Pneumococcal infective endocarditis in Brazil: a multicenter study on a severe condition.

BACKGROUND: Streptococcus pneumoniae bacteremia may result in Infective Endocarditis (IE). In the pre-antibiotic era, it caused 10 %‒15 % of IE, decreasing to < 3 % after penicillin availability. Although infrequent, it causes aggressive disease. METHODS: Retrospective analysis of endocarditis databases, prospectively implemented in 4 Brazilian institutions, 2005‒2023. RESULTS: From the prospective cohorts comprising 2321 adult patients with IE, we identified 11 (0.47%) with pneumococcal IE. Males represented 7/11 and mean age was 54 years (22‒77). All had native valve involvement; perivalvular abscess was present in 6/11. Only one patient had concurrent meningitis. Beta-lactams were the antibiotics used in 10/11. All had surgical indication, but only 6 had it, as the others were seriously ill. Overall, in hospital mortality was 6/11, but only 1/6 of those who underwent surgery died, compared to 5/5 of those who had an indication for surgery and did not have it. CONCLUSIONS: The high mortality rates and need for surgical intervention emphasize the need to promptly identify and manage pneumococcal endocarditis. Physicians ought to recommend vaccination to all patients at risk for severe pneumococcal disease.

Prophylactic antibiotics for preventing pneumococcal infection in children with sickle cell disease.

BACKGROUND: Sickle cell disease (SCD) is a group of inherited disorders that result in haemoglobin abnormalities and other complications. Injury to the spleen, among other factors, contribute to persons with SCD being particularly susceptible to infection. Infants and very young children are especially vulnerable. The 'Co-operative Study of Sickle Cell Disease' observed an incidence rate for pneumococcal septicaemia of 10 per 100 person-years in children under the age of three years. Vaccines, including customary pneumococcal vaccines, may be of limited use in this age group. Therefore, prophylactic penicillin regimens may be advisable for this population. This is an update of a Cochrane Review which was first published in 2002, and previously updated, most recently in 2017.  OBJECTIVES: To compare the effects of antibiotic prophylaxis against pneumococcus in children with SCD receiving antibiotic prophylaxis compared to those without in relation to: 1. incidence of Streptococcus pneumoniae infection; 2. mortality (as reported in the included studies); 3. drug-related adverse events (as reported in the included studies) to the individual and the community; 4. the impact of discontinuing at various ages on incidence of infection and mortality. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, which is comprised of references identified from comprehensive electronic database searches and also two clinical trials registries: ClinicalTrials.gov and the WHO International Registry Platform (not in 2020 given access issues relating to Covid-19 pandemic). Additionally, we carried out hand searching of relevant journals and abstract books of conference proceedings. Date of the most recent search: 25 January 2021. SELECTION CRITERIA: All randomised or quasi-randomised controlled trials comparing prophylactic antibiotics to prevent pneumococcal infection in children with SCD with placebo, no treatment or a comparator drug. DATA COLLECTION AND ANALYSIS: The standard methodological procedures expected by Cochrane were used. Both authors independently extracted data and assessed trial quality. The authors used the GRADE criteria to assess the certainty of the evidence. MAIN RESULTS: Six trials were identified by the searches, of which three trials were eligible for inclusion. A total of 880 children, who were between three months to five years of age at randomization were included. The included studies were conducted in centres in the USA and in Kingston, Jamaica. In trials that investigated initiation of penicillin on risk of pneumococcal infection, the odds ratio was 0.37 (95% confidence interval 0.16 to 0.86) (two trials, 457 children) (low-certainty evidence), while for withdrawal the odds ratio was 0.49 (95% confidence interval 0.09 to 2.71) (one trial, 400 children) (low-certainty evidence). Adverse drug effects were rare and minor. Rates of pneumococcal infection were found to be relatively low in children over the age of five years. Overall, the certainty of the evidence for all outcomes was judged to be low. The results from the risk of bias assessment undertaken identified two domains in which the risk of bias was considered to be high, these were incomplete outcome data (attrition bias) (two trials) and allocation concealment (selection bias) (one trial). Domains considered to have a low risk of bias for all three trials were selective reporting (reporting bias) and blinding (performance and detection bias). AUTHORS' CONCLUSIONS: The evidence examined was determined to be of low certainty and suggests that prophylactic penicillin significantly reduces risk of pneumococcal infection in children with homozygous SCD, and is associated with minimal adverse reactions. Further research may help to determine the ideal age to safely withdraw penicillin.

Fluoroquinolone treatment as a protective factor for 10-day mortality in Streptococcus pneumoniae bacteremia in cancer patients.

To evaluate the prognostic factors in adult cancer patients with pneumococcal bacteremia, describe episode features and the phenotypic characteristics of the isolated strains. We evaluated the episodes in patients admitted to a cancer hospital between 2009 and 2015. The outcomes were defined as 48 h mortality and mortality within 10 days after the episode. The variables evaluated were: age, sex, ethnicity, ECOG, Karnofsky score, SOFA, cancer type, metastasis, chemotherapy, radiotherapy, neutropenia, previous antibiotic therapy, community or healthcare-acquired infection, comorbidities, smoking, pneumococcal vaccination, infection site, presence of fever, polymicrobial infection, antimicrobial susceptibility, serotype and treatment. 165 episodes were detected in 161 patients. The mean age was 61.3 years; solid tumors were the most prevalent (75%). 48 h and 10-day mortality were 21% (34/161) and 43% (70/161) respectively. The 48 h mortality- associated risk factors were SOFA and polymicrobial bacteremia; 10-day mortality-associated risk factors were fever, neutropenia, ECOG 3/4, SOFA and fluoroquinolones as a protective factor. Pneumococcal bacteremia presented high mortality in cancer patients, with prognosis related to intrinsic host factors and infection episodes features. Fluoroquinolone treatment, a protective factor in 10-day mortality, has potential use for IPDs and severe community-acquired pneumonia in cancer patients.

Indicadores de saúde da COVID-19 nos primeiros quatro meses no estado de São Paulo / COVID-19 health indicators in the first four months in the state of São Paulo / Indicadores de salud COVID-19 en los primeros cuatro meses en el estado de São Paulo

Objetivo: Analisar a estimativa dos indicadores de saúde da COVID-19 nos quatro primeiros meses da pandemia a partir da confirmação do primeiro caso. Método: Estudo ecológico. Foram coletados os casos confirmados de COVID-19 do Estado de São Paulo (ESP) dos meses de fevereiro a junho, obtidos do Centro de Vigilância Epidemiológica do ESP. A análise dos dados foi realizada a partir de indicadores de saúde e a população foi obtida pela Fundação Sistema Estadual de Análise de Dados do ESP. O estudo não passou por Comitê de Ética e Pesquisa por se tratar de dados públicos. Resultado: Nos primeiros quatro meses da pandemia da COVID-19 no ESP houve aumento consecutivos do número de municípios afetados, casos confirmados, óbitos, coeficientes de incidência e mortalidade e declínio do coeficiente de letalidade. Conclusão: Verificamos diminuição dos óbitos da COVID-19 no ESP e isso pode estar associado ao aprimoramento do manejo clínico da doença.(AU)

Objective: To analyze the estimate of the health indicators of COVID-19 in the first four months of the pandemic from the confirmation of the first case. Method: Ecological study. Confirmed cases of COVID-19 from the State of São Paulo (ESP) from February to June were collected from the Center for Epidemiological Surveillance of ESP. Data analysis was carried out based on health indicators and the population was obtained by the ESP State System of Data Analysis Foundation. The study did not go through the Ethics and Research Committee because it is public data. Result: In the first four months of the COVID-19 pandemic in ESP, there was a consecutive increase in the number of affected municipalities, confirmed cases, deaths, incidence and mortality rates and a decline in the lethality rate. Conclusion: We verified a decrease in the deaths of COVID-19 in the ESP and this may be associated with the improvement of the clinical management of the disease.(AU)

Objetivo: Analizar la estimación de los indicadores de salud de COVID-19 en los primeros cuatro meses de la pandemia desde la confirmación del primer caso. Método: Estudio ecológico. Los casos confirmados de COVID-19 del Estado de São Paulo (ESP) de febrero a junio fueron recolectados del Centro de Vigilancia Epidemiológica de ESP. El análisis de los datos se realizó con base en indicadores de salud y la población fue obtenida por la Fundación Sistema Estatal de Análisis de Datos ESP. El estudio no pasó por el Comité de Ética e Investigación por tratarse de datos públicos. Resultado: En los primeros cuatro meses de la pandemia de COVID-19 en ESP, hubo un aumento consecutivo en el número de municipios afectados, casos confirmados, defunciones, tasas de incidencia y mortalidad y una disminución en la tasa de letalidad. Conclusión: Verificamos una disminución de las muertes por COVID-19 en el ESP y esto puede estar asociado a la mejora del manejo clínico de la enfermedad.(AU)

The pneumococcal two-component system SirRH is linked to enhanced intracellular survival of Streptococcus pneumoniae in influenza-infected pulmonary cells.

The virus-bacterial synergism implicated in secondary bacterial infections caused by Streptococcus pneumoniae following infection with epidemic or pandemic influenza A virus (IAV) is well documented. However, the molecular mechanisms behind such synergism remain largely ill-defined. In pneumocytes infected with influenza A virus, subsequent infection with S. pneumoniae leads to enhanced pneumococcal intracellular survival. The pneumococcal two-component system SirRH appears essential for such enhanced survival. Through comparative transcriptomic analysis between the ΔsirR and wt strains, a list of 179 differentially expressed genes was defined. Among those, the clpL protein chaperone gene and the psaB Mn+2 transporter gene, which are involved in the stress response, are important in enhancing S. pneumoniae survival in influenza-infected cells. The ΔsirR, ΔclpL and ΔpsaB deletion mutants display increased susceptibility to acidic and oxidative stress and no enhancement of intracellular survival in IAV-infected pneumocyte cells. These results suggest that the SirRH two-component system senses IAV-induced stress conditions and controls adaptive responses that allow survival of S. pneumoniae in IAV-infected pneumocytes.

Morbidity, mortality and antimicrobial resistance of pneumococcal infections in the Jamaican paediatric and adult populations.

BACKGROUND: Pneumococcal infections are a leading global cause of morbidity and mortality, complicated by the increasing antimicrobial resistance of pneumococcal isolates. OBJECTIVE: To evaluate morbidity and mortality associated with both invasive pneumococcal disease (IPD) and non-IPD in Jamaica in both the paediatric and adult population. Pneumococcal isolates (n= 94) were collected over a 2-year period (2008-2009). METHODS: Risk factors for poor clinical outcomes: death, complicated disease and length of hospitalization (LOH) were evaluated and antimicrobial resistance patterns were determined by Kirby-Bauer disc diffusion. RESULTS: The case fatality rate was 6.8%. Independent mortality risk factors included complicated disease [OR 30.9 (3.4-276.6)] and diabetes mellitus [OR 8.3 (1.4-48.8)]. Independent risk factors for the development of complicated disease included sickle cell disease [OR 36.5 (4.2-320.3)] and sepsis [OR 3.5 (1.2-10.4)]. The LOH was increased most in patients with invasive disease (4.6-fold) and resistance to ceftriaxone (4.3-fold). Penicillin (16.0%) and erythromycin (14.9%) resistance was most prevalent, while ceftriaxone (4.3%) resistance was least prevalent. CONCLUSIONS: The high burden of IPD in at-risk groups in our population and the associated increase in morbidity and mortality underlie the need for improved preventive and therapeutic management strategies in these patients.

Clinical Features, Diagnosis, and Outcome of Encephalitis in French Guiana.

The aim of our study was to describe the clinical features, the etiologies, and the factors associated with poor outcome of encephalitis in French Guiana. Our study was retrospective, including all cases of encephalitis hospitalized in the Cayenne General Hospital, from January 2007 to July 2017. Patients were included through the 2013 encephalitis consortium criteria and the outcome was evaluated using the Glasgow outcome scale at 3 months from the diagnosis of encephalitis. We included 108 patients, giving an approximate incidence rate of four cases/100,000 inhabitants/year. The origin of the encephalitis was diagnosed in 81 cases (75%), and 72 of them (66.7%) were from an infectious origin. The most common infectious causes were Cryptococcus sp. (18.5%) independently of the immune status, Toxoplasma gondii (13.9%), and Streptococcus pneumoniae (5.5%). In the follow-up, 48 patients (46.6%) had poor outcome. Independent risk factors associated with poor outcome at 3 months were "coming from inside area of the region" (P = 0.036, odds ratio [OR] = 4.19; CI 95% = 1.09-16.06), need for mechanical ventilation (P = 0.002, OR = 5.92; CI 95% = 1.95-17.95), and age ≥ 65 years (P = 0.049, OR = 3.99; CI 95% = 1.01-15.89). The most identified cause of encephalitis in French Guiana was Cryptococcus. The shape of the local epidemiology highlights the original infectious situation with some local specific pathogens.

Theoretical pneumococcal vaccine coverage: analysis of serotypes isolated from inpatients at a tertiary care hospital / Cobertura vacinal pneumocócica teórica: análise de sorotipos isolados de pacientes internados em hospital terciário

ABSTRACT Objective: To evaluate Streptococcus pneumoniae serotypes isolated from an inpatient population at a tertiary care hospital, in order to determine the theoretical coverage of the 13-valent pneumococcal conjugate vaccine (PCV13) and the 23-valent pneumococcal polysaccharide vaccine (PPV23). Methods: This was a cross-sectional study involving 118 inpatients at the Hospital São Lucas, in the city of Porto Alegre, Brazil, whose cultures of blood, cerebrospinal fluid, or other sterile body fluid specimens, collected between January 2005 and December 2016, yielded pneumococcal isolates. The theoretical vaccine coverage was studied in relation to the serotypes identified in the sample and their relationship with those contained in the pneumococcal vaccines available in Brazil. Results: The majority of the population was male (n = 66; 55.9%), with a median age of 57 years (interquartile range: 33-72 years). The most common manifestation was pneumonia, and the pneumococcus was most commonly isolated from blood cultures. More than one fourth of the study population had some degree of immunosuppression (n = 34; 28.8%). Of the total sample, 39 patients (33.1%) died. There were no significant associations between mortality and comorbidity type, ICU admission, or need for mechanical ventilation. The theoretical vaccine coverage of PPV23 alone and PCV13 plus PPV23 was 31.4% and 50.8%, respectively. Conclusions: If the patients in this sample had been previously vaccinated with PCV13 plus PPV23, theoretically, 50.8% of the cases of invasive pneumococcal disease that required hospital admission could potentially have been prevented. Invasive pneumococcal disease should be prevented by vaccination not only of children and the elderly but also of adults in their economically productive years, so as to reduce the socioeconomic costs, morbidity, and mortality still associated with the disease, especially in underdeveloped countries.

RESUMO Objetivo: Avaliar os sorotipos de Streptococcus pneumoniae isolados de uma população internada em um hospital terciário para verificar a cobertura vacinal teórica das vacinas conjugada pneumocócica 13-valente (VCP13) e pneumocócica polissacarídica 23-valente (VPP23). Métodos: Estudo transversal envolvendo 118 pacientes internados no Hospital São Lucas, na cidade de Porto Alegre (RS), cujas amostras de cultura de sangue, líquor ou outro líquido estéril apresentaram isolados de pneumococos entre janeiro de 2005 e dezembro de 2016. A cobertura vacinal teórica foi estudada em relação aos sorotipos observados na amostra e sua relação com os contidos nas vacinas pneumocócicas disponíveis no Brasil. Resultados: A maioria da população era masculina (n = 66; 55,9%), com mediana de idade de 57 anos (intervalo interquartil: 33-72 anos). O agravo mais frequente foi pneumonia, e o pneumococo foi mais frequentemente isolado em hemocultura. Mais de um quarto da população estudada tinha algum grau de imunossupressão (n = 34; 28,8%). Na amostra geral, 39 pacientes (33,1%) foram a óbito. Não houve associações significativas do número de óbitos com o tipo de comorbidades, internação em UTI ou necessidade de ventilação mecânica. A cobertura vacinal teórica da VPP23 e da combinação VCP13 + VPP23 foi de 31,4% e 50,8%, respectivamente. Conclusões: Nesta amostra, se os pacientes tivessem sido previamente vacinados com a combinação VCP13 seguida de VPP23, teoricamente, 50,8% dos casos de doença pneumocócica invasiva que necessitaram de internação hospitalar poderiam ter sido prevenidos potencialmente. Essa doença deve ser prevenida com a vacinação não só de crianças e idosos, mas também de adultos em idade economicamente ativa, para reduzir o custo socioeconômico, a morbidade e a mortalidade ainda associados à doença, especialmente em países subdesenvolvidos.

Theoretical pneumococcal vaccine coverage: analysis of serotypes isolated from inpatients at a tertiary care hospital.

OBJECTIVE: To evaluate Streptococcus pneumoniae serotypes isolated from an inpatient population at a tertiary care hospital, in order to determine the theoretical coverage of the 13-valent pneumococcal conjugate vaccine (PCV13) and the 23-valent pneumococcal polysaccharide vaccine (PPV23). METHODS: This was a cross-sectional study involving 118 inpatients at the Hospital São Lucas, in the city of Porto Alegre, Brazil, whose cultures of blood, cerebrospinal fluid, or other sterile body fluid specimens, collected between January 2005 and December 2016, yielded pneumococcal isolates. The theoretical vaccine coverage was studied in relation to the serotypes identified in the sample and their relationship with those contained in the pneumococcal vaccines available in Brazil. RESULTS: The majority of the population was male (n = 66; 55.9%), with a median age of 57 years (interquartile range: 33-72 years). The most common manifestation was pneumonia, and the pneumococcus was most commonly isolated from blood cultures. More than one fourth of the study population had some degree of immunosuppression (n = 34; 28.8%). Of the total sample, 39 patients (33.1%) died. There were no significant associations between mortality and comorbidity type, ICU admission, or need for mechanical ventilation. The theoretical vaccine coverage of PPV23 alone and PCV13 plus PPV23 was 31.4% and 50.8%, respectively. CONCLUSIONS: If the patients in this sample had been previously vaccinated with PCV13 plus PPV23, theoretically, 50.8% of the cases of invasive pneumococcal disease that required hospital admission could potentially have been prevented. Invasive pneumococcal disease should be prevented by vaccination not only of children and the elderly but also of adults in their economically productive years, so as to reduce the socioeconomic costs, morbidity, and mortality still associated with the disease, especially in underdeveloped countries.

Postintroduction Study of Cost-Effectiveness of Pneumococcal Vaccine PCV10 from Public Sector Payer's Perspective in the State of Santa Catarina, Brazil.

OBJECTIVES: To evaluate cost-effectiveness of 10-valent pneumococcal conjugate vaccine in the routine immunization program for children younger than 5 years in Brazil by a postintroduction study. METHODS: Ecological study of prevaccine (2006-2009) versus postvaccine (2011-2014) period related the changes in mortality rate and hospitalization rate to direct cost of pneumonia treatment from the payer's perspective to estimate the cost-effectiveness regarding lives saved, life-years gained, and disability-adjusted life-year for children younger than 5 years in the southern Brazilian state of Santa Catarina. All-cause pneumonia (ICD-10 J12-J18) deaths, hospital admissions, and associated costs were retrieved from the Brazilian Ministry of Health official Web site. Life expectancy at birth, population, ambulatory costs, cost savings, and plausible range of these parameters were used from published sources. Computer simulations with sensitivity analysis were performed to obtain the cost-effectiveness estimates. RESULTS: About 27 lives were saved and 2573 hospitalizations averted by the 10-valent pneumococcal conjugate vaccine vaccination in the 2011 to 2014 period at the cost of US $24,348 per life-year gained and US $27,748 per disability-adjusted life-year. The latter cost is 81% of Brazilian gross domestic product per capita over the same period. CONCLUSIONS: The vaccine was very cost-effective according to the World Health Organization criterion.

Evolução das taxas de hospitalização e mortalidade por doença pneumocócica invasiva em municípios da Região Sudeste do Brasil, no período de 2005 a 2015 / Evolution of hospitalization and mortality rates due to invasive pneumococcal disease in municipalities in the Southeast Region of Brazil, from 2005 to 2015

O presente estudo avaliou a evolução das taxas de hospitalização e mortalidade por doença pneumocócica invasiva (DPI) em crianças menores de 1 ano, nos municípios da região sudeste do país. Foram descritas as evoluções das taxas no período de 2005 a 2015, pré e pós introdução da vacina no programa nacional de imunização, nos municípios com mais de 100 mil habitantes e analisados os efeitos dos fatores socioeconômicos, acesso aos serviços de saúde, cobertura vacinal e esquema vacinal adotado. Trata-se de um estudo ecológico, no qual utilizou-se o modelo de regressão de joinpoint para descrever potenciais modificações nas tendências das taxas ao longo dos anos e o modelo de regressão de Poisson multinível para analisar os efeitos das variáveis independentes sobre as taxas. Tendências decrescentes foram identificadas tanto para as taxas de hospitalização, quanto para mortalidade. A introdução da vacina esteve associada a uma redução de 14% (RT=0,86; intervalo de 95% de confiança: [0,85-0,86]) na taxa de hospitalização e de 6% (RT=0,94 [0,90-0,97]) na mortalidade. No período pós-vacinal, após 2010, os resultados demonstraram que o índice de desenvolvimento humano municipal esteve associado a menores taxas de hospitalização e de mortalidade (RT=0,738 [0,577-0,943] e RT=0,467 [0,386-0,565], respectivamente). Maiores coberturas vacinais estiveram associadas a menores taxas de hospitalização (RT=0,995 [0,992-0,998]) enquanto o acesso a serviços de saúde apresentou relação direta com hospitalização (RT=1,22 [1,118-1,331]). O esquema vacinal com doses aos 3-5-7 meses em comparação ao esquema aos 2-4-6 meses associou-se a maior mortalidade (RT=1,921 [1,62-2,278]), enquanto o acesso aos serviços de saúde implicou em menor mortalidade (RT=0,906 [0,839-0,979]). As taxas de mortalidade não apresentaram padrão de evolução temporal similar às de hospitalização, com queda observada já no período pré-vacinal, o que pode estar relacionado a outros aspectos de ordem socioeconômica. Os resultados destacam a importância e as dificuldades das pesquisas realizadas com dados oriundos dos sistemas de informação de saúde e apontam para a necessidade da continuidade de estudos que busquem a compreensão do fenômeno por meio de diferentes abordagens, contribuindo para o aperfeiçoamento dos serviços de vigilância e para a consolidação das políticas públicas em saúde

The present study evaluated the evolution of hospitalization and mortality rates due to invasive pneumococcal disease (IPD) in children under one year of age in the municipalities of the southeastern region of the country. The evolution of rates between 2005 and 2015, before and after vaccination in the national immunization program, was described in municipalities with more than 100 thousand inhabitants and were analyzed the effects of socioeconomic factors, access to health services, vaccination coverage and vaccination schedule adopted. It is an ecological study in which the joinpoint regression model was used to describe potential changes in rate trends over years and the Poisson multilevel regression model to analyze the effects of the independent variables on rates. The decreasing trends were identified for both hospitalization and mortality rates. The introduction of the vaccine was associated with a reduction of 14% (RR =0.86, 95% confidence interval: [0.85-0.86]) in the hospitalization rate and 6% (RR = 0.94 [0.90-0.97]) in mortality. In the post-vaccination period, after 2010, the results showed that municipal human development index was associated with lower rates of hospitalization and mortality (RR = 0.738 [0.577-0.943] and RR = 0.467 [0.386-0.565], respectively). Higher vaccine coverage was associated with lower hospitalization rates (RR = 0.995 [0.992-0.998]), while access to health services was directly related to hospitalization (RR = 1.22 [1.118-1.331]). The vaccination schedule with doses at 3-5-7 months compared to the schedule at 2-4-6 months was associated with higher mortality (RR = 1.921 [1.62-2.278]), while access to health services was associated with lower mortality (RR = 0.906 [0.839-0.979]). The Mortality rates did not show a time evolution pattern similar to those of hospitalization, with a decrease observed in the pre-vaccination period, which can be related to other socioeconomic aspects. The results highlight the importance and the difficulties to investigate data from the currently available health information systems and point out to the need for continuity of studies that seek to understand the phenomenon through different approaches, contributing to the improvement of surveillance services and for the consolidation of public health policies

Impact of pneumococcal conjugate vaccine in children morbidity and mortality in Peru: Time series analyses.

Streptococcus pneumoniae is the leading cause of bacterial pneumonia, meningitis and sepsis in children worldwide. Despite available evidence on pneumococcal conjugate vaccine (PCV) impact on pneumonia hospitalizations in children, studies demonstrating PCV impact in morbidity and mortality in middle-income countries are still scarce. Given the disease burden, PCV7 was introduced in Peru in 2009, and then switched to PCV10 in late 2011. National public healthcare system provides care for 60% of the population, and national hospitalization, outpatient and mortality data are available. We thus aimed to assess the effects of routine PCV vaccination on pneumonia hospitalization and mortality, and acute otitis media (AOM) and all cause pneumonia outpatient visits in children under one year of age in Peru. We conducted a segmented time-series analysis using outcome-specific regression models. Study period was from January 2006 to December 2012. Data sources included the National information systems for hospitalization, mortality, outpatient visits, and RENACE, the national database of aggregated weekly notifications of pneumonia and other acute respiratory diseases (both hospitalized and non-hospitalized). Study outcomes included community acquired pneumonia outpatient visits, hospitalizations and deaths (ICD10 codes J12-J18); and AOM outpatient visits (H65-H67). Monthly age- and sex-specific admission, outpatient visit, and mortality rates per 100,000 children aged <1year, as well as weekly rates for pneumonia and AOM recorded in RENACE were estimated. After PCV introduction, we observed significant vaccine impact in morbidity and mortality in children aged <1year. Vaccine effectiveness was 26.2% (95% CI 16.9-34.4) for AOM visits, 35% (95% CI 8.6-53.8) for mortality due to pneumonia, and 20.6% (95% CI 10.6-29.5) for weekly cases of pneumonia hospitalization and outpatient visits notified to RENACE. We used secondary data sources which are usually developed for other non-epidemiologic purposes. Despite some data limitations, our results clearly demonstrate the overall benefit of PCV vaccination in Peru.

Clinical and microbiological implications of invasive pneumococcal disease in hospitalized patients (1998-2013)

Abstract Introduction Infections caused by Streptococcus pneumoniae (pneumococcus) still represent a challenge for health systems around the world. Objective The objective of this study was to assess microbiological and clinical aspects in hospitalized patients with invasive pneumococcus disease between 1998 and 2013. Materials and methods This was a retrospective study that analyzed the results of pneumococcus identification, serotyping, and susceptibility testing found in the Adolfo Lutz Institute databank. Personal variables, medical history and clinical outcome of patients admitted with invasive pneumococcal disease were analyzed. These were obtained from records of a public teaching hospital – Hospital das Clínicas Faculdade de Medicina Ribeirão Preto. Results The sample comprised 332 patients. Patient age ranged from less than one month to 89 years old (mean 20.3 years) and the sample was predominately male. Pneumonia (67.8%) was the most common disease, accounting for 18.2% of deaths. Serotypes 14, 1, 3, 9V, 6B, 6A, 23F, 19A, 18C, 19F, 12F, and 4 were the most common (75.3%). Most patients, or 67.5%, were cured without any complication (success), 6.9% had some type of sequela (failure), and 25.6% died (failure). In the case of deaths due to meningitis, strains of fully penicillin resistant pneumococcus were isolated. Furthermore, 68.2% of patients who died presented some type of comorbidity. The 60 and older age group presented the most significant association (Odds Ratio = 4.2), with outcome failure regardless of the presence of comorbidity. Serotype 18C was the most significant risk factor both in raw analysis (Odds Ratio = 3.8) and when adjusted for comorbidity (Odds Ratio = 5.0) or age (Odds Ratio = 5.4). The same occurred with serotype 12F (respectively, Odds Ratio = 5.1, Odds Ratio = 5.0, and Odds Ratio = 4.7) Conclusion The present findings highlight the importance of IPD among young adults and older adults. In the era of conjugate vaccines, monitoring serotypes in different age groups is essential to assess the impact and adequacy of immunization.

Clinical and microbiological implications of invasive pneumococcal disease in hospitalized patients (1998-2013).

INTRODUCTION: Infections caused by Streptococcus pneumoniae (pneumococcus) still represent a challenge for health systems around the world. OBJECTIVE: The objective of this study was to assess microbiological and clinical aspects in hospitalized patients with invasive pneumococcus disease between 1998 and 2013. MATERIALS AND METHODS: This was a retrospective study that analyzed the results of pneumococcus identification, serotyping, and susceptibility testing found in the Adolfo Lutz Institute databank. Personal variables, medical history and clinical outcome of patients admitted with invasive pneumococcal disease were analyzed. These were obtained from records of a public teaching hospital - Hospital das Clínicas Faculdade de Medicina Ribeirão Preto. RESULTS: The sample comprised 332 patients. Patient age ranged from less than one month to 89 years old (mean 20.3 years) and the sample was predominately male. Pneumonia (67.8%) was the most common disease, accounting for 18.2% of deaths. Serotypes 14, 1, 3, 9V, 6B, 6A, 23F, 19A, 18C, 19F, 12F, and 4 were the most common (75.3%). Most patients, or 67.5%, were cured without any complication (success), 6.9% had some type of sequela (failure), and 25.6% died (failure). In the case of deaths due to meningitis, strains of fully penicillin resistant pneumococcus were isolated. Furthermore, 68.2% of patients who died presented some type of comorbidity. The 60 and older age group presented the most significant association (Odds Ratio=4.2), with outcome failure regardless of the presence of comorbidity. Serotype 18C was the most significant risk factor both in raw analysis (Odds Ratio=3.8) and when adjusted for comorbidity (Odds Ratio=5.0) or age (Odds Ratio=5.4). The same occurred with serotype 12F (respectively, Odds Ratio=5.1, Odds Ratio=5.0, and Odds Ratio=4.7) CONCLUSION: The present findings highlight the importance of IPD among young adults and older adults. In the era of conjugate vaccines, monitoring serotypes in different age groups is essential to assess the impact and adequacy of immunization.

Cost-Effectiveness Analysis of Universal Vaccination of Adults Aged 60 Years with 23-Valent Pneumococcal Polysaccharide Vaccine versus Current Practice in Brazil.

OBJECTIVE: To evaluate the cost-effectiveness of introducing universal vaccination of adults aged 60 years with the 23-valent pneumococcal polysaccharide vaccine (PPV23) into the National Immunization Program (NIP) in Brazil. METHODS: Economic evaluation using a Markov model to compare two strategies: (1) universal vaccination of adults aged 60 years with one dose of PPV23 and 2) current practice (vaccination of institutionalized elderly and elderly with underlying diseases). The perspective was from the health system and society. Temporal horizon was 10 years. Discount rate of 5% was applied to costs and benefits. Clinical syndromes of interest were invasive pneumococcal disease (IPD) including meningitis, sepsis and others and pneumonia. Vaccine efficacy against IPD was obtained from a meta-analysis of randomized control trials and randomized studies, whereas vaccine effectiveness against pneumonia was obtained from cohort studies. Resource utilization and costs were obtained from the Brazilian Health Information Systems. The primary outcome was cost per life year saved (LYS). Univariate and multivariate sensitivity analysis were performed. RESULTS: The universal vaccination strategy avoided 7,810 hospitalizations and 514 deaths, saving 3,787 years of life and costing a total of USD$31,507,012 and USD$44,548,180, respectively, from the health system and societal perspective. The universal immunization would result in ICERs of USD$1,297 per LYS, from the perspective of the health system, and USD$904 per LYS, from the societal perspective. CONCLUSION: The results suggest that universal vaccination of adults aged 60 years with the 23-valent pneumococcal polysaccharide vaccine (PPV23) is a very cost-effective intervention for preventing hospitalization and deaths for IPD and pneumonia is this age group in Brazil.

Burden of pneumococcal infection in adults in Colombia.

INTRODUCTION: The burden of Streptococcus pneumoniae infections is highest in children. Estimates in adult population are uncommon. We determined the burden of disease associated with pneumococcus in adults in Colombia in year 2008. METHODOLOGY: Using different data sources (official mortality records, medical databases, published literature and local epidemiological data) we estimated prevalence, incidence, mortality and disability due to bacterial pneumonia, bacterial meningitis and bacteremia of any cause for year 2008, and the fraction of these that can be attributed to S. pneumoniae. RESULTS: A total of 63,463 DALYs are lost due to S. pneumoniae in Colombians age 15 or over. Most of this burden (51,848 DALYs, 81.7%) is due to pneumonia, followed by meningitis (9241 DALYs, 14.6%). The three conditions, overall, represent 2.03 DALYs per 1000 Colombians in that age range. CONCLUSIONS: Despite the lower incidence of pneumococcal disease in adults, as compared with children, its burden is still significant, comparable to that of schizophrenia or epilepsy. This study may provide a benchmark for future preventive interventions.

Immune response and protective efficacy of S9 ribosomal protein of Streptococcus pneumoniae in a model of sepsis.

Vaccination is the most promising strategy to reduce the incidence of pneumococcal infection. Although there are vaccines available, all of them are based on polysaccharide antigens (conjugated or not). In addition to their high cost, those vaccines do not cover all serotypes. To overcome these hindrances, we evaluated the immunogenicity and the protective efficacy of the S9 ribosomal protein of Streptococcus pneumoniae with the aim of developing a protein-based vaccine in the future. The gene encoding the S9 ribosomal protein was cloned in pET21-a expression vector, and the recombinant S9 protein was used to immunize mice. Significantly higher levels of anti-S9 immunoglobulin G were achieved (with predominance of immunoglobulin G1) in comparison with the control. Antibodies elicited against S. pneumoniae protein extract in rabbit recognized the recombinant S9 protein by Western blot, thus demonstrating its immunogenicity. Moreover, mice immunized with recombinant S9 protein and challenged with a virulent strain of S. pneumoniae presented a significant reduction of bacteremia after 24 h of infection as compared with the control. However, in the S9-immunized mice the onset of death was insignificantly delayed, but all of them died by the fourth day postinfection.

Prevention of pneumococcal disease through vaccination.

The Millennium Development Goals (MDGs), adopted by world leaders in the year 2000 with an aim to accomplish them by 2015, provide concrete benchmarks for tackling extreme poverty in its many dimensions. One aim is to reduce by two thirds the mortality rate among children <5 years of age. The deaths of nearly 3 million children under 5 each year worldwide can be attributed to diarrhea and pneumonia. Pneumonia, one form of pneumococcal disease, causes almost 1 in 5 deaths of children under 5 worldwide-more than 1.6 million children each year. Pneumococcal disease is preventable by vaccination; because antibiotic resistance is a growing problem worldwide, there is a great need to promote effective pneumococcal vaccines. Vaccines differ from other types of drugs, because they are administered to healthy individuals. Therefore, a good safety profile is required, there is a large governmental regulatory role, and low efficacy is unacceptable. Other important considerations are as follows: vaccines are often used in infants, are typically given in multiple doses, the manufacturing is a larger part of cost, requires high regulatory and quality control burden and minimization of costs. From a biological standpoint, the induction of vaccine-mediated protection is a complex procedure. Long-term protection typically requires the persistence of anti-microbial antibodies and/or the generation of immune memory cells capable of rapid and effective reactivation after microbial re-exposure. Appreciation of the predominant role of B cells in the efficacy of current vaccines should not minimize the importance of generating a T cell response, as this is essential for the induction of high affinity antibodies and immune memory. Pneumococcal capsular polysaccharides typically elicit B cell responses in a T-independent manner. Because of this, capsular polysaccharides are poorly immunogenic in children below 2 years of age and will generate an IgM isotype-based primary response with only short-lived protection. The conjugation of capsular polysaccharides to a protein carrier provides an antigenic complex in a form that can be presented to the immune system and thus recruit antigen specific CD4⁺ cells (T-dependent antibody). Pneumococcal conjugate vaccines (PCVs), comprising pneumococcal polysaccharides conjugated to a protein carrier, not only induce antibodies but also prime the immune system for protective memory response. These vaccines provide protection in children below 2 years of age, generate long-term protection (highly specific IgG antibodies), generate herd immunity (indirect protection of nonimmunized individuals) and have demonstrated effectiveness in regions that have incorporated them into the national immunization schedules. Global implementation of PCVs has contributed to substantial progress toward reducing childhood mortality, but increased vaccine uptake in developing regions such as Latin America and the Caribbean is necessary to continue toward accomplishing the goals outline in the MDGs.

The pharmacoeconomics of pneumococcal conjugate vaccines in Latin America.

Streptococcus pneumoniae continues to be the most important causative agent of invasive bacterial infections in children and is the most common cause of vaccine-preventable deaths in children less than 5 years of age. Due to some conditions in the Latin America region, economic assessments of pneumococcal conjugate vaccines (PCVs) have unique characteristics. First, distribution of S. pneumoniae serotypes, and thus coverage by vaccines that incorporate certain serotypes, varies within the region and compared with other parts of the world. Second, the mortality rate of pneumococcal infections in developing countries is significantly higher than in the US and Europe. Third, the economies of the Latin American region are very different from those of developed countries. For these reasons, the Pan American Health Organization (PAHO) is promoting the need for economic valuation studies of the impact of pneumococcal vaccines Latin America. Given the importance of pneumonia in the burden of pneumococcal disease in Latin America, the number of pneumonia cases prevented by the vaccine has a large impact on the economic valuation of PCVs, due to a strong correlation with numbers of deaths averted, quality-adjusted life-years (QALYs) gained or disability-adjusted life-years (DALYs) avoided. In terms of cost, analysis of impact on acute otitis media (short-term) and sequelae (long-term) show a significant and important expenditure avoided by vaccination. Cost-effectiveness is significantly modified by vaccine cost, mortality due to pneumonia, vaccine efficacy/effectiveness and herd immunity. Finally the validity of certain assumptions based on the uncertainty of the data should be considered in economic assessments of new PCVs. These include assumptions related to the impact on otitis media, estimates of efficacy/effectiveness based on measured antibody levels and the extrapolation to PCV10 and PCV13 of previous experience with PCV7.

[Economic evaluation of an infant immunization program in Mexico, based on 13-valent pneumococcal conjugated vaccines]. / Evaluación económica de un programa de inmunización infantil en México basado en la vacuna neumocócica conjugada 13-valente.

OBJECTIVES: Vaccination is an effective intervention for reduce child morbidity and mortality associated to pneumococcus. The availability of new anti-pneumococcal vaccines makes it necessary to evaluate its potential impact on public health and costs related to their implementation. The aim of this study was to estimate the cost-effectiveness and cost-utility of immunization strategies based on pneumococcal conjugated vaccines (PCV's) currently available in Mexico from a third payer perspective. MATERIAL AND METHODS: A decision tree model was developed to assess both, economic and health impact, of anti-pneumococcal vaccination in children <2 years (lifetime time horizon, discount rate: 5% annual). Comparators were: no-vaccination (reference) and strategies based on 7, 10 and 13-valent PCV's. Effectiveness measures were: child deaths avoided, life-years gained (LYG) and quality adjusted life years (QALY's) gained. Effectiveness, utility, local epidemiology and cost of treating pneumococcal diseases were extracted from published sources. Univariate sensitivity analysis were performed. RESULTS: Immunization dominates no-vaccination: strategy based on 13-valent vaccine prevented 16.205 deaths, gained 331.230 LY's and 332.006 QALY's and saved US$1.307/child vaccinated. Strategies based on 7 and 10-valent PCV's prevented 13.806 and 5.589 deaths, gained 282.193 and 114.251 LY's, 282.969 and 114.972 QALY's and saved US$1.084 and US$731/child vaccinated, respectively. These results were robust to variations in herd immunity and lower immunogenicity of 10-valent vaccine. CONCLUSIONS: In Mexico, immunization strategies based on 7, 10 and 13-valent PCV's would be cost-saving interventions, however, health outcomes and savings of the strategy based on 13-valent vaccine are greater than those estimated for 7 and 10-valent PCV's.