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Pleural effusion (PE), a complication of community-acquired pneumonia (CAP), is usually attributed to a bacterial infection. Nonetheless, viral infections have not been investigated routinely. We searched for bacterial and viral infections among 277 children hospitalized with CAP. Among these children 206 (74%) had radiographic confirmation, of whom 25 (12%) had PE. The aetiology was established in 18 (72%) PE cases: bacterial (n = 5; 28%), viral (n = 9; 50%), and viral-bacterial (n = 4; 22%) infections were found. Infection by rhinovirus (n = 3), enterovirus, Streptococcus pneumoniae (n = 2 each), Haemophilus influenzae, Moraxella catarrhalis, Mycoplasma pneumoniae, influenza A virus, and respiratory syncytial virus (RSV) (n = 1 each) were detected as probable sole infections. Parainfluenza virus 1/3 + influenza A virus and RSV + influenza A virus (n = 1 each) were identified as mixed viral-viral infections. Probable viral non-bacterial infection was identified in a third of the cases with CAP and PE. It is advisable to investigate viral as well as bacterial infections among children with CAP and PE.

Community-acquired pneumonia (CAP) is a common cause of morbidity among children. Evidence on seasonality, especially on the frequency of viral and bacterial causative agents is scarce; such information may be useful in an era of changing climate conditions worldwide. To analyze the frequency of distinct infections, meteorological indicators and seasons in children hospitalized for CAP in Salvador, Brazil, nasopharyngeal aspirate and blood were collected from 184 patients aged < 5 y over a 21-month period. Fourteen microbes were investigated and 144 (78%) cases had the aetiology established. Significant differences were found in air temperature between spring and summer (p = 0.02) or winter (p < 0.001), summer and fall (p = 0.007) or winter (p < 0.001), fall and winter (p = 0.002), and on precipitation between spring and fall (p = 0.01). Correlations were found between: overall viral infections and relative humidity (p = 0.006; r = 0.6) or precipitation (p = 0.03; r = 0.5), parainfluenza and precipitation (p = 0.02; r = -0.5), respiratory syncytial virus (RSV) and air temperature (p = 0.048; r = -0.4) or precipitation (p = 0.045; r = 0.4), adenovirus and precipitation (p = 0.02; r = 0.5), pneumococcus and air temperature (p = 0.04; r = -0.4), and Chlamydia trachomatis and relative humidity (p = 0.02; r = -0.5). The frequency of parainfluenza infection was highest during spring (32.1%; p = 0.005) and that of RSV infection was highest in the fall (36.4%; p < 0.001). Correlations at regular strength were found between several microbes and meteorological indicators. Parainfluenza and RSV presented marked seasonal patterns.

Empirical antibiotic use is prescribed in managing children with pneumonia worldwide. We assessed the usefulness of procalcitonin (PCT) and interferon-alpha (IFN-alpha) in differentiating viral from bacterial pneumonia. Among 159 hospitalized children, pneumonia was diagnosed based on clinical complaints plus pulmonary infiltrate. Aetiology was investigated for 9 viruses and 4 atypical and 3 typical bacteria. PCT and IFN-alpha were measured in the serum sample collected on admission. Eight patients had bacteraemic infections, 38 had non-bacteraemic typical infections, and 19 patients had atypical bacterial infections. Viral and unknown aetiology was established in 57 (36%) and 34 (21%) cases, respectively. Three patients with bacterial infection without collected blood culture were excluded. IFN-alpha (IU/ml) was detectable in 20 (13%) cases. The difference among median PCT values of the bacteraemic (4.22; 1.56-7.56), non-bacteraemic typical bacterial (1.47; 0.24-4.07), atypical bacterial (0.18; 0.06-1.03) and only viral (0.65; 0.11-2.22) subgroups was significant (p = 0.02). PCT was > or =2 ng/ml in 52 (33%) cases. The presence of IFN-alpha was associated with PCT <2 ng/ml (90% vs. 64%, p = 0.02). The negative predictive value (95% confidence interval) of PCT > or =2 ng/ml was 95% (89-100%), 89% (78-100%), 93% (85-100%) for differentiation of bacteraemic from viral, atypical bacterial and non-bacteraemic typical bacterial infection, respectively, and 58% (49-68%) for differentiation between bacterial and viral infection. PCT may be useful in identifying bacteraemia among children hospitalized with community-acquired pneumonia. IFN-alpha was uncommonly detected.

The present study investigated the utility of rapid microbiological methods in the aetiological diagnosis of community acquired pneumonia (CAP) according to the severity of CAP. Between 1999 and 2004, 384 adult patients with CAP were studied prospectively. In addition to standard microbiological methods, PCR and antigen detection techniques were used to identify pathogens. A total of 230 microbial agents in 209 patients were identified, with 134 (58.2%) identified by antigen detection or PCR tests. Of these 134 microbial agents, 95 (70.9%) were identified only by these rapid methods. Streptococcus pneumoniae urinary antigen detection was positive in 24.3% (81/333) of the patients with a diagnostic yield of 38.7% in those with severe pneumonia. Respiratory viral antigen detection was positive in 11.1% (35/314) of the patients with the highest diagnostic yield (20.3%) in patients with severe pneumonia. Mycoplasma pneumoniae PCR was positive in 7.5% (13/174) of the patients, all of whom were low-risk patients. Only 1 case of Chlamydia pneumoniae was identified by PCR. In conclusion, besides yielding the aetiological diagnosis rapidly, new methods add to the total diagnostic yield in CAP. The diagnostic yield of rapid methods differs according to the severity of the pneumonia.

The aim of the study was to evaluate whether IFN-alpha/beta-inducible MxA protein expression in children receiving anticancer treatment can be used as an indicator for virus infections during the febrile episodes. Twenty-six children with mainly hematological malignancies entered the study. Children with laboratory-confirmed virus infections had clearly elevated MxA protein levels compared to their counterparts with bacterial or unknown etiology. MxA protein expression increased moderately following the administration of cytostatic agents, even though these children had no clinical signs of infection.

Serological methods are routinely used in the diagnosis of viral and atypical bacterial respiratory infections. Recently, they have also been applied to typical bacteria, such as Streptococcus pneumoniae. The aim of this study was to determine the aetiology of paediatric community-acquired pneumonia (CAP) in both ambulatory and hospitalized patients, by using antibody assays. During a 15-month prospective surveillance, paired sera were studied for antibodies to 14 microbes in 101 children with symptoms of acute infection and infiltrates compatible with pneumonia on chest radiographs. A potential causative agent was detected in 66 (65%) patients. Evidence of bacterial, viral and mixed viral-bacterial infection was demonstrated in 44%, 42% and 20% of the CAP cases, respectively. The most commonly found agents included Mycoplasma pneumoniae (27%), Pneumococcus (18%) and respiratory syncytial virus (17%). Human metapneumovirus (hMPV) was detected in 5 (5%) children. Pneumococcal infections were evenly distributed among the age groups studied. Our results confirm the role of S. pneumoniae in paediatric CAP at all ages, those of M. pneumoniae at >2 y of age and emphasize the emerging role of hMPV. The high proportion of mixed viral-bacterial infections highlights the need to treat all children with CAP with antibiotics.

Only a few previous studies have focused on the use or bronchoalveolar lavage (BAL) in patients with community-acquired pneumonia (CAP). Our aim was to evaluate the diagnostic value of BAL in CAP in a routine clinical setting. 71 disease episodes were retrospectively analysed. The patients had undergone BAL for serious or slowly responding pneumonia. All procedures were performed during antimicrobial treatment of the patient. BAL fluid was cultivated for bacteria, fungi, and viruses. In 68 episodes, 1 or several specific polymerase chain reaction tests were performed. Only 1 (1.3%) quantitative bacterial culture was considered diagnostic for CAP, and indicated a change of antimicrobial treatment. The diagnostic yield increased to 9.8% when other methods were used. A respiratory virus was the only aetiology in 3 (6.0%) patients. In slowly responding pneumonia, also hospital-acquired pathogens and malignancies were identified, resulting in a total diagnostic yield of 20.0%. Thus, even when a large array of diagnostic assays was applied, the value of BAL in pretreated patients with CAP was very small, and its therapeutic implications minimal. In a subgroup of slowly responding pneumonia, the procedure was of some usefulness even after commencement of antimicrobial treatment.

To clarify when antibodies against cytomegalovirus (CMV), varicella-zoster virus (VZV) and herpes simplex virus (HSV) develop among young children, 1206 serum samples collected prospectively from 199 children born in 1989 and 1990 were studied. The samples were drawn at the ages of 7 and 13 months, then yearly until the age of 5 y and then at 7 and 8 y. In each age group at least 106 samples were collected. Immunoglobulin G class antibodies to the 3 viruses were measured using an enzyme immunoassay. At the age of 7 months 27% of the children had CMV antibodies, whereas only 3% had antibodies against VZV and 2% against HSV. The prevalence of seropositivity for CMV increased slowly to 41% by the age of 8 y. Seroconversions to VZV antibody positivity occurred frequently after 2 y of age, so that by 8 y 83% of children had VZV antibodies. The proportion of children with HSV antibodies remained low throughout the study, as only 17% of children had HSV antibodies at the age of 8 y. The data show that HSV infection is becoming acquired later in life and the proportion of uninfected children is increasing. The proportion of CMV infections during the perinatal period and early infancy remains high, in one-third of the children, and most children also have VZV infection during the early years of life.

To provide insight into the appearance and longitudinal course of Chlamydia pneumoniae antibodies in childhood, C. pneumoniae immunoglobulin G (IgG), IgA and, in selected children, IgM antibodies were measured annually in 199 healthy children, followed prospectively from age 7 months to age 8 y (number of samples 1225) using a commercial enzyme immunoassay kit. IgG antibodies to C. pneumoniae were common throughout the follow-up, and the values declined rapidly after apparent infections during early childhood. Of the 128 identified seroconversions, 94 were probably primary infections and 34 reinfections. IgM antibodies were detected in 28% of the samples that showed a clear increase in IgG. IgA antibodies were scarce before 2 y of age, but their proportion then increased gradually. At the ages of 7 and 8 y, 10% of the children had clearly positive IgG and IgA antibody values. Increases in IgG were not associated with clinical respiratory symptoms. This study shows that C. pneumoniae infections probably occur commonly already at an early age, and that the infections are often asymptomatic. Consecutive high IgG and IgA antibody concentrations at the ages of 7 and 8 y indicate that persistent seropositivity for both antibodies may already develop in young children.

A randomized, double-blind, placebo-controlled, parallel-group trial performed at 5 residential units of the Finnish Defence Forces was conducted to assess the antiviral activity, efficacy and safety of inhaled zanamivir for the treatment of naturally acquired influenza. Conscripts were recruited within 2 d of onset of typical influenza symptoms and received inhaled zanamivir 10 mg via a Diskhaler twice daily for 5 d or matching placebo. Time to alleviation of clinically significant symptoms of influenza was the primary endpoint. Viral load measurements were made using quantitative real-time polymerase chain reaction assays. 435/588 patients (74%) had laboratory-confirmed influenza infection. The mean area under the curve for viral load during the first 48 h of treatment was 8.48 [95% confidence interval (95% CI) 2.85 to 14.11] log10 vRNA copies/ml x h lower in the zanamivir group compared with placebo (p = 0.003). Zanamivir reduced the time to alleviation of symptoms versus placebo in the influenza-positive group (medians 2.0 vs 2.33 d; 95% CI-0.17 to 1.0 d, p = 0.08). Zanamivir rapidly reduced viral load following the start of therapy compared with placebo and was well tolerated.

Background: Chlamydia pneumoniae infection has been associated with atherosclerosis by sero-epidemiological, histopathological and interventional studies, and animal experiments. We hypothesized that if chlamydial infection is causative of atherosclerosis, the occurrence of antibodies against C. pneumoniae should be associated with coronary vasomotor dysfunction - an early sign of atherosclerosis., Aim: To study the association between C. pneumoniae infection and coronary vasomotor function in young men without signs of ischemic heart disease., Methods: Serum IgG and IgA antibody concentrations against C. pneumoniae were determined in 125 clinically healthy subjects undergoing positron emission tomography (PET) studies. Myocardial blood flow was measured at rest and during pharmacologically induced hyperemia using [15O]H2O Coronary flow reserve was calculated as the ratio of hyperemic blood flow to resting blood flow., Results: No association was found between serum C. pneumoniae antibody concentrations and myocardial blood flow parameters. In contrast, more conventional risk factors for coronary artery disease, such as total cholesterol and apolipoprotein B, were inversely associated with hyperemic flow and flow reserve., Conclusions: We found no association between C. pneumoniae antibodies and coronary vasomotor function in subjects without ischemic heart disease. Thus, these results do not support the role of C. pneumoniae infection as an early phase risk factor for coronary artery disease.

Enzyme immunoassays (EIAs) for the detection of secretory IgA antibody (sIgA) to Chlamydia pneumoniae and Mycoplasma pneumoniae from saliva are described. The presence of salivary sIgA in healthy laboratory personnel (mean age 40, range 25-62 years) was detected using conjugates of antibodies directed against secretory and alpha-chain domains. The EIA results for the detection of C pneumoniae sIgA antibodies were confirmed by a sensitive microimmunofluorescence method used as a reference. Circulating IgA antibody levels in sera were also determined using commercial EIAs. Secretory IgA antibodies to both C pneumoniae and M. pneumoniae were detectable only from persons with positive or borderline circulating IgA antibodies. Moreover, C. pneumoniae sIgA was found in the saliva of a clinically healthy person whose serum IgA antibody levels had been constantly elevated during the past 7 years. In conclusion, because of their specificity the described methods could be used in further delineation of the role of anti-C pneumoniae and M. pneumoniae sIgA antibodies. However, owing to the unexpected high frequency of these antibodies in saliva of clinically healthy persons, it seems unlikely that a single sIgA measurement from saliva is diagnostically more powerful than a single IgA measurement from serum to study and interpret the involvement of these pathogens in chronic respiratory diseases.

Viral etiology of clinically typical parotitis was studied by virus isolation and serology in 100 consecutive patients presented at the Department of Infectious Diseases, University of Turku, during a period of over 2 years. Mumps etiology was confirmed in 95 cases and in one case a probable parainfluenza type 3 infection was diagnosed by IgM serology. In the remaining 4 patients no etiological evidence of any of the viruses studied was obtained. When different methods to diagnose an acute mumps infection were compared, the most sensitive was the assay for specific IgM antibodies.