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 b Pathogenesis
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
Limited communicability implied from lack of secondary cases in household settings. Secondary cases may occur in some situations, such as day care settings.

8. Incidence*of Invasive Hib Disease, 1990-2004
Year
*Rate per 100,000 children <5 years of age

9. Haemophilus influenzae type b, 1986 Incidence* by Age Group
*Rate per 100,000 population, prevaccine era

10. Haemophilus influenzae type b—United States, 1996-2000
Incidence has fallen 99% since prevaccine era
341 confirmed Hib cases reported during (average of 68 cases per year)
Most recent cases in unvaccinated or incompletely vaccinated children

11. Haemophilus influenzae type b Risk 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
Vaccine
2 mo
4 mo
6 mo
12-18 mo
HbOC x
PRP-T
PRP-OMP

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 Vaccine Use 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 %-30% of recipients
Systemic reactions infrequent
Serious adverse reactions rare

19. Moderate or severe acute illness Age less than 6 weeks
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 Disease Clinical Syndromes
Pneumonia
Bacteremia
Meningitis

23. Pneumococcal Pneumonia Clinical 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

26. Pneumococcal Meningitis
Estimated 3, ,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 ,000
Meningitis
Death
Otitis media ,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 Group—1998
*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
valent polysaccharide vaccine licensed
valent polysaccharide vaccine licensed (PPV23)
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 1997;46(RR-8):1-24

39. Pneumococcal Conjugate Vaccine Recommendations
All children younger than 24 months of age
Unvaccinated children months with a high-risk medical condition
MMWR 2000;49(RR-9):1-35

40. Pneumococcal Conjugate Vaccine Recommendations
Doses at 2, 4, 6, months of age, booster dose at months of age
Unvaccinated children >7 months of age require fewer doses
MMWR 2000;49(RR-9):1-35

41. Pneumococcal Conjugate Vaccine
Children aged 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 2000;49(RR-9):1-35

42. Pneumococcal Polysaccharide Vaccine Revaccination
Routine revaccination of immunocompetent persons is not recommended
Revaccination recommended for persons age >2 years at highest risk of serious pneumococcal infection
Single revaccination dose >5 years after first dose
MMWR 1997;46(RR-8):1-24

43. Pneumococcal Polysaccharide Vaccine Candidates for Revaccination
Persons >2 years of age with:
functional or anatomic asplenia
immunosuppression
transplant
chronic renal failure
nephrotic syndrome
Persons vaccinated at <65 years of age
MMWR 1997;46(RR-8):1-24

44. Pneumococcal Vaccines Adverse Reactions
Local reactions
polysaccharide %-50%
conjugate %-20%
Fever, myalgia
polysaccharide <1%
conjugate %-24%
Severe adverse rare reactions

45. Pneumococcal Vaccines Contraindications and Precautions
Severe allergic reaction to vaccine component or following prior dose of vaccine
Moderate or severe acute illness

46. Pneumococcal Polysaccharide Vaccine Missed Opportunities
>65% 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