{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T18:11:06Z","timestamp":1780337466457,"version":"3.54.1"},"reference-count":87,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2019,9,9]],"date-time":"2019-09-09T00:00:00Z","timestamp":1567987200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Hantavirus and dengue virus (DENV) infections are caused by RNA viruses which infect immune systems\u2019 cells including monocytes, macrophages and dendritic cells and occur year-round in Barbados. A retrospective serological study (2008\u20132015) was conducted on hantavirus and dengue patient sera confirmed by IgM and IgG ELISA, NS1 and RT-PCR using Limulus amoebocyte lysate (LAL) kinetic turbidimetric method to determine serum endotoxin levels. Hantavirus patients were categorized into two groups, namely (a) hospitalized and (b) non-hospitalized. Dengue patients were categorized into 3 groups using 2009 WHO dengue guidelines (a) severe dengue (SD), (b) hospitalized non-severe dengue (non-SD) and (c) non-hospitalized non-SD. Statistical analyses were conducted to determine the association of endotoxin levels with hantavirus disease severity based on hospitalization and dengue disease severity. Serum endotoxin levels are associated with hantavirus disease severity and hospitalization and dengue disease severity (p &lt; 0.01). Similar studies have found an association of serum endotoxin levels with dengue disease severity but never with hantavirus infection. Co-detection of hantavirus- and DENV-specific IgM in some patients were observed with elevated serum endotoxin levels. In addition, previous studies observed hantavirus replication in the gut of patients, gastrointestinal tract as a possible entry route of infection and evidence of microbial translocation and its impact on hantavirus disease severity. A significant correlation of serum endotoxin and hantavirus disease severity and hospitalization in hantavirus infected patients is reported for the first time ever. In addition, serum endotoxin levels correlated with dengue disease severity. This study adds further support to the role of endotoxin in both hantavirus and dengue virus infection and disease severity and its role as a possible therapeutic target for viral haemorrhagic fevers (VHFs).<\/jats:p>","DOI":"10.3390\/v11090838","type":"journal-article","created":{"date-parts":[[2019,9,9]],"date-time":"2019-09-09T11:26:17Z","timestamp":1568028377000},"page":"838","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Serum LPS Associated with Hantavirus and Dengue Disease Severity in Barbados"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3409-870X","authenticated-orcid":false,"given":"Kirk","family":"Douglas","sequence":"first","affiliation":[{"name":"Faculty of Medical Sciences, University of the West Indies, Cave Hill, BB11000 St. Michael, Barbados"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thelma","family":"Samuels","sequence":"additional","affiliation":[{"name":"Faculty of Medical Sciences, University of the West Indies, Cave Hill, BB11000 St. Michael, Barbados"},{"name":"Epidemiology Research Unit, Caribbean Institute for Health Research (CAIHR), The University of the West Indies, Mona Kingston 7, Jamaica"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marquita","family":"Gittens-St. Hilaire","sequence":"additional","affiliation":[{"name":"Faculty of Medical Sciences, University of the West Indies, Cave Hill, BB11000 St. Michael, Barbados"},{"name":"Best-dos Santos Public Health Laboratory, Enmore #6, Lower Collymore Rock, St. Michael BB11155, Barbados"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,9,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1016\/S1473-3099(16)00026-8","article-title":"The global burden of dengue: An analysis from the Global Burden of Disease Study 2013","volume":"16","author":"Stanaway","year":"2016","journal-title":"Lancet Infect. Dis."},{"key":"ref_2","first-page":"w13937","article-title":"Human hantavirus infections: Epidemiology, clinical features, pathogenesis and immunology","volume":"144","author":"Manigold","year":"2014","journal-title":"Swiss Med. Wkly."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.3389\/fmicb.2015.01326","article-title":"Hantaviral proteins: Structure, functions, and role in hantavirus infection","volume":"6","author":"Muyangwa","year":"2015","journal-title":"Front. Microbiol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Kim, J.-A., Kim, W.-k., No, J.S., Lee, S.-H., Lee, S.-Y., Kim, J.H., Kho, J.H., Lee, D., Song, D.H., and Gu, S.H. (2016). Genetic diversity and reassortment of Hantaan virus tripartite RNA genomes in nature, the Republic of Korea. PLoS Negl. Trop. Dis., 10.","DOI":"10.1371\/journal.pntd.0004650"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3","DOI":"10.3855\/jidc.317","article-title":"Hantavirus infection: A review and global update","volume":"2","author":"Bi","year":"2008","journal-title":"J. Infect. Dev. Ctries."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1126\/science.131.3407.1102","article-title":"Viruses associated with epidemic hemorrhagic fevers of the Philippines and Thailand","volume":"131","author":"Hammon","year":"1960","journal-title":"Science"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"629","DOI":"10.4269\/ajtmh.1964.13.629","article-title":"Virological Findings in the 1960 Hemorrhagic Fever Epidemic (Dengue) in Thailand","volume":"13","author":"Hammon","year":"1964","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1172\/JCI103415","article-title":"The renal lesion in epidemic hemorrhagic fever","volume":"36","author":"Oliver","year":"1957","journal-title":"J. Clin. Investig."},{"key":"ref_9","first-page":"161","article-title":"A point source dengue outbreak in Canadian tourists in Barbados","volume":"24","author":"Bellon","year":"1998","journal-title":"Can. Commun. Dis. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1128\/CDLI.6.4.555-557.1999","article-title":"Evaluation of four methods for detection of immunoglobulin M antibodies to dengue virus","volume":"6","author":"Branch","year":"1999","journal-title":"Clin. Diagn. Lab. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"112","DOI":"10.4269\/ajtmh.2000.62.112","article-title":"Detection of dengue infection in patients investigated for leptospirosis in Barbados","volume":"62","author":"Levett","year":"2000","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1186\/1743-422X-5-152","article-title":"An analysis of the subtypes of dengue fever infections in Barbados 2003\u20132007 by reverse transcriptase polymerase chain reaction","volume":"5","year":"2008","journal-title":"Virol. J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1093\/trstmh\/trt007","article-title":"Epidemiological trends and clinical manifestations of Dengue among children in one of the English-speaking Caribbean countries","volume":"107","author":"Kumar","year":"2013","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_14","first-page":"37","article-title":"Epidemiological Trend and Clinical Observations among Children and Adults with Dengue in Barbados","volume":"64","author":"Kumar","year":"2015","journal-title":"West. Indian Med. J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1016\/j.jiph.2015.05.013","article-title":"Trends in the patterns of IgM and IgG antibodies in febrile persons with suspected dengue in Barbados, an English-speaking Caribbean country, 2006\u20132013","volume":"8","author":"Kumar","year":"2015","journal-title":"J. Infect. Public Health"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3855\/jidc.5566","article-title":"The clinical characteristics and outcome of children hospitalized with dengue in Barbados, an English Caribbean country","volume":"9","author":"Kumar","year":"2015","journal-title":"J. Infect. Dev. Ctries"},{"key":"ref_17","first-page":"17","article-title":"Dengue Fever Epidemiology and Control in the Caribbean: A Status Report (2012)","volume":"74","author":"Chadee","year":"2012","journal-title":"Caribb Med. J."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Douglas, K.O., Martina, B., Samuels, A., and Gittens-St. Hilaire, M. (2019). Epidemiology and Molecular Investigations of Clinical Dengue Infections in Barbados (2008\u20132016). Am. J. Trop. Med. Hyg., (manuscript in preparation for publication).","DOI":"10.20944\/preprints201907.0308.v1"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2011039","DOI":"10.4084\/mjhid.2011.039","article-title":"Clinical profile of dengue infection in patients with hematological diseases","volume":"3","author":"Sharma","year":"2011","journal-title":"Mediterr. J. Hematol. Infect. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1644","DOI":"10.1016\/S0140-6736(07)61687-0","article-title":"Dengue","volume":"370","author":"Halstead","year":"2007","journal-title":"Lancet"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Huy, N.T., van Giang, T., Thuy, D.H.D., Kikuchi, M., Hien, T.T., Zamora, J., and Hirayama, K. (2013). Factors associated with dengue shock syndrome: A systematic review and meta-analysis. PLoS Negl. Trop. Dis., 7.","DOI":"10.1371\/journal.pntd.0002412"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Liu, J.-W., Lee, I.-K., Wang, L., Chen, R.-F., and Yang, K.D. (2013). The usefulness of clinical-practice-based laboratory data in facilitating the diagnosis of dengue illness. Biomed. Res. Int., 2013.","DOI":"10.1155\/2013\/198797"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1179\/2047773215Y.0000000003","article-title":"WHO dengue case classification 2009 and its usefulness in practice: An expert consensus in the Americas","volume":"109","author":"Horstick","year":"2015","journal-title":"Pathog. Glob. Health"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/S0140-6736(06)69006-5","article-title":"The WHO dengue classification and case definitions: Time for a reassessment","volume":"368","author":"Deen","year":"2006","journal-title":"Lancet"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1053\/jinf.2002.1028","article-title":"Serological evidence of hantavirus in humans and rodents in Barbados","volume":"45","author":"Groen","year":"2002","journal-title":"J. Infect."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.jiph.2015.06.004","article-title":"Hantavirus infection among children hospitalized for febrile illness suspected to be dengue in Barbados","volume":"9","author":"Kumar","year":"2016","journal-title":"J. Infect. Public Health"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"45","DOI":"10.30954\/2277-940X.01.2019.6","article-title":"Antibodies Against Seoul Hantavirus in Brown rats (Rattus norvegicus) from Grenada, West Indies","volume":"9","author":"Sharma","year":"2019","journal-title":"J. Anim. Res."},{"key":"ref_28","first-page":"67","article-title":"Seroprevalence of hantavirus in Rattus norvegicus in Grenada, West Indies","volume":"8","author":"Keenan","year":"2008","journal-title":"West. Indian Vet. J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1080\/1059924X.2011.581534","article-title":"Serological Evidence of Hantavirus Infection in Farm and Abattoir Workers in Trinidad\u2014A Preliminary Study","volume":"16","author":"Adesiyun","year":"2011","journal-title":"J. Agromed."},{"key":"ref_30","first-page":"103","article-title":"Imported hantavirus cardiopulmonary syndrome in an Italian traveller returning from Cuba","volume":"36","author":"Rovida","year":"2013","journal-title":"New Microbiol"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1722","DOI":"10.3201\/eid2310.170842","article-title":"Hantavirus pulmonary syndrome caused by Maripa virus in French Guiana, 2008\u20132016","volume":"23","author":"Matheus","year":"2017","journal-title":"Emerg. Infect. Dis."},{"key":"ref_32","first-page":"1","article-title":"The characteristics and function of bacterial lipopolysaccharides and their endotoxic potential in humans","volume":"35","author":"Gnauck","year":"2015","journal-title":"Int. Rev. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1128\/jb.155.2.817-825.1983","article-title":"Spontaneous release of lipopolysaccharide by Pseudomonas aeruginosa","volume":"155","author":"Cadieux","year":"1983","journal-title":"J. Bacteriol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Williams, K.L. (2007). Endotoxins: Pyrogens, LAL Testing and Depyrogenation, CRC Press.","DOI":"10.3109\/9781420020595"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"S470","DOI":"10.1086\/432000","article-title":"Lipopolysaccharide: An endotoxin or an exogenous hormone?","volume":"41","author":"Marshall","year":"2005","journal-title":"Clin. Infect. Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1289\/ehp.0800439","article-title":"Endotoxin and cancer","volume":"117","author":"Lundin","year":"2009","journal-title":"Environ. Health Perspect."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/S0171-2985(11)80354-2","article-title":"The bactericidal\/permeability-increasing protein (BPI), a potent element in host-defense against gram-negative bacteria and lipopolysaccharide","volume":"187","author":"Elsbach","year":"1993","journal-title":"Immunobiology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1194\/jlr.M800156-JLR200","article-title":"Chylomicrons promote intestinal absorption of lipopolysaccharides","volume":"50","author":"Ghoshal","year":"2009","journal-title":"J. Lipid Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1177\/1753425915610643","article-title":"Modulation of host defense peptide-mediated human mast cell activation by LPS","volume":"22","author":"Gupta","year":"2016","journal-title":"Innate Immun."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3765","DOI":"10.1182\/blood-2002-06-1887","article-title":"The role of the endothelium in severe sepsis and multiple organ dysfunction syndrome","volume":"101","author":"Aird","year":"2003","journal-title":"Blood"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"9877","DOI":"10.1128\/JVI.76.19.9877-9887.2002","article-title":"Activation of terminally differentiated human monocytes\/macrophages by dengue virus: Productive infection, hierarchical production of innate cytokines and chemokines, and the synergistic effect of lipopolysaccharide","volume":"76","author":"Chen","year":"2002","journal-title":"J. Virol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1832","DOI":"10.1093\/infdis\/jiz005","article-title":"Serum Markers Associated with Severity and Outcome of Hantavirus Pulmonary Syndrome","volume":"219","author":"Maleki","year":"2019","journal-title":"J. Infect. Dis."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2650","DOI":"10.1128\/JVI.73.4.2650-2657.1999","article-title":"Bacterial lipopolysaccharide inhibits dengue virus infection of primary human monocytes\/macrophages by blockade of virus entry via a CD14-dependent mechanism","volume":"73","author":"Chen","year":"1999","journal-title":"J. Virol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Lustig, S., Danenberg, H., Kafri, Y., Kobiler, D., and Ben-Nathan, D. (1992). Viral neuroinvasion and encephalitis induced by lipopolysaccharide and its mediators. J. Exp. Med., 176.","DOI":"10.1084\/jem.176.3.707"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1146\/annurev-immunol-020711-075001","article-title":"Microbial translocation across the GI tract","volume":"30","author":"Brenchley","year":"2012","journal-title":"Annu. Rev. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1038\/nm1511","article-title":"Microbial translocation is a cause of systemic immune activation in chronic HIV infection","volume":"12","author":"Brenchley","year":"2006","journal-title":"Nat. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.jcv.2011.09.028","article-title":"Lipopolysaccharide levels are elevated in dengue virus infected patients and correlate with disease severity","volume":"53","author":"Koraka","year":"2012","journal-title":"J. Clin. Virol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.jcv.2010.10.009","article-title":"Dobrava\u2013Belgrade hantavirus infection mimics acute appendicitis","volume":"50","author":"Jakab","year":"2011","journal-title":"J. Clin. Virol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.jcv.2011.11.003","article-title":"Hantavirus and acute appendicitis\u2014The diagnosis behind the diagnosis?","volume":"53","author":"Latus","year":"2012","journal-title":"J. Clin. Virol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Latus, J., Tenner-Racz, K., Racz, P., Kitterer, D., Cadar, D., Ott, G., Alscher, M.D., Schmidt-Chanasit, J., and Braun, N. (2014). Detection of Puumala hantavirus antigen in human intestine during acute hantavirus infection. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0098397"},{"key":"ref_51","unstructured":"Centers for Disease Control and Prevention (2019, May 02). Hantavirus Infection, Non-Hantavirus Pulmonary Syndrome. 2015 Case Definition, Available online: https:\/\/wwwn.cdc.gov\/nndss\/conditions\/hantavirus-infection-non-hantavirus-pulmonary-syndrome\/case-definition\/2015\/."},{"key":"ref_52","unstructured":"Douglas, K.O., Cayol, C., Forbes, K., Samuels, A., Iheozor-Ejiofor, R., Vapalahti, O., Sironen, T., and Gittens-St. Hilaire, M. (2019). Epidemiology of Clinical Hantavirus Infections and Reservoir Investigations of rodents in Barbados. Viruses, (manuscript accepted with minor changes)."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"339","DOI":"10.2307\/2529083","article-title":"283. Note: On McNemar\u2019s Test for the 2 \u00d7 2 Table and Its Power Function","volume":"26","author":"Bennett","year":"1970","journal-title":"Biometrics"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1136\/bmj.312.7039.1153","article-title":"Statistics notes: The use of transformation when comparing two means","volume":"312","author":"Bland","year":"1996","journal-title":"Br. Med. J."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1136\/bmj.312.7038.1079","article-title":"Transformations, means, and confidence intervals","volume":"312","author":"Bland","year":"1996","journal-title":"Br. Med. J."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/ki.2012.360","article-title":"Hantavirus infection: An emerging infectious disease causing acute renal failure","volume":"83","author":"Zeier","year":"2013","journal-title":"Kidney Int."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2997","DOI":"10.1093\/ndt\/gfq118","article-title":"Characterization and outcome following Puumala virus infection: A retrospective analysis of 75 cases","volume":"25","author":"Braun","year":"2010","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1038\/nrmicro3066","article-title":"Uncovering the mysteries of hantavirus infections","volume":"11","author":"Vaheri","year":"2013","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Witkowski, P.T., Perley, C.C., Brocato, R.L., Hooper, J.W., J\u00fcrgensen, C., Schulzke, J.-D., Kr\u00fcger, D.H., and B\u00fccker, R. (2017). Gastrointestinal Tract As Entry Route for Hantavirus Infection. Front. Microbiol., 8.","DOI":"10.3389\/fmicb.2017.01721"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1002\/rmv.1722","article-title":"Hantavirus infections in Europe and their impact on public health","volume":"23","author":"Vaheri","year":"2013","journal-title":"Rev. Med. Virol."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Zapata, J.C., Cox, D., and Salvato, M.S. (2014). The role of platelets in the pathogenesis of viral hemorrhagic fevers. PLoS Negl. Trop. Dis., 8.","DOI":"10.1371\/journal.pntd.0002858"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Van de Weg, C.A., Pannuti, C.S., de Araujo, E.S., van den Ham, H.J., Andeweg, A.C., Boas, L.S., Felix, A.C., Carvalho, K.I., de Matos, A.M., and Levi, J.E. (2013). Microbial translocation is associated with extensive immune activation in dengue virus infected patients with severe disease. PLoS Negl. Trop. Dis., 7.","DOI":"10.1371\/journal.pntd.0002236"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Carrasco, L.R., Leo, Y.S., Cook, A.R., Lee, V.J., Thein, T.L., Go, C.J., and Lye, D.C. (2014). Predictive tools for severe dengue conforming to World Health Organization 2009 criteria. PLoS Negl. Trop. Dis., 8.","DOI":"10.1371\/journal.pntd.0002972"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Zhang, H., Zhou, Y., Peng, H., Zhang, X., Zhou, F., Liu, Z., and Chen, X. (2014). Predictive symptoms and signs of severe dengue disease for patients with dengue fever: A meta-analysis. Biomed. Res. Int., 2014.","DOI":"10.1155\/2014\/359308"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Lee, K., Liu, J.-W., and Yang, K.D. (2012). Fatal dengue hemorrhagic fever in adults: Emphasizing the evolutionary pre-fatal clinical and laboratory manifestations. PLoS Negl. Trop. Dis., 6.","DOI":"10.1371\/journal.pntd.0001532"},{"key":"ref_66","first-page":"79","article-title":"An evidence of intestinal mucosal injury in dengue infection","volume":"37","author":"Vejchapipat","year":"2006","journal-title":"Southeast. Asian J. Trop. Med. Public Health"},{"key":"ref_67","first-page":"8","article-title":"Endotoxin and dengue haemorrhagic fever","volume":"17","author":"Usawattanakul","year":"1986","journal-title":"Southeast. Asian J. Trop. Med. Public Health"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Lam, P.K., van Ngoc, T., Thuy, T.T.T., van, N.T.H., Thuy, T.T.N., Tam, D.T.H., Dung, N.M., Tien, N.T.H., Kieu, N.T.T., and Simmons, C. (2017). The value of daily platelet counts for predicting dengue shock syndrome: Results from a prospective observational study of 2301 Vietnamese children with dengue. PLoS Negl. Trop. Dis., 11.","DOI":"10.1371\/journal.pntd.0005498"},{"key":"ref_69","unstructured":"World Health Organization (2009). Dengue: Guidelines for Diagnosis, Treatment, Prevention and Control, World Health Organization."},{"key":"ref_70","first-page":"326","article-title":"Laboratory predictors of dengue shock syndrome during the febrile stage","volume":"41","author":"Chuansumrit","year":"2010","journal-title":"Southeast. Asian J. Trop. Med. Public Health"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Potts, J.A., Gibbons, R.V., Rothman, A.L., Srikiatkhachorn, A., Thomas, S.J., Supradish, P.-o., Lemon, S.C., Libraty, D.H., Green, S., and Kalayanarooj, S. (2010). Prediction of dengue disease severity among pediatric Thai patients using early clinical laboratory indicators. PLoS Negl. Trop. Dis., 4.","DOI":"10.1371\/journal.pntd.0000769"},{"key":"ref_72","first-page":"12","article-title":"Prognostic indicators for dengue infection severity","volume":"2","author":"Pongpan","year":"2013","journal-title":"Int. J. Clin. Pediatrics"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1177\/107602960401000111","article-title":"Can hematocrit and platelet determination on admission predict shock in hospitalized children with dengue hemorrhagic fever? A clinical observation from a small outbreak","volume":"10","author":"Wiwanitkit","year":"2004","journal-title":"Clin. Appl. Thromb. Hemost."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Assinger, A. (2014). Platelets and infection\u2013an emerging role of platelets in viral infection. Front. Immunol., 5.","DOI":"10.3389\/fimmu.2014.00649"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1497","DOI":"10.1086\/516486","article-title":"Dengue virus inhibits human hematopoietic progenitor growth in vitro","volume":"175","author":"Murgue","year":"1997","journal-title":"J. Infect. Dis."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2291","DOI":"10.1111\/j.1538-7836.2007.02754.x","article-title":"Antiplatelet autoantibodies elicited by dengue virus non-structural protein 1 cause thrombocytopenia and mortality in mice","volume":"5","author":"Sun","year":"2007","journal-title":"J. Thromb. Haemost."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"69","DOI":"10.3844\/ajidsp.2008.69.75","article-title":"Patient and mouse antibodies against dengue virus nonstructural protein 1 cross-react with platelets and cause their dysfunction or depletion","volume":"4","author":"Lin","year":"2008","journal-title":"Am. J. Infect. Dis."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"3405","DOI":"10.1182\/blood-2013-05-504449","article-title":"Platelets mediate increased endothelium permeability in dengue through NLRP3-inflammasome activation","volume":"122","author":"Hottz","year":"2013","journal-title":"Blood"},{"key":"ref_79","first-page":"201","article-title":"Features of DIC in dengue hemorrhagic fever","volume":"Volume 49","author":"Funahara","year":"1983","journal-title":"Disseminated Intravascular Coagulation"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1111\/jth.12178","article-title":"Dengue induces platelet activation, mitochondrial dysfunction and cell death through mechanisms that involve DC-SIGN and caspases","volume":"11","author":"Hottz","year":"2013","journal-title":"J. Thromb. Haemost."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"e22042","DOI":"10.1002\/jcla.22042","article-title":"Reliability of Parameters of Complete Blood Count with Different Storage Conditions","volume":"31","author":"Gunawardena","year":"2017","journal-title":"J. Clin. Lab. Anal."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Kulkarni, D., and Sharma, B. (2014). Dengue Fever-Induced Cold-Agglutinin Syndrome, SAGE Publications Sage UK.","DOI":"10.1177\/2049936114559918"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.tmaid.2009.01.001","article-title":"Dengue and aplastic anemia\u2013A rare association","volume":"7","author":"Albuquerque","year":"2009","journal-title":"Travel Med. Infect. Dis."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"539","DOI":"10.47102\/annals-acadmedsg.V40N12p539","article-title":"When less is more: Can we abandon prophylactic platelet transfusion in Dengue fever","volume":"40","author":"Kurukularatne","year":"2011","journal-title":"Ann. Acad. Med. Singap."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Lee, T.-H., Wong, J.G., Leo, Y.-S., Thein, T.-L., Ng, E.-L., Lee, L.K., and Lye, D.C. (2016). Potential harm of prophylactic platelet transfusion in adult dengue patients. PLoS Negl. Trop. Dis., 10.","DOI":"10.1371\/journal.pntd.0004576"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1086\/597773","article-title":"Lack of efficacy of prophylactic platelet transfusion for severe thrombocytopenia in adults with acute uncomplicated dengue infection","volume":"48","author":"Lye","year":"2009","journal-title":"Clin. Infect. Dis."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"ra142","DOI":"10.1126\/scitranslmed.aaa3863","article-title":"Dengue virus NS1 protein activates cells via Toll-like receptor 4 and disrupts endothelial cell monolayer integrity","volume":"7","author":"Modhiran","year":"2015","journal-title":"Sci. Transl. Med."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/11\/9\/838\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:17:59Z","timestamp":1760188679000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/11\/9\/838"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,9,9]]},"references-count":87,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2019,9]]}},"alternative-id":["v11090838"],"URL":"https:\/\/doi.org\/10.3390\/v11090838","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,9,9]]}}}