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

2. 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 3

4. Decline of Hib Meningitis Related to Vaccine Distribution 1980 1981 1982 19831984 1985 1986 1987 1988 19891990 1991 1992 1993 0 5 10 15 20 25 30 0 5 10 15 20 Year Incidence (per 100,000) Doses distributed (millions) Polysaccharide VaccineConjugate Vaccine

5. H. influenzae (Hi) Serotypes Encapsulated Unencapsulated Type b (Hib) Type non - b (a, c, d, e, f) Nontypeable (NT)

6. Encapsulated vs. Unencapsulated Capsule related to virulence NT genetically diverse NT viewed as colonizers

7. H. aegypitus 1 st 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 OR CA MN NM CO TN GA MD NY CT (pop. = 38.6 million) Participating counties or states

15. 20105 / 392 1999+20004 / 234 Blood, knee fluid, peritoneal fluid………. no CSF