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Objective: This study aimed to form astute deductions regarding the presentation, treatment and mortality of otogenic brain complications., Methods: A systematic literature search of four medical databases (PubMed, Embase, Web of Science and Scopus) was conducted. Studies associated with otogenic brain complications were considered eligible. Fixed- and random-effects model meta-analysis was developed to assess the proportion estimate for each outcome individually., Results: Twenty-eight studies, with 1650 patients in total, were included. In 66 per cent of patients there was a known history of chronic otitis media. The most common symptoms were purulent otorrhoea (84 per cent), headache (65 per cent) and otalgia (45 per cent). A brain abscess was observed in 49 per cent of patients, followed by meningitis (34 per cent) and sinus thrombosis (22 per cent). A combination of surgical and conservative therapy was chosen in 84.3 per cent of cases and the mortality rate approached 11.1 per cent., Conclusion: Otogenic brain complications are a possibly life-threatening condition. Prompt imaging examination may set the final diagnosis and lead to an effective treatment.

Objective: To analyze the spatiotemporal epidemiological dynamics of meningitis in Brazil, between 2010 and 2019., Methods: Descriptive ecological study with cases and deaths due to meningitis in Brazil (2010-2019) in the National Notifiable Diseases Information System (Sistema de Informações de Agravos de Notificação - SINAN). The following analyses were performed: (I) frequency analyses of cases and deaths, prevalence rates, mortality, lethality, Fisher's exact test, and chi-square test; (II) Prais-Winstein regression; and (III) Global, Local Moran's index, and Kernel density., Results: 182,126 cases of meningitis were reported in Brazil, of which 16,866 (9.26%) resulted in death, with prevalence rates of 9.03/100,000 inhabitants, mortality of 0.84/100,000 inhabitants, and lethality of 9.26%. There was a noted trend of decreasing prevalence rates (-9.5%, 95% confidence interval - 95%CI -13.92; -4.96, p<0.01) and mortality (-11.74%, 95%CI -13.92; -9.48, p<0.01), while lethality remained stable (-2.08%, 95%CI -4.9; 0.8; p<0.1941). The majority of cases were viral meningitis (45.7%), among 1-9 years old (32.2%), while the highest proportion of deaths was due to bacterial meningitis (68%), among 40-59 years old (26.3%). In the Moran and Kernel maps of prevalence and mortality rates, municipalities in the South, Southeast, and the capital of Pernambuco in the Northeast stood out with high rates; as for lethality, the North, Northeast, and Southeast coastal areas were highlighted., Conclusion: A decrease in meningitis cases and deaths was found in this study; however, the lethality rate was higher in areas with lower prevalence, emphasizing the need to enhance actions for identifying, monitoring, and providing health care for cases, as well as expanding vaccination coverage.

Background: Group B Streptococcus (GBS) disease is a leading cause of neonatal death, but its long-term effects have not been studied after early childhood. The aim of this study was to assess long-term mortality, neurodevelopmental impairments (NDIs), and economic outcomes after infant invasive GBS (iGBS) disease up to adolescence in Denmark and the Netherlands., Methods: For this cohort study, children with iGBS disease were identified in Denmark and the Netherlands using national medical and administrative databases and culture results that confirmed their diagnoses. Exposed children were defined as having a history of iGBS disease (sepsis, meningitis, or pneumonia) by the age of 89 days. For each exposed child, ten unexposed children were randomly selected and matched by sex, year and month of birth, and gestational age. Mortality data were analysed with the use of Cox proportional hazards models. NDI data up to adolescence were captured from discharge diagnoses in the National Patient Registry (Denmark) and special educational support records (the Netherlands). Health care use and household income were also compared between the exposed and unexposed cohorts., Findings: 2258 children-1561 in Denmark (born from Jan 1, 1997 to Dec 31, 2017) and 697 in the Netherlands (born from Jan 1, 2000 to Dec 31, 2017)-were identified to have iGBS disease and followed up for a median of 14 years (IQR 7-18) in Denmark and 9 years (6-11) in the Netherlands. 366 children had meningitis, 1763 had sepsis, and 129 had pneumonia (in Denmark only). These children were matched with 22 462 children with no history of iGBS disease. iGBS meningitis was associated with an increased mortality at age 5 years (adjusted hazard ratio 4·08 [95% CI 1·78-9·35] for Denmark and 6·73 [3·76-12·06] for the Netherlands). Any iGBS disease was associated with an increased risk of NDI at 10 years of age, both in Denmark (risk ratio 1·77 [95% CI 1·44-2·18]) and the Netherlands (2·28 [1·64-3·17]). A history of iGBS disease was associated with more frequent outpatient clinic visits (incidence rate ratio 1·93 [95% CI 1·79-2·09], p<0·0001) and hospital admissions (1·33 [1·27-1·38], p<0·0001) in children 5 years or younger. No differences in household income were observed between the exposed and unexposed cohorts., Interpretation: iGBS disease, especially meningitis, was associated with increased mortality and a higher risk of NDIs in later childhood. This previously unquantified burden underlines the case for a maternal GBS vaccine, and the need to track and provide care for affected survivors of iGBS disease., Funding: The Bill & Melinda Gates Foundation., Translations: For the Dutch and Danish translations of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests AvdE received grants from Pfizer for research on pneumococcal infections (investigator initiated project IIR WI173197) and for research on meningococcal infections (investigator initiated project IIR WI242174), outside the submitted work; participated in the Advisory Boards of Pfizer, GlaxoSmithKline, and Sanofi-Pasteur; and did consultancy activities for GlaxoSmithKline and Merck Sharp & Dohme (fees paid to Amsterdam University Medical Center). HTS reports that the Department of Clinical Epidemiology is involved in studies with institutional funding from regulators and from various pharmaceutical companies, as research grants to and administered by Aarhus University. None of these studies are related to the current study. All other authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: Competing interests: We have read and understood BMJ policy on declaration of interests and declare that we have no competing interests.

Objective: The purpose of this study was to examine trends in clinical characteristics and in-hospital mortality of HIV patients in a low resource setting in the period 2010 to 2016., Methods: Data on socio-demographic and clinical characteristics of 313 hospitalized HIV positive patients at the University College Hospital, Ibadan, Nigeria were retrospectively extracted, described and examined for trends. Factors independently associated with mortality were identified using multiple logistic regression., Results: The mean age was 39 years (SD = 9.8) and about two thirds were female. The proportion of females decreased significantly from 83.3% in 2010-2011 to 39.8% in 2016. There was a significant reduction in the diagnosis of disseminated tuberculosis and mortality from 19.4% and 42.9% in 2010-2011 to 4.8% and 27.9% in 2016 respectively. On multiple logistic regression, being male, having neurological features, meningitis, and shorter stay in hospital had significantly higher odds of mortality., Conclusion: There was a reduction in in-hospital mortality of HIV patients over the period from 2010 to 2016. Being male and presence of neurological features were associated with mortality. Larger prospective studies are needed to further investigate this observed reduction in mortality among hospitalised patients.

Sensitive tools are needed to accurately establish the diagnosis of tuberculosis (TB) at death, especially in low-income countries. The objective of this study was to evaluate the burden of TB in a series of patients who died in a tertiary referral hospital in sub-Saharan Africa using an in-house real time PCR (TB-PCR) and the Xpert MTB/RIF Ultra (Xpert Ultra) assay.Complete diagnostic autopsies were performed in a series of 223 deaths (56.5% being HIV-positive), including 54 children, 57 maternal deaths and 112 other adults occurring at the Maputo Central Hospital, Mozambique. TB-PCR was performed in all lung, cerebrospinal fluid and central nervous system samples in HIV-positive patients. All samples positive for TB-PCR or showing histological findings suggestive of TB were analysed with the Xpert Ultra assay.TB was identified as the cause of death in 31 patients: three out of 54 (6%) children, five out of 57 (9%)maternal deaths and 23 out of 112 (21%) other adults. The sensitivity of the main clinical diagnosis to detect TB as the cause of death was 19.4% (95% CI 7.5-37.5) and the specificity was 97.4% (94.0-99.1) compared to autopsy findings. Concomitant TB (TB disease in a patient dying of other causes) was found in 31 additional cases. Xpert Ultra helped to identify 15 cases of concomitant TB. In 18 patients, Mycobacterium tuberculosis DNA was identified by TB-PCR and Xpert Ultra in the absence of histological TB lesions. Overall, 62 (27.8%) cases had TB disease at death and 80 (35.9%) had TB findings.The use of highly sensitive, easy to perform molecular tests in complete diagnostic autopsies may contribute to identifying TB cases at death that would have otherwise been missed. Routine use of these tools in certain diagnostic algorithms for hospitalised patients needs to be considered. Clinical diagnosis showed poor sensitivity for the diagnosis of TB at death., Competing Interests: Conflict of interest: A.L. Garcia-Basteiro has nothing to disclose. Conflict of interest: J.C. Hurtado has nothing to disclose. Conflict of interest: P. Castillo has nothing to disclose. Conflict of interest: F. Fernandes has nothing to disclose. Conflict of interest: M. Navarro has nothing to disclose. Conflict of interest: L. Lovane has nothing to disclose. Conflict of interest: I. Casas has nothing to disclose. Conflict of interest: L. Quinto has nothing to disclose. Conflict of interest: D. Jordao has nothing to disclose. Conflict of interest: M.R. Ismail has nothing to disclose. Conflict of interest: C. Lorenzoni has nothing to disclose. Conflict of interest: C. Carrilho has nothing to disclose. Conflict of interest: A. Sanz has nothing to disclose. Conflict of interest: N. Rakislova has nothing to disclose. Conflict of interest: A. Mira has nothing to disclose. Conflict of interest: M.J. Alvarez-Martinez has nothing to disclose. Conflict of interest: A. Cossa has nothing to disclose. Conflict of interest: F. Cobelens has nothing to disclose. Conflict of interest: I. Mandomando has nothing to disclose. Conflict of interest: J. Vila has nothing to disclose. Conflict of interest: Q. Bassat has nothing to disclose. Conflict of interest: C. Menendez has nothing to disclose. Conflict of interest: J. Ordi has nothing to disclose. Conflict of interest: M.J. Martinez has nothing to disclose., (Copyright ©ERS 2019.)

Background: Definitive diagnosis of meningitis is made by analysis of cerebrospinal fluid (CSF) culture or polymerase chain reaction (PCR) obtained from a lumbar puncture (LP), which may take days. A timelier diagnostic clue of meningitis is pleocytosis on CSF analysis. However, meningitis may occur in the absence of pleocytosis on CSF. Areas of Uncertainty: A diagnosis of meningitis seems less likely without pleocytosis on CSF, leading clinicians to prematurely exclude this. Further, there is little available literature on the subject., Methods: Ovid/Medline and Google Scholar search was conducted for cases of CSF culture-confirmed meningitis with lack of pleocytosis. Inclusion criterion was reported cases of CSF culture-positive or PCR positive meningitis in the absence of pleocytosis on LP. Exclusion criteria were pleocytosis on CSF, cases in which CSF cultures/PCR were not performed, and articles that did not include CSF laboratory values., Results: A total of 124 cases from 51 articles were included. Causative organisms were primarily bacterial (99 cases). Outcome was reported in 86 cases, 27 of which died and 59 survived. Mortality in viral, fungal and bacterial organisms was 0, 56 and 31%, respectively. The overall percentage of positive initial CSF PCR/culture for viral, fungal and bacterial organisms was 100, 89 and 82%, respectively. Blood cultures were performed in 79 of the 124 cases, 56 (71%) of which ultimately cultured the causative organism. In addition to bacteremia, concomitant sources of infection occurred in 17 cases., Conclusions: Meningitis in the absence of pleocytosis on CSF is rare. If this occurs, causative organism is likely bacterial. We recommend ordering blood cultures as an adjunct, and, if clinically relevant, concomitant sources of infection should be sought. If meningitis is suspected, empiric antibiotics/antifungals should be administered regardless of initial WBC count on lumbar puncture.

For the last decades, the timing of antimicrobial therapy has remained a hotly debated topic in sepsis as well as other infectious diseases like community-acquired pneumonia (CAP) or bacterial meningitis (CABM). In CAP, a relationship between the time to antibiotic administration and mortality was found only in the largest cohort, but all these studies were retrospective and of low quality. In CABM, the level of evidence remains also limited, but there is now a good body of evidence linking the delay to antibiotic administration to unfavorable outcome. The European guidelines strongly suggest that time period should not exceed 1 hour. Finally, in sepsis, if the 1-hour cut-off remains debatable for sepsis patients, early administration (within 3 hours) is recommended in sepsis and sepsis shock as suggested by the surviving sepsis campaign recommendations. To conclude, all these data are in favor of a potential link between the time to antibiotic administration and survival, but we still miss randomized controlled studies to give a definite answer., Competing Interests: None., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Background/objective: Infection is the most common complication of external ventricular drain (EVD) placement. National trends in the annual incidence of meningitis among patients with traumatic brain injury (TBI) who have undergone EVD placement have not been reported., Methods: The Nationwide Inpatient Sample was used to select adults with a primary diagnosis of TBI who underwent EVD placement between 2002 and 2011. Annual rates of meningitis among patients who underwent EVD placement were determined. We also calculated mortality rates and length of stay (LOS). Potential factors associated with meningitis were evaluated in a binary logistic regression analysis., Results: Out of 1,571,927 adult discharges with a primary diagnosis of TBI between 2002 and 2011, 39,029 (2.5%) underwent EVD placement. Of these, 1544 (4.3%) patients developed meningitis. There was no significant trend in the annual incidence of meningitis (p = 0.88), mortality (p = 0.55), or mean LOS (p = 0.13) during the study period. Meningitis and mortality rates remained stable when stratifying patients by hospital volume. In the binary logistic regression, acquired immunodeficiency syndrome, sepsis, and cerebrospinal fluid leak were associated with meningitis., Conclusions: The incidence of meningitis in patients who underwent EVD placement remained stable between 2002 and 2011. Further prospective studies are needed to identify approaches for preventing these infections.

Objective: To evaluate the clinical impact of Meningitis/Encephalitis FilmArray® panel for the diagnosis of cerebral nervous system infection and to compare the results (including time for diagnosis) with those obtained by conventional microbiological techniques., Methods: A prospective observational study in an Intensive Care Unit of adults from a tertiary hospital was carried out. Cerebrospinal fluid from all patients was taken by lumbar puncture and assessed by the meningitis/encephalitis FilmArray® panel ME, cytochemical study, Gram, and conventional microbiological cultures., Results: A total of 21 patients admitted with suspicion of Meningitis/Encephalitis. Median age of patients was 58.4 years (RIQ 38.1-67.3), median APACHE II 18 (RIQ 12-24). Median stay in ICU and median hospital stay was 4 (RIQ 2-6) and 17 days (RIQ 14-28), respectively. The overall mortality was 14.3%. A final clinical diagnosis of meningitis or encephalitis was established in 16 patients, obtaining the etiological diagnosis in 12 of them (75%). The most frequent etiology was Streptococcus pneumoniae (8 cases). FilmArray® allowed etiological diagnosis in 3 cases in which the culture had been negative, and the results led to changes in the empirical antimicrobial therapy in 7 of 16 cases (43.8%). FilmArray® yielded a global sensitivity and specificity of 100% and 90%, respectively. The median time to obtain results from the latter and conventional culture (including antibiogram) was 2.9 hours (RIQ 2.1-3.8) and 45.1 hours (RIQ 38.9-58.7), respectively., Conclusions: The Meningitis/Encephalitis FilmArray® panel was able to establish the etiologic diagnosis faster than conventional methods. Also, it achieved a better sensitivity and led to prompt targeted antimicrobial therapy., (©The Author 2019. Published by Sociedad Española de Quimioterapia. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)(https://creativecommons.org/licenses/by-nc/4.0/).)

Background: Predominantly antibody deficiencies (PADs) are the most common primary immunodeficiencies, characterized by hypogammaglobulinemia and inability to generate effective antibody responses., Objective: We intended to report most common monogenic PADs and to investigate how patients with PAD who were primarily diagnosed as suffering from agammaglobulinemia, hyper-IgM (HIgM) syndrome, and common variable immunodeficiency (CVID) have different clinical and immunological findings., Methods: Stepwise next-generation sequencing and Sanger sequencing were performed for confirmation of the mutations in the patients clinically diagnosed as suffering from agammaglobulinemia, HIgM syndrome, and CVID., Results: Among 550 registered patients, the predominant genetic defects associated with agammaglobulinemia (48 Bruton's tyrosine kinase [BTK] and 6 μ heavy chain deficiencies), HIgM syndrome (21 CD40 ligand and 7 activation-induced cytidine deaminase deficiencies), and CVID (17 lipopolysaccharides-responsive beige-like anchor deficiency and 12 atypical Immunodeficiency, Centromeric instability, and Facial dysmorphism syndromes) were identified. Clinical disease severity was significantly higher in patients with μ heavy chain and CD40 ligand mutations compared with patients with BTK (P = .003) and activation-induced cytidine deaminase (P = .009) mutations. Paralysis following live polio vaccination was considerably higher in patients with μ heavy chain deficiency compared with BTK deficiency (P < .001). We found a genotype-phenotype correlation among patients with BTK mutations regarding clinical manifestation of meningitis and chronic diarrhea. Surprisingly, we noticed that first presentations in most patients with Immunodeficiency, Centromeric instability, and Facial dysmorphism were respiratory complications (P = .008), whereas first presentations in patients with lipopolysaccharides-responsive beige-like anchor deficiency were nonrespiratory complications (P = .008)., Conclusions: This study highlights similarities and differences in the clinical and genetic spectrum of the most common PAD-associated gene defects. This comprehensive comparison will facilitate clinical decision making, and improve prognosis and targeted treatment., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Childhood mortality remains high in resource-limited third world countries. Most childhood deaths in hospital often occur within the first 24 h of admission. Many of these deaths are from preventable causes. This study aims to describe the patterns of mortality in children presenting to the pediatric emergency department., Methods: This was a five-year chart review of deaths in pediatric patients aged 7 days to 13 years presenting to the Tikur Anbessa Specialized Tertiary Hospital (TASTH) from January 2012 to December 2016. Data were collected using a pretested, structured checklist, and analyzed using the SPSS Version 20. Multivariate analysis by logistic regression was carried out to estimate any measures of association between variables of interest and the primary outcome of death., Results: The proportion of pediatric emergency department (PED) deaths was 4.1% (499 patients) out of 12,240 PED presentations. This translates to a mortality rate of 8.2 deaths per 1000 patients per year. The three top causes of deaths were pneumonia, congestive heart failure (CHF) and sepsis. Thirty two percent of the deaths occurred within 24 h of presentation with 6.5% of the deaths being neonates and the most common co-morbid illness was malnutrition (41.1%). Multivariate analysis revealed that shortness of breath [AOR=2.45, 95% CI (1.22-4.91)], late onset of signs and symptoms [AOR=3.22, 95% CI (1.34-7.73)], fever [AOR=3.17, 95% CI (1.28-7.86)], and diarrhea [AOR=3.36, 95% CI (1.69-6.67)] had significant association with early mortality., Conclusion: The incidence of pediatric emergency mortality was high in our study. A delay in presentation of more than 48 hours, diarrheal diseases and shortness of breath were significantly associated with early pediatric mortality. Early identification and intervention are required to reduce pediatric emergency mortality.

Background: Meningitis remains a major cause of mortality and morbidity in patients in many countries of the world including Ethiopia. Information on clinical outcomes of meningitis, susceptibility of the causative microorganism to rationalize treatment and associated risk factors is scare. The objective of this study was to assess the risk factors and clinical outcomes of meningitis among children in Felege Hiwot Referral Hospital, Bahir Dar, Northwest Ethiopia., Method: A retrospective cross sectional study was conducted in Felege Hiwot Referral Hospital from January 2016 to May 2016. Data were checked for completeness, inconsistencies and entered into SPSS for windows version 20.0. Lottery method was used to select charts. One hundred seventy-nine pediatric patient files were used in the study., Result: About 15% children with meningitis developed poor outcomes: developed complication, referred to higher facility, died and left against medical advice. In this study, season of admission [AOR= 5 (1.191, 20.991)], immunization status [AOR= 20.912 (3.325, 131.502)], clinical presentations [AOR= 8.779 (1.599, 48.192)] and corticosteroid administration [AOR= 8.215 (1.220, 55.328)] were the determinant factors for clinical outcome of meningitis., Conclusion: In this study, about 15% of children with meningitis developed poor outcomes. The determinant factors for poor outcome of meningitis were: season of admission, immunization status, clinical presentations and corticoid administration. Creating community awareness about risk factors of meningitis, early diagnosis and treatment of cases, improving vaccination coverage and use of corticosteroids are recommended to improve the clinical outcome of children affected with meningitis.

Importance: Infectious diseases are mostly preventable but still pose a public health threat in the United States, where estimates of infectious diseases mortality are not available at the county level., Objective: To estimate age-standardized mortality rates and trends by county from 1980 to 2014 from lower respiratory infections, diarrheal diseases, HIV/AIDS, meningitis, hepatitis, and tuberculosis., Design and Setting: This study used deidentified death records from the National Center for Health Statistics (NCHS) and population counts from the US Census Bureau, NCHS, and the Human Mortality Database. Validated small-area estimation models were applied to these data to estimate county-level infectious disease mortality rates., Exposures: County of residence., Main Outcomes and Measures: Age-standardized mortality rates of lower respiratory infections, diarrheal diseases, HIV/AIDS, meningitis, hepatitis, and tuberculosis by county, year, and sex., Results: Between 1980 and 2014, there were 4 081 546 deaths due to infectious diseases recorded in the United States. In 2014, a total of 113 650 (95% uncertainty interval [UI], 108 764-117 942) deaths or a rate of 34.10 (95% UI, 32.63-35.38) deaths per 100 000 persons were due to infectious diseases in the United States compared to a total of 72 220 (95% UI, 69 887-74 712) deaths or a rate of 41.95 (95% UI, 40.52-43.42) deaths per 100 000 persons in 1980, an overall decrease of 18.73% (95% UI, 14.95%-23.33%). Lower respiratory infections were the leading cause of infectious diseases mortality in 2014 accounting for 26.87 (95% UI, 25.79-28.05) deaths per 100 000 persons (78.80% of total infectious diseases deaths). There were substantial differences among counties in death rates from all infectious diseases. Lower respiratory infection had the largest absolute mortality inequality among counties (difference between the 10th and 90th percentile of the distribution, 24.5 deaths per 100 000 persons). However, HIV/AIDS had the highest relative mortality inequality between counties (10.0 as the ratio of mortality rate in the 90th and 10th percentile of the distribution). Mortality from meningitis and tuberculosis decreased over the study period in all US counties. However, diarrheal diseases were the only cause of infectious diseases mortality to increase from 2000 to 2014, reaching a rate of 2.41 (95% UI, 0.86-2.67) deaths per 100 000 persons, with many counties of high mortality extending from Missouri to the northeastern region of the United States., Conclusions and Relevance: Between 1980 and 2014, there were declines in mortality from most categories of infectious diseases, with large differences among US counties. However, over this time there was an increase in mortality for diarrheal diseases.

Background: Health care-associated meningitis and ventriculitis (HCAMV) occurs in adults with intracranial hemorrhage (ICH) and is associated with high rates of morbidity and mortality, but the prognostic impact of this infectious complication in a controlled matched study of ICH is unknown., Methods: We conducted a case-control study of adult patients with ICH and HCAMV at a large tertiary care hospital in Houston, Texas, from 2003 to 2016. Cases were defined as patients with ICH and HCAMV as documented by a positive cerebrospinal fluid culture. Controls were defined as patients with ICH without evidence of HCAMV. An adverse clinical outcome was defined as a Glasgow Outcome Scale score of ≤4., Results: This study included 120 patients with ICH; 40 patients also had HCAMV, whereas 80 patients had ICH with no evidence of HCAMV. Cases and controls were appropriately matched by age, Glasgow Coma Scale score, and Acute Physiology and Chronic Health Evaluation II score (P > 0.05). Patients with ICH and meningitis had more comorbidities, higher rates of abnormal neurologic examination, hypoglycorrhachia, and elevated cerebrospinal fluid lactate levels (P < 0.05). Adverse clinical outcomes were greater in patients with HCAMV and ICH than in patients with ICH alone (83% vs. 30%; P < 0.001). On logistic regression analysis, independent risk factors associated with an adverse outcome were HCAMV and mechanical ventilation (P < 0.05)., Conclusions: HCAMV has a significant prognostic impact in adults with ICH., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Large epidemiological studies evaluating the etiologies, management decisions, and outcomes of adults with meningitis or encephalitis in the United States (US) are lacking., Methods: Adult patients (≥18 years) with meningitis or encephalitis by International Classification of Diseases, Ninth Revision codes available in the Premier Healthcare Database during 2011-2014 were analyzed., Results: A total of 26429 patients with meningitis or encephalitis were identified. The median age was 43 years; 53% were female. The most common etiology was enterovirus (13463 [51.6%]), followed by unknown (4944 [21.4%]), bacterial meningitis (3692 [14.1%]), herpes simplex virus (2184 [8.3%]), noninfectious (921 [3.5%]), fungal (720 [2.7%]), arboviruses (291 [1.1%]), and other viruses (214 [0.8%]). Empiric antibiotics, antivirals, and antifungals were administered in 85.8%, 53.4%, and 7.8%, respectively, and varied by etiologies. Adjunctive steroids were utilized in 15.9% of all patients and in 39.3% of patients with pneumococcal meningitis, with an associated decrease in mortality (6.67% vs 12.5%, P = .0245). The median length of stay was 4 days, with the longest duration in those with fungal (13), arboviral (10), and bacterial meningitis (7). Overall inpatient mortality was 2.9% and was higher in those with bacterial (8.2%), fungal (8.2%), or arboviral (8.9%) disease. Overall readmission rate at 30 days was 3.2%; patients with arboviral (12.7%), bacterial (6.7%), and fungal (5.4%) etiologies had higher rates., Conclusions: Viruses are the most common cause of meningitis and encephalitis in the United States and are treated with antibiotic therapy in the majority of cases. Adjunctive steroid treatment is underutilized in pneumococcal meningitis, where it has shown to decrease mortality., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com)

Background: Reliable data on causes of death form the basis for building evidence on health policy, planning, monitoring, and evaluation. In Ethiopia, the majority of deaths occur at home and civil registration systems are not yet functional. The main objective of verbal autopsy (VA) is to describe the causes of death at the community or population level where civil registration and death certification systems are weak and where most people die at home without having had contact with the health system., Methods: Causes of death were classified and prepared based on the International Classification of Diseases (ICD-10). The cause of a death was ascertained based on an interview with next of kin or other caregivers using a standardized questionnaire that draws information on signs, symptoms, medical history, and circumstances preceding death. The cause of death, or the sequence of causes that led to death, is assigned based on the data collected by the questionnaire. The complete VA questionnaires were given to two blinded physicians and reviewed independently. A third physician was assigned to review the case when disagreements in diagnosis arose., Results: Communicable diseases (519 deaths [48.0%]), non-communicable diseases (377 deaths [34.8%]), and external causes (113 deaths [10.4%]) were the main causes of death between 2007 and 2013. Of communicable diseases, tuberculosis (207 deaths [19.7%]), HIV/AIDS (96 deaths [8.9%]) and meningitis (76 deaths [7.0%]) were the most common causes of death., Conclusion: Tuberculosis, HIV/AIDS, and meningitis were the most common causes of deaths among adults. Death due to non-communicable diseases showed an increasing trend. Increasing community awareness of infections and their interrelationships, tuberculosis case finding, effective local TB programs, successful treatment, and interventions for HIV are supremely important.

The two opportunistic pathogens, Streptococcus suis (S. suis) and Aerococcus. viridans (A. viridans) were isolated from the brains of piglets suffered bacterial meningitis in a farm of China. The murine model has been established to evaluate the pathogenicity and symbiotic relationship of S. suis and A. viridans simultaneously infection. Our results demonstrated the ability of new serotype S. suis to cause the classical bacterial meningitis and death were greatly enhanced during co-infection with A. viridans in mice at a proportion. We also examined the distribution and titer of bacteria coinfection in organs, the titer of S. suis appeared a significant trend for an increase in the lung meanwhile the concentration titer of A. viridans maintain a low level. This is the first reported the A. viridans and S. suis coinfection cause the bacterial meningitis outbroke in the piglets and mice. Moreover, further investigation of the pathogenesis of A. viridans and S. suis is urgently needed in swine industry., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Vitamin A deficiency (VAD) is a major public health problem in low- and middle-income countries, affecting 190 million children under five years of age and leading to many adverse health consequences, including death. Based on prior evidence and a previous version of this review, the World Health Organization has continued to recommend vitamin A supplementation for children aged 6 to 59 months. There are new data available from recently published randomised trials since the previous publication of this review in 2010, and this update incorporates this information and reviews the evidence., Objectives: To assess the effects of vitamin A supplementation (VAS) for preventing morbidity and mortality in children aged six months to five years., Search Methods: In March 2016 we searched CENTRAL, Ovid MEDLINE, Embase, six other databases, and two trials registers. We also checked reference lists and contacted relevant organisations and researchers to identify additional studies., Selection Criteria: Randomised controlled trials (RCTs) and cluster-RCTs evaluating the effect of synthetic VAS in children aged six months to five years living in the community. We excluded studies involving children in hospital and children with disease or infection. We also excluded studies evaluating the effects of food fortification, consumption of vitamin A rich foods, or beta-carotene supplementation., Data Collection and Analysis: For this update, two reviewers independently assessed studies for inclusion and abstracted data, resolving discrepancies by discussion. We performed meta-analyses for outcomes, including all-cause and cause-specific mortality, disease, vision, and side effects. We used the GRADE approach to assess the quality of the evidence., Main Results: We identified 47 studies (4 of which are new to this review), involving approximately 1,223,856 children. Studies took place in 19 countries: 30 (63%) in Asia, 16 of these in India; 8 (17%) in Africa; 7 (15%) in Latin America, and 2 (4%) in Australia. About one-third of the studies were in urban/periurban settings, and half were in rural settings; the remaining studies did not clearly report settings. Most of the studies included equal numbers of girls and boys and lasted about a year. The included studies were at variable overall risk of bias; however, evidence for the primary outcome was at low risk of bias. A meta-analysis for all-cause mortality included 19 trials (1,202,382 children). At longest follow-up, there was a 12% observed reduction in the risk of all-cause mortality for vitamin A compared with control using a fixed-effect model (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.83 to 0.93; high-quality evidence). This result was sensitive to choice of model, and a random-effects meta-analysis showed a different summary estimate (24% reduction: RR 0.76, 95% CI 0.66 to 0.88); however, the confidence intervals overlapped with that of the fixed-effect model. Nine trials reported mortality due to diarrhoea and showed a 12% overall reduction for VAS (RR 0.88, 95% CI 0.79 to 0.98; 1,098,538 participants; high-quality evidence). There was no significant effect for VAS on mortality due to measles, respiratory disease, and meningitis. VAS reduced incidence of diarrhoea (RR 0.85, 95% CI 0.82 to 0.87; 15 studies; 77,946 participants; low-quality evidence) and measles (RR 0.50, 95% CI 0.37 to 0.67; 6 studies; 19,566 participants; moderate-quality evidence). However, there was no significant effect on incidence of respiratory disease or hospitalisations due to diarrhoea or pneumonia. There was an increased risk of vomiting within the first 48 hours of VAS (RR 1.97, 95% CI 1.44 to 2.69; 4 studies; 10,541 participants; moderate-quality evidence)., Authors' Conclusions: Vitamin A supplementation is associated with a clinically meaningful reduction in morbidity and mortality in children. Therefore, we suggest maintaining the policy of universal supplementation for children under five years of age in populations at risk of VAD. Further placebo-controlled trials of VAS in children between six months and five years of age would not change the conclusions of this review, although studies that compare different doses and delivery mechanisms are needed. In populations with documented vitamin A deficiency, it would be unethical to conduct placebo-controlled trials.

Background: Deceased organ donors, where the cause of death is meningitis or encephalitis, are a potential concern because of the risks of transmission of a potentially fatal infection to recipients., Methods: Using the UK Transplant Registry, a retrospective cohort analysis of deceased organ donors in the UK was undertaken to better understand the extent to which organs from deceased donors with meningitis and/or encephalitis (M/E) (of both known and unknown cause) have been used for transplantation, and to determine the associated recipient outcomes., Results: Between 2003 and 2015, 258 deceased donors with M/E were identified and the causative agent was known in 188 (72.9%). These donors provided 899 solid organs for transplantation (455 kidneys and 444 other organs). The only recorded case of disease transmission was from a donor with encephalitis of unknown cause at time of transplantation who transmitted a fatal nematode infection to 2 kidney transplant recipients. A further 3 patients (2 liver and 1 heart recipient) died within 30 days of transplantation from a neurological cause (cerebrovascular accident) with no suggestion of disease transmission. Overall, patient and graft survival in recipients of organs from donors with M/E were similar to those for all other types of deceased organ donor., Conclusion: Donors dying with M/E represent a valuable source of organs for transplantation. The risk of disease transmission is low but, where the causative agent is unknown, caution is required., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background & Objectives: Sepsis due to multidrug-resistant Gram-negative pathogens is a challenge for clinicians and microbiologists and has led to use of parenteral colistin. There is a paucity of data regarding safety and efficacy of intravenous colistin use in neonates. The objective of this retrospective analysis was to study the efficacy and safety of intravenous colistin in the treatment of neonatal sepsis., Methods: An audit of the data from neonates, admitted to a neonatal intensive care unit of a tertiary care hospital during January 2012 to December 2012, and who received intravenous colistin was carried out., Results: Sixty two neonates received intravenous colistin (52 preterm and 10 term) for the treatment of pneumonia, bloodstream infections and meningitis. The isolated pathogens in decreasing order of frequency were Acinetobacter baumannii, Klebsiella pneumonia and Pseudomonas aeruginosa. Of the total 62 neonates, 41 (66.12%) survived and 21 (33.87%) died. Significantly higher mortality was observed in neonates with lower body weights (P < 0.05). A significant association of mortality was found in those with sepsis due to Klebsiella species. Only one of seven with this infection survived as against 15 of the 23 who grew other organisms [P = 0.03; crude odds ratio = 11.25 (1.2, 110.5)]. None of the neonates developed neurotoxicity or nephrotoxicity., Interpretation & Conclusions: This retrospective study in neonates with sepsis showed that intravenous colistin was safe and effective in the treatment of neonatal sepsis. Further, well-controlled, prospective clinical trials need to be done to corroborate these findings.

Purpose: Infant mortality in Alaska is highest among Alaska Native people from western/northern Alaska, a population with a high prevalence of a genetic variant (c.1436C>T; the arctic variant) of carnitine palmitoyltransferase 1A (CPT1A)., Methods: We performed an unmatched case-control study to determine the relationship between the arctic variant and infant mortality. The cases were 110 Alaska Native infant deaths from 2006 to 2010 and the controls were 395 Alaska Native births from the same time period. In addition to the overall analysis, we conducted two subanalyses, one limited to subjects from western/northern Alaska and one limited to infants heterozygous or homozygous for the arctic variant., Results: Among western/northern Alaska residents, 66% of cases and 61% of controls were homozygous (adjusted odds ratio (aOR): 2.5; 95% confidence interval (CI): 1.3, 5.0). Among homozygous or heterozygous infants, 58% of cases and 44% of controls were homozygous (aOR: 2.3; 95% CI: 1.3, 4.0). Deaths associated with infection were more likely to be homozygous (OR: 2.9; 95% CI: 1.0-8.0). Homozygosity was strongly associated with a premorbid history of pneumonia, sepsis, or meningitis., Conclusion: Homozygosity for the arctic variant is associated with increased risk of infant mortality, which may be mediated in part by an increase in infectious disease risk. Further studies are needed to determine whether the association we report represents a causal association between the CPT1A arctic variant and infectious disease-specific mortality.Genet Med 18 9, 933-939.

Meningitis is a leading cause of morbidity and mortality worldwide in intensive care settings. The aim of this study was to assess the frequency and outcome in children with meningitis through a retrospective chart review done in pediatric intensive care unit of a tertiary care hospital from January 2000 to December 2014. During these 14 years, 64 patients were admitted with meningitis in pediatric intensive care unit. Out of 64, 36 were diagnosed with pyogenic meningitis, 18 patients with viral meningitis, and 10 with tuberculous meningitis. Most complications were observed in the initial 48 hours. Most common presentation was altered level of consciouness in 50 (78.1%), seizure in 38 (59.4%), and shock in 23 (35.9%) patients. Ventilatory support was required in 30 (46.9%) patients and inotropic support in 26 (40.6%). During stay in pediatric intensive care unit, there was 7.8% mortality. Although meningitis was an infrequent cause of hospitalization at the study centre, but it was an important infectious cause of mortality and morbidity in pediatric age group and associated with high neurological sequelae.

Importance: Infections and necrotizing enterocolitis, major causes of mortality and morbidity in preterm infants, are reduced in infants fed their own mother's milk when compared with formula. When own mother's milk is not available, human donor milk is considered a good alternative, albeit an expensive one. However, most infants at modern neonatal intensive care units are predominantly fed with own mother's milk. The benefits of add-on donor milk over formula are not clear., Objective: To determine whether providing donor milk instead of formula as supplemental feeding whenever own mother's milk is insufficiently available during the first 10 days of life reduces the incidence of serious infection, necrotizing enterocolitis, and mortality., Design, Settings, and Participants: The Early Nutrition Study was a multicenter, double-blind randomized clinical trial in very low-birth-weight infants (birth weight <1500 g) admitted to 1 of 6 neonatal intensive care units in the Netherlands from March 30, 2012, through August 17, 2014. Intent-to-treat analysis was performed., Interventions: Infants received pasteurized donor milk or preterm formula during the first 10 days of life if own mother's milk was not (sufficiently) available., Main Outcomes and Measures: The primary end point was cumulative occurrence of serious infection (sepsis or meningitis), necrotizing enterocolitis, or mortality during the first 60 days of life., Results: A total of 930 infants were screened for inclusion; 557 were excluded, resulting in 373 infants (183 receiving donor milk and 190 receiving formula) who were evaluated by intent-to-treat analysis (median birth weight, 1066 g; mean gestational age, 28.4 weeks). Own mother's milk comprised 89.1% and 84.5% of total mean intake during the intervention period for the donor milk and formula groups, respectively. The incidence of the combined outcome was not different (85 [44.7%] [formula] vs 77 [42.1%] [donor milk]; mean difference, 2.6%; 95% CI, -12.7% to 7.4%). The adjusted hazard ratio was 0.87 (95% CI, 0.63-1.19; P = .37)., Conclusions and Relevance: In the current study, pasteurized donor milk and preterm formula as supplemental feeding during the first 10 days of life yielded similar short-term outcomes in very low-birth-weight infants regarding safety and efficacy when own mother's milk availability was insufficient. Future studies investigating longer duration of use of human donor milk on short-term and long-term outcomes are necessary., Trial Registration: trialregister.nl Identifier: NTR3225.

Introduction: Malnutrition is a backdrop on which several infections are grafted. The aim of this study is to determine the most lethal infections, the median length of stay and the median daily weight gain of malnourished children., Method: A retrospective cohort study of malnutrition in children aged 0-59 months hospitalized in the Therapeutic Nutritional Center in Bukavu from 1 January 2011 to 31 December 2013. The evaluation of the risk of deaths related to infectious complication was made measuring the relative risk. Mann-Whitney test was used for comparing the medians. Adjusted odd ratios using logistic regression and 95% confidence interval for the risk of mortality were given for each infectious cause., Results: A total of 574 children were included in the study. Five hundred twenty-one (90.8%) children were cured, 10 (1.7%) had discontinued treatment and 43 (7.5%) had died. The median length of stay was 19 (13-26) days and the median daily weight gain was 7 (3-13) g/kg/j. There was a statistically significant association between mortality and sepsis/septic shock (p = 0.0004), meningitis (p = 0.00001) and HIV infection (p = 0.02)., Conclusion: A better management of acute malnutrition in our region should be based on the establishment of specialized and well equipped units for the treatment of malnutrition associated with severe infections.

Gram-negative post-operative meningitis due to carbapenem-resistant bacteria (CR-GNPOM) is a dire complication of neurosurgical procedures. We performed a nested propensity-matched historical cohort study aimed at examining the possible benefit of intrathecal or intraventricular (IT/IV) antibiotic treatment for CR-GNPOM. We included consecutive adults with GNPOM in two centres between 2005 and 2014. Patients receiving combined systemic and IT/IV treatment were matched to patients receiving systemic treatment only. Matching was done based on the propensity of the patients to receive IT/IV treatment. We compared patient groups with 30-day mortality defined as the primary outcome. The cohort included 95 patients with GNPOM. Of them, 37 received IT/IV therapy in addition to systemic treatment (22 with colistin and 15 with amikacin), mostly as initial therapy, through indwelling cerebrospinal fluid drains. Variables associated with IT/IV therapy in the propensity score included no previous neurosurgery, time from admission to meningitis, presence of a urinary catheter and GNPOM caused by carbapenem-resistant Gram-negative bacteria. Following propensity matching, 23 patients given IT/IV therapy and 27 controls were analysed. Mortality was significantly lower with IT/IV therapy: 2/23 (8.7%) versus 9/27 (33.3%), propensity-adjusted OR 0.19, 95% CI 0.04-0.99. Death or neurological deterioration at 30 days, 14-day and in-hospital mortality were lower with IT/IV therapy (OR <0.4 for all) without statistically significant differences. Among patients discharged alive, those receiving IT/IV therapy did not experience more neurological deterioration. Serious adverse events with IT/IV therapy were not documented. Our results support the early use of IT antibiotic treatment for CR-GNPOM when a delivery method is available., (Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objective: To measure mortality and its risk factors among children discharged from a health centre in rural Gambia., Methods: We conducted a cohort study between 12 May 2008 and 11 May 2012. Children aged 2-59 months, admitted with suspected pneumonia, sepsis, or meningitis after presenting to primary and secondary care facilities, were followed for 180 days after discharge. We developed models associating post-discharge mortality with clinical syndrome on admission and clinical risk factors., Findings: One hundred and five of 3755 (2.8%) children died, 80% within 3 months of discharge. Among children aged 2-11 and 12-59 months, there were 30 and 29 deaths per 1000 children per 180 days respectively, compared to 11 and 5 respectively in the resident population. Children with suspected pneumonia unaccompanied by clinically severe malnutrition (CSM) had the lowest risk of post-discharge mortality. Mortality increased in children with suspected meningitis or septicaemia without CSM (hazard ratio [HR] 2.6 and 2.2 respectively). The risk of mortality greatly increased with CSM on admission: CSM with suspected pneumonia (HR 8.1; 95% confidence interval (CI) 4.4 to 15), suspected sepsis (HR 18.4; 95% CI 11.3 to 30), or suspected meningitis (HR 13.7; 95% CI 4.2 to 45). Independent associations with mortality were: mid-upper arm circumference (MUAC) of 11.5-13.0 cm compared to >13.0 cm (HR 7.2; 95% CI 3.0 to 17.0), MUAC 10.5-11.4 cm (HR 24; 95% CI 9.4 to 62), and MUAC <10.5 cm (HR 44; 95% CI 18 to 108), neck stiffness (HR 10.4; 95% CI 3.1 to 34.8), non-medical discharge (HR 4.7; 95% CI 2.0 to 10.9), dry season discharge (HR 2.0; 95% CI 1.2 to 3.3), while greater haemoglobin (HR 0.82; 0.73 to 0.91), axillary temperature (HR 0.71; 95% CI 0.58 to 0.87), and oxygen saturation (HR 0.96; 95% CI 0.93 to 0.99) were associated with reduced mortality., Conclusion: Gambian children experience increased mortality after discharge from primary and secondary care. Interventions should target both moderately and severely malnourished children.

The Emperor Meiji had fifteen children, including five princes and ten princesses, but ten of them died of meningitis-like disease in their infancy. Those involved in the situation were apprehensive about reporting on circumstances that might suggest that the lineage of the imperial family was in a critical condition. The author considers that this disease was caused by the facial powder containing white lead used by wet-nurses.

Purpose: The purpose of the study was to determine the proportion of pediatric deaths investigated by HM Coronial autopsy which were potentially preventable deaths due to treatable natural disease, and what implications such findings may have for health policies to reduce their occurrence., Methods: A retrospective study of 1779 autopsies of individuals between 7 days and 14 years of age requested by HM Coroner, taking place in one specialist pediatric autopsy center, was undertaken. Cases were included if they involved a definite natural disease process in which appropriate recognition and treatment was likely to have affected their outcome. Strict criteria were used and cases were excluded where the individual had any longstanding condition which might have predisposed them to, or altered the recognition of, acute illness, or its response to therapy., Results: Almost 8% (134/1779) of the study group were potentially preventable deaths as a result of natural disease, the majority occurring in children younger than 2 years of age. Most individuals reported between 1 and 7 days of symptoms before their death, and the majority had sought medical advice during this period, including from general practitioners within working hours, and hospital emergency departments. Of those who had sought medical attention, around one-third had done so more than once (28%, 15/53). Sepsis and pneumonia accounted for the majority of deaths (46 and 34% respectively), with all infections (sepsis, pneumonia and meningitis) accounting for 110/134 (82%)., Conclusion: Around 10% of pediatric deaths referred to HM Coroner are potentially preventable, being the result of treatable natural acute illnesses. In many cases medical advice had been sought during the final illness. The results highlight how a review of autopsy data can identify significant findings with the potential to reduce mortality, and the importance of centralized investigation and reporting of pediatric deaths.

Study Objective: Early diagnosis of children with meningitis or septicemia remains a significant challenge in emergency medicine. We seek to describe the frequency of repeated emergency department (ED) visits among children admitted with meningitis or septicemia in Ontario, Canada., Methods: In this retrospective cohort study, using health administrative data, we included all children aged 30 days to 5 years who were hospitalized with a final diagnosis of meningitis or septicemia in Ontario between 2005 and 2010. ED visits at any hospital in the preceding 5 days were identified as potential repeated ED visits. We used generalized estimating equations to model the association of sex, age, triage score, immunocompromised state, visit timing, type of ED, and annual patient volume on the risk of repeated ED visits., Results: Of 521 children, 114 (21.9%) had repeated ED visits before admission. Children admitted on initial visit and those with repeated visits had similar median lengths of stay (13 versus 12 days), critical care use (21.1% versus 16.7%), and mortality (mean 2.9%). One in 3 children repeating visits returned to a different hospital. Repeated visits were associated with older age, a less acute triage score, and initial visit to a community hospital without available pediatric consultation., Conclusion: In this cohort, repeated ED visits among children with meningitis or septicemia were common, yet they had health outcomes similar to those of children admitted on initial visit. One in 3 returned to a different ED, making it unlikely that EDs and clinicians can learn from these critical events without a regionalized reporting system., (Copyright © 2014 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)

Leptomeningeal dissemination of tumor cells, also referred to as neoplastic meningitis, is most frequently seen in patients with late-stage cancer and mostly associated with a poor prognosis. Basically, neoplastic meningitis may affect all patients with a malignant tumor but is most common in patients affected by lung cancer, breast carcinoma, melanoma or hematologic neoplasms such as lymphoma and leukemia. Controlled clinical trials are largely lacking which results in various non-standardized treatment regimens. The presence of solid tumor manifestations in the CNS as well as the extracranial tumor load defines the most appropriate treatment approach. Radiation therapy, systemic chemotherapy and intrathecal treatment must be considered. For each patient, the individual situation needs to be carefully evaluated to determine the potential benefit as well as putative side effects associated with any therapy. A moderate survival benefit and particularly relief from pain and neurological deficits are the main treatment goals. Here, we summarize the management of patients with neoplastic meningitis and review the available treatment options.

The objective of the present study was to elucidate the specific clinical features of otogenic intracranial complications (ICC) encountered in the current otorhinolaryngological practice. The work is based on the results of the retrospective analysis of 106 adult patients presenting with otogenic intracranial complications admitted for the treatment to multidisciplinary clinics of Sankt-Peterburg and Krasnoyarsk. Forty six (42.5%) patients presented with acute otitis media. 90% of them had suppurative destructive mastoiditis. In sixty (56.6%) patients, chronic suppurative otitis media (epitympanophonia) was associated with the extensive destructive process spreading toward dura mater of the medial and posterior cranial fossae and onto the sigmoid sinus. The prevalence of intracranial complications among the adult patients suffering from suppurative otitis media and treated in the otorhinolaryngological clinics amounted to 3.17%. The overall structure of otogenic intracranial complications was as follows: meningitis 42.5%, brain and cerebellum abscess 24.5%, suppurative meningoencephalitis 19.8%, sinus thrombosis 5.7%, epidural and subdural empyemas 4.7%, the combined suppurative brain lesions 2.8%. Systemic inflammatory response syndrome (sepsis) was diagnosed in 33 (31%) patients with otogenic ICC. The high intrahospital mortality rate among the patients with this condition (20.8%) is emphasized. The main causes of the fatal outcome in the patients with otogenic intracranial complications are supposed to be brain oedema with the concomitant development of dyslocation syndrome and sepsis.

The article considers molecular genetic characteristic of RNA of human enterovirus detected in bio-test from child with serous meningitis. The nucleotide sequence of genome DNA is analyzed. In 98% it is identical to corresponding nucleotide sequences of strains of human enterovirus A serotype 71 detected in China.

Introduction: Meningitis is one of the leading causes of death among patients living with HIV in sub-Saharan Africa. There is no widespread tracking of the incidence rates of causative agents among patients living with HIV, yet the aetiologies of meningitis are different than those of the general population., Methods: We reviewed the scientific literature published in PubMed to determine the incidence rates of meningitis among hospitalized people living with HIV in sub-Saharan Africa and report our findings from seven studies across sub-Saharan Africa., Results: We found high rates of cryptococcal meningitis (19-68%). Tuberculous meningitis was lower (1-36%), although some centres included possible cases as "other" meningitis; therefore, this may not be a true representation of the total cases. Pyogenic meningitis ranged from 6 to 30% and "other" meningitis ranged from 7 to 28% of all reported cases of meningitis. Mortality rates ranged from 25 to 68%. This review describes the most common aetiologies and provides practical diagnostic, treatment and prevention considerations as they apply to the individual living with HIV in sub-Saharan Africa., Conclusions: Diagnosis is often limited, and wider availability of accurate and low-cost laboratory diagnostics is desperately needed for prompt diagnosis and initiation of appropriate treatment. Wider acceptance and adoption of available preventative modalities can decrease the incidence of potentially fatal central nervous system infections in African patients living with HIV.

Early differential diagnosis and timely follow-up are advantageous in the management of Angiostrongylus cantonensis infection. This study aimed to characterize angiostrongyliasis in the rat brain for an 8-week period using magnetic resonance imaging (MRI) with contrast-enhanced T1-weighted images (T1WI), T2-weighted imaging (T2WI), fluid attenuation inversion recovery (FLAIR) and R2 mapping sequences. The data were analysed with Mathematica and Matlab software programs for weekly changes in each brain following the infection of 20, 50, 100 and 300 third-stage larvae (L3), respectively. The results showed that the average subarachnoid space detected by T2WI technique was peaked up to 10% increase of original size on day 35 after 100 or 300 larvae infection, while those infected with 20 or 50 larvae showed less than 4% increase during the entire course of observation. This increase was relevant to the mortality of the infected rats, because those with 100 or 300 larvae infections showed a sharp decrease in survival rate before day 40. After day 40, the average subarachnoid space was decreased, but the average ventricle size was persistently increased, with the highest increase observed in the group infected with 300 larvae on day 56. Furthermore, the R2 mapping mean and R2 mapping size were significantly different between the brains with severe infection (100 and 300 larvae groups together) and those with mild infection (20 and 50 larvae groups together) on day 49, but not on day 35. Our results showed that diagnosis for different quantity of larvae infection using MRI is possible and follow-up characterization is informative in revealing the effects of angiostrongyliasis on different brain areas. In conclusion, our results support the use of MRI as a non-invasive diagnostic technique for eosinophilic meningitis caused by A. cantonensis infection., (© 2013 Blackwell Verlag GmbH.)

Object: To date, reports on the clinical efficacy of intraventricularly and intrathecally administered antibiotics for the treatment of neurosurgical ventriculitis and meningitis in adults are limited. The authors aimed to evaluate the efficacy and safety of the intraventricular (IVT) and lumbar intrathecal (IT) administration of antibiotics in critically ill neurosurgical patients., Methods: Thirty-four postneurosurgical patients with meningitis and ventriculitis were studied. Intraventricular/lumbar intrathecal antibiotics were administered due to positive CSF cultures persisting despite the use of intravenous antibiotics. The time period until CSF sterilization, changes in clinical state, and efficacy of different routes of antibiotic administration were evaluated., Results: The mean time necessary to obtain CSF sterilization was 2.9 ± 2.7 days (range 1-12 days). The CSF cultures became negative within 24 hours after the administration of IVT/IT antibiotics in 17 patients (50%) and up to 48 hours in a further 6 patients (18%). The clinical outcome of patients assessed by the modified Rankin Scale improved in 17 patients (50%), stayed unchanged in 10 patients (29%), and was impaired in 1 patient (3%). Six patients (18%) died; however, 2 of them died due to reasons not directly related to meningitis or ventriculitis, so the overall mortality rate for meningitis and/or ventriculitis was 11.8% in this group of patients. All patients with ventriculitis (n = 4) were treated by antibiotics administered via the IVT route. The average time to CSF sterilization was 6.5 days in the patients with ventriculitis. Thirty patients had clinical signs of meningitis without ventriculitis. Despite the higher ratio of unfavorable Gram-negative meningitis in the subgroup of patients treated via lumbar drainage, the mean duration of CSF sterilization was 2.2 days compared with 2.6 days in the subgroup treated via external ventricular drainage, a difference that was not statistically significant (p = 0.3). Adverse effects of IVT/IT antibiotics appeared in 3 of 34 patients and were of low clinical significance., Conclusions: Intraventricular/lumbar intrathecal antibiotics can lead to very quick CSF sterilization in postneurosurgical patients with meningitis and ventriculitis. The relapse rate of meningitis and/or ventriculitis is also very low among patients treated by IVT/IT antibiotics. Intraventricular/lumbar intrathecal administration of antibiotics appears to be an effective and safe treatment for infections of the CNS caused by multidrug-resistant organisms. In patients with signs of ventriculitis, the authors prefer the IVT route of antibiotics. This study did not prove a lower efficacy of administration of antibiotics via lumbar drainage compared with the ventricular route in patients with meningitis.

Background: Checklists can standardize patient care, reduce errors, and improve health outcomes. For meningitis in resource-limited settings, with high patient loads and limited financial resources, central nervous system diagnostic algorithms may be useful to guide diagnosis and treatment. However, the cost effectiveness of such algorithms is unknown., Methods: We used decision analysis methodology to evaluate the costs, diagnostic yield, and cost effectiveness of diagnostic strategies for adults with suspected meningitis in resource-limited settings with moderate/high HIV prevalence. We considered 3 strategies: (1) comprehensive "shotgun" approach of utilizing all routine tests; (2) "stepwise" strategy with tests performed in a specific order with additional tuberculosis (TB) diagnostics; (3) "minimalist" strategy of sequential ordering of high-yield tests only. Each strategy resulted in 1 of 4 meningitis diagnoses: bacterial (4%), cryptococcal (59%), TB (8%), or other (aseptic) meningitis (29%). In model development, we utilized prevalence data from 2 Ugandan sites and published data on test performance. We validated the strategies with data from Malawi, South Africa, and Zimbabwe., Results: The current comprehensive testing strategy resulted in 93.3% correct meningitis diagnoses costing $32.00 per patient. A stepwise strategy had 93.8% correct diagnoses costing an average of $9.72 per patient, and a minimalist strategy had 91.1% correct diagnoses costing an average of $6.17 per patient. The incremental cost-effectiveness ratio was $133 per additional correct diagnosis for the stepwise over minimalist strategy., Conclusions: Through strategically choosing the order and type of testing coupled with disease prevalence rates, algorithms can deliver more care more efficiently. The algorithms presented herein are generalizable to East Africa and Southern Africa.

Streptococcus agalactiae (GBS) is a major cause of severe morbidity and mortality in neonates and young infants, causing sepsis, pneumonia and meningitis. The survivors from this meningitis can suffer serious long-term neurological consequences, such as, seizures, hearing loss, learning and memory impairments. Neurotrophins, such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) control the neuronal cell death during the brain development and play an important role in neuronal differentiation, survival and growth of neurons. Neonate Wistar rats, received either 10μL of sterile saline as a placebo or an equivalent volume of GBS suspension at a concentration of 1×10(6)cfu/mL. Sixty days after induction of meningitis, the animals underwent behavioral tests, after were killed and the hippocampus and cortex were retired for analyze of the BDNF and NGF levels. In the open-field demonstrated no difference in motor, exploratory activity and habituation memory between the groups. The step-down inhibitory avoidance, when we evaluated the long-term memory at 24h after training session, we found that the meningitis group had a decrease in aversive memory when compared with the long-term memory test of the sham group. BDNF levels decreased in hippocampus and cortex; however the NGF levels decreased only in hippocampus. These findings suggest that the meningitis model could be a good research tool for the study of the biological mechanisms involved in the behavioral alterations secondary to GBS meningitis., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: Accurate and timely information on the causes of child deaths is essential in guiding efforts to improve child survival, by providing data from which health profiles can be constructed and relevant health policies formulated. The purpose of this study was to identify causes of death in children younger than 5 years-old in a tertiary hospital in South Africa., Methods: Death certificates from the Pietersburg/Mankweng hospital complex, for the period of January 1, 2008 through December 31, 2010, were obtained for all patients younger than 5 years and were retrospectively reviewed. Data were collected using a data collection form designed for the study. Information abstracted included: date of death, age, sex, and cause of death., Results: A total of 1266 deaths were recorded, the sex ratio was 1.26 boys per girl. About 611 (48%) of deaths were listed as neonatal deaths (0-28 days), 387 (31%) were listed as infant deaths (29 days-11 months), and 268 (21%) as children's death (1-4 years). For neonates the leading causes of death were: prematurity/low birth weight, birth asphyxia and pneumonia. For the infant death group, the leading causes of death were pneumonia, diarrhea, and HIV/AIDS; and in the children's group, the leading causes were injuries, diarrhea and pneumonia. There was no statistical significant difference in the proportions of causes of death based on the sex of children., Conclusion: The top 10 leading causes of death in children under-5 years old treated at Pietersburg/Mankweng Hospital Complex were in descending order: prematurity/low birth weight, pneumonia, diarrheal diseases, birth asphyxia, and severe malnutrition, HIV/AIDS, hydrocephalus, unintentional injuries, meningitis and other infections. These ten conditions represent 73.9% of causes of death at this facility. A mix of multi-faceted interventions is needed to address these causes of death in children.

Introduction: The burden of Streptococcus pneumoniae infections is highest in children. Estimates in adult population are uncommon. We determined the burden of disease associated with pneumococcus in adults in Colombia in year 2008., Methodology: Using different data sources (official mortality records, medical databases, published literature and local epidemiological data) we estimated prevalence, incidence, mortality and disability due to bacterial pneumonia, bacterial meningitis and bacteremia of any cause for year 2008, and the fraction of these that can be attributed to S. pneumoniae., Results: A total of 63,463 DALYs are lost due to S. pneumoniae in Colombians age 15 or over. Most of this burden (51,848 DALYs, 81.7%) is due to pneumonia, followed by meningitis (9241 DALYs, 14.6%). The three conditions, overall, represent 2.03 DALYs per 1000 Colombians in that age range., Conclusions: Despite the lower incidence of pneumococcal disease in adults, as compared with children, its burden is still significant, comparable to that of schizophrenia or epilepsy. This study may provide a benchmark for future preventive interventions., (Copyright © 2012 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.)

Background: Information about the distribution of causes of and time trends for child mortality should be periodically updated. We report the latest estimates of causes of child mortality in 2010 with time trends since 2000., Methods: Updated total numbers of deaths in children aged 0-27 days and 1-59 months were applied to the corresponding country-specific distribution of deaths by cause. We did the following to derive the number of deaths in children aged 1-59 months: we used vital registration data for countries with an adequate vital registration system; we applied a multinomial logistic regression model to vital registration data for low-mortality countries without adequate vital registration; we used a similar multinomial logistic regression with verbal autopsy data for high-mortality countries; for India and China, we developed national models. We aggregated country results to generate regional and global estimates., Findings: Of 7·6 million deaths in children younger than 5 years in 2010, 64·0% (4·879 million) were attributable to infectious causes and 40·3% (3·072 million) occurred in neonates. Preterm birth complications (14·1%; 1·078 million, uncertainty range [UR] 0·916-1·325), intrapartum-related complications (9·4%; 0·717 million, 0·610-0·876), and sepsis or meningitis (5·2%; 0·393 million, 0·252-0·552) were the leading causes of neonatal death. In older children, pneumonia (14·1%; 1·071 million, 0·977-1·176), diarrhoea (9·9%; 0·751 million, 0·538-1·031), and malaria (7·4%; 0·564 million, 0·432-0·709) claimed the most lives. Despite tremendous efforts to identify relevant data, the causes of only 2·7% (0·205 million) of deaths in children younger than 5 years were medically certified in 2010. Between 2000 and 2010, the global burden of deaths in children younger than 5 years decreased by 2 million, of which pneumonia, measles, and diarrhoea contributed the most to the overall reduction (0·451 million [0·339-0·547], 0·363 million [0·283-0·419], and 0·359 million [0·215-0·476], respectively). However, only tetanus, measles, AIDS, and malaria (in Africa) decreased at an annual rate sufficient to attain the Millennium Development Goal 4., Interpretation: Child survival strategies should direct resources toward the leading causes of child mortality, with attention focusing on infectious and neonatal causes. More rapid decreases from 2010-15 will need accelerated reduction for the most common causes of death, notably pneumonia and preterm birth complications. Continued efforts to gather high-quality data and enhance estimation methods are essential for the improvement of future estimates., Funding: The Bill & Melinda Gates Foundation., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Objective: To describe clinical and clinicopathologic findings and outcome of horses with meningitis and meningoencephalomyelitis., Design: Retrospective case series., Animals: 28 horses., Procedures: Medical records of horses admitted to the hospital during a 25-year period were reviewed. Horses with a definitive diagnosis of meningitis or meningoencephalomyelitis were included in this study. Information extracted from the medical records included signalment, history, reason for admission, clinical signs, results of clinicopathologic testing and diagnostic procedures, treatment, outcome, and necropsy findings., Results: 22 horses had confirmed infectious disease (19 bacterial, 2 parasitic, and 1 fungal), 4 had suspected infectious disease on the basis of CSF cytologic examination findings, and 2 had noninfectious meningitis or meningoencephalomyelitis. Trauma of the head and vertebral column with disruption of the blood-brain barrier and local ascending or hematogenous spread were the most common routes of infection. Common neurologic signs included abnormal mental status, cranial nerve deficits, vestibular dysfunction, ataxia, tetraparesis, and apparent neck pain. Common hematologic abnormalities included leukocytosis, neutrophilia, lymphopenia, and hyperfibrinogenemia. Cytologic examination of CSF samples revealed moderate to marked suppurative inflammation. Mortality rate was 96.4%. Microbial culture of CSF yielded bacterial growth in 15 of 23 horses (before death [2 horses], after death [11], and both [2])., Conclusions and Clinical Relevance: Results suggested that meningitis and meningoencephalomyelitis are uncommon disorders in horses. Infectious disease was more common than noninfectious disease. Local trauma, ascending infection, or hematogenous spread of infection were the most common causes of meningitis or meningoencephalomyelitis. Neurologic deficits, neutrophilia, lymphopenia, hyperfibrinogenemia, and CSF with neutrophilic pleocytosis were common findings in affected horses.

Objective: To identify clinical characteristics predicting death among inpatients who are infected with or exposed to human immunodeficiency virus (HIV) during a period of pediatric antiretroviral therapy scale-up in sub-Saharan Africa., Study Design: Retrospective review of medical records from every child with HIV infection (n = 834) or exposure (n = 351) identified by routine inpatient testing in Kamuzu Central Hospital, Lilongwe, Malawi, September 2007 through December 2008., Results: The inpatient mortality rate was high among children with HIV infection (16.6%) and exposure (13.4%). Clinically diagnosed Pneumocystis pneumonia or very severe pneumonia independently predicted death in inpatients with HIV infection (OR 14; 95% CI 8.2 to 23) or exposure (OR 21; CI 8.4 to 50). Severe acute malnutrition independently predicted death in children who are HIV infected (OR 2.2; CI 1.7 to 3.9) or exposed (OR 5.1; CI 2.3 to 11). Other independent predictors of death were septicemia, Kaposi sarcoma, meningitis, and esophageal candidiasis for children infected with HIV, and meningitis and severe anemia for inpatients exposed to HIV., Conclusions: Severe respiratory tract infections and malnutrition are both highly prevalent and strongly associated with death among hospitalized children who are HIV infected or exposed. Novel programmatic and therapeutic strategies are urgently needed to reduce the high mortality rate among inpatients with HIV infection and HIV exposure in African pediatric hospitals., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Angiostrongylus cantonensis infection causes eosinophilic meningitis in humans. Baicalein is a flavonoid originally isolated from the roots of Scutellaria baicalensis Georgi. In this study we evaluated the efficacy of the combination of albendazole and baicalein for treating eosinophilic meningitis in BALB/c mice. Therapeutic efficacy included the survival time, body weight, neurological function, leucocyte and eosinophil counts, eotaxin concentration, matrix metalloproteinase-9 (MMP-9) activity, larval recovery and histopathological examination. The results showed that the combination of albendazole and baicalein was more effective than either drug administered singly. Combination therapy increased the survival time, decreased body weight loss, neurological dysfunction, leucocyte response, eotaxin concentration and MMP-9 activity. Our results suggest that the combination of albendazole and baicalein may exhibit synergistic beneficial effects in the treatment of eosinophilic meningitis induced by A. cantonensis.

Objective: We examined if the CNS Penetration-Effectiveness (CPE) score of antiretroviral drugs was associated with survival after a diagnosis of HIV-related encephalopathy, progressive multifocal leukoencephalopathy (PML), cerebral toxoplasmosis, or cryptococcal meningitis., Methods: Using data from the FHDH-ANRS CO4, we compared the survival of 9,932 HIV-infected patients diagnosed with a first neurologic AIDS-defining event in the pre-combination antiretroviral therapy (cART) (1992-1995), early cART (1996-1998), or late cART (1999-2004) periods. Follow-up was subdivided (CPE < 1.5 and CPE ≥ 1.5), and relative rates (RR) of death were estimated using multivariable Poisson regression models., Results: In the pre-cART and early cART periods, regimens with CPE ≥ 1.5 were associated with lower mortality after HIV-related encephalopathy (RR 0.64; 95% confidence interval [CI] 0.47-0.86 and RR 0.45; 95% CI 0.35-0.58) and after PML (RR 0.79; 95% CI 0.55-1.12 and RR 0.45; 95% CI 0.31-0.65), compared to regimens with CPE < 1.5, while in the late cART period there was no association between the CPE score and the mortality. A higher CPE score was also associated with a lower mortality in all periods after cerebral toxoplasmosis (RR 0.68, 95% CI 0.56-0.84) or cryptococcal meningitis (RR 0.50, 95% CI 0.34-0.74). Whatever the neurologic event, these associations were not maintained after adjustment on updated plasma HIV-RNA (missing, <500, ≥500 copies/mL) with RR ranging from 0.82 (95% CI 0.36-1.91) to 1.02 (0.69-1.52)., Conclusion: At the beginning of the cART era, the CPE score was of importance for survival after severe neurologic event, while in the late cART period, the additional effect of CPE score vanished with more powerful antiretroviral regimens associated with plasma viral load control.

Neoplastic meningitis from breast cancer has a dismal prognosis and short survival. Treatment is based on the intrathecal administration of chemotherapeutic agents, cranial or craniospinal radiotherapy, and systemic chemotherapy. In this report we describe the case of a woman with neoplastic meningitis from breast carcinoma who developed an excellent response to letrozole combined with intrathecal methotrexate, resulting in long-term survival of more than 36 months. Based on the findings of this case report, we suggest that addition of letrozole to the standard therapeutic approach may be beneficial for some patients.

Background: Endonasal endoscopic skull base surgery (ESBS) is perceived as having a high risk of infection because it is performed through the sinuses, which are not sterile., Objective: To identify the bacteriological characteristics, incidence, mortality, and risk factors for intracranial infection after ESBS., Methods: A retrospective analysis of the first 1,000 ESBS procedures performed at the University of Pittsburgh Medical Center from 1998 to 2008., Results: In 18 cases (1.8%), the patient developed meningitis. In 2 cases, the patient died within 2 months after surgery, of noninfectious causes. In 11 cases, cerebrospinal fluid (CSF) cultures had positive results. There were no predominant pathogens. Male sex (odds ratio [OR], 3.97 [95% confidence interval {CI}, 1.21-13.03]; P = .02), history of a craniotomy or endonasal surgery (OR, 4.77 [95% CI, 1.68-13.56]; P = .02), surgery with higher levels of complexity (OR, 6.60 [95% CI, 1.77-24.70]; P = .003), the presence of an external ventricular drain or ventriculoperitoneal shunt at the time of surgery (OR, 6.38 [95% CI, 1.07-38.09]; P = .005), and postoperative CSF leak (OR, 12.99 [95% CI, 4.24-39.82]; P < .001) were risk factors for infection., Conclusion: The incidence of infection of 1.8% in ESBS is comparable to that in open craniotomy. The most important risk factor was a postoperative CSF leak. All patients recovered from their infection.

Background: Vitamin A deficiency (VAD) is a major public health problem in low and middle income countries affecting 190 million children under 5. VAD can lead to many adverse health consequences, including death., Objectives: To evaluate the effect of vitamin A supplementation (VAS) for preventing morbidity and mortality in children aged 6 months to 5 years., Search Strategy: We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2010 Issue 2),  MEDLINE (1950 to April Week 2 2010), EMBASE (1980 to 2010 Week 16), Global Health (1973 to March 2010), Latin American and Caribbean Health Sciences (LILACS), metaRegister of Controlled Trials and African Index Medicus (27 April 2010)., Selection Criteria: Randomised controlled trials (RCTs) and cluster RCTs evaluating the effect of synthetic VAS in children aged 6 months to 5 years living in the community. We excluded studies concerned with children in hospital and children with disease or infection. We excluded studies evaluating the effects of food fortification, consumption of vitamin A rich foods or beta-carotene supplementation., Data Collection and Analysis: Two review authors independently assessed studies for inclusion. Data were double abstracted and discrepancies were resolved by discussion. Meta-analyses were performed for outcomes including all-cause and cause-specific mortality, disease, vision, and side-effects., Main Results: 43 trials involving 215,633 children were included. A meta-analysis for all-cause mortality included 17 trials comprising 194,795 children with 3536 deaths in both groups. At follow-up, there was a 24% observed reduction in the risk of all-cause mortality for Vitamin A compared with Control (Relative risk (RR) = 0.76 [95% confidence interval (CI) 0.69, 0.83]). Seven trials reported diarrhoea mortality and a 28% overall reduction for VAS (RR = 0.72 [0.57, 0.91]). There was no significant effect of VAS on cause specific mortality of measles, respiratory disease and meningitis. VAS reduced incidence of diarrhoea (RR = 0.85 [0.82, 0.87]) and measles morbidity (RR = 0.50 [0.37, 0.67]); however, there was no significant effect on incidence of respiratory disease or hospitalisations due to diarrhoea or pneumonia. There was an increased risk of vomiting within the first 48 hours of VAS (RR = 2.75 [1.81, 4.19])., Authors' Conclusions: VAS is effective in reducing all-cause mortality by about 24% compared to no treatment. In our opinion, given the evidence that VAS causes considerable reduction in child mortality, further placebo-controlled trials of VAS in children between 6 months and 5 years of age are not required. There is a need for further studies comparing different doses and delivery mechanisms (for example, fortification).