Ritva Syrjänen

Bacteriology of acute otitis media in a cohort of finnish children followed for the first two years of life

Background. 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. Methods. 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. Results. 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). Conclusions. 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.

Natural Development of Antibodies to Pneumococcal Surface Protein A, Pneumococcal Surface Adhesin A, and Pneumolysin in Relation to Pneumococcal Carriage and Acute Otitis Media

Pneumococcal surface protein A (PspA), pneumococcal surface adhesin A (PsaA), and pneumolysin (Ply) are common to virtually all Streptococcus pneumoniae isolates. They are immunogenic and protective against pneumococcal challenge in animals and are the major candidates for a protein-based pneumococcal vaccine for humans. However, little is known of the natural development of antibodies to these proteins in humans. The objective of this study was to evaluate the natural development of antibodies to PspA, PsaA, and Ply in relation to pneumococcal infection and carriage in young children. Serum antibodies to these proteins were measured by EIA in children at ages 6, 12, 18, and 24 months and in their mothers. All age groups were capable of producing antibodies to the 3 proteins. The antibody concentrations increased with age and were strongly associated with pneumococcal exposure, whether by carriage or infection (acute otitis media).

Invasiveness of serotypes and clones of Streptococcus pneumoniae among children in Finland

ABSTRACT Streptococcus pneumoniae (the pneumococcus) causes diseases from otitis media to life-threatening invasive infection. The species is extremely antigenically and clonally diverse. We wished to determine odds ratios (ORs) for serotypes and clones of S. pneumoniae that cause invasive disease in Finland. A total of 224 isolates of S. pneumoniae from cases of invasive disease in children <2 years of age in Finland between 1995 and 1999 were serotyped, and sequence types (STs) were determined by multilocus sequence typing. These STs were compared with a previously published carriage data set. STs from invasive disease were significantly less diverse than those from carriage (invasive disease, 0.038 ± 0.01; carriage, 0.019 ± 0.005). The ORs of serotypes 14, 18C, 19A, and 6B were significantly greater than 1, indicating association with invasive disease. The ORs of 6A and 11A were significantly less than 1. The difference between 6A and 6B is significant, which suggests that relatively subtle changes in the capsule may have a dramatic effect upon disease potential. We found that ST 156, the Spain9V-3 clone which mainly expressed serotype 14 in Finland, is strongly associated with invasive disease (OR, 10.1; 95% confidence interval, 1.3 to 79.5). Significant associations with invasive disease were also detected for STs 482, 191, 124, and 138, and associations with carriage were detected for STs 485 and 62. These results demonstrate the invasive phenotype of the serotype 14 variant of the Spain9V-3 clone and differences between members of the same serogroup in invasive disease potential.

Using Multilocus Sequence Data To Define the Pneumococcus

We investigated the genetic relationships between serotypeable pneumococci and nonserotypeable presumptive pneumococci using multilocus sequence typing (MLST) and partial sequencing of the pneumolysin gene (ply). Among 121 nonserotypeable presumptive pneumococci from Finland, we identified isolates of three classes: those with sequence types (STs) identical to those of serotypeable pneumococci, suggesting authentic pneumococci in which capsular expression had been downregulated or lost; isolates that clustered among serotypeable pneumococci on a tree based on the concatenated sequences of the MLST loci but which had STs that differed from those of serotypeable pneumococci in the MLST database; and a more diverse collection of isolates that did not cluster with serotypeable pneumococci. The latter isolates typically had sequences at all seven MLST loci that were 5 to 10% divergent from those of authentic pneumococci and also had distinct and divergent ply alleles. These isolates are proposed to be distinct from pneumococci but cannot be resolved from them by optochin susceptibility, bile solubility, or the presence of the ply gene. Complete resolution of pneumococci from the related but distinct population is problematic, as recombination between them was evident, and a few isolates of each population possessed alleles at one or occasionally more MLST loci from the other population. However, a tree based on the concatenated sequences of the MLST loci in most cases unambiguously distinguished whether a nonserotypeable isolate was or was not a pneumococcus, and the sequence of the ply gene fragment was found to be useful to resolve difficult cases.

Presence of specific viruses in the middle ear fluids and respiratory secretions of young children with acute otitis media.

The purpose of the study was to investigate the presence of different viruses in middle ear fluids and nasopharyngeal aspirates in young children with acute otitis media. Two cohorts of children (N = 329 and 611) were followed from 2 to 24 months of age in Finland in two prospective studies (Finnish Otitis Media Cohort Study and Finnish Otitis Media Vaccine Trial). During the study period, nasopharyngeal and middle ear fluid specimens for each acute otitis media event were examined for eight (Cohort Study) or ten (Vaccine Trial) common respiratory viruses; adenoviruses, influenza viruses A and B, parainfluenza viruses 1, 2, and 3, respiratory syncytial virus (RSV), enteroviruses, parechoviruses, and rhinoviruses. Picornaviruses (rhinoviruses, enteroviruses, and parechoviruses) were determined by reverse transcription PCR while antigen detection was used for the other viruses. A virus was present in either nasopharyngeal or middle ear specimen in 54% of events in the first cohort and in 67% of events in the second. Rhinoviruses formed the most common virus group detected (41–32%), followed by enteroviruses (25%, sought in the second cohort only) and respiratory syncytial virus (RSV) (10%). All the other viruses represented jointly 8–10% of the events. In conclusion, using the methods described in this study, a specific virus infection was diagnosed in two thirds of all acute otitis media events in young children. Picornavirus RNA was detected in association with more than a half of all acute otitis media events. The use of PCR‐based methods for the other respiratory viruses might have increased further the overall virus detection rate in acute otitis media. J. Med. Virol. 72:241–248, 2004.

Ability of Pneumococcal Serotypes and Clones To Cause Acute Otitis Media: Implications for the Prevention of Otitis Media by Conjugate Vaccines

ABSTRACT The relative abilities of pneumococcal serotypes and strains (clones) to cause acute otitis media (AOM) were investigated by comparing the serotypes and genotypes of pneumococci recovered from cases of AOM (n = 149) in children <2 years of age with those from nasopharyngeal carriage (n = 288) in age-matched controls from the same region. The odds ratio (OR) for association of pooled vaccine serotypes with AOM was found to be slightly elevated over unity, although this was not significantly different from that of pooled nonvaccine or vaccine-related serotypes. Comparing individual serotypes, 19F and 23F had 2- to 2.5-fold higher ORs, although these were not markedly different from the ORs of nonvaccine serotypes. None of the major clones had an OR that was significantly greater than the average, and the differences in ORs among serotypes and clones were much less than those for invasive disease, suggesting little variation in their ability to cause AOM. We conclude that serotype replacement may reduce the long-term efficacy of these vaccines against AOM.

Pneumococcal acute otitis media in relation to pneumococcal nasopharyngeal carriage

Background: Acute otitis media (AOM) is closely associated with viral upper respiratory tract infections, but the most common microbial agent found in the middle ear fluid during AOM is Streptococcus pneumoniae (Pnc). Pnc is also a common colonizer of the nasopharynx, and its prevalence is further increased during the viral infection. The aim of this study was to investigate the interplay between viral infection, pneumococcal acquisition and carriage in the development of Pnc AOM. Methods: Pnc carriage was assessed in a longitudinal study of 329 infants at scheduled visits at 3, 6, 9, 12, 15 and 18 months of age (N = 1715). The clinical outcome of the first episode of respiratory infection (“sick visit,” N = 774) in the following 3-month period was recorded. The occurrence and timing of Pnc AOM in relation to serotype specific carriage at the start of the observation period were assessed. Results: The occurrence, timing and duration of symptoms of the sick visits or the frequency of overall AOM were not associated with preceding pneumococcal carriage. Pnc AOM was in each case associated with concurrent carriage and 3.8 times (95% confidence interval, 1.4–10.0) more often with carriage acquired after the start of the observation period than with carriage already present at the scheduled visit. In all, 79% (55 of 70) of Pnc AOM events were caused by a serotype acquired after the start of the period. Conclusion: The majority of Pnc AOM events develop in association with newly acquired carriage of pneumococcus.

Common Respiratory Infections Early in Life May Reduce the Risk of Atopic Dermatitis

Infections that occur early in life may protect against atopic disease later in life. To investigate the relationship between common acute respiratory infections and atopic dermatitis in early childhood, we closely observed a cohort of 329 children from the ages of 2 to 24 months. We assessed the effect of proven viral infections and acute otitis media on the occurrence of atopic dermatitis. If the child had his or her first respiratory infection before the age of 6 months, the childs remaining risk of developing atopic dermatitis was reduced by 49% (95% confidence interval, -24% to 79%). The individual risk of developing atopic dermatitis was similarly reduced after infection experienced at >/=6 months of age, but the remaining risk was low, because most cases of atopic dermatitis had manifested by this time. Our results are consistent with the hypothesis that early infections may reduce the risk of atopic disease.

Effectiveness of the live attenuated and the inactivated influenza vaccine in two-year-olds - a nationwide cohort study Finland, influenza season 2015/16.

Although widely recommended, influenza vaccination of children is part of the national vaccination programme only in few countries. In addition to Canada and the United States (US), in Europe Finland and the United Kingdom have introduced live attenuated influenza vaccine (LAIV) for healthy children in their programmes. On 22 June 2016, the US Advisory Committee on Immunizations Practices, voted against further use of LAIV due to no observed vaccine effectiveness (VE) over three consecutive influenza seasons (2013/14 to 2015/16). We summarise the results of a nationwide, register-based cohort study (N=55,258 of whom 8,086 received LAIV and 4,297 TIV); all outcome (laboratory-confirmed influenza), exposure (vaccination) and confounding variable data were retrieved from four computerised national health registers, which were linked via a unique personal identity code assigned to all permanent Finnish residents regardless of nationality. Our study provides evidence of moderate effectiveness against any laboratory-confirmed influenza of the quadrivalent LAIV vaccine (VE: 51%; 95% confidence interval (CI): 28–66%) as well as the inactivated trivalent vaccine (VE: 61%; 95% CI: 31–78%) among two-year-olds during the influenza season 2015/16 in Finland. Based on these data, Finland will continue using LAIV for young children in its National Immunisation Programme this coming influenza season.

The value of nasopharyngeal culture in predicting the etiology of acute otitis media in children less than two years of age

Background: In selecting treatment of acute otitis media (AOM), knowledge of its etiology would be valuable. We revisited the possibility to use the nasopharyngeal culture of Streptococcus pneumoniae (Pnc) and Haemophilus influenzae (Hi) for predicting their presence in the middle ear fluid (MEF) during AOM. Methods: The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of bacterial culture of the nasopharyngeal aspirate (NPA) in predicting the presence of the same pathogen in the MEF were assessed during AOM events among children followed from 2 to 24 months of age. Results: The data comprised 586 AOM events. For Pnc, the sensitivity and NPV were high, 99% (95% confidence interval = 95–100%) and >99% (97–100%), respectively. The specificity and PPV were relatively low, 63% (57–68%) and 50% (43–56%). For Hi, the sensitivity and the NPV were lower (77%, 69–83% and 93%, 90–95%) than for Pnc, but the specificity and the PPV were higher (88%, 85–91% and 64%, 56–71%). The quantity of Pnc and Hi in the NPA was clearly related to their presence in the MEF. If both Pnc and Hi were found in the nasopharynx, Hi was more likely cultured from MEF. Conclusion: Together with clinical and epidemiologic features of AOM, the nasopharyngeal culture can be helpful in selecting specific antimicrobial therapy.