The ever-changing landscape of rotavirus serotypes.
ABSTRACT Rotavirus is a double-stranded RNA virus that is characterized by substantial genetic diversity. The various serotypes of rotavirus have been determined by the presence of neutralizing epitopes on the outer capsid of the protein shell. At present, 5 rotavirus serotypes (G1, G2, G3, G4, G9) are the predominant circulating strains, accounting for approximately 95% of strains worldwide, although there is considerable geographic variability. Incidence rates for various serotypes also vary temporally with seasonal and year-to-year fluctuations. Unusual serotypes are generally uncommon, but new serotypes can emerge. In particular, G9[P8], a reassortment virus, was first identified in 1983 and in the last 10 to 15 years has become widely distributed worldwide. Indeed, G9[P8] has become highly prevalent in many countries in Europe and Australia, with somewhat lower incidence rates in South America, Africa, and Asia. The heterogeneity and ever-changing epidemiology of rotavirus underscores the need for continued surveillance to ensure that vaccination programs provide optimal protection.
Article: Rotavirus vaccines: an overview.[show abstract] [hide abstract]
ABSTRACT: Rotavirus infection is the most common cause of severe diarrhea disease in infants and young children worldwide and continues to have a major global impact on childhood morbidity and mortality. Vaccination is the only control measure likely to have a significant impact on the incidence of severe dehydrating rotavirus disease. In 1999, a highly efficacious rotavirus vaccine licensed in the United States, RotaShield, was withdrawn from the market after 14 months because of its association with intussusception. Two new live, oral, attenuated rotavirus vaccines were licensed in 2006: the pentavalent bovine-human reassortant vaccine (RotaTeq) and the monovalent human rotavirus vaccine (Rotarix). Both vaccines have demonstrated very good safety and efficacy profiles in large clinical trials in western industrialized countries and in Latin America. Careful surveillance has not revealed any increased risk of intussusception in the vaccinated groups with either vaccine. The new rotavirus vaccines are now introduced for routine use in a number of industrialized and developing countries. These new safe and effective rotavirus vaccines offer the best hope of reducing the toll of acute rotavirus gastroenteritis in both developed and developing countries.Clinical microbiology reviews 02/2008; 21(1):198-208. · 14.69 Impact Factor
Article: Prevention of rotavirus gastroenteritis among infants and children: recommendations of the Advisory Committee on Immunization Practices (ACIP).[show abstract] [hide abstract]
ABSTRACT: Rotavirus is the most common cause of severe gastroenteritis in infants and young children worldwide. Before initiation of the rotavirus vaccination program in the United States in 2006, approximately 80% of U.S. children had rotavirus gastroenteritis by age 5 years. Each year during the 1990s and early 2000s, rotavirus resulted in approximately 410,000 physician visits, 205,000272,000 emergency department visits, and 55,00070,000 hospitalizations among U.S. infants and children, with total annual direct and indirect costs of approximately $1 billion. In February 2006, a live, oral, human-bovine reassortant rotavirus vaccine (RotaTeq(R) [RV5]) was licensed as a 3-dose series for use among U.S. infants for the prevention of rotavirus gastroenteritis, and the Advisory Committee on Immunization Practices (ACIP) recommended routine use of RV5 among U.S. infants (CDC. Prevention of rotavirus gastroenteritis among infants and children: recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR 2006;55[No. RR-12]). In April 2008, a live, oral, human attenuated rotavirus vaccine (Rotarix(R) [RV1]) was licensed as a 2-dose series for use among U.S. infants, and in June 2008, ACIP updated its rotavirus vaccine recommendations to include use of RV1. This report updates and replaces the 2006 ACIP statement for prevention of rotavirus gastroenteritis. ACIP recommends routine vaccination of U.S. infants with rotavirus vaccine. RV5 and RV1 differ in composition and schedule of administration. RV5 is to be administered orally in a 3-dose series, with doses administered at ages 2, 4, and 6 months. RV1 is to be administered orally in a 2-dose series, with doses administered at ages 2 and 4 months. ACIP does not express a preference for either RV5 or RV1. The recommendations in this report also address the maximum ages for doses, contraindications, precautions, and special situations for the administration of rotavirus vaccine.MMWR. Recommendations and reports: Morbidity and mortality weekly report. Recommendations and reports / Centers for Disease Control 03/2009; 58(RR-2):1-25.
Article: Global distribution of rotavirus serotypes/genotypes and its implication for the development and implementation of an effective rotavirus vaccine.[show abstract] [hide abstract]
ABSTRACT: A safe and effective rotavirus vaccine is urgently needed, particularly in developing countries. Critical to vaccine development and implementation is a knowledge base concerning the epidemiology of rotavirus G and P serotypes/genotypes throughout the world. The temporal and geographical distribution of human rotavirus G and P types was reviewed by analysing a total of 45571 strains collected globally from 124 studies reported from 52 countries on five continents published between 1989 and 2004. Four common G types (G1, G2, G3 and G4) in conjunction with P or P represented over 88% of the strains analysed worldwide. In addition, serotype G9 viruses associated with P or P were shown to have emerged as the fourth globally important G type with the relative frequency of 4.1%. When the global G and/or P type distributions were divided into five continents/subcontinents, several characteristic features emerged. For example, the PG1 represented over 70% of rotavirus infections in North America, Europe and Australia, but only about 30% of the infections in South America and Asia, and 23% in Africa. In addition, in Africa (i) the relative frequency of G8 was as high as that of the globally common G3 or G4, (ii) P represented almost one-third of all P types identified and (iii) 27% of the infections were associated with rotavirus strains bearing unusual combinations such as PG8 or PG8. Furthermore, in South America, uncommon G5 virus appeared to increase its epidemiological importance among children with diarrhea. Such findings have (i) confirmed the importance of continued active rotavirus strain surveillance in a variety of geographical settings and (ii) provided important considerations for the development and implementation of an effective rotavirus vaccine (e.g. a geographical P-G type adjustment in the formulation of next generation multivalent vaccines).Reviews in Medical Virology 15(1):29-56. · 7.20 Impact Factor
The Ever-Changing Landscape of Rotavirus Serotypes
Miguel O’Ryan, MD
Abstract: Rotavirus is a double-stranded RNA virus that is characterized
by substantial genetic diversity. The various serotypes of rotavirus have
been determined by the presence of neutralizing epitopes on the outer
capsid of the protein shell. At present, 5 rotavirus serotypes (G1, G2, G3,
G4, G9) are the predominant circulating strains, accounting for approxi-
mately 95% of strains worldwide, although there is considerable geo-
graphic variability. Incidence rates for various serotypes also vary tempo-
rally with seasonal and year-to-year fluctuations. Unusual serotypes are
generally uncommon, but new serotypes can emerge. In particular, G9?P8?,
a reassortment virus, was first identified in 1983 and in the last 10 to 15
years has become widely distributed worldwide. Indeed, G9?P8? has
become highly prevalent in many countries in Europe and Australia, with
somewhat lower incidence rates in South America, Africa, and Asia. The
heterogeneity and ever-changing epidemiology of rotavirus underscores
the need for continued surveillance to ensure that vaccination programs
provide optimal protection.
Key Words: rotavirus, gastroenteritis, serotype, ribose nucleic acid
(Pediatr Infect Dis J 2009;28: S60–S62)
capsid, (2) an inner capsid, and (3) an internal core that surrounds
segments of double-stranded RNA.2There are 7 rotavirus groups
(A through G) that are determined by the antigenic specificities of
proteins encased in the triple-layer capsid.1Of these, Group A is
responsible for most endemic human disease.3There are also various
subgroups and serotypes with serotyping based on the presence of
neutralizing epitopes on outer capsid proteins (ie, VP4 and VP7).3
VP4 is designated as the P antigenic protein because it is cleaved by
the protease trypsin at the intestinal level and VP7 is designated as the
G antigenic protein because it is a glycosylated structure.2,3These
proteins have been considered relevant for the development of a
rotavirus vaccine because in vitro and animal-based studies indi-
cate that they are targets for neutralizing antibodies that provide
serotype-specific and, in some cases, cross-reactive protection.2
otavirus is a double-stranded RNA virus from the Reoviridae
family.1The virus is composed of 3 protein shells: (1) an outer
EPIDEMIOLOGY OF COMMON CIRCULATING
Rotaviruses are characterized by substantial diversity; there
are at least 42 different G/P strains with different serotype com-
binations.2However, 5 serotypes (G1?P8?, G2?P4?, G3?P8?,
G4?P8?, and G9?P8?) are the predominant circulating rotavirus G/P
serotypes.2,4,5However, there is substantial temporal and geo-
graphic variability in the epidemiology of rotavirus serotypes, and
multiple serotypes can cocirculate within the same region.2,5
Serotypes can also vary in different regions, even within the same
country. Further, the incidence of serotypes can fluctuate from year
to year within the same region. For example, Clark et al6followed
the prevalence of rotavirus strains in Philadelphia between 1994
and 1999. As shown in Figure 1,6the predominant circulating
strain varied significantly over the 5 seasons. In 1994 to 1995,
G3?P8? strains predominated. G9?P8? comprised more than 50% of
cases during a G9 outbreak in the 1995 to 1996 rotavirus season.
In 1996 to 1997 and 1997 to 1998 most disease was caused by
G1?P8?, and in 1998 to 1999 G1?P8? and G2?P4? were each
responsible for approximately 50% of infections.6
Rotavirus also exhibits a distinct seasonality, particularly in
temperate climates. In the United States, activity usually peaks in
the Southwest in November/December, spreading north and east
and reaching the northeastern states by April and May.4,7Figure 2
summarizes the distribution of rotavirus serotypes according to
continents during a prolonged surveillance period of approxi-
mately 15 years.5The distribution describes the global distribution
of human group A rotavirus G and P types from 1989 through
2004, based on the results of 124 studies from 52 countries.
Although the 5 most common rotavirus serotypes (G1–G4 and G9)
were responsible for approximately 95% of infections worldwide,
there are substantial geographic differences. For example, G1?P8?
was responsible for more than 70% of infections in North America,
Australia, and Europe but ?30% of infections in South America,
Asia, and Africa. G2?P4? was common in South America (23%)
and Asia (13%), whereas G3?P8? was common in Africa (21%).5
Unusual serotypes rise and fall in many parts of the world
during limited time periods, but because trends could change, they
require continued monitoring. Overall, strains that are considered
unusual represent only 4.9% of isolates.5These unusual P–G combi-
nations likely represent naturally occurring reassortments of the var-
ious human rotavirus genotypes, reassortments between human and
animal strains, or direct transmission from animals to human. Nota-
bly, unusual serotypes were more common in Africa (27%), Asia
(14%), and South America (11%) compared with North America,
Europe, and Australia (5%, 1.4%, 0.1%, respectively). For example,
G8 strains—mainly G8?P4? and G8?P6?—have been increasingly
reported in Africa since the mid-1990s, accounting for approxi-
mately 13% of infections. However, to date, these strains have
rarely been reported outside of Africa. Similarly, G5?P8? has
been reported almost exclusively in South America.5G12
strains with both P8 and P6 VP4 antigenicity are being increas-
ingly recognized worldwide, including in the United States.8
The relatively high frequency of unusual serotypes in some
geographic regions suggests that these serotypes may have genetic
they will sustain in a given population over time—indicating that they
are fit for human intestinal cell receptors—requires further monitor-
ing. In addition, most epidemiologic surveys have noted the occur-
rence of nontypeable rotavirus strains. This is likely due to the ability
of the virus to undergo constant genetic variation via sequential point
mutations (ie, antigenic drift), genetic reassortment (ie, antigenic
From the Institute of Biomedical Sciences, Faculty of Medicine, University of
Chile, Santiago, Chile.
Disclosure: Dr. O’Ryan has received honorarium and grant support from
GlaxoSmithKline, and consultant fees from Merck.
Address for correspondence: Miguel O’Ryan, MD, Institute of Biomedical
Sciences, Faculty of Medicine, University of Chile, Avda Independencia
1027, Santiago, Chile. E-mail: firstname.lastname@example.org.
Copyright © 2009 by Lippincott Williams & Wilkins
The Pediatric Infectious Disease Journal • Volume 28, Number 3, March 2009
shift), genomic rearrangement, or intragenic recombination. The in-
cidence rate of nontypeable strains in various surveys is dependent on
the type of assay used with the use of enzyme immunoassay generally
associated with higher rates of nontypeable strains compared with
studies that use reverse transcription polymerase chain reaction (RT-
PCR) assays. Nevertheless, even studies that use enzyme immunoas-
say, RT-PCR, and probe hybridization in combination report rates of
8% to 27% for nontypeable strains. Again, if these strains will prevail
in a given population, it will depend on their capacity to adapt to
human intestinal cell receptors.5
THE EMERGING G9 SEROTYPE
The G9 strain, usually in combination with P8 or P6, is
the only “new” serotype that has gained epidemiological rele-
vance in the past years. G9 as a cause of diarrhea was first
identified in Philadelphia, Pennsylvania, in 1983 and was rela-
tively rare until the last 10 to 15 years.6,9,10The G9 serotype
has subsequently become ubiquitous in the United States and
other countries and is now the fourth most common strain
worldwide, accounting for 4.1% of infections.5,6G9 strains
have been documented in a number of epidemiologic studies
conducted in the past 10 years. G9 has been identified in
Bulgaria,22Slovenia,23Italy,24,25North America,26South Amer-
ica,27,28Africa,29,30Saudi Arabia,31and Asia.10,32Rates of G9 in
any given year can fluctuate widely.6,11–16,33This is illustrated in
Table 1,11–16,34,35which presents rates reported in Australia, a coun-
FIGURE 1. Prevalence of rotavirus strains in Philadelphia from 1995 to 1999. Reprinted with permission.6
FIGURE 2. Geographical distribution of rotavirus serotypes. Reprinted with permission.5
The Pediatric Infectious Disease Journal • Volume 28, Number 3, March 2009Varying Epidemiology of Rotavirus Serotypes
© 2009 Lippincott Williams & Wilkins
SUMMARY AND CONCLUSIONS
Rotavirus is a common gastrointestinal pathogen that pro-
duces considerable morbidity and mortality. Currently, 5 serotypes
(G1–G4, G9) predominate, accounting for almost 95% of strains
worldwide. Circulating strains vary both regionally and tempo-
rally, with substantial year-to-year, seasonal, and geographic vari-
ability. In addition, reassortments of the various human rotavirus
genotypes can potentially allow new serotypes to emerge, although
new serotypes would have to be fit for human intestinal receptors
to prevail over time. The ever-changing epidemiology of rotavirus
may represent a substantial challenge to the development of
effective vaccines. This emphasizes the need for long-term rota-
virus surveillance to judge effectiveness of vaccines on circulating
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Serotypes in Australia From 1999 to 200711–16,34,35
Nationwide Incidence of Rotavirus
G1 G2G3 G4G9
*Percentages do not equal 100% because some serotypes could not be assigned and
some were mixed reactions.
The Pediatric Infectious Disease Journal • Volume 28, Number 3, March 2009
© 2009 Lippincott Williams & Wilkins