Sustained Reduction of Childhood Diarrhea-Related Mortality and Hospitalizations in Mexico After Rotavirus Vaccine Universalization
Sustained Reduction of Childhood Diarrhea-Related Mortality and Hospitalizations in Mexico After Rotavirus Vaccine Universalization
Correspondence: M. Esparza-Aguilar 1
National Center for Child 1
Adolescent Health 1
Min- istry of Health 1
Francisco de P. Miranda 1 2
nd Flr 1
Mexico City 1
Mexico (marea.b 1 3
@ gmail.com) . Clinical Infectious Diseases® 1
0 National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention , Atlanta , Georgia
1 The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions , e-mail
2 National Center for Child and Adolescent Health, Ministry of Health, Faculty of Medicine, National Autonomous University of Mexico , Mexico City
3 Ministry of Health, State of Morelos , Cuernavaca
Background. Mexico implemented routine childhood vaccination against rotavirus in 2007. We describe trends in hospitalization and deaths from diarrhea among children aged <5 years in Mexico before and 7 years after implementation of rotavirus vaccination. Methods. We obtained data on deaths and hospitalizations from diarrhea, from January 2003 through December 2014, in Mexican children <5 years of age. We compared diarrhea-related mortality and hospitalizations in the postvaccine era with the prevaccine baseline from 2003 to 2006. Results. Compared with the prevaccine baseline, we observed a 53% reduction (95% confidence interval [CI], 47%-58%) in diarrhea-related mortality and a 47% reduction (95% CI, 45%-48%) in diarrhea-related hospitalizations in postvaccine years, translating to 959 deaths and 5831 hospitalizations averted every year in Mexican children aged <5 years. Prevaccine peaks in diarrhearelated mortality and hospitalizations during the rotavirus season months were considerably diminished in postvaccine years, with greater declines observed during the rotavirus season compared with non-rotavirus season months. Conclusions. We document a substantial and sustained decline in diarrhea-related hospitalizations and deaths in Mexican children associated with implementation of rotavirus vaccination. These results highlight the public health benefits that could result in countries that adopt rotavirus vaccination into their national immunization programs.
Worldwide, diarrheal disease remains a leading cause of death
in children aged <5 years (hereafter “under 5”) . Rotavirus is
the most common cause of severe diarrhea in children and is
most frequently associated with cases of dehydration,
hospitalization, and death . Globally, it is responsible for about 40% of
all diarrhea-related hospitalizations and was estimated to cause
453 000 deaths in 2008 [2, 3]. Rotavirus infection has a strong
seasonal pattern [4, 5]; in Mexico, approximately 60%–70% of
the hospitalizations for laboratory-confirmed rotavirus
infection occur during the months of October–March [6, 7].
RotaTeq (Merck & Co, Whitehouse Station, New Jersey) and
Rotarix (GlaxoSmithKline Biologicals, Rixensart, Belgium), the
2 rotavirus vaccines available on the global market, have been
shown to be safe and effective in large-scale prelicensure studies
[8–17]. Since the recommendation of the World Health
Organization to introduce rotavirus vaccines into every country’s
national immunization program (NIP), >75 countries have
implemented rotavirus vaccines [18, 19]. Mexico was one of
the first nations to introduce, in May 2007, the rotavirus vaccine
in its national immunization program. Rotarix was used during
the first 5 years (2006–2011), administered in a 2-dose schedule.
In 2011, due to known similar efficacy for both vaccines, a
complete-schedule price competition was set by the government,
and monovalent vaccine was substituted with pentavalent
vaccine, RotaTeq, administered on a 3-dose schedule.
Monitoring the impact of rotavirus immunization against
diarrhea deaths and hospitalizations during routine use will be
important to better understand the potential of these vaccines.
Two years after implementation of rotavirus vaccination, a 35%
reduction in the mortality rate and a 40% reduction in the
hospitalization rate from diarrhea were observed in children under
5. These reductions were significant in children aged 0–23
months, but not in children aged 24–59 months [20, 21]. Once
4 annual cohorts were vaccinated with the monovalent vaccine
by 2010, the reduction in mortality was 50%, with a significant
reduction in all subgroups of children under 5 and with no
differences across regions with different socioeconomic levels of
Mexico [22, 23]. In this study, we include an additional 3 years of
postvaccine data to describe trends in hospitalization and deaths
from diarrhea among children under 5 in Mexico before and
7 years after implementation of universal rotavirus vaccination.
All-Cause and Diarrhea-Related Hospitalizations
We accessed data from the Ministry of Health’s National System
for Health Information to obtain monthly data on all-cause and
diarrhea-related hospitalizations among children aged <5 years,
from January 2003 to December 2014, for all of Mexico’s 677
Ministry of Health hospitals. These hospitals cover about 50%
of the hospitalizations nationwide in public hospitals.
International Classification of Diseases, Tenth Revision (ICD-10) codes
A00–A03, A04, A05, A06.0–A06.3, A06.9, A07.0–A07.2, A07.9,
and A08–A09 were used to select diarrhea-related
hospitalizations. No attempt was made to evaluate hospitalizations
specifically caused by rotavirus infection because there is no systematic
laboratory testing for rotavirus in children hospitalized for
diarrhea in Mexico.
For the period from January 2003 through December 2014, we
obtained data on diarrhea-related deaths among Mexican
children under 5 from the National Institute of Statistics,
Geography, and Informatics and the Ministry of Health’s General
Directorate of Health Information, which collects information
from all death certificates. We used the same ICD-10 codes
used to select diarrhea hospitalizations to select diarrhea-related
The Mexico National Health and Nutrition Survey for 2012
reports coverage with a complete rotavirus vaccine schedule of
63% for children <1 year and 80% for those <2 years of age
. Coverage from the National Health and Nutrition Survey
2012 could be underestimated due to underreporting of doses
applied in the national immunization and health card .
Other studies using administrative coverage data (doses
administered/the estimated target population) have estimated
the coverage rate for a complete vaccine series to be 90% for
children aged <1 year [22, 23, 25]. Administrative coverage
could be imprecise because the estimated population, in some
scenarios, could be higher or lower than the number of actual
Prevaccine and Postvaccine Periods
The prevaccine period was defined as January 2003 to
December 2006; 2007 was considered a transition year after vaccine
introduction. Postvaccine period was considered according to age
group to account for the moment when the first vaccinated
cohort reached the age group: <12 months from January 2008 to
December 2014, 12–23 months from January 2009 to December
2014, and 24–59 months from January 2010 to December 2014.
In addition, according to the timing of detection of rotavirus in
sentinel laboratory surveillance in Mexico, we defined the
rotavirus season as occurring from November to March.
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All analyses were restricted to children <5 years of age and were
stratified by age: ≤11 months, 12–23 months, and 24–59
months. National Population Council population estimates
were used as denominators .
We compared median annual diarrhea mortality rates and
median annual absolute number of diarrhea-related deaths in
the prevaccine and postvaccine periods. We also compared
the median absolute number and rate of diarrhea-related deaths
during the peak rotavirus season in the prevaccine and
Overall numbers of diarrhea-related hospitalizations from
January 2003 to December 2014 were examined. Because the
catchment populations of the study hospitals were not known,
rates of hospitalization for diarrhea per 100 hospitalizations
from all causes were calculated. The median annual rate of
diarrhea-related hospitalizations in the prevaccine period was
compared with the postvaccine period. To improve specificity
of vaccination effect on rotavirus disease, we also restricted
our analysis to hospitalizations during the rotavirus season
among children <5 years of age.
Diseases recorded on the same information systems where we
obtain the deaths and hospitalizations due to diarrhea were used
as controls to show that the reduction effect seen in diarrhea
mortality and hospitalizations was not an artifact of the record
or an unspecific trend. As controls we have included congenital
heart malformation mortality for diarrhea deaths, and
hospitalization due to injuries for diarrhea hospitalizations.
We estimated the national reductions in diarrhea-related
hospitalizations that could reasonably be attributed to the
rotavirus vaccinations by extrapolating the rates of diarrhea-related
hospitalization per 100 all-cause admissions—observed in the
Ministry of Health hospitals, which attend to about 50% of
the population—to the total number of hospital admissions
for all causes observed countrywide.
We calculated 95% confidence intervals (CIs) for the rate
reductions in diarrhea-related deaths and diarrhea-related
hospitalizations by CI for comparing 2 independent proportions. A
2-sided P value of <.05, as calculated with a χ2 test, was
considered significant. Analyses were performed with Microsoft Excel
(Microsoft Corporation, Redmond, Washington).
From January 2003 to December 2014, there were 14 808
registered deaths in Mexican children under 5, with 66.2% occurring
in children 0–11 months, 22.3% in children 12–23 months, and
11.5% in children 24–59 months of age. Monthly mortality
showed the strong seasonal pattern of high peaks in cold
months from January to April, mainly in the prevaccine period.
After the introduction and universalization of the rotavirus
vaccines, seasonal peaks were drastically reduced and
seasonality become less evident (Figure 1).
In the prevaccine years, there was a median number of 1198
diarrhea-related deaths annually in children 0–11 months, 421
in children 12–23 months, and 175 in children 24–59 months of
age, with median annual mortality rates of 52.7, 18.6, and 2.6
deaths per 100 000, respectively. In the postvaccine period, the
median number of annual deaths was reduced to 563 in
children 0–11 months, 158 in children 12–23 months, and 114 in
children 24–59 months of age, with median annual mortality
rates of 25.4, 7.1, and 1.7 deaths per 100 000, respectively. This
represents significant reductions in the mortality rate of 52%
(96% CI, 45%–59%), 62% (96% CI, 50%–73%), and 34% (96%
CI, 15%–55%) in children 0–11 months, 12–23 months, and
24–59 months of age, respectively. Overall in children under 5,
we observed a 53% reduction (95% CI, 47%–58%) in
diarrhearelated mortality rates post–vaccine introduction, with about
959 deaths averted every year in children under 5 (Table 1).
The reductions were more evident when the analysis was
restricted to the rotavirus season, showing a reduction in
mortality rate of 67% in children under 5 during the rotavirus season,
which highlights the impact on the diarrhea mortality of the
rotavirus vaccination (Table 2).
As a control, in the same population, in the same information
system, in the same periods, mortality due to congenital heart
malformations did not show any reduction (Table 1; Figure 1).
From January 2003 to December 2014, there were 189 837
diarrhea-related hospitalizations in children under 5, with 42.3%
Deaths 959 635 264
Absolute Reduction Death Rate (No. of Deaths per 100 000 Under-5 Children)
Median Annual No. of Diarrhea-Related Deaths
Median Annual DiarrheaRelated Death Rate (No. of Deaths per 100 000 Under-5 Children)
Postvaccine 835 563 158
Prevaccine 15.8 52.7 18.6
Postvaccine 7.5 25.4 7.1
Median No. of
Death Rate (No. of
Deaths per 100 000
Absolute Reduction in
No. of Deaths per 100 000
Prevaccine Postvaccine Prevaccine Postvaccine 997 684 241
Relative Reduction in Death Rate, % (95% CI)
P values were calculated with the use of a χ2 test. Negative values imply relative increase. Prevaccine period was defined as January 2003 to December 2006.
Abbreviation: CI, confidence interval.
occurring in children 0–11 months, 32.2% in children 12–23
months, and 25.4% in children 24–59 months of age. Monthly
hospitalization rates also showed a clear seasonal pattern of high
peaks in cold months, mainly in the prevaccine period. After
the introduction of rotavirus vaccines, seasonal peaks were
considerably reduced, with declines sustained throughout the
postvaccine period (Figure 2).
In prevaccine years, the median number of annual
hospitalizations was 8212 in children 0–11 months, 5823 in children
12–23 months, and 3728 in children 24–59 months of age,
with median annual hospitalization proportions of 5.6, 20.2,
and 7.9 hospitalizations per 100 hospitalizations in children
of these ages, respectively. In the postvaccine periods, the
median number of annual hospitalizations was reduced to 4926 in
children 0–11 months, 3445 in children 12–23 months, and
3562 in children 24–59 months of age, even when the total
number of hospitalizations increased by 26%. These median
frequencies corresponded to median annual hospitalization proportions
of 2.7, 10.2, and 5.5 diarrhea patients per 100 hospitalizations,
respectively. This represents significant reductions in
hospitalizations of 52% (96% CI, 50%–54%), 49% (96% CI, 47%–52%),
and 30% (96% CI, 26%–34%) in children 0–11 months, 12–23
months, and 24–59 months of age, respectively. Overall, in
children under 5, we estimate a 47% reduction (95% CI, 45%–48%)
in diarrhea-related hospitalizations, with about 5831
hospitalizations averted every year in children under 5 in Ministry of Health
(MOH) hospitals (about 11 662 in the country). As a control, in
the same population, in the information system, in the same
periods, hospitalizations due to injuries did not show a significant
important reduction (Figure 2; Table 3).
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Median Annual No. of
Hospitalizations Age Group
Median Annual DiarrheaRelated Hospitalizations, % Prevaccine 8.0
Absolute Reduction Proportion of Hospitalizations 3.7
In prevaccine years, 55% of diarrhea-related hospitalizations
occurred during the rotavirus season. After the introduction of
the rotavirus vaccine, during the rotavirus season, diarrhea-related
hospitalizations decreased 66% in children under 5, with
reductions of 68% in the group of 0–11 months and 12–23 months.
In postvaccine years, only 33% of all diarrhea-related
hospitalizations occur during the rotavirus season, showing a specific impact
of the rotavirus vaccines with more important reductions in the
rotavirus seasons (Table 4).
Rotavirus vaccine has contributed significantly toward reaching
the Millennium Development Goal 4 target in counties where
rotavirus vaccines have been introduced .
After the implementation of universal rotavirus vaccination
in Mexico in 2007, substantial declines in childhood diarrhea
deaths and admissions were observed [20–23]. Seven years
after the introduction of rotavirus vaccines in the NIP, diarrhea
mortality continues to decrease, with a decline of 53% in
diarrhea deaths, representing about 6328 averted deaths since
vaccine introduction. All-cause diarrhea-related hospitalizations
have also declined since 2007, with the highest impact observed
during rotavirus seasons. During these months, a reduction of
66% was seen for all diarrhea hospitalizations, with 37 050
hospitalizations adverted during fall/winter seasons in MOH
hospitals, and about 74 099 in the country.
We examined all-cause diarrhea-related deaths and
hospitalizations, as we did not have verifiable information on
laboratory-confirmed rotavirus events. Consequently, the results could
be affected by secular trends in diarrhea related to other
pathogens to some extent. Nevertheless, the seasonal pattern of all
diarrhea-related deaths and hospitalizations follow the same
fall/winter seasonality of rotavirus, allowing us to indirectly
assess the effect of vaccination on the mortality and the
proportion of diarrhea-related hospitalizations. In addition, the
stepped shape of the reduction by age groups, as they became
vaccine eligible, support the effect of the rotavirus vaccine. In
initial reports, no statistically significant reduction was observed
in diarrhea mortality or diarrhea hospitalizations in children
24–59 months of age. It was not until the entire annual cohort
of under-5 children was vaccinated that reduction was observed
in the group of children 24–59 months of age. Finally, there was
a noticeable flattening of the seasonal peaks in diarrhea
mortality and diarrhea-related hospitalizations, with the greatest
decrease seen during the rotavirus season, further supporting a
role for rotavirus vaccination in the observed decline.
During Rotavirus Season
Median No. of
Related Hospitalizations Median Diarrhea-Related Hospitalizations, Proportion Age Group
P values were calculated with the use of a χ2 test.
Abbreviation: CI, confidence interval.
Absolute Reduction Proportion of Hospitalization 6.4 4.8
Additionally, the data sources we used may have been subject
to some underreporting and classification error. Nevertheless,
underreporting would likely be similar during the periods
before and after the introduction of the vaccination program,
and thus unlikely to produce major bias. Furthermore, to
exclude the possibility of bias from changes in the reporting
system, we used other conditions as a control, and it was
reassuring that these control conditions did not demonstrate any
Our findings are in accord with other Latin American findings,
with decreases of 17%–55% in all-cause diarrhea hospitalizations
and effectiveness against rotavirus diarrhea hospitalizations
ranging from 17% to 94% [28–33]. Mexico’s reductions in
diarrhearelated deaths are similar to other Latin American countries,
which report a decline of 22%–50% [32, 34, 35]. These results
highlight the public health benefits that could result in countries
that adopt rotavirus vaccination as part of their NIPs.
In summary, we documented a substantial and sustained
decline in diarrhea-related hospitalizations and deaths in Mexican
children associated with implementation of rotavirus
vaccination. These data highlight the real-world value of vaccination
and should encourage other countries to consider vaccination
as a strategy to reduce the burden of severe childhood diarrhea.
Disclaimer. The findings and conclusions in this report are those of the
authors and do not necessarily represent the official position of the Centers
for Disease Control and Prevention (CDC). The views expressed by the
authors do not necessarily reflect the views of PATH, the CDC Foundation, the
Bill and Melinda Gates Foundation, or GAVI, the Vaccine Alliance.
Supplement sponsorship. This article appears as part of the supplement
“Health Benefits of Rotavirus Vaccination in Developing Countries,”
sponsored by PATH and the CDC Foundation through grants from the Bill and
Melinda Gates Foundation and GAVI, the Vaccine Alliance.
Potential conflicts of interest. All authors: No reported conflicts. All
authors have submitted the ICMJE Form for Disclosure of Potential
Conflicts of Interest. Conflicts that the editors consider relevant to the content
of the manuscript have been disclosed.
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 - 87 .
2. Kotloff KL , Nataro JP , Blackwelder WC , et al. Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): a prospective, case-control study . Lancet 2013 ; 382 : 209 - 22 .
3. Tate JE , Burton AH , Boschi-Pinto C , et al. 2008 estimate of worldwide rotavirusassociated mortality in children younger than 5 years before the introduction of universal rotavirus vaccination programmes: a systematic review and metaanalysis . Lancet Infect Dis 2012 ; 12 : 136 - 41 .
4. Villa S , Guiscafré H , Martínez H , Muñoz O , Gutiérrez G . Seasonal diarrhoeal mortality among Mexican children . Bull World Health Organ 1999 ; 77 : 375 - 80 .
5. Kapikian AZ , Kim HW , Wyatt RG , et al. Human reovirus-like agent as the major pathogen associated with “winter” gastroenteritis in hospitalized infants and young children . N Engl J Med 1976 ; 294 : 965 - 72 .
6. Velázquez FR , Garcia-Lozano H , Rodriguez E , et al. Diarrhea morbidity and mortality in Mexican children: impact of rotavirus disease . Pediatr Infect Dis J 2004 ; 23 (10 suppl): S149 - 55 .
7. Velázquez FR , Calva JJ , Guerrero ML , et al. Cohort study of rotavirus serotype patterns in symptomatic and asymptomatic infections in Mexican children . Pediatr Infect Dis J 1993 ; 12 : 54 - 61 .
8. Ruiz-Palacios GM , Pérez-Schael I , Velázquez R , Abate H , Breuer T , et al. Safety and efficacy of an attenuated vaccine against severe rotavirus gastroenteritis . N Engl J Med 2006 ; 354 : 11 - 22 .
9. Vesikari T , Matson DO , Dennehy P , Van Damme P , Santosham M , et al. Safety and efficacy of a pentavalent human-bovine (WC3) reassortant rotavirus vaccine . N Engl J Med 2006 ; 354 : 23 - 33 .
10. Iwata S , Nakata S , Ukae S , et al. Efficacy and safety of pentavalent rotavirus vaccine in Japan: a randomized, double-blind, placebo-controlled, multicenter trial . Hum Vaccin Immunother 2013 ; 9 : 1626 - 33 .
11. 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 2010 ; 376 : 615 - 23 .
12. Armah GE , Sow SO , Breiman RF , et al. Efficacy of pentavalent rotavirus vaccine against severe rotavirus gastroenteritis in infants in developing countries in subSaharan Africa: a randomised, double-blind, placebo-controlled trial . Lancet 2010 ; 376 : 606 - 14 .
13. Sow SO , Tapia M , Haidara FC , et al. Efficacy of the oral pentavalent rotavirus vaccine in Mali . Vaccine 2012 ; 30 (suppl 1): A71 - 8 .
14. Salinas B , Pérez Schael I , Linhares AC , et al. Evaluation of safety, immunogenicity and efficacy of an attenuated rotavirus vaccine, RIX4414: a randomized, placebo-controlled trial in Latin American infants . Pediatr Infect Dis J 2005 ; 24 : 807 - 16 .
15. 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 - 63 .
16. Ruiz-Palacios GM , Guerrero ML , Bautista-Márquez A , et al. Dose response and efficacy of a live, attenuated human rotavirus vaccine in Mexican infants . Pediatrics 2007 ; 120 : e253 - 61 .
17. Tate JE , Parashar UD . Rotavirus vaccines in routine use . Clin Infect Dis 2014 ; 59 : 1291 - 301 .
18. Patel MM , Steele D , Gentsch JR , Wecker J , Glass R , Parashar UD . Real-world impact of rotavirus vaccination . Pediatr Infect Dis J 2011 ; 30 ( 1 suppl): S1 - 5 .
19. Health Section of the Secretariat of the League of Nations. Conclusions and recommendations from the Immunization Strategic Advisory Group . Wkly Epidemiol Rec 2006 ; 81 : 2 - 11 .
20. 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 .
21. Quintanar-Solares M , Yen C , Richardson V , Esparza-Aguilar M , Parashar UD , Patel MM . Impact of rotavirus vaccination on diarrhea-related hospitalizations among children <5 years of age in Mexico . Pediatr Infect Dis J 2011 ; 30 ( 1 suppl): S11 - 5 .
22. Gastañaduy PA , Sánchez-Uribe E , Esparza-Aguilar M , et al. Effect of rotavirus vaccine on diarrhea mortality in different socioeconomic regions of Mexico . Pediatrics 2013 ; 131 : e1115 - 20 .
23. Esparza-Aguilar M , Gastañaduy PA , Sánchez-Uribe E , et al. Diarrhoearelated hospitalizations in children before and after implementation of monovalent rotavirus vaccination in Mexico . Bull World Health Organ 2014 ; 92 : 117 - 25 .
24. Gutierrez JP , Rivera-Dommarco J , Shamah-Levy T , et al. Encuesta Nacional de Salud y Nutrición 2012 . Resultados nacionales . Cuernavaca, México: Instituto Nacional de Salud Publica , 2012 .
25. Díaz-Ortega JL , Ferreira-Guerrero E , Trejo-Valdivia B , et al. Vaccination coverage in children and adolescents in Mexico: vaccinated, under vaccinated and non vaccinated [in Spanish] . Salud Publica Mex 2013 ; 55 (suppl 2): S289 - 99 .
26. Consejo Nacional de Población. Proyecciones de la población nacional 2010-2050 . México City: CONAPO , 2012 . Available at: http://www.conapo.gob.mx/es/ CONAPO/Proyecciones. Accessed 18 August 2015 .
27. Bustreo F , Okwo-Bele JM , Kamara L. World Health Organization perspectives on the contribution of the Global Alliance for Vaccines and Immunization on reducing child mortality . Arch Dis Child 2015 ; 100 (suppl 1): S34 - 7 .
28. Desai R , Oliveira LH , Parashar UD , Lopman B , Tate JE , Patel MM . Reduction in morbidity and mortality from childhood diarrhoeal disease after species A rotavirus vaccine introduction in Latin America-a review . Mem Inst Oswaldo Cruz 2011 ; 106 : 907 - 11 .
29. Yen C , Armero Guardado JA , Alberto P , et al. Decline in rotavirus hospitalizations and health care visits for childhood diarrhea following rotavirus vaccination in El Salvador . Pediatr Infect Dis J 2011 ; 30 ( 1 suppl): S6 - 10 .
30. do Carmo GM , Yen C , Cortes J , et al. Decline in diarrhea mortality and admissions after routine childhood rotavirus immunization in Brazil: a time‐series analysis . PLoS Med 2011 ; 8 : e1001024 .
31. Safadi MA , Berezin EN , Munford V , et al. Hospital‐based surveillance to evaluate the impact of rotavirus vaccination in Sao Paulo , Brazil. Pediatr Infect Dis J 2010 ; 29 : 1019 - 22 .
32. Gurgel RG , Bohland AK , Vieira SC , et al. Incidence of rotavirus and all‐cause diarrhea in northeast Brazil following the introduction of a national vaccination program . Gastroenterology 2009 ; 137 : 1970 - 5 .
33. 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 J 2011 ; 30 ( 1 suppl): S16 - 20 .
34. Lanzieri TM , Linhares AC , Costa I , et al. Impact of rotavirus vaccination on childhood deaths from diarrhea in Brazil . Int J Infect Dis 2011 ; 15 : e206 - 10 .
35. Bayard V , DeAntonio R , Contreras R , et al. Impact of rotavirus vaccination on childhood gastroenteritis‐related mortality and hospital discharges in Panama . Int J Infect Dis 2012 ; 16 : e94 - 8 .