Genetics, recombination and clinical features of human rhinovirus species C (HRV-C) infections; interactions of HRV-C with other respiratory viruses

To estimate the frequency, molecular epidemiological and clinical associations of infection with the newly described species C variants of human rhinoviruses (HRV), 3243 diagnostic respiratory samples referred for diagnostic testing in Edinburgh were screened using a VP4-encoding region-based selective polymerase chain reaction (PCR) for HRV-C along with parallel PCR testing for 13 other respiratory viruses. HRV-C was the third most frequently detected behind respiratory syncytial virus (RSV) and adenovirus, with 141 infection episodes detected among 1885 subjects over 13 months (7.5%). Infections predominantly targeted the very young (median age 6–12 months; 80% of infections in those <2 years), occurred throughout the year but with peak incidence in early winter months. HRV-C was detected significantly more frequently among subjects with lower (LRT) and upper respiratory tract (URT) disease than controls without respiratory symptoms; HRV-C mono-infections were the second most frequently detected virus (behind RSV) in both disease presentations (6.9% and 7.8% of all cases respectively). HRV variants were classified by VP4/VP2 sequencing into 39 genotypically defined types, increasing the current total worldwide to 60. Through sequence comparisons of the 5′untranslated region (5′UTR), the majority grouped with species A (n = 96; 68%, described as HRV-Ca), the remainder forming a phylogenetically distinct 5′UTR group (HRV-Cc). Multiple and bidirectional recombination events between HRV-Ca and HRV-Cc variants and with HRV species A represents the most parsimonious explanation for their interspersed phylogeny relationships in the VP4/VP2-encoding region. No difference in age distribution, seasonality or disease associations was identified between HRV-Ca and HRV-Cc variants. HRV-C-infected subjects showed markedly reduced detection frequencies of RSV and other respiratory viruses, providing evidence for a major interfering effect of HRV-C on susceptibility to other respiratory virus infections. HRV-C's disease associations, its prevalence and evidence for interfering effects on other respiratory viruses mandates incorporation of rhinoviruses into future diagnostic virology screening

Global Genetic Diversity of Human Metapneumovirus Fusion Gene

We analyzed 64 human metapneumovirus strains from eight countries. Phylogenetic analysis identified two groups (A and B, amino acid identity 93%–96%) and four subgroups. Although group A strains predominated, accounting for 69% of all strains, as many B as A strains were found in persons >3 years of age

Human rhinovirus infection in young African children with acute wheezing

<p>Abstract</p> <p>Background</p> <p>Infections caused by human rhinoviruses (HRVs) are important triggers of wheezing in young children. Wheezy illness has increasingly been recognised as an important cause of morbidity in African children, but there is little information on the contribution of HRV to this. The aim of this study was to determine the role of HRV as a cause of acute wheezing in South African children.</p> <p>Methods</p> <p>Two hundred and twenty children presenting consecutively at a tertiary children's hospital with a wheezing illness from May 2004 to November 2005 were prospectively enrolled. A nasal swab was taken and reverse transcription PCR used to screen the samples for HRV. The presence of human metapneumovirus, human bocavirus and human coronavirus-NL63 was assessed in all samples using PCR-based assays. A general shell vial culture using a pool of monoclonal antibodies was used to detect other common respiratory viruses on 26% of samples. Phylogenetic analysis to determine circulating HRV species was performed on a portion of HRV-positive samples. Categorical characteristics were analysed using Fisher's Exact test.</p> <p>Results</p> <p>HRV was detected in 128 (58.2%) of children, most (72%) of whom were under 2 years of age. Presenting symptoms between the HRV-positive and negative groups were similar. Most illness was managed with ambulatory therapy, but 45 (35%) were hospitalized for treatment and 3 (2%) were admitted to intensive care. There were no in-hospital deaths. All 3 species of HRV were detected with HRV-C being the most common (52%) followed by HRV-A (37%) and HRV-B (11%). Infection with other respiratory viruses occurred in 20/128 (16%) of HRV-positive children and in 26/92 (28%) of HRV-negative samples.</p> <p>Conclusion</p> <p>HRV may be the commonest viral infection in young South African children with acute wheezing. Infection is associated with mild or moderate clinical disease.</p

Evolution of Airway Inflammation in Preschoolers with Asthma-Results of a Two-Year Longitudinal Study

Fractional exhaled nitric oxide (FeNO) is a non-invasive marker for eosinophilic airway inflammation and has been used for monitoring asthma. Here, we assess the characteristics of FeNO from preschool to school age, in parallel with asthma activity. A total of 167 asthmatic children and 66 healthy, age-matched controls were included in the 2-year prospective PreDicta study evaluating wheeze/asthma persistence in preschool-aged children. Information on asthma/rhinitis activity, infections and atopy was recorded at baseline. Follow-up visits were performed at 6-month intervals, as well as upon exacerbation/cold and 4-6 weeks later in the asthmatic group. We obtained 539 FeNO measurements from asthmatics and 42 from controls. At baseline, FeNO values did not differ between the two groups (median: 3.0 ppb vs. 2.0 ppb, respectively). FeNO values at 6, 12, 18 and 24 months (4.0, CI: 0.0-8.6; 6.0, CI: 2.8-12.0; 8.0, CI: 4.0-14.0; 8.5, CI: 4.4-14.5 ppb, respectively) increased with age (correlation p <= 0.001) and atopy (p = 0.03). FeNO was non-significantly increased from baseline to the symptomatic visit, while it decreased after convalescence (p = 0.007). Markers of disease activity, such as wheezing episodes and days with asthma were associated with increased FeNO values during the study (p < 0.05 for all). Age, atopy and disease activity were found to be important FeNO determinants in preschool children. Longitudinal and individualized FeNO assessment may be valuable in monitoring asthmatic children with recurrent wheezing or mild asthma

Human Rhinovirus Infections in Rural Thailand: Epidemiological Evidence for Rhinovirus as Both Pathogen and Bystander

BACKGROUND: We describe human rhinovirus (HRV) detections in SaKaeo province, Thailand. METHODS: From September 1, 2003-August 31, 2005, we tested hospitalized patients with acute lower respiratory illness and outpatient controls without fever or respiratory symptoms for HRVs with polymerase chain reaction and molecularly-typed select HRVs. We compared HRV detection among hospitalized patients and controls and estimated enrollment adjusted incidence. RESULTS: HRVs were detected in 315 (16%) of 1919 hospitalized patients and 27 (9.6%) of 280 controls. Children had the highest frequency of HRV detections (hospitalized: <1 year: 29%, 1-4 year: 29%, ≥ 65 years: 9%; controls: <1 year: 24%, 1-4 year: 14%, ≥ 65 years: 2.8%). Enrollment adjusted hospitalized HRV detection rates were highest among persons aged <1 year (1038/100,000 persons/year), 1-4 years (457), and ≥ 65 years (71). All three HRV species were identified, HRV-A was the most common species in most age groups including children aged <1 year (61%) and all adult age groups. HRV-C was the most common species in the 1-4 year (51%) and 5-19 year age groups (54%). Compared to controls, hospitalized adults (≥ 19 years) and children were more likely to have HRV detections (odds ratio [OR]: 4.8, 95% confidence interval [CI]: 1.5, 15.8; OR: 2.0, CI: 1.2, 3.3, respectively) and hospitalized children were more likely to have HRV-A (OR 1.7, CI: 0.8, 3.5) or HVR-C (OR 2.7, CI: 1.2, 5.9) detection. CONCLUSIONS: HRV rates were high among hospitalized children and the elderly but asymptomatic children also had substantial HRV detection. HRV (all species), and HRV-A and HRV-C detections were epidemiologically-associated with hospitalized illness. Treatment or prevention modalities effective against HRV could reduce hospitalizations due to HRV in Thailand

Unravelling the Genetics of Ischaemic Stroke

Hugh Markus discusses genetic factors in stroke risk, and emphasizes the importance of large sample studies and rigorous replication of results in genetic stroke research

Childhood asthma outcomes during the COVID-19 pandemic: Findings from the PeARL multi-national cohort.

BACKGROUND: The interplay between COVID-19 pandemic and asthma in children is still unclear. We evaluated the impact of COVID-19 pandemic on childhood asthma outcomes. METHODS: The PeARL multinational cohort included 1,054 children with asthma and 505 non-asthmatic children aged between 4-18 years from 25 pediatric departments, from 15 countries globally. We compared the frequency of acute respiratory and febrile presentations during the first wave of the COVID-19 pandemic between groups and with data available from the previous year. In children with asthma, we also compared current and historical disease control. RESULTS: During the pandemic, children with asthma experienced fewer upper respiratory tract infections, episodes of pyrexia, emergency visits, hospital admissions, asthma attacks and hospitalizations due to asthma, in comparison to the preceding year. Sixty-six percent of asthmatic children had improved asthma control while in 33% the improvement exceeded the minimal clinically important difference. Pre-bronchodilatation FEV1 and peak expiratory flow rate were improved during the pandemic. When compared to non-asthmatic controls, children with asthma were not at increased risk of LRTIs, episodes of pyrexia, emergency visits or hospitalizations during the pandemic. However, an increased risk of URTIs emerged. CONCLUSION: Childhood asthma outcomes, including control, were improved during the first wave of the COVID-19 pandemic, probably because of reduced exposure to asthma triggers and increased treatment adherence. The decreased frequency of acute episodes does not support the notion that childhood asthma may be a risk factor for COVID-19. Furthermore, the potential for improving childhood asthma outcomes through environmental control becomes apparent

Evidence of Recombination and Genetic Diversity in Human Rhinoviruses in Children with Acute Respiratory Infection

International audienceOur study showed a high diversity of HRV strains that cause bronchitis and pneumonia in children. A predominance of HRV-C over HRV-A and HRV-B was observed, and two subspecies of HRV-C were identified, the diversity of which seemed to be related to recombination with former HRV-A strains. None of the HRV-C strains appeared to have a higher clinical impact than HRV-A or HRV-B on respiratory compromise