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Full-Text Articles in Medicine and Health Sciences

Classification Of Dengue Illness Based On Readily Available Laboratory Data, James Potts, Stephen Thomas, Anon Srikiatkhachorn, Pra-On Supradish, Wenjun Li, Ananda Nisalak, Suchitra Nimmannitya, Timothy Endy, Daniel Libraty, Robert Gibbons, Sharone Green, Alan Rothman, Siripen Kalayanarooj Jul 2015

Classification Of Dengue Illness Based On Readily Available Laboratory Data, James Potts, Stephen Thomas, Anon Srikiatkhachorn, Pra-On Supradish, Wenjun Li, Ananda Nisalak, Suchitra Nimmannitya, Timothy Endy, Daniel Libraty, Robert Gibbons, Sharone Green, Alan Rothman, Siripen Kalayanarooj

Sharone Green

The aim of this study was to examine retrospective dengue-illness classification using only clinical laboratory data, without relying on X-ray, ultrasound, or percent hemoconcentration. We analyzed data from a study of children who presented with acute febrile illness to two hospitals in Thailand. Multivariable logistic regression models were used to distinguish: (1) dengue hemorrhagic fever (DHF) versus dengue fever (DF), (2) DHF versus DF + other febrile illness (OFI), (3) dengue versus OFI, and (4) severe dengue versus non-severe dengue + OFI. Data from the second hospital served as a validation set. There were 1,227 patients in the analysis. The …


Impaired T Cell Proliferation In Acute Dengue Infection, Anuja Mathew, Ichiro Kurane, Sharone Green, David Vaughn, Siripen Kalayanarooj, Saroj Suntayakorn, Francis Ennis, Alan Rothman Jan 2014

Impaired T Cell Proliferation In Acute Dengue Infection, Anuja Mathew, Ichiro Kurane, Sharone Green, David Vaughn, Siripen Kalayanarooj, Saroj Suntayakorn, Francis Ennis, Alan Rothman

Sharone Green

Decreased proliferative responses to mitogens and recall Ags have been observed in PBMC obtained during several acute human viral infections. To determine whether cell-mediated responses are altered during acute dengue infection, we examined the proliferative responses of PBMC from children enrolled in a prospective study of dengue infections in Thailand. All responses of PBMC during acute illness were compared with the same patients' PBMC obtained at least 6 mo after their infection. Proliferative responses to PHA, anti-CD3, tetanus toxoid, and dengue Ags were decreased significantly in PBMC obtained during the acute infection. The proliferative responses to PHA were restored by …


T Cell Responses To An Hla-B*07-Restricted Epitope On The Dengue Ns3 Protein Correlate With Disease Severity, Iva Zivna, Sharone Green, David Vaughn, Siripen Kalayanarooj, Henry Stephens, Dasnayanee Chandanayingyong, Ananda Nisalak, Francis Ennis, Alan Rothman Jan 2014

T Cell Responses To An Hla-B*07-Restricted Epitope On The Dengue Ns3 Protein Correlate With Disease Severity, Iva Zivna, Sharone Green, David Vaughn, Siripen Kalayanarooj, Henry Stephens, Dasnayanee Chandanayingyong, Ananda Nisalak, Francis Ennis, Alan Rothman

Sharone Green

Dengue hemorrhagic fever (DHF), the severe manifestation of dengue virus (DV) infection characterized by plasma leakage, is more common in secondary DV infections in previously infected individuals and is associated with high levels of immune activation. To determine the Ag specificity of this immune response, we studied the response to an HLA-B*07-restricted T cell epitope, residues 221-232 of the DV NS3 protein, in 10 HLA-B*07(+) Thai children who were studied during and after acute DV infections. Peptide-specific T cells were detected in 9 of 10 subjects. The frequency of peptide-specific T cells was higher in subjects who had experienced DHF …


Predominance Of Hla-Restricted Cytotoxic T-Lymphocyte Responses To Serotype-Cross-Reactive Epitopes On Nonstructural Proteins Following Natural Secondary Dengue Virus Infection, Anuja Mathew, Ichiro Kurane, Sharone Green, Henry Stephens, David Vaughn, Siripen Kalayanarooj, Saroj Suntayakorn, Dasnayanee Chandanayingyong, Francis Ennis, Alan Rothman Jan 2014

Predominance Of Hla-Restricted Cytotoxic T-Lymphocyte Responses To Serotype-Cross-Reactive Epitopes On Nonstructural Proteins Following Natural Secondary Dengue Virus Infection, Anuja Mathew, Ichiro Kurane, Sharone Green, Henry Stephens, David Vaughn, Siripen Kalayanarooj, Saroj Suntayakorn, Dasnayanee Chandanayingyong, Francis Ennis, Alan Rothman

Sharone Green

We examined the memory cytotoxic T-lymphocytic (CTL) responses of peripheral blood mononuclear cells (PBMC) obtained from patients in Thailand 12 months after natural symptomatic secondary dengue virus infection. In all four patients analyzed, CTLs were detected in bulk culture PBMC against nonstructural dengue virus proteins. Numerous CD4+ and CD8+ CTL lines were generated from the bulk cultures of two patients, KPP94-037 and KPP94-024, which were specific for NS1.2a (NS1 and NS2a collectively) and NS3 proteins, respectively. All CTL lines derived from both patients were cross-reactive with other serotypes of dengue virus. The CD8+ NS1.2a-specific lines from patient KPP94-037 were HLA …


Determinants Of Inapparent And Symptomatic Dengue Infection In A Prospective Study Of Primary School Children In Kamphaeng Phet, Thailand, Timothy P. Endy, Kathryn B. Anderson, Ananda Nisalak, In-Kyu Yoon, Sharone Green, Alan L. Rothman, Stephen J. Thomas, Richard G. Jarman, Daniel H. Libraty, Robert V. Gibbons Jan 2014

Determinants Of Inapparent And Symptomatic Dengue Infection In A Prospective Study Of Primary School Children In Kamphaeng Phet, Thailand, Timothy P. Endy, Kathryn B. Anderson, Ananda Nisalak, In-Kyu Yoon, Sharone Green, Alan L. Rothman, Stephen J. Thomas, Richard G. Jarman, Daniel H. Libraty, Robert V. Gibbons

Sharone Green

BACKGROUND: Dengue viruses are a major cause of morbidity in tropical and subtropical regions of the world. Inapparent dengue is an important component of the overall burden of dengue infection. It provides a source of infection for mosquito transmission during the course of an epidemic, yet by definition is undetected by health care providers. Previous studies of inapparent or subclinical infection have reported varying ratios of symptomatic to inapparent dengue infection. METHODOLOGY/PRINCIPAL FINDINGS: In a prospective study of school children in Northern Thailand, we describe the spatial and temporal variation of the symptomatic to inapparent (S:I) dengue illness ratio. Our …


B-Cell Responses During Primary And Secondary Dengue Virus Infections In Humans, Anuja Mathew, Kim West, Siripen Kalayanarooj, Robert Gibbons, Anon Srikiatkhachorn, Sharone Green, Daniel Libraty, Smita Jaiswal, Alan Rothman Jan 2014

B-Cell Responses During Primary And Secondary Dengue Virus Infections In Humans, Anuja Mathew, Kim West, Siripen Kalayanarooj, Robert Gibbons, Anon Srikiatkhachorn, Sharone Green, Daniel Libraty, Smita Jaiswal, Alan Rothman

Sharone Green

Low-avidity serotype-cross-reactive antibodies are hypothesized to play a key role in triggering severe disease in patients with secondary dengue virus (DENV) infection. However, there is little systematic information about the frequency, avidity, and cross-reactivity of DENV-specific B cells in individuals experiencing primary instead of secondary infection. We compared DENV-specific B-cell responses in a cohort of Thai children with primary or secondary DENV infection. B cells specific for DENV precursor membrane protein, envelope (E) protein, and nonstructural protein 1 were detectable in immune peripheral blood mononuclear cells with the highest frequencies of DENV E-specific B cells detected in patients experiencing primary …


T Cell Receptor Vbeta Gene Usage In Thai Children With Dengue Virus Infection, Susan J. Gagnon, Anita M. Leporati, Sharone Green, Siripen Kalayanarooj, David W. Vaughn, Henry A. F. Stephens, Saroj Suntayakorn, Ichiro Kurane, Francis A. Ennis, Alan L. Rothman Jan 2014

T Cell Receptor Vbeta Gene Usage In Thai Children With Dengue Virus Infection, Susan J. Gagnon, Anita M. Leporati, Sharone Green, Siripen Kalayanarooj, David W. Vaughn, Henry A. F. Stephens, Saroj Suntayakorn, Ichiro Kurane, Francis A. Ennis, Alan L. Rothman

Sharone Green

T lymphocyte activation during dengue is thought to contribute to the pathogenesis of dengue hemorrhagic fever (DHF). We examined the T cell receptor Vbeta gene usage by a reverse transcriptase-polymerase chain reaction assay during infection and after recovery in 13 children with DHF and 13 children with dengue fever (DF). There was no deletion of specific Vbeta gene families. We detected significant expansions in usage of single Vbeta families in six subjects with DHF and three subjects with DF over the course of infection, but these did not show an association with clinical diagnosis, viral serotype, or HLA alleles. Differences …


Prediction Of Dengue Disease Severity Among Pediatric Thai Patients Using Early Clinical Laboratory Indicators, James A. Potts, Robert V. Gibbons, Alan L. Rothman, Anon Srikiatkhachorn, Stephen J. Thomas, Pra-On Supradish, Stephenie C. Lemon, Daniel H. Libraty, Sharone Green, Siripen Kalayanarooj Jan 2014

Prediction Of Dengue Disease Severity Among Pediatric Thai Patients Using Early Clinical Laboratory Indicators, James A. Potts, Robert V. Gibbons, Alan L. Rothman, Anon Srikiatkhachorn, Stephen J. Thomas, Pra-On Supradish, Stephenie C. Lemon, Daniel H. Libraty, Sharone Green, Siripen Kalayanarooj

Sharone Green

BACKGROUND: Dengue virus is endemic in tropical and sub-tropical resource-poor countries. Dengue illness can range from a nonspecific febrile illness to a severe disease, Dengue Shock Syndrome (DSS), in which patients develop circulatory failure. Earlier diagnosis of severe dengue illnesses would have a substantial impact on the allocation of health resources in endemic countries. METHODS AND FINDINGS: We compared clinical laboratory findings collected within 72 hours of fever onset from a prospective cohort children presenting to one of two hospitals (one urban and one rural) in Thailand. Classification and regression tree analysis was used to develop diagnostic algorithms using different …


Cytokine Gene Expression And Protein Production In Peripheral Blood Mononuclear Cells Of Children With Acute Dengue Virus Infections, Susan Gagnon, Masuko Mori, Ichiro Kurane, Sharone Green, David Vaughn, Siripen Kalayanarooj, Saroj Suntayakorn, Francis Ennis, Alan Rothman Jan 2014

Cytokine Gene Expression And Protein Production In Peripheral Blood Mononuclear Cells Of Children With Acute Dengue Virus Infections, Susan Gagnon, Masuko Mori, Ichiro Kurane, Sharone Green, David Vaughn, Siripen Kalayanarooj, Saroj Suntayakorn, Francis Ennis, Alan Rothman

Sharone Green

Plasma leakage in dengue hemorrhagic fever (DHF) is associated with elevated plasma levels of cytokines. To define further the contribution of immune activation to DHF and the source of cytokines, we analyzed the production of cytokines in peripheral blood mononuclear cells (PBMC) obtained from children with dengue, using RT-PCR and immunostaining. Tumor necrosis factor-alpha (TNF-alpha) and TNF-beta expression was detected in all samples by PCR and in < 50% of samples by immunostaining. Interferon-gamma (IFN-gamma) expression was detected in < 50% of samples by either method. Interleukin-2 (IL-2) and IL-4 expression was detected in a few samples by immunostaining but was not …


Virus-Induced Decline In Soluble Vascular Endothelial Growth Receptor 2 Is Associated With Plasma Leakage In Dengue Hemorrhagic Fever, Anon Srikiatkhachorn, Chuanpis Ajariyakhajorn, Timothy P. Endy, Siripen Kalayanarooj, Daniel H. Libraty, Sharone Green, Francis A. Ennis, Alan L. Rothman Jan 2014

Virus-Induced Decline In Soluble Vascular Endothelial Growth Receptor 2 Is Associated With Plasma Leakage In Dengue Hemorrhagic Fever, Anon Srikiatkhachorn, Chuanpis Ajariyakhajorn, Timothy P. Endy, Siripen Kalayanarooj, Daniel H. Libraty, Sharone Green, Francis A. Ennis, Alan L. Rothman

Sharone Green

Some individuals infected with dengue virus develop dengue hemorrhagic fever (DHF), a viral hemorrhagic disease characterized by a transient period of localized plasma leakage. To determine the importance of vascular endothelial growth factor A (VEGF-A) in this syndrome, we compared plasma levels of VEGF-A and the soluble forms of its receptors in patients with DHF to patients with dengue fever (DF), a milder form of dengue virus infection without plasma leakage. We observed a rise in the plasma levels of free, but not total VEGF-A in DHF patients at the time of plasma leakage. This was associated with a decline …