Risk Of Meningococcal Disease Research Articles

Use of the Pfizer Pentavalent Meningococcal Vaccine Among Persons Aged ≥10 Years: Recommendations of the Advisory Committee on Immunization Practices - United States, 2023.

Meningococcal disease is a life-threatening invasive infection caused by Neisseria meningitidis. Two quadrivalent (serogroups A, C, W, and Y) meningococcal conjugate vaccines (MenACWY) (MenACWY-CRM [Menveo, GSK] and MenACWY-TT [MenQuadfi, Sanofi Pasteur]) and two serogroup B meningococcal vaccines (MenB) (MenB-4C [Bexsero, GSK] and MenB-FHbp [Trumenba, Pfizer Inc.]), are licensed and available in the United States and have been recommended by CDC's Advisory Committee on Immunization Practices (ACIP). On October 20, 2023, the Food and Drug Administration approved the use of a pentavalent meningococcal vaccine (MenACWY-TT/MenB-FHbp [Penbraya, Pfizer Inc.]) for prevention of invasive disease caused by N. meningitidis serogroups A, B, C, W, and Y among persons aged 10-25 years. On October 25, 2023, ACIP recommended that MenACWY-TT/MenB-FHbp may be used when both MenACWY and MenB are indicated at the same visit for the following groups: 1) healthy persons aged 16-23 years (routine schedule) when shared clinical decision-making favors administration of MenB vaccine, and 2) persons aged ≥10 years who are at increased risk for meningococcal disease (e.g., because of persistent complement deficiencies, complement inhibitor use, or functional or anatomic asplenia). Different manufacturers' serogroup B-containing vaccines are not interchangeable; therefore, when MenACWY-TT/MenB-FHbp is used, subsequent doses of MenB should be from the same manufacturer (Pfizer Inc.). This report summarizes evidence considered for these recommendations and provides clinical guidance for the use of MenACWY-TT/MenB-FHbp.

Propositive follow-up: Long-term immune responses to the 4CMenB and MenACWY vaccines in people living with HIV.

People living with HIV have an increased risk of meningococcal disease. The Propositive trial evaluated co-administration of two doses of a four-component recombinant protein-based MenB vaccine (4CMenB) and a quadrivalent conjugate polysaccharide MenACWY vaccine (MenACWY-CRM197) given 1 month apart in people with HIV. The follow-up trial assessed the immunogenicity of these vaccines at 1.5 and 2.5 years after primary vaccination. Participants who completed the parent Propositive trial were invited to the follow-up study. Immunogenicity analysis was performed at 18 and 30 months after primary vaccination. Primary outcome measures were serum bactericidal antibody (SBA) geometric mean titres (GMTs) against three MenB reference strains and the proportion of participants maintaining a protective SBA titre of ≥4 at 18 and 30 months. Secondary outcome measures were SBA GMTs against MenA, C, W, and Y serogroups and the proportion of participants maintaining a protective SBA titre of ≥8 at 18 and 30 months. The trial is registered with Clinicaltrials.gov (NCT042394300). A total of 40 participants aged 22-47 years were enrolled. Geometric mean titres waned by 18 and 30 months but remained higher than pre-vaccination for all MenB strains and MenA, C, W, and Y. In total, 75%-85% of participants retained protective SBA titres by 30 months against individual MenB strains, whereas 68.8% of patients retained protective antibody titres against all three MenB strains. Antibodies against MenC waned more rapidly than did those against MenA, W, and Y. The proportion of participants with protective titres against MenC at 30 months was also lower (46.9%) than that with protective titres against MenA (87.5%), W (78.1%), and Y (87.5%). Immune responses against MenB in our cohort of people living with HIV at 2.5 years of follow-up were reassuring, with 68.8% of participants retaining protection against all three reference strains. However, responses against MenC were lower than those against MenA, W, and Y serogroups.

Expert Perspectives on the Vaccination of Individuals Who Are at Increased Risk of Meningococcal Disease Due to Medical Conditions: A Podcast.

Patients with functional or anatomic asplenia, including sickle cell anemia; complement component deficiency; or human immunodeficiency virus (HIV) infection have a significantly increased risk of developing meningococcal disease. The Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC) recommends vaccination with a quadrivalent meningococcal conjugate vaccine against serogroupsA, C, W, and Y (MenACWY) for individuals 2months of age or older who are diagnosed with functional or anatomic asplenia, complement component deficiency, or HIV infection. Vaccination with a meningococcal vaccine against serogroupB (MenB) is also recommended for individuals 10years of age or older who are diagnosed with functional or anatomic asplenia or complement component deficiency. Despite these recommendations, recent studies have shown that vaccination coverage in these populations is low. In this podcast, the authors discuss the challenges for implementing vaccine recommendations for individuals with medical conditions at increased risk of developing meningococcal disease and discuss strategies to increase coverage. Suboptimal vaccination rates could be addressed by better educating healthcare providers about recommendations for MenACWY and MenB vaccines in individuals at increased risk, increasing awareness of low vaccination coverage, and tailoring the education to the needs of particular healthcare providers and their respective patient populations. Barriers to vaccination could also be removed by administering vaccines at alternative sites of care, bundling preventative services, and implementing vaccination reminder systems that are tied to immunization information systems.

Meningococcal Vaccination Rates Among People With a New Diagnosis of HIV Infection in the US

In the United States, individuals with HIV infection have been recommended to receive a 2-dose series of the meningococcal A, C, W, Y (MenACWY) vaccine since 2016 owing to their increased risk of meningococcal disease. To examine uptake and time to receipt of the MenACWY vaccine among people with a new diagnosis of HIV. This cohort study used health insurance data from the US Optum Research Database from January 1, 2016, through March 31, 2018, to retrospectively identify 1208 individuals aged 2 years or older with 1 or more inpatient claim or 2 or more outpatient claims evidencing a new diagnosis of HIV infection and with continuous insurance enrollment for 12 or more months before and 6 or more months after diagnosis. Follow-up was 6 to 33 months. Statistical analysis was conducted from March 7, 2019, to January 5, 2022. Receipt of the MenACWY vaccine. The coprimary outcomes were uptake and time to receipt of 1 or more doses of the MenACWY vaccine after a new HIV diagnosis. Secondary outcomes included uptake and time to receipt of 2 or more doses of the MenACWY vaccine. Vaccination uptake and receipt were estimated by Kaplan-Meier analysis; factors associated with receipt of 1 or more doses of the MenACWY vaccine were identified with multivariable Cox proportional hazards regression analysis. Of 1208 individuals eligible for vaccination (1024 male patients [84.8%]; mean [SD] age, 38.8 [12.5] years; 35 [2.9%] Asian; 273 [22.6%] Black; 204 [16.9%] Hispanic; 442 [36.6%] White), 16.3% were estimated to have received a first dose of the MenACWY vaccine in the 2 years after a new HIV diagnosis. Among individuals who received a first dose, at 1 year or more of enrollment after the first dose, 66.2% were estimated to have received a second dose within 1 year of the first dose. Factors statistically significantly associated with uptake of the MenACWY vaccine included receipt of a pneumococcal vaccine (hazard ratio [HR], 23.03; 95% CI, 13.93-38.09), attendance at a well-care visit (HR, 3.67; 95% CI, 1.11-12.12), West or Midwest geographic region (West: HR, 2.24; 95% CI, 1.44-3.47; Midwest: HR, 1.78; 95% CI, 1.16-2.71), and male sex (HR, 2.72; 95% CI, 1.18-6.26), whereas age of 56 years or older was significantly associated with reduced uptake of the MenACWY vaccine (HR, 0.42; 95% CI, 0.18-0.97). This cohort study suggests that MenACWY vaccine uptake among people with a new diagnosis of HIV was low, highlighting the need to educate patients and clinicians about the recommendations for conditions such as HIV infection that increase the risk of meningococcal disease among high-risk populations.

Equity in vaccination policies to overcome social deprivation as a risk factor for invasive meningococcal disease

ABSTRACT Introduction Social deprivation is associated with poorer healthcare access. Vaccination is among the most effective public health interventions and achieving equity in vaccination access is vitally important. However, vaccines are often reimbursed by public funds only when recommended in national immunization programs (NIPs), which can increase inequity between high and low socioeconomic groups. Invasive meningococcal disease (IMD) is a serious vaccination-preventable disease. This review focuses on vaccination strategies against IMD designed to reduce inequity. Areas covered We reviewed meningococcal epidemiology and current vaccination recommendations worldwide. We also reviewed studies demonstrating an association between social deprivation and risk of meningococcal disease, as well as studies demonstrating an impact of social deprivation on uptake of meningococcal vaccines. We discuss factors influencing inclusion of meningococcal vaccines in NIPs. Expert opinion Incorporating meningococcal vaccines in NIPs is necessary to reduce inequity, but insufficient alone. Inclusion provides clear guidance to healthcare professionals and helps to ensure that vaccines are offered universally to all target groups. Beyond NIPs, cost of vaccination should be reimbursed especially for disadvantaged individuals. These approaches should help to achieve optimal protection against IMD, by increasing access and immunization rates, eventually reducing social inequities, and helping to protect those at greatest risk.

Identification of the nasopharyngeal carriage of Neisseria meningitidis by 16S rRNA Gene sequencing in asymptomatic adolescents and young adults in Cartagena, Colombia (2019–2020).

The bacterium Neisseria meningitidis, a strictly human pathogen, can cause meningitis, meningococcemia, sepsis, and death; repeatedly it scause outbreaks around the world. The frequency of asymptomatic carriage is often high in adolescents and young adults, increasing the invasive meningococcal disease risk and likelihood of transmission. However, detailed analyses of meningococcal carriage in this population in Colombia, particularly in coastal areas, are lacking. In this study, the prevalence and characteristics of Neisseria meningitidis carriage were evaluated in asymptomatic adolescents and young adults (11-25 years old) in Cartagena, Colombia. Oropharynx samples were collected from participants between August and December 2019. The phenotypic identification of bacteria was performed by conventional methods and biochemical testing. Molecular identification to the species level was performed by 16S rRNA gene sequencing. In total, 12 of 648 samples were positive for Neisseria meningitidis by 16S rRNA sequencing, indicating a prevalence of 1.9%. Isolates were classified into four invasive serogroups (A, B, C, and W) by a comparative sequence analysis of the ribosomal gene. Despite the occurrence of meningococcal disease in Cartagena city in the last several years, the frequency of oropharyngeal carriage in adolescents and young adults was low. Serogroup A had not been previously reported in nasopharyngeal samples in Colombia. This is the first report of Neisseria meningitidis on the Colombian Caribbean coast based on 16S rRNA sequencing and is expected to guide the development of vaccination and follow-up strategies.

4CMenB vaccine and its role in preventing transmission and inducing herd immunity

ABSTRACT Introduction Vaccination is the most effective method of protecting people from invasive meningococcal disease (IMD). Of all the capsular groups, B is the most common cause of invasive meningococcal disease in many parts of the world. Despite this, adolescent meningococcal B vaccine programs have not been implemented globally, partly due to the lack of evidence for herd immunity afforded by meningococcal B vaccines. Areas covered This review aims to synthesize the available evidence on recombinant 4 CMenB vaccines’ ability to reduce pharyngeal carriage and therefore provide indirect (herd) immunity against IMD. Expert opinion There is some evidence that the 4CMenB vaccine may induce cross-protection against non-B carriage of meningococci. However, the overall body of evidence does not support a clinically significant reduction in carriage of disease-associated or group B meningococci following 4CMenB vaccination. No additional cost-benefit from herd immunity effects should be included when modeling the cost-effectiveness of 4CMenB vaccine programs against group B IMD. 4CMenB immunization programs should focus on direct (individual) protection for groups at greatest risk of meningococcal disease. Future meningococcal B and combination vaccines being developed should consider the impact of the vaccine on carriage as part of their clinical evaluation.

Serogroup A, C, W, and Y meningococcal disease in persons previously vaccinated with a serogroup ACWY meningococcal vaccine – United States, 2014–2018

BackgroundThe Advisory Committee on Immunization Practices (ACIP) recommends routine vaccination with a quadrivalent meningococcal conjugate serogroup A,C,W,Y (MenACWY) vaccine at 11–12 years of age, with a booster dose at 16 years. ACIP also recommends meningococcal vaccination for persons at increased risk of meningococcal disease, including a 2-dose primary series and regular booster doses for persons at increased risk because of underlying medical conditions. U.S. cases of serogroup A, C, W, and Y meningococcal disease in persons previously vaccinated with MenACWY vaccine have not been systematically described since 2008. Characterization of these cases is important to understand potential factors leading to breakthrough disease. MethodsWe analyzed cases of serogroup A,C,W, and Y meningococcal disease reported through the National Notifiable Diseases Surveillance System (NNDSS) from 2014 through 2018. State health departments submitted additional information on risk factors and clinical course. ResultsDuring 2014–2018, 822 cases of serogroup A, C, W, and Y meningococcal disease were reported through NNDSS; 34 (4%) were in patients who previously received ≥ 1 dose of MenACWY vaccine. Twenty-three vaccinated patients were up-to-date on MenACWY vaccine per recommendations, and seven were not up-to-date; four were missing information on the number of doses received. Seventeen cases (50%) occurred > 3 years after the most recent dose. A significantly higher proportion of vaccinated patients were people living with HIV (PLWH) compared to unvaccinated patients. Eight of the 34 vaccinated patients were immunosuppressed, including five PLWH, one taking eculizumab, and two taking other immunosuppressive medications. The case fatality ratio did not differ between vaccinated and unvaccinated patients. ConclusionsImmunosuppression, incomplete vaccination, and waning immunity likely contributed to breakthrough cases of meningococcal disease among people who received MenACWY vaccine. Continued monitoring of serogroup A, C, W, and Y meningococcal disease in previously vaccinated persons will help inform meningococcal disease prevention efforts.

Serogroup B meningococcal disease in persons previously vaccinated with a serogroup B meningococcal vaccine – United States, 2014–2019

Since serogroup B meningococcal (MenB) vaccines became available in the United States, six serogroup B meningococcal disease cases have been reported in MenB-4C (n = 4) or MenB-FHbp (n = 2) recipients. Cases were identified and characterized through surveillance and health record review. All five available isolates were characterized using whole genome sequencing; four isolates (from MenB-4C recipients) were further characterized using flow cytometry, MenB-4C-induced serum bactericidal activity (SBA), and genetic Meningococcal Antigen Typing System (gMATS). Three patients were at increased meningococcal disease risk because of an outbreak or underlying medical conditions, and only four of the six patients had completed a full 2-dose MenB series. Isolates were available from 5 patients, and all contained sub-family A FHbp. The four isolates from MenB-4C recipients expressed NhbA but were mismatched for the other MenB-4C vaccine antigens. These four isolates were relatively resistant to MenB-4C-induced SBA, but predicted by gMATS to be covered. Overall, patient risk factors, incomplete vaccine series completion, waning immunity, and strain resistance to SBA likely contributed to disease in these six patients.

Alternative Complement Pathway Inhibition Does Not Abrogate Meningococcal Killing by Serum of Vaccinated Individuals.

Dysregulation of complement activation causes a number of diseases, including paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome. These conditions can be treated with monoclonal antibodies (mAbs) that bind to the complement component C5 and prevent formation of the membrane attack complex (MAC). While MAC is involved in uncontrolled lysis of erythrocytes in these patients, it is also required for serum bactericidal activity (SBA), i.e. clearance of encapsulated bacteria. Therefore, terminal complement blockage in these patients increases the risk of invasive disease by Neisseria meningitidis more than 1000-fold compared to the general population, despite obligatory vaccination. It is assumed that alternative instead of terminal pathway inhibition reduces the risk of meningococcal disease in vaccinated individuals. To address this, we investigated the SBA with alternative pathway inhibitors. Serum was collected from adults before and after vaccination with a meningococcal serogroup A, C, W, Y capsule conjugate vaccine and tested for meningococcal killing in the presence of factor B and D, C3, C5 and MASP-2 inhibitors. B meningococci were not included in this study since the immune response against protein-based vaccines is more complex. Unsurprisingly, inhibition of C5 abrogated killing of meningococci by all sera. In contrast, both factor B and D inhibitors affected meningococcal killing in sera from individuals with low, but not with high bactericidal anti-capsular titers. While the anti-MASP-2 mAb did not impair SBA, inhibition of C3 impeded meningococcal killing in most, but not in all sera. These data provide evidence that vaccination can provide protection against invasive meningococcal disease in patients treated with alternative pathway inhibitors.

Longitudinal study of meningococcal carriage rates in university entrants living in a dormitory in South Korea.

University students, especially those living in dormitories, are known to have a high risk of invasive meningococcal disease. We performed a longitudinal study to investigate the change in Neisseria meningitidis carriage rates and identify the risk factors for carriage acquisition in university students in South Korea. We recruited university entrants who were admitted to a student dormitory. Pharyngeal swabs were taken from participants at baseline, 1 month, and 3 months, and the subjects completed a questionnaire. Culture and real-time polymerase chain reaction (PCR) for species-specific ctrA and sodC genes were performed. The cultured isolates or PCR-positive samples were further evaluated for epidemiologic characterization using serogrouping, PorA typing, FetA typing, and multilocus sequence typing (MLST). At the first visit, we enrolled 332 participants who were predominantly male (64.2%) with a median age of 19 years. Meningococcal carriage rates increased from 2.7% (95% confidence interval [CI] 0.9–4.4%) at baseline to 6.3% (95% CI 3.4–9.0%) at 1 month and 11.8% (95% CI 7.8–15.6%) at 3 months. Nongroupable isolates accounted for 50.0% of all isolates, with serogroup B being the next most prevalent (24.1%). In the study population, male sex (OR 2.613, 95% CI 1.145–5.961, p = 0.022) and frequent pub or club visits (OR 3.701, 95% CI 1.536–8.919, p = 0.004) were significantly associated with meningococcal carriage. Based on serotype and MLST analyses, six carriers transmitted meningococci to other study participants. N. meningitidis carriage rates among new university entrants who lived in a dormitory significantly increased within the first 3 months of dormitory stay, probably owing to the transmission of identical genotype among students. Based on the risk of meningococcal disease, meningococcal vaccination should be considered for students before dormitory admission.

Shared clinical decision making important for MenB vaccines

CDC's Advisory Committee on Immunization Practices (ACIP) has published its 2020 recommendations for meningococcal vaccination, which cover use of the three quadrivalent conjugate vaccines—meningococcal serotypes A, C, W, and Y (MenACWY)—and two available meningococcal serogroup B (MenB) vaccines. The recommendations call on shared clinical decision making for the MenB vaccine for adolescents and young adults ages 16 to 23 years and highlight the importance of these vaccines for patients at increased risk. Shared clinical decision making allows providers and patients an opportunity to discuss the risks of infection and the benefits of vaccination suitable to each individual's needs. For the MenB vaccines, ACIP recommends a shared clinical decision making approach for those ages 16 to 23 years, with considerations given to the serious nature of meningococcal infections; the increased risk among college students, especially first-year students attending a 4-year university; and the protection provided by the MenB vaccines against most strains of serogroup B Neisseria meningitidis. “Pharmacists are in a unique position to have a shared clinical decision conversation with patients about the risks of serogroup B meningococcal disease,” said Adam C. Welch, PharmD, MBA, FAPhA, associate professor of pharmacy practice at East Tennessee State University Bill Gatton College of Pharmacy. “Pharmacists can use the strong relationships they have with their patients to inform MenB shared clinical decision making. They’ll know if someone's son or daughter is joining a fraternity or sorority and therefore will be at higher risk.” Shared decision making in health care is not a new concept. The Agency for Healthcare Research and Quality (AHRQ) developed The SHARE Approach: Essential Steps of Shared Decisionmaking, which can be applied to vaccinations. This tool outlines five steps health professionals can take to ensure that they are using shared decision making effectively with patients during clinical encounters (see sidebar at right). If patients decide to receive the MenB vaccination series, clinicians should be aware that two vaccines are available: MenB-FHbp (Trumenba—Pfizer) and MenB-4C (Bexsero—GlaxoSmithKline). Each requires two doses to be given at different times. The MenB-FHbp is given at 0 and 6 months, and the MenB-4C is given as two doses at least 1 month apart or longer. The preferred age for vaccination is between 16 and 18 years, and it is important to note that the MenB-FHbp and MenB-4C are not interchangeable. ACIP also recommends the use of MenB vaccines for patients ages 10 years or older who are at increased risk for MenB disease. These patients include those who have persistent complement component deficiencies, those receiving a complement inhibitor, those who have anatomic or functional asplenia, microbiologists routinely exposed to isolates of N. meningitidis, and those at high risk because of an outbreak. Both MenB vaccines are FDA approved for use in patients ages 10 years to 25 years. The ACIP recommendations also cover the appropriate use of MenACWY vaccination, with routine vaccination recommended for adolescents at age 11 or 12 years and a booster at age 16. In addition, routine vaccination is recommended for patients ages 2 months or older who are at increased risk for meningococcal disease. Three quadrivalent meningococcal conjugate vaccines are FDA-approved: MenACWY-D (Menactra—SanofiPasteur), MenACWY-CRM (Menveo—GlaxoSmithKline), and MenACWY-TT (MenQuadfi—Sanofi Pasteur). The three MenACWY vaccines are interchangeable, but use of the same vaccine is recommended (not required) for all doses. The SHARE Approach: Essential Steps of Shared Decisionmaking▪Step 1: Seek your patient's participation.▪Step 2: Help your patient explore and compare treatment options.▪Step 3: Assess your patient's values and preferences.▪Step 4: Reach a decision with your patient.▪Step 5: Evaluate your patient's decision. The SHARE Approach: Essential Steps of Shared Decisionmaking ▪Step 1: Seek your patient's participation.▪Step 2: Help your patient explore and compare treatment options.▪Step 3: Assess your patient's values and preferences.▪Step 4: Reach a decision with your patient.▪Step 5: Evaluate your patient's decision. “It is important to maintain complete documentation, preferably in an immunization information system [like a registry], as many of the meningococcal vaccines have timing considerations with other vaccines such as DTaP and PCV13 [pneumococcal 13-valent conjugate vaccine],” said Welch. He also noted that special care should be taken in documenting which MenB vaccine was administered, as the two formulations are not interchangeable.

Characteristics of and meningococcal disease prevention strategies for commercially insured persons receiving eculizumab in the United States.

IntroductionEculizumab is a licensed treatment for several rare, complement-mediated diseases. Eculizumab use is associated with an approximately 2,000-fold increased meningococcal disease risk. In the United States, meningococcal vaccines are recommended for eculizumab recipients but there are no recommendations on use of long-term antibiotic prophylaxis. We describe characteristics of and meningococcal vaccine and antibiotic receipt in U.S. eculizumab recipients to inform meningococcal disease prevention strategies.MethodsPersons in the IBM® MarketScan® Research Databases with ≥1 claim for eculizumab injection during 2007–2017 were included. Indication for eculizumab use, meningococcal vaccine receipt, and antibiotic receipt were assessed using International Classification of Diseases-9/10 diagnosis codes, vaccine administration procedure codes, and antibiotic codes from pharmacy claims, respectively.ResultsOverall 696 persons met the inclusion criteria. Paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS) were the most common indications for eculizumab use (41% and 37%, respectively); 20% had an undetermined indication. From June 2015 through December 2017, 28% (41/148) of continuously-enrolled patients received ≥1 serogroup B vaccine dose. For serogroup ACWY conjugate vaccine, 45% (91/201) of patients received ≥1 dose within five years of their most recent eculizumab dose, as recommended. Of eculizumab recipients with outpatient prescription data, 7% (41/579) received antibiotics for ≥50% of the period of increased risk for meningococcal disease.ConclusionMany eculizumab recipients had an undetermined indication for eculizumab use; few were up-to-date for recommended meningococcal vaccines or were prescribed antibiotics long-term. These findings can inform further investigation of how to best protect this population from meningococcal disease.

Management of Meningococcal Disease Risk in Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) on Complement Inhibitors: 18 Years' Experience from the UK National PNH Service in Leeds

Management of Meningococcal Disease Risk in Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) on Complement Inhibitors: 18 Years' Experience from the UK National PNH Service in Leeds

Safety of meningococcal B vaccine (4CMenB) in adolescents in Australia

BackgroundFour-component meningococcal B (4CMenB) vaccine is licensed in many countries but has had limited use in adolescents despite this age group being at increased risk of meningococcal disease. ObjectivesTo assess the safety profile of two doses of 4CMenB in adolescents. MethodsCluster randomised controlled trial of senior school students in South Australia (SA) with participating schools randomised to intervention (4CMenB) or control. Vaccine safety was monitored using the South Australian Vaccine Safety Surveillance System (SAVSS), a spontaneous reporting system for adverse events following immunisation (AEFI) with enhanced follow-up of AEFI. Results58,637 doses of 4CMenB vaccine were administered to 30,522 students (median age 16 years) during 2017–2018. Of 18,348 and 12,174 students vaccinated in 2017 and 2018, 97.3% and 84.3%, respectively, received both scheduled doses (N = 28,115). 193 AEFI in 187 students were reported with a reporting rate of 0.32% (95%CI: 0.28–0.39%). Seventy individuals sought medical review, including nine serious adverse events. 98% (166/169) of those who were contactable for AEFI follow-up (87.6% 169/193) reported resolution of the event. Most common AEFI were injection site reaction (126/193), headache (99/193) and nausea (61/193). AEFI were more frequently reported in females (aOR = 1.409 (95%CI: 1.002, 1.980)), schools with high level of educational advantage (adjusted Odds Ratio (aOR) = 1.515 (95%CI: 1.005, 2.284)), following first dose (aOR = 1.619 (95%CI: 1.168, 2.244)), and in 2017 (aOR = 1.437 (95%CI: 1.001, 2.064)). Reported AEFI declined with increasing age (aOR = 0.771 (95%CI: 0.673, 0.883)). ConclusionIn this largest post-licensure use of 4CMenB in adolescents, the low AEFI reporting rate provides real-world evidence of 4CMenB safety in this age group.(ClinicalTrials.gov number: NCT03089086).

Summary of the NACI Statement on the Use of Bivalent Factor H Binding Protein Meningococcal Serogroup B (MenB-fHBP) Vaccine for the Prevention of Meningococcal B Disease.

TrumenbaTM, a bivalent, factor-H binding protein meningococcal serogroup B (MenB-fHBP) vaccine was authorized for use in Canada in October 2017 for the prevention of invasive meningococcal disease (IMD) caused by Neisseria meningitidis serogroup B in individuals 10-25 years of age. The National Advisory Committee on Immunization (NACI) provides recommendations regarding the use of meningococcal vaccines to the Public Health Agency of Canada. To summarize NACI recommendations regarding the use of MenB-fHBP vaccine in Canada. The NACI Meningococcal Disease Working Group developed a predefined search strategy to identify all eligible studies, assessed the quality of these studies, and summarized and analyzed the findings. According to the NACI evidence-based process, the working group then proposed recommendations and identified the grade of evidence that supported them. In light of the evidence, the recommendations were then considered and approved by NACI. The two serogroup B meningococcal vaccines currently authorized for use in Canada are not interchangeable as they contain different antigens and there are no published studies on the immunogenicity resulting from a vaccination series combining the two products. Following the review of evidence, NACI recommends that MenB-fHBP vaccine may be considered as an option for use in individuals 10 years of age and older in situations when a serogroup B meningococcal vaccine should be offered: 1) during serogroup B meningococcal disease outbreaks or with the emergence of hyperendemic N. meningitidis strains that are predicted to be susceptible to the vaccine; 2) for individuals who are close contacts with a case of invasive meningococcal disease caused by serogroup B N. meningitidis; 3) for individuals with underlying medical conditions that would put them at higher risk of meningococcal disease than the general population; or 4) for individuals at higher risk of exposure to serogroup B meningococcal isolates than the general population. NACI also recommends that MenB-fHBP vaccine may be considered as an option for individuals 10-25 years of age who are not at higher risk of meningococcal disease than the general population, but who wish to reduce their risk of invasive serogroup B meningococcal disease. NACI recommends immunization against serogroup B IMD for all individuals who are at a higher risk of disease due to an underlying medical condition or an increased risk of exposure. In addition to providing guidance to public health decision-makers (i.e. provinces/territories making decisions for publicly-funded immunization programs), these NACI recommendations provide information to individuals, vaccine providers and organizations about vaccines that may not currently be included in publicly funded immunization programs. NACI continues to recommend against the use of the serogroup B vaccines in routine universal immunization programs in Canada at this time.

Influenza increases invasive meningococcal disease risk in temperate countries

ObjectivesInvasive meningococcal disease (IMD) is a severe bacterial infection that displays wintertime seasonality in temperate countries. Mechanisms driving seasonality are poorly understood and may include environmental conditions and/or respiratory virus infections. We evaluated the contribution of influenza and environmental conditions to IMD risk, using standardized methodology, across multiple geographical regions. MethodsWe evaluated 3276 IMD cases occurring between January 1999 and December 2011 in 11 jurisdictions in Australia, Canada, France and the United States. Effects of environmental exposures and normalized weekly influenza activity on IMD risk were evaluated using a case-crossover design. Meta-analytic methods were used to evaluate homogeneity of effects and to identify sources of between-region heterogeneity. ResultsAfter adjustment for environmental factors, elevated influenza activity at a 2-week lag was associated with increased IMD risk (adjusted odds ratio (OR) per standard deviation increase 1.29; 95% confidence interval, 1.04–1.59). This increase was homogeneous across the jurisdictions studied. By contrast, although associations between environmental exposures and IMD were identified in individual jurisdictions, none was generalizable. ConclusionsUsing a self-matched design that adjusts for both coseasonality and case characteristics, we found that surges in influenza activity result in an acute increase in population-level IMD risk. This effect is seen across diverse geographic regions in North America, France and Australia. The impact of influenza infection on downstream meningococcal risk should be considered a potential benefit of influenza immunization programmes.

A review of the immunogenicity, safety and current recommendations for the meningococcal serogroup B vaccine, MenB-FHbp.

This review describes invasive meningococcal disease (IMD) epidemiology in the United States, provides a brief overview of available meningococcal vaccines and discusses meningococcal serogroup B (MenB) vaccine development. Particular focus is given to the recombinant protein MenB vaccine, MenB-FHbp (Trumenba® , bivalent rLP2086) in light of recent publication of phase 3 data; the other MenB vaccine (Bexsero® , MenB-4C) has been recently reviewed. Current recommendations of the US Advisory Committee on Immunization Practices (ACIP) for MenB vaccination and potential barriers to immunization are also discussed. Using the published literature, this article reviews the development and use of MenB-FHbp to date, with a focus on the United States. Despite the availability of medical treatment, IMD is associated with significant mortality and frequently occurring serious permanent sequelae in surviving individuals. Worldwide, most IMD is caused by six serogroups (A, B, C, W, X and Y). MenB is the most common disease-causing meningococcal serogroup in the United States and has caused several recent university-based IMD outbreaks. MenB vaccines, including MenB-FHbp, are available in the United States. ACIP recommends that all individuals ≥10years of age at increased risk for meningococcal disease receive MenB vaccination; healthy individuals 16-23years of age are recommended MenB vaccines based on individual clinical decision-making. MenB-FHbp is used on a 2-dose schedule (0, 6months) when vaccinating healthy individuals and on a tailored 3-dose schedule (0, 1-2, 6months) in cases of increased risk. Because vaccination provides the most effective protection against IMD, pharmacists are in an excellent position to offer evidence-based vaccine information, as well as to encourage and provide meningococcal immunizations to adolescents and young adults.

Safety of quadrivalent meningococcal conjugate vaccine in infants and toddlers 2 to 23-months old

Abstract Introduction The quadrivalent meningococcal conjugate vaccine MenACWY-CRM is recommended for 2–23 month-old infants/toddlers at increased risk for meningococcal disease. This study adds to the current knowledge of MenACWY-CRM safety among this age group in a clinical care setting. Methods Kaiser Permanente Southern California members aged 2–23 months who received MenACWY-CRM between July 2014 and June 2017 were included. Electronic health records were searched for emergency department (ED) and hospitalization encounters, and diagnoses associated with these visits up to 6 months after each dose. Results There were 138 infants/toddlers who received MenACWY-CRM, with 59.4% being African American and 66.7% receiving only one dose. Most infants either had a high-risk condition (i.e., anatomic/functional asplenia or DiGeorge syndrome) (42.0%), or a travel indication (54.3%). The incidence rate of ED visits was 0.6/person-year (95% confidence interval [CI]: 0.5–0.8), 0.4/person-year (CI: 0.3–0.5) for hospitalizations, and 0.1/person-year (CI: 0.1–0.3) for ED to hospital transfers. Overall, 29.0% of recipients had an incident diagnosis in the ED or hospital setting. Fever and acute upper respiratory infections were the most common diagnoses, with 46 out of 47 diagnoses occurring among infants with high-risk conditions. Conclusions Data from this descriptive observational study do not suggest safety concerns associated with MenACWY-CRM when used as part of clinical care of 2–23 month-old infants/toddlers indicated for vaccination.

Comparative Evaluation of Complement Factor D, C3, and C5 Inhibitors on Serum Bactericidal Activity Against Neisseria Meningitidis Isolates

Introduction: Treatment of complement-associated disorders with the terminal complement inhibitor eculizumab brings a thousand-fold elevated risk of meningococcal disease due to blockage of serum bactericidal activity (SBA) and opsonophagocytosis against Neisseria meningitidis (Nm). Vaccination against Nm is recommended for eculizumab recipients yet infection remains a risk in immunized individuals. Eculizumab was reported to inhibit killing of Nm serogroups B and C in an in vitro study with whole blood from vaccinated donors; in contrast, the investigational complement factor D (FD) inhibitor danicopan (ACH-4471), currently in phase 2 trials for treatment of disorders including paroxysmal nocturnal hemoglobinuria (PNH), had much less effect in the same study. Danicopan also showed limited effect in a separate study of SBA against unencapsulated (non-groupable) Nm strains recovered from eculizumab recipients who developed invasive meningococcal disease, whereas eculizumab blocked all observed SBA. The present study undertakes a comparative evaluation of danicopan, eculizumab, and the complement C3 inhibitor compstatin against SBA with donor sera against Nm strains comprising multiple serogroups. Methods: Serum from three donors (1-3) was obtained before and after vaccination with MenB-4C against serogroup B and conjugate vaccine against serogroups A, C, W, and Y. Five Nm isolates were tested comprising serogroups B, C, W, and Y. SBA was considered positive when bacterial viability was half or less of that observed with inactive control serum following incubation in 20% serum for one hour. Results: Partial SBA was observed in pre-vaccination sera (positive in eight of 15 serum-strain pairings) whereas post-vaccination sera were positive in nearly all cases (13 of 15). Serum donor 3 was selected for comparative inhibitor studies; pre-vaccination serum was SBA-positive against three of five Nm isolates (serogroups C, W, and Y), whereas post-vaccination serum was SBA-positive against all five. Danicopan in pre-vaccination serum inhibited SBA against two of three serogroups (W and Y), likely indicating a requirement of AP activity for amplification when anti-Nm antibody titer is low. However, danicopan in post-vaccination serum had no effect on SBA against all five Nm isolates, indicating no AP requirement when anti-Nm antibody titer is sufficient. In contrast to danicopan, compstatin and eculizumab inhibited SBA of pre-vaccination and post-vaccination serum against all Nm isolates. Conclusions: We conclude that selective FD inhibition, such as by danicopan or the second-generation FD inhibitor ACH-5228, presents a reduced risk of meningococcal disease compared with treatment with C3 or C5 inhibitors. Disclosures Zhao: Achillion Pharmaceuticals, Inc.: Employment. Patel:Achillion Pharmaceuticals, Inc.: Employment. Thanassi:Achillion Pharmaceuticals, Inc: Employment. Huang:Achillion: Employment, Equity Ownership. Podos:Achillion Pharmaceuticals, Inc: Employment.