Efficacy assessment of a novel endolysin PlyAZ3aT for the treatment of ceftriaxone-resistant pneumococcal meningitis in an infant rat model.

BACKGROUND: Treatment failure in pneumococcal meningitis due to antibiotic resistance is an increasing clinical challenge and alternatives to antibiotics warrant investigation. Phage-derived endolysins efficiently kill gram-positive bacteria including multi-drug resistant strains, making them attractive therapeutic candidates. The current study assessed the therapeutic potential of the novel endolysin PlyAZ3aT in an infant rat model of ceftriaxone-resistant pneumococcal meningitis. METHODS: Efficacy of PlyAZ3aT was assessed in a randomized, blinded and controlled experimental study in infant Wistar rats. Meningitis was induced by intracisternal infection with 5 x 107 CFU/ml of a ceftriaxone-resistant clinical strain of S. pneumoniae, serotype 19A. Seventeen hours post infection (hpi), animals were randomized into 3 treatment groups and received either (i) placebo (phosphate buffered saline [PBS], n = 8), (ii) 50 mg/kg vancomycin (n = 10) or (iii) 400 mg/kg PlyAZ3aT (n = 8) via intraperitoneal injection. Treatments were repeated after 12 h. Survival at 42 hpi was the primary outcome; bacterial loads in cerebrospinal fluid (CSF) and blood were secondary outcomes. Additionally, pharmacokinetics of PlyAZ3aT in serum and CSF was assessed. RESULTS: PlyAZ3aT did not improve survival compared to PBS, while survival for vancomycin treated animals was 70% which is a significant improvement when compared to PBS or PlyAZ3aT (p<0.05 each). PlyAZ3aT was not able to control the infection, reflected by the inability to reduce bacterial loads in the CSF, whereas Vancomycin sterilized the CSF and within 25 h. Pharmacokinetic studies indicated that PlyAZ3aT did not cross the blood brain barrier (BBB). In support, PlyAZ3aT showed a peak concentration of 785 µg/ml in serum 2 h after intraperitoneal injection but could not be detected in CSF. CONCLUSION: In experimental pneumococcal meningitis, PlyAZ3aT failed to cure the infection due to an inability to reach the CSF. Optimization of the galenic formulation e.g. using liposomes might enable crossing of the BBB and improve treatment efficacy.

Estimating the economic burden of pneumococcal meningitis and pneumonia in northern Ghana in the African meningitis belt post-PCV13 introduction.

BACKGROUND: Ghana introduced 13-valent pneumococcal conjugate vaccine (PCV13) into the routine infant immunization program in 2012, using a three-dose primary series without a booster. Despite ≥ 88% reported three-dose vaccination coverage since 2013, PCV13-type pneumococcal meningitis outbreaks have occurred. We estimated the ongoing economic burden of PCV13-type pneumococcal meningitis and pneumonia in northern Ghana, an area within the African meningitis belt with seasonal increases of pneumococcal meningitis post-PCV13 introduction, to inform PCV13 vaccination policy. METHODS: We performed a cross-sectional survey among patients with pneumonia or meningitis at three hospitals in northern Ghana to determine patient-level costs (direct medical and nonmedical, indirect patient and caregiver costs) incurred in household, outpatient, and inpatient settings. Pneumonia burden was estimated using 2017-2018 administrative records. Pneumococcal meningitis burden was estimated using 2017-2018 case-based surveillance data. Economic burden was reported in 2019 U.S. dollars ($) from the societal perspective. RESULTS: For an area with a total population of 5,068,521, our model estimated 6,441 PCV13-type pneumonia cases and 286 PCV13-type meningitis cases occurred in a typical year post-PCV13. In the base case scenario, the total economic burden was $5,230,035 per year ($777 per case). By age group, cost per PCV13-type pneumonia case was $423 (<5 years), $911 (5-14 years), and $784 (≥15 years); cost per PCV13-type meningitis case was $2,128 (<5 years), $3,247 (5-14 years), and $2,883 (≥15 years). Most (78.0-93.4%) of the total societal cost was due to indirect costs related to deaths from PCV13-type diseases. CONCLUSIONS: The estimated economic burden of PCV13-type disease in northern Ghana remains substantial, especially in older children and adults who were expected to have benefited from indirect effects from infant immunization. Additional interventions such as changes in the infant immunization schedule, reactive vaccination, or catch-up PCV13 vaccination may be needed to control remaining vaccine-type disease.

Análise epidemiológica da meningite bacteriana no Estado do Amapá nos anos de 2013 a 2018 / Epidemiological analysis of bacterial meningitis in the State of Amapáin the years 2013 to 2018

A meningite é uma doença infectocontagiosa caracterizada pelo processo inflamatório das meninges aracnoide e pia-máter e do líquido cefalorraquidiano. Seus principais agentes etiológicos bacterianos são Neisseria meningitidis, Streptococcus pneumoniae e Haemophilus influenzae. O presente trabalho teve como objetivo realizar uma análise epidemiológica da meningite bacteriana no Estado do Amapá, nos anos de 2013 a 2018. Trata-se de um estudo documental descritivo, de caráter transversal, com dados obtidos através do Sistema de Informações de Agravos de Notificação (SINAN). Os resultados demostram que ocorreram, no período estudado, 26 casos de meningite bacteriana. Os agentes Streptococcus pneumoniae e Neisseria meningitidis foram responsáveis por 38% e 35% das ocorrências, respectivamente, enquanto 27% dos casos foram classificados somente como meningite bacteriana. A capital do estado, Macapá, foi responsável pelo maior número de casos confirmados (81%) e, quanto à sazonalidade, o mês de julho apresentou maior ocorrência (23%). Do total de casos avaliados 54% ocorreram em pessoas do sexo masculino, e 46% em pessoas do sexo feminino, e a principal faixa etária acometida foi de crianças menores de um ano (38%). Quanto à evolução da doença, 65% das pessoas receberam alta, enquanto 27% foram à óbito por meningite. Conclui-se que apesar de a maior parte dos casos evoluírem para alta, a porcentagem de pacientes que foram à óbito por meningite ressalta a necessidade de ações em saúde voltadas tanto para a faixa etária mais acometida quanto para as demais, em função da rápida evolução que a doença apresenta.(AU)

Meningitis is an infectious disease characterized by the inflammatory process of the arachnoid and pia mater meninges.and cerebrospinal fluid. Its main bacterial etiologic agents are Neisseria meningitidis, Streptococcuspneumoniae and Haemophilus influenzae. This study aimed to carry out an epidemiological analysisof bacterial meningitis in the State of Amapá, from 2013 to 2018. This is a descriptive documentary study,transversal, with data obtained through the Notifiable Diseases Information System (SINAN). YouResults show that, during the study period, there were 26 cases of bacterial meningitis. Streptococcus agentspneumoniae and Neisseria meningitidis were responsible for 38% and 35% of the occurrences, respectively, while27% of the cases were classified as bacterial meningitis only. The state capital, Macapá, was responsibleby the highest number of confirmed cases (81%) and, regarding seasonality, the month of July had the highest occurrence(23%). Of the total number of cases evaluated, 54% occurred in males, and 46% in females,and the main age group affected was children under one year old (38%). As for the evolution of the disease, 65% ofpeople were discharged, while 27% died of meningitis. It is concluded that although most casesprogress to discharge, the percentage of patients who died from meningitis highlights the need for actions inhealth care aimed at both the most affected age group and the others, due to the rapid evolution that thedisease presents.(AU)

Hospital cost of invasive pneumococcal disease in children aged under 15 years old in Tunisia.

BACKGROUND: Pneumococcal infections are an important cause of morbidity and mortality in the world and in Tunisia. Data on the economic burden of these infections are needed to inform decision-making to include pneumococcal vaccinations in routine childhood immunization. AIMS: This study aimed to estimate the medical cost of hospitalizations due to invasive pneumococcal disease (pneumonia and meningitis) among children aged under 15 years old in Tunisia. METHODS: A prospective multicentre study was conducted in 15 paediatric departments, across different socio-economic areas of Tunisia, from June 2014 to May 2015. All children aged under 15 years old who were hospitalized for pneumococcal pneumonia or confirmed bacterial meningitis were enrolled. A case report form was completed for every eligible case. Activity Based Costing method was used to estimate the hospital cost. Data entry and statistical analysis were conducted using SPSS, version 20.0. RESULTS: During the study period, 727 children were hospitalized for pneumococcal pneumonia and 60 children were hospitalized for bacterial meningitis, among them 21(35%) had confirmed pneumococcal meningitis. The median hospital cost for pneumococcal pneumonia was 353.910 Tunisian Dinars (TND) and TND 1680.632 for pneumococcal meningitis. Using overall data extrapolation, it was estimated that nearly 1091 hospitalizations for pneumococcal pneumonia and 69 hospitalizations for pneumococcal meningitis occurred each year in Tunisian children aged under 15 years of age, incurring total costs of TND 502 079.408. CONCLUSION: The economic burden of pneumococcal infections seems to be substantial in Tunisia. The estimated costs does not reflect the real costs of this infection. Cost-effectiveness studies would be helpful to inform policy-makers to take appropriate decisions.

How cost effective is switching universal vaccination from PCV10 to PCV13? A case study from a developing country.

BACKGROUND: Children immunization with pneumococcal conjugate vaccine (PCV) had profound public health effects across the globe. Colombian adopted PCV10 universal vaccination, but PCV incremental impact need to be revalued. The objective of this analysis was to estimate the cost-effectiveness of switch to PCV13 versus continue PCV10 in Colombian children. METHODS: A complete economic analysis was carried-out assessing potential epidemiological and economic impact of switching from PCV10 to PCV13. Epidemiological information on PCV10 impact was obtained from lab-based epidemiological surveillance on pneumococcal isolates at the Colombian National Institute of Health. Economic inputs were extracted from the literature. Incremental PCV13 effectiveness was based in additional serotypes included. Comparisons among alternatives were evaluated with the Incremental Cost-Effectiveness Ratio (ICER) at a willingness to pay of one GDP per capita (USD$ 6631) per Year of Live Saved (YLS). All costs were reported in 2014USD. Deterministic and probabilistic sensitivity analyses were performed, and 95% confidence interval reported. RESULTS: After four years using PCV10 for universal vaccination on children the Colombian health surveillance system showed a relative increment on non PCV10 isolates. To change from PCV10 to PCV13 would avoid 587 (CI95% -49-1008) ambulatory Rx community-acquired pneumoniae (CAP), 1622 (CI95% 591-2343) Inpatient RxCAP, 10 (CI 95% 6-11) pneumococcal meningitis, and 79 (CI95% 76-98) deaths. ICER per YLS was USD$ 2319 (CI95% Dominated - USD$ 4225) for Keep-PCV10 and USD$ 1771 (CI95% USD$ 1285-9884) for Switch-to PCV13. In spite of its cost-effectiveness Keep-PCV10 is an extended dominated alternative and Switch-to PCV13 would be preferred. Results are robust to parameters changes in the sensitivity analyses. CONCLUSION: A national immunization strategy based in Switch-to PCV13 was found to be good value for money and prevent additional burden of pneumococcal disease saving additional treatment costs, when compared with to Keep-PCV10 in Colombia, however additional criteria to decision making must be taken into account.

Economic burden of pneumococcal infections in children under 5 years of age.

The present study aimed to determine the cost of childhood pneumococcal infections under 5 years of age and to provide further data for future health economy studies. Electronic medical records of children diagnosed with meningitis caused by S. pneumoniae and all-cause pneumonia, and acute otitis media (AOM) between January 2013-April 2014 were retrospectively evaluated. Direct costs for the treatments of hospitalized patients (pneumonia and pneumococcal meningitis) including costs of healthcare services consisted of costs of hospital bed, examination, laboratory analyses, scanning methods, consultation, vascular access procedures, and infusion and intravenous treatments. Direct costs for patients (AOM) treated in outpatient setting included constant price paid for the examination and cost of prescribed antibiotics. Indirect costs included cost of work loss of parents and their transportation expenses. Data of 130 children with pneumococcal meningitis (n = 10), pneumonia (n = 53), and AOM (n = 67) were analyzed. The total median cost was €4,060.38 (direct cost: €3,346.38 and indirect cost: €829.18) for meningitis, €835.91 (direct cost: €480.66 and indirect cost: €330.09) for pneumonia, and €117.32 (direct cost: €17.59 and indirect cost: €99.73) for AOM. The medication cost (p = 0.047), indirect cost (p = 0.032), and total cost (p = 0.011) were significantly higher in pneumonia patients aged ≥36 months than those aged <36 months; however, direct cost of AOM were significantly higher in the patients aged <36 months (p = 0.049). Results of the present study revealed that the treatment cost was significantly enhanced for hospitalization and for advanced disease. Thus, preventive actions, mainly vaccination, should be conducted regularly.

Combined effect of PCV10 and meningococcal C conjugate vaccination on meningitis mortality among children under five years of age in Brazil.

The 10-valent pneumococcal conjugate vaccine (PCV10) was introduced in the Brazilian National Immunization Program in March 2010, scheduled at 2, 4, and 6 months, with a booster at 12-15 months of age. The meningococcal C conjugate vaccine (MCC) was introduced in November 2010, scheduled at 3 and 5 months, with a booster dose at 12-15 months of age and no catch-up for older age groups. In this interrupted time-series analysis study, we used Brazilian mortality data from 2005 to 2015 for children under five years of age (excluding data from the state of Bahia) to assess the combined impact of these vaccines on the overall burden of meningitis mortality among children aged 0-23 months and 2-4 years, as defined using meningitis and meningococcemia specific International Classification of Diseases - tenth revision codes. Secular trends and seasonality were taken into account. We found significant reductions for both age groups relative to those observed for the comparison group of diseases, with immediate effects after the transition period (2010-2011) of 29.2% and 27.5% for children aged 0-23 months and 2-4 years, respectively. These immediate effects were sustained throughout the post-vaccination period (2012-2015). In total, 337 deaths were averted by the combined effect of both vaccines, 238 (95%CI 169-319) for children aged 0-23 months and 99 (95%CI 56-144) for those aged 2-4 years. These results add strong evidence in support of investments in these vaccines by low and middle-income countries.

Perceptions of measles, pneumonia, and meningitis vaccines among caregivers in Shanghai, China, and the health belief model: a cross-sectional study.

BACKGROUND: In China, the measles vaccine is offered for free whereas the pneumococcal vaccine is a for-fee vaccine. This difference has the potential to influence how caregivers evaluate whether a vaccine is important or necessary for their child, but it is unclear if models of health behavior, such as the Health Belief Model, reveal the same associations for different diseases. This study compares caregiver perceptions of different diseases (measles, pneumonia and meningitis); and characterizes associations between Health Belief Model constructs and both pneumococcal vaccine uptake and perceived vaccine necessity for pneumonia, measles, and meningitis. METHODS: Caregivers of infants and young children between 8 months and 7 years of age from Shanghai (n = 619) completed a written survey on their perceptions of measles, pneumonia, and meningitis. We used logistic regression models to assess predictors of pneumococcal vaccine uptake and vaccine necessity. RESULTS: Only 25.2% of children had received a pneumococcal vaccine, although most caregivers believed that pneumonia (80.8%) and meningitis (92.4%), as well as measles (93.2%), vaccines were serious enough to warrant a vaccine. Perceived safety was strongly associated with both pneumococcal vaccine uptake and perceived vaccine necessity, and non-locals had 1.70 times higher odds of pneumonia vaccine necessity than non-locals (95% CI: 1.01, 2.88). CONCLUSIONS: Most factors had a similar relationship with vaccine necessity, regardless of disease, indicating a common mechanism for how Chinese caregivers decided which vaccines are necessary. Because more caregivers believed meningitis needed a vaccine than pneumonia, health care workers should emphasize pneumococcal vaccination's ability to protect against meningitis.

Evaluation of a rapid antigen test for detection of Streptococcus pneumoniae in cerebrospinal fluid.

Detection of Streptococcus pneumoniae antigen in cerebrospinal fluid (CSF) using lateral flow immunochromatography tests (ICTs) is an effective, rapid and low-cost method to diagnose pneumococcal meningitis. This study evaluated the diagnostic accuracy of the Uni-Gold ICT to detect pneumococcal antigen in CSF specimens, compared with gold standard bacteriology and quantitative real-time PCR (qPCR) testing. CSF specimens (n=69) from patients with suspected bacterial meningitis were included in the study. 13/69 (19%) were positive and 56/69 (81%) were negative for pneumococcus by the gold standard tests. The ICT had sensitivity of 85% (55%-98%), specificity of 96% (88%-100%), positive likelihood ratio of 23.7 (6-94) and negative likelihood ratio of 0.16 (0.04-0.57). Overall, a strong correlation between the ICT and qPCR results was seen (κ=0.81). In contrast, CSF microscopy and culture were exceptionally insensitive. The ICT method is sufficiently robust and accurate for use in algorithms to diagnose bacterial meningitis.

Economic studies applied to vaccines against invasive diseases: An updated budget impact analysis of age-based pneumococcal vaccination strategies in the elderly in Italy.

Many evaluations have been performed on the economic impact of pneumococcal vaccination in older adults (>64 y of age) in several countries, including Italy. However, these studies did not include the new data on the effectiveness of 13-valent conjugate pneumococcal vaccine (PCV13) in the elderly reported by the CAPiTA Study. The aim of the present study was to update our previous budget impact analysis of multi-cohort PCV13 vaccination in adults in Italy by including new scientific evidence. We also compared single-cohort vaccination strategies per year, in order to identify the cohort with the most favorable economic profile, in the event of the multi-cohort approach not being economically sustainable for the National Health System (NHS). The new impact analysis highlights that the vaccination of one, two or three adult cohorts per year in Italy would lead to a considerable reduction in pneumococcal disease and its related costs over 5 y. The strategies proved cost-effective (ICERs ranging from €14,605 to €15,412/QALY), i.e. well below the threshold of €50,000/QALY. The ICERs were slightly lower than those calculated in the first published analysis and vaccination continued to be economically favorable. In the case of a mono-cohort strategy, the vaccination of 65-year-old subjects, albeit more expensive, proved to be more favorable than the vaccination of 70- or 75-year-old cohorts. Finally, after the inclusion of the recent clinical evidence, the age-based PCV13 vaccination of the elderly in Italy continued to be economically justified from the NHS perspective in the short period. Vaccination of the elderly should therefore be strongly recommended nationwide in Italy.

A duplex real-time PCR for the detection of Streptococcus pneumoniae and Neisseria meningitidis in cerebrospinal fluid.

INTRODUCTION: Acute bacterial meningitis is one of the most severe infectious diseases. Rapid, accurate, and inexpensive diagnosis of bacterial meningitis is crucial for patient management. This study describes a duplex real-time (RT) PCR assay for detection of Neisseria meningitidis and Streptococcus pneumoniae in the cerebrospinal fluid (CSF) for meningitis diagnosis using SYBR Green-based RT-PCR method coupled with melting curve analysis. METHODOLOGY: We used SYBR Green-based RT-PCR method coupled with melting curve analysis to detect S. pneumoniae and N. meningitidis in CSF samples. The sensitivity, specificity, and limit of detection were determined. The gold standard for routine tests of CSF analysis is direct examination, culture, and/or latex agglutination. The assay was evaluated on 132 CSF samples to measure clinical sensitivity. RESULTS: A duplex RT-PCR assay for N. meningitidis and S. pneumoniae detection in CSF was evaluated. Two peaks at different melting temperatures (87.5°C and 85.5°C) for N. meningitidis and S. pneumoniae, respectively, were obtained. The sensitivity of RT-PCR was 100% (95% confidence limits [CI] = 82.4-100) for N. meningitidis and 100% (95% CI = 85.1-100) for S. pneumoniae. Specificity was the same (100%) for the bacteria (95% CI = 88.6-100). The percentage of cases accurately diagnosed with meningitis caused by N. meningitidis and S. pneumoniae increased to 50.7% and 28.6%, respectively, when RT-PCR was added to the standard microbiologic methods. CONCLUSIONS: Duplex RT-PCR and melting curve analysis with SYBR Green is an inexpensive, sensitive, and specific method to rapidly diagnose bacterial meningitis. Accurate identification of the bacterial causative agents will improve patient management and epidemiological investigations.

ASSESSMENT OF THE DIAGNOSTIC AND PROGNOSTIC ROLE OF CEREBEROSPINAL FLUID INTERLEUKIN-8 LEVEL IN ADULT PATIENTS WITH MENINGITIS.

Meningitis necessitates immediate diagnosis and therapy. It is important to distingu- ish bacterial from aseptic meningitis, as this help to avoid complications and unnece- ssary antibiotic use. This work assessed the diagnostic and prognostic role of cerebro-spinal fluid interleukin-8 (IL-8) level in adult patients with meningitis. Ninety adult patients with meningitis were studied. They were divided into 3 groups: bacterial, tuberculous and aseptic meningitis. Full clinical examination and laboratory workup of meningitis were done. Cerebrospinal fluid (CSF) IL-8 levels were assessed. Patients were followed up till discharge or death. CSF IL-8 level was significantly higher in bacterial and tuberculous meningitis in comparison to aseptic meningitis. At cut off value 121.77 pg/ml, the area under ROC curve was 0.774 with efficacy 69% for differentiating viral from non-viral meningitis. The test efficacy is low in differentiating tuberculous from bactedal meningitis. There is no correlation of CSF IL-8 levels and disease severity or prognosis.

[CLINICAL AND EPIDEMIOLOGICAL ASSESSMENT OF THE EFFECTIVENESS OF VAC- CINATION OF CHILDREN AGAINST PNEUMOCOCCAL INFECTION IN THE AMUR REGION].

AIM: To study the effectiveness of anti-pneumococcal vaccination of children in the organiza- tion of anti-epidemic measures in the areas of the flood in the Amur region. MATERIAL AND METHODS: The monitoring program included 4988 children aged 2 to 5 years who have risk factors for pneu- mococcal infection. Pneumococcal conjugate vaccine Prevenar- 13 was used for immunization. Data on the incidence of child with acute respiratory infection, acute otitis media, pneumonia, meningitis during the post-vaccination period were taken into account. To evaluate the effective- ness of vaccination we used indicators and specific criteria (coefficient prophylactic vaccination and infection index). RESULTS: The level of total morbidity of children in post-immunization pe- riod decreased by 13.6%; the number of cases ofpneumonia in the population of observed children decreased by 2.3 times; the total duration of the illness in children decreased by 14.6%, the number of.courses of antibiotic therapy was reduced by 21.3%, the number of hospital admissions of children - 38.4%, the number of days of temporary disability ofparents - 11.1%. Direct dependence of the degree of effectiveness of vaccination against pneumococcal disease by the age of children is determined. CONCLUSION: The findings suggest that implementation of the program of clinical and epidemiological monitoring and prevention of community-acquired pneumonia with use of a vaccine against pneumococcal infections in the territory of the Amur Region has a high level of medical and socio-economic efficiency.

Longitudinal DRG-based survey of all-cause and pneumococcal pneumonia and meningitis for inpatients in France (2005-2010).

OBJECTIVE: This population-based retrospective study quantified the burden of all-cause and pneumococcal pneumonia and meningitis in the Rhône-Alpes region of France from 2005 to 2010, when the 7-valent pneumococcal conjugate vaccine uptake increased from 50 to>90% in children. PATIENTS AND METHODS: Hospital admission data was obtained from the French Diagnosis Related Groups program database (French acronym PMSI). Patients were residents of the Rhône-Alpes region hospitalized for the diseases of interest during 2005-2010. Hospitalization and in-hospital mortality rates were calculated by age, sex, and year on the basis of the Rhône-Alpes region population. Hospitalization and in-hospital mortality rates were compared using Chi(2) tests with statistical significance adjusted for multiple comparisons. RESULTS: The highest hospitalization rates by age group were: all-cause pneumonia, oldest group (>65 years); all-cause and pneumococcal meningitis, youngest group (0-4 years), and pneumococcal pneumonia, youngest and oldest groups. Hospitalization rates significantly decreased for all-cause pneumonia (5-19 years: -12.71%) and all-cause meningitis (20-49 years: -29.22%). Pneumococcal disease rates did not significantly change in any age group. Mortality rates from all-cause pneumonia and meningitis were highest in the oldest age groups. CONCLUSIONS: The burden of all-cause and pneumococcal pneumonia and meningitis remains substantial. Significant changes (decreases) between 2005 and 2010 in hospitalization rates were limited and varied among age groups, most likely because this study began 2 years after PCV7 was first introduced in France for children at broadly-defined high risk. Further research is needed on the relationship between serotype epidemiology and clinical patterns of disease.

Burden of invasive pneumococcal disease (IPD) in Sri-Lanka: Deriving a reasonable measure for vaccine introduction decision making.

PURPOSE: The lack of evidence on the disease burden has been an obstacle for decision-making on introducing pneumococcal vaccines in Sri-Lanka. Hence, the purpose of this study is to determine the incidence of invasive pneumococcal disease among children under five-years of age in Sri-Lanka's Colombo district. METHODS: In a community-based study, using a sample of 2310 children, we identified syndromes associated with pneumococcal disease (pneumonia, meningitis, sepsis). The estimates of annual cumulative incidence of invasive pneumococcal disease were derived by having applied proportions of laboratory confirmed invasive pneumococcal disease among all-cause syndromes associated with pneumococcal infection obtained from the hospital-based invasive bacterial disease sentinel surveillance and findings of the community-based study to population parameters of the district. The estimates of invasive pneumococcal pneumonia and sepsis based on low-sensitive, culture confirmation were adjusted by a correction factor. RESULTS: The annual cumulative incidence of all-cause clinical syndromes associated with pneumococcal disease (pneumonia, meningitis, sepsis) were 1.3, 0.52, 0.39 per 100 children, respectively. The estimate of adjusted, invasive pneumococcal disease cumulative incidence was 206.3 per 100,000 while estimates of pneumococcal pneumonia, meningitis and sepsis cumulative incidence were 147.9, 13.2 and 45.2 per 100,000 under-five children. CONCLUSION: Reasonable estimates of invasive pneumococcal disease could be derived by using incidence of clinical syndromes associated with pneumococcal disease obtained from population-based studies and proportion of pneumococcal infection among all-cause clinical syndromes associated with pneumococcal disease generated from hospital-based sentinel surveillance. These estimates may help informed decision-making on introduction of pneumococcal conjugated vaccine.

Clinical burden of pneumonia, meningitis and septicemia in Norway 2 years after 7-valent pneumococcal conjugate vaccine introduction.

AIMS: This population-based, retrospective study quantified the rates of all-cause and pneumococcal pneumonia, meningitis and septicemia in Norway from 2008 to 2009 and determined the proportions of cases caused by pneumococcal vaccine serotypes. METHODS: Data on patients with all-cause and pneumococcal pneumonia, meningitis and septicemia were obtained from the Norwegian Patient Registry, which collects hospitalization data from all Norwegian public hospitals based on International Classification of Diseases codes. Norwegian Patient Registry case records linked to the Norwegian Surveillance System for Communicable Diseases provided serotype data for invasive pneumococcal disease in patients with microbiological cultures. RESULTS: In 2008 and 2009, hospitalization rates were relatively stable for all-cause pneumonia (5.28 and 5.35, respectively, per 1000), meningitis (10.70 and 9.67, respectively, per 100,000), and septicemia (from 171.81 to 161.46 per 100,000). In contrast, rates decreased for International Classification of Diseases-10 diagnosed pneumococcal pneumonia (from 13.66 to 10.52 per 100,000), although these cases may be under-reported because of inclusion in all-cause pneumonia. Rates also decreased in diagnosed pneumococcal meningitis (from 1.60 to 1.19 per 100,000) and diagnosed pneumococcal septicemia (from 9.08 to 7.94 per 100,000). Diagnosed pneumococcal disease rates were highest in younger children and older adults, peaking at ⩾ 60 years old. Pneumococcal pneumonia, meningitis and septicemia caused by serotypes included in the 7-valent pneumococcal conjugate vaccine decreased substantially during the study period, with corresponding serotype replacement by non-7-valent pneumococcal conjugate vaccine serotypes. CONCLUSIONS: From 2008 to 2009, International Classification of Diseases-10 diagnosed pneumococcal pneumonia, meningitis and septicemia decreased in most age groups but remained greatest among subjects aged 0-1 and ⩾ 60 years.

[Clinical burden of multi-cause and pneumococcal pneumonia, meningitis, and septicemia in Hungary. Results of a retrospective study (2006-2011)]. / Pneumococcus, illetve bármely kórokú pneumonia, meningitis és septikaemia miatti hospitalizáció és halálozás Magyarországon. Egy retrospektív értékelés eredménye (2006-2011).

INTRODUCTION: Assessment of the impact of pneumococcal conjugate vaccines on the burden of pneumonia, meningitis, and septicemia in Hungary is limited. AIM: The aim of this retrospective study was to quantify rates of hospitalized multi-cause and pneumococcal pneumonia, meningitis, and septicemia in all age groups in Hungary between 2006 and 2011. METHOD: Aggregate data were obtained from the Hungarian National Healthcare Fund using pre-specified ICD-10 codes. Comparisons included average rates pre-vaccine (2006-2007) versus post-vaccine (2010-2011) using a χ2 test. RESULTS: Hospitalization rates among children aged 0-4 years significantly declined for multi-cause pneumonia and meningitis, but increased for septicemia. There were significant increases in multi-cause pneumonia and septicemia in other age groups. In-hospital mortality rates increased with age. Limited use of pneumococcal-specific codes led to inconclusive findings for pneumococcal diseases. CONCLUSIONS: Declines in multi-cause pneumonia and meningitis in children aged 0-4 years suggest direct effects of pneumococcal conjugate vaccination on hospitalization rates.

[Economic cost of Streptococcus pneumoniae community-acquired pneumonia, meningitis and bacteremia in an adult population that required hospitalization in Bogotá, Colombia]. / Costos económicos de neumonía adquirida en comunidad, meningitis y bacteriemia por Streptococcus pneumoniae en una población adulta que requirió hospitalización en Bogotá, Colombia.

INTRODUCTION: Streptococcus pneumoniae infection in adults is related to pneumonia, meningitis and bacteremia. Its care costs in adults are not well documented in Colombia and it has a greater impact in people over 45 years old. OBJECTIVES: The aims of this study were to analyze the associated costs of pneumonia, bacteremia and meningitis in invasive S. pneumoniae infection in Colombia among hospitalized adults and to estimate outpatient costs for community-acquired pneumonia. Additionally, we wanted to serve as a starting point for future economic evaluations. MATERIALS AND METHODS: We performed a direct cost study associated with S. pneumoniae outpatient community-acquired pneumonia, bacteremia and meningitis costs confirmed by cultures. A cohort of hospitalized adults treated between January 2010 and June 2011 in three third level hospitals in Bogotá was analyzed. We evaluated 107 records and 60 bills charged to the payer. The data were classified according to care and treatment costs. We performed an estimate of direct costs for community-acquired pneumonia for outpatient cases through Delphi methodology using expert clinicians. RESULTS: The average direct costs associated with pneumococcal disease were US$ 6,283, US$ 3,886, and US$ 4,768 for pneumonia, meningitis and bacteremia, respectively (exchange rate 1 US$ = Col$ 1,938.34; average variation between 2010 and 2011). Pneumonia cases were 70% men and 30% women; the distribution for meningitis was the same for both genders (50%); and for bacteremia we had 67% men and 33% women. Outpatient cost of community-acquired pneumonia was estimated at US$ 82.2 ( Col $ 159,280 ) in adults. For special cases, direct cost increased to US$ 142 ( Col $ 274,427). CONCLUSIONS: The management of S. pneumoniae infection in people over 45 years old represents a high cost due to the use of drugs and hospitalization, which has a direct impact on health resources. Prevention and early treatment for pneumonia can reduce the cost and the burden of the disease.

Vaccination in Southeast Asia--reducing meningitis, sepsis and pneumonia with new and existing vaccines.

Streptococcus pneumoniae, Haemophilus influenzae type b and Neisseria meningitidis are leading causes of vaccine-preventable diseases such as meningitis, sepsis and pneumonia. Although there has been much progress in the introduction of vaccines against these pathogens, access to vaccines remains elusive in some countries. This review highlights the current S. pneumoniae, H. influenzae type b, and N. meningitidis immunization schedules in the 10 countries belonging to the Association of Southeast Asian Nations (ASEAN). Epidemiologic studies may be useful for informing vaccine policy in these countries, particularly when determining the cost-effectiveness of introducing new vaccines.

A retrospective study to assess the epidemiological and economic burden of pneumococcal diseases in adults aged 50 years and older in Taiwan.

OBJECTIVE: Invasive pneumococcal disease (IPD) and pneumococcal pneumonia cause substantial morbidity and mortality worldwide. This retrospective study was conducted to estimate the disease burden from pneumococcal disease in older adults in Taiwan from a health insurer's perspective. METHODS: Data for the years 2002-2009 from patients aged ≥50 years with insurance records indicating pneumococcal meningitis, pneumococcal bacteremia, or hospitalized or outpatient pneumonia were obtained from the National Health Insurance Research Database in Taiwan. Admission data for inpatients, visit data for outpatients, and associated costs were extracted from the database to estimate the incidence, case fatality rates, and direct and indirect costs of pneumococcal disease episodes. These data were applied to the estimated population of Taiwan in 2010 to provide an estimated disease burden for a single year from the payer perspective. RESULTS: The average incidence per 100,000 person years was 2.4 for IPD, 278.8 for hospitalized pneumococcal pneumonia, and 1376.4 for outpatient pneumococcal pneumonia. The average case fatality rate was 12.3% for IPD and 10.0% for hospitalized pneumonia. Hospitalized pneumonia accounted for over 90% of direct medical costs. The incidence of hospitalized pneumococcal pneumonia per 100,000 person years was 84.4 for adults of 50-64 years, 313.1 for adults of 65-74 years, 820.3 for adults of 75-84 years, and 1650.9 for adults of 85+ year of age. In 2010, it was estimated there were over 113,000 episodes of pneumococcal disease, causing almost 2000 deaths, with direct medical costs of more than NT$3.4 billion annually. CONCLUSIONS: Pneumococcal disease is a significant cause of mortality and excess healthcare expense among the elderly in Taiwan. Disease burden in older adults increases with advancing age.