Table 2. Methodological characteristics of health impact assessments of rotavirus vaccination programs conducted in Latin American and Caribbean countries, based on secondary data (vital statistics, health services utilization or surveillance data).

Author/Year	Country	Study design/Methodological comments	Data source	Clinical syndrome	Outcome	Main results
Secondary data
De Oliveira11 (2013)	Bolivia, El Salvador, Honduras, and Venezuela	Ecological (interrupted time-series analysis) Control: Argentina, which still had not introduced the vaccine into its national immunization program during the study period	Databases of the sentinel surveillance network of rotavirus diarrhea and records on hospitalizations and deaths from the ministries of health	All-cause diarrhea	Number of deaths and hospitalizations	Reductions in diarrhea-related deaths and hospitalization in all four countries as opposed to the control country
Rissardo45 (2010)	Brazil (Parana state)	Ecological (comparison of years before and after vaccine introduction) Limitations: short observation period after vaccine introduction; lack of adjustment for secular trends	National health information system on hospitalizations	All-cause diarrhea	Number and rates of hospitalizations	Significant decrease of diarrhea-related hospitalizations observed in children under one year of age after vaccine introduction. No impact evidenced among children aged one to four years
Do Carmo9 (2011)	Brazil	Ecological (interrupted time-series analysis, comparing event rates after vaccine introduction with expected rates estimated from prevaccine years) Adjustment for secular and seasonal trends	National mortality information system; national hospital information system, which covers the public health system	All-cause diarrhea	Mortality and hospitalization rates	Decreased rates of under-five diarrhea-related mortality and hospital admissions in the first three years after vaccine introduction, with largest reduction among children under two years of age
Lanzieri29 (2011)	Brazil	Ecological (comparison of years before and after vaccine introduction) Limitations: lack of adjustment for secular trends	Mortality information system; live birth information system	All-cause diarrhea	Mortality rates	Decreasing rates of diarrhea-related deaths previous to vaccine introduction
Gurgel22 (2011)	Brazil	Ecological (comparison of trends before and after vaccine introduction) Limitations: lack of adjustment for secular trends	National hospital information system (public health system)	All-cause diarrhea	Hospitalizations and deaths	Reduction in hospitalizations preceded the vaccine introduction
Fernandes17 (2014)	Brazil (Sao Paulo state)	Ecological (comparison of years before and after vaccine introduction)	National health information system (public health system)	All-cause diarrhea	Hospitalization rates by the human development index of each municipality and diarrhea-related hospitalization costs	Decreased rates of hospitalizations among under-five children in all categories of municipal development, with greater decrease in the least developed areas. Seasonal blunting in diarrhea hospitalizations. Savings in hospitalization costs in all municipal categories
Esparza-Aguilar14 (2009)	Mexico	Ecological (comparison of years before and after vaccine introduction)	National health information systems on mortality and population	All-cause diarrhea	Number of deaths and cumulative death rates	Decrease in diarrhea-related deaths previous to vaccine introduction. Greater mean annual reduction after vaccine introduction
Richardson44 (2010)	Mexico	Ecological (comparison of years before and after vaccine introduction)	National health information system on mortality and population	All-cause diarrhea	Deaths	Decline in diarrhea-related deaths after vaccination
Quintanar-Solares43 (2011)	Mexico	Ecological (comparison of years before and after vaccine introduction) Control: all-cause hospitalization	National health information system	All-cause diarrhea	Number of hospital admissions	Reduction in diarrhea-related hospitalizations only among children under 12 months of age in the first year after vaccine introduction, and among children under 24 months of age in the second year
Gastañaduy20 (2013)	Mexico	Ecological (comparison of years before and after vaccine introduction)	National health informatics system Data were classified into three regions, according to indicators of economic development	All-cause diarrhea	Deaths according to regional human development index	Reduction in diarrhea-related mortality sustained for four years after vaccine introduction. Comparable declines across the three regions of different levels of development
Esparza-Aguilar15 (2014)	Mexico	Ecological (comparison of years before and after vaccine introduction) Control: all-cause hospitalization	National health informatics system	All-cause diarrhea	Hospitalization rates according to the human development index of the state	Reduction in diarrhea-related hospitalizations of children under 24 months of age in all regions after vaccine introduction. Clear blunting of seasonal peaks
Nieto Guevara34 (2008)	Panama	Cross-sectional study (comparison of years before and after vaccine introduction) Limitations: short observation period	Statistics and medical records service database of one tertiary hospital	All-cause diarrhea	Number of hospitalizations; length of stay	No decrease in hospitalizations observed after vaccine introduction
Bayard6 (2012)	Panama	Ecological (comparison of years before and after vaccine introduction) Control: mean number of events in a prevaccination five-year period Limitations: short observation period	National mortality information system; hospital discharge database of five sentinel hospitals	All-cause diarrhea of presumed infectious origin	Mortality and hospital admissions	Decrease in diarrhea-related mortality and hospitalization rates after vaccine introduction
Yen59 (2011)	El Salvador	Ecological (comparison of years before and after vaccine introduction) Limitations: data on catchment population for the sentinel hospitals unavailable	Sentinel surveillance system (seven hospitals); national surveillance for diarrhea-related healthcare visits (inpatient and outpatient) in public healthcare facilities	All-cause diarrhea and rotavirus-positive diarrhea	Hospitalization rates and healthcare visits	Decreases in both hospitalizations and healthcare visits due to diarrhea
Orozco37 (2009)	Nicaragua	Ecological (comparison of years before and after vaccine introduction) Control: median number of events in a prevaccination four-year period. Limitations: Short observation period	National population-based surveillance for acute gastroenteritis events in healthcare facilities (Ministry of Health)	All-cause diarrhea	Number of outpatient visits and hospitalizations	Decreases in diarrhea-related hospitalizations and medical visits
Surveillance data
Molto32 (2011)	Panama	Ecological (monthly trend analysis – comparison of years before and after vaccine introduction) Control: all-cause hospitalizations Limitations: unknown catchment population for the sentinel sites	National surveillance for diarrhea (six hospitals)	All-cause diarrhea	Hospitalizations	Reduction in diarrhea-related hospitalizations. Greater reduction during rotavirus seasonal months. All regions showed reduction in the ratio of diarrhea-related to non-diarrhea hospitalizations in the second year after vaccine introduction
Laboratory-based surveillance data
Morillo33 (2010)	Brazil (Sao Paulo state)	Descriptive. Retrospective analyses of data collected in a five-year period, including two years before and two years after vaccine introduction	Laboratory-based data from diarrhea surveillance	Rotavirus-positive diarrhea	Proportion of rotavirus and rotavirus genotype distribution	Decrease in the proportion of rotavirus-positive samples before vaccine introduction. Emergence of the G2P[4] genotype after vaccine introduction
Carvalho-Costa10 (2011)	Brazil	Ecological	Laboratory-based surveillance: data from regional rotavirus reference laboratories in 18 of the 27 Brazilian federated units	Rotavirus-positive diarrhea, genotype characterization	Frequency of rotavirus and genotype distribution	Reduction in the proportion of rotavirus-related diarrhea in the years after vaccine introduction. Emergence of the G2P[4] genotype in the year before vaccination, with decrease in its detection in the last year of observation, probably reflecting natural genotype oscillations
Pereira39 (2011)	Brazil (Parana state)	Descriptive	Laboratory-based data from one tertiary hospital	Rotavirus-positive diarrhea	Proportion of rotavirus-positive samples	Decline in the proportion of rotavirus-positive cases two years before vaccine implementation
Dulgheroff13 (2012)	Brazil (Minas Gerais state)	Descriptive. Data from a four-year period after vaccine introduction were compared with prevaccination data from other studies conducted in the same region	Data from two laboratories that collect and analyze specimens from private and public hospitals and pediatric clinics from the region	Rotavirus-positive diarrhea and rotavirus genotype characterization	Proportion of rotavirus among hospitalized and outpatient acute gastroenteritis cases	Reduction in rotavirus-related diarrhea in comparison with prevaccination studies. Great reduction in genotype diversity with predominance of G2P[4]