Haemophilus influenzae type b

1
Haemophilus influenzae type b

• Severe bacterial infection, particularly among
  infants
• During late 19th century believed to cause
  influenza
• Immunology and microbiology clarified in 1930s

2
Haemophilus influenzae

• Aerobic gram-negative bacteria
• Polysaccharide capsule
• Six different serotypes (a-f) of polysaccharide
  capsule
• 95 of invasive disease caused by type b

3
Haemophilus influenzae type bPathogenesis

• Organism colonizes nasopharynx
• In some persons organism invades bloodstream and
  cause infection at distant site
• Antecedent upper respiratory tract infection may
  be a contributing factor

4

• Haemophilus influenzae type b
• Clinical Features

prevaccination era
5
Haemophilus influenzae type b Meningitis

• 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

6
Haemophilus influenzae type b Medical Management

• Hospitalization required
• Treatment with an effective 3rd generation
  cephalosporin, or chloramphenicol plus ampicillin
• Ampicillin-resistant strains now common
  throughout the United States

7
Haemophilus influenzae type b Epidemiology

• Reservoir Human Asymptomatic carriers
• Transmission Respiratory droplets
• Temporal pattern Peaks in Sept-Dec and
  March-May
• Communicability Generally limited but higher
  in some circumstances

8

• Incidenceof Invasive Hib Disease, 1990-2004

Year
Rate per 100,000 children lt5 years of age
9

• Haemophilus influenzae type b, 1986
• Incidence by Age Group

Rate per 100,000 population, prevaccine era
10
Haemophilus influenzae type bUnited States,
1996-2000

• Incidence has fallen 99 since prevaccine era
• 341 confirmed Hib cases reported during 1996-2000
  (average of 68 cases per year)
• Most recent cases in unvaccinated or incompletely
  vaccinated children

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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

12
Polysaccharide Conjugate Vaccines

• Stimulates T-dependent immunity
• Enhanced antibody production, especially in
  young children
• Repeat doses elicit booster response

13
Haemophilus influenzae type b Conjugate Vaccines

• 3 conjugate vaccines licensed for use in infants
  as young as 6 weeks of age
• All utilize different carrier proteins
• 2 combination vaccines available that contain Hib
  vaccine

14
Conjugate Hib Vaccines
HbOC Hibtiter PRP-T ActHIB,
TriHIBit PRP-OMP PedvaxHIB, Comvax
15
Haemophilus influenzae type b Vaccine Routine
Schedule
16
Haemophilus influenzae type b Vaccine
Interchangeability

• All conjugate Hib vaccines interchangeable for
  primary series and booster dose
• 3 dose primary series if more than one brand of
  vaccine used

17
Haemophilus influenzae type b VaccineUse in
Older Children and Adults

• Generally not recommended for persons older than
  59 months of age
• Consider for high-risk persons asplenia,
  immunodeficiency, HIV infection, HSCT
• One pediatric dose of any conjugate vaccine

18

Haemophilus influenzae type b Vaccine Adverse
Reactions

• Swelling, redness, or pain in 5-30 of
  recipients
• Systemic reactions infrequent
• Serious adverse reactions rare

19
Haemophilus influenzae type b Vaccine
Contraindications and Precautions

• Severe allergic reaction to vaccine component or
  following a prior dose
• Moderate or severe acute illness
• Age less than 6 weeks

20
Pneumococcal Disease

• S. pneumoniae first isolated by Pasteur in 1881
• Confused with other causes of pneumonia until
  discovery of Gram stain in 1884
• More than 80 serotypes described by 1940
• First U.S. vaccine in 1977

21
Streptococcus pneumoniae

• Gram-positive bacteria
• 90 known serotypes
• Polysaccharide capsule important virulence factor
• Type-specific antibody is protective

22
Pneumococcal DiseaseClinical Syndromes

• Pneumonia
• Bacteremia
• Meningitis

23
Pneumococcal PneumoniaClinical Features

• Abrupt onset
• Fever
• Shaking chills
• Pleuritic chest pain
• Productive cough
• Dyspnea, tachypnea, hypoxia

24
Pneumococcal Pneumonia

• Estimated 175,000 hospitalizations per year in
  the United States
• Up to 36 of adult community-acquired pneumonia
  and 50 of hospital-acquired pneumonia
• Common bacterial complication of influenza and
  measles

25
Pneumococcal Bacteremia

• More than 50,000 cases per year in the United
  States
• Rates higher among elderly and very young infants
• Case-fatality rate 20 up to 60 among the
  elderly

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Pneumococcal Meningitis

• Estimated 3,000 - 6,000 cases per year in the
  United States
• Case-fatality rate 30, up to 80 in the elderly
• Neurologic sequelae common among survivors

27
Pneumococcal Disease in Children

• Bacteremia without known site of infection most
  common clinical presentation
• S. pneumoniae leading cause of bacterial
  meningitis among children younger than 5 years of
  age
• Highest rate of meningitis among children younger
  than 1 year of age
• Common cause of acute otitis media

28
Burden of Pneumococcal Disease in Children
Syndrome Cases

• Bacteremia 13,000
• Meningitis 700
• Death 200
• Otitis media 5,000,000

Prior to routine use of pneumococcal conjugate
vaccine
29
Pneumococcal Disease Epidemiology

• Reservoir Human carriers
• Transmission Respiratory
• Temporal pattern Winter and early spring
• Communicability Unknown
  Probably as long as organism in
  respiratory secretions

30

• Invasive Pneumococcal Disease
• Incidence by Age Group1998

Rate per 100,000 population Source Active
Bacterial Core surveillance/EIP Network
31
Children at Increased Risk of Invasive
Pneumococcal Disease

• Functional or anatomic asplenia, especially
  sickle cell disease
• HIV infection
• Recipient of cochlear implant
• Out-of-home group child care
• African American children
• Alaska Native and American Indian children who
  live in Alaska, Arizona, or New Mexico
• Navaho children who live in Colorado and Utah

32
Pneumococcal Disease Outbreaks

• Outbreaks not common
• Generally occur in crowded environments (jails,
  nursing homes)
• Persons with invasive disease often have
  underlying illness
• May have high fatality rate

33
Pneumococcal Vaccines

• 1977 14-valent polysaccharide vaccine
  licensed
• 1983 23-valent polysaccharide vaccine
  licensed (PPV23)
• 2000 7-valent polysaccharide conjugate
  vaccine licensed (PCV7)

34
Pneumococcal Polysaccharide Vaccine

• Purified capsular polysaccharide antigen from 23
  types of pneumococcus
• Account for 88 of bacteremic pneumococcal
  disease
• Cross-react with types causing additional 8 of
  disease

35
Pneumococcal Conjugate Vaccine

• Pneumococcal polysaccharide conjugated to
  nontoxic diphtheria toxin (7 serotypes)
• Vaccine serotypes account for 86 of bacteremia
  and 83 of meningitis among children younger than
  6 years of age

36
Pneumococcal Polysaccharide Vaccine

• Purified pneumococcal polysaccharide (23 types)
• Not effective in children younger than 2 years
• 60-70 against invasive disease
• Less effective in preventing pneumococcal
  pneumonia

37
Pneumococcal Conjugate Vaccine

• Highly immunogenic in infants and young children,
  including those with high-risk medical conditions
• 97 effective against invasive disease caused by
  vaccine serotypes
• 73 effective against pneumonia
• 7 reduction in all episodes of acute otitis media

38
Pneumococcal Polysaccharide Vaccine
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 with increased risk

MMWR 199746(RR-8)1-24
39
Pneumococcal Conjugate Vaccine Recommendations

• All children younger than 24 months of age
• Unvaccinated children 24-59 months with a
  high-risk medical condition

MMWR 200049(RR-9)1-35
40
Pneumococcal Conjugate Vaccine Recommendations

• Doses at 2, 4, 6, months of age, booster dose at
  12-15 months of age
• Unvaccinated children gt7 months of age require
  fewer doses

MMWR 200049(RR-9)1-35
41
Pneumococcal Conjugate Vaccine

• Children aged 24-59 months at high risk and
  previously vaccinated with PPV23 should receive 2
  doses of PCV7
• Children at high risk who previously received
  PCV7 should receive PPV23 at age 2 years of age

MMWR 200049(RR-9)1-35
42
Pneumococcal Polysaccharide Vaccine Revaccination

• Routine revaccination of immunocompetent persons
  is not recommended
• Revaccination recommended for persons age gt2
  years at highest risk of serious pneumococcal
  infection
• Single revaccination dose gt5 years after first
  dose

MMWR 199746(RR-8)1-24
43
Pneumococcal Polysaccharide VaccineCandidates
for Revaccination

• Persons gt2 years of age with
• functional or anatomic asplenia
• immunosuppression
• transplant
• chronic renal failure
• nephrotic syndrome
• Persons vaccinated at lt65 years of age

MMWR 199746(RR-8)1-24
44
Pneumococcal Vaccines Adverse Reactions

• Local reactions
• polysaccharide 30-50
• conjugate 10-20
• Fever, myalgia
• polysaccharide lt1
• conjugate 15-24
• Severe adverse rarereactions

45
Pneumococcal VaccinesContraindications and
Precautions

• Severe allergic reaction to vaccine component or
  following prior dose of vaccine
• Moderate or severe acute illness

46
Pneumococcal Polysaccharide VaccineMissed
Opportunities

• gt65 of patients with severe pneumococcal disease
  had been hospitalized within preceding 3-5 years
  yet few had received vaccine
• May be administered simultaneously with influenza
  vaccine