Pediatric Rubella

4/12/14, 3:35 PM

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Pediatric Rubella
Author: Elias Ezike, MD; Chief Editor: Russell W Steele, MD more... Updated: May 13, 2013

Background
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.

Number of rubella cases per year.

Number of congenital rubella syndrome cases per year.

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Deaths from rubella per year.

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.

Pathophysiology
Postnatal rubella
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 620 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.

Epidemiology
Frequency
United States 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 schoolaged 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).

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Pediatric Rubella

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Number of rubella cases per year.

Number of congenital rubella syndrome cases per year.

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. International Rubella occurs worldwide.[1] 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.

Mortality/Morbidity
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).

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Deaths from rubella per year.

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. Table 1. Reported Cases of Rubella, Deaths From Rubella, and Number of Cases of Congenital Rubella Syndrome in the United States From 1969-2007[2, 3, 4, 5] (Open Table in a new window) Year Number of Cases Number of Deaths Cases of Congenital Rubella Syndrome 1969 57,686 1970 56,552 1971 45,086 1972 25,507 1973 27,804 1974 11,917 1975 16,652 1976 12,491 1977 20,395 1978 18,269 1979 11,795 1980 3,904 1981 2,077 1982 2,325 1983 970 1984 752 1985 630 1986 551 1987 306 1988 225 1989 396 1990 1,125 1991 1,401 1992 160 1993 192 1994 227 1995 128 1996 238 1997 181 1998 364 29 31 20 14 16 15 21 12 17 10 1 1 5 4 3 1 1 1 0 1 4 8 1 1 0 0 1 0 0 0 31 77 68 42 35 45 30 30 23 30 62 50 19 7 22 5 0 5 5 6 3 11 47 11 5 7 6 4 5 7

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1999 267 2000 176 2001 23 2002 18 2003 7 2004 10 2005 11 2006 11 2007 12

0 0 2 N/A N/A N/A N/A N/A N/A

9 9 3 1 1 0 1 1 0

Race
No ethnic difference in incidence has been clearly demonstrated, although the characteristic rash is more difficult to diagnose in persons with dark skin.

Sex
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.

Age
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.

Contributor Information and Disclosures

Author 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. Coauthor(s) Jocelyn Y Ang, MD Associate Professor, Department of Pediatrics, Division of Infectious Diseases, Children's Hospital of Michigan and Wayne State University Jocelyn Y Ang, MD is a member of the following medical societies: American Academy of Pediatrics, Infectious Diseases Society of America, and Pediatric Infectious Diseases Society Disclosure: Nothing to disclose. Specialty Editor Board Leonard R Krilov, MD Chief of Pediatric Infectious Diseases and International Adoption, Vice Chair, Department of Pediatrics, Professor of Pediatrics, Winthrop University Hospital 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, and Society for Pediatric Research Disclosure: Medimmune Grant/research funds Cliinical trials; Medimmune Honoraria Speaking and teaching; Medimmune Consulting fee Consulting Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
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Disclosure: Nothing to disclose. Robert W Tolan Jr, MD Chief, Division of Allergy, Immunology and Infectious Diseases, The Children's Hospital at Saint Peter's University Hospital; Clinical Associate Professor of Pediatrics, Drexel University College of Medicine Robert W Tolan Jr, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, American Society for Microbiology, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, Phi Beta Kappa, and Physicians for Social Responsibility Disclosure: Novartis Honoraria Speaking and teaching Chief Editor Russell W Steele, MD Head, Division of Pediatric Infectious Diseases, Ochsner Children's Health Center; Clinical Professor, Department of Pediatrics, Tulane University School of Medicine 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, and Southern Medical Association Disclosure: Nothing to disclose. Additional Contributors 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.

References
1. Pandolfi E, Chiaradia G, Moncada M, Rava L, Tozzi AE. Prevention of congenital rubella and congenital varicella in Europe. Euro Surveill. Mar 5 2009;14(9):16-20. [Medline]. 2. CDC. Summary of notifiable diseases, United States, 1996. MMWR Morb Mortal Wkly Rep. Oct 31 1997;45(53):1-87. [Medline]. 3. CDC. Reported Cases of Notifiable Diseases-United States, 1972-2003. MMWR. Apr 2005;52(54):73-78. 4. CDC. Provisional cases of infrequently reported notifiable diseases. MMWR. January 9, 2009;57(53):1420-1431. 5. CDC. Provisional Cases of Infrequently Reported Notifiable Diseases-United States. MMWR. Jan 2009;55(19):538. 6. Rafiei Tabatabaei S, Esteghamati AR, Shiva F, Fallah F, Radmanesh R, Abdinia B, et al. Detection of serum antibodies against measles, mumps and rubella after primary measles, mumps and rubella (MMR) vaccination in children. Arch Iran Med. Jan 2013;16(1):38-41. [Medline]. 7. Institute for Clinical Systems Improvement. Immunizations. Bloomington, MN: ICSI; 2008. 8. Klein NP, Fireman B, Yih WK, Lewis E, Kulldorff M, Ray P, et al. Measles-mumps-rubella-varicella combination vaccine and the risk of febrile seizures. Pediatrics. Jul 2010;126(1):e1-8. [Medline]. 9. Hviid A. Measles-mumps-rubella-varicella combination vaccine increases risk of febrile seizure. J Pediatr. Jan 2011;158(1):170. [Medline]. [Full Text]. 10. [Guideline] Marin M, Broder KR, Temte JL, Snider DE, Seward JF. Use of combination measles, mumps,
http://emedicine.medscape.com/article/968523-overview Page 6 of 8

Pediatric Rubella

4/12/14, 3:35 PM

rubella, and varicella vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. May 7 2010;59:1-12. [Medline]. [Full Text]. 11. Huang LM, Lee BW, Chan PC, Povey M, Henry O. Immunogenicity and safety of combined measlesmumps-rubella-varicella vaccine using new measles and rubella working seeds in healthy children in Taiwan and Singapore: A phase II, randomized, double-blind trial. Hum Vaccin Immunother. Feb 20 2013;9(6):[Medline]. 12. O'Leary ST, Suh CA, Marin M. Febrile seizures and measles-mumps-rubella-varicella (MMRV) vaccine: what do primary care physicians think?. Vaccine. Nov 6 2012;30(48):6731-3. [Medline]. 13. American Academy of Pediatrics; Committee on Infectious Diseases. Policy Statement--Prevention of Varicella: Update of Recommendations for Use of Quadrivalent and Monovalent Varicella Vaccines in Children. Pediatrics. Aug 28 2011;[Medline]. 14. Dontigny L, Arsenault MY, Martel MJ, et al. Rubella in pregnancy. J Obstet Gynaecol Can. Feb 2008;30(2):152-68. [Medline]. 15. American Academy of Pediatrics. 2003 Red Book: Report of the Committee on Infectious Diseases. 26th ed. American Academy of Pediatrics; 2003. 16. Bale JF Jr, Murph JR. Congenital infections and the nervous system. Pediatr Clin North Am. Aug 1992;39(4):669-90. [Medline]. 17. Bialecki C, Feder HM Jr, Grant-Kels JM. The six classic childhood exanthems: a review and update. J Am Acad Dermatol. Nov 1989;21(5 Pt 1):891-903. [Medline]. 18. Bullens D, Smets K, Vanhaesebrouck P. Congenital rubella syndrome after maternal reinfection. Clin Pediatr (Phila). Feb 2000;39(2):113-6. [Medline]. 19. CDC. Elimination of rubella and congenital rubella syndrome--United States, 1969-2004. MMWR Morb Mortal Wkly Rep. Mar 25 2005;54(11):279-82. [Medline]. 20. CDC. Progress toward elimination of measles and prevention of congenital rubella infection--European region, 1990-2004. MMWR Morb Mortal Wkly Rep. Feb 25 2005;54(7):175-8. [Medline]. 21. CDC. Quarterly immunization table. MMWR. July 1997. 22. CDC. Reportable diseases (1998 provisional data). MMWR. 2000;48:1183-89. 23. CDC. Rubella among Hispanic adults--Kansas, 1998, and Nebraska, 1999. MMWR Morb Mortal Wkly Rep. Mar 24 2000;49(11):225-8. [Medline]. 24. CDC. Rubella outbreak--Westchester County, New York, 1997-1998. MMWR Morb Mortal Wkly Rep. Jul 9 1999;48(26):560-3. [Medline]. 25. Cherry JD. Contemporary infectious exanthems. Clin Infect Dis. February 1993;16(2):199-205. [Medline]. 26. Cherry JD. Rubella virus. In: Feigin RD, Cherry JD, eds. Textbook of Pediatric Infectious Diseases. Vol 2. 4th ed. WB Saunders Co; 1998:1922-49. 27. Cherry JD. Viral exanthems. Curr Probl Pediatr. Apr 1983;13(6):1-44. [Medline]. 28. Editorial. TORCH syndrome and TORCH screening. Lancet. Jun 30 1990;335(8705):1559-61. [Medline]. 29. Englund J, Glezen WP, Piedra PA. Maternal immunization against viral disease. Vaccine. AugustSeptember 1998;16(14-15):1456-1463. [Medline]. 30. Freij BJ, South MA, Sever JL. Maternal rubella and the congenital rubella syndrome. Clin Perinatol. Jun 1988;15(2):247-57. [Medline]. 31. Giles CL. Uveitis in childhood - Part III Posterior. Ann Ophthalmol. January 1989;21(1):23-28. [Medline]. 32. Gold E. Almost extinct diseases: measles, mumps, rubella, and pertussis. Pediatr Rev. Apr 1996;17(4):120-7. [Medline].
http://emedicine.medscape.com/article/968523-overview Page 7 of 8

Pediatric Rubella

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33. Horstmann DM. Rubella. In: Evans AS, ed. Viral Infections of Humans, Epidemiology and Control. 3rd ed. Premium Medical Book Co; 1991:617-30. 34. Kimberlin DW. Rubella immunization. Pediatr Ann. Jun 1997;26(6):366-70. [Medline]. 35. Lindegren ML, Fehrs LJ, Hadler SC, Hinman AR. Update: rubella and congenital rubella syndrome, 19801990. Epidemiol Rev. 1991;13:341-8. [Medline]. 36. Lutwick LI. Postexposure prophylaxis. Infect Dis Clin North Am. Dec 1996;10(4):899-915. [Medline]. 37. Maldonado YA. Rubella virus. In: Long SS, Pickering LK, Prober CG, eds. Principles and Practice of Pediatric Infectious Diseases. Churchill Livingstone; 1997:1228-37. 38. Miller E. Rubella reinfection. Arch Dis Child. Aug 1990;65(8):820-1. [Medline]. 39. Morgan-Capner P. Diagnosing rubella. BMJ. Aug 5 1989;299(6695):338-9. [Medline]. 40. Munoz FM, Englund JA. A step ahead. Infant protection through maternal immunization. Pediatr Clin North Am. Apr 2000;47(2):449-63. [Medline]. 41. Parkman PD. Making vaccination policy: the experience with rubella. Clin Infect Dis. Jun 1999;28 Suppl 2:S140-6. [Medline]. 42. Powell S, Schochet SS Jr. Selected pediatric viral infections. Semin Pediatr Neurol. Sep 1995;2(3):211-9. [Medline]. 43. Reef S, Zimmerman-Swain L, Coronado V. Rubella. In: VPD Surveillance Manual. 1999:11. 44. Robinson J, Lemay M, Vaudry WL. Congenital rubella after anticipated maternal immunity: two cases and a review of the literature. Pediatr Infect Dis J. Sep 1994;13(9):812-5. [Medline]. 45. Rosa C. Rubella and rubeola. Semin Perinatol. Aug 1998;22(4):318-22. [Medline]. 46. Watson JC, Hadler SC, Dykewicz CA, et al. Measles, mumps, and rubella--vaccine use and strategies for elimination of measles, rubella, and congenital rubella syndrome and control of mumps: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. May 22 1998;47(RR-8):1-57. [Medline]. 47. Webster WS. Teratogen update: congenital rubella. Teratology. Jul 1998;58(1):13-23. [Medline]. 48. Weiter JJ, Roh S. Viral infections of the choroid and retina. Infect Dis Clin North Am. Dec 1992;6(4):87591. [Medline]. 49. Wharton M, Cochi SL, Williams WW. Measles, mumps, and rubella vaccines. Infect Dis Clin North Am. Mar 1990;4(1):47-73. [Medline]. Medscape Reference 2011 WebMD, LLC

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