Transcript pertussis slides

N. meningitidis;
From Global to Local Perspectives
Professor Fahad Al-Zamil
Professor and Consultant Pediatric Infectious Diseases,
Head of Infectious Disease Unit
King Saud University
Edward Jenner
Edward Anthony Jenner (17
May 1749 – 26 January 1823)
was an English scientist who
studied his natural surroundings
in Berkeley, Gloucestershire.
Jenner is widely credited as the
pioneer of smallpox vaccine,[1]
and is sometimes referred to as
the "Father of Immunology"; his
works have been said to have
"saved more lives than the work
of any other man".[2][3][4]
James Phipps
James Phipps (1788-1853), as an
eight year old boy, and the son of
Edward Jenner's gardener, was the
first person given the cowpox
vaccine by Edward Jenner. Phipps
was often used as an living proof
that Jenner's vaccine worked.
Phipps was exposed to the
smallpox virus multiple times over
the next twenty years, but
successfully resisted infection,
proving the efficacy of Jenner's
vaccination.
Edward Jenner Vaccinating 8 year old James
Phipps on 14 May 1796
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Louis Pasteur
27 December, 1822 – 28 September, 1895
 The great revolution in the
vaccination science occurred
thanks to the genius French
chemist and microbiologist
Louis Pasteur who developed
an attenuated vaccines to
prevent cholera, anthrax and
rabies.
 Louis Pasteur was the first
person to use the terms
Vaccine and attenuated.
 His body lies beneath the
Institute Pasteur in France
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Joseph Meister
Joseph Meister (21 February 1876 - 16
June 1940) was the first person to be
inoculated against rabies by Louis
Pasteur, and the first person to be
successfully treated for the infection.
In 1885, nine-year-old Meister was
bitten by a rabid dog after provoking it
by poking it with a stick. Pasteur
decided to treat the boy with a rabies
virus grown in rabbits and weakened by
drying, a treatment he had earlier tried
on dogs. The treatment was successful
and the boy did not develop rabies.
Article from the French newspaper “Le Petit Journal” regarding Joseph Meister’s reported suicide
during the German occupation of Paris during World War 1. During the German occupation of Paris,
Meister committed suicide by shooting himself with his World War I service revolver rather than
allow German soldiers enter Pasteur’s crypt(secret burial place or tomb).
Meningococcal Disease
Global epidemiology
Local epidemiology
Shortcomings of Meningococcal polysaccharide vaccines
Conclusion
 Four-month-old female with gangrene of hands and lower extremities
due to meningococcemia
8
Four-month-old female with gangrene of feet due to
meningococcemia
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Four-month-old female with gangrene of hands due to
meningococcemia
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Four-month-old female with gangrene of hand due to
meningococcemia
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Neisseria meningitidis; The pathogen
 Strictly human pathogen
 Transmission by aerosol droplet, crowding facilitates
 Asymptomatic carriage in 10-30%
 Under 1% of carriers become symptomatic
 Invasive diseases include:
meningitis, meningococcemia,
pneumonia, septic arthritis
 High capacity DNA transformation
and recombination systems allow
acquisition of genes by horizontal
gene transfer
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Difficult to Diagnose, Rapidly Lethal1
Typical time course of meningococcemia and meningitis
4–8 hours
Nonspecific
Fever, irritability,
nausea or vomiting,
drowsiness, poor
appetite, sore throat,
coryza, general aches
12–15 hours
Characteristic
Hemorrhagic rash,
neck pain,
meningismus,
photophobia
15–~24 hours
Late
Confusion or
delirium, seizure,
unconsciousness;
possible death
Hospital admission at median of ~19 hours
Reference: 1. Thompson MJ, et al. Lancet. 2006;367(9508):397-403.
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Clinical Presentation
Meningitis
 Fever and headache
(flu-like symptoms)
 Stiff neck
 Altered mental
status
 Seizures
3%–10% fatality
rate
Meningococcemia
 Rash
 Vascular damage
 Disseminated
intravascular
coagulation
 Tissue damage
 Shock
 Death within 24 hours
20%–40% fatality
rate
Apicella MA. In: Principles and Practice of Infectious Diseases. 1995:1896-1909;
Jodar L, et al. Lancet. 2002;359:1499;
Granoff DM, et al. In: Plotkin SA, ed. Vaccines. 4th ed. Philadelphia: W.B. Saunders Co; 2004;
Rosenstein NE, et al. N Engl J. 2001;344:1378
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Serious Outcomes of Meningococcal
Disease
 Death (10%15%)
 Long-term sequelae (10%15%)
–
–
–
–
Deafness
Cranial nerve palsy
Retardation
Limb loss
Granoff DM, et al. In: Plotkin SA, ed. Vaccines. 4th ed. Philadelphia: W.B. Saunders Co; 2004
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Meningococcal Disease
Global epidemiology
Local epidemiology
Shortcomings of Meningococcal polysaccharide vaccines
Conclusion
N. meningitidis Serogroup Characteristics
A
B
 Leading cause of disease worldwide due to large African epidemics
 Major cause of endemic disease in Africa, China, Russia, India
 Rare in Americas, Western Europe
Major cause of endemic disease in Europe, the Americas,
Southeast Asia, Oceana
C
Major cause of endemic disease in Europe, the Americas, Oceania
Y
Small percentage of infections worldwide
Increasing problem in North America among adolescents
W-135
X, 29E, Z, …
Small percentage of infections worldwide
Recent worldwide outbreaks related to Hajj pilgrimage
Potential agent for large-scale epidemics (Africa)
Very rare cause of infections worldwide
Adapted from Granoff DM, Feavers IM, Borrow R. Meningococcal vaccines. In: Plotkin SA, Orenstein WA, editors.
Vaccines. 4th ed. Philadelphia: Saunders; 2004: 959-87
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Global Serogroup Distribution in the early
2000’s
Other
Y 1,0%
2,3%
Other
1%
W-135
7%
W-135
2%
C
24%
Other
6%
C
21%
W-135
3,6%
B
64%
B
32%
Y
25%
B
44%
RUSSIA 2002-2004
(n=1,899)
WESTERN
EUROPE 2002
(n=3,982)
Canada 2003*
(n=148)
W-135
20%
W-135
3%
C
14%
A
79%
C
57%
COLOMBIA 2004
(n=37)
W-135
Other
1%
5%
Y
2%
C
14%
Other
C 6%
11%
B
83%
CHILE 2003
(n=193)
URUGUAY 2001
(n=53)
SAUDI ARABIA
2002
(n=21)
AFRICAN
MENINGITIS BELT
2003-2004
(n=501)
BRAZIL 2003
Sao Paulo state
(n=426)
B
78%
W-135
17%
Y
19%
Other
2%
A
6%
C
5%
Other
0,5%
TAIWAN 2001
(n=43)
B
81%
THAILAND 2001
(n=36)
W-135
3,6%
Y
2,4%
A
0,3%
C
21%
Y
13%
B
14%
W-135
41%
B
33%
W-135
76%
B
51%
B
39%
A
14%
Other
1,2%
Other
4%
Y
32%
C
2,3%
A
4,7%
B
10%
Y
27%
UNITED STATES 2003
(n=200)
A
36%
C
22%
C
29%
B
43%
Other
10%
A
0,1%
B
73%
W-135
62%
Y
W-135 0,4%
3,6%
Other
0,8%
C
8%
AUSTRALIA 2004
(n=335)
SOUTH AFRICA 2005
(n=414)
* Provisional data
(N is total serogrouped strains. Other includes other serogroups and non groupable strains)
B
87%
NEW ZEALAND 2004
(n=252)
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General Epidemiological Pattern of
Invasive Meningococcal Disease
Different populations have widely varying incidence
rates of invasive meningococcal infection
Industrialized
countries (9-11)
1-3/100,000/yr
Military recruits
2 to 5/100,000/yr
(7-8)
Freshmen in dormitories (4-6)
5 to 13/100,000/yr
Hajj pilgrims (3)
25/100,000/yr
African Meningitis Belt countries
100 to 800 cases/100,000/yr
(1-2)
[1] World Health Organization. Control of Epidemic Meningococcal Disease. WHO Practical Guidelines. WHO/EMC/BAC/98.3. 2nd ed. Geneva, Switzerland, World Health
Organization, 1998. Available at: http://www.who.int/emc-documents/meningitis/whoemcbac983c.html. Accessed April 12, 2005. [2] WHO. Wkly Epidemiol Rec 2003;78:2946; [3] Wilder-Smith A, et al. Clin Infect Dis 2003;36:679-83; [4] Harrison LH, et al. JAMA 2001;286:694-9; [5] CDC. MMWR Recomm Rep 2000;49(RR-7):11-20; [6] Neal KR,
et al. Epidemiol Infect 1999;122:351-7; [7] Brundage, JF, et al. Clin Infect Dis 2002;35:1376-81; [8] Spiegel A, et al. Santé 1996;6:383-8; [9] CDC. MMWR Morbid Mortal
Wkly Rep 2004;51(53):1-84; [10] Squires SG, et al. Can Commun Dis Rep 2004; 30:17-28; [11] European Union Invasive Bacterial Infection Surveillance network. Invasive
Neisseria meningitidis in Europe 2002. Dec 2003. Available at http://www.euibis.org/documents/2002_meningo.pdf. Accessed April 12, 2005.
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Hajj and Umra Visitors
2007
Europe
168,946 visitors
Middle East
3,449,212 visitors
South Asia
1,755,992 visitors
Americas
7,576 visitors
Africa
369,727 visitors
E.Asia & Pacific
169,437 visitors
Map courtesy of BYU Geography Department, Data from Kingdom of Saudi Arabian Department of Tourism
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Meningococcal Disease
Global epidemiology
Local epidemiology
Shortcomings of Meningococcal polysaccharide vaccines
Conclusion
Reported Cases of Meningococcal
Disease
Saudi Arabia, 1970 – 2008
number of reported cases
3000
2500
2000
1500
1000
500
0
1970
1975
1980
1985
1990
1995
2000
2005
year
Source: Kingdom of Saudi Arabia, Ministry of Health, February 2009
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Reported Cases of Meningococcal
Disease
Saudi Arabia, 1994 – 2008
number of reported cases
400
350
300
250
200
150
100
50
0
1995
1998
2001
2004
2007
year
Source: Kingdom of Saudi Arabia, Ministry of Health, February 2009
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number of reported cases
Meningococcal Cases by Region,
Saudi Arabia, 1999 - 2003
350
Others
300
Riyadh
250
Jeddah
200
Madinah
Makkah
150
100
50
0
1999
2000
2001
2002
2003
year
Source: Kingdom of Saudi Arabia, Ministry of Health, February 2009
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number of reported cases
Meningococcal Cases by Age Group,
Saudi Arabia, 1999 - 2003
350
45 +
300
15 - 44 yrs
250
5 - 14 yrs
200
1 - 4 yrs
< 1yr
150
100
50
0
1999
2000
2001
2002
2003
year
Source: Kingdom of Saudi Arabia, Ministry of Health, February 2009
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Meningococcal Disease by Serogroup*
Saudi Arabia, 1994 – 2008
* Cases for whom a serogroup
was identified and reported
number pf reported cases
A
B
C
W-135
Y
other
250
200
150
100
50
0
1994-1998
1999-2003
2004-2008
5-year period
Source: Kingdom of Saudi Arabia, Ministry of Health, February 2009
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Meningococcal Disease
Global epidemiology
Local epidemiology
Shortcomings of Meningococcal polysaccharide
vaccines
Conclusion
Shortcomings of current of
polysaccharide Vaccine







T-cell-independent immune response producing no memory
Absence of herd immunity in unvaccinated population
No effect on carriage status
Frequent revaccination needed each 3 years.
Hypo-responsiveness occurred upon revaccination.
No Boosting effect.
Poor immunogenicity among the younger age groups.
Dose those shortcomings of local impact?
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Demonstrated hyporesponsiveness upon MPSV
repeated vaccination
 Serogroup C rSBA titers pre and
1month post MPSV vaccination
800
700
600
500
rSBA GMTs
400
300
200
100
0
MPSV naïve
Vaccinated once
Prior to vaccination

Vaccinated > once
1M post vaccination
Jokhdar H, Borrow R, Sultan A et al. Immunologic Hyporesponsiveness to Serogroup C but Not Serogroup A following Repeated
Meningococcal A/C Polysaccharide Vaccination in Saudi Arabia. Clin Diagn Lab Immunol. 2004;11:83-88
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AlMazrou Y, Khalil M, Borrow R, et al. Serologic responses to ACYW135
polysaccharide meningococcal vaccine in Saudi children under 5 years of age.
Infection and Immunity 2005;73:2932-39.
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 In Saudi Arabia, very young children demonstrated
relatively poor immune response to Meningococcal
Polysaccharide Vaccine

AL-Mazrou Y, Khalil M, Borrow R et al. Serologic Responses to ACYW135 Polysaccharide Meningococcal Vaccine in Saudi Children
under 5 Years of Age. Infect Immun. 2005;73:2932-39
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Conclusion
 Meningococcal disease is sever and
devastating.
 Saudi Arabia is at high risk due to several
factors
 The currently used MPSV4 having several
limitations.
 The solution is to shift to the modern MCV4
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Expanded Program of Immunization
in Saudi Arabia - 2011
AGE
EPI 1991
EPI 2002
EPI 2011
At birth
BCG HepB1
BCG HepB1
BCG HepB1
6 weeks
DTwP1 HepB2 OPV1
DTwP-Hib1 HepB2 OPV1
DTwP-Hib1-HepB2 IPV1 PCV131
DTwP-Hib2 OPV2
DTwP-Hib2-HepB3 OPV1 PCV132
DTwP-Hib3 HepB3 OPV3
DTwP-Hib3-HepB4 OPV2 PCV133
2 months
3 months
DTwP2 OPV2
4 months
5 months
DTwP3 OPV3
6 months
Measles HepB3
9 months
Measles + MCV4
12 months
MMR
MMR1
MCV4 MMR1 OPV3 Varicella1 PCV134
18 months
DTwP4 OPV4
DTwP-Hib4 OPV4
DTwP-Hib4 OPV4 HepA1
24 months
DTwP5 OPV5
MMR2 DTwP5 OPV5
HepA2
4-6 years
MMR2 Varicella2 DTwP5 OPV5
Meshkhas AA. Guidelines to Expanded Program of Immunization staff (Arabic title). Riyadh: Saudi Ministry of Health;
2006.
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