Pediatric Rubella Workup
- Author: Elias Ezike, MD; Chief Editor: Russell W Steele, MD more...
A clinical diagnosis of rubella may be difficult to make because many exanthematic diseases may mimic rubella infection. In addition, as many as 50% of rubella infections may be subclinical; therefore, laboratory studies are important to confirm the diagnosis of acute rubella infection.
The laboratory diagnosis of rubella can be made either though serologic testing or by viral culture. The serologic diagnosis consists of demonstrating the presence of rubella-specific immunoglobulin M (IgM) antibody in a single serum sample or observation of a significant (>4-fold) rise in rubella-specific immunoglobulin G (IgG) antibody titer between the acute and convalescent serum specimens drawn 2-3 weeks apart.
False-positive rubella IgM test results have been reported in persons with other viral infections (eg, acute Epstein-Barr virus [EBV], infectious mononucleosis, cytomegalovirus [CMV] infection, parvovirus B19 infection) and in the presence of rheumatoid factor (RF).
To demonstrate a 4-fold rise in rubella-specific IgG antibody, a serum sample should be obtained as soon as possible during the acute phase of infection and tested for rubella-specific IgG antibody. An aliquot of this serum should be frozen and stored for repeat testing later. Then, a second serum specimen is collected at 2-3 weeks and tested in the same laboratory at the same time with the first serum sample. The levels of rubella-specific IgG are compared between the first and the second sample to show a significant rise in antibody titers.
Several techniques are available for serologic testing, including the following:
Enzyme-linked immunosorbent assay (ELISA)
Immunofluorescent assay (IFA)
Latex agglutination (LA) test
Hemagglutination inhibition (HI) test
Complement fixation (CF) test
Passive hemagglutination antibody (PHA) test
Among all the serologic tests available, ELISA is the most widely used because it is relatively inexpensive, technically easy to perform, rapid, and very sensitive.
Rubella viral cultures are time consuming, expensive, not readily available, and used mainly for tracking the epidemiology of rubella virus during an outbreak.
The most commonly used method for isolation of rubella virus from clinical specimens, taken from an infected person, is the interference technique using African green monkey kidney (AGMK) cells and an enterovirus.
The specimen (urine or nasopharyngeal swab) is inoculated onto primary AGMK monolayers. After 9-12 days, the cultures are challenged with an enterovirus. If rubella is present, it interferes with the challenge virus and no cytopathic effect (CPE) is observed on the AGMK cells. HI, CF, and immunofluorescence techniques have also been used to detect rubella-specific antigens in tissue culture.
Congenital rubella in infants and children is diagnosed by viral isolation or by serologic testing. In contrast to postnatal infection, viral isolation is the preferred technique in congenital rubella syndrome because rubella serology may be difficult to interpret in view of transplacental passage of rubella-specific maternal IgG antibody. In addition, rubella-specific IgM antibody may not be detectable at the time of evaluation. Congenital rubella syndrome has also been diagnosed using placental biopsy, rubella antigen detection by monoclonal antibody, and polymerase chain reaction (PCR).
Specimens used for viral isolation in congenital rubella include nasopharyngeal swab, urine, cerebrospinal fluid, and buffy coat of the blood.
In some infants with congenital rubella syndrome, rubella virus can persist and can be isolated from the nasopharyngeal and urine cultures throughout the first year of life or later.
The same serologic testing methods (ELISA, IFA, LA, HI, CF) discussed for postnatal rubella can be used to detect specific antibodies in congenital infection.
Rubella-specific IgM antibody is actively produced by the fetus or neonate and may be detected in the cord blood or neonatal serum.
Congenital rubella syndrome should be strongly suspected in infants older than 3 months if rubella-specific IgG antibody levels are observed and do not decline at the rate expected from passive transfer of maternal antibody (ie, equivalent of a 2-fold decline in HI titer per mo) in a compatible clinical situation.
Patients with concomitant immunodeficiency, such as agammaglobulinemia or dysgammaglobulinemia, may have a false-negative serology result for rubella. Therefore, viral isolation is required to confirm the diagnosis in this group of patients.
Imaging studies are usually not performed in postnatal rubella.
Congenital rubella syndrome
Chest radiography is indicated for infants who develop respiratory distress or other respiratory symptoms to exclude rubella-related interstitial pneumonitis or pulmonary edema that may result from congestive heart failure in children with severe or complicated congenital heart anomalies.
Radiography of the long bones may reveal radiolucencies in the metaphyses of long bones.
Echocardiography is important for patients with congenital heart defects to help diagnose the type of heart anomaly and evaluate the severity of the heart defect so that appropriate surgical plans can be made.
CT scanning of the head may reveal intracranial calcifications and enlargement of the ventricles.
MRI of the head may reveal cortical atrophy and white matter changes in patients with late-onset progressive panencephalitis.
CBC count may reveal leukopenia and thrombocytopenia. It is used to monitor the course of thrombocytopenia.
Liver function tests, such as total and direct bilirubin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and gamma-glutamyl transpeptidase levels may reveal hepatic injury due to disseminated rubella infection, especially in neonates.
Lumbar puncture is indicated to evaluate for possible causes in children who develop signs and symptoms of meningoencephalitis, such as full anterior fontanelle, irritability, hypotonia, seizures, lethargy, head retraction, and arching of the back.
In patients with rubella-related meningoencephalitis, CSF examination usually reveals normal glucose levels, normal or slightly elevated protein levels, and mild pleocytosis (20-100 WBC/mcL) with lymphocyte predominance.
Histologically cutaneous lesions are nonspecific and demonstrate only a mild, superficial, perivascular, lymphocytic infiltrate.
The gross neuropathologic features that present during autopsy of babies who are stillborn include microcephaly and various other malformations (ie, polymicrogyria, nonhemorrhagic subependymal germinal matrix cysts). Histologically, chronic inflammatory cells are found in the meninges and surrounding the intraparenchymal blood vessels. The vessel walls also show foci of subintimal fibrosis and mineralization.
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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%|