[Historical review of the epidemic situation, prevention and control of epidemic cerebrospinal meningitis during 1966 to 1967].

During the winter and spring of 1966 to 1967, the nationwide revolution networking not only exerted great pressure on food, housing and transportation, but also triggered the most serious nationwide epidemic cerebrospinal meningitis outbreak in history. The students of the revolution networking were the disseminators of the disease and the first group of patients. The unprecedented scale and scope of the epidemic, the destroyed medical and health order and other factors exacerbated the epidemic situation. Zhou Enlai restarted the " prevention and treatment by masses " mode to gradually control the epidemic. Fifty years later, looking back on the history of the epidemic situation and prevention and control of epidemic cerebrospinal meningitis, many problems are worth pondering deeply.

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.

Notes from the Field: Expanded Chemoprophylaxis Offered in Response to a Case of Meningococcal Meningitis in an Elementary School - Indiana, 2015.

On December 11, 2015, the Fort Wayne-Allen County (Indiana) Department of Health was notified by a local hospital laboratory of a suspected case of meningococcal meningitis based on Gram stain results of cerebrospinal fluid. The county health department interviewed close family members and friends of the patient to establish an infectious period, timeline of events, and possible exposures. Close medical and household contacts were offered chemoprophylaxis (1). This case was associated with an elementary school. The patient had intermittent, close, potentially face-to-face contact with many students, and was reported to have had a persistent, productive cough throughout the exposure period. In light of these unusual circumstances, and the fact that elementary school-aged children are not routinely vaccinated against meningococcal disease,* local and state health officials, with CDC support, decided to offer chemoprophylaxis to the patient's contacts. A total of 581 child and adult contacts were identified.

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.

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.

Management of a rifampicin-resistant meningococcal infection in a teenager.

We report a secondary case of rifampicin-resistant meningococcal disease and our experience in managing contact cases. Rifampicin resistance resulting from rpoB gene mutations is still uncommon enough that changing the current recommendations for chemoprophylaxis is unwarranted. However, ensuring limited but appropriate chemoprophylaxis may prevent the development of antimicrobial resistance. Thus, the definition of contact cases should be strictly respected. In the case of culture-positive Neisseria meningitidis, in vitro susceptibility testing to rifampicin must be systematically performed in order to detect rifampicin-resistant strains and, thus, institute appropriate prophylaxis in order to prevent secondary transmission.

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.

New vaccines require potent adjuvants like AFPL1 and AFCo1.

Neisseria meningitidis B proteoliposome (AFPL1 when used as adjuvant) and its derivative-Cochleate (AFCo1) contain immunopotentiating and immunomodulating properties and delivery system capacities required for a good adjuvant. Additionally, they contain meningococcal protective antigens and permit packaging of other antigens and pathogen-associated molecular patterns (PAMP). Consequently, we hypothesized that they would function as good vaccine adjuvants for their own antigens and also for non-related antigens. AFPL1 is a detergent-extracted outer membrane vesicle of N. meningitidis B transformed into AFCo1 in calcium environment. Both are produced at Finlay Institute under good manufacture practices (GMP) conditions. We show their exceptional characteristics: combining in the same structure, the potentiator activity, polarizing agents and delivery system capacities; presenting multimeric protein copies; containing multiprotein composition and multi and synergistic PAMP components; acting with incorporated or co-administrated antigens; inducing type I IFN-gamma and IL-12 cytokines suggesting the stimulation of human plasmocytoid precursor and conventional dendritic cells, respectively, inducing a preferential Th1 immune response with TCD4(+), TCD8(+), cross-presentation and cytotoxic T-lymphocyte (CTL) in vivo responses; and functioning by parenteral and mucosal routes. AFPL1-AFCo1 protective protein constitutions permit per se their function as a vaccine. In addition to Phase IV Men BC vaccine, AFPL1 has ended the preclinical stage in an allergy vaccine and is concluding the preclinical stage of a nasal meningococcal vaccine. In conclusion, AFPL1 and AFCo1 induced signal 1, 2 and 3 polarizing to a Th1 (including CTL) response when they acted directly as vaccines or were used as adjuvants with incorporated or co-administered antigens by parenteral or mucosal routes. Both are very promising adjuvants.

Evaluation of recombinant lipidated P2086 protein as a vaccine candidate for group B Neisseria meningitidis in a murine nasal challenge model.

Neisseria meningitidis is a major causative agent of bacterial meningitis in human beings, especially among young children (

A randomized, placebo-controlled study of oral cimetidine as an immunopotentiator of parenteral immunization with a group B meningococcal vaccine.

Cimetidine (CIM) is an H2-receptor antagonist with a long history of clinical use in peptic ulcer disease. In addition to its inhibitory effect upon gastric acid secretion, CIM can also block histamine-mediated immunosuppression by inhibiting H2 receptors on suppressor T cells. CIM results in immunoaugmentation of both cellular and humoral immunity by this mechanism and has been used clinically in the treatment of chronic infectious and neoplastic diseases. We postulated that orally administered CIM, like an adjuvant, could augment the immunologic response to a parenteral vaccine. To test this hypothesis, a randomized placebo (PLB)-controlled, double-blinded study in 14 healthy volunteers was performed using a Group B meningococcal outer membrane protein (OMP) vaccine administered twice, 6 weeks apart. Volunteers were randomized within pairs defined by their screening OMP antibody titers to receive either CIM or PLB which was administered for 5 days, beginning 2 days before each of the two immunizations. All 14 volunteers completed the study with excellent compliance. Sera were tested for anti-OMP and bactericidal antibodies. The groups were comparable in terms of gender distribution, age and baseline anti-OMP titers. Reactogenicity to the vaccine was mild and comparable between groups. There was little effect of CIM (over PLB) on anti-OMP or functional bactericidal antibody levels over time. Geometric means of maximum OMP antibody increase over baseline was 3.3-fold (95% CI: 1.8-6.3) for CIM and 2.4 for PLB (CI: 1.6-3.7). CIM had a corresponding 3.9-fold increase (CI: 1.9-8.3) in bactericidal antibody level compared to 2.2 for PLB (CI: 1.4-3.4). We conclude that oral CIM was not effective as an immunopotentiator of immunization with this group B meningococcal vaccine.

[A system for the mass combined vaccination of the adult population against influenza, viral hepatitis, typhoid, meningitis and diphtheria]. / Sistema massovoi kompleksnoi vaktsinatsii vzroslogo naselennia protiv grippa, virusnogo gepatita, briushnogo tifa, meningita i difterii.

A safe, moderately reactogenic and immunologically effective scheme of complex (combined) immunization against meningitis A, diphtheria, typhoid fever, viral hepatitis A and influenza has been developed as the result of experimental and clinico-immunological studies. Depending on the epidemiological situation, the newly developed scheme can be used in two variants. According to the first variant of this scheme, the following preparations are injected subcutaneously into three different sites: a mixture of group A meningococcal vaccine and diphtheria toxoid, typhoid vaccine and influenza vaccine. The second variant of the scheme differs from its first variant in using intramuscular injection of normal human immunoglobulin instead of injection of influenza vaccine. Moreover, in practical realization these variants may be altered by excluding vaccines, unnecessary under present conditions. The newly developed scheme of vaccinal prophylaxis is recommended for practical use.

[The protective activity of polyclonal and monoclonal antibodies to the lipopolysaccharide of Neisseria meningitidis serogroup A in in vivo experiments]. / Protektivnaia aktivnost' poliklonal'nykh i monoklonal'nykh antitel k lipopolisakharidu Neisseria meningitidis serogruppy A v opytakh in vivo.

The protective activity of the sera of mice immunized with the preparations of native and detoxified N. meningitidis lipopolysaccharide (LPS), group A, as well as with monoclonal antibodies to N. meningitidis antigens, groups A and B, was studied on the mucin model of meningococcal infection. The study showed that the maximum level of anti-LPS antibodies in mice was observed on day 7 after the injection of LPS. Immune sera obtained from mice were capable of protecting the animals from fetal meningococcemia induced by N. meningitidis strains of homologous and heterologous groups. As shown by the results of this study, the alkaline treatment of N. meningitidis native LPS did not decrease the protective properties of antibodies. The monoclonal antibodies under study were found to possess high preventive activity in mice challenged with N. meningitidis, groups A and B. Anti-LPS monoclonal antibodies showed greater protective activity than antipolysaccharide monoclonal antibodies.

Evaluation of single-dose ciprofloxacin in the eradication of Neisseria meningitidis from nasopharyngeal carriers.

The ability of a single oral 750-mg dose of ciprofloxacin to eradicate Neisseria meningitidis from persistent nasopharyngeal carriers was prospectively evaluated in a placebo-controlled, randomized, double-blinded study. Cultures of specimens taken from all 23 ciprofloxacin-dosed subjects 1 day postdose were negative; cultures from 96% of these subjects were negative at 7 and 21 days postdose, including a specimen from a subject colonized with a minocycline-resistant strain. Of 22 placebo recipients, 20 (91%) remained culture positive. Single-dose ciprofloxacin appears efficacious for meningococcal prophylaxis.

Comparative efficacy of ceftriaxone and rifampicin in eradicating pharyngeal carriage of group A Neisseria meningitidis.

During an outbreak of meningococcal meningitis in Saudi Arabia, oral rifampicin (four doses in two days) was compared with a single intramuscular dose of ceftriaxone for prophylaxis in family contacts of patients with meningococcal disease. Pharyngeal samples were taken for culture before and 1 and 2 weeks after administration. Both follow-up cultures indicated that ceftriaxone was significantly more effective. At 1 week the eradication rates for ceftriaxone and rifampicin were 97% and 75%; at 2 weeks they were 97% and 81%, respectively. No serious side-effects were associated with either agent. Ceftriaxone may provide an effective alternative to rifampicin for prophylaxis in meningococcal contacts.

[Preventive and therapeutic action of sera to the Re mutant of Salmonella minnesota in experimental generalized meningococcal infection]. / Preventivnoe i lechenoe deistvie syvorotok k Re-mutantu Salmonella minnesota pri éksperimental'noi generalizovannoi meningokokkovoi infektsii.

The preparations of the blood plasma of humans and the sera of animals immunized with enterobacterial vaccine proved to have elevated titers of antibodies to deep determinants of the core of the gram-negative bacterial endotoxin molecule (to glycolipid of chemotype Re) and protected animals from infection with live cultures or serogroup A, B, or C meningococcal endotoxins. Sera from nonimmunized animals and normal donor blood plasma showed no protective activity. In experiments carried out on different models immune plasma possessed both a pronounced protective activity and a curative effect. The efficacy of protection depended not on the serogroup of the infective agent, but on the virulence of the strain used in the experiment, being statistically significant in all cases.

Chemoprophylaxis for Neisseria meningitidis in an isolated Arctic community.

Community chemoprophylaxis with a regimen of sequential minocycline/rifampin (adults) or rifampin alone (children [less than 12 years of age]) was undertaken in a remote Arctic community one year after an outbreak of meningitis due to Neisseria meningitidis serogroup B. Nasopharyngeal carriage rates of N. meningitidis before prophylaxis were 32.4% in Inuit (Eskimos) and 6% in Caucasians, with maximal carriage (44.8%) in adolescents. Serogroup B accounted for 63.9% of all isolates before prophylaxis. One week after prophylaxis, the nasopharyngeal carriage rates were 0.8% in Inuit who had received prophylaxis and 33.3% in those who had not received prophylaxis (P less than 0.005). This reduction persisted at nine weeks after prophylaxis, when carriage rates were 1.2% in those who had received prophylaxis and 22.6% in individuals who had not received prophylaxis. Of the strains obtained before prophylaxis, 7.8% were sulfadiazine-resistant, whereas 35% of all isolates obtained from prophylaxis were sulfadiazine-resistant. Rifampin- or minocycline-resistant strains were not identified either before or after prophylaxis.

[Meningococcus profilaxis (author's transl)]. / Profilaxis meningocócica.

In a General Hospital in San Sebastian, 96 cases of Neisseria meningitidis infections were detected in a two years period. By the use of the disk diffusion method, we found that all causative meningococcal strains but 4 were resistant to sulfonamide (with a 300 microgram sulfadiazine disk, all isolates with a zone diameter of less than 20 mm were considered to be resistant of sulfadiazine, whereas those with zone diameters of greater than 30 mm were considered susceptible). No rifampin nor minocycline-resistant meningococci were isolated. All strains had a disk zone diameter (30 micrograms rifampin and 30 micrograms tetracycline) of greater than 20 mm. The serogroups of meningococcal strains were as follows: group A, 1; group B, 67; group C, 5 and 23 were no typed. Children less than four years of age were most frequently attacked (67,7%). The attack rate was only slightly higher in males than in females (52 and 44).