Invasive haemophilus influenzae infection. Clinical, immunologic and pathogenic aspects

Abstract

Invasive Haemophilus influenzae (Hi) infection, predominantly manifested as acute meningitis and epiglottitis, is a serious disease with associated mortality and residual handicap. Prevention of the disease is possible by vaccination against Hi serotype b (Hib). In a prospective study in a Swedish population before large scale Hib vaccination of infants was introduced, the incidence of invasive Hi infection, in children 0-4 years of age, was 55/100.000/year. Hib caused 98 % of the cases. In a study on laboratory reports, the incidence in Sweden was reduced by 90 % two years after the initiation of the vaccination programme. The pre vaccination incidence in adults was high; 2.8/100.000/year and 51% of the cases were caused by Hib. No significant impact on the incidence in children older than 4 years and adults was found by the vaccination programme during the first two years. Acute epiglottitis during the pre vaccination era was studied retrospectively, and the incidence was higher than previously reported. Blood cultures confirmed Hi as the most prevalent etiologic pathogen in children, but in adult epiglottitis, the aetiology was often unknown. Cultures from nasopharynx had a low diagnostic value. The case fatality rate of invasive Hi infection was 2.9 % and residual sequelae were diagnosed in 5.8 %. These cases were all caused by Hib. The most prevalent sequelae was sensorineural hearing loss after meningitis. Adults who had recovered from Hi meningitis in childhood were investigated and the prevalence of a late progression of pure tone audiometric abnormality was documented. In these cases, hearing loss was peripheral, with cochlea as the suspected site of the lesion, and subclinical vestibular pathology was over-represented. However, brain dysfunction and central auditory disturbance, unpredictable by conventional audiometry was also found. The functional capacity of Hib vaccination induced antibodies was studied with three assays. The induced serum bactericidal and opsonophagocytic activity usually correlated to the serum concentration of antibodies against the Hib capsular polysaccharide (PRP). However, the prevalence of non-functional antibodies indicates that a functional evaluation is desirable in addition to serum concentrations of antibodies in bacterial vaccine trials. A chemiluminescence (CL)-index assay proved more useful than phagocytic killing in measuring serum opsonic action, and the ELISA and CL-index showed that PRP conjugated to diphtheria toxoid was more immunogenic than PRP conjugated to outer membrane protein complex of meningococcus serogroup B. In an overlay assay of radiolabeled bacteria by thin-layer chromatography, Hi recognised three glycosphingolipid (GSL) specificities; lactosylceramide, gangliotri-/gangliotetraosylceramide and neolactotetraosylceramide. Target tissues for Hi were investigated for relevant GSLs and Hi bound to neolactotetraosylceramide of polymorphonuclear leukocytes and oropharyngeal epithelium. The epithelial expression of neolactotetraosylceramide, although as a minor compound, serve as a relevant carbohydrate receptor for Hi in the upper respiratory tract.