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Rotavirus Disease and Vaccines: Frequently Asked Questions
January 1, 2016
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Contents
Abbreviations .............................................................................................................. iv
A. Rotavirus disease overview ................................................................................. 1
1. What is rotavirus? .................................................................................................................... 1
2. How many young children die from or are hospitalized for rotavirus each year? ................... 1
3. What percentage of diarrhea-related deaths and hospitalizations is due to rotavirus? ............. 1
4. What percentage of all child deaths is due to rotavirus? .......................................................... 1
5. What is the leading cause of moderate-to-severe diarrhea in low-income countries? What did
the Global Enteric Multicenter Study (GEMS) find? .............................................................. 1
6. Who is at risk for rotavirus infection? ..................................................................................... 2
7. Can a child become infected with rotavirus multiple times? ................................................... 2
8. What are the symptoms of rotavirus? ...................................................................................... 2
9. How is rotavirus spread?.......................................................................................................... 2
10. What is the treatment for rotavirus? ......................................................................................... 2
11. How can we prevent rotavirus?................................................................................................ 3
12. How big of a threat is rotavirus to children’s health and well-being? ..................................... 3
13. Where can I find more information on rotavirus disease? ....................................................... 3
B. Rotavirus vaccines overview ................................................................................ 4
1. Why are rotavirus vaccines needed/necessary? ....................................................................... 4
2. Are rotavirus vaccines approved and recommended by the World Health Organization
(WHO)? ................................................................................................................................... 4
3. What rotavirus vaccines are available? .................................................................................... 4
4. How are rotavirus vaccines administered?............................................................................... 5
5. When do children receive rotavirus vaccines? ......................................................................... 5
6. When did the currently globally available rotavirus vaccines, Rotarix® and RotaTeq®,
become licensed and prequalified? .......................................................................................... 5
7. Was there another/earlier rotavirus vaccine? What about RotaShield®? ................................ 5
8. How many countries are now using rotavirus vaccines? ......................................................... 6
9. Which Gavi-eligible countries have introduced rotavirus vaccines? ....................................... 6
10. Will Gavi support the introduction of rotavirus vaccines in more countries? .......................... 6
C. Rotavirus vaccine efficacy, effectiveness, and impact ........................................ 7
1. What is the “real-world” impact of rotavirus vaccines? Have countries experienced
reductions in death and hospitalizations after introducing rotavirus vaccines? ....................... 7
ii
2. Do rotavirus vaccines also protect children and adults who have not been vaccinated? Do
they enable herd immunity? ..................................................................................................... 7
3. How many lives can be saved with these vaccines? ................................................................ 7
4. Does the vaccine provide 100 percent protection against rotavirus? Can you still get
rotavirus even with the vaccine? .............................................................................................. 8
5. How long do rotavirus vaccines provide protection against rotavirus? Does protection
decline over time? .................................................................................................................... 8
6. Do rotavirus vaccines work equally well in both high- and low-income countries? ............... 8
7. Why is rotavirus vaccine efficacy different between high- and low-income countries? .......... 8
8. Will rotavirus vaccines be useful in low-income countries even if the efficacy is lower? ...... 9
9. Are rotavirus vaccines cost-effective? ..................................................................................... 9
10. Are there different strains of rotavirus? What rotavirus strains are contained in the currently
globally licensed rotavirus vaccines, Rotarix® and RotaTeq®? ............................................... 9
11. Do rotavirus vaccines protect against strains not found in the vaccine? .................................. 9
12. Does strain variation have any effect on vaccine efficacy? ................................................... 10
13. Where can I find more information on the real-world impact (effectiveness) of rotavirus
vaccines? ................................................................................................................................ 10
D. Rotavirus vaccine safety and potential side effects .......................................... 10
1. Are rotavirus vaccines safe? .................................................................................................. 10
2. What are potential side effects of rotavirus vaccination? ...................................................... 10
3. What is intussusception? ........................................................................................................ 11
4. What causes intussusception and who is susceptible to intussusception? .............................. 11
5. Why do a small number of infants develop intussusception after rotavirus vaccination, while
most infants who get vaccinated do not? ............................................................................... 11
6. How is intussusception diagnosed and treated? ..................................................................... 11
7. Is there a link between currently globally licensed rotavirus vaccines Rotarix® and
RotaTeq® and intussusception? ............................................................................................ 12
8. What are the positions of the World Health Organization (WHO) and of immunization
advisory committees in countries with published intussusception studies on the safety and
continued use of Rotarix® and RotaTeq®? ........................................................................... 12
9. Were large-scale clinical trials conducted to assess the safety of Rotarix® and RotaTeq®
rotavirus vaccines before introduction? ................................................................................. 13
10. How do the rates of intussusception in RotaShield® (withdrawn from market in 1999)
compare to the rates of intussusception found with the newer vaccines, Rotarix® and
RotaTeq®? ............................................................................................................................. 13
11. Has the new Indian-developed rotavirus vaccine ROTAVAC® been evaluated for a risk of
intussusception? ..................................................................................................................... 13
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12. Why are WHO, regulatory agencies, immunization advisory committees, and rotavirus
vaccine manufacturers evaluating rotavirus vaccines so carefully for intussusception? ........ 14
13. Where can I find more information on intussusception? ....................................................... 14
14. Do rotavirus vaccines contain a pig virus (porcine circovirus)? ............................................ 15
15. Is there a safety risk associated with the porcine circovirus that has been found in rotavirus
vaccines? ................................................................................................................................ 15
16. Where can I find more information on porcine circovirus? ................................................... 15
References ................................................................................................................. 16
iv
Abbreviations
CDC United States Centers for Disease Control and Prevention
EMA European Medicines Agency (previously EMEA)
FDA United States Food and Drug Administration
GACVS Global Advisory Committee on Vaccine Safety
GSK GlaxoSmithKline
WHO World Health Organization
Rotavirus Diseases and Vaccines: FAQs
Page 1 of 20
A. Rotavirus disease overview
1. What is rotavirus?
Rotavirus is a contagious virus that can cause diarrheal illness, also known as gastroenteritis,
which may be severe particularly in infants and young children. It is often accompanied by
vomiting and fever, and if left untreated it can lead to severe dehydration and death. While not
the only cause of diarrhea, rotavirus is the leading cause of severe diarrhea in young children
worldwide.
2. How many young children die from or are hospitalized for rotavirus each year?
Globally, rotavirus is responsible for more than 450,000 deaths each year in children younger
than five years of age and is responsible for millions of hospitalizations and clinic visits each
year.1;2 It affects children around the world in high- and low-income countries alike. While
rotavirus deaths and hospitalizations vary by region and country, the vast majority (95 percent)
of rotavirus deaths in young children are found in low-income countries in Africa and Asia.1
Five percent of all deaths in children younger than five years of age are due to rotavirus.1
3. What percentage of diarrhea-related deaths and hospitalizations is due to rotavirus?
Rotavirus is estimated to cause 37 percent of the approximately 800,000 diarrheal deaths and
40 percent of the 9 million diarrhea-related hospitalizations in children under five years of age
worldwide.1-3
4. What percentage of all child deaths is due to rotavirus?
Rotavirus diarrhea accounts for an estimated 5 percent of all deaths in children under five.1
Diarrhea from all causes is responsible for approximately 9 percent of all under-five deaths
worldwide.4
5. What is the leading cause of moderate-to-severe diarrhea in low-income countries?
What did the Global Enteric Multicenter Study (GEMS) find?
The public health burden of rotavirus was confirmed by the Global Enteric Multicenter Study
(GEMS), the first comprehensive global study of childhood diarrheal disease, which was
conducted in seven study sites in sub-Saharan Africa and South Asia. GEMS found that
rotavirus is the overall leading cause of moderate-to-severe diarrhea among infants and
toddlers under two years of age and a major cause among children under five years of age in
these settings.5
Rotavirus Diseases and Vaccines: FAQs
Page 2 of 19
6. Who is at risk for rotavirus infection?
Nearly every child is at risk of infection, regardless of location, hygiene practices, or access to
safe drinking water or sanitation. Children six months to two years of age are most vulnerable
to infection, along with premature infants, the elderly, and those with weakened immune
systems. While older children and adults can get rotavirus infections, these are usually
asymptomatic or mild.6
7. Can a child become infected with rotavirus multiple times?
Vaccinated and unvaccinated children may develop rotavirus disease more than once because
neither the vaccine nor natural infection provides full immunity (protection) from future
infections.6 Usually a person’s first infection with rotavirus causes the most severe symptoms.6
8. What are the symptoms of rotavirus?
Once a person has been exposed to rotavirus, it takes about two days for symptoms to appear.
Symptoms include diarrhea, vomiting, fever, and abdominal pain. Vomiting and watery
diarrhea may last from three to eight days in a child infected with rotavirus. Additional
symptoms include loss of appetite and dehydration, which can be especially harmful for young
children and lead to death.
9. How is rotavirus spread?
Rotavirus is shed (passed from a person’s body into the environment) in the feces (stool) of
infected persons. The virus spreads by the fecal–oral route; this means that the virus must be
shed by an infected person in his/her feces and then enter a susceptible person’s mouth to
cause infection.
Rotavirus is highly contagious and resilient. It spreads easily from person to person through
contaminated hands and objects, such as toys and surfaces. Rotavirus can live on contaminated
hands for hours and surfaces for days. Children can spread the virus both before and after they
become sick with diarrhea. They also can pass rotavirus to family members and other people
with whom they have close contact.
10. What is the treatment for rotavirus?
Rotavirus cannot be treated with antibiotics or other drugs. Mild rotavirus infections can be
treated effectively in the same manner as other forms of diarrhea, by providing fluids and salts
(oral rehydration therapy) until the disease runs its course. However, children with severe
rotavirus diarrhea urgently need intravenous fluids, or they risk dying from dehydration. In
low-income countries, this type of urgent health care is often inaccessible or unavailable,
making rotavirus prevention through vaccination critical to saving children’s lives.
Rotavirus Diseases and Vaccines: FAQs
Page 3 of 19
11. How can we prevent rotavirus?
Vaccination is the best way to protect children from rotavirus and the dehydrating diarrhea that
it can cause. Improvements in water quality, hygiene, and sanitation stop bacteria and parasites
that cause other forms of diarrhea but do not adequately prevent the spread of rotavirus.
Lifesaving rotavirus vaccines should be introduced as part of a comprehensive approach to
control diarrheal disease, along with other interventions including oral rehydration therapy,
exclusive breastfeeding, zinc treatment, and improvements in water and sanitation.7
12. How big of a threat is rotavirus to children’s health and well-being?
Rotavirus is the most common cause of severe diarrhea in children. Rotavirus is estimated to
cause approximately 37 percent of diarrheal deaths in children under age five worldwide,
killing more than 450,000 children each year.1 It also causes about 40 percent of all
hospitalizations for diarrheal disease in children under age five worldwide.3 While every child
is at risk of rotavirus infection, more than 95 percent of rotavirus deaths occur in low-income
countries, where access to treatment for severe rotavirus-related diarrhea may be limited or
unavailable.1 Rotavirus vaccines provide the best protection against rotavirus and are saving
children’s lives and improving health where they are in use.
13. Where can I find more information on rotavirus disease?
More information on rotavirus disease is available from the US Centers for Disease Control
and Prevention (CDC): Rotavirus page.8
Rotavirus Diseases and Vaccines: FAQs
Page 4 of 19
B. Rotavirus vaccines overview
1. Why are rotavirus vaccines needed/necessary?
Vaccines are the best way to protect children from rotavirus and the dehydrating diarrhea that
it can cause. Improvements in hygiene, water quality, and sanitation that stop many bacteria
and parasites that cause other types of diarrhea do not adequately prevent the spread of
rotavirus.9 Rotavirus vaccines are a critical part of a comprehensive strategy to prevent and
manage diarrheal disease. Introducing rotavirus vaccines with other diarrhea prevention and
treatment methods, such as oral rehydration therapy, zinc supplementation, exclusive
breastfeeding, improved hygiene, water quality, sanitation, and nutrition, can significantly
reduce child illnesses and deaths.7
2. Are rotavirus vaccines approved and recommended by the World Health
Organization (WHO)?
Rotavirus vaccines Rotarix® and RotaTeq® are both approved and recommended by WHO.
The vaccines were initially approved for use in Europe and America on the basis of efficacy
data from these regions in 2006.10 Subsequently, after proof of efficacy in Asia and Africa,
WHO recommended that rotavirus vaccines be introduced into every country’s national
immunization program, particularly in countries where diarrheal disease is a major health
problem.11
3. What rotavirus vaccines are available?
There are two orally administered rotavirus vaccines available on the global market today:
Rotarix®, manufactured by GlaxoSmithKline (GSK).
RotaTeq®, manufactured by Merck & Co., Inc.
There are three orally administered rotavirus vaccines licensed for national markets only:
ROTAVAC®, manufactured by Bharat Biotech International Limited and licensed for
use in India in 2014.
Rotavin-M1®, manufactured by the Center for Research and Production of Vaccines
and licensed for use in Vietnam in 2007.
Lanzhou Lamb Rotavirus Vaccine, manufactured by the Lanzhou Institute of
Biological Products and licensed for use in China in 2000.
Other new vaccines are being developed by manufacturers in India, China, and Brazil, and
may be available soon.
Rotavirus Diseases and Vaccines: FAQs
Page 5 of 19
4. How are rotavirus vaccines administered?
Both Rotarix® and RotaTeq® are given orally, with each dose having a volume of ~2 cubic
centimeters given through a nozzle that has to pass through the lips and be deposited on the
inside of the cheek.
5. When do children receive rotavirus vaccines?
Each country has its own immunization schedule. Both rotavirus vaccines are given orally but
differ in the number of doses given. In general, in low-income countries, RotaTeq® is given in
three doses at 6 weeks, 10 weeks, and 14 weeks of age, and Rotarix® is given in two doses at 6
weeks and 10 weeks of age. In middle- and upper-income countries, RotaTeq® is given in
three doses at 2 months, 4 months, and 6 months of age, and Rotarix® is given in two doses at
2 months and 4 months of age. Differences in rotavirus immunization schedules are generally
due to existing routine immunization program schedules and the logistics of delivering
multiple vaccines at the same time.a
In many low-income countries, due to challenges related to health service access, children may
not receive their vaccines on schedule. WHO recommends in its rotavirus position paper that
countries consider providing rotavirus vaccination to these children even if later than the
immunization schedule because the benefits of rotavirus vaccination, including preventing
hospitalizations and deaths from diarrhea, far exceed any possible low-level risks associated
with the vaccine.12
6. When did the currently globally available rotavirus vaccines, Rotarix® and
RotaTeq®, become licensed and prequalified?
The FDA licensed Merck’s RotaTeq® in February of 2006 and GSK’s Rotarix® in April of
2008. The European Commission and the European Medicines Agency (EMA) licensed
GSK’s Rotarix® in February 2006 and Merck’s RotaTeq® in June 2006. WHO prequalified
Rotarix® in January 2007 and RotaTeq® in October 2008.
7. Was there another/earlier rotavirus vaccine? What about RotaShield®?
RotaShield® was the first rotavirus vaccine available in the US in 1998. In 1999, RotaShield®
was voluntarily withdrawn from the market by the manufacturer because intussusception was
found to be a rare but potential side effect (1 case of intussusception for every 10,000 infants
vaccinated). While a small risk of intussusception has also been associated with current
vaccines, the risk (between 1 to 6 excess cases per 100,000 vaccinated infants13) is much
smaller than that of RotaShield®. WHO and immunization advisory committees in countries
a In South Africa, for example, Rotarix® is given at 6 and 14 weeks of age.
Rotavirus Diseases and Vaccines: FAQs
Page 6 of 19
with published intussusception studies have unanimously upheld their recommendation for
universal rotavirus vaccination because the substantial benefits of vaccination far outweigh the
potential low-level risk of intussusception.12;14-16
To learn more about intussusception, please see section D, “Rotavirus vaccines safety and
potential side effects,” below.
8. How many countries are now using rotavirus vaccines?
As of January 1, 2016, 80 countries have introduced rotavirus vaccines in their national
immunization programs (i.e., public sector).17 Other countries, such as Canada, the
Philippines, and Thailand, have introduced rotavirus vaccines in pilot or regional
introductions. Rotavirus vaccines are also available in more than 100 countries through the
private market.
To learn more about worldwide rotavirus vaccine introductions, please visit PATH’s Rotavirus
Vaccine Access and Delivery website: Country introductions of rotavirus vaccines.17
9. Which Gavi-eligible countries have introduced rotavirus vaccines?
Gavi, the Vaccine Alliance, began offering support for rotavirus vaccines in 2006. As of
January 1, 2016, rotavirus vaccines have been introduced in 37 Gavi-eligible countries:17
2006: Nicaragua
2008: Bolivia
2009: Honduras
2010: Guyana
2011: Sudan
2012: Ghana, Rwanda, Moldova, Yemen, Armenia, Malawi, Tanzania
2013: Georgia, Haiti, The Gambia, Burkina Faso, Ethiopia, Zambia, and Burundi
2014: Mali, Cameroon, Sierra Leone, Republic of the Congo, Angola, Zimbabwe,
Madagascar, Uzbekistan, Togo, Djibouti, Kenya, Niger, Eritrea, Senegal, Mauritania
2015: Tajikistan, Mozambique, Guinea-Bissau
For more information on Gavi and Gavi eligibility criteria, please visit www.gavi.org. To learn
more about Gavi-supported rotavirus vaccine introductions, please visit PATH’s Rotavirus
Vaccine Access and Delivery website: Country introductions of rotavirus vaccines.17
10. Will Gavi support the introduction of rotavirus vaccines in more countries?
As of January 1, 2016, Gavi has approved three additional countries for rotavirus vaccine
support: Central African Republic, Côte d’Ivoire, and Liberia.18
Rotavirus Diseases and Vaccines: FAQs
Page 7 of 19
C. Rotavirus vaccine efficacy, effectiveness, and impactb
1. What is the “real-world” impact of rotavirus vaccines? Have countries experienced
reductions in death and hospitalizations after introducing rotavirus vaccines?
Rotavirus vaccines are dramatically improving the health and well-being of children around
the world by substantially reducing severe diarrhea. Swift and significant declines in
hospitalizations and deaths due to rotavirus and all-cause diarrhea have been observed in many
of the countries that have introduced rotavirus vaccines into their national immunization
programs, including Austria, Australia, Belgium, Bolivia, Brazil, El Salvador, Finland,
Honduras, Mexico, Nicaragua, Panama, the United States, and Venezuela.19
A recent review of available clinical trial data from countries routinely using rotavirus
vaccines in their national immunization programs (excluding those that have introduced
recently due to data not yet being available), found that rotavirus vaccines have reduced
rotavirus hospitalizations by 49-92 percent and all-cause diarrhea hospitalizations by 17-55
percent.20 In addition, the review found that all-cause diarrhea deaths were reduced by 22-50
percent in some settings.20
To learn more about the impact of rotavirus vaccines, please visit PATH’s Rotavirus Vaccine
Access and Delivery website: Tables | Rotavirus vaccine impact.19
2. Do rotavirus vaccines also protect children and adults who have not been
vaccinated? Do they enable herd immunity?
In some countries where rotavirus vaccines have been introduced, researchers are finding
significant reductions in rotavirus diarrhea hospitalizations in unvaccinated adults and
children, suggesting the benefits of rotavirus vaccines extend beyond infants and provide
indirect protection to unvaccinated children and adults by reducing spread of the virus (an
effect called herd immunity).19;21
3. How many lives can be saved with these vaccines?
In Gavi-eligible countries, where 95 percent of deaths due to rotavirus occur, more than 2.4 million
child deaths can be prevented by 2030 by accelerating access to lifesaving rotavirus vaccines.22 If
used in all Gavi-eligible countries, rotavirus vaccines could prevent an estimated 180,000 deaths
and avert 6 million clinic and hospital visits each year, thereby saving US$68 million annually in
treatment costs.22
b Effectiveness refers to how well a vaccine works against a disease outcome in a setting of routine vaccine use
(“real-world” use). Vaccine impact is the overall reduction in disease burden due to the vaccine. How well a
vaccine works in controlled settings such as a clinical trial is referred to as efficacy.
Rotavirus Diseases and Vaccines: FAQs
Page 8 of 19
4. Does the vaccine provide 100 percent protection against rotavirus? Can you still get
rotavirus even with the vaccine?
While no medical intervention or product is 100 percent effective, rotavirus vaccines do
provide the best protection available today against rotavirus, the most common cause of severe
diarrhea. Research suggests that rotavirus vaccines are most effective at preventing the most
severe and life-threatening cases of rotavirus.23 A small proportion of vaccinated infants may
develop rotavirus disease more than once because neither the vaccine nor natural infection
provides full protection from future infections.6 Usually, a person’s first infection with
rotavirus causes the most severe symptoms.6
5. How long do rotavirus vaccines provide protection against rotavirus? Does
protection decline over time?
In high-income countries, rotavirus vaccines have been shown to protect infants through the
third year of life. In low-income countries, the rotavirus threat is greatest during the first year
of life. In clinical studies in Africa and Asia, rotavirus vaccines have been shown to provide
the greatest protection during this first year.24-26 Efficacy in the second year of life may be
lower in low-income countries, but further evaluation is required to understand in which
populations and under what circumstances vaccine efficacy declines.24-28
6. Do rotavirus vaccines work equally well in both high- and low-income countries?
Clinical studies have shown that rotavirus vaccine efficacy against severe rotavirus during the
first year of life has ranged from 85 to 98 percent in middle- to high-income countries,29-32
including in Latin America, and 51 to 64 percent in low-income countries in Africa and
Asia.24-26;28
7. Why is rotavirus vaccine efficacy different between high- and low-income countries?
Data from clinical studies in middle- and high-income countries demonstrate higher vaccine
efficacy than data from low-income countries.33;34 While we do not know why this difference
in efficacy exists, lower efficacy of oral vaccines is typical in impoverished, high-mortality
settings. This is seen with other orally administered vaccines like polio, cholera, and typhoid.
Several factors may contribute to lower efficacy, such as the age of the child when the vaccine
is administered, co-administration with oral polio vaccine, possible interference by maternal
antibodies, micronutrient deficiencies, persistent exposure to pathogens, higher prevalence of
co-infections, or wide varieties of virus strains.27;33;34 The Vaccine Implementation Technical
Assistance Consortium (VITAC), PATH, and others are studying these factors so that national
health ministries will ultimately be able to optimize rotavirus vaccination strategies and
provide children the best possible protection.
Rotavirus Diseases and Vaccines: FAQs
Page 9 of 19
8. Will rotavirus vaccines be useful in low-income countries even if the efficacy is
lower?
Although lower vaccine efficacy was observed in some clinical trials in certain low-income
countries compared with data from high-income countries, rotavirus vaccines are expected to
have a major public health impact in areas where the rotavirus burden is greatest—such as in
low-resource settings in Africa and Asia.23;35 Efficacy is only one factor in assessing the
potential impact of a vaccine; the other critical factor is the incidence of severe disease. The
vaccine likely will have a greater impact than we have seen elsewhere, even at a lower
efficacy rate, because rotavirus vaccines will still substantially reduce severe cases of rotavirus
diarrhea—those that are most life threatening.23;35
9. Are rotavirus vaccines cost-effective?
Rotavirus vaccines are cost-effective and not only improve child health, but they also save lives.
Vaccination lessens the tremendous economic and health burden of rotavirus disease, thereby
contributing to poverty reduction and economic growth. Published studies have consistently
concluded that the introduction of rotavirus vaccines into low-income countries would be cost-
effective using internationally established critera.36
10. Are there different strains of rotavirus? What rotavirus strains are contained in the
currently globally licensed rotavirus vaccines, Rotarix® and RotaTeq®?
Globally, five rotavirus strains comprise approximately 90 percent of all typed strains.37
Rotarix® is derived from a single strain that was isolated from an infant with rotavirus
diarrhea.32 RotaTeq® is derived from a collection of five different strains made from mixtures
(reassortants) of human and bovine rotaviruses.10 Rotavirus strains vary by region and by
country. In general, rotavirus strain diversity is greatest in low-resource regions.37
11. Do rotavirus vaccines protect against strains not found in the vaccine?
Yes. Current rotavirus vaccines protect against a wide variety of strain types, even those not
contained in the vaccines.25;38-41 Rotavirus strain diversity is a complex issue as new strains
emerge or evolve and appear in the human population through instances such as natural,
molecular evolution.42;43 Although the diversity and distribution of rotavirus strains differ from
year to year and region to region, clinical trials and post-licensure evaluations of the two
rotavirus vaccines currently on the market, including studies in low-income countries in Africa
and Asia, found that these vaccines provide protection against a broad range of rotavirus
strains.25;38-41;44
Rotavirus Diseases and Vaccines: FAQs
Page 10 of 19
12. Does strain variation have any effect on vaccine efficacy?
In settings with a diversity of circulating rotavirus strains, studies show that rotavirus vaccines
provide protection against a broad range of rotavirus strains, even strains not included in the
vaccines.24;26;38;39;41
13. Where can I find more information on the real-world impact (effectiveness) of
rotavirus vaccines?
More information on the real-world impact of rotavirus vaccines is available on PATH’s
Rotavirus Vaccine Access and Delivery website: Tables ǀ Rotavirus vaccine impact.19
D. Rotavirus vaccine safety and potential side effects
1. Are rotavirus vaccines safe?
Both vaccines on the global market today, Rotarix®, manufactured by GlaxoSmithKline, and
RotaTeq®, manufactured by Merck & Co., Inc., have strong safety records, including clinical
trials involving tens of thousands of infants as well as clinical experience with millions of
recipients in the more than 65 countries around the world that have introduced the vaccines
into national immunization programs, and the benefits of these vaccines are substantial and far
exceed any possible low-level risks.11;45-49 However, no medical products, such as drugs or
vaccines, are 100 percent safe.
The ROTAVAC® safety profile has been evaluated by the WHO Global Advisory Committee
on Vaccine Safety (GACVS) based only on data from pre-licensure clinical trials, as
ROTAVAC® has been recommended for inclusion but not yet rolled out into India’s
Universal Immunization Programme. GACVS concluded that it supports further use of the
vaccine.50
2. What are potential side effects of rotavirus vaccination?
Most children who get vaccinated will not experience any side effects. However, there is a
slight chance of a few minor symptoms, which include diarrhea, vomiting, and irritability. In
rare cases, a condition called intussusception has been associated with rotavirus vaccination.
WHO and immunization advisory committees in countries with published vaccine safety data
have unanimously upheld their recommendations for universal rotavirus vaccination because
the substantial benefits of vaccination to prevent hospitalizations and death far outweigh the
potential low-level risk of intussusception.12;14-16
Rotavirus Diseases and Vaccines: FAQs
Page 11 of 19
3. What is intussusception?
Intussusception is when one portion of the bowel slides into the next, much like the pieces of a
telescope. When this occurs, it creates a blockage in the bowel. If it is not detected and treated
early, it can cause internal bleeding, a hole in the intestines, and infection in the abdomen,
because the intestinal tissue has died from the decreased blood flow. In some cases surgery
might be required. If untreated, intussusception can be fatal.
4. What causes intussusception and who is susceptible to intussusception?
Intussusception is a rare event but occurs worldwide. It occurs naturally in about 74 per
100,000 children globally and 50 per 100,000 children in the United States and other high-
income countries.51 In most cases the cause is unknown. Some cases may be caused by a polyp
or tumor in the bowel—both of these are groups of cells growing in the bowel that are not
normal. Although people of any age can get intussusception, it is most common among infants
in the first year of life, generally between the ages of four and seven months.
Studies have shown a small increase in cases of intussusception shortly after the first or second
dose of rotavirus vaccine (within three weeks of the first dose in the US and Australia).13;52
These studies have not determined whether rotavirus vaccines affect the overall incidence of
intussusception among all infants in a population.
5. Why do a small number of infants develop intussusception after rotavirus
vaccination, while most infants who get vaccinated do not?
The reasons why some infants develop intussusception after rotavirus vaccination are not
known. The reasons why unvaccinated infants develop intussusception are also not known in
most cases.
6. How is intussusception diagnosed and treated?
Intussusception can be detected by examining the abdomen or performing an ultrasound. The
best procedure to diagnose intussusception is a special type of enema, where liquid and/or air
is put into the back passage using a catheter. This procedure is usually done in a hospital. The
procedure is often successful in unblocking the bowel and the baby can usually go home after
a short period of observation. If this procedure is unavailable, an operation is needed to
unblock the bowel. After surgery, babies will need to stay in hospital for a few days and be
given intravenous fluids until able to feed normally.
Some countries lack surveillance systems and clinical staff to monitor and diagnose
intussusception. It is therefore imperative when giving a rotavirus vaccine for the vaccinator to
remind caregivers about how to recognize danger signs of intussusception and when to seek
health care.
Rotavirus Diseases and Vaccines: FAQs
Page 12 of 19
7. Is there a link between currently globally licensed rotavirus vaccines Rotarix® and
RotaTeq® and intussusception?
Yes. Studies have been conducted in Australia, Brazil, Mexico, and the United States to assess
safety following the introduction of Rotarix® and RotaTeq® rotavirus vaccines. Results from
these studies show a potential low-level risk of intussusception shortly after the first or second
dose of rotavirus vaccine:
Table 1. Estimated risk of intussusception and benefits of rotavirus vaccination in Australia,
Brazil, Mexico, and the United States13
Country Diarrhea
hospitalizations
(deaths) prevented by
vaccination
Intussusception
hospitalizations (deaths)
potentially caused by
vaccination
Australia14 7,000 (0) 6 (0)
Brazil5 69,600 (640) 55 (3)
Mexico5 11,600 (663) 41 (2)
United States6 53,444 (14) 35-166 (0.1-0.5)
Note: Table is derived from Table 6 in Yen et al, 2014. Estimates are for one fully vaccinated
birth cohort followed to age 5 years.13
However, the World Health Organization (WHO)’s Global Advisory Committee on Vaccine
Safety, the US Centers for Disease Control and Prevention (CDC), the US Food and Drug
Administration, the European Medicines Agency, and immunization advisory committees in
countries with published intussusception studies have reviewed the data and determined that
the benefits of rotavirus vaccination to prevent severe rotavirus diarrhea outweigh the low-
level risk of intussusception.12;14-16;46;53 WHO, CDC, and immunization advisory committees in
countries with published intussusception studies have upheld their recommendations to
administer rotavirus vaccines to infants to prevent severe rotavirus diarrhea.12;14-16
8. What are the positions of the World Health Organization (WHO) and of
immunization advisory committees in countries with published intussusception
studies on the safety and continued use of Rotarix® and RotaTeq®?
Based on the established benefits of rotavirus vaccination to prevent hospitalizations and death
and the rare occurrence of intussusception, WHO, CDC, and immunization advisory
committees in countries with published intussusception studies recommend the continued use
of rotavirus vaccines for infants to prevent severe rotavirus diarrhea.12;14-16
The benefits of rotavirus vaccination are substantial and include prevention of hospitalization
for severe rotavirus diarrhea and death. The benefits of the vaccines outweigh the small
increased risk of intussusception. Many countries that have introduced rotavirus vaccines have
Rotavirus Diseases and Vaccines: FAQs
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experienced significant reductions in severe diarrhea, underscoring the incredible potential for
rotavirus vaccines to improve child health and save lives.
9. Were large-scale clinical trials conducted to assess the safety of Rotarix® and
RotaTeq® rotavirus vaccines before introduction?
Yes. The risk of intussusception for Rotarix® and RotaTeq® was assessed in large clinical trials
prior to licensure in the Unites States, Finland, and Latin America.29-32 Each trial involved
more than 60,000 participants and no increased risk for intussusception was observed.
Researchers found that the risk of intussusception was similar among children who received
the vaccine and those who received a placebo, indicating that the currently available vaccines
are safe for use.29-32
However, the clinical trials were not large enough to detect the low-level of risk of
intussusception identified in the post-licensure studies. In addition, while clinical trials are
useful for assessing safety, they are conducted in specific populations under restricted
conditions, which may differ from routine use of the vaccine. Thus, post-licensure surveillance
is essential to detect any unexpected or rare side effects that require careful follow-up on
hundreds of thousands of infants.
10. How do the rates of intussusception in RotaShield® (withdrawn from market in
1999) compare to the rates of intussusception found with the newer vaccines,
Rotarix® and RotaTeq®?
The low-level risks of intussusception observed with the currently globally licensed vaccines
Rotarix® and RotaTeq® are lower than the risk identified with the first rotavirus vaccine,
RotaShield®, which was withdrawn from the market in 1999.54 RotaShield® posed an excess
risk of intussusception in approximately 1 per 10,000 vaccinated infants in the US. The risk of
intussusception with Rotarix® or RotaTeq® ranges from 1 to 6 excess cases per 100,000
vaccinated infants.13;52
11. Has the new Indian-developed rotavirus vaccine ROTAVAC® been evaluated for a
risk of intussusception?
Yes, during pre-licensure clinical trials, as ROTAVAC® has been recommended for inclusion
but not yet rolled out into India’s Universal Immunization Programme. During the Phase 3
clinical trials of the vaccine, infants receiving ROTAVAC® did not experience a significantly
higher level of adverse events compared to infants receiving placebo.55 At its meeting in June
2014, the WHO Global Advisory Committee on Vaccine Safety (GACVS) reviewed the safety
profile of ROTAVAC® using this clinical trial data. Because no cases of intussusception
occurred in proximity to the time of vaccination, GACVS noted that the available evidence
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“argues strongly against” a causative relationship between ROTAVAC® and intussusception
and concluded that it supports further use of the vaccine.50
Because clinical trials are not large enough to assess low levels of risk such as the risk of
intussusception, GACVS also recommends continued post-licensure safety surveillance—
including intussusception surveillance—in India as well as in all countries that have
introduced rotavirus vaccines.
12. Why are WHO, regulatory agencies, immunization advisory committees, and
rotavirus vaccine manufacturers evaluating rotavirus vaccines so carefully for
intussusception?
Currently globally licensed rotavirus vaccines Rotarix® and RotaTeq® are closely evaluated for
a risk of intussusception because the first generation rotavirus vaccine, RotaShield®, which
was withdrawn from the market in 1999, was associated with a small risk of intussusception
after its routine introduction into the United States market.
Although neither Rotarix® or RotaTeq® were associated with intussusception during the
clinical trials, post-marketing surveillance of rotavirus vaccines in Australia, Brazil, Mexico,
and the United States has indicated there is a small increased risk of intussusception associated
with rotavirus vaccines.13;15;45;52;56-60
While clinical trials are useful for assessing safety, they are not large enough to assess low
levels of risk and they are conducted in specific populations under restricted conditions, which
may differ from routine use of the vaccine. Thus, post-licensure monitoring and surveillance
studies (such as case-series studies) are essential to detect any unexpected or rare side effects.
13. Where can I find more information on intussusception?
More information on intussusception is available from:
US Centers for Disease Control and Prevention:
o Vaccine Safety: Rotavirus
o Rotavirus Vaccine Information Statement
o Rotavirus Vaccine and Intussusception Update: CDC Expert Commentary
[video].
US Food and Drug Administration:
o RotaTeq (Rotavirus Vaccine) Questions and Answers
o Information on Rotarix- Labeling Revision Pertaining to Intussusception
World Health Organization:
o Update on intussusception following rotavirus vaccine administration
(GACVS report Dec 2013)
o Rotavirus vaccines: WHO position paper—January 2013 (Weekly
Epidemiological Record February 2013 [N.B. The 2013 WHO rotavirus
Rotavirus Diseases and Vaccines: FAQs
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position paper replaces the August 2007 position paper and December 2009
update])
o Rotavirus Vaccines and Intussusception (GACVS report Dec 2011)
o Rotavirus Vaccines and Intussusception (Global Advisory Committee on
Vaccine Safety [GACVS] report Dec 2010)
Australian Government Department of Health
o Rotavirus vaccination and the risk of intussusception (Therapeutic Goods
Administration)
o Rotavirus vaccine and intussusception information for Parents and Guardians
(Immunise Australia)
14. Do rotavirus vaccines contain a pig virus (porcine circovirus)?
In March 2010, DNA fragments of porcine circovirus were found in both globally licensed
rotavirus vaccines. Porcine circovirus is a small, circular virus composed of a single strand of
DNA. Porcine circovirus is not pig or animal material but a virus commonly found in pigs that
is not known to cause illness in humans.61 While porcine circovirus has sometimes been
referred to as the “pig virus” by the media, this is only because the virus is commonly found in
pigs.62 DNA from porcine circovirus can be found in an enzyme obtained from pig pancreas.
The DNA was found in rotavirus vaccines because this enzyme is used during some
manufacturing steps in the production of rotavirus vaccines.62
15. Is there a safety risk associated with the porcine circovirus that has been found in
rotavirus vaccines?
The US Food and Drug Administration (FDA), the European Medicines Agency (EMA), and
the World Health Organization (WHO) Global Advisory Committee on Vaccine Safety
(GACVS) reviewed the safety data from clinical trials and the spontaneous reports of porcine
circovirus and concluded that there was no evidence of a public health risk.47;48;63 Additionally,
the regulatory agencies and WHO found that all data supported the continued safety of the
vaccines and that the proven benefits of vaccination far outweighed any known risk associated
with use of rotavirus vaccines.49
16. Where can I find more information on porcine circovirus?
More information on porcine circovirus is available from:
US Food and Drug Administration: Information for Parents and Caregivers.47
• World Health Organization: Porcine circoviruses and rotavirus vaccines.63
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