Detection of Host Response to Viral Respiratory Infection by Measurement of Messenger RNA for MxA, TRIM21, and Viperin in Nasal Swabs.

Respiratory viruses frequently cause symptomatic infections in children but are often detected also in healthy children. We investigated myxovirus resistance protein A (MxA), viperin, and tripartite-motif 21 (TRIM21) messenger RNA indexes in nasal swabs as potential biomarkers of viral respiratory infection in children. Respiratory viruses were detected by polymerase chain reaction in the same swabs. Nasal MxA and viperin indexes were increased in symptomatic virus-positive children. Nasal viperin index was found to be a robust marker of viral respiratory tract infection with a sensitivity of 80% and specificity of 94% in distinguishing children with symptomatic virus infections from asymptomatic virus-negative children.

Rhinovirus Infections in the First 2 Years of Life.

BACKGROUND AND OBJECTIVES: Rhinoviruses frequently cause respiratory infections in young children. We aimed to establish the burden of acute respiratory infections caused by rhinovirus during the first 2 years of life. METHODS: In this prospective birth cohort study, we followed 923 children for acute respiratory infections from birth to 2 years of age. Data on respiratory infections were collected by daily symptom diaries, study clinic visits, and from electronic registries. Respiratory viruses were detected by reverse transcription-polymerase chain reaction and antigen assays during respiratory infections and at the age of 2, 13, and 24 months. The rates of rhinovirus infections and associated morbidities were determined. RESULTS: We documented 8847 episodes of acute respiratory infections, with an annual rate of 5.9 per child (95% confidence interval [CI], 5.7-6.1). Rhinovirus was detected in 59% of acute respiratory infections analyzed for viruses. Rhinovirus was associated with 50% of acute otitis media episodes, 41% of wheezing illnesses, 49% of antibiotic treatments, and 48% of outpatient office visits for acute respiratory infections. The estimated mean annual rate of rhinovirus infections was 3.5 per child (95% CI, 3.3-3.6), 47 per 100 children (95% CI, 42-52) for rhinovirus-associated acute otitis media, and 61 per 100 children (95% CI, 55-68) for rhinovirus-associated antibiotic treatment. The prevalence of rhinovirus at 2, 13, or 24 months of age was 14 to 24%, and 9% of asymptomatic children were positive for rhinovirus. CONCLUSIONS: Rhinovirus infections impose a major burden of acute respiratory illness and antibiotic use on young children.

Blood MxA protein as a marker for respiratory virus infections in young children.

BACKGROUND: Type I interferon induced MxA response can differentiate viral from bacterial infections, but MxA responses in rhinovirus or asymptomatic virus infections are not known. OBJECTIVE: To study MxA protein levels in healthy state and during respiratory virus infection of young children in an observational prospective cohort. STUDY DESIGN: Blood samples and nasal swabs were collected from 153 and 77 children with and without symptoms of respiratory infections, respectively. Blood MxA protein levels were measured by an enzyme immunoassay and PCR methods were used for the detection of respiratory viruses in nasal swabs. RESULTS: Respiratory viruses were detected in 81% of symptomatic children. They had higher blood MxA protein levels (median [interquartile range]) than asymptomatic virus-negative children (695 [345-1370] µg/L vs. 110 [55-170] µg/L; p < 0.001). Within asymptomatic children, no significant difference was observed in MxA responses between virus-positive and virus-negative groups. A cut-off level of 175 µg/L had 92% sensitivity and 77% specificity for a symptomatic respiratory virus infection. Rhinovirus, respiratory syncytial virus, parainfluenza virus, influenza virus, coronavirus, and human metapneumovirus infections were associated with elevated MxA responses. Asymptomatic virus-negative children vaccinated with a live virus vaccine had elevated MxA protein levels (240 [120-540] µg/L), but significantly lower than children with an acute respiratory infection, who had not received vaccinations (740 [350-1425] µg/L; p<0.001). CONCLUSION: Blood MxA protein levels are increased in young children with symptomatic respiratory virus infections, including rhinovirus infections. MxA is an informative general marker for the most common acute virus infections.

Pandemic influenza A (H1N1) virus in households with young children.

BACKGROUND: Influenza viruses may cause a severe infection in infants and young children. The transmission patterns of pandemic 2009 influenza A (H1N1) within households with young children are poorly characterized. METHODS: Household members of six children younger than 1·5 years with documented 2009 influenza A (H1N1) infection were studied by daily symptom diaries and serial parent-collected nasal swab samples for detection of influenza A by reverse transcription polymerase chain reaction (RT-PCR) assay. RESULTS: Laboratory-confirmed, symptomatic influenza was documented in 11 of 15 household contacts of young children with pandemic influenza (73%; 95% CI, 48-99). In five contact cases symptoms started earlier, in three cases on the same day, and in three cases after the onset of symptoms in the youngest child. The first case with influenza A (H1N1) within the household was an elder sibling in two households, father in two households, the youngest child in one household, and the youngest child at the same time with a sibling in one household. The median copy number of influenza virus was higher in children than in adults (4·2 × 10(7) versus 4·9 × 10(4), P = 0·02). CONCLUSIONS: This study demonstrates the feasibility of nasal swab sampling by parents in investigation of household transmission of influenza. The results support influenza vaccination of all household contacts of young children.

Time-resolved fluorescence imaging of islet cell autoantibodies.

Time-resolved fluorescence of lanthanide chelates has been widely used in bioanalytical assays. Long fluorescence time, large Stokes shift, and minute fading out of the fluorescence over years are major advantages of the lanthanides over the conventional fluorescent dyes. We have now applied time-resolved fluorescence imaging (TRFI) also for measurement of type 1 diabetes mellitus (T1DM)-related islet cell autoantibodies (ICA). Retaining the accuracy of conventional ICA, TRFI has over 10 times better signal-to-noise ratio than the conventional fluorochromes. The technology allows objective determination of fluorescence intensity with the camera and computer software, and serial dilutions for obtaining the antibody titer in autoantibody-positive samples are unnecessary. We now describe the TRFI as a method and its application for measurement of ICA.