Long-term health and socioeconomic consequences of childhood and adolescent onset of meningococcal meningitis.

We estimated the long-term socioeconomic consequences and health care costs of Neisseria meningitidis meningitis (NM). The prospective cohort study included Danish individuals with onset of NM in childhood and adolescence, diagnosed between 1980 and 2009. Health care costs and socioeconomic data were obtained from nationwide administrative and health registers. Two thousand nine hundred two patients were compared with 11,610 controls matched for age, gender, and other sociodemographic characteristics. In the follow-up analysis at the age of 30 years, 1028 patients were compared with 4452 controls. We found that (1) NM caused increased mortality at disease onset, but after adequate treatment, the mortality rate was similar to that of the general population; (2) neurological and eye diseases were more frequently observed in patients; (3) patients had significantly lower grade-point averages; (4) patients had lower income even when transfer payments were taken into account; and (5) patients' initial health care costs were elevated.Conclusion: NM has significant influence on mortality, morbidity, education, and income. We suggest that the management of patients with previous meningococcal meningitis should focus on early educational and social interventions to improve social and health outcomes. What is known: • Meningococcal meningitis is a severe infectious disease affecting children and adolescents with high rates of mortality and complications. What is new: • Meningococcal meningitis causes increased mortality at disease onset, but after adequate treatment the mortality rate is similar to that of the general population. • Meningococcal meningitis in childhood and adolescence has a major long-term effect on morbidity, health care costs, education, employment, and income.

Costs of Neisseria meningitidis Group A Disease and Economic Impact of Vaccination in Burkina Faso.

BACKGROUND: Five years since the successful introduction of MenAfriVac in a mass vaccination campaign targeting 1- to 29-year-olds in Burkina Faso, consideration must be given to the optimal strategies for sustaining population protection. This study aims to estimate the economic impact of a range of vaccination strategies in Burkina Faso. METHODS: We performed a cost-of-illness study, comparing different vaccination scenarios in terms of costs to both households and health systems over a 26-year time horizon. These scenarios are (1) reactive vaccination campaign (baseline comparator); (2) preventive vaccination campaign; (3) routine immunization at 9 months; and (4) a combination of routine and an initial catchup campaign of children under 5. Costs were estimated from a literature review, which included unpublished programmatic documents and peer-reviewed publications. The future disease burden for each vaccination strategy was predicted using a dynamic transmission model of group A Neisseria meningitidis. RESULTS: From 2010 to 2014, the total costs associated with the preventive campaign targeting 1- to 29-year-olds with MenAfriVac were similar to the estimated costs of the reactive vaccination strategy (approximately 10 million US dollars [USD]). Between 2015 and 2035, routine immunization with or without a catch-up campaign of 1- to 4-year-olds is cost saving compared with the reactive strategy, both with and without discounting costs and cases. Most of the savings are accrued from lower costs of case management and household costs resulting from a lower burden of disease. After the initial investment in the preventive strategy, 1 USD invested in the routine strategy saves an additional 1.3 USD compared to the reactive strategy. CONCLUSIONS: Prevention strategies using MenAfriVac will be significantly cost saving in Burkina Faso, both for the health system and for households, compared with the reactive strategy. This will protect households from catastrophic expenditures and increase the development capacity of the population.

Economic benefits of keeping vaccines at ambient temperature during mass vaccination: the case of meningitis A vaccine in Chad.

OBJECTIVE: To evaluate the potential economic benefits of keeping a meningitis A vaccine at or near ambient temperature for up to 4 days during a mass vaccination campaign. METHODS: During a 10-day mass vaccination campaign against meningitis A in three regions of Chad in 2011, the costs associated with storage and transport of the vaccine in a traditional cold chain system were evaluated. A mathematical model was used to estimate the savings that could have been achieved if the vaccine had been stored at or near ambient temperature--in a "controlled temperature" chain--at the peripheral levels of the supply chain system. FINDINGS: The cost of the cold chain and associated logistics used in the campaign in Chad was 0.24 United States dollars (US$) per person vaccinated. In the modelled scenario for a controlled temperature chain, however, these costs dropped by 50% and were estimated to be only US$ 0.12 per person vaccinated. CONCLUSION: The implementation of a "controlled temperature" chain at the most peripheral levels of the supply chain system--assuming no associated loss of vaccine potency, efficacy or safety--could result in major economic benefits and allow vaccine coverage to be extended in low-resource settings.

Cost of acute hospitalization and post-discharge follow-up care for meningococcal disease in the US.

The combined costs of acute hospitalization and post-discharge follow-up care in patients with meningococcal disease have not been widely documented. In this study, data were retrospectively analyzed from three large databases of hospital discharge records and commercial insurance claims in the US. Cases of meningococcal disease were defined as admissions with an ICD-9-CM diagnosis code in the range of 036.x. From the 2005 HCUP Nationwide Inpatient Sample, 349 (weighted N=1,710) meningococcal-related hospitalizations were identified with a mean facility cost (in 2009 dollars) of $19,526 per admission. Similar estimates ($18,119 and $20,066, respectively) were obtained from 268 admissions identified in the LifeLink (formerly PharMetrics) database during 1999-2007 and from 1,058 hospitalizations in the Perspective Comparative Database (PCD) during 2000-2007. Using insurance claims from LifeLink, we estimated that payers incur an additional $26,178 in non-facility (professional and other ancillary) costs during the course of a meningococcal admission, as well as $22,230 in additional medical and pharmacy expenses for post-discharge care during the ensuing year. The majority of follow-up costs ($14,637) were attributed to repeat hospitalizations. Mean length of stay for meningococcal disease was consistently estimated across databases at 8 to 9 days. Data from the PCD further suggested that meningococcal disease carries, on average, nearly 2 days of intensive care unit utilization. In conclusion, hospital admissions for meningococcal disease are costly to payers. These costs are heightened when non-facility services and post-discharge care are also considered. Awareness of the full cost burden of meningococcal disease is needed when evaluating vaccination programs targeting the disease.

Pediatric meningococcocal meningitis in the acute phase: how much does it cost?

BACKGROUND: Meningococcal meningitis (MM) is known to be responsible of high cost for the Public Health Administration. Aim of the work is to calculate the costs for the hospitalization of pediatric patients affected by MM. METHODS: We calculate the costs for the hospitalization of pediatric patients affected by MM in the acute phase (HAP) over a nine year period. We performed a MEDLINE search to verify the cost of MM HAP reported in other studies. RESULTS: At Bambino Gesù Children Hospital, the median cost of HAP was of 12,604 euro (range from 9203 to 35,050 euro). Comparing our data with the previous studies, we find out similar results of approximately 16,750 euro (range 12,000-20,000 euro). DISCUSSION: Despite the relative rarety of the disease, MM is associated to direct high cost of HAP. CONCLUSIONS: Hospital costs are an important end-point in health economic evaluation of the disease and may be useful to policy makers and health economists to understand the potential benefit of improving meningococcal vaccination programmes.

Economics of an adolescent meningococcal conjugate vaccination catch-up campaign in the United States.

BACKGROUND: In June 2005, the Advisory Committee on Immunization Practices recommended the newly licensed quadrivalent meningococcal conjugate vaccine for routine use among all US children aged 11 years. A 1-time catch-up vaccination campaign for children and adolescents aged 11-17 years, followed by routine annual immunization of each child aged 11 years, could generate immediate herd immunity benefits. The objective of our study was to analyze the cost-effectiveness of a catch-up vaccination campaign with quadrivalent meningococcal conjugate vaccine for children and adolescents aged 11-17 years. METHODS: We built a probabilistic model of disease burden and economic impacts for a 10-year period with and without a program of adolescent catch-up meningococcal vaccination, followed by 9 years of routine immunization of children aged 11 years. We used US age- and serogroup-specific surveillance data on incidence and mortality. Assumptions related to the impact of herd immunity were drawn from experience with routine meningococcal vaccination in the United Kingdom. We estimated costs per case, deaths prevented, life-years saved, and quality-adjusted life-years saved. RESULTS: With herd immunity, the catch-up and routine vaccination program for adolescents would prevent 8251 cases of meningococcal disease in a 10-year period (a 48% decrease). Excluding program costs, this catch-up and routine vaccination program would save US$551 million in direct costs and $920 million in indirect costs, including costs associated with permanent disability and premature death. At $83 per vaccinee, the catch-up vaccination would cost society approximately $223,000 per case averted, approximately $2.6 million per death prevented, approximately $127,000 per life-year saved, and approximately $88,000 per quality-adjusted life-year saved. Targeting counties with a high incidence of disease decreased the cost per life-year saved by two-thirds. CONCLUSIONS: Although costly, catch-up and routine vaccination of adolescents can have a substantial impact on meningococcal disease burden. Because of herd immunity, catch-up and routine vaccination cost per life-year saved could be up to one-third less than that previously assessed for routine vaccination of children aged 11 years.

Lifetime cost of meningococcal disease in France: Scenarios of severe meningitis and septicemia with purpura fulminans.

Invasive meningococcal disease (IMD) is life-threatening and can result in severe sequelae. In France, no data have been published on the costs of severe IMD cases. Two realistic scenarios were developed with national experts (clinicians and social workers): a 6-year-old child with purpura fulminans with amputation of both legs below the knee (case A) and a 3-year-old with meningitis and severe neurological sequelae (case B). Additional scenarios included other typical sequelae of IMD such as chronic kidney disease (CKD), profound deafness and epilepsy. Data on healthcare, disability, educational and other resource use were obtained from experts and families of patients with similar sequelae. Unit costs (2013) were mainly obtained from the literature and the National Health Insurance (NHI). Time horizon was based on life expectancies of patients (77 and 55 years, respectively). A 4% discount rate decreasing to 2% after 30 years was applied. Costs are presented from the perspective of the NHI, publicly funded organizations and patients' families or their private health insurances. purpura fulminans with amputations is associated with a lifelong discounted cost of €768,875. Adding CKD doubles the amount (€1,480,545). Meningitis with severe neuro-cognitive sequelae results in a lifelong discounted cost of €1,924,475. Adding profound deafness and epilepsy slightly increases the total cost (€2,267,251). The first year is the most expensive in both scenarios (€166,890 and €160,647 respectively). The main cost drivers for each scenario are prostheses and child/adult stays in healthcare facilities, respectively. Overall, patients' families or his private insurance had to pay around 13% of total cost (101,833€ and 258,817€, respectively). This study fills a gap in the body of knowledge on IMD sequelae care and lifetime costs in France. The potentially high economic burden of IMD, in addition to its physical, psychological and social burden, reinforces the need for prevention.

Review of the cost effectiveness of immunisation strategies for the control of epidemic meningococcal meningitis.

Outbreaks of meningococcal disease have caused devastation worldwide. Effective vaccines have not been used routinely, due to perceived limitations of the duration of effectiveness as well as immunogenicity when administered during infancy. Given the sporadic nature of outbreaks, the optimal use of these vaccines to control both short-term epidemic and endemic meningococcal disease has been the subject of much debate. Seven economic studies on the use of polysaccharide vaccination strategies help to highlight the relevant epidemiological and economic issues surrounding the decisions for their use. Five of these studies were based in Africa, the region where annual incidence rates can be several orders of magnitude greater than the rest of the world. These studies demonstrated that vaccination against meningococcal disease during outbreak situations is suboptimal given the inability to rapidly immunise populations in a timely fashion in resource-poor areas. However, depending on the disease incidence and the ability to deliver vaccines, the polysaccharide vaccine can be cost effective for preventive strategies when given prior to the start of outbreaks, either through presumptive vaccination or through a modified routine delivery strategy. Economic analyses of mass immunisation campaigns and modelled routine vaccination suggest that routine use of meningococcal vaccines for preventive strategies could be within the range of cost-effective public health interventions in those regions of the world where meningococcal disease is endemic. This includes the meningococcal belt of Africa, the Sahelian region.

Four days of penicillin therapy for meningococcal meningitis.

Fifty consecutive patients with meningococcal meningitis aged 7 to 75 years (mean, 29 years) were treated with intravenous penicillin G sodium (2 to 3 X 10(5) U/kg/d) for four days. Two of the patients (both teenagers) died of fulminant infection during the first 36 hours of therapy and one elderly woman developed aspiration pneumonia requiring penicillin therapy to be prolonged beyond four days. The remaining 47 patients recovered from the infection. On the fourth day, fever, mild meningeal signs, and moderate elevations of cerebrospinal fluid cell counts and protein contents persisted in some patients; nevertheless, all patients were cured without relapse. The results of our study suggest that meningococcal meningitis may be successfully treated with a four-day course of intravenous penicillin G.

Evaluation of meningococcal meningitis vaccination strategies for the meningitis belt in Africa.

BACKGROUND: Although the meningococcal polysaccharide vaccine has contributed to the control of Group A meningitis in the "meningitis belt" of Africa, recurrent large outbreaks have led to questions regarding vaccination strategy. We evaluated current and hypothetical vaccination strategies for the region. METHODS: A model was formulated to analyze the effectiveness and costs of vaccine campaigns in response to outbreaks based on 7 years of weekly incidence data from Burkina Faso. Additional models analyzed the potential impact and costs of either a 1- or 4-dose routine scheduled delivery of meningococcal polysaccharide vaccine based on data reported to the World Health Organization from 16 countries during 1948 through 1996. Vaccine efficacy, vaccination coverage and economic data from literature reviews provided model assumptions. RESULTS: For Burkina Faso neither 1- nor 4-dose vaccination schedules would prevent >30% of meningitis cases compared with the 42% prevented through an outbreak response program of vaccinating districts, which reach an incidence of 15 per 100000 persons for 2 weeks. For the entire meningitis belt, routine coverage with the 1- or 4-dose schedule meningococcal vaccine would require 4.9 and 19.6 million doses annually, respectively, for an annual net cost of $4.4 to $12.3 million and prevent an average 10300 to 12600 cases (23 to 28%), assuming a long term vaccine efficacy of 50%. In addition an initial "catch-up" campaign costing up to $72 million to vaccinate the population from 1 to 30 years of age would be required before achieving that level of effectiveness. CONCLUSION: Given the relatively poor routine vaccination coverage in this region, current strategies of vaccination campaigns that achieve higher coverage would generally be more effective and less costly than the modeled routine scheduled programs, assuming that campaigns can be rapidly implemented. Until a better vaccine is available, countries in this region would be more efficient in improving the response times to outbreaks, perhaps through improved surveillance, and in bolstering existing vaccination infrastructures rather than embarking on strategies of questionable effectiveness.

Control of epidemic group A meningococcal meningitis in Nepal.

During the first six months of 1983, an epidemic of serogroup A meningococcal meningitis occurred in the Kathmandu valley of Nepal, resulting in 875 cases and 95 deaths. The annual attack rate was 103 cases per 100,000 population, with a peak attack rate occurring in April. Epidemic meningococcal disease had not been recognized previously in Nepal. Early in 1984, a review of hospital-based data on pyogenic meningitis in Kathmandu showed three times as many cases per month compared with the same period the previous year, suggesting that a recurrent epidemic was unfolding. Beginning in February 1984, a vaccination campaign directed at a high-risk target population of people aged 1-24 years was launched; over 329,000 doses of bivalent A/C meningococcal vaccine were given, achieving approximately 64% coverage of the target population. A dramatic decline in the number of new meningitis cases occurred coincident with the initiation of the mass vaccination campaign. This experience demonstrates that it is possible, with appropriate surveillance efforts, to detect an evolving epidemic of meningococcal disease early in its course and to institute control measures in advance of the expected epidemic peak.

Neisseria meningitidis serogroup A vaccines: an overview.

A recent report by the Weekly Epidemiological Record of an outbreak of Neisseria meningitidis serogroup A in the Great Lakes region shows that meningococcal epidemics are an unsolved problem in resource-poor countries, particularly in Africa [1]. During the last epidemic wave in the 1990s, about 350,000 people developed meningitis and 1000 people died [101]. An effective polysaccharide vaccine has been available since the early 1970s. Unfortunately, attempts to contain the epidemics by timely detection of cases through active surveillance and prompt mass vaccination campaigns have failed to prevent the deaths of thousands of people in several African countries in the 1980s and 1990s. This article describes the epidemiology of N. meningitidis serogroup A, the available polysaccharide vaccines, their advantages and limitations. The current vaccination policies and their economic implications are discussed, to clarify why the use of an effective vaccine has, to date, been disappointing. The recent exciting developments with respect to conjugate vaccines are described.

A cost-effectiveness analysis of vaccination strategies against N. meningitidis meningitis in sub-Saharan African countries.

This analysis evaluates the cost-effectiveness (C/E) of routine vaccination against Neisseria meningitidis. Three different preventive strategies are analyzed: mass vaccination during epidemics (the current standard of care), routine preventive vaccination and a combination strategy of routine vaccination with mass vaccination during epidemics. A Markov model is used to simulate the epidemics of meningitis in a cohort of 5-year old children and compare these different strategies. The results show that mass vaccination strategy is dominated by the two other strategies. The incremental C/E ratios are US$50/QALY for the routine vaccination, and US$199/QALY for the combination strategy. The costs per fatal case averted are US$1161 for the routine vaccination, and US$2397 for the combination strategy. The C/E ratios are sensitive to: the incidence of meningococcal meningitis, the costs of treating cases, the costs of routine vaccination and the costs and effectiveness of mass immunization campaign. However the rank ordering of the strategies is almost never altered. In conclusion, the results of this analysis suggest that mass vaccination in sub-Saharan Africa in case of epidemics should be reconsidered. Routine vaccination against meningococcal meningitis at an early age, with or without mass vaccination during epidemics is more effective, with a C/E ratio within the range of other vaccination strategies currently in place in Africa.

[Microeconomic evaluation of a mass preventive immunisation campaign against meningococcal meningitis and yellow fever in Senegal in 1997]. / Evaluation des coûts opérationnels d'une campagne de masse préventive contre la méningite à méningocoque et la fièvre jaune au Sénégal, en 1997.

Large epidemics of group A meningococcal meningitis occurred in 1995 and 1996 in several countries of the Sub-Saharan Africa zone known as the "meningitis belt", and more particularly in West Africa. Most of these countries affected by the epidemics met difficulties to set up the strategy recommended by the World Health Organization and which includes: Epidemiological surveillance and epidemic incidence threshold calculation to detect early meningitis epidemics and emergency vaccination campaigns with meningococcal A + C polysaccharide vaccine, if possible within the 4-to-6 weeks following the moment the threshold is reached. In this context of epidemics, notably in Mali, and in front of the risk of resurgence of yellow fever, the Ministry of Health of Senegal decided to conduct mass preventive immunization campaigns in 1997 against meningo- coccal meningitis and yellow fever in the districts located in the eastern part of the country and where emergency vaccination would have been difficult in case of epidemic because these area are difficult to reach. A short-term microeconomic evaluation of additional costs that are necessary to organize one of these mass preventive immunization campaigns was conducted in 1997 in the Matam District, in the Northeast part of Senegal. The method rested on value attribution and accounting procedure. The cost was defined as the monetary value of all mobilized resources to product the campaign corresponding to a plurality of charges and representing all of the effective expenses and donations. During this campaign, 85,925 people were vaccinated and a total number of 163,981 doses of both polysaccharide A + C meningococcal and yellow fever vaccines were administered within 3 weeks. Four intervention strategies were involved: Three for vaccination (mobile, fixed and outreach strategy) and one for coordination, information and training. The total cost of the campaign was 55,322.75 euros. Vaccines and solvents represented 60% of the total cost of the campaign, materiel for injection and safety of injection 26%, vaccination staff 7%, and logistics 7%. The mean cost was 0.34 euro per administered dose and 0.64 euro per vaccinee. The mean cost per administered dose of meningococcal vaccine was 0.44 euro. The mean cost of preventive meningococcal immunization was not higher than the mean cost of meningococcal vaccination during mass emergency immunization campaigns in other countries. The addition of yellow fever antigen brought down the campaign mean cost by 0.11 euro and it allowed economies of scales. Direct unit costs per administered dose were higher when people were vaccinated through the outreach strategy (0.35 euro) than when fixed and mobile strategies were used (0.318 and 0.323 euro, respectively). Costs related to transportation and staff were proportionally higher for the outreach strategy. Direct unit costs per administered dose were higher when vaccinations were done in rural areas (0.32 euro) than when done in urban areas (0.31 euro). Direct unit costs increased when the size of target communities decreased (in communities with less than 100 people to vaccinate versus 0.38 euro in communities with more than 2,000 people to vaccinate). This study allowed us to set up a method to measure, describe and analyze the costs of a mass preventive campaign. It demonstrated the economic impact of using multiple antigens during a single preventive campaign.

Costs of surviving meningococcal disease in Spain: evaluation for two cases of severe meningitis and septicaemia.

OBJECTIVES: The aim of this study was to count the lifelong rehabilitation costs associated with surviving meningococcal disease with major sequelae from the perspective of the Spanish National Healthcare System (NHS) and the national government. METHODS: Two severe scenarios describing meningococcal disease were developed, one case that represented meningococcal septicaemia and another case for meningococcal meningitis. The scenarios were developed based on a literature review on severe sequelae of meningococcal disease, and discussions with paediatricians who have been responsible for the treatment of children with this disease in Spain. Second, a detailed list of all health, educational and social care resources used by survivors during their acute illness and during the rest of their lives and by family members was obtained by interviewing survivors and their families. Professionals in health and social care were also interviewed to complete the list of resources and ensure the scenario's were accurate. The costs attributed to these resources were obtained from tariff lists, catalogues and published information by the national authorities. All costs were based on a life expectancy of a survivor of 70 years and expressed in EUR 2012. RESULTS: In this study it was estimated that the lifelong discounted rehabilitation costs associated with the treatment of long-term sequelae due to meningococcal disease are approximately €1180,000-€1400,000. Medical care and social care were the main cost drivers for both septicaemia and meningitis. Annual costs showed to be the largest in the first year after diagnosis of the disease for both cases, due to high hospital admission and medical care costs during this period and decreased significantly over the years. CONCLUSION: This study shows that the lifelong rehabilitation costs associated with the survival of meningococcal disease with severe sequelae place an important burden on the NHS budget and governmental resources in Spain.

The inpatient costs and hospital service use associated with invasive meningococcal disease in South Australian children.

BACKGROUND: Invasive meningococcal disease (IMD) remains a serious public health concern due to a sustained high case fatality rate and morbidity in survivors. This study aimed to estimate the hospital service costs associated with IMD and variables associated with the highest costs in Australian children admitted to a tertiary paediatric hospital. METHODS: Clinical details were obtained from medical records and associated inpatient costs were collected and inflated to 2011 Australian dollars using the medical and hospital services component of the Australian Consumer Price Index. Both unadjusted and adjusted analyses were undertaken. Multivariate regression models were used to adjust for potential covariates and determine independent predictors of high costs and increased length of hospital stay. RESULTS: Of 109 children hospitalised with IMD between May 2000 and April 2011, the majority were caused by serogroup B (70.6%). Presence of sequelae, serogroup B infection, male gender, infants less than one year of age, and previous medical diagnosis were associated with higher inpatient costs and length of stay (LOS) in hospital (p<0.001) during the acute admissions. Children diagnosed with septicaemia had a longer predicted LOS (p=0.033) during the acute admissions compared to those diagnosed with meningitis alone or meningitis with septicaemia. Serogroup B cases incurred a significantly higher risk of IMD related readmissions (IRR: 21.1, p=0.008) for patients with sequelae. Serogroup B infection, male gender, diagnosis of septicaemia, infants less than one year of age, and no previous medical diagnosis were more likely to have higher inpatient costs and LOS during the IMD related readmissions for patients with sequelae (p<0.05). CONCLUSION: Although IMD is uncommon, the disease severity and associated long-term sequelae result in high health care costs, which should be considered in meningococcal B vaccine funding considerations.