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      Invasive Haemophilus influenzae infections in Germany: impact of non-type b serotypes in the post-vaccine era

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          Abstract

          Background

          Haemophilus influenzae type b (Hib) vaccination led to a significant decrease in invasive bacterial infections in children. The aim of this study was to assess a potential shift to more non-type b invasive infections in a population with high Hib vaccination coverage and to compare the burden of suffering between children with Hib, capsulated non-b and non-capsulated Hi infections.

          Methods

          Cases with confirmed invasive Hi infections were ascertained through two independent nationwide active surveillance systems in 1998–2005. Information on possible predisposing conditions and clinical information was available from 2001 onwards.

          Results

          The total number of reported non-type b Hi cases varied between 10 cases in 1998, 27 in 2000 and 14 in 2005. In each year, non-capsulated serotypes outnumbered capsulated non-type b ones. 192 cases were detected in 2001–2005, more than one half was non-type b and 88% of the non-type b cases were non-capsulated. For cases with Hib/capsulated non-type b infections the most common clinical presentation was meningitis (67% each); 89%/78% had no potential predisposing condition, 75%/72% completely recovered from disease and 6% (each) died. In contrast, meningitis was diagnosed in 34% of the non-capsulated Hi infections, septicaemia in 28% and pneumonia 21%; 62% had no potential predisposing condition, 83% completely recovered and 3% died.

          Conclusion

          There was no increase in non-type b Hi invasive infections during 8 years of active surveillance in Germany. Invasive disease due to non-type b Hi is not confined to children with risk factors. In patients with capsulated non-type b Hi infections the proportion of meningitis cases is similar to Hib, but double as high as in non-capsulated Hi.

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          Most cited references30

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          PCR for capsular typing of Haemophilus influenzae.

          A PCR method for the unequivocal assignment of Haemophilus influenzae capsular type (types a to f) was developed. PCR primers were designed from capsule type-specific DNA sequences cloned from the capsular gene cluster of each of the six capsular types. PCR product was amplified only from the capsular type for which the primers were designed. Product was confirmed by using either an internal oligonucleotide or restriction endonuclease digestion. A total of 172 H. influenzae strains of known capsular type (determined genetically) comprising all capsular types and noncapsulate strains were tested by PCR capsular typing. In all cases the PCR capsular type corresponded to the capsular genotype determined by restriction fragment length polymorphism analysis of the cap region. When used in conjunction with PCR primers derived from the capsular gene bexA, capsulate, noncapsulate, and capsule-deficient type b mutant strains could be differentiated. PCR capsular typing overcomes the problems of cross-reaction and autoagglutination associated with the serotyping of H. influenzae strains. The rapid and unequivocal capsular typing method that is described will be particularly important for typing invasive H. influenzae strains isolated from recipients of H. influenzae type b vaccine.
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            Decline of childhood Haemophilus influenzae type b (Hib) disease in the Hib vaccine era.

            Effective Haemophilus influenzae type b (Hib) conjugate vaccines were first licensed for use in US children at least 18 months old in December 1987 and for infants at least 2 months old in October 1990. We evaluated trends in Hib disease associated with licensure of Hib conjugate vaccines. Data from two sources, an intensive laboratory-based active surveillance system and the National Bacterial Meningitis Reporting System (NBMRS), were used separately to evaluate disease incidence. Data from vaccine manufacturers on Hib vaccine doses distributed in the United States were compared with trends in Hib disease incidence. The age-specific incidence of Hib disease among children less than 5 years old decreased by 71% from 37 per 100,000 persons in 1989 to 11 per 100,000 persons in 1991 (active surveillance data). Haemophilus influenzae meningitis incidence decreased by 82% between 1985 and 1991 (NBMRS data). Increases in doses of Hib vaccine distributed in the United States coincided with steep declines in Hib disease. Both surveillance systems showed decreased rates of Hib disease in infants less than 1 year old before vaccine was licensed for use in this age group. Haemophilus influenzae type b disease incidence in persons at least 12 years old and pneumococcal meningitis incidence in children less than 5 years old did not change substantially during the same period; therefore, decreased Hib disease in children less than 5 years old is not likely to be explained solely by changes in surveillance sensitivity or decreases in bacterial disease due to changes in medical practice. Our data suggest that conjugate vaccines have already had a marked impact on the incidence of Hib disease in the United States, preventing an estimated 10,000 to 16,000 cases of Hib disease in 1991. The decline of disease in infants less than 1 year old before licensure for this age group warrants further investigation.
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              A taxonomic study of the genus Haemophilus, with the proposal of a new species.

              M Kilian (1976)
              A collection of 426 Haemophilus strains isolated from people with infectious diseases and from the normal flora of mucous membranes in humans and various animal species was studied in an attempt to revise and improve the taxonomy of the genus Haemophilus. The examinations included the determination of a number of biochemical and physiological properties, of which several had not previously been applied to the taxonomy of haemophili. The resulting data reavealed many hitherto unrecognized characters of taxonomic significance and several of the species can now be more accurately defined. The classification presented is supported by the DNA base composition of a large number of representative strains. A diagnostic key to the different taxa is presented. Haemophilus influenzae and H. parainfluenzae have been subdivided into a number of biotypes. It is possible to demonstrate a relationship between the individual biotypes of H. influenzae and the origin of the strains assigned to them. The results indicate that H. aegyptius, H. parahaemolyticus and H. paraphrohaemolyticus do not merit specific status. Four unnamed taxa of V-factor-dependent haemophili have been recognized. The name Haemophilus segnis is proposed for one of these taxa, which consists mainly of strains isolated from the human oral cavity. It is demonstrated that the name H. Ducreyi has been used for different groups of bacteria, and that only one of these groups can legitimately be assigned to the genus Haemophilus. Haemolytic V-factor-dependent strains from swine, previously included in H. parahaemolyticus, are significantly different from strains of human origin and should be named H. pleuropneumoniae. None of the strains from swine and fowls were haemin-dependent. The relationships of these strains to the species H. suis and H. gallinarum, and to H. parasuis and H. paragallinarum are discussed. Haemophilus piscium is shown not to belong to the genus Haemophilus. The taxonomic position of H. aphrophilus is uncertain and its possible relationship to Actinobacillus actinomycetemcomitans requires further study. The positive correlation found between the ecology of the strains studied and their affiliation with the different taxa is discussed.
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                Author and article information

                Journal
                BMC Infect Dis
                BMC Infectious Diseases
                BioMed Central
                1471-2334
                2009
                20 April 2009
                : 9
                : 45
                Affiliations
                [1 ]Department Epidemiology, Institute for Social Pediatrics and Adolescent Medicine, Ludwig-Maximilians-University, Munich, Germany
                [2 ]Robert-Koch-Institute, Berlin, Germany
                [3 ]Division Paediatric Infectiology, Johannes-Gutenberg-University, Mainz, Germany
                Article
                1471-2334-9-45
                10.1186/1471-2334-9-45
                2678273
                19379490
                218e9861-23a5-4319-8aba-b598f2540865
                Copyright ©2009 Kalies et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 25 November 2008
                : 20 April 2009
                Categories
                Research Article

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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