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Tag words: Haemophilus, Haemophilus influenzae, H influenzae, H flu, Hib vaccine, meningitis, Hib meningitis.

Haemophilus influenzae

Kingdom: Bacteria
Phylum: Proteobacteria
Class: Gamma Proteobacteria
Order: Pasteurellales
Family: Pasteurellaceae
Genus: Haemophilus
Species: H. influenzae








Kenneth Todar currently teaches Microbiology 100 at the University of Wisconsin-Madison.  His main teaching interests include general microbiology, bacterial diversity, microbial ecology and pathogenic bacteriology.

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Haemophilus influenzae and Hib Meningitis (page 4)

(This chapter has 4 pages)

© Kenneth Todar, PhD

Prevention

Bacterial meningitis is a major cause of death and disability in children worldwide: >1,000,000 cases and 200,000 deaths are estimated to occur each year. Neisseria meningitidis, Haemophilus influenzae type b (Hib), and Streptococcus pneumoniae are major causative agents of bacterial meningitis in children.

Until the implementation of widespread vaccination programs in 1985, type b H. influenzae was the most common cause of meningitis in children between the ages of 6 months and 2 years ( Figure 6), resulting in 12,000 to 20,000 cases and over 500 deaths annually in the U.S. The use of the Hib conjugate vaccines has reduced the number of cases in the Twenty-first Century to a few hundred per year.



Figure 6. Age-specific incidence of bacterial meningitis caused by Haemophilus influenzae, Neisseria meningitidis and Streptococcus pneumoniae prior to 1985.

The use of polyribosyl ribitol phosphate (PRP) vaccine and, more recently, protein-conjugated PRP, has vastly reduced the frequency of infection due to type b H. influenzae. The PRP vaccine consists of the type b capsular polysaccharide. Like most bacterial polysaccharides, it elicits a strong primary antibody response, but with little induction of memory. H. influenzae type b Hib conjugate vaccines, which couple the polysaccharide to a protein, induce memory type antibody responses in children and are effective in younger infants who are at higher risk for the disease.

There are several types of Hib conjugate vaccines available for use (Table 1). All of the vaccines are approved for use in children 15 months of age and older and some are approved for use in children beginning at 2 months of age. All of the vaccines are considered effective. The vaccines are given by injections. More than 90% of infants obtain long term immunity with 2-3 doses of the vaccine.

All children should have a vaccine approved for infants beginning at 2 months. Depending on the type used, the recommended schedule for infants will vary. All unvaccinated children 15 - 59 months old should receive a single dose of conjugate vaccine. Children 60 months of age or older and adults normally do not need to be immunized.

Whether the vaccine provides protection against ear infections is not known. It also does not protect against diseases caused by other types of Haemophilus. nor does it protect against meningitis caused by other types of bacteria.


Table 1. Hib conjugate vaccines licensed for use among children
Vaccine Trade name
(manufacturer)
Polysaccharide  Linkage Protein carrier
PRP-D(1)
ProHIBiT 
(Connaught)
Medium 6-carbon Diphtheria toxoid
HbOC(2)(5)  HibTITER 
(Wyeth-Lederle)
Small None CRM197 mutant Corynebacterium diphtheriae toxin protein
PRP-OMP(2)(3) PedvaxHIB 
(Merck)
Medium Thioether Neisseria meningitidis outer membrane protein complex
PRP-T(2)(4) ActHIB(Sanofi Pasteur)
OmniHIB 
(GlaxoSmithKline)
Large 6-carbon Tetanus toxoid

TABLE NOTES

(1) ProHIBiT is indicated for immunization against invasive diseases caused by Haemophilus influenzae type b. ProHIBiT may be administered as a booster vaccination at 12 to 15 months of age in children who received primary immunization with HbOC or PRP-OMP conjugate vaccines. The vaccine also may be administered as primary immunization at 15 months of age in children who have not received primary immunization with any licensed Hib conjugate vaccine.

(2) Three conjugate Hib vaccines are licensed for use in infants (beginning at 2 months of age) and children in the United States: HbOC (HibTiTER, Wyeth-Lederle), PRP-OMP (PedvaxHIB, Merck & Co., Inc.), and PRP-T (ActHIB, Sanofi Pasteur; OmniHIB, GlaxoSmithKline).

(3) PRP-OMP vaccine is available as a combined product with hepatitis Bvaccine (Comvax).

(4) PRP-T (ActHIB) and acellular pertussis vaccine (DTaP, Tripedia) are available in the same package and can be combined by the provider; the combined product is called TriHIBit. TriHIBit is licensed for use only as the fourth dose of the Hib and DTaP series. According to the CDC it should not be given for the first, second, or third doses of the Hib series.

(5) HbOC may be combined with DPT as DPT-HbOC (Tetrammune). DPT represents DTwP which contains the whole cell pertussis vaccine. The combination vaccine provides protection against diphtheria, tetanus, pertussis and Hib disease. According to the Clinical Assessment Program (CAP) of the American Osteopathic Foundation (AOF), there is good evidence for the safety and immunogenicity of heterogenous Hib conjugate vaccine series. Therefore, immunization at the recommended intervals (2, 4, 6, and 12-15 months) should not be delayed by efforts to determine the type of vaccine previously received. When this information is unavailable, any of the conjugate vaccines approved for use in infants may be given to complete the series. Licensed combined vaccines, such as DTP-HbOC may be substituted for the relevant individual vaccines in cases where both vaccines would normally be given in order to reduce the total number of injections given.

The apparent discrepancy between (4) CDC's recommendation AGAINST the use of a combined vaccine at 2-12 months, and (5) AOF's recommendation FOR the use of a combined vaccine at 2-12 months may be explained by immunogenic differences between acellular pertussis in the TriHIBit vaccine and whole cell pertussis in the DPT-HbOC vaccine, as suggested in this article that appeared in Emerging Infectious Diseases in June 2006. However, if the whole cell vaccine is used in preference to the acellular pertussis vaccine, the risks of the former must be weighed. Johnson, N. G., et al. Haemophilus influenzae Type b Reemergence after Combination Immunization Emerging Infectious Disease. 12 (6) 2006.

Summary: The authors provided evidence that DTaP-Hib vaccines (acellular pertussis) result in lower Hib antibody concentrations after vaccination when compared with DTwP-Hib (whole cell) vaccines. After the introduction of conjugate Hib vaccines In 1992, the incidence of invasive Hib disease in England and Wales dramatically declined. From 1990 to 1992, the annual incidence in children <5 years of age was 20.5�22.9 per 100,000 and by 1998 it had fallen to 0.65 per 100,000. However, since 1999 the number of invasive Hib infections has risen, with an increase every year in the number of cases in children born from 1996 to 2001; by 2002 the disease incidence had reached 4.58 per 100,000. This rise coincided with a temporary change in the type of Hib vaccine combinations given for primary immunization. An acellular pertussis combination vaccine (DTaP-Hib) was used from 1999 to 2002 because of a shortage of the whole cell pertussis combination (DTwP-Hib) vaccine. However, a significant and lasting effect on anti-PRP antibody levels of the type of DTP-Hib combination vaccine used for primary vaccination. Participants who received all 3 primary doses as DTaP-Hib had antibody concentrations 2�4 years later that were approximately half those of participants who received all 3 primary doses as DTwP-Hib.



Tailpiece

Before 1985, Haemophilus influenzae type b (Hib) was the most common cause of bacterial meningitis in children under 5 years of age (approximately 12,000 cases per year, most in children younger than 18 months). Approximately 5% of affected children died, and neurologic sequelae developed in 15% to 30% of the surviving children. An additional estimated 7,500 cases of other invasive Hib infections also occurred annually in young children. The cumulative risk for Hib invasive disease before the age of 5 was one in 200 children, similar to the risk for poliomyelitis during the 1950s.

In 1985, the first Hib polysaccharide vaccines were licensed for use in the United States. These vaccines contained purified polyribosylribitol phosphate (PRP) capsular material from the type b serovar. Antibody against PRP was shown to be the primary component of serum bactericidal activity against the organism. PRP vaccines were ineffective in children less than 18 months of age because of the T-cell-independent nature of the immune response to PRP polysaccharide.

Conjugation of the PRP polysaccharide with protein carriers confers T-cell-dependent characteristics to the vaccine and substantially enhances the immunologic response to the PRP antigen. In 1989, the first Hib conjugate vaccines were licensed for use among children 15 months of age or older. In 1990, two new vaccines were approved for use among infants.

The incidence of Hib invasive disease among children aged 4 years or younger has declined by 98% since the introduction of Hib conjugate vaccines. One goal of the Childhood Immunization Initiative was to eliminate invasive Hib disease among children aged 4 years or younger by 1996. However, approximately 300 cases of Haemophilus influenzae invasive disease per year continue to be reported in the U.S., mainly in non immunized children. Most cases are caused by nontypable Haemophilus influenzae. The bar graph below (Figure 7) shows the age distribution of cases in 1996, representing data comparable to Figure 6, but from the post immunization era.


Figure 7. Age-specific incidence of bacterial meningitis in children caused by Haemophilus influenzae in 1996.




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