Immunisations and Mass Gatherings: Hajj, Olympics, Youth Days

Prof Robert Booy MBBS, MSc, MD, PRACP

National Centre for Immunisation Research & Surveillance

Children’s Hospital Westmead, University of Sydney

Acknowledgements • Dr Harunor Rashid: Epidemiology Fellow NCIRS

• Dr Mohamed Tashani: PhD student NCIRS

• I have received financial support from leading vaccine companies in Australia to attend scientific meetings, conduct research and give lectures: any honoraria are not personally accepted but paid into an NCIRS research account

Outline • Travelers & immigrants = key elements in

spread of old & emerging contagions

• What are the risks and issues? – focus on annual Muslim pilgrimage, The Hajj

• Multiple vaccines frequently indicated

• Discuss some research issues eg interactions of Conjugate vaccines with other vaccines: Carrier priming or suppression

What is a mass gathering?

WHO Definition

A gathering of “a specified number of persons (>1000) at a

specific location for a specific purpose for a defined period of time”

Mass Gathering Medicine is a new field that focuses on the

health risks

Types of mass gatherings

Health Hazards of Mass Gatherings

1. Communicable: cholera,

meningococcal disease, influenza, pertussis

2. Non-communicable:

stampede, fire, riots, violence

Kumbh Mela ~60 million gathered in 2001

Outbreaks of Cholera in Kumbh Mela

Ref: Rogers L. Trans R Soc Trop Med Hyg 1954;48(1):42-9.

Automated system to detect infectious diseases Olympics 2012

based on a set of algorithms known as Robust Poisson Regression

Outbreak detection starts with the detection of unusual number

reported cases of a particular infection in a given time and space.

Computer programs used to compare the observed number with

expected values

When an increase is detected, the program raises an alert, which

epidemiologists assess to determine if further investigation

• The system offers a comprehensive way to detect outbreaks

• The challenge in designing large multiple outbreak detection systems is to control the proportion of false alarms without impairing the detection of genuine outbreaks

• UCL, London WHO Collaborating Centre Mass Gathering Research

Catholic World Youth Days • Influenza outbreaks during World Youth Day

2008 mass gathering

• Numerous strains identified: oseltamivir-R influenza A (H1N1), oseltamivir-S flu A (H1N1), influenza A (H3N2) and strains from both influenza B lineages (B/Florida/4/2006-like and B/Malaysia/2506/2004-like)

• complex, and unpredictable effects on community influenza activity

Hajj pilgrimage approx 2-3 million annually

History of Infections at Hajj

Hajj started in 632 AD

Thousands gathered;

pilgrims had a febrile illness known as ‘Yethrib fever’

(possibly malaria)

Farid MA. Bull World Health Organ1956:15(3-5):828-33.

Plague in Mecca

The medieval Black Death of Europe advanced east &

was introduced into Mecca by the pilgrims in 1348-49,

killing “large numbers” of people including students

and local residents

Ref:

Dols, M.W., 1979. The Black Death in the Middle East, New Jersey: Princeton Uni Press.

John Lewis Burckhardt (1784–1817)

Burckhardt noted that there was

an outbreak of an unspecified

‘pestilence’ circa 1424 associated

with 2,000 deaths during the Hajj

Burckhardt himself witnessed

malaria, typhus fever, diphtheria, I

and dysenteries in Mecca in 1813

Cholera Epidemics History of El Tor Vibrio cholerae

Epidemics of cholera from

1831 to 1918. Quarantine

stations were established,

one was the El Tor station

where Felix Gotschlich

isolated for the first time

El Tor Vibrio cholerae

Risk factors: Crowding Day and Night

Annually about 2.5 million pilgrims gather in Mecca to perform Hajj

Inside the tent

Very Dusty

And Hot in of Mecca

0

5

10

15

20

25

30

35

40

45

Jan Feb Mar Apr May Jun July Aug Sept Oct Nov Dec

Tem

pera

ture

(°C)

Average max temp Average min temp

N. Meningitidis A outbreak in 1987

N. meningitidis W-135 outbreak, 2000

Netherlands (9) Norway (1) Sweden (2) Finland (2)

Denmark (1)

Belgium (1) France (24)

USA (4)

Morocco (3)

Singapore (4)

Indonesia (14)

Saudi Arabia (241)

Oman (18) Kuwait (3)

Germany (10) UK (51)

Iran (2)

Mauritius (4)

Types of vaccines:

• Live attenuated viruses : MMR & varicella

• Inactivated (or killed): Inactivated polio, Hep A • Killed whole cell: Cholera • Purified proteins: acellular pertussis

• Toxin produced by the bacteria: D or T • Polysaccharide capsule: Pneumococcus and

Meningococcus

• Conjugate Vaccines: Pneumococcal conjugate vaccine (PCV) ,

M i l j t i (M CV)

Polysaccharides vaccines Encapsulated organisms- polysaccharides capsule

Conjugate vaccine= Sugar+ Protein How does it work ?

Polysaccharides vaccines: • Have a poor and short lasting immune response

• T-cell independent

B cell

MenV

Carrier Priming Improved antibody response to a conjugate vaccine when an individual has been previously primed with the carrier protein

Carrier Priming:

TT → MenCV-TT → ↑ MenC-TT

Carrier Induced Epitopic Suppression (CIES):

DT → MenCV-DT → ↓ MenC-DT

• Conjugate vaccine interactions have not been examined thoroughly: almost no data among adults

• We will be examining the effect of administering DPT before, with, after 2 conjugate vaccines: PCV13 & MenCV4

Hajj

High proportion of pilgrims have pre-existing medical conditions

There is a need for multiple vaccines Can they all be given Together?

Group1 (n= 214 )

Group2 (n= 214 )

Group3 (n= 214 )

MCV4 + PCV 13 +

MCV4 + PCV 13

MCV4 + PCV 13

• By comparing the results of immune response of the 3 groups, we will be able to assess the effect of DPT on the conjugate vaccines (PCV-13 and MCV4)

• All vaccines supplied free; All work done pre-Hajj

• Influenza vaccine given at conclusion

• Diary cards / adverse effects / safety and tolerability

• Recommendations for the best combination/order of conjugate vaccines

Methods

Conclusion

• DPT before MenCV and PCV

• Evidence of carrier priming or suppression?

• Can we reduce the required doses and costs of conjugate vaccines

• Guidelines for new immunisation schedule and travel vaccines