Background As dengue spreads to new geographical regions and the force of infection changes in existing endemic areas, a greater breadth of clinical presentations is being recognised. Clinical experience suggests that adults manifest a pattern of complications different from those observed in children, but few reports have described the age-related spectrum of disease in contemporaneous groups of patients recruited at the same geographical location. Methodology/Principal Findings Using detailed prospectively collected information from ongoing studies that encompass the full spectrum of hospitalised dengue cases admitted to a single hospital in southern Vietnam, we compared clinical and laboratory features, management, and outcome for 647 adults and 881 children with confirmed dengue. Signs of vascular leakage and shock were more frequent and more severe in children than adults, while bleeding manifestations and organ involvement were more common in adults. Additionally, adults experienced significantly more severe thrombocytopenia. Secondary infection but not serotype was independently associated with greater thrombocytopenia, although with a smaller effect than age-group. The effect of age-group on platelet count was also apparent in the values obtained several weeks after recovery, indicating that healthy adults have intrinsically lower counts compared to children. Conclusions/Significance There are clear distinctions between adults and children in the pattern of complications seen in association with dengue infection, and these depend partly on intrinsic age-dependent physiological differences. Knowledge of such differences is important to inform research on disease pathogenesis, as well as to encourage development of management guidelines that are appropriate to the age-groups at risk.
References
[1]
World Health Organization (2009) Dengue: Guideline for diagnosis, treatment, prevention and control. WHO, Geneva, Switzerland.
[2]
Wichmann O, Hongsiriwon S, Bowonwatanuwong C, Chotivanich K, Sukthana Y, et al. (2004) Risk factors and clinical features associated with severe dengue infection in adults and children during the 2001 epidemic in Chonburi, Thailand. Trop Med Int Health 9: 1022–1029. doi: 10.1111/j.1365-3156.2004.01295.x
[3]
Kittigul L, Pitakarnjanakul P, Sujirarat D, Siripanichgon K (2007) The differences of clinical manifestations and laboratory findings in children and adults with dengue virus infection. J Clin Virol 39: 76–81. doi: 10.1016/j.jcv.2007.04.006
[4]
Anders KL, Nguyet NM, Chau NV, Hung NT, Thuy TT, et al. (2011) Epidemiological factors associated with dengue shock syndrome and mortality in hospitalized dengue patients in Ho Chi Minh City, Vietnam. Am J Trop Med Hyg 84: 127–134. doi: 10.4269/ajtmh.2011.10-0476
[5]
Nagao Y, Koelle K (2008) Decreases in dengue transmission may act to increase the incidence of dengue hemorrhagic fever. Proc Natl Acad Sci U S A 105: 2238–2243. doi: 10.1073/pnas.0709029105
[6]
Cummings DA, Iamsirithaworn S, Lessler JT, McDermott A, Prasanthong R, et al. (2009) The impact of the demographic transition on dengue in Thailand: insights from a statistical analysis and mathematical modeling. PLoS Med 6: e1000139. doi: 10.1371/journal.pmed.1000139
[7]
Thomas L, Brouste Y, Najioullah F, Hochedez P, Hatchuel Y, et al. (2010) Prospective and descriptive study of adult dengue cases in an emergency department, in Martinique. Med Mal Infect 40: 480–489. doi: 10.1016/j.medmal.2009.10.001
[8]
Hammond SN, Balmaseda A, Perez L, Tellez Y, Saborio SI, et al. (2005) Differences in dengue severity in infants, children, and adults in a 3-year hospital-based study in Nicaragua. Am J Trop Med Hyg 73: 1063–1070.
[9]
Malavige GN, Velathanthiri VG, Wijewickrama ES, Fernando S, Jayaratne SD, et al. (2006) Patterns of disease among adults hospitalized with dengue infections. Qjm 99: 299–305. doi: 10.1093/qjmed/hcl039
[10]
Hanafusa S, Chanyasanha C, Sujirarat D, Khuankhunsathid I, Yaguchi A, et al. (2008) Clinical features and differences between child and adult dengue infections in Rayong Province, southeast Thailand. Southeast Asian J Trop Med Public Health 39: 252–259.
[11]
Wills BA, Nguyen MD, Ha TL, Dong TH, Tran TN, et al. (2005) Comparison of three fluid solutions for resuscitation in dengue shock syndrome. N Engl J Med 353: 877–889. doi: 10.1056/NEJMoa044057
[12]
Wills B, Tran VN, Nguyen TH, Truong TT, Tran TN, et al. (2009) Hemostatic changes in Vietnamese children with mild dengue correlate with the severity of vascular leakage rather than bleeding. Am J Trop Med Hyg 81: 638–644. doi: 10.4269/ajtmh.2009.08-0008
[13]
Trung DT, Thao le TT, Hien TT, Hung NT, Vinh NN, et al. (2010) Liver involvement associated with dengue infection in adults in Vietnam. Am J Trop Med Hyg 83: 774–780. doi: 10.4269/ajtmh.2010.10-0090
[14]
Hang VT, Nguyet NM, Trung DT, Tricou V, Yoksan S, et al. (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. doi: 10.1371/journal.pntd.0000360
[15]
Fox A, Le NM, Simmons CP, Wolbers M, Wertheim HF, et al. (2011) Immunological and viral determinants of dengue severity in hospitalized adults in Ha Noi, Viet Nam. PLoS Negl Trop Dis 5: e967. doi: 10.1371/journal.pntd.0000967
[16]
Schmidt WP, Suzuki M, Thiem VD, Yoshida LM, Matsubayashi T, et al. (2011) User fee exemption does not affect lower rates of hospital admission of girls in Vietnam. Health Policy Plan. doi: 10.1093/heapol/czr079
[17]
Guzman MG, Kouri G, Bravo J, Valdes L, Vazquez S, et al. (2002) Effect of age on outcome of secondary dengue 2 infections. Int J Infect Dis 6: 118–124. doi: 10.1016/S1201-9712(02)90072-X
[18]
Gamble J, Bethell D, Day NP, Loc PP, Phu NH, et al. (2000) Age-related changes in microvascular permeability: a significant factor in the susceptibility of children to shock? Clin Sci (Lond) 98: 211–216. doi: 10.1042/CS19990296
[19]
Lee IK, Liu JW, Yang KD (2008) Clinical and laboratory characteristics and risk factors for fatality in elderly patients with dengue hemorrhagic fever. Am J Trop Med Hyg 79: 149–153. doi: 10.1093/heapol/czr079
[20]
Leo YS, Thein TL, Fisher DA, Low JG, Oh HM, et al. (2011) Confirmed adult dengue deaths in Singapore: 5-year multi-center retrospective study. BMC Infect Dis 11: 123. doi: 10.1186/1471-2334-11-123
[21]
Wills BA, Oragui EE, Stephens AC, Daramola OA, Dung NM, et al. (2002) Coagulation abnormalities in dengue hemorrhagic Fever: serial investigations in 167 Vietnamese children with Dengue shock syndrome. Clin Infect Dis 35: 277–285. doi: 10.1086/341410
[22]
Giacomini A, Legovini P, Gessoni G, Antico F, Valverde S, et al. (2001) Platelet count and parameters determined by the Bayer ADVIA 120 in reference subjects and patients. Clin Lab Haematol 23: 181–186. doi: 10.1046/j.1365-2257.2001.00391.x
[23]
Thomas L, Kaidomar S, Kerob-Bauchet B, Moravie V, Brouste Y, et al. (2009) Prospective observational study of low thresholds for platelet transfusion in adult dengue patients. Transfusion 49: 1400–1411. doi: 10.1111/j.1537-2995.2009.02132.x
[24]
Lye DC, Lee VJ, Sun Y, Leo YS (2009) Lack of efficacy of prophylactic platelet transfusion for severe thrombocytopenia in adults with acute uncomplicated dengue infection. Clin Infect Dis 48: 1262–1265. doi: 10.1086/597773
[25]
Polson J, Lee WM (2005) AASLD position paper: the management of acute liver failure. Hepatology 41: 1179–1197. doi: 10.1002/hep.20703
[26]
Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P (2004) Acute renal failure - definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care 8: R204–212. doi: 10.1186/cc2872