Pneumococcal and
Influenza vaccine
Dr. Amukoye
KEMRI
Epidemiologymorbidity/mortality

Kenya has a young population with 43%
under the age 15 years

Under 5ve mortality had reached 12% though
this has improved to 7.4%

2-3% of under 5ves suffer
from severe pneumonia yearly
Under Five Mortality Rates by
Provinces of Kenya, KDHS 2008.
Pneumoccocal








10.6 million children under five years of age die each year;
90% of these deaths occur in developing countries.
Streptococcus pneumoniae, is a leading cause of pneumonia,
meningitis and septicemia,
1.6 million people die each year including 700,000 to 1 million
children under five.
PPV23 is estimated to be effectiveness to between 50 and
60% of IPD in children aged 24 to 59 months
Pneumococcal bacteremia of 597/100,000 children less than 5
years of age per year (Kenya).
Case fatality ratios range from 5-20% for bacteremia to 4050% for meningitis.
pneumococcal pneumonia in a pandemic influenza setting is
anticipated to range from 5 to 13%.
Serotype





Nasopharynx is the reservoir for pneumoccocal
90+ serotypes based on capsular polysaccharide
Approximately 20 serotypes account for over 70% of invasive
disease;
Just about 10 serotypes are commonly associated with pediatric
infections -1,4,6,3,7f,9v,14,18c, 19f, 23f
Based on molecular typing of multiple housekeeping genes,
pneumococcal strains can be characterized into clones. there is a
strong association between



serotype and clones.
specific clones, serotypes and antimicrobial resistance pattern.
The majority of these are associated with antibiotic resistance. Strains that are
penicillin-resistant are much more likely also to contain genes conferring resistance to
other drug classes
Serotype


The global distribution of serotypes varies.
PCV 7- 4,6B, 9V, 14, 18C, 19F and 23F conjugated to an immunogenic
mutant diphtheria toxin, CRM197
 PCV 10- 1,5,7F, 4,6B, 9V, 14, 18C,19F,23F
 PCV 13- 3, 19A, 6A,1,5,7F, 4,6B, 9V, 14, 18C,19F,23F


Some serotypes 1 and 5 are common in developing countries.
Serotypes associated with invasive infections among HIV infected children are
similar to the serotypes that infect healthy children.
Polysaccharide vs conjugate



Pneumococcal capsular polysaccharides, serves as the
primary pneumococcal antigens eliciting a host immune
response, induce a T-cell independent immune response which is
not develop in children until around two years of age
Conjugate vaccine- polysaccharides are covalently coupled to
immunogenic proteins such as the mutant diphtheria toxin
CRM197 used in PCV7 and PCV9, a T cell-dependent response
is elicited.
conjugate vaccines can confer both systemic and mucosal
immunity. Serum IgG and secretory IgA can be detected in the
saliva of toddlers and infants after parenteral vaccination with
PCV formulations.
Immunogenecity



WHO expert panel determined that an antibody
concentration of 0.35 mcg/ML for all vaccineincluded serotypes corresponded to clinical efficacy
against invasive disease due to vaccine-included
serotypes
PCV was as immunogenic in low birth weight and
preterm infants as in normal birth weight and full
term infants
Replacement disease (19A)
Preventing pneumonia by immunization



Measles -Immunization coverage is 80% in Kenya
HIB – meningitis more or less eradicated in Kiliffi
Pneumoccal-There are 814,000 pneumococcal
deaths in children aged <5 years in developing
countries
 1-4 million episodes of pneumococcal pneumonia
yearly in Africa alone.
 Introduction of PCV will be effective where there is
a demonstrable burden of IPD attributable to
vaccine serotypes but herd protection and serotype
replacement effects are unpredictable.


Influenza
Others-, Pertusis, RSV
Prospect of vaccines




The incidence of invasive pneumococcal disease (IPD) in
young children decreased by over two-thirds following the
programmatic introduction of pneumococcal conjugate
vaccination in the United States
In the developing world, the prospects for prevention by
vaccination are uncertain.
In South Africa, vaccination was shown to reduce IPD by 83%
among human immunodeficiency virus-negative children.
In The Gambia, vaccine efficacies were 77% against IPD and
37% against radiological proven pneumonia
Prevention and Education
It is recommended that immunizations which prevent CAP be kept upto-date, including:

PCV10,13 heptavalent conjugated pneumococcal vaccine
(PCV7, Prevnar®),
annual influenza vaccine for




It is recommended that measures to prevent pneumonia infections be
discussed with families, including:




all children 6 to 23 months of age, and
children aged >6 months with certain risk factors
(including but not limited to asthma, cardiac
disease, sickle cell disease, human
immunodeficiency virus [HIV] and diabetes)
handwashing, especially when exposed to individuals with
respiratory infections (Morton & Schultz, 2004 [A]; Roberts et al.,
2000 [A])
breastfeeding (Levine et al., 1999 [C])
limiting exposure to other children
PRIORITY GROUP FOR VACCINE






Asplenia or splenic
dysfunction (including sickle
cell
disease and coeliac disease).
Chronic renal disease,
nephrotic syndrome or renal
transplant.
Chronic heart, lung, or liver
disease, including cirrhosis.
Diabetes mellitus.
Complement deficiency
(particularly early component
deficiencies C1, C2, C3, C4).
Immunosuppressive conditions
(e.g. some B- and T-cell
disorders,







HIV infection, leukaemia,
lymphoma, Hodgkin’s disease)
and those
immunosuppressive therapies.
CSF leaks either congenital or
complicating skull fracture or
neurosurgery.
Intracranial shunt.
Children under 5 years of age
following invasive
pneumococcal disease,
irrespective of vaccine history
Smokers and alcoholics
Way forward




Malnutrition
 Macronutrient
 Micronutrient (zinc, Vit. A,D.,)
Pollution control-indoor (biomass fuel, cigarette)
Access to health care
 No and distribution, case management
Vaccine

Pneumococal, HIB, measles, pertusis
Influenza…..
References



Williams BG, Gouws E, Boschi-Pinto C, et al. Estimates of
world-wide distribution of child deaths from acute respiratory
infections. Lancet Infect Dis 2002;2(1):25-32
Mulholland K. Childhood pneumonia mortality- a permanent
global emergency.Lancet. 2007 ;370(9583) :285-9.
Zar HJ. Pneumonia in HIV-infected and uninfected children in
developing countries –epidemiology, clinical features and
management. Curr Opin Pulm Med. 2004;10(3):176-182
VIRAL PNEUMONIA

Viruses -occur in 30-40% of acute respiratory infections in hospitalised children
RSV-

Influenza virus-

Adenovirus
Paramyxovirus
Metapneumovirus
Measles (ribeola virus)










------------------------------------------------------------------------------------------Seasonal influenza causes an estimated annual average of
226 000 hospitalizations and 36 000 deaths in the United
States. The highest rates of influenza-associated hospitalizations
and death occur among the elderly, young children,
and persons with certain high-risk medical conditions.
Influenza: the virus
. Classification
Family:
ORTHOMYXOVIRIDAE
RNA virus
Genus:
Influenza virus
Influenza C virus
Types:
Type A
Type B
Type C
Specificity:
Man
Animal
Man
Man
Kingsbury D. W., Virology, IInd edition, New York, 1990, 1076-87
Structure of the virus
Nucleocapsid:
Nucleoprotein (NP) -RNA (7 or 8
segments)
Internal
antigens
Matrix protein (M)
Lipid bilayer
Haemaglutinin (HA)
Neuraminidase (NA)
80 to 120 nm
Kingsbury D. W., Virology, IInd edition, New York, 1990, 1076-87
Surface
antigens
Antigenic variation : intelligence
of influenza viruses




Frequent with Influenza A, less for type B, never for type C
To escape population immunity
Involves the external antigens : HA and NA
Two types of mutations depending on whether the RNA segment
variation is small or great :


Antigenic drift
Antigenic shift
Each year, evolution can induce a different virus
Betts FR, Douglas RG, Mandell G.L., Douglas R. G., Bennett J.E., Principles and practice of infectious diseases, 3rd ed., 1990;39:1306-25
Influenza : true image of a serious and devastating disease
"Flu spreads across the world and ages"
1977
"Russian" flu
1968
"Hong Kong" flu
1957
Epidemic recorded
by Hippocrates
1933
"Asian flu"
First human influenza virus isolated
1918 "Spanish influenza" killed 20-40 million people
412 B.C 1781 & 1830
Middle ages
Epidemics spread across Russia from Asia
Numerous episodes described
Murphy B.R., Webster R.G., Virology, IInd edition, New York, 1990, 1091-2
Ghendon Y. Introduction to pandemic influenza through history Eur Jour of Epid, 1994;10: 451-453
Seasonal Occurrence of Influenza, RSV and Parainfluenza Viruses, United
States,1996-99
35
30
positive
% respiratory specimens
40
25
20
15
10
5
0
7/96
1/97
7/97
Influenza
1/98
RSV
7/98
Para 1
1/99
Para 3
7/99
Results
Seasonal Influenza Trends 2004 - 2007
140
120
100
80
Neg
Pos
60
40
20
0
2004
|
2005
|
2006
|
2007
J F M A M J J A S O N D J F M A M J J A S O N D J F M A M J J A S O N D J F M A M J J A S O N D
Influenza impact : a yearly infection that occurs worldwide
Every year, about 10% of the world's
population catch influenza :
some 600 million people.
Attack rates of 40% in pre-school and 30% in school age
children.
Factors which favor contagion :
 Humid or cold weather
 Indoor life
 Crowded public transport
 Speed of modern intercountry travel
Ghendon Y. Influenza - its impact and control Rapp. trimest. sanit. mond. 1992;45:306-11
Impact of influenza in children:
Annual attack rate of 15-40%: the spread of flu vaccination in the family
starts with school going children. Children shed the virus for a longer
time and shed higher titres.
13.8 –16 million illness years in the USA in individuals under 20 years.
30-40% of all acute Otitis Media cases in children are related to influenza.
More severe in at risk children: 4-fold increased hospitalisation rate.
Economical benefits: absenteeims both at school and the work place.
Excess number for out patient visits.
10-30% increased antibiotic use.
Increased hospitalizations.
Death : Rare and
mainly in under ones
The burden of influenza in young healthy children is as high as that
in the elderly and high risk groups.
Betts FR et al principles and of infectious disease 3rd edtion 1990.39: 1302-5. A call to action, improving influenza and pneumococcal infectins among high
risk adults http://www.nfid.org./ncai/publications/roundtable/. The american lung association asthma lung clincial research centers.
Impact of Respiratory Viruses on
Illness in Children Aged < 5 Years
Percent
90
80
70
60
50
40
30
20
10
0
Paraflu
RSV
Flu
LRI
URI
Fever >39
Reed G et al. J Infect Dis 1997; 175:807.
AOM
Clinical Courses of Croup in
Finland
Age (median)
Influenza
(n=29)
1.7 years
Parainfluenza
(n=88)
1.4 years
Hospital stay
4 days (1-11)
2 days (1-27)
Steroid rx
18 (62%)
28 (32%)
Supp. O2
7 (24%)
3 (3%)
ICU stay
8 (28%)
10 (11%)
Pneumonia
19 (66%)
34 (40%)
Peltola et al. Pediatr Infect Dis J 2002; 21: 76-78
INFLUENZA: Groups at increased risk for influenzarelated
complications and mortality:







Persons > 50 years of age,
Residents of nursing homes,
Adults and children with chronic disorders of the pulmonary or
cardiovascular systems,
Adults and children with chronic metabolic diseases, renal
dysfunction, or hemoglobinopathies ( such as Sickle cell disease),
Immunocompromised adults and children, including HIV infected
persons and users of immunosuppressive medications
Pregnant women belonging to the high-risk groups.
Newly recognized: Healthy children aged 6-24 months(5 years)
Each year one out of every three persons is infected by influenza
ACIP, MMWR 1999; 48 [No RR-4]: 1-29.
Palache A. M., Influenza subunit vaccine - ten years experience. European journal of clinical research 1992;3:117-138