Rotavirus

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Rotavirus

● Reovirus (RNA)

● VP7 and VP4 proteins define

virus serotype and induce

neutralizing antibody

● G1 and G12 strains account for

most infections

● Very stable and may remain

viable for weeks or months if

not disinfected

Diarrheal disease has been recognized in humans since 

antiquity. Until the early 1970s, a bacterial, viral, or parasitic 

etiology of diarrheal disease in children could be detected in 

fewer than 30% of cases. In 1973, Ruth Bishop and colleagues 

observed a virus particle in the intestinal tissue of children 

with diarrhea by using electron micrography. This virus was 

subsequently called “rotavirus” because of its similarity in 

appearance to a wheel (rota is Latin for wheel). By 1980, 

rotavirus was recognized as the most common cause of severe 

gastroenteritis in infants and young children in the United 

States. In the prevaccine era, the majority of children were 

infected by age 5 years, and rotavirus was responsible for up to 

500,000 deaths among children annually worldwide. A vaccine 

to prevent rotavirus gastroenteritis was first licensed in the 

United States in 1998 but was withdrawn in 1999 because of 

its association with intussusception, a type of bowel blockage 

when the bowel folds into itself like a telescope. Secondgeneration vaccines were licensed in the United States in 

2006 and 2008.

Rotavirus

Rotavirus is a double-stranded RNA virus of the family 

Reoviridae. The virus is composed of three concentric shells that 

enclose 11 gene segments. The outermost shell contains two 

important proteins: VP7, or G-protein, and VP4, or P-protein. 

VP7 and VP4 induce neutralizing antibodies that are believed 

to be involved in immune protection. From 1996 through 2005, 

five genotypes of rotavirus (G1P[8], G2P[4], G3P[8], G4P[8] and 

G9P[8]) accounted for 90% of strains isolated from children 

younger than age 5 years in the United States. Of these, 

genotype G1P[8] accounted for more than 75% of strains. In the 

recent past, G12P[8] has become the most common genotype 

identified in the United States. 

Rotavirus is very stable and may remain viable in the 

environment for weeks or months if disinfection does not occur.

Pathogenesis

The virus enters the body through the mouth. Viral replication 

occurs in the villous epithelium of the small intestine. Up to 

two-thirds of children with severe rotavirus gastroenteritis show 

the presence of rotavirus antigen in serum (antigenemia) and 

children can have rotavirus RNA detected in serum. 

Infection may result in decreased intestinal absorption of 

sodium, glucose, and water, and decreased levels of intestinal 

lactase, alkaline phosphatase, and sucrase activity, and may lead 

to isotonic diarrhea.

Margaret M. Cortese, MD and Penina Haber, MPH

Rotavirus

● First identified as cause

of diarrhea in 1973

● Most common cause of

severe gastroenteritis in infants

and children*

● Nearly universal infection

by age 5 years*

● Responsible for up to

500,000 diarrheal deaths

each year worldwide*

*Prevaccine era

https://www.cdc.gov/vaccines/pubs/pinkbook/rota.html Aug 2021
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The immune correlates of protection from rotavirus are not 

fully understood. Serum and mucosal antibodies against VP7 

and VP4 are probably important for protection from disease. 

Cell-mediated immunity probably plays a role in protection and 

in recovery from infection.

Recovery from a first rotavirus infection usually does not 

lead to permanent immunity. Reinfection can occur at any 

age. A cohort study in Mexico found that after a single 

natural infection, 38% of children were protected against any 

subsequent rotavirus infection, 77% were protected against 

rotavirus diarrhea, and 87% were protected against severe 

diarrhea. Subsequent infections conferred progressively greater 

protection and were generally less severe than the first. 

Clinical Features

The incubation period for rotavirus diarrhea is short, usually 

less than 48 hours. The clinical manifestations of infection vary 

and depend on whether it is the first infection or reinfection. 

Infection may be asymptomatic, may cause self-limited watery 

diarrhea, or may result in severe dehydrating diarrhea with fever 

and vomiting. Up to one-third of infected children may have a 

temperature greater than 39°C (102°F). The first infection after 3 

months of age is generally the most severe. The gastrointestinal 

symptoms generally resolve in 3 to 7 days.

Infants younger than age 3 months have relatively low rates 

of rotavirus infection, probably because of passive maternal 

antibody, and possibly because of breastfeeding. Rotavirus 

infection of adults is usually asymptomatic but may cause 

diarrheal illness.

The clinical features and stool characteristics of rotavirus 

diarrhea are nonspecific, and similar illness may be caused by 

other pathogens. As a result, confirmation of a diarrheal illness 

as rotavirus requires laboratory testing.

Complications

Rotavirus infection in infants and young children can lead 

to severe diarrhea, dehydration, electrolyte imbalance, 

and metabolic acidosis. Treatment is supportive; feeding 

should be continued during the illness. Children who are 

immunocompromised because of congenital immunodeficiency 

or because of bone marrow or solid organ transplantation may 

experience severe or prolonged rotavirus gastroenteritis and 

may have evidence of resulting abnormalities in multiple organ 

systems, particularly the kidney and liver.

Rotavirus Pathogenesis

● Entry through mouth

● Replication in epithelium of

small intestine

● In severe infections – rotavirus

antigen detectable in serum

● Infection leads to isotonic

diarrhea

Rotavirus Complications

● Severe diarrhea

● Dehydration

● Electrolyte imbalance

● Metabolic acidosis

● Children who are

immunocompromised

may have more severe or

persistent disease

Rotavirus Clinical Features

● Short incubation period (usually

less than 48 hours)

● May be asymptomatic or result

in severe dehydrating diarrhea

with fever and vomiting

● First infection after age 3

months generally most severe

● Gastrointestinal symptoms

generally resolve in 3 to 7 days
Rotavirus

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Laboratory Testing

Several commercial test kits are available for testing stool 

samples that detect a rotavirus antigen (VP6) common to 

human rotaviruses by enzyme linked immunoassay (EIA). These 

kits are simple to use, inexpensive, and very sensitive. With the 

marked reduction in rotavirus disease in children in the United 

States due to rotavirus vaccination, the positive predictive value 

of EIA is expected to be lower (and the negative predictive 

value to be higher) compared with that from the prevaccine era. 

Multi-pathogen polymerase chain reaction (PCR)-based assays 

for stool samples that include the ability to detect rotavirus RNA 

are being increasingly used in clinical laboratories. The clinical 

interpretation of results from these very sensitive assays may 

be challenging because detection of nucleic acid of rotavirus or 

other pathogens in stool may indicate a previous infection and 

not necessarily the cause of a current illness. Sequence analysis 

and viral culture are available in research laboratories. 

Epidemiology

Occurrence

Rotavirus occurs throughout the world. In the prevaccine era, 

the proportion of severe diarrhea in children younger than age 

5 years that was due to rotavirus was similar (about 35% to 

40%) in developed and developing countries, suggesting that 

improved sanitation alone is not sufficient to prevent infection. 

The distribution of specific rotavirus genotypes can differ by 

geographic area and time period. 

Reservoir

The reservoir of rotavirus is the gastrointestinal tract and stool 

of infected humans. Although rotavirus infection occurs in many 

nonhuman mammals, transmission of animal rotaviruses to 

humans is believed to be uncommon and probably does not 

lead to clinical illness. These animal strains are antigenically 

distinct from those causing human infection, and they rarely 

cause infection in humans. Although immunocompromised 

persons may shed rotavirus for a prolonged period, a true carrier 

state has not been described.

Transmission

Rotaviruses are shed in high concentration in the stool of 

infected persons. Transmission is by fecal-oral route, both 

through close person-to-person contact and by fomites (such as 

toys and other environmental surfaces contaminated by stool). 

Transmission of rotavirus through contaminated water or food 

appears to be uncommon. 

Rotavirus Epidemiology

● Reservoir

■ Human-GI tract and stool

● Transmission

■ Fecal-oral, person-to-person 

and fomites

● Temporal pattern

■ Fall and winter (temperate 

areas)

● Communicability

■ 2 days before onset 

of diarrhea
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Temporal Pattern

In temperate climates, disease is more prevalent during fall 

and winter. In the United States in the prevaccine era, annual 

epidemic peaks usually progressed from the Southwest during 

November and December to the Northeast by April and May. 

Following vaccine introduction, a biennial pattern of disease 

activity has emerged with less notable differences in timing 

by geographic region. In tropical climates, the disease is less 

seasonal than in temperate areas. 

Communicability

Rotavirus is highly communicable, as evidenced by the nearly 

universal infection of children by age 5 years in the prevaccine 

era. Infected persons shed large quantities of virus in their stool 

beginning 2 days before the onset of diarrhea and for several 

days after the onset of symptoms. Rotavirus may be detected 

in the stool of immunocompromised persons for more than 

30 days after infection. Spread is common within families, 

institutions, hospitals, and child care settings.

Secular Trends in the United States

In the prevaccine era, an estimated 2.7 million rotavirus 

infections occurred every year in the United States and 95% of 

children experienced at least one rotavirus infection by age 5 

years. Rotavirus infection was responsible for 410,000 physician 

visits, more than 200,000 emergency department visits, 55,000 

to 70,000 hospitalizations, and 20 to 60 deaths annually in 

children younger than age 5 years. Rotavirus accounted for 30% 

to 50% of all hospitalizations for gastroenteritis among children 

younger than age 5 years; the incidence of clinical illness was 

highest among children age 3 to 35 months. 

Rotavirus activity has been monitored through data on routine 

testing for rotavirus performed at a set of clinical laboratories 

across the country. A biennial pattern of rotavirus activity 

emerged after vaccine introduction, with odd numbered years 

having small, short seasons starting in late winter or early 

spring and even numbered years having extremely low levels of 

circulation without a defined season.

The marked reduction in rotavirus disease burden in the 

United States following the introduction of rotavirus vaccine 

in 2006 has been documented by data on hospitalizations 

and emergency department care for diarrhea among young 

children. An evaluation of claims data of commercially 

insured children estimated that an average annual 280,000 

clinic visits, 62,000 emergency department visits, and 45,000 

hospitalizations for rotavirus disease were averted among U.S. 

children younger than age 5 years during 2007–2011 by routine 

vaccination. Indirect protection to previously uninfected and 

Rotavirus Secular Trends 

in the United States

Prevaccine era:

● Estimated 2.7 million cases 

per year

● 95% of children infected by 

5 years of age

Following the introduction of 

rotavirus vaccine:

● Annually averted:

■ 280,000 clinic visits

■ 62,000 emergency 

department visits

■ 45,000 hospitalizations
Rotavirus

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unimmunized children, as well as to some adults, has been 

described, illustrating the important role that infants play as 

drivers of rotavirus infection. 

Rotavirus vaccination coverage among U.S. children continues 

to be lower than coverage for other vaccines administered 

during infancy, in part due to the narrow age restrictions for 

the doses and particularly the age restriction for completing 

the series. Among children born during 2015–2016, 73.6% 

completed the rotavirus vaccine series by age 8 months, the 

maximum age for the final dose. 

Rotavirus Vaccines

In 1998, a rhesus-based tetravalent rotavirus vaccine (RRV-TV 

[Rotashield]) was licensed and recommended for use in 

the United States. However, RRV-TV vaccine was withdrawn 

from the U.S. market within 1 year of its introduction after 

post-marketing surveillance detected an association with 

intussusception. The risk of intussusception was most elevated 

within 3 to 14 days after receipt of the first dose, with a 

smaller increase in risk within 3 to 14 days after the second 

dose. Overall, the risk associated with the first dose of RRV-TV 

vaccine was estimated to be about one case per 10,000 

vaccine recipients. 

Two live, oral rotavirus vaccines are currently licensed for use, 

RV5 (RotaTeq) and RV1 (Rotarix) vaccines. 

Characteristics

RV5 vaccine contains approximately 2 x 106 infectious units of 

each of the five reassortant strains developed from human and 

bovine rotavirus strains. RV1 vaccine contains one strain of live, 

attenuated human strain 89-12 (type G1P1A[8]) rotavirus. Each 

dose contains at least 106 median cell culture infective units of 

virus. RV1 and RV5 vaccines are administered orally. RV5 and 

RV1 vaccines contain no adjuvant, antibiotic, or preservative. 

The RV1 vaccine oral applicator contains latex rubber.

Vaccination Schedule and Use

Rotavirus vaccine is routinely recommended for infants. The 

vaccine should be administered orally as a series of either two 

doses (at age 2 and 4 months) for RV1 vaccine or three doses 

(at age 2, 4, and 6 months) for RV5 vaccine. The vaccination 

series for both vaccines may be started as early as age 6 weeks. 

The minimum interval between doses is 4 weeks. 

The Advisory Committee on Immunization Practices (ACIP) 

developed age recommendations that vary from those of the 

manufacturers. ACIP recommendations state that the maximum 

age for the first dose of each vaccine is 14 weeks 6 days. The 

minimum interval between doses of both rotavirus vaccines 

Rotavirus Vaccination Schedule

● Routine vaccination 

of all infants without a 

contraindication

● 2-dose series for RV1 vaccine 

(at age 2 and 4 months)

● 3-dose series for RV5 vaccine 

(at age 2, 4, and 6 months)

● For both rotavirus vaccines

■ May be started as early as 

age 6 weeks

■ Maximum age for first dose is 

14 weeks 6 days*

■ Minimum interval between 

doses is 4 weeks

■ Maximum age for any dose is 

8 months 0 days*

● ACIP did not define a maximum 

interval between doses

● No rotavirus vaccine should be 

administered to infants older 

than 8 months 0 days*

*Off-label use 

Rotavirus Vaccines

● RV5 (RotaTeq)

● RV1 (Rotarix)

Rotavirus Vaccine Characteristics

● RV5 (RotaTeq)

■ Contains five reassortant 

strains developed from 

human and bovine parent 

rotavirus strains

■ Administered orally

● RV1 (Rotarix)

■ Contains one strain of live 

attenuated human rotavirus 

(type G1PA[8])

■ Administered orally

■ Oral applicator contains 

latex rubber
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Rotavirus

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is 4 weeks. The maximum age for any dose of either rotavirus 

vaccine is 8 months 0 days. No rotavirus vaccine should be 

administered to infants older than 8 months 0 days of age. This 

is an off-label recommendation for both vaccines, because the 

labeled maximum age for RV1 vaccine is 24 weeks, and the 

labeled maximum age for RV5 vaccine is 32 weeks.

If any dose in the series was RV5 vaccine or the vaccine brand 

used for any prior dose in the series is not known, a total of 

three doses of rotavirus vaccine should be administered.

Rotavirus vaccine should be given at the same visit as other 

recommended vaccines.

ACIP considers the benefits of rotavirus vaccination of preterm 

infants to outweigh the risks of adverse events. ACIP supports 

vaccination of a preterm infant according to the same schedule 

and precautions as a full-term infant, provided the following 

conditions are met: the infant’s chronological age is at least 

6 weeks, the infant is clinically stable, and the vaccine is 

administered at the time of discharge or after discharge from 

the neonatal intensive care unit or nursery. The American 

Academy of Pediatrics will be providing updated guidance 

on administering vaccine to hospitalized infants in early 2021 

through the Red Book. 

Breastfeeding does not appear to diminish immune response 

to rotavirus vaccine. Infants who are being breastfed should be 

vaccinated on schedule.

Infants documented to have had rotavirus gastroenteritis before 

receiving the full course of rotavirus vaccination should still 

begin or complete the 2- or 3-dose series following the age 

recommendations, as the initial infection may provide only 

partial protection against subsequent rotavirus disease.

Immunogenicity and Vaccine Efficacy

Phase III clinical efficacy trials of RV5 vaccine were conducted 

in Finland and United States. The efficacy of the 3-dose series 

against G1-G4 rotavirus gastroenteritis of any severity was 74%, 

and against severe G1-G4 rotavirus gastroenteritis was 98% 

during the first full rotavirus season after vaccination. In a large 

health care utilization study evaluating children during the 

first 2 years of life, RV5 vaccine reduced the incidence of office 

visits for G1-G4 rotavirus gastroenteritis by 86%, emergency 

department visits for that outcome by 94%, and hospitalizations 

for that outcome by 96%. 

Phase III clinical efficacy trials of RV1 vaccine were conducted 

in Latin America and Europe. In the Latin American study, 

the efficacy of the 2-dose series against severe rotavirus 

gastroenteritis to age 1 year was 85%. In the European study, 

Rotavirus Vaccine Recommendations

● Any remaining doses should be 

administered on schedule

● Complete the series with 

the same product whenever 

possible

● If product used for a prior dose 

or doses is not available or not 

known, continue or complete 

the series with the product that 

is available

● If any dose in the series was 

RV5 (RotaTeq) or the vaccine 

brand used for any prior dose 

is not known, a total of 3 doses 

of rotavirus vaccine should be 

administered

● Infants documented to have 

had rotavirus gastroenteritis 

before receiving the full course 

of rotavirus vaccinations should 

still begin or complete the 2- or 

3-dose schedule

Rotavirus Vaccine and

 Preterm Infants

● ACIP supports vaccination of a 

preterm infant if:

■ Chronological age is at least 

6 weeks

■ Clinically stable 

■ Vaccine is administered at 

time of discharge or after 

discharge from neonatal 

intensive care unit or nursery
Rotavirus

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19

the efficacy against severe rotavirus gastroenteritis was 96% 

through the first rotavirus season, and against any rotavirus 

gastroenteritis was 87%. Additionally, the efficacy against 

hospitalization for rotavirus gastroenteritis was 96% through the 

second season after vaccination. 

RV5 vaccine was introduced in the United States in 2006 and 

RV1 vaccine was introduced in 2008; hence, most early postintroduction data from the United States were based on RV5 

vaccine. Several RV5 and RV1 case-control vaccine effectiveness 

evaluations have been performed in the United States, usually 

among children younger than age 2 or 3 years. A meta-analysis 

using data published through 2017 found that the vaccine 

effectiveness for a full series against the combined outcome 

of emergency department visit or hospitalization for rotavirus 

disease was 84% for RV5 vaccine and 83% for RV1 vaccine. 

Vaccine effectiveness estimates tend to increase with increasing 

rotavirus disease severity. Both vaccines have demonstrated 

broad effectiveness across rotavirus genotypes.

The duration of immunity from rotavirus vaccine is not precisely 

known, although good efficacy has been demonstrated through 

the first 2 to 3 years of life in the United States. In low-income 

countries, vaccine effectiveness has generally been lower in the 

second year of life compared to the first year.

Contraindications and Precautions 

to Vaccination

As with other vaccines, a history of a severe allergic reaction 

(anaphylaxis) to a vaccine component or following a prior 

dose is a contraindication to further doses. Moderate or severe 

acute illness (with or without fever) in a patient is considered a 

precaution to vaccination, although persons with minor illness 

may be vaccinated. 

Latex rubber is contained in the RV1 vaccine oral applicator, 

so infants with a severe allergy to latex should not receive 

RV1 vaccine. The RV5 vaccine dosing tube is latex free. Some 

experts prefer that infants with spina bifida or bladder 

exstrophy, who are at high risk for acquiring latex allergy, 

receive RV5 vaccine instead of RV1 vaccine to minimize latex 

exposure in these children.

In response to reported cases of vaccine-acquired rotavirus 

infection following rotavirus vaccine administration in infants 

with severe combined immunodeficiency (SCID), ACIP added 

SCID as a contraindication to rotavirus vaccination. For children 

with known or suspected immune deficiency, consultation 

with an immunologist or infectious diseases specialist before 

administration of rotavirus vaccine should occur. Children who 

are immunocompromised because of congenital immunodefiRotavirus Vaccine Efficacy

● Any rotavirus gastroenteritis: 

74%-87%

● Severe gastroenteritis: 

85%-98%

● Both vaccines significantly 

reduced physician visits for 

diarrhea, and reduced rotavirusrelated hospitalization

Rotavirus Vaccine Contraindications 

and Precautions

● Contraindication

■ Severe allergic reaction to 

a vaccine component or 

following a prior dose of 

vaccine 

■ Latex rubber is contained in 

the RV1 oral applicator, so 

infants with a severe allergy 

to latex should not receive 

RV1 vaccine; some experts 

prefer that infants with spina 

bifida or bladder exstrophy, 

who are at high risk for 

acquiring latex allergy, receive 

RV5 instead of RV1 vaccine

■ History of intussusception

■ Severe combined 

immunodeficiency (SCID)

● Precaution

■ Moderate or severe 

acute illnesses, including 

gastroenteritis (defer until 

symptoms improve)

■ Altered immunocompetence 

(SCID is a contraindication)

■ Limited data do not indicate 

a different safety profile 

in HIV-infected versus 

HIV-uninfected infants

■ Chronic gastrointestinal 

disease (data regarding the 

safety of rotavirus vaccine 

for infants with preexisting 

chronic gastrointestinal 

conditions are lacking)
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Rotavirus

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ciency, or hematopoietic stem cell or solid organ transplantation, sometimes experience severe, prolonged, and even fatal 

wild-type rotavirus gastroenteritis. 

The limited data available at the time of the ACIP 

recommendations in 2009 did not indicate that rotavirus 

vaccines had a substantially different safety profile in human 

immunodeficiency virus (HIV)-infected infants that are clinically 

asymptomatic or mildly symptomatic compared with infants 

that are not HIV infected. Additional data are available from 

evaluations in HIV-infected infants as well as infants who were 

HIV exposed but uninfected; rotavirus vaccine was found to be 

well tolerated and immunogenic. 

Post-marketing studies of the currently licensed vaccines 

have detected an increased risk for intussusception following 

rotavirus vaccine administration. As a result, a history of 

intussusception is a contraindication to rotavirus vaccination. 

Rotavirus vaccine should generally be deferred in infants with 

acute, moderate or severe gastroenteritis, or other acute illness 

until the condition improves. However, infants with mild acute 

gastroenteritis or other mild acute illness can be vaccinated, 

particularly if a delay in vaccination will postpone the first dose 

of vaccine beyond 14 weeks 6 days of age. Data regarding the 

safety of rotavirus vaccine for infants with preexisting chronic 

gastrointestinal conditions are lacking. Infants with chronic 

gastrointestinal diseases (e.g., Hirschsprung’s disease, short-gut 

syndrome, or congenital malabsorption syndromes) who are 

not undergoing immunosuppressive therapy should benefit 

from rotavirus vaccination.

Infants living in households with persons who are 

immunocompromised can be vaccinated. The indirect 

protection for the immunocompromised household member 

provided by vaccinating the infant in the household 

outweighs the small risk for transmitting vaccine virus to the 

immunocompromised household member.

Infants living in households with pregnant women should 

be vaccinated according to the routine schedule. Because 

the majority of women of childbearing age have pre-existing 

immunity to rotavirus, the risk for infection by the attenuated 

vaccine virus is considered to be very low. It is prudent for 

all members of the household to employ measures to avoid 

contact with feces of the vaccinated infant, such as good hand 

washing after changing a diaper. 

Vaccine Safety

In RV5 vaccine clinical trials, detailed information on adverse 

events were collected in a subset of participants for 42 days 

after each vaccination. In the first week after any dose, RV5 

Rotavirus Vaccine - Conditions Not 

Considered to be Precautions

● Infants living in households 

with immunocompromised 

persons

● Infants living in households 

with pregnant women
Rotavirus

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19

vaccine recipients had a small but statistically significant 

increased rate of diarrhea (18.1% in RV5, 15.3% in placebo 

group) and vomiting (11.6% in RV5, 9.9% in placebo). During 

the 42-day period following any dose, statistically significantly 

greater rates of diarrhea, vomiting, otitis media, nasopharyngitis, and bronchospasm occurred in RV5 recipients compared 

to placebo recipients. The incidence of serious adverse events 

(including death) within 42 days of any dose was similar among 

RV5 and placebo recipients. A similar rate of gastroenteritis 

occurring any time after a dose was reported in both RV5 and 

placebo recipients (0.2% in RV5, 0.3% in placebo group).

In RV1 clinical trials, participants were monitored for adverse 

events in the 31-day period after vaccination. During the 

31-day period after vaccination, the following unsolicited 

adverse events occurred at a statistically higher incidence 

among vaccine recipients: irritability (11.4% in RV1 group, 8.7% 

in placebo group) and flatulence (2.2% in RV1 group, 1.3% in 

placebo group). The rate of serious adverse events (including 

death) was similar in RV1 and placebo recipients. Detailed 

information on adverse events were collected in a subset of 

participants during the first week following each dose. Rates of 

adverse events in this subset were similar in RV1 and placebo 

recipients except for grade 3 (i.e., those that prevented normal 

everyday activities) cough or runny nose, which occurred at a 

slightly but statistically higher rate in the RV1 vaccine group 

(3.6 %) compared to the placebo group (3.2%). 

Post-marketing strain surveillance in the United States and 

other countries has occasionally detected rotavirus vaccine 

reassortant strains in stool samples of children with diarrhea. In 

some of these reports, the reassortant virus seemed to be the 

likely cause of the diarrheal illness. 

Large phase III clinical trials (more than 60,000 infants each) of 

RV5 and RV1 vaccine evaluated the occurrence of intussusception after vaccination. No increased risk for intussusception was 

observed for either vaccine. However, post-licensure monitoring 

was planned to evaluate for a possible risk of intussusception at 

a lower level than that able to be evaluated in the clinical trials. 

Post-licensure evaluations of RV5 vaccine and/or RV1 vaccine 

in some middle and high income countries have identified a 

low-level increased risk of intussusception following vaccination. 

In the United States, the risk is estimated as 1 excess case of 

intussusception per 20,000 to 100,000 vaccinated infants. The 

risk appears to be primarily during the first week following the 

first or second dose, but may extend up to 21 days following the 

first dose. Parents and health care providers should be aware 

of the low-level increased risk of intussusception following 

rotavirus vaccine so that infants with possible intussusception 

can be promptly evaluated.

Rotavirus Vaccine Safety 

● RV5

■ Diarrhea 18.1%

■ Vomiting 11.6%

■ Also greater rates of otitis 

media, nasopharyngitis, 

and bronchospasm

● RV1

■ Irritability 11.4%

■ Cough or runny nose 3.6%

■ Flatulence 2.2%

● Intussusception

■ Postlicensure-evaluation of 

RV1 and/or RV5 identified low 

level risk of intussusception; 

1 excess case per 20,000 to 

100,000 in the U.S.
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Vaccine Storage and Handling

Rotavirus vaccine should be maintained at refrigerator temperature between 2°C and 8°C (36°F and 46°F). 

Manufacturer package inserts contain additional information, 

including information on storage of the diluent in oral 

applicators for RV1. For complete information on best practices 

and recommendations, please refer to CDC’s Vaccine Storage 

and Handling Toolkit, www.cdc.gov/vaccines/hcp/admin/

storage/toolkit/storage-handling-toolkit.pdf. 

Surveillance and Reporting of Rotavirus 

Rotavirus gastroenteritis is not a nationally notifiable disease in 

the United States. Estimates of incidence and disease burden 

are based on special surveys, cohort studies, and hospital 

discharge data. Methods of surveillance for rotavirus disease at 

the national level include review of national hospital discharge 

databases for rotavirus-specific or rotavirus-compatible 

diagnoses, surveillance for rotavirus disease at sites that 

participate in the New Vaccine Surveillance Network, and 

reports of rotavirus detection from a sentinel system of laboratories. Special evaluations (e.g., case control and retrospective 

cohort methods) have been used to measure the effectiveness 

of rotavirus vaccine under routine use in the United States. 

CDC has also established a national strain surveillance system 

of sentinel laboratories that monitors circulating rotavirus 

strains. For information on guidance for state and local health 

department staff who are involved in surveillance activities for 

vaccine-preventable diseases, please consult the Manual for the 

Surveillance of Vaccine-Preventable Diseases, www.cdc.gov/

vaccines/pubs/surv-manual/chapters.html.
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Acknowledgements

The editors would like to acknowledge Valerie Morelli and 

Ginger Redmon for their contributions to this chapter. 

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effects of infant rotavirus vaccination across all ages in the 

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data set. Clin Infect Dis 2019;5;68(6):976–83. 

Bowen M, Mijatovic-Rustempasic S, Esona M, et al. Rotavirus 

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CDC. Addition of severe combined immunodeficiency as a 

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