Association between serum albumin levels and disease severity in adult patients with dengue: A 7-year retrospective cohort study in mainland China

Abstract

Objective: To identify the association between serum albumin levels and disease severity among adult patients with dengue in mainland China. Methods: This retrospective cohort study analyzed the data of adult patients (aged ≥ 18 years) hospitalized with laboratory-confirmed dengue in a tertiary center for infectious diseases from 2013 to 2019 in mainland China. Serum albumin levels were estimated and compared between patients with severe dengue and non-severe dengue. Additionally, the association between serum albumin levels and severe dengue was evaluated using a generalized linear model [relative risks (RR)]. Multivariate logistic regression analysis was performed to identify the potential predictors of severe dengue. Results: Overall, 1 568 patients were included in this study. Of these patients, 34 (2.17%) developed severe dengue. The median serum albumin levels were significantly lower in patients with severe dengue than that in those with non-severe dengue (33 g/L vs. 37 g/L, P<0.001). After adjustment for age, sex, and comorbidities, hypoalbuminemia (RR 4.877, 95% CI 2.193-11.461, P<0.001) was found to be a predictor of severe dengue. Serum albumin levels (OR 1.303, 95% CI 1.161-1.462, P<0.001)] and age (OR 1.038, 95% CI 1.017-1.061, P<0.001) were significant risk factors for severe dengue. The area under the curve for serum albumin levels to distinguish severe dengue was 0.787. Conclusions: Lower serum albumin levels were significantly associated with disease severity in adult patients with dengue. Hypoalbuminemia on admission resulted in at least a four-fold increased risk of severe dengue.

Keywords

Dengue / Severe dengue / Serum albumin / Hypoalbuminemia / Prediction

References

[1] Castro MC, Wilson ME, Bloom DE. Disease and economic burdens of dengue. Lancet Infect Dis 2017; 17(3):e70-e78.

[2] World Health Organization. Dengue: Guidelines for diagnosis, treatment, prevention and control: New edition; 2009. [Online]. Available from:https://www.who.int/publications/i/item/9789241547871. [Accessed on 21 April 2009].

[3] Guzman MG, Harris E. Dengue. Lancet 2015; 385(9966):453-465.

[4] World Health Organization. Handbook for clinical management of dengue; 2012. [Online]. Available from:https://www.who.int/publications/i/item/9789241504713. [Accessed on 13 November 2012].

[5] Wilder-Smith A, Ooi EE, Horstick O, Wills B. Dengue. Lancet 2019; 393(10169):350-363.

[6] Thein TL, Gan VC, Lye DC, Yung CF, Leo YS. Utilities and limitations of the World Health Organization 2009 warning signs for adult dengue severity. PloS Negl Trop Dis 2013; 7(1):e2023.

[7] Huy BV, Toản NV. Prognostic indicators associated with progresses of severe dengue. PLoS One 2022; 17(1):e262096.

[8] Md Sani SS, Han WH, Bujang MA, Ding HJ, Ng KL, Amir Shariffuddin MA. Evaluation of creatine kinase and liver enzymes in identification of severe dengue. BMC Infect Dis 2017; 17(1):505.

[9] Hsieh CC, Cia CT, Lee JC, Sung JM, Lee NY, Chen PL, et al. A cohort study of adult patients with severe dengue in Taiwanese intensive care units: The elderly and APTT prolongation matter for prognosis. PLoS Negl Trop Dis 2017; 11(1):e5270.

[10] Sangkaew S, Ming D, Boonyasiri A, Honeyford K, Kalayanarooj S, Yacoub S, et al. Risk predictors of progression to severe disease during the febrile phase of dengue: A systematic review and meta-analysis. Lancet Infect Dis 2021; 21(7):1014-1026.

[11] Ferrer R, Mateu X, Maseda E, Yébenes JC, Aldecoa C, De Haro C, et al. Non-oncotic properties of albumin. A multidisciplinary vision about the implications for critically ill patients. Expert Rev Clin Pharmacol 2018; 11(2):125-137.

[12] Miller A, Jedrzejczak WW. Albumin--biological functions and clinical significance. Postepy Hig Med Dosw 2001; 55(1):17-36.

[13] Wang Y, Shi L, Wang Y, Duan G, Yang H. Albumin and total bilirubin for severity and mortality in coronavirus disease 2019 patients. J Clin Lab Anal 2020; 34(7):e23412.

[14] Sheng S, Zhang YH, Ma HK, Huang Y. Albumin levels predict mortality in sepsis patients with acute kidney injury undergoing continuous renal replacement therapy: A secondary analysis based on a retrospective cohort study. BMC Nephrol 2022; 23(1):52.

[15] Kularatnam GAM, Jasinge E, Gunasena S, Samaranayake D, Senanayake MP, Wickramasinghe VP. Evaluation of biochemical and haematological changes in dengue fever and dengue hemorrhagic fever in Sri Lankan children: A prospective follow up study. BMC Pediatr 2019; 19(1):87.

[16] Fernando S, Wijewickrama A, Gomes L, Punchihewa CT, Madusanka SDP, Dissanayake H, et al. Patterns and causes of liver involvement in acute dengue infection. BMC Infect Dis 2016; 16(1):319.

[17] Jog S, Prayag S, Rajhans P, Zirpe K, Dixit S, Pillai L, et al. Dengue infection with multiorgan dysfunction: Sofa score, arterial lactate and serum albumin levels are predictors of outcome. Intensive Care Med 2015; 41(11):2029-2030.

[18] Suwarto S, Hidayat MJ, Widjaya B. Dengue score as a diagnostic predictor for pleural effusion and/or ascites: External validation and clinical application. BMC Infect Dis 2018; 18(1):90.

[19] Yuan K, Chen Y, Zhong M, Lin Y, Liu L. Risk and predictive factors for severe dengue infection: A systematic review and meta-analysis. PLoS One 2022; 17(4):e267186.

[20] Thach TQ, Eisa HG, Hmeda AB, Faraj H, Thuan TM, Abdelrahman MM, et al. Predictive markers for the early prognosis of dengue severity: A systematic review and meta-analysis. PLoS Negl Trop Dis 2021; 15(10):e0009808.

[21] Lai S, Huang Z, Zhou H, Anders KL, Perkins TA, Yin W, et al. The changing epidemiology of dengue in china, 1990-2014: A descriptive analysis of 25 years of nationwide surveillance data. BMC Med 2015; 13:100.

[22] Lun X, Wang Y, Zhao C, Wu H, Zhu C, Ma D, et al. Epidemiological characteristics and temporal-spatial analysis of overseas imported dengue fever cases in outbreak provinces of China, 2005-2019. Infect Dis Poverty 2022; 11(1):12.

[23] Xiao JP, He JF, Deng AP, Lin HL, Song T, Peng ZQ, et al. Characterizing a large outbreak of dengue fever in Guangdong province, China. Infect Dis Poverty 2016; 5:44.

[24] Rowe EK, Leo YS, Wong JG, Thein TL, Gan VC, Lee LK, et al. Challenges in dengue fever in the elderly: Atypical presentation and risk of severe dengue and hospital-acquired infection [corrected]. PLoS Negl Trop Dis 2014; 8(4):e2777.

[25] Yue Y, Liu Q, Liu X, Wu H, Xu M. Comparative analyses on epidemiological characteristics of dengue fever in Guangdong and Yunnan, China, 2004-2018. BMC Public Health 2021; 21(1):1389.

[26] Zhao L, Huang X, Hong W, Qiu S, Wang J, Yu L, et al. Slow resolution of inflammation in severe adult dengue patients. BMC Infect Dis 2016; 16:291.

[27] Zhang FC, He JF, Peng J, Tang XP, Qin CF, Lu HZ, et al. Guidelines for the diagnosis and treatment of dengue in China. Infect Dis Immun 2021; 1(3):144-152.

[28] Hong HW, Wang CT, Zhao LZ, Xie DY, Liu N, Chen R, et al. Clinical features of adult patients with severe dengue in Guangdong province from 2013 to 2019. Chinese J Infect Dis 2022; 40(6):13-19.

[29] Delong ER, Delong DM, Clarke-Pearson DL. Comparing the areas under two or more correlated receiver operating characteristic curves: A nonparametric approach. Biometrics 1988; 44(3):837-845.

[30] Rosenberger KD, Alexander N, Martinez E, Lum L, Dempfle CE, Junghanss T, et al. Severe dengue categories as research endpoints-results from a prospective observational study in hospitalised dengue patients. PLoS Negl Trop Dis 2020; 14(3):e0008076.

[31] Kan FK, Tan CC, Von Bahr GT, Khalid KE, Supramaniam P, Hed MI, et al. Dengue infection complicated by hemophagocytic lymphohistiocytosis: Experiences from 180 patients with severe dengue. Clin Infect Dis 2020; 70(11):2247-2255.

[32] Md-Sani SS, Md-Noor J, Han WH, Gan SP, Rani NS, Tan HL, et al. Prediction of mortality in severe dengue cases. BMC Infect Dis 2018; 18(1):232.

[33] Lee JC, Cia CT, Lee NY, Ko NY, Chen PL, Ko WC. Causes of death among dengue patients causes of death among hospitalized adults with dengue fever in tainan, 2015: Emphasis on cardiac events and bacterial infections. J Microbiol Immunol Infect 2022; 55(2):207-214.

[34] Ngwe Tun MM, Muthugala R, Nabeshima T, Rajamanthri L, Jayawardana D, Attanayake S, et al. Unusual, neurological and severe dengue manifestations during the outbreak in Sri Lanka, 2017. J Clin Virol 2020; 125:104304.

[35] Ye Y, Chen W, Gu M, Xian G, Pan B, Zheng L, et al. Serum globulin and albumin to globulin ratio as potential diagnostic biomarkers for periprosthetic joint infection: A retrospective review. J Orthop Surg Res 2020; 15(1):459.

[36] Huang J, Cheng A, Kumar R, Fang Y, Chen G, Zhu Y, et al. Hypoalbuminemia predicts the outcome of COVID-19 independent of age and co-morbidity. J Med Virol 2020; 92(10):2152-2158.

[37] Baitha U, Halkur Shankar S, Kodan P, Singla P, Ahuja J, Agarwal S, et al. Leucocytosis and early organ involvement as risk factors of mortality in adults with dengue fever. Drug Discov Ther 2021; 14(6):313-318.

[38] Suwarto S, Nainggolan L, Sinto R, Effendi B, Ibrahim E, Suryamin M, et al. Dengue score: A proposed diagnostic predictor for pleural effusion and/or ascites in adults with dengue infection. BMC Infect Dis 2016; 16(1):322.

[39] Shahid Ansari M, Jain D, Harikumar H, Rana S, Gupta S, Budhiraja S, et al. Identification of predictors and model for predicting prolonged length of stay in dengue patients. Health Care Manag Sci 2021; 24(4):786-798.

[40] World Health Organization Regional Office for South-East Asia. Comprehensive guideline for prevention and control of dengue and dengue haemorrhagic fever. Revised and expanded edition; 2011. [Online]. Available from:https://apps.who.int/iris/handle/10665/204894. [Accessed on 16 April 2016].

[41] Lee I, Hsieh CJ, Lee CT, Liu JW. Diabetic patients suffering dengue are at risk for development of dengue shock syndrome/severe dengue: Emphasizing the impacts of co-existing comorbidity(ies) and glycemic control on dengue severity. J Microbiol Immunol Infect 2020; 53(1):69-78.

[42] Opal SM, Girard TD, Ely EW. The immunopathogenesis of sepsis in elderly patients. Clin Infect Dis 2005; 41(Suppl 7):S504-S512.

[43] Waheed I, Khalid S, Jamil Z. Predictors of complicated dengue infections in endemic region of Pakistan. Asian Pac J Trop Med 2022; 15:496-502.

[44] Nguyen MT, Ho TN, Nguyen VV, Nguyen TH, Ha MT, Ta VT, et al. An evidence-based algorithm for early prognosis of severe dengue in the outpatient setting. Clin Infect Dis 2017; 64(5):656-663.

[45] Liao B, Tang Y, Hu F, Zhou W, Yao X, Hong W, et al. Serum levels of soluble vascular cell adhesion molecules may correlate with the severity of dengue virus-1 infection in adults. Emerg Microbes Infect 2015; 4(4):e24.