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Risk prediction for severe disease and better diagnostic accuracy in early dengue infection; the Colombo dengue study

BACKGROUND: A major challenge in dengue management in resource limited settings is the confirmation of diagnosis. Clinical features of dengue often overlap with other infections and molecular diagnostic tools are not readily accessible to clinicians at hospitals. In addition, the prediction of plasm...

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Autores principales: Sigera, Ponsuge Chathurani, Amarasekara, Ranmalee, Rodrigo, Chaturaka, Rajapakse, Senaka, Weeratunga, Praveen, De Silva, Nipun Lakshita, Huang, Chun Hong, Sahoo, Malaya K., Pinsky, Benjamin A., Pillai, Dylan R., Tissera, Hasitha A., Jayasinghe, Saroj, Handunnetti, Shiroma, Fernando, Sumadhya D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6676631/
https://www.ncbi.nlm.nih.gov/pubmed/31370795
http://dx.doi.org/10.1186/s12879-019-4304-9
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author Sigera, Ponsuge Chathurani
Amarasekara, Ranmalee
Rodrigo, Chaturaka
Rajapakse, Senaka
Weeratunga, Praveen
De Silva, Nipun Lakshita
Huang, Chun Hong
Sahoo, Malaya K.
Pinsky, Benjamin A.
Pillai, Dylan R.
Tissera, Hasitha A.
Jayasinghe, Saroj
Handunnetti, Shiroma
Fernando, Sumadhya D.
author_facet Sigera, Ponsuge Chathurani
Amarasekara, Ranmalee
Rodrigo, Chaturaka
Rajapakse, Senaka
Weeratunga, Praveen
De Silva, Nipun Lakshita
Huang, Chun Hong
Sahoo, Malaya K.
Pinsky, Benjamin A.
Pillai, Dylan R.
Tissera, Hasitha A.
Jayasinghe, Saroj
Handunnetti, Shiroma
Fernando, Sumadhya D.
author_sort Sigera, Ponsuge Chathurani
collection PubMed
description BACKGROUND: A major challenge in dengue management in resource limited settings is the confirmation of diagnosis. Clinical features of dengue often overlap with other infections and molecular diagnostic tools are not readily accessible to clinicians at hospitals. In addition, the prediction of plasma leakage in dengue is also difficult. Hematocrit level and ultrasound scans (combined with clinical parameters) are helpful to detect plasma leakage once it has happened, not before. METHODS: Colombo Dengue Study (CDS) is a prospective cohort study of clinically suspected adult dengue patients recruited from the National hospital of Sri Lanka (within the first 3 days of fever) that aimed to a) identify clinical and basic laboratory test parameters to differentiate dengue from non-dengue fever, b) evaluate the comparative efficacy of loop-mediated isothermal amplification (LAMP) for dengue diagnosis (vs. NS1 antigen test and RT-qPCR) and c) identify early associations that are predictive of plasma leakage or severe dengue. The basic laboratory tests considered here included hematological parameters, serum biochemistry and inflammatory markers. RESULTS: Only 70% of clinically suspected patients were confirmed as having dengue by either the NS1 antigen test or RT-qPCR. On a Bayesian latent class model which assumes no “gold standard”, LAMP performed equally or better than RT-qPCR and NS1 antigen test respectively. When confirmed dengue patients were compared with others, the earlier group had significantly lower lymphocyte counts and higher aspartate aminotransferase levels (AST) within the first 3 days of fever. Confirmed dengue patients with plasma leakage had a lower mean age and a higher median baseline AST level compared to those without plasma leakage (p < 0.05). CONCLUSION: Clinical suspicion overestimates the true number of dengue patients. RT-LAMP is a potentially useful low-cost diagnostic tool for dengue diagnosis. Confirmed dengue patients had significantly higher AST levels and lower lymphocyte counts in early disease compared to others. In confirmed dengue patients, younger age and a higher AST level in early infection were associated with subsequent plasma leakage. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12879-019-4304-9) contains supplementary material, which is available to authorized users.
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spelling pubmed-66766312019-08-06 Risk prediction for severe disease and better diagnostic accuracy in early dengue infection; the Colombo dengue study Sigera, Ponsuge Chathurani Amarasekara, Ranmalee Rodrigo, Chaturaka Rajapakse, Senaka Weeratunga, Praveen De Silva, Nipun Lakshita Huang, Chun Hong Sahoo, Malaya K. Pinsky, Benjamin A. Pillai, Dylan R. Tissera, Hasitha A. Jayasinghe, Saroj Handunnetti, Shiroma Fernando, Sumadhya D. BMC Infect Dis Research Article BACKGROUND: A major challenge in dengue management in resource limited settings is the confirmation of diagnosis. Clinical features of dengue often overlap with other infections and molecular diagnostic tools are not readily accessible to clinicians at hospitals. In addition, the prediction of plasma leakage in dengue is also difficult. Hematocrit level and ultrasound scans (combined with clinical parameters) are helpful to detect plasma leakage once it has happened, not before. METHODS: Colombo Dengue Study (CDS) is a prospective cohort study of clinically suspected adult dengue patients recruited from the National hospital of Sri Lanka (within the first 3 days of fever) that aimed to a) identify clinical and basic laboratory test parameters to differentiate dengue from non-dengue fever, b) evaluate the comparative efficacy of loop-mediated isothermal amplification (LAMP) for dengue diagnosis (vs. NS1 antigen test and RT-qPCR) and c) identify early associations that are predictive of plasma leakage or severe dengue. The basic laboratory tests considered here included hematological parameters, serum biochemistry and inflammatory markers. RESULTS: Only 70% of clinically suspected patients were confirmed as having dengue by either the NS1 antigen test or RT-qPCR. On a Bayesian latent class model which assumes no “gold standard”, LAMP performed equally or better than RT-qPCR and NS1 antigen test respectively. When confirmed dengue patients were compared with others, the earlier group had significantly lower lymphocyte counts and higher aspartate aminotransferase levels (AST) within the first 3 days of fever. Confirmed dengue patients with plasma leakage had a lower mean age and a higher median baseline AST level compared to those without plasma leakage (p < 0.05). CONCLUSION: Clinical suspicion overestimates the true number of dengue patients. RT-LAMP is a potentially useful low-cost diagnostic tool for dengue diagnosis. Confirmed dengue patients had significantly higher AST levels and lower lymphocyte counts in early disease compared to others. In confirmed dengue patients, younger age and a higher AST level in early infection were associated with subsequent plasma leakage. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12879-019-4304-9) contains supplementary material, which is available to authorized users. BioMed Central 2019-08-01 /pmc/articles/PMC6676631/ /pubmed/31370795 http://dx.doi.org/10.1186/s12879-019-4304-9 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Sigera, Ponsuge Chathurani
Amarasekara, Ranmalee
Rodrigo, Chaturaka
Rajapakse, Senaka
Weeratunga, Praveen
De Silva, Nipun Lakshita
Huang, Chun Hong
Sahoo, Malaya K.
Pinsky, Benjamin A.
Pillai, Dylan R.
Tissera, Hasitha A.
Jayasinghe, Saroj
Handunnetti, Shiroma
Fernando, Sumadhya D.
Risk prediction for severe disease and better diagnostic accuracy in early dengue infection; the Colombo dengue study
title Risk prediction for severe disease and better diagnostic accuracy in early dengue infection; the Colombo dengue study
title_full Risk prediction for severe disease and better diagnostic accuracy in early dengue infection; the Colombo dengue study
title_fullStr Risk prediction for severe disease and better diagnostic accuracy in early dengue infection; the Colombo dengue study
title_full_unstemmed Risk prediction for severe disease and better diagnostic accuracy in early dengue infection; the Colombo dengue study
title_short Risk prediction for severe disease and better diagnostic accuracy in early dengue infection; the Colombo dengue study
title_sort risk prediction for severe disease and better diagnostic accuracy in early dengue infection; the colombo dengue study
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6676631/
https://www.ncbi.nlm.nih.gov/pubmed/31370795
http://dx.doi.org/10.1186/s12879-019-4304-9
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