Commentary: Results of Efficacy Trials in Alaska and Finland of Haemophilus influenzae Type b Conjugate Vaccine

One of the currently licensed Haemophilus influenzae type b polysaccharide conjugate vaccines currently recommended for use in children 18 months of age and older, polyribosylribitol-phosphate-diphtheria toxoid (PRP-D, Connaught Laboratories), has been evaluated in two studies for its protective efficacy in children immunized before 6 months of age.1 The peak incidence of invasive disease caused by H. influenzae type b occurs in children 6 to 18 months of age; therefore, prevention of this disease depends on the efficacy of vaccines in this younger age group. In a large, randomized, unblinded trial conducted in Finland, relatively low levels of antibody were induced after a series of three primary PRP-D immunizations at 3, 4, and 6 months of age. Despite these limited immunogenicity results, a high level of protective efficacy was shown during a 3-year period (protective efficacy of 87%, 95% confidence intervals 50% to 96%). Another trial, which was randomized, double blind, and placebo controlled, was conducted among 2113 Native Alaskan infants immunized (20 µg/0.5 mL) at 2, 4, and 6 months of age as part of their routine childhood immunizations. This population was chosen for the trial because it has the highest known incidence of invasive disease caused by H influenzae type b, and a trial in such a high-risk population could be conducted more carefully, with fewer study subjects, and in a shorter period of time. As in the Finnish trial, in this younger age group immune responses to PRP-D vaccine were meager, apparent only after the third dose of vaccine at 6 months of age.

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Protective Efficacy of Haemophilus influenzae Type b Polysaccharide Vaccine

PEDIATRICS ◽

10.1542/peds.85.4.643 ◽

1990 ◽

Vol 85 (4) ◽

pp. 643-647

Author(s):

Eugene D. Shapiro ◽

Anne T. Berg

Keyword(s):

United States ◽

Haemophilus Influenzae ◽

Protective Efficacy ◽

The United States ◽

Invasive Disease ◽

Polysaccharide Vaccine ◽

Haemophilus Influenzae Type ◽

Haemophilus Influenzae Type B ◽

Type B ◽

Increased Risk

There has been uncertainty and controversy about the protective efficacy of Haemophilus influenzae type b polysaccharide vaccine almost since it first was licensed in the United States. This article will briefly review the available epidemiologic data about the protective efficacy of this vaccine in children with no recognized underlying illnesses. H influenzae type b polysaccharide vaccine was licensed in the United States in April 1985, based on the results of a randomized clinical trial that was conducted in Finland.1 That study indicated that the vaccine's protective efficacy was 90% against invasive disease caused by H influenzae type b in children 18 to 71 months of age. Authorities recommended that all children receive the vaccine at 2 years of age and that it be administered to children up to the age of 60 months.2,3 The Immunization Practices Advisory Committee also recommended that children at increased risk (such as those who attend group day care) receive the vaccine at 18 months and again at 24 months of age because of its inconsistent immunogenicity when administered to 18-month-old children.2 Soon after its licensure, however, reports of vaccine failures began to appear. In some instances the vaccine failure could be attributed to an identifiable immune deficiency.4,5 However, Granoff et al6 reported 54 apparently normal children who had received the H influenzae type b polysaccharide vaccine but subsequently developed invasive disease caused by H influenzae type b. The majority of these children had normal serum concentrations of total immunoglobulins, IgG2, hemolytic complement, and antibody to tetanus toxoid (a T-cell-dependent antigen).

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Impact of Haemophilus influenzae type b conjugate vaccination on hospitalization for invasive disease in children fifteen years after its introduction in Italy

Vaccine ◽

10.1016/j.vaccine.2017.09.077 ◽

2017 ◽

Vol 35 (46) ◽

pp. 6297-6301 ◽

Cited By ~ 3

Author(s):

Domenico Martinelli ◽

Chiara Azzari ◽

Paolo Bonanni ◽

Susanna Esposito ◽

Elisabetta Franco ◽

...

Keyword(s):

Haemophilus Influenzae ◽

Invasive Disease ◽

Haemophilus Influenzae Type ◽

Haemophilus Influenzae Type B ◽

Type B ◽

Conjugate Vaccination

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Invasive disease due to Haemophilus influenzae type b during the first six years of general vaccination of Swedish children

CrossRef Listing of Deleted DOIs ◽

10.1080/080352500750028212 ◽

2000 ◽

Vol 89 (4) ◽

pp. 471-474 ◽

Cited By ~ 18

Author(s):

Ö Garpenholt ◽

S Hugosson ◽

H Fredlund ◽

J Giesecke ◽

P Olcén

Keyword(s):

Haemophilus Influenzae ◽

Invasive Disease ◽

Haemophilus Influenzae Type ◽

Haemophilus Influenzae Type B ◽

Type B

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Epidemiology of Haemophilus Type B Invasive Disease in Childhood in Glasgow

Scottish Medical Journal ◽

10.1177/003693309303800107 ◽

1993 ◽

Vol 38 (1) ◽

pp. 18-20 ◽

Cited By ~ 3

Author(s):

A Coggins ◽

C.W. Shepherd ◽

F. Cockburn

Keyword(s):

Haemophilus Influenzae ◽

Invasive Disease ◽

Annual Incidence ◽

Childhood Vaccination ◽

Haemophilus Influenzae Type ◽

Haemophilus Influenzae Type B ◽

Type B ◽

Neurological Sequelae ◽

The United Kingdom

The objective of this study was to investigate the epidemiology of invasive disease due to Haemophilus influenzae type b in childhood in Glasgow. A retrospective study has been made on the hospital records of 252 children aged 0 to 12 years admitted to Glasgow hospitals during 1981–1990. The annual incidence of invasive Haemophilus influenzae type b disease in Glasgow was estimated at 39 per 100,000 children less than five years of age per year. The figure for Haemophilus meningitis was 23.8 per 100,000 children less than five years of age per year. Ninety-five per cent of all cases occurred in children less than five years of age and 72.1% of meningitis cases occurred before two years of age. There was a mortality of 2.77%. Long-term neurological sequelae were found in 15.3% of the survivors. The annual incidence of Haemophilus influenzae type b disease is slightly higher in Glasgow than previously reported for the United Kingdom. The study provides baseline data to help assess efficacy of proposed early childhood vaccination.

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Disease Caused by Haemophilus influenzae Type b in the Immediate Period After Homologous Immunization: Immunologic Investigation

PEDIATRICS ◽

10.1542/peds.85.4.698 ◽

1990 ◽

Vol 85 (4) ◽

pp. 698-704

Author(s):

Sunil K. Sood ◽

Robert S. Daum

Keyword(s):

United States ◽

Haemophilus Influenzae ◽

Capsular Polysaccharide ◽

The United States ◽

Invasive Disease ◽

Haemophilus Influenzae Type ◽

Haemophilus Influenzae Type B ◽

Type B ◽

Background Rate ◽

Protein Conjugate

Several Haemophilus influenzae type b vaccines have been licensed and recommended for administration to children in the United States. These vaccines have consisted of purified polyribosylribitol-phosphate (PRP), the capsular polysaccharide of H influenzae type b,1 alone or covalently bound to one of several carrier proteins. Two of these saccharide-protein conjugate vaccines are now licensed, a polysaccharide-diphtheria toxoid conjugate (PRP-D)2 and an oligosaccharide-mutant diphtheria toxin conjugate (HbOC).3 Two others, a polysaccharide- Neisseria meningitidis outer membrane protein conjugate (PRP-OMPC)4 and a polysaccharide-tetanus toxoid conjugate (PRP-T),5 are currently in clinical trials. One concern with the use of PRP vaccine was the suggestion that the incidence of invasive disease caused by H influenzae type b in the immediate period after immunization might be increased; this idea was supported by evidence from several sources. In a case-control study of the efficacy of PRP vaccine, Black et al6 found that 4 children were hospitalized for invasive disease within 1 week of immunization, a rate of invasive disease 6.4 times greater (95% confidence interval [CI], 2.1 to 19.2) than the background rate in unvaccinated children. In Minnesota, the relative risk for invasive disease in the first week after immunization was 6.2 (95% CI, 0.6 to 45.9),7 and the results of a study conducted by the Centers for Disease Control in six areas of the United States revealed a 1.8-fold (95% CI, 0.3 to 10.2) increase in the occurrence of invasive disease caused by H influenzae type b in the first week after immunization.8 Moreover, among 16 cases of disease caused by H influenzae type b occurring within 14 days of immunization that were passively reported to the FDA,9 10 were clustered within the first 72 hours.

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The Practice Of Pediatrics in the Era of Vaccines Effective Against Haemophilus influenzae Type b

PEDIATRICS ◽

10.1542/peds.93.4.680 ◽

1994 ◽

Vol 93 (4) ◽

pp. 680-681

Author(s):

Laurence B. Givner ◽

Charles R. Woods ◽

Jon S. Abramson

Keyword(s):

Haemophilus Influenzae ◽

Invasive Disease ◽

Haemophilus Influenzae Type ◽

Rapid Decline ◽

Haemophilus Influenzae Type B ◽

Type B ◽

The Past ◽

Dramatic Decline ◽

The Everyday ◽

The Subject

The practice of pediatrics is forever altered when a vaccine is effective in dramatically reducing the incidence of (or even eradicating) an infectious disease. As the targeted disease is rapidly declining in incidence, there are often exciting changes in the practice of pediatrics, with far-reaching effects in the everyday treatment of patients. Such is the case now due to the effectiveness of the conjugated polysaccharide vaccines against Haemophilus influenzae type b (Hib). The resultant rapid decline in the incidence of invasive disease due to Hib during the past several years has been documented in numerous studies.1-3 The effects of this dramatic decline in Hib disease on the approach to children who have (presumed) infectious diseases are the subject of this editorial.

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