El declive de la incidencia de enfermedad meningocócica en Barcelona entre 1988 y 2015: la influencia de la vacunación frente al serogrupo C / The decline of the incidence of meningococcal disease in Barcelona between 1988 and 2015: the influence of the vaccine against serogroup C

Introducción y objetivo: El objetivo es conocer la evolución de la enfermedad meningocócica en la ciudad de Barcelona entre 1988 y 2015 y evaluar el impacto de la vacuna contra el serogrupo C. Materiales y métodos: Se analizó la evolución de casos de enfermedad meningocócica y por serogrupo a partir del registro de enfermedades de declaración obligatoria. Se comparó la incidencia de todos los serogrupos antes y después de la introducción de la vacunación contra el serogrupo C en el año 2000. Se analizó la cobertura vacunal entre los casos, el serogrupo entre casos vacunados y la tasa de mortalidad y letalidad. Resultados: La enfermedad meningocócica ha pasado de una incidencia en menores de un año de 63,09 casos por 100.000 en 1997-2000 a 15,44 en 2001-2015. Todos los serogrupos han disminuido su incidencia tras la implementación vacunal, especialmente en niños de uno a 4 años para el C. A partir del 2000 la cobertura vacunal en los casos por este serogrupo era del 7,6% y en los afectos por el B era del 35,0% (p<0,01). De los vacunados, el 66,4% de los casos fue serogrupo B y un 5,2% fue C (p<0,01). La tasa global de letalidad y de mortalidad fue del 7,7% y del 0,19/100.000 respectivamente, sin cambios significativos en el tiempo en cuanto a la letalidad. Conclusiones: La incidencia por serogrupo C y también por B ha disminuido tras la vacunación sistemática contra el serogrupo C. La vacunación contra el serogrupo B podría reducir aún más esta grave enfermedad con una letalidad importante que no ha disminuido en todo el periodo

Introduction and objective: The purpose of this study was to describe the evolution of meningococcal disease (MD) in the city of Barcelona between 1988 and 2015 and to assess the impact of the vaccine against serogroup C. Materials and methodology: The evolution of MD and by serogroup was analysed using the information included in the mandatory notification diseases registry. Incidences of all serogroups between the periods of before and after the implementation of the serogroup C vaccine in 2000 were compared. Vaccination coverage among cases, serogroup among vaccinated cases and mortality and case fatality rates were analysed. Results: MD has evolved from an incidence rate in children aged under 1 of 63.09 cases per 100,000 in 1997-2000 to 15.44 per 100,000 in 2001-2015. All MD serogroups incidences decreased after the implementation of the vaccine, especially for serogroup C among children aged between 1 and 4. Since 2000 vaccine coverage in MD cases by this serogroup was 7.6% while in those affected by serogroup B it was 35.0% (p<.01). Among those vaccinated, 66.4% of cases were serogroup B and 5.2% were C (p<.01). Mortality and case fatality rates were 7.7% and 0.19/100,000 respectively, without significant changes in time regarding case fatality. Conclusions: Incidence caused by serogroups B and C has decreased after the systematic vaccination against serogroup C. Vaccination against serogroup B could further reduce the impact of this lethal disease which has not decreased during this period

Post-licensure safety surveillance study of routine use of quadrivalent meningococcal diphtheria toxoid conjugate vaccine (MenACWY-D) in infants and children.

BACKGROUND: Menactra® vaccine (MenACWY-D) was licensed in the United States in 2005 for persons 11-55 years of age, in 2007 for children 2-10 years of age, and in 2011 for infants/toddlers 9-23 months of age. We conducted two studies at Kaiser Permanente Northern California (KPNC), an integrated health care organization, to assess the safety of MenACWY-D in 2-10-year-olds and 9-23-month-olds receiving the vaccine during routine clinical care. METHODS: We conducted observational, retrospective studies of MenACWY-D in 2-10-year-olds (October 2007-October 2010) and in 9-23-month-olds (June 2011-June 2014). We monitored all subjects for non-elective hospitalizations, emergency department visits, and selected outpatient outcomes (specified neurological conditions, hypersensitivity reactions and new-onset autoimmune diseases) up to 6 months after vaccination, depending on the study. Using a self-control risk-interval design, we calculated incidence rate ratios (IRRs) comparing outcomes during the post-vaccination risk interval (0-30 days) with those during more remote post-vaccination comparison intervals (31-60 and 31-180 days [children] or 31-75 days [infants/toddlers]). RESULTS: There were 1421 children aged 2-10 years and 116 infants/toddlers aged 9-23 months who received MenACWY-D. Approximately 30% of the 2-10-year-olds and 67% of the 9-23-month-olds were considered at increased risk of meningococcal disease. Among 2-10-year-olds, there was 1 hospitalization on post-vaccination day 5 for fever, which was considered possibly related to vaccination. The only significantly elevated outcome among 2-10-year-olds was cellulitis/abscess (2 cases occurred during the risk interval versus 0 during comparison interval; IRR not evaluable [NE], 95% CI: 1.42, NE). After medical record review, the 2 cases were considered unrelated to vaccination. Among 9-23-month-olds, no outcomes were significantly elevated after vaccination and there were no hospitalizations. There were no deaths observed during the three-year accrual and subsequent six-month surveillance period for either study. CONCLUSIONS: Immunization of infants and young children with MenACWY-D vaccine was not associated with any new safety concerns; however, these small studies had limited power to detect rare or uncommon safety events. ClinicalTrials.gov Identifiers are NCT00728260 and NCT01689155.

ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: an infectious diseases perspective (Soluble immune effector molecules [II]: agents targeting interleukins, immunoglobulins and complement factors).

BACKGROUND: The present review is part of the ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies. AIMS: To review, from an Infectious Diseases perspective, the safety profile of agents targeting interleukins, immunoglobulins and complement factors and to suggest preventive recommendations. SOURCES: Computer-based MEDLINE searches with MeSH terms pertaining to each agent or therapeutic family. CONTENT: Patients receiving interleukin-1 (IL-1) -targeted (anakinra, canakinumab or rilonacept) or IL-5-targeted (mepolizumab) agents have a moderate risk of infection and no specific prevention strategies are recommended. The use of IL-6/IL-6 receptor-targeted agents (tocilizumab and siltuximab) is associated with a risk increase similar to that observed with anti-tumour necrosis factor-α agents. IL-12/23-targeted agents (ustekinumab) do not seem to pose a meaningful risk of infection, although screening for latent tuberculosis infection may be considered and antiviral prophylaxis should be given to hepatitis B surface antigen-positive patients. Therapy with IL-17-targeted agents (secukinumab, brodalumab and ixekizumab) may result in the development of mild-to-moderate mucocutaneous candidiasis. Pre-treatment screening for Strongyloides stercoralis and other geohelminths should be considered in patients who come from areas where these are endemic who are receiving IgE-targeted agents (omalizumab). C5-targeted agents (eculizumab) are associated with a markedly increased risk of infection due to encapsulated bacteria, particularly Neisseria spp. Meningococcal vaccination and chemoprophylaxis must be administered 2-4 weeks before initiating eculizumab. Patients with high-risk behaviours and their partners should also be screened for gonococcal infection. IMPLICATIONS: Preventive strategies are particularly encouraged to minimize the occurrence of neisserial infection associated with eculizumab.

Dental provider practices and perceptions regarding adolescent vaccination.

OBJECTIVE: To assess dental providers' clinical practices and perceptions regarding adolescent vaccinations. METHODS: We surveyed 234 dental providers in an integrated health care setting in Portland, Oregon, in March-April 2015. We assessed participants' knowledge of adolescent vaccines, barriers to recommending vaccines, and their perceived role in the promotion of vaccination and preventive medical care. RESULTS: Over 80 percent of respondents correctly identified influenza, tetanus-diphtheria-acellular pertussis, and human papillomavirus as vaccinations recommended for adolescents; 60 percent correctly identified meningococcal conjugate. Forty-four percent of providers reported previously discussing vaccination with their adolescent patients. Lack of knowledge (66 percent), uncertainty about whether patients would accept recommendations (62 percent), and lack of time (61 percent) were commonly reported barriers. While few providers expressed personal concerns about the safety (13 percent) and effectiveness (10 percent) of adolescent vaccines, most believed parents had concerns about safety (70 percent) and effectiveness (60 percent). Although 80 percent endorsed the premise that providers should discuss preventive medical care with their patients, only 54 percent said they should discuss vaccinations specifically. CONCLUSIONS: Dental providers reported several barriers to recommending vaccines. While comfortable with discussing preventive medical care in general, providers are less comfortable making vaccine recommendations to their patients. Vaccine recommendations are not a traditional practice among dental providers and may require additional education and communication tools.

National, Regional, State, and Selected Local Area Vaccination Coverage Among Adolescents Aged 13-17 Years - United States, 2016.

The Advisory Committee on Immunization Practices (ACIP) recommends that adolescents routinely receive tetanus, diphtheria, and acellular pertussis vaccine (Tdap), meningococcal conjugate vaccine (MenACWY), and human papillomavirus (HPV) vaccine (1) at age 11-12 years. ACIP also recommends catch-up vaccination with hepatitis B vaccine, measles, mumps, and rubella (MMR) vaccine, and varicella vaccine for adolescents who are not up to date with childhood vaccinations. ACIP recommends a booster dose of MenACWY at age 16 years (1). In December 2016, ACIP updated HPV vaccine recommendations to include a 2-dose schedule for immunocompetent adolescents initiating the vaccination series before their 15th birthday (2). To estimate adolescent vaccination coverage in the United States, CDC analyzed data from the 2016 National Immunization Survey-Teen (NIS-Teen) for 20,475 adolescents aged 13-17 years.* During 2015-2016, coverage increased for ≥1 dose of Tdap (from 86.4% to 88.0%) and for each HPV vaccine dose (from 56.1% to 60.4% for ≥1 dose). Among adolescents aged 17 years, coverage with ≥2 doses of MenACWY increased from 33.3% to 39.1%. In 2016, 43.4% of adolescents (49.5% of females; 37.5% of males) were up to date with the HPV vaccination series, applying the updated HPV vaccine recommendations retrospectively.† Coverage with ≥1 HPV vaccine dose varied by metropolitan statistical area (MSA) status and was lowest (50.4%) among adolescents living in non-MSA areas and highest (65.9%) among those living in MSA central cities.§ Adolescent vaccination coverage continues to improve overall; however, substantial opportunities exist to further increase HPV-associated cancer prevention.

Analysis of novel meningococcal vaccine formulations.

The protective effect of meningococcal vaccines targeting disease causing serogroups exemplified by the introduction of MenAfriVac™ in Africa, is well established and documented in large population-based studies. Due to the emergence of other meningococcal disease causing serogroups, novel vaccine formulations are needed. There is a high potential for novel nanotechnology-based meningococcal vaccine formulations that can provide wider vaccine coverage. The proposed meningococcal vaccine formulation contains spherical shaped micro and nanoparticles that are biological mimics of Niesseria meningitidis, therefore present to immune system as invader and elicit robust immune responses. Vaccine nanoparticles encapsulate meningococcal CPS polymers in a biodegradable material that slowly release antigens, therefore enhance antigen presentation by exerting antigen depot effect. The antigenicity of meningococcal vaccine delivered in nanoparticles is significantly higher when compared to vaccine delivered in solution. Preclinical studies are required to assess the immunogenicity of novel vaccine formulations. Therefore, implementing various in-vitro human immune cell-based assays that mimic in-vivo interactions, would provide good insight on optimal antigen dose, effective antigen presentation, facilitate screening of various vaccine and adjuvant combinations and predict in-vivo immunogenicity. This rapid approach is cost-effective and provides data required for the preclinical immunogenicity assessment of novel meningococcal vaccine formulations.

Preventative Care in the Patient with Inflammatory Bowel Disease: What Is New?

Patients with inflammatory bowel disease (IBD) do not receive routine preventative care at the same rate as general medical patients. This patient population is at increased risk of vaccine preventable illness such as influenza and pneumococcal pneumonia. This review will discuss health maintenance needs and preventative care issues in patients with IBD.

Background Paper for the update of meningococcal vaccination recommendations in Germany: use of the serogroup B vaccine in persons at increased risk for meningococcal disease.

In December 2013 Bexsero® became available in Germany for vaccination against serogroup B meningococci (MenB). In August 2015 the German Standing Committee on Vaccination (STIKO) endorsed a recommendation for use of this vaccine in persons at increased risk of invasive meningococcal disease (IMD). This background paper summarizes the evidence underlying the recommendation. Bexsero® is based on surface protein antigens expressed by about 80% of circulating serogroup B meningococci in Germany. The paper reviews available data on immunogenicity and safety of Bexsero® in healthy children and adolescents; data in persons with underlying illness and on the effectiveness in preventing clinical outcomes are thus far unavailable.STIKO recommends MenB vaccination for the following persons based on an individual risk assessment: (1) Persons with congenital or acquired immune deficiency or suppression. Among these, persons with terminal complement defects and properdin deficiency, including those under eculizumab therapy, are at highest risk with reported invasive meningococcal disease (IMD) incidences up 10,000-fold higher than in the general population. Persons with asplenia were estimated to have a ~ 20-30-fold increased risk of IMD, while the risk in individuals with other immune defects such as HIV infection or hypogammaglobulinaemia was estimated at no more than 5-10-fold higher than the background risk. (2) Laboratory staff with a risk of exposure to N. meningitidis aerosols, for whom an up to 271-fold increased risk for IMD has been reported. (3) Unvaccinated household (-like) contacts of a MenB IMD index case, who have a roughly 100-200-fold increased IMD risk in the year after the contact despite chemoprophylaxis. Because the risk is highest in the first 3 months and full protective immunity requires more than one dose (particularly in infants and toddlers), MenB vaccine should be administered as soon as possible following identification of the serogroup of the index case.

Characterization of Propylene Glycol-Mitigated Freeze/Thaw Agglomeration of a Frozen Liquid nOMV Vaccine Formulation by Static Light Scattering and Micro-Flow Imaging.

UNLABELLED: The purpose of this work was to investigate the susceptibility of an aluminum adjuvant and an aluminum-adjuvanted native outer membrane vesicle (nOMV) vaccine formulation to freeze/thaw-induced agglomeration using static light scattering and micro-flow Imaging analysis; and to evaluate the use of propylene glycol as a vaccine formulation excipient by which freeze/thaw-induced agglomeration of a nOMV vaccine formulation could be mitigated. Our results indicate that including 7% v/v propylene glycol in an nOMV containing aluminum adjuvanted vaccine formulation, mitigates freeze/thaw-induced agglomeration. LAY ABSTRACT: We evaluated the effect of freeze-thawing on an aluminum adjuvant and an aluminum adjuvanted native outer membrane vesicle (nOMV) vaccine formulation. Specifically, we characterized the freeze/thaw-induced agglomeration through the use of static light scattering, micro-flow imaging, and cryo-electron microscopy analysis. Further, we evaluated the use of 0-9% v/v propylene glycol as an excipient which could be included in the formulation for the purpose of mitigating the agglomeration induced by freeze/thaw. The results indicate that using 7% v/v propylene glycol as a formulation excipient is effective at mitigating agglomeration of the nOMV vaccine formulation, otherwise induced by freeze-thawing.

Depressive symptoms and immune response to meningococcal conjugate vaccine in early adolescence.

Research findings in psychoneuroimmunology document reliable, bidirectional linkages among psychological processes, the nervous system, and the immune system. However, available data are based almost entirely on animal and adult human studies; the application to children and adolescents is uncertain. We capitalized on the experimental leverage provided by a routine vaccination to examine the link between mood symptoms and the immune response to a vaccine challenge in early adolescence. One hundred twenty-six 11-year-olds for whom vaccine response data were available were assessed at prevaccination and 4 weeks, 3 months, and 6 months following vaccination; self-report ratings of depression and anxiety as well as measures of psychosocial and somatic risk were assessed prior to vaccine response. Analyses indicated that children's internalizing mood symptoms were associated with elevated and persistently higher antibody responses, with evidence extending to two of the four serogroups. The associations remained after controlling for multiple possible confounders (social class, body mass index, sleep, psychosocial risk, and pubertal status). The observed enhanced vaccine response associated with depressive and anxious symptoms in early adolescence may reflect an important developmental difference in immune system-brain interplay between adults and children, and it underscores the need for further developmental studies of psychoneuroimmunology.

Preclinical immunogenicity study of trivalent meningococcal AWX-OMV vaccines for the African meningitis belt.

In the recent decade, epidemic meningitis in the African meningitis belt has mostly been caused by Neisseria meningitidis of serogroups A, W and X (MenA, MenW and MenX, respectively). There is at present no licensed vaccine available to prevent MenX meningococcal disease. To explore a trivalent MenAWX vaccine concept, we have studied the immunogenicity in mice of MenX outer membrane vesicles (X-OMV) or MenX polysaccharide (X-PS) when combined with a bivalent A-OMV and W-OMV (AW-OMV) vaccine previously shown to be highly immunogenic in mice. The vaccine antigens were produced from three representative wild type strains of MenA (ST-7), MenW (ST-11) and MenX (ST-751) isolated from patients in the African meningitis belt. Groups of mice were immunized with two doses of X-OMV or X-PS combined with the AW-OMV vaccine or as individual components. All vaccine preparations were adsorbed to Al(OH)3. Sera from immunized mice were tested by ELISA and immunoblotting. Functional antibody responses were measured as serum bactericidal activity (SBA) and opsonophagocytic activity (OPA). Immunization of mice with X-OMV, alone or in combination with AW-OMV induced high levels of anti-X OMV IgG. Moreover, X-OMV alone or in combination with the AW-OMV vaccine induced high SBA and OPA titers against the MenX target strain. X-PS alone was not immunogenic in mice; however, addition of the AW-OMV vaccine to X-PS increased the immunogenicity of X-PS. Both AWX vaccine formulations induced high levels of IgG against A- and W-OMV and high SBA titers against the MenA and MenW vaccine strains. These results suggest that a trivalent AWX vaccine, either as a combination of OMV or OMV with X-PS, could potentially prevent the majority of meningococcal disease in the meningitis belt.

National, regional, state, and selected local area vaccination coverage among adolescents aged 13-17 years--United States, 2013.

The Advisory Committee on Immunization Practices (ACIP) recommends that adolescents routinely receive 1 dose of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine, 2 doses of meningococcal conjugate (MenACWY) vaccine, and 3 doses of human papillomavirus (HPV) vaccine.* ACIP also recommends administration of "catch-up"† vaccinations, such as measles, mumps, and rubella (MMR), hepatitis B, and varicella, and, for all persons aged ≥6 months, an annual influenza vaccination. ACIP recommends administration of all age-appropriate vaccines during a single visit. To assess vaccination coverage among adolescents aged 13-17 years, CDC analyzed data from the 2013 National Immunization Survey-Teen (NIS-Teen).§ This report summarizes the results of that analysis, which show that from 2012 to 2013, coverage increased for each of the vaccines routinely recommended for adolescents: from 84.6% to 86.0% for ≥1 Tdap dose; from 74.0% to 77.8% for ≥1 MenACWY dose; from 53.8% to 57.3% for ≥1 HPV dose among females, and from 20.8% to 34.6% for ≥1 HPV dose among males. Coverage varied by state and local jurisdictions and by U.S. Department of Health and Human Services (HHS) region. Healthy People 2020 vaccination targets for adolescents aged 13-15 years were reached in 42 states for ≥1 Tdap dose, 18 for ≥1 MenACWY dose, and 11 for ≥2 varicella doses. No state met the target for ≥3 HPV doses.¶ Use of patient reminder and recall systems, immunization information systems, coverage assessment and feedback to clinicians, clinician reminders, standing orders, and other interventions can help make use of every health care visit to ensure that adolescents are fully protected from vaccine-preventable infections and cancers (5), especially when such interventions are coupled with clinicians' vaccination recommendations.

Preclinical immunogenicity and functional activity studies of an A+W meningococcal outer membrane vesicle (OMV) vaccine and comparisons with existing meningococcal conjugate- and polysaccharide vaccines.

Meningococci of serogroups A and W (MenA and MenW) are the main causes of epidemic bacterial meningitis outbreaks in sub-Saharan Africa. In this study we prepared a detergent extracted outer membrane vesicle (dOMV) vaccine from representative African MenA and MenW strains, and compared the immunogenicity of this vaccine with existing meningococcal conjugate and polysaccharide (PS) vaccines in mice. NMRI mice were immunized with preclinical batches of the A+W dOMV vaccine, or with commercially available vaccines; a MenA conjugate vaccine (MenAfriVac(®), Serum Institute of India), ACYW conjugate vaccine (Menveo(®), Novartis) or ACYW PS vaccine (Mencevax(®), GlaxoSmithKline). The mice received 2 doses of 1/10 or 1/50 of a human dose with a three week interval. Immune responses were tested in ELISA, serum bactericidal activity (SBA) and opsonophagocytic activity (OPA) assays. High levels of IgG antibodies against both A and W dOMV were detected in mice receiving the A+W dOMV vaccine. High SBA titers against both MenA and MenW vaccine strains were detected after only one dose of the A+W dOMV vaccine, and the titers were further increased after the second dose. The SBA and OPA titers in mice immunized with dOMV vaccine were significantly higher than in mice immunized with the ACYW-conjugate vaccine or the PS vaccine. Furthermore, the A+W dOMV vaccine was shown to induce SBA and OPA titers against MenA of the same magnitude as the titers induced by the A-conjugate vaccine. In conclusion, the A+W dOMV vaccine induced high levels of functional antibodies to both MenA and MenW strains, levels that were shown to be higher or equal to the levels induced by licensed meningococcal vaccines. Thus, an A+W dOMV vaccine could potentially serve as an alternative or a supplement to existing conjugate and PS vaccines in the African meningitis belt.

Pilot scale production of the vaccine adjuvant Proteoliposome derived Cochleates (AFCo1) from Neisseria meningitidis serogroup B.

The use of new adjuvants in vaccine formulations is a subject of current research. Only few parenteral adjuvants have been licensed. We have developed a mucosal and parenteral adjuvant known as AFCo1 (Adjuvant Finlay Cochleate 1, derived from proteoliposomes of N. meningitidis B) using a dialysis procedure to produce them on lab scale. The immunogenicity of the AFCo1 produced by dialysis has been already evaluated, but it was necessary to demonstrate the feasibility of a larger-scale manufacturing process. Therefore, we used a crossflow diafiltration system (CFS) that allows easy scale up to obtain large batches in an aseptic environment. The aim of this work was to produce AFCo1 on pilot scale, while conserving the adjuvant properties. The proteoliposomes (raw material) were resuspended in a buffer containing sodium deoxycholate and were transformed into AFCo1 under the action of a calcium forming buffer. The detergent was removed from the protein solution by diafiltration to a constant volume. In this CFS, we used a hollow fiber cartridge from Amicon (polysulfona cartridge of 10 kDa porosity, 1mm channel diameter of fiber and 0.45 m² area of filtration), allowing production of a batch of up to 20 L. AFCo1 were successfully produced by tangential filtration to pilot scale. The batch passed preliminary stability tests. Nasal immunization of BALB/c mice, induced specific saliva IgA and serum IgG. The induction of Th1 responses were demonstrated by the induction of IgG2a, IFNγ and not IL-5. The adjuvant action over Neisseria (self) antigens and with co-administered (heterologous) antigens such as ovalbumin and a synthetic peptide from haemolytic Streptococcus B was also demonstrated.

Preclinical evaluation of MenB vaccines: prerequisites for clinical development.

Despite the widespread use of polysaccharide and conjugate vaccines against disease caused by several serogroups of Neisseria meningitidis, vaccines targeting meningococci expressing the serogroup B capsule (MenB) have focused on subcapsular antigens, due to crossreactivity of the polysaccharide with human glycoproteins. Protein vaccines composed of outer membrane vesicles have been used successfully to control epidemics of MenB disease in several countries; however, these are specific for epidemic strains. Currently, a single serogroup B vaccine, aiming to provide comprehensive coverage, has been approved for use, and several others are undergoing clinical trials. Data on potential new vaccine candidates, from discovery to initial preclinical evaluation, are regularly published. In this review, the data required to progress from preclinical to clinical development of MenB vaccines are outlined, with reference to relevant regulatory guidelines. The issues caused by a lack of reliable animal models, particularly with respect to determination of protective efficacy, are also discussed.

Toward a meningitis-free world.

Meningococcal meningitis is a devastating disease that is often fatal. Vaccines against the five major meningococcal serogroups causing disease are about to become available, a conjugate vaccine against meningococcus A is in use for mass vaccination in Africa, and a protein-based vaccine against meningococcal B is ready for licensure. With the availability of these new vaccines, the world can finally be rid of meningococcal meningitis, thus rewriting a new chapter in medical history.

Cost-effectiveness analysis of a universal infant immunization program with meningococcal C conjugate vaccine in Brazil.

OBJECTIVE: To analyze the cost-effectiveness of a meningococcal C vaccination program in Brazil. METHODS: A hypothetical cohort of 3,194,038 children born in Brazil in 2006 was followed for 10 years. A decision tree model was developed using the TreeAge Pro 2007 software program to compare universal infant vaccination with the current program. Epidemiological and cost estimates were based on data retrieved from National Health Information Systems and the literature. The analysis was conducted from the public health care system and societal perspectives. Costs are expressed in 2006 Brazilian reals (R$). RESULTS: At 94% coverage, the program would avoid 1,218 cases, 210 deaths, and 14,473 life-years lost, a reduction of, respectively, 45%, 44%, and 44%, for the 10-year period. Vaccination costs of R$320.9 million would not be offset by R$4 to R$7.9 million decreases in disease treatment costs. A national vaccination program would cost R$21,620 per life-year saved from the perspective of the health-care system and R$21,896 per life-year saved from society's perspective. Results were most sensitive to case fatality rate, disease incidence, and vaccine cost. CONCLUSIONS: A universal childhood vaccination program against meningococcal C proved to be a cost-effective strategy, supporting the recent decision of the Brazilian government. These results could contribute to defining the most favorable price of the vaccine and to monitoring its impact on the population.