Disease severity in children with bronchiolitis is not associated with infection by multiple viruses. We conclude that other factors, such as age, contribute to disease severity to a larger extent.

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BackgroundRespiratory viral infections follow an unpredictable clinical course in young children ranging from a common cold to respiratory failure. The transition from mild to severe disease occurs rapidly and is difficult to predict. The pathophysiology underlying disease severity has remained elusive. There is an urgent need to better understand the immune response in this disease to come up with biomarkers that may aid clinical decision making.MethodsIn a prospective study, flow cytometric and genome-wide gene expression analyses were performed on blood samples of 26 children with a diagnosis of severe, moderate or mild Respiratory Syncytial Virus (RSV) infection. Differentially expressed genes were validated using Q-PCR in a second cohort of 80 children during three consecutive winter seasons. FACS analyses were also performed in the second cohort and on recovery samples of severe cases in the first cohort.ResultsSevere RSV infection was associated with a transient but marked decrease in CD4+ T, CD8+ T, and NK cells in peripheral blood. Gene expression analyses in both cohorts identified Olfactomedin4 (OLFM4) as a fully discriminative marker between children with mild and severe RSV infection, giving a PAM cross-validation error of 0%. Patients with an OLFM4 gene expression level above -7.5 were 6 times more likely to develop severe disease, after correction for age at hospitalization and gestational age.ConclusionBy combining genome-wide expression profiling of blood cell subsets with clinically well-annotated samples, OLFM4 was identified as a biomarker for severity of pediatric RSV infection.

Background: current tools to predict the severity of respiratory syncytial virus (RsV) infection might be improved by including immunological parameters. We hypothesized that a combination of inflammatory markers would differentiate between severe and mild disease in RsV-infected children. Methods: Blood and nasopharyngeal samples from 52 RsVinfected children were collected during acute infection and after recovery. Retrospectively, patients were categorized into three groups based on disease severity: mild (no supportive treatment), moderate (supplemental oxygen and/or nasogastric feeding), and severe (mechanical ventilation). clinical data, number of flow-defined leukocyte subsets, and cytokine concentrations were compared. results: children with severe RsV infection were characterized by young age; lymphocytopenia; increased interleukin (IL)-8, granulocyte colony-stimulating factor (G-csF), and IL-6 concentrations; and decreased chemokine (c-c motif ) ligand (ccL-5) concentrations in plasma. The combination of plasma levels of IL-8 and ccL-5, and cD4 + T-cell counts, with cutoff values of 67 pg/ml, 13 ng/ml, and 2.3 × 10 6 /ml, respectively, discriminated severe from mild RsV infection with 82% sensitivity and 96% specificity. conclusion: This study demonstrates that the combination of cD4 + T-cell counts and IL-8 and ccL-5 plasma concentrations correlates with disease severity in RsV-infected children. In addition to clinical features, these immunological markers may be used to assess severity of RsV infection and guide clinical management.

Respiratory syncytial virus (RSV) causes infections that range from common cold to severe lower respiratory tract infection requiring high-level medical care. Prediction of the course of disease in individual patients remains challenging at the first visit to the pediatric wards and RSV infections may rapidly progress to severe disease. In this study we investigate whether there exists a genomic signature that can accurately predict the course of RSV. We used early blood microarray transcriptome profiles from 39 hospitalized infants that were followed until recovery and of which the level of disease severity was determined retrospectively. Applying support vector machine learning on age by sex standardized transcriptomic data, an 84 gene signature was identified that discriminated hospitalized infants with eventually less severe RSV infection from infants that suffered from most severe RSV disease. This signature yielded an area under the receiver operating characteristic curve (AUC) of 0.966 using leave-one-out cross-validation on the experimental data and an AUC of 0.858 on an independent validation cohort consisting of 53 infants. A combination of the gene signature with age and sex yielded an AUC of 0.971. Thus, the presented signature may serve as the basis to develop a prognostic test to support clinical management of RSV patients.

Respiratory syncytial virus (RSV) is Respiratory syncytial virus (RSV) is the leading cause of severe lower respiratory tract infections in children, being responsible for up to 80% of the cases of acute bronchiolitis and frequent subsequent hospital admission in industrialized countries (1, 2). It has been estimated that RSV causes 33.8 million acute lower respiratory tract infections globally each year, resulting in 66,000 to 199,000 deaths among children under 5 years of age, 99% of which occur in developing countries (3). In addition to young children, immunocompromised individuals and the elderly are at increased risk for severe RSV disease and hospitalization. A licensed RSV vaccine is currently not available, and the development of a vaccine against RSV infection has proven to be very difficult. Formalin-inactivated RSV (FI-RSV) vaccine trials in the 1960s failed to induce protection upon natural RSV infection and even predisposed patients for enhanced disease, resulting in two deaths and hospitalization of 80% of the vaccinated subjects (4-7). Experimental inactivated and subunit vaccines tend to prime for the induction of unbalanced, type 2 T-helper (Th2) host responses that result in enhanced disease accompanied by an influx of inflammatory cells (8). On the other hand, development of live attenuated RSV vaccines that are more likely to induce balanced host responses appears difficult to tune and these live vaccines tend either to be over-or underattenuated (9, 10). Several RSV infection animal models have been developed, and these are exploited for vaccine research and studies on virus-induced (immuno)pathology. Multiple virological and immunological parame-

The efficacy and tolerability of a new erythromycin derivative, erythromycin acistrate (EA), were compared with that of erythromycin stearate (ES) in 42 patients with infected atopic eczema. The dosage of EA was 400 mg tid and that of ES 500 mg tid. The duration of treatment ranged from five to 12 days. The patients were hospitalized and evaluated before treatment and on the last day in hospital. The infective pathogen was usually Staphylococcus aureus in both groups. Without local antibacterial treatment both drugs eradicated the bacteria in more than 60% of the cases. Gastrointestinal side effects were frequently reported with both drugs, more often in the ES- than in the EA-group, but the difference was only statistically significant (p less than 0.05) with respect to diarrhoea. One patient in each group discontinued treatment because of gastrointestinal side effects. No elevations in liver enzymes of clinical significance were reported in either group.

Infectious diseases are an important cause of death among children under the age of 5 (Stein et al., 2004). Most of these deaths are caused by preventable or curable infections. Limited access to medical care, antibiotics, and vaccinations remains a major problem in developing countries. But infectious diseases also continue to be an important public health issue in developed countries. With the help of modern technologies, some infections have been effectively controlled; however, new diseases such as SARS and West Nile virus infections are constantly emerging. In addition, other diseases such as malaria, tuberculosis, and bacterial pneumonia are increasingly resistant to antimicrobial treatment.