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Haemophilus influenzae: Then and now

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Abstract

Haemophilus influenzae has long been recognised as a major cause of serious infection and mortality in children less than 5 years old. Prior to the introduction ofHaemophilus influenzae type b (Hib) immunisation, the incidence of a child suffering an invasiveHaemophilus infection was 20–50/100,000 in industrialised countries and up to ten times higher in developing regions. The introduction of a Hib vaccine programme results in a rapid and dramatic decline in the incidence of Hib infection in the susceptible childhood population. For example, within two years of the introduction of routine Hib vaccination of infants in the UK, the risk of serious Hib infection had fallen from 1∶600 to 1∶30,000 by 5 years of age. Many other European countries have introduced, or are in the process of introducing, a routine Hib immunisation programme. Because the epidemiology ofHaemophilus influenzae infection is changing so dramatically, it is opportune to reviewHaemophilus influenzae as it was perceived in the pre-vaccine era (the past) and during vaccine implementation (the present), and how its role may change in the post-vaccination era (the future). This review will summarise the historical landmarks that have led to our present-day understanding ofHaemophilus influenzae pathogenicity, the concerns about antibiotic resistance, the features of the host immune response toHaemophilus influenzae, and the introduction of the Hib vaccine. Furthermore, the possible importance of this organism in the future will be discussed.

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References

  1. Turk DC, May JR:Haemophilus influenzae: its clinical importance. English Universities Press, London, 1967, p. 1–134.

    Google Scholar 

  2. Anderson P, Peter G, Johnston RB, Wetterlow LH, Smith DH: Immunization of humans with polyribo-phosphate, the capsular antigen ofHaemophiius influenzae, type b. Journal of Clinical Investigation 1972, 51: 39–44.

    PubMed  Google Scholar 

  3. Moxon ER, Smith AL, Averill DR, Smith DH:Haemophilus influenzae meningitis in infant rats after intranasal inoculation. Journal of Infectious Diseases 1974, 129: 154–162.

    PubMed  Google Scholar 

  4. Peltola H, Käyhty H, Sivonen A, Mäkelä PH:Haemophilus influenzae type b capsular polysaccharide vaccine in children: a double-blind field study of 100,000 vaccinees 3 months to 5 years of age in Finland. Pediatrics 1977, 60: 730–737.

    PubMed  Google Scholar 

  5. Eskola J, Peltola H, Takala AK, Käyhty H, Hakulinen M, Karanko V, Kela E, Rekola P, Ronnberg PR, Samuelson JS, Gordon IK, Makela PH: Efficacy ofHaemophilus influenzae type b polysaccharide-diphtheria toxoid conjugate vaccine in infancy. New England Journal of Medicine 1987, 317: 717–722.

    PubMed  Google Scholar 

  6. Slack MPE, Crook DWM, Jordens JZ, Anderson EC, Falla T, Leaves NI, Booy R, Moxon ER, Connellan T: Molecular and epidemiological aspects ofHaemophilus influenzae infection. Public Health Laboratory Service Microbiology Digest 1993, 10: 122–128.

    Google Scholar 

  7. Nazareth B, Slack MPE, Howard AJ, Waight PA, Begg NT: A survey of invasiveHaemophilus influenzae infections. Communicable Disease Report. CDR Review 1992, 2: R13–R16.

    PubMed  Google Scholar 

  8. Anderson EC, Begg NT, Crawshaw SC, Hargreaves RM, Howard AJ, Slack MPE: Epidemiology of invasiveHaemophilus influenzae infections in England and Wales in the pre-vaccination era (1990–1992). Epidemiology and Infection 1995, 115: 89–100.

    PubMed  Google Scholar 

  9. Gratten M, Barker J, Shann F, Gerega G, Montgomery J, Kajoi M, Lupiwa T: Non-type bHaemophilus influenzae meningitis. Lancet 1985, i: 1343–1344.

    Google Scholar 

  10. Wall RA, Mabey DCW, Corrah PT:Haemophilus influenzae non type b. Lancet 1985, ii: 845.

    Google Scholar 

  11. Bijlmer HA, van Alphen L, Greenwood BM, Brown J, Schneider G, Hughes A, Menon A, Zanen HC, Valkenburg HA: The epidemiology ofHaemophilus influenzae meningitis in children under five years of age in the Gambia, West Africa. Journal of Infectious Diseases 1990, 161: 1210–1215.

    PubMed  Google Scholar 

  12. Lehmann D: Epidemiology of acute respiratory tract infections, especially those due toHaemophilus influenzae, in Papua New Guinean children. Journal of Infectious Diseases 1992, 165, Supplement 1: 20–25.

    Google Scholar 

  13. Weinberg GA, Ghafoor A, Ishaq Z, Nomani NK, Kabeer M, Anwar F, Burney MI, Quershi AW, Musser JM, Selander RK, Granoff DM: Clonal analysis ofHaemophilus influenzae isolated from children from Pakistan with lower respiratory tract infections. Journal of Infectious Diseases 1989, 160: 634–643.

    PubMed  Google Scholar 

  14. Bijlmer HA: World-wide epidemiology ofHaemophilus influenzae meningitis: industrialized versus non-industrialized countries. Vaccine 1991, 9, Supplement: 5–9.

    Google Scholar 

  15. Ward JI, Lum MKW, Hall DB, Silimperi DR, Bender TR: InvasiveHaemophilus influenzae type b disease in Alaska: background epidemiology for a vaccine efficacy trial. Journal of Infectious Diseases 1986, 153: 17–26.

    PubMed  Google Scholar 

  16. Gilbert GL, Clements DA, Broughton S:Haemophilu influenzae type b infections in Victoria, Australia, 1985–87. A population based study to determine the need for immunisation. Pediatric Infectious Disease Journal 1990, 9: 252–257.

    PubMed  Google Scholar 

  17. Farley MM, Stephens DS, Brachman PS, Harvey RC, Smith JD, Wenger JD, the CDC Meningitis Surveillance Group: InvasiveHaemophilus influenzae disease in adults. Annals of Internal Medicine 1992, 116: 806–812.

    PubMed  Google Scholar 

  18. Steinhart R, Reingold AL, Taylor F, Anderson G, Wenger JD: InvasiveHaemophilus influenzae infections in men with HIV infection. Journal of the American Medical Association 1992, 268: 3350–3352.

    PubMed  Google Scholar 

  19. McIntyre P, Jepson R, Leeder S, Irwig L: The outcome of childhoodHaemophilus influenzae meningitis. A population based study. Medical Journal of Australia 1993, 159: 766–772.

    PubMed  Google Scholar 

  20. Murphy TF: InvasiveH. influenzae infections in adults? Another clinical pearl down the drain! Infectious Diseases in Clinical Practice 1994, 3: 41–43.

    Google Scholar 

  21. Deulofeu F, Nava JM, Bella F, Marti C, Morera MA, Font B, Fontanals D, Lite J, Garau J, Calderon A, Coll MT, Uriz S, Pineda V: Prospective epidemiological study of invasiveHaemophilus influenzae disease in adults. European Journal of Clinical Microbiology & Infectious Diseases 1994, 13: 633–638.

    Google Scholar 

  22. Berman S: Epidemiology of acute respiratory infections in children of developing countries. Reviews of Infectious Diseases 1991, 13, Supplement 6: 454–462.

    Google Scholar 

  23. Falla TJ, Dobson SRM, Crook DWM, Kraak WAG, Nichols WW, Anderson EC, Jordens JZ, Slack MPE, Mayon-White D, Moxon ER: Population-based study of non-typableHaemophilus influenzae invasive disease in children and neonates. Lancet 1993, 341: 851–854.

    PubMed  Google Scholar 

  24. van Alphen L, Spanjaard L, Dankert J: Non-typableHaemophilus influenzae invasive disease. Lancet 1993, 341: 1536.

    Google Scholar 

  25. Kostman JR, Sherry BL, Fligner CL, Egaas S, Sheeran P, Baken L, Bauwens JE, Clausen C, Sherer DM, Plorde JJ, Stull ST, Mendelman PM: InvasiveHaemophilus influenzae infections in older children and adults in Seattle. Clinical Infectious Diseases 1993, 17: 389–396.

    PubMed  Google Scholar 

  26. Forbes KJ, Morgan MG, Williams A, Gould IM: Molecular epidemiology of invasiveHaemophilus influenzae in Scotland. Communicable Diseases Scotland 1994, 28: 4–9.

    Google Scholar 

  27. Falla TJ, Crook DWM, Anderson EC, Ward JI, Santosham M, Eskola J, Moxon ER: Characterization of capsular genes inHaemophilus influenzae isolates fromH. influenzae type b vaccine recipients. Journal of Infectious Diseases 1995, 171: 1075–1076.

    PubMed  Google Scholar 

  28. Kroll JS, Hopkins I, Moxon ER: Capsule loss inH. influenzae type b occurs by recombination-mediated disruption of a gene essential for polysaccharide export. Cell 1988, 53: 347–356.

    PubMed  Google Scholar 

  29. Casin I, Grimont F, Grimont PAD: Deoxyribonucleic acid relatedness betweenHaemophilus aegyptius andHaemophilus influenzae. Annals de l'Institut Pasteur/Microbiology 1986, 137B: 155–163.

    Google Scholar 

  30. Quentin R, Goudeau A, Wallace RJ, Smith AL, Selander RK, Musser JM: Urogenital, maternal and neonatal isolates ofHaemophilus influenzae: identification of unusually virulent serologically non-typable clone families and evidence for a newHaemophilus species. Journal of General Microbiology 1990, 136: 1203–1209.

    PubMed  Google Scholar 

  31. Quentin R, Martin C, Musser JM, Pasquier-Picard N, Goudeau A: Genetic characterization of a cryptic genospecies ofHaemophilus causing urogenital and neonatal infections. Journal of Clinical Microbiology 1993, 31: 1111–1116.

    PubMed  Google Scholar 

  32. Takala AK, Clements DA: Socioeconomic risk factors for invasiveHaemophilus influenzae type b disease. Journal of Infectious Diseases 1992, 165, Supplement 1: 11–15.

    Google Scholar 

  33. Fogarty J, Moloney AC, Newell JB: The epidemiology ofHaemophilus influenzae type b disease in the Republic of Ireland. Epidemiology and Infection 1995, 114: 451–463.

    PubMed  Google Scholar 

  34. Howard AJ, Dunkin KT, Millar GW: Nasopharyngeal carriage and antibiotic resistance ofHaemophilus influenzae in healthy children. Epidemiology and Infection 1988, 100: 193–203.

    PubMed  Google Scholar 

  35. Barbour ML, Crook DW, Mayon-White RT: An improved antiserum agar method for detecting carriage ofHaemophilus influenzae type b. European Journal of Clinical Microbiology & Infectious Diseases 1993, 12: 215–217.

    Google Scholar 

  36. Barbour ML, Mayon-White RT, Coles C, Crook DWM, Moxon ER: The impact of conjugate vaccine on carriage ofHaemophilus influenzae type b. Journal of Infectious Diseases 1995, 171: 93–98.

    PubMed  Google Scholar 

  37. Granoff DM, Daum RS: Spread ofHaemophilus influenzae type b: recent epidemiologic and therapeutic considerations. Journal of Pediatrics 1980, 97: 854–860.

    PubMed  Google Scholar 

  38. Plaut AG, Qiu J, Grundy F, Wright A: Growth ofHaemophilus influenzae in human milk: synthesis, distribution, and activity of IgA protease as determined by study ofiga+ and mutantiga− cells. Journal of Infectious Diseases 1992, 166: 43–52.

    PubMed  Google Scholar 

  39. Zwahlen A, Kroll JS, Rubin LG, Moxon ER: The molecular basis of pathogenicity inHaemophilus influenzae: comparative virulence of genetically-related capsular transformants and correlation with changes at the capsulation locus cap. Microbial Pathogenesis 1989, 7: 225–235.

    PubMed  Google Scholar 

  40. Moxon ER, Kroll JS: The role of bacterial polysaccharide capsules as virulence factors. Current Topics in Microbiology and Immunology 1990, 150: 65–85.

    PubMed  Google Scholar 

  41. Tunkel AR, Scheid WM: Pathogenesis and pathophysiology of bacterial meningitis. Clinical Microbiology Reviews 1993, 6: 118–136.

    PubMed  Google Scholar 

  42. Moxon ER, Maskell D:Haemophilus influenzae lipopolysaccharide: the biochemistry and biology of a virulence factor. In: Hormaeche CE, Penn CW, Smyth CJ (ed): Molecular biology of bacterial infection. Society for General Microbiology, Cambridge, 1992, p. 75–96.

    Google Scholar 

  43. Weiser JN: Relationship between colony morphology and the life cycle ofHaemophilus influenzae: the contribution of lipopolysaccharide phase variation to pathogenesis. Journal of Infectious Diseases 1993, 168: 672–680.

    PubMed  Google Scholar 

  44. Weber A, Harris K, Lohrke S, Forney L, Smith AL: Inability to express fimbriae results in impaired ability ofHaemophilus influenzae b to colonize the nasopharynx. Infection and Immunity 1991, 59: 4724–4728.

    PubMed  Google Scholar 

  45. van Alphen L, van Ham SM: Adherence and invasion ofHaemophilus influenzae. Reviews in Medical Microbiology 1994, 5: 245–255.

    Google Scholar 

  46. Sanders JD, Cope LD, Jarosik GP, Maciver I, Latimer JL, Toews GB, Hansen EJ: Reconstitution of a porindeficient mutant ofHaemophilus influenzae type b with a porin gene from nontypeableH. influenzae. Infection and Immunity 1993, 61: 3966–3975.

    PubMed  Google Scholar 

  47. Burroughs M, Prasad S, Cabellos C, Mendelman PM, Tuomanen E: The biologic activities of peptidoglycan in experimentalHaemophilus influenzae meningitis. Journal of Infectious Diseases 1993, 167: 464–468.

    PubMed  Google Scholar 

  48. Roord JJ, Apicella M, Scheid WM: The induction of meningeal inflammation and blood-brain barrier permeability byHaemophilus influenzae type b peptidoglycan. Journal of Infectious Diseases 1994, 170: 254–256.

    Google Scholar 

  49. Leake ER, Holmes K, Lim DJ, DeMaria TP: Peptidoglycan isolated from nontypeableHaemophilus influenzae induces experimental otitis media in the chinchilla. Journal of Infectious Diseases 1994, 170: 1532–1538.

    PubMed  Google Scholar 

  50. Jarosik GP, Sanders JD, Cope LD, Muller-Eberhard U, Hansen EJ: A functional tonB gene is required for both utilization of heme and virulence expression byHaemophilus influenzae type b. Infection and Immunity 1994, 62: 2470–2477.

    PubMed  Google Scholar 

  51. Jankowski R, Wayoff M, Lion C, Burdin JC, Foliguet B: Virulence ofHaemophilus influenzae. In: Ringelmann R (ed): Update onHaemophilus influenzae: how virulence, incidence and resistance affect treatment. Royal Society of Medicine Services, London, 1987, p. 41–48.

    Google Scholar 

  52. Moxon ER, Wilson R: The role ofHaemophilus influenzae in the pathogenesis of pneumonia. Reviews of Infectious Diseases 1991, 13, Supplement 6: 518–527.

    Google Scholar 

  53. LiPuma JJ, Sharetzsky C, Edlind TD, Stull TL: Haemocin production by encapsulated and nonencapsulatedHaemophilus influenzae. Journal of Infectious Diseases 1992, 165, Supplement 1: 118–119.

    Google Scholar 

  54. Murphy TF, Apicella MA: NontypableHaemophilus influenzae: a review of clinical aspects, surface antigens, and the human immune response to infection. Reviews of Infectious Diseases 1987, 9: 1–14.

    PubMed  Google Scholar 

  55. Sirakova T, Kolattukudy PE, Murwin D, Billy J, Leake E, Lim D, deMaria T, Bakaletz L: Role of fimbriae expressed by nontypeableHaemophilus influenzae in pathogenesis of and protection against otitis media and relatedness of the fimbrin subunit to outer membrane protein A. Infection and Immunity 1994, 62:2002–2020.

    PubMed  Google Scholar 

  56. Rubin LG, St. Gerne JW: Role of lipooligosaccharide in virulence of the Brazilian purpuric fever clone ofHaemophilus influenzae biogroup aegyptius for infant rats. Infection and Immunity 1993, 61: 650–655.

    PubMed  Google Scholar 

  57. Falla TJ, Anderson EC, Chappell MM, Slack MPE, Crook DWM: Cross-reaction of spontaneous capsule-deficientHaemophilus influenzae type b mutants with type-specific antisera. European Journal of Clinical Microbiology & Infectious Diseases 1993, 12: 147–148.

    Google Scholar 

  58. Kroll JS, Ely S, Moxon ER: Capsular typing ofHaemophilus influenzae with a DNA probe. Molecular and Cellular Probes 1991, 5: 375–379.

    PubMed  Google Scholar 

  59. Leaves NI, Falla TJ, Crook DWM: The elucidation of novel capsular genotypes ofHaemophilus influenzae type b using the polymerase chain reaction. Journal of Medical Microbiology 1995, 43: 120–124.

    PubMed  Google Scholar 

  60. Jordens JZ, Falla T, Slack MPE:Haemophilus influenzae — the past, the present and the future. In: Duerden BI (ed): 25 years on — an update on topics selected from the first volume of the journal. Journal of Medical Microbiology 1994, 41: 149–167.

  61. Falla TJ, Crook DWM, Brophy LN, Maskell D, Kroll JS, Moxon ER: PCR for capsular typing ofHaemophilus influenzae. Journal of Clinical Microbiology 1994, 32: 2382–2386.

    PubMed  Google Scholar 

  62. Anderson JR, Smith MD, Kibbler CC, Holton J, Scott GM: A nosocomial outbreak due to non-encapsulatedHaemophilus influenzae: analysis of plasmids coding for antibiotic resistance. Journal of Hospital Infection 1994, 27: 17–27.

    PubMed  Google Scholar 

  63. Jordens JZ, Leaves NI, Anderson EC, Slack MPE: Polymerase chain reaction-based strain characterization of noncapsulateHaemophilus influenzae. Journal of Clinical Microbiology 1993, 31: 2981–2987.

    PubMed  Google Scholar 

  64. Goetz MB, O'Brien H, Musser JM, Ward JI: Nosocomial transmission of disease caused by nontypeable strains ofHaemophilus influenzae. American Journal of Medicine 1994, 96: 342–347.

    PubMed  Google Scholar 

  65. van Alphen L: The molecular epidemiology ofHaemophilus influenzae. Reviews in Medical Microbiology 1993, 4: 159–166.

    Google Scholar 

  66. Leaves NI, Jordens JZ: Development of a ribotyping scheme forHaemophilus influenzae type b. European Journal of Clinical Microbiology & Infectious Diseases 1994, 13: 1038–1045.

    Google Scholar 

  67. Pennington TH:Haemophilus species and clones. Reviews in Medical Microbiology 1993, 4: 50–59.

    Google Scholar 

  68. Musser JM, Kroll JS, Granoff DM, Moxon ER, Brodeur BR, Campos J, Dabemaut H, Frederiksen W, Hamel J, Hammond G, Helby EA, Jonsdottir KE, Kabeer M, Kallings I, Khan WN, Killan M, Knowles K, Koornhof HJ, Law B, Li KI, Montgomery J, Pattison PE, Piffaretti J-C, Takala AK, Thong ML, Wall RA, Ward JI, Selander RK: Global genetic structure and molecular epidemiology of encapsulatedHaemophilus influenzae. Reviews of Infectious Diseases 1990, 12: 75–111.

    PubMed  Google Scholar 

  69. van Alphen L, Geelen L, Jonsdottir K, Takala AK, Käyhty H, Zanen HC: Distinct geographic distribution of subtypes ofHaemophilus influenzae type b in western Europe. Journal of Infectious Diseases 1987, 156:216–218.

    PubMed  Google Scholar 

  70. Bijlmer HA, van Alphen L, Geelen-van den Broek L, Greenwood BM, Valkenburg HA, Dankert J: Molecular epidemiology ofHaemophilus influenzae type b in the Gambia. Journal of Clinical Microbiology 1992, 30:386–390.

    PubMed  Google Scholar 

  71. Gilbert GL, Clements DA: Distribution ofHaemophilus influenzae type b outer membrane protein subtypes in different ethnic groups in Australia. Journal of Infectious Diseases 1993, 168: 255.

    PubMed  Google Scholar 

  72. van Belkum A, Duim B, Regelink A, Möller L, Quint W, van Alphen L: Genomic DNA fingerprinting of clinicalHaemophilus influenzae isolates by polymerase chain reaction amplification: comparison with major outermembrane protein and restriction fragment length polymorphism analysis. Journal of Medical Microbiology 1994, 41: 63–68.

    PubMed  Google Scholar 

  73. Forbes KJ, Bruce KD, Ball A, Pennnington TH: Variation in length and sequence of porin (ompP2) alleles of non-capsulateHaemophilus influenzae. Molecular Microbiology 1992, 6: 2107–2112.

    PubMed  Google Scholar 

  74. Hobson RP, Williams A, Rawal K, Pennington TH, Forbes KJ: Incidence and spread ofHaemophilus influenzae on an Antarctic base determined using the polymerase chain reaction. Epidemiology and Infection 1995, 114: 93–103.

    PubMed  Google Scholar 

  75. Coté S, Sanschagrin F, Dargis M, Simard JL, Roy PH, MacDonald NE, Rabin HR, Bergeron MG, Malouin F: Molecular typing ofHaemophilus influenzae using a DNA probe and multiplex PCR. Molecular and Cellular Probes 1994, 8: 23–37.

    PubMed  Google Scholar 

  76. Smith-Vaughan HC, Sriprakash KS, Mathews JD, Kemp DJ: Long PCR-ribotyping of nontypeableHaemophilus influenzae. Journal of Clinical Microbiology 1995, 33: 1192–1195.

    PubMed  Google Scholar 

  77. Machka K: Development of antimicrobial resistance toHaemophilus influenzae in Europe. In: Ringelmann R (ed): Update onHaemophilus influenzae: how virulence, incidence and resistance affect treatment. Royal Society of Medicine Services, London, 1987, p. 1–9.

    Google Scholar 

  78. Powell M, Williams JD: Detection of ampicillin resistantHaemophilus influenzae in United Kingdom laboratories. Journal of Clinical Pathology 1988, 41: 716–719.

    PubMed  Google Scholar 

  79. Snell JJS: Problems in susceptibility testing — findings of UK NEQAS for microbiology. Journal of Antimicrobial Chemotherapy 1994, 33: 1–6.

    Google Scholar 

  80. Scriver SR, Hoban DJ, McGeer A, Moore TC, Walmsley SL, Low DE: Surveillance of susceptibility testing methodologies forHaemophilus influenzae in Canada, including evaluation of disk diffusion test. Journal of Clinical Microbiology 1994, 32: 2013–2015.

    PubMed  Google Scholar 

  81. Rubin LG, Medeiros AA, Yolken RH, Moxon ER: Ampicillin treatment failure of apparently β-lactamase-negativeHaemophilus influenzae type b meningitis due to novel β-lactamase. Lancet 1981, ii: 1008–1010.

    Google Scholar 

  82. Tenover FC, Huang MB, Rasheed JK, Persing DH: Development of PCR assays to detect ampicillin resistance genes in cerebrospinal fluid samples containingHaemophilus influenzae. Journal of Clinical Microbiology 1994, 32: 2729–2737.

    PubMed  Google Scholar 

  83. Powell M, Fah YS, Seymour A, Yuan M, Williams JD: Antimicrobial resistance inHaemophilus influenzae from England and Scotland in 1991. Journal of Antimicrobial Chemotherapy 1992, 29: 547–554.

    PubMed  Google Scholar 

  84. van Alphen L, Bol P, Arends A, Riemens T, Geelen L: Comparison of antibiotic resistant and sensitive strains ofHaemophilus influenzae type b in the Netherlands by outer-membrane protein subtyping. European Journal of Clinical Microbiology & Infectious Diseases 1988, 7: 309–311.

    Google Scholar 

  85. James PA, Hossain FK, Lewis DA, White DG: β-lactam susceptibility ofHaemophilus influenzae strains showing reduced susceptibility to cefuroxime. Journal of Antimicrobial Chemotherapy 1993, 32: 239–246.

    PubMed  Google Scholar 

  86. Powell M: Antimicrobial resistance inHaemophilus influenzae. Journal of Medical Microbiology 1988, 27: 81–87.

    PubMed  Google Scholar 

  87. Jorgensen JH: Summary of the 1986 USA NationalHaemophilus influenzae Surveillance Study. In: Ringelmann R (ed): Update onHaemophilus influenzae: how virulence, incidence and resistance affect treatment. Royal Society of Medicine Services, London, 1987, p. 11–16.

    Google Scholar 

  88. Kibsey PC, Rennie RP, Rushton JE: Disk diffusion versus broth microdilution susceptibility testing ofHaemophilus species andMoraxella catarrhalis using seven oral antimicrobial agents: application of updated susceptibility guidelines of the National Committee for Clinical Laboratory Standards. Journal of Clinical Microbiology 1994, 32: 2786–2790.

    PubMed  Google Scholar 

  89. Gould IM, Forbes KJ, Gordon GS: Quinolone resistantHaemophilus influenzae. Journal of Antimicrobial Chemotherapy 1994, 33: 187–188.

    PubMed  Google Scholar 

  90. van Ketel RJ, de Wever B, van Alphen L: Detection ofHaemophilus influenzae in cerebrospinal fluids by polymerase chain reaction DNA amplification. Journal of Medical Microbiology 1990, 33: 271–276.

    PubMed  Google Scholar 

  91. Rådström P, Bäckman A, Qian N, Kragsbjerg P, Påhlson C, Olcén P: Detection of bacterial DNA in cerebrospinal fluid by an assay for simultaneous detection ofNeisseria meningitidis, Haemophilus influenzae, and streptococci using a seminested PCR strategy. Journal of Clinical Microbiology 1994, 32: 2738–2744.

    PubMed  Google Scholar 

  92. Levy J, Verhaegen G, de Mol P, Couturier M, Dekegel D, Butzler JP: Molecular characterization of resistance plasmids in epidemiologically unrelated strains of multiresistantHaemophilus influenzae. Journal of Infectious Diseases 1993, 168: 177–187.

    PubMed  Google Scholar 

  93. Lévesque C, Piché L, Larose C, Roy PH: PCR mapping of integrons reveals several novel combinations of resistance genes. Antimicrobial Agents and Chemotherapy 1995, 39: 185–191.

    PubMed  Google Scholar 

  94. Dimopoulou ID, Kraak WAG, Anderson EC, Nichols WW, Slack MPE, Crook DW: Molecular epidemiology of unrelated clusters of multiresistant strains ofHaemophilus influenzae. Journal of Infectious Diseases 1992, 165: 1069–1075.

    PubMed  Google Scholar 

  95. Clairoux N, Picard M, Brochu A, Rousseau N, Gourde P, Beauchamp D, Parr TR, Bergeron MG, Malouin F: Molecular basis of the non-β-lactamase-mediated resistance to β-lactam antibiotics in strains ofHaemophilus influenzae isolated in Canada. Antimicrobial Agents and Chemotherapy 1992, 36: 1504–1513.

    PubMed  Google Scholar 

  96. Georgeopapadakou NH: Penicillin-binding proteins and bacterial resistance to β-lactams. Antimicrobial Agents and Chemotherapy 1993, 37: 2045–2053.

    PubMed  Google Scholar 

  97. Reid AJ, Simpson IN, Harper PB, Amyes SGB: Ampicillin resistance inHaemophilus influenzae: identification of resistance mechanisms. Journal of Antimicrobial Chemotherapy 1987, 20: 645–656.

    PubMed  Google Scholar 

  98. Cartwright KAV, Begg NT, Hull D: Chemoprophylaxis for secondaryHaemophilus influenzae type b disease. Communicable Diseases Report 1991, 1: R2-R6.

    Google Scholar 

  99. Green M, Li KI, Wald ER, Guerra N, Byers C: Duration of rifampin chemoprophylaxis for contacts of patients infected withHaemophilus influenzae type b. Antimicrobial Agents and Chemotherapy 1992, 36: 545–547.

    PubMed  Google Scholar 

  100. Perkins BA, Tondella MLC, Bortolotto IM, Takano OA, da Silva GA, Irino K, de Cunto Brandileone MC, Harrison LH, Wenger JD, Broome CV, the Brazilian Purpuric Fever Study Group: Comparative efficacy of oral rifampin and topical chloramphenicol in eradicating conjunctival carriage ofHaemophilus influenzae biogroup aegyptus. Pediatric Infectious Disease Journal 1992, 11: 717–721.

    PubMed  Google Scholar 

  101. Murphy TV, White KE, Pastor P, Gabriel L, Medley F, Granoff DM, Osterholm MT: Declining incidence ofHaemophilus influenzae type b disease since introduction of vaccination. Journal of the American Medical Association 1993, 269: 246–248.

    PubMed  Google Scholar 

  102. Wenger JD: Impact ofHaemophilus influenzae type b vaccines on the epidemiology of bacterial meningitis. Infectious Agents and Disease 1994, 2: 324–332.

    Google Scholar 

  103. Booy R, Taylor SA, Dobson SRM, Isaacs D, Sleight G, Aitken S, Griffiths H, Chapel H, Mayon-White RT, Macfarlane JA, Moxon ER: Immunogenicity and safety of PRP-T conjugate vaccine given according to the British accelerated immunisation schedule. Archives of Disease in Childhood 1992, 67: 475–178.

    PubMed  Google Scholar 

  104. Kaplan SL, Lauer BA, Ward MA, Wiedermann BL, Boyer KM, Dukes CM, Schaffer DM, Paisley J, Mendelson R, Pedreira F, Fritzell B: Immunogenicity and safety ofHaemophilus influenzae type b-tetanus protein conjugate vaccine alone or mixed with diphtheria-tetanuspertussis vaccine in infants. Journal of Pediatrics 1994, 124: 323–327.

    PubMed  Google Scholar 

  105. Clemens JD, Ferreccio C, Levine MM, Horwitz I, Rao MR, Edwards KM, Fritzell B: Impact ofHaemophilus influenzae type b polysaccharide-tetanus protein conjugate vaccine on responses to concurrently administered diphtheria-tetanus-pertussis vaccine. Journal of the American Medical Association 1992, 267: 673–678.

    PubMed  Google Scholar 

  106. Teare EL, Fairley CK, White J, Begg NT: Efficacy of Hib vaccine. Lancet 1994, 344: 828–829.

    Google Scholar 

  107. Peltola H, Kilpi T, Anttila M: Rapid disappearance ofHaemophilus influenzae type b meningitis after routine childhood immunisation with conjugate vaccines. Lancet 1992, 340: 592–594.

    PubMed  Google Scholar 

  108. van Alphen L, Spanjaard L, van der Ende A, Dankert J: Predicted disappearance ofHaemophilus influenzae type b meningitis in Netherlands. Lancet 1994, 344: 195.

    Google Scholar 

  109. Zielen S, Ahrens P, Hofmann D: Efficacy of Hib vaccine. Lancet 1994, 344: 828.

    Google Scholar 

  110. von Kries R, Windfuhr A, Lúcking A: PreventingHaemophilus influenzae meningitis: Germany's experience. Lancet 1994, 344: 469.

    Google Scholar 

  111. Bulkow LR, Wainwright RB, Letson GW, Chang SJ, Ward JI: Comparative immunogenicity of fourHaemophilus influenzae type b conjugate vaccines in Alaska Native infants. Pediatric Infectious Disease Journal 1993, 12: 484–492.

    PubMed  Google Scholar 

  112. Barington R, Gyhrs A, Kristensen K, Heilmann C: Opposite effects of actively and passively acquired immunity to the carrier on responses of human infants to aHaemophilus influenzae type b conjugate vaccine. Infection and Immunity 1994, 62: 9–14.

    PubMed  Google Scholar 

  113. Kim KH, Park MK, Peeters CC, Poolman JT, Shearer MH, Kennedy RC, Nahm MH: Comparison of nonhuman primate antibodies againstHaemophilus influenzae type b polysaccharide with human antibodies in oligoclonality and in vivo protective potency. Infection and Immunity 1994, 62: 2426–2431.

    PubMed  Google Scholar 

  114. Barbour ML, Booy R, Crook DWM, Griffiths H, Chapel HM, Moxon ER, Mayon-White D:Haemophilus influenzae type b carriage and immunity four years after receiving theHaemophilus influenzae oligosaccharide-CRM197 (HbOC) conjugate vaccine. Pediatric Infectious Disease Journal 1993, 12: 478–484.

    PubMed  Google Scholar 

  115. Mohle-Boetani JC, Ajello G, Breneman E, Deaver KA, Harvey C, Plikaytis BD, Farley MM, Stephens DS, Wenger JD: Carriage ofHaemophilus influenzae type b in children after widespread vaccination with conjugateHaemophilus influenzae type b vaccines. Pediatric Infectious Disease Journal 1993, 12: 589–693.

    PubMed  Google Scholar 

  116. Takala AK, Santosham M, Almeido-Hill J, Wolff M, Newcomer W, Reid R, Käyhty H, Esko E, Mäkelä PH: Vaccination withHaemophilus influenzae type b meningococcal protein conjugate vaccine reduces oropharyngeal carriage ofHaemophilus influenzae type b among American Indian children. Pediatric Infectious Disease Journal 1993, 12: 593–599.

    PubMed  Google Scholar 

  117. Kauppi M, Saarinen L, Käyhty H: Anti-capsular polysaccharide antibodies reduce nasopharyngeal colonization byHaemophilus influenzae type b in infant rats. Journal of Infectious Diseases 1993, 167: 365–371.

    PubMed  Google Scholar 

  118. Slack MPE: InvasiveHaemophilus influenzae disease: the impact of Hib immunisation. Journal of Medical Microbiology 1995, 42: 75–77.

    PubMed  Google Scholar 

  119. Marsh MJ, Murdoch IA: Acute epiglottitis after Hib vaccination. Lancet 1994, 344: 829.

    Google Scholar 

  120. Greenberg DP, Vadheim CM, Partridge S, Chang S-J, Chiu C-Y, Ward JI, the Kaiser-UCLA Vaccine Study Group: Immunogenicity ofHaemophilus influenzae type b tetanus toxoid conjugate vaccine in young infants. Journal of Infectious Diseases 1994, 70: 76–81.

    Google Scholar 

  121. Walter EB, Simmons SS, Clements DA: Anti-polyribosylribitol phosphate antibody levels 5 years after a primary series ofHaemophilus influenzaetype b conjugate vaccine. Journal of Infectious Diseases 1994, 170: 1050–1051.

    PubMed  Google Scholar 

  122. Musser JM, Kroll JS, Moxon ER, Seiander RK: Evolutionary genetics of the encapsulated strains ofHaemophilus influenzae. Proceedings of the National Academy of Sciences of the USA 1988, 85: 7758–7762.

    PubMed  Google Scholar 

  123. Kroll JS, Moxon ER, Loynds BM: An ancestral mutation enhancing the fitness and increasing the virulence ofHaemophilus influenzae type b. Journal of Infectious Diseases 1993, 168: 172–176.

    PubMed  Google Scholar 

  124. Kroll JS, Moxon ER, Loynds BM: Natural genetic transfer of a putative virulence-enhancing mutation toHaemophilus influenzae type a. Journal of Infectious Diseases 1994, 169: 676–679.

    PubMed  Google Scholar 

  125. Musser JM, Barenkamp SJ, Granoff DM, Seiander RK: Genetic relationships of serologically nontypable and serotype b strains ofHaemophilus influenzae. Infection and Immunity 1986, 52: 183–191.

    PubMed  Google Scholar 

  126. St. Gerne JW, Takala A, Esko E, Falkow S: Evidence for capsule gene sequences among pharyngeal isolates of nontypeableHaemophilus influenzae. Journal of Infectious Diseases 1994, 169: 337–342.

    PubMed  Google Scholar 

  127. Kroll JS, Moxon ER: Capsulation in distantly related strains ofHaemophilus influenzae type b: genetic drift and gene transfer at the capsulation locus. Journal of Bacteriology 1990, 172: 1374–1379.

    PubMed  Google Scholar 

  128. Bell J, Grass S, Jeanteur D, Munson RS: Diversity of the P2 protein among nontypeableHaemophilus influenzae isolates. Infection and Immunity 1994, 62: 2639–2643.

    PubMed  Google Scholar 

  129. Duim B, van Alphen L, Eijk P, Jansen HM, Danken J: Antigenic drift of nonencapsulatedHaemophilus influenzae major outer membrane protein P2 in patients with chronic bronchitis is caused by point mutations. Molecular Microbiology 1994, 11: 1181–1189.

    PubMed  Google Scholar 

  130. Nelson MB, Murphy TF, van Keulen H, Rekosh D, Apicella MA: Studies on P6, an important outer-membrane protein antigen ofHaemophilus influenzae. Reviews of Infectious Diseases 1988, 10, Supplement 2: 331–336.

    Google Scholar 

  131. Janson H, Ruan M, Forsgren A: Limited diversity of the protein D gene (hpd) among encapsulated and nonencapsulatedHaemophilus influenzae strains. Infection and Immunity 1993, 61: 4546–4552.

    PubMed  Google Scholar 

  132. Williams P, Griffiths E: Bacterial transferrin receptors-structure, function and contribution to virulence. Medical Microbiology and Immunology 1992, 181: 301–322.

    PubMed  Google Scholar 

  133. Hampton CM, Barenkamp SJ, Granoff DM: Comparison of outer membrane protein subtypes ofHaemophilus influenzae type b isolates from healthy children in the general population and from diseased patients. Journal of Clinical Microbiology 1983, 18: 596–600.

    PubMed  Google Scholar 

  134. Kroll JS: The genetics of encapsulation inHaemophilus influenzae. Journal of Infectious Diseases 1992, 165, Supplement 1: 93–96.

    PubMed  Google Scholar 

  135. Givner LB, Woods CR, Abramson JS: The practice of pediatrics in the era of vaccines effective againstHaemophilus influenzae type b. Pediatrics 1994, 93: 680–681.

    PubMed  Google Scholar 

  136. Baer M, Vuento R, Vesikari T: Increase in bacteraemic pneumococcal infections in children. Lancet 1995, 345: 661.

    Google Scholar 

  137. Jones DM: Current and future trends in immunization against meningitis. Journal of Antimicrobial Chemotherapy 1993, 31: 93–99.

    PubMed  Google Scholar 

  138. Fleischmann RD, Adams MD, White O, Clayton RA, Kirkness EF, Kerlavage AR, Bult CJ, Tomb J-F, Dougherty BA, Merrick JM, McKenney K, Sutton G, FitzHugh W, Fields C, Gocayne JD, Scott J, Shirley R, Li-Ing L, Glodek A, Kelley JM, Waldman JF, Phillips CA, Spriggs T, Hadblom E, Cotton MD, Utterback TR, Hanna MC, Nguyen DT, Saudek DM, Brandon RC, Fine LD, Fritchman JL, Fuhrmann JL, Geoghagen NSM, Gnehm CK, McDonald LA, Small KA, Fraser CM, Smith HO, Venter JC: Whole-genome random sequencing and assembly ofHaemophilus influenzae Rd. Science 1995, 269: 496–512.

    PubMed  Google Scholar 

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  1. Public Health Laboratory Service Haemophilus Reference Laboratory, John Radcliffe Hospital, Level 6/7, OX3 9DU, Headington, Oxford, UK

    J. Z. Jordens & M. P. E. Slack

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Jordens, J.Z., Slack, M.P.E. Haemophilus influenzae: Then and now. Eur. J. Clin. Microbiol. Infect. Dis. 14, 935–948 (1995). https://doi.org/10.1007/BF01691374

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