Corrigendum: Rethinking immunization programs through the life course approach.

[This corrects the article DOI: 10.3389/fpubh.2024.1355384.].

Rethinking immunization programs through the life course approach.

The world continues to undergo a profound demographic shift toward increasing longevity -but quality of life is not improving correspondingly. At the same time, countries are taking stock of the negative impacts of the COVID-19 pandemic on national immunization programs. The pandemic exacerbated the declines in vaccination coverage for multiple vaccine-preventable diseases (VPD). To ensure that all persons receive all the vaccines for which they are eligible, it is time to consider how applying a life course approach (LCA) to immunization programs can help reinvigorate and redesign actions for greater vaccine uptake. In this mini review, we present the key concepts and principles of the LCA as applied to national immunization programs. Also, we offer recommendations on how health systems can achieve regional and national goals to ensure all people receive the recommended vaccine doses at every stage of life, thus ensuring the greatest benefits for individuals and societies.

Impact of the 'Health on Wheels' (HoW) strategy on COVID-19 vaccination coverage in hard-to-reach communities in Alta Verapaz, Guatemala, 2022.

BACKGROUND: In April 2022, after a year of COVID-19 vaccination, there were large differences in coverage between urban and rural areas in Guatemala. To address barriers in rural communities, the "Health on Wheels" (HoW) strategy was implemented. The strategy deployed mobile brigades with a dedicated team of health workers and a culturally sensitive health promotion plan in selected communities in 15 districts in Alta Verapaz, a health area with low COVID-19 vaccination uptake and a high-level of COVID-19 vaccine hesitancy. This study evaluates the impact of the HoW strategy. METHODS: We measured the relative increase in COVID-19 doses administered prior and during the HoW implementation period in the 190 intervened communities and compared to 188 communities without the intervention. Communities were grouped by health district and the impact analyses were stratified by number of COVID-19 vaccine dose (1st, 2nd, and 3rd doses) and history of vaccine hesitancy. RESULTS: The increase in 1st, 2nd, and 3rd dose-COVID-19 vaccination coverage between before and during HoW implementation was 2.4, 2.2 and 2.6 times higher in intervened communities (20 %, 21 % and 37 % increase in 1st, 2nd and 3rd dose, respectively) than in non-intervened communities (8 %, 10 % and 14 % increase in 1st, 2nd and 3rd dose respectively). For the 1st dose, increase in dose administration was 2.9 times higher in intervened communities (n = 24) with hesitancy (24 % increase) compared to non-intervened communities (n = 188) without hesitancy (8 % increase). CONCLUSION: The deployment of mobile brigades with a dedicated team of vaccinators and culturally sensitive health promotion through the HoW strategy successfully accelerated the increase in COVID-19 vaccination coverage in rural communities in Guatemala.

Early impact of COVID-19 vaccination on older populations in four countries of the Americas, 2021.

Objective: To estimate the early impact of coronavirus disease 2019 (COVID-19) vaccination on cases in older populations in four countries (Chile, Colombia, Guatemala, and the United States of America), and on deaths in Chile and Guatemala. Methods: Data were obtained from national databases of confirmed COVID-19 cases and deaths and vaccinations between 1 July 2020 and 31 August 2021. In each country, pre- and post-vaccination incidence ratios were calculated for COVID-19 cases and deaths in prioritized groups (50-59, 60-69, and ≥70 years) compared with those in the reference group (<50 years). Vaccination effect was calculated as the percentage change in incidence ratios between pre- and post-vaccination periods. Results: The ratio of COVID-19 cases in those aged ≥50 years to those aged <50 years decreased significantly after vaccine implementation by 9.8% (95% CI: 9.5 to 10.1%) in Chile, 22.5% (95% CI: 22.0 to 23.1%) in Colombia, 20.8% (95% CI: 20.6 to 21.1%) in Guatemala, and 7.8% (95% CI: 7.6 to 7.9%) in the USA. Reductions in the ratio were highest in adults aged ≥70 years. The effect of vaccination on deaths, with time lags incorporated, was highest in the age group ≥70 years in both Chile and Guatemala: 14.4% (95% CI: 11.4 to 17.4%) and 37.3% (95% CI: 30.9 to 43.7%), respectively. Conclusions: COVID-19 vaccination significantly reduced morbidity in the early post-vaccination period in targeted groups. In the context of a global pandemic with limited vaccine availability, prioritization strategies are important to reduce the burden of disease in high-risk age groups.

Early impact of COVID-19 vaccination on older populations in four countries of the Americas, 2021

[ABSTRACT]. Objective. To estimate the early impact of coronavirus disease 2019 (COVID-19) vaccination on cases in older populations in four countries (Chile, Colombia, Guatemala, and the United States of America), and on deaths in Chile and Guatemala. Methods. Data were obtained from national databases of confirmed COVID-19 cases and deaths and vac- cinations between 1 July 2020 and 31 August 2021. In each country, pre- and post-vaccination incidence ratios were calculated for COVID-19 cases and deaths in prioritized groups (50–59, 60–69, and ≥70 years) compared with those in the reference group (<50 years). Vaccination effect was calculated as the percentage change in incidence ratios between pre- and post-vaccination periods. Results. The ratio of COVID-19 cases in those aged ≥50 years to those aged <50 years decreased signifi- cantly after vaccine implementation by 9.8% (95% CI: 9.5 to 10.1%) in Chile, 22.5% (95% CI: 22.0 to 23.1%) in Colombia, 20.8% (95% CI: 20.6 to 21.1%) in Guatemala, and 7.8% (95% CI: 7.6 to 7.9%) in the USA. Reduc- tions in the ratio were highest in adults aged ≥70 years. The effect of vaccination on deaths, with time lags incorporated, was highest in the age group ≥70 years in both Chile and Guatemala: 14.4% (95% CI: 11.4 to 17.4%) and 37.3% (95% CI: 30.9 to 43.7%), respectively. Conclusions. COVID-19 vaccination significantly reduced morbidity in the early post-vaccination period in targeted groups. In the context of a global pandemic with limited vaccine availability, prioritization strategies are important to reduce the burden of disease in high-risk age groups.

[RESUMEN]. Objetivo. Estimar el impacto temprano sobre los casos de enfermedad por coronavirus 2019 (COVID-19) obtenido con la vacunación contra la COVID-19 en los grupos poblacionales de edad avanzada en cuatro países (Chile, Colombia, Estados Unidos de América y Guatemala), así como el efecto en la mortalidad en Chile y Guatemala. Métodos. Los datos se obtuvieron a partir de las bases de datos nacionales sobre vacunaciones y sobre casos de COVID-19 y muertes debidas a esta enfermedad entre el 1 de julio del 2020 y el 31 de agosto del 2021. Para cada país, se calcularon las razones de incidencia de casos de COVID-19 y de muertes por COVID-19 anteriores y posteriores a la vacunación en los grupos priorizados (50-59, 60-69 y ≥70 años) en comparación con las del grupo de referencia (<50 años). Se calculó el efecto de la vacunación expresado en forma de variación porcentual de la razón de las incidencias entre el período anterior y el posterior a la vacunación. Resultados. Tras la introducción de la vacuna, la razón de los casos de COVID-19 entre las personas ≥50 años y las <50 disminuyó significativamente en un 9,8% (IC del 95%: 9,5% a 10,1%) en Chile, en un 22,5% (IC del 95%: 22,0% a 23,1%) en Colombia, en un 7,8% (IC del 95%: 7,6% a 7,9%) en Estados Unidos de América y en un 20,8% (IC del 95%: 20,6% a 21,1%) en Guatemala. Las reducciones de la razón fueron máximas en las personas adultas ≥70 años. El efecto de la vacunación sobre las muertes, una vez incorporados los desfases cronológicos, fue máximo en el grupo de personas ≥70 años, tanto en Chile como en Guatemala: 14,4% (IC 95%: 11,4% a 17,4%) y 37,3% (IC 95%: 30,9% a 43,7%), respectivamente. Conclusiones. La vacunación contra la COVID-19 redujo significativamente la morbilidad en el período inmediato posterior a la vacunación en los grupos destinatarios. En el contexto de una pandemia con disponibilidad limitada de vacunas a nivel mundial, las estrategias de asignación de prioridades son un factor importante para reducir la carga de morbilidad en los grupos etarios de alto riesgo.

[RESUMO]. Objetivo. Estimar o impacto inicial da vacinação contra a doença pelo coronavírus 2019 (COVID-19) nos casos em populações idosas de quatro países (Chile, Colômbia, Guatemala e Estados Unidos da América) e nas mortes no Chile e na Guatemala. Métodos. Os dados foram obtidos de bancos de dados nacionais de casos e mortes confirmados por COVID-19 e de vacinações entre 1º de julho de 2020 e 31 de agosto de 2021. Em cada país, foram calculadas taxas de incidência pré e pós-vacinação de casos e mortes por COVID-19 em grupos priorizados (50 a 59, 60 a 69 e ≥70 anos) em comparação com o grupo de referência (<50 anos). O efeito da vacinação foi calculado como a mudança percentual nas taxas de incidência entre os períodos pré e pós-vacinação. Resultados. A incidência de casos de COVID-19 em pessoas com idade ≥50 anos em relação às com idade <50 anos diminuiu significativamente após a implementação da vacina, em 9,8% (IC 95%: 9,5 a 10,1%) no Chile, 22,5% (IC 95%: 22,0 a 23,1%) na Colômbia, 20,8% (IC 95%: 20,6 a 21,1%) na Guatemala e 7,8% (IC 95%: 7,6 a 7,9%) nos EUA. As reduções na incidência foram maiores em adultos com idade ≥70 anos. O efeito da vacinação sobre as mortes, com defasagens temporais incorporadas, foi maior na faixa etária ≥70 anos no Chile e na Guatemala, 14,4% (IC de 95%: 11,4 a 17,4%) e 37,3% (IC de 95%: 30,9 a 43,7%), respectivamente. Conclusões. A vacinação contra a COVID-19 reduziu significativamente a morbidade no início do período pós-vacinação nos grupos-alvo. No contexto de uma pandemia mundial com disponibilidade limitada de vacinas, estratégias de priorização são importantes para reduzir a carga de doença em grupos etários de alto risco.

Early impact of COVID-19 vaccination on older populations in four countries of the Americas, 2021 / Impacto temprano de la vacunación contra la COVID-19 en adultos mayores en cuatro países de las Américas, 2021 / Impacto inicial da vacinação contra a COVID-19 em populações idosas em quatro países das Américas, 2021

ABSTRACT Objective. To estimate the early impact of coronavirus disease 2019 (COVID-19) vaccination on cases in older populations in four countries (Chile, Colombia, Guatemala, and the United States of America), and on deaths in Chile and Guatemala. Methods. Data were obtained from national databases of confirmed COVID-19 cases and deaths and vaccinations between 1 July 2020 and 31 August 2021. In each country, pre- and post-vaccination incidence ratios were calculated for COVID-19 cases and deaths in prioritized groups (50-59, 60-69, and ≥70 years) compared with those in the reference group (<50 years). Vaccination effect was calculated as the percentage change in incidence ratios between pre- and post-vaccination periods. Results. The ratio of COVID-19 cases in those aged ≥50 years to those aged <50 years decreased significantly after vaccine implementation by 9.8% (95% CI: 9.5 to 10.1%) in Chile, 22.5% (95% CI: 22.0 to 23.1%) in Colombia, 20.8% (95% CI: 20.6 to 21.1%) in Guatemala, and 7.8% (95% CI: 7.6 to 7.9%) in the USA. Reductions in the ratio were highest in adults aged ≥70 years. The effect of vaccination on deaths, with time lags incorporated, was highest in the age group ≥70 years in both Chile and Guatemala: 14.4% (95% CI: 11.4 to 17.4%) and 37.3% (95% CI: 30.9 to 43.7%), respectively. Conclusions. COVID-19 vaccination significantly reduced morbidity in the early post-vaccination period in targeted groups. In the context of a global pandemic with limited vaccine availability, prioritization strategies are important to reduce the burden of disease in high-risk age groups.

RESUMEN Objetivo. Estimar el impacto temprano sobre los casos de enfermedad por coronavirus 2019 (COVID-19) obtenido con la vacunación contra la COVID-19 en los grupos poblacionales de edad avanzada en cuatro países (Chile, Colombia, Estados Unidos de América y Guatemala), así como el efecto en la mortalidad en Chile y Guatemala. Métodos. Los datos se obtuvieron a partir de las bases de datos nacionales sobre vacunaciones y sobre casos de COVID-19 y muertes debidas a esta enfermedad entre el 1 de julio del 2020 y el 31 de agosto del 2021. Para cada país, se calcularon las razones de incidencia de casos de COVID-19 y de muertes por COVID-19 anteriores y posteriores a la vacunación en los grupos priorizados (50-59, 60-69 y ≥70 años) en comparación con las del grupo de referencia (<50 años). Se calculó el efecto de la vacunación expresado en forma de variación porcentual de la razón de las incidencias entre el período anterior y el posterior a la vacunación. Resultados. Tras la introducción de la vacuna, la razón de los casos de COVID-19 entre las personas ≥50 años y las <50 disminuyó significativamente en un 9,8% (IC del 95%: 9,5% a 10,1%) en Chile, en un 22,5% (IC del 95%: 22,0% a 23,1%) en Colombia, en un 7,8% (IC del 95%: 7,6% a 7,9%) en Estados Unidos de América y en un 20,8% (IC del 95%: 20,6% a 21,1%) en Guatemala. Las reducciones de la razón fueron máximas en las personas adultas ≥70 años. El efecto de la vacunación sobre las muertes, una vez incorporados los desfases cronológicos, fue máximo en el grupo de personas ≥70 años, tanto en Chile como en Guatemala: 14,4% (IC 95%: 11,4% a 17,4%) y 37,3% (IC 95%: 30,9% a 43,7%), respectivamente. Conclusiones. La vacunación contra la COVID-19 redujo significativamente la morbilidad en el período inmediato posterior a la vacunación en los grupos destinatarios. En el contexto de una pandemia con disponibilidad limitada de vacunas a nivel mundial, las estrategias de asignación de prioridades son un factor importante para reducir la carga de morbilidad en los grupos etarios de alto riesgo.

RESUMO Objetivo. Estimar o impacto inicial da vacinação contra a doença pelo coronavírus 2019 (COVID-19) nos casos em populações idosas de quatro países (Chile, Colômbia, Guatemala e Estados Unidos da América) e nas mortes no Chile e na Guatemala. Métodos. Os dados foram obtidos de bancos de dados nacionais de casos e mortes confirmados por COVID-19 e de vacinações entre 1º de julho de 2020 e 31 de agosto de 2021. Em cada país, foram calculadas taxas de incidência pré e pós-vacinação de casos e mortes por COVID-19 em grupos priorizados (50 a 59, 60 a 69 e ≥70 anos) em comparação com o grupo de referência (<50 anos). O efeito da vacinação foi calculado como a mudança percentual nas taxas de incidência entre os períodos pré e pós-vacinação. Resultados. A incidência de casos de COVID-19 em pessoas com idade ≥50 anos em relação às com idade <50 anos diminuiu significativamente após a implementação da vacina, em 9,8% (IC 95%: 9,5 a 10,1%) no Chile, 22,5% (IC 95%: 22,0 a 23,1%) na Colômbia, 20,8% (IC 95%: 20,6 a 21,1%) na Guatemala e 7,8% (IC 95%: 7,6 a 7,9%) nos EUA. As reduções na incidência foram maiores em adultos com idade ≥70 anos. O efeito da vacinação sobre as mortes, com defasagens temporais incorporadas, foi maior na faixa etária ≥70 anos no Chile e na Guatemala, 14,4% (IC de 95%: 11,4 a 17,4%) e 37,3% (IC de 95%: 30,9 a 43,7%), respectivamente. Conclusões. A vacinação contra a COVID-19 reduziu significativamente a morbidade no início do período pós-vacinação nos grupos-alvo. No contexto de uma pandemia mundial com disponibilidade limitada de vacinas, estratégias de priorização são importantes para reduzir a carga de doença em grupos etários de alto risco.

Adoption of digital tools in the context of the COVID-19 pandemic in the Region of the Americas - the Go.Data experience.

The COVID-19 pandemic has accelerated the growth of digital health tools. Although a number of different tools exist to support field data collection in the context of outbreak response, they have not been sufficient. This prompted the World Health Organization (WHO) to collaborate with the Global Outbreak Alert and Response Network (GOARN) and GOARN partners to develop a comprehensive system, Go.Data. Go.Data, a digital tool for outbreak response has simplified how countries operationalize and monitor case and contact data. Since the start of the pandemic, WHO and GOARN partners have provided support to Go.Data projects in 65 countries and territories, yet the demand by countries to have documented success cases of Go.Data implementations continues to grow. This viewpoint documents the successful Go.Data implementation frameworks in two countries, Argentina and Guatemala and an academic institution, the University of Texas at Austin.

Global burden of Clostridium difficile infections: a systematic review and meta-analysis.

BACKGROUND: Clostridium difficile is a leading cause of morbidity and mortality in several countries. However, there are limited evidence characterizing its role as a global public health problem. We conducted a systematic review to provide a comprehensive overview of C. difficile infections (CDI) rates. METHODS: Seven databases were searched (January 2016) to identify studies and surveillance reports published between 2005 and 2015 reporting CDI incidence rates. CDI incidence rates for health care facility-associated (HCF), hospital onset-health care facility-associated, medical or general intensive care unit (ICU), internal medicine (IM), long-term care facility (LTCF), and community-associated (CA) were extracted and standardized. Meta-analysis was conducted using a random effects model. RESULTS: 229 publications, with data from 41 countries, were included. The overall rate of HCF-CDI was 2.24 (95% confidence interval CI = 1.66-3.03) per 1000 admissions/y and 3.54 (95%CI = 3.19-3.92) per 10 000 patient-days/y. Estimated rates for CDI with onset in ICU or IM wards were 11.08 (95%CI = 7.19-17.08) and 10.80 (95%CI = 3.15-37.06) per 1000 admission/y, respectively. Rates for CA-CDI were lower: 0.55 (95%CI = 0.13-2.37) per 1000 admissions/y. CDI rates were generally higher in North America and among the elderly but similar rates were identified in other regions and age groups. CONCLUSIONS: Our review highlights the widespread burden of disease of C. difficile, evidence gaps, and the need for sustainable surveillance of CDI in the health care setting and the community.

The relative invasive disease potential of Streptococcus pneumoniae among children after PCV introduction: A systematic review and meta-analysis.

OBJECTIVES: Burden of pneumococcal disease depends on the prevalence and invasive disease potential of serotypes. We aimed to estimate the invasive disease potential of serotypes in children under 5 years of age by combining data from different settings with routine immunisation with pneumococcal conjugate vaccines (PCV). METHODS: We conducted a systematic review, supplemented by unpublished data, to identify data on the frequency of pneumococcal serotypes in carriage and invasive pneumococcal disease (IPD). We estimated the invasive disease potential of serotypes as the ratio of IPD in relation to carriage (odds ratio and 95%CI) compared with 19A (reference serotype) by meta-analysis. We report results based on a random effects model for children aged 0-23, 24-29, and 0-59 months and by invasive clinical syndromes. RESULTS: In comparison with 19A, serotypes 1, 7F, and 12F had a significantly higher invasive disease potential in children aged 0-23 and 0-59 months for all IPD and clinical syndromes (OR > 5). Several non-vaccine types (NVTs) (6C, 15A, 15BC, 16F, 23B, in these two age groups) had a lower invasive disease potential than 19A (OR 0.1-0.3). NVTs 8, 12F, 24F, and 33F were at the upper end of the invasiveness spectrum. CONCLUSIONS: There is substantial variation among pneumococcal serotypes in their potential to cause IPD and disease presentation, which is influenced by age and time after PCV introduction. Surveillance of IPD and carriage is critical to understand the expected effectiveness of current PCVs (in the longer term) and guide the development of future vaccines.

Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in young children in 2015: a systematic review and modelling study.

BACKGROUND: We have previously estimated that respiratory syncytial virus (RSV) was associated with 22% of all episodes of (severe) acute lower respiratory infection (ALRI) resulting in 55 000 to 199 000 deaths in children younger than 5 years in 2005. In the past 5 years, major research activity on RSV has yielded substantial new data from developing countries. With a considerably expanded dataset from a large international collaboration, we aimed to estimate the global incidence, hospital admission rate, and mortality from RSV-ALRI episodes in young children in 2015. METHODS: We estimated the incidence and hospital admission rate of RSV-associated ALRI (RSV-ALRI) in children younger than 5 years stratified by age and World Bank income regions from a systematic review of studies published between Jan 1, 1995, and Dec 31, 2016, and unpublished data from 76 high quality population-based studies. We estimated the RSV-ALRI incidence for 132 developing countries using a risk factor-based model and 2015 population estimates. We estimated the in-hospital RSV-ALRI mortality by combining in-hospital case fatality ratios with hospital admission estimates from hospital-based (published and unpublished) studies. We also estimated overall RSV-ALRI mortality by identifying studies reporting monthly data for ALRI mortality in the community and RSV activity. FINDINGS: We estimated that globally in 2015, 33·1 million (uncertainty range [UR] 21·6-50·3) episodes of RSV-ALRI, resulted in about 3·2 million (2·7-3·8) hospital admissions, and 59 600 (48 000-74 500) in-hospital deaths in children younger than 5 years. In children younger than 6 months, 1·4 million (UR 1·2-1·7) hospital admissions, and 27 300 (UR 20 700-36 200) in-hospital deaths were due to RSV-ALRI. We also estimated that the overall RSV-ALRI mortality could be as high as 118 200 (UR 94 600-149 400). Incidence and mortality varied substantially from year to year in any given population. INTERPRETATION: Globally, RSV is a common cause of childhood ALRI and a major cause of hospital admissions in young children, resulting in a substantial burden on health-care services. About 45% of hospital admissions and in-hospital deaths due to RSV-ALRI occur in children younger than 6 months. An effective maternal RSV vaccine or monoclonal antibody could have a substantial effect on disease burden in this age group. FUNDING: The Bill & Melinda Gates Foundation.

Risk factors for Clostridium difficile infections - an overview of the evidence base and challenges in data synthesis.

BACKGROUND: Recognition of a broad spectrum of disease and development of Clostridium difficile infection (CDI) and recurrent CDI (rCDI) in populations previously considered to be at low risk has renewed attention on differences in the risk profile of patients. In the absence of primary prevention for CDI and limited treatment options, it is important to achieve a deep understanding of the multiple factors that influence the risk of developing CDI and rCDI. METHODS: We conducted a review of systematic reviews and meta-analyses on risk factors for CDI and rCDI published between 1990 and October 2016. RESULTS: 22 systematic reviews assessing risk factors for CDI (n = 19) and rCDI (n = 6) were included. Meta-analyses were conducted in 17 of the systematic reviews. Over 40 risk factors have been associated with CDI and rCDI and can be classified into three categories: pharmacological risk factors, host-related risk factors, and clinical characteristics or interventions. Most systematic reviews and meta-analyses have focused on antibiotic use (n = 8 for CDI, 3 for rCDI), proton pump inhibitors (n = 8 for CDI, 4 for rCDI), and histamine 2 receptor antagonists (n = 4 for CDI) and chronic kidney disease (n = 4 for rCDI). However, other risk factors have been assessed. We discuss the state of the evidence, methods, and challenges for data synthesis. CONCLUSION: Several studies, synthesized in different systematic review, provide valuable insights into the role of different risk factors for CDI. Meta-analytic evidence of association has been reported for factors such as antibiotics, gastric acid suppressants, non-selective NSAID, and some co-morbidities. However, despite statistical significance, issues of high heterogeneity, bias and confounding remain to be addressed effectively to improve overall risk estimates. Large, prospective primary studies on risk factors for CDI with standardised case definitions and stratified analyses are required to develop more accurate and robust estimates of risk effects that can inform targeted-CDI clinical management procedures, prevention, and research.

Serotype distribution of Streptococcus pneumoniae causing invasive disease in children in the post-PCV era: A systematic review and meta-analysis.

BACKGROUND: Routine immunisation with pneumococcal conjugate vaccines (PCV7/10/13) has reduced invasive pneumococcal disease (IPD) due to vaccine serotypes significantly. However, an increase in disease due to non-vaccine types, or serotype replacement, has been observed. Serotypes' individual contributions to IPD play a critical role in determining the overall effects of PCVs. This study examines the distribution of pneumococcal serotypes in children to identify leading serotypes associated with IPD post-PCV introduction. METHODS: A systematic search was performed to identify studies and surveillance reports (published between 2000 and December 2015) of pneumococcal serotypes causing childhood IPD post-PCV introduction. Serotype data were differentiated based on the PCV administered during the study period: PCV7 or higher valent PCVs (PCV10 or PCV13). Meta-analysis was conducted to estimate the proportional contributions of the most frequent serotypes in childhood IPD in each period. RESULTS: We identified 68 studies reporting serotype data among IPD cases in children. We analysed data from 38 studies (14 countries) where PCV7 was administered and 20 (24 countries) where PCV10 or PCV13 have been introduced. Studies reported early and late periods of PCV7 administration (range: 2001∓13). In these settings, serotype 19A was the most predominant cause of childhood IPD, accounting for 21.8% (95%CI 18.6∓25.6) of cases. In countries that have introduced higher valent PCVs, study periods were largely representative of the transition and early years of PCV10 or PCV13. In these studies, the overall serotype-specific contribution of 19A was lower (14.2% 95%CI 11.1∓18.3). Overall, non-PCV13 serotypes contributed to 42.2% (95%CI 36.1∓49.5%) of childhood IPD cases. However, regional differences were noted (57.8% in North America, 71.9% in Europe, 45.9% in Western Pacific, 28.5% in Latin America, 42.7% in one African country, and 9.2% in one Eastern Mediterranean country). Predominant non-PCV13 serotypes overall were 22F, 12F, 33F, 24F, 15C, 15B, 23B, 10A, and 38 (descending order), but their rank order varied by region. CONCLUSION: Childhood IPD is associated with a wide number of serotypes. In the early years after introduction of higher valent PCVs, non-PCV13 types caused a considerable proportion of childhood IPD. Serotype data, particularly from resource-limited countries with high burden of IPD, are needed to assess the importance of serotypes in different settings. The geographic diversity of pneumococcal serotypes highlights the importance of continued surveillance to guide vaccine design and recommendations.

Infection prevention and control of Clostridium difficile: a global review of guidelines, strategies, and recommendations.

BACKGROUND: Clostridium difficile is the leading cause of health care-associated infections. Given the high incidence of C. difficile infection (CDI) and the lack of primary prevention through immunization, health care professionals should be aware of the most current guidance, as well as strengths and limitations of the evidence base underpinning this guidance. METHODS: We identified publicly available national or organizational guidelines related to CDI infection and prevention control (IPC) published between 2000 and 2015 and for any health care setting through an internet search using the Google search engine. We reviewed CDI-targeted IPC recommendations and describe the assessment of evidence in available guidelines. RESULTS: We identified documents from 28 countries/territories, mainly from acute care hospitals in North America, the Western Pacific, and Europe (18 countries). We identified only a few specific recommendations for long-term care facilities (LTCFs) and from countries in South America (Uruguay and Chile), South East Asia (Thailand), and none for Africa or Eastern Mediterranean. Of 10 IPC areas, antimicrobial stewardship was universally recognized as essential and supported by high quality evidence. Five other widely reported "strong" recommendations were: effective environment cleaning (including medical equipment), case isolation, use of personal protective equipment, surveillance, and education. Several unresolved and emerging issues were documented and currently available evidence was classified mainly as of mixed quality. CONCLUSION: Our review underlines the need for targeted CDI IPC guidelines in several countries and for LTCFs. International harmonisation on the assessment of the evidence for best practices is needed as well as more robust evidence to support targeted recommendations.

Cost of hospital management of Clostridium difficile infection in United States-a meta-analysis and modelling study.

BACKGROUND: Clostridium difficile infection (CDI) is the leading cause of infectious nosocomial diarrhoea but the economic costs of CDI on healthcare systems in the US remain uncertain. METHODS: We conducted a systematic search for published studies investigating the direct medical cost associated with CDI hospital management in the past 10 years (2005-2015) and included 42 studies to the final data analysis to estimate the financial impact of CDI in the US. We also conducted a meta-analysis of all costs using Monte Carlo simulation. RESULTS: The average cost for CDI case management and average CDI-attributable costs per case were $42,316 (90 % CI: $39,886, $44,765) and $21,448 (90 % CI: $21,152, $21,744) in 2015 US dollars. Hospital-onset CDI-attributable cost per case was $34,157 (90 % CI: $33,134, $35,180), which was 1.5 times the cost of community-onset CDI ($20,095 [90 % CI: $4991, $35,204]). The average and incremental length of stay (LOS) for CDI inpatient treatment were 11.1 (90 % CI: 8.7-13.6) and 9.7 (90 % CI: 9.6-9.8) days respectively. Total annual CDI-attributable cost in the US is estimated US$6.3 (Range: $1.9-$7.0) billion. Total annual CDI hospital management required nearly 2.4 million days of inpatient stay. CONCLUSIONS: This review indicates that CDI places a significant financial burden on the US healthcare system. This review adds strong evidence to aid policy-making on adequate resource allocation to CDI prevention and treatment in the US. Future studies should focus on recurrent CDI, CDI in long-term care facilities and persons with comorbidities and indirect cost from a societal perspective. Health-economic studies for CDI preventive intervention are needed.

Risk factors for respiratory syncytial virus associated with acute lower respiratory infection in children under five years: Systematic review and meta-analysis.

BACKGROUND: Respiratory syncytial virus (RSV) is the most common pathogen identified in young children with acute lower respiratory infection (ALRI) as well as an important cause of hospital admission. The high incidence of RSV infection and its potential severe outcome make it important to identify and prioritise children who are at higher risk of developing RSV-associated ALRI. We aimed to identify risk factors for RSV-associated ALRI in young children. METHODS: We carried out a systematic literature review across 4 databases and obtained unpublished studies from RSV Global Epidemiology Network (RSV GEN) collaborators. Quality of all eligible studies was assessed according to modified GRADE criteria. We conducted meta-analyses to estimate odds ratios with 95% confidence intervals (CI) for individual risk factors. RESULTS: We identified 20 studies (3 were unpublished data) with "good quality" that investigated 18 risk factors for RSV-associated ALRI in children younger than five years old. Among them, 8 risk factors were significantly associated with RSV-associated ALRI. The meta-estimates of their odds ratio (ORs) with corresponding 95% confidence intervals (CI) are prematurity 1.96 (95% CI 1.44-2.67), low birth weight 1.91 (95% CI 1.45-2.53), being male 1.23 (95% CI 1.13-1.33), having siblings 1.60 (95% CI 1.32-1.95), maternal smoking 1.36 (95% CI 1.24-1.50), history of atopy 1.47 (95% CI 1.16-1.87), no breastfeeding 2.24 (95% CI 1.56-3.20) and crowding 1.94 (95% CI 1.29-2.93). Although there were insufficient studies available to generate a meta-estimate for HIV, all articles (irrespective of quality scores) reported significant associations between HIV and RSV-associated ALRI. CONCLUSIONS: This study presents a comprehensive report of the strength of association between various socio-demographic risk factors and RSV-associated ALRI in young children. Some of these amenable risk factors are similar to those that have been identified for (all cause) ALRI and thus, in addition to the future impact of novel RSV vaccines, national action against ALRI risk factors as part of national control programmes can be expected to reduce burden of disease from RSV. Further research which identifies, accesses and analyses additional unpublished RSV data sets could further improve the precision of these estimates.

Contact hypersensitivity to oxazolone provokes vulvar mechanical hyperalgesia in mice.

The interplay among pain, allergy and dysregulated inflammation promises to yield significant conceptual advances in immunology and chronic pain. Hapten-mediated contact hypersensitivity reactions are used to model skin allergies in rodents but have not been utilized to study associated changes in pain perception in the affected skin. Here we characterized changes in mechanical hyperalgesia in oxazolone-sensitized female mice challenged with single and repeated labiar skin exposure to oxazolone. Female mice were sensitized with topical oxazolone on their flanks and challenged 1-3 times on the labia. We then measured mechanical sensitivity of the vulvar region with an electronic pressure meter and evaluated expression of inflammatory genes, leukocyte influx and levels of innervation in the labiar tissue. Oxazolone-sensitized mice developed vulvar mechanical hyperalgesia after a single labiar oxazolone challenge. Hyperalgesia lasted up to 24 hours along with local influx of neutrophils, upregulation of inflammatory cytokine gene expression, and increased density of cutaneous labiar nerve fibers. Three daily oxazolone challenges produced vulvar mechanical hyperalgesic responses and increases in nerve density that were detectable up to 5 days post-challenge even after overt inflammation resolved. This persistent vulvar hyperalgesia is resonant with vulvodynia, an understudied chronic pain condition that is remarkably prevalent in 18-60 year-old women. An elevated risk for vulvodynia has been associated with a history of environmental allergies. Our pre-clinical model can be readily adapted to regimens of chronic exposures and long-term assessment of vulvar pain with and without concurrent inflammation to improve our understanding of mechanisms underlying subsets of vulvodynia and to develop new therapeutics for this condition.

TNF-alpha neutralizing antibody blocks thermal sensitivity induced by compound 48/80-provoked mast cell degranulation.

BACKGROUND: Neuro-inflammatory circuits in the tissue regulate the complex pathophysiology of pain. Protective nociceptive pain serves as an early warning system against noxious environmental stimuli. Tissue-resident mast cells orchestrate the increased thermal sensitivity following injection of basic secretagogue compound 48/80 in the hind paw tissues of ND4 mice. Here we investigated the effects of pre-treatment with TNF-α neutralizing antibody on compound 48/80-provoked thermal hyperalgesia. METHODS: We treated ND4 Swiss male mice with intravenous anti-TNF-α antibody or vehicle 30 minutes prior to bilateral, intra-plantar compound 48/80 administration and measured changes in the timing of hind paw withdrawal observed subsequent to mice being placed on a 51oC hotplate. We also assessed changes in tissue swelling, TNF-α gene expression and protein abundance, mast cell degranulation, and neutrophil influx in the hind paw tissue. FINDINGS: We found that TNF-α neutralization significantly blocked thermal hyperalgesia, and reduced early tissue swelling. TNF-α neutralization had no significant effect on mast cell degranulation or neutrophil influx into the tissue, however. Moreover, no changes in TNF-α protein or mRNA levels were detected within 3 hours of administration of compound 48/80. INTERPRETATION:   The neutralizing antibodies likely target pre-formed TNF-α including that stored in the granules of tissue-resident mast cells. Pre-formed TNF-α, released upon degranulation, has immediate effects on nociceptive signaling prior to the induction of neutrophil influx. These early effects on nociceptors are abrogated by TNF-α blockade, resulting in compromised nociceptive withdrawal responses to acute, harmful environmental stimuli.

Mast cell degranulation mediates compound 48/80-induced hyperalgesia in mice.

Mast cells mediate allergies, hypersensitivities, host defense, and venom neutralization. An area of recent interest is the contribution of mast cells to inflammatory pain. Here we found that specific, local activation of mast cells produced plantar hyperalgesia in mice. Basic secretagogue compound 48/80 induced plantar mast cell degranulation accompanied by thermal hyperalgesia, tissue edema, and neutrophil influx in the hindpaws of ND4 Swiss mice. Blocking mast cell degranulation, neutrophil extravasation, and histamine signaling abrogated these responses. Compound 48/80 also produced edema, pain, and neutrophil influx in WT C57BL/6 but not in genetically mast cell-deficient C57BL/6-Kit(W-sh)(/)(W-sh) mice. These responses were restored following plantar reconstitution with bone marrow-derived cultured mast cells.