Chapter 12: Congenital Rubella Syndrome.
Susan Reef, MD and Victor Coronado, MD
I. Disease description
Rubella is a viral illness caused by a togavirus of the genus Rubivirus. Children usually develop few or no constitutional symptoms, but adults may experience a 1-5 day prodrome of low-grade fever, headache, malaise, mild coryza, and conjunctivitis. Arthralgia or arthritis may occur in up to 70% of adult women with rubella. When rubella infection occurs during pregnancy, especially during the first trimester, fetal infection is likely and often causes congenital rubella syndrome (CRS), resulting in abortions, miscarriages, stillbirths, and severe birth defects. Up to 20% of the infants born to mothers infected during the first half of pregnancy have CRS. The most common congenital defects are cataracts, heart disease, sensorineural deafness, and mental retardation.
The number of reported cases of congenital rubella syndrome in the United States has declined more than 97.4% from 77 cases in 1970 to a total of 2 cases in 1996.1-3 Between 1990 and 1996, 92 cases of CRS have been reported to the National Congenital Rubella Syndrome Registry. Of these cases, 75 (82%) were indigenous, and 17 (18%) were imported.
III. Importance of rapid case identification
Infants with CRS should be identified as early in life as possible in order to prevent further spread of the virus. Additionally, early diagnosis will facilitate early intervention for specific disabilities. Infants with CRS may shed virus for a prolonged period and should be considered infectious until they are at least 1 year old or until their urine and pharyngeal viral cultures, taken every month, are repeatedly negative for rubella.
IV. Importance of surveillance
The goal of a rubella vaccination program is to prevent CRS. Surveillance data are used to identify groups of persons or areas in which additional disease control efforts (such as immunization) are required to reduce disease incidence, and to evaluate the effectiveness of disease prevention programs and policies.
V. Disease reduction goals
As part of the year 2000 objectives, a goal was established for the elimination of indigenous rubella and CRS in the United States by the year 2000.
VI. Case definitions
The following case definition for congenital rubella syndrome has been approved by the Council of State and Territorial Epidemiologists (CSTE), and was published in May 1997 (Appendix 1).4
An illness, usually manifesting in infancy, resulting from rubella infection in utero and characterized by signs or symptoms from the following categories:
Presence of any defects or laboratory data consistent with congenital rubella infection.
Laboratory criteria for diagnosis
Suspected: A case with some compatible clinical findings but not meeting the criteria for a probable case.
Probable: A case that is not laboratory confirmed and that has any two complications listed in first paragraph of the clinical description or one complication from first paragraph and one from second paragraph, and lacks evidence of any other etiology.
Confirmed: A clinically compatible case that is laboratory confirmed.
Infection only: A case that demonstrates laboratory evidence of infection, but without any clinical symptoms or signs.
Note: In probable cases, either or both of the eye-related findings (cataracts and congenital glaucoma) count as a single complication. In cases classified as infection only, if any compatible signs or symptoms (e.g., hearing loss) are identified later, the case is reclassified as confirmed.
Indigenous case. Any case which cannot be proved to be imported.
Imported case. A case which has its source outside the reporting state.
Laboratory confirmation can be obtained by any of the following:
The serologic tests available for laboratory confirmation of CRS infections vary among laboratories. The following tests are widely available and may be used for screening for laboratory confirmation of disease. The state health department can provide guidance on available laboratory services and preferred tests.
Rubella virus can be isolated from nasal, blood, throat, urine, and cerebrospinal fluid specimens from rubella and CRS cases. Efforts should be made to obtain clinical specimens (particularly pharyngeal swabs and urine specimens) for viral isolation from infants at the time of the initial investigation (Appendix 5). However, infants with CRS may shed virus for a prolonged period so specimens obtained later may also yield rubella virus. Specimens for virus isolation (urine specimens and pharyngeal swabs) should be obtained monthly until cultures are repeatedly negative.
Virus isolates are extremely important for molecular epidemiologic surveillance to help determine 1) the origin of the virus, 2) virus strains circulating in the U.S., and 3) whether these strains have become endemic in the U.S.5 Specimens for virus isolation should be sent to CDC for molecular typing as directed by the state health department.
Polymerase chain reaction (PCR)
Although detection of rubella virus by PCR is not included as confirmatory in the case definition, the test does provide presumption evidence of rubella infection. In the United Kingdom, there has been extensive evaluation of PCR for detection of rubella virus in clinical specimens, documenting its usefulness. 6,7 Clinical specimens obtained for virus isolation and sent to CDC are routinely screened by PCR. Further validation is needed of classification of cases that test positive by PCR in the absence of virus isolation.
Each state and territory has regulations and/or laws governing the reporting of diseases and conditions of public health importance (Appendix 2).8 These regulations/laws list the diseases which are to be reported, and describe those persons or groups who are responsible for reporting, such as health care providers, hospitals, laboratories, schools, day care facilities, and other institutions. Contact your state health department for reporting requirements in your state.
Reporting to CDC
Provisional reports of rubella and CRS cases should be sent by the state health department to CDC via the National Electronic Telecommunications System for Surveillance (NETSS) within 14 days of the initial report to the state or local health department. Reporting should not be delayed because of incomplete information or lack of confirmation.
In addition, each possible and confirmed case of CRS should be reported to the National Congenital Rubella Syndrome Registry (NCRSR), National Immunization Program (NIP), CDC. The NCRSR case report form (Appendix 17) is used to collect clinical and laboratory information on cases of CRS that are reported by state and local health departments. NCRSR cases are classified by year of patient's birth. Although case report forms should be as complete as possible before case reporting, lack of complete information should not delay the reporting.
Information to collect
The following data are epidemiologically important and should be collected in the course of case investigation. Additional information may also be collected at the direction of the state health department.
Maternal history including
--Date of rubella vaccination(s)
--Dates and results of previous serologic tests for rubella immunity
--History or documentation of rubella infection during pregnancy
--If possible, country of birth
Clinical details (e.g., cataracts, hearing loss, mental retardation, type of congenital heart defect, meningoencephalitis, microcephaly)
Laboratory information including types and results of laboratory testing performed on both mother and child
Although use of rubella vaccine is contraindicated in pregnant women or women planning pregnancy within 3 months, inadvertent administration of the vaccine to pregnant women does occur. In order to evaluate the risk to the fetus of exposure to attenuated rubella vaccine virus, a pregnancy registry was established. By April 1989 when the registry was discontinued, vaccination of 700 women with the RA 27/3 rubella vaccine within 3 months of conception was reported. Among the 289 women who were known to be susceptible at the time of vaccination, outcomes of pregnancy are known for 275 (94%); 83% delivered living infants, all 229 of whom were free of defects associated with CRS. Rubella-specific IgM was detected in three infants, but all three were normal on physical examination. These data are consistent with results reported from other countries, suggesting that if live attenuated rubella vaccine causes defects associated with CRS, it does so at a very low rate (<1.6%).
X. Enhancing Surveillance
The following activities may be undertaken to improve the detection and reporting of cases, and to improve the comprehensiveness and quality of surveillance for rubella and CRS. Additional guidelines for enhancing surveillance are given in Chapter 16.
Active surveillance. Following an outbreak of rubella, an active surveillance system for CRS should be established among health care providers, clinics, and hospitals in the outbreak area beginning 6-9 months after the rubella outbreak.
Searching laboratory records. Audits of laboratory records may provide reliable evidence of previously unreported serologically confirmed or culture-confirmed cases of congenital rubella syndrome. Infants with CRS have been identified by including the serological results for TORCH agents in audits of laboratory records.
Comparing other data sets. Birth defects registries may reveal unreported CRS cases.(1)Ç rubella syndrome, 1980-1990. Epidemiol Rev 1991;13:341-8.
3. CDC. Rubella and congenital rubella syndrome - United States, 1994-1997. MMWR 1997;46:350-4.
4. CDC. Case definitions for infectious conditions under public health surveillance. MMWR 1997;46(RR-10):30.
5. Frey TK, Abernathy ES. Identification of strain-specific nucleotide sequences in the RA 27/3 rubella virus vaccine. J Infect Dis 1993;168:854-64.
6. Bosma TJ, Corbett KM, O'Shea S, Banatvala JE, Best JM. PCR for detection of rubella virus RNA in clinical samples. J Clin Micro 1995;33:1075-9.
7. Bosma TJ, Corbett KM, Eckstein MB, O'Shea S, Vijayalakshmi P, Banatvala JE, Morton K, Best JM. Use of PCR for prenatal and postnatal diagnosis of congenital rubella. J Clin Micro 1995;33:2881-7.
8. CDC. Mandatory reporting of infectious diseases by clinicians. MMWR 1990;39(RR-9):1-17.
9. Garner JS. Guideline for isolation precautions in hospitals. The Hospital Infection Control Practices Advisory Committee. Infect Cont Hosp Epid 1996;17:53-80.
10. Greaves WL, Orenstein WA, Stetler HC, et al.
Prevention of rubella transmission in medical facilities. JAMA 1982;248:861-4.