Haemophilus influenzae and Hib Meningitis (page 4)
(This chapter has 4 pages)
© Kenneth Todar, PhD
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
programs in 1985, type b H. influenzae
was the most common cause of
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
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
protein-conjugated PRP, has vastly reduced the frequency of infection
to type b H. influenzae. The PRP vaccine consists of
type b capsular polysaccharide. Like most bacterial polysaccharides, it
elicits a strong primary antibody response, but with little induction
memory. H. influenzae type b Hib conjugate vaccines,
couple the polysaccharide to a protein, induce memory type antibody
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
use (Table 1). All of the vaccines are approved for use in children 15
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
are given by injections. More than 90% of infants obtain long term
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
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
known. It also does not protect against diseases caused by other types
of Haemophilus. nor does it protect against meningitis caused
other types of bacteria.
Table 1. Hib
vaccines licensed for use among children
||CRM197 mutant Corynebacterium
diphtheriae toxin protein
outer membrane protein complex
(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
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;
(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
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
N. G., et al. Haemophilus influenzae
Type b Reemergence after Combination Immunization
Emerging Infectious Disease. 12 (6) 2006.
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
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.
Before 1985, Haemophilus influenzae type b (Hib) was the most
cause of bacterial meningitis in children under 5 years of age
12,000 cases per year, most in children younger than 18 months).
5% of affected children died, and neurologic sequelae developed in 15%
to 30% of the surviving children. An additional estimated 7,500 cases
other invasive Hib infections also occurred annually in young children.
The cumulative risk for Hib invasive disease before the age of 5 was
in 200 children, similar to the risk for poliomyelitis during the
In 1985, the first Hib polysaccharide vaccines were licensed for use
in the United States. These vaccines contained purified
phosphate (PRP) capsular material from the type b serovar. Antibody
PRP was shown to be the primary component of serum bactericidal
against the organism. PRP vaccines were ineffective in children less
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
the immunologic response to the PRP antigen. In 1989, the first Hib
vaccines were licensed for use among children 15 months of age or
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
One goal of the Childhood Immunization Initiative was to
invasive Hib disease among children aged 4 years or younger by 1996.
approximately 300 cases of Haemophilus influenzae invasive
per year continue to be reported in the U.S., mainly in non immunized
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
7. Age-specific incidence of bacterial meningitis in children caused by
influenzae in 1996.
END OF CHAPTER
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