Regulators of endothelial integrity as severity predictors in dengue

Claudia Lucía Figueroa, Margarita Gélvez, Jürg Niederbacher, .

Keywords: Endothelium, dengue, severe dengue, risk, capillary permeability, forecasting

Abstract

Introduction: Dengue is currently among the mosquito-borne diseases of greatest global impact. The clinical course of the disease can be unpredictable, so proper handling in its early stages is critical to ensure optimal outcomes. Objective: To evaluate serum regulators of endothelial integrity (VEGF, sICAM-1, sEndoglina, Ang-1, and Ang-2) as predictive markers of dengue severity. Materials and methods: We conducted a case-control study nested in an appropriate cohort. Endothelial regulator levels were first measured by ELISA, after which analysis was performed using logistic regression of clinical and regulatory variables, with severity as an output variable. A possible severity prediction model, based on the variables of interest and output, was defined using the best area under the ROC curve. Results: The median subject age was 24 years. Severe cases were associated with Ang-2 serum levels of ≥1,490 ng/ml (OR=3.1; p=0.015). Serum levels of Ang-2 (≥1,490 ng/ml) contributed to the severity prediction model, as did a 0.73 area under the ROC curve, together with the variables rash, impaired consciousness and abdominal pain, with an OR of 3.2 (CI 95%: 1.16 to 8.9; p=0.024). Conclusion: The endothelial regulator Ang-2 could be a predictor of severity in dengue.

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  • Claudia Lucía Figueroa Grupo GERMINA, Departamento de Medicina Interna, Escuela de Medicina, Facultad de Salud, Universidad Industrial de Santander, Bucaramanga, Colombia
  • Margarita Gélvez Centro de Investigaciones Epidemiológicas, Facultad de Salud, Universidad Industrial de Santander, Bucaramanga, Colombia
  • Jürg Niederbacher Departamento de Pediatría, Escuela de Medicina, Facultad de Salud, Universidad Industrial de Santander, Bucaramanga, Colombia

References

World Health Organization. Dengue and severe dengue. Fecha de consulta: 1º de marzo de 2013. Disponible en: http://www.who.int/mediacentre/factsheets/fs117/en

Bello SL. Comportamiento epidemiológico del dengue en Colombia, año 2011. Fecha de consulta: 1º de diciembre de 2012. Disponible en: http://www.ins.gov.co/lineas-de-accion/Subdireccion-Vigilancia/Informe%20de%20Evento%20Epidemiolgico/Dengue%202011.pdf

Ministerio de Salud y Protección Social. Informe de actividades al Congreso 2012-2013. Bogotá: Ministerio de Salud y Protección Social; 2013. p. 76-7. Fecha de consulta: 1º de noviembre de 2013. Disponible en: https://www.minsalud.gov.co/Documentos%20y%20Publicaciones/Informe%20al%20Congreso%202012-2013.pdf

Basu A, Chaturvedi UC. Vascular endothelium: The battlefield of dengue viruses. FEMS Immunol Med Microbiol. 2008;53:287-99. http://dx.doi.org/10.1111/j.1574-695X.2008.00420.x

Vervaeke P, Vermeire K, Liekens S. Endothelial dysfunc-tion in dengue virus pathology. Rev Med Virol. 2015;25:50-67. http://dx.doi.org/10.1002/rmv.1818

Dietmann A, Helbok R, Lackner P, Fischer M, Reindl M, Lell B, et al. Endoglin in African children with Plasmodium falciparum malaria. A novel player in severe malaria pathogenesis? J Infect Dis. 2009;200:1842-8. http://dx.doi.org/10.1086/648476

Conroy AL, Gélvez M, Hawkes M, Rajwans N, Liles WC, Villar-Centeno LA, et al. Host biomarker distinguish dengue from leptospirosis in Colombian: A case-control study. BMC Infect Dis. 2014;14:35. http://dx.doi.org/10.1186/1471-2334-14-35

van Meurs M, Kümpers P, Ligtenberg JJ, Meertens JH, Molema G, Zijlstra JG. Bench-to-bedside review: Angiopoietin signalling in critical illness – a future target? Crit Care. 2009;13:207. http://dx.doi.org/10.1186/cc7153

Michels M, van der Ven AJ, Djamiatun K, Fijnheer R, de Groot PG, Griffioen AW, et al. Imbalance of angiopoietin-1 and angiopoetin-2 in severe dengue and relationship with thrombocytopenia, endothelial activation, and vascular stability. Am J Trop Med Hyg. 2012;87:943-6. http://dx.doi.org/10.4269/ajtmh.2012.12-0020

Ong SP, Ng ML, Chu JJ. Differential regulation of angiopoietin 1 and angiopoietin 2 during dengue virus infection of human umbilical vein endothelial cells: Implications for endothelial hyperpermeability. Med Microbiol Immunol. 2013;202:437-52. http://dx.doi.org/10.1007/s00430-013-0310-5

Srikiatkhachorn A, Ajariyakhajorn C, Endy TP, Kalayanarooj S, Libraty DH, Green S, et al. Virus-induced decline in soluble vascular endothelial growth receptor 2 is associated with plasma leakage in dengue hemorrhagic fever. J Virol. 2007;81:1592-600. http://dx.doi.org/10.1128/JVI.01642-06

van de Weg CA, Pannuti CS, van den Ham HJ, de Araújo ES, Boas LS, Felix AC, et al. Serum angiopoietin-2 and soluble VEGF receptor 2 are surrogate markers for plasma leakage in patients with acute dengue virus infection. J Clin Virol. 2014;60:328-35. http://dx.doi.org/10.1016/j.jcv. 2014.05.001

Lawson C, Wolf S. ICAM-1 signaling in endothelial cells. Pharmacol Rep. 2009;61:22-32.

Khongphatthanayothin A, Phumaphuti P, Thongchaiprasit K, Poovorawan Y. Serum levels of sICAM-1 and sE-selectin in patients with dengue virus infection. Jpn J Infect Dis. 2006;59:186-8.

Page AV, Liles WC. Biomarkers of endothelial activation/dysfunction in infectious diseases. Virulence 2013;4:507-16. http://dx.doi.org/10.4161/viru.24530

World Health Organization. Clinical diagnosis. En: Dengue haemorrhagic fever: Diagnosis, treatment, prevention and control. Second edition. Geneva: WHO; 1997. p. 12-23.Fecha de consulta: 11 de agosto de 2012. Disponible en: http://www.who.int/entity/csr/resources/publications/dengue/012-23.pdf

Conroy AL1, Lafferty EI, Lovegrove FE, Krudsood S, Tangpukdee N, Liles WC, et al. Whole blood angiopoietin-1 and -2 levels discriminate cerebral and severe (non-cerebral) malaria from uncomplicated malaria. Malar J. 2009;8:295. http://dx.doi.org/10.1186/1475-2875-8-295

Ministerio de Salud. Resolución N° 0008430 de 1993. República de Colombia, 1993. Fecha de consulta: 23 de septiembre de 2012. Disponible en: https://www.invima.gov.co/images/pdf/medicamentos/resoluciones/etica_res_8430_1993.pdf

Conroy A, Gélvez M, Hawkes M, Rajwans N, Tran V, Liles WC, et al. Host biomarkers are associated with progression to dengue haemorrhagic fever: A nested case-control study. Int J Infect Dis. 2015;40:45-53. http://dx.doi.org/10.1016/j.ijid.2015.07.027

Simmons CP, Farrar JJ, Nguyen VV, Wills B. Dengue. N Engl J Med. 2012;366:1423-32. http://dx.doi.org/10.1056/NEJMra1110265

Srikiatkhachorn A, Kelley JF. Endothelial cells in dengue hemorrhagic fever. Antiviral Res. 2014;109:160-70. http://dx.doi.org/10.1016/j.antiviral.2014.07.005

Spiropoulou C, Srikiatkhchachorn A. The role of endothelial activation in dengue hemorrhagic and hantavirus pulmonary syndrome. Virulence. 201315;4:525-36. http://dx. doi.org/10.4161/viru.25569

Tseng CS, Lo HW, Teng HC, Lo WC, Ker CG. Elevated levels of plasma VEGF in patients with dengue hemorrhagic fever. FEMS Immunol Med Microbiol. 2005;43:99-102. http://dx.doi.org/10.1016/j.femsim.2004.10.004

Azizan A, Sweat J, Espino C, Gemmer J, Stark L, Kazanis D. Differential proinflammatory and angiogenesis-specific cytokine production in human pulmonary endothelial cells, HPMEC-ST1.6R infected with dengue-2 and dengue-3 virus. J Virol Methods. 2006;138:211-7. http://dx.doi.org/10. 1016/j.jviromet.2006.08.010

Villar-Centeno LA, Lozano-Parra A, Salgado-García D, Herrán O. Alteraciones bioquímicas como marcadores predictores de gravedad en pacientes con fiebre por dengue. Biomédica. 2013;33:63-9. http://dx.doi.org/10.7705/biomedica.v33i0.732

Fiedler U, Scharpfenecker M, Koidl S, Hegen A, Grunow V, Schmidt JM, et al. The Tie-2 ligand angiopoietin-2 is stored in and rapidly released upon stimulation from endothelial cell Weibel-Palade bodies. Blood. 2004;103: 4150-6. http://dx.doi.org/10.1182/blood-2003-10-3685

Giuliano JS Jr, Lahni PM, Harmon K, Wong HR, Doughty LA, Carcillo JA, et al. Admission angiopoietin levels in children with septic shock. Shock. 2007;28:650-4. http://dx.doi.org/10.1097/shk.0b013e318123867b

Dalrymple NA, Mackow ER. Roles for endothelial cells in dengue virus infection. Adv Virol. 2012;2012:840654. http://dx.doi.org/10.1155/2012/840654

Ricciuto DR, dos Santos CC, Hawkes M, Toltl LJ, Conroy AL, Rajwans N, et al. Angiopoietin-1 and angiopoietin-2 as clinically informative prognostic biomarkers of morbidity and mortality in severe sepsis. Crit Care Med. 2011;39:702-10. http://dx.doi.org/10.1097/CCM.0b013e318206d285.

How to Cite
1.
Figueroa CL, Gélvez M, Niederbacher J. Regulators of endothelial integrity as severity predictors in dengue. biomedica [Internet]. 2016 Aug. 1 [cited 2024 May 18];36(Sup2):148-55. Available from: https://revistabiomedica.org/index.php/biomedica/article/view/2878

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Published
2016-08-01

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