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Haemophilus b disease after vaccination with Haemophilus b polysaccharide or conjugate vaccine.

The reported frequency of invasive Haemophilus influenzae type b disease occurring within 1 year after immunization was compared in American children who received either Praxis Biologics' Haemophilus b polysaccharide vaccine or Connaught Laboratories' Haemophilus b conjugate vaccine during the first year of distribution. All domestic cases reported to the Food and Drug Administration or the Centers for Disease Control were included in the study. An estimated 4.5 million and 2.0 million doses of polysaccharide and conjugate vaccines were administered, respectively. Approximately three cases of early-onset disease (disease developing less than 15 days after vaccination) per million doses were reported for the polysaccharide compared with four cases per million doses for the conjugate vaccine. There were 30.7 reported vaccine failures per million doses of the polysaccharide vaccine compared with 9.0 per million doses of the conjugate vaccine, a 3.4-fold difference. The reporting rate ratios (cases of vaccine failure to cases of early-onset disease) for the polysaccharide and conjugate were 11.5 and 2.3, respectively, a fivefold difference. Thus, compared with recipients of the polysaccharide vaccine, vaccine failures reported among recipients of the conjugate vaccine were 80% fewer than expected.

Bacterial Capsules↗

Haemophilus b conjugate vaccines for prevention of Haemophilus influenzae type b disease among infants and children two months of age and older. Recommendations of the immunization practices advisory committee (ACIP).

These recommendations include information on use of two vaccines recently licensed for use with infants: Haemophilus b Conjugate Vaccine (Diphtheria CRM197 Protein Conjugate) (HbOC), manufactured by Praxis Biologics, Inc., and Haemophilus b Conjugate Vaccine (Meningococcal Protein Conjugate) (PRP-OMP), manufactured by Merck Sharp and Dohme, newly licensed for use with infants. This statement also updates recommendations for use of these and other Haemophilus b conjugate vaccines with older children and adults.

Adult↗

Immunogenicity of Haemophilus b conjugate vaccine (meningococcal protein conjugate) in children with prior invasive Haemophilus influenzae type b disease.

Children younger than 2 years of age with previous invasive Haemophilus influenzae (Hib) type b disease may not develop protective antibodies to antigens of Hib and may be at risk of developing a second episode of Hib disease. Twenty-three children with prior Hib disease were immunized with Haemophilus b conjugate vaccine (meningococcal protein conjugate). Children 12 to 24 months of age were given one dose of vaccine and children younger than 12 months of age were given 2 doses 2 months apart. Antibody to the polysaccharide capsule of Hib (PRP) was measured by radioimmunoassay. Eighteen children had preimmunization serum antibody concentrations less than 0.150 micrograms/ml. All 18 children responded with greater than 0.150 micrograms/ml of antibody after a single dose of vaccine. Only 1 of the 23 children had a preimmunization serum antibody concentration greater than 1.000 micrograms/ml. Seventeen children ultimately responded with greater than 1.000 micrograms/ml of antibody (P less than 0.0001), concentrations of antibody thought to correlate with protection. Haemophilus b conjugate vaccine (meningococcal protein conjugate) is immunogenic in children with invasive Hib disease. Children younger than 2 years of age with invasive Hib disease should be subsequently immunized with a Hib conjugate vaccine.

Age Factors↗

Prevalence of Haemophilus influenzae carriers in the Catalan preschool population. Working Group on Invasive Disease Caused by Haemophilus influenzae.

This study was designed to determine the prevalence of healthy Haemophilus influenzae carriers in a random sample of the preschool population in Catalonia. Oropharyngeal swabs were collected and cultured on chocolate agar supplemented with 260 microg/ml of bacitracin. Four hundred two of the 734 (54.8%) children studied were detected as Haemophilus influenzae carriers: 7 (0.9%) carried serotype b, 14 (1.9%) serotype e, 6 (0.8%) serotype f, and 375 (51%) carried nontypable strains. The results show that, although the prevalence of Haemophilus influenzae carriers is similar to figures reported from other countries, the prevalence of Haemophillus influenzae serotype b carriers is lower and corresponds with the low incidence of invasive disease observed in the Catalan community.

Carrier State↗

Determination of biotypes of Haemophilus influenzae and Haemophilus parainfluenzae a comparison of methods and a description of a new biotype (VIII) of H. parainfluenzae.

A total of 180 strains of Haemophilus influenzae and 119 strains of Haemophilus parainfluenzae were characterized with respect to biotype (i.e., production of indole, urease, and ornithine decarboxylase) using conventional biochemical methods and two commercially available biotyping systems: Trio-Tube Haemophilus system (Carr Microbiologicals) and the Rapid NH System (Inovative Diagnostic Systems). Concordance between the results of the Trio-Tube system and conventional biochemicals was achieved with 294 of the 299 test organisms (98.3%). With the Rapid NH System, concordance with the results of conventional biochemical tests was observed with 275 of the 299 tests strains (92.0%). One previously unrecognized biotype of H. parainfluenzae, designated biotype VIII, is described. Typical reactions of this biotype include indole production but no production of urease or ornithine decarboxylase.

Haemophilus↗

Cellular fatty acid composition of Haemophilus species, Pasteurella multocida, Actinobacillus Actinomycetemcomitans and Haemophilus vaginalis (Corynebacterium vaginale).

The fatty acid composition of 35 Haemophilus influenzae strains was found to be grossly similar and characterized by relatively large amounts of 14:0, 3-OH-14:0, 16:1 and 16:0. The three C18 fatty acids 18:2, 18:1 and 18:0 were also present, but in much lower concentrations. This general pattern was also found for most of the other species of Haemophilus examined (H. aegyptius, H. aphrophilus, H. canis, H. gallinarum, H. haemolyticus, and H. parainfluenzae). Small but distinct quantitative discrepancies were detected for H. ducreyi and the haemin-independent species H. paraphrohaemolyticus, H. paraphrophilus and H. suis. Actinobacillus actinomycetemcomitans was found to be indistinguishable from H. influenzae. Pasteurella multocida also exhibited a fatty acid pattern closely related to that of Haemophilus, but could be distinguished by its higher concentration levels of the C18 fatty acids. The fatty acid pattern of H. vaginalis was considerably different from those of the other species examined. This species lacked 3-OH-14:0 and 18:2 and contained small amounts of 14:0 and 16:0, whereas 18:1 and 18:0 were the major constituents.

Actinobacillus↗

Insertion sequence IS1016 and absence of Haemophilus capsulation genes in the Brazilian purpuric fever clone of Haemophilus influenzae biogroup aegyptius.

Brazilian purpuric fever (BPF) strains of Haemophilus influenzae biogroup aegyptius form a clone of organisms distinct from more innocuous, conjunctivitis-associated isolates. There has been controversy over whether the virulence of BPF strains might derive from the presence of a polysaccharide capsule analogous to that found in conventional invasive H. influenzae, a controversy fuelled by the observation (G. M. Carlone, L. Gorelkin, L. L. Gheesling, A. L. Erwin, S. K. Hoiseth, M. H. O. Mulks, S. P. Connor, R. S. Weyant, J. Myrick, L. Rubin, R. S. Mumford III, E. H. White, R. J. Arko, B. Swaminathan, L. M. Graves, L. W. Mayer, M. K. Robinson, S. P. Caudill, and the Brazilian Purpuric Fever Study Group, J. Clin, Microbiol. 27:609-614, 1989) that a capsulation DNA probe from H. influenzae type b hybridized uniquely to BPF strains. In this work, the basis for this hybridization has been established as the possession by BPF strains, but not by non-BPF strains, of the Haemophilus insertion element IS1016. Although IS1016 is associated with the capsulation locus in some Haemophilus spp., a Southern hybridization study suggests that in BPF strains there are no capsulation genes.

Base Sequence↗

Comparison of outer membrane protein and biochemical profiles of Haemophilus aegyptius and Haemophilus influenzae biotype III.

Haemophilus aegyptius and Haemophilus influenzae biotype III are morphologically and biochemically similar; however, their outer membrane protein (Sarkosyl insoluble) profiles are distinct. Of 18 strains of H. aegyptius examined, 15 had a type 1 protein profile, and 3 had a type 2 profile, whereas the 5 strains of H. influenzae biotype III examined had three other protein profile types. All Haemophilus strains examined had 31- and 76-kilodalton (kDa) proteins and minor proteins with molecular masses between 20 and 100 kDa. H. aegyptius, with a type 1 protein profile, had major outer membrane proteins with apparent molecular masses of 27, 35.5, and 41.5 kDa, and H. aegyptius, with a type 2 protein profile, had 26-, 29-, 39.5-, and 41-kDa proteins. The type strain of H. influenzae biotype III had three major outer membrane proteins with apparent molecular masses of 29, 38.5 and 40 kDa. Four other strains designated as H. influenzae biotype III had major outer membrane proteins between 27 and 41.5 kDa representing two additional protein profiles.

Bacterial Outer Membrane Proteins↗

Identification of Neisseria spp., Haemophilus spp., and other fastidious gram-negative bacteria with the MicroScan Haemophilus-Neisseria identification panel.

The Haemophilus-Neisseria identification (HNID) panel (American MicroScan, Sacramento, Calif.) is a 4-h microdilution format system for identification of Haemophilus and Neisseria spp., Branhamella (Moraxella) catarrhalis, and Gardnerella vaginalis. The HNID panel was evaluated by using 423 clinical isolates and stock strains of these organisms, and HNID identifications were compared with those obtained by conventional methods. In addition, 32 isolates representing six genera not included in the HNID data base were tested to determine whether these organisms would produce unique biotype numbers for possible inclusion in the data base. The HNID panel correctly identified 95.3% of 86 Neisseria gonorrhoeae strains, 96% of 25 G. vaginalis strains, and 100% of 28 Neisseria lactamica strains and 48 B. catarrhalis strains. Only 64.7% of 68 Neisseria meningitidis isolates were identified correctly owing to false-negative or equivocal carbohydrate and/or aminopeptidase reactions. Among the Haemophilus spp., 98.8% of 83 H. influenzae strains, 97.1% of 34 H. parainfluenzae strains, and 80% of 15 H. aphrophilus and H. paraphrophilus strains were correctly identified. Eight strains of Neisseria cinerea, a species not included in the data base, produced profiles identical with those for B. catarrhalis and N. gonorrhoeae. Isolates of other species not included in the data base, including Eikenella corrodens, Kingella spp., and Cardiobacterium hominis, produced unique biochemical reaction patterns on the panel. Modification of interpretative criteria for certain tests, expansion of the data base to include other species, and suggestions for additional confirmatory tests will increase the accuracy and utility of the HNID panel.

Gardnerella vaginalis↗

Septicemia and meningoencephalitis in pastured cattle caused by a Haemophilus-like organism ("Haemophilus somnus").

Septicemia and meningoencephalitis developed in 10 pastured cattle 7 months to 3 years of age. Two unrelated herds were involved. Necropsy findings were similar to those previously reported in cattle infected with a Haemophilus-like organism, including multifocal intramuscular hemorrhages, suppurative polyarthritis, and multifocal hemorrhagic thrombi in the brain. A Haemophilus-like organism was isolated from one animal. It was characterized by growth on blood agar or tryptose agar plus a feeder streak under raised carbon dioxide tension, and lack of response to Haemophilus growth factors X and V.

Animals↗

Outer membrane protein profiling to distinguish between Haemophilus aegyptius and non-capsulate Haemophilus influenzae biotype III.

Outer membrane protein profiling was used to assist in determining the identity of an isolate of Haemophilus spp. that was presumptively identified as non-capsulate Haemophilus influenzae biotype III. The possibility that this strain was in fact Haemophilus aegyptius was queried because of clinical information and the source of the isolate. Sodium dodecyl-sulphate polyacrylamide gel electrophoresis was used to establish the identity of the isolate as non-capsulate H. influenzae biotype III and no H. aegyptius. Generally, protein profiling compared very favourably with other standard tests for identifying H. aegyptius: the method was easily and rapidly performed and gave an unequivocal result.

Bacterial Outer Membrane Proteins↗

Septicemia and meningoencephalitis in pastured cattle caused by a Haemophilus-like organism ("Haemophilus somnus").

Septicemia and meningoencephalitis developed in 10 pastured cattle 7 months to 3 years of age. Two unrelated herds were involved. Necropsy findings were similar to those previously reported in cattle infected with a Haemophilus-like organism, including multifocal hemorrhages in some muscles, suppurative polyarthritis, and multifocal hemorrhagic thrombi in the brain. A Haemophilus-like organism was isolated from one animal. It was characterized by growth on blood agar or tryptose agar plus a feeder streak under raised carbon dioxide tension, and lack of response to Haemophilus growth factors X and V.

Animals↗

Antimicrobial susceptibility patterns of Haemophilus isolates from children in eleven developing nations. BOSTID Haemophilus Susceptibility Study Group.

The antimicrobial susceptibilities of 426 isolates of Haemophilus species, which were collected as part of a worldwide study of the etiology of acute respiratory disease in children in selected developing countries, were determined. Eleven antibiotics were tested using the recently described Haemophilus Test Medium. There was a low prevalence of antibiotic resistance; 6% of strains were resistant to ampicillin, and 1.6% were resistant to chloramphenicol. Strains resistant to both ampicillin and chloramphenicol were recovered only from Thailand. Susceptibility to penicillin G was also determined; the minimum inhibitory concentrations for penicillin and ampicillin were concordant within one 2-fold dilution in 97% of the isolates. Thus, Haemophilus isolates were as susceptible to penicillin G as they were to ampicillin, and penicillin resistance was infrequent overall. These data provide support for the current protocols for the management of acute respiratory infections in children in developing countries, in which penicillin G is a first-line agent.

Anti-Bacterial Agents↗

Antimicrobial susceptibility of Haemophilus influenzae, Haemophilus parainfluenzae and Moraxella catarrhalis isolated from adult patients with respiratory tract infections in four southern European countries. The ARISE project.

Over a 7-month period in 2000-2001, 1213 Haemophilus influenzae, 112 Haemophilus parainfluenzae and 142 Moraxella catarrhalis isolates were recovered from adult patients with respiratory tract infections. Patients were from four southern European countries (Spain, Italy, Portugal and Greece). The antimicrobial susceptibility of the isolates to 11 antibiotics was determined in a central laboratory. The most active drugs on the basis of MICs were levofloxacin, cefditoren, cefotaxime, cefpodoxime and amoxicillin/clavulanate. MICs > or = 2 mg/l for amoxicillin were found in 19.5, 28.6, and 75.4% of H. influenzae, H. parainfluenzae and M. catarrhalis isolates, respectively. Isolates of H. influenzae and H. parainfluenzae with reduced susceptibility or that were fully resistant to amoxicillin/clavulanate, cefuroxime and clarithromycin were detected (0.2-1.8%) as well as M. catarrhalis resistant to clarithromycin (0.7%). Regular surveys of resistance patterns for antimicrobial agents are necessary.

Adult↗

Decreased Haemophilus colonization in children vaccinated with Haemophilus influenzae type b conjugate vaccine.

OBJECTIVE: The incidence of invasive Haemophilus disease has unexpectedly decreased in unvaccinated children since the introduction of conjugate vaccine in the United States. The purpose of this study was to determine whether conjugate vaccination decreases colonization with Haemophilus influenzae type b. DESIGN: This study was a prospective, bimonthly survey of pharyngeal colonization with H. influenzae type b in children attending day care from October 1987 through September 1989. Vaccination status was determined from the medical record. SUBJECTS: We obtained 1188 pharyngeal cultures from 283 healthy children, 18 to 59 months of age; 51 children had received unconjugated polysaccharide vaccine (PRP), and 89 had received conjugate vaccine (94% PRP-diphtheria toxoid). MEASUREMENTS AND RESULTS: Multivariate analysis was used to test the possibility of an association between vaccination status and the rate of colonization with H. influenzae type b. Among children known to be exposed to at least one child with a positive culture result, the efficacy of conjugate vaccination to prevent H. influenzae type b colonization in an unmatched analysis was 64% (95% confidence interval: 5%, 86%; p = 0.02) and in a matched analysis 81% (95% confidence interval: 7%, 96%; p = 0.02). No effect on colonization was found with PRP vaccination. CONCLUSIONS: Conjugate vaccination decreases H. influenzae type b pharyngeal colonization and thereby may decrease transmission of this agent among healthy children.

Bacterial Proteins↗

Immunogenicity of Haemophilus influenzae type b polysaccharide-outer membrane protein conjugate vaccine in patients who acquired Haemophilus disease despite previous vaccination with type b polysaccharide vaccine.

To investigate the basis of the immune defect in children who acquire invasive Haemophilus disease despite previous vaccination with Haemophilus influenzae type b (Hib) polysaccharide vaccine, we determined the ability of vaccine failure patients with low levels of serum anticapsular antibody (less than 1 microgram/ml) to respond to reimmunization. Thirty-four patients, ranging in age from 27 to 61 months, were vaccinated with either Hib polysaccharide (n = 20) or Hib polysaccharide-outer membrane protein conjugate vaccine (n = 14). All but three of the children had normal serum concentrations of immunoglobulins, including IgG2. The geometric mean serum anticapsular antibody concentration of the group given polysaccharide vaccine increased from 0.27 microgram/ml before vaccination to 0.65 microgram/ml 1 month later (p less than 0.05), but the magnitude of the response was nearly 10-fold less than that of 31 age-matched control children given polysaccharide vaccine (6.3 micrograms/ml, p less than 0.001). In contrast, all 14 patients with vaccine failure who were given conjugate vaccine showed increases of fivefold or more in serum anticapsular antibody (geometric means 0.35 and 12.8 micrograms/ml, respectively; p less than 0.001). All patients with vaccine failure who did not respond to polysaccharide vaccine were subsequently given conjugate vaccine, and all had high antibody responses. Most patients tested showed increases in complement-mediated serum bactericidal activity. These data suggest that immunization with conjugate vaccine confers protection against Hib disease to children who, because of genetic or other reasons, cannot respond to the unconjugated form of the polysaccharide vaccine.

Age Factors↗

Haemophilus haemolyticus: a human respiratory tract commensal to be distinguished from Haemophilus influenzae.

BACKGROUND: Haemophilus influenzae is a common pathogen in adults with chronic obstructive pulmonary disease (COPD). In a prospective study, selected isolates of apparent H. influenzae had an altered phenotype. We tested the hypothesis that these variant strains were genetically different from typical H. influenzae. METHODS: A prospective study of adults with COPD was conducted. Strains of apparent H. influenzae obtained from a range of clinical sources were evaluated by ribosomal DNA sequence analysis, multilocus sequence analysis, DNA-DNA hybridization, and sequencing of the conserved P6 gene. RESULTS: Variant strains were determined to be Haemophilus haemolyticus by means of 4 independent methods. Analysis of 490 apparent H. influenzae strains, identified by standard methods, revealed that 39.5% of sputum isolates and 27.3% of nasopharyngeal isolates were H. haemolyticus. Isolates obtained from normally sterile sites were all H. influenzae. In a prospective study, acquisitions of new strains of H. haemolyticus were not associated with exacerbations of COPD, whereas 45% of acquisitions of new strains of H. influenzae were associated with exacerbations. CONCLUSIONS: Standard methods do not reliably distinguish H. haemolyticus from H. influenzae. H. haemolyticus is a respiratory tract commensal. The recognition that some strains of apparent H. influenzae are H. haemolyticus substantially strengthens the association of true H. influenzae with clinical infection.

Haemophilus↗