ABSTRACT

OBJECTIVE

To describe methods and challenges faced in the health impact assessment of vaccination programs, focusing on the pneumococcal conjugate and rotavirus vaccines in Latin America and the Caribbean.

METHODS

For this narrative review, we searched for the terms "rotavirus", "pneumococcal", "conjugate vaccine", "vaccination", "program", and "impact" in the databases Medline and LILACS. The search was extended to the grey literature in Google Scholar. No limits were defined for publication year. Original articles on the health impact assessment of pneumococcal and rotavirus vaccination programs in Latin America and the Caribbean in English, Spanish or Portuguese were included.

RESULTS

We identified 207 articles. After removing duplicates and assessing eligibility, we reviewed 33 studies, 25 focusing on rotavirus and eight on pneumococcal vaccination programs. The most frequent studies were ecological, with time series analysis or comparing pre- and post-vaccination periods. The main data sources were: health information systems; population-, sentinel- or laboratory-based surveillance systems; statistics reports; and medical records from one or few health care services. Few studies used primary data. Hospitalization and death were the main outcomes assessed.

CONCLUSIONS

Over the last years, a significant number of health impact assessments of pneumococcal and rotavirus vaccination programs have been conducted in Latin America and the Caribbean. These studies were carried out few years after the programs were implemented, meet the basic methodological requirements and suggest positive health impact. Future assessments should consider methodological issues and challenges arisen in these first studies conducted in the region.

Health Impact Assessment; Immunization Programs; Mass Vaccination, organization & administration; Rotavirus Vaccines; Pneumococcal Vaccines

RESUMO

OBJETIVO

Descrever métodos e desafios enfrentados na avaliação do impacto de programas de vacinação, com foco nas vacinas pneumocócica conjugada e de rotavírus nos países da América Latina e Caribe.

MÉTODOS

Para esta revisão narrativa, foi realizada busca nas bases de dados Medline e Lilacs, usando os termos "rotavirus", "pneumococcal", "conjugate vaccine", "vaccination", "program", e "impact". A busca foi estendida à literatura cinza no Google Acadêmico. Não houve limitação por ano de publicação. Foram incluídos estudos originais de avaliação do impacto dos programas de vacinação de pneumococo e rotavírus na América Latina e Caribe, publicados em inglês, espanhol ou português.

RESULTADOS

Foram identificados 207 artigos. Após remover duplicatas e avaliar elegibilidade, 33 estudos foram revisados, 25 sobre programas de vacinação de rotavírus e oito de pneumococo. Estudos ecológicos, com análise de série temporal ou comparação de períodos antes e após a vacinação, foram mais frequentes. As principais fontes de dados foram: sistemas de informação em saúde; sistemas de vigilância de base populacional, sentinela ou laboratorial; relatórios estatísticos; e prontuários médicos de um ou poucos serviços de saúde. Poucos estudos utilizaram dados primários. Hospitalizações e mortes foram os principais desfechos avaliados.

CONCLUSÕES

Nos últimos anos, número significativo de avaliações do impacto dos programas de vacinação de pneumococo e rotavírus foram realizados nos países da América Latina e Caribe. Esses estudos foram conduzidos poucos anos após a implementação dos programas, preenchem os requisitos metodológicos básicos e sugerem impacto positivo dos programas. Futuras avaliações devem considerar questões metodológicas e desafios que surgiram nesses primeiros estudos conduzidos na região.

Avaliação do Impacto na Saúde; Programas de Imunização; Vacinação em Massa, organização & administração; Vacinas contra Rotavirus; Vacinas Pneumocócicas

INTRODUCTION

In the last thirty years, scientific and technological advances have resulted in the development and marketing of several new vaccines, increasing the opportunities to prevent morbidity and mortality related to infectious diseases of public health importance.⁵⁵55. Wang SA, Hyde TB, Mounier-Jack S, Brenzel L, Favin M, Gordon WS et al. New vaccine introductions: assessing the impact and the opportunities for immunization and health systems strengthening. Vaccine. 2013;31 Suppl 2:B122-B18. DOI:10.1016/j.vaccine.2012.10116 In the 2000s, global and regional initiatives and commitment to immunization reduced prices of these new vaccines, which became accessible for low- and middle-income countries. Consequently, national immunization programs have been offering new vaccines.⁵⁵55. Wang SA, Hyde TB, Mounier-Jack S, Brenzel L, Favin M, Gordon WS et al. New vaccine introductions: assessing the impact and the opportunities for immunization and health systems strengthening. Vaccine. 2013;31 Suppl 2:B122-B18. DOI:10.1016/j.vaccine.2012.10116 For instance, Brazil has provided eight new vaccines in the last eight years: rotavirus, in 2006; 10-valent pneumococcal conjugate and meningococcal C conjugate, in 2010; inactivated polio vaccine (IPV), in 2012; varicella, in 2013; and hepatitis A, in 2014, all of those in childhood schedule; in 2014, the human papilloma virus (HPV) vaccine, for teenage girls, and the tetanus-diphtheria-acellular pertussis (Tdap) vaccine, for pregnant women, were also introduced in 2014.

Once a new vaccine is introduced into routine immunization, it is necessary to monitor vaccine coverage, vaccine effectiveness and safety as well as the health impact of the vaccination program. Country differences in burden of disease, serotype and genotype distribution, health services organization and access, clinical practices, and surveillance systems prevent the use of international evidence as a guarantee of good results after implementing a program. Furthermore, vaccination programs may result in complex effects, changing the average age of infection, seasonal patterns of disease and genotype or serotype distribution.

Published studies use conflicting terms to describe different types of effects.²⁴24. Hanquet G, Valenciano M, Simondon F, Moren A. Vaccine effects and impact of vaccination programmes in post-licensure studies. Vaccine. 2013;31(48):5634-42. DOI:10.1016/j.vaccine.2013.07.006 Vaccine effectiveness is defined as the ability of a vaccine to protect against disease when used under field conditions (routine practice).²⁴24. Hanquet G, Valenciano M, Simondon F, Moren A. Vaccine effects and impact of vaccination programmes in post-licensure studies. Vaccine. 2013;31(48):5634-42. DOI:10.1016/j.vaccine.2013.07.006 Vaccine effectiveness refers to the protection conferred by individual immunization on vaccinated persons.²⁴24. Hanquet G, Valenciano M, Simondon F, Moren A. Vaccine effects and impact of vaccination programmes in post-licensure studies. Vaccine. 2013;31(48):5634-42. DOI:10.1016/j.vaccine.2013.07.006 Vaccination programs affect all people, even if only part of the population is vaccinated. When many people are immunized, the pathogen transmission decreases, which reduces the disease incidence and, consequently, protects the unvaccinated ones (indirect effect or herd protection). The health impact of a vaccination program refers to the total effects of the program, meaning the total (direct and indirect) effect on the vaccinees and the indirect effect on unvaccinated persons.²⁴24. Hanquet G, Valenciano M, Simondon F, Moren A. Vaccine effects and impact of vaccination programmes in post-licensure studies. Vaccine. 2013;31(48):5634-42. DOI:10.1016/j.vaccine.2013.07.006

Real-life effects of a vaccine administered in a health program are mainly evaluated in observational studies as experimental designs are no longer ethical once the vaccine is part of a health policy. Vaccine effectiveness may be estimated by comparing vaccinated and unvaccinated persons from the same population in cohort or case-control studies. The health impact of a vaccination program is estimated by comparing all individuals of the population affected by the vaccination program with a reference population unaffected by any program, usually the same population before and after program implementation. Different methodological approaches of differing complexity may be used.²⁴24. Hanquet G, Valenciano M, Simondon F, Moren A. Vaccine effects and impact of vaccination programmes in post-licensure studies. Vaccine. 2013;31(48):5634-42. DOI:10.1016/j.vaccine.2013.07.006

Countries with national health information systems, academic expertise in health services research, disease burden measurement and technology assessment in health care, policy makers, epidemiological surveillance, and immunization program professionals with experience in vaccine evaluations might have a more favorable context to conduct a health impact assessment (HIA) of vaccination programs.⁵¹51. Sinha A, Augustovski F, Alcaraz A, García Marti S. Perspectives on the challenge of Streptococcus pneumoniae disease burden estimation for policymakers in Latin American and the Caribbean: from theory to practice. Vaccine. 2013;31 Suppl 3:C30-2. DOI:10.1016/j.vaccine.2013.05.052 Nevertheless, introducing a new vaccine may be the opportunity for countries to create conditions for this evaluation, and others to follow, particularly if international organizations stimulate and support these initiatives.

The World Health Organization recommended that all national immunization programs offer rotavirus vaccine and pneumococcal conjugate vaccine (PCV),⁵⁶56. World health Organization. Pneumococcal vaccines WHO position paper – 2012. Wkly Epidemiol Rec. 2012;87(14):129-44.,⁵⁷57. World Health Organization. Rotavirus vaccine. WHO position paper – January 2013. Wkly Epidemiol Rec. 2013;88(5):49-64. which have been introduced in Latin America and the Caribbean (LAC) from 2006 and 2008, respectively (Table 1). Hence, LAC countries have already had time to conduct HIA of rotavirus and pneumococcal vaccination.

The objective of this study was to describe the methodological approaches (study design, data sources and outcomes of interest) used and the challenges to conduct HIA of PCV and rotavirus vaccination programs, with focus on LAC countries.

METHODS

This is a narrative literature review of HIA of PCV and rotavirus vaccination programs, with focus on LAC countries. A search in Medline and LILACS, using the terms "rotavirus", "pneumococcal", "conjugate vaccine", "vaccination", "program", and "impact", was conducted on June 10, 2013 (PCV) and September 20, 2013 (rotavirus) and repeated on April 30, 2014. The review was supplemented with a search in Google Scholar to assess grey literature such as articles published in non-indexed journals, guidelines, and technical reports. There were no limits for publication year. Studies published in English, Spanish and Portuguese were eligible.

Three reviewers screened the identified abstracts and full texts and selected original articles that assessed the health impact of vaccination programs in LAC countries. Economic evaluations, mathematic models, vaccine efficacy or effectiveness studies and impact reviews were excluded. The references of all included articles were cross-checked and a hand search was carried out to identify further articles.

Data were extracted by one reviewer using a template developed specifically for this study and checked for accuracy by a second one. Data extracted from each study included: author, year, country, study design, data sources, clinical syndrome of interest, outcomes, and main results. Differences between reviewers were solved by discussion.

ANALYSIS OF RESULTS

We initially identified 207 articles in the search: 92 on pneumococcal and 115 on rotavirus vaccination programs. After applying the exclusion criteria based on title and abstract reading, and checking for duplicates, we read 37 articles on PCV and 60 articles on rotavirus vaccine in full. The search update added seven articles to the set. Finally, we reviewed 33 studies on HIA of vaccination programs conducted in LAC, 25 of which assessed rotavirus and eight, PCV vaccination programs.

Of the 20 Latin American countries, 14 have introduced rotavirus vaccine in their immunization programs since 2006, and we identified at least one published HIA for eight of them (Table 1).¹²12. De Oliveira LH, Toscano CM, Sanwogou NJ, Ruiz-Matus C, Tambini G, Roses-Periago M et al. Systematic documentation of new vaccine introduction in selected countries of Latin American Region. Vaccine. 2013;31 Suppl 3:C114-22. DOI:10.1016/j.vaccine.2013.05.032,²⁷27. Johns Hopkins Bloomberg School of Public Health, International Vaccine Access Center. VIMS report: global vaccine introduction. Baltimore; 2014 [cited 2014 April 20]. Available from: http://www.jhsph.edu/research/centers-and-institutes/ivac/vims/IVAC-VIMS-Report-2014-Mar.pdf
http://www.jhsph.edu/research/centers-an... In the Caribbean, only three of 25 countries have introduced rotavirus vaccine in their immunization programs since 2009 and no published HIA was identified. Since 2008, 17 Latin American countries have introduced PCV in their immunization programs and we identified at least one published HIA for five of them. Since 2009, five countries in the Caribbean have introduced PCV in their immunization programs and no published vaccination HIA was identified (Table 1).¹²12. De Oliveira LH, Toscano CM, Sanwogou NJ, Ruiz-Matus C, Tambini G, Roses-Periago M et al. Systematic documentation of new vaccine introduction in selected countries of Latin American Region. Vaccine. 2013;31 Suppl 3:C114-22. DOI:10.1016/j.vaccine.2013.05.032 The 33 included LAC studies are described in Tables 2, 3 and 4 according to vaccine, data sources, country, and study design. In most LAC countries, rotavirus vaccines have been introduced earlier than PCV. Consequently, more HIA of rotavirus vaccination programs have been performed and published (25/33, 75.8%). Most studies were conducted in Brazil (15/33, 45.5%), mainly on rotavirus (13/25, 52.0%). Three of the eight studies on pneumococcal vaccine were conducted in Uruguay, one of the first LAC countries to implement a PCV childhood vaccination program.²⁵25. Hortal M, Estevan M, Iraola I, De Mucio B. A population-based assessment of the disease burden of consolidated pneumonia in hospitalized children under five years of age. Int J Infect Dis. 2007;11(3):273-7. DOI:10.1016/j.ijid.2006.05.006,²⁶26. Hortal M, Estevan M, Laurani H, Iraola I, Meny M. Hospitalized children with pneumonia in Uruguay: pre and post introduction of 7 and 13-valent pneumococcal conjugated vaccines into the National Immunization Program. Vaccine. 2012;30(33):4934-8. DOI:10.1016/j.vaccine.2012.05.054,⁴¹41. Pírez MC, Algorta G, Cedrés A, Sobrero H, Varela A, Giachetto G et al. Impact of universal pneumococcal vaccination on hospitalizations for pneumonia and meningitis in children in Montevideo, Uruguay. Pediatr Infect Dis J. 2011;30(8):669-74. DOI:10.1097/INF.0b013e3182152bf1,⁴²42. Pírez MC, Algorta G, Chamorro F, Romero C, Varela A, Cedrés A et al. Changes in hospitalizations for pneumonia after universal vaccination with pneumococcal conjugate vaccines 7/13 valent and Haemophilus influenzae type b conjugate vaccine in a pediatric referral hospital in Uruguay. Pediatr Infect Dis J. 2014;33(7):753-9. DOI:10.1097/INF.0000000000000294

Ecological studies (interrupted time series analyses and other studies comparing pre- and postvaccination periods) were the most frequent (25/33, 75.7%). Cohorts (3), case series (3) and cross-sectional (2) studies were also conducted. Data sources were mainly secondary epidemiological or administrative databases (16/33, 48.5%). Surveillance data (8/33, 24.2%) and primary data collection (7/33, 21.2%) were also used. Two studies mixed data from both surveillance and health information systems.⁶6. Bayard V, DeAntonio R, Contreras R, Tinajero O, Castrejon MM, Ortega-Barría E et al. Impact of rotavirus vaccination on childhood gastroenteritis-related mortality and hospital discharges in Panama. Int J Infect Dis. 2012;16(2):e94-8. DOI:10.1016/j.ijid.2011.09,¹¹11. De Oliveira LH, Giglio N, Ciapponi A, García Martí S, Kuperman M, Sanwogou NJ et al. Temporal trends in diarrhea-related hospitalizations and deaths in children under age 5 before and after the introduction of the rotavirus vaccine in four Latin American countries. Vaccine. 2013;31 Suppl 3:C99-108. DOI:10.1016/j.vaccine.2013.05.065 The study design was tied to data characteristics.

Study design

Ecological studies are frequently used to evaluate epidemiological impact, especially when using large non-disease-specific databases, as they allow tracking population disease trends over time in relation to the timing of interventions. They allow both short- and long-term assessment of the vaccination program in a general population, but the establishment and measurement of causal relationship are limited because changes in disease incidence after vaccine introduction cannot be attributed exclusively to the intervention. Natural variations and secular trends affect disease incidences in the absence of vaccination.¹¹11. De Oliveira LH, Giglio N, Ciapponi A, García Martí S, Kuperman M, Sanwogou NJ et al. Temporal trends in diarrhea-related hospitalizations and deaths in children under age 5 before and after the introduction of the rotavirus vaccine in four Latin American countries. Vaccine. 2013;31 Suppl 3:C99-108. DOI:10.1016/j.vaccine.2013.05.065 Changes in social and health conditions and improvement in access to healthcare system during the study may also influence the results of before-after studies.¹¹11. De Oliveira LH, Giglio N, Ciapponi A, García Martí S, Kuperman M, Sanwogou NJ et al. Temporal trends in diarrhea-related hospitalizations and deaths in children under age 5 before and after the introduction of the rotavirus vaccine in four Latin American countries. Vaccine. 2013;31 Suppl 3:C99-108. DOI:10.1016/j.vaccine.2013.05.065 Strategies to control the effects of possible confounding factors include study design (comparison with other diseases or similar countries) and analyses (statistical methods to estimate the expected occurrence of the outcome using patterns before vaccine introduction, for example).

The rates of diarrhea-related hospitalizations and deaths of under-five children have been declining in LAC countries in the last three decades due to safe water supply, improvements in sanitation and hygiene, breastfeeding promotion, better nutrition, enhanced access to health care, and proper treatment of diarrhea, including oral rehydration therapy.¹⁴14. Esparza-Aguilar M, Bautista-Márquez A, González-Andrade MC, Richardson-López-Collada VL. Mortalidad por enfermedad diarreica en menores, antes y después de la introducción de la vacuna contra el rotavirus. Salud Publica Mex. 2009;51(4):285-90. This decline may be misinterpreted, overestimating the impact of vaccination. In some LAC studies, this decrease was already evident before vaccine introduction.¹⁴14. Esparza-Aguilar M, Bautista-Márquez A, González-Andrade MC, Richardson-López-Collada VL. Mortalidad por enfermedad diarreica en menores, antes y después de la introducción de la vacuna contra el rotavirus. Salud Publica Mex. 2009;51(4):285-90.,²²22. Gurgel RQ, Ilozue C, Correia JB, Centenari C, Oliveira SM, Cuevas LE. Impact of rotavirus vaccination on diarrhoea mortality and hospital admissions in Brazil. Trop Med Int Health. 2011;16(9):1180-4. DOI:10.1111/j.1365-3156.2011.02844.x,²⁹29. Lanzieri TM, Linhares AC, Costa I, Kolhe DA, Cunha MH, Ortega-Barria E et al. Impact of rotavirus vaccination on childhood deaths from diarrhea in Brazil. Int J Infect Dis. 2011;15(3):e206-10. DOI:10.1016/j.ijid.2010.11.007 Few studies adjusted for these secular trends appropriately in the analyses.⁹9. Carmo GM, Yen C, Cortes J, Siqueira AA, Oliveira WK, Cortez-Escalante JJ et al. Decline in diarrhea mortality and admissions after routine childhood rotavirus immunization in Brazil: a time-series analysis. PLoS Med. 2011;8(4):e1001024. DOI:10.1371/journal.pmed.1001024,¹¹11. De Oliveira LH, Giglio N, Ciapponi A, García Martí S, Kuperman M, Sanwogou NJ et al. Temporal trends in diarrhea-related hospitalizations and deaths in children under age 5 before and after the introduction of the rotavirus vaccine in four Latin American countries. Vaccine. 2013;31 Suppl 3:C99-108. DOI:10.1016/j.vaccine.2013.05.065,¹⁵15. Esparza-Aguilar M, Gastañaduy PA, Sánchez-Uribe E, Desai R, Parashar UD, Richardson V et al. Diarrhoea-related hospitalizations in children before and after implementation of monovalent rotavirus vaccination in Mexico. Bull World Health Organ. 2014;92(2):117-25. DOI:10.2471/BLT.13.125286,⁴³43. 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. DOI:10.1097/INF.0b013e3181fefb32 A Brazilian study used a generalized linear model to compare the postvaccination years with expected rates estimated from prevaccination years adjusted for secular and seasonal trends.⁹9. Carmo GM, Yen C, Cortes J, Siqueira AA, Oliveira WK, Cortez-Escalante JJ et al. Decline in diarrhea mortality and admissions after routine childhood rotavirus immunization in Brazil: a time-series analysis. PLoS Med. 2011;8(4):e1001024. DOI:10.1371/journal.pmed.1001024 Two studies, in Mexico, used all-cause hospitalization to control these secular trends.¹⁵15. Esparza-Aguilar M, Gastañaduy PA, Sánchez-Uribe E, Desai R, Parashar UD, Richardson V et al. Diarrhoea-related hospitalizations in children before and after implementation of monovalent rotavirus vaccination in Mexico. Bull World Health Organ. 2014;92(2):117-25. DOI:10.2471/BLT.13.125286,⁴³43. 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. DOI:10.1097/INF.0b013e3181fefb32 A neighbor and similar country that had not implemented rotavirus vaccination was used as a control for possible secular trends in a HIA of rotavirus vaccination in four LAC countries.¹¹11. De Oliveira LH, Giglio N, Ciapponi A, García Martí S, Kuperman M, Sanwogou NJ et al. Temporal trends in diarrhea-related hospitalizations and deaths in children under age 5 before and after the introduction of the rotavirus vaccine in four Latin American countries. Vaccine. 2013;31 Suppl 3:C99-108. DOI:10.1016/j.vaccine.2013.05.065

Rotavirus disease classically shows natural year-to-year variation, making it difficult to determine to which extent changes in disease trends are related to vaccination or to natural changes. Biennial increase in rotavirus activity has been reported in the postvaccine era.⁵⁵55. Wang SA, Hyde TB, Mounier-Jack S, Brenzel L, Favin M, Gordon WS et al. New vaccine introductions: assessing the impact and the opportunities for immunization and health systems strengthening. Vaccine. 2013;31 Suppl 2:B122-B18. DOI:10.1016/j.vaccine.2012.10116 Unimmunized susceptible children accumulate during seasons with low rotavirus activity and the higher number of susceptible individuals facilitates transmission during a subsequent season.⁵³53. Tate JE, Haynes A, Payne DC, Cortese MM, Lopman BA, Patel MM et al. Trends in national rotavirus activity before and after introduction of rotavirus vaccine into the national immunization program in the United States, 2000 to 2012. Pediatr Infect Dis J. 2013;32(7):741-4. DOI:10.1097/INF.0b013e31828d639c Temporal variability in rotavirus genotype distribution also occurs naturally, independent of vaccination.⁴4. Bányai K, László B, Duque J, Steele AD, Nelson EA, Gentsch JR et al. Systematic review of regional and temporal trends in global rotavirus strain diversity in the pre rotavirus vaccine era: insights for understanding the impact of rotavirus vaccination programs. Vaccine. 2012;30 Suppl 1:A122-30. DOI:10.1016/j.vaccine.2011.09.111,¹⁰10. Carvalho-Costa FA, Volotão EM, Assis RM, Fialho AM, Andrade JS, Rocha LN et al. Laboratory-based rotavirus surveillance during the introduction of a vaccination program, Brazil, 2005-2009. Pediatr Infect Dis J. 2011;30(1 Suppl):S35-41. DOI:10.1097/INF.0b013e3181fefd5f Proper assessment of vaccination impact requires monitoring for longer periods and careful interpretation.¹⁰10. Carvalho-Costa FA, Volotão EM, Assis RM, Fialho AM, Andrade JS, Rocha LN et al. Laboratory-based rotavirus surveillance during the introduction of a vaccination program, Brazil, 2005-2009. Pediatr Infect Dis J. 2011;30(1 Suppl):S35-41. DOI:10.1097/INF.0b013e3181fefd5f

There is evidence of decreasing trends in pneumonia incidence and mortality in low- and middle-income countries from 2000 to 2010, attributed to economic and social developments, reduction in the prevalence of risk factors, expansion and improvement in case management and also the implementation of PCV and Haemophilus influenzae type b (Hib) childhood vaccination programs.⁴⁶46. Rudan I, O'Brien KL, Nair H, Liu L, Theodoratou E, Qazi S et al. Epidemiology and etiology of childhood pneumonia in 2010: estimates of incidence, severe morbidity, mortality, underlying risk factors and causative pathogens for 192 countries. J Global Health. 2013;3(1):010401. DOI:10.7189/jogh.03.010401 Pneumonia also has a seasonal pattern and the observation period must last at least a year to consider these variations. Two LAC studies adjusted for possible secular trends in pneumonia rates using nonrespiratory and diarrhea events as controls (Table 4).¹1. Afonso ET, Minamisava R, Bierrenbach AL, Cortez Escalante JJ, Alencar AP, Domingues CM et al. Effect of 10-valent pneumococcal vaccine on pneumonia among children, Brazil. Emerg Infect Dis. 2013;19(4):589-97.,⁷7. Becker-Dreps S, Amaya E, Liu L, Moreno G, Rocha J, Briceño R et al. Changes in childhood pneumonia and infant mortality rates following introduction of the 13-valent pneumococcal conjugate vaccine in Nicaragua. Pediatr Infect Dis J. 2014;33(6):637-42. DOI:10.1097/INF.0000000000000269

Data sources

Health information system databases were the main data source for HIA of vaccination programs in LAC. Thirteen studies assessed the impact of rotavirus vaccination based on health information systems, mainly mortality and hospitalization data at national level (Table 2).⁶6. Bayard V, DeAntonio R, Contreras R, Tinajero O, Castrejon MM, Ortega-Barría E et al. Impact of rotavirus vaccination on childhood gastroenteritis-related mortality and hospital discharges in Panama. Int J Infect Dis. 2012;16(2):e94-8. DOI:10.1016/j.ijid.2011.09,⁹9. Carmo GM, Yen C, Cortes J, Siqueira AA, Oliveira WK, Cortez-Escalante JJ et al. Decline in diarrhea mortality and admissions after routine childhood rotavirus immunization in Brazil: a time-series analysis. PLoS Med. 2011;8(4):e1001024. DOI:10.1371/journal.pmed.1001024,¹¹11. De Oliveira LH, Giglio N, Ciapponi A, García Martí S, Kuperman M, Sanwogou NJ et al. Temporal trends in diarrhea-related hospitalizations and deaths in children under age 5 before and after the introduction of the rotavirus vaccine in four Latin American countries. Vaccine. 2013;31 Suppl 3:C99-108. DOI:10.1016/j.vaccine.2013.05.065,¹⁴14. Esparza-Aguilar M, Bautista-Márquez A, González-Andrade MC, Richardson-López-Collada VL. Mortalidad por enfermedad diarreica en menores, antes y después de la introducción de la vacuna contra el rotavirus. Salud Publica Mex. 2009;51(4):285-90.,¹⁵15. Esparza-Aguilar M, Gastañaduy PA, Sánchez-Uribe E, Desai R, Parashar UD, Richardson V et al. Diarrhoea-related hospitalizations in children before and after implementation of monovalent rotavirus vaccination in Mexico. Bull World Health Organ. 2014;92(2):117-25. DOI:10.2471/BLT.13.125286,¹⁷17. Fernandes EG, Sato HK, Leshem E, Flannery B, Konstantyner TC, Veras MA et al. Impact of rotavirus vaccination on diarrhea-related hospitalizations in São Paulo State, Brazil. Vaccine. 2014;32(27):3402-8. DOI:10.1016/j.vaccine.2014.04.015, ²⁰20. Gastañaduy PA, Sánchez-Uribe E, Esparza-Aguilar M, Desai R, Parashar UD, Patel M et al. Effect of rotavirus vaccine on diarrhea mortality in different socioeconomic regions of Mexico. Pediatrics. 2013;131(4):e1115-20. DOI:10.1542/peds.2012-2797,²²22. Gurgel RQ, Ilozue C, Correia JB, Centenari C, Oliveira SM, Cuevas LE. Impact of rotavirus vaccination on diarrhoea mortality and hospital admissions in Brazil. Trop Med Int Health. 2011;16(9):1180-4. DOI:10.1111/j.1365-3156.2011.02844.x,²⁹29. Lanzieri TM, Linhares AC, Costa I, Kolhe DA, Cunha MH, Ortega-Barria E et al. Impact of rotavirus vaccination on childhood deaths from diarrhea in Brazil. Int J Infect Dis. 2011;15(3):e206-10. DOI:10.1016/j.ijid.2010.11.007,³⁴34. Nieto Guevara J, López O, González G. Impacto de la introducción de la vacuna contra el rotavirus en la hospitalización por gastroenteritis aguda grave en el Hospital del Niño de la Ciudad de Panamá. Rev Panam Salud Publica. 2008;24(3):189-94. DOI:10.1590/S1020-49892008000900005,⁴³43. 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. DOI:10.1097/INF.0b013e3181fefb32

44. Richardson V, Hernandez-Pichardo J, Quintanar-Solares M, Esparza-Aguilar M, Johnson B, Gomez-Altamirano CM et al. Effect of rotavirus vaccination on death from childhood diarrhea in Mexico. N Engl J Med. 2010;362(4):299-305. DOI:10.1056/NEJMoa0905211-⁴⁵45. Rissardo LK, Furlan MCR, Marcon SS, Mendes Ferrer AL, Oliveira RG. Hospital morbidity before and after vaccination program against rotavirus in the state of Paraná-Brazil: exploratory- descriptive study. Online Braz J Nurs. 2010 [cited 2015 May 19];9(2). Available from: http://www.objnursing.uff.br/index.php/nursing/article/view/j.1676-4285.2010.3053/696
http://www.objnursing.uff.br/index.php/n... One Brazilian study on the HIA of pneumococcal vaccination on hospitalizations used health information systems.¹1. Afonso ET, Minamisava R, Bierrenbach AL, Cortez Escalante JJ, Alencar AP, Domingues CM et al. Effect of 10-valent pneumococcal vaccine on pneumonia among children, Brazil. Emerg Infect Dis. 2013;19(4):589-97. The identification of hospitalizations or deaths in health information system databases relied on International Classification of Diseases (ICD) codes in discharge summaries or death certificates. Health information system databases are increasingly being used in research and health assessment. Some advantages are the broad coverage, lower costs of data collection, easy access to data, and the possibility of longitudinal follow-up. Major disadvantages are lack of standardization in data collection, which affects the quality of the information, time and space variation in coverage, and lack of important information for the analysis. There may also be delays on database availability. Changes in coding practices during the studied period may also affect the analyses.⁹9. Carmo GM, Yen C, Cortes J, Siqueira AA, Oliveira WK, Cortez-Escalante JJ et al. Decline in diarrhea mortality and admissions after routine childhood rotavirus immunization in Brazil: a time-series analysis. PLoS Med. 2011;8(4):e1001024. DOI:10.1371/journal.pmed.1001024 Failure to assign codes for gastroenteritis is a major reason for underestimating the burden of rotavirus disease and the impact of the vaccination program when using these data sources.³¹31. Matson DO, Staat MA, Azimi P, Itzler R, Bernstein DI, Ward RL et al. Burden of rotavirus hospitalisations in young children in three paediatric hospitals in the United States determined by active surveillance compared to standard indirect methods. J Paediatr Child Health. 2012;48(8):698-704. DOI:10.1111/j.1440-1754.2012.02445.x Underdiagnosing or underreporting may also be an issue when estimating burden of disease and HIA of the vaccination program, leading to the development of models that use international data when adequate local data are unavailable.⁵¹51. Sinha A, Augustovski F, Alcaraz A, García Marti S. Perspectives on the challenge of Streptococcus pneumoniae disease burden estimation for policymakers in Latin American and the Caribbean: from theory to practice. Vaccine. 2013;31 Suppl 3:C30-2. DOI:10.1016/j.vaccine.2013.05.052

Important issues to be considered when using health information system databases are the completeness and reliability of the available data, coverage (proportion of population included), representativeness (whether persons included are similar to those not included), and sustainability (if the database is part of the health system and will be maintained long enough to monitor the effects of the program, independent of specific sponsoring). When using administrative databases, it is essential to consider the rules that govern the system and possible changes over time.⁵⁸58. World Health Organization, Department of Immunization, Vaccines and Biologicals. Generic protocol for monitoring impact of rotavirus vaccination on gastroenteritis disease burden and viral strains. Geneva; 2008 [cited 2014 May 4]. (WHO/IVB/08.16). Available from: http://www.who.int/immunization/documents/WHO_IVB_08.16/en/
http://www.who.int/immunization/document...

In general, mortality databases are more reliable than morbidity or health services utilization databases because death is a single event and data are less affected by administrative or economic conditions. On the other hand, it measures only the effect on severe disease, and changes in less severe conditions will not be identified. Deaths occurring outside the health system, particularly in impoverished or rural areas, may not be registered in mortality systems.⁶6. Bayard V, DeAntonio R, Contreras R, Tinajero O, Castrejon MM, Ortega-Barría E et al. Impact of rotavirus vaccination on childhood gastroenteritis-related mortality and hospital discharges in Panama. Int J Infect Dis. 2012;16(2):e94-8. DOI:10.1016/j.ijid.2011.09,⁴⁴44. Richardson V, Hernandez-Pichardo J, Quintanar-Solares M, Esparza-Aguilar M, Johnson B, Gomez-Altamirano CM et al. Effect of rotavirus vaccination on death from childhood diarrhea in Mexico. N Engl J Med. 2010;362(4):299-305. DOI:10.1056/NEJMoa0905211 Additionally, undefined causes of death may constitute an important proportion of all deaths in developing countries. These factors might affect the analyses, particularly if changes occurred during the study period.³⁶36. Oliveira JFM, Boing AF, Waldman EA, Antunes JLF. Ecological study on mortality from influenza and pneumonia before and after influenza vaccination in the Northeast and South of Brazil. Cad Saude Publica. 2013;29(12):2535-45. DOI:10.1590/s0102-311X00028413

Access to hospitalization information systems is increasing and they have been considered very useful as data sources in vaccination program impact analysis (Table 2).⁹9. Carmo GM, Yen C, Cortes J, Siqueira AA, Oliveira WK, Cortez-Escalante JJ et al. Decline in diarrhea mortality and admissions after routine childhood rotavirus immunization in Brazil: a time-series analysis. PLoS Med. 2011;8(4):e1001024. DOI:10.1371/journal.pmed.1001024,¹⁵15. Esparza-Aguilar M, Gastañaduy PA, Sánchez-Uribe E, Desai R, Parashar UD, Richardson V et al. Diarrhoea-related hospitalizations in children before and after implementation of monovalent rotavirus vaccination in Mexico. Bull World Health Organ. 2014;92(2):117-25. DOI:10.2471/BLT.13.125286,¹⁷17. Fernandes EG, Sato HK, Leshem E, Flannery B, Konstantyner TC, Veras MA et al. Impact of rotavirus vaccination on diarrhea-related hospitalizations in São Paulo State, Brazil. Vaccine. 2014;32(27):3402-8. DOI:10.1016/j.vaccine.2014.04.015,⁴⁴44. Richardson V, Hernandez-Pichardo J, Quintanar-Solares M, Esparza-Aguilar M, Johnson B, Gomez-Altamirano CM et al. Effect of rotavirus vaccination on death from childhood diarrhea in Mexico. N Engl J Med. 2010;362(4):299-305. DOI:10.1056/NEJMoa0905211 A study in Goiania, Midwestern Brazil, used database linkage of secondary administrative hospitalization data and primary population-based surveillance data and found similar hospitalization rates for community-acquired pneumonia in children.⁵⁰50. Sgambatti S, Minamisava R, Afonso ET, Toscano CM, Bierrenbach AL, Andrade AL. Appropriateness of administrative data for vaccine impact evaluation: the case of pneumonia hospitalizations and pneumococcal vaccine in Brazil. Epidemiol Infect. 2015;143(2):334-42. DOI:10.1017/S0950268814000922

In many countries, burden of pneumococcal and rotavirus disease estimates are based on national sentinel-based surveillance data and the HIA of vaccination program relies on these data. Seven LAC studies evaluated the impact of rotavirus vaccination based on surveillance data (Table 2).¹⁰10. Carvalho-Costa FA, Volotão EM, Assis RM, Fialho AM, Andrade JS, Rocha LN et al. Laboratory-based rotavirus surveillance during the introduction of a vaccination program, Brazil, 2005-2009. Pediatr Infect Dis J. 2011;30(1 Suppl):S35-41. DOI:10.1097/INF.0b013e3181fefd5f,¹³13. Dulgheroff ACB, Figueiredo EF, Moreira LP, Moreira KC, Moura LMS, Gouvêa VS et al. Distribution of rotavirus genotypes after vaccine introduction in the Triângulo Mineiro region of Brazil: 4-year follow-up study. J Clin Virol. 2012;55(1):67-71. DOI:101016/j.jcv.2012.06.003,³²32. Molto Y, Cortes JE, De Oliveira LH, Mike A, Solis I, Suman O 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. DOI:10.1097/INF.0b013e3181fefc68,³³33. Morillo SG, Luchs A, Cilli A, Costa FF, Carmona RC, Timenetsky MC. Characterization of rotavirus strains from day care centers: pre- and post-rotavirus vaccine era. J Pediatr (Rio J). 2010;86(2):155-8. DOI:10.2223/JPED.1981,³⁷37. Orozco M, Vasquez J, Pedreira C, De Oliveira LH, Amador JJ, Malespin O et al. Uptake of rotavirus vaccine and national trends of acute gastroenteritis among children in Nicaragua. J Infect Dis. 2009;200 Suppl 1:S125-30. DOI:10.1086/605053,³⁹39. Pereira LA, Raboni SM, Nogueira MB, Vidal LR, Almeida SM, Debur MC et al. Rotavirus infection in a tertiary hospital: laboratory diagnosis and impact of immunization on pediatric hospitalization. Braz J Infect Dis. 2011;15(3):215-9. DOI:10.1590/S1413-86702011000300006,⁵⁹59. Yen C, Armero Guardado JA, Alberto P, Rodriguez Araujo DS, Mena C, Cuellar E 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. DOI:10.1097/INF.0b013e3181fefa05 Information on the catchment population of the sentinel hospitals is unavailable for most sites, precluding incidence rates estimation, which constitutes a limitation.³²32. Molto Y, Cortes JE, De Oliveira LH, Mike A, Solis I, Suman O 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. DOI:10.1097/INF.0b013e3181fefc68,⁵⁹59. Yen C, Armero Guardado JA, Alberto P, Rodriguez Araujo DS, Mena C, Cuellar E 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. DOI:10.1097/INF.0b013e3181fefa05 Depending on the number of sentinel sites and their location, these data cannot be generalized for the entire population.³²32. Molto Y, Cortes JE, De Oliveira LH, Mike A, Solis I, Suman O 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. DOI:10.1097/INF.0b013e3181fefc68,⁵⁹59. Yen C, Armero Guardado JA, Alberto P, Rodriguez Araujo DS, Mena C, Cuellar E 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. DOI:10.1097/INF.0b013e3181fefa05 The World Health Organization has proposed a sentinel surveillance system for rotavirus and invasive bacterial diseases,^aa World Health Organization, Department of Immunization, Vaccines and Biologicals, Expanded Programme on Immunization. Summary report and action plan for 2012 from the Global Meeting on Surveillance for Vaccine Preventable Invasive Bacterial Diseases (VP-IBD) and Rotavirus; 22-24 Sept 2010; Geneva, Switzerland. Geneva: WHO; 2010 [cited 2014 May 4]. Available from: http://www.who.int/immunization/monitoring_surveillance/resources/Full_2010_Surv_Mtg_Report-21_Jan_2011.pdf but some LAC countries established population-based surveillance for diarrhea with data collection for hospitalizations and outpatient visits at public health facilities. These population-based systems were used in HIA of rotavirus vaccination in Nicaragua and El Salvador, the latter in combination with sentinel hospital data.³⁷37. Orozco M, Vasquez J, Pedreira C, De Oliveira LH, Amador JJ, Malespin O et al. Uptake of rotavirus vaccine and national trends of acute gastroenteritis among children in Nicaragua. J Infect Dis. 2009;200 Suppl 1:S125-30. DOI:10.1086/605053,⁵⁹59. Yen C, Armero Guardado JA, Alberto P, Rodriguez Araujo DS, Mena C, Cuellar E 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. DOI:10.1097/INF.0b013e3181fefa05 Population-based surveillance data were also used in HIA of a PCV program in Uruguay.²⁵25. Hortal M, Estevan M, Iraola I, De Mucio B. A population-based assessment of the disease burden of consolidated pneumonia in hospitalized children under five years of age. Int J Infect Dis. 2007;11(3):273-7. DOI:10.1016/j.ijid.2006.05.006,²⁶26. Hortal M, Estevan M, Laurani H, Iraola I, Meny M. Hospitalized children with pneumonia in Uruguay: pre and post introduction of 7 and 13-valent pneumococcal conjugated vaccines into the National Immunization Program. Vaccine. 2012;30(33):4934-8. DOI:10.1016/j.vaccine.2012.05.054

The sensitivity of surveillance systems may change over time: variations in methods, case definitions, population under surveillance and reporting patterns may affect the results of before-after studies. In the era of PCV and rotavirus vaccines, most countries strengthened their surveillance systems to inform for decisions on vaccine policies.⁵⁴54. Vergison A, Hanquet G. Challenges in estimating the impact of pneumococcal conjugate vaccines through surveillance. Pediatr Infect Dis J. 2012;31(4):400-3. DOI:10.1097/INF.0b013e31824bc1f0 Furthermore, vaccine introduction increases disease awareness, testing and reporting.²³23. Hanquet G, Lernout T, Vergison A, Verhaegen J, Kissling E, Tuerlinckx D et al. Impact of conjugate 7-valent vaccination in Belgium: addressing methodological challenges. Vaccine. 2011;29(16):2856-64. DOI:10.1016/j.vaccine.2011.02.016

In LAC, invasive bacterial diseases surveillance was first organized as a laboratory-based surveillance system, the Sistema de Redes de Vigilancia de los Agentes Bacterianos Responsables de Neumonia y Meningitis (SIREVA II – Surveillance Network System for the Bacterial Agents Responsible for Pneumonia and Meningitis), created in 1993, initially in six countries (Argentina, Brazil, Chile, Colombia, Mexico, and Uruguay).¹⁹19. Gabastou JM, Agudelo CI, Brandileone MCC, Castañeda E, Lemos APS, Di Fabio JL et al. Caracterización de aislamientos invasivos de S. pneumoniae, H. influenzae y N. meningitidis en América Latina y el Caribe: SIREVA II, 2000-2005. Rev Panam Salud Publica. 2008;24(1):1-15. DOI:10.1590/S1020-49892008000700001 The SIREVA II Regional 2012 Report contains data on pneumococcal serotypes and antibiotic resistance from 19 Latin American countries and the Caribbean Epidemiology Center.^bb Organizacion Panamericana de la Salud. Informe Regional de SIREVA II, 2012: datos por país y por grupos de edad sobre las características de los aislamientos de Streptococcus pneumoniae, Haemophilus influenzae y Neisseria meningitidis en procesos invasores. Washington (DC); 2013 [cited 2014 May 4]. Available from: http://www.paho.org/hq/index.php?option=com_content&view=article&id=5461:sireva-ii-sistema-de-redes-de-vigilancia-de-los-agentes-responsables-de-neumonias-y-meningitis-bacterianas-&Itemid=3953&lang=pt SIREVA II is a voluntary reporting system and its coverage varies a lot among countries, and caution is advised when using it to estimate invasive pneumococcal disease incidence and impact of PCV. In general, laboratory-based data lacks demographic and clinical information, which limits the analyses.⁵²52. Tate JE, Parashar UD. Monitoring impact and effectiveness of rotavirus vaccination. Expert Rev Vaccines. 2011;10(8):1123-5. DOI:10.1586/erv.11.94 Furthermore, laboratory procedures to identify the pathogen may change over time.³3. Atchison CJ, Lopman BA, Harris CJ, Tam CC, Iturriza Gómara M, Gray JJ. Clinical laboratory practices for the detection of rotavirus in England and Wales: can surveillance based on routine laboratory testing data be used to evaluate the impact of vaccination? Euro Surveill. 2009;14(20):pii:19217.,²⁸28. Lambert SB, Faux CE, Hall L, Birrell FA, Peterson KV, Selvey CE et al. Early evidence for direct and indirect effects of the infant rotavirus vaccine program in Queensland. Med J Aust. 2009;191(3):157-60. DOI:lam10091_fm Despite these limitations, SIREVA II is the best source of data on pneumococcal serotype distribution in the region and may allow assessing serotype replacement after vaccine introduction. Understanding serotype replacement is critical in low- and middle-income countries, where most deaths from pneumococcus occur, with greater diversity of serotypes causing disease and nasopharyngeal colonization early in infancy.¹⁶16. Feikin DR, Kagucia EW, Loo JD, Link-Gelles R, Puhan MA, Cherian T et al. Serotype-specific changes in invasive pneumococcal disease after pneumococcal conjugate vaccine introduction: a pooled analysis of multiple surveillance sites. PLoS Med. 2013;10(9):e1001517. DOI:10.1371/journal.pmed.1001517

Reports of laboratory-confirmed rotavirus infections from clinical microbiology laboratories that constitute a national- or sentinel-laboratory surveillance system were also used.¹⁰10. Carvalho-Costa FA, Volotão EM, Assis RM, Fialho AM, Andrade JS, Rocha LN et al. Laboratory-based rotavirus surveillance during the introduction of a vaccination program, Brazil, 2005-2009. Pediatr Infect Dis J. 2011;30(1 Suppl):S35-41. DOI:10.1097/INF.0b013e3181fefd5f,¹³13. Dulgheroff ACB, Figueiredo EF, Moreira LP, Moreira KC, Moura LMS, Gouvêa VS et al. Distribution of rotavirus genotypes after vaccine introduction in the Triângulo Mineiro region of Brazil: 4-year follow-up study. J Clin Virol. 2012;55(1):67-71. DOI:101016/j.jcv.2012.06.003,³³33. Morillo SG, Luchs A, Cilli A, Costa FF, Carmona RC, Timenetsky MC. Characterization of rotavirus strains from day care centers: pre- and post-rotavirus vaccine era. J Pediatr (Rio J). 2010;86(2):155-8. DOI:10.2223/JPED.1981,³⁹39. Pereira LA, Raboni SM, Nogueira MB, Vidal LR, Almeida SM, Debur MC et al. Rotavirus infection in a tertiary hospital: laboratory diagnosis and impact of immunization on pediatric hospitalization. Braz J Infect Dis. 2011;15(3):215-9. DOI:10.1590/S1413-86702011000300006 These data allow assessing the impact of vaccination on rotavirus-confirmed diarrhea and genotype distribution.

Local secondary data including the hospital discharge summary database and medical records of a single hospital have been used as data sources for HIA of vaccination programs.³⁴34. Nieto Guevara J, López O, González G. Impacto de la introducción de la vacuna contra el rotavirus en la hospitalización por gastroenteritis aguda grave en el Hospital del Niño de la Ciudad de Panamá. Rev Panam Salud Publica. 2008;24(3):189-94. DOI:10.1590/S1020-49892008000900005,⁴¹41. Pírez MC, Algorta G, Cedrés A, Sobrero H, Varela A, Giachetto G et al. Impact of universal pneumococcal vaccination on hospitalizations for pneumonia and meningitis in children in Montevideo, Uruguay. Pediatr Infect Dis J. 2011;30(8):669-74. DOI:10.1097/INF.0b013e3182152bf1,⁴²42. Pírez MC, Algorta G, Chamorro F, Romero C, Varela A, Cedrés A et al. Changes in hospitalizations for pneumonia after universal vaccination with pneumococcal conjugate vaccines 7/13 valent and Haemophilus influenzae type b conjugate vaccine in a pediatric referral hospital in Uruguay. Pediatr Infect Dis J. 2014;33(7):753-9. DOI:10.1097/INF.0000000000000294 The major limitation of these data is that study results cannot be generalized to the entire population.³⁰30. Leboreiro JI, Zapata IB, Montessoro GM, León Aguilar CE, Rendón Macías ME. La vacuna antirrotavirus y la demanda de atención hospitalaria de niños con diarrea. Rev Mex Pediatr. 2013;80(1):15-21.,³⁵35. Nieto Guevara J, Daza C, Smith R. Decrease in hospitalizations for pneumonia in children under five years of age in an Indian reservation in Panama after the introduction of the Heptavalent Pneumococcal Conjugate Vaccine (PCV7). Int J Pediatr. 2013;2013:514-78. DOI:10.1155/2013/514578

Primary data collection was conducted in HIA of PCV⁵⁰50. Sgambatti S, Minamisava R, Afonso ET, Toscano CM, Bierrenbach AL, Andrade AL. Appropriateness of administrative data for vaccine impact evaluation: the case of pneumonia hospitalizations and pneumococcal vaccine in Brazil. Epidemiol Infect. 2015;143(2):334-42. DOI:10.1017/S0950268814000922 and rotavirus²2. Assis ASF, Valle DA, Antunes GR, Tibiriça SHC, Assis RMS, Leite JPG et al. Rotavirus epidemiology before and after vaccine introduction. J Pediatr (Rio J). 2013;89(5):470-6. DOI:10.1016/j.jped.2013.02.019,⁸8. Borges AMT, Souza MD, Fiaccadori FS, Cardoso DDP. Monitoring the circulation of rotavirus among children after the introduction of the Rotarix TM vaccine in Goiânia, Brazil. Mem Inst Oswaldo Cruz. 2011;106(4):499-501. DOI:10.1590/S0074-02762011000400018,²¹21. Gouvea VS, Dias GS, Aguiar EA, Pedro AR, Fichman ER, Chinem ES et al. Acute gastroenteritis in a pediatric hospital in Rio de Janeiro in pre- and post-rotavirus vaccination settings. Open Virol J. 2009;3:26-30. DOI:10.2174/1874357900903010026,³⁰30. Leboreiro JI, Zapata IB, Montessoro GM, León Aguilar CE, Rendón Macías ME. La vacuna antirrotavirus y la demanda de atención hospitalaria de niños con diarrea. Rev Mex Pediatr. 2013;80(1):15-21.,⁴⁸48. Sáfadi MAP, Berezin EN, Munford V, Almeida FJ, Moraes JC, Pinheiro CF, et al. Hospital-based surveillance to evaluate the impact of rotavirus vaccination in São Paulo, Brazil. Pediatr Infect Dis J. 2010;29(11):1019-22. DOI:10.1097/INF.0b013e3181e7886a vaccination programs in LAC countries (Tables 3 and 4). Primary data collection may be particularly useful in settings where health information system databases are unavailable or unreliable and the surveillance system has not been appropriately implemented. Also, it can provide information unavailable on other data sources, such as rotavirus genotype circulation (Table 3).²2. Assis ASF, Valle DA, Antunes GR, Tibiriça SHC, Assis RMS, Leite JPG et al. Rotavirus epidemiology before and after vaccine introduction. J Pediatr (Rio J). 2013;89(5):470-6. DOI:10.1016/j.jped.2013.02.019,⁴⁸48. Sáfadi MAP, Berezin EN, Munford V, Almeida FJ, Moraes JC, Pinheiro CF, et al. Hospital-based surveillance to evaluate the impact of rotavirus vaccination in São Paulo, Brazil. Pediatr Infect Dis J. 2010;29(11):1019-22. DOI:10.1097/INF.0b013e3181e7886a Limitations of studies based on primary data include the small sample size collected in just one or few sites, precluding generalizing the results to the whole population.²2. Assis ASF, Valle DA, Antunes GR, Tibiriça SHC, Assis RMS, Leite JPG et al. Rotavirus epidemiology before and after vaccine introduction. J Pediatr (Rio J). 2013;89(5):470-6. DOI:10.1016/j.jped.2013.02.019,⁸8. Borges AMT, Souza MD, Fiaccadori FS, Cardoso DDP. Monitoring the circulation of rotavirus among children after the introduction of the Rotarix TM vaccine in Goiânia, Brazil. Mem Inst Oswaldo Cruz. 2011;106(4):499-501. DOI:10.1590/S0074-02762011000400018,³⁰30. Leboreiro JI, Zapata IB, Montessoro GM, León Aguilar CE, Rendón Macías ME. La vacuna antirrotavirus y la demanda de atención hospitalaria de niños con diarrea. Rev Mex Pediatr. 2013;80(1):15-21. Additionally, prospective design may be quite expensive, hampering the sustainability of the study and long-term HIA of the vaccination program.

Study outcome definition

Choosing the clinical syndrome of interest in HIA of vaccination program is an issue. HIA of rotavirus vaccination used mainly all-cause diarrhea as the syndrome of interest and hospitalization or mortality rates as outcomes. Only two LAC studies that used population-based surveillance data assessed the impact of rotavirus vaccination on outpatient care (number of healthcare visits).³⁷37. Orozco M, Vasquez J, Pedreira C, De Oliveira LH, Amador JJ, Malespin O et al. Uptake of rotavirus vaccine and national trends of acute gastroenteritis among children in Nicaragua. J Infect Dis. 2009;200 Suppl 1:S125-30. DOI:10.1086/605053,⁵⁹59. Yen C, Armero Guardado JA, Alberto P, Rodriguez Araujo DS, Mena C, Cuellar E 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. DOI:10.1097/INF.0b013e3181fefa05 The etiological diagnosis of rotavirus gastroenteritis requires laboratory tests, which are rarely performed in clinical practice since they do not alter the treatment.¹⁷17. Fernandes EG, Sato HK, Leshem E, Flannery B, Konstantyner TC, Veras MA et al. Impact of rotavirus vaccination on diarrhea-related hospitalizations in São Paulo State, Brazil. Vaccine. 2014;32(27):3402-8. DOI:10.1016/j.vaccine.2014.04.015,⁵⁹59. Yen C, Armero Guardado JA, Alberto P, Rodriguez Araujo DS, Mena C, Cuellar E 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. DOI:10.1097/INF.0b013e3181fefa05 Rotavirus testing is done at the discretion of the physician, based on institutional practices, which may change over time.⁵³53. Tate JE, Haynes A, Payne DC, Cortese MM, Lopman BA, Patel MM et al. Trends in national rotavirus activity before and after introduction of rotavirus vaccine into the national immunization program in the United States, 2000 to 2012. Pediatr Infect Dis J. 2013;32(7):741-4. DOI:10.1097/INF.0b013e31828d639c Although more specific and precise, using rotavirus-related diarrhea in studies based on secondary data may underestimate the true burden of disease and the impact of the vaccination program. Furthermore, "measuring impact on all-cause diarrhea may be more valuable to decision makers and the public health community because it provides an estimate of the preventable fraction of diarrhea deaths and admissions attributable to rotavirus".⁹9. Carmo GM, Yen C, Cortes J, Siqueira AA, Oliveira WK, Cortez-Escalante JJ et al. Decline in diarrhea mortality and admissions after routine childhood rotavirus immunization in Brazil: a time-series analysis. PLoS Med. 2011;8(4):e1001024. DOI:10.1371/journal.pmed.1001024

Most of the eight HIA of PCV in LAC evaluated pneumonia,¹1. Afonso ET, Minamisava R, Bierrenbach AL, Cortez Escalante JJ, Alencar AP, Domingues CM et al. Effect of 10-valent pneumococcal vaccine on pneumonia among children, Brazil. Emerg Infect Dis. 2013;19(4):589-97.,⁷7. Becker-Dreps S, Amaya E, Liu L, Moreno G, Rocha J, Briceño R et al. Changes in childhood pneumonia and infant mortality rates following introduction of the 13-valent pneumococcal conjugate vaccine in Nicaragua. Pediatr Infect Dis J. 2014;33(6):637-42. DOI:10.1097/INF.0000000000000269,²⁵25. Hortal M, Estevan M, Iraola I, De Mucio B. A population-based assessment of the disease burden of consolidated pneumonia in hospitalized children under five years of age. Int J Infect Dis. 2007;11(3):273-7. DOI:10.1016/j.ijid.2006.05.006,²⁶26. Hortal M, Estevan M, Laurani H, Iraola I, Meny M. Hospitalized children with pneumonia in Uruguay: pre and post introduction of 7 and 13-valent pneumococcal conjugated vaccines into the National Immunization Program. Vaccine. 2012;30(33):4934-8. DOI:10.1016/j.vaccine.2012.05.054,³⁵35. Nieto Guevara J, Daza C, Smith R. Decrease in hospitalizations for pneumonia in children under five years of age in an Indian reservation in Panama after the introduction of the Heptavalent Pneumococcal Conjugate Vaccine (PCV7). Int J Pediatr. 2013;2013:514-78. DOI:10.1155/2013/514578,⁴¹41. Pírez MC, Algorta G, Cedrés A, Sobrero H, Varela A, Giachetto G et al. Impact of universal pneumococcal vaccination on hospitalizations for pneumonia and meningitis in children in Montevideo, Uruguay. Pediatr Infect Dis J. 2011;30(8):669-74. DOI:10.1097/INF.0b013e3182152bf1,⁴²42. Pírez MC, Algorta G, Chamorro F, Romero C, Varela A, Cedrés A et al. Changes in hospitalizations for pneumonia after universal vaccination with pneumococcal conjugate vaccines 7/13 valent and Haemophilus influenzae type b conjugate vaccine in a pediatric referral hospital in Uruguay. Pediatr Infect Dis J. 2014;33(7):753-9. DOI:10.1097/INF.0000000000000294 two evaluated invasive pneumococcal disease³⁸38. Parra EL, De La Hoz F, Díaz PL, Sanabria O, Realpe ME, Moreno J. Changes in Streptococcus pneumoniae serotype distribution in invasive disease and nasopharyngeal carriage after the heptavalent pneumococcal conjugate vaccine introduction in Bogotá, Colombia. Vaccine. 2013;31(37):4033-8. DOI:10.1016/j.vaccine.2013.04.074,⁵⁰50. Sgambatti S, Minamisava R, Afonso ET, Toscano CM, Bierrenbach AL, Andrade AL. Appropriateness of administrative data for vaccine impact evaluation: the case of pneumonia hospitalizations and pneumococcal vaccine in Brazil. Epidemiol Infect. 2015;143(2):334-42. DOI:10.1017/S0950268814000922 and one evaluated meningitis.¹1. Afonso ET, Minamisava R, Bierrenbach AL, Cortez Escalante JJ, Alencar AP, Domingues CM et al. Effect of 10-valent pneumococcal vaccine on pneumonia among children, Brazil. Emerg Infect Dis. 2013;19(4):589-97. We did not identify any LAC study evaluating the impact of PCV on acute otitis media.

Diagnosing invasive pneumococcal diseases require laboratory tests. In some countries, such as the USA, blood cultures (BC) are performed in routine care for every child with fever without a focus in both hospital and outpatient care, whereas in others, such as most LAC countries, BC are limited to severely ill hospitalized children. BC practices may affect the burden of disease estimates (invasive pneumococcal disease incidence increases parallel to the number of BC samples in a population), the relative frequency of clinical syndromes (higher frequency of bacteremia without focus in countries with higher frequency of BC samples) and the serotype distribution. Previous use of antibiotics before sample collection also affects diagnostic sensitivity.⁴⁰40. Pérez A, Herranz M, Segura M, Padilla E, Gil F, Durán G et al. Epidemiologic impact of blood cultures practices and antibiotic consumption on pneumococcal bacteremia in children. Eur J Clin Microbiol Infect Dis. 2008;27(8):717-24. DOI:10.1007/s10096-008-0498-2,⁵⁴54. Vergison A, Hanquet G. Challenges in estimating the impact of pneumococcal conjugate vaccines through surveillance. Pediatr Infect Dis J. 2012;31(4):400-3. DOI:10.1097/INF.0b013e31824bc1f0 Changes in medical practices may also influence the results of before-after studies. A study of invasive pneumococcal disease before and after the PCV7 program implementation in England and Wales evaluated control pathogens that also depend on blood culture practices and reporting, but for which there had been no public health intervention (Escherichia coli and non-pyogenic streptococci).¹⁸18. Flasche S, Slack M, Miller E. Long term trends introduce a potential bias when evaluating the impact of the pneumococcal conjugate vaccination programme in England and Wales. Euro Surveill. 2011;16(20):19868. Similar trends (increasing rates) for invasive pneumococcal disease and the control pathogens suggested that the sensitivity of surveillance was increasing prior to vaccine introduction. Ignoring prevaccination trends could lead to underestimating the reduction in invasive pneumococcal disease and overestimating the degree of replacement disease.¹⁸18. Flasche S, Slack M, Miller E. Long term trends introduce a potential bias when evaluating the impact of the pneumococcal conjugate vaccination programme in England and Wales. Euro Surveill. 2011;16(20):19868.

Technical developments may increase the sensitivity of diagnostic tests.⁵⁴54. Vergison A, Hanquet G. Challenges in estimating the impact of pneumococcal conjugate vaccines through surveillance. Pediatr Infect Dis J. 2012;31(4):400-3. DOI:10.1097/INF.0b013e31824bc1f0 Introduction of polymerase chain reaction (PCR) in the cerebral spinal fluid for diagnosing bacterial meningitis may increase the number of laboratory-confirmed pneumococcal meningitis cases.⁴⁷47. Sacchi CT, Fukasawa LO, Gonçalves MG, Salgado MM, Shutt KA, Carvalhanas TR et al. Incorporation of real-time PCR into routine public health surveillance of culture negative bacterial meningitis in São Paulo, Brazil. PLoS One. 2011;6(6):e20675. DOI:10.1371/journal.pone.0020675 This must be considered when analyzing changes in diagnostic test results throughout the period evaluated.

Pneumonia definition is a challenge.⁴⁶46. Rudan I, O'Brien KL, Nair H, Liu L, Theodoratou E, Qazi S et al. Epidemiology and etiology of childhood pneumonia in 2010: estimates of incidence, severe morbidity, mortality, underlying risk factors and causative pathogens for 192 countries. J Global Health. 2013;3(1):010401. DOI:10.7189/jogh.03.010401 Bacteremia occurs only in a small proportion of cases. The etiological diagnosis of non-bacteremic pneumonia by current tests is insufficiently sensitive and specific, and rarely performed in clinical practice. Due to difficulties to isolate the etiological agent, most studies focused their analyses in all-cause pneumonia.¹1. Afonso ET, Minamisava R, Bierrenbach AL, Cortez Escalante JJ, Alencar AP, Domingues CM et al. Effect of 10-valent pneumococcal vaccine on pneumonia among children, Brazil. Emerg Infect Dis. 2013;19(4):589-97.,²⁵25. Hortal M, Estevan M, Iraola I, De Mucio B. A population-based assessment of the disease burden of consolidated pneumonia in hospitalized children under five years of age. Int J Infect Dis. 2007;11(3):273-7. DOI:10.1016/j.ijid.2006.05.006,²⁶26. Hortal M, Estevan M, Laurani H, Iraola I, Meny M. Hospitalized children with pneumonia in Uruguay: pre and post introduction of 7 and 13-valent pneumococcal conjugated vaccines into the National Immunization Program. Vaccine. 2012;30(33):4934-8. DOI:10.1016/j.vaccine.2012.05.054,³⁵35. Nieto Guevara J, Daza C, Smith R. Decrease in hospitalizations for pneumonia in children under five years of age in an Indian reservation in Panama after the introduction of the Heptavalent Pneumococcal Conjugate Vaccine (PCV7). Int J Pediatr. 2013;2013:514-78. DOI:10.1155/2013/514578,⁴¹41. Pírez MC, Algorta G, Cedrés A, Sobrero H, Varela A, Giachetto G et al. Impact of universal pneumococcal vaccination on hospitalizations for pneumonia and meningitis in children in Montevideo, Uruguay. Pediatr Infect Dis J. 2011;30(8):669-74. DOI:10.1097/INF.0b013e3182152bf1,⁴²42. Pírez MC, Algorta G, Chamorro F, Romero C, Varela A, Cedrés A et al. Changes in hospitalizations for pneumonia after universal vaccination with pneumococcal conjugate vaccines 7/13 valent and Haemophilus influenzae type b conjugate vaccine in a pediatric referral hospital in Uruguay. Pediatr Infect Dis J. 2014;33(7):753-9. DOI:10.1097/INF.0000000000000294 Some of them also evaluated pneumococcal pneumonia (PP).⁴¹41. Pírez MC, Algorta G, Cedrés A, Sobrero H, Varela A, Giachetto G et al. Impact of universal pneumococcal vaccination on hospitalizations for pneumonia and meningitis in children in Montevideo, Uruguay. Pediatr Infect Dis J. 2011;30(8):669-74. DOI:10.1097/INF.0b013e3182152bf1,⁴²42. Pírez MC, Algorta G, Chamorro F, Romero C, Varela A, Cedrés A et al. Changes in hospitalizations for pneumonia after universal vaccination with pneumococcal conjugate vaccines 7/13 valent and Haemophilus influenzae type b conjugate vaccine in a pediatric referral hospital in Uruguay. Pediatr Infect Dis J. 2014;33(7):753-9. DOI:10.1097/INF.0000000000000294 Definitions of pneumonia vary among studies. In general, studies based on secondary data used the diagnosis given by the attending physician, but diagnostic criteria vary among clinicians, health services and health information system databases.³⁵35. Nieto Guevara J, Daza C, Smith R. Decrease in hospitalizations for pneumonia in children under five years of age in an Indian reservation in Panama after the introduction of the Heptavalent Pneumococcal Conjugate Vaccine (PCV7). Int J Pediatr. 2013;2013:514-78. DOI:10.1155/2013/514578 Prospective cohorts used more standardized criteria, mainly radiologically-confirmed pneumonia.²⁵25. Hortal M, Estevan M, Iraola I, De Mucio B. A population-based assessment of the disease burden of consolidated pneumonia in hospitalized children under five years of age. Int J Infect Dis. 2007;11(3):273-7. DOI:10.1016/j.ijid.2006.05.006,²⁶26. Hortal M, Estevan M, Laurani H, Iraola I, Meny M. Hospitalized children with pneumonia in Uruguay: pre and post introduction of 7 and 13-valent pneumococcal conjugated vaccines into the National Immunization Program. Vaccine. 2012;30(33):4934-8. DOI:10.1016/j.vaccine.2012.05.054

Although the clinical diagnosis of acute otitis media does not require additional exams, and the collection of material to isolate pathogens is easier than for pneumonia, LAC countries lack high quality data on acute otitis media incidence and health resource use.⁵5. Bardach A, Ciapponi A, Garcia-Marti S, Glujovsky D, Mazzoni A, Fayad A et al. Epidemiology of acute otitis media in children of Latin America and the Caribbean: a systematic review and meta-analysis. Int J Pediatr Otorhinolaryngol. 2011;75(9):1062-70. DOI:10.1016/j.ijporl.2011.05.014 Generally, acute otitis media is treated in outpatient services, for which registered information is limited in LAC, hindering the HIA of pneumococcal vaccination on this disease.

Main results of the health impact assessment of rotavirus and pneumococcal vaccination programs in Latin America

Most studies showed decreased rates of diarrhea-related deaths, hospital admissions and healthcare visits after rotavirus vaccination implementation (Tables 2, ³3. Atchison CJ, Lopman BA, Harris CJ, Tam CC, Iturriza Gómara M, Gray JJ. Clinical laboratory practices for the detection of rotavirus in England and Wales: can surveillance based on routine laboratory testing data be used to evaluate the impact of vaccination? Euro Surveill. 2009;14(20):pii:19217. and ⁴4. Bányai K, László B, Duque J, Steele AD, Nelson EA, Gentsch JR et al. Systematic review of regional and temporal trends in global rotavirus strain diversity in the pre rotavirus vaccine era: insights for understanding the impact of rotavirus vaccination programs. Vaccine. 2012;30 Suppl 1:A122-30. DOI:10.1016/j.vaccine.2011.09.111). Blunting or delay of seasonal peaks of diarrheal disease after vaccine introduction has also been reported.¹⁵15. Esparza-Aguilar M, Gastañaduy PA, Sánchez-Uribe E, Desai R, Parashar UD, Richardson V et al. Diarrhoea-related hospitalizations in children before and after implementation of monovalent rotavirus vaccination in Mexico. Bull World Health Organ. 2014;92(2):117-25. DOI:10.2471/BLT.13.125286,¹⁷17. Fernandes EG, Sato HK, Leshem E, Flannery B, Konstantyner TC, Veras MA et al. Impact of rotavirus vaccination on diarrhea-related hospitalizations in São Paulo State, Brazil. Vaccine. 2014;32(27):3402-8. DOI:10.1016/j.vaccine.2014.04.015,³²32. Molto Y, Cortes JE, De Oliveira LH, Mike A, Solis I, Suman O 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. DOI:10.1097/INF.0b013e3181fefc68,⁴⁸48. Sáfadi MAP, Berezin EN, Munford V, Almeida FJ, Moraes JC, Pinheiro CF, et al. Hospital-based surveillance to evaluate the impact of rotavirus vaccination in São Paulo, Brazil. Pediatr Infect Dis J. 2010;29(11):1019-22. DOI:10.1097/INF.0b013e3181e7886a Two studies in Mexico and another in Brazil assessed the impact of rotavirus vaccination on diarrhea mortality or hospitalization rates according to the socioeconomic level or human development index of the region.¹⁵15. Esparza-Aguilar M, Gastañaduy PA, Sánchez-Uribe E, Desai R, Parashar UD, Richardson V et al. Diarrhoea-related hospitalizations in children before and after implementation of monovalent rotavirus vaccination in Mexico. Bull World Health Organ. 2014;92(2):117-25. DOI:10.2471/BLT.13.125286,¹⁷17. Fernandes EG, Sato HK, Leshem E, Flannery B, Konstantyner TC, Veras MA et al. Impact of rotavirus vaccination on diarrhea-related hospitalizations in São Paulo State, Brazil. Vaccine. 2014;32(27):3402-8. DOI:10.1016/j.vaccine.2014.04.015,²⁰20. Gastañaduy PA, Sánchez-Uribe E, Esparza-Aguilar M, Desai R, Parashar UD, Patel M et al. Effect of rotavirus vaccine on diarrhea mortality in different socioeconomic regions of Mexico. Pediatrics. 2013;131(4):e1115-20. DOI:10.1542/peds.2012-2797 The Mexican studies observed comparable reduction in diarrhea-related deaths and hospitalization in all areas, whereas the Brazilian study showed great reduction in hospitalization rates of under-five children in the least developed areas.¹⁵15. Esparza-Aguilar M, Gastañaduy PA, Sánchez-Uribe E, Desai R, Parashar UD, Richardson V et al. Diarrhoea-related hospitalizations in children before and after implementation of monovalent rotavirus vaccination in Mexico. Bull World Health Organ. 2014;92(2):117-25. DOI:10.2471/BLT.13.125286,¹⁷17. Fernandes EG, Sato HK, Leshem E, Flannery B, Konstantyner TC, Veras MA et al. Impact of rotavirus vaccination on diarrhea-related hospitalizations in São Paulo State, Brazil. Vaccine. 2014;32(27):3402-8. DOI:10.1016/j.vaccine.2014.04.015,²⁰20. Gastañaduy PA, Sánchez-Uribe E, Esparza-Aguilar M, Desai R, Parashar UD, Patel M et al. Effect of rotavirus vaccine on diarrhea mortality in different socioeconomic regions of Mexico. Pediatrics. 2013;131(4):e1115-20. DOI:10.1542/peds.2012-2797

All eight HIA of pneumococcal vaccination programs in LAC showed reduction in the events of interest, mainly hospitalization, after PCV introduction (Table 4). Nonvaccine serotypes increased in Colombia and Uruguay after vaccine introduction.³⁸38. Parra EL, De La Hoz F, Díaz PL, Sanabria O, Realpe ME, Moreno J. Changes in Streptococcus pneumoniae serotype distribution in invasive disease and nasopharyngeal carriage after the heptavalent pneumococcal conjugate vaccine introduction in Bogotá, Colombia. Vaccine. 2013;31(37):4033-8. DOI:10.1016/j.vaccine.2013.04.074,⁴¹41. Pírez MC, Algorta G, Cedrés A, Sobrero H, Varela A, Giachetto G et al. Impact of universal pneumococcal vaccination on hospitalizations for pneumonia and meningitis in children in Montevideo, Uruguay. Pediatr Infect Dis J. 2011;30(8):669-74. DOI:10.1097/INF.0b013e3182152bf1,⁴²42. Pírez MC, Algorta G, Chamorro F, Romero C, Varela A, Cedrés A et al. Changes in hospitalizations for pneumonia after universal vaccination with pneumococcal conjugate vaccines 7/13 valent and Haemophilus influenzae type b conjugate vaccine in a pediatric referral hospital in Uruguay. Pediatr Infect Dis J. 2014;33(7):753-9. DOI:10.1097/INF.0000000000000294

Table 5 presents a summary of advantages and limitations of study design, data sources, and outcomes used in HIA of vaccination programs.

Despite the strategies to access grey literature, country reports and other local documents may not be included in this review. The classification of epidemiological study designs was heterogeneous and we used the authors' classification. Furthermore, some studies lack methodological information. These two limitations may affect our analysis and synthesis of knowledge production on HIA of PCV and rotavirus vaccination programs.

The challenges in conducting HIA of vaccination programs are easier to face in countries with reliable and sustainable health information systems and surveillance data as well as expertise in health evaluation. However, LAC countries have managed to do a lot in HIA of pneumococcal and rotavirus vaccination programs in a relatively short time after program implementation. Almost all met basic methodological requirements for HIA and suggested a positive health impact. High-quality studies have been conducted in small countries without tradition in research that have prioritized surveillance and registers. Future HIA of vaccination programs should consider the methodological issues and challenges that arose in these first studies conducted in the region as well as in studies from other regions. HIA of vaccination programs should be considered essential in the planning phase of vaccine introduction, with the definition of outcomes, data sources, and responsibilities for data collection and resources. They can also contribute to the validation and methodological development of vaccine cost-effectiveness studies.

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