SUPPLEMENT
Real-world Impact of Rotavirus Vaccination
Manish M. Patel, MSc, MD,* Duncan Steele, PhD,† Jon R. Gentsch, PhD,* John Wecker, PhD,†
Roger I. Glass, MD, PhD,* and Umesh D. Parashar, MB BS, MPH*
W orldwide, diarrhea is the second most common cause of fatal
childhood disease, estimated to cause approximately 1.34
million deaths among children aged ⬍5 years.1 Rotavirus is the
leading cause of severe diarrhea in young children and is respon-
sible for approximately one-third of all diarrheal deaths.2 Two
effective rotavirus vaccines, a single-strain attenuated human ro-
tavirus vaccine (Rotarix, GlaxoSmithKline Biologicals) and a
multistrain bovine-human reassortant vaccine (RotaTeq, Merck
and Company), are now available and recommended for routine
immunization of all infants by the World Health Organization
(WHO).3 Efficacy of these vaccines has ranged from 80% to 98%
in industrialized countries,4 –7 including Latin America, and 39%
to 77% in developing countries, such as Africa and Asia.8 –10 On
the basis of efficacy data from Europe and America, the WHO
initially approved use of the vaccines in these regions in 2006 and
within 2 years several countries added rotavirus vaccination into
their routine immunization programs. Subsequently, after proof of
efficacy in Asia and Africa, the WHO recommendation was
expanded to all infants worldwide in 2009.3
As rotavirus vaccines are implemented within national
childhood immunization programs, evaluation of their effect is
important for several reasons.11,12 First, routine immunization
occurs in real-world conditions different from ideal clinical trial
settings. Thus, monitoring postlicensure impact on rotavirus dis-
ease is crucial for ensuring that appropriate gains in terms of
expected vaccination benefits are attained. Second, changes in the
epidemiology of rotavirus disease might occur in the postlicensure
era, such as shifts in average age at infection, seasonality of
disease, and serotype distribution after vaccination or appearance
of unusual genetic variants. Third, ensuring that protection is
conferred through the first and second years of life when most
severe disease and mortality from rotavirus occur will be crucial
for the success of a rotavirus vaccination program. Finally, assess-
ing whether vaccination has an affect on rotavirus transmission in
the community, thus providing benefits to unvaccinated groups, is
important. Monitoring impact with focus on these public health
considerations will not only allow assessment of the effectiveness
of rotavirus vaccines in routine use, but also generate the necessary
evidence to inform public health policy decision-making and
continued investment in rotavirus vaccines.
The articles in this supplement elegantly describe the expe-
rience of early-introducer countries in Europe, America, and Aus-
tralia, and address these relevant postlicensure topics (Table 1).
The effect of rotavirus vaccines on burden of severe childhood
Accepted for publication September 28, 2010.
From the *National Center for Immunization and Respiratory Diseases, Centers for
Disease Control and Prevention, Atlanta, GA; and †PATH, Seattle, WA.
The findings and conclusions in this report are those of the authors and do not
necessarily represent the views of the Centers for Disease Control and
Prevention (CDC). This article did receive clearance through the appropriate
channels at the CDC prior to submission.
Address for correspondence: Manish M. Patel, MSc, MD, Viral Gastroenteritis
Section, MS-A47, Centers for Disease Control and Prevention, 1600 Clifton
Road, NE, Atlanta, GA 30333. E-mail: Aul3@CDC.GOV.
Copyright © 2010 by Lippincott Williams & Wilkins
ISSN: 0891-3668/11/3001-0001
DOI: 10.1097/INF.0b013e3181fefa1f
The Pediatric Infectious Disease Journal • Volume 30, Number 1, January 2011
diarrhea in these early introducer countries has been rapid, easily
measured, and substantial, demonstrating the health value of rota-
virus vaccination. Two of the most interesting and unanticipated
findings in the early rotavirus vaccine era have included indirect
protection and changes in rotavirus seasonality.13,14 The lessons
learned to-date will be valuable for other countries, considering the
introduction of rotavirus vaccines into their childhood immuniza-
tion programs.
HEALTH IMPACT OF ROTAVIRUS VACCINATION
Some of the questions related to vaccine performance,
duration of protection, and indirect benefits can be answered by
clinical trials, and targeted studies designed to specifically
address a priori study questions. However, a more cost-efficient
and practical assessment that comprehensively addresses the
question of whether the country investments are providing
intended results could include analysis of pre-existing databases
to assess issues suitable for the needs of decision-makers and
parents.12 The first set of articles in the supplement use existing
databases to evaluate the health impact of rotavirus vaccination in
a variety of low-middle, middle, and high income countries. Yen
et al demonstrate a large reduction in laboratory-confirmed rota-
virus disease that was sustained for 2 years after rotavirus vaccine
introduction in El Salvador, a low-middle income country in
Central America.15 Moreover, the substantial nationwide reduc-
tions in diarrhea from all causes, and of all severity, in this study
show the overall value of vaccination for improving child health in
developing regions of the world. In the neighboring country of
Mexico, where a previously published study showed a large
decline in diarrhea mortality after rotavirus vaccination,16 Quinta-
nar-Solares et al also reported significant reductions in hospital-
izations for childhood diarrhea during the winter months when
rotavirus predominates, confirming the value of investments in
vaccination in a large middle income setting.17 Similarly, impres-
sive reductions in all-cause diarrhea hospitalizations were also
observed by Molto et al in Panama, another middle-income coun-
try in the Americas.18 In the United States, Belgium, and Australia,
data from national passive surveillance systems of rotavirus testing
were evaluated by Tate et al,19 Braeckman et al,20 and Buttery et
al,21 respectively, to illustrate that rotavirus vaccination has dra-
matically reduced childhood rotavirus disease within a year or 2 of
vaccine introduction in these high income countries.
All in all, the countries represented in this section of the
supplement have a combined birth cohort of ⬃7 million infants,
most of whom are now receiving rotavirus vaccination. The
rigorous national-level data from these settings published in this
supplement provide a real-world measure of the large toll of
severe and fatal rotavirus disease that is preventable through
rotavirus vaccination of these infants. The observed reductions
in these early introducer countries suggest that the fraction of
diarrhea caused by rotavirus is greater than that estimated on
the basis of prevaccine surveillance, further emphasizing the
importance of rotavirus as one of the most common cause of
preventable childhood diseases.
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Patel et al The Pediatric Infectious Disease Journal • Volume 30, Number 1, January 2011

TABLE 1. Summary of Studies in the Current Supplement That Assess Health Impact, Indirect Benefits, or Strain
Changes After Rotavirus Vaccination

Location (Ref) Vaccine Key Findings Interpretation

Health impact
El Salvador RV1 ⬃35%– 48% decline in all cause diarrhea events The consistency of the findings across regions, predominantly
(15) (outpatient and inpatient) and ⬃69%– 81% during seasons when rotavirus predominates, with
decline in rotavirus hospitalizations among increasing effect among children in ages with the highest
children ⬍5 years vaccination rates strongly supports vaccination as the
Mexico (17) RV1 ⬃11%– 40% reduction in all cause diarrhea primary cause of the observed declines in diarrhea
hospitalizations among children ⬍5
Panama (18) RV1 ⬃22%–37% reduction in all cause diarrhea The sustained declines in disease for 2–3 year after
hospitalizations among children ⬍5 vaccination indicates that duration of protection in these
Belgium (20) RV1 ⬃65%– 83% reduction in rotavirus settings was sufficient to impact the youngest children
hospitalizations who bear the greatest burden of severe rotavirus diarrhe
Australia (21) RV1 & RV5 ⬃89%–94% vaccine efficacy against rotavirus Large declines in all-cause diarrhea hospitalizations indicate
hospitalizations among children ⬍5; 68%– that rotavirus may be a more important cause of childhood
93% reduction in under-1 rotavirus admits diarrhea than previously estimated
United States RV5* No rotavirus epidemic occurred in January–
(19) June 2010, the first time in 19 years of US
surveillance within this system
Indirect benefits
El Salvador RV1 ⬃41%– 68% decline during 2008 in children Indirect benefits of vaccination in the early (1–2) years after
(15) older than 2 yr who were unvaccinated vaccination suggests that young infants may be the
United States RV5* ⬃42%– 45% reduction among children too primary drivers of epidemic spread (at least in middle and
(23) young or old to be vaccinated high income settings)
Australia (21) RV1 & RV5 ⬎50% reduction in rotavirus hospitalizations In poorer countries such as El Salvador, the total protection
among children older than 2 years who were at a population level as a result of indirect benefits of
unvaccinated vaccination has the potential to offset the lower efficacy
directly afforded to the vaccine
Strain monitoring
Brazil (45) RV1 Increase in G2P关4兴 for 2 year after vaccination Epidemiologic assessments, such as case-control vaccine
effectiveness, and robust longitudinal surveillance are
needed to best assess interaction between rotavirus
vaccination and strain ecology
Australia (47) RV1 & RV5 G1P关8兴 was the predominant strain nationally, Existing strain surveillance data, vaccine effectiveness
however, some transient increase in G2P关4兴 results, and the dramatic declines in disease burden in
and G3P关8兴 prevalence occurred in Rotarix countries with rotavirus vaccination support natural
and RotaTeq states, respectively variation in strain ecology as the likely explanation for the
reported observations in short-term changes in strains
after vaccination
United States RV5* Higher prevalence of G3P关8兴 in some US cities Ongoing disease and strain surveillance is needed to assess
(46) after rotavirus vaccination longer term evolution in stain ecology and potential impact
on disease burden
*In the United States, RV5 was introduced in 2006, whereas RV1 was introduced in 2008; thus currently available impact data relate mostly to RV5.
RV5 indicates RotaTeq; RV1, Rotarix.

INDIRECT BENEFITS (IE, HERD IMMUNITY) AFTER
ROTAVIRUS VACCINATION
Indirect protection occurs as a result of decreased transmis-
sion of the infectious agent in the community, and amplifies the
direct benefits of vaccination among both vaccinated and unvac-
cinated individuals.22 From the perspective of other diseases
where large indirect benefits have been noted after routine
vaccination (eg, pneumococcal), perhaps the findings of indirect
benefits in El Salvador,15 United States,23 and Australia21 that
are published in this supplement should not be surprising.
However, the demonstration of indirect effects in several coun-
tries has led to a paradigm shift in our understanding of
rotavirus transmission. Rotavirus is a highly infectious patho-
gen, suspected to be transmitted through the fecal-oral route,
with repeat mild and asymptomatic infections being common
throughout life.24 –26 Although protection from natural rotavirus
infection against subsequent severe disease is high, protection
against infection and milder disease is lower.24 For these reasons,
secondary spread of rotavirus infection occurs at a high rate after
all primary and repeat infections, whether symptomatic or asymp-
tomatic, leading to the suspicion that interruption of transmission
would be unlikely to occur after rotavirus vaccination. However,
the postvaccination data from the early years after vaccination
indicate large reductions in rotavirus disease among members of
age groups who are too old to be vaccinated.13–15,21,23 Because
these indirect benefits are noted in the first or the second year after
vaccine introduction when only infants are eligible to receive
vaccination, these data potentially implicate infants as the primary
transmitters of infection. That is, not all rotavirus infections
transmit as efficiently as the first infection, which generally results
in the most severe disease.
Why is it important to measure indirect benefits? Perhaps
indirect benefits are less relevant in the longer term in industrial-
ized countries where efficacy and coverage exceed 90%. In con-
trast, in developing country settings, where efficacy and coverage
tend to be lower, a vaccine with indirect protection could provide
substantially greater benefits than expected on the basis of direct
efficacy. However, these vaccines would have to protect children
from infection, not just from severe disease, for indirect protection
to be realized. Although clinical trials show that rotavirus vaccines
protect against severe rotavirus disease, the level of vaccine
protection against infection is unknown in developing country
settings. Population level impact data could help improve our
understanding of rotavirus transmission dynamics in developing
country settings and realize the full potential of these vaccines. If
indirect benefits of rotavirus vaccination in industrialized settings

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The Pediatric Infectious Disease Journal • Volume 30, Number 1, January 2011
were replicated in other poor regions of the world, this would be
welcome news for oral rotavirus vaccines with lower efficacy in
these challenging populations.
CHANGING EPIDEMIOLOGY AND SEASONALITY
OF ROTAVIRUS DISEASE AFTER VACCINATION
Surveillance and disease monitoring after vaccine introduc-
tion can yield valuable information addressing issues relevant to a
broader public health perspective, including duration of protection,
changes in age-specific and seasonal incidence of disease, and
timing of epidemics.12 For example, although rotavirus vaccines
have shown sustained efficacy for first 2 to 3 years of life in the
United States and Europe,4 –7,27 preliminary data from developing
countries indicate decrease in protection after the first year of
life.8,10,28,29 However, from a public health perspective this de-
crease in protection may not be relevant for 2 reasons. First, a vast
proportion of severe rotavirus disease (60%– 80%) occurs by 12 to
15 months of age in these settings. Second, if indirect benefits
occur in African and Asian countries, and infants experiencing
their first rotavirus infection are the primary source of transmission
of rotavirus, a higher protection during the first year of life could
reduce transmission in the community and offset the effect of
waning immunity among older individuals. Findings from El
Salvador support this contention.15 In a recent study, vaccine
effectiveness in El Salvador decreased from 82% during infancy to
59% among those older than 1 year of age.28 However, the study
by Yen et al15 in this supplement indicated that the effect of the
reduced protection on the total burden of disease was minimal.
The postlicensure studies from various regions in this sup-
plement have also identified a remarkably consistent finding with
regard to timing and spread of epidemics. The studies from the
United States19 and Belgium20 show that in addition to the overall
decline in epidemic peak, a shift in the onset of the epidemic by 1
to 2 months has occurred after rotavirus vaccination— during the
2010 rotavirus season in the United States, rotavirus activity was
below the epidemic threshold, a finding that has never occurred in
the 19 years of rotavirus surveillance within that system.30,31 In
particular, Curns et al elegantly showed the impressive alterations
in the spatiotemporal spread of rotavirus disease in the United
States after vaccination.32 These findings might have some poten-
tial relevance for guiding surveillance programs in other countries.
First, biennial epidemic peaks have been predicted to occur after
rotavirus vaccination,33 thus emphasizing the need for ongoing
surveillance in countries such as the United States, where marked
reduction in disease has occurred in the first few years after
vaccination. Second, in countries with seasonal epidemics of
rotavirus, surveillance might need to be extended to the months of
the year when rotavirus is not typically expected, to fully under-
stand the public health importance of shifts in average age of cases
and timing of epidemics. Finally, postvaccination data are not
available from countries with less seasonal variation of rotavirus
disease, and will be important to gather for understanding the
epidemiological consequences of vaccination in those settings.
EFFECT OF VACCINATION ON ROTAVIRUS
STRAINS
Three inter-related questions remain with regard to effect of
vaccination on rotavirus strains. What is the serotype specific
efficacy of the vaccines? Will rotavirus vaccination cause an
emergence of unusual rotavirus strains or strains escaping vaccine
protection? Will significant increases in disease burden occur that
relate to strain changes after vaccination?
Two surface rotavirus proteins, VP7 (a glycoprotein—G
protein) and VP4 (a protease-cleaved protein—P protein), induce
© 2010 Lippincott Williams & Wilkins
Rotavirus Vaccine: Commentary
homotypic and heterotypic neutralizing antibody responses that are
suspected to partly provide protective immunity after natural
infection and vaccination.25,34 –36 However, it is important to note
that immunity to rotavirus is not fully understood, and other
rotavirus proteins (eg, VP6, NSP4) besides VP4 and VP7 have also
been suspected to modulate immunity. Surveillance has lead to the
characterization of at least 12 G types and 15 P types in human
beings and because rotavirus has a segmented genome, gene
reassortment could theoretically lead to almost 200 different G and
P combinations. However, while ⬎60 G-P combinations have
been found in human beings, 5 strains (P关8兴, G1; P关4兴, G2; P关8兴,
G3; P关8兴, G4; and P关8兴, G9) are associated with 80% to 90% of the
childhood rotavirus disease burden globally.37–39 Of these com-
mon strains, the P关4兴G2 rotavirus strain belongs to a different G
serotype, P subtype, and genogroup (defined by the total virus
genome of 11 segments and not only the G and P types40) than the
other globally common strains. Thus, P关4兴G2 strains also differ
from the human monovalent vaccine strain, Rotarix, by G- and
P-type and genogroup. P关4兴G2 strains also belong to a different P
subtype and genogroup compared with the bovine-human pentava-
lent vaccine, RotaTeq, which contains a G2 reassortant but not the
P关4兴 reassortant.41 Although the pentavalent vaccine contains ei-
ther the G or P antigen for all common strains, serotype-specific
immune response ranged from ⬃21% to 76% in the pivotal clinical
trial with the lowest response against the P关8兴G3 reference strain.4
Therefore, the question of either vaccine providing sufficient
cross-protection against the various strains is pertinent.
Similar to natural rotavirus infection, the pentavalent and
the single-strain rotavirus vaccines both provided good cross-
protection against the common circulating strains in trials in
Europe and the United States. In the Latin American trial, the
single-strain vaccine appeared to provide lesser protection against
the fully heterotypic P关4兴G2 rotavirus strains (vaccine efficacy ⫽
44%; 95% confidence interval 关CI兴 ⱕ0 – 88),6 but it is important to
note the wide confidence limits because the P关4兴G2 strain was not
circulating in Latin America during the study period; only 7 cases
of diarrhea occurred from this strain among the placebo group
during the entire study period, and thus the study did not attain
power to conclusively assess protection against this strain. How-
ever, in a 2-year efficacy study conducted in 6 European countries,
the single strain vaccine provided 85% protection (95% CI ⫽
24 –98) against severe rotavirus gastroenteritis caused by P关4兴G2
strains.5 This finding was confirmed in a postlicensure vaccine
effectiveness study from Brazil that was conducted during 2 years
when P关4兴G2 strain circulation predominated.42 In this study,
Rotarix effectiveness was 81% (95% CI ⫽ 47–93) against severe
rotavirus disease caused by this strain during the first year of life.
In a similar case-control study from Australia, during an outbreak
of P关4兴G2-related gastroenteritis among an indigenous population,
effectiveness of the single strain vaccine was 86% (95% CI ⫽
24 –98).43 The pentavalent vaccine has also been found to have high
efficacy against all strains circulating in the clinical trials.4 Of note, a
recently published postlicensure study from the United States re-
ported high effectiveness of this vaccine against severe disease
due to P关8兴G3 strain,44 against which lower neutralizing im-
mune responses were previously noted.4 In more recently pub-
lished trials from Asia and Africa, both vaccines had similar
efficacy against a wide range of strains circulating during the
study period.8,10
Against this background of good homo- and heterotypic
protection vis-à-vis common circulating strains, 3 nationwide lon-
gitudinal strain surveillance studies in this supplement address the
issue of strain ecology before and after routine childhood vacci-
nation. Carvalho-Costa et al identified a nationwide predominance
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Patel et al The Pediatric Infectious Disease Journal • Volume 30, Number 1, January 2011
of P关4兴G2 strains in the first 2 years after introduction of the single
strain vaccine in Brazil.45 In the United States, Hull et al noted a
surge in P关8兴G3 strains after introduction of the pentavalent
vaccine.46 In Australia, which uses both vaccines, Kirkwood et al
observed a higher prevalence of P关4兴G2 strains in states who were
exclusively using the single-strain vaccine compared with states
with pentavalent vaccine introduction that had a higher prevalence
of P关8兴G3 strains.47
Although intriguing, all authors appropriately caution
against any strong conclusions with regard to role of vaccination in
observing these strain changes postvaccination for several reasons.
First, similar findings of periodic strain emergence in the absence
of vaccination have been extensively documented in other settings
and will likely continue to occur in the postlicensure period.
Second, the strain changes in these settings were transient (1 or 2
years), and were followed by increase in prevalence of P关8兴G1,
which is covered by both vaccines. And finally, vaccine effective-
ness studies from all 3 settings have shown high effectiveness
against hospitalizations related to these predominant strains (ie,
P关4兴G2 in Brazil42 and Australia,43 and P关8兴G3 in the US44), and
large nationwide declines in overall disease burden have been
observed.14,48 These robust effectiveness data and the clinical trial
efficacy suggest that a natural shift in strain, unrelated to vaccina-
tion, is the most plausible explanation for the observed short-term
changes postvaccination. However, these studies highlight the
need for robust longitudinal surveillance and epidemiologic stud-
ies to better assess long-term interaction between rotavirus vacci-
nation and strain ecology. These longer term studies could help
assess whether the continued high level of immunity to vaccine
serotypes eventually leads to evolution of strains that evade vac-
cine immunity. Matthijnssens et al estimated that the worldwide
spread of such escape mutants may not take more than a decade,
supporting the need to conduct monitoring of strain ecology.49
WHERE DO WE GO FROM HERE?
Since the first introduction of rotavirus vaccines in national
immunization programs in 2006, dramatic reductions in severe and
fatal childhood diarrhea in a variety of low-middle, middle, and
high income countries have been observed. The preponderance of
existing data on vaccine efficacy and effectiveness support that
both vaccines provide protection against severe rotavirus disease
from a wide variety of circulating strains in industrialized and
developing countries. The decline in deaths and hospitalizations
after rotavirus vaccination in low-middle and middle income Latin
American countries is perhaps a good litmus test for adequacy of
vaccine performance in challenging target populations of Africa
and Asia. Despite the lower efficacy of the vaccines in developing
countries, trials have also shown that effect was greater in the
poorest settings in terms of the absolute number of severe cases of
rotavirus prevented through vaccination.9 It remains to be seen
whether vaccination reduces transmission in developing country
populations to a similar degree as observed in developed countries.
If this pattern holds, greater total effectiveness than expected on
the basis of direct protection could be attained in developing
country settings.
All in all, the powerful data published in this supplement
will allow parents, health care providers, and decision makers to
appreciate the health benefits of vaccination in reducing the burden
of severe rotavirus disease. Decision makers and donors world-
wide should urgently recognize that strong reasons exist to intro-
duce rotavirus vaccines today—these vaccines have had a substan-
tial affect on diarrhea deaths and hospitalizations; therefore, they
are recommended by WHO for all regions of the world; and donor
S4 | www.pidj.com
funding is available for the poorest nations. The time to introduce
these lifesaving interventions is now.
REFERENCES
1. Black RE, Cousens S, Johnson HL, et al. Global, regional, and national
causes of child mortality in 2008: a systematic analysis. Lancet. 2010;375:
1969 –1987.
2. Parashar UD, Burton A, Lanata C, et al. Global mortality associated with
rotavirus disease among children in 2004. J Infect Dis. 2009;200(suppl 1):
S9–S15.
3. WHO. Meeting of the strategic advisory group of experts on immunization,
October 2009 — conclusions and recommendations. Wkly Epidemiol Rec.
2009;84:518.
4. Vesikari T, Matson DO, Dennehy P, et al. Safety and efficacy of a
pentavalent human-bovine (WC3) reassortant rotavirus vaccine. N Engl
J Med. 2006;354:23–33.
5. Vesikari T, Karvonen A, Prymula R, et al. Efficacy of human rotavirus
vaccine against rotavirus gastroenteritis during the first 2 years of life in
European infants: randomised, double-blind controlled study. Lancet. 2007;
370:1757–1763.
6. Ruiz-Palacios GM, Perez-Schael I, Velazquez FR, et al. Safety and efficacy
of an attenuated vaccine against severe rotavirus gastroenteritis. N Engl
J Med. 2006;354:11–22.
7. Linhares AC, Velazquez FR, Perez-Schael I, et al. Efficacy and safety of an oral
live attenuated human rotavirus vaccine against rotavirus gastroenteritis during
the first 2 years of life in Latin American infants: a randomised, double-blind,
placebo-controlled phase III study. Lancet. 2008;371:1181–1189.
8. Zaman K, Dang DA, Victor JC, et al. Efficacy of pentavalent rotavirus
vaccine against severe rotavirus gastroenteritis in infants in developing
countries in Asia: a randomised, double-blind, placebo-controlled trial.
Lancet. 376:615– 623.
9. Madhi SA, Cunliffe NA, Steele D, et al. Effect of human rotavirus vaccine
on severe diarrhea in African infants. N Engl J Med. 2010;362:289 –298.
10. Armah GE, Sow SO, Breiman RF, et al. Efficacy of pentavalent rotavirus
vaccine against severe rotavirus gastroenteritis in infants in developing
countries in sub-Saharan Africa: a randomised, double-blind, placebo-
controlled trial. Lancet. 376:606 – 614.
11. WHO. Generic protocol for monitoring impact of rotavirus vaccination on
rotavirus disease burden and viral strains. Geneva: WHO; 2009:1–73.
Document WHO/IVB/0816.
12. Patel MM, Parashar UD. Assessing the effectiveness and public health
impact of rotavirus vaccines after introduction in immunization programs.
J Infect Dis. 2009;200(suppl 1):S291–S299.
13. Tate JE, Panozzo CA, Payne DC, et al. Decline and change in seasonality
of US rotavirus activity after the introduction of rotavirus vaccine. Pediat-
rics. 2009;124:465– 471.
14. Curns AT, Steiner CA, Barrett M, et al. Reduction in acute gastroenteritis
hospitalizations among US children after introduction of rotavirus vaccine:
analysis of hospital discharge data from 18 US states. J Infect Dis.
2010;201:1617–1624.
15. Yen CY, Guardado JA, Alberto P, et al. Decline in Rotavirus Hospitaliza-
tions and Health Care Visits for Diarrhea among Children ⬍5 Years of Age
following Implementation of Rotavirus Vaccination in El Salvador. Pediatr
Infect Dis. 20011;30:S6 –S10.
16. Richardson V, Hernandez-Pichardo J, Quintanar-Solares M, et al. Effect of
rotavirus vaccination on death from childhood diarrhea in Mexico. N Engl
J Med. 2010;362:299 –305.
17. Quintanar-Solares M, Yen CY, Esparza-Aguilar M, et al. Impact of rota-
virus vaccination on diarrhea-related hospitalizations among children ⬍5
years of age in Mexico. Pediatr Infect Dis. 2011;30:S11–S15.
18. Molto Y, Cortes JE, de Oliveira LH, et al. Reduction of diarrhea-associated
hospitalizations among children aged ⬍5 years in Panama following the
introduction of rotavirus vaccine. Pediatr Infect Dis. 2011;30:S16 –S20.
19. Tate J, Mutuc JD, Payne DC, et al. Sustained decline in rotavirus detections
in the United States following introduction of rotavirus vaccine in 2006.
Pediatr Infect Dis.2011;30:S30 –S34.
20. Braeckman T, Van Herck K, Raes M, et al. Rotavirus vaccines in Belgium:
policy and impact. Pediatr Infect Dis. 2011;30:S21–S24.
21. Buttery JP, Lambert SB, Grimwood K, et al. Reduction in Rotavirus-
associated Acute Gastroenteritis Following Introduction of Rotavirus Vac-
cine Into Australia’s National Childhood Vaccine Schedule. Pediatr Infect
Dis. 2011;30:S25–S29.
© 2010 Lippincott Williams & Wilkins
The Pediatric Infectious Disease Journal • Volume 30, Number 1, January 2011
22. Anderson RM, May RM. Immunisation and herd immunity. Lancet. 1990;
335:641– 645.
23. Tate J, Cortese M, Payne DC, et al. Uptake, impact, and effectiveness of
rotavirus vaccination in the United States—review of the first 3 years of
post-licensure data. Pediatr Infect Dis. 2011;30:S56 –S60.
24. Velazquez FR, Matson DO, Calva JJ, et al. Rotavirus infections in infants as
protection against subsequent infections. N Engl J Med. 1996;335:1022–1028.
25. Estes MK, Kapikian A. Rotaviruses. In: Knipe DM, Howley PM, Griffin
DE, et al, eds. Fields Virology. 5th ed. Philadelphia: Wolters Kluwer
Health/Lippincott Williams & Wilkins; 2007:1917–1974.
26. Anderson EJ, Weber SG. Rotavirus infection in adults. Lancet Infect Dis.
2004;4:91–99.
27. Vesikari T, Itzler R, Karvonen A, et al. RotaTeq, a pentavalent rotavirus
vaccine: efficacy and safety among infants in Europe. Vaccine. 2009;28:
345–351.
28. de Palma O, Cruz L, Ramos H, et al. Effectiveness of rotavirus vaccination
against childhood diarrhoea in El Salvador: case-control study. BMJ.
2010;340:c2825.
29. Patel M, Pedreira C, De Oliveira LH, et al. Association between pentavalent
rotavirus vaccine and severe rotavirus diarrhea among children in Nicara-
gua. JAMA. 2009;301:2243–2251.
30. Torok TJ, Kilgore PE, Clarke MJ, et al. Visualizing geographic and
temporal trends in rotavirus activity in the United States, 1991 to 1996.
National respiratory and enteric virus surveillance system collaborating
laboratories. Pediatr Infect Dis J. 1997;16:941–946.
31. Turcios RM, Curns AT, Holman RC, et al. Temporal and geographic trends
of rotavirus activity in the United States, 1997–2004. Pediatr Infect Dis J.
2006;25:451– 454.
32. Curns AT, Panozzo CA, Tate J, et al. Remarkable post-vaccination spatio-
temporal changes in United States rotavirus activity. Pediatr Infect Dis.
2011;30:S54 –S55.
33. Pitzer VE, Viboud C, Simonsen L, et al. Demographic variability, vacci-
nation, and the spatiotemporal dynamics of rotavirus epidemics. Science.
2009;325:290 –294.
34. Jiang V, Jiang B, Tate J, et al. Performance of rotavirus vaccines in
developed and developing countries. Hum Vaccin. 2010;6.
35. Perez-Schael I, Garcia D, Gonzalez M, et al. Prospective study of diarrheal
diseases in Venezuelan children to evaluate the efficacy of rhesus rotavirus
vaccine. J Med Virol. 1990;30:219 –229.
36. Perez-Schael I, Guntinas MJ, Perez M, et al. Efficacy of the rhesus
rotavirus-based quadrivalent vaccine in infants and young children in
Venezuela. N Engl J Med. 1997;337:1181–1187.
© 2010 Lippincott Williams & Wilkins
Rotavirus Vaccine: Commentary
37. Gentsch JR, Laird AR, Bielfelt B, et al. Serotype diversity and reassortment
between human and animal rotavirus strains: implications for rotavirus
vaccine programs. J Infect Dis. 2005;192(suppl 1):S146 –S159.
38. Matthijnssens J, Bilcke J, Ciarlet M, et al. Rotavirus disease and
vaccination: impact on genotype diversity. Future Microbiol. 2009;4:
1303–1316.
39. Santos N, Hoshino Y. Global distribution of rotavirus serotypes/genotypes
and its implication for the development and implementation of an effective
rotavirus vaccine. Rev Med Virol. 2005;15:29 –56.
40. Nakagomi O, Oyamada H, Kuroki S, et al. Molecular identification of a
novel human rotavirus in relation to subgroup and electropherotype of
genomic RNA. J Med Virol. 1989;28:163–168.
41. Bernstein DI, Ward RL. Rotarix: development of a live attenuated mono-
valent human rotavirus vaccine. Pediatr Ann. 2006;35:38 – 43.
42. Correia JB, Patel MM, Nakagomi O, et al. Effectiveness of monovalent
rotavirus vaccine (Rotarix) against severe diarrhea caused by serotypically
unrelated G2P关4兴 strains in Brazil. J Infect Dis. 2010;201:363–369.
43. Snelling TL, Andrews RM, Kirkwood CD, et al. Evaluation of the Mono-
valent human rotavirus vaccine RIX4414 following a G2P关4兴 outbreak
关abstract兴. Presented at: The 49th Annual Interscience Conference on
Antimicrobial Agents and Chemotherapy (ICAAC); September 12–15,
2009; San Francisco, CA.
44. Boom JA, Tate JE, Sahni LC, et al. Effectiveness of pentavalent rotavirus
vaccine in a large urban population in the United States. Pediatrics.
2010;125:e199 – e207.
45. Carvalho-Costa FA, Volotao E, Santos de Assis RM, et al. Laboratory-
based rotavirus surveillance during the introduction of a vaccination pro-
gram, Brazil, 2005–2009. Pediatr Infect Dis. 2011;30:S35–S41.
46. Hull JJ, Teel E, Kerin T, et al. United States rotavirus surveillance from
2005 to 2008: genotype prevalence before and after vaccine introduction.
Pediatr Infect Dis. 2011;30:S42–S47.
47. Kirkwood C, Boniface K, Barnes GL, et al. Distribution of Rotavirus
Genotypes after introduction of rotavirus vaccines, Rotarix and RotaTeq
into the national immunization program of Australia. Pediatr Infect Dis.
2011;30:S48 –S53.
48. Field EJ, Vally H, Grimwood K, et al. Pentavalent rotavirus vaccine and
prevention of gastroenteritis hospitalizations in Australia. Pediatrics. 2010;
126:e506 – e512.
49. Matthijnssens J, Heylen E, Zeller M, et al. Phylodynamic analyses of
rotavirus genotypes G9 and G12 underscore their potential for swift global
spread. Mol Biol Evol. 2010;27:2431–2436.
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