Elja Herva

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.

Nasopharyngeal Carriage of Streptococcus pneumoniae in Finnish Children Younger Than 2 Years Old

To describe the natural course of nasopharyngeal carriage of Streptococcus pneumoniae and its relationship to acute otitis media (AOM), 329 Finnish children were followed from ages 2 to 24 months. In total, 3024 nasopharyngeal (NP) swabs (obtained at 10 scheduled healthy visits) and 2007 NP aspirates (obtained during respiratory infections) were cultured. Carriage during health increased gradually (9%-43%) with age. Within 4 age intervals, carriage was lower during health (13%-43%) than during respiratory infection without AOM (22%-45%). Higher proportions of positive samples were found during AOM (45%-56%), in particular during pneumococcal AOM (97%-100%). Antimicrobial treatment reduced carriage only temporarily. The most frequent NP serotypes were 6B, 6A, 11, 19F, and 23F. Both age and health status were important determinants of NP carriage of S. pneumoniae and these features should be considered carefully during analysis of carriage rates.

Incremental effectiveness of pneumococcal vaccine on simultaneously administered influenza vaccine in preventing pneumonia and pneumococcal pneumonia among persons aged 65 years or older.

The effectiveness of simultaneously administered influenza and pneumococcal vaccines vs. influenza vaccine alone in preventing pneumonia, pneumococcal pneumonia and pneumococcal bacteraemia among the elderly was studied. The vaccines were offered to all persons aged 65 years or older (N=43,500) living in 35 administrative districts in Northern Finland. A total of 26,925 persons (62%) decided to participate. Allocation to the vaccination groups took place by year of birth (odd/even). The total follow-up of those vaccinated consisted of 38,037 person years. The incremental effectiveness of the pneumococcal vaccine was -20 (95% CI -50- + 10%) for pneumonia, -20 (95% CI -90- + 20%) for pneumococcal pneumonia and + 60% (95% CI -40- +90%) for pneumococcal bacteraemia. Thus the pneumococcal polysaccharide vaccine did not offer any additional protection from pneumonia among elderly people in Finland although it reduced the incidence of bacteraemia.

Prevention ofotitis media in children by pneumococcal vaccination

A total of 3,340 infants, 95 per cent of them 7 to 9 months old, were randomly vaccinated in a double-blind fashion with either the 14-valent pneumococcal (Pn) polysaccharide vaccine or a saline placebo in three urban areas in Finland. The second dose of the vaccine was given 5 months later. Age and sex distribution, recruitment of infants, and their otitis-related treatment and follow-up were similar in the study areas. Side effects after vaccination were mild and fewer than among older children. Antibody responses to vaccine polysaccharides varied from type to type, but were generally poor, especially to types most prevalent in otitis media. After the first dose of vaccine, the occurrence of otitis visits among the Pn-vaccinated, as compared with controls, showed inter-area differences, but ranged from not more than a 30 per cent reduction at its best to an increase in some areas and in some clinical categories. The respective figures for children with acute otitis media were similar between the vaccination groups and the study areas. The effect of the vaccine on acute otitis media caused by specific Pn types/groups represented in the vaccine was variable but generally poor. Group 6 attacks especially seemed to behave problematically. The second dose of the vaccine did not give additional benefit serologically or clinically. The efficacy of currently available pneumococcal vaccine against otitis media seemed poor in infants.

Demonstration of pneumolysin antibodies in circulating immune complexes—a new diagnostic method for pneumococcal pneumonia☆

Abstract We isolated immune complexes (IC) from the sera obtained from 129 adult patients with community-acquired pneumonia and from 120 healthy controls and measured antibodies to pneumococcal pneumolysin in dissociated complexes. None of the healthy controls had demonstrable pneumolysin-specific IC in their sera irrespective of whether they had high or low serum antibody titers to pneumolysin. By contrast, 62 (48%) of pneumonia patients had pneumolysin-IC in one or more of serum specimens. All 11 patients with positive blood culture for pneumococcus and 86% of those in whom pneumococcal involvement was suggested by culture or antigen detection in sputum or who showed serum antibody response to pneumolysin had pneumolysin antibodies in circulating IC. In addition, pneumolysin-IC were detected in 17 patients without other evidence of pneumococcal infection. The lack of pneumolysin-IC in healthy controls and their presence in patients with pneumococcal pneumonia suggest that the demonstration pneumolysin-IC is a sensitive, reliable method for the diagnosis of pneumococcal pneumonia.

Longitudinal study on pneumococcal carriage during the first year of life in Bangladesh.

Background: The strong herd immunity effect and the serotype replacement associated with the use of the pneumococcal conjugate vaccine have highlighted the importance of asymptomatic pneumococcal carriage. To describe the development of pneumoccoccal carriage in a developing country setting we carried out a longitudinal pneumococcal carriage study in Bangladesh. Methods: Ninety-nine children, born in Savar, Bangladesh between May 2000 and April 2001, were enrolled in the study with their families. Nasopharyngeal samples were collected at prescheduled 2–4 week intervals from the index children and from their family members. The nasopharyngeal swabs were cultured for pneumococcal growth and pneumococci were identified and serotyped by standard methods. Results: We collected 1459 samples (92% of those planned) from the 99 index children and 2865 samples from other family members. The data showed high point prevalences of pneumococcal carriage among newborns (40–50% from 8 weeks of age on), a rapid pneumococcal acquisition with age (50% of the children had been colonized by pneumococci at least once by the age of 8 weeks) and a wide range of different serogroups/types (SGT). SGT 6 and 19 accounted for 35% of the pneumococci isolated from children <1-year-old, followed by SGT 15, 23, and 10 for a total of 56%. The SGT distribution in children up to 9-year-old was similar to that among the <1 year olds, with SGT 6 and 19 predominating. Older children and adults differed from the younger children by not having clearly predominating SGTs. Conclusions: The features found in our study are typical of pneumococcal carriage in developing countries. We believe that results from longitudinal modeling of carriage based on these extensive data can have wide geographic application.

Epidemiological Evidence for Serotype‐Independent Acquired Immunity to Pneumococcal Carriage

BACKGROUND Asymptomatic nasopharyngeal carriage is the main reservoir for transmission of Streptococcus pneumoniae. The rate of both carriage and pneumococcal disease decreases with age. To what extent these changes are the result of developing natural immunity is currently a subject of debate. OBJECTIVE To study the hypothesis that previous carriage induces serotype-independent protective immunity to new colonization. METHODS We compared the rates of pneumococcal acquisition for children with different previous carriage histories. We identified 435 episodes of carriage during the first year of life in follow-up data for 99 Bangladeshi children. Cox regression analysis was adjusted for serotype-specific exposure within the family and other confounding factors. RESULTS Previous pneumococcal carriage was associated with serotype-independent protection from subsequent acquisition (hazard ratio, 0.60 [95% confidence interval, 0.39-0.90]), whereas recent serotype-specific exposure within the family was associated with an 8-fold increase in the rate of acquisition for that serotype. CONCLUSION Our findings are consistent with the hypothesis that serotype-independent protective immunity is stimulated in young children by previous pneumococcal carriage and reduces the rate of new colonization. This immunity has the potential to modulate the development of carriage, irrespective of the colonizing serotype, and to do so starting early in infancy.

Lymphocyte blast transformation responses to mitogens and specific antigens in different clinical phases of multiple sclerosis: a follow-up study

ABSTRACT 28 MS patients were studied at least 5 times for lymphocyte blast transformation responses to several mitogens (PHA, Con, PWM) and specific antigens (PPD, herpes simplex, measles, mumps, rubella), the mean duration of the follow‐up being 15.3 months. Comparison of responses during remissions, exacerbations and ACTH treatment revealed no straight‐forward association between the strength of response and clnical disease activity. Mitogen responses did not differ among various disease phases, but the PPD response was significantly lower during exacerbations than during remissions and still lower during ACTH treatment (P < 0.05, Wilcoxon paired test). In responses to viral antigens, there was the same trend as in the PPD response. However, there were great individual differences in the behaviour of all antigen and mitogen induced lymphocyte responses.

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.

Haemophilus Influenzae in Acute Otitis Media

We studied the occurrence of Haemophilus influenzae (Hi) in 2625 middle ear fluid (MEF) specimens obtained from 523 children with otitis media, aged 3 months to 6 years, between October 1977 and May 1979. In clinically acute cases 12.3% of the MEFs grew Hi; 6.3% (13/206) of the strains were of type b and 4.9% (10/206) were beta-lactamase producing. In the very first acute case of a child 8.0% (21/263) of the MEFs grew Hi, but in acute recurrences it was cultured in 17.0% (184/1082) (p less than 0.001). In non-acute persistent MEFs obtained during control visits Hi was found in no less than 21.7% (198/913); as many as 12.6% (25/198) of them were beta-lactamase producing. Both of these figures, but not the proportion of type b strains (8.6%), were significantly (p less than 0.001 and p less than 0.01, respectively) greater than in clinically acute MEFs. Hi was grown in 13.1% of the acute MEFs taken from children less than 4 years old, but in only 8.6% of the older children (p less than 0.05). The annual survey of all the 1816 Hi strains isolated from the MEFs of acute or subacute cases of otitis media in one laboratory in 1976-81 showed the proportion of beta-lactamase producing strains of all Hi strains to be gradually increasing from 8.0% (17/212) in 1976 to 15.2% (16/105) in 1981 (p less than 0.05).