Vaccine effectiveness and impact of meningococcal vaccines against gonococcal infections: A systematic review and meta-analysis.

OBJECTIVES: To systematically review and synthesis the evidence of vaccine effectiveness (VE) and impact (VI) of meningococcal vaccines in preventing gonorrhoea. METHODS: We systematically evaluated studies. Literature searches were conducted in PubMed, Embase, Cochrane Library, CINAHL, Google Scholar, clinical trial registries, and major health and immunisation conferences. Meta-analysis was performed with the DerSimonian-Laird random-effects model to estimate the pooled VE. RESULTS: Twelve studies met the criteria for inclusion. VE of meningococcal B (MenB) outer membrane vesicle (OMV) vaccines was evaluated in nine studies, with one study evaluating a non-OMV vaccine, MenB-FHbp. The majority of studies targeted individuals aged 15-30 years. Adjusted VE for OMV vaccines against gonorrhoea ranged from 22% to 46%. MenB-FHbp did not show protection against gonorrhoea. The pooled VE estimates of OMV vaccines against any gonorrhoea infection following the full vaccine series were 33-34%. VI was assessed for 4CMenB in Canada and Australia, for VA-MENGOC-BC in Cuba; and for MenBvac in Norway. VI ranged from a 30% to 59% reduction in gonorrhoea incidence. CONCLUSIONS: 4CMenB and other MenB-OMV vaccines show moderate effectiveness against gonorrhoea. Further research is required to explore the factors associated with vaccine protection, informing more effective vaccination strategies for the management of gonococcal infections.

The Bacterial Meningitis Epidemic in Banalia in the Democratic Republic of Congo in 2021.

BACKGROUND: The Banalia health zone in the Democratic Republic of Congo reported a meningitis epidemic in 2021 that evolved outside the epidemic season. We assessed the effects of the meningitis epidemic response. METHODS: The standard case definition was used to identify cases. Care was provided to 2651 in-patients, with 8% of them laboratory tested, and reactive vaccination was conducted. To assess the effects of reactive vaccination and treatment with ceftriaxone, a statistical analysis was performed. RESULTS: Overall, 2662 suspected cases of meningitis with 205 deaths were reported. The highest number of cases occurred in the 30-39 years age group (927; 38.5%). Ceftriaxone contributed to preventing deaths with a case fatality rate that decreased from 70.4% before to 7.7% after ceftriaxone was introduced (p = 0.001). Neisseria meningitidis W was isolated, accounting for 47/57 (82%), of which 92% of the strains belonged to the clonal complex 11. Reactive vaccination of individuals in Banalia aged 1-19 years with a meningococcal multivalent conjugate (ACWY) vaccine (Menactra®) coverage of 104.6% resulted in an 82% decline in suspected meningitis cases (incidence rate ratio, 0.18; 95% confidence interval, 0.02-0.80; p = 0.041). CONCLUSION: Despite late detection (two months) and reactive vaccination four months after crossing the epidemic threshold, interventions implemented in Banalia contributed to the control of the epidemic.

Neisseria gonorrhoeae lipooligosaccharide glycan epitopes recognized by bactericidal IgG antibodies elicited by the meningococcal group B-directed vaccine, MenB-4C.

Introduction: Outer membrane vesicles (OMVs) of Neisseria meningitidis in the group B-directed vaccine MenB-4C (BexseroR) protect against infections with Neisseria gonorrhoeae. The immunological basis for protection remains unclear. N. meningitidis OMV vaccines generate human antibodies to N. meningitidis and N. gonorrhoeae lipooligosaccharide (LOS/endotoxin), but the structural specificity of these LOS antibodies is not defined. Methods: Ten paired human sera obtained pre- and post-MenB-4C immunization were used in Western blots to probe N. meningitidis and N. gonorrhoeae LOS. Post-MenB-4C sera (7v5, 19v5, and 17v5), representing individual human variability in LOS recognition, were then used to interrogate structurally defined LOSs of N. meningitidis and N. gonorrhoeae strains and mutants and studied in bactericidal assays. Results and discussion: Post-MenB-4C sera recognized both N. meningitidis and N. gonorrhoeae LOS species, ~10% of total IgG to gonococcal OMV antigens. N. meningitidis and N. gonorrhoeae LOSs were broadly recognized by post-IgG antibodies, but with individual variability for LOS structures. Deep truncation of LOS, specifically a rfaK mutant without α-, ß-, or γ-chain glycosylation, eliminated LOS recognition by all post-vaccine sera. Serum 7v5 IgG antibodies recognized the unsialyated L1 α-chain, and a 3-PEA-HepII or 6-PEA-HepII was part of the conformational epitope. Replacing the 3-PEA on HepII with a 3-Glc blocked 7v5 IgG antibody recognition of N. meningitidis and N. gonorrhoeae LOSs. Serum 19v5 recognized lactoneotetrose (LNT) or L1 LOS-expressing N. meningitidis or N. gonorrhoeae with a minimal α-chain structure of Gal-Glc-HepI (L8), a 3-PEA-HepII or 6-PEA-HepII was again part of the conformational epitope and a 3-Glc-HepII blocked 19v5 antibody binding. Serum 17v5 LOS antibodies recognized LNT or L1 α-chains with a minimal HepI structure of three sugars and no requirement for HepII modifications. These LOS antibodies contributed to the serum bactericidal activity against N. gonorrhoeae. The MenB-4C vaccination elicits bactericidal IgG antibodies to N. gonorrhoeae conformational epitopes involving HepI and HepII glycosylated LOS structures shared between N. meningitidis and N. gonorrhoeae. LOS structures should be considered in next-generation gonococcal vaccine design.

On The Horizon: Novel Approaches to Sexually Transmitted Infection Prevention.

Rates of sexually transmitted infections (STIs), especially cases of infectious and congenital syphilis, are increasing in the United States. Novel strategies for STI prevention are being explored and include doxycycline post-exposure prophylaxis and the potential utility of vaccines against gonorrhea. Self-collection of samples and point of care testing for STI are increasingly being employed in a variety of settings. Both can improve uptake of screening and lead to earlier detection and treatment of incident STI in target populations. Overcoming existing regulatory issues and optimizing implementation of current evidence-based strategies will be key to maximizing future STI prevention efforts. Here we provide an update for primary care providers on selected new strategies for STI prevention either currently available or under development for possible future use.

E-mail as a way of communication during the ACWY meningococcal vaccination campaign in adolescents and young adults in the Region of Murcia.

In 2019, ACWY meningococcal vaccination for people born between 2001 and 2007 was recommended. In Murcia, during the first 9 months, the coverage was 52.89%. This study is aimed to evaluate the effects of e-mail reminders on vaccination coverage. A longitudinal, prospective trial was performed on non-vaccinated individuals with e-mail addresses. An e-mail reminder was sent to people assigned to the intervention group (born in any month, except January and July), and 4 weeks later, the same was sent to the control group. Vaccination coverage was assessed before and 4 weeks after each intervention. After the first intervention, 5.15% of the participants in the intervention group were vaccinated (1.57% in the control group). The increased likelihood of being vaccinated if a person had been sent an e-mail was 1.033 (95% confidence interval, 1.019-1.047; p = 0.001). This study highlighted the impact of e-mail as an appropriate method of communication for vaccination programmes.

Impact of Meningococcal ACWY Vaccination Program during 2017-18 Epidemic, Western Australia, Australia.

The rising incidence of invasive meningococcal disease (IMD) caused by Neisseria meningitidis serogroup W in Western Australia, Australia, presents challenges for prevention. We assessed the effects of a quadrivalent meningococcal vaccination program using 2012-2020 IMD notification data. Notification rates peaked at 1.8/100,000 population in 2017; rates among Aboriginal and Torres Strait Islander populations were 7 times higher than for other populations. Serogroup W disease exhibited atypical manifestations and increased severity. Of 216 cases, 20 IMD-related deaths occurred; most (19/20) were in unvaccinated persons. After the 2017-2018 targeted vaccination program, notification rates decreased from 1.6/100,000 population in 2018 to 0.9/100,000 population in 2019 and continued to decline in 2020. Vaccine effectiveness (in the 1-4 years age group) using the screening method was 93.6% (95% CI 50.1%-99.2%) in 2018 and 92.5% (95% CI 28.2%-99.2%) in 2019. Strategic planning and prompt implementation of targeted vaccination programs effectively reduce IMD.

Neisseria meningitidis on Sinonasal Culture for Sinusitis: A Case Series and Literature Review.

Neisseria meningitidis is carried asymptomatically in the nasopharynx and is most known for causing septicemia and meningitis; however, the pathogenesis and incidence rates of N. meningitidis sinusitis are not well described. This case series describes four patients from a tertiary medical center who presented with culture-positive N. meningitidis sinusitis within a nine-month period. Three patients had complete resolution of symptoms after treatment with the appropriate antibiotic regimen, with one patient requiring functional endoscopic sinus surgery. We encourge providers to advocate for vaccination in their young adult unvaccinated patients, as each patient here was not appropriately vaccinated according to CDC guidelines. Laryngoscope, 134:1603-1605, 2024.

Bioinformatics Analysis of Global Diversity in Meningococcal Vaccine Antigens over the Past 10 Years: Vaccine Efficacy Prognosis.

Neisseria meningitidis (N. meningitidis) serogroup B (MenB) is the leading cause of invasive meningococcal disease worldwide. The pathogen has a wide range of virulence factors, which are potential vaccine components. Studying the genetic variability of antigens within a population, especially their long-term persistence, is necessary to develop new vaccines and predict the effectiveness of existing ones. The multicomponent 4CMenB vaccine (Bexsero), used since 2014, contains three major genome-derived recombinant proteins: factor H-binding protein (fHbp), Neisserial Heparin-Binding Antigen (NHBA) and Neisserial adhesin A (NadA). Here, we assessed the prevalence and sequence variations of these vaccine antigens in a panel of 5667 meningococcal isolates collected worldwide over the past 10 years and deposited in the PubMLST database. Using multiple amino acid sequence alignments and Random Forest Classifier machine learning methods, we estimated the potential strain coverage of fHbp and NHBA vaccine variants (51 and about 25%, respectively); the NadA antigen sequence was found in only 18% of MenB genomes analyzed, but cross-reactive variants were present in less than 1% of isolates. Based on our findings, we proposed various strategies to improve the 4CMenB vaccine and broaden the coverage of N. meningitidis strains.

Aceptación y desigualdades socioeconómicas en la vacunación frente a meningococo B en la Comunidad de Madrid en el periodo anterior a su inclusión en el calendario / Acceptance and socioeconomic inequalities in meningococcal B vaccination in the community of Madrid prior to its inclusion in the immunization schedule

Introducción: La principal medida de prevención frente a la enfermedad meningocócica invasiva es la vacunación. El objetivo de este estudio es evaluar la aceptabilidad y las desigualdades socioeconómicas en el acceso a la vacuna frente a meningococo B (MenB) en la Comunidad de Madrid en el periodo previo a la introducción de la misma en el calendario. Materiales y métodos: Se realizó un estudio observacional descriptivo en la cohorte de niños/as nacidos entre 2016 y 2019, de tipo ecológico, empleando registros poblacionales electrónicos. Se describieron las coberturas de vacunación, se analizaron los factores asociados al estado vacunal, se describieron las distribuciones espaciales de cobertura de vacunación y de índice de privación (IP) y se analizó la asociación entre ambas mediante regresión espacial. Resultados: Se observó una tendencia creciente de las coberturas de primovacunación, pasando de un 44% en la cohorte de nacidos en el año 2016 a un 68% en la cohorte de 2019. Se encontró asociación estadísticamente significativa entre el estado vacunal y el IP (OR de primovacunación en zonas con IP5 respecto a zonas con IP1: 0,38; IC 95%: 0,39-0,50; p<0,001). El análisis espacial mostró correlación inversa entre el IP y la cobertura de vacunación. Conclusiones: El ascenso de las coberturas de esta vacuna muestra aceptación por parte de la población. La relación entre nivel socioeconómico y cobertura de vacunación confirma la existencia de una desigualdad en salud, y subraya la importancia de su inclusión en el calendario.(AU)

Introduction: The main preventive measure against invasive meningococcal disease is vaccination. The aim of our study was to evaluate the acceptability of the meningococcal B (MenB) vaccine and socioeconomic inequalities in the access to the vaccine in the Community of Madrid in the period prior to its introduction in the immunization schedule. Materials and methods: We conducted an observational and ecological descriptive study in the cohort of children born between 2016 and 2019 using population-based electronic records. We calculated the vaccination coverage and analysed factors associated with vaccination status, determined the spatial distribution of vaccination coverage and the deprivation index (DI) and assessed the association between them by means of spatial regression. Results: We observed an increasing trend in primary vaccination coverage, from 44% in the cohort born in 2016 to 68% in the 2019 cohort. We found a statistically significant association between vaccination status and the DI (OR of primary vaccination in areas with DI5 compared to areas with DP1, 0.38; 95% confidence interval: 0.39-0.50; P<.001). The spatial analysis showed an inverse correlation between the DI and vaccination coverage. Conclusions: The rise in the coverages of the MenB vaccine shows acceptance by the population. The association between socioeconomic level and vaccination coverage confirms the existence of health inequality and underlines the importance including this vaccine in the immunization schedule.(AU)

Acceptance and socioeconomic inequalities in meningococcal B vaccination in the community of Madrid prior to its inclusion in the immunization schedule.

INTRODUCTION: The main preventive measure against invasive meningococcal disease is vaccination. The aim of our study was to evaluate the acceptability of the meningococcal B (MenB) vaccine and socioeconomic inequalities in the access to the vaccine in the Community of Madrid in the period prior to its introduction in the immunization schedule. MATERIALS AND METHODS: We conducted an observational and ecological descriptive study in the cohort of children born between 2016 and 2019 using population-based electronic records. We calculated the vaccination coverage and analysed factors associated with vaccination status, determined the spatial distribution of vaccination coverage and the deprivation index (DI) and assessed the association between them by means of spatial regression. RESULTS: We observed an increasing trend in primary vaccination coverage, from 44% in the cohort born in 2016 to 68% in the 2019 cohort. We found a statistically significant association between vaccination status and the DI (OR of primary vaccination in areas with DI5 compared to areas with DP1, 0.38; 95% confidence interval, 0.39-0.50; P<.001). The spatial analysis showed an inverse correlation between the DI and vaccination coverage. CONCLUSIONS: The rise in the coverages of the MenB vaccine shows acceptance by the population. The association between socioeconomic level and vaccination coverage confirms the existence of health inequality and underlines the importance including this vaccine in the immunization schedule.

Real-world impact and effectiveness of MenACWY-TT.

In response to escalating cases of serogroup W (MenW) invasive meningococcal disease (IMD), multiple countries introduced quadrivalent conjugate MenACWY vaccines into their national immunization programs (NIPs). Here, we summarize the real-world impact and vaccine effectiveness (VE) data of MenACWY-TT from Chile, England, the Netherlands, and Australia. Incidence rate reductions (IRRs) and VE from baseline to post-NIP period were extracted from publications or calculated. After the administration of a single dose of MenACWY-TT, substantial IRRs of MenCWY were observed across the countries in vaccine-eligible age groups (83%-85%) and via indirect protection in non-vaccine-eligible age groups (45%-53%). The impact of MenACWY-TT was primarily driven by MenW IRRs, as seen in vaccine-eligible age groups (65%-92%) and non-vaccine-eligible age groups (41%-57%). VE against MenW was reported in vaccine-eligible toddlers (92%) in the Netherlands and in vaccine-eligible adolescents/young adults (94%) in England. These real-world data support the implementation and continued use of MenACWY-TT in NIPs.

Serogroup B Meningococcal Sepsis and Meningitis Associated With Meningococcal Acute Otitis Media, and Paranasal Sinusitis in an Infant: A Case Report.

Meningococcal disease (MD) is a potentially lethal condition. Typically, following infection, MD manifests with high fever, with signs and symptoms of severe septicemia with or without purpura, and in more than half of cases with meningitis. Acute otitis media (AOM) caused by Neisseria meningitidis has scarcely been reported, mostly without severe MD, and there are no reports of meningococcal paranasal sinusitis (PS). We present the case of a previously healthy 11-month-old infant who started with fever and cough and further developed intense irritability and right spontaneous purulent otorrhea, with subsequent increased fever and seizures. Blood, cerebrospinal, and middle ear fluid cultures were positive for N. meningitidis serogroup B, and a CT scan showed both maxillary and ethmoidal sinusitis. Intravenous ceftriaxone was administered for eight days, and three months following discharge, no sequelae were identified. This is the first report of a patient with MD associated with sepsis, meningitis, AOM, and PS.

Association between Meningococcal Meningitis and Santa Ana Winds in Children and Adolescents from Tijuana, Mexico: A Need for Vaccination.

BACKGROUND: Based on previous studies (regional and national), Tijuana, Baja California, Mexico (across the border from San Diego, California, USA), has been shown to have the highest rate of meningococcal meningitis (MeM) in the country. However, the reason for this high incidence has not yet been established. To explain this regional/endemic public health problem, we aimed to evaluate whether there is a climatic association with MeM in the region. In the "African Meningitis Belt," the Harmattan seasons are associated with MeM outbreaks; similarly, the Santa Ana winds (SAWs) seasons are characterized by hot and dry winds (similar to Harmattan seasons) that occur seasonally in Southwest California, USA, and Northwest Baja California, Mexico. OBJECTIVES: We aimed to determine a potential association of SAWs with MeM in Tijuana, Baja California, Mexico, which in turn may partially explain the high rate of this disease in the region. METHODS: Based on our previously published data obtained from thirteen years of active surveillance of MeM and a 65-year review showing the seasonal occurrence of SAWs, we estimated the risk ratio (RR) for the total case numbers of MeM (51 cases of children < 16 years old) vs. bacterial meningitis not caused by Neisseria meningitidis (NMeM, 30 cases, same age group) during seasons with and without SAWs. RESULTS: We found an association between SAWs and MeM, but not with NMeM (RR = 2.06, p = 0.02 (95% CI 1.1 to 3.8), which may partially explain the high endemicity of this deadly disease in this part of the globe. CONCLUSION: This study shows a new potential climatic association with MeM and provides more information that justifies universal meningococcal vaccination in Tijuana, Mexico.

Efficacy and Safety of Quadrivalent Conjugate Meningococcal Vaccines: A Systematic Review and Meta-Analysis.

Over the last decades, different quadrivalent antimeningococcal vaccine formulations (diphteria toxoid conjugate, MenACWY-D; tetanus toxoid conjugate, MenACWY-TT; CRM197 protein conjugate, MenACWY-CRM) have been developed. However, their availability varies, both in terms of authorized formulations and of inclusion in vaccination schedules. Furthermore, several countries include only the monovalent meningococcal C (MenC) vaccine in their immunization programmes. Finally, there is currently no updated systematic review that directly compares the MenACWY formulations. Thus, we summarized the evidence on efficacy and safety through four parallel, independent systematic literature reviews with meta-analysis which included randomized controlled trials comparing the abovementioned vaccines. A total of 16 studies have been included. In terms of efficacy, MenACWY-TT outperformed MenACWY-D and MenACWY-CRM for A, W-135, and Y serogroups, while no significant difference was found for serogroup C. Furthermore, we did not find significant differences in efficacy between MenC and MenACWY-TT. Regarding the safety, we were able to perform a quantitative analysis only between MenACWY-TT and MenC, finding no significant differences. Similarly, among the different MenACWY formulations no relevant differences were identified. These findings suggest that MenACWY-TT could be preferable to other formulations to improve current vaccination programs and to better develop future immunization policies.

A National Advisory Committee on Immunization (NACI) update on invasive meningococcal disease (IMD) epidemiology and program-relevant considerations for preventing IMD in individuals at high risk of exposure.

Following recent outbreaks of invasive meningococcal disease (IMD) in Canada and updates to provincial vaccination guidelines, the National Advisory Committee on Immunization (NACI) conducted a targeted review of evidence with a focus on immunization of adolescents and young adults. NACI reviewed national and international immunization recommendations for populations at high-risk of IMD, national IMD epidemiology and program-relevant considerations. Given the varied IMD epidemiology, NACI determined that recommending a pan-Canadian targeted program is currently challenging and that regional programs may be better suited to prevent IMD in population groups considered to be at high-risk of exposure. Further data is needed to ascertain contemporary risk factors for IMD (including activities and settings associated with bacterial acquisition, carriage and transmission) and estimate the true cost of meningococcal vaccine-preventable infections in Canada. To support provinces and territories in their decision-making, an outline of program-relevant elements for provincial and territorial consideration is provided.

Vaccine Uptake to Prevent Meningitis and Encephalitis in Shanghai, China.

Multiple vaccines may prevent meningitis and encephalitis (M/E). In China, the meningococcal vaccine and Japanese encephalitis vaccine (JEV) have been included in the expanded program of immunization (EPI). The pneumococcal vaccine, Haemophilus influenzae type b (Hib) vaccine, rotavirus vaccine, and enterovirus 71 (EV-71) vaccine are non-EPI vaccines and are self-paid. We aim to investigate the uptake of these M/E vaccines in children and the related knowledge and health beliefs among family caregivers. A total of 1011 family caregivers with children aged 1-6 years in Shanghai, China were included in the study. The uptake of the pneumococcal vaccine, Hib-containing vaccine, rotavirus vaccine, and EV-71 vaccine remained at 44.0-48.1% in children, compared with the higher uptake of the meningococcal vaccine (88.8%) and JEV (87.1%). Moreover, family caregivers had limited knowledge on the M/E pathogens and possible vaccines. Their health beliefs were moderate to high. Then, a health belief model (HBM) and a structural equation model were established. The uptake of four non-EPI vaccines was significantly influenced by family income (ß = 0.159), knowledge (ß = 0.354), self-efficacy (ß = 0.584), and perceived susceptibility (ß = 0.212) within an HBM. Therefore, it warrants further improving the uptake rate for these non-EPI vaccines to prevent potential M/E in children. A specific health promotion may empower the caregivers' decision-making on childhood vaccination.