1. Overview of Haemophilus influenzae and related bacteria
Leonard Mayer, Ph. D.
Chief, Meningitis Laboratory
MVPDB/DBD/CDC

2. Haemophilus influenzae (Hi)
gram negative coccobacillus
Serotypes a-f, and HiNT
Meningitis, pneumonia, sepsis, otitis media, among others
Vaccine for serotype b (Hib)
Non-b Hi cases are more visible after Hib vaccine implementation

3. Haemophilus influenzae (Hi)
Severe bacterial infection, particularly among infants
Before the introduction of effective vaccines, Hi type b (Hib) was a leading cause of bacterial meningitis in children <5 years
Introduction of conjugate vaccines in 1991 in U.S. led to rapid decline in Hi type b disease
Most disease in the United States and other developed countries is now due to non-b serotypes and nontypeable (NT) strains
Now in U.S., NT currently most common; serotypes a-f less common

4. Decline of Hib Meningitis Related to Vaccine Distribution5 10 15 20 25 30 5 10 15 20
Doses distributed (millions)
Incidence (per 100,000)
Disease rates of Haemophilus influenzae b, or Hib, dramatically declined after the introduction of the Hib vaccine as shown here –
the yellow line is the incidence of Hib meningitis per 100,000 children under 5 years, and the bars represent distributed doses of first the polysaccharide vaccine (designated by yellow bars),
followed by distribution of the more efficacious Hib conjugate vaccine (here in pink bars).
This was one of the public health success stories of the 1980’s.
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
Year
Polysaccharide Vaccine
Conjugate Vaccine

5. H. influenzae (Hi) Serotypes
Encapsulated Unencapsulated
Type b (Hib)
Type non - b (a, c, d, e, f)
Nontypeable (NT)
The bacteria, Haemophilus influenzae, is categorized into encapsulated and unencapsulated strains.
Based on the structure of the polysaccharide capsule, 6 distinct encapsulated strains have been designated serotypes a to f. Hib refers to type b, and non-b refers to the remaining encapsulated types.
The unencapsulated strains are collectively called nontypeable Hi or NT.

6. Encapsulated vs. Unencapsulated
Capsule related to virulence
NT genetically diverse
NT viewed as colonizers
The bacterial capsule plays a key role in virulence.
The strains without capsules (NT) are genetically diverse, and have been considered to be colonizers and less pathogenic.
Before vaccination, over 95% of Hi was due to serotype b.
Elimination of Hib has raised concerns about the emergence of other pathogenic Hi types. This issue becomes increasingly important as we move toward global Hib elimination.

7. H. aegypitus
1st described by Robert Koch while investigating cholera in Egypt in 1883
Causes conjuntivitis (pink eye); purulent with no permanent damage
<1986 never isolated from sterile site
Now called Haemophilus influenzae biogroup aegyptius

8. Brasilian Purpuric Fever (BPF)
Harrison ClinMicroRev 21:594 ‘08

9. “He got more purple I was in a room with him and the doctor asked me to leave so I wouldn’t see. And right after the doctor came out and said he had died. It was really fast. The disease didn’t even last 24 hours. It was really fast.” Mother of a child with BPF —What’s Killing the Children?, NOVA documentary, WGBHTV, Boston, MA, 18 December 1990.

11. Same unique clone by: Plasmid restriction profile
SDS-PAGE protein profile
rRNA “ribotyping”
MLEE
Seroagglutination
Antibiotic susceptibility testing

12. HiNT
BPF

13. H. haemolyticus
“H. haemolyticus is nonpathogenic, in contrast to the pathogenic H. influenzae.” Wikipedia
Common in carriage isolates
Biochemically similar to H. influenzae
Require hemin (factor X) and NAD (factor V)
Lose hemolytic activity by yet un known mechanism

14. Active Bacterial Core Surveillance (ABCs) Sites, 2004
(pop. = 38.6 million) OR MN NY CT CA CO MD
We used data from an ongoing active bacterial surveillance system (also known as ABCs) which is a multi site, population based system representing over 38 million people in 2004.
Cases were identified between Jan. 1, 1989 through Dec. 31, 2004.
All isolates were confirmed at the state or CDC laboratories.
A standardized case report form was used to collect information from a medical chart review. TN NM GA
Participating counties or states

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Blood, knee fluid, peritoneal fluid………. no CSF