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      Meningococcal Disease Outbreaks: A Moving Target and a Case for Routine Preventative Vaccination

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          Outbreaks of invasive meningococcal disease (IMD) are unpredictable, can be sudden and have devastating consequences. We conducted a non-systematic review of the literature in PubMed (1997–2020) to assess outbreak response strategies and the impact of vaccine interventions. Since 1997, IMD outbreaks due to serogroups A, B, C, W, Y and X have occurred globally. Reactive emergency mass vaccination campaigns have encompassed single institutions (schools, universities) through to whole sections of the population at regional/national levels (e.g. serogroup B outbreaks in Saguenay–Lac-Saint-Jean region, Canada and New Zealand). Emergency vaccination responses to IMD outbreaks consistently incurred substantial costs (expenditure on vaccine supplies, personnel costs and interruption of other programmes). Impediments included the limited pace of transmission of information to parents/communities/healthcare workers; issues around collection of informed consents; poor vaccine uptake by older adolescents/young adults, often a target age group; issues of reimbursement, particularly in the USA; and difficulties in swift supply of large quantities of vaccines. For serogroup B outbreaks, the need for two doses was a significant issue that contributed substantially to costs, delayed onset of protection and non-compliance with dose 2. Real-world descriptions of outbreak control strategies and the associated challenges systematically show that reactive outbreak management is administratively, logistically and financially costly, and that its impact can be difficult to measure. In view of the unpredictability, fast pace and potential lethality of outbreak-associated IMD, prevention through routine vaccination appears the most effective mitigation tool. Highly effective vaccines covering five of six disease-causing serogroups are available. Preparedness through routine vaccination programmes will enhance the speed and effectiveness of outbreak responses, should they be needed (ready access to vaccines and need for a single booster dose rather than a primary series).

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          National, Regional, State, and Selected Local Area Vaccination Coverage Among Adolescents Aged 13–17 Years — United States, 2019

          Three vaccines are recommended by the Advisory Committee on Immunization Practices (ACIP) for routine vaccination of adolescents aged 11–12 years to protect against 1) pertussis; 2) meningococcal disease caused by types A, C, W, and Y; and 3) human papillomavirus (HPV)-associated cancers ( 1 ). At age 16 years, a booster dose of quadrivalent meningococcal conjugate vaccine (MenACWY) is recommended. Persons aged 16–23 years can receive serogroup B meningococcal vaccine (MenB), if determined to be appropriate through shared clinical decision-making. CDC analyzed data from the 2019 National Immunization Survey-Teen (NIS-Teen) to estimate vaccination coverage among adolescents aged 13–17 years in the United States.* Coverage with ≥1 dose of HPV vaccine increased from 68.1% in 2018 to 71.5% in 2019, and the percentage of adolescents who were up to date † with the HPV vaccination series (HPV UTD) increased from 51.1% in 2018 to 54.2% in 2019. Both HPV vaccination coverage measures improved among females and males. An increase in adolescent coverage with ≥1 dose of MenACWY (from 86.6% in 2018 to 88.9% in 2019) also was observed. Among adolescents aged 17 years, 53.7% received the booster dose of MenACWY in 2019, not statistically different from 50.8% in 2018; 21.8% received ≥1 dose of MenB, a 4.6 percentage point increase from 17.2% in 2018. Among adolescents living at or above the poverty level, § those living outside a metropolitan statistical area (MSA) ¶ had lower coverage with ≥1 dose of MenACWY and with ≥1 HPV vaccine dose, and a lower percentage were HPV UTD, compared with those living in MSA principal cities. In early 2020, the coronavirus disease 2019 (COVID-19) pandemic changed the way health care providers operate and provide routine and essential services. An examination of Vaccines for Children (VFC) provider ordering data showed that vaccine orders for HPV vaccine; tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap); and MenACWY decreased in mid-March when COVID-19 was declared a national emergency (Supplementary Figure 1, https://stacks.cdc.gov/view/cdc/91795). Ensuring that routine immunization services for adolescents are maintained or reinitiated is essential to continuing progress in protecting persons and communities from vaccine-preventable diseases and outbreaks. NIS-Teen is a random-digit-dial telephone survey** conducted annually to monitor vaccination coverage among adolescents aged 13–17 years in the 50 states, the District of Columbia, selected local areas, and selected U.S. territories. †† Sociodemographic information is collected during the telephone interview with a parent or guardian, and a request is made for consent to contact the adolescent’s vaccination provider(s). If consent is obtained, a questionnaire is mailed to the vaccination provider(s) to request the adolescent’s vaccination history. Vaccination coverage estimates are determined from these provider-reported immunization records. This report provides vaccination coverage estimates on 18,788 adolescents aged 13–17 years. §§ The overall Council of American Survey Research Organizations (CASRO) ¶¶ response rate was 19.7%, and 44.0% of adolescents for whom household interviews were completed had adequate provider data. Data were weighted and analyzed to account for the complex sampling design.*** T-tests were used to assess vaccination coverage differences between sociodemographic subgroups. P-values 20 might not be reliable. § Includes percentages receiving Tdap at age ≥10 years. ¶ Statistically significant difference (p 20 might not be reliable. ¶ Includes percentages receiving Tdap at age ≥10 years. ** Includes percentages receiving MenACWY and meningococcal-unknown type vaccine. †† Statistically significant difference (p<0.05) in estimated vaccination coverage by MSA; referent group was adolescents living in MSA principal city areas. §§ ≥2 doses of MenACWY or meningococcal-unknown type vaccine. Calculated only among adolescents aged 17 years at interview. Does not include adolescents who received 1 dose of MenACWY at age ≥16 years. ¶¶ HPV vaccine, nine-valent (9vHPV), quadrivalent (4vHPV), or bivalent (2vHPV). *** HPV UTD includes those who’ve received ≥3 doses and those with 2 doses when the first HPV vaccine dose was initiated before age 15 years and there was at least 5 months minus 4 days between the first and second dose. This update to the HPV recommendation occurred in December of 2016. ††† In July 2020, ACIP revised recommendations for Hepatitis A vaccination to include catch-up vaccination for children and adolescents aged 2–18 years who have not previously received Hepatitis A vaccine at any age (http://dx.doi.org/10.15585/mmwr.rr6905a1). §§§ By parent/guardian report or provider records. Trends in HPV Vaccination by Birth Cohort HPV vaccination initiation by age 13 years increased an average of 5.3 percentage points for each consecutive birth year, from 19.9% among adolescents born in 1998 to 62.6% among those born in 2006 (Supplementary Figure 2, https://stacks.cdc.gov/view/cdc/91796). Being HPV UTD by age 13 years increased an average of 3.4 percentage points for each consecutive birth year, from 8.0% among adolescents born in 1998 to 35.5% among those born in 2006. Discussion In 2019, coverage with HPV vaccine and with MenACWY improved compared with coverage in 2018. Improvements in ≥1 dose HPV and HPV UTD vaccination coverage were observed among females and males. In addition, more teens began HPV vaccination on time (by age 13 years) in 2019, suggesting that more parents are making the decision to protect their teens against HPV-associated cancers. Efforts from federal, state, and other stakeholders to prioritize HPV vaccination among adolescents, and reducing the number of recommended HPV vaccine doses from a 3-dose to a 2-dose series ( 2 ), likely contributed to these improvements. Coverage with ≥1 dose of MenACWY increased to 88.9%; coverage with ≥2 doses remained low at 53.7%, indicating that continued efforts are needed to improve receipt of the booster dose. Despite progress in adolescent HPV vaccination and MenACWY coverage, disparities remain; all adolescents are not equally protected against vaccine-preventable diseases. As in previous years, compared with adolescents living in MSA principal cities, HPV UTD status and coverage with ≥1 dose each of HPV vaccine and MenACWY continue to be lower among adolescents in non-MSA areas ( 3 ). However, these geographic disparities were present only for adolescents at or above the poverty level in 2019. This finding is consistent with another study that found socioeconomic status to be a moderating factor in the association between HPV vaccination and MSA ( 4 ). The lack of an MSA disparity among adolescents below the poverty level might reflect the access that low-income adolescents have to the VFC program****; previous studies have reported higher HPV vaccination coverage rates among adolescents living below the poverty level ( 5 , 6 ). Reasons for the MSA disparity among higher socioeconomic status adolescents are less clear but might be an indicator of lower vaccine confidence. More work is needed to understand the relationship between socioeconomic status and geographic disparities and the barriers that might be contributing to such differences. The findings in this report are subject to at least two limitations. First, the CASRO response rate to NIS-Teen was 19.7%, and only 44.0% of households with completed interviews had adequate provider data. A portion of the questionnaires sent to vaccination provider(s) to request the adolescent’s vaccination history were mailed in early 2020. A lower response rate was observed for those requests, likely because of the effect of the COVID-19 pandemic on health care provider operations. †††† Second, even with adjustments for household and provider nonresponse, landline-only households, and phoneless households, a bias in the estimates might remain. §§§§ The COVID-19 pandemic has the potential to offset historically high vaccination coverage with Tdap and MenACWY and to reverse gains made in HPV vaccination coverage. Orders for adolescent vaccines have decreased among VFC providers during the pandemic. A recent analysis using VFC provider ordering data showed a decline in vaccine orders for several VFC-funded noninfluenza childhood vaccines since mid-March when COVID-19 was declared a national emergency ( 7 ). CDC, along with other national health organizations, continues to stress the importance of well-child visits and vaccinations as essential services ( 8 ). The majority of practices appear to be open and resuming vaccination activities for their pediatric patients ( 9 , 10 ). Providers can take several steps to ensure that adolescents are up to date with recommended vaccines. These include 1) promoting well-child and vaccination visits; 2) following guidance on safely providing vaccinations during the COVID-19 pandemic ¶¶¶¶ ; 3) leveraging reminder and recall systems to remind parents of their teen’s upcoming appointment, and recalling those who missed appointments and vaccinations; and 4) educating eligible patients and parents, especially those who might have lost employer-funded insurance benefits, about the availability of publicly funded vaccines through the VFC program. In addition, state, local, and territorial immunization programs can consider using available immunization information system data***** to identify local areas and sociodemographic groups at risk for undervaccination related to the pandemic, and to help prioritize resources aimed at improving adolescent vaccination coverage. Summary What is already known about this topic? Three vaccines are routinely recommended for adolescents to prevent diseases that include pertussis, meningococcal disease, and cancers caused by human papillomavirus (HPV). What is added by this report? Adolescent vaccination coverage in the United States continues to improve for HPV and for meningococcal vaccines, with some disparities. Among adolescents living at or above the poverty level, those living outside a metropolitan statistical area (MSA) had lower coverage with HPV and meningococcal vaccines than did those living in MSA principal cities. What are the implications for public health care? Ensuring routine immunization services for adolescents, even during the COVID-19 pandemic, is essential to continuing progress in protecting individuals and communities from vaccine-preventable diseases and outbreaks.
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            Antigenic similarities between brain components and bacteria causing meningitis. Implications for vaccine development and pathogenesis.

            Glycopeptides containing polysialic acid units were isolated from human and rat brain and tested for reactivity with antibodies against meningococcal capsules. The polysialosyl glycopeptides bound specifically to horse antiserum against meningococcus group B. The interaction was inhibited by capsular polysaccharides from meningococcus group B but not groups A or C. The capsular polysaccharide of Escherichia coli K1, which is immunochemically similar to the group B polysaccharide, also inhibited binding. These findings could explain the failure to develop efficient vaccines against group B meningococcus or E coli K1 and also suggest that immunological tolerance could be a factor in the pathogenesis of meningitis caused by these bacteria. The presence of the cross-reactive brain component calls for caution in efforts to develop capsular polysaccharide vaccines from these bacteria or the proposed use of passively administered antibodies as immunotherapy of neonatal meningitis.
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              Planning, registration, and implementation of an immunisation campaign against meningococcal serogroup C disease in the UK: a success story.

              The introduction of meningococcal C conjugate (MCC) vaccine in the UK in November 1999 as a routine 3 dose infant immunisation course, with a single catch-up dose for all children aged between 12 months and 17 years, was the result of an intensive 5 year collaborative research programme funded by the Department of Health for England and involving public bodies, academia and vaccine manufacturers. The research programme established the safety and immunogenicity of MCC vaccines in infants, toddlers, pre-school and school-aged children. The nature and frequency of common adverse events in school-aged children was similar to that after a booster dose of diphtheria and tetanus vaccine given to the same age groups. The recommendation that a single dose was adequate for children aged 12 months and above was based on antibody levels measured by serum bactericidal assay and evidence of induction of immunological memory as shown by maturation of antibody avidity. Licensure by the Medicines Control Agency was based on serological criteria alone without direct evidence of efficacy and has set a precedent for other meningococcal conjugate polysaccharide vaccines. Vaccine coverage of around 85% was achieved in the targeted age groups and has resulted in a drop in the incidence of serogroup C disease in these groups of over 80% within 18 months of the start of the vaccination programme. Early post-licensure efficacy estimates for toddlers and teenagers (88 and 96%, respectively, in the first 16 months after vaccination) validate the serological criteria used for licensure. Surveillance of the prevalent serogroups and serosubtypes among invasive case isolates has shown no evidence of any capsular switching to serogroup B during the first 18 months of the MCC vaccination programme.
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                Author and article information

                Contributors
                lamine.m.soumahoro@gsk.com
                Journal
                Infect Dis Ther
                Infect Dis Ther
                Infectious Diseases and Therapy
                Springer Healthcare (Cheshire )
                2193-8229
                2193-6382
                11 August 2021
                11 August 2021
                December 2021
                : 10
                : 4
                : 1949-1988
                Affiliations
                [1 ]GRID grid.425090.a, GSK, ; Avenue Fleming 20, 1300 Wavre, Belgium
                [2 ]GRID grid.476503.3, ISNI 0000 0001 0023 6425, GSK, ; Rueil-Malmaison, France
                [3 ]GRID grid.418019.5, ISNI 0000 0004 0393 4335, GSK, ; Rockville, USA
                [4 ]GRID grid.419014.9, ISNI 0000 0004 0576 9812, Department of Pediatrics, , Santa Casa de São Paulo School of Medical Sciences, ; São Paulo, Brazil
                Article
                499
                10.1007/s40121-021-00499-3
                8572905
                34379309
                a6ed3d2f-22b3-4600-b5ea-90853ac71b82
                © The Author(s) 2021

                Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.

                History
                : 7 May 2021
                : 5 July 2021
                Funding
                Funded by: GlaxoSmithKline Biologicals SA
                Categories
                Review
                Custom metadata
                © The Author(s) 2021

                epidemic,neisseria meningitidis,meningitis,outbreak,vaccine
                epidemic, neisseria meningitidis, meningitis, outbreak, vaccine

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