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
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 (%)
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?
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
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
Carriage
• ~ 2-5% population
• Variation by age
• Highest in adolescents
• Herd protection
• Variation by serogroup
• Variation by geographical location –
time
• ? Relationship with disease
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
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.
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