Invasive Meningococcal Disease (IMD) An update on prevention in Australia Prof Robert Booy, NCIRS Declaration of interests: RB consults to vaccine companies but does not accept personal payment Invasive Meningococcal Disease Caused by the bacterium Neisseria meningitidis1 • Meningococci are classified into serogroups that are determined by the components of the polysaccharide capsule1 • Globally, 6 serogroups most commonly cause disease2 A B C W X Y • In Australia, three serogroups cause the majority of IMD3 B W Y Cross-section of N. meningitidis bacterial cell wall (adapted from Rosenstein et al)4 1. Australian Technical Advisory Group on Immunisation (ATAGI). The Australian Immunisation Handbook 10th Edition (2018 update) . Canberra: Australian Government Department of Health, 2018 [Accessed September 2018] 2. Meningococcal meningitis factsheet No 141. World Health Organization website. http://www.who.int/mediacentre/factsheets/fs141/en/ [Accessed February 2017] 3. Lahra and Enriquez. Commun Dis Intell 2016; 40 (4):E503-E511 4. Rosenstein NE, et al. N Engl J Med. 2001; 344:1378-1388 Invasive meningococcal disease (IMD) in Australia • Overall, the national incidence of invasive meningococcal disease (IMD) in Australia is low • From 2003 to 2013, there was a large decrease in the number AUS notifications: 99% drop in Men C! - after the introduction of 2003 meningococcal C (Men C) dose at 12 months to National Immunisation Program (NIP) – catch-up vacc’n 2-19 year olds (herd immunity <1 & >20yrs) • & reduced smoking +improved SES: 55% drop in Men B! Without a vaccine program • However, in recent years the rate of IMD has increased: 2017 had the highest rate in 10 years • Men W and Y now important in older adults Notifications of invasive meningococcal disease, Australia, 1992- 2017, by year, all serogroups 2013-2017: 4 yrs 3rd Age peak 60-64 yrs W and Y 2017:2018: 383281 cases Highest2019: number? fewer of cases since 2006 Nat’l Men C program from 2003 Adapted from National Notifiable Diseases Surveillance System1 1. National Notifiable Disease Surveillance System (NNDSS). http://www9.health.gov.au/cda/source/rpt_3.cfm [Accessed October 2018] Meningococcal disease by age, NSW, 2018 Breakdown by age bands 25 Men B Men W Men Y NG Men C 20 Men B 15 10 Men Y & W Number of Notifications 5 0 0 - 4 5 - 9 10 - 14 15 - 19 20 - 24 25 - 29 30 - 34 35 - 39 40 - 44 45 - 49 50 - 54 55 - 59 60 - 64 65 - 69 70 - 74 75 - 79 80 - 84 85 + Age group (years) NSW Health - [Accessed Feb 2019] https://www1.health.nsw.gov.au Introduction of Men C vaccine to NIP 99% C change; 55% B change Australia, 1997- 2017, by year and bacterial serogroup 300 B 250 C MenB W 200 Y Other 150 MenC MenC vaccine on the NIP 100 Number of notifications of Number Surge from 2013 50 0 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 Adapted from the Annual reports of the meningococcal surveillance program1 and the Department of Health, 20172 Note: “Other” includes other serogroups not singled out, cases where meningococcal isolates could not be identified, other isolates not grouped and cases where serogroup was not known. 1. Annual reports of the Australian Meningococcal Surveillance programme, 1997-2016 http://www.health.gov.au/internet/main/publishing.nsf/Content/cda-pubs-annlrpt-menganrep.htm [Accessed January 2018] 2. Department of Health. Invasive Meningococcal Disease National Surveillance Report: with a focus on MenW. 31 December 2017. http://www.health.gov.au/internet/main/publishing.nsf/Content/5FEABC4B495BDEC1CA25807D001327FA/$File/31-Dec17-IMD-Surveillance- report.pdf [Accessed February 2018] Why 2017 so bad? Meningococcus Sequence type 11 (cc 11) • Associated with C and later W strains (some B) • Hyper-invasive: greater mortality/morbidity; more outbreaks C disease: teens/young adults W disease: Babies, young adults, older adults Wider presentations eg arthritis, pneumonia, epiglottitis, gastro Large flu year in 2017 in Australia • In 19 of 20 seasons, influenza peaked≤2 weeks before IMD • peaks were highly correlated in time (ρ = 0.95; P <.001). • H3N2 and H1N1 peaks were highly synchronized with IMD • pandemic H1N1, B, and respiratory syncytial virus were not • over 20 years, 12.8% (95% CI, 9.1–15.0) of IMD attributable to ‘flu in preceding weeks • during the height of ‘flu season, weekly attributable fractions reach 59%. • vaccination against meningococcal disease is the most important prevention strategy • influenza vaccination could provide further protection http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0107486 Symptoms are difficult to diagnose at early onset and develop rapidly1,2 Medical intervention often does not occur until late 13-24 HOURS 0-7 HOURS POTENTIALLY NON SPECIFIC LETHAL SYMPTOMS Most progressed from non-specific initial symptoms to close to 24 • Fever death within 24 hours • Irritability • Nausea or vomiting HOURS • Poor appetite or ~ 13 hours - Median time feeding to first hospitalisation* • Drowsiness • Headache^ • Neck pain and stiffness • Sore throat • Hemorrhagic rash • Thirst # • Floppy muscle tone • Leg pain • Bulging fontanelle* • General aches • Photophobia 8 – 12 HOURS • Confusion and delirium^ • Seizure ~8 hrs – Median time to first GP consultation* ^in children > 1 year *in infants <1 year • Cold hands and feet #in children < 5 years • Abnormal skin colour ^in children > 1 year • Breathing difficulty • Increased thirst • Diarrhoea *in infants <1 year 1. Thompson MJ, et al. Lancet 2006; 367:397–403 2. van Deuren M, et al. Clin Microbiol Rev 2000: 13:144–166 Meningococcal disease can be deadly and devastating1-3 • Significant morbidity and mortality despite early diagnosis and appropriate medical treatment • ~10% of cases are fatal1,2 (more in older adults) • 1 in 5 survivors of IMD (all serogroups) have permanent sequelae1,2 • Child survivors may experience major sequelae eg limb amputations, seizures and hearing loss3 • ~30% experience other deficits such as psychological Top image: Courtesy of Centers for Disease Control and Prevention and Dr. Gust. 3 disorders, digit amputations and unilateral hearing loss Bottom image: Courtesy of Meningitis Research Foundation UK. Available at • Google Eliza Meningococcal www.meningitis.org 1. Meningococcal meningitis factsheet No 141. World Health Organization website. http://www.who.int/mediacentre/factsheets/fs141/en/ 2. Rosenstein NE, et al. N Engl J Med. 2001; 344:1378-1388 3. Viner RM, et al. Lancet Neurol. 2012; 11:774-783. IMD has a higher case fatality rate compared with other VPDs rapid and deadly!! 15 Meningococcal disease1 10 Diphtheria1 Pneumococcal pneumonia1 5 Paralytic polio1 Pertussis Hib meningitis1 1918 pandemic flu2 Estimated case fatality rate (%) rate fatality case Estimated 5 0 By infectious disease Notes: Meningococcal disease and Hib meningitis: despite appropriate antimicrobial therapy; paralytic polio: in children; 1918 pandemic flu: in young adults; varicella: in children and adolescents; A/H1N1 2009 flu: worldwide; measles: US, 1985‒1992; rotavirus: US general population; pertussis: infants <6 months of age, US, 2001–2003. 1. Centers for Disease Control and Prevention (CDC). Epidemiology and Prevention of Vaccine-Preventable Diseases. 12th ed. Atkinson W, et al, eds. Washington, DC: Public Health Foundation; 2012. http://www.cdc.gov/vaccines/pubs/pinkbook/index.html#chapters; 2. Taubenberger JK, et al. Emerg Infect Dis. 2006;12:15-22; 3. Pandemic H1N1 2009 Overview. CIDRAP website. http://www.cidrap.umn.edu/cidrap/content/influenza/ swineflu/biofacts/h1n1_panview.html; 4. Gerba CP, et al. Wat Res. 1996:30;2929-2940; 5. Centers for Disease Control and Prevention (CDC). MMWR Morb Mortal Wkly Rep. 2005;54:1283-1286. IMD = invasive meningococcal disease VPDs = vaccine preventable diseases IMD Australia: Breakdown by State or Territory, 20181 Most cases in NSW, QLD, Vic 80 70 60 50 40 30 20 Number of notifications 10 0 ACT NSW NT QLD SA TAS VIC WA 1. Adapted from the National Notifiable Diseases Database Surveillance System and Australian Government (accessed 10 Feb 2019). 14 IMD Australia: Breakdown by State or Territory, 2017 Peak disease: B in SA, NSW, QLD W in Vic, WA, NT hence, state- based Other Y W C B approaches 100 90 80 70 60 50 40 30 20 Number of notifications 10 0 ACT NSW NT QLD SA TAS VIC WA Note: “Other” includes where meningococcal isolates could not be identified, other isolates not grouped and cases where serogroup was not known. Adapted from Department of Health. Invasive Meningococcal Disease National Surveillance Report: with a focus on MenW. 31 December 2017. http://www.health.gov.au/internet/main/publishing.nsf/Content/5FEABC4B495BDEC1CA25807D001327FA/$File/31-Dec17-IMD- 15 Surveillance-report.pdf [Accessed February 2018] IMD in Australia: Breakdown by State or Territory, 20181 Rate per 100,000 population per year: overall Australian notification rate 1.1 per 100,000 Smallest populations but highest incidences Rate per 100,000 population per year(overall0.5 Australian0.9 notification4.4 rate 1.1 per1.2 100,000) 2 2.1 0.8 1.5 80 MenB MenC MenE MenW MenY NG* 70 60 50 40 30 20 Number of notifications 10 0 ACT NSW NT QLD SA TAS VIC WA Adapted from the Department of Health, 20181 *NG includes where meningococcal isolates could not be identified (‘not groupable’), other isolates not grouped and where serogroup was not known. 0.5 0.9 4.4 1.2 2 2.1 0.8 1.5 1. Department of Health. Invasive Meningococcal Disease National Surveillance Report. Quarter 4, 2018. 1 October to 31 December 2018 http://www.health.gov.au/internet/main/publishing.nsf/Content/5FEABC4B495BDEC1CA25807D001327FA/$File/1Oct- 31Dec19-qrt3-IMD.pdf [Accessed April 2019] Australia-wide, 1 January to 30 September 2018# Breakdown by age Nb <1 year & 15-24 years B = #1 Cf 25-64 years W & Y common By 5 yr bands, highest no.