A nation-wide survey of the prevalence of antimicrobial resistance in Haemophilus influenzae was conducted on isolates collected in 1988-90 from middle ear fluid (MEF), blood, or cerebrospinal fluid (CSF) in infected children or throat samples of healthy children. Altogether 885 strains were examined regarding capsular type b, beta-lactamase production and the minimal inhibitory concentration (MIC) of ampicillin, cefaclor, erythromycin, tetracycline, chloramphenicol, trimethoprim and trimethoprim-sulfamethoxazole for these strains was determined by the agar dilution method. 99% (578/585) of MEF isolates, 93% (112/121) of throat isolates, but only 6% (10/179) of blood/CSF isolates were not of type b (Hib). The rate of beta-lactamase production was 11.4% among Hib strains, 8.0% among non-type b MEF isolates, and 4.5% among non-type b throat isolates. No increase in the prevalence of beta-lactamase production in H. influenzae has taken place in Finland since the early 1980s. Resistance to ampicillin among strains that lacked beta-lactamase activity was rare (0.2%). Of the non-type b MEF and throat isolates, 5.9% and 2.7%, respectively, were resistant to trimethoprim and 3.6% and 2.7%, respectively, to trimethoprim-sulfamethoxazole. Resistance to other drugs was rare (
Consecutive Hemophilus influenzae type b (Hib) isolates (333 total) from children with invasive disease in Finland in 1985-1986 were analyzed. All belonged to the common genetic clusters described in the USA and Europe. However, detailed typing demonstrated some characteristics unique to Hib strains in Finland. Of the isolates, 86% belonged to one of four distinct patterns according to the combination of outer membrane protein subtype, biotype, and lipopolysaccharide serotype: 1-I-1 (25%), 1-II-9 (8%), and 1c-I-1 (18%). Pattern 1-II-9 has not been previously reported; it was most commonly found in the most densely populated area of Finland and among children cared for outside the home. Multilocus enzyme electrophoresis revealed that 87% of isolates with the pattern 1c-I-1 belonged to the electrophoretic type 21.8, which is seldom recovered from patients with invasive Hib disease in other countries.
Timely information on the bacteriology of primary, noncomplicated acute otitis media (AOM) may today be needed more than ever, because of the increasing antimicrobial resistance of its major bacterial causes and because of the potential of new pneumococcal and other bacterial vaccines for prevention of AOM.
The study followed 329 children from 2 to 24 months of age at scheduled healthy visits and sick visits at the study clinic. Whenever AOM was diagnosed during the follow-up, myringotomy was performed and middle ear fluid was aspirated for bacterial culture.
At least one middle ear fluid sample was available from 772 AOM events; Streptococcus pneumoniae (Pnc) was isolated in 201 (26%), Moraxella catarrhalis (Mc) in 177 (23%) and Haemophilus influenzae (Hi) in 174 events (23%). The incidence of Pnc AOM peaked at 12 months of age, whereas the incidence of Mc AOM showed the first peak at 6 months and Hi AOM at 20 months. Pnc AOM showed less prominent seasonality in occurrence than Mc and Hi AOM. Hi was a rare cause of the first 2 AOM episodes (13%) but became increasingly common from the third episode on (32% on average).
Pnc, Mc and Hi were almost equally common findings in AOM. Pnc seems to be the most pathogenic of these three, the role of Mc is increasing and Hi is clearly associated with recurrent AOM.
Isolates from 646 consecutive Finnish Haemophilus influenzae type b (Hib) patients with systemic disease, collected before and during large-scale vaccinations with Hib conjugate vaccines, were analyzed by major outer membrane protein (OMP) subtyping, lipopolysaccharide (LPS) serotyping, and biotyping (BT). Strains with OMP-BT-LPS combinations (clones) 1-I-1 and 1c-I-1 disappeared at the same rate as the disease they were associated with. A preferential decrease in the number of isolates of clone 1-II-1 was recorded, whereas the reduction in disease caused by strains of clone 1-II-9 occurred at a lower rate than expected. The latter clone occurred mainly in the most densely populated area of Finland. Strains belonging to all the common Hib clones were isolated from the 16 infants who acquired Hib disease despite being (partially) vaccinated. Thus, Hib clones disappeared during mass vaccination with conjugate vaccines, although at different rates.
On the basis of intensified surveillance in Finland we report the epidemiology of invasive Haemophilus influenzae type b disease based on 333 consecutive culture-proved cases recorded during 1985 and 1986. The annual incidence rate among children younger than 5 years of age was 52/100,000; 46% of patients had meningitis, 29% had epiglottitis and 25% had other forms of invasive disease. The median age of patients was 27 months, with 45% younger than 2 years of age. Meningitis and epiglottitis were found more often among boys than among girls, whereas the opposite was found among patients with other types of invasive disease (P = 0.015). Among the latter 68% of children with pneumonia or septicemia were 2 years or older compared with 32% of patients with arthritis, cellulitis or pyelonephritis (P = 0.009). These background data are essential for correct interpretation and application of results from trials with H. influenzae type b conjugate vaccines that are currently ongoing in Finland.
The first Finnish trial with Haemophilus influenzae type b vaccine was conducted during 1973-1974. It demonstrated that the polysaccharide vaccine was 90% efficacious in children greater than or equal to 18-24 months old. The immunologically superior polysaccharide-protein conjugate vaccines have been used since 1986 in randomized trials. The PRP-D vaccine (polysaccharide conjugated to diphtheria toxoid) was 90% efficacious when given at 3, 4, and 6 months of age to 58,000 infants. In 1988-1989, the PRP-D vaccine was compared with the HbOC vaccine (oligosaccharide conjugated to CRM197 protein). Follow-up is continuing, but both vaccines seem to be efficacious after two doses in infancy.
Natural immunity to Haemophilus influenzae type b (Hib) invasive disease is based on antibodies arising in response to encounters with Hib or cross-reactive (CR) bacteria. The relative importance of Hib and CR contacts is unknown. We applied a statistical model to estimate the total rate of immunizing infections of Hib and CR prior to wide-scale vaccinations in Finland and the UK. The average rates of these contacts were 0.7 and 1.2 per year per child in Finland and the UK, respectively. Using a rough estimate of 0.1 Hib acquisitions per year per child in the UK based on carriage rates, the proportion of Hib among all immunizing contacts was in the order of 10%, suggesting that CR bacteria have a major role. In general, varying frequency of CR contacts may explain some differences in the pre-vaccination incidence and age-distribution of invasive disease in different countries.
A hierarchical Bayesian regression model is fitted to longitudinal data on Haemophilus influenzae type b (Hib) serum antibodies. To estimate the decline rate of the antibody concentration, the model accommodates the possibility of unobserved subclinical infections with Hib bacteria that cause increasing concentrations during the study period. The computations rely on Markov chain Monte Carlo simulation of the joint posterior distribution of the model parameters. The model is used to predict the duration of immunity to subclinical Hib infection and to a serious invasive Hib disease.