A novel electronic algorithm using host biomarker point-of-care tests for the management of febrile illnesses in Tanzanian children (e-POCT): A randomized, controlled non-inferiority trial.
Ontology highlight
ABSTRACT:
SUBMITTER: Keitel K
PROVIDER: S-EPMC5653205 | biostudies-literature | 2017 Oct
REPOSITORIES: biostudies-literature
Publications
A novel electronic algorithm using host biomarker point-of-care tests for the management of febrile illnesses in Tanzanian children (e-POCT): A randomized, controlled non-inferiority trial.
Keitel Kristina K Kagoro Frank F Samaka Josephine J Masimba John J Said Zamzam Z Temba Hosiana H Mlaganile Tarsis T Sangu Willy W Rambaud-Althaus Clotilde C Gervaix Alain A Genton Blaise B D'Acremont Valérie V
PLoS medicine 20171023 10
<h4>Background</h4>The management of childhood infections remains inadequate in resource-limited countries, resulting in high mortality and irrational use of antimicrobials. Current disease management tools, such as the Integrated Management of Childhood Illness (IMCI) algorithm, rely solely on clinical signs and have not made use of available point-of-care tests (POCTs) that can help to identify children with severe infections and children in need of antibiotic treatment. e-POCT is a novel elec ...[more]
Similar Datasets
Project description:ABSTRACT Background. Acute Kawasaki disease (KD) is difficult to distinguish from other acute rash/fever illnesses, in part because the etiologic agent(s) and pathophysiology remain poorly characterized. As a result, diagnosis and critical therapies may be delayed. Methods. We used DNA microarrays to identify possible diagnostic features of KD. We compared gene expression patterns in the blood of 23 children with acute KD and 18 age-matched febrile children with three illnesses that resemble KD. Results. Genes associated with platelet and neutrophil activation were expressed at higher levels in KD patients than in patients with acute adenovirus infections or systemic adverse drug reactions but not in patients with scarlet fever; genes associated with B cell activation were also expressed at higher levels in KD patients than in controls. A striking absence of interferon-stimulated gene expression in the KD patients was confirmed in an independent cohort of KD subjects. We successfully predicted the diagnosis in 21 of 23 KD patients and 7 of 8 adenovirus patients using a set of 38 gene transcripts. Conclusions. These findings provide insight into the molecular features that distinguish KD from other febrile illnesses, and support the feasibility of developing novel diagnostic reagents for KD based on the host response. A disease state experiment design type is where the state of some disease such as infection, pathology, syndrome, etc is studied. Disease State: One of Kawasaki Disease (KD) or control (C) of Scarlet fever (C-sf), adenovirus infection (C-ai) or drug reaction (C-dr)
2009-08-12 | GSE15297 | GEO
Project description:ObjectivesKawasaki disease (KD) is an acute pediatric vasculitis of infants and young children with unknown etiology and no specific laboratory-based test to identify. A specific molecular diagnostic test is urgently needed to support the clinical decision of proper medical intervention, preventing subsequent complications of coronary artery aneurysms. We used a simple and low-cost colorimetric sensor array to address the lack of a specific diagnostic test to differentiate KD from febrile control (FC) patients with similar rash/fever illnesses.Study designDemographic and clinical data were prospectively collected for subjects with KD and FCs under standard protocol. After screening using a genetic algorithm, eleven compounds including metalloporphyrins, pH indicators, redox indicators and solvatochromic dye categories, were selected from our chromatic compound library (n = 190) to construct a colorimetric sensor array for diagnosing KD. Quantitative color difference analysis led to a decision-tree-based KD diagnostic algorithm.ResultsThis KD sensing array allowed the identification of 94% of KD subjects (receiver operating characteristic [ROC] area under the curve [AUC] 0.981) in the training set (33 KD, 33 FC) and 94% of KD subjects (ROC AUC: 0.873) in the testing set (16 KD, 17 FC). Color difference maps reconstructed from the digital images of the sensing compounds demonstrated distinctive patterns differentiating KD from FC patients.ConclusionsThe colorimetric sensor array, composed of common used chemical compounds, is an easily accessible, low-cost method to realize the discrimination of subjects with KD from other febrile illness.
| S-EPMC4747548 | biostudies-literature
Project description:ABSTRACT Background. Acute Kawasaki disease (KD) is difficult to distinguish from other acute rash/fever illnesses, in part because the etiologic agent(s) and pathophysiology remain poorly characterized. As a result, diagnosis and critical therapies may be delayed. Methods. We used DNA microarrays to identify possible diagnostic features of KD. We compared gene expression patterns in the blood of 23 children with acute KD and 18 age-matched febrile children with three illnesses that resemble KD. Results. Genes associated with platelet and neutrophil activation were expressed at higher levels in KD patients than in patients with acute adenovirus infections or systemic adverse drug reactions but not in patients with scarlet fever; genes associated with B cell activation were also expressed at higher levels in KD patients than in controls. A striking absence of interferon-stimulated gene expression in the KD patients was confirmed in an independent cohort of KD subjects. We successfully predicted the diagnosis in 21 of 23 KD patients and 7 of 8 adenovirus patients using a set of 38 gene transcripts. Conclusions. These findings provide insight into the molecular features that distinguish KD from other febrile illnesses, and support the feasibility of developing novel diagnostic reagents for KD based on the host response. A disease state experiment design type is where the state of some disease such as infection, pathology, syndrome, etc is studied. Disease State: One of Kawasaki Disease (KD) or control (C) of Scarlet fever (C-sf), adenovirus infection (C-ai) or drug reaction (C-dr) disease_state_design
2010-06-24 | E-GEOD-15297 | biostudies-arrayexpress
Project description:Kawasaki disease is an acute vasculitis of infants and young children that is recognized through a constellation of clinical signs that can mimic other benign conditions of childhood. The etiology remains unknown and there is no specific laboratory-based test to identify patients with Kawasaki disease. Treatment to prevent the complication of coronary artery aneurysms is most effective if administered early in the course of the illness. We sought to develop a diagnostic algorithm to help clinicians distinguish Kawasaki disease patients from febrile controls to allow timely initiation of treatment.Urine peptidome profiling and whole blood cell type-specific gene expression analyses were integrated with clinical multivariate analysis to improve differentiation of Kawasaki disease subjects from febrile controls.Comparative analyses of multidimensional protein identification using 23 pooled Kawasaki disease and 23 pooled febrile control urine peptide samples revealed 139 candidate markers, of which 13 were confirmed (area under the receiver operating characteristic curve (ROC AUC 0.919)) in an independent cohort of 30 Kawasaki disease and 30 febrile control urine peptidomes. Cell type-specific analysis of microarrays (csSAM) on 26 Kawasaki disease and 13 febrile control whole blood samples revealed a 32-lymphocyte-specific-gene panel (ROC AUC 0.969). The integration of the urine/blood based biomarker panels and a multivariate analysis of 7 clinical parameters (ROC AUC 0.803) effectively stratified 441 Kawasaki disease and 342 febrile control subjects to diagnose Kawasaki disease.A hybrid approach using a multi-step diagnostic algorithm integrating both clinical and molecular findings was successful in differentiating children with acute Kawasaki disease from febrile controls.
| S-EPMC3251532 | biostudies-literature
Project description:Viral infections are the leading cause of childhood acute febrile illnesses motivating consultation in sub-Saharan Africa. The majority of causal viruses are never identified in low-resource clinical settings as such testing is either not part of routine screening or available diagnostic tools have limited ability to detect new/unexpected viral variants. An in-depth exploration of the blood virome is therefore necessary to clarify the potential viral origin of fever in children. Metagenomic next-generation sequencing is a powerful tool for such broad investigations, allowing the detection of RNA and DNA viral genomes. Here, we describe the blood virome of 816 febrile children (<5 years) presenting at outpatient departments in Dar es Salaam over one-year. We show that half of the patients (394/816) had at least one detected virus recognized as causes of human infection/disease (13.8% enteroviruses (enterovirus A, B, C, and rhinovirus A and C), 12% rotaviruses, 11% human herpesvirus type 6). Additionally, we report the detection of a large number of viruses (related to arthropod, vertebrate or mammalian viral species) not yet known to cause human infection/disease, highlighting those who should be on the radar, deserve specific attention in the febrile paediatric population and, more broadly, for surveillance of emerging pathogens.Trial registration: ClinicalTrials.gov identifier: NCT02225769.
| S-EPMC8171259 | biostudies-literature
Project description:BackgroundIn the absence of proper guidelines and algorithms, available rapid diagnostic tests (RDTs) for common acute undifferentiated febrile illnesses are often used inappropriately.MethodsUsing prevalence data of 5 common febrile illnesses from India and Cambodia, and performance characteristics (sensitivity and specificity) of relevant pathogen-specific RDTs, we used a mathematical model to predict the probability of correct identification of each disease when diagnostic testing occurs either simultaneously or sequentially in various algorithms. We developed a web-based application of the model so as to visualize and compare output diagnostic algorithms when different disease prevalence and test performance characteristics are introduced.ResultsDiagnostic algorithms with appropriate sequential testing predicted correct identification of etiology in 74% and 89% of patients in India and Cambodia, respectively, compared with 46% and 49% with simultaneous testing. The optimally performing sequential diagnostic algorithms differed in India and Cambodia due to varying disease prevalence.ConclusionsSimultaneous testing is not appropriate for the diagnosis of acute undifferentiated febrile illnesses with presently available tests, which should deter the unsupervised use of multiplex diagnostic tests. The implementation of adaptive algorithms can predict better diagnosis and add value to the available RDTs. The web application of the model can serve as a tool to identify the optimal diagnostic algorithm in different epidemiological settings, while taking into account the local epidemiological variables and accuracy of available tests.
| S-EPMC7245147 | biostudies-literature
Project description:Fever is the leading cause of paediatric outpatient consultations in Sub-Saharan Africa. Although most are suspected to be of viral origin, a putative causative pathogen is not identified in over a quarter of these febrile episodes. Using a de novo assembly sequencing approach, we report the detection (15.4%) of dicistroviruses (DicV) RNA in sera collected from 692 febrile Tanzanian children. In contrast, DicV RNA was only detected in 1/77 (1.3%) plasma samples from febrile Tanzanian adults, suggesting that children could represent the primary susceptible population. Estimated viral load by specific quantitative real-time RT-PCR assay ranged from < 1.32E3 to 1.44E7 viral RNA copies/mL serum. Three DicV full-length genomes were obtained, and a phylogenetic analyse on the capsid region showed the presence of two clusters representing tentative novel genus. Although DicV-positive cases were detected throughout the year, a significantly higher positivity rate was observed during the rainy season. This study reveals that novel DicV RNA is frequently detected in the blood of Tanzanian children, paving the way for further investigations to determine if DicV possibly represent a new agent in humans.
| S-EPMC6493270 | biostudies-literature
Project description:BackgroundThe decline of malaria in Southeast Asia means other causes of fever are increasingly relevant, but often undiagnosed. The objective of this study was to assess the feasibility of point-of-care tests to diagnose acute febrile illnesses in primary care settings.MethodsA mixed-methods study was conducted at nine rural health centres in western Cambodia. Workshops introduced health workers to the STANDARD(TM) Q Dengue Duo, STANDARD(TM) Q Malaria/CRP Duo and a multiplex biosensor detecting antibodies and/or antigens of eight pathogens. Sixteen structured observation checklists assessed users' performances and nine focus group discussions explored their opinions.ResultsAll three point-of-care tests were performed well under assessment, but sample collection was difficult for the dengue test. Respondents expressed that the diagnostics were useful and could be integrated into routine clinical care, but were not as convenient to perform as standard malaria rapid tests. Health workers recommended that the most valued point-of-care tests would directly inform clinical management (e.g. a decision to refer a patient or to provide/withhold antibiotics).ConclusionsDeployment of new point-of-care tests to health centres could be feasible and acceptable if they are user-friendly, selected for locally circulating pathogens and are accompanied by disease-specific education and simple management algorithms.
| S-EPMC10629948 | biostudies-literature
Project description:ObjectiveTo assess the impact of rapid diagnostic tests on the diagnostic accuracy and treatment of malaria and non-severe fever in an Asian setting.DesignPatient randomised trial in primary level clinics.SettingTwo areas of Afghanistan where Plasmodium vivax and Plasmodium falciparum are endemic; one area with moderate transmission (eastern region) and one with low transmission (northern region).Participants5794 patients of all ages with suspected malaria enrolled by 80 clinicians in 22 clinics.InterventionsMalaria rapid diagnostic tests were compared with clinical diagnosis where no parasite diagnostic test was available, longer established field microscopy, and recently introduced microscopy.Main outcome measuresProportion of patients appropriately treated with an antimalarial, defined as patients with P vivax who received chloroquine, patients with P falciparum who received artemisinin based combination therapy, and patients with no malaria parasites who did not receive an antimalarial. Secondary outcomes included diagnostic test accuracy and the proportion of patients negative for malaria who received antibiotics and antimalarials.ResultsIn the low transmission area, comparing rapid diagnostic tests with clinical diagnosis, 65% (212/325) versus 12% (40/321) of febrile patients were appropriately treated for malaria (adjusted odds ratio 92.7, 95% confidence interval 12.4 to 694.1, P<0.001). The proportion of patients who were negative for malaria and received an antibiotic was 57% (185/325) in the rapid diagnostic test arm compared with 14% (46/321) in the clinical diagnosis arm (16.9, 3.8 to 75.4, P<0.001). In the comparison of rapid diagnostic test with microscopy in the moderate transmission area, 83.6% (1696/2028) versus 76.3% (1512/1983) of patients were appropriately treated for malaria (1.70, 1.30 to 2.23, P<0.001). A higher proportion of P falciparum cases received appropriate treatment with artemisinin based combination therapy when malaria was diagnosed by rapid diagnostic test (82%, 58/71 v 32%, 24/76; 9.2, 3.88 to 21.66, P<0.001).ConclusionsIn South and central Asian regions of low to moderate malaria transmission where clinics lack capacity for diagnosis with rapid diagnostic tests or microscopy, the introduction of the tests should be considered to improve clinical care, reduce the overuse of antimalarials, and improve disease surveillance.
| S-EPMC4064827 | biostudies-literature
Project description:Whole blood transcriptional profiles of patients with (1) active pulmonary ['AdjuVIT active TB' and 'New active pulmonary'] and (2) extrapulmonary TB ['New active-extrapulmonary'] at time of diagnosis, (3) long-term recovery after treatment for active pulmonary TB ['AdjuVIT active TB'], (4) febrile illnesses presenting to hospital ['Fever mixed infection'] and (5) febrile pneumonia ['Fever pneumonia'] before antibiotic treatment, and (6) healthy vounteers. Each array sample represents a separate individual in each group. This submission includes two human whole genome Agilent Array Designs: A-MEXP-2104 and A-AGIL-28. Each of the individual raw array files are included as well as a single processed file representing the data matrix of all the merged and normalised data for the probes that are shared by the two array designs.
2016-10-28 | E-MTAB-4257 | biostudies-arrayexpress