Pneumococcal surface adhesin A (PsaA) and pneumolysin (Ply) are common to virtually all Streptococcus pneumoniae isolates, and they are immunogenic and protective against pneumococcal challenge in experimental animals. We have recently shown production of antibodies to PsaA and Ply in young children, but data on the immune response to these antigens during culture-confirmed pneumococcal infection are lacking.
To evaluate whether young children respond to S. pneumoniae by producing antibodies to PsaA and Ply during acute otitis media (AOM).
A cohort of 329 children was followed prospectively from the age of 2 months to the age of 2 years. Paired sera were obtained during episodes of AOM and used to measure antibodies to PsaA and Ply by enzyme-linked immunosorbent assay. S. pneumoniae cultured from the middle ear fluid was taken as evidence of pneumococcal AOM. The presence of S. pneumoniae in the nasopharyngeal aspirate collected in connection of AOM or any other respiratory infection or in the nasopharyngeal swab collected at scheduled visits was taken to indicate pneumococcal carriage and thus a history of previous contact with S. pneumoniae.
Children with previous pneumococcal contacts had high anti-PsaA and anti-Ply concentrations in the acute phase sera regardless of the nature (AOM or carriage) of the current pneumococcal contact. Of the children with no previous pneumococcal contact, those with current pneumococcal AOM had lower antibody concentrations than those with current pneumococcal carriage only. Anti-PsaA and anti-Ply responses were found in children with current pneumococcal contact. The antibody response was strongly associated with low acute phase antibody concentration, but not significantly with age and the nature of the current pneumococcal contact.
We showed that infants are capable of developing a specific antibody response to the pneumococcal proteins PsaA and Ply during AOM.
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.
To explore the effect of a pneumococcal conjugate vaccine on the risk of otitis media with effusion and to search for subgroups in which the vaccine had a higher or lower effect.
Analyses were performed on data from the Finnish Otitis Media Vaccine Trial, a randomised controlled double-blind trial to evaluate the efficacy of pneumococcal conjugate vaccination against acute otitis media. Data on the vaccination effect against otitis media with effusion were obtained by means of symptom interview and pneumatic otoscopy during pre-scheduled follow-up visits at the age of 7 and 24 months. Two endpoint definitions were considered: otitis media/tube (otitis media or tympanostomy tube in situ (OM/T)) as the primary endpoint and otitis media with effusion as the secondary endpoint. No evidence was found of an age-dependent association with vaccination effect. Therefore, the final marginal logistic regression analyses were performed on the combined data from the two follow-up visits.
The risk of otitis media tended to be lower in the pneumococcal vaccine group. The odds ratio for otitis media/tube was 0.94 (95% confidence interval 0.77-1.14) and the odds ratio for otitis media with effusion was 0.90 (95% confidence interval 0.69-1.19). Presence of older siblings increased the risk of otitis media/tube and otitis media with effusion at 7 months of age. In addition, it appeared that children without older siblings and attending day-care at 24 months of age tended to benefit more from the pneumococcal conjugate vaccine. In this subgroup, the odds ratio for otitis media/tube was 0.81 (95% confidence interval 0.55-1.20) and for otitis media with effusion the odds ratio was 0.43 (95% confidence interval 0.22-0.86).
The effect of pneumococcal conjugate vaccination on the risk of otitis media with effusion was concordant with the efficacy seen against acute otitis media, although not distinguishable from no effect in the overall analysis. In children without older siblings, vaccination appeared to reduce the point prevalence of otitis media with effusion; this effect was not apparent in children with older siblings.
To assess the effect of a recent previous visit to a physician on the outcome of meningitis in children.
Evaluation of data from children examined by a physician and sent home, either the previous day or 2 to 4 days before meningitis was diagnosed, and children whose meningitis was diagnosed at once. The patients were examined daily during hospitalization, neurologic examinations were repeated at 2 weeks and 3 and 6 months after discharge, and hearing was assessed 2 or more months after discharge.
Eighteen pediatric hospitals in Finland from 1984 through 1991.
A total of 325 children aged 3 months to 15 years with bacterial meningitis.
Clinical and laboratory findings on admission, recovery during hospitalization, mortality, and neurologic abnormalities at 6 months of follow-up.
In 74% of the patients, meningitis was diagnosed at once, 14% had visited a physician on the previous day, and 11% had seen a physician 2 to 4 days before diagnosis. The group seen 2 to 4 days earlier had a better level of consciousness, less frequent seizures, and more respiratory symptoms and otitis media than the other groups. The cerebrospinal fluid leukocyte count, white blood cell count, and erythrocyte sedimentation rate were highest and the cerebrospinal fluid glucose concentration was lowest in the children who had visited a physician 2 to 4 days earlier, although they also had lower cerebrospinal fluid protein and urine sodium and potassium levels. This group had the most rapid return to normal consciousness. There was no difference in the incidence of hearing impairment or neurologic sequelae. Even the mortality was virtually the same in the three groups: 4%, 4%, and 3% in the "same day," "previous day," and "2 to 4 days earlier" groups, respectively.
Children who had visited a physician the previous day or 2 to 4 days before meningitis was diagnosed did not exhibit an increased frequency of hearing impairment, other neurologic abnormalities, or overall adverse outcome compared with children whose meningitis was diagnosed at once.
Viral upper respiratory infections (URIs) are considered major risk factors for acute otitis media (AOM) in young children. We studied the epidemiology and relative roles of different viruses in respiratory infections in a cohort of 329 Finnish children followed from 2 months to 2 years of age.
A nasopharyngeal aspirate (NPA) was collected whenever the child had signs and/or symptoms of URI and tested for the presence of common respiratory virus antigens or infectivity/nucleic acid (only rhinoviruses). Possible repeated detections of a given virus during a 30-day period were considered to represent a single designated virus-specific episode. AOM and URI episodes were defined in a similar way.
At least one virus was detected in 837 (41.7%) of the 2005 NPA specimens examined. Rates of URI and virus-specific episodes showed expected seasonal variation with major peak occurrences coinciding with or preceding those of AOM. The proportions of rhinoviruses, respiratory syncytial (RS) virus, parainfluenza virus (PIV) type 3, influenza virus A and adenoviruses were 63.1, 14.7, 6.7, 6.7 and 6.2% of the total of 761 virus-specific episodes. Influenza virus B, PIV1 and PIV2 were each responsible for approximately 1% of the episodes. AOM was diagnosed in 870 URI cases (43.4%) and in 43.3% of cases associated with a virus-positive NPA. The latter figure was clearly higher (57.7%) for RS virus-positive specimens.
The seasonal coincidence of URI and AOM demonstrated the obvious role of URI in the pathogenesis of AOM. The occurrence of rhinoviruses and RS virus in URI was strikingly more common than that of any other virus tested. Although rhinoviruses were definitely the most frequently found viruses in NPA specimens, the association of RS virus with concurrent AOM was relatively higher than that of any other virus.
The interpretation of negative pressure tympanograms as indicators of the presence of middle ear fluid has been ambiguous. Our purpose was to assess the occurrence and implications of negative pressure tympanograms and to study their association with bacterial pathogens in otitis media.
Altogether 329 infants were enrolled at a well-baby clinic for the Finnish Otitis Media Cohort Study, a longitudinal prospective cohort study. The children were closely followed in a special study clinic from 2 to 24 months of age for respiratory diseases, especially acute otitis media. Children were examined at the study clinic with tympanometry and pneumatic otoscopy whenever visiting the study clinic for respiratory disease. Myringotomy with aspiration was performed if middle ear fluid was suspected in otoscopy. Occurrence of middle ear fluid in ears with negative pressure tympanograms (less than -100 daPa) was assessed. Nested case control design matched by visit type (acute or follow-up visit) and month of visit was used for analysis of association of bacterial pathogens and tympanometric results.
Middle ear fluid was encountered in 15% of ears with negative tympanometric peak pressure, a lower proportion than described previously. In otitis media with a negative tympanometric peak pressure, 71% of bacterial cultures remained negative for the main pathogens, compared to 36% in matched controls (P
Mortality from meningitis caused by Haemophilus influenzae type b (Hib), a disease that affects mainly infants and young children, can reach 5% in industrialised countries and ten times that in non-industrialised countries. To determine the efficacy of vaccination against Hib, we carried out a retrospective survey of the incidence of Hib meningitis over five decades in the Greater Helsinki area of Finland, where all children with bacterial meningitis are treated in one of three centres. Except for a meningococcal epidemic in the early 1970s, Hib was the leading cause of childhood bacterial meningitis until the Hib conjugate vaccines changed the picture profoundly. In 1986-87 the polysaccharide-diphtheria toxoid conjugate (PRP-D) was given experimentally to 50% of infants. In 1988-89 all infants were vaccinated, 50% with PRP-D, 50% with another conjugate vaccine, the oligosaccharide-CRM197 protein conjugate (HbOC). Since 1990 a third conjugate vaccine, the polysaccharide-tetanus toxoid (PRP-T), has been administered routinely to all infants. The vaccines were administered at age 3-6 months, with a booster dose at 14-18 months. In the first 5 years of the Hib vaccination programme the number of cases of Hib meningitis in children aged 0-4 years fell sharply, from 30 in 1986 (the first year of the programme) to none in 1991. The decline contrasts sharply with the rising trend up to the mid 1980s. Vaccination seems to be the only explanation for the observed change in the epidemiology of Hib meningitis.