7/30/2017 Pediatric Rubella: Background, Pathophysiology, Epidemiology

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Pediatric Rubella
Updated: Feb 09, 2017
Author: Elias Ezike, MD; Chief Editor: Russell W Steele, MD more...

OVERVIEW

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.

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 6-20 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.
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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 school-aged 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. A median of 11 rubella cases was reported in the United
States (range: 418) each year from 2005 through 2011. Additionally, there were two rubella
outbreaks reported involving three cases, as well as four total CRS cases. Twenty-eight (42%) of the
67 rubella cases reported from 2005 through 2011 were known importations. [1] See the images below.

Number of rubella and congenital rubella syndrome (CRS) cases United States, 19662011. Courtesy of
Centers for Disease Control (CDC).
View Media Gallery

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. Furthermore, an expert panel
reviewed available data and unanimously agreed in December 2011 that rubella elimination has been
maintained in the United States. Rubella elimination is defined as the absence of endemic rubella
transmission (i.e., continuous transmission lasting 12 months). [1]

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
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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.

From 2000 to 2012, rising numbers of WHO member states began using rubella-containing vaccines
(RCVs) in their immunization program and began reporting rubella and congenital rubella syndrome
(CRS) surveillance data. As of December 2012, 132 (68%) WHO member states had introduced RCV,
a 33% increase from 99 member states in 2000. Some 43% of infants had received a RCV dose in
2012, a 96% increase from the 22% of infants who had been vaccinated against rubella in 2000. A
total of 94,030 rubella cases were reported to WHO in 2012 from 174 member states, an 86%
decrease from the 670,894 cases reported in 2000 from 102 member states. [2, 3]

International

Rubella occurs worldwide. [4] 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).

Deaths from rubella per year.

View Media Gallery

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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 [5, 6, 7, 8] (Open Table in a new window)

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

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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

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
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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.

Clinical Presentation

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Media Gallery

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.
Number of rubella and congenital rubella syndrome (CRS) cases United States, 19662011.
Courtesy of Centers for Disease Control (CDC).

of 5

Tables

Table 1. Reported Cases of Rubella, Deaths From Rubella, and Number of Cases of Congenital
Rubella Syndrome in the United States From 1969-2007 [5, 6, 7, 8]
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

Table 1. Reported Cases of Rubella, Deaths From Rubella, and Number of Cases of Congenital
Rubella Syndrome in the United States From 1969-2007 [5, 6, 7, 8]

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
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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

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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

General

Intrauterine growth
Common Early ...
retardation

Prematurity Uncommon Early ...

Stillbirth Uncommon Early ...

Abortion Uncommon Early ...

Cardiovascular system

Patent ductus arteriosus Common Early May occur with

pulmonary artery
stenosis
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Pulmonary artery Caused by intimal

Common Early
stenosis proliferation

Coarctation of the aorta Uncommon Early ...

Myocarditis Uncommon Early ...

Ventricular septal defect Uncommon Early ...

Atrial septal defect Uncommon Early ...

Eye

Cataract Common Early Unilateral or bilateral

Salt-and-pepper
appearance; visual
Retinopathy Common Early
acuity unaffected;
frequently unilateral

Cloudy cornea Uncommon Early Spontaneous resolution

Glaucoma Uncommon Early/Delayed May be bilateral

Common in patients
Microphthalmia Common Early
with unilateral cataract

Retinopathy with
Subretinal
Uncommon Delayed macular scarring and
neovascularization
loss of vision

Ear

Usually bilateral; mostly

sensorineural; may be
central in origin; rare
Hearing loss Common Early/Delayed when maternal rubella
occurs >4 months'
gestation; sometimes
progressive

CNS

Meningoencephalitis Uncommon Early Transient

May be associated with

Microcephaly Uncommon Early
normal intelligence

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Intracranial calcifications Uncommon Early ...

Encephalographic Usually disappear by

Common Early
abnormalities age 1 y

Mental retardation Common Delayed ...

Frequently related to
Behavioral disorders Common Delayed
deafness

Autism Uncommon Delayed ...

Chronic progressive Manifest in second

Uncommon Delayed
panencephalitis decade of life

Hypotonia Uncommon Early Transitory defect

Uncommon in absence
Speech defects Common Delayed
of hearing loss

Skin

Represents dermal
Blueberry muffin spots Uncommon Early
erythropoiesis

Usually generalized;
Chronic rubelliform rash Uncommon Early
lasts several weeks

Dermatoglyphic
Common Early ...
abnormalities

Lungs

Generalized; probably
Interstitial pneumonia Uncommon Delayed immunologically
mediated

Liver

Hepatosplenomegaly Common Early Transient

Usually appears in the

Jaundice Uncommon Early
first day of life

May not be associated

Hepatitis Uncommon Early
with jaundice

Blood
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Blood

Transient; no response
Thrombocytopenia Common Early
to steroid therapy

Anemia Uncommon Early Transient

Hemolytic anemia Uncommon Early Transient

Altered blood group

Uncommon Early ...
expression

Immune system

Hypogammaglobulinemia Uncommon Delayed Transient

Lymphadenopathy Uncommon Early Transient

Thymic hypoplasia Uncommon Early Fatal

Bone

Transient; most
Radiographic lucencies Common Early common in distal femur
and proximal tibia

Large anterior fontanel Uncommon Early ...

Micrognathia Uncommon Early ...

Endocrine glands

Usually becomes
Diabetes mellitus Common Delayed apparent in second or
third decade of life

Hypothyroidism,
Thyroid disease Uncommon Delayed hyperthyroidism, and
thyroiditis

Growth hormone
Uncommon Delayed ...
deficiency

Genitourinary system

Cryptorchidism Uncommon Early ...

Polycystic kidney Uncommon Early ...

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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 < 15% < 15% < 15% < 14%
lymphocytes)

Back to List

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, 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
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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.

Acknowledgements

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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