See Spot Run Meningococcal update 2017

Transcription

1 See Spot Run Meningococcal update 2017 Jim Buttery Infection and Immunity Monash Children s Hospital Monash Health Monash University SAEFVIC

2 How serious a disease is N meningitidis? Meningococcal disease has a case fatality rate of approximately 10%, however more deaths are caused by septicaemia than by meningitis

3 Nasophayngeal colonisation Scanning electron micrograph: attachment of N. meningitidis by pili to the microvilli of noncilited cells in the nasopharynx Colonisation Common transient Increased in adolescence Majority- totally asymptomatic

4 Invasive Meningococcal Disease Age specific notification rates of invasive meningococcal disease, Australia

5 Risk factors: meningococcal disease Immature Immune System 1 Impaired Immune System 2,3 Nasopharyngeal Irritation 3 Social Factors 3,4 Infants Asplenia Smoking Close contact - case Waning Ab PS response Complement deficiency Humoral deficiency Respiratory-tract infection Crowding Mult kissing contacts Prematurity HIV/AIDS Pubs/Discos Most cases of meningococcal disease occur in previously healthy persons without identified risk factors 1. Rosenstein NE,et al. N Eng J Med. 2001;344: ; 2. Figueroa JE, et al. Clin Microbiol Rev. 1991;4: ; 3. Bilukha OO, et al. MMWR Recomm Rep. 2005;54:1 21; 4. Imrey PB, et al. J Clin Microbiol. 1995;33:

6 Meningococcal Epidemiology Victoria

7 Meningococcal notifications Vic population Courtesy Lucinda Franklin/Kath Taylor, DHHS Victoria

8 Meningococcal immunity Goldschneider et al. J. Exp. Med. 129:1307, 1969

9 Invasive meningococcal disease Serogroup and Year Victoria: 2000 to 2017 (YTD) MenCCV 12mo dose (from Jan 2003) catch-up 1-19yo's ( ) Y W C B Number of notifications A Not further specified Q1 Q3 Q1 Q3 Q1 Q3 Q1 Q3 Q1 Q3 Q1 Q3 Q1 Q3 Q1 Q3 Q1 Q3 Q1 Q3 Q1 Q3 Q1 Q3 Q1 Q3 Q1 Q3 Q1 Q3 Q1 Q3 Q1 Q3 Q Year and quarter Courtesy Lucinda Franklin, DHHS Victoria

10 Invasive meningococcal disease Serogroup and Year Victoria: 2013 to 2017 (YTD) 90 Number of Notifications not further specified 2 Y 9 W C B (till 21 June) Year Courtesy Lucinda Franklin, DHHS Victoria 2 January 2018

11 Invasive meningococcal disease Serogroup and Age Victoria: 2013 to 2017 YTD 50 Number of Notifications Not further specified Y W C B Age (years) Courtesy Lucinda Franklin, DHHS Victoria 2 January 2018

12 Invasive meningococcal disease Age group by year Victoria: 2013 to 2017 YTD 90 Number of Notifications Age (years) Courtesy Lucinda Franklin, DHHS Victoria 2 January 2018

13 MenW Victoria: (YTD) Female to Male = 50:36 ICU = 44% 5 deaths ages 18, 19, 46, 69 and 73 yrs Courtesy Lucinda Franklin, DHHS Victoria 2 January 2018

14 Meningococcal vaccine history Aust 1970 s Polysaccharides developed incl ACWY 1991 MenACWY PS 1 st recommendation (Haj) st Men C conjugate licensed 2003 Funded MenC program (12m) 2010 Hib MenC registered st Men ACWY conjugate registered st Men B (4vMenB) registered 2017 Men ACWY conj jurisdictions funded yr one Men ACWY conjugate age lowered to 2m

15 Meningococcal ACWY Glycoconjugate Vaccines Menactra (MCV4-D) Licensed 2005 US: 2010 Australia Approved for use in those 9 months 55 years, IM A,C,Y,W-135 conjugated to diphtheria toxoid Does not require reconstitution Menveo (MCV4-CRM) Licensed 2011 Approved for use in those 2 months 55 years, IM A,C,Y,W-135 conjugated to CRM197 Requires reconstitution Nimenrix (MCV4-TT) Licensed 2013 Approved for use in those 6w months 55 years, IM A,C,Y,W-135 conjugated to CRM197 Requires reconstitution

16 Victoria Adolescent program: Meningococcal ACWY conjugate Began term All young people aged 15 to 19 years between 18 April 2017 and 31 December dose Menactra Secondary school program - Also available from GPs or local council community immunisation service

17 4CMenB GpB PS- polymer of sialic acid: chemically identical to polysaccharides found in human tissues during development (2 8)-α-Neu5Ac as a self antigen of humans potential cause of immunopathology

18 4CMenB: Bexsero Capsular PS: shared by all Proteins: more variable between strains of Group B Aust strains will share 0-4 of vaccine peptides

19 MATS: infant immuno & persistence Immunogenicity varies between proteins Immune response wanes: amount also varies

20 100 BEXSERO Tolerability in Infants Solicited systemic reactions when BEXSERO is given with routine vaccines post dose 1 BEXSERO+Routine MenC+Routine Routine Severe 80 % of infants Changed eating habits Sleepiness Vomiting Diarrhea Irritability Unusual crying Post dose 1 Rash Fever 38.5 C *No increase in the incidence or severity of the adverse reactions was seen with subsequent doses of the vaccination series. Routine vaccines: PCV7 and DTaP-HBV-IPV/Hib; BEXSERO+Routine: N=2478; MenC+Routine: N=490; Routine: N=659. Fever was categorized as severe if temperature was 40 C. All other reactions were categorized as severe if subject was unable to perform normal daily activities. 1. Vesikari T, et al. Lancet. 2013;381: ; 2. Data on file, Novartis Vaccines and Diagnostics; 3. TGA Approved Product Information, 14 August 2013

21 When Fever Occurred, it Generally Followed a Predictable Pattern, With the Majority Resolving the Day After Vaccination BEXSERO given with routine vaccines post dose Post dose 1 (2-4-6 month dosing schedule) BEXSERO+Routine* MenC+Routine* Routine* 40 C % of infants C <40.0 C 38.5 C <39 C hrs 24 hrs 48 hrs 72 hrs Time Inform your patients about the likelihood of fever lasting one to two days *Routine vaccines: PCV7 and DTaP-HBV-IPV/Hib; BEXSERO+Routine: N= ; MenC+Routine: N= ; Routine only: N= Fever was defined as rectal temperature 38.5 C. 1. Vesikari T, et al. Lancet. 2013;381: ; 2. Data on file, Novartis Vaccines and Diagnostics; 3. TGA Approved Product Information, 14 August 2013

22 Prophylactic Paracetamol at the Time of and Closely After Vaccination Reduced Fever When BEXSERO is given concomitantly with routine infant vaccines % of subjects Post dose 1 (of month dosing schedule) NPP PP NPP PP NPP PP 6 hrs 48 hrs 72 hrs Time 40 C 39 C <40.0 C 38.5 C <39 C Prophylactic Paracetamol Did Not Impact Immunogenicity of Routine Vaccines Advise your patients that the prophylactic administration of paracetamol at the time and closely after vaccination can reduce the incidence and intensity of post-vaccination febrile reactions NPP: no prophylactic paracetamol (N=182); PP: with prophylactic paracetamol (N= ). Routine vaccines: PCV7 and DTaP-HBV-IPV/Hib. 1. Prymula R, et al. Presented at: 29th Annual Meeting of the European Society for Paediatric Infectious Disease (ESPID); June 7-10, 2011; The Hague, The Netherlands. Poster #631; 2. Data on file, Novartis Vaccines and Diagnostics; 3. TGA Approved Product Information, 14 August 2013

23 Predicted Coverage of MenB Strains Indicates BEXSERO Has the Potential to Impact MenB Disease 66% 91% 85% 85% 73% 73% 82% 82% 74% 85% 85% 87% 87% 69% 88% 81% 76% Canada: Bettinger J, et al. Presented at: 5th Vaccine & ISV Annual Global Congress; October 2-4, 2011; Seattle, WA; US: Kim E, et al. Presented at: 19th IPNC. September 9-14, Würzburg, Germany. Poster P270; Brazil: Lemos AP, et al. Presented at: 19th IPNC. September 9-14, Würzburg, Germany. Poster P272; Europe: Vogel U, et al. Lancet Infect Dis. 2013;13: ; Greece: Data on file, Novartis Vaccines and Diagnostics; Australia: Nissen M, et al. Presented at: 19th IPNC. September 9-14, Würzburg, Germany. Poster P269.

24 In March 2014, the Department of Health s Technical Advisory Group on Immunisation issued Advice for immunisation providers regarding the use of Bexsero

25 Recommendations Based on their higher disease risk, 4CMenB is recommended for: Infants and young children, particularly those aged <24 months Adolescents aged 15 to 19 years Children and adults with medical conditions that place them at a high risk of IMD, such as functional or anatomical asplenia or complement component disorders (see Chapter 4.10 of The Australian Immunisation Handbook, 10th edition1) Laboratory personnel who frequently handle Neisseria meningitidis. 4CMenB is also recommended for all children and young adults who wish to reduce their risk of MenB IMD.

26 DOH Australian Technical Advisory Group on Immunisation (ATAGI) Advice Table 1. Recommended schedule of 4CMenB by age group Age at commencement of vaccine course Primary immunisation Interval between primary doses Age for booster dose 2 months* 3 doses, delivered at ~2*, 4 and 6 months of age; (intervals ~2 months, at least 1 month) 12 months 3 to 5 months 3 doses 1 2 months 12 months 6 to 11 months 2 doses 2 months 12 months, or 2 months after previous dose, whichever is later 12 months to 10 years 2 doses 2 months No booster required 11 years and above 2 doses 1 2 months No booster required * 4CMenB is registered for use in persons 2 months of age; however, the 1st dose of 4CMenB may be administered as early as 6 weeks of age to align with the NIP infant schedule. The need for a booster dose for this age group is as yet uncertain. There are currently no data on the use of 4CMenB in individuals aged over 50 years, however, based on first principles, ATAGI recommends that 4CMenB can be used in older persons who are at high risk of IMD.

27 Known unknowns Will it work? Modified serology says yes Early data encouraging Will it provide herd immunity? reduction in NP carriage 12.6% ( 15.9%, 34.1%) Will protection last? Will there be escape strains? Will it increase fever/ febrile convulsions? Early data encouraging Will Australians follow paracetamol advice? Will that change febrile seizure risk anyway? How will we register adolescent doses?

28 Two-dose vaccine effectiveness was 82 9% (95% CI ) against all MenB cases

29 Safety (UK) Routine 3 doses paracetamol (?compliance) No increase in Febrile Seizure presentations HPA Increase in 2 and 4 m infants febrile presentations to ED Septic work ups Nainani, Archives Dis Child 2017 No increase ED presentations at 12m Neda So, 2017 (in press)

30 Life is like a box of chocolates

31 Conclusions Men W increasing esp adults Jurisdictional based programs ACWY Year 10 MenB Failed x 3 PBAC waiting on UK data More reactogenic but appears to be effective and safe (used with paracetamol)

32 Thank you