Exploring Important Attributes, the Potential Use Cases and Feasibility of Introduction of Measles and Rubella Microarray Patches (MR-MAPs): Insights from Nine Countries.

Background: Microarray patches (MAPs) are innovative, needle-free vaccine delivery systems, suitable for administration by minimally trained health care workers or trained community health workers. Their introduction may transform immunization programmes, particularly for vaccines where high coverage is required for population immunity, such as measles, and where vaccine delivery is challenging, such as in low- and middle-income countries. Recognizing the need to understand how best to tailor these products to reflect country priorities, workshops on measles and rubella MAPs (MR-MAPs) were conducted in multiple regions to collect insights on needs and preferences from relevant stakeholders at country level. Methods: The CAPACITI Innovation Framework was used to structure stakeholder discussions in nine countries in the period from August 2022 to July 2023. The discussions, building on the findings from a situation analysis on the barriers related to measles and rubella vaccine delivery, followed the four-step process outlined in the framework. Results: Key barriers hindering delivery of measles and rubella vaccines across the countries were in the categories of human resource management, service delivery, and demand generation. MR-MAP attributes that stakeholders believed would reduce or eliminate these barriers included ease of preparation and administration, improved thermostability, fewer (ancillary) components, and single-dose presentation. Some attributes such as the site of administration, wear time, and storage volume could exacerbate certain barriers. Based on an understanding of key barriers, product attributes, and underserved populations, stakeholders identified several potential use cases for MR-MAPs: (i) delivery at a fixed health post, (ii) delivery through outreach sessions conducted by health workers, and (iii) administration by community health workers. To enable robust national decision making about the introduction of MR-MAPs and successful implementation, global and national evidence on feasibility and acceptability of MR-MAPs should be generated. To prepare for the potential introduction of MR-MAPs, immunization programmes should evaluate their immunization policies based on their preferred use cases and modify them if needed, for example, to enable community health workers to administer vaccines, along with making programmatic adjustments to waste management and training. Conclusions: MR-MAPs have the potential to reduce key barriers to MR delivery. Yet, their future impact depends on the ability of global stakeholders to steer the development of MR-MAPs to be responsive to country needs and preferences. The generation of evidence to enable robust decision making, timely modification of vaccine policies, and addressing programmatic considerations will be key to successful uptake.

Global Status Report for the Verification of Measles and Rubella Elimination, 2022.

Since the World Health Assembly (WHA) in 2012 endorsed the Global Vaccine Action Plan (GVAP), which included regional measles and rubella elimination goals by 2020, global progress towards verification of measles and rubella elimination has been incremental. Even though the 2020 elimination goals were not achieved, commitment towards achieving measles and rubella elimination has been firmly established in the Immunization Agenda 2030 (IA2030) and the Measles and Rubella Strategic Framework (MRSF) 2021-2030. In 2023, the six Regional Verification Commissions for measles and rubella elimination (RVCs) reviewed data as of 31 December 2022 and confirmed that 82 (42%) Member States have been verified for measles elimination, and 98 (51%) Member States have been verified for rubella elimination. The six RVCs are composed of independent public health and immunization experts who are well-placed to support accelerating measles and rubella elimination. RVCs should be leveraged not only to review elimination documents but also to advocate for and champion public health programming that supports measles and rubella activities. The verification of elimination process is one of many tools that should be deployed to reinforce and accelerate efforts towards achieving a world free of measles and rubella.

Sustaining the Elimination of Measles, Rubella and Congenital Rubella Syndrome in the Americas, 2019-2023: From Challenges to Opportunities.

This report reviews national data from all Member States on measles, rubella, and congenital rubella syndrome (CRS) elimination in the Region of the Americas during 2019-2023. It includes an analysis of compliance with vaccination coverage, surveillance indicators, and measles outbreaks, as well as an analysis of the response capacity of the laboratory network and a country case study that meets all indicators. The sources of information were the integrated epidemiological surveillance system for measles and rubella of the Pan American Health Organization (PAHO)/World Health Organization (WHO) and the Joint Reporting Form (eJRF), among others. From 2020 to 2022, regional coverage with first (MMR-1) and second doses (MMR-2) decreased to rates below 90%. The regional suspected case notification rate was maintained above the minimum expected 2.0 suspect cases per 100,000 population, except in 2021. During 2019 to 2023, 18 countries experienced outbreaks, with two of the outbreaks resulting in re-established endemic transmission. In conclusion, two countries in the Americas have not maintained measles elimination, but by the end of 2023 no country showed endemic measles transmission. One of the countries that lost its certification of elimination in 2018 managed to be reverified in 2023; the other is pending reverification. All countries maintained rubella elimination. Despite these challenges, the sustainability of the elimination of these diseases remains a health priority in the Region.

Using FHIR to Support COVID-19 Vaccine Safety Electronic Case Reports in America.

During the COVID-19 pandemic, the Pan American Health Organization (PAHO) promoted several activities to strengthen the countries' emergency response. Vaccines represented a breakthrough in the pandemic evolution, even though they have not been equitably distributed. As most vaccines have received emergency authorizations for their timely delivery, vaccine safety surveillance has been highlighted for detecting early signals of potential adverse events following immunization (AEFI, also known as ESAVI). The objective of this article is to share the different steps, methodologies, and preliminary results of a regional policy to strengthen the ESAVI surveillance system in the Americas, including the adoption of HL7 FHIR for health information exchange between countries and PAHO.

Estimating the future global dose demand for measles-rubella microarray patches.

Background: Progress toward measles and rubella (MR) elimination has stagnated as countries are unable to reach the required 95% vaccine coverage. Microarray patches (MAPs) are anticipated to offer significant programmatic advantages to needle and syringe (N/S) presentation and increase MR vaccination coverage. A demand forecast analysis of the programmatic doses required (PDR) could accelerate MR-MAP development by informing the size and return of the investment required to manufacture MAPs. Methods: Unconstrained global MR-MAP demand for 2030-2040 was estimated for three scenarios, for groups of countries with similar characteristics (archetypes), and four types of uses of MR-MAPs (use cases). The base scenario 1 assumed that MR-MAPs would replace a share of MR doses delivered by N/S, and that MAPs can reach a proportion of previously unimmunised populations. Scenario 2 assumed that MR-MAPs would be piloted in selected countries in each region of the World Health Organization (WHO); and scenario 3 explored introduction of MR-MAPs earlier in countries with the lowest measles vaccine coverage and highest MR disease burden. We conducted sensitivity analyses to measure the impact of data uncertainty. Results: For the base scenario (1), the estimated global PDR for MR-MAPs was forecasted at 30 million doses in 2030 and increased to 220 million doses by 2040. Compared to scenario 1, scenario 2 resulted in an overall decrease in PDR of 18%, and scenario 3 resulted in a 21% increase in PDR between 2030 and 2040. Sensitivity analyses revealed that assumptions around the anticipated reach or coverage of MR-MAPs, particularly in the hard-to-reach and MOV populations, and the market penetration of MR-MAPs significantly impacted the estimated PDR. Conclusions: Significant demand is expected for MR-MAPs between 2030 and 2040, however, efforts are required to address remaining data quality, uncertainties and gaps that underpin the assumptions in this analysis.

Public health responses during measles outbreaks in elimination settings: Strategies and challenges.

In late September 2016, the Americas became the first region in the world to have eliminated endemic transmission of measles virus. Several other countries have also verified measles elimination, and countries in all six World Health Organization regions have adopted measles elimination goals. The public health strategies used to respond to measles outbreaks in elimination settings are thus becoming relevant to more countries. This review highlights the strategies used to limit measles spread in elimination settings: (1) assembly of an outbreak control committee; (2) isolation of measles cases while infectious; (3) exclusion and quarantining of individuals without evidence of immunity; (4) vaccination of susceptible individuals; (5) use of immunoglobulin to prevent measles in exposed susceptible high-risk persons; (6) and maintaining laboratory proficiency for confirmation of measles. Deciding on the extent of containment efforts should be based on the expected benefit of reactive interventions, balanced against the logistical challenges in implementing them.

Risk analysis for the reintroduction and transmission of measles in the post-elimination period in the Americas

[ABSTRACT]. Objective. To propose and test a model for analyzing municipalities’ level of risk of reintroduction and transmission of the measles virus in the post-elimination period in the Americas. Methods. An ecological-analytical study was conducted using data on the measles epidemic that occurred in 2013–2015 in northeastern Brazil. The variables for analysis were selected after an extensive review of scientific literature on the risk of importation of measles cases. A univariate analysis considering the presence or absence of confirmed cases of measles in 184 municipalities in the state of Ceará, Brazil, was carried out to evaluate the association between the dependent variable and 23 independent variables, grouped into four categories: 1) characteristics of the municipalities; 2) quality indicators for immunization programs and epidemiological surveillance; 3) organizational structure for the public health response; and 4) selected impact indicators. A P value < 0.05 was considered significant. All variables with P < 0.200 were analyzed using multivariate logistic regression. Based on the results, the municipalities were categorized by four levels of risk (“low,” “medium,” “high,” and “very high”). Results. The model sensitivity was 95% for concordance between municipalities classified as “high risk” and “very high risk” and those that had an epidemic between 2013 and 2015 in Ceará. Of the 38 municipalities that had an epidemic, 76% (29/38) were classified as “high risk” and “very high risk”; 146 municipalities did not report cases (P < 0.0002). Conclusions. Given the imminent risk of reintroduction of measles circulation in the post-elimination period in the Americas, this model may be useful in identifying areas at greater risk for reintroduction and continued transmission of measles. Knowledge of vulnerable areas could trigger appropriate surveillance and monitoring to prevent sustained transmission.

[RESUMEN]. Objetivo. Proponer y poner a prueba un modelo para analizar el nivel de riesgo de reintroducción y transmisión del virus del sarampión que existe en los municipios durante el período posterior a la eliminación en la Región de las Américas. Métodos. Se realizó un estudio ecológico y analítico empleando datos sobre la epidemia de sarampión que afectó al noreste del Brasil del 2013 al 2015. Las variables para el análisis se seleccionaron después de efectuar un amplio examen de las publicaciones científicas sobre el riesgo de importación de casos de sarampión. Se llevó a cabo un análisis con una sola variable considerando la presencia o ausencia de los casos de sarampión confirmados en 184 municipios del estado de Ceará (Brasil) para evaluar la asociación entre la variable dependiente y 23 variables independientes, que se agruparon en cuatro categorías: 1) características de los municipios; 2) indicadores de calidad de los programas de vacunación y la vigilancia epidemiológica; 3) estructura de organización de la respuesta de salud pública, y 4) indicadores del impacto seleccionados. Se consideró significativo un valor de P < 0,05. Todas las variables con un valor P < 0,200 se analizaron empleando una regresión logística con varias variables. Teniendo en cuenta los resultados, los municipios se clasificaron en función de cuatro niveles de riesgo (“bajo”, “medio”, “alto” y “muy alto”). Resultados. El modelo tenía una sensibilidad de 95% en el caso de la concordancia entre los municipios clasificados dentro de las categorías de “riesgo alto” y “riesgo muy alto” y los que tuvieron una epidemia entre el 2013 y el 2015 en Ceará. De los 38 municipios que tuvieron una epidemia, 76% (29/38) se clasificaron dentro de las categorías de “riesgo alto” y “riesgo muy alto”; 146 municipios no notificaron casos (P < 0,0002). Conclusiones. Dado el riesgo inminente de reintroducción de la circulación del sarampión durante el período posterior a la eliminación en la Región de las Américas, este modelo puede ser útil para reconocer las zonas en las que existe un mayor riesgo de reintroducción y transmisión continua del sarampión. El conocimiento de las zonas vulnerables podría desembocar en actividades de vigilancia y seguimiento apropiadas para evitar la transmisión sostenida.

[RESUMO]. Objetivo. Elaborar e testar um modelo para analisar o risco de reintrodução e transmissão do vírus do sarampo ao nível municipal no período pós-eliminação nas Américas. Métodos. Um estudo analítico-ecológico foi realizado com base nos dados da epidemia de sarampo ocorrida em 2013–2015 no nordeste do Brasil. As variáveis para análise foram selecionadas após extensa revisão da literatura científica sobre o risco de importação de casos de sarampo. Uma análise univariada considerando a presença ou a ausência de casos confirmados de sarampo em 184 municípios no Estado do Ceará foi conduzida para avaliar a associação entre a variável dependente e 23 variáveis independentes divididas em quatro grupos: 1) características dos municípios, 2) indicadores de qualidade dos programas de vacinação e da vigilância epidemiológica, 3) estrutura organizacional para resposta em saúde pública e 4) indicadores de impacto selecionados. Um nível de significância de 5% foi definido. Todas as variáveis com P < 0,200 foram analisadas por regressão logística multivariada e, segundo os resultados, os municípios foram categorizados em quatro níveis de risco: baixo, intermediário, alto e muito alto. Resultados. A sensibilidade do modelo foi de 95% para concordância entre os municípios categorizados como “risco alto” e “risco muito alto” e os que registraram a ocorrência de epidemia entre 2013 e 2015 no Ceará. Dos 38 municípios onde ocorreu uma epidemia, 76% (29/38) apresentaram “risco alto” e “risco muito alto” de reintrodução e transmissão do vírus do sarampo e 146 municípios não notificaram casos (P < 0,0002). Conclusão. Diante do risco iminente de reintrodução da circulação do vírus do sarampo no período pós-eliminação nas Américas, este modelo pode servir para identificar as áreas de maior risco de reintrodução e transmissão contínua do vírus do sarampo. Conhecer as áreas vulneráveis incentiva a adoção de procedimentos adequados de vigilância e monitoramento a fim de prevenir a transmissão sustentada

Risk analysis for the reintroduction and transmission of measles in the post-elimination period in the Americas.

OBJECTIVE: To propose and test a model for analyzing municipalities' level of risk of reintroduction and transmission of the measles virus in the post-elimination period in the Americas. METHODS: An ecological-analytical study was conducted using data on the measles epidemic that occurred in 2013-2015 in northeastern Brazil. The variables for analysis were selected after an extensive review of scientific literature on the risk of importation of measles cases. A univariate analysis considering the presence or absence of confirmed cases of measles in 184 municipalities in the state of Ceará, Brazil, was carried out to evaluate the association between the dependent variable and 23 independent variables, grouped into four categories: 1) characteristics of the municipalities; 2) quality indicators for immunization programs and epidemiological surveillance; 3) organizational structure for the public health response; and 4) selected impact indicators. A P value < 0.05 was considered significant. All variables with P < 0.200 were analyzed using multivariate logistic regression. Based on the results, the municipalities were categorized by four levels of risk ("low," "medium," "high," and "very high"). RESULTS: The model sensitivity was 95% for concordance between municipalities classified as "high risk" and "very high risk" and those that had an epidemic between 2013 and 2015 in Ceará. Of the 38 municipalities that had an epidemic, 76% (29/38) were classified as "high risk" and "very high risk"; 146 municipalities did not report cases (P < 0.0002). CONCLUSIONS: Given the imminent risk of reintroduction of measles circulation in the post-elimination period in the Americas, this model may be useful in identifying areas at greater risk for reintroduction and continued transmission of measles. Knowledge of vulnerable areas could trigger appropriate surveillance and monitoring to prevent sustained transmission.

Risk analysis for the reintroduction and transmission of measles in the post-elimination period in the Americas / Análisis del riesgo de reintroducción y transmisión del sarampión durante el período posterior a la eliminación en la Región de las Américas / Análise do risco de reintrodução e transmissão do sarampo no período pós-eliminação nas Américas

ABSTRACT Objective To propose and test a model for analyzing municipalities' level of risk of reintroduction and transmission of the measles virus in the post-elimination period in the Americas. Methods An ecological-analytical study was conducted using data on the measles epidemic that occurred in 2013-2015 in northeastern Brazil. The variables for analysis were selected after an extensive review of scientific literature on the risk of importation of measles cases. A univariate analysis considering the presence or absence of confirmed cases of measles in 184 municipalities in the state of Ceará, Brazil, was carried out to evaluate the association between the dependent variable and 23 independent variables, grouped into four categories: 1) characteristics of the municipalities; 2) quality indicators for immunization programs and epidemiological surveillance; 3) organizational structure for the public health response; and 4) selected impact indicators. A P value < 0.05 was considered significant. All variables with P < 0.200 were analyzed using multivariate logistic regression. Based on the results, the municipalities were categorized by four levels of risk ("low," "medium," "high," and "very high"). Results The model sensitivity was 95% for concordance between municipalities classified as "high risk" and "very high risk" and those that had an epidemic between 2013 and 2015 in Ceará. Of the 38 municipalities that had an epidemic, 76% (29/38) were classified as "high risk" and "very high risk"; 146 municipalities did not report cases (P < 0.0002). Conclusions Given the imminent risk of reintroduction of measles circulation in the post-elimination period in the Americas, this model may be useful in identifying areas at greater risk for reintroduction and continued transmission of measles. Knowledge of vulnerable areas could trigger appropriate surveillance and monitoring to prevent sustained transmission.

RESUMEN Objetivo Proponer y poner a prueba un modelo para analizar el nivel de riesgo de reintroducción y transmisión del virus del sarampión que existe en los municipios durante el período posterior a la eliminación en la Región de las Américas. Métodos Se realizó un estudio ecológico y analítico empleando datos sobre la epidemia de sarampión que afectó al noreste del Brasil del 2013 al 2015. Las variables para el análisis se seleccionaron después de efectuar un amplio examen de las publicaciones científicas sobre el riesgo de importación de casos de sarampión. Se llevó a cabo un análisis con una sola variable considerando la presencia o ausencia de los casos de sarampión confirmados en 184 municipios del estado de Ceará (Brasil) para evaluar la asociación entre la variable dependiente y 23 variables independientes, que se agruparon en cuatro categorías: 1) características de los municipios; 2) indicadores de calidad de los programas de vacunación y la vigilancia epidemiológica; 3) estructura de organización de la respuesta de salud pública, y 4) indicadores del impacto seleccionados. Se consideró significativo un valor de P < 0,05. Todas las variables con un valor P < 0,200 se analizaron empleando una regresión logística con varias variables. Teniendo en cuenta los resultados, los municipios se clasificaron en función de cuatro niveles de riesgo ("bajo", "medio", "alto" y "muy alto"). Resultados El modelo tenía una sensibilidad de 95% en el caso de la concordancia entre los municipios clasificados dentro de las categorías de "riesgo alto" y "riesgo muy alto" y los que tuvieron una epidemia entre el 2013 y el 2015 en Ceará. De los 38 municipios que tuvieron una epidemia, 76% (29/38) se clasificaron dentro de las categorías de "riesgo alto" y "riesgo muy alto"; 146 municipios no notificaron casos (P < 0,0002). Conclusiones Dado el riesgo inminente de reintroducción de la circulación del sarampión durante el período posterior a la eliminación en la Región de las Américas, este modelo puede ser útil para reconocer las zonas en las que existe un mayor riesgo de reintroducción y transmisión continua del sarampión. El conocimiento de las zonas vulnerables podría desembocar en actividades de vigilancia y seguimiento apropiadas para evitar la transmisión sostenida.

RESUMO Objetivo Elaborar e testar um modelo para analisar o risco de reintrodução e transmissão do vírus do sarampo ao nível municipal no período pós-eliminação nas Américas. Métodos Um estudo analítico-ecológico foi realizado com base nos dados da epidemia de sarampo ocorrida em 2013-2015 no nordeste do Brasil. As variáveis para análise foram selecionadas após extensa revisão da literatura científica sobre o risco de importação de casos de sarampo. Uma análise univariada considerando a presença ou a ausência de casos confirmados de sarampo em 184 municípios no Estado do Ceará foi conduzida para avaliar a associação entre a variável dependente e 23 variáveis independentes divididas em quatro grupos: 1) características dos municípios, 2) indicadores de qualidade dos programas de vacinação e da vigilância epidemiológica, 3) estrutura organizacional para resposta em saúde pública e 4) indicadores de impacto selecionados. Um nível de significância de 5% foi definido. Todas as variáveis com P < 0,200 foram analisadas por regressão logística multivariada e, segundo os resultados, os municípios foram categorizados em quatro níveis de risco: baixo, intermediário, alto e muito alto. Resultados A sensibilidade do modelo foi de 95% para concordância entre os municípios categorizados como "risco alto" e "risco muito alto" e os que registraram a ocorrência de epidemia entre 2013 e 2015 no Ceará. Dos 38 municípios onde ocorreu uma epidemia, 76% (29/38) apresentaram "risco alto" e "risco muito alto" de reintrodução e transmissão do vírus do sarampo e 146 municípios não notificaram casos (P < 0,0002). Conclusão Diante do risco iminente de reintrodução da circulação do vírus do sarampo no período pós-eliminação nas Américas, este modelo pode servir para identificar as áreas de maior risco de reintrodução e transmissão contínua do vírus do sarampo. Conhecer as áreas vulneráveis incentiva a adoção de procedimentos adequados de vigilância e monitoramento a fim de prevenir a transmissão sustentada.

Effectiveness of monovalent rotavirus vaccine in Bolivia: case-control study.

OBJECTIVE: To evaluate the effectiveness of two doses of a monovalent rotavirus vaccine (RV1) against hospital admission for rotavirus in Bolivia. DESIGN: Case-control study. SETTING: Six hospitals in Bolivia, between March 2010 and June 2011. PARTICIPANTS: 400 hospital admissions for rotavirus, 1200 non-diarrhea hospital controls, and 718 rotavirus negative hospital controls. MAIN OUTCOME MEASURES: Odds of antecedent vaccination between case patients and controls; effectiveness of vaccination ((1-adjusted odds ratio)×100), adjusted for age and other confounders; and stratified effectiveness by dose, disease severity, age group, and serotype. RESULTS: In comparison with non-diarrhea controls, case patients were more likely to be male and attend day care but less likely to have chronic underlying illness, higher level maternal education, and telephones and computers in their home. Rotavirus negative controls were somewhat more similar to case patients but also were more likely to be male and attend day care and less likely to have higher level maternal education and computers in their homes. The adjusted effectiveness of RV1 against hospital admission for rotavirus was 69% (95% confidence interval 54% to 79%) with rotavirus negative controls and 77% (65% to 84%) with non-diarrhea controls. The effectiveness of one dose of RV1 was 36% and 56%, respectively. With both control groups, protection was sustained through two years of life, with similar efficacy against hospital admission among children under 1 year (64% and 77%) and over 1 year of age (72% and 76%). RV1 provided significant protection against diverse serotypes, partially and fully heterotypic to the G1P[8] vaccine. Effectiveness using the two control groups was 80% and 85% against G9P[8], 74% and 93%% against G3P[8], 59% and 69% against G2P[4], and 80% and 87% against G9P[6] strains. CONCLUSION: The monovalent rotavirus vaccine conferred high protection against hospital admission for diarrhea due to rotavirus in Bolivian children. Protection was sustained through two years of life against diverse serotypes different from the vaccine strain.

Impact of vaccination against Haemophilus influenzae type b with and without a booster dose on meningitis in four South American countries.

To inform World Health Organization recommendations regarding use of Haemophilus influenzae type b (Hib) vaccines in national immunization programs, a multi-country evaluation of trends in Hib meningitis incidence and prevalence of nasopharyngeal Hib carriage was conducted in four South American countries using either a primary, three-dose immunization schedule without a booster dose or with a booster dose in the second year of life. Surveillance data suggest that high coverage of Hib conjugate vaccine sustained low incidence of Hib meningitis and low prevalence of Hib carriage whether or not a booster dose was used.

Rubella and congenital rubella syndrome elimination activities: Colombia, 2005-2006.

As part of regional commitments in the Americas aimed at elimination of rubella and congenital rubella syndrome, and consolidation of measles elimination, Colombia conducted mass vaccination of males and females aged 14-39 years in 2005-2006. The target population included 18,238< 443 persons (44% of the entire population). Vaccination activities were extended because of limited participation and public concerns about vaccine safety. Over a 10-month peroid, 17,697,717 doses of measles-rubella vaccine were administered, reaching 97% of the target population, including 96.4% of females and 97.6% of males. Estimated coverage exceeded 95% in 33 of 36 departments and districts, and in 3 others, it ranged from 92% to 95%. In rapid monitoring conducted in 504 (45%) of 1119 municipalities, 95% of persons in the target population were vaccinated. The Colombian experience underscores the importance of social mobilization at the local level, political commitment, and microplanning and offers lessons for future mass vaccination campaigns.

Decline in rotavirus hospitalizations and health care visits for childhood diarrhea following rotavirus vaccination in El Salvador.

BACKGROUND: A recent postlicensure study from El Salvador showed that the monovalent rotavirus vaccine conferred 76% protection against rotavirus hospitalizations. We further examined the impact of rotavirus vaccination on the national burden of childhood diarrhea to help assess the total public health benefits of vaccination. METHODS: We compared all-cause diarrhea and rotavirus-specific hospitalization rates during prevaccine year 2006, with postvaccine years 2008 and 2009 in children < 5 years of age from 7 sentinel surveillance hospitals. We also compared annual rates of diarrhea-related healthcare events during prevaccine years 2005 and 2006 with postvaccine years 2008 and 2009 to examine the national burden of healthcare utilization for all-cause diarrhea. RESULTS: Among sentinel surveillance hospitals, rotavirus hospitalization rates among children < 5 years of age declined by 81% (95% confidence interval [CI]: 78%-84%) in 2008 when 2-dose rotavirus vaccine coverage was 50% among infants < 1 year; the decline was 69% (95% CI: 65%-73%) in 2009 when 2-dose vaccine coverage was 61% among infants < 1 year, compared with 2006. The greatest declines were observed in children ≤ 1 year of age, although sizeable reductions were also observed among children ≥ 2 years in 2008. National diarrhea-related healthcare visits during rotavirus season decreased by 48% (95% CI: 47%-48%) in 2008 and by 35% (95% CI: 34%-35%) in 2009 compared with the mean rate from the 2005 and 2006 rotavirus seasons. CONCLUSIONS: Rotavirus vaccination had a substantial public health impact on rotavirus disease and overall diarrhea events in El Salvador. Important age-related changes in diarrheal incidence emphasize the need for ongoing rotavirus surveillance after vaccine introduction.

Effectiveness of rotavirus vaccination against childhood diarrhoea in El Salvador: case-control study.

OBJECTIVE: To evaluate the effectiveness of a monovalent rotavirus vaccine against severe rotavirus disease and to assess its impact on diarrhoea in children aged less than 2 years after national introduction in El Salvador, a low-middle income country in Central America. DESIGN: Matched case-control study. SETTING: Seven hospitals in cities across El Salvador, January 2007 to June 2009. PARTICIPANTS: 323 children aged less than 2 years admitted with laboratory confirmed rotavirus diarrhoea and 969 healthy controls matched for age and neighbourhood. MAIN OUTCOME MEASURE: Effectiveness of rotavirus vaccination ((1-adjusted odds ratio of vaccination)x100) against rotavirus diarrhoea requiring hospital admission. RESULTS: Cases and controls were similar for breast feeding, premature birth, maternal education, and socioeconomic variables. G1P[8] strains were identified in 92% of rotavirus cases. Effectiveness of two doses of vaccination against diarrhoea requiring hospital admission was 76% (95% confidence interval 64% to 84%). Protection was significantly lower (P=0.046) among children aged 12 months or more (59%, 27% to 77%) compared with children aged 6-11 months (83%, 68% to 91%). One dose of vaccine was 51% (26% to 67%) effective. At the sentinel hospitals, all admissions for diarrhoea among children under 5 declined by 40% in 2008 and by 51% in 2009 from the prevaccine year 2006. CONCLUSIONS: A monovalent rotavirus vaccine was highly effective against admissions for rotavirus diarrhoea in children aged less than 2 years in El Salvador and substantially reduced the number of such admissions in this low-middle income setting. The impact on disease epidemiology after vaccination, particularly among older children, warrants future attention.

Resistencia a antibióticos no betalactámicos de aislamientos invasores de Streptococcus pneumoniae en niños latinoamericanos: SIREVA II, 2000-2005 / Resistance to non-beta-lactam antibiotics in the clinical isolates of Streptococcus pneumoniae of children in Latin America: SIREVA II, 2000-2005

OBJETIVO. Determinar la evolución de la resistencia a la eritromicina, el cloranfenicol, el trimetoprim-sulfametozaxol (SXT) y la vancomicina de aislamientos invasores de Streptococcus pneumoniae obtenidos de niños de 10 países de América Latina y del Caribe en seis años de vigilancia. MÉTODOS. Se analizaron 8 993 aislamientos de S. pneumoniae recuperados entre 2000 y 2005 de niños menores de 6 años con infecciones invasoras, procedentes de Argentina, Brasil, Chile, Colombia, Cuba, México, Paraguay, República Dominicana, Uruguay y Venezuela. La sensibilidad a los antibióticos se determinó mediante los métodos establecidos y estandarizados en el proyecto SIREVA. La resistencia a múltiples antibióticos se definió como la resistencia a tres o más familias de antibióticos, de los no betalactámicos analizados en este estudio o de los betalactámicos evaluados en un estudio previo en el que 37,8% de estos aislamientos presentaron sensibilidad disminuida a la penicilina. RESULTADOS. Se encontró algún grado de resistencia al SXT y la eritromicina (56,4% y 15,4% de los aislamientos estudiados, respectivamente) y 4,6% presentó alta resistencia al cloranfenicol. Todos los aislamientos fueron sensibles a la vancomicina. Se observó la mayor frecuencia de resistencia al SXT en los aislamientos de neumonía y a la eritromicina en los casos de sepsis (61,6% y 25,5%, respectivamente; P < 0,01). La mayor frecuencia de resistencia al SXT se observó en Brasil (71,9%) y a la eritromicina en México (38,2%) y Venezuela (32,9%). Los serotipos 14, 6B, 19F y 23F fueron los que más frecuentemente se asociaron con la resistencia a los antibióticos estudiados. CONCLUSIONES. Se observó una elevada y creciente frecuencia de aislamientos resistentes al SXT y la eritromicina, y una disminución en la proporción de aislamientos resistentes al cloranfenicol. Estas tendencias mostraron diferencias entre los países estudiados.

OBJECTIVE. To examine the development of resistance to erythromycin, chloramphenicol, trimethoprim-sulfamethoxazole (TMP-SMZ), and vancomycin of the invasive isolates of Streptococcus pneumoniae obtained from children in 10 Latin American/Caribbean countries during six years of surveillance. METHODS. Analysis of 8 993 isolates of S. pneumoniae recovered in 2000­2005 from children with invasive infections, who were less than 6 years of age, and from Argentina, Brazil, Chile, Colombia, Cuba, Dominican Republic, Mexico, Paraguay, Uruguay, or Venezuela. Antibiotic susceptibility was determined through the methods established and standardized by the SIREVA project. Multidrug resistance was defined as: resistance to three or more antibiotics of the same class; to the non-beta-lactams analyzed by this study; or, to the beta-lactams evaluated by a previous study, in which 37.8% of these isolates showed decreased susceptibility to penicillin. RESULTS. Some degree of resistance was found to TMP-SMZ and erythromycin (56.4% and 15.4% of the isolates studied, respectively), with 4.6% highly resistant to chloramphenicol. All isolates were susceptible to vancomycin. The highest prevalence of TMP-SMZ resistance was observed in the pneumonia isolates; and that of erythromycin, in cases of sepsis (61.6% and 25.5%, respectively; P < 0.01). The highest prevalence of TMP-SMZ resistance was found in Brazil (71.9%), and that of erythromycin, in Mexico (38.2%) and Venezuela (32.9%). The 14, 6B, 19F, and 23F serotypes were most often associated with resistance to the antibiotics in the study. CONCLUSIONS. High and increasing rates of isolates resistant to TMP-SMZ and erythromycin were observed, as well as a decreasing percentage of isolates resistant to chloramphenicol. These trends highlight differences among the countries studied

[The economic costs of pneumonia in children under 2 years of age in Colombia]. / Costos económicos de las neumonías en niños menores de 2 años de edad, en Colombia.

OBJECTIVE: To analyze the costs of pneumonias presumed to be of viral or bacterial origin, as diagnosed by chest X ray, in four reference center hospitals in three cities in Colombia. METHODS: A total of 128 cases of pneumonia (64 bacterial cases and 64 viral cases) that had consecutively entered the hospitals in the study between July 2001 and January 2003 were investigated. The diagnosis of pneumonia was based on chest X rays. The study population was composed of children under 2 years of age who required hospitalization. In order to estimate the costs for bacterial pneumonias and viral pneumonias, the cost of each activity was determined for each case, and then average costs were calculated. RESULTS: The average cost of the presumably bacterial pneumonia cases was US $611.50 (95% confidence interval (95% CI), US $532.20-690.80); that of the presumably viral cases was US $472.20 (95% CI, US $331.80-612.60). The observed differences were due to direct expenses, especially drugs (antibiotics), special services, and diagnostic tests. In the two groups the families were similar in their incomes and the indirect costs that they had to bear, so the indirect costs were not considered relevant in terms of distinguishing between the costs caused by the two forms of pneumonia. CONCLUSIONS: The study found differences in the direct costs of care between the presumably bacterial cases and the presumably viral ones. The study results also gave an approximation of the indirect costs to the patients' families caused by the pneumonias. The differences found in the direct costs also indicate that X-ray diagnosis is useful for differentiating between viral and bacterial pneumonia. Few studies in Latin America have assessed the economic costs of pneumonia in children, so this study can serve as a reference for future research on the impact of interventions against pneumonia.

Costos económicos de las neumónias en niños menores de 2 años de edad, en Colombia / The economic costs of pneumonia in children under 2 years of age in Colombia

Objective. To analyze the costs of pneumonias presumed to be of viral or bacterial origin, as diagnosed by chest X ray, in four reference center hospitals in three cities in Colombia. Methods. A total of 128 cases of pneumonia (64 bacterial cases and 64 viral cases) that had consecutively entered the hospitals in the study between July 2001 and January 2003 were investigated. The diagnosis of pneumonia was based on chest X rays. The study population was composed of children under 2 years of age who required hospitalization. In order to estimate the costs for bacterial pneumonias and viral pneumonias, the cost of each activity was determined for each case, and then average costs were calculated. Results. The average cost of the presumably bacterial pneumonia cases was US$ 611.50 (95% confidence interval (95% CI), US$ 532.20­690.80); that of the presumably viral cases was US$ 472.20 (95% CI, US$ 331.80­612.60). The observed differences were due to direct expenses, especially drugs (antibiotics), special services, and diagnostic tests. In the two groups the families were similar in their incomes and the indirect costs that they had to bear, so the indirect costs were not considered relevant in terms of distinguishing between the costs caused by the two forms of pneumonia. Conclusions. The study found differences in the direct costs of care between the presulybacterial cases and the presumably viral ones. The study results also gave an approximation of the indir ect costs to the patients' families caused by the pneumonias. The differences found in the direct costs also indicate that X-ray diagnosis is useful for differentiating between viral and bacterial pneumonia. Few studies in Latin America have assessed the economic costs of pneumonia in children, so this study can serve as a reference for future research on the impact of interventions against pneumonia

Objetivos. Analizar los costos de las neumonías presuntamente virales y bacterianas diagnosticadas por radiografía en centros de referencia de tres ciudades colombianas. Métodos. Se estudiaron 128 casos de neumonía, 64 bacterianas y 64 virales, que ingresaron consecutivamente a los hospitales del estudio en Cartagena, Medellín y Santa Fe de Bogotá entre julio de 2001 y enero de 2003. Los diagnósticos de neumonía se fundamentaron en la radiografía de tórax y la población de estudio se compuso de niños menores de 2 años que requirieron hospitalización. Para estimar los costos de cada intervención se utilizó el método de determinación de costos por actividad para cada caso, después de lo cual se estimaron los costos medios. Resultados. Los costos de las neumonías presuntamente bacterianas fueron de 611,50 dólares estadounidenses (US$) (IC95%, 532,20­690,80) y los de las presuntamente virales, de 472,20 US$ (IC95%, 331,80­612,60). Las diferencias observadas se explican por los costos directos, en particular de los medicamentos (antibióticos), servicios especiales y pruebas diagnósticas. Dada la similar procedencia de las familias de ambas poblaciones, los costos indirectos no mostraron diferencias y su participación en los costos totales no se consideró relevante. Conclusiones. El estudio reveló diferencias en los costos de la atención de las neumonías presuntamente bacterianas y virales, y se aproximó a los costos indirectos generados por estas entidades patológicas. Tales diferencias permiten inferir que el método de diagnóstico utilizado, que fue la radiografía de tórax, tuvo la capacidad de diferenciar los sucesos de interés. Puesto que en la Región son escasos los estudios económicos que valoren los costos de la neumonía en niños, el presente puede servir de referencia para futuras investigaciones sobre el impacto de las intervenciones en las neumonías