Update re: BCG

and

Meningococcal Vaccine(s)

Nigel Crawford

TVU, RCH, Melbourne, August 2017

BCG-Background

• BCG- Isolated from a cow with TB

[Mycobacterium bovis]

• Attenuated over a 10 year period - early

1900s- used since 1921

• ‘7 daughter strains’- different

laboratories

• Uncertainty… re differences in efficacy

and safety

BCG Rationale

• Highest efficacy for infants in the 1st

year of life

• ~ 70-90% TB meningitis and miliary TB

• Australian recommendations

[state funded]• Children, < 5 years, who will be travelling to countries where

annual TB incidence is > 40/100,000

• >1-month; frequent trips (cumulative)

• Aboriginal and Torres Strait Islander neonates living in high-

incidence areas

• Neonates born to parents with leprosy or a family history of

leprosy.

Current Vaccines Australia

Name Strain Administration

BCG 10 [Poland] 0.1 mL contains 1.5–6×105 cfu of Brazilian Moreau strain, Polish variant

Multi dose vial (MDV)Intradermal0.05ml < 12-months0.1 ml > 1 year

Serum Institute India (SII) 0.1 mL contains 2–8×105 cfu of Moscow strain (also known as BCG-Russia)

As above

Pragmatics: BCG in Oz

2013 BCG Connaught strain replaced with BCG Denmark strain

– Denmark higher rate disseminated disease in HIV

– 100 dose vials rather than 10 dose

2015 BCG Connaught strain

2016 World wide shortage: NTAC

– BCG Moreau strain made in Poland

• Not TGA licensed

Slide Acknowledgement Jim Buttery

https://www.tga.gov.au/form/authorised-prescribers

RCH

• Public clinic (weekly) for infants < 12-months

http://www.rch.org.au/immunisation/clinics/

BCG policy: Victoria [N. Wong: data submitted for publication]

• Distribution of BCG vaccine in

Victoria: 2012 to 2015

• A total of 3904 patients received BCG

vaccine:

• 1704 at Monash

• 2200 from RCH (Detailed data 830)

• Median age 6.9 months (IQR 3.9-11.3)

BCG policy: Victoria

• 98.9% (2575/2604) received BCG

vaccine prior to overseas travel

• 96.0% (2474/2575) were travelling to

countries in Asia

• Only 13/2604 (0.5%) were given BCG

vaccine prior to travel to a country with

low incidence of TB.

Nicole Wong, submitted for publication 2017

0 10 20 30 40 50 60 70 80 90 100

Africa

Asia

E. Europe

W.Europe

MiddleEast

Pacific

S.America

US/Canada

Study population (MH + RCH) - maternal country of birth (%) Birth rates (Monash health) by maternal country of birth (%)

BCG policy: Victoria

Nicole Wong, Jock Lawrie et al. submitted for publication 2017

BCG policy: National

http://www.health.gov.au/internet/main/publishing.nsf/Content/cda-cdi4101f.htm

BCG policy: National

http://www.health.gov.au/internet/main/publishing.nsf/Content/cda-cdi4101f.htm

BCG policy: National

http://www.health.gov.au/internet/main/publishing.nsf/Content/cda-cdi4101f.htm

Vaccine safety

• RCH Ethics (authorised prescriber)

• Consent to obtain follow-up via Email

• 6-months post BCG administration

• Did you have an unexpected event following

the vaccine?

https://link.springer.com/article/10.1007%2Fs40264-014-0248-6

Outline

• BCG

• Background

• Global shortage….

• Which vaccines available in Australia?

• National and jurisdictional data

• IMD

• Background

• Disease burden

• Vaccines

• Traveller advice

SAEFVIC: BCG AEFI

49%

27%

3%

7%

2%

2%

5%

3% 2%

Primary reaction

Abscess

Lymphadenopathy

Rash

Injection site reaction -minor/common/expectedHypotonic–hyporesponsive episode - HHEUrticaria/Hives/Allergic Rash

Drug error (Program error)

Nodule at injection site

http://www.who.int/vaccine_safety/committee/topics/bcg/June_2017/en/

Invasive Meningococcal Disease (IMD)

• Neisseria meningitidis, often referred to

as meningococcus, is a Gram-negative

bacterium

• Six main serogroups that cause

disease:

• A, B, C, W135, Y (and X….)

IMD presentation

• Typical

• Septicaemia

• Meningitis

• Atypical

• Pneumonia

• Septic arthritis

• Pericarditis

IMD Outcome

• Mortality 5-10%

• Long term sequelae 10-20 %

• Significant burden

• Scars (5%), neurological deficits (2.6%)

• Partial/full amputation of limbs (1.7%)

• Deafness (0.9%),

Global Epidemiology

• 13 serogroups of N. meningitides

• A, B, C, W-135, X and Y accounting for

the majority of IMD

• National and international variability

https://www.researchgate.net/figure/278724367_fig1_Fig-1-Global-Meningococcal-Serogroup-Distribution-1-National-Advisory-Committee-on

National IMD

Age specific rates [2012-16]

Carriage

• ~ 2-5% population

• Variation by age

• Highest in adolescents

• Herd protection

• Variation by serogroup

• Variation by geographical location –

time

• ? Relationship with disease

Chritanssen, Lancet ID, 2010:http://doi.org/10.1016/S1473-3099(10)70251-6

IMD- vaccine preventable

• National Immunisation Program (NIP)

• Hib-Men C @ 12-months

MENINGOCOCCAL

VACCINES 2017

PROGRAMS

Darwin

Northern Territory

Queensland

Brisbane

Western Australia

Perth

South Australia

AdelaideSydney

Canberra

VictoriaMelbourne

TasmaniaHobart

New South Wales

Meningococcal vaccines available

• Cover ‘five’ letters of the alphabet

• Men ACWY (conjugate vaccine)

• Menveo [GSK]

• Menactra [Sanofi]

• Nimenrix [Pfizer]

• MenB

• Bexsero [GSK]

36

Men ACWY

[polysaccharide vaccines]

• Menomune [Sanofi]

• Mencevax [Pfizer]

• Not on market since

~ March 2017

Victorian state program

• MenACWY [Menactra]

• Funded for young people 15 to 19 years

• Commenced term 2 – 2017• currently until Dec 31, 2017.

• School based program (Years 10-12)

• General Practitioners

https://www.betterhealth.vic.gov.au/health/healthyliving/meningococcal-disease-immunisation

Opportunistic travel advice

• IMD vaccines

• Should be in the fridge….

• Adolescent – Year 10 trip to South America

• Pre-teen- school trip to Vietnam

• Infant 6-months*, who came for BCG only!

• Also recommend an influenza vaccine

• *note vaccine recommendations in infants < 2-

years vary by MenACWY brand

Hajj

Mecca- Hajj

• WHO defintion mass gathering

• “a specified number of persons (>1000), at

a specific location, for a specific purpose,

for a defined period of time”

• Hajj ~2.3 million people annually

• Started 632 AD

• Outbreaks: plague, chlorea, malaria,

influenza

• IMD 1987…..

• 264 suspected cases of meningococcal

disease in Mecca

• 253 (96%) lab confirmed with 179 (71%)

positive by CSF or blood culture

• Seventy patients died, for a case-fatality

rate of 28%

Hajj vaccine recommendations

https://wwwnc.cdc.gov/travel/yellowbook/2018/select-destinations/saudi-arabia-hajj-umrah-pilgrimage

MENINGOCOCCAL VACCINE

The Kingdom of Saudi Arabia will not issue Hajj or Umrah visas without

proof of meningococcal vaccination at least 10 days and no more than 3

years before arrival for polysaccharide vaccine and no more than 8 years

before arrival for conjugate vaccine.

All pilgrims must have received a single dose of quadrivalent ACWY

vaccine and must show proof of vaccination on a valid International

Certificate of Vaccination or Prophylaxis.

Men A conjugate vaccine program

• Marc Laforce

http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(17)30301-8/abstract

Incidence of suspected meningitis cases declined by 57%

(95% CI 55–59) in vaccinated compared with unvaccinated

populations, with some heterogeneity observed by

country…..

In fully vaccinated populations, the incidence of confirmed

group A disease was reduced by more than 99%.

Take away points

• BCG vaccine delivery

• Available & recommended children

• esp <12-months

• but TGA approval and issues - equity of access

• Invasive meningococcal disease

• potentially vaccine preventable @ all ages

• B & ACWY

• Victorian funded MenACWY school program

• 15-19 years

• Consider for all travellers; particularly the Hajj

Acknowledgements

• RCH Immunisation service

• SAEFVIC- vaccine safety service

• Nicole Wong- BCG policy

• Victorian DH – Immunisation section

• CPMG travel clinic staff