The Global Burden & Changing Epidemiology of Meningococcal Disease: Implications for Prevention J. Simon Kroll, MA, BM BCh Marco A. P. Safadi, MD, PhD Dean/Professor of Paediatrics Assistant Professor of Pediatrics Imperial College London FCM da Santa Casa de Sao Paulo St Mary’s Hospital Campus So Paulo, Brazil London, United Kingdom ledscape EDUCATION’Program Overview * The pathogenesis, clinical features, and transmission of meningococcal disease * The global burden and epidemiology of the disease * Implications for vaccine developmentOverview of Meningococcal Disease * Caused by Neisseria meningitidis * High morbidity * High case fatality rates (up to 20%) * Associated infectious syndromes: — Bacteremia (37.5%), including meningococcemia, the most severe manifestation — Meningitis (50%) - Pneumonia (9%)—more common in adults — Less common syndromes—conjunctivitis, septic arthritis, purulent pericarditis, urethritis, chronic meningococcemia Centers for Disease Control and Prevention. http://vww.cde.gov/vaccines/pubs/pinkbook/mening.html . Cohn AC, et al. Cin infect Dis 2030;50(2)184-101 Medscape Image courtesy of CDC Public Health Image Library/James VolkCarriage and Transmission * Transmitted by person-to-person contact * Pharyngeal acquisition sets the scene for invasive meningococcal disease * N meningitidis is predominately carried by teenagers/young adults Meningococcal carriage prevalence — peak among adolescents/young adults 23.7% 7.8% 45% Infants 19 year olds 50 year olds Adapted from Christensen H, et al. Lancet Infect Dis. 2010;10(12):853-861Sequelae Associated With Meningococcal Disease * 10%-20% of disease survivors have significant sequelae * Complications include: — Hearing impairment and hearing loss Neurologic impairment — Visual impairment — Skin scarring - Limb amputation Kaplan SL, et al. Pediatrics. 2006;118(4):2979-984. Pace D, et al. Vaccine. 2012;30(Suppl 2):83-9. Medscape Image courtesy of M. Safadi, MD. See eeeWho Is at Risk for Meningococcal Disease * During endemic periods: — Infants and young children — Second peak among adolescents — Third peak among older adults * During outbreaks and epidemics — Higher number of cases among older children, adolescents, and young adults Most cases (> 90%) occur in previously healthy people with no identified risk factors. Rosenstein NE, et al.N Engl Med. 2001;244(28):13781388 Medscape Kaplan SL, et al. Pediatrics. 2006;118(4):e979-984.Diagnosis of Meningococcal Disease * Diagnosis usually based on clinical suspicion — Rapidly progressing disease — Emergency department admission * Laboratory diagnosis — Culture: eg, blood, CSF — Antigen detection: latex agglutination testing and CIE in CSF and blood — Gram staining: CSF, petechial lesions, blood — PCR: CSF, blood (even when micro- organisms are nonviable after antimicrobial treatment CIE = counter immunoelectrophoresis; CSF = cerebrospinal fluid; PCR = polymerase chain reaction . ED! leds cape World Health Organization. Wkly Epidemiol Rec. 2011;86:521-539.Treatment of Meningococcal Disease In hospital, in an intensive care unit if available Empiric treatment with broad- spectrum antibiotics, usually third- generation cephalosporin 5- to 7-day treatment standard Supportive care, especially for shock or meningococcemia — Early and rapid resuscitation, inotropicand ventilatory support Centers for Disease Control and Prevention. http://vww.cde.gov/vaccines/pubs/pinkbook/mening.html World Health Organization. Wkly Epidemiol Rec. 2011;86:521-539. Image courtesy of M. Safadi, MD. \ MedscapeMeningococcal Serogroups * 6responsible for almost all meningococcal disease—A, B, C, W135, X,Y * Serogroup distribution varies geographically and with time Reduction in serogroup C disease after introduction of Men C vaccine in England and Wales ™ Other 3000 @ Ungrouped/ungroupable 2500 = Group C = G B a ™ Grou % 1500 E 2 % 1000 Qo 500 i o+ 1 eal 1 2° cs # a = ¢ 4 © &§ 2 @ os aa $ sss 8 83 888588 8888 $s s 8 8§ § § § 8 8 §§ & & 8 ss 8&8 &§ &§ &§ &§ &§ S§ & RS BB a Ss Ss Se 8S 8 ee 8 et @e¢s 2s 8 $28 5 8 = S$ F & @ 8 8 8 8 8s 8 8 8 38 & 8 § § § § § §§ § 8 § § & 8 S33 8 &§ & & & & SR KR KARA Source: Public Health England, Meningococcal Reference Unit, Invasive meningococcal infections laboratory reports, England and Wales, 2012. cape Halperin SA, et al. Vaccine. 2012:30{Suppl 2)826-36; Harrison OB, et al. Emerg Infect Dis. 2013;1914)566-573; EDUCATION World Health Organization. Wkly Epidemiol Rec. 2011;86:521-539.Regional Variations in Meningococcal Serogroup Distribution* a es Mic Y Hi wi3s Adapted from Halperin SA, et al. Vaccine. 2012;30{Suppl 2):826-36. Serogroup distribution is very unpredictabl *Most prevalent serogroups shown for each region. World Health Organization. Wkly Epidemiol Rec. 2011;86:521-539.Recent Changes in the Epidemiology of Meningococcal Disease * Latin America: B and C serogroups predominant, but W135 emerging! - Argentina (> 50% cases) - Chile (> 60% cases) — Also Southern Brazil = Same clonal complex as in Asia outbreak > 10 years ago and Haj pilgrimage outbreaks —international spread * Africa: serogroup A predominant; also W135"; Xx emerging!“ Meningococcal disease occurs in cycles, especially serogroup B—every 8-12 years. SétaiMA, eal plemia infect 201384447488 Séfadi MA, el, Expert Rev Vaccines 201 press Medscape ge eet eeMeningococal Disease Surveillance * 2 types—passive and active * Most countries use passive surveillance * High-quality active surveillance gives a true picture of meningococcal disease — eg, United States—ABCs; United Kingdom—ESMD * Surveillance quality very variable—needs improvement in parts of Latin America, Asia, and Africa ABC = Active Bacterial Core Surveillance; ESMD = Enhanced Surveillance of Meningococcal Disease Harrison LH, et al. Vaccine. 2009;27(Suppl2):B51-63. M ae Centers for Disease Contral and Prevention. http /unww.cd gov/abes/ndex. html Medscape Public Health England. http://www.gov.uk/government/organisations/public-health-englandVaccines for Meningococcal Disease Serogroups Covered Number of Vaccines Polysaccharide A, C, W-135,Y 3 vaccines AC 7 c 3 Polysaccharide- x 1 protein conjugates A, C, W-135,Y a B 2 Outer membrane vesicle (OMV) vaccines 8 2 (+ C polysaccharide capsule) urrently no vaccine offers protection for all age groups against all serogroups. Terranella A, et al. Infect Drug Resist. 2011;4:161-169. Medscape World Health Organization. Wkly Epidemiol Rec. 2011;86:521-539, EDUCATIONLimitations of Polysaccharide Vaccines * Low immunogenicity in children <2 years 700 1 previous dose 708 2 previous doses * Induce short-duration immune 600 | No previous doses response = 500 * Partial and transient effect on 2 2 2 40 carriage < cee 5 ” 300 * Diminished antibody responses after repeated vaccinations 200 against serogroup C Fea (hyporesponsiveness) o psac~meni ' eee Response to Serogroup C = meningococcal serogroup A/C polysaccharide vaccine; (GM = serum bactericidal antibody geometric mean titers fimonth: after eS8C) Jokhdar H, et al. Clin Diagn Lab Immunol. 2004;11(1):83-88. Medscape Satadi MA, et al. J Pediatr (Rio J). 2006;82(Suppl):S35-S44, EDUCATIONMeningococcal Conjugate Vaccines * Tetanus toxoid and CRM,.7 carrier proteins * Immunogenic from early infancy (> 2 months) * Induce immunologic memory—booster response * Prevent acquisition of carriage (eg, Men C vaccine) * Offer longer duration of protection than polysaccharide vaccines * Direct protection and herd immunity Direct protection Meningococcal ea conjugate _ RierS Herd immunity vaccines Pollard AJ, et al. Nat Rev Immunol. 2009:9(3}:213-220. CRM = Corynebacterium diphtheriae Medscape Terranella A, etal. Infect Drug Resist. 2011;4:161-168, cartier protein EDUCATIONOMV Vaccines for Meningococcal Serogroup B Disease ° Have been efficacious in controlling outbreaks or epidemics (eg, Cuba, Normandy, New Zealand) * Short duration of protection * Strain specific so no cross-protection against strains not in the vaccine * Meningococcus B polysaccharide capsule lacks immunogenicity Granoff DM. Clin Infect Dis. 2010;50(Supp! 2):S54-S65. ve World Health Organization. Wkly Epidemiol Rec. 2011;86:521-539, Medscap eNew Vaccines for Meningococcal Serogroup B Disease * New protein-based meningococcal vaccines offer broad coverage against serogroup B disease * One in phase 3 trials * 4-component vaccine has now been licensed in the European Union * Offers the possibility of controlling meningococcal serogroup B disease Neisseria heparin-binding antigen omv ee PorA > Ne ctor H binding protein Nelsserial adhesin Mi cs migescap See transcript for references.Summary Meningococcal disease is associated with serious outcomes, such as long-lasting disability/death. Most cases occur in healthy persons without identified risk factors. The distribution of serogroups responsible for most meningococcal disease is varied and dynamic, making it difficult to predict epidemiologic trends. Vaccines are available for different serogroups, but no one vaccines covers them all. Vaccines for serogroup B have proved elusive in the past, but new protein-based vaccines are being developed, and one was recently licensed in the European Union. ledscape EDUCATION’Thank you for participating in this activity. To proceed to the CME Post-Test and Activity Evaluation, click on the Earn CME Credits link on this page. Medscape