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AbstractObjectivesMethodsResultsConclusionsThis study details the accumulated experience of more than 31 years using a low-dose systematic dexamethasone protocol with mannitol and antiseizure prophylaxis for the treatment of suspected pneumococcal meningitis.Data have been prospectively collected for the period1977–2018. From 1987, patients with suspected pneumococcal meningitis received 12 mg dexamethasone followed by 4 mg/6 h for 48 h, started before or with the first antibiotic dose. They also received (1) a single intravenous dose of 0.5–1 g/Kg mannitol, and (2) antiseizure prophylaxis with phenytoin.In total, 363 episodes of pneumococcal meningitis were recorded. Of these, 242 were treated with the dexamethasone protocol after 1987 and 121 were treated without the protocol. Overall mortality was 11.6% (28/242) among patients treated with dexamethasone and 35% (43/121) among those treated without dexamethasone (p = 0.000). Early mortality was significantly lower at 5.8% (14/242) with dexamethasone and 24% (29/121) without dexamethasone (p = 0.000). Finally, neurological mortality was significantly lower at 7.4% (18/242) with dexamethasone and 23% (28/121) without dexamethasone (p = 0.000).A low dose of dexamethasone along with a single dose of mannitol and antiseizures prophylaxis might be useful for reducing both overall and early mortality in pneumococcal meningitis in adult patients. [ABSTRACT FROM AUTHOR]

Background: Invasive pneumococcal disease (IPD) is a significant health concern in children worldwide. In this study, we aimed to analyze the clinical features, antibiotic resistance, and risk variables for poor outcomes in patients with IPD in Hangzhou. Methods: A retrospective single-centre study was performed using the pediatric intensive care (PIC) database from 2010 to 2018. The clinical characteristics, laboratory data, antimicrobial resistance, and risk factors for in-hospital mortality and sepsis in patients with IPD in intensive care units (ICUs) were analyzed systematically. Results: A total of 178 IPD patients were included in the study. The majority of the IPD children were 2–10 years old. Antimicrobial resistance tests of S. pneumoniae isolates revealed high resistance to erythromycin, tetracycline and compound sulfamethoxazole (SMZ-Co). All the isolates were sensitive to vancomycin, linezolid, moxifloxacin, telithromycin, ofloxacin, and levofloxacin. IPD patients may experience poor outcomes, including death and sepsis. The in-hospital mortality was 3.93%, and 34.27% of patients suffered from sepsis. Temperature (OR 3.80, 95% CI 1.62–8.87; P = 0.0021), Partial Pressure of Oxygen in Arterial Blood (PaO2) (OR 0.99, 95% CI 0.98-1.00; P = 0.0266), and albumin (OR 0.89, 95% CI 0.80–0.99; P = 0.0329) were found to be independent risk factors for sepsis in children with IPD. Conclusion: Pediatric IPD deserves attention in China. Appropriate surveillance and antibiotic selection are crucial in managing resistant strains. Early identification of high-risk individuals with risk factors contributes to the development of appropriate treatment strategies. [ABSTRACT FROM AUTHOR]

Purpose: To compare the performance of multiple international guidelines in selecting patients for head CT prior to lumbar puncture (LP) in suspected meningitis, focusing on identification of potential contraindications to immediate LP. Methods: Retrospective study of 196 patients with suspected meningitis presenting to an emergency department between March 2013 and March 2023 and undergoing head CT prior to LP. UK Joint Specialist Society Guidelines (UK), European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and Infectious Diseases Society of America (IDSA) guidelines were evaluated by cross-referencing imaging criteria with clinical characteristics present at time of presentation. Sensitivity of each guideline for recommending neuroimaging in cases with brain shift on CT was evaluated, along with the number of normal studies and incidental or spurious findings. Results: 2/196 (1%) patients had abnormal CTs with evidence of brain shift, while 14/196 (7%) had other abnormalities on CT without brain shift. UK, ESCMID and IDSA guidelines recommended imaging in 10%, 14% and 33% of cases respectively. All three guidelines recommended imaging pre-LP in 2/2 (100%) cases with brain shift. IDSA guidelines recommended more CT studies with normal findings (59 vs 16 and 24 for UK and ESCMID guidelines respectively) and CT abnormalities without brain shift (4 vs 1 and 2 respectively) than the other guidelines. Conclusion: UK, ESCMID and IDSA guidelines are all effective at identifying the small cohort of patients who benefit from a head CT prior to LP. Following the more selective UK/ESCMID guidelines limits the number of normal studies and incidental or spurious CT findings. [ABSTRACT FROM AUTHOR]

The objective of this study was to determine the role of cerebrospinal fluid (CSF) bacterial load in adults with pneumococcal meningitis. We quantified bacterial load in CSF samples from the diagnostic lumbar puncture of adults with community-acquired pneumococcal meningitis. We also measured CSF concentrations of complement component 5a (C5a), and determined associations between bacterial load, clinical characteristics, C5a and unfavourable outcome (Glasgow Outcome Scale score <5). Bacterial load was quantified in 152 CSF samples. Median age of these patients was 61 years (interquartile range [IQR] 51–68), and 69 of 152 (45%) were female. Median CSF bacterial load was 1.6 × 104 DNA copies/mL (IQR 3.4 × 103–1.2 × 105), and did not correlate with CSF white cell count nor with CSF protein concentrations. Median CSF C5a concentration was 35.8 mg/L (IQR 15.9–105.6), and was moderately correlated with CSF bacterial loads (Spearman's rho = 0.42; p < 0001). High bacterial loads were associated with development of complications, such as circulatory shock (OR per logarithmic increase: 2.4, 95% CI: 2.0–2.9; p < 0.001) and cerebrovascular complications [OR: 1.9, 95% CI: 1.6–2.3; p < 0.001]). High bacterial loads were also associated with unfavourable outcome (OR: 2.8, 95% CI: 2.4–3.3; p < 0.001) and death (OR: 3.1, 95% CI: 2.6–3.8; p < 0.001). In a multivariable regression model including age, immunocompromised state, extrameningeal infection focus, admission Glasgow Coma Scale score and CSF C5a concentration, CSF bacterial load remained an independent predictor of unfavourable outcome (adjusted OR: 2.5, 95% CI: 1.6–3.9; p < 0.001). High CSF bacterial load predicts the development of complications and unfavourable outcome in adults with pneumococcal meningitis. [ABSTRACT FROM AUTHOR]

Introduction: In Argentina, vaccination with 13-valent pneumococcal conjugate vaccine (PCV13) followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23; PCV13 → PPSV23) has been recommended for all adults aged ≥ 65 years and younger adults with chronic medical ("moderate-risk") or immunocompromising ("high-risk") conditions since 2017. With the approval of a 20-valent PCV (PCV20), we evaluated the cost-effectiveness of PCV20 versus current recommendations for moderate-/high-risk adults aged 18–64 years and all adults 65–99 years. Methods: A probabilistic cohort model was used to project lifetime outcomes and costs associated with invasive pneumococcal disease (IPD) and all-cause non-bacteremic pneumonia (NBP), and the expected impact of vaccination. Clinical outcomes were projected annually based on Argentinean data. Economic costs were estimated based on cases and corresponding medical costs (adjusted to 2023 USD) and costs of vaccine and administration. Cost-effectiveness of PCV20 was evaluated versus the current strategy, PCV13 → PPSV23, and alternatively, versus sequentially administered 15-valent PCV and PPSV23 (PCV15 → PPSV23), and presented as cost per quality-adjusted life year gained; a healthcare system perspective was used. Costs and benefits were discounted at 3%/year. Results: PCV20 in lieu of PCV13 → PPSV23 among moderate-/high-risk adults aged 18–64 years and all adults 65–99 years (N = 13.4M) prevented 3838 IPD, 4377 inpatient NBP, and 6003 outpatient NBP cases, and 1865 disease-related deaths; relative to PCV15 → PPSV23 the corresponding reductions were 2775, 3285, 4518, and 1348. PCV20 was projected to be the dominant strategy versus PCV13 → PPSV23 and PCV15 → PPSV23 as overall costs were lower by $87.6M and $80.8M, respectively. In probabilistic sensitivity analyses, PCV20 was dominant (i.e., more effective, less costly) in 100% of 1000 simulations. Conclusions: Analyses suggest implementing a PCV20 vaccination program in moderate-/high-risk adults aged 18–64 years and all adults ≥ 65 years—in lieu of PCV13 → PPSV23—would yield substantial reductions in pneumococcal disease and would be cost saving to the Argentinean healthcare system. Plain Language Summary: Pneumococcal pneumonia has a high disease burden in both children and adults. Older adults and those with certain underlying conditions are more susceptible to severe pneumococcal disease resulting in considerable economic burden on the healthcare system. In Argentina, vaccination with 13-valent pneumococcal conjugate vaccine (PCV13) followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23) a year later is recommended for all adults aged ≥ 65 years and adults aged 18–64 years with underlying risk conditions. Despite vaccination efforts, prevalence of pneumococcal disease remains high. Two higher-valent PCVs—15-valent PCV (PCV15) and 20-valent PCV (PCV20)—are available for use in adults with PCV20 offering additional serotype coverage. This study assessed the cost-effectiveness of replacing current (PCV13 → PPSV23) and alternative (PCV15 → PPSV23) vaccination strategies with PCV20 alone. The use of PCV20 was evaluated among Argentinean adults aged 18–64 years with underlying risk conditions and all adults aged 65–99 years (N = 13 million). Over a lifetime time horizon, compared to PCV13 → PPSV23, PCV20 use would avert 14,218 cases and 1865 deaths, and increase quality-adjusted life years by 8655. Compared to PCV15 → PPSV23, PCV20 reduced cases and deaths by 10,578 and 1348, respectively, and increased quality-adjusted life years by 6341. In both comparisons, PCV20 use was cost saving with $87.6 million and $80.8 million lower costs compared to PCV13 → PPSV23 and PCV15 → PPSV23, respectively. Results of the cost-effectiveness analyses suggest that the use of PCV20 is a cost-saving strategy, reducing overall costs to the healthcare system and improving public health. [ABSTRACT FROM AUTHOR]

La vaccination pneumococcique conjuguée (7- puis 13-valente) a considérablement modifié le profil des méningites à pneumocoque en faisant disparaître les souches virulentes les plus résistantes aux bêtalactamines en France. L'observatoire national des méningites bactériennes de l'enfant du Groupe de pathologie infectieuse pédiatrique (GPIP) de la Société française de pédiatrie ainsi que le Centre national de référence des pneumocoques n'ont pas répertorié de cas de méningite due à des pneumocoques résistants aux céphalosporines de troisième génération (C3G), même si des souches de profil moins favorable (sérotype 15) ont semblé émerger en 2021. Ces données récentes justifient de reconduire les recommandations de 2016 et à limiter l'usage de la vancomycine à la phase secondaire de traitement des méningites à pneumocoque lorsque la CMI de la souche isolée vis-à-vis des C3G injectables est > 0,5 mg/L. La seule modification notable proposée par le GPIP dans cette actualisation 2023 de ses recommandations porte sur la suppression de l'association de la ciprofloxacine au céfotaxime dans les méningites à Escherichia coli du nouveau-né et du jeune nourrisson. L'observatoire national des méningites de l'enfant est un outil précieux en raison de sa bonne exhaustivité et de sa pérennité depuis 15 ans. Le maintien de la surveillance épidémiologique permettra d'adapter si nécessaire, les nouveaux schémas thérapeutiques à l'évolution des profils de sensibilité des pneumocoques et aux changements sérotypiques éventuels à venir. Les abcès cérébraux communautaires sont des maladies rares, mais leur prise en charge nécessite une approche rigoureuse : une imagerie de qualité, un prélèvement bactériologique avant l'antibiothérapie dans la mesure du possible, et un traitement antibiotique incluant le métronidazole en plus du céfotaxime. Ces abcès cérébraux nécessitent toujours une collaboration multidisciplinaire, incluant les professionnels des maladies infectieuses et un avis neurochirurgical. In France, conjugated pneumococcal vaccination has considerably modified the profile of pneumococcal meningitis by eliminating the most virulent strains resistant to beta-lactams. Over recent years, the nationwide pediatric meningitis network of the Pediatric Infectious Disease Group (GPIP) and the National Reference Centre of Pneumococci have not recorded any cases of meningitis due to pneumococcus resistant to third-generation cephalosporins (C3G), even though in 2021, strains with a less favorable profile appeared to emerge. These recent data justify renewal of the 2016 recommendations and limitation of vancomycin to the secondary phase of treatment of pneumococcal meningitis when the MIC of the isolated strain against injectable C3Gs is > 0.5 mg/L. The only major change proposed by the GPIP in this 2023 update of its recommendations is discontinuation of the recommendation of a combination of ciprofloxacin and cefotaxime in Escherichia coli meningitis in newborns and young infants. The nationwide observatory of meningitis in children is a valuable tool because of its completeness and its continuity over the past 15 years. The maintenance of epidemiological surveillance will allow us to adapt new therapeutic regimens to the evolution of pneumococcal susceptibility profiles and to future serotype-specific changes. Community-acquired cerebral abscesses are rare diseases, of which the management requires a rigorous approach: high-quality imaging, bacteriological sampling prior to antibiotic therapy whenever possible, and antibiotic treatment including metronidazole in addition to cefotaxime. Multidisciplinary collaboration, including infectious disease and neurosurgical advice, is always called for. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aim: The pneumococcal conjugate vaccine, which covered seven serotypes of Streptococcus pneumoniae (PCV7), was introduced in Stockholm, Sweden, in 2007. It was replaced by a 13‐valent vaccine (PCV13) in 2011. We previously reported a decreased incidence of pneumonia and sinusitis among young children 4 years after the introduction of the PCV7. This study followed the incidence of pneumonia, sinusitis, mastoiditis and meningitis for four more years. Methods: We studied validated hospital registry data covering children up to 17 years of age, who were hospitalised in the Stockholm region from 2003 to 2016, when the child population peaked at 485 687. All 11 115 cases diagnosed with pneumonia, coded as bacterial pneumonia, sinusitis, mastoiditis, bacterial meningitis or empyema, were identified. The controls had viral pneumonia or pyelonephritis. Results: The incidence rates for children under 2 years of age hospitalised for sinusitis, mastoiditis and meningitis decreased significantly by 61%–79% during the eight‐year post‐vaccination period. Hospitalisations for bacterial pneumonia decreased by 19%–25% in the same age group. These changes were probably due to both the vaccines and changes in diagnosis routines. Conclusion: The effect of vaccination on children under 2 years of age was sustained 8 years after the introduction of the pneumococcal conjugate vaccines. [ABSTRACT FROM AUTHOR]

Bordetella holmesii is a bacterium recently recognized in 1995. It is a gram-negative coccobacillus that can cause pertussis-like symptoms in humans as well as invasive infections. It is often confused with Bordetella pertussis because routine diagnostic tests for whooping cough are not species-specific. The prevalence of B. holmesii as a cause of pertussis has increased in several countries. Therefore, B. holmesii assays are important for determining the epidemiology of pertussis, for the choice of an effective treatment, and for detecting vaccination failures. [ABSTRACT FROM AUTHOR]

Necrotizing pneumonia (NP) is a serious and rare disease in children. Pediatric data on NP are limited and the impact of the 13-valent pneumococcal conjugate vaccine has been very poorly evaluated. We conducted a retrospective study at Toulouse University Hospital between 2008 and 2018. Children who presented with thin-walled cavities in the areas of parenchymal consolidation on imaging were included in the study. The incidence of NP did not decrease during this period. Bacterial identification occurred in 56% of cases (14/25) and included six cases of Streptococcus pneumoniae , five of Staphylococcus aureus , two of Streptococcus pyogenes , and one of Streptococcus viridans. Streptococcus pneumoniae NP are more frequently associated with empyema/parapneumonic effusion compared to S. aureus NP (p = 0.02). Patients with S. pyogenes NP more often required volume expansion than did S. pneumoniae cases (p = 0.03). When comparing children born before and after implementation of the 13-valent pneumococcal conjugate vaccine, we identified a relative modification of the bacterial epidemiology, with an increase in the proportion of S. pyogenes NP and S. aureus NP and a decrease in the proportion of NP caused by S. pneumoniae. Future studies are needed to assess the epidemiology of NP in children. Continued surveillance of identified pneumococcal serotypes is essential to document epidemiological changes in the coming years. [ABSTRACT FROM AUTHOR]

Introduction: A 20-valent pneumococcal conjugate vaccine (PCV20) was recently recommended for use among US children. We evaluated the cost-effectiveness of PCV20 among children aged 6 years with chronic medical conditions (CMC+) and children aged 6 years with immunocompromising conditions (IC) versus one and two doses of 23-valent pneumococcal polysaccharide vaccine (PPSV23), respectively. Methods: A probabilistic model was employed to depict 10-year risk of clinical outcomes and economic costs of pneumococcal disease, reduction in life years from premature death, and expected impact of vaccination among one cohort of children with CMC+ and IC aged 6 years. Vaccine uptake was assumed to be 20% for both PCV20 and PPSV23. Cost per quality-adjusted life year (QALY) gained was evaluated from the US societal and healthcare system perspectives; deterministic and probabilistic sensitivity analyses (DSA/PSA) were also conducted. Results: Among the 226,817 children with CMC+ aged 6 years in the US, use of PCV20 (in lieu of PPSV23) was projected to reduce the number cases of pneumococcal disease by 5203 cases, medical costs by US$8.7 million, and nonmedical costs by US$6.2 million. PCV20 was the dominant strategy versus PPSV23 from both the healthcare and societal perspectives. In the PSA, 99.9% of the 1000 simulations yielded a finding of dominance for PCV20. Findings in analyses of children with IC aged 6 years in the USA were comparable (i.e., PCV20 was the dominant vaccination strategy). Scenario analyses showed that increasing PCV20 uptake to 100% could potentially prevent > 22,000 additional cases of pneumococcal disease and further reduce medical and nonmedical costs by US$70.0 million among children with CMC+ and IC. Conclusions: Use of PCV20 among young children with CMC+ and IC in the USA would reduce the clinical burden of pneumococcal disease and yield overall cost savings from both the US healthcare system and societal perspectives. Higher PCV20 uptake could further reduce the number of pneumococcal disease cases in this population. [ABSTRACT FROM AUTHOR]

Non-vaccine serotype (NVT) pneumococcal pneumonia in Japan has increased with the spread of pneumococcal vaccinations. However, there is no data regarding the clinical background and antimicrobial susceptibility of NVT isolates compared with those of vaccine serotype (VT) isolates in adult pneumococcal pneumonia. The serotypes and antimicrobial susceptibilities of pneumococcal isolates obtained from patients with pneumonia at the University of Occupational and Environmental Health, Japan, from January 2011 to December 2020 were retrospectively evaluated along with the patients' clinical information. In total, 252 patients with pneumococcal pneumonia (98 NVT and 154 VT isolates) were included. Among NVTs, the most common serotype was 35B, followed by 15A, 34, 6C, 23A, and 15C. The MIC 50 and MIC 90 of each antibiotic in 35B and 15A tend to be higher than those in 34, 6C, and 23A. Regarding background characteristics, the percentages of patients with dementia and liver disease were significantly higher in patients in the VT group than in those in the NVT group (p = 0.048 and p = 0.012, respectively). There were no significant differences in the severity of pneumonia and mortality rate between patients with the VT and NVT isolates. This study first demonstrated that NVT isolates included those with reduced susceptibility to antibiotics in adult pneumonia in Japan. The data of the present study can be useful in optimizing treatment strategies for pneumococcal pneumonia because of the increasing number of NVT cases in Japan. [ABSTRACT FROM AUTHOR]

Background: Streptococcus pneumoniae infections, including Invasive Pneumococcal Diseases (IPDs), pose a substantial public health challenge, causing significant morbidity and mortality, especially among children and older adults. Vaccination campaigns have played a vital role in reducing pneumococcal-related deaths. However, obstacles related to accessibility and awareness might impede optimal vaccine adoption. This study aims to provide comprehensive data on pneumococcal vaccine coverage and attitudes within at-risk groups in Italy, with the goal of informing public health strategies and addressing vaccination barriers. Methods: Between April 11 and May 29, 2022, a questionnaire investigating vaccine uptake and attitudes toward several vaccinations was administered to 10,000 Italian adults, chosen through population-based sampling. Respondents who were targets of the campaign according to the 2017–2019 National Vaccination Plan, accessed questions regarding pneumococcal vaccination. Data on uptake, awareness of having the right to free vaccination, opinion on vaccine safety, concern with pneumococcal disease, and ease of access to vaccination services were summarized and presented based on statistical regions. Multinomial logistic regression analysis was used to explore factors influencing vaccine uptake. Results: Out of 2357 eligible adult respondents (42.6% women; mean age: 58.1 ± 15.7), 39.5% received pneumococcal vaccination. Uptake differed among at-risk groups: respondents aged ≥65 (33.7%), with lung disease (48.4%), cardiovascular disease (46.6%), and diabetes (53.7%). Predictors of not being vaccinated and unwilling to included female gender, residing in rural areas, lower education, low concern about pneumococcal disease, vaccine safety concerns, and associations with vaccine-opposed acquaintances. Health access issues predicted willingness to be vaccinated despite non-vaccination. Pneumopathy, heart disease, diabetes, and living in Northeastern or Central Italy were linked to higher uptake. Among the 1064 parents of eligible children, uptake was 79.1%. Parental unawareness of children's free vaccination eligibility was a predictor of non-vaccination. Vaccine safety concerns correlated with reluctance to vaccinate children, while perceived healthcare access challenges were associated with wanting but not having received vaccination. Conclusions: Pneumococcal vaccination uptake within prioritized groups and children in Italy remains inadequate. Scarce awareness of vaccine availability and obstacles in accessing vaccinations emerge as principal barriers influencing this scenario. [ABSTRACT FROM AUTHOR]

Background: Non-small-cell lung cancer (NSCLC) is one of the most frequently diagnosed diseases among all types of lung cancer. Infectious diseases contribute to morbidity and mortality by delaying appropriate anti-cancer therapy in patients with NSCLC. Methods: The study aimed to evaluate the effectiveness of vaccination with the 13-valent pneumococcal conjugate vaccine (PCV13) in 288 newly diagnosed NSCLC patients. The analysis of the post-vaccination response was performed after vaccination by assessing the frequency of plasmablasts via flow cytometry and by assessing the concentration of specific anti-pneumococcal antibodies using enzyme-linked immunosorbent assays. Results: The results of the study showed that NSCLC patients responded to the vaccine with an increase in the frequencies of plasmablasts and antibodies but to a lesser extent than healthy controls. The immune system response to PCV13 vaccination was better in patients with lower-stage NSCLC. We found higher antibody levels after vaccination in NSCLC patients who survived 5 years of follow-up. Conclusions: We hope that our research will contribute to increasing patients′ and physicians′ awareness of the importance of including PCV13 vaccinations in the standard of oncological care, which will extend the survival time of patients and improve their quality of life. [ABSTRACT FROM AUTHOR]

Starting in June 2016, the 13-valent pneumococcal conjugate vaccine (PCV13) was introduced into the routine immunization program of Mongolia by using a 2+1 dosing schedule, phased by district. We used prospective hospital surveillance to evaluate the vaccine's effect on pneumonia incidence rates among children 2-59 months of age over a 6-year period. Of 17,607 children with pneumonia, overall adjusted incidence rate ratios showed decreased primary endpoint pneumonia, very severe pneumonia, and probable pneumococcal pneumonia until June 2021. Results excluding and including the COVID-19 pandemic period were similar. Pneumonia declined in 3 districts that introduced PCV13 with catch-up campaigns but not in the 1 district that did not. After PCV13 introduction, vaccinetype pneumococcal carriage prevalence decreased by 44% and nonvaccine-type carriage increased by 49%. After PCV13 introduction in Mongolia, the incidence of more specific pneumonia endpoints declined in children 2-59 months of age; additional benefits were conferred by catch-up campaigns. [ABSTRACT FROM AUTHOR]

Pneumonia is a significant cause of death in Japan, particularly among individuals over the age of 65. The country's aging population has led to an increase in nursing and healthcare-associated pneumonia (NHCAP), which is distinct from community-acquired and hospital-acquired pneumonia. Streptococcus pneumoniae is the leading bacterial cause of pneumonia in Japan, and while pneumococcal vaccines have been introduced, the vaccination rate among older adults remains low. Additionally, there has been a shift in the serotypes of S. pneumoniae, which may impact the effectiveness of current vaccines. The COVID-19 pandemic has also influenced the incidence of pneumonia, with a decrease in cases during the pandemic. Efforts to improve education and understanding of the importance of pneumococcal vaccination are needed in Japan. [Extracted from the article]

Background: Current guidelines for adult patients with pneumococcal meningitis (PM) recommend initial management in intermediate or intensive care units (ICU), but evidence to support these recommendations is limited. We aimed to describe ICU admission practices of patients with PM. Methods: We conducted a retrospective analysis of the French medico administrative database of consecutive adult patients with PM and sepsis criteria hospitalized between 2011 and 2020. We defined two groups, "Direct ICU" corresponding to a direct ICU admission and "Delayed ICU" corresponding to a secondary ICU admission. Results: We identified 4052 patients hospitalized for a first episode of PM, including 2006 "Direct ICU" patients (50%) and 2046 "delayed ICU" patients (50%). The patients were mainly males [n = 2260 (56%)] with median age of 61 years [IQR 50–71] and a median Charlson index of 1 [0–3]. Among them, median SAPS II on admission was 46 [33–62], 2173 (54%) had a neurological failure on admission with 2133 (53%) in coma, 654 (16%) with brainstem failure, 488 (12%) with seizures and 779 (19%) with focal signs without coma. PM was frequently associated with pneumonia [n = 1411 (35%)], and less frequently with endocarditis [n = 317 (8%)]. The median ICU length of stay and hospital length of stay were 6 days [2–14] and 21 days [13–38], respectively. In-hospital mortality was 27% (n = 1100) and 640 (16%) patients were secondarily transferred to rehabilitation care unit. Direct ICU group was significantly more severe but after adjustment for age, sex, comorbidities, organ failures on admission and admission from home, direct ICU admission was significantly associated with a lower mortality (Odds ratio 0.67 [0.56–0.80], p < 0.01). This corresponded to one death avoided for 11 PM directly admitted in ICU. Conclusions: Among patients with PM and sepsis, direct ICU admission was associated with lower mortality rates when compared to delayed admission. [ABSTRACT FROM AUTHOR]

Background: Pneumococcal disease caused by Streptococcus pneumoniae is an important cause of morbidity and mortality across all ages, particularly in younger children and older adults. Here, we describe pneumococcal disease hospitalizations at Ministry of Health (MoH) facilities in Malaysia between 2013 and 2015. Methods: This was a retrospective databases analysis. Tabular data from the Malaysian Health Data Warehouse (MyHDW) were used to identify microbiologically confirmed, pneumococcal disease hospitalizations and deaths during hospitalization, using hospital-assigned ICD-10 codes (i.e., classified as meningitis, pneumonia, or non-meningitis non-pneumonia). Case counts, mortality counts, and case fatality rates were reported by patient age group and by Malaysian geographic region. Results: A total of 683 pneumococcal disease hospitalizations were identified from the analysis: 53 pneumococcal meningitis hospitalizations (5 deaths and 48 discharges), 413 pneumococcal pneumonia hospitalizations (24 deaths and 389 discharges), and 205 non-meningitis non-pneumonia pneumococcal disease hospitalizations (58 deaths and 147 discharges). Most hospitalizations occurred in children aged < 2 years. Crude mortality was highest among children aged < 2 years (for all three disease categories), among adults aged ≥ 65 years (for pneumococcal pneumonia), or among adults aged 65–85 years (for non-meningitis non-pneumonia pneumococcal disease). The case fatality rate, all ages included, was 5.8% for pneumococcal pneumonia, 9.1% for pneumococcal meningitis, and 28.3% for non-meningitis non-pneumonia pneumococcal disease. Conclusions: Our study is the first to document pneumococcal disease hospitalizations and deaths during hospitalization in Malaysia. Although this database analysis likely underestimated case counts, and the true disease burden could be even greater, the study demonstrates a substantial burden of pneumococcal disease. Public health measures, including vaccination, would significantly contribute to the prevention of hospitalizations and deaths associated with pneumococcal disease in Malaysia. [ABSTRACT FROM AUTHOR]

Background: Pneumococcal disease caused by Streptococcus pneumoniae is an important cause of morbidity and mortality across all ages, particularly in younger children and older adults. Here, we describe pneumococcal disease hospitalizations at Ministry of Health (MoH) facilities in Malaysia between 2013 and 2015. Methods: This was a retrospective databases analysis. Tabular data from the Malaysian Health Data Warehouse (MyHDW) were used to identify microbiologically confirmed, pneumococcal disease hospitalizations and deaths during hospitalization, using hospital-assigned ICD-10 codes (i.e., classified as meningitis, pneumonia, or non-meningitis non-pneumonia). Case counts, mortality counts, and case fatality rates were reported by patient age group and by Malaysian geographic region. Results: A total of 683 pneumococcal disease hospitalizations were identified from the analysis: 53 pneumococcal meningitis hospitalizations (5 deaths and 48 discharges), 413 pneumococcal pneumonia hospitalizations (24 deaths and 389 discharges), and 205 non-meningitis non-pneumonia pneumococcal disease hospitalizations (58 deaths and 147 discharges). Most hospitalizations occurred in children aged < 2 years. Crude mortality was highest among children aged < 2 years (for all three disease categories), among adults aged ≥ 65 years (for pneumococcal pneumonia), or among adults aged 65–85 years (for non-meningitis non-pneumonia pneumococcal disease). The case fatality rate, all ages included, was 5.8% for pneumococcal pneumonia, 9.1% for pneumococcal meningitis, and 28.3% for non-meningitis non-pneumonia pneumococcal disease. Conclusions: Our study is the first to document pneumococcal disease hospitalizations and deaths during hospitalization in Malaysia. Although this database analysis likely underestimated case counts, and the true disease burden could be even greater, the study demonstrates a substantial burden of pneumococcal disease. Public health measures, including vaccination, would significantly contribute to the prevention of hospitalizations and deaths associated with pneumococcal disease in Malaysia. [ABSTRACT FROM AUTHOR]

Background: Although it has been reported that patients with pneumococcal pneumonia may develop meningitis, lumbar puncture is not systematically recommended in these patients, even in patients with associated bacteremia or invasive pneumococcal disease. The aim of this study was to determine the characteristics and outcomes of patients admitted to intensive care unit (ICU) for pneumococcal community-acquired pneumonia who developed meningitis. Methods: We retrospectively included all consecutive patients admitted to our ICU from January 2006 to December 2020 for severe pneumococcal community-acquired pneumonia according to American Thoracic Society criteria. Meningitis was defined as pleocytosis > 5 cells/mm3 or a positive culture of cerebrospinal fluid for Streptococcus pneumoniae in lumbar puncture. The primary endpoint was the proportion of patients with meningitis during their ICU stay. Results: Overall, 262 patients [64(52–75) years old] were included: 154(59%) were male, 80(30%) had chronic respiratory disease, 105(39%) were immunocompromised and 6(2%) were vaccinated against S. pneumoniae. A lumbar puncture was performed in 88(34%) patients with a delay from ICU admission to puncture lumbar of 10.5 (2.8–24.1) h and after the initiation of pneumococcal antibiotherapy in 81(92%) patients. Meningitis was diagnosed in 14 patients: 16% of patients with lumbar puncture and 5% of patients in the whole population. Patients with meningitis had more frequently human immunodeficiency virus positive status (29 vs. 5%, p = 0.02), neurological deficits on ICU admission (43 vs. 16%, p = 0.03) and pneumococcal bacteremia (71 vs. 30%, p < 0.01) than those without. The ICU mortality rate (14 vs. 13%, p = 0.73) and the mortality rate at Day-90 (21 vs. 15%, p = 0.83) did not differ between patients with and without meningitis. The proportion of patients with neurological disorders at ICU discharge was higher in patients with meningitis (64 vs. 23%, p < 0.001) than in those without. The other outcomes did not differ at ICU discharge, Day-30 and Day-90 between the two groups of patients. Conclusion: Meningitis was diagnosed in 16% of patients with severe pneumococcal community-acquired pneumonia in whom a lumbar puncture was performed, was more frequent in patients with pneumococcal bacteremia and was associated with more frequent neurological disorders at ICU discharge. Further studies are needed to confirm these results. [ABSTRACT FROM AUTHOR]

Background: Patients with bacterial meningitis can be severely ill necessitating intensive care unit (ICU) treatment. Here, we describe clinical features and prognostic factors of adults with bacterial meningitis admitted to the ICU in a nationwide prospective cohort study. Methods: We prospectively assessed clinical features and outcome of adults (age > 16 years) with community-acquired bacterial meningitis included in the MeninGene study between March 1, 2006 and July 1, 2022, that were initially admitted to the ICU. We identified independent predictors for initial ICU admission and for unfavourable outcome (Glasgow Outcome Scale score between 1–4) by multivariable logistic regression. Results: A total of 2709 episodes of bacterial meningitis were included, of which 1369 (51%) were initially admitted to the ICU. We observed a decrease in proportion of patients being admitted to the ICU during the Covid-19 pandemic in 2020 (decreased to 39%, p = 0.004). Median age of the 1369 patients initially admitted to the ICU was 61 years (IQR 49–69), and the rates of unfavourable outcome (47%) and mortality (22%) were high. During the Covid-19 pandemic, we observed a trend towards an increase in unfavourable outcome. Prognostic factors predictive for initial ICU admission were younger age, immunocompromised state, male sex, factors associated with pneumococcal meningitis, and those indicative of systemic compromise. Independent predictors for unfavourable outcome in the initial ICU cohort were advanced age, admittance to an academic hospital, cranial nerve palsies or seizures on admission, low leukocyte count in blood, high C-reactive protein in blood, low CSF: blood glucose ratio, listerial meningitis, need for mechanical ventilation, circulatory shock and persistent fever. 204 of 1340 episodes (15%) that were initially not admitted to the ICU were secondarily transferred to the ICU. The rates of unfavourable outcome (66%) and mortality (30%) in this group were high. Conclusions: The majority of patients with community-acquired bacterial meningitis are admitted to the ICU, and the unfavourable outcome and mortality rates of these patients remain high. Patients that are initially admitted to non-ICU wards but secondarily transferred to the ICU also had very high rates of unfavourable outcome. [ABSTRACT FROM AUTHOR]

Background: Brain pericytes participate in the regulation of cerebral blood flow and the maintenance of blood–brain barrier integrity. Because of their perivascular localization, their receptor repertoire, and their potential ability to respond to inflammatory and infectious stimuli by producing various cytokines and chemokines, these cells are also thought to play an active role in the immune response to brain infections. This assumption is mainly supported by in vitro studies, investigations in in vivo disease models are largely missing. Here, we analysed the role of brain pericytes in pneumococcal meningitis, in vitro and in vivo in two animal models of pneumococcal meningitis. Methods: Primary murine and human pericytes were stimulated with increasing concentrations of different serotypes of Streptococcus pneumoniae in the presence or absence of Toll-like receptor inhibitors and their cell viability and cytokine production were monitored. To gain insight into the role of pericytes in brain infection in vivo, we performed studies in a zebrafish embryo model of pneumococcal meningitis in which pericytes were pharmacologically depleted. Furthermore, we analyzed the impact of genetically induced pericyte ablation on disease progression, intracranial complications, and brain inflammation in an adult mouse model of this disease. Results: Both murine and human pericytes reacted to pneumococcal exposure with the release of selected cytokines. This cytokine release is pneumolysin-dependent, TLR-dependent in murine (but not human) pericytes and can be significantly increased by macrophage-derived IL-1b. Pharmacological depletion of pericytes in zebrafish embryos resulted in increased cerebral edema and mortality due to pneumococcal meningitis. Correspondingly, in an adult mouse meningitis model, a more pronounced blood–brain barrier disruption and leukocyte infiltration, resulting in an unfavorable disease course, was observed following genetic pericyte ablation. The degree of leukocyte infiltration positively correlated with an upregulation of chemokine expression in the brains of pericyte-depleted mice. Conclusions: Our findings show that pericytes play a protective role in pneumococcal meningitis by impeding leukocyte migration and preventing blood–brain barrier breaching. Thus, preserving the integrity of the pericyte population has the potential as a new therapeutic strategy in pneumococcal meningitis. [ABSTRACT FROM AUTHOR]

Introduction: Streptococcus pneumoniae is the leading cause of meningitis, with a case fatality of up to about 50%. Children younger than 5 years are at greater risk for pneumococcal meningitis compared with other populations. It is of significant importance to provide a comprehensive understanding of the burden of pneumococcal meningitis among under-fives in the low pneumococcal conjugate vaccine (PCV) coverage period in China. Methods: A systematic review was conducted. We searched both English (PubMed, Ovid-EMBASE, Biosis, Web of Science, and Cochrane) and Chinese (CNKI, Wanfang, and ViP) databases for studies on bacterial meningitis in China published between January 1980 and July 2022. Ineligible studies were excluded based on study design and data integrity. Heterogeneity was assessed with I2 and estimates of bacterial meningitis morbidity and mortality were pooled using random-effects models. Subgroup analysis was conducted to trace the source of the heterogeneity and summarize average estimates. Results: A total of 13,082 studies were identified in the literature, and 56 studies were finally included for data analysis. The estimated incidence of pneumococcal meningitis was 2.10 cases per 100,000 children younger than 5 years each year (95% CI: 0.59–7.46), with a pooled case fatality rate of 24.59% (95%CI: 19.35–30.28%) in China. It was estimated that 1617.16 (95% CI: 454.35–5744.78) pneumococcal meningitis cases and 548.86 (95% CI: 474.80–627.62) deaths occurred among under-fives in China in 2020. Streptococcus pneumoniae played an important role in the etiology of confirmed bacterial meningitis cases, with a pooled proportion of 22.05% (95% CI: 17.83–26.27%). The most prevalent serotypes were 6B, 14, 19F, 19A, and 23F, which were preventable with a vaccine. Conclusions: Pneumococcal meningitis remains one of the most important health problems among children younger than 5 years in China. Immunization programs should be promoted to avoid preventable cases and deaths. [ABSTRACT FROM AUTHOR]

Spider angioma is a cutaneous nevus caused by a vascular abnormality, characterized by a central red area with radiating reddish, web-like extensions. It is typically associated with liver cirrhosis, hyperestrogenism, and alcohol consumption. In this case report, we present a unique instance of a patient who developed spider angioma at the injection site of the meningitis vaccine as a long-term adverse effect. The lesion was treated with electrocautery and diminished within one week of treatment. This case highlights the potential for spider angioma to develop as a long-term adverse effect of the meningitis vaccine, a possibility that has not been previously reported. Further research is required to understand the underlying mechanisms and identify potential risk factors for this rare adverse effect. [ABSTRACT FROM AUTHOR]

Ongoing surveillance after pneumococcal conjugate vaccination (PCV) deployment is essential to inform policy decisions and monitor serotype replacement. We report serotype and disease severity trends in 3,719 adults hospitalized for pneumococcal disease in Bristol and Bath, United Kingdom, during 2006–2022. Of those cases, 1,686 were invasive pneumococcal disease (IPD); 1,501 (89.0%) had a known serotype. IPD decreased during the early COVID-19 pandemic but during 2022 gradually returned to prepandemic levels. Disease severity changed throughout this period: CURB65 severity scores and inpatient deaths decreased and ICU admissions increased. PCV7 and PCV13 serotype IPD decreased from 2006–2009 to 2021–2022. However, residual PCV13 serotype IPD remained, representing 21.7% of 2021–2022 cases, indicating that major adult PCV serotype disease still occurs despite 17 years of pediatric PCV use. Percentages of serotype 3 and 8 IPD increased, and 19F and 19A reemerged. In 2020–2022, a total of 68.2% IPD cases were potentially covered by PCV20. [ABSTRACT FROM AUTHOR]

Introduction: Neuroimaging plays an important role in the assessment of meningitis, but conventional Magnetic Resonance Imaging (MRI) is insensitive for early and specific diagnosis. Diffusion Tensor Imaging (DTI) can illustrate disturbances in white matter integrity before they become obvious on conventional MRI. Aim: To determine DTI parameters, specifically Fractional Anisotropy (FA) and Apparent Diffusion Coefficient (ADC), in patients with meningitis and compare them with controls. Materials and Methods: This case-control study was conducted over a period of 18 months at Teerthanker Mahaveer Medical College and Research Centre in Moradabad, Uttar Pradesh, India. The study included a total of 61 clinically diagnosed meningitis patients, aged 18 years and above, who were referred to the Department of Radiodiagnosis for an MRI Brain. Additionally, 61 controls were included. Conventional MRI images were obtained followed by DTI. FA and ADC values were calculated by placing Regions Of Interest (ROI) at different levels for both groups. DTI parameters for different causative organisms (bacterial, viral, tubercular, and fungal) were compared. Data was analysed using Statistical Package for the Social Sciences (SPSS) software version 24.0, and Analysis of Variance (ANOVA) test was used to identify significant differences. The p-value <0.05 was considered as statistically significant. Results: FA values were significantly lower in cases compared to controls at all levels in the brain (mean whole brain FA value of 0.30±0.036 in cases vs 0.43±0.030 in controls). ADC values were significantly higher in cases at the cerebellum, brainstem, and whole brain levels compared to controls (mean whole brain ADC value of 0.812±0.095 in cases vs 0.758±0.026 in controls) (p-value<0.05 considered statistically significant). These differences were evident in patients with clinically proven meningitis who had a normal appearance on conventional MRI, demonstrating the superiority of DTI over conventional MRI for the diagnosis of meningitis. Statistically significant differences were also found among different aetiological agents, highlighting the potential utility of DTI in the differential diagnosis of meningitis cases (mean whole brain FA of 0.31±0.038 in bacterial cases, 0.029±0.037 in viral cases, 0.299±0.034 in tubercular cases, and 0.27±0.00 in fungal cases vs. 0.43±0.030 in controls (p-value <0.01) and mean whole brain ADC values of 0.80±0.051 in bacterial, 0.85±0.14 in viral, 0.79±0.058 in tubercular, 1.03±0.00 in fungal cases vs. 0.758±0.026 in controls (p-value <0.01)). Conclusion: DTI is more sensitive than conventional MRI and is a useful early indicator of inflammatory process in patients with meningitis. [ABSTRACT FROM AUTHOR]

Background: Brain pericytes participate in the regulation of cerebral blood flow and the maintenance of blood–brain barrier integrity. Because of their perivascular localization, their receptor repertoire, and their potential ability to respond to inflammatory and infectious stimuli by producing various cytokines and chemokines, these cells are also thought to play an active role in the immune response to brain infections. This assumption is mainly supported by in vitro studies, investigations in in vivo disease models are largely missing. Here, we analysed the role of brain pericytes in pneumococcal meningitis, in vitro and in vivo in two animal models of pneumococcal meningitis. Methods: Primary murine and human pericytes were stimulated with increasing concentrations of different serotypes of Streptococcus pneumoniae in the presence or absence of Toll-like receptor inhibitors and their cell viability and cytokine production were monitored. To gain insight into the role of pericytes in brain infection in vivo, we performed studies in a zebrafish embryo model of pneumococcal meningitis in which pericytes were pharmacologically depleted. Furthermore, we analyzed the impact of genetically induced pericyte ablation on disease progression, intracranial complications, and brain inflammation in an adult mouse model of this disease. Results: Both murine and human pericytes reacted to pneumococcal exposure with the release of selected cytokines. This cytokine release is pneumolysin-dependent, TLR-dependent in murine (but not human) pericytes and can be significantly increased by macrophage-derived IL-1b. Pharmacological depletion of pericytes in zebrafish embryos resulted in increased cerebral edema and mortality due to pneumococcal meningitis. Correspondingly, in an adult mouse meningitis model, a more pronounced blood–brain barrier disruption and leukocyte infiltration, resulting in an unfavorable disease course, was observed following genetic pericyte ablation. The degree of leukocyte infiltration positively correlated with an upregulation of chemokine expression in the brains of pericyte-depleted mice. Conclusions: Our findings show that pericytes play a protective role in pneumococcal meningitis by impeding leukocyte migration and preventing blood–brain barrier breaching. Thus, preserving the integrity of the pericyte population has the potential as a new therapeutic strategy in pneumococcal meningitis. [ABSTRACT FROM AUTHOR]

Introduction: The introduction of pneumococcal conjugate vaccines (PCV) into the national immunization programs (NIPs) has significantly reduced the number of pneumococcal infections. However, infections caused by isolates of non-vaccine serotypes (NVT) started spreading shortly thereafter and strains of NVT 19A have become the main cause of invasive pneumococcal disease burden worldwide. The aim of the study was to characterize serotype 19A invasive pneumococci of GPSC1/CC320 circulating in Poland before the introduction of PCV into the Polish NIP in 2017 and to compare them to isolates from other countries where PCVs were implemented much earlier than in Poland. Methods: All the GPSC1/CC320 isolates were analyzed by serotyping, susceptibility testing, and whole genome sequencing followed by analyses of resistome, virulome, and core genome multilocus sequence typing (cgMLST), including comparative analysis with isolates with publicly accessible genomic sequences (PubMLST). Results: During continuous surveillance the NRCBM collected 4237 invasive Streptococcus pneumoniae isolates between 1997 and 2016, including 200 isolates (4.7%) of serotype 19A. The most prevalent among 19A pneumococci were highly resistant representatives of Global Pneumococcal Sequence Cluster 1/Clonal Complex 320, GPSC1/CC320 (n = 97, 48.5%). Isolates of GPSC1/CC320 belonged to three sequence types (STs): ST320 (75.2%) ST4768 (23.7%), and ST15047 (1.0%), which all represented the 19A-III cps subtype and had complete loci for both PI-1 and PI-2 pili types. On the basis of the cgMLST analysis the majority of Polish GPSC1/CC320 isolates formed a group clearly distinct from pneumococci of this clone observed in other countries. Conclusion: Before introduction of PCV in the Polish NIP we noticed an unexpected increase of serotype 19A in invasive pneumococcal infections, with the most common being representatives of highly drug-resistant GPSC1/CC320 clone, rarely identified in Europe both before and even after PCV introduction. [ABSTRACT FROM AUTHOR]

Background This retrospective hospital-based surveillance aimed to assess the epidemiology, causative pathogens trend, and serotypes distribution of pneumococcal meningitis among children aged under 5 years with bacterial meningitis in Southern Vietnam after the introduction of pentavalent vaccine in the Expanded Program on Immunization (EPI). Methods From 2012 to 2021, cerebrospinal fluid samples were collected from children aged under 5 years with suspected bacterial meningitis at Children's Hospitals 1 and 2 in Ho Chi Minh City. Probable bacterial meningitis (PBM) cases were identified using biochemistry and cytology. Real-time polymerase chain reaction was used to confirm cases of confirmed bacterial meningitis (CBM) caused by Streptococcus pneumoniae , Haemophilus influenzae , or Neisseria meningitidis. Streptococcus pneumoniae serotyping was performed. Results Of the 2560 PBM cases, 158 (6.2%) were laboratory-confirmed. The CBM proportion decreased during the 10-year study and was associated with age, seasonality, and permanent residence. Streptococcus pneumoniae was the most common pathogen causing bacterial meningitis (86.1%), followed by H influenzae (7.6%) and N meningitidis (6.3%). The case-fatality rate was 8.2% (95% confidence interval, 4.2%–12.2%). Pneumococcal serotypes 6A/B, 19F, 14, and 23F were the most prevalent, and the proportion of pneumococcal meningitis cases caused by the 10-valent pneumococcal conjugate vaccine (PCV) serotypes decreased from 96.2% to 57.1% during the PCV eras. Conclusions Streptococcus pneumoniae is the most frequent causative agent of bacterial meningitis in children aged under 5 years in Southern Vietnam over the last decade. Policymakers may need to consider introducing PCVs into the EPI to effectively prevent and control bacterial meningitis. [ABSTRACT FROM AUTHOR]

In this study, we aimed to clarify the risk factors associated with unfavorable outcomes in adults with pneumococcal meningitis (PnM). Surveillance was conducted between 2006 and 2016. Adults with PnM (n = 268) were followed up for outcomes within 28 days after admission using the Glasgow Outcome Scale (GOS). After classifying the patients into the unfavorable (GOS1–4) and favorable (GOS5) outcome groups, i) the underlying diseases, ii) biomarkers at admission, and iii) serotype, genotype, and antimicrobial susceptibility for all isolates were compared between both groups. Overall, 58.6% of patients with PnM survived,15.3% died, and 26.1% had sequelae. The number of living days in the GOS1 group was highly heterogeneous. Motor dysfunction, disturbance of consciousness, and hearing loss were the commonest sequelae. Of the underlying diseases identified in 68.9% of the PnM patients, liver and kidney diseases were significantly associated with unfavorable outcomes. Of the biomarkers, creatinine and blood urea nitrogen, followed by platelet and C-reactive protein had the most significant associations with unfavorable outcomes. There was a significant difference in the high protein concentrations in the cerebrospinal fluid between the groups. Serotypes 23F, 6C, 4, 23A, 22F, 10A, and 12F were associated with unfavorable outcomes. These serotypes were not penicillin-resistant isolates possessing three abnormal pbp genes (pbp1a , 2x , and 2b), except for 23F. The expected coverage rate of the pneumococcal conjugate vaccine (PCV) was 50.7% for PCV15 and 72.4% for PCV20. In the introduction of PCV for adults, the risk factors for underlying diseases should be prioritized over age, and serotypes with unfavorable outcomes should be considered. [ABSTRACT FROM AUTHOR]

Objectives: Congenital cerebrospinal fluid (CSF) leaks of the ear can be a potential cause of recurrent meningitis. Diagnosing the otogenic cause can be a challenge due to the spectrum of presentations. We aim at studying the various modes of presentation, radiology, and intraoperative findings of such CSF leaks. Methodology: This was a retrospective study of six patients of recurrent meningitis. Detailed history and clinical signs were noted. Audiometry was done. Computed tomography (CT) scan of the paranasal sinus and high-resolution CT of the temporal bone were done. CT cisternography was done for confirmation. Magnetic resonance brain was done in the immediate postmeningitic phase when CT cisternography is contraindicated. All the cases were explored surgically to identify and repair the site of the leak. Results: One had unilateral deafness and five had bilateral deafness. Two had incomplete partition (IP)-I deformity and four had IP-II. Surgical exploration revealed the leak site as only oval window in three patients and both round and oval windows in two. Conclusion: Otorhinology consultation is a must for all cases of recurrent meningitis. It is important to pick up subtle clinical signs for diagnosis. Multiple leak sites should be anticipated in such cases intra-operatively. [ABSTRACT FROM AUTHOR]

Background: In pneumococcal community-acquired pneumonia (CAP), bacteremia is associated with increased mortality, but initial clinical severity scores frequently fail to identify bacteremic patients at risk. We have previously shown that gastrointestinal symptoms are common among patients admitted to the hospital with pneumococcal bacteremia. The aim of this study was to examine gastrointestinal symptoms and inflammatory responses in bacteremic and non-bacteremic pneumococcal CAP in a prospective cohort of immunocompromised and immunocompetent patients hospitalized with CAP. Methods: Logistic regression analysis was used to estimate the predictive value of gastrointestinal symptoms for pneumococcal bacteremia in patients with CAP. The Mann–Whitney test was used to compare inflammatory responses in patients with bacteremic vs. non-bacteremic pneumococcal CAP. Results: Eighty-one patients with pneumococcal CAP were included, of whom 21 (26%) had bacteremia. Immunocompetent patients with pneumococcal CAP had an odds ratio of 16.5 (95% CI 3.0–90.9, p = 0.001) for bacteremia if nausea was present, whereas no such association was found in the immunocompromised patients (OR 0.22, 95% CI 0.02–2.05, p = 0.18). The serum levels of C-reactive protein, procalcitonin and interleukin 6 were significantly higher in the patients with bacteremic pneumococcal CAP compared to non-bacteremic pneumococcal CAP patients (p < 0.001, p = 0.005, and p = 0.019, respectively). Conclusions: In immunocompetent patients hospitalized with pneumococcal CAP, nausea may be a predictor of bacteremia. Bacteremic pneumococcal CAP patients display an increased inflammatory response compared to non-bacteremic pneumococcal CAP patients. [ABSTRACT FROM AUTHOR]

CO-13 Impact of patient's position on esophageal and transpulmonary pressures Gaëlle Fouqué1, Julien Hagry1, Christopher Lai1, Rui Shi1, Daniela Rosalba1, Xavier Monnet1,... 1Hôpital de Bicêtre, APHP, Paris, France Correspondence: Tai Pham (tai.pham@aphp.fr) I Annals of Intensive Care i 2013, B 13(Suppl 1): b CO-13 B Rationale: b Intubated patients with the acute respiratory distress syndrome (ARDS) usually receive protective ventilation limiting plateau pressure below 30 cmH2O and, if possible, a driving pressure under 15 cmH2O. CO-01 PRESS-KT-KID: Prevalence of Severe Sepsis due to catheter related infection in children Manon Passard1, Aurélie Portefaix2, Yves Gillet3, Olivier Dauwalder4, Carine Halfon Domenech5... 1Réanimation pédiatrique-HFME-HCL, Bron, France; 2CIC-HCL, Bron, France; 3Urgences pédiatriqu... Correspondence: Manon Passard (manon.passard@chu-lyon.fr) I Annals of Intensive Care i 2013, B 13(Suppl 1): b CO-01 B Rationale: b Central lines (CL) are frequent in pediatrics but implicate some severe complications. Day-90 mortality in patients with HM was higher than patients with no cancer (64.4% vs 46.6% p = 0.0001) but there was no significant difference when comparing to patients with solid cancer (64.4% vs 61.4%, p = 0.091). CO-18 Acute respiratory distress syndrome in patients with hematological malignancies: a nati... Pierre-Nicolas Bris1, Sami Hraiech1, Vanessa Pauly3, Veronica Orleans3, Laurent Boyer2 1CHU Nord-Assistance publique des Hôpitaux de Marseille, Marseille, France; 2Faculté de médec... Correspondence: Pierre-Nicolas Bris (pierrenicolasbris@free.fr) I Annals of Intensive Care i 2013, B 13(Suppl 1): b CO-018 B Rationale: b Acute respiratory distress syndrome (ARDS) occurring in patients with hematological malignancies (HM) is a life-threatening condition with specific features. [Extracted from the article]

Background: Community-acquired bacterial meningitis is a rare but severe central nervous system infection that may be associated with cerebrovascular complications (CVC). Our objective is to assess the prevalence of CVC in patients with community-acquired bacterial meningitis and to determine the first-48 h factors associated with CVC. Methods: We analyzed data from the prospective multicenter cohort study (COMBAT) including, between February 2013 and July 2015, adults with community-acquired bacterial meningitis. CVC were defined by the presence of clinical or radiological signs (on cerebral CT or MRI) of focal clinical symptom. Factors associated with CVC were identified by multivariate logistic regression. Results: CVC occurred in 128 (25.3%) of the 506 patients in the COMBAT cohort (78 (29.4%) of the 265 pneumococcal meningitis, 17 (15.3%) of the 111 meningococcal meningitis, and 29 (24.8%) of the 117 meningitis caused by other bacteria). The proportion of patients receiving adjunctive dexamethasone was not statistically different between patients with and without CVC (p = 0.84). In the multivariate analysis, advanced age (OR = 1.01 [1.00-1.03], p = 0.03), altered mental status at admission (OR = 2.23 [1.21–4.10], p = 0.01) and seizure during the first 48 h from admission (OR = 1.90 [1.01–3.52], p = 0.04) were independently associated with CVC. Conclusions: CVC were frequent during community-acquired bacterial meningitis and associated with advanced age, altered mental status and seizures occurring within 48 h from admission but not with adjunctive corticosteroids. [ABSTRACT FROM AUTHOR]

Meningitis is an inflammatory disease of the leptomeninges surrounding the spinal cord and brain. Streptococcus pneumoniae (S. pneumoniae) is the most common cause of bacterial meningitis in infants and children older than one month. In this report, we present a 13-month-old infant who, after receiving three doses of the 13-valent conjugated pneumococcal vaccine, had nervus hypoglossus paralysis as a result of serotype 7 S. pneumoniae meningitis. She was admitted into our center with complaints of high fever for 2 days, apathy that started in the last 24 hours, and a tendency for sleeping. Penicillin and ceftriaxone susceptible S. pneumoniae grew in cerebrospinal fluid culture. Antibiotic treatment was completed in six weeks as she had a millimetric abscess in MR imaging. Considering common variable immunodeficiency in the patient who was examined for immunodeficiency, intravenous immunoglobulin treatment was started. The physical examination results of the patient were entirely improved. In conclusion, meningitis is a pediatric emergency with a high mortality and complication rate. If meningitis is managed on time and correctly it can heal without sequelae. Vaccination is crucial for prevention. Despite vaccination, although rare, infection with vaccine strains may occur. Patients infected with vaccine strains may require evaluation in terms of immunodeficiency. [ABSTRACT FROM AUTHOR]

Introduction: This study estimates the annual population-level impact of 13-valent pneumococcal conjugate vaccine (PCV13) infant national immunization programs (NIPs) on vaccine-type and non-vaccine type invasive pneumococcal disease (IPD) incidence across all ages using national surveillance data. Methods: We identified countries (Australia, Canada, England and Wales, Israel, and the US) with national IPD active surveillance data that introduced the seven-valent PCV (PCV7) followed by PCV13, which also reported annual serotype- and age group-specific incidence. We extracted IPD incidence by serotype groupings [PCV13 minus PCV7 (PCV13-7) serotypes; PCV13-7 serotypes excluding serotype 3; non-PCV13 serotypes; and the 20-valent (PCV20) minus PCV13 (PCV20-13) serotypes] and by age groups (< 2 years, 2–4 years, 5–17 years, 18–34 years, 35–49 years, 50–64 years, and ≥ 65 years). For each country, we calculated the annual relative change in IPD incidence (percent change), and the corresponding incidence rate ratio (IRR), for 7 years post introduction compared to the year prior to PCV13 program initiation. Results: PCV13-7 vaccine-type IPD incidence consistently decreased over time following introduction of PCV13 across countries, reaching an approximate steady state after 3–4 years in ages < 5 years, with roughly 60–90% decrease (IRRs = 0.1–0.4) and after 4–5 years in ages ≥ 65 years with approximately 60–80% decrease (IRRs = 0.2–0.4). Incidence declines were more substantial for the PCV13-7 grouping when excluding serotype 3. Non-PCV13 serotype incidence was variable by country and age group, ranging from virtually no serotype replacement compared to the PCV7 period across ages in the US to increases for other countries ranging from 10 to 204% (IRRs = 1.10–3.04) in children < 5 years and 41% to 123% (IRRs = 1.41–2.23) in ages ≥ 65 years. Conclusions: Countries with longstanding PCV13 infant NIPs have observed substantial direct and indirect benefits, which are demonstrated in this study by the reduction in PCV13-7 IPD incidence compared to PCV7 period in all age groups. Over time, non-PCV13 serotypes have emerged in response to the reduction of incidence of PCV13-unique serotypes. Higher-valent PCVs are needed to address this emerging pneumococcal disease burden as well as the direct vaccination of both pediatric and adult populations against the most prevalent circulating serotypes. [ABSTRACT FROM AUTHOR]

Key clinical message: Delayed presentation of cerebrospinal fluid rhinorrhea is rare following head trauma. It is frequently complicated by meningitis if not addressed in time. This report highlights the importance of its timely management, the lack of which can lead to a fatal outcome. A 33‐year‐old man presented with meningitis in septic shock. He had a history of severe traumatic brain injury 5 years back following which he had a history of intermittent nasal discharge for the past 1 year. On investigation, he was found to have Streptococcus pneumoniae meningitis, and CT scan of his head showed defects in the cribriform plate which established the diagnosis of meningoencephalitis secondary to cerebrospinal fluid rhinorrhea. The patient did not survive despite appropriate antibiotics. [ABSTRACT FROM AUTHOR]

The leading infectious cause of death in children worldwide is lower acute respiratory infection (LARI), particularly pneumonia. We enrolled a total of 538 acute respiratory infection (ARI) cases according to WHO criteria and age-sex matched 514 controls in the Forcibly Displaced Myanmar National (FDMN) refugee camps in Cox's Bazar, Bangladesh, between June 2018 and March 2020 to investigate the role of bacteria, viruses, and their co-infection patterns and observe Streptococcus pneumoniae (S. pneumoniae) serotype distribution. According to the etiological findings, children ≤5 years of age have a higher bacterial positivity (90%) and viral positivity (34%) in nasopharyngeal samples (NPS) compared to those >5 years of age, in both ARI cases as well as for the control group. Among the bacteria, S. pneumoniae was predominant in both cases and controls (85% and 88%). Adenovirus (ADV)(34), influenza virus A and B (IFV-A, B)(32,23), and respiratory syncytial virus (RSV)(26) were detected as the highest number among the viruses tested for the ARI cases. The total number of viruses was also found higher in ≤5 years of age group. Within this group, positive correlation was observed between bacteria and viruses but negative correlation was observed between bacteria. Both single and co-infection for viruses were found higher in the case group than the control group. However, co-infection was significantly high for Streptococcus aureus (S. aureus) and Haemophilus influenzae b (H. influenza b) (p<0.05). Additionally, semi-quantitative bacterial and viral load was found higher for the ARI cases over control considering Cycle threshold (Ct)≤30. Pathogen identification from blood specimens was higher by qRT-PCR than blood culture (16% vs 5%, p<0.05). In the S. pneumoniae serotype distribution, the predominant serotypes in ARI cases were 23F, 19A, 16F, 35B, 15A, 20 and 10F, while 11A, 10A, 34, 35A and 13 serotypes were predominant in the control group. Pathogen correlation analysis showed RSV positively correlated with human metapneumovirus (HMPV), S. aureus and H. influenza b while S. pneumoniae was negatively correlated with other pathogens in ≤5 years age group of ARI cases. However, in >5 years age group, S. aureus and H. influenza b were positively correlated with IFVs, and S. pneumoniae was positively correlated with HMPV and ADV. Logistic regression data for viruses suggested among the respondents in cases were about 4 times more likely to be RSV positive than the control. Serotype distribution showed 30% for PCV10 serotypes, 41% for PCV13 and 59% for other serotypes. Also, among the 40 serotypes of S. pneumoniae tested, the serotypes 22F, Sg24, 9V, 38, 8, and 1 showed strong positive correlation with viruses in the case group whereas in the control group, it was predominant for serotypes 14, 38, 17F and 39 ARI cases were prevalent mostly in monsoon, post-monsoon, and winter periods, and peaked in September and October. Overall these region-specific etiological data and findings, particularly for crisis settings representing the FDMNs in Cox's Bazar, Bangladesh, is crucial for disease management and disease prevention control as well as immunization strategies more generally in humanitarian crisis settings. Author summary: Acute respiratory infections (ARIs) are one of the most common communicable diseases in crisis settings, causing significant morbidity and mortality. Non-comparable as well as little aetiological data from refugee camps and surveillance, make it difficult to compare the prevalence of ARI disease between crisis and non-crisis contexts. In the world's largest refugee settlement situated in Cox's Bazar, Bangladesh, very little is known about the etiology of ARIs. To our best knowledge, this is the first case-control prospective study to evaluate the level of involvement of each etiological agent in the onset of LARI etiology, and the association between respiratory viral infections and invasive pneumococcal infections, S. pneumoniae serotype distribution, antimicrobial resistance pattern both in case and control group. Our study showed that ≤5 years age group was the most vulnerable, having the highest number of bacteria as well as viruses both in the case and control group. S. pneumoniae was the predominant bacteria, whereas, among the viruses ADV, IFVs, and RSV were predominant. Semi-quantitative bacterial as well as viral load was found higher in the case group. Positive correlation between viruses and other pathogens was higher in cases of RSV than in the control group. However, single as well as co-infection between viruses were significantly high among the ARI case while for bacteria it was comparable between the case and control group. ARI case enrollment peaked in September and October in the FDMN camps in Bangladesh. [ABSTRACT FROM AUTHOR]

Streptococcus pneumoniae is a leading cause of bacterial meningitis worldwide. Conventional microbiological assays take several days and require the use of various drugs for empirical treatment. Rapid antigen tests in cerebrospinal fluid (CSF) may be useful to triage pneumococcal meningitis immediately. To elucidate whether rapid antigen tests in CSF are useful in the triage of pneumococcal meningitis. Data sources Cochrane CENTRAL, MEDLINE, EMBASE, World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov databases were searched. Study eligibility criteria All types of cohort studies except multiple-group studies, where the sensitivity and specificity of rapid antigen tests in CSF compared with CSF culture can be extracted. Participants Patients with suspected meningitis. Tests Rapid antigen tests in CSF. Reference standards One or more of the following: blood culture, CSF culture, and polymerase chain reaction in CSF. Assessment of risk of bias The methodological quality of the included studies was assessed using QUADAS-2. Methods of data synthesis We used a random-effects bivariate model for the meta-analysis. We conducted a subgroup analysis by dividing studies into types of antigen tests, adults and children, low-income and high-income countries, and with or without exposure to antibiotics before lumbar puncture. Forty-four studies involving 14 791 participants were included. Most studies had a moderate-to-low methodological quality. Summary sensitivity and specificity were 99.5% (95% confidence interval (CI), 92.4–100%) and 98.2% (95% CI, 96.9–98.9%), respectively. Positive predictive values and negative predictive values at the median prevalence (4.2%) in the included studies were 70.8% (95% CI, 56.6–79.9%) and 100% (95% CI, 99.7–100%), respectively. The diagnostic accuracy was consistent across the various subgroups, except for slightly reduced sensitivity in high-income countries. Rapid antigen tests in CSF would be useful in triaging pneumococcal meningitis. Further studies are warranted to investigate the clinical benefit of ruling out pneumococcal meningitis based on the results of rapid antigen tests. [ABSTRACT FROM AUTHOR]

Introduction: Studies that estimate the economic burden of pediatric pneumococcal disease often only report direct medical costs and omit indirect non-medical costs. Given these indirect costs are not included in most calculations, the full economic burden attributable to pneumococcal conjugate vaccine (PCV) serotypes is often underestimated. This study seeks to quantify the full broader economic burden of pediatric pneumococcal disease associated with PCV serotypes. Methods: We conducted a reanalysis of a previous study where non-medical costs associated with caregiving for a child with pneumococcal disease are considered. The annual indirect non-medical economic burden attributed to PCV serotypes was subsequently calculated for 13 countries. We included five countries with 10-valent (PCV10) national immunization programs (NIPs) (Austria, Finland, The Netherlands, New Zealand, and Sweden) and eight countries with 13-valent (PCV13) NIPs (Australia, Canada, France, Germany, Italy, South Korea, Spain, and the UK). Input parameters were derived from published literature. Indirect costs were inflated to 2021 values in US dollars (USD). Results: The total annual indirect economic burden associated with pediatric pneumococcal diseases attributable to PCV10, PCV13, the 15-valent (PCV15), and the 20-valent (PCV20) serotypes were $46.51 million, $158.95 million, $223.00 million, and $413.97 million, respectively. The five countries with PCV10 NIPs bear a greater societal burden associated with PCV13 serotypes, whereas the residual societal burden in the eight countries with PCV13 NIPs was primarily attributable to non-PCV13 serotypes. Conclusion: The inclusion of non-medical costs nearly tripled the total economic burden compared with only including direct medical costs estimated from a previous study. The results from this reanalysis can help inform decision-makers on the broader economic societal burden associated with PCV serotypes and the need for higher-valent PCVs. [ABSTRACT FROM AUTHOR]

Streptococcus pneumoniae causes invasive diseases of significant public health concern, such as meningitis. The culture of cerebrospinal fluid (CSF) samples, the standard technique for meningitis diagnoses, is not always positive. Consequently, meaningful information about the etiological agent is lost, which can compromise effective epidemiological surveillance and the improvement of immunization policies. This study aims to standardize a method to genotype pneumococcus in the CSF samples which could mitigate the absence of isolated strains, and also evaluate the prediction of this assay. We applied eight multiplex PCR (mPCR) assays to CSF samples paired with the Quellung reaction applied to the isolated strains. We also compared different master mix kits in the mPCR. Moreover, a retrospective study was conducted with CSF samples considered pneumococcus positive due to the presence of the lytA gene. Results showed that genotyping by the mPCR correlated 100% with the Quellung reaction, and genotyping was dependent on the master mix applied. In the retrospective study (2014–2020), 73.4% were successfully genotyped. The analyses of the receiver operating characteristic curve showed that the cycle threshold (Ct value) around 30 for the lytA gene had a 75% positive chance of successful genotyping, whereas with a Ct value > 35, the chance was 12.5%. Finally, we observed that genotype 19A was prevalent in the period (12%), information unknown until now due to the lack of isolated strains. Therefore, the mPCR of CSF samples can efficiently predict S. pneumoniae serotypes, especially in the absence of isolated strains, which can be a great tool for pneumococcal serotype surveillance. [ABSTRACT FROM AUTHOR]

Background Monitoring changes in pharyngeal carriage of pneumococcus in children following 13-valent pneumococcal conjugate vaccine (PCV13) introduction in the United Kingdom in 2010 informs understanding of patterns of invasive pneumococcal disease (IPD) incidence. Methods Nasopharyngeal swabs from healthy children vaccinated with PCV13 according to schedule (2, 4, and 12 months) were cultured and serotyped. Results for children aged 13–48 months were compared between 2014–2015 and 2017–2019 and with children aged 6–12 months (2017–2020). Blood was obtained from a subset of children for pneumococcal serotype-specific immunoglobulin G (IgG). Results Total pneumococcal carriage at 13–48 months was 47.9% (473/988) in 2014–2015 and 51.8% (412/795) in 2017–2019 (P =.10); at age 6–12 months this value was 44.6% (274/615). In 2017–2019, 2.9% (95% confidence interval, 1.8%–4.3%) of children aged 13–48 months carried PCV13 serotypes (mainly 3 [1.5%] and 19A [0.8%]) and >20% carried the additional 20-valent PCV (PCV20) serotypes. Similar proportions of children had IgG ≥0.35 IU/mL for each serotype in 2014–2015 and 2017–2019. Serotype 7C carriage increased significantly (P <.01) between 2014–2015 and 2017–2019. Carriage of PCV20 serotypes 8 and 12F, both major causes of IPD, was rare. Conclusions Introduction of PCV20, if licensed for children, could significantly change the composition of pneumococcal serotypes carried in the pharynx of UK children. Clinical Trials Registration NCT03102840. [ABSTRACT FROM AUTHOR]

The aim of the study was to assess the pneumococcal antibody response in autoimmune inflammatory rheumatic disease (AIIRD) patients receiving 23-valent pneumococcal polysaccharide vaccine (PPV23) as a prime vaccination or revaccination. Antibodies to 12 serotypes occurring in the commonly applied pneumococcal vaccines in Denmark were measured in AIIRD patients receiving biological disease-modifying anti-rheumatic drug (bDMARD) treatment for rheumatoid arthritis, spondyloarthritis, or psoriatic arthritis. Patients with a non-protective level of pneumococcal antibodies (geometric mean pneumococcal antibody level < 1 μg/mL) were invited to receive vaccination with PPV23 followed by control of antibody titre 3 months later. In total, 224 (74%) of 301 patients were included in the analyses, of whom 126 patients had previously received PPV23 vaccination. Post-vaccination antibody measurement revealed that only 80 patients (36%) achieved a protective level of antibodies. In a multivariable logistic regression analysis, significantly more patients without a previous PPV23 vaccination history achieved a protective antibody level compared with patients with a history of PPV23 vaccination less than 5 years ago (p = 0.005). This difference was not seen when comparing the former group with patients vaccinated 5 years ago or more. Methotrexate (MTX) treatment at the time of vaccination was associated with a non-protective antibody level (p < 0.001). Only 36% of patients with a non-protective antibody level achieved a protective level in response to pneumococcal vaccination. Pneumococcal vaccination within the last 5 years and MTX treatment at the time of vaccination were independently associated with a poor antibody response. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

To retrospectively assess the impact of regular yearly administration of recombinant influenza and single administration of pneumococcal conjugate vaccines on the occurrence of serious respiratory infection including COVID-19 in patients with type 2 diabetes mellitus. Hundred patients with type 2 diabetes mellitus were given Vaxigrip and Prevnar13® vaccines and were evaluated by comprehensive clinical review, airflow screening questionnaire, and routine laboratory investigations with follow-up during the COVID-19 pandemic and compared to a control group of diabetic patients with the same inclusion criteria (n = 100). After Vaxigrip and Prevnar13, there is a significant improvement in respiratory symptoms and a decrease in the airflow screening questionnaire (p = 0.0001) with a significant improvement in inflammatory parameters as neutrophil–lymphocyte ratio, ESR, CRP, and platelet count. Four patients had mild COVID-19 (4%), mainly gastrointestinal with no complications. Twenty-one out of 32 (65.6%) patients in the control group had severe COVID-19. The hazard ratios of significant respiratory tract infection and death due to COVID-19 were 2.29 and 10.24 in the non-vaccinated control (p = 0.001).The severity of COVID-19 in diabetes correlated with HBA1C (p = 0.007), combined Vaxigrip and Prevnar13 vaccination (p = 0.0001), serum creatinine (p = 0.001), neutrophil–lymphocyte ratio (p = 0.001), and thrombocytopenia (p = 0.003). The present study suggested that the combination of Prevnar13 and Vaxigrip may be related to decreased occurrence of serious respiratory infections including COVID-19. Further randomized control trials may be needed to establish a direct causation between the two and clarify these associations. [ABSTRACT FROM AUTHOR]

Introduction: The introduction of PCV13 to the Malawi infant immunization schedule in 2011 has been associated with reduced disease from Streptococcus pneumoniae. Improved understanding of serotypes with high invasive potential can guide future vaccination interventions. We aimed to estimate pneumococcal serotypes associated with acute respiratory infection (ARI) and invasive pneumococcal disease (IPD) in hospitalized children in Blantyre, Malawi. Methods: We analysed data from healthy children under 5 years in the community in Blantyre and children admitted to Queen Elizabeth Central Hospital with ARI between 2015 and 2018. Nasopharyngeal swabs from children were tested for S. pneumoniae and serotyped by latex agglutination if positive. We analysed culture-positive blood and cerebrospinal fluid samples from admitted children between 2012 and 2018 to identify cases of IPD after the introduction of PCV13. We calculated the age-adjusted odds ratio (OR) of carriage for S. pneumoniae vaccine serotypes (VT) comparing those with ARI to healthy children. We also calculated age-adjusted ORs comparing serotypes causing IPD to carriage in the community with OR > 1 indicating high invasive potential. Results: Serotypes 5 (OR 24.73 [95% CI 7.90–78.56] p < 0.001), 1 (OR 23.38 [95% CI 9.75–56.06] p < 0.001), and 6B (OR 4.73 [95% CI 1.66–11.64] p = 0.001) had high invasive potential. Serotype 6B was no longer significant (OR 1.34 [95% CI 0.07–6.87] p = 0.777) in a sensitivity analysis accounting for year of recruitment. The prevalence of S. pneumoniae carriage in the community was 72.6% [95% CI 71.3–74.0] (3078/4238) and 23.4% (719/3078) of positive community samples were VT. The carriage prevalence in those hospitalised with ARI was 45.5% [95% CI 42.1–48.9] (389/855) and 43.8% of hospital attendees reported antibiotic use prior to admission. We did not identify significant associations with carriage of any serotypes in those with ARI. Conclusions: Pneumococcal serotypes 5 and 1 are associated with high invasive potential. Despite high community pneumococcal carriage, pre-hospital antibiotic usage likely reduces pneumococcal detection among children admitted in this setting and further research is needed to investigate serotypes associated with ARI. Data from this study can guide future preventative vaccination strategies in Malawi. [ABSTRACT FROM AUTHOR]

Background: Streptococcus pneumoniae (S. pneumoniae), remains a major cause of mortality and morbidity worldwide. The objective of this study was to determine the trends of invasive pneumococcal diseases (IPD) in adult and elderly population in Casablanca (Morocco) before and after introduction of pneumococcal conjugate vaccine (PCV) by determining the distribution of pneumococcal serotypes and antibiotic resistance profile of isolated strains. Method: The proposed study is a retrospective laboratory-based surveillance of IPD in hospitalized adult (15–59 years old) and elderly (≥ 60 years old) patients in Ibn Rochd University Hospital Centre from 2007 to 2019 (13 years). All the 250 non-duplicate clinical invasive isolates from adult and elderly patients, confirmed as S. pneumoniae according to the laboratory standard identification procedures, are included in this study. Results: A significant decrease of the overall incidence in IPD was observed only in adults from 0.71 to 0.54/100000 populations (P = 0.02) and to 0.47/100000 populations (P = 0.0137) in the early and mature post-vaccine period respectively compared to the pre-vaccine period. Our results also showed a significant reduction in the overall prevalence of vaccine serotypes from 28.17 to 6.90% (P = 0.0021) for the PCV-10 serotypes, and from 46.48 to 25.86% (P = 0.0164) for the PCV-13 serotypes only in the mature post-vaccine period (2015–2019). In parallel, the rate of non-vaccine serotypes did not significantly change in the early post-vaccine period (2011–2014) while it increased considerably from 54 to 74.14% (P = 0.0189) during the mature post-vaccine period. The rate of penicillin non-susceptible pneumococcal isolates decreased significantly from 23.94 to 8.77% (P = 0.02) in adult patients, and the rate of cotrimoxazole non-susceptible pneumococcal isolates significantly decreased from 29.58 to 8.77% in the early post-vaccine period (P = 0.003) and to 7.24% in the mature post-vaccine period (P = 0.0007). Conclusion: Although childhood vaccination has considerably reduced the incidence of IPD in adult population through the herd effect, IPD remain a real public health problem due to the alarming increase in non-vaccine serotypes (NVS) and the lack of herd effect among elderly population. The rate of antibiotic resistance was relatively low. Nevertheless, resistance constitutes a serious problem to the therapeutic arsenal due to the known capacity for genetic dissemination in the pneumococcus. [ABSTRACT FROM AUTHOR]

Background: Infection with viruses, bacteria, or other pathogens can lead to inflammation of the meninges. Finding the pathogen and identifying the most common type is necessary for each country. Using multi-locus sequence typing (MLST), the aim of this study was to determine the genetic relationship among S. pneumoniae isolated from CSF in children with bacterial meningitis. Materials and methods: Fourteen isolates of S. pneumoniae from CSF in children with bacterial meningitis were included in this study. The seven housekeeping genes, primer, and analysis of the sequencing used in MLST were extracted from PubMLST. Results: The sequencing analysis showed four MLST types in the studied strains. The most frequent type is ST13649 and the least frequent are ST708 and ST285. Conclusion: Finding the bacterial sequence types (ST) enables comparing the ST in different, especially neighbouring, countries. [ABSTRACT FROM AUTHOR]

Neisseria meningitidis (Nm) is the pathogen carried asymptomatically in the nasopharynx but which under certain conditions can produce meningitis or even multi-organ failure. Experimental induction of meningitis in an animal model is necessary for testing new nanopharmaceutical products. Thus, the aim of the study was to establish the concentration of Nm capable of inducing the disease. We carried out 2 studies where we tested different concentrations of Nm obtained by the nephelometric and spectrophotometric methods. In the first study we included 20 BALB/c mice, and in the second 24. Local and general clinical signs, complete with body temperature values, body weight, hematological, microbiological and histopathological examination were important indicators for the assessment of the establishment of meningitis. The clinical results have pronounced depression in the first 2 days after inoculation, then the general condition will appear. The microbiological and histopathological examination indicated the presence of bacteria at the brain level and specific meningeal lesions only in the case of the second attempt, but the early mortality, requires additional testing of the bacterial concentration that induces meningites in a stable and persistent way so that treatment against the condition can be tested later. [ABSTRACT FROM AUTHOR]

Background: We aimed to discuss the successful treatment of cerebrospinal fluid (CSF)-cutaneous fistula which is caused by combined spinal epidural anesthesia (CSE), with an autologous epidural blood patch (EBP), further investigation and antibiotherapy. Case: CSE was applied for a total hip replacement. Since CSF was seen in the first attempt, CSE was achieved in the second attempt using the same Tuohy needle. Postoperatively epidural catheter was used for analgesic purposes for 2 days. After the catheter removal, anesthesia consultation was requested due to the patient's wet back. A clear fluid leak at the needle insertion point was observed. A sample was taken and the differential diagnosis of CSF-skin fistula was made biochemically with the presence of glucose and chloride. The patient denied headaches. Neurological examination was normal. With patient's consent, EBP was performed. During the injection CSF leak was slowed down, the last drops were macroscopically hemorrhagic and eventually the leak stopped. Headache, dizziness, and nausea occurred on the 2nd day after EBP. Neurological examination was normal. No dural defect or CSF collection was observed in brain CT, brain diffusion MR and contrast-enhanced MR myelography. Ceftriaxone, metronidazole and a pneumococcal vaccine were added for meningitis prophylaxis in consensus with infection and neurology consultants. 1-month follow-up was performed telephonically and the patient was completely cured. Conclusion: Cerebrospinal fluid (CSF)-cutaneous fistula is a rare complication of neuraxial anesthesia techniques. Since there are no sufficient guidelines for management, the decision on the treatment method depends on the clinician's aspect. We consider that it would be advantageous to prefer EBP primarily in cases with CSF-skin fistula and that the benefit/harm ratio is higher than the complications to be caused by a subarachnoid space that is fistulized to skin and opened out to cutaneous flora. In the literature, the development of meningitis has been reported in some cases followed up under conservative treatment or skin sutures. Although prophylactic use should be avoided as possible due to increasing antibiotic resistance, our opinion is that clinicians should decide for each case, taking into account the conditions such as hospital infection surveillance and the flora of inpatient service. [ABSTRACT FROM AUTHOR]