Cranial Imaging Before Lumbar Puncture in Adults With Community-Acquired Meningitis: Clinical Utility and Adherence to the Infectious Diseases Society of America Guidelines.

BACKGROUND.: The Infectious Diseases Society of America (IDSA) guidelines delineate criteria for the use of computed tomography (CT) scan of the head before lumbar puncture (LP) in adults with community-acquired meningitis (CAM). There are limited data to document adherence to these guidelines and assess the clinical utility of brain imaging. METHODS.: This was a retrospective analysis from January 2005 to January 2010 in Houston, Texas. RESULTS.: Among 614 adults with CAM, 407 patients (66.3%) did not have an indication for a head CT scan and 207 (33.7%) did. Patients with a CT scan indication were older, had more comorbidities, were sicker, and had more urgent treatable etiologies and adverse clinical outcomes (P < .001). A CT scan was ordered before the LP in 549 patients (89%). Overall, clinicians did not adhere to clinical guidelines in 368 of 614 (60%) subjects. A CT of the head was ordered when not indicated in 355 of 549 patients (64%), and not done when indicated in 13 of 207 patients (0.6%). CT of the head revealed intracranial abnormalities in 35 of 193 patients (18.1%) with an indication for brain imaging, compared with only 2 of 356 (0.05%) with no indication (P < .05). Major intracranial findings were seen in only 15 of 549 (2.7%) patients, all with an indication for brain imaging. Furthermore, only 8 patients had abnormalities that affected clinical management. CONCLUSIONS.: Most clinicians do not adhere to IDSA guidelines, delaying diagnostic LP and increasing costs. Usefulness of head CT in patients with CAM without an indication for imaging is limited and has no impact in clinical management.

Specific detection of common pathogens of acute bacterial meningitis using an internally controlled tetraplex-PCR assay.

Accurate and timely diagnosis of acute bacterial meningitis is critical for antimicrobial treatment of patients. Although PCR-based methods have been widely used for the diagnosis of acute meningitis caused by bacterial pathogens, the main disadvantage of these methods is their high cost. This disadvantage has hampered the widespread use of molecular assays in many developing countries. The application of multiplex assays and "in-house" protocols are two main approaches that can reduce the overall cost of a molecular test. In the present study, an internally controlled tetraplex-PCR was developed and validated for the specific detection of Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae in cerebrospinal fluid (CSF) samples. The analysis of a panel of other human pathogens showed no cross-reactivity in the assay. The analytical sensitivity of the in-house assay was 792.3 copies/ml, when all three bacteria were presentin the specimens. This value was calculated as 444.5, 283.7, 127.8 copies/ml when only S. pneumoniae, N. meningitidis and H. influenzae, respectively, were present. To demonstrate the diagnostic performance of the assay, a total of 150 archival CSF samples were tested and compared with a commercial multiplex real-time PCR kit. A diagnostic sensitivity of 92.8% and a specificity of 95.1% were determined for the present tetraplex-PCR assay. The results indicate that the established method is sensitive, specific and cost-effective, and can be used particularly in situations where the high cost of commercial kits prevents the use of molecular methods for the diagnosis of bacterial meningitis.

The actual and potential costs of meningitis surveillance in the African meningitis belt: Results from Chad and Niger.

BACKGROUND: The introduction of serogroup A meningococcal conjugate vaccine in the African meningitis belt required strengthened surveillance to assess long-term vaccine impact. The costs of implementing this strengthening had not been assessed. METHODOLOGY: The ingredients approach was used to retrospectively determine bacterial meningitis surveillance costs in Chad and Niger in 2012. Resource use and unit cost data were collected through interviews with staff at health facilities, laboratories, government offices and international partners, and by reviewing financial reports. Sample costs were extrapolated to national level and costs of upgrading to desired standards were estimated. RESULTS: Case-based surveillance had been implemented in all 12 surveyed hospitals and 29 of 33 surveyed clinics in Niger, compared to six out of 21 clinics surveyed in Chad. Lumbar punctures were performed in 100% of hospitals and clinics in Niger, compared to 52% of the clinics in Chad. The total costs of meningitis surveillance were US$ 1,951,562 in Niger and US$ 338,056 in Chad, with costs per capita of US$ 0.12 and US$ 0.03, respectively. Laboratory investigation was the largest cost component per surveillance functions, comprising 51% of the total costs in Niger and 40% in Chad. Personnel resources comprised the biggest expense type: 37% of total costs in Niger and 26% in Chad. The estimated annual, incremental costs of upgrading current systems to desired standards were US$ 183,299 in Niger and US$ 605,912 in Chad, which are 9% and 143% of present costs, respectively. CONCLUSIONS: Niger's more robust meningitis surveillance system costs four times more per capita than the system in Chad. Since Chad spends less per capita, fewer activities are performed, which weakens detection and analysis of cases. Countries in the meningitis belt are diverse, and can use these results to assess local costs for adapting surveillance systems to monitor vaccine impact.

The economic burden of childhood invasive pneumococcal diseases and pneumonia in Taiwan: Implications for a pneumococcal vaccination program.

Invasive pneumococcal disease (IPD) and pneumonia are the major causes of morbidity and deaths in children in the world. The management of IPD and pneumonia is an important economic burden on healthcare systems and families. The aim of this study was to assess the economic burden of IPD and pneumonia among younger children in Taiwan. We used a cost-illness approach to identify the cost categories for analysis in this study according to various perspectives. We obtained data of admission, outpatient, and emergency department visit data from the National Health Insurance Research (NHIR) database for children <5 y of age between January 2008 and December 2008. A prospective survey was administered to the families of patients to obtain detailed personal costs. All costs are presented in US dollars and were estimated by extrapolating 2008 cost data to 2013 price levels. We estimated the number of pneumococcal disease cases that were averted if the PCV-13 vaccine had been available in 2008. The total annual social and hospital costs for IPD were US $4.3 million and US $926,000, respectively. The total annual social and hospital costs for pneumonia were US $150 million and US $17 million, respectively. On average, families spent US $653 or US $218 when their child was diagnosed with IPD or pneumonia, respectively. This cost is approximately 27%-81% of the monthly salary of an unskilled worker. In conclusion, a safe and effective pediatric pneumococcal vaccine is needed to reduce the economic burden caused by pneumococcal infection.

Health and economic outcomes of introducing the new MenB vaccine (Bexsero) into the Italian routine infant immunisation programme.

INTRODUCTION: In January 2013 a novel type of multicomponent protein-based vaccine against group B meningococcal disease was licensed by the European Medicines Agency. With the widespread use of the meningococcal serogroup C conjugate vaccines, serogroup B remains now the major cause of bacterial meningitis and septicaemia in young children in Europe. The aim of this study is to investigate the health and the economic outcomes of MenB vaccine introduction into the Italian routine mass vaccination programme. METHODS: The present work is structured in two main parts. Firstly, we assess the epidemiological burden of group B meningococcal disease using official hospitalisation and notification data from two of the most populated Italian regions (Lombardia and Piemonte) during a 6-year study period (2007-2012). Secondly, we evaluate the cost-effectiveness of the immunisation programme in Italy from the public health payer perspective under base case parameters assumptions and performing a comprehensive sensitivity analysis to assess the robustness and the uncertainty of our model results. RESULTS: MenB serotype is responsible for 59% of the 341 cases of Invasive Meningococcal Disease in Lombardia and Piemonte. Incidence rate for MenB infection is estimated to be 0.21/100,000/y resulting at the highest level in children ≤4 years of age. Although the new MenB vaccine can potentially prevent about one third of the disease cases in the Italian population, model results show this strategy is unlikely to be cost-effective (ICER value over €350,000/QALY) with a vaccine that prevents disease only. These results are robust under most of the sensitivity scenarios except when allowing for lower discount rates. DISCUSSION: The introduction of the novel vaccine into the routine immunisation schedule needs to be carefully evaluated. The new MenB vaccine has the potential to reduce the disease burden at the population level. However, from the Italian Health Service perspective, the immunisation programme is unlikely to be cost-effective at the current incidence levels and vaccine price.

Clinical and economic results of ventriculoperitoneal shunt infections in children.

AIM: This study evaluated the clinical and economic outcomes of ventriculoperitoneal shunt infections. MATERIAL AND METHODS: Patients diagnosed with ventriculoperitoneal shunt infections for the first time between 1 January 2007 and 31 December 2011 were included in this study. Demographic, clinical, and economic data were analyzed retrospectively. A cost coefficient (total cost/follow-up period) and hospitalization coefficient (duration of hospitalization/follow-up period) were calculated for each patient. RESULTS: In total, 132 shunt infections (mean follow-up, 734 ± 367 days) were evaluated in 51 patients (mean age, 16.6 ± 9.22 months; median age, 3 months; range, 1-88 months; 28 females, 21 males). In 23 patients (45%), shunt infections were seen in the first 2 months following shunt placement. Seven patients died during the follow-up. There was a negative correlation between the age at diagnosis and the hospitalization duration (p = 0.005, r = -0.381). The average cost of hospitalization per patient was 6397 ± 4338 TL. There was a negative correlation between the cost index and the age at diagnosis (p = 0.04, r = -0.292). CONCLUSION: Ventriculoperitoneal shunt infections have significant medical and economic impacts. Younger the diagnosis of patients, the hospitalization duration and treatment cost were higher.

[Social-epidemiologic and economic effect of implementation of a program of vaccination of young children in Russia against pneumococcal infection].

Literature data on the evaluation of clinical-epidemiologic and social effectiveness of implementation of programs of vaccination against pneumococcal infection in various countries are presented in the review. A prognosis of pharmacoeconomic effectiveness of a universal vaccination of children at the first years of life during realization of program in Russia, where more than 3000 children yearly suffer from pneumococcal bacteremia, around 39 000 have pneumococcal pneumonia and more than 700 000--pneumococcal otitis is given. The frequency of lethal outcomes from pneumococcal meningitis in Russia is 20-40% and exceeds similar parameters of meningitis of other etiology. Cost for the state from the therapy ofpneumococcal infections is no less than 30 646 milliards of RUR (Russian ruble) based on 2009 calculations. In Russia 5 years after an implementation of yearly mass immunization in children aged from 2 months against pneumococcal infection an overall economic effect of the program of mass vaccination would be 39.19 milliards of RUR. With direct costs reducing by 19.69 milliards of RUR, and indirect costs (temporarily disability allowance payment, reduction of losses of gross domestic product)--by 37.4 milliards of RUR.

Costs and infant outcomes after implementation of a care process model for febrile infants.

OBJECTIVE: Febrile infants in the first 90 days may have life-threatening serious bacterial infection (SBI). Well-appearing febrile infants with SBI cannot be distinguished from those without by examination alone. Variation in care resulting in both undertreatment and overtreatment is common. METHODS: We developed and implemented an evidence-based care process model (EB-CPM) for the management of well-appearing febrile infants in the Intermountain Healthcare System. We report an observational study describing changes in (1) care delivery, (2) outcomes of febrile infants, and (3) costs before and after implementation of the EB-CPM in a children's hospital and in regional medical centers. RESULTS: From 2004 through 2009, 8044 infants had 8431 febrile episodes, resulting in medical evaluation. After implementation of the EB-CPM in 2008, infants in all facilities were more likely to receive evidence-based care including appropriate diagnostic testing, determination of risk for SBI, antibiotic selection, decreased antibiotic duration, and shorter hospital stays (P < .001 for all). In addition, more infants had a definitive diagnosis of urinary tract infection or viral illness (P < .001 for both). Infant outcomes improved with more admitted infants positive for SBI (P = .011), and infants at low risk for SBI were more often managed without antibiotics (P < .001). Although hospital admissions were shortened by 27%, there were no cases of missed SBI. Health Care costs were also reduced, with the mean cost per admitted infant decreasing from $7178 in 2007 to $5979 in 2009 (-17%, P < .001). CONCLUSIONS: The EB-CPM increased evidence-based care in all facilities. Infant outcomes improved and costs were reduced, substantially improving value.

Cost-effectiveness of the introduction of the pneumococcal polysaccharide vaccine in elderly Colombian population.

BACKGROUND: Streptococcus pneumoniae causes community-acquired pneumonia, otitis media and meningitis, with higher incidences at the extremes of life. PPV-23 vaccine is widely used in prevention of pneumonia and invasive pneumococcal disease in older adults in developed countries. We developed an evaluation of cost-effectiveness of implementing PPV-23 in Colombian population over 60 years. METHODS: The number of cases of pneumonia and meningitis in patients over 60 years and the proportion by S. pneumoniae was estimated based on a review of literature. A decision tree model with a 5-year time horizon was built to evaluate the cost-effectiveness of the implementation of the PPV-23 in this population. Direct health care costs of out- and in-patients were calculated based on expenditure records from the Bogota public health system. Incremental cost-effectiveness ratios per life saved and per year of life gained were estimated based on the decision tree model. Deterministic and probabilistic sensitivity analyses were performed. RESULTS: Without vaccination 4460 (range 2384-8162) bacteremic pneumococcal pneumonias and 141 (range 73-183) pneumococcal meningitis would occur among people over 60 years old in Colombia. In the first year, vaccination with PPV-23 at US$8/dose would save 480 (range 100-1753) deaths due to Invasive and non-invasive pneumococcal disease. Vaccination would results in US$3400/deaths averted (range US$1028-10,862) and US$1514/life years gained (range US$408-5404). CONCLUSION: Vaccination with PPV-23 in over 60 years is a highly cost-effective public health measure in Colombia. Despite some limitations, the results are robust, and may help developing countries to perform informed decisions about the introduction of the vaccine.

Rapid assessment of Hib disease burden in Vietnam.

BACKGROUND: Several countries have applied the Haemophilus influenzae type b (Hib) rapid assessment tool (RAT) to estimate the burden of Hib disease where resources for hospital- or population-based surveillance are limited. In Vietnam, we used the Hib RAT to estimate the burden of Hib pneumonia and meningitis prior to Hib vaccine introduction. METHODS: Laboratory, hospitalization and mortality data were collected for the period January 2004 through December 2005 from five representative hospitals. Based on the WHO Hib RAT protocol, standardized MS Excel spreadsheets were completed to generate meningitis and pneumonia case and death figures. RESULTS: We found 35 to 77 Hib meningitis deaths and 441 to 957 Hib pneumonia deaths among children < 5 years of age annually in Vietnam. Overall, the incidence of Hib meningitis was estimated at 18/100,000 (95% confidence interval, CI, 15.1-21.6). The estimated Hib meningitis incidence in children < 5 years age was higher in Ho Chi Minh City (22.5/100,000 [95% CI, 18.4-27.5]) compared to Hanoi (9.8/100,000 [95% CI, 6.5-14.8]). The Hib RAT suggests that there are a total of 883 to 1,915 cases of Hib meningitis and 4,414 to 9,574 cases of Hib pneumonia per year in Vietnam. CONCLUSIONS: In Hanoi, the estimated incidence of Hib meningitis for children < 5 years of age was similar to that described in previous population-based studies of Hib meningitis conducted from 1999 through 2002. Results from the Hib RAT suggest that there is a substantial, yet unmeasured, disease burden associated with Hib pneumonia in Vietnamese children.

Impact of bacterial meningitis-associated conditions on pediatric inpatient resource utilization.

OBJECTIVE: To define the epidemiology of systemic complications and focal infections associated with bacterial meningitis and quantify how the presence of such complications affects in-hospital healthcare resource utilization. METHODS: Retrospective cohort study using administrative data from 27 children's hospitals. Children <18 years of age diagnosed with bacterial meningitis from 2001 to 2006 were eligible. The primary exposure of interest was the presence of a bacterial meningitis-associated condition, classified as either systemic complications (eg, sepsis), associated focal infections (eg, pneumonia) or both. The primary outcomes were total in-hospital charges and length of stay (LOS). RESULTS: A total of 574 of 2319 (25%) of children had a systemic complication or an associated focal infection. Compared with children without complications, in-hospital charges were significantly higher in children with systemic complications (136% increase), associated focal infections (118% increase), and both conditions (351% increase). LOS was also significantly increased in those with systemic complications (by 72%), associated focal infections (by 78%), or both conditions (by 211%). The presence of systemic complications was more common in younger children while the presence of an associated focal infection was more common in older children. CONCLUSIONS: Children with bacterial meningitis often have additional morbidity due to systemic complications or associated focal infections indicated by increase use of acute in-hospital resource utilization. The apparent increase in in-hospital morbidity related to these conditions should be considered in future evaluations of vaccine efficacy, novel therapeutics, and hospital resource allocation.

Costs for households and community perception of meningitis epidemics in burkina faso.

Bacterial meningitis in the African meningitis belt remains 1 of the most serious threats to health. The perceptions regarding meningitis in local populations and the cost of illness for households are not well described. We conducted an anthropologic and economic study in Burkina Faso, in the heart of the meningitis belt. Respondents reported combining traditional and modern beliefs regarding disease etiology, which in turn influenced therapeutic care-seeking behavior. Households spent US $90 per meningitis case, or 34% of the annual gross domestic product per capita, and up to US $154 more when meningitis sequelae occurred. Much of this cost was attributable to direct medical expenses, which in theory are paid by the government. Preventive immunization against meningitis will overcome limitations imposed by traditional beliefs and contribute to poverty reduction goals.

Application of a diagnostic decision rule in children with meningeal signs: a cost-minimization study.

OBJECTIVES: Recently, we developed a diagnostic rule for the diagnosis and treatment of children with meningeal signs. This rule may provide the physician with a rationale to decide on the use of diagnostic and treatment procedures in these children and to improve their care. In this study, we estimated cost savings of the rule compared with current practice. METHODS: Routine care data of 360 children visiting the emergency department of the Sophia Children's Hospital with meningeal signs between 1988 and 1998 were used. Costs of diagnostic tests and treatment were estimated by using financial accounts of an academic and a general pediatric hospital. The number of procedures actually performed and the resulting cost estimates (i.e. unit costs x volume) were compared with the estimated figures after application of the decision rule. RESULTS: The population of children with meningeal signs comprised 99 with bacterial meningitis (27%), 36 with another serious bacterial infection (10%), and 225 with a self-limiting disease (63%). Application of the rule would reduce lumbar punctures by 12% and hospitalizations for empirical treatment by 15% with the same diagnostic accuracy as current practice. Cost savings were estimated at Euro292 per patient (relative reduction 10%) and were mainly achieved in the treatment course (Euro259). CONCLUSIONS: A diagnostic decision rule for children with meningeal signs has the potential to improve the appropriate use of medical resources, to be cost-effective, and to ascertain the absence of bacterial meningitis earlier.

Cost-utility analysis of patient care in children with meningeal signs.

OBJECTIVES: We designed a model of diagnostic and therapeutic interventions applied in children with meningeal signs. Using this model, we determined in a cost-utility analysis the consequences for society of different diagnostic strategies in terms of quality-adjusted life-years (QALYs) and costs. METHODS: Data were used from 360 children (0.1-15 years) visiting the pediatric emergency department of the Sophia Children's Hospital Rotterdam, The Netherlands (1988-98) with meningeal signs. Model inputs included probabilities of meningitis and adverse outcome, QALYs for years lived with long-term sequelae, and costs of tests and treatments. Mean outcome measures were costs and effects of diagnostic and therapeutic interventions in children suspected of bacterial meningitis, key determinants of the model outcomes, and evaluation of alternative diagnostic strategies and two vaccination programs in an analysis. RESULTS: The population comprised 99 children with bacterial meningitis (adverse outcome in 10), 36 with serious other bacterial infections, and 225 with self-limiting diseases. Key determinants were the risk of bacterial meningitis or sequelae, costs of treatment, and long-term morbidity. Minimizing lumbar punctures and empirical treatments using a diagnostic decision rule, without missing a single case of meningitis, was a dominant strategy to actual practice. Vaccination strategies of Streptococcus pneumoniae and Neisseria meningitidis resulted in our model in incremental cost-utility ratios of 401,965 Euro dollar ([symbol: see text])/QALY and [symbol: see text]22,635/QALY, respectively. CONCLUSIONS: Costs of long-term morbidity of bacterial meningitis largely outweigh diagnostic and treatment costs. Modeling interventions in children at risk of bacterial meningitis should include long-term consequences in terms of costs and QALYs.

Quality assurance study of bacterial antigen testing of cerebrospinal fluid.

Bacterial antigen testing (BAT) of cerebrospinal fluid (CSF) by latex agglutination is a low-yield procedure in patients whose CSF specimens have normal laboratory parameters. Between August 1992 and August 1994, we evaluated 287 bacterial antigen (BA) test requests to determine whether yields could be improved and whether patient costs could be reduced by cancelling BAT for those patients with normal CSF parameters (cell count, protein, glucose) after consultation with physicians. A total of 171 (68%) BA tests were canceled by this approach. None of these CSF specimens was culture positive for an organism detectable by BAT. Of the remaining 116 CSF specimens tested, only 3 were positive by BAT, one each for Neisseria meningitidis, Streptococcus pneumoniae, and group B streptococcus. Only 43 of the CSF specimens tested had at least two abnormal parameters; the 3 positive CSF specimens were included in this group. In light of the low rate of positivity, the number of BA tests can be further reduced by establishing criteria that must be met before a CSF specimen is accepted for BAT. After review of our data and the literature concerning this topic, we concluded that only specimens with leukocyte counts of > or = 50 cells per mm3 should be tested. Of 287 specimens evaluated in our study, only 36 met this criterion, including the 3 BA-positive specimens. Enacting such a restriction would have reduced the total number of BA tests by 251 (87%) without compromising patient care. A laboratory cost savings of $6,500 per year would have been realized, with a substantial reduction in the cost per positive test. Patient charges would have been reduced by $12,500 per year.