Haemophilus influenzae: from the post-vaccination era to antibiotic resistance

Abstract

27 September 2000In the last decade, two major scientific achievements havedeeply changed our understanding of the epidemiology, clinicalsignificance and laboratory research of the human pathogenHaemophilus influenzae: the dramatic effect of H. influenzae typeb(Hib)conjugatevaccinesinpreventing invasiveinfectionsduetothisorganismintheearly1990s,andthepublicationoftheH.influenzae genome sequence in 1995, which has provided greatoportunities for research in the fields of gene expression andfunction, evolutionary biology, pathogenicity and others [1–3].In addition, in the last 5 years, acquisition of new antibioticresistance to drugs like fluorquinolones and amoxicillin-clavulanic acid has been described [4,5].H. INFLUENZAETYPE B CONJUGATE VACCINESAND SEROTYPE REPLACEMENTBefore vaccination, the annual European incidence rate ofinvasive Hib diseases in children under 5 years of age wasbetween 20 and 60 per 100000, with wide geographic varia-tions.About 60%ofcasesweremeningitis.Countrieswithhighvaccination coverage have experienced sharp reductions (90–100%) in their Hib incidence. In 1998, the crude Europeanincidence (per 100000 population) of Hib invasive disease forchildren under 5years, and children under 1year was 1.28 and2.88, respectively [6]. Several studies have indicated that Hibcarriage is reduced by vaccination with conjugate vaccine [7],conferringso-calledherdimmunity,whichmayalsoexplainthereduction of Hib infections in non-vaccinated groups, like veryyoung and older children [8]. Although Hib is predominantly adisease of childhood, infections can occur in the adult popula-tion, who may serve as a continuing reservoir of infection forsusceptible individuals [6]. Hib conjugate vaccines differ inbiochemicalcompositionandimmunogenicity,andmayvaryintheir long-term efficacyand effect on Hib carriage. It would beadvisable to maintain carriage surveillance of Hib and otherHaemophilus serotypes in populations with immunizationprograms.In the USA, after widespread use of conjugate vaccines inthe general population, the number of reported Hib invasivediseasecaseshasdeclinedby99%intheperiod1987–97makingfeasible the goal to eliminate Hib disease [9]. However, re-emergence of Hib invasive disease in a well-vaccinated popula-tion in Alaska has been reported recently following a change inHibvaccine regimen; ongoing carriage and transmission of Hibin the population contributed to disease resurgence [10].The worldwide analysis of the Hib diseases burden, beforeand after the Hib vaccine became available, has recently beencarriedoutindetail[11].Itisestimatedthatintherichestpartofthe world, which can afford Hib vaccination programs, 38000cases of all Hib invasive diseases in children 0–4years old areprevented each year; worldwide figures are far less impressive asonly 8.5% of cases of Hib invasive infection in children (38000out of 445000) are estimated to be prevented, not includingpneumonia [11]. According to the World Health Organization,Hib still causes 3 million cases of serious disease and 400000–700000 deaths per year in young children worldwide [11].In the Hib post-vaccination era, accurate laboratory surveil-lance of serotype should be carried out for all cases of invasiveH. influenzae disease. Serotype information is essential to [1]:evaluate vaccine efficacy and eventual vaccine failure cases[2]; evaluate changes in the epidemiology of invasive infectionsdue to othercapsule types and/or non-typeablestrains. InvasiveH. influenzae infections including meningitis can occur in fullyHibvaccinatedchildren;thissituationmayor maynotindicateapossible case of Hibvaccine failure. Careful serotype evaluationis needed; to avoid false-positive and false-negative results,polymerasechainreaction(PCR)-basedgenotyping isavailable.Although Hib disease now occurs primarily among under-vaccinated children and infants too young to have completedthe primary series of vaccination, cases of true vaccine failureoccur [12]. A systematic evaluation of risk factors associatedwith vaccine failure should always be carried out [9]. Amongthe cases of vaccine failure, potentially predisposing host factorslike prematurity, malignancy and immunoglobulin deficiency