC to isolate the rubella virus, which is then identified using immunofluorescence.
(4) Serum Antibody Detection: Tests such as red blood cell agglutination, neutralization, complement fixation, and immunofluorescence are used. A fourfold or greater increase in antibody titer between paired sera is considered positive. The red blood cell agglutination inhibition test is the most commonly used due to its speed, simplicity, and reliability. This antibody appears at the time of eruption, rises rapidly within 1–2 weeks, and declines to baseline levels after 4–12 months, but persists for life. Rubella-specific secretory IgA antibodies can be detected in the nasopharynx, aiding diagnosis. Dot hybridization can also be used to detect rubella virus RNA for diagnosing rubella infection.
Specific rubella IgM antibodies are diagnostically significant. If congenital rubella is suspected during the neonatal period, it is best to test both maternal and infant samples simultaneously and conduct dynamic observations to determine whether the neonatal infection markers are due to passively acquired maternal antibodies. Rubella antibodies gradually decline with age. If follow-up shows a gradual increase in rubella antibodies, this indicates infant infection. Therefore, it is advisable to monitor multiple indicators.
(1) Diagnosis The diagnosis of a typical rubella patient is mainly based on epidemiological history and clinical manifestations, such as a short prodromal period, upper respiratory tract inflammation, low fever, characteristic maculopapular rash, and tenderness of the postauricular and occipital lymph nodes. However, during an epidemic, atypical patients and those with subclinical infections far outnumber typical cases. For such patients, virus isolation or serum antibody testing must be performed to confirm the diagnosis. Specific IgM antibodies have diagnostic value. These IgM antibodies disappear 4-8 weeks after the onset of illness, leaving only IgG antibodies.
For infants born to women suspected of rubella infection during pregnancy, regardless of the presence of symptoms or signs, rubella virus isolation and IgM antibody testing should be conducted. A positive result confirms the diagnosis of congenital rubella. The specific IgM antibodies in congenital rubella differ from those in natural infections. By the 16th week of gestation, the fetus produces its own specific IgM antibodies, which continue to rise for six months after birth before gradually declining, though they remain detectable within the first year of life. Maternal IgG antibodies decline several months after birth, while the infant's own IgG rubella antibodies continue to rise.
Rubella retinitis is often an important or even the sole sign for diagnosing congenital rubella. The retina typically shows brown or dark brown punctate or streaky pigmented spots of varying sizes. In severe cases, besides larger spots, yellow lens opacities may also be present. The retinal blood vessels are often narrower than normal.
bubble_chart Treatment Measures
(1) General and symptomatic treatment: Rubella patients generally have mild symptoms and do not require special treatment. For those with more pronounced symptoms, bed rest and a liquid or semi-liquid diet are recommended. Symptomatic treatment can be provided for high fever, headache, cough, and conjunctivitis.
(2) Treatment of complications: For encephalitis with high fever, drowsiness, unconsciousness, or convulsions, treatment should follow the principles for epidemic encephalitis B. In cases of severe bleeding tendency, adrenal corticosteroids may be used, and fresh whole blood transfusion may be administered if necessary.
(3) Congenital rubella: From an early age, good care and education should be provided. Medical personnel should work closely with the child’s parents, nursery caregivers, and school teachers to monitor the child’s growth and development, assess hearing, correct deformities, and perform surgical interventions for conditions such as glaucoma, cataracts, and congenital heart disease when necessary. Efforts should be made to help the child learn life skills and develop work abilities to overcome congenital defects.
(4) Drug treatment: In addition to symptomatic treatment, interferon, ribavirin, and other medications may help alleviate the condition.
The prognosis of rubella is generally good. Deaths due to complications such as meningitis or intracranial hemorrhage caused by thrombocytopenia are rare. However, if a woman contracts rubella during the first three months of pregnancy, the fetus may develop congenital rubella, leading to stillbirth, premature labor, or various congenital malformations, resulting in a severe prognosis. Therefore, preventive measures for pregnant women must be taken seriously.
Since the symptoms of this disease are mostly mild and the prognosis is generally good, special prevention does not seem necessary. However, congenital rubella is highly harmful, potentially causing dead fetus, premature labor, or various congenital malformations. Therefore, prevention efforts should focus on congenital rubella.
(1) Isolation and Quarantine Patients should be isolated until 5 days after the eruption. However, due to the mild symptoms and the high number of asymptomatic carriers, the disease is easily overlooked, making complete isolation difficult. Generally, contacts do not require quarantine, but pregnant women, especially those in the early stages of pregnancy, should avoid contact with rubella patients during outbreaks.
(2) Active Immunization Internationally, the widespread use of attenuated rubella vaccines over the past decade has proven safe and effective. The antibody seroconversion rate post-vaccination exceeds 95%, with only a few individuals experiencing short-term reactions such as fever, rash, lymphadenopathy, and joint pain. Immunity from vaccination typically lasts for more than 7 years. Vaccination targets vary by country. For example, the U.S. recommends immunization for children aged 1 year through adolescence, particularly those in preschool and elementary school, as they have the highest incidence of rubella and can spread it to adults, including pregnant women. Adolescent and adult women should also be vaccinated, leading to a significant reduction in congenital rubella. Although the impact of rubella vaccine strains on humans and fetuses is not yet fully understood, the attenuated virus in live vaccines can cross the placenta and cause fetal malformations. Thus, pregnant women should not receive live vaccines. Rubella vaccines are often combined with measles and mumps vaccines, yielding excellent results. China has also developed an attenuated live rubella vaccine, with some regions already implementing its use and gradually incorporating it into routine immunization programs. Key targets include women of childbearing age before marriage, such as female students in their final years of high school and junior high.
The effectiveness of immunoglobulin in preventing rubella remains uncertain to date.
Rubella generally presents with mild symptoms and few complications. Only a small number of patients may develop complications such as otitis media, pharyngitis, bronchitis, pneumonia, myocarditis, pancreatitis, hepatitis, gastrointestinal bleeding, thrombocytopenic purpura, hemolytic anemia, nephrotic syndrome, acute or chronic nephritis, etc. The more severe complications include the following:
(1) **Encephalitis**: Rare, with an incidence of 1:6,000, mainly seen in children. It usually occurs 1–7 days after the eruption, presenting with headache, drowsiness, vomiting, diplopia, neck stiffness, unconsciousness, convulsions, ataxia, limb paralysis, etc. Cerebrospinal fluid changes resemble those of other viral encephalitides. The course is relatively short, with most patients recovering spontaneously within 3–7 days, though a few may experience sequelae. Chronic progressive panencephalitis may also occur. During the peak of the rubella epidemic in 1993, 86% of rubella cases admitted to the Pediatric Hospital of Shanghai Medical University were complicated by encephalitis, including 7 severe cases with unconsciousness. Although the course was prolonged, all patients recovered with treatment.
(2) **Myocarditis**: Patients report chest tightness, palpitations, dizziness, and weakness, with changes in electrocardiograms and cardiac enzyme profiles. Most recover within 1–2 weeks. It may coexist with other complications such as encephalitis.
(3) **Arthritis**: Primarily seen in adults, especially women, though cases of rubella-associated arthritis in children have been reported in China. The exact pathogenesis remains unclear but may involve direct viral invasion of the joint cavity or immune reactions. During the full eruption stage, joints such as the fingers, wrists, and knees may exhibit redness, swelling, and pain, with joint effusions containing mononuclear cells. Sometimes, multiple joints may become swollen and painful sequentially, resembling rheumatic polyarthritis, but most symptoms resolve spontaneously within 2–30 days.
(4) **Hemorrhagic Tendency**: Rare, caused by thrombocytopenia and increased capillary permeability. Sudden bleeding may occur after the eruption, manifesting as petechiae, ecchymoses on the skin and mucous membranes, hematemesis, hematochezia, or hematuria. Most cases resolve spontaneously within 1–2 weeks, but intracranial hemorrhage in a few patients may lead to death.
Other possible complications include abnormal liver or kidney function.
(2) Differential Diagnosis The rash morphology of rubella patients falls between that of measles and scarlet fever, so emphasis should be placed on differentiating these three common febrile eruptive diseases. Additionally, rubella must be distinguished from roseola infantum, drug eruptions, infectious mononucleosis, and enterovirus infections, such as coxsackievirus A group types 2, 4, 9, and 16, B group types 1, 3, and 5, and echovirus types 4, 9, and 16 (see the chapter on measles). Congenital rubella syndrome also requires differentiation from intrauterine infections such as toxoplasmosis, cytomegalovirus infection, and herpes simplex virus infection. These three intrauterine infections share symptoms similar to those of congenital rubella.
