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Rhinovirus genome variation during chronic upper and lower respiratory tract infections.

ABSTRACT: Routine screening of lung transplant recipients and hospital patients for respiratory virus infections allowed to identify human rhinovirus (HRV) in the upper and lower respiratory tracts, including immunocompromised hosts chronically infected with the same strain over weeks or months. Phylogenetic analysis of 144 HRV-positive samples showed no apparent correlation between a given viral genotype or species and their ability to invade the lower respiratory tract or lead to protracted infection. By contrast, protracted infections were found almost exclusively in immunocompromised patients, thus suggesting that host factors rather than the virus genotype modulate disease outcome, in particular the immune response. Complete genome sequencing of five chronic cases to study rhinovirus genome adaptation showed that the calculated mutation frequency was in the range observed during acute human infections. Analysis of mutation hot spot regions between specimens collected at different times or in different body sites revealed that non-synonymous changes were mostly concentrated in the viral capsid genes VP1, VP2 and VP3, independent of the HRV type. In an immunosuppressed lung transplant recipient infected with the same HRV strain for more than two years, both classical and ultra-deep sequencing of samples collected at different time points in the upper and lower respiratory tracts showed that these virus populations were phylogenetically indistinguishable over the course of infection, except for the last month. Specific signatures were found in the last two lower respiratory tract populations, including changes in the 5'UTR polypyrimidine tract and the VP2 immunogenic site 2. These results highlight for the first time the ability of a given rhinovirus to evolve in the course of a natural infection in immunocompromised patients and complement data obtained from previous experimental inoculation studies in immunocompetent volunteers.

SUBMITTER: Tapparel C

PROVIDER: S-EPMC3119694 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Rhinovirus genome variation during chronic upper and lower respiratory tract infections.

Tapparel Caroline C Cordey Samuel S Junier Thomas T Farinelli Laurent L Van Belle Sandra S Soccal Paola M PM Aubert John-David JD Zdobnov Evgeny E Kaiser Laurent L

PloS one 20110621 6

Routine screening of lung transplant recipients and hospital patients for respiratory virus infections allowed to identify human rhinovirus (HRV) in the upper and lower respiratory tracts, including immunocompromised hosts chronically infected with the same strain over weeks or months. Phylogenetic analysis of 144 HRV-positive samples showed no apparent correlation between a given viral genotype or species and their ability to invade the lower respiratory tract or lead to protracted infection. B ...[more]

PMID: 21713005

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Project description:BackgroundSeveral studies have reported that birth by caesarean section is associated with increased risk of lower respiratory tract infections in the child, but it is unclear whether this applies to any caesarean section or specifically to planned caesareans. Furthermore, although infections of the upper respiratory tract are very common during childhood, there is a scarcity of studies examining whether caesarean is also a risk factor for this site of infection.MethodsWe obtained data from two UK cohorts: the Millennium Cohort Study (MCS) and linked administrative datasets of the population of Wales through the Secure Anonymised Information Linkage (SAIL) databank. The study focused on term-born singleton infants and included 15,580 infants born 2000-2002 (MCS) and 392,145 infants born 2002-2016 (SAIL). We used information about mode of birth (vaginal delivery, assisted vaginal delivery, planned caesarean and emergency caesarean) from maternal report in the MCS and from hospital birth records in SAIL. Unplanned hospital admission for lower respiratory tract infection (LRTI) was ascertained from maternal report in the MCS and from hospital record ICD codes in SAIL. Information about admissions for upper respiratory tract infection (URTI) was available from SAIL only. Cox regression was used to estimate hazard ratios for each outcome and cohort separately while accounting for a wide range of confounders. Gestational age at birth was further examined as a potential added, indirect risk of planned caesarean birth due to the early delivery.FindingsThe rate of hospital admission for LRTI was 4.6 per 100 child years in the MCS and 5.9 per 100 child years in SAIL. Emergency caesarean was not associated with LRTI admission during infancy in either cohort. In the MCS, planned caesarean was associated with a hazard ratio of 1.39 (95% CI 1.03, 1.87) which further increased to 1.65 (95% CI 1.24, 2.19) when gestational age was not adjusted for. In SAIL, the adjusted hazard ratio was 1.10 (95% CI 1.05, 1.15), which increased to 1.17 (95% CI 1.12, 1.22) when gestational age was not adjusted for. The rate of hospital admission for URTI was 5.9 per 100 child years in SAIL. Following adjustments, emergency caesarean was found to have a hazard ratio of 1.09 (95% CI 1.05, 1.14) for hospital admission for URTI. Planned caesarean was associated with a hazard ratio of 1.11 (95% CI 1.06, 1.16) which increased to 1.17 (95% CI 1.12, 1.22) when gestational age was not adjusted for.ConclusionsThe risk of severe LRTIs during infancy is moderately elevated in infants born by planned caesarean compared to those born vaginally. Infants born by any type of caesarean may also be at a small increased risk of severe URTIs. The estimated effect sizes are stronger if including the indirect effect arising from planning the caesarean birth for an earlier gestation than would have occurred spontaneously. Further studies are needed to confirm these results.

Project description:Bronchiolitis and pneumonia are leading causes of pediatric hospitalizations. Identifying geographic patterns in hospitalization rates across small geographic areas could be particularly relevant to targeted patient-level and population-level health care.To determine whether lower respiratory tract infection hospitalization rates varied geographically across a single county and whether such variability was associated with socioeconomic conditions.Cross-sectional, population-based study of children hospitalized at one institution for lower respiratory tract infections between January 1, 2010, and December 31, 2013. The setting was Cincinnati Children's Hospital Medical Center, a large, academic, stand-alone pediatric facility located in Hamilton County, Ohio. During the study period, 99.6% of in-county children hospitalized for lower respiratory tract infections were admitted to Cincinnati Children's Hospital Medical Center. Participants were children younger than 2 years who were hospitalized with bronchiolitis and children younger than 18 years who were hospitalized with pneumonia. Patients were identified using discharge diagnosis codes and then geocoded to their home census tract.Primary exposures, linked to each geocoded patient, included census tract-level socioeconomic measures obtained from the 2008 to 2012 American Community Survey (eg, adult educational attainment, unemployment, and poverty). Patient-level variables examined included demographics, presence of a complex chronic condition, length of stay, and cost.We calculated bronchiolitis and pneumonia hospitalization rates for Hamilton County and for each of 222 in-county census tracts. Associations between hospitalization rate quintiles and underlying socioeconomic conditions were assessed using the Kruskal-Wallis test. Geographic clustering was assessed using the Getis-Ord Gi* statistic.There were 1495 bronchiolitis hospitalizations and 1231 pneumonia hospitalizations during the study period. The county rates were 17.5 (range across census tracts, 0-71.4) hospitalizations per 1000 children per year for bronchiolitis and 1.6 (range across census tracts, 0-4.3) hospitalizations per 1000 children per year for pneumonia. There was significant variation in the median hospitalization rates by census tract quintile for bronchiolitis (32.8, 20.8, 14.0, 10.4, and 5.1 per 1000) and for pneumonia (3.3, 2.1, 1.4, 0.9, and 0.3 per 1000). There were also significant, graded differences in socioeconomic measures by hospitalization rate quintile. Hot spots were localized to inner-city, impoverished neighborhoods.Bronchiolitis and pneumonia hospitalization rates varied considerably in ways that were related to underlying socioeconomic conditions. Clinical and public health interventions, targeted accordingly, could improve patient-level and population-level management of acute conditions at a reduced cost.

Dataset Information

Rhinovirus genome variation during chronic upper and lower respiratory tract infections.

Publications

Rhinovirus genome variation during chronic upper and lower respiratory tract infections.

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