Encapsulated Bacterial Pathogens

Question 1

H. influenzae: morphology, method for diagnosis, major virulence factors

Answer 1

• Morphology
  
  • Coccobacillus
• Method/potential problems for diagnosis
  
  • Gram negative
  • Need special medium: chocolate agar + NAD + heme
  • Identify with Ab to capsule
• Major virulence factors
  
  • Polysaccharide capsule
  • Endotoxin also called LPS
  • IgA protease

Question 2

N. meningitidis: morphology, method for diagnosis, major virulence factors

Answer 2

• Morphology
  
  • Bean-shaped diplococci
• Method/potential problems for diagnosis
  
  • Gram negative
  • Ferments maltose and glucose
  • Identify with antibody to capsule
• Major virulence factors
  
  • Polysaccharide capsule
  • Endotoxin also called LPS
  • IgA protease

Question 3

S. pneumoniae: morphology, method for diagnosis, major virulence factors

Answer 3

• Morphology
  
  • Diplococci
  • Can show as long chains too
• Method/potential problems for diagnosis
  
  • Gram positive
  • a-hemolytic
  • Catalase-negative
  • Identify with Ab to capsule
• Major virulence factors
  
  • Polysaccharide capsule
  • Pneumolysin
  • IgA protease

Question 4

Causes of meningitis for newborns (0-6 months)

Answer 4

• Group B streptococci
• E. coli
• Listeria

Question 5

Causes of meningitis for children (6 months - 6 years)

Answer 5

• N. meningtidis
• S. pneumoniae
• H. influenzae type B
• Enteroviruses

Question 6

Causes of meningitis for persons 6-60 years

Answer 6

• S. pneumoniae
• N. meningitidis
• Enteroviruses
• HSV

Question 7

Causes of meningitis for adults 60+ years

Answer 7

• S. pneumoniae
• Gram (-) rods
• Listeria

Question 8

H. influenzae: variants, disease association, cross-reactivity, vaccine

Answer 8

• Variants
  
  • 6 serotypes a-f
• Disease association
  
  • > 90% caused by serotype b in unvaccinated population
• Cross-reactivity
  
  • Teichoic acids of gram (+) organisms
• Vaccine
  
  • Type B only: polysaccharide + carrier protein

Question 9

S. pneumoniae: variants, disease association, cross-reactivity, vaccine

Answer 9

• Variants
  
  • > 80 serotypes
• Disease association
  
  • 12 types responsible for > 80% of disease
• Cross-reactivity
  
  • Human ABO antigens
• Vaccine
  
  • 23 serotype vaccine OR
  • 13 serotype vaccine
  • Polysaccharide
  • Not for infants

Question 10

N. meningitidis

Answer 10

• Variants
  
  • 9 serogroups
• Disease association
  
  • Type A responsible for most epidemics
• Cross-reactivity
  
  • K1 capsule of E. coli, brain gangliosides
• Vaccine
  
  • All but group B
  • Conjugate
  • Not for infants

Question 11

Immunogenicity of H. influenzae capsule

Answer 11

• Same polysaccharide found in serogroup B found in almost all Gram-positive organisms (in teichoic acids)
• In medical sense, this is important because these other bacteria may induce a protective immune response against H. influenzae
• Understanding this principle has led to development of new highly effective vaccines

Question 12

Immunogenicity of N. meningitidis capsule

Answer 12

• Type B polysaccharide is composed of a polymer of N-acetyl neuraminic acid
• Medically important because unlike other capsular groups, group B capsule is non-immunogenic in humans because N-acetyl neuraminic acid (sialic acid) is extensively found in humans (e.g. brains, kidneys)
• This has prevented development of polysaccharide capsular vaccine against this group
• Also, group B capsule is identical to K1, capsule of E. coli, which causes meningitis in neonates (0-6 months)

Question 13

Use of antibodies to capsules to identify organisms/diagnose disease

Answer 13

• If patient is infected with encapsulated form of one of these organisms, the organism may shed its capsule in blood, urine, or spinal fluid
• May be possible to detect capsular material in body fluids with antiserum directed at specific capsular polysaccharide without being able to culture organism
• Several different methods available commercially:
  
  • Latex agglutination
  • Countercurrent Immuno-Electrophoresis (CIE)

Question 14

Precautions that need to be recognized when using antisera for diagnosis

Answer 14

• Some of capsules or teichoic acids of S. pneumoniae will crossreact with H. influenzae type B capsule
• Antiserum against H. influenzae serotype B will react with some capsular types of S. pneumoniae and with its teichoic acid because it is Gram (+)
• Medically important because cross-reactions may lead to misdiagnosis of H. influenzae or S. pneumoniae infection

Question 15

Importance of identification of capsular types of N. meningitidis

Answer 15

• There is no vaccine against the serogroup B of N. meningitidis

Question 16

Basis for vaccine against H. influenzae

Answer 16

• Linking T-cell independent Ag (like polysaccharide) to carrier protein converts it to T-cell dependent antigen
• T-cell dependent antigen able to induce protective immune response in newborn infants
  
  • Does not cause tolerance to antigen with booster immunization like discontinued H. influenzae polysaccharide-only vaccine did
• TETRAMUNE = CRM197 conjugate vaccine for H. influenzae combined with standard DPT vaccine
• Recommended that primary immunizations be administered at 2,4,6, and 15-18 months of age with booster dose at 4-6 years of age

Question 17

Basis for/composition of vaccine against N. meningitidis

Answer 17

• Two vaccines against N. meningitidis available in US
  
  • Meningococcal polysaccharide vaccine (MPSV4, Menomune) approved by FDA and available since 1981
    
    • Should be used for children 2-10 years of age
  • Meningococcal conjugate vaccine (MCV, MenactraT) licensed in 2005
    
    • Provides better and longer-lasting immunity than Menomune
    • Preferred vaccine for people 11-55 years old
    • Recommended for all children at routine preadolescent visit (11 to 12 years of age) - or at high school/college entry for those who have never gotten it previously
    • Other groups at high risk: college freshmen in dorms, microbiologists, US military recruits, asplenic patients, patients with terminal complement deficiency, those with possible exposure
• Both vaccines can prevent 4 types of meningococcal disease, including 2 of 3 types most common in US (serogroup C, Y, and W-135) and type that causes epidemics in Africa (serogroup A)
• Meningococal vaccines cannot prevent all types of disease, but they do protect many people who may become sick if they didn’t get the vaccine
• Currently no available vaccine against group B strains because the capsule is not immunogenic in humans

Question 18

Basis for/composition of vaccine against S. pneumoniae: Pneumovax

Answer 18

• Contains purified capsular materials of 23 types of S. pneumo that most frequently cause disease
• Originally tested in two groups of people at high risk for pneumococcal pneumoniae (New Guinea Highlanders, South African gold miners)
  
  • Proved to be 80-90% effective against pneumococcal serotypes that were included in vaccine for these groups
• Vaccine has no value in protecting elderly and chronically ill patients against pneumococcal pneumonia
  
  • In some trials, higher mortality rate in persons who were vaccinated
  • 55-60% effective against pneumococcal bacteremia - requires assessment of cost-effectiveness?

Question 19

Basis for/composition of vaccine against S. pneumoniae: Prevnar

Answer 19

• About 2 years ago, a new version of the S. pneumoniae vaccine was approved by FDA
• Vaccine is against 13 capsular types of S. pneumoniae that cause > 90% of invasive (e.g. meningitis) diseases in children < 6 years of age in the US
• Cost of pneumococcal disease in this age group estimated to be > $1.5 billion annually
• Capsular polysaccharides from these 13 serotypes are conjuated to mutant, nontoxic Diphtheria toxin protein called CRM197 to make Prevnar
• Have only been relatively minor side effects seen with this vaccine so far
• Recommended for:
  
  • Infants and toddlers ages up to 23 months (4 doses starting at 2 months)
  • Certain older children 24-59 months
    
    • African Americans, especially those with Sickle Cell Disease
    • Native Americans, Alaskan Americans, children with HIV, immunocompromised children, or children with chronic diseases
  • Higher priority for 24-59 months: children in daycare centers, socially or economically disadvantaged children, children with frequent or chronic otitis media

Question 20

Safety & efficacy of vaccines

Answer 20

• Safety
  
  • Don’t contain thimerosol or mercury
  • Only relatively minor side effects seen with this vaccine so far
• Efficacy
  
  • Meningitis from H. influenzae is rare since advent of vaccine, usually only occurs in unvaccinated children
  • Prevnar: 13-Ag S. pneumoniae vaccine decreases pneumococcal disease by:
    
    • 64% in 5-19 year olds
    • 36% in 40-59 year olds
  • Presence of IgG or IgM in bloodstream protects against serious and invasive disease like meningitis
• Not effective in all age groups: children < 6 years old who are most susceptible to disease do not respond well to T-cell independent antigens like capsular polysaccharides

Question 21

Vaccinations effective only against some capsular serotypes or serogroups

Answer 21

• N. meningiditis type B polysaccharide is non-immunogenic in humans because N-acetyl neuraminic acid (sialic acid) is extensively found in humans
  
  • Has prevented development of polysaccharide capsular vaccine against this group
  • Group B capsule is identical to K1 capsule of E. coli, which causes meningitis in neonates (0-6 months)

Question 22

Effectiveness of capsular polysacscharides conjugated to proteins

Answer 22

• More effective as vaccines than polysaccharides alone
• Initiate T-cell response and Ab class switching
• Effective in children < 6

Question 23

Prophylactic antibiotic administration for meningococcal/pneumococcal disease

Answer 23

• Chemoprophylaxis (rifampin, ciprofloxacin)
• Given to people who have come in contact with other people diagnosed with meningitis caused by H. influenzae, S. pneumoniae, most frequently N. meningitidis to prevent the spread of these diseases
  
  • Ex. daycare situations or in college dormitories when there is an outbreak of bacterial meningitis, rifampin is administered to anyone who came in contact with the victim
• Can also be used for prophylaxis of people who are asymptomatic carriers of these organisms so that they don’t spread their organisms to others