phenylephrine-hydrochloride and Respiratory-Syncytial-Virus-Infections

Viral infections of the respiratory tract can be complicated by bacterial superinfection, resulting in a significantly longer duration of illness and even a fatal outcome. In this review, we focused on interactions between S. aureus and non-influenza viruses. Clinical data evidenced that rhinovirus infection may increase the S. aureus carriage load in humans and its spread. In children, respiratory syncytial virus infection is associated with S. aureus carriage. The mechanisms by which some non-influenza respiratory viruses predispose host cells to S. aureus superinfection can be summarized in three categories: i) modifying expression levels of cellular patterns involved in S. aureus adhesion and/or internalization, ii) inducing S. aureus invasion of epithelial cells due to the disruption of tight junctions, and iii) decreasing S. aureus clearance by altering the immune response. The comprehension of pathways involved in S. aureus-respiratory virus interactions may help developing new strategies of preventive and curative therapy.

Topics: Animals; Bacterial Adhesion; Carrier State; Disease Models, Animal; Epithelial Cells; Host-Pathogen Interactions; Humans; Mice; Microbial Interactions; Nose; Picornaviridae Infections; Respiratory Syncytial Virus Infections; Respiratory System; Respiratory Tract Infections; Rhinovirus; Staphylococcal Infections; Staphylococcus aureus; Superinfection; Virus Diseases

Three different rapid strip tests: TRU RSV, BinaxNOW RSV and RSV Respi-strip were compared with RT-PCR and ELISA BRSV Ag for the ability to detect bovine respiratory syncytial virus (BRSV) in nasal swabs collected from calves experimentally vaccinated with live vaccine Rispoval RS-PI3. The reference strains of BRSV (375 and A51908) were detected by ELISA BRSV Ag whereas the strains of human respiratory syncytial virus (HRSV) and bovine parainfluenza virus type 3 (BPIV-3) were not. All rapid strip tests as well as RT-PCR reacted positively both to HRSV and BRSV reference strains and negatively to BPIV-3. The detection limit for RT-PCR was 39.1 TCID50 (strain 375 of BRSV), whereas for each of the rapid tests it was approximately 156 TCID50 and 312 TCID50 for antigen ELISA. Diagnostic sensitivity in detecting BRSV in nasal swabs for TRU RSV and RSV Respi-strip tests was 33% and 50% for BinaxNOW RSV. Diagnostic specificity of TRU RSV was 100%, whereas for both BinaxNOW and Respi-strip it was 87%. We concluded that TRU RSV could be used as a supportive rapid test for BRSV screening in nasal swabs taken directly on a farm. However, due to the small group of animals used in the experiment, the results should be regarded as preliminary and the study should be repeated on a larger number of animals.

Topics: Animals; Antibodies, Viral; Antigens, Viral; Cattle; Cattle Diseases; Enzyme-Linked Immunosorbent Assay; Humans; Nose; Reagent Strips; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Bovine; Respiratory Syncytial Virus, Human; Reverse Transcriptase Polymerase Chain Reaction; RNA, Viral; Sensitivity and Specificity; Species Specificity; Viral Vaccines

To determine whether a combination modified-live bovine respiratory syncytial virus (BRSV) vaccine can stimulate protective immunity in young BRSV-seropositive calves following intranasal (IN) administration.. Controlled challenge study.. 66 Holstein bull calves, 3 to 8 days old.. In experiment 1, BRSV-seropositive and -seronegative calves were vaccinated IN with a commercially available combination modified-live virus vaccine formulated for SC administration; calves underwent BRSV challenge 4.5 months later. In experiment 2, BRSV-seronegative calves were vaccinated IN or SC (to examine the effect of route of administration) with the same combination vaccine that instead had a 1/100 dose of BRSV (to examine the effect of dose); calves underwent BRSV challenge 21 days later.. In experiment 1, BRSV challenge resulted in severe respiratory tract disease with low arterial partial pressures of oxygen and lung lesions in most calves from all groups. Maximum change in rectal temperature was significantly greater in seropositive IN vaccinated calves, compared with seronegative IN vaccinated and seropositive control calves. Number of days of BRSV shedding was significantly lower in seronegative IN vaccinated calves than in seropositive IN vaccinated and seropositive control calves. In experiment 2, maximum change in rectal temperature was significantly greater in seronegative control calves, compared with seronegative IN and SC vaccinated calves. Shedding of BRSV was significantly reduced in seronegative IN and SC vaccinated calves, compared with control calves; also, lung lesions were reduced in seronegative IN and SC vaccinated calves.. Maternal antibodies may inhibit priming of protective responses by IN delivered BRSV vaccines.

Topics: Administration, Intranasal; Animals; Antibodies, Viral; Cattle; Cattle Diseases; Lung; Male; Nose; Pneumonia, Viral; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Bovine; Viral Vaccines; Virus Shedding

Forty-one previously healthy children <2 years of age who required mechanical ventilation for respiratory syncytial virus (RSV) infection were randomized to receive dexamethasone (0.5 mg/kg; n=22) or saline placebo (n=19) intravenously every 12 h for 4 days. RSV quantity was measured by quantitative plaque assay in fresh tracheal and nasal aspirates obtained at intervals of 24+/-3 h on days 0, 1, 2, 5, and 7 following entry. Analysis by linear mixed-effects modeling demonstrated a significantly greater decline in mean tracheal RSV quantity in the placebo group than in the dexamethasone group from day 0 to day 1 (0.82 vs. 0.21 log pfu/mL; P=.01) and from day 0 to day 2 (1.45 vs. 0.53 log pfu/mL; P=.03). No differences were found between groups in nasal RSV quantity, white blood cell counts in tracheal or nasal aspirates, serum neutralizing antibody titers during convalescence, or duration of mechanical ventilation, intensive care unit stay, or hospital stay.

Topics: Antibodies, Viral; Dexamethasone; Double-Blind Method; Female; Humans; Infant; Infant, Newborn; Length of Stay; Leukocyte Count; Male; Nose; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Trachea; Viral Load

Respiratory syncytial virus (RSV) is a leading cause of severe respiratory illness worldwide, particularly in infants and older adults. Vaccines targeting the fusion glycoprotein (F protein) -one of the surface antigens of RSV- are highly effective in preventing RSV-associated severe lower respiratory tract disease. However, the efficacy of these vaccines against upper respiratory tract challenge needs improvement. Here, we aimed to examine the efficacy of F protein vaccines with or without CpG oligodeoxynucleotide (CpG ODN) as an adjuvant in the upper and lower respiratory tracts in mice. F + CpG ODN induced higher levels of F-specific IgG than that induced by F alone; however, levels of neutralizing antibodies did not increase compared to those induced by F alone. F + CpG ODN induced T helper 1 (Th1) cells while F alone induced T helper 2 (Th2) cells. Moreover, F + CpG ODN improved the protection against RSV challenge in the upper respiratory tract compared to F alone, which was largely dependent on CD4

Topics: Aged; Animals; Antibodies, Neutralizing; Antibodies, Viral; Humans; Mice; Mice, Inbred BALB C; Nose; Oligodeoxyribonucleotides; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Th1 Cells; Vaccines

Topics: Humans; Infant; Microbiota; Nose; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Respiratory System

Maternal anti-respiratory syncytial virus (RSV) antibodies acquired by the fetus through the placenta protect neonates from RSV disease through the first weeks of life. In the cotton rat model of RSV infections, we previously reported that immunization of dams during pregnancy with virus-like particles assembled with mutation stabilized pre-fusion F protein as well as the wild type G protein resulted in robust protection of their offspring from RSV challenge. Here we describe the durability of those protective responses in dams, the durability of protection in offspring, and the transfer of that protection to offspring of two consecutive pregnancies without a second boost immunization. We report that four weeks after birth, offspring of the first pregnancy were significantly protected from RSV replication in both lungs and nasal tissues after RSV challenge, but protection was reduced in pups at 6 weeks after birth. However, the overall protection of offspring of the second pregnancy was considerably reduced, even at four weeks of age. This drop in protection occurred even though the levels of total anti-pre-F IgG and neutralizing antibody titers in dams remained at similar, high levels before and after the second pregnancy. The results are consistent with an evolution of antibody properties in dams to populations less efficiently transferred to offspring or the less efficient transfer of antibodies in elderly dams.

Topics: Animals; Antibodies, Neutralizing; Antibodies, Viral; Female; Humans; Immunization; Lung; Nose; Pregnancy; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus Vaccines; Respiratory Syncytial Virus, Human; Sigmodontinae

Respiratory syncytial virus (RSV) is a leading cause of infant respiratory disease. Infant airway microbiota has been associated with respiratory disease risk and severity. The extent to which interactions between RSV and microbiota occur in the airway, and their impact on respiratory disease susceptibility and severity, are unknown.. We carried out 16S rRNA microbiota profiling of infants in the first year of life from (1) a cross-sectional cohort of 89 RSV-infected infants sampled during illness and 102 matched healthy controls, and (2) a matched longitudinal cohort of 12 infants who developed RSV infection and 12 who did not, sampled before, during, and after infection.. We identified 12 taxa significantly associated with RSV infection. All 12 taxa were differentially abundant during infection, with 8 associated with disease severity. Nasal microbiota composition was more discriminative of healthy vs infected than of disease severity.. Our findings elucidate the chronology of nasal microbiota dysbiosis and suggest an altered developmental trajectory associated with RSV infection. Microbial temporal dynamics reveal indicators of disease risk, correlates of illness and severity, and impact of RSV infection on microbiota composition.

Topics: Cross-Sectional Studies; Dysbiosis; Humans; Infant; Microbiota; Nose; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; RNA, Ribosomal, 16S; Severity of Illness Index

Acute wheezing is one of the most common hospital presentations for young children. Respiratory syncytial virus (RSV) and rhinovirus (RV) species A, B and the more recently described species C are implicated in the majority of these presentations. However, the relative importance and age-specificities of these viruses have not been defined. Hence, this study aimed to establish these relationships in a large cohort of prospectively recruited hospitalized children.. The study cohort was 390 children 0-16 years of age presenting with acute wheezing to a children's emergency department, 96.4% being admitted. A nonwheezing control population of 190 was also recruited. Nasal samples were analyzed for viruses.. For the first 6 months of life, RSV was the dominant virus associated with wheezing (P < 0.001). From 6 months to 2 years, RSV, RV-A and RV-C were all common but none predominated. From 2 to 6 years, RV-C was the dominant virus detected (50-60% of cases), 2-3 times more common than RV-A and RSV, RSV decreasing to be absent from 4 to 7 years. RV-B was rare at all ages. RV-C was no longer dominant in children more than 10 years of age. Overall, RV-C was associated with lower mean oxygen saturation than any other virus (P < 0.001). Controls had no clear age distribution of viruses.. This study establishes a clear profile of age specificity of virus infections causing moderate to severe wheezing in children: RSV as the dominant cause in the first 6 months and RV-C in preschool-age children.

Topics: Acute Disease; Adolescent; Age Factors; Child; Child, Preschool; Cohort Studies; Female; Hospitalization; Humans; Infant; Infant, Newborn; Male; Nose; Oxygen Saturation; Picornaviridae Infections; Prospective Studies; Respiratory Sounds; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Rhinovirus

We investigated the association between age, duration of clinical symptoms and viral shedding in outpatient children infected with respiratory syncytial virus (RSV) in Japan.. Outpatients younger than 2 years of age, with suspected RSV infection between 2014 and 2018, were enrolled in the study. Following informed consent, nasal samples were collected at first and second clinic visits (with 0-9 days gap). RSV-A or -B infection and viral load were determined by real-time polymerase chain reaction. Clinical symptoms were recorded at first clinic visit, and fever and symptoms were recorded at home for up to 8 days. Association between clinical symptoms and patient characteristics, such as age, sex and birth weight, were analyzed using ordered logistic regression analysis. The association between viral reduction and estimated shedding period was examined using linear regression analysis.. Among the 205 cases enrolled in the study, no difference was found in patient characteristics between RSV-A and -B infection. Duration of fever was prolonged with increased age. Duration of rhinorrhea and cough was shorter in females than in males and in groups with birth weight ≥3 kg than in those with <2.5 kg. Daily viral reduction increased and estimated viral elimination period decreased with age.. Fever duration was found to increase while viral shedding decreased with patient age.

Topics: Female; Humans; Infant; Japan; Logistic Models; Male; Nose; Outpatients; Prospective Studies; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Respiratory Tract Infections; Viral Load; Virus Shedding

Human respiratory syncytial virus (HRSV) is the leading cause of severe respiratory tract disease in infants. Most HRSV infections remain restricted to the upper respiratory tract (URT), but in a small percentage of patients the infection spreads to the lower respiratory tract, resulting in bronchiolitis or pneumonia. We have a limited understanding of HRSV pathogenesis and what factors determine disease severity, partly due to the widespread use of tissue-culture-adapted viruses. Here, we studied early viral dissemination and tropism of HRSV in cotton rats, BALB/cJ mice and C57BL/6 mice. We used a novel recombinant (r) strain based on a subgroup A clinical isolate (A11) expressing EGFP [rHRSV

Topics: Animals; Bronchiolitis, Viral; Disease Models, Animal; Humans; Lung; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Nose; Olfactory Mucosa; Respiratory Mucosa; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Respiratory System; Respiratory Tract Infections; Rhinitis; Sigmodontinae; Viral Load; Viral Tropism; Virus Replication

Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections and hospital visits during infancy and childhood. Although risk factors for RSV infection have been identified, the role of microbial species in the respiratory tract is only partially known. We aimed to understand the impact of interactions between the nasal microbiome and host transcriptome on the severity and clinical outcomes of RSV infection. We used 16 S rRNA sequencing to characterize the nasal microbiome of infants with RSV infection. We used RNA sequencing to interrogate the transcriptome of CD4

Topics: Bacteria; CD4-Positive T-Lymphocytes; Computational Biology; Female; Gene Expression Profiling; Gene Regulatory Networks; Haemophilus influenzae; Humans; Infant; Male; Microbiota; Nose; Respiratory Syncytial Virus Infections; RNA, Ribosomal, 16S; Sequence Analysis, RNA; Severity of Illness Index; Software

The characteristics and risk factors of respiratory syncytial virus (RSV) infection among children has not yet been fully understood. To address the characteristics of RSV-associated illness and risk factors of RSV infection among children under 5 years of age in Suzhou, China. From April 2011 to March 2014, we conducted a prospective surveillance among children in Suzhou, China. Nasal or throat swabs were collected from outpatients with influenza-like illness (ILI) and inpatients with severe acute respiratory infections (SARI). RSV was detected by reverse-transcriptase polymerase chain reaction and direct fluorescent antibody assay for children with ILI and SARI, respectively. Multivariable logistic-regression models were constructed to explore risk factors and symptoms of RSV infection. Of 3267 ILI and 1838 SARI children enrolled in the study, 192 (5.9%) and 287 (15.6%) tested positive for RSV, respectively. Among ILI patients, children with RSV infections visited clinics more often (P = 0.005) and had longer duration of fever (P = 0.032) than those without RSV infection. All RSV-positive children had an increased risk of having cough (OR = 2.9), rhinorrhea (OR = 1.6), breathing difficulty (OR = 3.4), wheezing (OR = 3.3), and irritability (OR = 2.7). Children aged <2 years, had history of prematurity (OR = 2.0) and recent respiratory infections (OR = 1.3) were more likely to get infected by RSV. Children with SARI had higher positive rate of RSV than those with ILI. Cough, rhinorrhea, and wheezing were the most common symptoms in RSV infection. Children aged <2 years, had history of prematurity and recent respiratory infections were the potential risk factors for RSV infection.

Topics: Child, Preschool; China; Coinfection; Cough; Epidemiological Monitoring; Female; Fever; Humans; Infant; Influenza, Human; Male; Nose; Orthomyxoviridae; Outpatients; Pharynx; Polymerase Chain Reaction; Prospective Studies; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Respiratory Tract Infections; Risk Factors; Virus Diseases; Viruses

The respiratory syncytial virus (RSV) is recognized as an important cause of respiratory tract infections. Immunocompromised patients, healthcare workers (HCWs) and children contacts are at increased risk of acquiring the infection. However, the impact of asymptomatic infection in transmission has not been well studied.. this study evaluated the frequency and viral load (VL) of RSV in nasal swab samples of individuals with different risk factors for acquiring infection in a university hospital in Sao Paulo, Brazil.. We included 196 symptomatic children and their 192 asymptomatic caregivers, 70 symptomatic and 95 asymptomatic HCWs, 43 samples from symptomatic HIV-positive outpatients, and 100 samples of asymptomatic HIV patients in the period of 2009-2013.. RSV infection was detected in 10.1% (70/696) of samples, 4.4% (17/387) of asymptomatic patients, and 17.1% (53/309) from symptomatic patients. (P < .0001). The VL of symptomatic patients (4.7 log copies/mL) was significantly higher compared to asymptomatic patients (2.3 log copies/mL). RSV detection among asymptomatic caregivers (6.8%; 13/192) was significantly higher compared to other asymptomatic adults, HIV and HCWs (2.0%; 4/195; P = .0252). A close contact with an infected child at home was an important risk to RSV acquisition [OR 22.6 (95% CI 4.8-106.7)]. Children who possibly transmitted the virus to their asymptomatic contacts had significantly higher viral load than children who probably did not transmit (P < .0001).. According to our results, it is important to know if people circulating inside the hospital have close contact with acute respiratory infected children.

Topics: Adult; Asymptomatic Infections; Brazil; Caregivers; Child; Child, Preschool; Female; Health Personnel; Hospitals, University; Humans; Infant; Male; Middle Aged; Nose; Real-Time Polymerase Chain Reaction; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Risk Factors; Viral Load

To assess MUC5AC as a biomarker for respiratory syncytial virus (RSV) disease severity, we tested nasal aspirates from RSV+ children with mild, moderate, and severe disease. Levels were significantly higher in those in the severe and moderate groups compared to mild group, indicating MUC5AC may be a useful biomarker for RSV disease severity.

Topics: Argentina; Biomarkers; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Male; Mucin 5AC; Nose; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; ROC Curve; Severity of Illness Index

Respiratory symptoms in RSV persist long after the virus is no longer detected by culture. Current concepts of RSV pathogenesis explain this by RSV inducing a long-lasting pathogenic immune cascade. We alternatively hypothesized that prolonged unrecognized RSV replication may be responsible and studied this possibility directly in a human wild-type RSV experimental infection model.. The objective of the current report was to define the duration of true human RSV replication by studying it directly in immunocompetent adults experimentally infected with a clinical strain of RSV utilizing this previously established safe and reproducible model.. 35 healthy adult volunteers were inoculated with RSV-A (Memphis-37, a low11 passage clinical strain virus, manufactured from a hospitalized bronchiolitic infant) and evaluated over 12 days. Viral load by culture, parallel quantitative PCR (genomic, message) and RSV-specific IgA, were measured twice daily from serially collected nasal washes.. After inoculation, 77% (27/35) of volunteers became RSV infected. As expected, culture-detectable RSV ceased abruptly by the 5-6 t h 15 infection day. However, infected volunteers demonstrated prolonged RSV presence by both genomic and message PCR. RSV-specific IgA rose within respiratory secretions of infected volunteers during same time frame.. RSV replication appears to continue in humans far longer than previously thought. The rise in nasal RSV-specific IgA shortly after infection likely neutralizes culture detectable virus producing misleadingly short durations of infection. Prolonged viral replication helps explain RSV's extended disease manifestations and increases the potential utility of antivirals.

Topics: Adolescent; Adult; Antibodies, Viral; Antiviral Agents; Female; Healthy Volunteers; Humans; Immunocompetence; Immunoglobulin A; Male; Middle Aged; Nose; Polymerase Chain Reaction; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Viral Load; Virus Replication; Young Adult

Respiratory syncytial virus is the most common cause of lower respiratory tract infections in infants and young children. While the majority of infants display only mild upper respiratory tract infection or occasionally otitis media, around one-third will develop an infection of the lower respiratory tract, usually bronchiolitis. There is now convincing evidence from a number of cohorts that respiratory syncytial virus is a significant, independent risk factor for later wheezing, at least within the first decade of life. The wide variation in response to respiratory syncytial virus infection suggests that susceptibility and disease are influenced by multiple host-intrinsic factors.. A 2-year-old white girl presented to our Pediatric Allergy Clinic with recurrent crackles in addition to cough, fevers, and labored breathing since her first respiratory syncytial virus infection at the age of 7 months. She had been under the care of pulmonologists, who suspected childhood interstitial lung disease. She was hospitalized eight times due to exacerbation of symptoms and prescribed systemic and inhaled steroids, short-acting β2-mimetics, and antileukotriene. There was no short-term clinical improvement at that time between hospitalizations. During her hospital stay at the Pneumonology and Cystic Fibrosis Department in Rabka a bronchoscopy with bronchoalveolar lavage was performed. Laboratory bacteriological tests found high colony count of Moraxella catarrhalis (β-lactamase positive), sensitive to amoxicillin-clavulanate, in bronchial secretions and swabs from her nose. After this, infections were treated with antibiotics; she remained in good condition without symptoms. Crackles and wheezing recurred only during symptoms of infections. Therefore, we hypothesize that respiratory syncytial virus infection at an early age might cause severe damage of the lung epithelium and prolonged clinical symptoms, mainly crackles and wheezing, each time the child has a respiratory infection.. This case illustrates the importance of respiratory syncytial virus infection in an immunocompetent child. Pediatricians need to have a high index of suspicion and knowledge of recurrent symptoms associated with severe damage of the lung epithelium to establish the correct diagnosis.

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Bronchiolitis; Bronchoalveolar Lavage Fluid; Child, Preschool; Female; Humans; Moraxella catarrhalis; Moraxellaceae Infections; Nose; Respiratory Sounds; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Respiratory Tract Infections

Respiratory syncytial virus (RSV) is an important cause of acute lower respiratory tract infection (ALRI) in infants and young children globally. RSV presents two antigenic groups RSV-A and -B. Genetic variability is also very high within each group. RSV circulation varies year to year and even varies among different regions. Data on circulatory pattern of RSV are available from other parts of India except Kerala. The aim of the study was to generate data about groups and genotypes of circulating RSV in Kerala. In this study, RSV positive samples received during January, 2012 to December, 2014 were used for genetic characterization. The samples were tested by using nucleocapsid (N) gene-based conventional multiplex reverse transcriptase polymerase chain reaction (RT-PCR) to identify the RSV group. Genotyping was done by nucleotide sequencing of the C-terminal region of the glycoprotein (G) gene. Out of the 130 patient samples tested, 49 samples were positive for RSV. Among the positive samples, 32 belong to the RSV-A and 17 belong to RSV-B virus. Phylogenetic analysis revealed that all RSV-A sequences (n = 22) belonged to NA1 genotype and five of the sequences showed the novel 72 nucleotide duplication and clustered into the newly designated ON1 genotype. All RSV-B sequences (n = 17) were clustered into the BA (BA9 and 10) genotype. From this study, we concluded both RSV-A and -B were co-circulated in Kerala and RSV-A was observed predominantly in 2012 and RSV-B in 2014. As per our best of knowledge, BA10 genotype is first observed in India.

Topics: Child, Preschool; Female; Genetic Variation; Genotype; Humans; India; Infant; Infant, Newborn; Male; Nose; Pharynx; Phylogeny; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Respiratory Tract Infections; RNA, Viral; Sequence Analysis, DNA

High-flow nasal cannula (HFNC) therapy provides noninvasive respiratory support for infant bronchiolitis and its use has increased following good clinical experiences. This national study describes HFNC use in Finland during a severe respiratory syncytial virus (RSV) epidemic.. A questionnaire on using HFNC for infant bronchiolitis during the 2015-2016 RSV epidemic was sent to the head physicians of 18 Finnish children's hospitals providing inpatient care for infants: 17 hospitals answered, covering 77.5% of the infants born in Finland in 2015.. Most (85%) HFNC was given on paediatric wards. The mean incidence for bronchiolitis treated with HFNC in infants under the age of one in 15 of 17 hospitals was 3.8 per 1000 per year (range: 1.4-8.1): one hospital did not supply the relevant data and one supplied a figure of 34.1 due to a different treatment policy. Instructions on how to start and wean HFNC therapy were present in 71% and 61% of the hospitals, respectively, weighted to the population. Providing weaning instructions was associated with shorter weaning times.. High-flow nasal cannula was actively used for infants with bronchiolitis, with no substantial overuse. Randomised controlled studies are needed before any evidence-based guidelines can be constructed for using HFNC in infant bronchiolitis.

Topics: Biomedical Research; Bronchiolitis; Cannula; Evidence-Based Medicine; Finland; Health Care Surveys; Humans; Infant; Needs Assessment; Nose; Oxygen Inhalation Therapy; Practice Guidelines as Topic; Respiratory Syncytial Virus Infections

Respiratory syncytial virus (RSV) is the most important viral cause of pneumonia in children. RSV-specific antibody (ab) protects infants from disease, and may be increased by a potential strategy of maternal RSV vaccination.. To describe the effect of RSV antibody on RSV infection risk in infants in a resource-limited setting.. Transplacental transfer of RSV antibody from mother to the fetus was highly efficient in mother-infant pairs in rural Nepal, though higher antibody concentrations were not protective against earlier or more severe RSV infection in infants.

Topics: Antibodies, Viral; Female; Fetal Blood; Humans; Immunity, Maternally-Acquired; Immunization, Passive; Infant; Infant, Newborn; Male; Nepal; Nose; Polymerase Chain Reaction; Pregnancy; Premature Birth; Prospective Studies; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Rural Population

This study was established to provide direct evidence on the incidence of laboratory-confirmed influenza virus and respiratory syncytial virus (RSV) infections in older adults in two cities in Jiangsu Province, China, and the potential impact of acute respiratory infections on frailty.. The cohort was enrolled in Suzhou and Yancheng, two cities in Jiangsu Province in Eastern China. Between November 2015 and March 2016, we enrolled 1532 adults who were 60-89 years of age, and collected blood samples along with baseline data on demographics, general health, chronic diseases, functional status and cognitive function through face-to-face interviews using a standardised questionnaire. Participants are being followed weekly throughout the year to identify acute respiratory illnesses. We schedule home visits to ill participants to collect mid-turbinate nasal and oropharyngeal swabs for laboratory testing and detailed symptom information for the acute illness. Regular follow-up including face-to-face interviews and further blood draws will take place every 6-12 months.. As of 3 September 2016, we had identified 339 qualifying acute respiratory illness events and 1463 (95%) participants remained in the study. Laboratory testing is ongoing.. We plan to conduct laboratory testing to estimate the incidence of influenza virus and RSV infections in older adults. We plan to investigate the impact of these infections on frailty and functional status to determine the association of pre-existing immune status with protection against influenza and RSV infection in unvaccinated older adults, and to assess the exposure to avian influenza viruses in this population.

Topics: Age Factors; Aged; Aged, 80 and over; Aging; Animals; China; Female; Frailty; Humans; Incidence; Influenza, Human; Male; Middle Aged; Nose; Oropharynx; Orthomyxoviridae; Prospective Studies; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Respiratory Tract Infections; Surveys and Questionnaires; Urban Population

 Vaccines and antivirals against respiratory syncytial virus (RSV) are being developed, but there are scarce data on the full impact of RSV infection on outpatient children..  We analyzed the burden of RSV illness in a prospective cohort study of children aged ≤13 years during 2 consecutive respiratory seasons in Turku, Finland (2231 child-seasons of follow-up). We examined the children and obtained nasal swabs for the detection of RSV during each respiratory illness. The parents filled out daily symptom diaries throughout the study..  Of 6001 medically attended respiratory infections, 302 (5%) were caused by RSV. Per 1000 children, the average annual RSV infection incidence rates among children aged <3, 3-6, and 7-13 years were 275, 117, and 46 cases, respectively. In children aged <3 years, acute otitis media developed in 58%, and 66% of children in this age group received antibiotics. The mean duration of RSV illness was longest (13.0 days) and the rate of parental work absenteeism was highest (136 days per 100 children with RSV illness) in children aged <3 years..  The burden of RSV is particularly great among outpatient children aged <3 years. Young children are an important target group for the development of RSV vaccines and antivirals.

Topics: Acute Disease; Antiviral Agents; Child; Child, Preschool; Cost of Illness; Female; Finland; Hospitalization; Humans; Infant; Male; Nose; Otitis Media; Prospective Studies; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus Vaccines; Respiratory Syncytial Virus, Human; Risk Factors; Seasons; Socioeconomic Factors

Nosocomial transmission of respiratory syncytial virus (RSV) occurs in children within the neonatal intensive care unit (NICU). During peak community RSV transmission, three swabs were collected from the nose, hand and personal clothing of visitors and health care workers (HCW) in NICU once every week for eight weeks. Nasal swabs were collected from every third neonate and from any neonate clinically suspected of having a respiratory infection. Environmental sampling of high touch areas was done once during the study period. All swabs were tested for RSV using real time RT-PCR. There were 173 (519 total) and 109 (327 total) swabs, each of nose, hand and dress from 84 HCWs and 80 visitors respectively and 81 nasal swabs from 55 neonates collected. Thirty five environmental swabs from surfaces of the beds, side tables, counter tops, chairs, tables and computers were collected. Overall 1% of nasal swabs from each of HCWs, visitors and neonates, 4% of dress specimens from visitors and 9% of environmental swabs were positive for RSV-RNA. The results suggest that though the risk for RSV in the NICU remains low, personnel clothing are contaminated with RSV-RNA and may have a role in transmission.

Topics: Adolescent; Adult; Child; Child, Preschool; Cross Infection; Environmental Microbiology; Female; Hand; Humans; Infant; Infant, Newborn; Intensive Care Units, Neonatal; Male; Nose; Prospective Studies; Real-Time Polymerase Chain Reaction; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Reverse Transcriptase Polymerase Chain Reaction; RNA, Viral

An acute viral respiratory tract infection might prevent infections by other viruses because of the antiviral innate immune response. However, with the use of PCR methods, simultaneous detection of two or more respiratory viruses is frequent. We analysed the effect of respiratory syncytial virus (RSV) infection on the occurrence of simultaneous rhinovirus (RV) infection in children within a birth cohort study setting. We used PCR for virus detection in nasal swabs collected from children with an acute respiratory tract infection at the age of 0-24 months and from healthy control children, who were matched for age and date of sample collection. Of 226 children with RSV infections, 18 (8.0%) had co-infections with RV, whereas RV was detected in 31 (14%) of 226 control children (p 0.049 by chi-square test). Adjustment for sex, number of siblings and socio-economic status strengthened the negative association between RSV and RV (OR 0.46, 95% CI 0.24-0.90; p 0.02). The median durations of symptoms (cough, rhinorrhoea, or fever) were 11 days in children with single RSV infections and 14 days in children with RSV-RV co-infections (p 0.02). Our results suggest that the presence of RSV reduces the probability of RV infection, but that, if a co-infection occurs, both viruses cause clinical symptoms.

Topics: Coinfection; Female; Humans; Infant; Infant, Newborn; Male; Nose; Picornaviridae Infections; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Respiratory Tract Infections; Rhinovirus; Risk Factors

Human respiratory syncytial virus (hRSV) and human metapneumovirus (hMPV) are major causes of illness among children, the elderly, and the immunocompromised. No vaccine has been licensed for protection against either of these viruses. We tested the ability of two Venezuelan equine encephalitis virus-based viral replicon particle (VEE-VRP) vaccines that express the hRSV or hMPV fusion (F) protein to confer protection against hRSV or hMPV in African green monkeys. Animals immunized with VEE-VRP vaccines developed RSV or MPV F-specific antibodies and serum neutralizing activity. Compared to control animals, immunized animals were better able to control viral load in the respiratory mucosa following challenge and had lower levels of viral genome in nasopharyngeal and bronchoalveolar lavage fluids. The high level of immunogenicity and protective efficacy induced by these vaccine candidates in nonhuman primates suggest that they hold promise for further development.

Topics: Alphavirus; Animals; Antibodies, Neutralizing; Antibodies, Viral; Bronchoalveolar Lavage Fluid; Chlorocebus aethiops; Encephalitis Virus, Venezuelan Equine; Immunoglobulin G; Metapneumovirus; Neutralization Tests; Nose; Paramyxoviridae Infections; Replicon; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Viral Fusion Proteins; Viral Vaccines

This study reports the results of a systematic screening for respiratory viruses in pediatric outpatients from an emergency department (ED) in southern Brazil during two consecutive influenza seasons. Children eligible for enrollment in this study were aged 24-59 months and presented with acute respiratory symptoms and fever. Naso- and oropharyngeal swabs were collected and multiplex reverse transcription PCR (RT-PCR) was performed to identify the respiratory viruses involved. In total, 492 children were included in this study: 248 in 2010 and 244 in 2011. In 2010, 136 samples (55%) were found to be positive for at least one virus and the most frequently detected viruses were human rhinovirus (HRV) (18%), adenovirus (AdV) (13%), and human coronavirus (CoV) (5%). In 2011, 158 samples (65%) were found to be positive for at least one virus, and the most frequently detected were HRV (29%), AdV (12%), and enterovirus (9%). Further, the presence of asthma (OR, 3.17; 95% CI, 1.86-5.46) was independently associated with HRV infection, whereas fever was associated with AdV (OR, 3.86; 95% CI, 1.31-16.52) and influenza infections (OR, 3.74; 95% CI, 1.26-16.06). Ten patients (2%) were diagnosed with pneumonia, and six of these tested positive for viral infection (4 HRV, 1 RSV, and 1 AdV). Thus, this study identified the most common respiratory viruses found in preschool children in the study region and demonstrated their high frequency, highlighting the need for improved data collection, and case management in order to stimulate preventive measures against these infections. J. Med. Virol. 88:1325-1333, 2016. © 2016 Wiley Periodicals, Inc.

Topics: Adenoviridae; Adenoviridae Infections; Brazil; Child; Child, Preschool; Female; Humans; Infant; Influenza A virus; Influenza, Human; Male; Multiplex Polymerase Chain Reaction; Nose; Oropharynx; Outpatients; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Respiratory Tract Infections; Rhinovirus; Seasons; Virus Diseases; Viruses

Respiratory viruses are a cause of upper respiratory tract infections (URTI), but can be associated with severe lower respiratory tract infections (LRTI) in immunocompromised patients. The objective of this study was to investigate the genetic variability of influenza virus, parainfluenza virus and respiratory syncytial virus (RSV) and the duration of viral shedding in hematological patients. Nasopharyngeal swabs from hematological patients were screened for influenza, parainfluenza and RSV on admission as well as on development of respiratory symptoms. Consecutive swabs were collected until viral clearance. Out of 672 tested patients, a total of 111 patients (17%) were infected with one of the investigated viral agents: 40 with influenza, 13 with parainfluenza and 64 with RSV; six patients had influenza/RSV or parainfluenza/RSV co-infections. The majority of infected patients (n = 75/111) underwent stem cell transplantation (42 autologous, 48 allogeneic, 15 autologous and allogeneic). LRTI was observed in 48 patients, of whom 15 patients developed severe LRTI, and 13 patients with respiratory tract infection died. Phylogenetic analysis revealed a variety of influenza A(H1N1)pdm09, A(H3N2), influenza B, parainfluenza 3 and RSV A, B viruses. RSV A was detected in 54 patients, RSV B in ten patients. The newly emerging RSV A genotype ON1 predominated in the study cohort and was found in 48 (75%) of 64 RSV-infected patients. Furthermore, two distinct clusters were detected for RSV A genotype ON1, identical RSV G gene sequences in these patients are consistent with nosocomial transmission. Long-term viral shedding for more than 30 days was significantly associated with prior allogeneic transplantation (p = 0.01) and was most pronounced in patients with RSV infection (n = 16) with a median duration of viral shedding for 80 days (range 35-334 days). Long-term shedding of respiratory viruses might be a catalyzer of nosocomial transmission and must be considered for efficient infection control in immunocompromised patients.

Topics: Adult; Aged; Aged, 80 and over; Cohort Studies; Communicable Disease Control; Cross Infection; Female; Genotype; Hematologic Diseases; Humans; Influenza, Human; Male; Middle Aged; Mutation; Nose; Orthomyxoviridae; Parainfluenza Virus 3, Human; Paramyxoviridae Infections; Phylogeny; Polymerase Chain Reaction; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Retrospective Studies; Sequence Analysis, DNA; Time Factors; Transplantation, Homologous; Virus Shedding; Young Adult

It is not clearly established if coinfections are more severe than single viral respiratory infections.The aim of the study was to study and to compare simple infections and viral coinfections of respiratory syncytial virus (RSV) in hospitalized children.From September 2005 to August 2013, a prospective study was conducted on children younger than 14 years of age, admitted with respiratory infection to the Pediatric Department of the Severo Ochoa Hospital, in Spain. Specimens of nasopharyngeal aspirate were taken for virological study by using polymerase chain reaction, and clinical data were recorded. Simple RSV infections were selected and compared with double infections of RSV with rhinovirus (RV) or with human bocavirus (HBoV).In this study, 2993 episodes corresponding to 2525 children were analyzed. At least 1 virus was detected in 77% (2312) of the episodes. Single infections (599 RSV, 513 RV, and 81 HBoV) were compared with 120 RSV-RV and 60 RSV-HBoV double infections. The RSV-RV coinfections had fever (63% vs 43%; P < 0.001) and hypoxia (70% vs 43%; P < 0.001) more often than RV infections. Hypoxia was similar between single or dual infections (71%). Bronchiolitis was more frequent in the RSV simple group (P < 0.001). Pediatric intensive care unit admission was more common in RSV simple or RSV-RV groups than in the RV monoinfection (P = 0.042).Hospitalization was longer for both RSV simple group and RSV-HBoV coinfection, lasting about 1 day (4.7 vs 3.8 days; P < 0.001) longer than in simple HBoV infections. There were no differences in PICU admission. RSV single group was of a younger age than the other groups.Coinfections between RSV-RV and RSV-HBoV are frequent. Overall viral coinfections do not present greater severity, but have mixed clinical features.

Topics: Adolescent; Bronchiolitis; Child; Coinfection; Female; Human bocavirus; Humans; Male; Nose; Parvoviridae Infections; Picornaviridae Infections; Prospective Studies; Respiratory Syncytial Virus Infections; Rhinovirus

Respiratory syncytial virus (RSV) is a major cause of infectious lower respiratory disease in infants and the elderly. As there is no vaccine for RSV, we developed a genetic vaccine approach that induced protection of the entire respiratory tract from a single parenteral administration. The approach was based on adenovirus vectors derived from newly isolated nonhuman primate viruses with low seroprevalence. We show for the first time that a single intramuscular (IM) injection of the replication-deficient adenovirus vectors expressing the RSV fusion (F0) glycoprotein induced immune responses that protected both the lungs and noses of cotton rats and mice even at low doses and for several months postimmunization. The immune response included high titers of neutralizing antibody that were maintained ≥ 24 weeks and RSV-specific CD8+ and CD4+ T cells. The vectors were as potently immunogenic as a human adenovirus 5 vector in these two key respiratory pathogen animal models. Importantly, there was minimal alveolitis and granulocytic infiltrates in the lung, and type 2 cytokines were not produced after RSV challenge even under conditions of partial protection. Overall, this genetic vaccine is highly effective without potentiating immunopathology, and the results support development of the vaccine candidate for human testing.

Topics: Animals; Antibodies, Neutralizing; Antibodies, Viral; Cell Line; Disease Models, Animal; Humans; Lung; Mice; Nose; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus Vaccines; Respiratory Syncytial Virus, Human; Sigmodontinae; T-Lymphocytes; Vaccines, Synthetic

Respiratory syncytial virus (RSV) is a leading cause of respiratory tract illnesses worldwide. Although the prevalence and clinical manifestations of the two subtypes, RSV-A and RSV-B, have been studied in some detail in infants and young children, they have not been determined in adults. To evaluate the prevalence of the RSV subtypes and disease severity between RSV-A and RSV-B infections in adults, nasal and throat swabs that were collected from patients ≥15 years old who sought medical care for acute respiratory infections at the Fever Clinic of the Peking Union Medical College Hospital in Beijing, China between May 2005 and April 2010. The samples were tested for RSV infection using PCR and sequencing analysis. RSV was detected in 95 (1%) of the adult patients, of whom 53 (55.8%) were positive for RSV-A and 42 (44.2%) for RSV-B. The incidence of RSV infections increased with age (χ(2) = 37.17, P = 1.66E-07). Demographic data and clinical manifestations of RSV-A were similar to those of RSV-B. Although RSV-A and RSV-B co-circulated during the 2005-2006 and 2008-2009 seasons, RSV-A was predominant in the 2006-2008 seasons, whereas RSV-B was predominant in the 2009-2010 season. Upper respiratory tract infections were diagnosed in most RSV-infected patients (n = 80, 84.2%), and three patients suffered from pulmonary infection. This is the first study to provide data on the prevalence and clinical manifestations of RSV subgroups among Chinese adults with fever and acute illness, over five successive epidemic seasons.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; China; DNA, Viral; Female; Humans; Incidence; Male; Middle Aged; Nose; Pharynx; Polymerase Chain Reaction; Prevalence; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Respiratory Tract Infections; Sequence Analysis, DNA; Young Adult

Respiratory syncytial virus (RSV), a common respiratory pathogen in infants and the older population, causes pulmonary inflammation and airway occlusion that leads to impairment of lung function. Here, we have established a role for receptor for advanced glycation end products (RAGE) in RSV infection. RAGE-deficient (ager(-/-)) mice were protected from RSV-induced weight loss and inflammation. This protection correlated with an early increase in type I interferons, later decreases in proinflammatory cytokines, and a reduction in viral load. To assess the contribution of soluble RAGE (sRAGE) to RSV-induced disease, wild-type and ager(-/-) mice were given doses of sRAGE following RSV infection. Of interest, sRAGE treatment prevented RSV-induced weight loss and neutrophilic inflammation to a degree similar to that observed in ager(-/-) mice. Our work further elucidates the roles of RAGE in the pathogenesis of respiratory infections and highlights the opposing roles of membrane and sRAGE in modulating the host response to RSV infection.

Topics: Animals; Glycation End Products, Advanced; Lung; Mice; Mice, Knockout; Nose; Protein Isoforms; Receptor for Advanced Glycation End Products; Receptors, Immunologic; Respiratory Syncytial Virus Infections; Viral Load

To determine the optimal level of nasal continuous positive airway pressure (nCPAP) in infants with severe hypercapnic viral bronchiolitis as assessed by the maximal unloading of the respiratory muscles and improvement of breathing pattern and gas exchange.. A prospective physiological study in a tertiary paediatric intensive care unit (PICU). Breathing pattern, gas exchange, intrinsic end expiratory pressure (PEEPi) and respiratory muscle effort were measured in ten infants with severe hypercapnic viral bronchiolitis during spontaneous breathing (SB) and three increasing levels of nCPAP.. During SB, median PEEPi was 6 cmH(2)O (range 3.9-9.2 cmH(2)O), median respiratory rate was 78 breaths/min (range 41-96), median inspiratory time/total duty cycle (T (i)/T (tot)) was 0.45 (range 0.40-0.48) and transcutaneous carbon dioxide pressure (P (tc)CO(2)) was 61.5 mmHg (range 50-78). In all the infants, an nCPAP level of 7 cmH(2)O was associated with the greatest reduction in respiratory effort with a mean reduction in oesophageal and diaphragmatic pressure swings of 48 and 46%, respectively, and of the oesophageal and diaphragmatic pressure time product of 49 and 56%, respectively. During nCPAP, median respiratory rate decreased to 56 breaths/min (range 39-108, p < 0.05), median T (i)/T (tot) decreased to 0.40 (range 0.34-0.44, p < 0.50) and P (tc)CO(2) decreased to 49 mmHg (range 35-65, p < 0.05). Only one infant with associated bacterial pneumonia required intubation and all the infants were discharged alive from the PICU after a median stay of 5.5 (range 3-27 days).. In infants with hypercapnic respiratory failure due to acute viral bronchiolitis, an nCPAP level of 7 cmH(2)O is associated with the greatest unloading of the respiratory muscles and improvement of breathing pattern, as well as a favourable short-term clinical outcome.

Topics: Bronchiolitis, Viral; Continuous Positive Airway Pressure; Female; France; Humans; Hypercapnia; Infant; Intensive Care Units, Pediatric; Male; Nose; Prospective Studies; Pulmonary Gas Exchange; Respiration; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Severity of Illness Index

The efficacy of a single dose of an inactivated bovine respiratory syncytial virus (BRSV)--Parainfluenaza type 3 (PI3)--Mannheimia haemolytica (Mh) combination vaccine, in calves positive for maternal antibodies, was established in a BRSV infection study.. As expected the single vaccination did not have any effect on the decline of BRSV-specific neutralising or ELISA antibody. The cellular immune system was however primed by the vaccination. In the vaccinated group virus excretion with nasal discharge was reduced, less virus could be re-isolated from lung tissues and the lungs were less affected.. These results indicate that a single vaccination with an inactivated BRSV vaccine was able to break through the maternal immunity and induce partial protection in very young calves. It can be speculated that the level and duration of protection will improve after the second dose of vaccine is administered. A two-dose basic vaccination schedule is recommended under field conditions.

Topics: Animals; Antibodies, Viral; Body Temperature; Cattle; Cattle Diseases; Lung; Nose; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Bovine; Vaccines, Inactivated; Viral Vaccines

Acute respiratory infections (ARI) play a major role in hospitalizations in the Middle East, but the specific viral causes are unknown. We conducted prospective viral surveillance in children <5 y of age admitted with ARI and/or fever at 2 dissimilar hospitals in Amman, Jordan during peak respiratory syncytial virus (RSV) season. We collected prospective clinical and demographic data and obtained nose/throat swabs for testing for RSV by real-time polymerase chain reaction (RT-PCR). We obtained clinical and laboratory data for 728/743 (98%) subjects enrolled. The children's median age was 4.3 months, 58.4% were males, 87% were breastfed, 4% attended day care, 67% were exposed to smokers, 7% were admitted to the intensive care unit, and 0.7% died (n = 5). Out of 728 subjects, 467 (64%) tested positive by RT-PCR for RSV. Comparing RSV-positive with RSV-negative subjects, the RSV-positive subjects had lower median age (3.6 vs 6.4 months, p < 0.001) and fewer males (55% vs 64%, p = 0.02). RSV-positive children had higher rates of oxygen use (72% vs 42%, p < 0.001), a longer hospital stay (5 vs 4 days, p = 0.001), and higher hospital charges (US$538 vs US$431, p < 0.001) than RSV-negative children. In young hospitalized Jordanian infants, the medical and financial burden of RSV was found to be high. Effective preventive measures, such as an RSV vaccine, would have a significant beneficial impact.

Topics: Age Factors; Cost of Illness; Female; Hospitalization; Humans; Infant; Jordan; Length of Stay; Male; Middle East; Nose; Pharynx; Prevalence; Prospective Studies; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Reverse Transcriptase Polymerase Chain Reaction; RNA, Viral; Sex Factors; United States

Human metapneumovirus (HMPV) has recently been identified as an important cause of acute respiratory infections (ARI) in children worldwide. However, there is little systematic data on its frequency and importance as a cause of ARI in the Middle East. We conducted a viral surveillance study in children <5 years of age admitted with respiratory symptoms and/or fever at two major tertiary care hospitals in Amman, Jordan from 1/18-3/29/07. Nose and throat swabs were collected and tested for HMPV and other respiratory viruses by real-time RT-PCR. A total of 743 subjects were enrolled. Forty-four (6%) subjects were positive for HMPV, 467 (64%) were positive for RSV and 13 (1.3%) had co-infection with both HMPV and RSV. The frequency of HMPV in January, February, and March was 4.1%, 3.0%, and 11.9% respectively. Clinical features associated with HMPV infection were similar to those of other respiratory viruses, except children with HMPV were more likely to present with fever than children not infected with HMPV. Children with HMPV and RSV co-infection were administered supplemental oxygen and were admitted to the ICU more frequently than children infected with HMPV alone or RSV alone, though these differences did not reach statistical significance. We conclude that HMPV is an important cause of acute respiratory infections in children in Amman, Jordan. Longer surveillance studies are needed to better understand the seasonal epidemiology of HMPV and to assess if co-infection with HMPV and RSV leads to more severe illness.

Topics: Child, Hospitalized; Comorbidity; Female; Humans; Incidence; Infant; Jordan; Male; Metapneumovirus; Nose; Paramyxoviridae Infections; Pharynx; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Reverse Transcriptase Polymerase Chain Reaction; Seasons

Although the most frequent extra-pulmonary manifestations of respiratory syncytial virus (RSV) infection involve the cardiovascular system, no data regarding heart function in infants with bronchiolitis associated with RSV infection have yet been systematically collected. The aim of this study was to verify the real frequency of heart involvement in patients with bronchiolitis associated with RSV infection, and whether infants with mild or moderate disease also risk heart malfunction.. A total of 69 otherwise healthy infants aged 1-12 months with bronchiolitis hospitalised in standard wards were enrolled. Pernasal flocked swabs were performed to collect specimens for the detection of RSV by real-time polymerase chain reaction, and a blood sample was drawn to assess troponin I concentrations. On the day of admission, all of the infants underwent 24-hour Holter ECG monitoring and a complete heart evaluation with echocardiography. Patients were re-evaluated by investigators blinded to the etiological and cardiac findings four weeks after enrollment.. Regardless of their clinical presentation, sinoatrial blocks were identified in 26/34 RSV-positive patients (76.5%) and 1/35 RSV-negative patients (2.9%) (p < 0.0001). The blocks recurred more than three times over 24 hours in 25/26 RSV-positive patients (96.2%) and none of the RSV-negative infants. Mean and maximum heart rates were significantly higher in the RSV-positive infants (p < 0.05), as was low-frequency power and the low and high-frequency power ratio (p < 0.05). The blocks were significantly more frequent in the children with an RSV load of ≥100,000 copies/mL than in those with a lower viral load (p < 0.0001). Holter ECG after 28 ± 3 days showed the complete regression of the heart abnormalities.. RSV seems associated with sinoatrial blocks and transient rhythm alterations even when the related respiratory problems are mild or moderate. Further studies are needed to clarify the mechanisms of these rhythm problems and whether they remain asymptomatic and transient even in presence of severe respiratory involvement or chronic underlying disease.

Topics: Bronchiolitis; Echocardiography; Female; Heart; Heart Rate; Humans; Infant; Male; Nose; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Sinoatrial Block; Troponin

The objective of this study was to calculate sensitivity values for the detection of major respiratory viruses of childhood by using combined nose-throat swabs and nasopharyngeal aspirates.. Children who had symptoms and presented to a pediatric teaching hospital and had a diagnostic respiratory specimen collected were enrolled, and paired nose-throat swab and nasopharyngeal aspirate specimens were collected. Parents were asked to collect the nose-throat swab specimen in the first instance but could defer to a health care worker if unwilling. Nose-throat swab collectors were asked to rate perceived quality of collection. All nasopharyngeal aspirates were collected by a health care worker by using a standard protocol. Real-time polymerase chain reaction for 8 respiratory viruses was performed in our hospital's diagnostic laboratory.. Paired nose-throat swab/nasopharyngeal aspirate specimens were collected during 303 illnesses, with at least 1 respiratory virus identified in 186 (61%). For the major pathogens of childhood, influenza A virus and respiratory syncytial virus, collection by using the nose-throat swab had a sensitivity of 91.9% and 93.1%, respectively. A health care worker collected 219 (72%) of the nose-throat swab specimens; concordance with the nasopharyngeal aspirate was not related to health care worker collection or perceived quality of collection.. Nose-throat swab specimens, in combination with sensitive molecular testing, are a less invasive diagnostic respiratory specimen with adequate sensitivity for use in the clinic and hospital outpatient settings and large-scale community studies through parent collection. For children who present to a hospital in which an avian or pandemic strain of influenza virus is reasonably part of the differential diagnosis, nasopharyngeal aspirates or a similar collection technique (eg, nasal washes) should continue to be used.

Topics: Adolescent; Child; Child, Preschool; Diagnosis, Differential; DNA, Viral; Female; Humans; Incidence; Infant; Infant, Newborn; Influenza A virus; Influenza, Human; Male; Nasopharynx; Nose; Polymerase Chain Reaction; Queensland; Reproducibility of Results; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Retrospective Studies

Influenza virus and respiratory syncytial virus (RSV) are among the most common viruses causing infections of the lower respiratory tract in young children. Although there are important differences in the immunopathogenesis of these 2 viral pathogens, little is known about how they affect antigen-presenting cells in children with acute infections.. To characterize the immune cells that are mobilized to the respiratory tract by influenza virus and RSV, we analyzed nasal wash and blood samples obtained from children hospitalized with acute respiratory infections.. Influenza virus and RSV mobilize immune cells, including myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs), to the nasal mucosa. Patients with influenza virus infection had greater numbers of mDCs, pDCs, and monocytes in nasal wash samples than did patients with RSV infection. The frequencies of respiratory tract and blood T cell subsets were not affected by infection with influenza virus or RSV. Monocyte chemoattractant protein-1 concentrations in nasal wash samples were significantly increased in patients with influenza virus infection but not in those with RSV infection. RANTES (regulated on activation, normally T cell expressed and secreted) concentrations were increased only in the blood of patients with influenza virus infection.. Infection with influenza virus or RSV mobilizes antigen-presenting cells to the respiratory tract. The differences in antigen-presenting cell numbers and cytokine concentrations suggest that there are distinctive, early immune responses to these 2 viruses.

Topics: Chemokine CCL2; Chemokine CCL5; Child, Preschool; Cytokines; Dendritic Cells; Female; Humans; Infant; Infant, Newborn; Influenza, Human; Male; Monocytes; Nose; Orthomyxoviridae; Respiratory Mucosa; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; T-Lymphocyte Subsets

Calls to a UK national telephone health helpline (NHS Direct) have been used for syndromic surveillance, aiming to provide early warning of rises in community morbidity. We investigated whether self-sampling by NHS Direct callers could provide viable samples for influenza culture. We recruited 294 NHS Direct callers and sent them self-sampling kits. Callers were asked to take a swab from each nostril and post them to the laboratory. Forty-two per cent of the samples were returned, 16.2% were positive on PCR for influenza (16 influenza A(H3N2), three influenza A (H1N1), four influenza B) and eight for RSV (5.6%). The mean time between the NHS Direct call and laboratory analysis was 7.4 days. These samples provided amongst the earliest influenza reports of the season, detected multiple influenza strains, and augmented a national syndromic surveillance system. Self-sampling is a feasible method of enhancing community-based surveillance programmes for detection of influenza.

Topics: Adult; Aged; Aged, 80 and over; Female; Humans; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H3N2 Subtype; Influenza B virus; Influenza, Human; Male; Middle Aged; Nose; Polymerase Chain Reaction; Population Surveillance; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Self-Examination; Time Factors; United Kingdom

Reverse transcription polymerase chain reaction (RT-PCR) is a powerful tool that allows the detection of minute quantities of viral RNA. Because of the sensitivity of these assays it is possible that the finding of viral RNA indicates not only active infection but also transient colonization or residual nucleic acid from a distant infection. Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) are two viruses for which RT-PCR is now frequently used for diagnosis in adult disease.. We evaluated nasal secretions from adults with and without respiratory illnesses by nested, one-tube RT-PCR for RSV and hMPV to determine if rates of detectable RNA were significantly higher among ill subjects compared to controls suggesting a causal relationship with respiratory illness.. Adults presenting to a health care provider with complaints of respiratory illness were recruited as "cases" and those visiting for non-respiratory complaints were recruited as "controls". Subjects were enrolled during a 3-month period (January to April) when both viruses were expected to be prevalent in the community. Nasal swab samples were obtained and subjected to one-tube nested RT-PCR for RSV and hMPV.. Of 146 ill subjects, 17 (11.6%) tested positive for RSV and 5 (3.4%) were positive for hMPV. Of the 158 control subjects, one was RT-PCR positive for RSV and none tested positive for hMPV. The rates of RT-PCR positive cases compared to controls were significantly different for RSV (p<.0001) and hMPV (p<.02). Subjects remained RSV RT-PCR positive on average until day 7.1+/-2.8 of symptoms with a range of 3-10 days. No subject had a positive swab on days 14, 21 or 28.. Asymptomatic carriage of RSV or hMPV is uncommon. RT-PCR should be a useful method for the diagnosis of these viral illnesses in adults.

Topics: Adult; Aged; Aged, 80 and over; Female; Humans; Male; Metapneumovirus; Middle Aged; Nose; Paramyxoviridae Infections; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Respiratory Tract Infections; Reverse Transcriptase Polymerase Chain Reaction; RNA, Viral; Specimen Handling

The underlying relationship between viral infections and allergic diseases of the upper respiratory tract has not been well clarified.. In order to clarify the relationship between viral infection and nasal hypersensitivity, mice were sensitized with ovalbumin (OVA) and then infected intranasally with respiratory syncytial virus (RSV), after which their nasal sensitivity to histamine or antigen was examined.. Non-sensitized mice showed transient mild nasal hypersensitivity following nasal administration of histamine after intranasal RSV inoculation. In mice sensitized with OVA, RSV infection significantly exaggerated their nasal hypersensitivity to histamine and OVA. Treatment of these mice with a neurokinin (NK)-1/NK-2 receptor antagonist, but not with anti-IL-5 antibodies, reduced their hypersensitivity. The infiltration of nasal mucosa with eosinophils was temporarily associated with accelerated rate of RSV elimination in these animals.. RSV infection induced transient nasal hypersensitivity. Several mechanisms, including impairment of nasal epithelial cells are thought to mediate this effect. In allergen-sensitized mice, RSV inoculation strongly enhanced nasal hypersensitivity.

Topics: Administration, Intranasal; Animals; Antibodies; Eosinophils; Histamine; Interleukin-5; Male; Mice; Mice, Inbred C57BL; Nasal Mucosa; Neurokinin-1 Receptor Antagonists; Nose; Ovalbumin; Receptors, Neurokinin-1; Receptors, Neurokinin-2; Respiratory Hypersensitivity; Respiratory Syncytial Virus Infections; Virus Replication

Surveillance of winter respiratory viral illness has been carried out for nearly 30 years using a clinical diagnosis by general practitioners as part of the Scottish Sentinel General Practice (SSGP) network. Contemparaneous laboratory diagnosis has not been available previously.. To assess the proportion of influenza-like illness (ILI) attributable to influenza, respiratory syncytial virus (RSV) and picornavirus infection during the winter season. To compare the influenza PCR data with serology of paired blood samples.. Combined nose and throat swabs, from patients with ILI attending 15 general practices across Scotland, were submitted to the laboratory in virus PCR sample solution (VPSS). The extracted nucleic acid was tested using a multiplex reverse-transcription polymerase chain reaction (RT-PCR) assay. Serological analysis was performed on paired serum samples using complement fixation assays. The rate of influenza virus positivity was compared with reports of ILI obtained from the SSGP network.. Of 240 samples received at the laboratory, 132 (55%) were PCR positive for influenza A virus. There were nine (3.8%) picornavirus and three (1.2%) RSV PCR positives, two (0.8%) were dual influenza A/picornavirus infections. Ninety four (39.2%) were negative for all viruses tested. Results on paired sera from 89 patients showed a rising titre to influenza A in 48 of the 57 PCR positive samples (84.2%). One PCR negative patient displayed a significant rising titre to influenza A. Virological data paralleled the SSGP data but was available at least a week earlier.. Influenza A infection was detected in the majority of patients with ILI; picornavirus infection was also shown to be an important cause of illness. PCR is a rapid and sensitive method for respiratory virus surveillance. Serology is slow, insensitive and difficult to interpret at low titres.

Topics: Adolescent; Adult; Aged; Antibodies, Viral; Child; Child, Preschool; Community-Acquired Infections; Complement Fixation Tests; Female; Humans; Influenza, Human; Male; Middle Aged; Nose; Orthomyxoviridae; Pharynx; Picornaviridae; Picornaviridae Infections; Population Surveillance; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Reverse Transcriptase Polymerase Chain Reaction; Scotland

Long-lasting protective antibody is not normally generated in children following primary respiratory syncytial virus (RSV) infection, frequently leading to reinfection. We used the BALB/c mouse model to examine the role of the nasal-associated lymphoid tissue and the bone marrow in the generation of RSV-specific long-lasting plasma cells, with a view to further understanding the mechanisms responsible for the poorly sustained RSV antibody levels following primary infection. We show here that substantial numbers of RSV-specific plasma cells were generated in the bone marrow following challenge, which were maintained thereafter. In contrast, in the nasal-associated lymphoid tissue, RSV-specific plasma cell numbers waned quickly both after primary infection and after challenge and were not maintained at a higher level after boosting. These data indicate that the inability to generate a robust local mucosal response in the nasal tissues may contribute substantially to the likelihood of subsequent reinfection and that the presence of serum anti-RSV antibody without local protection is not enough to protect against reinfection.

Topics: Animals; Antibodies, Viral; Disease Models, Animal; Female; Immunoglobulin G; Lung; Lymphoid Tissue; Mice; Mice, Inbred BALB C; Nose; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human

Despite the documented disease burden of respiratory syncytial virus (RSV) in the elderly, little is known about the underlying risk factors or pathogenesis of RSV in a geriatric population. This report describes an age-dependent change of RSV clearance in the lung and nose of the cotton rat. Six days postinfection with RSV, lung and nose viral titers were significantly higher in all older age groups as compared with 4- to 6-week old cotton rats (P < 0.05). When comparing the 4- to 6-week old animals to the 15- to 16-month old animals 6 days postinfection, there was over an 800- and 100-fold increase in lung and nose viral titers, respectively. The cotton rat may prove to be a useful model in eliciting mechanisms of severe RSV disease in the elderly.

Topics: Aging; Animals; Disease Models, Animal; Female; Humans; Lung; Male; Nose; Rats; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Sigmodontinae; Virus Replication

To determine the usefulness of nasal swabs as a simple method for detection of respiratory viruses, we compared nasal swabs and nasopharyngeal aspirates obtained at the same time from the opposite nostrils of 230 children with upper respiratory infection. The sensitivity of nasal swabs was comparable to that of nasopharyngeal aspirates for the detection of all major respiratory viruses except respiratory syncytial virus.

Topics: Adolescent; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Male; Mucus; Nasopharynx; Nose; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Respiratory Tract Infections; Sensitivity and Specificity; Specimen Handling; Virus Diseases; Viruses

The design and synthesis of a new potent and selective inhibitor of the respiratory syncytial virus are described. This compound, RFI-641, emerged from analysis of the structure-activity relationship in a series of biphenyl triazine anionic compounds possessing specific anti-RSV activity. The key synthetic step involves coupling of diaminobiphenyl 11 with two equivalents of chlorotriazine 10 under microwave conditions. RFI-641 inhibited RSV in vitro and in vivo models.

Topics: Animals; Antiviral Agents; Cells, Cultured; Chlorocebus aethiops; Cytomegalovirus; Disease Models, Animal; Drug Design; Enzyme-Linked Immunosorbent Assay; Herpesvirus 1, Human; Humans; Inhibitory Concentration 50; Mice; Nose; Rats; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Sensitivity and Specificity; Structure-Activity Relationship; Sulfonamides; Triazenes; Triazines

Respiratory syncytial virus (RSV) has emerged as a leading cause of pneumonia, with high mortality, in bone marrow transplant (BMT) recipients, as well as in other profoundly immunocompromised patients, such as myelosuppressed adults with leukemia. We tested the efficacy of immunoglobulin with high anti-RSV neutralizing antibody levels (RSVIG) for prophylaxis and therapy of RSV infection in cotton rats undergoing prolonged immunosuppression with cyclophosphamide. These animals experience persistent infection, a model which is similar to the disease seen in post-BMT humans. Both prophylaxis and therapy reduced pulmonary viral replication over 500-fold to nearly undetectable levels. In animals receiving continual immunosuppression, the use of multiple therapeutic doses of RSVIG was able to prevent rebound viral replication, though virus was not completely eliminated.

Topics: Animals; Antibodies, Viral; Cyclophosphamide; Disease Models, Animal; Dose-Response Relationship, Immunologic; Immunoglobulins, Intravenous; Immunosuppressive Agents; Lung; Nose; Rats; Rats, Inbred Strains; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Sigmodontinae; Virus Replication

Although interleukin-4 (IL-4) expression has been implicated in vaccine-enhanced respiratory syncytial virus (RSV) disease, its role in mediating the immune response to primary RSV infection remains unclear. To assess the effect of IL-4 production on typical RSV infection, transgenic mice which either overexpress or fail to express IL-4 were challenged intranasally with RSV and their responses were compared to those of the parent strains. IL-4-deficient mice eliminated virus from the lung as quickly as did C57BL/6 controls. In contrast, mice which constitutively overexpress IL-4 showed delayed virus clearance compared with mice of the FVB/N control strain, although peak viral titers did not differ. IL-4 overexpression increased the magnitude of the subsequent antibody response. Lung lymphocytes harvested from IL-4-overexpressing mice post-RSV challenge showed diminished RSV-specific cytolytic activity compared with controls. Both IL-4-deficient and IL-4-overexpressing strains resisted rechallenge. These data imply that constitutive IL-4 expression delays or suppresses the development of a virus-specific cytotoxic lymphocyte population important in clearing primary RSV infection.

Topics: Animals; Antibodies, Viral; Cytotoxicity, Immunologic; Interleukin-4; Lung; Mice; Mice, Inbred C57BL; Mice, Transgenic; Nose; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; T-Lymphocytes, Cytotoxic; Virus Replication

To evaluate four methods of rapid diagnosis of respiratory syncytial virus (RSV) infection in older adults and to compare sensitivities with serologic analysis.. Prospective comparative analysis.. Two adult daycenters.. Frail older persons attending the daycenter who developed signs or symptoms of acute respiratory illness between the months of December and February.. Viral cultures performed by standard technique and bedside inoculation: antigen detection by indirect immunofluorescence assay (IFA) and Directigen enzyme immunoassay (EIA) on nasal brush samples; serologic analysis of acute and convalescent sera using EIA.. RSV infection was documented by serology in 11 of 54 (20%) subjects during the study period. Bedside viral cultures were the most sensitive assay and were positive in 6/9 infections. Standard viral culture detected 5/11 cases. Both methods of rapid antigen detection were found to be insensitive, with 1/11 detected by IFA and 0/11 detected by EIA.. Rapid antigen tests for the diagnosis of RSV in older persons should be used with caution.

Topics: Aged; Antigens, Viral; Evaluation Studies as Topic; Fluorescent Antibody Technique, Indirect; Frail Elderly; Humans; Immunoenzyme Techniques; Nose; Prospective Studies; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Sensitivity and Specificity; Serologic Tests

The modulatory effects of passive antibody on viral replication, illness, and immunity were investigated in a murine model of respiratory syncytial virus (RSV) infection. Nasally administered RSV-specific immune globulin (RSVIG) given prophylactically in a large volume (100 microL) reduced illness and RSV replication in lung after primary challenge. However, passive antibody treatment diminished the host antibody response to primary RSV infection. This resulted in greater susceptibility to reinfection and an alteration in the composition of the immune response after rechallenge. RSV infection of lung during primary infection was necessary for complete protection of lung from RSV rechallenge. Nasal infection alone during primary infection was not sufficient to protect against RSV rechallenge of lung, suggesting that the immune responses in the murine system are compartmentalized. The influence of compartmentalized immunity and modulation of immune responses will be important considerations as new approaches for topical immunoprophylaxis of RSV are developed.

Topics: Administration, Intranasal; Administration, Topical; Animals; Antibodies, Viral; Female; Immunization, Passive; Interferon-gamma; Interleukin-4; Lung; Mice; Mice, Inbred BALB C; Nose; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Virus Replication

The cotton rat model was used to test whether systemically administered immunoglobulin could protect nasal tissues against low challenge doses of respiratory syncytial virus (RSV). Animals were pretreated by intraperitoneal injection of human immunoglobulin with moderate (1:2226) or high (1:15,000) neutralizing antibody titers to RSV (day 0), challenged intranasally with RSV Long at doses ranging from 10(1) to 10(5) pfu (day 1), and sacrificed for virus titration (day 5). Pretreatment with moderate-titer immunoglobulin effected complete or near complete nasal protection against low to moderate (10(1)-10(3) pfu) RSV challenge doses and a significant reduction in nasal RSV titers at high (10(4)-10(5) pfu) challenge doses. Pretreatment with high-titer immunoglobulin effected near complete nasal protection at an RSV challenge dose of 10(3) pfu and highly significant and significant reductions in nasal RSV titers at challenge doses of 10(4) and 10(5) pfu, respectively. Immunoprophylaxis effected complete or near complete pulmonary protection at all RSV challenge doses.

Topics: Animals; Antibodies, Viral; Humans; Immunization, Passive; Immunoglobulin G; Immunoglobulins, Intravenous; Lung; Neutralization Tests; Nose; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Sigmodontinae