Guzmán MG, Halstead SB, Artsob H, Buchy P, Farrar J, Gubler DJ, Hunsperger E, Kroeger A, Margolis HS, Martínez E, Nathan MB, Pelegrino JL, Simmons C, Yoksan S, Peeling RW, 2010. Dengue: a continuing global threat. Nat Rev Microbiol 12 (Suppl): S7–S16.
Peeling RW, Artsob H, Pelegrino JL, Buchy P, Cardosa MJ, Devi S, Enria DA, Farrar J, Gubler DJ, Guzman MG, Halstead SB, Hunsperger E, Kliks S, Margolis HS, Nathanson CM, Nguyen VC, Rizzo N, Vázquez S, Yoksan S, 2010. Evaluation of diagnostic tests: dengue. Nat Rev Microbiol 8: S30–S38.
Coller BA, Clements DE, 2011. Dengue vaccines: progress and challenges. Curr Opin Immunol 23: 391–398.
Clyde K, Kyle JL, Harris E, 2006. Recent advances in deciphering viral and host determinants of dengue virus replication and pathogenesis. J Virol 80: 11418–11431.
Noisakran S, Perng GC, 2008. Alternate hypothesis on the pathogenesis of dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS) in dengue virus infection. Exp Biol Med 233: 401–408.
Martina BE, Koraka P, Osterhaus AD, 2009. Dengue virus pathogenesis: an integrated view. Clin Microbiol Rev 22: 564–581.
Simmons CP, Farrar JJ, van Vinh Cahu N, Wills B, 2012. Dengue. N Engl J Med 366: 1423–1432.
Rothmann AL, 2011. Immunity to dengue virus: a tale of original antigenic sin and tropical cytokine storms. Nat Rev Immunol 11: 532–543.
Flammand M, Megret F, Mathieu M, Lepault J, Rey F, Deubel V, 1999. Dengue virus type 1 nonstructural protein NS1 is secreted from mammalian cells as a soluble hexamer in a glycosylation-dependent fashion. J Virol 73: 6104–6110.
Alcon S, Talarmin A, Debruine M, Falcona A, Deuvel V, Flammand M, 2002. Enzyme-linked immunosorbent assay specific to dengue virus type 1 nonstructural protein NS1 reveals circulation of the antigen in the blood during the acute phase of disease in patients experiencing primary and secondary infections. J Clin Microbiol 40: 376–381.
Young PR, Hilditch PA, Bletchly C, Halloran W, 2000. An antigen capture enzyme-linked immunosorbent assay reveals high levels of the dengue virus protein NS1 in the sera of infected patients. J Clin Microbiol 38: 1053–1057.
Shu PY, Huang JH, 2004. Current advances in dengue diagnosis. Clin Diagn Lab Immunol 11: 642–650.
Libraty DH, Young PR, Pickering D, Endy TP, Kalayanarooj S, Green S, Vaughn DW, Nisalak A, Ennis FA, Rothman AL, 2002. High circulating levels of the dengue virus nonstructural protein NS1 early in dengue illness correlate with the development of dengue hemorrhagic fever. J Infect Dis 186: 1165–1168.
Avirutnan P, Punyadee N, Noisakran S, Komoltri C, Thiemmeca S, Auethavornanan K, Jairungsri A, Kanlaya R, Tangthawornchaikul N, Puttikhunt C, Pattanakitsakul S, Yenchitsomanus P, Mongkolsapaya J, Kasinrerk W, Sittisombut N, Husmann M, Blettner M, Vasanawathana S, Bhakdi S, Malasit P, 2006. Vascular leakage in severe dengue virus infections: a potential role for the nonstructural viral protein ns1 and complement. J Infect Dis 193: 1078–1088.
Watanabe S, Tan KH, Rathore APS, Rozen-Gagnon K, Shuai W, Rueld C, 2012. The magnitude of dengue virus protein secretion is strain dependent and does not correlate with severe pathologies in the mouse infection model. J Virol 86: 5508–5514.
Thomas L, Najioullah F, Verlaeten O, Martial J, Bricher S, Kaidomar S, Moravie V, Cabie A, Cesaire R, 2010. Short report: relationship between nonstructural protein 1 detection and plasma virus load in dengue patients. Am J Trop Med Hyg 83: 696–699.
Duoung V, Ly S, Lorn Try P, Tuiskunen A, Ong S, Chroeung N, Lundkvist A, Leparc-Goffart I, Duvel V, Vong S, Buchy P, 2011. Clinical and virological features influencing the performance of a NS1 antigen-capture assay and potential uses as a maker of dengue disease severity. PLoS Negl Trop Dis 5: e1244.
Duyen HT, Ngoc TV, Ha DT, Hang VT, Kieu NT, Young PR, Farrar JJ, Simmons CP, Wolbers M, Wills BA, 2011. Nonstructural protein 1 concentration in dengue: differential effects according to serotype and immune status. J Infect Dis 203: 1292–1300.
Vaughn DW, Green S, Kalayanarooj S, Innis BL, Nimmannitya S, Suntayakorn S, Endy TP, Raengsakulrach B, Rothman AL, Ennis FA, Nisalak A, 2000. Dengue viremia titer, antibody response pattern, and virus serotype correlate with disease severity. J Infect Dis 181: 2–9.
Tricou V, Minh NN, Farrar J, Tran HT, Simmons CP, 2011. Kinetics of viremia and NS1 antigenemia are shaped by immune status and virus serotype in adults with dengue. PLoS Negl Trop Dis 5: e1309.
World Health Organization, 1997. Dengue Haemorragic Fever: Diagnosis, Treatment, Diagnosis and Control. Second Edition. Geneva: World Health Organization.
Johnson BW, Russell BJ, Lanciotti RS, 2005. Serotype-specific detection of dengue viruses in a fourplex real-time reverse transcriptase PCR assay. J Clin Microbiol 43: 4977–4983.
Mosso C, Galván-Mendoza I, Ludert JE, Del Angel RM, 2008. Endocytic pathway followed by dengue virus to infect the mosquito cell line C6/36 HT. Virology 378: 193–199.
Vázquez S, Hafner G, Ruiz D, Calzada N, Guzmán MG, 2007. Evaluation of immunoglobulin M and G capture enzyme-linked immunosorbent assay Panbio kits for diagnostic dengue infection. J Clin Virol 39: 194–198.
Ahmed F, Mursalin H, Alam MT, Amin R, Sekaran SD, Wang SM, Tan YY, Sil BK, Hossain MA, 2010. Evaluation of ASSURE Dengue IgA Rapid Test using dengue-positive and dengue-negative samples. Diagn Microbiol Infect Dis 68: 339–344.
Allonso D, da Silva Rosa M, Coelho DR, da Costa SM, Nogueira RM, Bozza FA, Santos FB, de Barcelos Alves AM, Mohana-Borges R, 2011. Polyclonal antibodies against properly folded dengue virus NS1 protein expressed in E. coli enable sensitive and early dengue diagnosis. J Virol Methods 175: 109–116.
Pawitan JA, 2011. Dengue virus infection: predictors for severe dengue. Acta Med Indones 43: 129–135.
Srikiatkhachorn A, Green S, 2010. Markers of dengue disease severity. Curr Top Microbiol Immunol 338: 67–82.
Yeh WT, Chen RF, Wang L, Liu JW, Shaio MF, Yang KD, 2006. Implications of previous subclinical dengue infection but not virus load in dengue hemorrhagic fever. FEMS Immunol Med Microbiol 48: 84–90.
Thayan R, Huat TL, See LL, Tan CP, Khairullah NS, Yusof R, Devis S, 2009. The use of two-dimension electrophoresis to identify serum biomarkers from patients with dengue haemorrhagic fever. Trans R Soc Trop Med Hyg 103: 413–419.
Dussart P, Labeau B, Lagathu G, Louis P, Nunes MR, Rodrigues SG, Storck-Herrmann C, Cesaire R, Morvan J, Flamand M, Baril L, 2006. Evaluation of an enzyme immunoassay for detection of dengue virus NS1 antigen in human serum. Clin Vaccine Immunol 13: 1185–1189.
Hang VT, Nguyet NM, Trung DT, Tricou V, Yoksan S, Dung NM, Van Ngoc T, Hien TT, Farrar J, Wills B, Simmons CP, 2009. Diagnostic accuracy of NS1 ELISA and lateral flow rapid tests for dengue sensitivity, specificity and relationship to viraemia and antibody responses. PLoS Negl Trop Dis 3: e360.
Ramírez AH, Moros Z, Comach G, Zambrano JL, Bravo L, Pinto B, Vielma S, Cardier J, Liprandi F, 2009. Evaluation of dengue NS1 antigen detection tests with acute sera from patients infected with dengue virus in Venezuela. Diagn Microbiol Infect Dis 65: 247–253.
Bessoff K, Delorey M, Sun W, Hunsperger E, 2008. Comparison of two commercially available dengue virus (DENV) NS1 capture enzyme-linked immunosorbent assays using a single clinical sample for diagnosis of acute DENV infection. Clin Vaccine Immunol 15: 1513–1518.
Vázquez S, Pérez AB, Ruiz D, Rodríguez R, Pupo M, Calzada N, González L, González D, Castro O, Serrano T, Guzmán MG, 2005. Serological markers during dengue 3 primary and secondary infections. J Clin Virol 33: 132–137.
Falconar AK, 2007. Antibody responses are generated to immunodominant ELK/KLE-type motifs on the nonstructural-1 glycoprotein during live dengue virus infections in mice and humans: implications for diagnosis, pathogenesis, and vaccine design. Clin Vaccine Immunol 14: 493–504.
Balmaseda A, Saborio S, Tellez Y, Mercado JC, Perez L, Hammond SN, Rocha C, Kuan G, Harris E, 2008. Evaluation of immunological markers in serum, filter-paper, blood spots, and saliva for dengue diagnosis and epidemiological studies. J Clin Virol 43: 287–291.
De Rivera IL, Parham L, Murillo W, Moncada W, Vázquez S, 2008. Humoral immune response of dengue hemorrhagic fever cases in children from Tegucigalpa, Honduras. Am J Trop Med Hyg 79: 262–266.
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Higher levels of viremia and circulating nonstructural protein 1 (NS1) have been associated with dengue disease severity. In this study, viremia and circulating NS1 levels were determined in 225 serum samples collected from patients in Mexico infected with dengue virus serotypes 1 and 2 (DENV-1 and DENV-2). Patients with dengue hemorrhagic fever (DHF) who were infected with DENV-1 showed higher levels of circulating NS1 than patients with dengue fever (DF) (P = 0.0175). Moreover, NS1 levels were higher in patients with primary infections with DENV-1 than in patient infected with DENV-2 (P < 0.0001) and in patients with primary infections with DENV-2 than in patients with secondary infections with DENV-2 (P = 0.0051). Unexpectedly, viremia levels were higher in patients with DF than in those with DHF infected with either DENV-1 or DENV-2 (P = 0.0019 and P = 0.001, respectively) and in patients with primary infections than those with secondary DENV-2 infections (P < 0.0001). Results indicate that levels of circulating NS1 vary according to the infecting serotype, immunologic status (primary or secondary infection), and dengue disease severity.
Financial support: This study was partially supported by grant 112118 from Consejo Nacional de Ciencia y Tecnología, Mexico and grant 248 from Instituto de Ciencia y Techlogía-D.F., Mexico. The PLATELIA™ Dengue NS1 Antigen Assays and the PanBio ELISAs used in this study were kindly donated by Bio-Rad Laboratories and CTR Scientific, Mexico, respectively.
Authors' addresses: Sergio I. de la Cruz-Hernández, Hilario Flores-Aguilar, Silvia González-Mateos, Irma López-Martinez, and Celia Alpuche-Aranda, Instituto de Diagnostico y Referencia Epidemiológicos, Prolongación Carpio No. 470, Colonia Santo Tomás, Delegación Miguel Hidalgo, CP 11340, Mexico City DF, Mexico, E-mails: sidlch@yahoo.com.mx, hilario.flores@salud.gob.mx, sigomateos@yahoo.com, lopezmi74@gmail.com, and celia.alpuche@salud.gob.mx. Juan E. Ludert and Rosa M. del Angel, Departamento de Infectómica y Patogénesis Molecular, Centro de Investigación y Estudios Avanzados del Instituto Politécnico Nacional, Av. IPN 2508, Colonia San Pedro Zacatenco, Mexico City DF 07360, Mexico, E-mails: jludert@cinvestav.mx and rmangel@cinvestav.mx.
Guzmán MG, Halstead SB, Artsob H, Buchy P, Farrar J, Gubler DJ, Hunsperger E, Kroeger A, Margolis HS, Martínez E, Nathan MB, Pelegrino JL, Simmons C, Yoksan S, Peeling RW, 2010. Dengue: a continuing global threat. Nat Rev Microbiol 12 (Suppl): S7–S16.
Peeling RW, Artsob H, Pelegrino JL, Buchy P, Cardosa MJ, Devi S, Enria DA, Farrar J, Gubler DJ, Guzman MG, Halstead SB, Hunsperger E, Kliks S, Margolis HS, Nathanson CM, Nguyen VC, Rizzo N, Vázquez S, Yoksan S, 2010. Evaluation of diagnostic tests: dengue. Nat Rev Microbiol 8: S30–S38.
Coller BA, Clements DE, 2011. Dengue vaccines: progress and challenges. Curr Opin Immunol 23: 391–398.
Clyde K, Kyle JL, Harris E, 2006. Recent advances in deciphering viral and host determinants of dengue virus replication and pathogenesis. J Virol 80: 11418–11431.
Noisakran S, Perng GC, 2008. Alternate hypothesis on the pathogenesis of dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS) in dengue virus infection. Exp Biol Med 233: 401–408.
Martina BE, Koraka P, Osterhaus AD, 2009. Dengue virus pathogenesis: an integrated view. Clin Microbiol Rev 22: 564–581.
Simmons CP, Farrar JJ, van Vinh Cahu N, Wills B, 2012. Dengue. N Engl J Med 366: 1423–1432.
Rothmann AL, 2011. Immunity to dengue virus: a tale of original antigenic sin and tropical cytokine storms. Nat Rev Immunol 11: 532–543.
Flammand M, Megret F, Mathieu M, Lepault J, Rey F, Deubel V, 1999. Dengue virus type 1 nonstructural protein NS1 is secreted from mammalian cells as a soluble hexamer in a glycosylation-dependent fashion. J Virol 73: 6104–6110.
Alcon S, Talarmin A, Debruine M, Falcona A, Deuvel V, Flammand M, 2002. Enzyme-linked immunosorbent assay specific to dengue virus type 1 nonstructural protein NS1 reveals circulation of the antigen in the blood during the acute phase of disease in patients experiencing primary and secondary infections. J Clin Microbiol 40: 376–381.
Young PR, Hilditch PA, Bletchly C, Halloran W, 2000. An antigen capture enzyme-linked immunosorbent assay reveals high levels of the dengue virus protein NS1 in the sera of infected patients. J Clin Microbiol 38: 1053–1057.
Shu PY, Huang JH, 2004. Current advances in dengue diagnosis. Clin Diagn Lab Immunol 11: 642–650.
Libraty DH, Young PR, Pickering D, Endy TP, Kalayanarooj S, Green S, Vaughn DW, Nisalak A, Ennis FA, Rothman AL, 2002. High circulating levels of the dengue virus nonstructural protein NS1 early in dengue illness correlate with the development of dengue hemorrhagic fever. J Infect Dis 186: 1165–1168.
Avirutnan P, Punyadee N, Noisakran S, Komoltri C, Thiemmeca S, Auethavornanan K, Jairungsri A, Kanlaya R, Tangthawornchaikul N, Puttikhunt C, Pattanakitsakul S, Yenchitsomanus P, Mongkolsapaya J, Kasinrerk W, Sittisombut N, Husmann M, Blettner M, Vasanawathana S, Bhakdi S, Malasit P, 2006. Vascular leakage in severe dengue virus infections: a potential role for the nonstructural viral protein ns1 and complement. J Infect Dis 193: 1078–1088.
Watanabe S, Tan KH, Rathore APS, Rozen-Gagnon K, Shuai W, Rueld C, 2012. The magnitude of dengue virus protein secretion is strain dependent and does not correlate with severe pathologies in the mouse infection model. J Virol 86: 5508–5514.
Thomas L, Najioullah F, Verlaeten O, Martial J, Bricher S, Kaidomar S, Moravie V, Cabie A, Cesaire R, 2010. Short report: relationship between nonstructural protein 1 detection and plasma virus load in dengue patients. Am J Trop Med Hyg 83: 696–699.
Duoung V, Ly S, Lorn Try P, Tuiskunen A, Ong S, Chroeung N, Lundkvist A, Leparc-Goffart I, Duvel V, Vong S, Buchy P, 2011. Clinical and virological features influencing the performance of a NS1 antigen-capture assay and potential uses as a maker of dengue disease severity. PLoS Negl Trop Dis 5: e1244.
Duyen HT, Ngoc TV, Ha DT, Hang VT, Kieu NT, Young PR, Farrar JJ, Simmons CP, Wolbers M, Wills BA, 2011. Nonstructural protein 1 concentration in dengue: differential effects according to serotype and immune status. J Infect Dis 203: 1292–1300.
Vaughn DW, Green S, Kalayanarooj S, Innis BL, Nimmannitya S, Suntayakorn S, Endy TP, Raengsakulrach B, Rothman AL, Ennis FA, Nisalak A, 2000. Dengue viremia titer, antibody response pattern, and virus serotype correlate with disease severity. J Infect Dis 181: 2–9.
Tricou V, Minh NN, Farrar J, Tran HT, Simmons CP, 2011. Kinetics of viremia and NS1 antigenemia are shaped by immune status and virus serotype in adults with dengue. PLoS Negl Trop Dis 5: e1309.
World Health Organization, 1997. Dengue Haemorragic Fever: Diagnosis, Treatment, Diagnosis and Control. Second Edition. Geneva: World Health Organization.
Johnson BW, Russell BJ, Lanciotti RS, 2005. Serotype-specific detection of dengue viruses in a fourplex real-time reverse transcriptase PCR assay. J Clin Microbiol 43: 4977–4983.
Mosso C, Galván-Mendoza I, Ludert JE, Del Angel RM, 2008. Endocytic pathway followed by dengue virus to infect the mosquito cell line C6/36 HT. Virology 378: 193–199.
Vázquez S, Hafner G, Ruiz D, Calzada N, Guzmán MG, 2007. Evaluation of immunoglobulin M and G capture enzyme-linked immunosorbent assay Panbio kits for diagnostic dengue infection. J Clin Virol 39: 194–198.
Ahmed F, Mursalin H, Alam MT, Amin R, Sekaran SD, Wang SM, Tan YY, Sil BK, Hossain MA, 2010. Evaluation of ASSURE Dengue IgA Rapid Test using dengue-positive and dengue-negative samples. Diagn Microbiol Infect Dis 68: 339–344.
Allonso D, da Silva Rosa M, Coelho DR, da Costa SM, Nogueira RM, Bozza FA, Santos FB, de Barcelos Alves AM, Mohana-Borges R, 2011. Polyclonal antibodies against properly folded dengue virus NS1 protein expressed in E. coli enable sensitive and early dengue diagnosis. J Virol Methods 175: 109–116.
Pawitan JA, 2011. Dengue virus infection: predictors for severe dengue. Acta Med Indones 43: 129–135.
Srikiatkhachorn A, Green S, 2010. Markers of dengue disease severity. Curr Top Microbiol Immunol 338: 67–82.
Yeh WT, Chen RF, Wang L, Liu JW, Shaio MF, Yang KD, 2006. Implications of previous subclinical dengue infection but not virus load in dengue hemorrhagic fever. FEMS Immunol Med Microbiol 48: 84–90.
Thayan R, Huat TL, See LL, Tan CP, Khairullah NS, Yusof R, Devis S, 2009. The use of two-dimension electrophoresis to identify serum biomarkers from patients with dengue haemorrhagic fever. Trans R Soc Trop Med Hyg 103: 413–419.
Dussart P, Labeau B, Lagathu G, Louis P, Nunes MR, Rodrigues SG, Storck-Herrmann C, Cesaire R, Morvan J, Flamand M, Baril L, 2006. Evaluation of an enzyme immunoassay for detection of dengue virus NS1 antigen in human serum. Clin Vaccine Immunol 13: 1185–1189.
Hang VT, Nguyet NM, Trung DT, Tricou V, Yoksan S, Dung NM, Van Ngoc T, Hien TT, Farrar J, Wills B, Simmons CP, 2009. Diagnostic accuracy of NS1 ELISA and lateral flow rapid tests for dengue sensitivity, specificity and relationship to viraemia and antibody responses. PLoS Negl Trop Dis 3: e360.
Ramírez AH, Moros Z, Comach G, Zambrano JL, Bravo L, Pinto B, Vielma S, Cardier J, Liprandi F, 2009. Evaluation of dengue NS1 antigen detection tests with acute sera from patients infected with dengue virus in Venezuela. Diagn Microbiol Infect Dis 65: 247–253.
Bessoff K, Delorey M, Sun W, Hunsperger E, 2008. Comparison of two commercially available dengue virus (DENV) NS1 capture enzyme-linked immunosorbent assays using a single clinical sample for diagnosis of acute DENV infection. Clin Vaccine Immunol 15: 1513–1518.
Vázquez S, Pérez AB, Ruiz D, Rodríguez R, Pupo M, Calzada N, González L, González D, Castro O, Serrano T, Guzmán MG, 2005. Serological markers during dengue 3 primary and secondary infections. J Clin Virol 33: 132–137.
Falconar AK, 2007. Antibody responses are generated to immunodominant ELK/KLE-type motifs on the nonstructural-1 glycoprotein during live dengue virus infections in mice and humans: implications for diagnosis, pathogenesis, and vaccine design. Clin Vaccine Immunol 14: 493–504.
Balmaseda A, Saborio S, Tellez Y, Mercado JC, Perez L, Hammond SN, Rocha C, Kuan G, Harris E, 2008. Evaluation of immunological markers in serum, filter-paper, blood spots, and saliva for dengue diagnosis and epidemiological studies. J Clin Virol 43: 287–291.
De Rivera IL, Parham L, Murillo W, Moncada W, Vázquez S, 2008. Humoral immune response of dengue hemorrhagic fever cases in children from Tegucigalpa, Honduras. Am J Trop Med Hyg 79: 262–266.
Past two years | Past Year | Past 30 Days | |
---|---|---|---|
Abstract Views | 62 | 62 | 21 |
Full Text Views | 795 | 382 | 0 |
PDF Downloads | 301 | 47 | 0 |