carga global de la enfermedad neumocóciaprincipales causas de muertes por enfermedades infecciosas...
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Carga globalde la enfermedad neumocócia
Adam L. Cohen, MD MPHCenters for Disease Control and Prevention
Atlanta, GA
Santiago, Chile, December 2007
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Pneumococcal Carriage and Disease
Ear infections
Nose and throat(Healthy persons)
Blood stream infections
Meningitis
Pneumonia
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Principales Causas de Muertes porEnfermedades Infecciosas (estimados)
Dea
ths
(mill
ions
)
< 5 years old > 5 years old
0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
Pneumonia SIDA Diarrea TB Malaria Sarampión
3.5
2.7
2.2
1.7
1.1 0.9
Fuente: WHO, 2000
S. pneumoniae:~1.6 millones
muertes, incluyen~800,000 muertes en
niños
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DTP/Polio
Measles
HepB
YF
MenAC
S. pneumo
Rotavirus
Hib
WHO estimates 2.7M childhood deaths from vaccine preventable illnesses.
Pneumo, Hib & Rotavirus account for
~60% of vaccine
preventable deaths in children
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WHO Global Disease Burden Project • Objective: to generate country-specific Hib and Pneumo
burden estimates• Database of evidence
– Systematically collected– Publicly available
• Methods for estimation– Transparent methods– Communication of uncertainty of estimates
• Independent expert committee review x 2• Clearance through WHO-EIP
– Compatibility with other disease burden estimates• Country consultation prior to release of country-level
estimates
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Sample template
countries have received
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Timeline of Disease Burden Project
• Country Consultation Letters: August 2007• Responses due by September-October (6
weeks) • Final numbers by October-November 2007• Publication in Winter-spring 2008• Website with numbers• Tool for calculating disease burden in other
years/evaluating impact of implementing vaccination programme
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Pneumococcal Epidemiology:Invasive disease basics
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Incidence and Case Fatality Ratio by Age GroupInvasive Pneumococcal Disease
ABCs 1998
020406080
100120140160180
<2 2-4 5-1718-34
35-4950-64
65-7980+
Age group, years
Inci
denc
e (c
ases
/100
,000
po
p)
0
5
10
15
20
25
30
Cas
e fa
talit
y ra
tio (%
)Case fatality ratio Incidence
Robinson et al JAMA 1998
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1143 48 59
92
294341
432
0
100
200
300
400
500
Healthy Chronicheart
Diabetes Chroniclung
Heavydrinker
Solidcancer
HIV/AIDS Bloodcancer
Cas
es p
er 1
00,0
00 p
erso
nsInvasive pneumococcal disease in healthy adults
and adults with selected comorbiditiesUnited States, 2000
Kyaw M et al JID 2005
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Risk Factors for Invasive Pneumococcal Disease
Nuorti et al. NEJM 2000 Kupronis et al. J Am Geriatr Soc 2003
J Watt et al, CID 2003
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Invasive Pneumococcal Disease in Navajo and White Mountain Apache vs. White and
Black Persons in the General U.S. Population, 1997-8
0
50
100
150
200
250
18-64 65+
Cas
es p
er 1
00,0
00 p
op.
White (ABCs)Black (ABCs)Navajo
J Watt et al, CID 2003
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Epidemiology of Serotypes• Over 90 different pneumococcal serotypes• Pneumococcal serotypes causing invasive disease vary
– Geographically– With age– With immune status– Between some racial/ethnic groups– In ability to be carried– In invasiveness– In disease manifestations they cause– In amount of resistance to antibiotics
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Pneumococcal disease prevention and treatment
• Case-management– antibiotics, oxygen, supportive care
• Improved nutrition– breastfeeding, micronutrients, improved feeding
• Risk factor reduction– indoor air pollution, hand washing, HIV prevention
• Immunizations
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Pneumococcal Conjugate Vaccine (PCV7)
• Prev(e)nar (Wyeth Lederle) 7-valentvaccine
•Poly- or oligosaccharides of serotypes 4, 6B, 9V, 14, 18C, 19F, 23F
•Conjugated to CRM197
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Considerations for PCV Introduction
• Disease burden– Serotype coverage: Just a part of the story– Absolute burden of vaccine-type disease
• Cost effectiveness• Feasibility
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National Programs Using Conjugate Vaccine
• National programs– USA, Canada, Australia, Luxemburg, Qatar
• Routine introduction announced for 2006– UK, Holland, Norway, Greece
• Countries with moderate vaccine use– France (broad “at risk” program) – Italy (universal recommendation in 15 / 20
regions)– Spain, Portugal (private markets with high
coverage).
Source: Wyeth
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Serotype coverage with 7-valent vaccine* in the US and Australia
92%83%
56%
0%10%20%30%40%50%60%70%80%90%
100%
Australia US US - Navajo
Based on serotype coverage alone,
Australia would get the “highest
priority” for vaccine introduction, and Navajo would get “lowest priority”
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“Preventable incidence” rate is the important measure
0
20
40
60
80
100
120
140
Prev
enta
ble
case
s pe
r 10
0,00
0 ch
ildre
n <5
yo
Australia US US - Navajo
Navajo should be “highest”, not lowest priority
Preventable incidence = ST coverage x Incidence of disease
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Status of national programs and licensure of 7-valent (Apr 2006)
Red = Registered and universal infant use or equivalent recommendation (n=13)Blue = Registered but no universal use recommendation (n=61)
Map source: www.preventpneumo.org June, 2006
2008 intro expected in 2-6 GAVI countries
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Multi-national
LaunchedClinical trialPhase III
Clinical trialPhase II
Clinical trialPhase I
9-valent
11-valent
Prevnar(7-valent)
13-valent
7-valent
Pre-clinical stage
>4 multi-valent conjugate vaccine projects
Emerging suppliers
Expected launch
2008 (US, Europe)
~20 vaccinesin research/Pre-clinical
stage(includes
conjugate &protein-based
vaccines)
Discontinued
1Completed first Phase III trial; results announced in Jun05
DevelopmentStage
Vaccine Supply EnvironmentPneumococcal vaccine pipeline
Source: BCG Global Supply Strategy 2005
PneumoADIP team analysis
GSK1 10-valent
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Pneumo vaccine supply outlook
2000-2007 2008-2010 2011-2015 2016-2020
7-valentSingle dose
syringe
7 valent and 10 valent
Single vials ?multi-dose
10 - 13 valentsSingle and multi-dose?Proteins?
4-14 valents?Proteins?Single and multi-dose
1 Multi-National Supplier
2 Multi-National
Suppliers
2 -3 Suppliers
Multi-nationals
+ Emerging later
>3 Suppliers
Multi-nationals and Emerging
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Surveillance as a cornerstone of vaccine introduction
• Provides baseline data before vaccine introduction
• Provides local disease burden data and where possible serotype data
• Pneumococcal surveillance poses challenges– Multiple syndromes (some very common)– Limited diagnostics– Importance of serotypes
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Global Framework on Immunization Monitoring and Surveillance (GFIMS)WHO and CDC joint vision• By 2010, a strengthened and more integrated
epidemiological and laboratory network for vaccine preventable diseases (VPD) surveillance
• Network that provides high quality information to measure disease burden and impact of vaccines
• Link with seasonal/pandemic influenza & emerging threats