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Fedson, Musher, in Vaccines, 1994Musher, in Principles and Practice of Infectious Diseases, 1995
Nasopharyngeal carriage may occur in up to 60% of healthy pre-schoolchildren and up to 30% of healthy older children and adults
Nasopharynx: siteof colonisation
Trachea
Dissemination
Inhalation
Patient withpneumococcaldisease
Asymptomaticcarrier
Aerosol
Nasal cavity
Nasopharyngeal carriage of Pneumococcus
10
20
30
40
50
Preschool Grammar school
Jr. HighSchool
Car
riage
rate
(%)
6060%
35%
25%
0Households with children
Householdswithout children
29%
6%
1 Presentation by Mark A. Fletcher, M.D., on Epidemiology of Streptococcus pneumoniae: “Pneumococcus”
Bacteremia 13,000Meningitis 700Death 200Otitis media 5,000,000
Syndrome Cases
Burden of Pneumococcal Disease in Children*
*Prior to routine use of pneumococcal conjugate vaccine
4
Conditions That Increase Risk for Invasive Pneumococcal Disease
• Decreased immune function
• Asplenia (functional or anatomic)
• Chronic heart, pulmonary, liver or renal disease
• Cigarette smoking
• Cerebrospinal fluid (CSF) leak
Children at Increased Risk of Invasive Pneumococcal Disease
• Functional or anatomic asplenia, especially sickle cell disease
• HIV infection• Recipient of cochlear implant• Out-of-home group child care• African American children• Alaska Native and American Indian children
who live in Alaska, Arizona, or New Mexico• Navaho children who live in Colorado and
Utah
5
PNEUMOCOCCAL DISEASE
Invasive pneumococcal disease is serious and has a high risk of mortalityRisk factors include old age, chronic illness, asplenia and immunodeficiencyMortality remains high despite appropriate antibiotic therapyS. pneumoniae resistance to antimicrobials is increasing (with concomitant increasing cost of management)
Prevention of pneumococcal disease among high-risk groups is a priority
Invasive Pneumococcal DiseaseIncidence by Age Group, 1998 and 2002
050
100150200250
<1 1 2-4 5-17 18-34 35-49 50-64 65+
Age Group (Yrs)
Rat
e *
1998 2002
* Rate per 100,000 populationSource: Active Bacterial Core Surveillance/EIP Network
Invasive Pneumococcal Disease (IPD) in BC (2002 – 2006)
CCDR 2006; 32(14)
6
IPD in BC in < 3 y/o (2002 – 2006)
CCDR 2006; 32(14)
IPD in Calgary Infants 0 – 23 mo.(1998 – 2007)
Kellner JD, et al. CID 2009; 49:205 – 212.
IPD Calgary ≥ 65 y/o (1998 – 2007)
Kellner JD, et al. CID 2009; 49:205 – 212.
7
Herd immunity (or community immunity)
• describes a type of immunity that occurs when the vaccination of a portion of the population (or herd) provides protection to unvaccinated individuals. (John TJ, Samuel R, 2000)
• This is accomplished because, by having a large percentage of the population vaccinated, it reduces the spread of the pathogen within the community.
• Unvaccinated individuals can be individuals in older age groups like in the pneumococcal example.
• It can also be in groups that can’t be vaccinated, ex. newborns or those with chronic illnesses or individuals allergic to vaccines
Pneumococcal Conjugate Vaccines (1)
• Current pneumococcal vaccines• conjugate with diphtheria CRM197 protein: Prevnar®
7 valent (provides coverage against 7 strains of pneumococcus)
• Children with high risk- sickle cell anaemia or splenectomized
Problems with polysaccharide vaccine in children
• Not effective in children less than 2 years• No effect on nasal carriage• No herd effect• Absence of immunologic memory• Antibody level to several serotypes decline to
pre-vaccination values within 3-7 years corresponding to a decline of clinical protection
protein• licensed in Canada December 2009• proposed indications – prevention of:
− invasive pneumococcal disease− pneumonia− otitis media
• impact: replaces Prevnar® 7broader coverage with more relevant serotypes
• FPT governments to determine product
11
Serotype Composition
19A7F6A53123F19F18C149V6B4Prevnar® 13
7F5123F19F18C149V6B4Synflorix™
23F19F18C149V6B4Prevnar®
Proportion of pediatric pneumococcal disease prevented by vaccination
92%
87%
89%
87%
73%
86%
13-valent
Changing Epidemiology
• pediatric PCV7 programs in Canada produced a > 80% decline in pediatric IPD
• herd immunity benefits in adults
• incidence of non-vaccine serotypes has increased (so lesser reduction in overall incidence of IPD)
• 2004-2009: widespread community-based outbreak of serotype 5 in adults in western Canada
• increasing incidence of disease due to serotype 19A. including multidrug resistant 19A
12
(A) Pneumococcal mastoiditis cases caused by serotype 19A among children at Texas Children’s Hospital between 1995 and June 2007. (B) Pneumococcal isolates and the proportion that were serotype 19A recovered from middle ear fluid cultures obtained from children at Texas Children’s Hospital between 1995 and June 2007
01020304050607080
Perc
enta
ge o
f iso
late
s w
ithse
roty
pes
incl
uded
in th
e va
ccin
e
BC QC TIBDN AB ICSSurveillance system
PCV7PCV10PCV13
Percentage of isolates causing IPD in children aged 6 months to 5 years of age during 2007 and 2008 with
serotypes included in different conjugate vaccines
13
Summary
• 2 new conjugate vaccines against Streptococcal pneumoniae disease
• significant differences in carrier protein with additional benefits• e.g. acute otitis media
• changing epidemiology of IPD may drive choice of product
• degree of cross-protection from PCV7 and PCV10?
14
(1) Kaplan, Sheldon L. et al. Serotype 19A Is the Most Common Serotype Causing Invasive Pneumococcal Infections in Children. PediatricsVolume 125, Number 3, March 2010.
(2) Rapport d'activites 2008-2009 du Laboratoire de santé publique du Quebec, Institut National De Sante Publique du Quebec.
(3) Bettinger, Julie A. et al. The effect of routine vaccination on invasive pneumococcal infections in Canadian children, Immunization Monitoring Program, Active 2000-2007.
(4) Kellner JD, Church DL, MacDonald J, et al. Progress in the prevention of pneumococcal infection. CMAJ. 173; 10: 1149 - 1151.
(5) WHO. Wkly epi record 2008; Worldwide progress in introducing pneumococcal conjugate vaccine 2000-2008. No. 43, 2008, 83, 385-392
(6) Health Canada. Pneumococcal Vaccine. http://www.hc-sc.gc.ca/hl-vs/iyh-vsv/med/pneum-eng.php. Accessed April 2010.