Pneumococcal and Influenza vaccine

1
Pneumococcal and Influenza vaccine

• Dr. Amukoye
• KEMRI

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Epidemiology-morbidity/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

3
Under Five Mortality Rates by Provinces of
Kenya, KDHS 2008.


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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 40-50 for meningitis.
• pneumococcal pneumonia in a pandemic influenza
  setting is anticipated to range from 5 to 13.

5
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

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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.

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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.

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Immunogenecity

• WHO expert panel determined that an antibody
  concentration of 0.35 mcg/ML for all
  vaccine-included 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)

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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 lt5 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

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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

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Prevention and Education

• It is recommended that immunizations which
  prevent CAP be kept up-to-date, including
• PCV10,13 heptavalent conjugated pneumococcal
  vaccine (PCV7, Prevnar),
• annual influenza vaccine for
• all children 6 to 23 months of age, and
• children aged gt6 months with certain risk factors
  (including but not limited to asthma, cardiac
  disease, sickle cell disease, human
  immunodeficiency virus HIV and diabetes)
• It is recommended that measures to prevent
  pneumonia infections be discussed with families,
  including
• 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

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PRIORITY GROUP FOR VACCINE

• HIV infection, leukaemia, lymphoma, Hodgkins
  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

• 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,

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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..

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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 20022(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. 200410(3)176-182

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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.

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Influenza the virus. Classification
Family
ORTHOMYXOVIRIDAE
RNA virus
Genus
Influenza virus
Influenza C virus
Types
Type A
Type B
Type C
Man Animal
Specificity
Man
Man
Kingsbury D. W., Virology, IInd edition, New
York, 1990, 1076-87
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Structure of the virus
Nucleocapsid Nucleoprotein (NP) -RNA (7 or 8
segments) Matrix protein (M) Lipid
bilayer Haemaglutinin (HA) Neuraminidase (NA)
Internal antigens
Surface antigens
80 to 120 nm
Kingsbury D. W., Virology, IInd edition, New
York, 1990, 1076-87
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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., 1990391306-25
19
Influenza true image of a serious
and devastating disease
"Flu spreads across the world and ages"
1977
"Russian" flu
1968
"Hong Kong" flu
1957
"Asian flu"
First human influenza virus isolated
1933
Epidemic recorded by Hippocrates
"Spanish influenza" killed 20-40 million people  
1918
412 B.C
1781 1830
Epidemics spread across Russia from Asia
Middle ages
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, 199410 451-453
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Seasonal Occurrence of Influenza, RSV and
Parainfluenza Viruses, United States,1996-99
7/99
7/97
7/98
1/98
7/96
1/99
1/97
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Results
Seasonal Influenza Trends 2004 - 2007
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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. 199245306-11
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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.
24
Impact of Respiratory Viruses on Illness in
Children Aged lt 5 Years
Percent
Reed G et al. J Infect Dis 1997 175807.
25
Clinical Courses of Croup in Finland
Influenza (n29) Parainfluenza (n88)
Age (median) 1.7 years 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
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INFLUENZA Groups at increased risk for
influenza-related complications and
mortality

• Persons gt 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 19923117-138