Reef SE, Frey TK, Theall K, Abernathy E, Burnett CL, Icenogle J, McCauley MM, Wharton M. The Changing Epidemiology of Rubella in the 1990sOn the Verge of Elimination and New Challenges for Control and Prevention. JAMA. 2002;287(4):464-472. doi:10.1001/jama.287.4.464
Author Affiliations: National Immunization Program (Drs Reef and Wharton and Ms McCauley) and National Center for Infectious Diseases (Dr Icenogle), Centers for Disease Control and Prevention; Georgia State University (Dr Frey and Ms Abernathy), and Emory University School of Public Health (Ms Theall), Atlanta; and Utah Department of Health, Salt Lake City (Ms Burnett).
Context In 1989, the United States established a goal to eliminate indigenous
rubella and congenital rubella syndrome (CRS) by 2000. Reported rubella cases
are at record low levels; however, cases and outbreaks have occurred, primarily
among unvaccinated foreign-born adults.
Objective To evaluate the current epidemiology of rubella and CRS and assess progress
Design, Setting, and Subjects Analysis of rubella cases reported to the National Notifiable Diseases
Surveillance System from 1990 through 1999 and CRS cases reported to the National
Congenital Rubella Syndrome Registry from 1990 through 1999. Since 1996, US
and international viral isolates have been sequenced.
Main Outcome Measures Incidence and characteristics of rubella and CRS cases; molecular typing
of virus isolates.
Results Annually from 1990 through 1999, the median number of reported rubella
cases was 232 (range, 128-1412), and between 1992 and 1999, fewer than 300
rubella cases were reported annually, except in 1998. During the 1990s, the
incidence of rubella in children younger than 15 years decreased (0.63 vs
0.06 per 100 000 in 1990 vs 1999), whereas the incidence in adults
aged 15 to 44 years increased (0.13 vs 0.24 per 100 000). In 1992,
incidence among Hispanics was 0.06 per 100 000 and increased to a
high in 1998 of 0.97 per 100 000. From 1997 through 1999, 20 (83%)
of 24 CRS infants were born to Hispanic mothers, and 21 (91%) of 23 CRS infants
were born to foreign-born mothers. Molecular typing identified 3 statistically
distinct genotypic groups. In group 1, the close relatedness of viruses suggests
that a single imported source seeded an outbreak that did not spread beyond
the Northeast. Similarly, within groups 2 and 3, relatedness of viruses obtained
from clusters of cases suggests that single imported sources seeded each one.
Diversity of viruses found in 1 state is consistent with the conclusion that
several viruses were imported. Moreover, the similarity of viruses found across
the country, combined with a lack of epidemiologic evidence of endemic transmission,
support the conclusion that some viruses that are common abroad, particularly
in Latin America and the Carribean, were introduced into the United States
on several separate occasions.
Conclusions The epidemiology of rubella and CRS has changed significantly in the
last decade. These changes and molecular typing suggest that the United States
is on the verge of elimination of the disease. To prevent future rubella outbreaks
and CRS, current strategies must be enhanced and new strategies developed.
The current epidemiology of rubella and congenital rubella syndrome
(CRS) in the United States reflects the overwhelming success of rubella and
CRS control strategies that were initiated 31 years ago, when rubella vaccine
became available. While the US vaccination program has mainly focused on attaining
high rates of childhood immunization, the goal of the program is to prevent
fetal infection. When intrauterine rubella occurs in the first trimester of
pregnancy, the results can include miscarriage, stillbirth, and CRS—a
pattern of fetal anomalies that includes cataracts, hearing impairment, cardiac
disease, and developmental delay.1
After the vaccination program began in 1969, the number of rubella and
CRS cases declined steadily. That year, 57 600 rubella cases and 62 CRS
cases were reported. By 1988, an all-time low of 223 rubella cases and 4 CRS
cases were reported.2 However, in 1989, the
number of reported rubella cases increased nearly 2-fold to 396.3
This increase occurred concurrently with the measles resurgence, which was
attributed in part to failure to ensure timely vaccination of preschool-aged
In 1989, a goal was established to eliminate indigenous rubella transmission
and CRS in the United States by 2000.4 Four
years later, with the establishment of the 1993 Childhood Immunization Initiative,
efforts to attain high vaccination coverage were intensified.5
To measure the success of rubella control and prevention strategies and to
ensure that progress toward rubella elimination could be accurately documented,
surveillance was evaluated and enhanced to meet identified needs. For example,
during the 1990s, additional data were collected in case reports, and US health
officials increased collaborative efforts with nongovernmental organizations
representing high-risk populations in the United States and other countries
and with international organizations, including the Pan American Health Organization.
Also during the 1990s, new tools for rubella surveillance were developed;
in particular, molecular typing of rubella virus isolates proved to be a valuable
aid in understanding transmission of rubella in the United States.6
This article reviews the epidemiology of rubella and CRS in the United
States from 1990 through 1999. Significant changes have occurred. These changes
demand improved strategies for rubella control among foreign-born populations
and enhanced surveillance to document interruption of transmission of indigenous
rubella and CRS in the United States.
We analyzed data from rubella cases reported from 1990 through 1999
to the National Notifiable Diseases Surveillance System (NNDSS). For each
case, demographic information regarding age, sex, race/ethnicity, case classification,
and relationship to an outbreak was collected. In 1993, the NNDSS was extended
to include clinical information, vaccination history, and pregnancy information,
as well as source of exposure (imported or indigenous) and site of transmission.
Beginning in 1997, the National Immunization Program of the Centers for Disease
Control and Prevention collected country of origin and length of US residence
for cases and country of exposure for imported cases.
Rubella cases included in this report were classified as confirmed,
probable, suspected, or unknown according to the Council of State and Territorial
Epidemiologists' case definition.7 The classification
scheme is based on the clinical description and criteria for laboratory confirmation.
A clinical case of rubella is defined as a person who has an acute onset of
generalized maculopapular rash and a temperature of more than 99°F (37.2°C),
if measured, as well as 1 of 3 characteristics: arthritis/arthralgia, lymphadenopathy,
or conjunctivitis. Criteria for laboratory confirmation of rubella infection
include rubella virus isolation, detection of serum rubella IgM, or a significant
rise in serum IgG levels between acute- and convalescent-phase titers. A confirmed
case of rubella is defined as a person who has laboratory-confirmed rubella
or a person who meets the clinical case definition and is epidemiologically
linked to a laboratory-confirmed case. A probable rubella case meets the clinical
case definition but has no or noncontributory serologic or virologic testing
and is not epidemiologically linked to a laboratory-confirmed case. A suspected
case of rubella has some compatible clinical findings but does not meet the
criteria for a probable case. Cases of rubella were classified by year of
To be classified as an imported rubella case, the source of exposure
must have occurred outside the United States or the onset of rash must have
occurred within 14 to 23 days after entering the United States. All rubella
cases that do not satisfy either of these criteria are classified as indigenous.8
We analyzed data from CRS cases reported from 1990 through 1999 to the
National Congenital Rubella Syndrome Registry (NCRSR), a passive surveillance
system. Initiated in 1969, the NCRSR is maintained by the National Immunization
Program and receives reports from state and local health departments of US-born
infants with CRS, including clinical and demographic data about infants with
CRS and their mothers. Since 1996, mothers' country of birth and country of
exposure have been collected along with the other demographic data. Cases
of CRS are classified by year of birth.
Cases of CRS that were classified as confirmed or probable were included
in this analysis. A confirmed case of CRS is defined as a child with congenital
anomalies compatible with CRS and laboratory evidence of rubella virus infection
documented in the first year of life. Laboratory confirmation of CRS in infants
includes rubella virus isolation, detection of serum rubella IgM, or serum
IgG levels that persist longer than expected from passive transfer of maternal
IgG (ie, decreases at <2-fold dilution per month). A probable CRS case
lacks laboratory confirmation of rubella infection but has a clinical presentation
consistent with CRS. A clinical case of CRS includes at least 1 of the following:
cataracts or congenital glaucoma, heart defect, loss of hearing, or pigmentary
retinopathy, along with another of the preceding signs or 1 of the following:
purpura, splenomegaly, jaundice, microcephaly, mental retardation, meningoencephalitis,
or radiolucent bone disease.
Since 1984, CRS cases have been classified as imported or indigenous.2 An imported case of CRS is defined as CRS in a US
citizen or non–US citizen whose mother was outside of the United States
during her presumed exposure to rubella. If the timing of exposure to rubella
cannot be determined, classification as imported requires that the mother
be outside the United States throughout the 21 days before conception and
the first 20 weeks of pregnancy. All CRS cases that do not satisfy these criteria
are classified as indigenous.
To supplement case reports, we obtained additional information from
state and local health departments on outbreak investigations and control
measures. An outbreak was defined as 5 or more epidemiologically related cases.
For outbreaks with cases in more than 1 setting (ie, school, worksite) the
outbreak setting was classified as communitywide. Outbreaks were classified
by the year in which the first case was identified.
Since 1996, virus isolation was attempted on 236 clinical specimens,
usually obtained from throat swabs, of suspected rubella case-patients from
the 1990-1991 rubella outbreaks in California and from suspected rubella and
CRS case-patients, particularly in the United States but also from Latin America
and the Caribbean, during 1997 through 2000. The nucleotide sequence of a
portion of the virus genome was determined from successful virus isolations.
Isolation of rubella virus from clinical specimens by culturing in Vero cells,
extraction of the single-strand rubella virus RNA from the cultures, and amplification
of the E1 gene (by reverse transcriptase polymerase
chain reaction) were performed as previously described.6
From the E1 gene amplification product, the sequence
of nucleotides 8869 to 9469 was determined bidirectionally using BigDye Terminator
Cycle Sequencing Ready Reaction DNA Sequencing kits (PE Applied Biosystems,
Foster City, Calif) and an ABI Prism 377 DNA Sequencer apparatus (PE Applied
Biosystems). To cover sequencing of this region, 2 forward primers (351 ACGTCACCACTGAACACCCG
[nucleotides 8787-8806] and 615 CTCCACATACGCGCTGGAC [nucleotides 9122-9140])
and 1 reverse primer (86 TGGTGTGTGTGCCATAC [complementary to nucleotides 9529-9545])
Phylogenetic analysis of 59 viruses, including 49 US isolates, 2 laboratory
reference strains (Therien wild type and RA/27/3 vaccine), and 8 recent isolates
from other countries in the Western Hemisphere, was conducted. We used the
heuristic tree search algorithm with parsimony criterion of the PAUPSearch
program of Wisconsin Package Version 10 software (Genetics Computer Group,
Madison, Wis). Bootstrap resampling with 100 replicates was done with the
"bootstrap analysis using heuristic search" algorithm of this software to
place confidence values on nodes within the tree.
Data from CRS case reports were entered and analyzed using Epi Info
Version 6.1 (Centers for Disease Control and Prevention, Atlanta, Ga). Data
from rubella case reports were analyzed in SAS 6.12 (SAS Institute Inc, Cary,
NC). For trend analysis, the χ2 test was used, and for stratified
analysis, the Cochran-Mantel-Haenszel χ2 test was used.
The incidence of rubella decreased dramatically, from 0.45 per 100 000
in 1990 to 0.1 per 100 000 in 1999. Annually from 1990 through 1999,
the median number of reported rubella cases was 232 (range, 128-1412) (Figure 1). From 1992 through 1997, fewer
than 300 rubella cases were reported annually, with an all-time low in 1995
of 128 cases. From 1997 to 1998, cases increased 100%, from 181 to 364. In
1999, the total was 272.
During the 1990s, cases of rubella were reported from all but 3 states.
In 1990 and 1991, approximately three quarters of the states reported rubella
cases; however, since 1992, fewer than half of the states reported cases of
rubella, with 4 or fewer states annually reporting a majority of the cases.
During the 1990s, the characteristics (ie, age distribution, sex, and
race/ethnicity) of rubella cases changed significantly (Table 1). In 1990, incidence was higher among children younger than
15 years than among persons aged 15 to 44 years (0.63 and 0.13 per 100 000,
respectively); however, since the mid 1990s, incidence has increased among
persons aged 15 to 44 years to 0.24 in 1998 (range in 1996 through 1999, 0.16
to 0.24 per 100 000) and decreased among children younger than 15
years to 0.08 in 1998 (range in 1996 through 1999, 0.03 to 0.08 per 100 000).
In 1990, children younger than 15 years accounted for 69% of cases (338/488),
declining to a low in 1997 of 11% (20/181). Since 1996, the highest percentage
of cases occurred among persons aged 20 to 29 years, with a high in 1999 of
49% (131/269). This shift to adults began earlier in California; in 1990,
although ages for the suspected California cases were not reported to the
NNDSS, an investigation revealed that the majority of the 411 reported cases
occurred among persons aged 20 years or older.
The age shift was accompanied by a shift in the distribution of cases
by sex. Since the mid 1990s, significantly fewer cases were reported among
women than among men (P<.001). However, every
year since 1992, more than 50% of the cases among women occurred among those
of childbearing age (15-44 years). In 1996 through 1999, rubella was reported
in 281 women of childbearing age; of these, 71 (26%) were pregnant at the
time of rash onset. Of 50 women with known data on trimester, 27 (54%) were
in their first trimester, 9 (18%) were in their second trimester, and 14 (28%)
were in their third trimester.
In the 1990s, a shift in the distribution of cases by race/ethnicity
occurred. Since the mid 1990s, most of the reported cases occurred among persons
of Hispanic ethnicity; of these persons, most were born outside the United
States. In 1992, incidence among Hispanics was 0.06 per 100 000 and
increased to a high in 1998 of 0.97 per 100 000; however, incidence
among non-Hispanics was stable. When adjusting for sex and age group, Hispanic
ethnicity (P≤.001) remained the most significant
factor. In 1998, of cases with known country of origin, 79% (231/291) were
born outside the United States. Of these, 91% were from the Western Hemisphere:
Mexico (43%), Guatemala (21%), El Salvador (16%), Honduras (4%), Colombia
(4%), and Cuba (3%). In 1999, 65% of cases (92/141) with known country of
origin occurred among persons born outside the United States. Of these, 98%
were from the Western Hemisphere: Mexico (81%) and El Salvador (14%).
During the 1990s, the percentage of confirmed cases increased. From
1992 through 1994, the percentage of confirmed cases increased from 28% (44/157)
to 83% (188/227). In 1995, 76% were reported as confirmed, but only 50% of
cases had documented laboratory confirmation, epidemiologic linkage, or both.
Since 1996, at least 93% of cases are classified as confirmed each year, with
at least 84% of these cases being laboratory confirmed, epidemiologically
linked, or both.
During the 1990s, surveillance for source of exposure was improved and
data became more complete. In 1992, 73% of reports did not include a source;
however, among case reports that did, 47% (20/43) were classified as imported.
From 1997 to 1999, 17% were classified as unknown source; however, among case
reports with a known source, 8% were classified as imported. From 1997 through
1999, of the 55 imported cases, 52 had information on country of exposure.
Countries of exposure included Mexico (33%), Japan (12%), Russia (13%), and
the Philippines (8%).
Since 1996, at least 93% of case reports have included vaccination status.
From 1996 through 1999, 8% to 14% reported receiving vaccine, 48% to 57% had
never been vaccinated, and 29% to 41% reported unknown vaccination status.
For the cases in 1998 born outside the United States, most (88%) either
were unvaccinated (134 [58%] of 231) or had unknown vaccination status (68
[29%] of 231). Of the 29 persons (12%) who were vaccinated, 24 (83%) were
vaccinated within 14 days prior to rash onset, 7 within 7 days prior, and
7 between 7 and 14 days prior. In 1999, the same pattern was noted.
Even though rubella occurred mainly among foreign-born adults in 1998
and 1999, we stratified vaccination status by age and country of origin to
evaluate the vaccination status of persons born inside the United States.
In 1998, 51 cases occurred among US-born persons who were age-eligible for
vaccination. Of these, 36 cases had known vaccination status and 13 of these
had received vaccine. Of the 13 vaccinated persons, 8 (62%) were among children
younger than 15 years. In 1999, the same pattern was noted.
From 1990 through 1999, 117 cases of CRS were reported to the NCRSR
(Figure 1). Of these, 110 (94%)
were classified as confirmed and 7 (6%) as probable. Of the 117 infants with
CRS, 66 (56%) were born during 1990 and 1991. Of these, 43 occurred in 2 clusters.
The first cluster of 21 infants was associated with a multicounty rubella
outbreak in southern California in 1989.9 The
second cluster was associated with a 1991 rubella outbreak among an Amish
community in Pennsylvania.10 Each year from
1992 through 1999, an average of 6 infants with CRS were born.
Mothers of infants with CRS tended to be young, Hispanic, and foreign-born.
Of 113 mothers with known age, the median age was 23 years (range, 15-38 years).
Among the 102 mothers whose race/ethnicity was known, 84 (82%) were white,
9 (9%) were black, and 5 (5%) were Asian/Pacific Islander. Of the 115 mothers
with known ethnicity, 57 (50%) were Hispanic; overall in the United States,
Hispanics accounted for 17% of all births.11
Since 1997, 83% (20/24)of the infants with CRS were born to Hispanic women,
and 21 of the 23 mothers with known country of birth were born outside the
United States. The countries of the mothers' births include Mexico (n = 13),
Philippines (n = 2), Dominican Republic (n = 2), Columbia (n = 1), Pakistan
(n = 1), Honduras (n = 1), and Guyana (n = 1). Only 1 of these women had received
rubella-containing vaccine prior to birth of an infant with CRS.
During the beginning of the 1990s, most of the mothers were exposed
to rubella in the United States; however, by the end of the decade, almost
half of the cases were imported. Of the 114 cases with known import status,
75% (86/114) were classified as indigenous; that is, exposure to disease occurred
in the United States. Since 1997, when complete data on country of exposure
were available, 42% of CRS cases (10/24) were imported; 6 mothers (60%) were
exposed in Mexico, and 1 each in the Philippines, Pakistan, Venezuela, and
From 1990 through 1999, 65 outbreaks were reported; of these, 34 (52%)
occurred in 1990-1991. Settings that predominated at the beginning of the
decade did not account for the majority of outbreaks by the end of the decade.
In 1990-1991, the 34 reported outbreaks accounted for 41% of cases reported
(1046/2536). Common outbreak settings included religious communities (14/34),
correctional facilities (9/34), and higher education institutions (4/34).
The percentages of cases for each type of outbreak were 72%, 15%, and 4%,
respectively. Outbreaks in religious communities were larger than those in
correctional facilities (median size, 22.5 and 9.5; range, 9-128 and 5-36,
Since 1993, of the 31 outbreaks that were reported, the most predominant
setting has been worksites (n = 13), followed by communities (n = 10) and
correctional facilities (n = 5). Some of these outbreaks were initially identified
as workplace outbreaks, and subsequent investigation revealed spread to the
community. After the 1990-1991 outbreaks, the largest outbreak in the rest
of the decade occurred in Massachusetts in 1993-1994 involving 128 cases.12 Six pregnant women were infected, 4 of whom were
in their first trimester; 3 chose to terminate their pregnancies.
Since 1995, when most cases occurred among Hispanic persons, most outbreaks
also predominantly affected Hispanic adults (Table 2). In 1995, 2 outbreaks occurred, accounting for 30% (n =
38) of reported cases among mainly Hispanic adults. Since 1996, more than
half of the cases were associated with outbreaks.13
In 1997, country of origin data was collected in most of the outbreaks.
The data show that almost all subsequent outbreaks were in the foreign-born
population. In the first half of 1997, 6 outbreaks occurred; 4 of these involved
workplaces, such as meat processing plants and cruise ships, that employed
foreign-born workers. The fifth outbreak occurred in a community of persons
in New York, NY, from the Caribbean and Guyana. One infant with CRS was born
as a result of this outbreak. In late 1997, 3 outbreaks began that comprised
37% (n = 135) of the 364 cases reported in 1998.14
In 1999, 4 outbreaks occurred in the United States.15
Three of the 4 were workplace-associated; however, 1 of these, which occurred
in Nebraska, spread into the community, including infecting children and adults
in a day-care center.16,17 As
a result of this outbreak, 1 infant with CRS was born.
In 1997-1999, despite enhanced passive and active surveillance in hospitals,
health care practitioners' offices, clinics, and schools, cases of rubella
were not reported among vaccinated school-aged children.
The 49 viruses isolated in the United States distribute into 3 statistically
meaningful genotypic groups (Figure 2).
Group 1 include isolates from community outbreaks in late 1997 and 1998 in
New York and Connecticut,18 1 CRS case and
1 infection-only case in New York (the mother of the infection-only case was
exposed in Guyana), and cruise ship outbreaks in Florida in 1997. These isolates
are very similar to each other and to 2 viruses obtained from an outbreak
in 1997 in Manitoba and individual isolates from the English-speaking Caribbean
and Suriname. Outlying viruses in this group include 2 viruses from 2 US-born
infants with CRS whose mothers were exposed in the Philippines (CA/97) and
Venezuela (NY/98); both mothers were born outside the United States. Another
virus in group 1 (MA/98) was isolated from a case acquired in Ukraine. Two
older viruses, the current US rubella vaccine virus (RA/27/3; the parent of
this virus was isolated in Philadelphia, Pa, in 1964) as well as TH/US/64
(Therien strain isolated in Connecticut), a standard laboratory strain used
as the "outgroup" in construction of the tree, also appear on side branches
at the base of group 1. The 2 viruses that are very similar to the RA/27/3
vaccine strain (KS-a/98 and AR/99) were isolated from vaccinated persons who
developed a rash after receipt of measles-mumps-rubella vaccine as part of
outbreak control measures.
Viruses in group 2 include isolates from an outbreak in Kansas in 1998
(KS: 98), an outbreak in Nebraska in 1999 (NE-a/99 through NE-d/99, plus a
CRS case resulting from this outbreak, NE/00), and outbreaks and clusters
in North Carolina in both 1998 and 1999 (Chatham NC/98; Robeson NC-a/98 through
Robeson NC-c/98; Robeson NC/99; Union NC-a/99 and Union NC-b/99; Iredale NC/99).
Group 2 also includes several viruses from isolated CRS cases in Minnesota
(MN/98), South Carolina (SC/97), Arizona (AZ-a/96, AZ-b/96, and AZ-a/99),
California (CA/97), and Colorado (CO/99). Foreign viruses in group 2 include
2 viruses from Ecuador isolated in 1999 and a virus isolated from a CRS case
in Mexico (Mexico/97); additionally, the MN/98 virus was from a CRS case whose
mother contracted rubella during pregnancy in Veracruz, Mexico.
Group 3 contains viruses from cluster in North Carolina (Wake NC/99),
2 cluster/outbreaks in Texas (TX-a/98 through TX-b/98 were from the 1997-1998
Immigration and Naturalization Service outbreak, while TX-d/98 was associated
with a different cluster), and 1 isolate from Arizona. Two viruses from the
1990 Los Angeles, Calif, outbreak are at the base of this group, indicating
that these viruses are progenitors of current group 3 viruses and that evolution
has occurred during the intervening period.
Viruses from all 3 genotypic groups were involved in clusters and outbreaks.
We were successful in isolating multiple viruses from 5 clusters/outbreaks
(New York–Connecticut, 1998, 8 isolates; Robeson County, North Carolina,
1998, 3 isolates; Union County, North Carolina, 1999, 2 isolates; Nebraska,
1999, 5 isolates; and the INS outbreak in Texas, 1997-1998, 2 isolates). In
all of these cases, the viruses isolated from a single cluster/outbreak were
genetically similar if not identical. Among the clusters/outbreaks, 1 pair
of geographically isolated clusters/outbreaks was caused by identical viruses
(Kansas and Chatham County, NC, in 1998) and the Robeson County cluster in
1998 and Union County outbreak in 1999 were caused by closely related viruses.
However, in general, clusters and outbreaks were caused by dissimilar viruses;
for example, the virus from the 1999 Robeson County cluster was more distant
to the 1998 Robeson County virus than was the 1999 Union County virus. Similarly,
independent clusters/outbreaks in 4 counties in North Carolina in 1999 (Union,
Robeson, Iredale, and Wake) were caused by 3 distantly related group 2 viruses
and 1 group 3 virus. Interestingly, some of the viruses from clusters/outbreaks
were most closely related to viruses from isolated CRS cases; for example,
the Iredale NC/99 and MA/00 viruses were very similar to the CO/99 CRS virus,
and the Robeson NC/99 cluster virus was most closely related to 3 CRS viruses
(AZ-a/96, AZ-b/96, and SC/98).
After the rubella resurgence in 1990-1991, the number of reported rubella
cases continued to decline, as had occurred in the 1970s and 1980s.19,20 However, since the beginning of the
1990s, the demographics of the rubella and CRS cases and the characteristics
of the outbreaks have changed significantly. Rubella now occurs mainly among
foreign-born Hispanic adults who are either unvaccinated or whose vaccination
status is unknown, with very limited spread and circulation among the US resident
population. These changes and data from the molecular typing of viruses from
rubella and CRS cases suggest that the United States is on the verge of elimination
of indigenous rubella and CRS. However, rubella cases continue to occur in
the United States, and the threat of CRS remains, particularly among women
of childbearing age who were born outside the United States. Therefore, control
efforts now must focus on at-risk populations such as foreign-born adults.
The most important change in the epidemiology of rubella in the United
States is that most cases now occur among Hispanics, particularly those born
in countries where rubella vaccination programs do not exist or were recently
implemented. This trend also has been identified in infants with CRS whose
mothers were born outside the United States. In the California outbreak in
1990, one of the risk factors for infants with CRS was to have a mother who
Both US-born and foreign-born individuals with rubella were more likely
to be unvaccinated or have unknown vaccination status. Among the foreign-born
persons vaccinated, usually as part of outbreak control measures, many were
vaccinated within 2 weeks prior to rash onset. This finding demonstrates failure
to vaccinate, not vaccine failure or waning immunity, to be the reason for
rubella continuing in the United States. Additionally, mothers of infants
with CRS were also more likely not to have been vaccinated.
In the late 1990s, as previously described in the late 1970s and 1980s,
outbreaks continued to occur in settings where adults congregated,21- 26
but outbreaks occur primarily among foreign-born persons. Even though certain
US populations (eg, inner city) may be undervaccinated, the lack of outbreaks
in these populations suggests that surrounding herd immunity may have a protective
effect. In the outbreak areas, limited spread to the unvaccinated US population
demonstrates that the US program has been successful and that vaccine failure
and waning immunity are not factors for rubella occurring in the United States.
Molecular typing, which provides important data on the origin of viruses
from cases and outbreaks, identified 3 different groups from the 1990s. Group
1 viruses, which were isolated from 3 outbreaks (Westchester, NY, Fairfield,
Conn, and a Florida cruise ship), exhibited little internal diversity. This
finding suggests that a single source seeded these outbreaks. Most likely,
this source came from the Caribbean because of the close relationship of this
group with viruses from the Bahamas, Suriname, and Venezuela.
In groups 2 and 3, cases within clusters/outbreaks again do not exhibit
high sequence diversity, which suggests that a unique source seeded each cluster/outbreak.
However, viruses from different clusters/outbreaks were often diverse, indicating
independent seeding of each of these outbreaks rather than endemic activity.
For example, viruses from 4 cluster/outbreaks in North Carolina in 1999 (Union-a/99
and Union-b/99, Robeson/99, Iredale/99, and Wake/99) were diverse, indicating
independent seeding of each of these outbreaks rather than endemic activity.
However, viruses from 21 998 clusters in North Carolina (Chatham/98 and
Robeson-a/98, Robeson-b/98, and Robeson-c/98) were similar; thus, they could
have been seeded by a single source. These 2 clusters may reflect endemic
circulation, but they may also reflect multiple introductions of a single
Conversely, within groups 2 and 3, there are several examples of similar
viruses isolated from widely geographically separated cases (Iredale NC/99,
CO/99, and MA/00), much like the group 1 pattern. This situation is consistent
with multiple introductions of a single virus. Based on the inclusion of 1
virus from Mexico (Mexico/97) and 2 from Ecuador (Ecuador-a/99 and Ecuador-b/99)
in group 2 and the Mexican origin of the mothers of several CRS cases (MN/98,
SC/98, AZ-a/96, AZ-b/96, AZ/99, and NE/00), group 2 appears to have come from
Latin America. Considering that routine vaccination began in the late 1990s
in these countries, it appears that groups 2 and 3 indicate the endemic transmission
that occurs in neighboring countries, which is reflected in cases that occur
in the United States as a result of multiple or continuous import of viruses.
It is anticipated that the number of group 2 viruses found in the United States
When a random sample of viruses isolated in the 1990s were analyzed
along with viruses from the 1960s and 1970s, the resulting phylogenetic tree
revealed that viruses isolated earlier are more similar to one another than
they are to viruses isolated in the 1990s. This distant relationship between
viruses from the 1990s and those available from the 1960s and 1970s provides
no evidence for endemic circulation of prevaccine viruses in the United States.
Before vaccination began in the United States, viruses similar to those in
the United States circulated in Europe and Japan. After the institution of
vaccination programs in these countries, distinct genotypes evolved in the
United States, Europe, and Japan. A similar pattern is likely to develop in
many countries in the Western Hemisphere as vaccination programs are established.
A limitation of our interpretations is the uncertain completeness of
case ascertainment. Even though states have enhanced surveillance for rubella
during the last 5 years, identification of cases is challenging because 20%
to 50% of rubella cases are mild or asymptomatic. The pattern of viruses from
molecular typing for the last 3 to 4 years is consistent with seeding from
external sources, however, additional data from viruses occurring in the United
States and other countries, particularly in the Western Hemisphere, are needed
to substantiate this interpretation.
The primary goal of a rubella vaccination program is to eliminate congenital
rubella infections. Ensuring immunity among women of childbearing age is critical.
In the United States, in addition to childhood vaccination, prenatal rubella
testing and postpartum vaccination will prevent some of the CRS cases; however,
not all CRS cases can be prevented because less than half of the mothers have
had previous pregnancies.
Some states are exploring strategies for controlling rubella in at-risk
populations, including forming partnerships with employers to offer vaccination
to employees and offering vaccination to at-risk women through the Special
Supplemental Program for Women, Infants, and Children, which reaches approximately
40% of US mothers of neonates each year. A major challenge to the workplace
approach is a high turnover rate among industries that currently employ at-risk
Rubella and CRS cases that occur in the United States demand attention
both nationally and regionally. As of January 2001, 44 of the 47 countries
in the Americas (excluding the Dominican Republic, Peru, and Guatemala) have
implemented childhood rubella vaccination programs.27
However, most of these programs have been ongoing for fewer than 3 years.
The current epidemiology in the United States demonstrates the effectiveness
of a successful rubella vaccination program. If all countries in the Western
Hemisphere achieve and maintain high childhood immunization coverage and ensure
immunity in women of childbearing age, the goal of eliminating indigenous
transmission is achievable.