Respiratory syncytial virus: host genetic susceptibility and factors associated with disease severity in a cohort of pediatric patients.

BACKGROUND: Respiratory syncytial virus (RSV) infections are the leading cause of hospitalization in young children. We assessed the epidemiology, severity, clinical characteristics, molecular profile and genetic factors of RSV infections compared to acute respiratory illness (ARI) caused by other respiratory viruses. METHODS: Prospective cohort study was conducted from 2017 to 2018 with children under 2 years old hospitalized with ARI. Detection of respiratory viruses was carried out using RT-PCR. RSVs were genotyped via nucleotide sequencing, and host interleukin 28B (IL28B) single nucleotide polymorphisms (SNPs) were determined using SNP TaqMan® Genotyping Assays. RESULTS: A total of 468 children were included; 288 (61.5%) had an infection by a single virus: 202 (70.1%) cases by RSV followed by rhinovirus 36 (12.5%) and influenza 16 (5.6%). Of the RSV cases, 36% were genotyped with a higher prevalence of RSV B (62.1%). The RSV group presented median age of 2.7 months (1.6-6.8), higher frequency in: intensive care unit admission (p = 0.004), mechanical ventilation use (p = 0.018), wheezing (p < 0.001), antimicrobial use (p < 0.001) and low oxygen saturation (p < 0.001). Prematurity (27.2%) was the most frequent comorbidity. RSV patients without comorbidities demonstrated a higher frequency in the combination of IL28B rs12979860 CT/IL28B rs8099917 TG and IL28B rs12979860 TT/IL28B rs8099917 TT genotypes. Viral coinfection was detected in 27 (5.7%) children, with the most frequent being RSV and rhinovirus (14.2%). CONCLUSIONS: This study highlighted the burden of RSV infection in children under 2 years of age, without comorbidities, with a higher need for pediatric ICU admission. Some IL28B allele combinations had a significant association with RSV frequency of infections.

Clinical and epidemiological features of respiratory virus infections in preschool children over two consecutive influenza seasons in southern Brazil.

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.

Assessment of clinical and microbiota responses to fecal microbial transplantation in adult horses with diarrhea.

BACKGROUND AND AIMS: Fecal microbial transplantation (FMT) is empirically implemented in horses with colitis to facilitate resolution of diarrhea. The purpose of this study was to assess FMT as a clinical treatment and modulator of fecal microbiota in hospitalized horses with colitis. METHODS: A total of 22 horses with moderate to severe diarrhea, consistent with a diagnosis of colitis, were enrolled at two referral hospitals (L1: n = 12; L2: n = 10). FMT was performed in all 12 patients on 3 consecutive days at L1, while treatment at L2 consisted of standard care without FMT. Manure was collected once daily for 4 days from the rectum in all colitis horses, prior to FMT for horses at L1, and from each manure sample used for FMT. Fecal samples from 10 clinically healthy control horses housed at L2, and 30 healthy horses located at 5 barns in regional proximity to L1 were also obtained to characterize the regional healthy equine microbiome. All fecal microbiota were analyzed using 16S amplicon sequencing. RESULTS AND CONCLUSIONS: As expected, healthy horses at both locations showed a greater α-diversity and lower ß-diversity compared to horses with colitis. The fecal microbiome of healthy horses clustered by location, with L1 horses showing a higher prevalence of Kiritimatiellaeota. Improved manure consistency (lower diarrhea score) was associated with a greater α-diversity in horses with colitis at both locations (L1: r = -0.385, P = 0.006; L2: r = -0.479, P = 0.002). Fecal transplant recipients demonstrated a greater overall reduction in diarrhea score (median: 4±3 grades), compared to untreated horses (median: 1.5±3 grades, P = 0.021), with a higher incidence in day-over-day improvement in diarrhea (22/36 (61%) vs. 10/28 (36%) instances, P = 0.011). When comparing microbiota of diseased horses at study conclusion to that of healthy controls, FMT-treated horses showed a lower mean UniFrac distance (0.53±0.27) than untreated horses (0.62±0.26, P<0.001), indicating greater normalization of the microbiome in FMT-treated patients.

Respiratory mechanics and results of cytologic examination of bronchoalveolar lavage fluid in healthy adult alpacas.

OBJECTIVE: To evaluate respiratory mechanical function and bronchoalveolar lavage (BAL) cytologic results in healthy alpacas. ANIMALS: 16 client-owned adult alpacas. PROCEDURES: Measurements of pulmonary function were performed, including functional residual capacity (FRC) via helium dilution, respiratory system resistance via forced oscillatory technique (FOT), and assessment of breathing pattern by use of respiratory inductive plethysmography (RIP) in standing and sternally recumbent alpacas. Bronchoalveolar lavage was performed orotracheally during short-term anesthesia. RESULTS: Mean ± SD measurements of respiratory function were obtained in standing alpacas for FRC (3.19 ± 0.53 L), tidal volume (0.8 ± 0.13 L), and respiratory system resistance at 1 Hz (2.70 ± 0.88 cm H(2)O/L/s), 2 Hz (2.98 ± 0.70 cm H(2)O/L/s), 3 Hz (3.14 ± 0.77 cm H(2)O/L/s), 5 Hz (3.45 ± 0.91 cm H(2)O/L/s), and 7 Hz (3.84 ± 0.93 cm H(2)O/L/s). Mean phase angle, as a measurement of thoracoabdominal asynchrony, was 19.59 ± 10.06°, and mean difference between nasal and plethysmographic flow measurements was 0.18 ± 0.07 L/s. Tidal volume, peak inspiratory flow, and peak expiratory flow were significantly higher in sternally recumbent alpacas than in standing alpacas. Cytologic examination of BAL fluid revealed 58.52 ± 12.36% alveolar macrophages, 30.53 ± 13.78% lymphocytes, 10.95 ± 9.29% neutrophils, 0% mast cells, and several ciliated epithelial cells. CONCLUSIONS AND CLINICAL RELEVANCE: Pulmonary function testing was tolerated well in nonsedated untrained alpacas. Bronchoalveolar lavage in alpacas yielded samples with adequate cellularity that had a greater abundance of neutrophils than has been reported in horses.

FGF signaling pathway in the developing chick lung: expression and inhibition studies.

BACKGROUND: Fibroblast growth factors (FGF) are essential key players during embryonic development. Through their specific cognate receptors (FGFR) they activate intracellular cascades, finely regulated by modulators such as Sprouty. Several FGF ligands (FGF1, 2, 7, 9, 10 and 18) signaling through the four known FGFRs, have been implicated in lung morphogenesis. Although much is known about mammalian lung, so far, the avian model has not been explored for lung studies. METHODOLOGY/PRINCIPAL FINDINGS: In this study we provide the first description of fgf10, fgfr1-4 and spry2 expression patterns in early stages of chick lung development by in situ hybridization and observe that they are expressed similarly to their mammalian counterparts. Furthermore, aiming to determine a role for FGF signaling in chick lung development, in vitro FGFR inhibition studies were performed. Lung explants treated with an FGF receptor antagonist (SU5402) presented an impairment of secondary branch formation after 48 h of culture; moreover, abnormal lung growth with a cystic appearance of secondary bronchi and reduction of the mesenchymal tissue was observed. Branching and morphometric analysis of lung explants confirmed that FGFR inhibition impaired branching morphogenesis and induced a significant reduction of the mesenchyme. CONCLUSIONS/SIGNIFICANCE: This work demonstrates that FGFRs are essential for the epithelial-mesenchymal interactions that determine epithelial branching and mesenchymal growth and validate the avian embryo as a good model for pulmonary studies, namely to explore the FGF pathway as a therapeutic target.