Haemophilus influenzae type b

• Severe bacterial infection,particularly among infants

• During late 19th century believed tocause influenza

• Immunology and microbiologyclarified in 1930s

Haemophilus influenzae

• Aerobic gram-negative bacteria

• Polysaccharide capsule

• Six different serotypes (a-f) ofpolysaccharide capsule

• 95% of invasive disease causedby type b

Haemophilus influenzae type bPathogenesis

• Organism colonizes nasopharynx

• In some persons organism invadesbloodstream and cause infection atdistant site

• Antecedent upper respiratory tractinfection may be a contributingfactor

Cellulitis

6%

Arthritis

8% Bacteremia

2%

Meningitis

50%

Epiglottitis

17%

Pneumonia

15%

Osteomyelitis

2%

Haemophilus influenzae type bClinical Features*

*prevaccination era

Haemophilus influenzae type bMeningitis

• Accounted for approximately50%-65% of cases in theprevaccine era

• Hearing impairment or neurologicsequelae in 15%-30%

• Case-fatality rate 2%-5% despite ofeffective antimicrobial therapy

Haemophilus influenzae type bMedical Management

• Hospitalization required

• Treatment with an effective 3rdgeneration cephalosporin, orchloramphenicol plus ampicillin

• Ampicillin-resistant strains nowcommon throughout the UnitedStates

Haemophilus influenzae type bEpidemiology

• Reservoir Human Asymptomatic carriers

• Transmission Respiratory droplets

• Temporal pattern Peaks in Sept-Decand March-May

• Communicability Generally limited buthigher in somecircumstances

0

5

10

15

20

25

1990 1992 1994 1996 1998 2000 2002 2004

Incidence

Incidence*of Invasive HibDisease, 1990-2004

*Rate per 100,000 children <5 years of age

Year

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)

Inc

ide

nc

e

Haemophilus influenzae type b, 1986Incidence* by Age Group

*Rate per 100,000 population, prevaccine era

Haemophilus influenzae typeb—United States, 1996-2000

• Incidence has fallen 99% sinceprevaccine era

• 341 confirmed Hib cases reportedduring 1996-2000 (average of 68cases per year)

•Most recent cases in unvaccinatedor incompletely vaccinatedchildren

Haemophilus influenzae type bRisk Factors for Invasive Disease

• Exposure factors–household crowding–large household size–child care attendance–low socioeconomic status–low parental education–school-aged siblings

• Host factors–race/ethnicity–chronic disease

Polysaccharide ConjugateVaccines

• Stimulates T-dependent immunity

• Enhanced antibody production,especially in young children

• Repeat doses elicit boosterresponse

Haemophilus influenzae type bConjugate Vaccines

• 3 conjugate vaccines licensed foruse in infants as young as 6 weeksof age

• All utilize different carrier proteins

• 2 combination vaccines availablethat contain Hib vaccine

HbOC Hibtiter

PRP-T ActHIB, TriHIBit

PRP-OMP PedvaxHIB, Comvax

Conjugate Hib Vaccines

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 Vaccine

Routine Schedule

Haemophilus influenzae type bVaccine Interchangeability

• All conjugate Hib vaccinesinterchangeable for primary seriesand booster dose

• 3 dose primary series if more thanone brand of vaccine used

Haemophilus influenzae type bVaccine

Use in Older Children and Adults

• Generally not recommended forpersons older than 59 months ofage

• Consider for high-risk persons:asplenia, immunodeficiency, HIVinfection, HSCT

• One pediatric dose of anyconjugate vaccine

• Swelling, redness, or pain in5%-30% of recipients

• Systemic reactions infrequent

• Serious adverse reactions rare

Haemophilus influenzae type bVaccine

Adverse Reactions

Haemophilus influenzae type bVaccine

Contraindications and Precautions

• Severe allergic reaction to vaccinecomponent or following a priordose

•Moderate or severe acute illness

• Age less than 6 weeks

Pneumococcal Disease

• S. pneumoniae first isolated byPasteur in 1881

• Confused with other causes ofpneumonia until discovery of Gramstain in 1884

• More than 80 serotypes describedby 1940

• First U.S. vaccine in 1977

Streptococcus pneumoniae

•Gram-positive bacteria

• 90 known serotypes

• Polysaccharide capsuleimportant virulence factor

• Type-specific antibody isprotective

Pneumococcal DiseaseClinical Syndromes

• Pneumonia

• Bacteremia

•Meningitis

Pneumococcal PneumoniaClinical Features

• Abrupt onset

• Fever

• Shaking chills

• Pleuritic chest pain

• Productive cough

• Dyspnea, tachypnea, hypoxia

Pneumococcal Pneumonia

• Estimated 175,000 hospitalizations peryear in the United States

• Up to 36% of adult community-acquiredpneumonia and 50% of hospital-acquired pneumonia

• Common bacterial complication ofinfluenza and measles

Pneumococcal Bacteremia

•More than 50,000 cases per year inthe United States

• Rates higher among elderly andvery young infants

• Case-fatality rate ~20%; up to 60%among the elderly

Pneumococcal Meningitis

• Estimated 3,000 - 6,000 cases peryear in the United States

• Case-fatality rate ~30%, up to 80%in the elderly

• Neurologic sequelae commonamong survivors

Pneumococcal Disease in Children

• Bacteremia without known site ofinfection most common clinicalpresentation

• S. pneumoniae leading cause ofbacterial meningitis among childrenyounger than 5 years of age

• Highest rate of meningitis amongchildren younger than 1 year of age

• Common cause of acute otitis media

Bacteremia 13,000

Meningitis 700

Death 200

Otitis media 5,000,000

Syndrome Cases

Burden of PneumococcalDisease in Children*

*Prior to routine use of pneumococcal conjugate vaccine

Pneumococcal DiseaseEpidemiology

• Reservoir Human carriers

• Transmission Respiratory

• Temporal pattern Winter and early spring

• Communicability Unknown Probably as long as organism in respiratory secretions

Invasive Pneumococcal DiseaseIncidence by Age Group—1998

0

50

100

150

200

250

<1 1 2 3 4 5-17 18-34 35-49 50-64 65+

Age Group (Yrs)

Ra

te*

*Rate per 100,000 population

Source: Active Bacterial Core surveillance/EIP Network

Children at Increased Risk ofInvasive Pneumococcal Disease

• Functional or anatomic asplenia, especiallysickle cell disease

• HIV infection

• Recipient of cochlear implant

• Out-of-home group child care

• African American children

• Alaska Native and American Indian childrenwho live in Alaska, Arizona, or New Mexico

• Navaho children who live in Colorado andUtah

Pneumococcal DiseaseOutbreaks

• Outbreaks not common

• Generally occur in crowdedenvironments (jails, nursinghomes)

• Persons with invasive diseaseoften have underlying illness

•May have high fatality rate

Pneumococcal Vaccines

1977 14-valent polysaccharide vaccine licensed

1983 23-valent polysaccharide vaccine licensed (PPV23)

2000 7-valent polysaccharide conjugate vaccine licensed (PCV7)

PneumococcalPolysaccharide Vaccine

• Purified capsular polysaccharideantigen from 23 types ofpneumococcus

• Account for 88% of bacteremicpneumococcal disease

• Cross-react with types causingadditional 8% of disease

Pneumococcal ConjugateVaccine

• Pneumococcal polysaccharideconjugated to nontoxicdiphtheria toxin (7 serotypes)

• Vaccine serotypes account for86% of bacteremia and 83% ofmeningitis among childrenyounger than 6 years of age

PneumococcalPolysaccharide Vaccine

• Purified pneumococcalpolysaccharide (23 types)

• Not effective in children youngerthan 2 years

• 60%-70% against invasive disease

• Less effective in preventingpneumococcal pneumonia

Pneumococcal ConjugateVaccine

• Highly immunogenic in infants andyoung children, including those withhigh-risk medical conditions

• 97% effective against invasivedisease caused by vaccine serotypes

• 73% effective against pneumonia

• 7% reduction in all episodes of acuteotitis media

Pneumococcal PolysaccharideVaccine Recommendations

• Adults 65 years of age or older

• Persons 2 years or older with

–chronic illness

–anatomic or functional asplenia

–immunocompromised (disease,chemotherapy, steroids)

–HIV infection

–environments or settings withincreased risk

MMWR 1997;46(RR-8):1-24

Pneumococcal ConjugateVaccine Recommendations

• All children younger than 24months of age

• Unvaccinated children 24-59months with a high-risk medicalcondition

MMWR 2000;49(RR-9):1-35

Pneumococcal ConjugateVaccine Recommendations

• Doses at 2, 4, 6, months of age,booster dose at 12-15 months ofage

• Unvaccinated children >7months of age require fewerdoses

MMWR 2000;49(RR-9):1-35

Pneumococcal ConjugateVaccine

• Children aged 24-59 months athigh risk and previouslyvaccinated with PPV23 shouldreceive 2 doses of PCV7

• Children at high risk whopreviously received PCV7 shouldreceive PPV23 at age 2 years ofage

MMWR 2000;49(RR-9):1-35

Pneumococcal PolysaccharideVaccine Revaccination

• Routine revaccination ofimmunocompetent persons is notrecommended

• Revaccination recommended forpersons age >2 years at highestrisk of serious pneumococcalinfection

• Single revaccination dose >5years after first dose

MMWR 1997;46(RR-8):1-24

Pneumococcal Polysaccharide VaccineCandidates for Revaccination

• Persons >2 years of age with:

–functional or anatomic asplenia

–immunosuppression

–transplant

–chronic renal failure

–nephrotic syndrome

• Persons vaccinated at <65 years ofage

MMWR 1997;46(RR-8):1-24

Pneumococcal VaccinesAdverse Reactions

• Local reactions–polysaccharide 30%-50%

–conjugate 10%-20%

• Fever, myalgia–polysaccharide <1%

–conjugate 15%-24%

• Severe adverse rarereactions

Pneumococcal VaccinesContraindications and Precautions

• Severe allergic reaction to vaccinecomponent or following prior doseof vaccine

•Moderate or severe acute illness

Pneumococcal Polysaccharide VaccineMissed Opportunities

• >65% of patients with severepneumococcal disease had beenhospitalized within preceding 3-5years yet few had received vaccine

•May be administeredsimultaneously with influenzavaccine