Mortality Of Pneumococcal Meningitis Research Articles

A 30-year perspective of low-dose dexamethasone, a single dose of mannitol and antiseizures prophylaxis on the prognosis of pneumococcal meningitis

Objectives This 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. Methods 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. Results 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). Conclusions 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.

1722. Impact of Universal Conjugate Pneumococcal Vaccination in Infants on the Incidence and Mortality of Pneumococcal Meningitis in the General Population in Uruguay, South America (2005 – 2022).

Abstract Background Universal vaccination of children with conjugate vaccines was introduced using the 7 – valent pneumococcal conjugate vaccine (PCV7), which was changed to PCV13 (2 + 1 schedule, years 2008 to 2010), with nationwide coverage of 95 %. The objective of this study is to analyze the impact of universal children vaccination with PCV7 and PCV13 on the incidence and mortality of pneumococcal meningitis (PM) in the general population in Uruguay. Methods This is a descriptive, retrospective study that includes all cases (children and adults) reported to the Department of Health Surveillance of the Ministry of Public Health with a diagnosis of PM between January 1, 2005, and December 31, 2022. Variables: cases per year, sex, age (≤ 15 years and > 15 years), identified serotype, and deaths by year. The average rates of cases per 100,000 inhabitants are described in two periods: Period 1 or pre – universal vaccination (P1) from 2005 to 2007 and Period 2 or post – universal vaccination (P2) from 2011 to 2022, with their respective confidence intervals. Statistical analysis were established based on frequency distribution and statistical significance tests as appropriate, considering a value of p equal to or less than 0.05 as statistically significant. The research was approved by the institutional Ethics Committee. Results The total number of cases (N) is 555, 56.5% are men. 102 cases from the vaccine introduction period (2008 to 2010) were excluded. The N for P1 is 149 (3 years), while for P2 it is 304 (12 years). The main results of incidence and mortality are shown in Table 1 and in the attached graphs. Lethality remains high (26.5% average for the total period). The vaccine serotypes (VS) decrease from 28.2% (95% CI: 20 to 35) in P1 to 12.2% (95% CI: 8.4 to 15) in P2, p: 0.00006. The non – VS increase from 18.1% (95% CI: 11 to 24) in P1 to 44.7% (95% CI: 39.1 to 50.3) in P2, p: 0.00000001. The predominant VS in P1 is 14 (26.2%, 95% CI: 13-39); in P2 there are 8.1%, 95% CI: 0.7-16.9), p: 0.071. The predominant VS in P2 is 3 (46%, 95% CI: 30-62); in P1 9.5% (95% CI: 0.6-18), p: 0.0003. The non – VS predominant in both periods is 12F. Evolution of incidence rates of PM in the general population and in people under and over 15 years of age as a function of time (in years). Mortality rates Conclusion The incidence and mortality of PM statistically decreased in children under 15 years old and in the general population, which can be attributed to herd immunity. Disclosures Marcos Delfino, Pediatrician, Pediatric Infectious Diseases, Pfizer: Finna María Catalina Pírez, Pediatrician, Pediatric infectologist, microbiologist Professor of pediatric, Degree V, Merck, Pfizer: Expert Testimony|Merck, Pfizer: Honoraria

Impact of 10-valent pneumococcal conjugate (PCV 10) vaccination on incidence and mortality rates of pneumococcal meningitis in children under 5 in Brazil

The objective of this study was to assess the impact of 10-valent pneumococcal conjugate (PCV10) vaccination on the incidence and mortality of pneumococcal meningitis in children under 5 in Brazil. A descriptive ecological, population-based quantitative study of secondary data from SINAN records for 2003-2009 and 2011-2017 and on vaccine coverage for 2011-2017 was conducted. The study was approved under permit CAAE 23629719.6.0000.5181. After PCV10 vaccine introduction, a substantial consistent reduction in incidence of and mortality rates of pneumococcal meningitis (70.33% Northeast, 69.49% Southeast) was observed across all regions of Brazil. Although the Human Development Index (HDI) improved during the study period, lethality rates remained high (North = 34.45% pre versus 40.08% post-vaccination), with no clear pattern of reduction associated with improved HDI in Brazil. In the final years of the study, a concerning decline in vaccination coverage rates was evident. Only the South (96.52%) and Mid-West (96.17%) regions attained the ≥ 95% vaccine coverage recommended by the Ministry of Health. This situation highlights the need for urgent measures to restore coverage rates and prevent recrudescence in cases and deaths associated with potentially preventable diseases.

Complement factor H contributes to mortality in humans and mice with bacterial meningitis

BackgroundThe complement system is a vital component of the inflammatory response occurring during bacterial meningitis. Blocking the complement system was shown to improve the outcome of experimental pneumococcal meningitis. Complement factor H (FH) is a complement regulatory protein inhibiting alternative pathway activation but is also exploited by the pneumococcus to prevent complement activation on its surface conferring serum resistance.MethodsIn a nationwide prospective cohort study of 1009 episodes with community-acquired bacterial meningitis, we analyzed whether genetic variations in CFH influenced FH cerebrospinal fluid levels and/or disease severity. Subsequently, we analyzed the role of FH in our pneumococcal meningitis mouse model using FH knock-out (Cfh−/−) mice and wild-type (wt) mice. Finally, we tested whether adjuvant treatment with human FH (hFH) improved outcome in a randomized investigator blinded trial in a pneumococcal meningitis mouse model.ResultsWe found the major allele (G) of single nucleotide polymorphism in CFH (rs6677604) to be associated with low FH cerebrospinal fluid concentration and increased mortality. In patients and mice with bacterial meningitis, FH concentrations were elevated during disease and Cfh−/− mice with pneumococcal meningitis had increased mortality compared to wild-type mice due to C3 depletion. Adjuvant treatment of wild-type mice with purified human FH led to complement inhibition but also increased bacterial outgrowth which resulted in similar disease outcomes.ConclusionLow FH levels contribute to mortality in pneumococcal meningitis but adjuvant treatment with FH at a clinically relevant time point is not beneficial.

Epidemiological Aspects of Pneumococcal Meningitis in the Russian Federation

Introduction. Pneumococcal meningitis (PM) refers to severe manifestations of pneumococcal disease with high mortality and frequent post-infectious complications. In the context of the introduction of vaccination against pneumococcal infections in the Russian Federation healthcare practice increases the importance of close monitoring of the spread of the PM in the country, identifying areas of concern, the definition of risk and serotype structure of pneumococcus, which is an essential component of the assessment of the effectiveness of vaccination. Materials and methods. We collected 1380 cases identified by the PM on the territory of the Russian Federation in 2010 - 2014. We analyzed the incidence, mortality, mortality, age distribution, social belonging PM patients in the whole country, and in the federal districts. Determined serotype affiliation 35 pneumococcal strains isolated from patients with PM in Russia in 2015. Results. The proportion of pneumococci in the etiological structure of bacterial meningitis during the 2010 - 2014 fluctuated in the range of 18.4 - 24.8% and averaged 22.1%. The incidence of the PM in the Russian Federation in 2010 - 2014 determined at the level of 0.19, the death rate - 0.03. The level of mortality in pneumococcal meningitis in the Russian Federation in 2010 - 2014 increased from 13 (2010) to 21.1% (2014), the average was 17.1%. The most vulnerable age groups were adults over 25 years old and children up to 6 years. Among children under the age of 6 years mortality was 10.7%. The study of serotypes of 35 pneumococcal strains showed that in 2015 serotype structure of invasive pneumococcal vaccine serotypes maintained dominance, the proportion reached 75% for PCV13 and 54% for PCV10. Conclusion. The problem of pneumococcal meningitis remains valid in the Russian Federation. Active use of vaccines, especially in children, will reduce the incidence of this infection and the severity of its consequences.

Dramatic reduction of mortality in pneumococcal meningitis.

BackgroundAcute bacterial meningitis is still a life threatening disease.MethodsWe performed a retrospective observational study on the clinical characteristics of consecutively admitted patients with acute pneumococcal meningitis in a single tertiary care center in central Europe (from 2003 until 2015). Data were compared with a previously published historical group of 87 patients treated for pneumococcal meningitis at the same hospital (from 1984 until 2002).ResultsFifty-five consecutive patients with microbiologically proven pneumococcal meningitis were included. Most striking, mortality was down to 5.5 %, which was significantly lower than in the historical group where 24.1 % of the patients did not survive. Intracranial complications during the course of the disease were common and affected half of the patients. Unlike in the historic group, most of the intracranial complications (except ischemic stroke) were no longer associated with a low Glasgow Outcome Score at discharge.ConclusionThe drastic reduction of mortality proves there have been important advances in the treatment of pneumococcal meningitis. Nevertheless, the fact that only 44.2 % of survivors had a full recovery indicates that the search for new adjunctive treatment options must be ongoing.

Functional polymorphisms of macrophage migration inhibitory factor as predictors of morbidity and mortality of pneumococcal meningitis

Pneumococcal meningitis is the most frequent and critical type of bacterial meningitis. Because cytokines play an important role in the pathogenesis of bacterial meningitis, we examined whether functional polymorphisms of the proinflammatory cytokine macrophage migration inhibitory factor (MIF) were associated with morbidity and mortality of pneumococcal meningitis. Two functional MIF promoter polymorphisms, a microsatellite (-794 CATT5-8; rs5844572) and a single-nucleotide polymorphism (-173 G/C; rs755622) were genotyped in a prospective, nationwide cohort of 405 patients with pneumococcal meningitis and in 329 controls matched for age, gender, and ethnicity. Carriages of the CATT7 and -173 C high-expression MIF alleles were associated with unfavorable outcome (P= 0.005 and 0.003) and death (P= 0.03 and 0.01). In a multivariate logistic regression model, shock [odds ratio (OR) 26.0, P= 0.02] and carriage of the CATT7 allele (OR 5.12,P= 0.04) were the main predictors of mortality. MIF levels in the cerebrospinal fluid were associated with systemic complications and death (P= 0.0002). Streptococcus pneumoniae strongly up-regulated MIF production in whole blood and transcription activity of high-expression MIF promoter Luciferase reporter constructs in THP-1 monocytes. Consistent with these findings, treatment with anti-MIF immunoglogulin G (IgG) antibodies reduced bacterial loads and improved survival in a mouse model of pneumococcal pneumonia and sepsis. The present study provides strong evidence that carriage of high-expression MIF alleles is a genetic marker of morbidity and mortality of pneumococcal meningitis and also suggests a potential role for MIF as a target of immune-modulating adjunctive therapy.

Incidence, Seasonality, Age Distribution, and Mortality of Pneumococcal Meningitis in Burkina Faso and Togo

Streptococcus pneumoniae causes a substantial proportion of meningitis cases in the African meningitis belt; however, few reports exist to quantify its burden and characteristics. We conducted population-based and sentinel hospital surveillance of acute bacterial meningitis among persons of all ages in Burkina Faso and Togo in 2002-2006. S. pneumoniae and other organisms were identified by culture, polymerase chain reaction, or detection of antigen in cerebrospinal fluid (CSF). Information was collected on 2843 patients with suspected acute bacterial meningitis. CSF specimens were collected from 2689 (95%) of the patients; of these 2689, 463 (17%) had S. pneumoniae identified, 234 (9%) had Haemophilus influenzae type b identified, and 400 (15%) had Neisseria meningitidis identified. Of the 463 cases of S. pneumoniae meningitis, 99 (21%) were aged <1 year, 71 (15%) were aged 1-4 years, 95 (21%) were aged 5-14 years, and 189 (41%) were aged >or=15 years (age was unknown for 9 [2%]). In Burkina Faso, the annual incidence rate of pneumococcal meningitis was 14 cases per 100,000 persons, with annual incidence rates of 77, 33, 10, and 11 cases per 100,000 persons aged <1 year, <5 years, 5-14 years, and >or=15 years, respectively. The case-fatality ratio for S. pneumoniae meningitis was 47% (range for age groups, 44%-52%), and 53% of deaths occurred among those aged >5 years. S. pneumoniae meningitis had an epidemic pattern similar to that of N. meningitidis meningitis. Of 48 isolates tested for serotype, 18 were from children aged <5 years; of these 18, 3 isolates (17%) each were serotypes 1, 2, and 5, and 5 isolates (28%) were serotype 6A. The 7-, 10-, and 13-valent pneumococcal conjugate vaccines would cover 6%, 39%, and 67% of serotypes identified among children aged <5 years, respectively. Of the 30 serotypes identified for patients aged >or=5 years, 18 (60%) were serotype 1, whereas no other serotype constituted >10%. The 7-, 10-, and 13-valent vaccines would cover 7%, 70%, and 77% of serotypes. Epidemic pneumococcal meningitis in the African meningitis belt countries of Burkina Faso and Togo is common, affects all age groups, and is highly lethal. On the basis of a modest number of isolates from a limited area that includes only meningitis cases, 7-valent pneumococcal conjugate vaccine might have only a limited and short-term role. By contrast, the proposed 10- and 13-valent vaccines would cover most of the identified serotypes. To better inform vaccine policy, continued and expanded surveillance is essential to document serotypes associated with pneumonia, changes in serotype distribution across time, and the impact of vaccine after vaccine introduction.

Morbidity and mortality of pneumococcal meningitis and serotypes of causative strains prior to introduction of the 7-valent conjugant pneumococcal vaccine in England

To assess the incidence of pneumococcal meningitis, associated deaths and serotypes of causative pneumococci in England prior to the inclusion of the 7-valent conjugated pneumococcal vaccine in the routine childhood immunisation programme in 2006. Cases were identified using hospital episode statistics (HES) and voluntary reports or submission of isolates to the Health Protection Agency. Mortality data and population estimates were from the Office for National Statistics. Based on HES, the annual incidence of pneumococcal meningitis was about 1 case per 100,000 population between 1998 and 2005 (an average of approximately 480 cases per year) with case fatality rates increasing from 5% in <15 year olds to 30% in >64 year olds. Enhanced surveillance comprising a combination of voluntary reporting of cases and referral of isolates gave case ascertainment rates of 50-70% compared to those derived from HES, and similar case fatality rates. The age distribution of pneumococcal meningitis was similar with both datasets, infection being reported mostly commonly in children aged less than 5 years, with the highest incidence in children aged 2-11 months. Based on the serotype distribution of isolates obtained in 2005, the serotype coverage afforded by the 7-valent conjugate vaccine is 72% for patients aged less than 2 years. These data provide baseline information on the incidence of pneumococcal meningitis and associated mortality, together with the serotypes of infecting strains of pneumococci, which will be critical for evaluation of the public health impact of the 7-valent conjugated pneumococcal vaccine in England.

Aquaporin-4 Gene Disruption in Mice Reduces Brain Swelling and Mortality in Pneumococcal Meningitis

The astroglial water channel aquaporin-4 (AQP4) facilitates water movement into and out of brain parenchyma. To investigate the role of AQP4 in meningitis-induced brain edema, Streptococcus pneumoniae was injected into cerebrospinal fluid (CSF) in wild type and AQP4 null mice. AQP4-deficient mice had remarkably lower intracranial pressure (9 +/- 1 versus 25 +/- 5 cm H2O) and brain water accumulation (2 +/- 1 versus 9 +/- 1 microl) at 30 h, and improved survival (80 versus 0% survival) at 60 h, through comparable CSF bacterial and white cell counts. Meningitis produced marked astrocyte foot process swelling in wild type but not AQP4 null mice, and slowed diffusion of an inert macromolecule in brain extracellular space. AQP4 protein was strongly up-regulated in meningitis, resulting in a approximately 5-fold higher water permeability (P(f)) across the blood-brain barrier compared with non-infected wild type mice. Mathematical modeling using measured P(f) and CSF dynamics accurately simulated the elevated lower intracranial pressure and brain water produced by meningitis and predicted a beneficial effect of prevention of AQP4 upregulation. Our findings provide a novel molecular mechanism for the pathogenesis of brain edema in acute bacterial meningitis, and suggest that inhibition of AQP4 function or up-regulation may dramatically improve clinical outcome.