Pneumococcal and Influenza vaccine

Dr. Amukoye

KEMRI

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

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 40-

50% 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 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)

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 countries1-4 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 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 >6 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

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

RNA virus

Type A Type B

Influenza virus

Type C

Influenza C virus

ORTHOMYXOVIRIDAEFamily:

Genus:

Types:

Specificity:Man

Animal Man Man

Kingsbury D. W., Virology, IInd edition, New York, 1990, 1076-87

Internalantigens

Kingsbury D. W., Virology, IInd edition, New York, 1990, 1076-87

Structure of the virus

Nucleocapsid:Nucleoprotein (NP) -RNA (7 or 8 segments)

Matrix protein (M)

Lipid bilayer

Haemaglutinin (HA)

Neuraminidase (NA)

80 to 120 nm

Surfaceantigens

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

Antigenic variation : intelligence of influenza viruses

"Flu spreads across the world and ages" "Flu spreads across the world and ages"

Murphy B.R., Webster R.G., Virology, IInd edition, New York, 1990, 1091-2Ghendon Y. Introduction to pandemic influenza through history Eur Jour of Epid, 1994;10: 451-453

"Spanish influenza" killed 20-40 million people  

412 B.C412 B.C

Middle agesMiddle ages1781 & 18301781 & 1830

19181918

19331933

19571957

19619688

19771977

"Asian flu"

"Hong Kong" flu

"Russian" flu

First human influenza virus isolated

Epidemics spread across Russia from Asia

Numerous episodes described

Epidemic recorded by Hippocrates

Influenza : true image of a serious and devastating disease

Seasonal Occurrence of Influenza, RSV and Parainfluenza Viruses, United Seasonal Occurrence of Influenza, RSV and Parainfluenza Viruses, United States,1996-99States,1996-99

0

5

10

15

20

25

30

35

40

% r

espir

ato

ry s

pecim

ens

posit

ive

Influenza RSV Para 1 Para 3

7/997/97 7/981/987/96 1/991/97

Results

Seasonal Influenza Trends 2004 - 2007

Ghendon Y. Influenza - its impact and control Rapp. trimest. sanit. mond. 1992;45:306-11

Factors which favor contagion :Factors which favor contagion : Humid or cold weatherHumid or cold weather

Indoor lifeIndoor life Crowded public transportCrowded public transport

Speed of modern intercountry travelSpeed of modern intercountry travel

Every year, about 10% of the world'spopulation catch influenza :

some 600 million people.Attack rates of 40% in pre-school and 30% in school

age children.

Influenza impact : a yearly infection that occurs worldwide

Impact of influenza in children:

The burden of influenza in young healthy children is as high as that in the elderly and high risk groups.

30-40% of all acute Otitis Media cases in children are related to influenza.

Economical benefits: absenteeims both at school and the work place.

More severe in at risk children: 4-fold increased hospitalisation rate.

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.

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.

Excess number for out patient visits.10-30% increased antibiotic use.Increased hospitalizations.

Death : Rare and mainly in under ones

Impact of Respiratory Viruses on Impact of Respiratory Viruses on Illness in Children Aged < 5 YearsIllness in Children Aged < 5 Years

0102030405060708090

LRI URI Fever >39 AOM

Parafl u

RSV

Flu

Reed G et al. J Infect Dis 1997; 175:807.

Percent

Clinical Courses of Croup in Clinical Courses of Croup in FinlandFinland

Peltola et al. Pediatr Infect Dis J 2002; 21: 76-78

Influenza

(n=29)

Parainfluenza

(n=88)

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%)

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)

INFLUENZA: Groups at increased risk for influenza-related

complications and mortality:

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