Invasive pneumococcal diseases in Chinese children: a multicentre hospital-based active surveillance from 2019 to 2021.

This study aimed to provide data for the clinical features of invasive pneumococcal disease (IPD) and the molecular characteristics of Streptococcus pneumoniae isolates from paediatric patients in China. We conducted a multi-centre prospective study for IPD in 19 hospitals across China from January 2019 to December 2021. Data of demographic characteristics, risk factors for IPD, death, and disability was collected and analysed. Serotypes, antibiotic susceptibility, and multi-locus sequence typing (MLST) of pneumococcal isolates were also detected. A total of 478 IPD cases and 355 pneumococcal isolates were enrolled. Among the patients, 260 were male, and the median age was 35 months (interquartile range, 12-46 months). Septicaemia (37.7%), meningitis (32.4%), and pneumonia (27.8%) were common disease types, and 46 (9.6%) patients died from IPD. Thirty-four serotypes were detected, 19F (24.2%), 14 (17.7%), 23F (14.9%), 6B (10.4%) and 19A (9.6%) were common serotypes. Pneumococcal isolates were highly resistant to macrolides (98.3%), tetracycline (94.1%), and trimethoprim/sulfamethoxazole (70.7%). Non-sensitive rates of penicillin were 6.2% and 83.3% in non-meningitis and meningitis isolates. 19F-ST271, 19A-ST320 and 14-ST876 showed high resistance to antibiotics. This multi-centre study reports the clinical features of IPD and demonstrates serotype distribution and antibiotic resistance of pneumococcal isolates in Chinese children. There exists the potential to reduce IPD by improved uptake of pneumococcal vaccination, and continued surveillance is warranted.

Vacunación antineumocócica: situación actual / Pneumococcal vaccination: current status

Las infecciones por Streptococcus pneumoniae originan una importante morbilidad y mortalidad. Entre las personas más susceptibles a su desarrollo se encuentran las de mayor edad, los pacientes inmunodeprimidos y aquellos con comorbilidad, pudiendo presentar además una mayor gravedad y una evolución más desfavorable. Las pautas de vacunación frente al neumococo tienen como objetivo disminuir la incidencia de estas infecciones. Las recomendaciones para ello han ido cambiando a lo largo de los años. La reciente aprobación de la vacuna neumocócica conjugada 20-valente simplifica la pauta previa, al unificar las indicaciones de vacunación en población adulta a partir de los 60 años con y sin factores predisponentes, así como en menores de 60 años con condiciones de riesgo. Está autorizada para mayores de 18 años, por lo que en menores se mantiene la pauta previa: a) si no hay factores ni condiciones de riesgo, se indican tres dosis de vacuna neumocócica conjugada 13 o 15-valente a los 2, 4 y 11 meses; b) si existen factores o condiciones de riesgo, a partir de los 2 años de edad puede ser necesario asociar la vacuna neumocócica de polisacáridos de 23 serotipos. (AU)

Streptococcus pneumoniae infections cause significant morbidity and mortality. Among the people most susceptible to infections are the elderly, immunosuppressed patients, and those with comorbidities, presenting a greater severity and a more unfavorable condition. Vaccination guidelines against pneumococcus aim to reduce the incidence of these infections, whose recommendations have changed over the years. The recent approval of the 20-valent conjugate pneumococcal vaccine simplifies the previous regimen, by unifying the indications for vaccination in the adult population aged 60 years and older with and without predisposing factors, as well as in those aged under 60 years with conditions of risk. It is authorized for the individuals aged over 18 years, so the previous regimen has been maintained in minors: a) if there are no risk factors or conditions, three doses are indicated: 13- or 15-valent pneumococcal conjugate vaccine at 2, 4, and 11 months and b) if there are risk factors or conditions, it may be necessary to associate the 23 serotypes pnemococcal polysaccharide vaccine from 2 years of age. (AU)

Pneumococcal meningitis in adults in 2014-2018 after introduction of pediatric 13-valent pneumococcal conjugate vaccine in Japan.

We assessed the impact of the pediatric 13-valent pneumococcal conjugate vaccine (PCV13) on pneumococcal meningitis in adults in Japan in 2014-2018 by comparing epidemiological characteristics of adults with invasive pneumococcal disease with (n = 222) and without (n = 1258) meningitis. The annual incidence of pneumococcal meningitis in 2016-2018 was 0.20-0.26 cases/100,000 population. Age (p < 0.001) and case fatality rate (p = 0.003) were significantly lower in patients with meningitis than in those without meningitis. The odds of developing meningitis were higher in asplenic/hyposplenic or splenectomized patients (adjusted odds ratio [aOR] 2.29, 95% CI 1.27-4.14), for serotypes 10A (aOR 3.26, 95% CI 2.10-5.06) or 23A (aOR 3.91, 95% CI 2.47-6.19), but lower for those aged ≥ 65 years (aOR 0.59, 95% CI 0.44-0.81). PCV13 had an indirect effect on nonmeningitis, but its impact on meningitis was limited because of an increase in non-PCV13 serotypes. Of meningitis isolates, 78 (35.1%) and 3 (1.4%) were penicillin G- or ceftriaxone-resistant, respectively. We also confirmed an association of the pbp1bA641C mutation with meningitis (aOR 2.92, 95% CI 1.51-5.65).

Prognostic factors for mortality in invasive pneumococcal disease in adult: a system review and meta-analysis.

Risk factors associated with mortality in invasive pneumococcal disease remain unclear. The present work is a meta-analysis of studies that enrolled only patients with invasive pneumococcal disease and reported on mortality. Potentially eligible reports were identified from PubMed, CHAHL, and Web of Science, comprising 26 reports in total. Overall mortality for invasive pneumococcal disease was reported as 20.8% (95% confidence interval (CI) 17.5-24%). Factors associated with mortality were age (odds ratio (OR) 3.04, 95% CI 2.5-3.68), nursing home (OR 1.62, 95% CI 1.13-2.32), nosocomial infection (OR 2.10, 95% CI 1.52-2.89), septic shock (OR 13.35, 95% CI 4.54-39.31), underlying chronic diseases (OR 2.34, 95% CI 1.78-3.09), solid organ tumor (OR 5.34, 95% CI 2.07-13.74), immunosuppressed status (OR 1.67, 95% CI 1.31-2.14), and alcohol abuse (OR 3.14, 95% CI 2.13-4.64). Mortality rates with invasive pneumococcal disease remained high, and these findings may help clinicians provide appropriate initial treatment for this disease.

Clinical characteristics and serotype distribution of invasive pneumococcal disease in pediatric patients from Beijing, China.

Invasive pneumococcal disease (IPD) is associated with significant morbidity and mortality. However, limited studies have reported clinical features of IPD cases among Chinese children. This study aimed to evaluate clinical characteristics as well as serotype distribution of hospitalized IPD children in Beijing, China. Children with confirmed IPD were retrospectively recruited from January 2014 to December 2019. Clinical data were gathered from medical records, and serotypes of Streptococcus pneumoniae isolates were detected. Clinical differences between deaths and survivors were also compared, and risk factors associated with death were determined. Of sixty-eight children diagnosed with IPD, 58 (85.3%) were < 5 years. 19F was the predominant serotype (23, 33.8%), followed by 19A (14, 20.6%), 14 (12, 17.6%), 23F (5, 7.4%), and non-vaccine serotype (NVT) 15A (3, 4.4%). The coverage rate of 13-valent pneumococcal conjugate vaccine (PCV) was 92.6% (63). After introduction of PCV-13, there was a significant increase of IPD due to NVTs (p = 0.047). Sixteen (23.5%) children died, and diagnoses of 11 (68.8%) were meningitis. Risk factors for death were < 2 years (odds ratio [OR] [95% confidence interval {CI}]: 6.64 [1.14-32.10]; p = 0.019), altered mental status (OR [95%CI]: 10.10 [2.11-48.31]; p = 0.004), and septic shock (OR [95%CI]: 6.61 [1.11-39.50]; p = 0.038). This study revealed that the case fatality rate of hospitalized IPD children was high in this hospital. Fatal cases were more likely to be children < 2 years, presented with changed mental status and septic shock. Notably, we found that NVTs increased after PCV13 availability in China.

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.

Health and economic impact of the pneumococcal conjugate vaccine in hindering antimicrobial resistance in China.

Antimicrobial resistance (AMR) poses a serious threat to global public health. However, vaccinations have been largely undervalued as a method to hinder AMR progression. This study examined the AMR impact of increasing pneumococcal conjugate vaccine (PCV) coverage in China. China has one of the world's highest rates of antibiotic use and low PCV coverage. We developed an agent-based DREAMR (Dynamic Representation of the Economics of AMR) model to examine the health and economic benefits of slowing AMR against commonly used antibiotics. We simulated PCV coverage, pneumococcal infections, antibiotic use, and AMR accumulation. Four antibiotics to treat pneumococcal diseases (penicillin, amoxicillin, third-generation cephalosporins, and meropenem) were modeled with antibiotic utilization, pharmacokinetics, and pharmacodynamics factored into predicting AMR accumulation. Three PCV coverage scenarios were simulated over 5 y: 1) status quo with no change in coverage, 2) scaled coverage increase to 99% in 5 y, and 3) accelerated coverage increase to 85% over 2 y followed by 3 y to reach 99% coverage. Compared to the status quo, we found that AMR against penicillin, amoxicillin, and third-generation cephalosporins was significantly reduced by 6.6%, 10.9%, and 9.8% in the scaled scenario and by 10.5%, 17.0%, and 15.4% in the accelerated scenario. Cumulative costs due to AMR, including direct and indirect costs to patients and caretakers, were reduced by $371 million in the scaled and $586 million in the accelerated scenarios compared to the status quo. AMR-reducing benefits of vaccines are essential to quantify in order to drive appropriate investment.

Changes in epigenetic profiles throughout early childhood and their relationship to the response to pneumococcal vaccination.

BACKGROUND: Pneumococcal infections are a major cause of morbidity and mortality in young children and immaturity of the immune system partly underlies poor vaccine responses seen in the young. Emerging evidence suggests a key role for epigenetics in the maturation and regulation of the immune system in health and disease. The study aimed to investigate epigenetic changes in early life and to understand the relationship between the epigenome and antigen-specific antibody responses to pneumococcal vaccination. METHODS: The epigenetic profiles from 24 healthy children were analyzed at 12 months prior to a booster dose of the 13-valent pneumococcal conjugate vaccine (PCV-13), and at 24 months of age, using the Illumina Methylation 450 K assay and assessed for differences over time and between high and low vaccine responders. RESULTS: Our analysis revealed 721 significantly differentially methylated positions between 12 and 24 months (FDR < 0.01), with significant enrichment in pathways involved in the regulation of cell-cell adhesion and T cell activation. Comparing high and low vaccine responders, we identified differentially methylated CpG sites (P value < 0.01) associated with HLA-DPB1 and IL6. CONCLUSION: These data imply that epigenetic changes that occur during early childhood may be associated with antigen-specific antibody responses to pneumococcal vaccines.

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.

Estimated impact of the pneumococcal conjugate vaccine on pneumonia mortality in South Africa, 1999 through 2016: An ecological modelling study.

BACKGROUND: Data on the national-level impact of pneumococcal conjugate vaccine (PCV) introduction on mortality are lacking from Africa. PCV was introduced in South Africa in 2009. We estimated the impact of PCV introduction on all-cause pneumonia mortality in South Africa, while controlling for changes in mortality due to other interventions. METHODS AND FINDINGS: We used national death registration data in South Africa from 1999 to 2016 to assess the impact of PCV introduction on all-cause pneumonia mortality in all ages, with the exclusion of infants aged <1 month. We created a composite (synthetic) control using Bayesian variable selection of nondiarrheal, nonpneumonia, and nonpneumococcal deaths to estimate the number of expected all-cause pneumonia deaths in the absence of PCV introduction post 2009. We compared all-cause pneumonia deaths from the death registry to the expected deaths in 2012 to 2016. We also estimated the number of prevented deaths during 2009 to 2016. Of the 9,324,638 deaths reported in South Africa from 1999 to 2016, 12·6% were pneumonia-related. Compared to number of deaths expected, we estimated a 33% (95% credible interval (CrI) 26% to 43%), 23% (95%CrI 17% to 29%), 25% (95%CrI 19% to 32%), and 23% (95%CrI 11% to 32%) reduction in pneumonia mortality in children aged 1 to 11 months, 1 to 4 years, 5 to 7 years, and 8 to 18 years in 2012 to 2016, respectively. In total, an estimated 18,422 (95%CrI 12,388 to 26,978) pneumonia-related deaths were prevented from 2009 to 2016 in children aged <19 years. No declines were estimated observed among adults following PCV introduction. This study was mainly limited by coding errors in original data that could have led to a lower impact estimate, and unmeasured factors could also have confounded estimates. CONCLUSIONS: This study found that the introduction of PCV was associated with substantial reduction in all-cause pneumonia deaths in children aged 1 month to <19 years. The model predicted an effect of PCV in age groups who were eligible for vaccination (1 months to 4 years), and an indirect effect in those too old (8 to 18 years) to be vaccinated. These findings support sustaining pneumococcal vaccination to reduce pneumonia-related mortality in children.

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)

Effect of Vitamin A Deficiency in Dysregulating Immune Responses to Influenza Virus and Increasing Mortality Rates After Bacterial Coinfections.

BACKGROUND: Secondary bacterial coinfections are ranked as a leading cause of hospitalization and morbid conditions associated with influenza. Because vitamin A deficiency (VAD) and insufficiency are frequent in both developed and developing countries, we asked how VAD influences coinfection severity. METHODS: VAD and control mice were infected with influenza virus for evaluation of inflammatory cytokines, cellular immune responses, and viral clearance. Influenza-infected mice were coinfected with Streptococcus pneumoniae to study weight loss and survival. RESULTS: Naive VAD mouse lungs exhibited dysregulated immune function. Neutrophils were enhanced in frequency and there was a significant reduction in RANTES (regulated on activation of normal T cells expressed and secreted), a chemokine instrumental in T-cell homing and recruitment. After influenza virus infection, VAD mice experienced failures in CD4+ T-cell recruitment and B-cell organization into lymphoid structures in the lung. VAD mice exhibited higher viral titers than controls and slow viral clearance. There were elevated levels of inflammatory cytokines and innate cell subsets in the lungs. However, arginase, a marker of alternatively activated M2 macrophages, was rare. When influenza-infected VAD animals were exposed to bacteria, they experienced a 100% mortality rate. CONCLUSION: Data showed that VAD dysregulated the immune response. Consequently, secondary bacterial infections were 100% lethal in influenza-infected VAD mice.

Predictors of mortality in invasive pneumococcal disease: a meta-analysis.

OBJECTIVES: To assess risk factors for mortality in invasive pneumococcal disease (IPD). METHODS: We conducted a systemic literature search in January 2019. The main outcome measure included death within 30 days after diagnosis of IPD. The study protocol was registered in PROSPERO (CRD42019120189). RESULTS: After reviewing 2514 potentially relevant records, remaining 190 articles were included in the analysis. A total of 228,782 IPD patients were identified and the mortality rate was 17.2% in the included articles. No significant evidence of publication bias was found according to the funnel plot and Egger's test (t = 1.464, p = 0.145). Male sex, older age, alcohol abuse, previous tuberculosis, meningitis, hospital acquired infections, multilobar infiltrate or effusion, Pitt bacteremia score≥4, Pneumonia Severity Index≥4, clinical conditions requiring intensive care, underlying clinical conditions, disease caused by serotypes 3, 6B, 9 N, 10A, 11A, 16 F, 17 F, 19, 19 F, 22 F, 23A, 23 F, 31 and 35 F, previous antibiotic use, inappropriate initial antibiotic therapy, penicillin resistance, and vancomycin use during the course of treatment were predicators of 30-day mortality. CONCLUSIONS: This meta-analysis highlights important risk factors for IPD-related mortality, many of which may be targeted through preventive measures.

Incidence of invasive pneumococcal disease after introduction of the 13-valent conjugate pneumococcal vaccine in British Columbia: A retrospective cohort study.

BACKGROUND: A significant reduction in invasive pneumococcal disease (IPD) has been reported, across all ages, following the implementation of 7-valent conjugate pneumococcal vaccine (PCV7) globally, as part of infant immunization programs. We explored the additional impact of PCV13 on IPD over a 14-year period. METHODS: Using provincial laboratory surveillance and hospitalization data (N = 5791), we calculated the annual incidence of IPD following the implementation of PCV13 vaccine. Poisson regression was used to evaluate changes in the overall incidence of IPD, and serotype-specific IPD between PCV7 (2004-10) and PCV13 (2011-2015) eras. RESULTS: Overall, IPD rates have seen a modest decline in the PCV13 compared to the PCV7 era (IRR 0.84; 95% CI: 0.79-0.89); this was seen in children ≤2 years of age, and the majority of the adult cohort. Rates of vaccine-type IPD (PCV7 and PCV13) also decreased in the PCV13 era. In contrast, IPD incidence related to non-PCV13 (IRR: 1.56; 95%CI:1.43-1.72) and non-vaccine serotypes (IRR: 2.12; 95%CI:1.84-2.45) increased in the PCV13 era compared to the PCV7 era. CONCLUSIONS: A modest reduction in IPD from the PCV13 vaccine was observed, with gains limited to the immunized cohort and adults. However, a significant increase in non-vaccine serotypes emphasizes the need for continued surveillance.

Early clinical predictors for the prognosis of invasive pneumococcal disease.

BACKGROUND: Risk factors related to mortality due to invasive pneumococcal disease (IPD) have been unveiled previously, but early clinical manifestations of IPD based on prognosis remain uncovered. METHODS: The demographic characteristics, clinical features, serotype, antibiotic susceptibility, and outcomes of 97 hospitalized children with laboratory-confirmed IPD from Suzhou, China, were collected and analyzed retrospectively. RESULTS: The median age was 0.69 (0.49-1.55) years in the non-survivor group compared with 2.39 (0.90-3.81) years in the survivor group. The mortality of 97 children with laboratory-confirmed IPD was 17.5% (17/97), and 53.6% of them were aged less than 2 years. Pathogens were mainly from the blood and cerebrospinal fluid, and sepsis was the most frequent type. Statistically significant differences were found in hyperpyrexia, vomiting, anorexia, lethargy, poor perfusion of extremities, Hb level, and Plt count between the nonsurvival and survival groups. Further, the multivariate regression analysis showed that early signs, including hyperpyrexia, vomiting, anorexia, lethargy, and poor perfusion of extremities, were independent risk factors for the in-hospital mortality of children with laboratory-confirmed IPD. The mortality was also associated with antimicrobial sensitivity in pneumococcal isolates. The microbes in 1/17 (5.9%) children who were prescribed an antibiotic showed antimicrobial sensitivity in the nonsurvival group, compared with 21/80 (26.3%) children who survived. The most common serotypes identified were 6B (35.3%, 6/17), 14 (23.5%, 4/17), 19F (23.5%, 4/17), 19A (5.9%, 1/17), 23F (5.9%, 1/17), and 20 (5.9%, 1/17) in the nonsurvival group. The coverage of IPD serotypes of the 7-valent pneumococcal conjugate vaccine (PCV7) was 88.2% (15/17), while that of the 13-valent S. pneumoniae vaccine (PCV13) was 94.1% (16/17) of the coverage in the nonsurvival group. CONCLUSIONS: Recurrent hyperpyrexia, vomiting, anorexia, lethargy, and poor perfusion of extremities in the early stage were independent predictors for the in-hospital mortality of children with laboratory-confirmed IPD. Appropriate use of antibiotics and PCV immunization were the keys to improve the outcome of IPD.

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.

Burden of pneumococcal disease: 8-year retrospective analysis from a single centre in Hong Kong.

PURPOSE: Streptococcus pneumoniae is a common pathogen involved in community-acquired pneumonia. Invasive pneumococcal disease is often associated with higher co-morbidity rates, but mortality-related findings have been inconclusive. This study investigated predictors of 30-day mortality and invasive pneumococcal disease. METHODS: This retrospective analysis included adults with pneumococcal disease who were admitted to Pamela Youde Nethersole Eastern Hospital from 1 January 2011 to 31 December 2018. Demographics, microbiological characteristics, and outcomes were compared between 30-day survivors and non-survivors, and between patients with invasive disease and those with non-invasive disease. Intensive care unit (ICU) subgroup analysis was performed. The primary outcome was 30-day all-cause mortality; secondary outcomes were ICU and hospital mortalities, and ICU and hospital lengths of stay. RESULTS: In total, 792 patients had pneumococcal disease; 701 survived and 91 (11.5%) died within 30 days. Notably, 106 (13.4%) patients had invasive pneumococcal disease and 170 (21.5%) patients received intensive care. Vasopressor use (odds ratio [OR]=4.96, P<0.001), chronic kidney disease (OR=3.62, P<0.001), positive urinary antigen test results (OR=2.57, P=0.001), and advanced age (OR=2.19, P=0.010) were independent predictors for 30-day mortality by logistic regression analysis. Among critically ill patients, chronic kidney disease (OR=4.64, P<0.001), higher APACHE IV score (OR=3.73, P=0.016), and positive urinary antigen test results (OR=2.94, P=0.008) were predictors for 30-day mortality. Logistic regression analysis revealed that chronic kidney disease (OR=3.10, P<0.001) was a risk factor for invasive pneumococcal disease. CONCLUSION: Advanced age, vasopressor use, chronic kidney disease, and positive urinary antigen test results were independent predictors for 30-day mortality in patients with pneumococcal disease.

Gastrointestinal symptoms in invasive pneumococcal disease: a cohort study.

BACKGROUND: The study aimed to assess whether gastrointestinal (GI) symptoms at admission are associated with increased short-term mortality in patients with invasive pneumococcal disease (IPD). METHODS: We included all patients with IPD at Aker University Hospital in Oslo, Norway, from 1993 to 2008. Clinical data were registered. Survival data were retrieved from official registries. We used Cox regression and Kaplan-Meier curve to compare mortality within 28 days of admission in patients with and without GI symptoms. RESULTS: Four hundred sixteen patients were included. Of these, 108 patients (26%) presented with GI symptoms, and 47 patients (11%) with GI symptoms only. Patients with GI symptoms were younger (p < 0.001) and had less cardiovascular disease (p < 0.001), pulmonary disease (p = 0.048), and cancer (p = 0.035) and received appropriate antibiotic treatment later. After adjusting for risk factors, we found an increased hazard ratio of 2.28 (95% CI 1.31-3.97) in patients presenting with GI symptoms. In patients with GI symptoms only there was an increased hazard ratio of 2.24 (95% CI 1.20-4.19) in univariate analysis, which increased to 4.20 (95% CI 2.11-8.39) after multivariate adjustment. Fewer patients with GI symptoms only received antibiotics upon admission. CONCLUSIONS: A large proportion of IPD patients present with GI symptoms only or in combination with other symptoms. GI symptoms in IPD are associated with increased short-term mortality.

Epidemiology, vaccine effectiveness, and risk factors for mortality for pneumococcal disease among hospitalised adults in Singapore: a case-control study.

BACKGROUND: Streptococcus pneumoniae infections can lead to severe morbidity and mortality, especially in patients with invasive pneumococcal disease (IPD). This study evaluated factors associated with pneumococcal disease, pneumococcal vaccine effectiveness, and risk factors for all-cause mortality in hospitalised adults with pneumococcal disease in Singapore. METHODS: Retrospective case-control study of patients tested for pneumococcal disease with streptococcal urinary antigen testing and at least one sterile site culture, during their admission to a tertiary hospital in Singapore from 2015 to 2017. Patients were defined as cases of IPD or non-IPD, or as controls, based on laboratory results and clinical diagnoses. Multivariable models were constructed to determine factors associated with IPD/non-IPD, and risk factors for mortality from pneumococcal disease. Vaccine effectiveness against IPD/non-IPD was estimated using a variation of the test-negative design. RESULTS: We identified 496 pneumococcal disease cases, of whom 92 (18.5%) had IPD. The mean age of cases was 69.1 ± 15.4 years, and 65.5% were male. Compared with controls (N = 9181), IPD patients were younger (mean age 61.5 ± 16.3 years, vs 72.2 ± 16.1 years in controls; p < 0.001) and with less co-morbidities [median Charlson's score 1 (IQR 0-4), vs 3 (1-5) in controls; p < 0.001]. IPD patients also had the highest proportions with intensive care unit (ICU) admission (20.7%), inpatient mortality (26.1%) and longest median length of stay [9 (IQR 8-17) days]. On multivariable analysis, IPD was negatively associated with prior pneumococcal vaccination (adjusted relative risk ratio = 0.20, 95%CI 0.06-0.69; p = 0.011). Risk factors for mortality among pneumococcal disease patients were ICU admission, diagnosis of IPD, age ≥ 85 years and Charlson's score > 3. CONCLUSION: Patients with pneumococcal disease (especially IPD) were younger and had less co-morbidities than controls, but had higher risk of severe clinical outcomes and mortality. Pneumococcal vaccination effectiveness against IPD was estimated to be about 80%, and should be encouraged among high-risk patients.