Austrian syndrome: Report of one case and a systematic review of case reports - new insights.

OBJECTIVE: The objective of this review was to gain new insight into the rare condition, Austrian syndrome: the triad of endocarditis, meningitis and pneumonia caused by Streptococcus pneumoniae. METHODS: A systematic review of case reports was conducted using the PRISMA guideline. Cases were rigorously screened to meet a set of well-defined inclusion criteria. Relevant data was aggregated and reported using descriptive statistics. RESULTS: Seventy-one cases from 69 case reports were included in the final review. The mean age was 56.5 years with a male-to-female ratio of 2.4:1. Alcoholism was reported in 41% of patients. Altered mental state (69%) and fever (65%) (mean temperature on admission = 38.9°C) were the commonest presenting symptoms. The mean duration of symptoms before presentation to the hospital was 8 days. The aortic valve was most commonly affected (56%). The mean duration of antibiotic therapy was 5.6 weeks. Seventy percent of patients were admitted to the intensive care unit (ICU). Fifty-six percent of patients had valvular surgery. The average length of stay in the hospital was 36.9 days. Mortality was recorded in 28% of patients. CONCLUSION: Austrian syndrome is rare but deadly. The true incidence is unknown but is commoner in middle-aged men and in alcoholics. Affected patients are usually critically unwell, often requiring ICU admission and prolonged hospital stays. Treatment is aggressive including prolonged courses of antibiotics and often, surgery. Despite these, the case fatality rate is high, with death occurring in over a quarter of patients. Surgery appears to be associated with better prognosis.

Oral Self-Care, Pneumococcal Vaccination, and Pneumonia Among Japanese Older People, Assessed With Machine Learning.

BACKGROUND: Pneumonia is a leading cause of death worldwide. It is a particularly serious burden in older people, as they tend to have a weakened immune response. Identifying the role of oral self-care and pneumococcal vaccination in healthy, independent older people can aid pneumonia prevention among them. This study investigated the associations between oral self-care, pneumococcal vaccination, and pneumonia experience among independent older people. METHODS: This cross-sectional study used data from the 2016 Japan Gerontological Evaluation Study. We used machine learning to examine the association between oral self-care and the experience of pneumonia over the previous year, stratified by pneumococcal vaccination. The covariates were sex, age, years of education, equivalent annual income, medical history of stroke, oral health status (choking, dryness, number of teeth), and smoking status. The analysis included 17 217 independent older people aged 65 and over. RESULTS: The prevalence of pneumonia experienced among those who brushed their teeth once or less per day was 4.5% and 5.3% for those with and those without pneumococcal vaccinations, respectively. In the unvaccinated group, the odds ratio of pneumonia experience for those who brushed their teeth once or less a day was 1.57 (95% confidence interval: 1.15-2.14) compared to those who brushed their teeth 3 or more times a day. By contrast, there was no significant association between the frequency of toothbrushing and the experience of pneumonia among people who received pneumococcal vaccination. CONCLUSIONS: Oral care influenced the experience of pneumonia among independent older people who did not receive pneumococcal vaccination.

Incidence and risk factors of pneumococcal pneumonia in adults: a population-based study.

BACKGROUND: Infection caused by Streptococcus pneumoniae, mainly invasive pneumococcal disease (IPD) and pneumococcal pneumonia (PP), are a major public health problem worldwide. This study investigated population-based incidence and risk of PP among Catalonian persons ≥ 50 years-old with and without specific underlying conditions/comorbidities, examining the influence of single and multi-comorbidities in the risk of suffering PP. METHODS: Population-based cohort study involving 2,059,645 persons ≥ 50 years-old in Catalonia, Spain, who were retrospectively followed between 01/01/2017-31/12/2018. The Catalonian information system for development of research in primary care (SIDIAP) was used to establish baseline characteristics of the cohort (comorbidities/underlying conditions), and PP cases were collected from discharge codes (ICD-10: J13) of the 68 referral Catalonian hospitals. RESULTS: Global incidence rate (IR) was 90.7 PP cases per 100,000 person-years, with a 7.6% (272/3592) case-fatality rate (CFR). Maximum IRs emerged among persons with history of previous IPD or all-cause pneumonia, followed by haematological neoplasia (475.0), HIV-infection (423.7), renal disease (384.9), chronic respiratory disease (314.7), liver disease (232.5), heart disease (221.4), alcoholism (204.8), solid cancer (186.2) and diabetes (159.6). IRs were 42.1, 89.9, 201.1, 350.9, 594.3 and 761.2 in persons with 0, 1, 2, 3, 4 and ≥ 5 comorbidities, respectively. In multivariable analyses, HIV-infection (hazard ratio [HR]: 5.16; 95% CI: 3.57-7.46), prior all-cause pneumonia (HR: 3.96; 95% CI: 3.45-4.55), haematological neoplasia (HR: 2.71; 95% CI: 2.06-3.57), chronic respiratory disease (HR: 2.66; 95% CI: 2.47-2.86) and prior IPD (HR: 2.56; 95% CI: 2.03-3.24) were major predictors for PP. CONCLUSION: Apart of increasing age and immunocompromising conditions (classically recognised as high-risk conditions), history of prior IPD/pneumonia, presence of chronic pulmonary/respiratory disease and/or co-existing multi-comorbidity (i.e., two or more underlying conditions) are major risk factors for PP in adults, with an excess risk near to immunocompromised subjects. Redefining risk categories for PP, including all the above-mentioned conditions into the high-risk category, could be necessary to improve prevention strategies in middle-aged and older adults.

The COVID-19 pandemic as an opportunity for unravelling the causative association between respiratory viruses and pneumococcus-associated disease in young children: a prospective study.

BACKGROUND: In young children, rates of lower respiratory infections (LRI) and invasive pneumococcal disease (IPD) have been associated with respiratory syncytial virus (RSV), human metapneumovirus (hMPV), influenza (flu), and parainfluenza (PIV) (collectively termed here as pneumonia and pneumococcal disease-associated viruses [PDA-viruses]). However, their contribution to the pathogenesis of these disease endpoints has not yet been elucidated. The COVID-19 pandemic provided a unique opportunity to examine the question. METHODS: This prospective study comprised all children <5 years, living in southern Israel, during 2016 through 2021. The data were previously collected in multiple ongoing prospective surveillance programs and include: hospital visits for community-acquired alveolar pneumonia (CAAP), non-CAAP LRI; nasopharyngeal pneumococcal carriage (<3 years of age); respiratory virus activity; and nationwide, all-ages COVID-19 episodes and IPD in children <5 years. A hierarchical statistical model was developed to estimate the proportion of the different clinical endpoints attributable to each virus from monthly time series data, stratified by age and ethnicity. A separate model was fit for each endpoint, with covariates that included a linear time trend, 12-month harmonic variables to capture unexplained seasonal variations, and the proportion of tests positive for each virus in that month. FINDINGS: During 2016 through 2021, 3,204, 26,695, 257, and 619 episodes of CAAP, non-CAAP LRI, pneumococcal bacteremic pneumonia and non-pneumonia IPD, respectively, were reported. Compared to 2016-2019, broad declines in the disease endpoints were observed shortly after the pandemic surge, coincident with a complete disappearance of all PDA-viruses and continued circulation of rhinovirus (RhV) and adenovirus (AdV). From April 2021, off-season and abrupt surges of all disease endpoints occurred, associated with similar dynamics among the PDA-viruses, which re-emerged sequentially. Using our model fit to the entire 2016-2021 period, 82% (95% CI, 75-88%) of CAAP episodes in 2021 were attributable to the common respiratory viruses, as were 22%-31% of the other disease endpoints. Virus-specific contributions to CAAP were: RSV, 49% (95% CI, 43-55%); hMPV, 13% (10-17%); PIV, 11% (7-15%); flu, 7% (1-13%). RhV and AdV did not contribute. RSV was the main contributor in all endpoints, especially in infants. Pneumococcal carriage prevalence remained largely stable throughout the study. INTERPRETATION: RSV and hMPV play a critical role in the burden of CAAP and pneumococcal disease in children. Interventions targeting these viruses could have a secondary effect on the burden of disease typically attributed to bacteria. FUNDING: There was no funding for this study.

Effectiveness of Pneumococcal Conjugate Vaccination Against Virus-Associated Lower Respiratory Tract Infection Among Adults: A Case-Control Study.

BACKGROUND: Interactions of Streptococcus pneumoniae with viruses feature in the pathogenesis of numerous respiratory illnesses. METHODS: We undertook a case-control study among adults at Kaiser Permanente Southern California between 2015 and 2019. Case patients had diagnoses of lower respiratory tract infection (LRTI; including pneumonia or nonpneumonia LRTI diagnoses), with viral infections detected by multiplex polymerase chain reaction testing. Controls without LRTI diagnoses were matched to case patients by demographic and clinical attributes. We measured vaccine effectiveness (VE) for 13-valent (PCV13) against virus-associated LRTI by determining the adjusted odds ratio for PCV13 receipt, comparing case patients and controls. RESULTS: Primary analyses included 13 856 case patients with virus-associated LRTI and 227 887 matched controls. Receipt of PCV13 was associated with a VE of 24.9% (95% confidence interval, 18.4%-30.9%) against virus-associated pneumonia and 21.5% (10.9%-30.9%) against other (nonpneumonia) virus-associated LRTIs. We estimated VEs of 26.8% (95% confidence interval, 19.9%-33.1%) and 18.6% (9.3%-27.0%) against all virus-associated LRTI episodes diagnosed in inpatient and outpatient settings, respectively. We identified statistically significant protection against LRTI episodes associated with influenza A and B viruses, endemic human coronaviruses, parainfluenza viruses, human metapneumovirus, and enteroviruses but not respiratory syncytial virus or adenoviruses. CONCLUSIONS: Among adults, PCV13 conferred moderate protection against virus-associated LRTI. The impacts of pneumococcal conjugate vaccines may be mediated, in part, by effects on polymicrobial interactions between pneumococci and respiratory viruses.

Mortality changes for patients with pneumococcal pneumonia from 2012 to 2017 in Japan.

INTRODUCTION: Pneumococcal pneumonia has a high morbidity and mortality in adults, especially those ≥65 years old. In the past decade, pneumococcal vaccination programs have been initiated worldwide, however, few data concerning mortality changes are available in pneumococcal pneumonia patients and there are no reports clarifying these current changes in Japan. METHODS: Japanese patients ≥65 years old hospitalized with pneumococcal pneumonia between April 2012 and March 2018 were analyzed using the Diagnostic Procedure Combination database. In-hospital mortality was evaluated, and the odds ratios for this outcome in each fiscal year compared with that in 2012 was analyzed using multivariable logistic regression models. RESULTS: Between 2012 and 2017, data of 47,375 pneumococcal pneumonia patients ≥65 years old were extracted. The incidence per 1000 person-years for in-hospital mortality was 60.4 in 2012, 56.8 in 2013, 63.2 in 2014, 56.1 in 2015, 73.0 in 2016, and 67.4 in 2017 and the odds ratios for in-hospital mortality in 2013, 2014, 2015, 2016, and 2017 compared with that in 2012 were 1.00, 1.05, 1.04, 1.06, and 0.98, respectively. There were no significant differences between 2012 and each year from 2013 to 2017. Low BMI; low ADL score; high A-DROP score; comorbid malignancy and heart failure; the coexistence of invasive pneumococcal infection; and the use of invasive mechanical ventilation were independent risk factors for in-hospital mortality. CONCLUSIONS: There were no changes in in-hospital mortality in pneumococcal pneumonia patients between 2012 or each year from 2013 to 2017 and further epidemiological observations are necessary.

Cumulative occupational exposure to inorganic dust and fumes and invasive pneumococcal disease with pneumonia.

PURPOSE: Occupational exposure to inorganic dust and fumes in the year preceding disease has been associated with increased pneumococcal pneumonia risk, but the impact of prior cumulative exposure has not been characterized. METHODS: We studied 3184 cases of invasive pneumococcal disease with pneumonia. The case index date was the day the infection was diagnosed. We selected six controls for each case from the Swedish population registry; each control was assigned the index date of their corresponding case. We linked job histories to a job-exposure matrix to calculate a cumulative exposure index, intensity-years, by multiplying the duration (maximum 5 years) of each exposure with the level of exposure (0 for unexposed, 1 for low and 4 for high). We used conditional logistic analyses to estimate the odds ratio (OR) of invasive pneumococcal disease with pneumonia adjusted for comorbidities, educational level, income and other occupational exposures. RESULTS: Taking other occupational exposures into account, greater than 5 intensity-years of exposure to silica dust or to fumes was each associated with increased odds for invasive pneumococcal disease with pneumonia (OR 2.53, 95% CI 1.49-4.32) and (OR 2.24, 95% CI 1.41-3.55), respectively. Five intensity-years or less of exposure to silica dust or fumes manifested lower odds (OR 1.45, 95% CI 1.20-1.76) and (OR 1.05, 95% CI 0.94-1.16), respectively. CONCLUSION: This study adds evidence that the risk of pneumococcal pneumonia increases with increasing cumulative exposure to dust and fumes, indicating the importance of cumulative exposure.

Pneumococcal pneumonia on the job: Uncovering the past story of occupational exposure to metal fumes and dust.

The objectives of this study are to elucidate the early history of risk for pneumococcal pneumonia from occupational exposure to metal fumes and dusts, and to demonstrate the importance of searching older literature when performing reviews. We performed manual searching for articles in the Library of the Surgeon General's Office (the precursor to Index Medicus), in the Hathi Trust database, in PubMed, andby screening reference lists in literature appearing before the introduction of PubMed. An early body of literature, from the 1890s onward, recognized that pneumonia was linked to "Thomas slag," a steel industry byproduct containing iron, manganese, and lime. Researchers, mainly in Germany, showed that workers in metal-dust-exposed occupations, especially using manganese, manifested an increased incidence of pneumococcal pneumonia. An outbreak of pneumococcal pneumonia in the 1930s implicated manganese fume in its etiology. In the immediate post-World War II period, there was a brief flurry of interest in pneumonia from exposure to potassium permanganate that was soon dismissed as a chemical pneumonitis. After a hiatus of two decades, epidemiologic investigations drew attention to the pneumonia risks of welding and related metal fume exposure, bringing renewed interest to the forgotten role of pneumococcal pneumonia as an occupational disease. Occupational or environmental inhalation of manganese, iron, or irritants may be causally related to increased pneumococcal pneumonia risk. In particular, the risk associated with manganese seems to be overlooked in recent literature. An important conclusion is the importance of obtaining additional evidence through a deeper assessment of the literature in a broad historical context.

Incidence and Predictors of Community-Acquired Pneumonia in Patients With Hematological Cancers Between 2016 and 2019.

BACKGROUND: Patients with hematological cancers (HC) are at high risk of infections, in particular community-acquired pneumonia (CAP). Recent data on incidence and predictors of CAP among patients with HC are scarce. METHODS: We performed a cohort study (2016-2019) in 2 hospitals in the Netherlands among adults with HC to calculate incidence rates (IRs) of CAP. In addition, we performed a nested case-control study to identify predictors of CAP. RESULTS: We identified 275 CAP cases during 6264 patient-years of follow-up. The IR of CAP was 4390/100 000 patient-years of follow-up. Compared with the general population, IR ratios ranged from 5.4 to 55.3 for the different HCs. The case fatality and intensive care unit (ICU) admission rates were 5.5% and 9.8%, respectively. Predictors for CAP in patients with HC were male sex, anemia, lymphocytopenia, chronic kidney disease, cardiovascular disease, autologous and allogeneic stem cell transplantation, treatment with immunosuppressive medication for graft-vs-host disease, treatment with rituximab in the past year, and treatment with immunomodulators (lenalidomide, thalidomide, pomalidomide and/or methotrexate) in the past month. Independent predictors of a severe disease course (death or ICU admission) included neutropenia (odds ratio, 4.14 [95% confidence interval, 1.63-10.2]), pneumococcal pneumonia (10.24 [3.48-30.1]), chronic obstructive pulmonary disease (6.90 [2.07-23.0]), and the use of antibacterial prophylaxis (2.53 [1.05-6.08]). CONCLUSIONS: The burden of CAP in patients with HC is high, with significant morbidity and mortality rates. Therefore, vaccination against respiratory pathogens early in the disease course is recommended, in particular before starting certain immunosuppressive therapies.

Risk factors for pneumococcal disease in persons with chronic medical conditions: Results from the LIFE Study.

OBJECTIVES: This study aimed to identify the risk factors for pneumococcal disease. METHODS: The study was performed using insurance claims data from the residents of 12 Japanese municipalities. Based on recorded diagnoses, we identified chronic medical conditions in each patient between April 2015 and March 2016 and examined the subsequent occurrence of a pneumococcal disease from April 2016 onward. Cox proportional hazards models were used to estimate the hazard ratio of each chronic medical condition for a pneumococcal disease occurrence. RESULTS: The study was conducted on 732,235 patients, of whom, 61,306 (8.4%) were aged 0-18 years, 184,367 (25.2%) were aged 19-49 years, 126,078 (17.2%) were aged 50-64 years, and 360,484 (49.2%) were aged ≥65 years. A higher number of conditions was associated with a higher incidence of pneumococcal disease. Significant risk factors for pneumococcal disease in all patients included chronic heart disease, chronic lung disease, diabetes mellitus, cancer, and chronic renal disease. Furthermore, chronic lung disease, diabetes mellitus, aspiration pneumonia, and immunosuppressant use were risk factors among patients aged 50-64 years. CONCLUSIONS: Persons aged 50-64 years with multiple chronic medical conditions or with specific conditions are at a higher risk of developing pneumococcal disease, indicating a need to consider their inclusion in routine vaccination programs.

Associations between Combined Influenza and Pneumococcal Pneumonia Vaccination and Cardiovascular Outcomes.

BACKGROUND: In 2017, the CDC listed heart disease as the leading cause of death, with pneumonia and influenza being the eighth cause of death. Several studies have suggested the protective effects of influenza vaccination on myocardial infarction (MI). Available evidence supports the use of influenza vaccination in decreasing cardiovascular events, and the Joint Commission considers influenza vaccination a metric of quality care for hospitalized patients. Our specific aim was to evaluate the combined use of pneumococcal pneumonia vaccine (PPV) and influenza vaccine on cardiovascular outcomes and mortality. METHODS: A retrospective observational study was conducted using the 2012-2015 US National Inpatient Sample (NIS) database, to compare cardiovascular events in adult patients who did and did not receive vaccination during their hospitalization. ICD-9 codes were used to extract data for specific variables. The outcomes included MI, transient ischemic attacks, cardiac arrest, stroke, heart failure, and death. Adjusted relative risks (RR) were calculated using survey-weighted generalized linear models after adjusting for gender, race, socioeconomic status, diabetes, hypertension, hyperlipidemia, smoking status, prior coronary artery disease, and cerebrovascular disease. The effect of vaccination on in-hospital mortality was assessed in each subgroup of cardiovascular events using RR regressions. RESULTS: This study included 22,634,643 hospitalizations, of which 21,929,592 did not receive immunization. Vaccination solely against influenza was associated with lower MI (RR = 0.84, 95% CI: 0.82-0.87, p < 0.001), TIA (RR = 0.93, 95% CI: 0.9-0.96, p < 0.001), cardiac arrest (RR = 0.36, 95% CI: 0.33-0.39, p < 0.001), stroke (RR = 0.94, 95% CI: 0.91-0.97, p < 0.001), and mortality (RR = 0.38, 95% CI: 0.36-0.4, p < 0.001). Vaccination with PPV alone was associated with MI (RR = 1.13, 95% CI: 1.11-1.16, p < 0.001), TIA (RR = 1.28, 95% CI: 1.26-1.31, p < 0.001), stroke (RR = 1.21, 95% CI: 1.18-1.24, p < 0.001), and lower mortality (RR = 0.47, 95% CI: 0.45-0.49, p < 0.001). Combined PPV and influenza vaccine was associated with lower mortality (2.21% vs. 1.03%, p < 0.001) and lower cardiac arrest (0.61% vs. 0.51%, p < 0.001). In the adjusted analysis, the RR was 0.46 (95% CI: 0.43, 0.49) for mortality in the combined vaccinated cohort. The combined vaccination group also had a significantly reduced risk of mortality among those admitted with MI (RR = 0.46), transient ischemic attacks (RR = 0.58), and stroke (RR = 0.42) compared to the nonvaccinated group. CONCLUSIONS: Our study shows a significantly reduced risk of mortality with influenza vaccine and PPV and with combined pneumococcal and influenza vaccination. These data suggest that in-hospital administration of pneumonia and influenza vaccines appears safe and supports the use of combined vaccination during hospitalization due to their cardiovascular benefits.

Burden of pneumococcal pneumonia requiring ICU admission in France: 1-year prognosis, resources use, and costs.

BACKGROUND: Community-acquired pneumonia (CAP), especially pneumococcal CAP (P-CAP), is associated with a heavy burden of illness as evidenced by high rates of intensive care unit (ICU) admission, mortality, and costs. Although well-defined acutely, determinants influencing long-term burden are less known. This study assessed determinants of 28-day and 1-year mortality and costs among P-CAP patients admitted in ICUs. METHODS: Data regarding all hospital and ICU stays in France in 2014 were extracted from the French healthcare administrative database. All patients admitted in the ICU with a pneumonia diagnosis were included, except those hospitalized for pneumonia within the previous 3 months. The pneumococcal etiology and comorbidities were captured. All hospital stays were included in the cost analysis. Comorbidities and other factors effect on the 28-day and 1-year mortality were assessed using a Cox regression model. Factors associated with increased costs were identified using log-linear regression models. RESULTS: Among 182,858 patients hospitalized for CAP in France for 1 year, 10,587 (5.8%) had a P-CAP, among whom 1665 (15.7%) required ICU admission. The in-hospital mortality reached 22.8% at day 28 and 32.3% at 1 year. The mortality risk increased with age > 54 years, malignancies (hazard ratio (HR) 1.54, 95% CI [1.23-1.94], p = 0.0002), liver diseases (HR 2.08, 95% CI [1.61-2.69], p < 0.0001), and the illness severity at ICU admission. Compared with non-ICU-admitted patients, ICU survivors remained at higher risk of 1-year mortality. Within the following year, 38.2% (516/1350) of the 28-day survivors required at least another hospital stay, mostly for respiratory diseases. The mean cost of the initial stay was €19,008 for all patients and €11,637 for subsequent hospital stays within 1 year. One-year costs were influenced by age (lower in patients > 75 years old, p = 0.008), chronic cardiac (+ 11% [0.02-0.19], p = 0.019), and respiratory diseases (+ 11% [0.03-0.18], p = 0.006). CONCLUSIONS: P-CAP in ICU-admitted patients was associated with a heavy burden of mortality and costs at one year. Older age was associated with both early and 1-year increased mortality. Malignant and chronic liver diseases were associated with increased mortality, whereas chronic cardiac failure and chronic respiratory disease with increased costs. TRIAL REGISTRATION: N/A (study on existing database).

Incidence and Risk of Pneumococcal Pneumonia in Adults with Distinct Underlying Medical Conditions: A Population-Based Study.

PURPOSE: This study investigated the incidence of pneumococcal pneumonia requiring hospitalisation among middle-aged and older adults with and without specific underlying medical conditions, evaluating the influence of these conditions in the risk of developing pneumonia. METHODS: Population-based prospective cohort study included 2,025,730 individuals ≥ 50 years around Catalonia, Spain. The Catalonian information system for the development of research in primary care (SIDIAP) was used to establish baseline characteristics of the cohort (comorbidities and underlying medical conditions). Hospitalisations from pneumococcal pneumonia occurred among cohort members between 01/01/2015 and 31/12/2015 were collected from hospital discharge codes of 68 reference Catalonian hospitals. Cox regression was used to estimate the association between baseline conditions and the risk of developing pneumonia. RESULTS: Global incidence rate (IR) of hospitalised pneumococcal pneumonia was 82.8 cases per 100,000 persons-year. Maximum IRs (per 100,000 persons-year) emerged among persons with haematological neoplasia (837.4), immunodeficiency (709.2), HIV infection (474.7), severe renal disease (407.5) and chronic pulmonary disease (305.7). In the multivariable analyses, apart from increasing age, HIV infection (hazard ratio [HR] 6.78), haematological neoplasia (HR 6.30), prior all-cause pneumonia (HR 5.27), immunodeficiency (HR 4.57) and chronic pulmonary disease (HR 2.89) were the conditions most strongly associated with an increasing risk. Pneumococcal vaccination did not emerge associated with a reduced risk in our study population (nor PPsV23 neither PCV13). CONCLUSION: Old age, immunocompromising conditions and chronic pulmonary/respiratory disease are major risk factors for pneumococcal pneumonia in adults. Our data underline the need for better prevention strategies in these persons.

Exposure to diesel exhaust particles increases susceptibility to invasive pneumococcal disease.

BACKGROUND: The World Health Organization estimates that air pollution is responsible for 7 million deaths per annum, with 7% of these attributable to pneumonia. Many of these fatalities have been linked to exposure to high levels of airborne particulates, such as diesel exhaust particles (DEPs). OBJECTIVES: We sought to determine whether exposure to DEPs could promote the progression of asymptomatic nasopharyngeal carriage of Streptococcus pneumoniae to invasive pneumococcal disease. METHODS: We used mouse models and in vitro assays to provide a mechanistic understanding of the link between DEP exposure and pneumococcal disease risk, and we confirmed our findings by using induced sputum macrophages isolated from healthy human volunteers. RESULTS: We demonstrate that inhaled exposure to DEPs disrupts asymptomatic nasopharyngeal carriage of S pneumoniae in mice, leading to dissemination to lungs and blood. Pneumococci are transported from the nasopharynx to the lungs following exposure to DEPs, leading to increased proinflammatory cytokine production, reduced phagocytic function of alveolar macrophages, and consequently, increased pneumococcal loads within the lungs and translocation into blood. These findings were confirmed by using DEP-exposed induced sputum macrophages isolated from healthy volunteers, demonstrating that impaired innate immune mechanisms following DEP exposure are also at play in humans. CONCLUSION: Lung inhaled DEPs increase susceptibility to pneumococcal disease by leading to loss of immunological control of pneumococcal colonisation, increased inflammation, tissue damage, and systemic bacterial dissemination.

Incidence and Risk Factors for Invasive Pneumococcal Disease and Community-acquired Pneumonia in Human Immunodeficiency Virus-Infected Individuals in a High-income Setting.

BACKGROUND: Although people living with human immunodeficiency virus (PLWH) are at increased risk of invasive pneumococcal disease (IPD) and community-acquired pneumonia (CAP), it is unclear whether this remains the case in the setting of early initiation of combination antiretroviral therapy (cART), at high CD4 cell counts. This is important, as pneumococcal vaccination coverage in PLWH is low in Europe and the United States, despite longstanding international recommendations. METHODS: We identified all CAP and IPD cases between 2008 and 2017 in a cohort of PLWH in a Dutch HIV referral center. We calculated incidence rates stratified by CD4 count and cART status and conducted a case-control study to identify risk factors for CAP in PLWH receiving cART. RESULTS: Incidence rates of IPD and CAP in PLWH were 111 and 1529 per 100 000 patient-years of follow-up (PYFU). Although IPD and CAP occurred more frequently in patients with CD4 counts <500 cells/µL (incidence rate ratio [IRR], 6.1 [95% confidence interval, 2.2-17] and IRR, 2.4 [95% confidence interval, 1.9-3.0]), the incidence rate in patients with CD4 counts >500 cells/µL remained higher compared with the general population (946 vs 188 per 100 000 PYFU). All IPD isolates were vaccine serotypes. Risk factors for CAP were older age, CD4 counts <500 cells/µL, smoking, drug use, and chronic obstructive pulmonary disease. CONCLUSIONS: The incidence of IPD and CAP among PLWH remains higher compared with the general population, even in those who are virally suppressed and have high CD4 counts. With all serotyped IPD isolates covered by pneumococcal vaccines, our study provides additional argumentation against the poor current adherence to international recommendations to vaccinate PLWH.

Clinical and microbiological characteristics of community-acquired pneumonia associated with Streptococcus pneumoniae in adult patients in Mexico / Características clínicas y microbiológicas de la neumonía adquirida en la comunidad asociada con Streptococcus pneumoniae en pacientes adultos en México

The aim of this study was to assess the risk factors and clinical and microbiological characteristics of community-acquired pneumonia (CAP) in adult patients in Mexico. Streptococcus pneumoniae classified as the causative agent of CAP in adult patients and patients with invasive S. pneumoniae isolates presented to three tertiary teaching hospitals during the 15-year study period were selected. Serotyping and susceptibility testing were performed for all included isolates. Clinical and demographic data were recorded. A total of 96 patients infected with S. pneumoniae (71 with CAP, 25 with invasive disease) were included. The CAP group involved more males (74.6%) than the invasive disease group (p = 0.03). Head trauma was more common in the CAP group (21.1%) than in the invasive disease group (4.0%; p = 0.03). The most prevalent serotype was 19A, followed by serotypes 3 and 23F. After the introduction of the heptavalent conjugated pneumococcal vaccine (PCV7), the prevalence of included serotypes declined significantly; no such change was found after the introduction of the PCV13 vaccine, including in the prevalence of serotype 19A. Susceptibility to all antimicrobials tested except vancomycin declined over the study period. In conclusion, head trauma was the most common comorbidity in the CAP group. The most prevalent serotype was 19A. Decreased susceptibility to most antimicrobials tested was observed.

El objetivo de este estudio fue evaluar los factores de riesgo y las características clínicas y microbiológicas de la neumonía adquirida en la comunidad (NAC) en pacientes adultos en México. Se seleccionaron pacientes adultos con NAC con Streptococcus pneumoniae como agente causal y pacientes con aislamientos invasivos de S. pneumoniae que concurrieron a tres hospitales de enseñanza de tercer nivel durante el período de estudio de 15 anos (2000-2015). Se realizaron pruebas de serotipificación y sensibilidad con todos los aislados incluidos. Se colectaron los datos clínicos y demográficos. Se incluyeron en total 96 pacientes infectados con S. pneumoniae (71 con NAC y 25 con enfermedad invasiva). El grupo con NAC incluía más varones (74,6%) que el grupo de enfermedad invasiva (p = 0,03). El traumatismo craneoencefálico fue más frecuente en el grupo NAC (21,1%) queen el grupo con enfermedad invasiva (4,0%; p = 0,03). El serotipo más frecuente fue 19A, seguido de los serotipos 3 y 23F. Después de la introducción de la vacuna antineumocócica conjugada heptavalente (PCV7), la prevalencia de los serotipos incluidos en aquella disminuyó significativamente; no sucedió lo mismo después de la introducción de la PCV13, incluso en relación con la prevalencia del serotipo 19A. La sensibilidad a todos los antimicrobianos evaluados, excepto la vancomicina, disminuyó durante el período de estudio. En conclusión, el traumatismo craneoencefálico fue la comorbilidad más frecuente en el grupo con NAC. El serotipo más frecuente fue el 19A, y se observó disminución de la sensibilidad a la mayoría de los antimicrobianos probados a lo largo del período considerado.

Childhood pneumonia in low-and-middle-income countries: An update.

OBJECTIVES: To review epidemiology, aetiology and management of childhood pneumonia in low-and-middle-income countries. DESIGN: Review of published English literature between 2013 and 2019. RESULTS: Pneumonia remains a major cause of morbidity and mortality. Risk factors include young age, malnutrition, immunosuppression, tobacco smoke or air pollution exposure. Better methods for specimen collection and molecular diagnostics have improved microbiological diagnosis, indicating that pneumonia results from several organisms interacting. Induced sputum increases microbiologic yield for Bordetella pertussis or Mycobacterium tuberculosis, which has been associated with pneumonia in high TB prevalence areas. The proportion of cases due to Streptococcus pneumoniae and Haemophilus influenzae b has declined with new conjugate vaccines; Staphylococcus aureus and H. influenzae non-type b are the commonest bacterial pathogens; viruses are the most common pathogens. Effective interventions comprise antibiotics, oxygen and non-invasive ventilation. New vaccines have reduced severity and incidence of disease, but disparities exist in uptake. CONCLUSION: Morbidity and mortality from childhood pneumonia has decreased but a considerable preventable burden remains. Widespread implementation of available, effective interventions and development of novel strategies are needed.

Predictive value of Thomsen-Friedenreich antigen activation for Streptococcus pneumoniae infection and severity in pediatric lobar pneumonia.

BACKGROUND: Most cases of complicated pneumonia in children are caused by pneumococcal infections. Thomsen-Friedenreich antigen (TA) is present on erythrocytes, platelets and glomeruli, and it can be activated during pneumococcal infection. The aim of this study was to investigate the predictive value of TA activation for pneumococcal infection and association with the severity of complicated pneumonia. MATERIALS AND METHODS: Patients with lobar pneumonia were routinely tested for TA at the Department of Pediatrics, Mackay Memorial Hospital from January 2010 to December 2015. We retrospectively reviewed and analyzed their charts and data including age, sex, etiology of infection, chest tube insertion or video-assisted thoracoscopic surgery, length of hospital stay, TA activation, white blood cell count and level of C reactive protein. RESULTS: A total of 142 children with lobar pneumonia were enrolled, including 35 with empyema, 31 with effusion, 11 with necrotizing pneumonia and four with lung abscess. Streptococcus pneumoniae was the most commonly identified pathogen. Twenty-two patients (15.4%) had activated TA, all of whom were infected with S. pneumoniae. TA activation had 100% specificity and 100% positive predictive value for pneumococcal infection. In the multivariate analysis in lobar pneumonia, TA activation (OR, 15.8; 95% CI, 3.0-83.5; p = 0.001), duration of fever before admission (OR, 1.2; 95% CI, 1.1-1.5; p = 0.013) and initial CRP level (OR, 1.1; 95% CI, 1.0-1.1; p = 0.004) were independent predictors of empyema. CONCLUSIONS: TA activation is a specific marker for pneumococcal pneumonia and might indicate higher risk for complicated pneumonia.