Gene expression classifiers identify bacterial and viral etiologies of acute respiratory illness in Sri Lanka.
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE149947 | GEO | 2020/07/06
REPOSITORIES: GEO
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Project description:Acute respiratory illness (ARI) is the leading cause of asthma exacerbations yet the mechanisms underlying this association remain unclear. To address the deficiencies in our understanding of the molecular mechanisms driving ARI-induced asthma exacerbations, we undertook a transcriptional profiling study of the nasal mucosa over the course of ARI amongst individuals with a history of asthma, allergic rhinitis and no underlying respiratory disease. We found that ARI is characterized by dynamic, time-specific transcriptional profiles whose magnitudes of expression are influenced by underlying respiratory disease and the mucosal repair signature evoked during ARI. Most strikingly, we report that asthmatics that experience ARI-induced exacerbations are characterized by a reduced but prolonged inflammatory immune response, inadequate activation of mucosal repair and the expression of a newly described exacerbation-specific signature. Findings from our study represent a significant contribution towards clarifying the complex molecular interactions which typify ARI-induced asthma exacerbations.
2013-08-02 | GSE46171 | GEO
Project description:Gene expression classifiers identify bacterial and viral etiologies of acute respiratory illness in Sri Lanka.
| PRJNA630674 | ENA
Project description:Acute respiratory illness (ARI) is the leading cause of asthma exacerbations yet the mechanisms underlying this association remain unclear. To address the deficiencies in our understanding of the molecular mechanisms driving ARI-induced asthma exacerbations, we undertook a transcriptional profiling study of the nasal mucosa over the course of ARI amongst individuals with a history of asthma, allergic rhinitis and no underlying respiratory disease. We found that ARI is characterized by dynamic, time-specific transcriptional profiles whose magnitudes of expression are influenced by underlying respiratory disease and the mucosal repair signature evoked during ARI. Most strikingly, we report that asthmatics that experience ARI-induced exacerbations are characterized by a reduced but prolonged inflammatory immune response, inadequate activation of mucosal repair and the expression of a newly described exacerbation-specific signature. Findings from our study represent a significant contribution towards clarifying the complex molecular interactions which typify ARI-induced asthma exacerbations. Upon the onset of ‘common cold’, volunteers were instructed to attend the first of three required visits to the study clinic. The first and second visits were designed to obtain samples and clinical data during the early and late stages of symptomatic illness respectively, whereas the third visit would occur when volunteers were asymptomatic and serve as a prospective baseline (BL) for the study.
2013-08-02 | E-GEOD-46171 | biostudies-arrayexpress
Project description:We report the accuracy of various existing blood transcriptional signatures in distinguishing TB and LTBI individuals in a South Indian cohort
2018-01-24 | GSE101705 | GEO
Project description:BackgroundPathogen-based diagnostics for acute respiratory infection (ARI) have limited ability to detect etiology of illness. We previously showed that peripheral blood-based host gene expression classifiers accurately identify bacterial and viral ARI in cohorts of European and African descent. We determined classifier performance in a South Asian cohort.MethodsPatients ≥15 years with fever and respiratory symptoms were enrolled in Sri Lanka. Comprehensive pathogen-based testing was performed. Peripheral blood ribonucleic acid was sequenced and previously developed signatures were applied: a pan-viral classifier (viral vs nonviral) and an ARI classifier (bacterial vs viral vs noninfectious).ResultsRibonucleic acid sequencing was performed in 79 subjects: 58 viral infections (36 influenza, 22 dengue) and 21 bacterial infections (10 leptospirosis, 11 scrub typhus). The pan-viral classifier had an overall classification accuracy of 95%. The ARI classifier had an overall classification accuracy of 94%, with sensitivity and specificity of 91% and 95%, respectively, for bacterial infection. The sensitivity and specificity of C-reactive protein (>10 mg/L) and procalcitonin (>0.25 ng/mL) for bacterial infection were 100% and 34%, and 100% and 41%, respectively.ConclusionsPreviously derived gene expression classifiers had high predictive accuracy at distinguishing viral and bacterial infection in South Asian patients with ARI caused by typical and atypical pathogens.
| S-EPMC7314590 | biostudies-literature
Project description:BackgroundChikungunya virus (CHIKV) re-emerged in Sri Lanka in late 2006 after a 40-year hiatus. We sought to identify and characterize acute chikungunya infection (CHIK) in patients presenting with acute undifferentiated febrile illness in unstudied rural and semi-urban southern Sri Lanka in 2007.Methodology/principal findingsWe enrolled febrile patients ? 2 years of age, collected uniform epidemiologic and clinical data, and obtained serum samples for serology, virus isolation, and real-time reverse-transcriptase PCR (RT-PCR). Serology on paired acute and convalescent samples identified acute chikungunya infection in 3.5% (28/797) patients without acute dengue virus (DENV) infection, 64.3% (18/28) of which were confirmed by viral isolation and/or real-time RT-PCR. No CHIKV/DENV co-infections were detected among 54 patients with confirmed acute DENV. Sequencing of the E1 coding region of six temporally distinct CHIKV isolates (April through October 2007) showed that all isolates posessed the E1-226A residue and were most closely related to Sri Lankan and Indian isolates from the same time period. Except for more frequent and persistent musculoskeletal symptoms, acute chikungunya infections mimicked DENV and other acute febrile illnesses. Only 12/797 (1.5%) patients had serological evidence of past chikungunya infection.Conclusions/significanceOur findings suggest CHIKV is a prominent cause of non-specific acute febrile illness in southern Sri Lanka.
| S-EPMC3846738 | biostudies-literature
Project description:Dengue, a mosquito-borne viral infection that affects millions around the world, poses a substantial economic burden in endemic countries. We conducted a prospective costing study in hospitalized pediatric dengue patients at the Lady Ridgeway Hospital for Children (LRHC), a public pediatric hospital in Colombo district, Sri Lanka, to assess household out-of-pocket and hospitalization costs of dengue in pediatric patients during peak dengue transmission season. Between August and October 2013, we recruited 216 hospitalized patients (aged 0-3 years, 27%; 4-7 years, 29%; 8-12 years, 42%) who were clinically or laboratory diagnosed with dengue. Using 2013 US dollars, household out-of-pocket spending, on average, was US$59 (SD 49) per episode and increased with disease severity (DF, US$52; DHF/DSS, US$78). Pediatric dengue patients received free-of-charge medical care during hospitalization at LRHC, and this places a high financial burden on hospitals. The direct medical cost of hospitalization was US$68 (SD 31.4) for DF episode, and US$122.7 (SD 65.2) for DHF/DSS episode. Yet a hospitalized dengue illness episode still accounted for 20% to 35% of household monthly income due to direct and indirect costs. Additionally, a majority of caregivers (70%) sought outpatient care before hospitalization, most of whom (81%) visited private health facilities. Our findings indicate that hospitalized pediatric dengue illness poses a nontrivial cost burden to households and healthcare systems, emphasizing the importance of preventing and controlling the transmission of dengue in endemic countries.
| S-EPMC8274749 | biostudies-literature
Project description:Acute respiratory infections caused by bacterial or viral pathogens are among the most common reasons for seeking medical care. Despite improvements in pathogen-based diagnostics, most patients receive inappropriate antibiotics. Host response biomarkers offer an alternative diagnostic approach to direct antimicrobial use. This observational cohort study determined whether host gene expression patterns discriminate noninfectious from infectious illness and bacterial from viral causes of acute respiratory infection in the acute care setting. Peripheral whole blood gene expression from 273 subjects with community-onset acute respiratory infection (ARI) or noninfectious illness, as well as 44 healthy controls, was measured using microarrays. Sparse logistic regression was used to develop classifiers for bacterial ARI (71 probes), viral ARI (33 probes), or a noninfectious cause of illness (26 probes). Overall accuracy was 87% (238 of 273 concordant with clinical adjudication), which was more accurate than procalcitonin (78%, P < 0.03) and three published classifiers of bacterial versus viral infection (78 to 83%). The classifiers developed here externally validated in five publicly available data sets (AUC, 0.90 to 0.99). A sixth publicly available data set included 25 patients with co-identification of bacterial and viral pathogens. Applying the ARI classifiers defined four distinct groups: a host response to bacterial ARI, viral ARI, coinfection, and neither a bacterial nor a viral response. These findings create an opportunity to develop and use host gene expression classifiers as diagnostic platforms to combat inappropriate antibiotic use and emerging antibiotic resistance.
| S-EPMC4905578 | biostudies-literature
Project description:BackgroundDespite a relatively good national case reporting system in Sri Lanka, detailed maps of malaria distribution have not been publicly available.MethodsIn this study, monthly records over the period 1995 - 2000 of microscopically confirmed malaria parasite positive blood film readings, at sub-district spatial resolution, were used to produce maps of malaria distribution across the island. Also, annual malaria trends at district resolution were displayed for the period 1995 - 2002.ResultsThe maps show that Plasmodium vivax malaria incidence has a marked variation in distribution over the island. The incidence of Plasmodium falciparum malaria follows a similar spatial pattern but is generally much lower than that of P. vivax. In the north, malaria shows one seasonal peak in the beginning of the year, whereas towards the south a second peak around June is more pronounced.ConclusionThis paper provides the first publicly available maps of both P. vivax and P. falciparum malaria incidence distribution on the island of Sri Lanka at sub-district resolution, which may be useful to health professionals, travellers and travel medicine professionals in their assessment of malaria risk in Sri Lanka. As incidence of malaria changes over time, regular updates of these maps are necessary.
| S-EPMC183859 | biostudies-literature
Project description:To study influenza viruses in pigs in Sri Lanka, we examined samples from pigs at slaughterhouses. Influenza (H3N2) and A(H1N1)pdm09 viruses were prevalent during 2004-2005 and 2009-2012, respectively. Genetic and epidemiologic analyses of human and swine influenza viruses indicated 2 events of A(H1N1)pdm09 virus spillover from humans to pigs.
| S-EPMC3647653 | biostudies-literature