VACCINE PREVENTABLE DISEASES AND VACCINATION

VACCINE PREVENTABLE DISEASES AND VACCINATION

Najwa Khuri-Bulos 2012

1

Jenner

Strong Tools Available/Expected

1960 1980 2000// //Diphtheria

Pertussis

Tetanus

YF Influenza

Polio

Measles

JERubella HepBHib (conj)

Typhoid

Cholera Pneumo (conj)RotavirusHPVMening (conj)

Dengue

Malaria TB

HIV/AIDS

Traditional EPI

UnderutilizedVaccines

Future

1960 1980 2000// //Diphtheria

Pertussis

Tetanus

YF Influenza

Polio

Measles


Typhoid


Dengue

Malaria TB

HIV/AIDS

1960 1980 2000// //Diphtheria

Pertussis

Tetanus

YF Influenza

Polio

Measles


Typhoid


Dengue

Malaria TB

HIV/AIDS

Traditional EPI

UnderutilizedVaccines

Future

Diphtheria 175,885 4 -99.99Measles 503,282 81 -99.98Mumps 152,209 323 -99.79Pertussis 147,271 6,755 -95.41Polio (wild) 16,316 0 -100Rubella 47,745 152 -99.68Cong. Rubella Synd. 823 7 -99.15Tetanus 1,314 26 -98.02Invasive Hib Disease 20,000 167 -99.16

Disease 20th Century Annual Morbidity* 2000** % change

* Maximum cases reported in pre-vaccine era and year

+ Estimated because no national reporting existed in the prevaccine era^ Adverse events after vaccines against diseases shown on Table = 5,296** Provisional

Total 1,064,845 7,515 -99.29

Vaccine Adverse Events 0 13,497^ +++

Comparison of Annual and Current Reported Morbidity, Vaccine-Preventable Diseases and Vaccine Adverse Events, United States

0

1000

2000

3000

4000

5000

6000

7000

8000

No

. of

case

s

0

20

40

60

80

100

120

Co

vera

ge

rate

No. of Cases 1st dose Measles coverage

2nd dose measles coverage (MMR)

2nd

dose

Measles poliomyelitis

Impact of the EPI

Reported poliomyelitis & VAPP 1979-2008 Jordan

0

5

10

15

20

25

# C

ases

polio wild

VAPP

NIDs SNIDs

OPV

Case Study, Jordan, a great success storyImmunization Coverage for Infants and MMR1

1990-2008, Jordan

0

20

40

60

80

100

120

% C

overa

ge

Measles

OPV 3

OPV 4

DPT 3

HBV 3

Hib 3

MMR

Diphtheria

outline

Importance of vaccines and vaccinations Basics of vaccination. General principles Routine vaccines in Jordan Recently introduced vaccines world wide Important vaccine information sources

6

Basics of vaccination

Active versus passive immunization Live versus killed vaccines Component vaccines, protein versus

polysacharide General rules about minimum age at

vaccination General rules about concommitent use of

vaccines General rules about vaccine interruption General rules about different vaccine schedules

7

Principles of Vaccination

Active Immunity = Antigen long duration, maybe lifelong

Passive Immunity = Antibody limited public health impact, immune compromised hosts, limited duration

Types of vaccine antigens9

Live attenuated organisms Viral Bacterial Recently parasitic (Malaria)

Inactivated Whole organisms

Viral bacterial

Fractional Protein Polysaccharides Conjugate polysacharide vaccines

Inactivated vaccines general principles

Inactivated whole organism and fractional vaccines

Safe in immune compromised hosts and pregnancy

Protein, better antigens, TH2 response, effective before age two yearsPolysacharide vaccines, Not effective

before 2 years of age, TH1 responseIn general inactivated by freezingUsually do not interfere with each otherNeed for booster doses to maintain immunity

10

Polysaccharide versus conjugate vaccines

Polysaccharide Vaccines: T-cell independent Not effective in children

under 2 years and in the immunocompromised

Result in a primarily IgM response

Do not induce immunological memory and hence cannot be boosted

Do not reduce mucosal carriage of pneumococcus1

Pneumococcal Conjugate Vaccines1:

T-cell dependent Induce an effective immune

response in infants Stimulate an initial

response involving both IgM and IgG while subsequent doses stimulate a primarily IgG response

Induce immunological memory and can be boosted

1Eskola J. PIDJ 2000. 19 (4): 388-93.

Live vaccines general considerationsLive vaccines can be frozen

induce longer lasting immunitySHOULD NOT be given to immune compromised and to pregnant womenmaternal antibody may neutralize the

vaccine and make it less effective in early life

12

Common Live vaccines

BCG OPV MMR Rotavirus Chickenpox Intranasal influenza vaccine Live typhoid vaccines

13

Killed or fractional vaccines IPV Hepatitis a

vaccine

DTP DTaP IPV HB HIB Pneumoccal vaccine Meningococcal vaccines Injectable influenza HPV

14

Vaccines in use for children in Jordan and worldwide

Vaccines in use in Jordan

Diptheria Tetanus Pertussis Polio both IPV and

OPV Measles, Mumps Rubella Hemophilus

influenza b Hepatitis b BCG

Vaccines not yet introduced in Jordan

Chickenpox Pneumococcus ( recent

donation) Chickenpox/VZV

vaccine Rotavirus Hepatitis a Influenza vaccine Acellular pertussis

vaccine for adolescents and adults

Meningococcal vaccine HPV vaccine

15

History of Expanded program on

Immunization (EPI) – Jordan 16

1979 National Program on Immunization was established Diphtheria, Pertussis, Tetanus, Polio, BCG 1982 First dose Measles 1982 Tetanus toxoid for women in child bearing age 1993 4th dose of polio 1995 Hepatitis “B” and second dose Measles 2000 MMR replaced 2nd dose of Measles 2001 HIB introduced 2003 IPV first dose instead of OPV 2006 IPV second dose Plus OPV

Vaccination scheduleJordan 2008 17

Age Vaccine

1st contact2 months23 months4 months9 months18 Months

BCGDTP + HepB1 +Hib1 + IPV

DTP+HepB2+Hib2+ IPV,OPV

DTP+HepB3+Hib3 + OPVMeasles + OPVMMR +DTP booster1+OPV booster1

1st & 10th class Td (OPV for 1st class)

Vaccination to school age children 18

1st elementary class Td +OPV booster2

Validation of measles and MMR

10th class Td

Second dose of MMR

Vaccine to be discussed

Diphtheria Tetanus Pertussis Polio Measles Mumps Rubella HIB

HB Hep A Chickenpox Pneumococcal Rotavirus HPV Influenza

19

Diphtheria20

Greek diphtheria (leather hide)

Gram positive rod, a human pathogen that is transmitted by droplets, both asymptomatic and symptomatic individuals may transmit infection

There are four biotypes mitis, intermedius,

belfanti, and gravis). All biotypes of C diphtheriae may be either toxigenic or nontoxigenic.

Diphtheria is caused by toxigenic

strains of Corynebacterium

diphtheriae.

Epidemiology of diphtheria

Only human pathogen Can be carried in the nasopharynx Bacteriophage induces toxin production Transmitted by droplet Vaccinated individuals can carry the

organism but do not get sick

21

Diphtheria pathogenesis

Toxigenic strains express an exotoxin that consists of an enzymatically active A domain and a binding B domain, which promotes the entry of A into the

cell. The toxin gene, tox, is carried by a family of

related corynebacteria bacteriophages. The toxin inhibits protein synthesis in all cells,

including myocardial, renal, and peripheral nerve

cells, resulting in myocarditis, acute tubular necrosis, and delayed peripheral nerve conduction. Nontoxigenic strains of C diphtheriae can cause sore throat and other invasive infections.

22

Diptheria clinical considerations Usually sick looking and tonsils have a membrane

which is grayish and difficult to remove Membrane may involve more than the tonsils Toxin production most important and initially may

have difficulty in breathing Arrhythmia with cardiac toxicity occurs in the

second week Most common cause of death is cardiac toxicity Neurologic complications occur after three to four

weeks Antitoxin should be given before four days

23

Diphtheria vaccine, toxin only 24

Formalin-inactivated diphtheria toxin Protein antigen Must administer by deep IM Do not freeze Efficacy Approximately 95% Duration Approximately 10 years Amount of antigen higher in children Should be administered with tetanus toxoid

as DTP. DTaP, DT, Td, or Tdap

DTP, DTaP, DT, and Td25

DTP,DTaP, DT

Td, Tdap (adult)

Diphtheria7-8 Lf units

2-2.5 Lf units

Tetanus5-12.5 Lf units

5 Lf units

DTP, DTaP and pediatric DT used through age 6 years. Adult Td for persons 7 years and older. Tdap for persons 10-18 years (Boostrix) or 11-64 years (Adacel)

Diphtheria vaccine, schedule, same as Tetanus and pertussis

Three doses before the age of one year starting at the age of 2 months

Each to be given one to two months apart

Repeat booster dose at 18 months Repeat booster dose at 4-6 years Every ten years thereafter Give only small d after the age of 6

years of life

26

Diphtheria and Tetanus ToxoidsAdverse Reactions and contraindications27

Reactions Local reactions (erythema, induration) Exaggerated local reactions (Arthus-

type) Fever and systemic symptoms not

commonContraindications Severe allergic reaction to vaccine

component or following a prior dose Moderate or severe acute illness

Tetanus28

First described by Hippocrates Cl tetani Anaerobic gram-positive, spore-

forming bacteria, Spores found in the environment, soil, animal feces; may persist for months to years

Multiple toxins produced with growth of bacteria

Tetanospasmin estimated human lethal dose = 2.5 ng/kg

It is not contagious to others Clostridium tetani is present in the

environment

Pathogenesis of tetanus

Anaerobic conditions allow germination of spores but there is little inflammation at the site of infection

The vegetative form of C tetani produces a potent plasmid-encoded exotoxin (tetanospasmin)

This binds to gangliosides at the myoneural junction of skeletal muscle and on neuronal membranes in the spinal cord, blocking inhibitory impulses to motor neurons.

This Leads to unopposed muscle contraction and spasm. The movements mimic seizures

29

Tetanus Clinical Features30

Incubation period; 8 days (range, 3-21 days)

The shorter the incubation period the more severe is the disease

Three clinical forms: local (uncommon), cephalic (rare), generalized (most common)

Generalized tetanus: descending symptoms of trismus (lockjaw), difficulty swallowing, muscle rigidity, spasms

Spasms continue for 3-4 weeks; complete recovery may take months

In the newborn only generalized tetanus occurs

Maternal vaccination during pregnancy provides maternal antibodies that cross the placenta and help provide antitoxin antibodies to the new born infant

Tetanus Complications31

The disease lasts for weeks Must be treated with antitoxin and

antibiotics but contractions continue LaryngospasmFractures Hypertension Nosocomial infections Pulmonary embolism, Aspiration

pneumonia In the newborn often times the infants

become malnourished and wasted

Tetanus vaccine (Tetanus Toxoid)32

Formalin-inactivated tetanus toxin , Protein antigen

Schedule Initially Three or four doses + boosterBooster every 10 years

Efficacy Approximately 100%

Duration Approximately 10 years

Vaccine content same for children and adults

Preferable administered with diphtheria toxoid as DTP, DTaP, DT, Td, or Tdap

post exposure wound prophylaxisTetanus Wound Management33

Vaccination History

Unknown or <3 doses

3+ doses

Td TIG

Yes No

No* No

Td TIG

Yes Yes

No** No

Clean, minorwounds

All otherwounds

* Yes, if >10 years since last dose** Yes, if >5 years since last dose

Dose of TIG is 250 units regardless of age and weight

Pertussis34

Highly contagious respiratory infection caused by Bordetella pertussis a fastidious gram negative bacterium, only humans

Outbreaks first described in 16th century Bordetella pertussis isolated in 1906 Estimated 285,000 deaths worldwide

in 2001 Recently increased in some parts Transmission Respiratory droplets Communicability Maximum in catarrhal stage

Secondary attack rateup to 80%

Pertussis Pathogenesis35

Attachment to cilia in respiratory tract leading to Local tissue damage in respiratory tract, Systemic disease may be toxin mediated, no bacteremia

Antigenic and biologically active components: pertussis toxin (PT) filamentous hemagglutinin (FHA) agglutinogens adenylate cyclase pertactin tracheal cytotoxin

NO Bacteremia

Pertussis Clinical Features36

Incubation period 7-10 days (range 4-21 days) Catarrhal stage 1-2 weeks Paroxysmal

cough stage 1-6 weeks Convalescence Weeks to months

Fever usually minimal throughout course of illness unless complicated by superinfection

In adults and older children Infection may be asymptomatic, or may present as classic pertussis, these serve as sources of infection to children

Pertussis Complications*37

ConditionPneumoniaSeizuresEncephalopathyHospitalizationDeath

Percent reported5.20.80.1200.2

*Cases reported to CDC 1997-2000 (N=28,187)

Pertussis Complications by Age

0

10

20

30

40

50

60

70

<6 m 6-11 m 1-4 y 5-9 y 10-19 y 20+ y

Age group

Pe

rce

nt

Pneumonia Hospitalization38

*Cases reported to CDC 1997-2000 (N=28,187)

Pertussis vaccines

Both are inactivated vaccines Whole cell (WC) or acellular pertussis (aP) WC contraindicated after 6 years of age Immunity decreases with time and hence

re vaccination in older individuals is needed but with acellular smaller doses only

ONLY acellular P are allowed for use in adolescents and older individuals

39

Whole-Cell Pertussis Vaccine

40 Developed in mid-1930s and combined as DTP in mid-1940s

70%-90% efficacy after 3 doses

Protection for 5-10 years Fever 40% Local reactions 35% Seizures 1/1750 HHE 1/1750 Encephalopathy 1/110,000

Acellular Pertussis Vaccines41

Local reactions (pain, redness, or swelling at the site of injection)

Local reactions more common following 4th and 5th doses

Reports of swelling of entire limb

Extensive swelling after 4th dose NOT a contraindication to 5th dose

Low-grade fever

Composition* of Acellular Pertussis Vaccines42

Product

Daptacel

Infanrix

Tripedia

Boostrix

Adacel

PT

10

25

23

8

2.5

PERT

3

8

--

2.5

3

FHA

5

25

23

8

5

*mcg per dose

FIM

5

--

--

--

5

DTP/DTaP Contraindications43

Severe allergic reaction to vaccine component or following a prior dose

Encephalopathy not due to another identifiable cause occurring within 7 days after vaccination

Progressive CNS disease

DTP/DTaP Precautions*44

Moderate or severe acute illness

Temperature >105°F (40.5°C) or higher within 48 hours with no other identifiable cause

Collapse or shock-like state (hypotonic hyporesponsive episode) within 48 hours

Persistent, inconsolable crying lasting >3 hours, occurring within 48 hours

Convulsions with or without fever occurring within 3 days

*may consider use in outbreaks

Poliomyelitis45

First described by Michael Underwood in 1789 Enterovirus, Strict human pathogen Three serotypes: 1, 2, 3 Minimal heterotypic immunity between serotypes Rapidly inactivated by heat, formaldehyde,

chlorine, ultraviolet light Entry into mouth/ Replication in pharynx, GI tract,

local lymphatics Hematologic spread to lymphatics and central

nervous system/Viral spread along nerve fibers Destruction of anterior horn cell (motor neurons)

with resultant paralysis

46

Outcomes of poliovirus infection

0 20 40 60 80 100

Percent

Asymptomatic Minor non-CNS illness Aseptic menigitis Paralytic

47 140

120

100

80

60

40

20

01978 1979 1980 1981 1982 1983 1984 1985 1988 1989 1990 1991 1992 1993

Years

No.

of

Cas

es

POLIOMYELITIS IN JORDAN1978-2001

1994 2001

Khuri-Bulos (bull WHO 1984)

History of Poliovirus Vaccine48

1955 Inactivated vaccine

1961 Types 1 and 2 monovalent OPV

1962 Type 3 monovalent OPV

1963 Trivalent OPV

1987 Enhanced-potency IPV (IPV)

Oral Polio Vaccine (Sabin)49

Types 1,2,3 live vaccine Shed in stool for up to 6 weeks Shed for prolonged periods in

immunecompromised individuals Highly effective in producing immunity to

poliovirus 50% immune after 1 dose >95% immune after 3 doses Immunity probably lifelong Immunity less in developing countries?? Other

enteroviruses interfere with immunity Induces both local and systemic immunity

Inactivated Polio Vaccine50

Contains 3 serotypes of vaccine virus Grown on monkey kidney (Vero) cells Inactivated with formaldehyde Highly effective in producing immunity to

poliovirus >90% immune after 2 doses >99% immune after 3 doses Duration of immunity not known with certainty Does not induce high local intestinal immunity

and allows for replication in the gut Immune individuals can transmit the virus to

others but are themselves immune and not sick

Polio Vaccine Adverse Reactions51

Rare local reactions (IPV) No serious reactions to IPV have been

documented Vaccine associated Paralytic

poliomyelitis VAPP ONLY with OPV More likely with the first dose(80%) Rate is 2.5 million dose Increased risk in persons >18 years Increased risk in persons with

immunodeficiency Most cases in healthy children and their

household contacts

Polio VaccineContraindications and Precautions

52

Immune suppression Pregnancy prednisone in excess of 2 mg/kg/day Contacts of immunecompromised

patients Severe allergic reaction to a vaccine

component or following a prior dose of vaccine


Measles53

Highly contagious viral illness, infects humans only

Almost always clinically apparent illness First described in 7th century Paramyxovirus (RNA), one antigenic type Respiratory transmission of virus Persists in the air for one or more hours Near universal infection of childhood in

prevaccination era Death risk increased if acquired <2 yrs

and in malnourished children Communicability 4 days before to 4

days after rash onset

Measles Pathogenesis54

Respiratory transmission of virus Replication in nasopharynx and regional

lymph nodes Primary viremia 2-3 days after exposure Secondary viremia 5-7 days after

exposure with spread to tissues

Measles Clinical Features55

Incubation period 10-12 days Stepwise increase in fever to

103°F or higher The 3 Cs, Cough, coryza,

conjunctivitis Koplik spots on day or 24 hours

before rash These are pathognomonic of measles

Measles Clinical Features56

2-4 days after prodrome, 14 days after exposure

Maculopapular rash, becomes confluent Begins on face and head Persists 5-6 days Fades in order of appearance

Measles57

measles58

Measles Koplic spots59

Measles Complications60

ConditionDiarrheaOtitis mediaPneumoniaEncephalitisHospitalizationDeath

Percent reported876

0.1180.2

Based on 1985-1992 surveillance data

Death rate higher in malnourished and very young children

61

Measles Complications by Age Group

0

5

10

15

20

25

30

<5 5-19 20+

Age group (yrs)

Pe

rce

nt

Pneumonia Hospitalization

Measles Vaccines62

1963 Live attenuated and killed vaccines

1965 Live further attenuated vaccine

1967 Killed vaccine withdrawn

1968 Live further attenuated vaccine

(Edmonston-Enders strain)

1971 Licensure of combined measles-

mumps-rubella vaccine

1989 Two dose schedule

2005 Licensure of MMRV

Measles Vaccine63

Composition Live virus Efficacy 95% (range, 90%-98%) Duration of

Immunity Lifelong Schedule 2 doses Should be administered with mumps and rubella as

MMR to All infants >12 months of age Susceptible adolescents and adults without

documented evidence of immunity should also receive the vaccine

MMR Adverse Reactions64

Fever 5%-15% Rash 5% Joint symptoms 25% Thrombocytopenia <1/30,000 doses

Parotitis rare Deafness rare Encephalopathy <1/1,000,000 doses

MMR VaccineContraindications and Precautions

65

Severe allergic reaction Pregnancy Immunosuppression Moderate or severe acute illness Studies have demonstrated safety of

MMR in egg allergic children even though it is grown in chick embryo

Vaccinate without testing, but with observation

Mumps66

Acute viral illness, caused by mumps virus, a parmyxovirus, an RNA virus one serotype

Parotitis and orchitis described by Hippocrates in 5th century BCE

Viral etiology described by Johnson and Goodpasture in 1934

Frequent cause of outbreaks among military personnel in prevaccine era

Mumps Epidemiology67

Reservoir Human Asymptomatic infections

may transmit Transmission Respiratory drop nuclei

Temporal pattern Peak in late winter and spring Communicability Three days before to four days

after Respiratory transmission of virus Replication in nasopharynx and regional lymph nodes Viremia 12-25 days after exposure with spread to

tissues Multiple tissues infected during viremia

Mumps Clinical Features68

Incubation period 14-18 days Nonspecific prodrome of myalgia,

malaise, headache, low-grade fever Parotitis in 30%-40% Up to 20% of infections asymptomatic

Mumps Complications69

CNS involvementAseptic meningitis

Orchitis

Pancreatitis

Deafness

Death

15% of clinical cases

20%-50% in post- pubertal males

2%-5%

1/20,000

Average 1 per year (1980 – 1999)

Mumps Vaccine70 Composition Live virus (Jeryl Lynn strain

Efficacy 95% (Range, 90%-97%) Duration of

Immunity Lifelong Schedule 2 doses after the age of one

year Should be administered with measles and

rubellaAll infants >12 months of age including susceptible adolescents and adults

Contraindicated in pregnancy and immunocompromise

71

Rubella

Rubella72

From Latin meaning "little red TogavirusRNA virus/one antigenic typeRapidly inactivated by chemical agents, ultraviolet light, low pH, and heatRespiratory transmission of virus

Human infection only /transmitted by droplet, respiratory Replication in nasopharynx and regional lymph nodes Viremia 5-7 days after exposure with spread to tissues Placenta and fetus infected during viremiaOnly primary infection leads to viremia and congenital

infectionInfection may be symptomatic which makes it mandatory

that all mothers who are exposed should be tested. Best is prevention

Rubella Clinical Features/complications Incubation period 14 days (range 12-23 days) Prodrome of low-grade fever Maculopapular rash 14-17 days after exposure Lymphadenopathy in second week Complications include arthralgia and arthritis in

older females Thrombocytopenia Major complication is that of infection of the fetus This occurs only with primary infection This occurs in early pregnancy less than 16

weeks

73

rubella74

Congenital rubella

catarract Rash of rubella

76

Congenital Rubella Syndrome

77

Occurs only with primary maternal infection and mainly in the first trimester 85% of fetuses

Infection may affect all organs. May lead to fetal death or premature delivery

Deafness Cataracts Heart defects Microcephaly Mental retardation Bone alterations Liver and spleen damage

Severity of damage to fetus depends on gestational age

Rubella Vaccine78

Composition Live virus (RA 27/3 strain)

Efficacy 95% (Range, 90%-97%) Duration ofImmunity Lifelong Schedule >1 Dose Acute arthralgia in about 25% of susceptable

adult women, Acute arthritis-like signs and symptoms occurs in about 10%

Rare reports of chronic or persistent symptoms Population-based studies have not confirmed

association

MMR VaccineContraindications and Precautions

79

Severe allergic reaction to vaccine component or following a prior dose

Pregnancy Immunosuppression Moderate or severe acute illness Recent blood product

Haemophilus influenzae80

Aerobic gram-negativecoccobacillus Transmitted from the NP of humans only Polysaccharide capsule determines serotype

and virulence, antibody to this is protective Six different serotypes (a-f) of polysaccharide

capsule,95% of invasive disease caused by type b

Organism colonizes nasopharynx only about 4% Invasion of the blood stream leads to invasive

disease, Antecedent upper respiratory tract infection may be a contributing factor

81

HIB

82

Haemophilus influenzae type b, 1986Incidence* by Age Group

0

20

40

60

80

100

120

140

160

180

200

0-1 12-13 24-25 36-37 48-49 60

Age group (mos)

Inci

den

ce

*Rate per 100,000 population, prevaccine era

83

Haemophilus influenzae type bClinical Features*

Cellulitis6%

Arthritis8% Bacteremia

2%

Meningitis50%

Epiglottitis17%

Pneumonia15%

Osteomyelitis2%

*prevaccination era

85

HIB

86

HIB

Haemophilus influenzae type b Meningitis

87

Accounted for approximately 50%-65% of cases in the prevaccine era

Hearing impairment or neurologic sequelae in 15%-30%

Case-fatality rate 2%-5% despite of effective antimicrobial therapy

Vaccine use almost eradicated the infection Vaccine use also protected the uninfected

by decreasing the nasopharyngeal carraige

Haemophilus influenzae type b Conjugate Vaccines

88

Active ingredient made from polysacharide capsule

Polysacharide Not effective before age of two years.

Must conjugate with a protein to make effective Indicated after age of 6 weeks, NEVER before Give three doses one to two months apart Not indicated after age of 5 years unless

immunecompromised Three types of vaccines available all are

effective

89

Vaccine 2 mo 4 mo 6 mo 12-18 mo

HbOC x x x x

PRP-T x x x x

PRP-OMP x x x

Haemophilus influenzae type b VaccineRoutine Schedule

90

Swelling, redness, or pain in 5%-30% of recipients

Systemic reactions infrequent Serious adverse reactions rareDo not give if Severe allergic reaction to vaccine

component or following a prior dose Moderate or severe acute illness Age <6 weeks

Haemophilus influenzae type b Vaccine Adverse Reactions

91

AA““Infectious”Infectious”

““Serum”Serum”

Viral Viral hepatitishepatitis

EntericallyEntericallytransmittedtransmitted

ParenterallyParenterallytransmittedtransmitted

otherother

EE

““NANB”NANB”

BB DD

CC

Viral Hepatitis – Historical Perspective

Hepatitis vaccines

Hepatitis a Hepatitis b

No vaccines for the other viruses

C,D,E

92

93

Hepatitis Cannot distinguishOn clinical groundsalone

94

Viral Hepatitis Overview

Source ofvirus

Route oftransmission

Chronicinfection

Prevention

modification

feces blood/blood-derived

body fluids

blood/blood-derived

body fluids

blood/blood-derived

body fluids

feces

fecal-oral percutaneouspermucosal

percutaneouspermucosal

percutaneouspermucosal

fecal-oral

no yes yes yes no

pre-exposure

immunization

pre/post-exposure

immunization

blood donorscreening;

risk behaviormodification

pre/post-exposure

immunization;risk behavior

ensure safedrinking

water

Types of Viral Hepatitis

A B C D E

Outcome of HBV Infection95

Infection

AsymptomaticSymptomatic

acute hepatitis B

ResolvedImmune

Chronic infection

AsymptomaticCirrhosis

Liver cancer

ResolvedImmune

Chronic infection

AsymptomaticCirrhosis

Liver cancer

96

HBsAg

HBcAg

HBeAg

Hepatitis B Virus

Hepatitis B Virus97

Hepadnaviridae family (DNA) Numerous antigenic components Humans are only known host May retain infectivity for at least 1 month at

room temperature Stable in the enviroment and can infect if

microabrasions in the skin Contagious also by intimate contact and

exposure to blood and all body secretions that may be contaminted with blood

Hepatitis B Clinical Features98

Incubation period 60-150 days (average 90 days)

Nonspecific prodrome of malaise, fever, headache, myalgia

Illness not specific for hepatitis B At least 50% of infections asymptomatic

Global Patterns of Chronic HBV Infection

99

High (>8%): 45% of global population lifetime risk of infection >60% early childhood infections common

Intermediate (2%-7%): 43% of global population lifetime risk of infection 20%-60% infections occur in all age groups

Low (<2%): 12% of global population lifetime risk of infection <20% most infections occur in adult risk groups

Hepatitis B Complications100

Fulminant hepatitis Hospitalization Cirrhosis Hepatocellular carcinoma Death

101

• Incubation period: Average 60-90 days Range 45-180 days

• Clinical illness <5 yrs, <10%(jaundice): >5 yrs, 30%-50%

• Acute case-fatality rate: 0.5%-1%

• Chronic infection: <5 yrs, 30%-90% >5 yrs, 2%-10%

• Premature mortality fromchronic liver disease: 15%-25%

Hepatitis B – Clinical Features

Hepatitis B Epidemiology102

Reservoir Human

Transmission Bloodborne Subclinical cases

can also transmit infection

Communicability 1-2 months beforeand after onset ofsymptoms

Chronic carriers major source of infection Assume in health care setting that ALL patients

may be contagious

Hepatitis B Perinatal Transmission*

103

If mother positive for HBsAg and HBeAg 70%-90% of infants infected 90% of infected infants become chronically

infected If positive for HBsAg only

5%-20% of infants infected 90% of infected infants become chronically

infected

*in the absence of postexposure prophylaxis

104

Ch

ron

ic I

nfe

ctio

n (

%)

Sym

pto

matic In

fect ion

(%)

100100

Symptomatic Infection

Chronic Infection

Birt

h

1-6

mos

7-12

mos

1-4

yrs

Old

er

Chi

ldre

nan

d A

dul

ts

0

20

40

60

8080

60

40

20

0

Outcome of Hepatitis B Virus Infectionby Age at Infection

105

Risk of Chronic HBV Carriage by Age of Infection

0

10

20

30

40

50

60

70

80

90

100

Birth 1-6 mo 7-12 mo 1-4 yrs 5+ yrs

Age of infection

Carr

ier

risk (

%)

Hepatitis B Vaccine composed only of Surface antigen

106

1965 Discovery of Australian antigen

1973 Successful HBV infection of chimpanzees

1981 Licensure of plasma-derived vaccine

1986 Licensure of recombinant vaccine

1991 Universal infant vaccination

1996 Universal adolescent vaccination

Hepatitis B Vaccine, surface antigen only

107

Composition Recombinant HBsAg

Efficacy 95% (Range, 80%-100%)

Duration ofImmunity >15 years

Schedule 3 Doses

Booster doses not routinely recommended

Hepatitis B Vaccine Formulations

108

Recombivax HB (Merck) - 5 mcg/0.5 mL (pediatric) - 10 mcg/1 mL (adult) - 40 mcg/1 mL (dialysis)

Engerix-B (GSK) - 10 mcg/0.5 mL (pediatric) - 20 mcg/1 mL (adult)

Protection* by Age Group and Dose109

Dose Infants** Teens and Adults***

1 16%-40% 20%-30%

2 80%-95% 75%-80%

3 98%-100% 90%-95%

* Anti-HBs antibody titer of 10 mIU/mL or higher

** Preterm infants less than 2 kg have been shown to respond to vaccination less often

*** Factors that may lower vaccine response rates are age >40 years, male gender, smoking, obesity, and immune deficiency

110

Recommended Dose of Hepatitis B Vaccine

Infants and children<11 years of age

Adolescents 11-19 years

Adults >20 years

Recombivax HB

Dose (mcg)0.5 mL (5)

0.5 mL (5)

1.0 mL (10)

Engerix-B

Dose (mcg)0.5 mL (10)

0.5 mL (10)

1.0 mL (20)

Hepatitis B VaccineLong-term Efficacy

111

Immunologic memory established following vaccination

Exposure to HBV results in anamnestic anti-HBs response

Chronic infection rarely documented among vaccine responders

112

Hepatitis B Vaccine

Routine booster doses are NOT routinely recommended for any group

113

Dose+

Primary 1Primary 2Primary 3

Usual Age

Birth 1- 2 months6-18 months*

MinimumInterval

- - - 4 weeks 8 weeks**

Hepatitis B VaccineRoutine Infant Schedule

* infants who mothers are HBsAg+ or whose HBsAg status is unknown should receive the third dose at 6 months of age** at least 16 weeks after the first dose+an additional dose at 4 months is acceptable if the clinician prefers to use a combination vaccine that contains hepatitis B vaccine

Preterm Infants114

Birth dose and HBIG if mother HBsAg positive

Preterm infants <2,000 grams have a decreased response to vaccine administered before 1 month of age

Delay first dose until chronologic age 1 month if mother HBsAg negative

Prevention of Perinatal Hepatitis B Virus Infection

115

Begin treatment within 12 hours of birth

Hepatitis B vaccine (first dose) and HBIG at different sites

Complete vaccination series at 6 months of age

Test for response at 9-18 months of age

Hepatitis B VaccineAdverse Reactions

116

Pain at injection site

Mild systemic complaints(fatigue, headache)

Temperature ≤99.9°F (37.7°C)

Severe systemic reactions

Adults13%-29%

11%-17%

1%

rare

Infants and Children3%-9%

0%-20%

0.4%-6%

rare

Hepatitis B VaccineContraindications and Precautions117

Severe allergic reaction to a vaccine component or following a prior dose


The pneumococcus and the vaccine The pneumococcus Diseases caused by the pneumococcus and the

global disease burden Immune response to pneumococcus Types of pneumococcal vaccines Pneumococcal conjugate vaccine Importance of serotype and moving forward with

the decision to include the vaccine in the Jordan EPI

Streptococcus pneumoniae

Gram positive diplococci Many serotypes (90) Serotypes depend on polysaccharide capsule Serotypes define invasiveness and protective

antibody Acquired by close contact with humans Invasive disease more common in early childhood

and in certain high risk individuals Immunity mainly serotype specific Major impact on child health

119

120

Pneumococcal disease burden in childhood

Otitis media

Pneumonia

Bacteremia

Meningitis

Dis

ease

sev

erit

y

For each case of pneumococcal meningitis in a year:

X 1000 to 10,000

X 100 to 1000

X 10

Prevalen

ce

Invasive

Non-invasive

IPD

Adapted from Abramson JS et al., Pediatrics, 2000,; 106(2):362-6

Pneumonia is the Leading Killer of Children Worldwide

WHO, Pneumonia: The Forgotten Killer of Children, 2006

Bryce J et al. WHO estimates of the causes of death in children. Lancet, 2005; 365: 1147–52

Proportion of childhood deaths due to pneumonia by WHO region

Proportion of childhood deaths due to pneumonia by WHO region

Bryce J, et al. Lancet 2005; 265: 1147-52.

Vaccine-preventable Deaths in Children <5 Years of Age, Globally

The WHO estimates that Streptococcus pneumoniae (SP) causes >1.6 million deaths/yr

800,000 are in children <5 yrs Pneumonia is the leading cause of

pneumococcal deaths worldwide Of all causes of bacterial

meningitis, SP has the highest case fatality rate

Rotavirus causes approximately 400,000 death/yr in those <5 yrs

HPV is a vaccine-preventable cause of deaths in adults, estimated to be 260,000 deaths annually worldwide

Bilous J. Lancet. 2006;367:1464-1465.WHO Global Immunization Vision and Strategy, April 2005www.who.int/vaccines/GIVS/english/Global_imm._data_EN.pdf.www.who.int/reproductive-health/publications/hpvvaccines_techinfo/index.html.

Rotavirus

16%

N. meningitidis

<1%

S. pneumoniae

28%

Measles

21%

Hib

15%

Pertussis

12%Tetanus

8%SP is the most common cause of vaccine-preventable deaths worldwide

WHO. 2004 Global Immunization Data. Available at: http://www.who.int/immunization_monitoring/data/GlobalImmunizationData.pdf. Accessed July 11, 2008.

Pneumococcal disease

Measles Rotavirus Hib Pertussis Tetanus Other* Meningococcus

*Polio, diphtheria, yellow fever

Est

imat

ed n

um

ber

of

dea

ths

(WH

O 2

002)

Global PerspectiveVaccine-preventable Deaths (WHO)

Streptococcus pneumoniae is the leading cause of vaccine-preventable deaths globally

Antibodies to the polysaccharide capsule produce serotype-specific host immunity

Some cross-reactivity of anti-polysaccharide capsule antibodies within serogroups

Antibodies to certain pneumococcal proteins also appear to be protective and effective against a wide array of serotypes in animal models

Antibody response to the Pneumococcus

Three types of inactivated pneumococcal vaccine

Polysaccharide vaccines: long chains of sugars taken from the capsule of various pneumococcal serotypes

Pneumococcal conjugate vaccines (PCV): the serotype-specific capsular polysaccharide is linked with a carrier protein

Protein vaccines: use bacterial proteins to evoke an immune response and may be effective over a wide array of pneumococcal serotypes

USAID. Immunization Essentials: A Practical Field Guide. 2003.WHO. State of the Art of New Vaccines: Research and Development. 2006.

Polysaccharide versus conjugate vaccines

Polysaccharide Vaccines: T-cell independent Not effective in children

under 2 years and in the immunocompromised

Result in a primarily IgM response

Do not induce immunological memory and hence cannot be boosted

Do not reduce mucosal carriage of pneumococcus1

Pneumococcal Conjugate Vaccines1:

T-cell dependent Induce an effective immune

response in infants Stimulate an initial

response involving both IgM and IgG while subsequent doses stimulate a primarily IgG response

Induce immunological memory and can be boosted

1Eskola J. PIDJ 2000. 19 (4): 388-93.

Distribution of Pneumococcal Serotypes by Frequency:Children <2 years, USA (1999)

7-valent PCV serotypes

Non- vaccine serotypes

PCV-7 serotypes account for most disease in young US children

Distribution of Serotypes by Penicillin Resistance: Children <2 years, USA (1999)

7-valent PCV serotypes

Non- vaccine serotypes

PCV-7 serotypes account for most antibiotic resistance in young US children

PCV-7 has dramatically reduced vaccine-type IPD in US children

Adapted from Black S, Shinefield H, et al. PIDJ 2004; 23(6): 485-9.

>98% reduction

in VT IPD cases

Inci

dence

(ca

ses/

10

0,0

00

p-y

)

Hicks LA et al, (CDC) The Journal of Infectious Diseases (Nov 1) 2007;196:1346-1354

Rates of invasive pneumococcal disease among children aged <5 years (A) and adults aged > 65 years (B), by serotype and year. The 7-valent pneumococcal conjugate vaccine (PCV7) includes serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F

PCV has an indirect effect on reducing IPD in the community as a whole

The indirect effect of PCV provides protection against pneumococcal disease even among unimmunized individuals

Lower NP colonization of vaccine serotypes in immunized children decreases transmission to others in the community

This type of immunity is also known as herd immunity

O’Brien KL, Dagan R. Vaccine 2003; 21: 1815-25.Hammitt LL, Bruden DL, et al. JID 2006; 193: 1487-94.

PCV Impact: Key Points

Less IPD in all age groups in US due to herd immunity

Less antibiotic-resistant pneumococcal disease in US

Reduces nasopharyngeal (NP) colonization with vaccine serotypes

In US, disease prevented by PCV use outweighs small increase in non-vaccine type IPD

What about pneumococcal vaccine for our region??

134

• There are over 90 strains (or serotypes) of the pneumococcal bacterium. • The distribution of disease –causing

pneumococcal serotypes affecting children varies geographically.

• Seven pneumococcal serotypes are common to all regions and comprise 58-66% of invasive childhood pneumococcal disease in every region of the world8*

•Seven common serotypes are: 1, 5, 6A, 6B, 14, 19F, 23F

Source: 8. Johnson HL, Deloria-Knoll M, Levine OS, et al: Pneumococcal global serotype project. Submitted 12/09.

Information courtesy of the International Vaccine Access Center (IVAC)

Source: 9. PneumoADIP. Pneumococcal Regional Serotype Distribution for Pneumococcal TPP (2008).


Includes the Middle East

7-valent (PCV7): 4, 6B, 9V, 14, 18C, 19F, and 23F

10-valent (PCV10):7-valent serotypes + 1, 5, 7F

13-valent (PCV13):10-valent serotypes + 3, 6A, 19A


Serotypes included in PCV formulations

Formulation 1 3 4 5 6A 6B 7F 9V 14 18C 19A 19F 23F

PCV-7

PCV-9

PCV-10

PCV-11

PCV-13

Serotype included in the vaccine

Serotype eliciting cross-protection

143

Rationale for inclusion of additional serotypes in PCV13

1

•Cause of epidemic disease•Important cause of pneumococcal pneumonia; predominant serotype in empyema in children •Important cause of pneumococcal disease in many regions

3

•Important cause of pneumococcal disease including pneumonia and AOM•Among the leading serotypes in CAP and IPD in adults•Increasingly reported in IPD in Europe

5 •Cause epidemic disease•Among the leading serotypes in Africa and South America

6A

•Important cause of pneumococcal disease, particularly AOM •Commonly found in carriage and frequently antibiotic resistant•Decrease in 6A pediatric IPD following use of PCV7, remaining disease may be mostly 6C

7F•Cause epidemic disease•Important cause of pneumococcal disease globally, increasing in many European countries

19A

•Significantly increased in IPD globally•Commonly found in AOM•Commonly found in carriage and frequently antibiotic resistant•19F antibodies from PCV7 vaccination do not cross-protect for 19A infection

Dagan et al. J Infect Dis 2008;197(8):1094-102. Dagan et al. Clin Infect Dis 2000;30(2):319-21. Brueggemann et al. Journal of Clinical Microbiology 2003;41(11):4966-70, Gratten Med J Aust 1993;158(5):340-2, Nunes et al. Clin Microbiol Infect 2008;14(1):82-4, Romney et al. Clin Infect Dis 2008;47(6):768-74, Ruckinger et al. Pediatr Infect Dis J 2009;28(2):118-22, Whitney et al. Lancet 2006;368(9546):1495-502, Dagan & Klugman Lancet Infect Dis, 8(12), 785-795 (2008), Byington et al. Pediatr Infect Dis J, 25(3), 250-254 (2006), Fletcher et al. Pediatr Infect Dis J, 25(6), 559-560 (2006), Cohen et al. Vaccine, (2009) in press, Hausdorff WP, Vaccine, 25(13), 2406-2412 (2007), Imohl et alClin Microbiol Infect, (2009), in press)

Global IPD serotype distribution among children <5 years – before pneumococcal conjugate vaccination

*Weighted by regional disease burden

Serotype

Ser

otyp

ed is

olat

es (

%)

Cu

mu

lati

ve d

istr

ibu

tion

(%

)Serotypes by rank order and cumulative serotype distribution

Pneumococcal Global Serotype Project (version 2), 30 November 2008. Prepared by GAVI’s PneumoADIP

Prevenar 13 targets serotypes responsible for most of the IPD burden in children < 5 years of age

0

2

4

6

8

10

12

14 18C 19F 6B 23F 4 9V 5 1 7F 3 19A 6A 9A 11A 22F 28A 29 8 9N 15C 24 15A 10A 42 6C 15 33F 31 UT

Serotypes causing IPD in children less than 5 yrsSerotypes causing IPD in children less than 5 yrs

(n= 49)(n= 49)

71.4 % (71.9% if 6A is included) PCV7

77 % PCV10

86% PCV13

Meningitis

Pneumonia

Bacteremia/Sepsis

Sinusitis

Mastoidiitis

Others

Country 7-V*Lives Saved

per Year 10-VLives Saved

per Year 13-VLives Saved

per Year

Iraq 52.75 1,905 69.7 3,093 73.7 5,451

Jordan 52.75 60 69.7 159 73.7 171

Kuwait 52.75 4 69.7 10 73.7 11

Lebanon 52.75 25 69.7 63 73.7 72

Oman 44.91 10 71.9 30 76.9 32

Qatar 52.75 1 69.7 2 73.7 2

Saudi Arabia 52.75 200 69.7 518 73.7 571

Syrian Arab Republic 52.75 174 69.7 467 73.7 499

United Arab Emirates 52.75 3 69.7 8 73.7 9

Yemen 52.75 1,746 69.7 4,017 73.7 4,998

Information courtesy of the International Vaccine Access Center (IVAC)*Figures are approximate; for more information contact IVAC at

www.jhsphu.edu/ivac

Strains Resistant to Erythromycin

Strains Resistant

to Penicillin

Strains Resistant

to both

PCV7 75% 75% 70%

PCV10 79% 75% 70 %

PCV13 79% 75% 70 %

Prevention of Resistant Strains with Vaccination

Dbaibo

CountryPCV Current Vaccine Use

Status

2008 Birth Cohort

(UNICEF)

# of PCV Doses Needed per

Birth Cohort on a 3 Dose Schedule

Total Pneumococcal Deaths among

Children <5 (2000)*

Pneumococcal Mortality Rate

per 100,000 among

Children <5 (2000)*

% of <5 deaths from Pneumonia

(WHO, 2004)

JordanNo

Decision 157000 471000 257 36 10.5


Proportion of pediatric pneumococcal disease prevented by PCV-13

92%

87%

89%

87%

73%

86%

Assumes cross protection within serogroup 6

Conclusions

The pneumococccus is the leading cause of vaccine preventable disease worldwide

Conjugate pneumococcal vaccines have proved efficacious and safe in infants as young as two months of age

Conjugate vaccines have proved efficacious in preventing invasive pneumococcal infections in both children as well as the elderly due to decrease in the NP carraige rate

Conclusions

Serotype coverage with the recently introduced PCV 13 covers more types that are of importance both in the westernized countries where non vaccine serotypes emerged as well as in developing countries

There is currently enough evidence to suggest that the PCV be seriously considered for introduction into the Jordan EPI.

151

VACCINE PREVENTABLE DISEASES AND VACCINATION

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