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Haemophilus influenzae type b

Haemophilus influenzae type b. Severe bacterial infection, particularly among infants During late 19th century believed to cause influenza Immunology and microbiology clarified in 1930s. Haemophilus influenzae. Aerobic gram-negative bacteria Polysaccharide capsule

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Haemophilus influenzae type b

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  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. 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 1996-2000 (average of 68 cases per year) • Most recent cases in unvaccinated or incompletely vaccinated children

  11. 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. 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

  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

  26. 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* Bacteremia 13,000 Meningitis 700 Death 200 Otitis media 5,000,000 SyndromeCases *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 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 1997;46(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 2000;49(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 >7 months of age require fewer doses MMWR 2000;49(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 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 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 of age MMWR 1997;46(RR-8):1-24

  44. Pneumococcal Vaccines Adverse Reactions • Local reactions • polysaccharide 30%-50% • conjugate 10%-20% • Fever, myalgia • polysaccharide <1% • 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 • >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

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