Original Article
Effect of Rotavirus Vaccination on Death from Childhood Diarrhea in Mexico
N Engl J Med 2010; 362:299-305January 28, 2010
- Abstract
Background
A phased introduction of a monovalent rotavirus vaccine occurred in Mexico from February 2006 through May 2007. We assessed the effect of vaccination on deaths from diarrhea in Mexican children in 2008 and 2009.
Methods
We obtained data on deaths from diarrhea, regardless of cause, from January 2003 through May 2009 in Mexican children under 5 years of age. We compared diarrhea-related mortality in 2008 and during the 2008 and 2009 rotavirus seasons with the mortality at baseline (2003–2006), before the introduction of the rotavirus vaccine. Vaccine coverage was estimated from administrative data.
Results
By December 2007, an estimated 74% of children who were 11 months of age or younger had received one dose of rotavirus vaccine. In 2008, there were 1118 diarrhea-related deaths among children younger than 5 years of age, a reduction of 675 from the annual median of 1793 deaths during the 2003–2006 period. Diarrhea-related mortality fell from an annual median of 18.1 deaths per 100,000 children at baseline to 11.8 per 100,000 children in 2008 (rate reduction, 35%; 95% confidence interval [CI], 29 to 39; P<0.001). Among infants who were 11 months of age or younger, diarrhea-related mortality fell from 61.5 deaths per 100,000 children at baseline to 36.0 per 100,000 children in 2008 (rate reduction, 41%; 95% CI, 36 to 47; P<0.001). As compared with baseline, diarrhea-related mortality was 29% lower for children between the ages of 12 and 23 months, few of whom were age-eligible for vaccination. Mortality among unvaccinated children between the ages of 24 and 59 months was not significantly reduced. The reduction in the number of diarrhea-related deaths persisted through two full rotavirus seasons (2008 and 2009).
Conclusions
After the introduction of a rotavirus vaccine, a significant decline in diarrhea-related deaths among Mexican children was observed, suggesting a potential benefit from rotavirus vaccination.
Media in This Article
Figure 1
Number of Diarrhea-Related Deaths among Children 59 Months of Age or Younger from July 2002 through May 2009 in Mexico, According to Age Group.Figure 2
Number of Diarrhea-Related Deaths per Month among Children 23 Months of Age or Younger after the Introduction of Rotavirus Vaccination in Mexico, as Compared with the Baseline Period (2003–2006).Article Activity
- Article
Despite the improved safety of food, water, and sanitation and the aggressive promotion of noninvasive interventions (e.g., oral rehydration therapy) and prevention strategies (e.g., increased breast-feeding), diarrhea remains the second leading infectious cause of childhood death worldwide, accounting for approximately 1.8 million annual deaths in children under 5 years of age.1 Rotavirus is the single most important cause of severe childhood diarrhea globally and annually causes more than half a million deaths among children under 5 years of age.2,3 In a large clinical trial conducted in Latin America, the monovalent human rotavirus vaccine Rotarix (GlaxoSmithKline Biologicals) showed a protective efficacy of 85% against severe rotavirus disease and of 42% against severe diarrhea from any cause.4-7 On the basis of these encouraging data, several countries in the Americas began including a rotavirus vaccine in their routine childhood immunization program in 2006.8,9
In Mexico, substantial reductions in diarrhea-related deaths and complications occurred from 1990 to 2002 as a result of improved sanitation and safe water, the promotion of breast-feeding and oral rehydration, and supplementation with a megadose of vitamin A.10-12 These measures have reduced the number of diarrhea-related deaths occurring in the spring and summer months that were attributable to bacterial pathogens, but deaths during the fall and winter months, when the prevalence of rotavirus is increased, have persisted.10 Because of the persistent burden of diarrhea-related deaths and hospitalizations from rotavirus, in 2006, Mexico became one of the first countries worldwide to introduce the monovalent rotavirus vaccine in its national immunization program.
Because prelicensure trials did not assess the effect of rotavirus vaccination on mortality from diarrhea, the assessment of whether the use of these vaccines will prevent diarrhea-related death is a high public health priority.13 In this study, we examined trends in diarrhea-related deaths among Mexican children before and after the introduction of rotavirus vaccination and correlated these trends with data on vaccine coverage.
Methods
Population
Mexico has an annual birth cohort of 1.9 million infants. In Mexico, vaccines for children are obtained by one of three health care institutions: the Ministry of Health through the National Center for Child and Adolescent Health (CENSIA) purchases vaccine for 50% of Mexican infants; Instituto Mexicano del Seguro Social (IMSS) purchases vaccine for all workers and their families, constituting approximately 43% of the Mexican population; and Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado (ISSSTE) purchases vaccine for all federal employees, representing approximately 7% of the population. In February 2006, the Ministry of Health introduced the monovalent rotavirus vaccine in impoverished regions of selected states in Mexico, accounting for less than 5% of the Mexican birth cohort. In November 2006, the vaccine was also made available for children who were insured through the IMSS, and in May 2007, the Ministry of Health extended the program to include all Mexican children born after February 1, 2007. It was recommended that infants receive two doses of vaccine, at 2 and 4 months of age.
Vaccine Coverage Data
There were no surveys of rotavirus vaccine coverage during the years of our study. However, as the supplier of vaccine for half of Mexican infants, CENSIA maintains administrative coverage data for this population. Thus, we assessed vaccination coverage data available through CENSIA for this cohort of children. CENSIA, which purchases and distributes the vaccine to the states, uses an electronic registration system through which the Mexican states (territorial jurisdictions and health centers) report on the number of vaccine doses that have been administered (either one or two doses for the rotavirus vaccine). The recording and reporting of doses generally follow the recommendations of the World Health Organization (WHO).
At the local level, clinic workers maintain a tally sheet for the number of administered vaccine doses. A supervisor is responsible for checking the quality of the data at the local level. Each month, the clinics report to the state the number of doses that have been administered. State health workers subsequently transmit the aggregated data to CENSIA. We used the administrative method to assess rates of vaccine coverage.14 The administrative method provides a crude estimate of coverage, which equals the annual number of doses administered, divided by the birth cohort that is eligible to receive vaccine purchased through CENSIA.
We calculated rotavirus vaccine coverage among children who were 11 months of age or younger and among those between the ages of 12 and 23 months at the end of 2007. A determination of vaccine coverage according to age at the end of 2007 allowed us to estimate the number of children who potentially would be protected from severe rotavirus disease during 2008.
Diarrhea-Related Deaths
For the period from January 2003 through May 2009, we obtained data on diarrhea-related deaths among Mexican children from the National Institute of Statistics, Geography, and Informatics and the Ministry of Health's General Directorate of Health Information, which collates all information from death certificates for children under 5 years of age. Data were accessed through the National System for Health Information.15 From these data, we abstracted information on diarrhea-related deaths, using the following codes from the International Classification of Diseases, 10th Revision: A00–A03, A04, A05, A06.0–A06.3, A06.9, A07.0–A07.2, A07.9, and A08–A09.
Effect of Rotavirus Vaccine
We calculated the median rate of diarrhea-related death for each of the surveillance years, using population estimates for Mexico from the National Population Council for those years. We compared the rate of diarrhea-related death in 2008 with baseline data from 2003 through 2006. We also compared the absolute number of diarrhea-related deaths during the peak rotavirus-season months of December through May in 2008 and 2009 with the median number of deaths during the same months in baseline years. Because the rotavirus vaccine was introduced in 2006 and early 2007, we considered 2007 as a transitional year and excluded it from our analysis.
Statistical Analysis
We stratified our analysis according to age group: 0 to 11 months, 12 to 23 months, and 24 to 59 months. We calculated 95% confidence intervals for the reduction in the death rate. A two-sided P value of less than 0.05, as calculated with a chi-square test, was considered to indicate statistical significance. Analyses were performed with the use of SAS statistical software, version 9.2, and Microsoft Excel.
Results
Vaccine Coverage
On the basis of CENSIA data, before the 2008 rotavirus season, 826,112 first doses and 565,797 second doses of monovalent rotavirus vaccine were administered in a target population that included 1.12 million infants who were 11 months of age or younger, for an overall vaccine coverage of 74% for the first dose and 51% for the second dose. Approximately 69,600 of the total doses (5%) were administered during 2006 in selected impoverished regions of 14 Mexican states. Because infants in these regions constitute less than 5% of the overall birth cohort in Mexico, it was unlikely that the vaccine program would have a major effect on the rate of diarrhea-related death nationwide. In addition, before the 2008 rotavirus season, CENSIA vaccine coverage was low among children between 12 and 23 months of age, with an estimated coverage of 4% for the first dose and 2% for the second dose in January 2008.
Diarrhea-Related Deaths
Of all diarrhea-related deaths in children under 5 years of age during the baseline years from 2003 through 2006, 67% occurred among infants who were 11 months of age or younger, 23% among those between 12 and 23 months of age, and 10% among those between 24 and 59 months of age. The rate of diarrhea-related death during the 2003–2006 period was markedly seasonal in both infants who were 11 months of age or younger and those between 12 and 23 months of age, with 65% of the deaths occurring from December through May (Figure 1Figure 1
Number of Diarrhea-Related Deaths among Children 59 Months of Age or Younger from July 2002 through May 2009 in Mexico, According to Age Group.). In 2008, the seasonal peak in diarrhea-related deaths appeared to be substantially blunted among infants who were 11 months of age or younger but not among children between 12 and 23 months of age. In 2009, the reduction in deaths was sustained among infants 11 months of age or younger but was also evident among children between 12 and 23 months of age.During the 2003–2006 period, an annual median of 1793 diarrhea-related deaths (range, 1464 to 2002) was reported in Mexico among children under 5 years of age, for a median annual rate of diarrhea-related death of 18.1 per 100,000 children; the median rates per 100,000 children were 19.6 in 2003, 17.7 in 2004, 18.7 in 2005, and 15.1 in 2006. During 2008, the number of diarrhea-related deaths among children in this age group fell by 675 to a total of 1118, for a rate of death of 11.8 per 100,000 children, a relative reduction of 35% (95% confidence interval [CI], 29 to 39; P<0.001) (Table 1Table 1
Changes in Diarrhea-Related Mortality among Children 59 Months of Age or Younger in 2008 in Mexico, as Compared with the Baseline Period (2003–2006), According to Age Group.).The decline in the rate of diarrhea-related death in 2008 was greatest among infants who were 11 months of age or younger, from a median of 61.5 per 100,000 children during the 2003–2006 period to 36.0 per 100,000 children in 2008, a relative reduction of 41% (95% CI, 36 to 47; P<0.001) (Table 1). In this age group, there were 680 deaths in 2008, as compared with 1197 during the baseline years, a reduction of 517 deaths. Among children between 12 and 23 months of age in 2008, there was also a significant decline in the number of diarrhea-related deaths, from 421 to 285 deaths, with a decrease in the rate per 100,000 children of 21.1 to 15.0, a relative reduction of 29% (95% CI, 17 to 39; P<0.001). In contrast, among children between 24 and 59 months of age, the decline in the number of diarrhea-related deaths, from 175 to 153, was not significant, with a relative rate reduction from 2.9 to 2.7, or 7% (95% CI, –14 to 26; P=0.44).
Among infants who were 11 months of age or younger, the peak in diarrhea-related deaths during the rotavirus-season months of December through May was substantially reduced in 2008 and 2009, as compared with both the median and the minimum number of deaths during these months in the 2003–2006 period (Figure 2Figure 2
Number of Diarrhea-Related Deaths per Month among Children 23 Months of Age or Younger after the Introduction of Rotavirus Vaccination in Mexico, as Compared with the Baseline Period (2003–2006).). During 2008, there was an absolute reduction of 517 deaths among infants 11 months of age or younger (Table 1). Of this reduction, 355 deaths (69%) were averted from December through May, from 789 deaths at baseline to 434 (Figure 3Figure 3
Number of Diarrhea-Related Deaths among Children 23 Months of Age or Younger during Rotavirus Seasons in 2008 and 2009, as Compared with the Baseline Period (2003–2006).); an additional 162 deaths (31%) were averted between June and November. The reduction persisted and was greater during the 2009 rotavirus season, when 520 fewer deaths occurred, a relative reduction of 66% as compared with baseline (Figure 3).Among children between 12 and 23 months of age, the peak in diarrhea-related deaths occurred 1 to 2 months later during the 2008 rotavirus season than during the baseline period but was substantially blunted during the 2009 rotavirus season (Figure 2). As compared with the 290 diarrhea-related deaths in this age group during the baseline rotavirus season, the number of deaths during the rotavirus season was 184 in 2008 (a relative reduction of 37%) and 92 in 2009 (a relative reduction of 68%) (Figure 3).
Discussion
The recent addition of a monovalent rotavirus vaccine to Mexico's routine childhood immunization program may have contributed to a reduction in deaths related to diarrhea from any cause among Mexican children. These findings provide strong suggestive evidence of the beneficial effects of the vaccine against fatal illness from rotavirus. In the first two rotavirus seasons after the immunization program began, we noted a large reduction in the absolute number of deaths related to diarrhea from any cause, as compared with the prevaccine baseline period. Approximately two thirds of this reduction in mortality occurred during the months of December through May, when 62 to 68% of laboratory-confirmed cases of rotavirus diarrhea requiring hospitalization are reported to occur in Mexico.10 Given that a third of the cases of severe rotavirus disease in Mexico occur between June and November, our finding of a reduction during these months is not unexpected.
Although our ecologic analysis cannot provide definitive evidence that vaccination prevented deaths, the notable blunting of the typical seasonal peak in diarrhea-related deaths during two consecutive rotavirus seasons, especially among infants who were 11 months of age or younger and who received the greatest vaccine coverage, supports the premise that vaccination may have contributed to the reduction in diarrhea-related mortality. Moreover, because of the increasing number of older vaccinated children in 2009, the increased relative reduction in deaths among children between 12 and 23 months of age during the 2009 season (68%), as compared with the reduction of 37% in 2008, also supports a vaccine effect. Secular trends in declining mortality from diarrhea in Mexican children because of other factors (e.g., improvements in hygiene, sanitation, and access to care) also may have contributed to the decline, but the marked reduction in diarrhea-related deaths in 2008 and 2009, as compared with 2006, suggests that such environmental factors are unlikely to fully account for the decline. If the reduction in disease is sustained during future years, these data will provide an estimate of the vaccine-preventable burden of childhood diarrhea-related deaths attributable to rotavirus before the introduction of vaccine.
Our findings must be interpreted with some caveats. First, we did not have precise vaccine-coverage estimates for Mexico and could not quantify the reduction in the number of diarrhea-related deaths attributable to vaccination. Our vaccine-coverage estimates were based on data for children who were eligible to receive vaccine purchased by the Ministry of Health (through CENSIA) and did not reflect coverage estimates for all of Mexico. However, because CENSIA data account for approximately 50% of infants in Mexico, and because vaccine was made available to children who were insured through IMSS 6 months before it was available to those covered by CENSIA, these coverage estimates could underestimate nationwide coverage.
Second, secular variations in disease, including changes in coding practices, might also have affected the trends in diarrhea-related deaths. In addition, underreporting of diarrhea-related death is likely but would have been similar during the periods before and after the introduction of the vaccination program. The WHO estimates that approximately 3100 diarrhea-related deaths occur annually among children under the age of 5 years in Mexico,2 and it is possible that many of these deaths occur outside the hospital, perhaps in impoverished areas where residents have limited access to health care. Access to vaccine and the effect of vaccination might differ between these areas and developed regions and thus warrant further assessment.
Third, because of challenges in obtaining fecal specimens to confirm the cause of diarrhea in children who died (especially since most deaths occurred outside medical facilities), we were unable to examine trends in deaths from rotavirus specifically. Nevertheless, the marked winter seasonality of rotavirus in Mexico10 that was mimicked by the seasonal pattern of all diarrhea-related deaths allowed us to indirectly assess the effect of vaccination on the rate of death.
Finally, although case–control studies would provide a more specific measure of the effectiveness of vaccine in reducing mortality than ecologic assessments, such assessments are difficult, given the inherent diagnostic challenges in identifying rotavirus-related deaths.16
The significant reduction in diarrhea-related mortality among children between 12 and 23 months of age during 2008 was intriguing. Before 2008, vaccine coverage was less than 5% in this age group among children who were vaccinated through CENSIA. Although we did not have coverage data for IMSS, only 10 to 15% of the children between 12 and 23 months of age nationwide would have been age-eligible for rotavirus immunization before 2008. Thus, although vaccine uptake in these children might account for some reduction, the substantial decline of 29% in mortality from diarrhea from any cause in children between 12 and 23 months of age raises the possibility that vaccination may have reduced transmission of rotavirus disease in Mexico and induced herd protection. A recent analysis of severe nonfatal rotavirus disease in the United States also showed a decline that was substantially greater than expected on the basis of vaccination rates alone, including a reduction in disease among children who were not age-eligible for vaccination.17,18 Besides direct benefits to vaccinated infants, it is possible that vaccination of a proportion of the population could reduce overall transmission of rotavirus in the community and thus also lead to a reduction in the rate of disease among unvaccinated children.
In summary, our findings indicate an encouraging reduction in diarrhea-related mortality among Mexican children during two consecutive rotavirus seasons after the addition of a rotavirus vaccine to the childhood immunization schedule. Ongoing monitoring of diarrhea-related deaths and epidemiologic case–control studies of vaccine effectiveness against hospitalization for such illness would be useful for confirming the association between a reduction in severe diarrhea-related events with vaccine introduction. Although cautious interpretation is required, the results of our assessment indicate that routinely collected data on mortality related to diarrhea from any cause could prove to be a useful source of monitoring of the effect of rotavirus vaccination.
The findings and conclusions in this article are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention.
No potential conflict of interest relevant to this article was reported.
Source Information
From the National Center for Child and Adolescent Health, Ministry of Health, Mexico City (V.R., J.H.-P., M.Q.-S., M.E.-A., C.M.G.-A.); and the National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta (B.J., U.P., M.P.).
Address reprint requests to Dr. Patel at the Centers for Disease Control and Prevention, 1600 Clifton Rd., MS A-47, Atlanta, GA 30333, or at mpatel@cdc.gov.
- References
References
1
Bryce J ,Boschi-Pinto C ,Shibuya K ,Black RE . WHO estimates of the causes of death in children. Lancet 2005;365:1147-1152
CrossRef | Web of Science | Medline2
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
CrossRef | Web of Science | Medline3
Parashar UD ,Gibson CJ ,Bresse JS ,Glass RI . Rotavirus and severe childhood diarrhea. Emerg Infect Dis 2006;12:304-306
Web of Science | Medline4
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
CrossRef | Web of Science | Medline5
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
Full Text | Web of Science | Medline6
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
CrossRef | Web of Science | Medline7
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
Full Text | Web of Science | Medline8
Patel M ,Pedreira C ,De Oliveira LH , et al. Association between pentavalent rotavirus vaccine and severe rotavirus diarrhea among children in Nicaragua. JAMA 2009;301:2243-2251
CrossRef | Web of Science | Medline9
de Oliveira LH ,Danovaro-Holliday MC ,Matus CR ,Andrus JK . Rotavirus vaccine introduction in the Americas: progress and lessons learned. Expert Rev Vaccines 2008;7:345-353
CrossRef | Web of Science | Medline10
Velazquez 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:Suppl:S149-S155
CrossRef | Medline11
Villa S ,Guiscafre H ,Martinez H ,Munoz O ,Gutierrez G . Seasonal diarrhoeal mortality among Mexican children. Bull World Health Organ 1999;77:375-380
Web of Science | Medline12
Gonzalez-Cossio T ,Moreno-Macias H ,Rivera JA , et al. Breast-feeding practices in Mexico: results from the Second National Nutrition Survey 1999. Salud Publica Mex 2003;45:Suppl 4:S477-S489
CrossRef | Web of Science | Medline13
Glass RI ,Parashar UD ,Bresee JS , et al. Rotavirus vaccines: current prospects and future challenges. Lancet 2006;368:323-332
CrossRef | Web of Science | Medline14
Burton A ,Monasch R ,Lautenbach B , et al. WHO and UNICEF estimates of national infant immunization coverage: methods and processes. Bull World Health Organ 2009;87:535-541
CrossRef | Web of Science | Medline15
Secretaría de Salud, Instituto Nacional de Estadística, Geografía e Informatica. Mortalidad (INEGI). Dirección general de información en salud, Secretaría de Salud (México). (Accessed December 31, 2009, at http://sinais.salud.gob.mx/basesdedatos/index.html.)
16
Generic protocol for monitoring impact of rotavirus vaccination on rotavirus disease burden and viral strains: document WHO/IVB/0816. Geneva: World Health Organization, 2009:1-73.
17
Tate JE ,Panozzo CA ,Payne DC , et al. Decline and change in seasonality of US rotavirus activity after the introduction of rotavirus vaccine. Pediatrics 2009;124:465-471
CrossRef | Web of Science | Medline18
Parashar UD ,Glass RI . Rotavirus vaccines -- early success, remaining questions. N Engl J Med 2009;360:1063-1065
Full Text | Web of Science | Medline
- Citing Articles (55)
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1
Nicole Le Saux, Julie Bettinger, Pierre Déry, Joanne Embree, Wendy Vaudry, Scott A. Halperin, Andrew McDermid, Timothy F. Booth, Doug Coyle. (2012) The Hidden Costs and Characteristics of Childhood Rotavirus Emergency Visits in Canada. The Pediatric Infectious Disease Journal 31:2, 159-163
CrossRef2
Penelope H. Dennehy. (2012) Effects of vaccine on rotavirus disease in the pediatric population. Current Opinion in Pediatrics 24:1, 76-84
CrossRef3
Jacqueline E Tate, Manish M Patel, Margaret M Cortese, Benjamin A Lopman, Jon R Gentsch, Jessica Fleming, A Duncan Steele, Umesh D Parashar. (2012) Remaining issues and challenges for rotavirus vaccine in preventing global childhood diarrheal morbidity and mortality. Expert Review of Vaccines 11:2, 211-220
CrossRef4
Tomás López, Daniela Silva-Ayala, Susana López, Carlos F. Arias. (2012) Methods suitable for high-throughput screening of siRNAs and other chemical compounds with the potential to inhibit rotavirus replication. Journal of Virological Methods 179:1, 242-249
CrossRef5
Carlo Giaquinto, Amy E.M. Jackson, Timo Vesikari. (2011) Report of the Second European Expert Meeting on Rotavirus Vaccination. Vaccine
CrossRef6
Rolando Ulloa-Gutierrez, Greta Miño, Carla Odio, María L Avila-Aguero, José Brea. (2011) Vaccine-preventable diseases and their impact on Latin American children. Expert Review of Vaccines 10:12, 1671-1673
CrossRef7
Miguel O’Ryan, Yalda Lucero, Alexandre C Linhares. (2011) Rotarix ® : vaccine performance 6 years postlicensure. Expert Review of Vaccines 10:12, 1645-1659
CrossRef8
Magda Campins Martí, Fernando A. Moraga-Llop. (2011) Vacunas antirrotavirus. Un largo y difícil camino. Gastroenterología y Hepatología 34:10, 694-700
CrossRef9
Esmeralda Vizzi, Oscar Piñeros, Germán Gabriel González, José L. Zambrano, Juan E. Ludert, Ferdinando Liprandi. (2011) Genotyping of human rotaviruses circulating among children with diarrhea in Valencia, Venezuela. Journal of Medical Virology 83:12, 2225-2232
CrossRef10
Vicente Bayard, Rodrigo DeAntonio, Rodolfo Contreras, Olga Tinajero, Maria Mercedes Castrejon, Eduardo Ortega-Barría, Romulo E. Colindres. (2011) Impact of rotavirus vaccination on childhood gastroenteritis-related mortality and hospital discharges in Panama. International Journal of Infectious Diseases
CrossRef11
D. Moreno-Pérez, F.J. Álvarez García, J. Arístegui Fernández, F. Barrio Corrales, M.J. Cilleruelo Ortega, J.M. Corretger Rauet, J. González-Hachero, T. Hernández-Sampelayo Matos, M. Merino Moína, L. Ortigosa del Castillo, J. Ruiz-Contreras. (2011) Calendario de vacunaciones de la Asociación Española de Pediatría: recomendaciones 2012. Anales de Pediatría
CrossRef12
D. Moreno-Pérez, F.J. Álvarez García, J. Aristegui Fernández, F. Barrio Corrales, M.J. Cilleruelo Ortega, J.M. Corretger Rauet, J. González-Hachero, T. Hernández-Sampelayo Matos, M. Merino Moína, L. Ortigosa del Castillo, J. Ruiz-Contreras. (2011) Immunization schedule of the Spanish Association of Pediatrics: 2012 recommendations. Anales de Pediatría
CrossRef13
Kosuke Kawai, Megan A. O’Brien, Michelle G. Goveia, T. Christopher Mast, Antoine C. El Khoury. (2011) Burden of rotavirus gastroenteritis and distribution of rotavirus strains in Asia: A systematic review. Vaccine
CrossRef14
V. E. Pitzer, C. Viboud, B. A. Lopman, M. M. Patel, U. D. Parashar, B. T. Grenfell. (2011) Influence of birth rates and transmission rates on the global seasonality of rotavirus incidence. Journal of The Royal Society Interface 8:64, 1584-1593
CrossRef15
Douglas H. Esposito, Robert C. Holman, Dana L. Haberling, Jacqueline E. Tate, Laura Jean Podewils, Roger I. Glass, Umesh Parashar. (2011) Baseline Estimates of Diarrhea-associated Mortality Among United States Children Before Rotavirus Vaccine Introduction. The Pediatric Infectious Disease Journal 30:11, 942-947
CrossRef16
Y. H. Doan, T. Nakagomi, N. A. Cunliffe, B. D. Pandey, J. B. Sherchand, O. Nakagomi. (2011) The occurrence of amino acid substitutions D96N and S242N in VP7 of emergent G2P[4] rotaviruses in Nepal in 2004-2005: a global and evolutionary perspective. Archives of Virology 156:11, 1969-1978
CrossRef17
Greg L. Plosker. (2011) Rotavirus Vaccine RIX4414 (Rotarix™). PharmacoEconomics 29:11, 989-1009
CrossRef18
M. Aubert, H. Aumaître, J. Beytout, K. Bloch, D. Bouhour, P. Callamand, C. Chave, J. Cheymol, B. Combadière, A. Dahlab, F. Denis, L. De Pontual, B. Dodet, M.-A. Dommergues, V. Dufour, A. Gagneur, J. Gaillat, J. Gaudelus, G. Gavazzi, Y. Gillet, C. Gras-le-Guen, H. Haas, T. Hanslik, I. Hau-Rainsard, S. Larnaudie, O. Launay, M. Lorrot, P. Loulergue, D. Malvy, S. Marchand, G. Picherot, D. Pinquier, C. Pulcini, C. Rabaud, F. Regnier, P. Reinert, C. Sana, C. Savagner, B. Soubeyrand, J.-L. Stephan, C. Strady. (2011) Actualités en matière de vaccination. Archives de Pédiatrie 18:11, 1234-1246
CrossRef19
Sean Fitzwater, Aruna Chandran, Margaret Kosek, Mathuram Santosham. 2011. Infectious Diarrhea. , 47-70.
CrossRef20
J. Clemens. (2011) Evaluation of vaccines against enteric infections: a clinical and public health research agenda for developing countries. Philosophical Transactions of the Royal Society B: Biological Sciences 366:1579, 2799-2805
CrossRef21
Jacqueline E Tate, Anthony H Burton, Cynthia Boschi-Pinto, A Duncan Steele, Jazmin Duque, Umesh D Parashar. (2011) 2008 estimate of worldwide rotavirus-associated mortality in children younger than 5 years before the introduction of universal rotavirus vaccination programmes: a systematic review and meta-analysis. The Lancet Infectious Diseases
CrossRef22
Ricardo Q. Gurgel, Chinenye Ilozue, Jailson B. Correia, Chiara Centenari, Sandala M. T. Oliveira, Luis E. Cuevas. (2011) Impact of rotavirus vaccination on diarrhoea mortality and hospital admissions in Brazil. Tropical Medicine & International Health 16:9, 1180-1184
CrossRef23
Rebecca L. McClarren, Brodi Lynch, Neelima Nyayapati. (2011) Acute Infectious Diarrhea. Primary Care: Clinics in Office Practice 38:3, 539-564
CrossRef24
C. Yen, J. R. Figueroa, E. S. Uribe, L. d. Carmen-Hernandez, J. E. Tate, U. D. Parashar, M. M. Patel, V. Richardson Lopez-Collado. (2011) Monovalent Rotavirus Vaccine Provides Protection Against an Emerging Fully Heterotypic G9P[4] Rotavirus Strain in Mexico. Journal of Infectious Diseases 204:5, 783-786
CrossRef25
Richardson, Vesta, , Parashar, Umesh, Patel, Manish, . (2011) Childhood Diarrhea Deaths after Rotavirus Vaccination in Mexico. New England Journal of Medicine 365:8, 772-773
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Patel, Manish M.López-Collada, Vesta RichardsonBulhões, Marília MattosDe Oliveira, Lucia HelenaMárquez, Aurora BautistaFlannery, BrendanEsparza-Aguilar, MarcelinoMontenegro Renoiner, Ernesto IsaacLuna-Cruz, María EdiliaSato, Helena KeicoHernández-Hernández, Luz del CarmenToledo-Cortina, GerardoCerón-Rodríguez, MagdalenaOsnaya-Romero, NeydiMartínez-Alcazar, MarioAguinaga-Villasenor, Rocío GabrielaPlascencia-Hernández, ArturoFojaco-González, FranciscoHernández-Peredo Rezk, GuillermoGutierrez-Ramírez, Sixto FortinoDorame-Castillo, RobertoTinajero-Pizano, RogelioMercado-Villegas, BerniceBarbosa, Marilia ReicheltMaluf, Eliane Mara CesárioFerreira, Lucimar Bozzade Carvalho, Francisca Mariados Santos, Ana RosaCesar, Eduardo Dolabellade Oliveira, Maria Elisa PaulaOsterno Silva, Carmem Lúciade los Angeles Cortes, MariaRuiz Matus, CuauhtemocTate, JacquelineGargiullo, PaulParashar, Umesh D.. (2011) Intussusception Risk and Health Benefits of Rotavirus Vaccination in Mexico and Brazil. New England Journal of Medicine 364:24, 2283-2292
Full Text27
Greenberg, Harry B., . (2011) Rotavirus Vaccination and Intussusception — Act Two. New England Journal of Medicine 364:24, 2354-2355
Full Text28
Shasta D. McClenahan, Philip R. Krause, Christine Uhlenhaut. (2011) Molecular and infectivity studies of porcine circovirus in vaccines. Vaccine 29:29-30, 4745-4753
CrossRef29
M. Aubert, H. Aumaître, J. Beytout, K. Bloch, D. Bouhour, P. Callamand, C. Chave, J. Cheymol, B. Combadière, A. Dahlab, F. Denis, L. De Pontual, B. Dodet, M.-A. Dommergues, V. Dufour, A. Gagneur, J. Gaillat, J. Gaudelus, G. Gavazzi, Y. Gillet, C. Gras-le-Guen, H. Haas, T. Hanslik, I. Hau-Rainsard, S. Larnaudie, O. Launay, M. Lorrot, P. Loulergue, D. Malvy, S. Marchand, G. Picherot, D. Pinquier, C. Pulcini, C. Rabaud, F. Regnier, P. Reinert, C. Sana, C. Savagner, B. Soubeyrand, J.-L. Stephan, C. Strady.. (2011) Actualités en matière de vaccination. Médecine et Maladies Infectieuses 41:5, 278-290
CrossRef30
J.-M. Garnier, E. Grimprel, R. Cohen. (2011) Vaccins rotavirus : résultats et effets secondaires. Archives de Pédiatrie 18:5, H188-H189
CrossRef31
Marcelo Takahiro Mitui, Paul K.S. Chan, E. Anthony S. Nelson, Ting Fan Leung, Akira Nishizono, Kamruddin Ahmed. (2011) Co-dominance of G1 and emerging G3 rotaviruses in Hong Kong: A three-year surveillance in three major hospitals. Journal of Clinical Virology 50:4, 325-333
CrossRef32
Alexandre C. Linhares, Juan A. Stupka, Agustín Ciapponi, Ariel E. Bardach, Demián Glujovsky, Patricia K. Aruj, Agustina Mazzoni, Jefferson A. Buendía Rodriguez, Analía Rearte, Tatiana M. Lanzieri, Eduardo Ortega-Barria, Romulo Colindres. (2011) Burden and typing of rotavirus group A in Latin America and the Caribbean: systematic review and meta-analysis. Reviews in Medical Virology 21:2, 89-109
CrossRef33
Karla Soares-Weiser, Harriet MacLehose, Irit Ben-Aharon, Elad Goldberg, Femi Pitan, Nigel Cunliffe. (2011) Cochrane review: Vaccines for preventing rotavirus diarrhoea: vaccines in use. Evidence-Based Child Health: A Cochrane Review Journal 6:2, 567-754
CrossRef34
Mercedes Paredes-Paredes, Pablo C. Okhuysen, Jose Flores, Jamal A. Mohamed, Ranjit S. Padda, Alexei Gonzalez-Estrada, Clinton A. Haley, Lily G. Carlin, Parvathy Nair, Herbert L. DuPont. (2011) Seasonality of Diarrheagenic Escherichia coli Pathotypes in the US Students Acquiring Diarrhea in Mexico. Journal of Travel Medicine 18:2, 121-125
CrossRef35
Leila C. Sahni, Julie A. Boom. (2011) Commentary on “Vaccines for preventing rotavirus diarrhoea: vaccines in use”. Evidence-Based Child Health: A Cochrane Review Journal 6:2, 757-758
CrossRef36
Tatiana M. Lanzieri, Alexandre C. Linhares, Iolanda Costa, Devayani A. Kolhe, Maria Helena Cunha, Eduardo Ortega-Barria, Romulo E. Colindres. (2011) Impact of rotavirus vaccination on childhood deaths from diarrhea in Brazil. International Journal of Infectious Diseases 15:3, e206-e210
CrossRef37
Nigel W Crawford, Julie E Bines, Jenny Royle, Jim P Buttery. (2011) Optimizing immunization in pediatric special risk groups. Expert Review of Vaccines 10:2, 175-186
CrossRef38
Carl D. Kirkwood, Karen Boniface, Graeme L. Barnes, Ruth F. Bishop. (2011) Distribution of Rotavirus Genotypes After Introduction of Rotavirus Vaccines, Rotarix® and RotaTeq®, into the National Immunization Program of Australia. The Pediatric Infectious Disease Journal 30, S48-S53
CrossRef39
Manjari Quintanar-Solares, Catherine Yen, Vesta Richardson, Marcelino Esparza-Aguilar, Umesh D. Parashar, Manish M. Patel. (2011) Impact of Rotavirus Vaccination on Diarrhea-related Hospitalizations Among Children <5 Years of Age in Mexico. The Pediatric Infectious Disease Journal 30, S11-S15
CrossRef40
Manish M. Patel, Duncan Steele, Jon R. Gentsch, John Wecker, Roger I. Glass, Umesh D. Parashar. (2011) Real-world Impact of Rotavirus Vaccination. The Pediatric Infectious Disease Journal 30, S1-S5
CrossRef41
YanMei Yang, Xia Li, Hui Yang, Yuan Qian, You Zhang, RongXiang Fang, XiaoYing Chen. (2011) Immunogenicity and virus-like particle formation of rotavirus capsid proteins produced in transgenic plants. Science China Life Sciences 54:1, 82-89
CrossRef42
Christa L Fischer Walker, Robert E Black. (2011) Rotavirus vaccine and diarrhea mortality: quantifying regional variation in effect size. BMC Public Health 11:Suppl 3, S16
CrossRef43
Robert F Breiman, George Armah, K Zaman, Samba Sow, Dang Duc Anh, Max Ciarlet, Kathleen M Neuzil. (2010) Rotavirus vaccine efficacy in African and Asian countries – Authors' reply. The Lancet 376:9756, 1898
CrossRef44
Manish M. Patel, Jacqueline Tate, Margaret Cortese, Daniel C. Payne, Greg Armstrong, Umesh D. Parashar, Ben Lopman. (2010) The impact of indirect benefits of vaccination on postlicensure vaccine effectiveness estimates: A scenario analysis. Vaccine 28:50, 7987-7992
CrossRef45
Andrew C Serazin, Laura A Shackelton, Christopher Wilson, Maharaj K Bhan. (2010) Improving the performance of enteric vaccines in the developing world. Nature Immunology 11:9, 769-773
CrossRef46
E Anthony S Nelson, Roger I Glass. (2010) Rotavirus: realising the potential of a promising vaccine. The Lancet 376:9741, 568-570
CrossRef47
Bo Zhou, Yongliang Zhang, Xianbing Wang, Jiangli Dong, Bin Wang, Chenggui Han, Jialin Yu, Dawei Li. (2010) Oral administration of plant-based rotavirus VP6 induces antigen-specific IgAs, IgGs and passive protection in mice. Vaccine 28:37, 6021-6027
CrossRef48
Keith Grimwood, Stephen B. Lambert, Richard J. Milne. (2010) Rotavirus Infections and Vaccines. Pediatric Drugs 12:4, 235-256
CrossRef49
George E Armah, Samba O Sow, Robert F Breiman, Michael J Dallas, Milagritos D Tapia, Daniel R Feikin, Fred N Binka, A Duncan Steele, Kayla F Laserson, Nana A Ansah, Myron M Levine, Kristen Lewis, Michele L Coia, Margaret Attah-Poku, Joel Ojwando, Stephen B Rivers, John C Victor, Geoffrey Nyambane, Abraham Hodgson, Florian Schödel, Max Ciarlet, Kathleen M Neuzil. (2010) 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. The Lancet 376:9741, 606-614
CrossRef50
V. Schuster. (2010) Rückgang der Rotavirusgastroenteritis nach breiter Anwendung der Schluckimpfung. Prävention und Gesundheitsförderung 5:S1, 10-15
CrossRef51
Karla Soares-Weiser, Harriet MacLehose, Irit Ben-Aharon, Elad Goldberg, Femi Pitan, Nigel Cunliffe, Karla Soares-Weiser. 2010. Vaccines for preventing rotavirus diarrhoea: vaccines in use. .
CrossRef52
Jacqueline E Tate, Manish M Patel, A Duncan Steele, Jon R Gentsch, Daniel C Payne, Margaret M Cortese, Osamu Nakagomi, Nigel A Cunliffe, Baoming Jiang, Kathleen M Neuzil, Lucia H de Oliveira, Roger I Glass, Umesh D Parashar. (2010) Global impact of rotavirus vaccines. Expert Review of Vaccines 9:4, 395-407
CrossRef53
Rachel Jones. (2010) Infection: Rotavirus vaccination shows beneficial effects in Mexican and African children. Nature Reviews Gastroenterology & Hepatology 7:4, 181-181
CrossRef54
(2010) News in brief. Nature Medicine 16:3, 252-253
CrossRef55
Santosham, Mathuram, . (2010) Rotavirus Vaccine — A Powerful Tool to Combat Deaths from Diarrhea. New England Journal of Medicine 362:4, 358-360
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