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Pediatric Rubella Workup

  • Author: Elias Ezike, MD; Chief Editor: Russell W Steele, MD  more...
Updated: Dec 18, 2014

Laboratory Studies

Postnatal rubella

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
  • Hemolysis-in-gel 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

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

Postnatal rubella

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.


Other Tests

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.


Histologic Findings

Postnatal rubella

Histologically cutaneous lesions are nonspecific and demonstrate only a mild, superficial, perivascular, lymphocytic infiltrate.

Congential rubella

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.

Contributor Information and Disclosures

Elias Ezike, MD Consulting Staff, Beaumont Pediatric Center, PLLC

Elias Ezike, MD is a member of the following medical societies: American Academy of Pediatrics

Disclosure: Nothing to disclose.


Jocelyn Y Ang, MD, FAAP, FIDSA Associate Professor, Department of Pediatrics, Wayne State University School of Medicine; Consulting Staff, Division of Infectious Diseases, Children's Hospital of Michigan

Jocelyn Y Ang, MD, FAAP, FIDSA is a member of the following medical societies: American Academy of Pediatrics, Infectious Diseases Society of America, Pediatric Infectious Diseases Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Chief Editor

Russell W Steele, MD Clinical Professor, Tulane University School of Medicine; Staff Physician, Ochsner Clinic Foundation

Russell W Steele, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Immunologists, American Pediatric Society, American Society for Microbiology, Infectious Diseases Society of America, Louisiana State Medical Society, Pediatric Infectious Diseases Society, Society for Pediatric Research, Southern Medical Association

Disclosure: Nothing to disclose.

Additional Contributors

Leonard R Krilov, MD Chief of Pediatric Infectious Diseases and International Adoption, Vice Chair, Department of Pediatrics, Winthrop University Hospital; Professor of Pediatrics, Stony Brook University School of Medicine

Leonard R Krilov, MD is a member of the following medical societies: American Academy of Pediatrics, American Pediatric Society, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, Society for Pediatric Research

Disclosure: Nothing to disclose.


Leslie L Barton, MD Professor Emerita of Pediatrics, University of Arizona College of Medicine

Leslie L Barton, MD is a member of the following medical societies: American Academy of Pediatrics, Association of Pediatric Program Directors, Infectious Diseases Society of America, and Pediatric Infectious Diseases Society

Disclosure: Nothing to disclose.

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Number of rubella cases per year.
Number of congenital rubella syndrome cases per year.
Deaths from rubella per year.
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.
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]
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
Table 2. Clinicopathologic Abnormalities in Congenital Rubella
Abnormality Common/Uncommon Early/Delayed Comment
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 ...
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
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
Blueberry muffin spots Uncommon Early Represents dermal erythropoiesis
Chronic rubelliform rash Uncommon Early Usually generalized; lasts several weeks
Dermatoglyphic abnormalities Common Early ...
Interstitial pneumonia Uncommon Delayed Generalized; probably immunologically mediated
Hepatosplenomegaly Common Early Transient
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
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
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 ...
Table 3. Age-Specific CD4 + T-lymphocyte Count and Percentage of Total Lymphocytes as a Criteria for Severe Immunosuppression in Persons with HIV
  Age Range
< 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%
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