- Email: [email protected]
Atypical presentations of dengue disease in the elderly visiting the ED
American Journal of Emergency Medicine 31 (2013) 783–787
Contents lists available at SciVerse ScienceDirect
American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajem
Original Contribution
Atypical presentations of dengue disease in the elderly visiting the ED Ching-Chi Lee MD a, Hsiang-Chin Hsu MD b, Chia-Ming Chang MD a, Ming-Yuan Hong MD b, Wen-Chien Ko MD a, c,⁎ a b c
Department of Internal Medicine, National Cheng Kung University Hospital, Tainan 704, Taiwan Department of Emergency Medicine, National Cheng Kung University Hospital, Tainan 704, Taiwan Department of Medicine, National Cheng Kung University Medical College, Tainan 704, Taiwan
a r t i c l e
i n f o
Article history: Received 30 October 2012 Received in revised form 12 January 2013 Accepted 13 January 2013
a b s t r a c t Objective: The objective was to compare the clinical characteristics of elderly and young adult patients with dengue in the emergency department (ED). Methods: Demographic characteristics, clinical presentation, disease severity, laboratory characteristics, and outcomes were analyzed prospectively as a case-control study. Results: Of the 193 adults with serologically confirmed dengue disease in 2007, 31 (16.1%) were elderly patients (aged ≥65) and 162 were young adults (aged b 65). More dengue hemorrhagic fever (12.9% vs 2.5%, P = .02), a longer ED stay (13.3 vs 8.6 hours, P = .004), a longer hospital stay (7.4 vs 3.4 days, P b .001), a higher Simplified Acute Physiology Score II in the ED (29.7 vs 17.4, P b .001), and a higher rate of at least 1 comorbidity (61.8 vs 22.8%, P b .001) were found in the elderly. However, the length of the intensive care unit stay (elderly 0.7 vs young adults 0.3 day, P = .47) and the 14-day mortality rate (0% vs 0.6%, P = 1.00) were similar. Of note, in terms of clinical presentations of dengue in the ED, there were more elderly patients with isolated fever (41.9% vs 17.9%, P = .003) and fewer with typical presentation (41.9% vs 75.9%, P = b .001) than there were young adults. Conclusions: The present study found a higher number of atypical presentations, a longer hospitalization, and a higher degree of clinical illness in elderly patients with dengue. © 2013 Elsevier Inc. All rights reserved.
1. Introduction Dengue is an important arboviral disease of humans; and it has emerged as a global public health problem, especially in tropical and subtropical areas [1]. The dengue case burden and the number of countries reporting outbreaks have increased 10-fold in the last 30 years. In southern Taiwan, several outbreaks of dengue fever have been reported in recent years [1,2]. In a previous study conducted between 2002 and 2007, a common pattern of dengue transmission was noted. Every year, the epidemic was initiated by the importation of the virus from abroad in the summer, spread in southern Taiwan, and came to an end of the epidemic in the winter. Most of the affected patients were adults, mainly those aged between 50 and 54 [2]. In 2007, 2179 symptomatic cases of dengue were reported in Taiwan, resulting in an incidence of 0.0095%; and most (1888, 86.6%) patients were adults [3].
⁎ Corresponding author. Department of Internal Medicine, National Cheng Kung University Hospital, Tainan 70403, Taiwan. Tel.: +886 6 2353535x3596; fax: +886 6 2752038. E-mail address: [email protected] (W.-C. Ko). 0735-6757/$ – see front matter © 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.ajem.2013.01.011
Dengue fever is characterized by a sudden onset of high-grade fever and often associated with nonspecific constitutional symptoms [1]. Fever has been found to be the third leading reason for visiting the emergency department (ED) and the chief concern in 5% of all ED visits [4]. Therefore, for adult visitors, dengue fever should be put into the list of differential diagnosis of febrile illness. However, aging is associated with significant changes in the adaptive humoral and cellmediated immunity [5]. Poor cytokine responses to sepsis have been discovered in the elderly [6], which lead to atypical clinical presentation and the well-recognized increase in mortality among the elderly due to various infections [7–11]. Moreover, the increased prevalence of chronic, degenerative diseases; frequent prescription of immunosuppressive or antineoplastic drugs in the elderly; and the susceptibility of the elderly to frequent exacerbations of preexisting conditions result in the elderly becoming frequent visitors of the ED [12,13]. Because primary dengue infections are observed in young children and travelers immunologically naive to dengue virus exhibit the same symptoms of dengue infection as the initial infection observed in children, symptomatic dengue generally occurs during secondary dengue infections in adults and city residents [1,14]. This conclusion was compatible with a study in Taiwan [2], in which most cases of symptomatic dengue were adults. Several investigations have
784
C.-C. Lee et al. / American Journal of Emergency Medicine 31 (2013) 783–787
discussed the differences of clinical manifestations of dengue diseases between children and adults [15–18]. However, there were few investigations focusing on dengue diseases in the elderly [19,20]. In the English literature, no study addressing their presentation in the ED has been found. Thus, we conducted this study to describe the clinical presentation and the outcome of dengue in elderly patients by a comparison with dengue infections in young adults in the ED. 2. Materials and methods 2.1. Study design and population A prospective case-control study was conducted between January 2007 and December 2007 at a medical center of approximately 1000 beds in southern Taiwan; and 64,345 annual visits to the ED were recorded during the study period. The local institutional review board approved this study. The analysis included the records of adults who visited the ED during the study period and had suspected dengue as determined by ED clinicians. Demographic information and clinical characteristics, severity scores, comorbidities, and laboratory data of adults suspected to have dengue were prospectively collected in a predetermined record form immediately after their arrival at the ED. However, the study excluded those with a serologically negative result of dengue disease. For the eligible adults, elderly patients (≧ 65 years) were regarded as the case group; and young adults (b65 years) were regarded as control patients. The medical records were reviewed for hospital course and clinical outcome by 2 of the authors, an ED clinician and an internist. If any discrepancy was found, the medical records were inspected by these 2 authors together. The primary outcome was the overall mortality in the 14 days immediately after visiting the ED. If the patients were discharged within 14 days after ED arrival and not followed up at our hospital, their outcome information was obtained by a telephone call. The patients not reached by the telephone were excluded. 2.2. Dengue reporting system and diagnosis According to the guideline of the Taiwan Centers for Disease Control Taiwan, dengue is a category II notifiable infectious disease; and physicians are obliged to report any suspected dengue cases to the health department within 24 hours of clinical diagnosis. All sera were tested in the Kaohsiung laboratory. Routine diagnosis includes molecular analysis by real-time transcriptase-polymerase chain reaction, serologic testing using captured immunoglobulin (Ig) M/ IgG enzyme-linked immunosorbent assay (ELISA), and viral isolation by cell culture. Dengue viral infection is defined as one of the following: a positive IgM antibody detection by ELISA, a positive real-time transcriptase-polymerase chain reaction for dengue virus, or at least a 4-fold increase in dengue-specific hemagglutination inhibition titers in convalescent serum compared with those in acute-phase serum [2,3]. However, as previously described [3], patients diagnosed by a dengue-specific IgM ELISA in the acute phase must also be concomitantly serologically negative for the specific IgM for Japanese encephalitis virus. 2.3. Definitions Elderly patients were defined as patients 65 years or older, whereas those aged less than 65 years were considered as young adults. Underlying malignancies included hematological malignancies or solid tumors, and the definitions of comorbidities were previously described [21]. The hemorrhage phenomena of dengue included a positive tourniquet test result, petechiae, ecchymosis, epistaxis, gingival bleeding, gastrointestinal bleeding, hematuria, hypermenorrhea, or vaginal bleeding, whereas conscious disturbance, intracranial hemorrhage, vessel occlusion, or cerebral anoxia was considered to be
its neurologic signs. The typical presentation of dengue diseases in the adults included fever plus at least 1 of the following: bone pain, myalgia, arthralgia, retroorbital pain, headache, and maculopapular rash [1]. In patients with a serological confirmation of dengue, a diagnosis of dengue hemorrhage fever (DHF) was made based on World Health Organization criteria, that is, the presence of fever, hemorrhagic phenomena, thrombocytopenia, and the existence of hemoconcentration (≥20% rise in hematocrit above the baseline value or the presence of pleural effusion or ascites) [22]. Moreover, the severity of DHF was categorized into grades I to IV according to the World Health Organization criteria: DHF grade III was defined as circulatory failure manifested by a rapid and weak pulse, with narrowing pulse pressure (less than 20 mm Hg); DHF grade IV was defined as profound shock, with undetectable pulse or blood pressures; and DHF grades III and IV were collectively grouped as dengue shock syndrome (DDS). The severity of dengue was also graded by a Simplified Acute Physiology Score II (SAPS II) [23]. 2.4. Data analysis Statistical analyses were performed using the Statistical Package for the Social Sciences for Windows, Version 15.0 (SPSS, Chicago, IL). Continuous variables were expressed as the means ± standard deviations (SDs) and compared using Student t test. Categorical variables, expressed as numbers and percentages, were compared using a χ 2 test or Fisher exact test. A P value of less than .05 was considered significant. 3. Results 3.1. Demographics and clinical characteristics of all dengue patients During the 1-year period, of the total 64,345 ED visits, 266 adults had suspected dengue; and their sera were examined by the Taiwan Centers for Disease Control laboratory. A total of 193 adults had a dengue virus infection, whereas 58 were not infected with dengue virus. The results of 15 patients were undetermined because of a lack of convalescent serum. Moreover, no patients were excluded because of the loss of follow-up within 14 days after ED arrival. Of the 193 eligible adults, elderly patients accounted for 16.1% (31 patients); and 91 patients (47.2%) were male, as shown in Fig. Most patients (179, 92.7%) visited the ED from the community, but 14 (7.3%) were transferred from other hospitals. Only one (0.5%) had been hospitalized within 28 days before the ED visit. Common comorbidities included hypertension (36 patients, 18.7%), diabetes mellitus (22, 11.4%), coronary artery disease (10, 5.2%), chronic renal insufficiency (5, 2.6%), malignancy (4, 2.1%), chronic obstructive pulmonary disease (4, 2.1%), liver cirrhosis (3, 1.6%), and old stroke (3, 1.6%); and no comorbidity was identified in 129 (66.8%) of the patients. Most patients (136, 70.5%) were admitted to general wards, 4 (2.1%) were admitted to intensive care units (ICUs), and 57 (29.5%) were discharged from the ED. Eight (4.1%) patients evolved into DHF at discharge, whereas 1 patient (0.5%) with DDS died. No patients died during the ED stay or within 14 days of their ED arrival. Therefore, the overall 14-day mortality rate was 0.5%. 3.2. Clinical characteristics and presentation in the case and control patients Clinical variables of the elderly patients and young adults in the ED, including demographics, severity, comorbidities, and laboratory data, are compared in Table 1. Longer ED stay, more blood cultures sampled, more antibiotics prescribed, more admission through the ED, higher SAPS scores, and more comorbidities, including hypertension, diabetes mellitus, malignancy, and coronary artery diseases, were present in the elderly, whereas no comorbidity was noted more
C.-C. Lee et al. / American Journal of Emergency Medicine 31 (2013) 783–787
785
Fig. Patient flowchart.
often in young adults. With respect to laboratory data, fewer cases of leukopenia or normal serum levels of C-reactive protein were observed in the elderly, whereas fewer young adults exhibited elevated levels of blood urea nitrogen (N20 mg/dL) or serum creatinine (N 1.5 mg/dL).
Table 1 Clinical characteristics and laboratory data of elderly patients (aged ≥65) and young adults (aged b65) with dengue virus infection in an ED Clinical characters
Male Comorbidity None ≥1 Comorbidity ≥2 Comorbidities Hypertension Diabetes mellitus Coronary artery diseases Chronic renal insufficiency Chronic obstructive pulmonary disease Liver cirrhosis Malignancy Old stroke Events in the ED Length of stay (h), mean ± SD Blood culture sampling Antimicrobial agents prescription Severity of illness in the ED SAPS II, mean ± SD Ward admission through the ED ICU admission through the ED Laboratory data in the ED Leukocyte b4000/mm3 Bandemia (≥10% bands) Hemoglobulin b10 mg/dL Platelet b100,000/mm3 C-reactive protein b7 mg/Lb Blood urea nitrogen N20 mg/dL Serum creatinine N1.5 mg/dL ALT or AST N3×c
Patient number (%)a
P values
Young patients, n = 162
Elderly patients, n = 31
76 (46.9)
15 (48.4)
1.00
120 (74.1) 37 (22.8) 14 (8.6) 25 (15.4) 14 (8.6) 6 (3.7) 4 (2.5) 3 (1.9)
9 (29.0) 19 (61.8) 10 (32.3) 11 (35.3) 8 (25.8) 4 (12.9) 1 (3.2) 1 (3.2)
b.001 b.001 .001 .009 .01 .05 .59 .51
2 (1.2) 1 (0.6) 1 (0.6)
1 (3.2) 3 (9.7) 2 (6.50)
.41 .01 .07
8.6 ± 8.3 119 (73.5) 35 (21.6)
13.3 ± 8.7 30 (96.8) 19 (61.3)
.004 .005 b.001
17.4 ± 6.7 107 (66.0) 2 (1.2)
29.7 ± 10.7 29 (93.5) 2 (6.5)
b.001 .002 .12
122 (75.3) 46 (28.4) 2 (1.9) 76 (46.9) 77 (47.5) 5/151 (3.3) 6/154 (3.9) 55 (34.0)
17 (54.8) 12 (38.7) 3 (6.5) 18 (58.1) 7 (22.6) 6 (19.4) 5 (16.1) 12 (38.7)
.02 .25 .18 .26 .01 .004 .02 .61
ALT, alanine aminotransferase; AST; aspartate aminotransferase. a Data are expressed as case numbers (percentages), unless indicated specifically. b Within the reference range. c More than 3 times the upper limit of the reference range.
The differences in clinical presentations between elderly patients and young adults are listed in Table 2. A shorter period between symptom onset and ED arrival, more patients with isolated fever, and fewer patients with typical presentations of dengue were observed among elderly patients during their ED stay. With respect to the clinical symptoms/signs between the 2 groups, fewer cases with maculopapular rash were observed in the elderly. 3.3. Clinical outcome, hospital stay, and serotype of dengue in elderly patients and young adults More patients with DHF and a longer hospital stay were observed among the elderly; but the 14-day crude mortality rate and the length of ICU stay were similar in the 2 groups, as shown in Table 3.
Table 2 Clinical presentation and duration of dengue in elderly patients (aged ≥65) and young adults (aged b65) in an ED Clinical variable
Patient number (%)a Young patients, n = 162
The period between symptoms 3.9 ± 2.4 onset and ED arrival, mean ± SD Symptom/signs of dengue during the ED stay Isolated fever 29 (17.9) 123 (75.9) Typical presentations of dengueb Detailed symptom/signs Fever 160 (98.8) Maculopapular rash 60 (37.5) Headache 50 (30.9) Myalgia 41 (25.3) General malaise 38 (23.5) Bone pain 36 (22.2) Hemorrhagec 34 (21.0) Retroorbital pain 7 (4.3) Arthralgia 6 (3.7) d Neurologic abnormality 1 (0.6) a
P values
Elderly patients, n = 31 2.3 ± 1.8
.001
13 (41.9) 13 (41.9)
.003 b.001
29 (93.5) 2 (6.5) 7 (22.6) 6 (19.4) 8 (25.8) 4 (12.9) 6 (19.4) 0 (0) 1 (3.2) 1 (3.2)
.12 .001 .35 .48 .78 .24 1.00 .60 1.00 .30
Data are expressed as case numbers (percentages), unless indicated specifically. Fever plus at least 1 of following symptoms: bone pain, myalgia, arthralgia, retroorbital pain, headache, and maculopapular rash. c Includes positive tourniquet test result, petechiae, ecchymosis, epistaxis, gingival bleeding, gastrointestinal bleeding, hematuria, hypermenorrhea, or vaginal bleeding. d Includes consciousness disturbance, intracranial hemorrhage, vessel occlusion, or cerebral anoxia. b
786
C.-C. Lee et al. / American Journal of Emergency Medicine 31 (2013) 783–787
Table 3 Clinical outcome, serotype, and hospitalization of dengue in elderly patients (aged ≥65) and young adults (aged b65) in an ED Clinical variables
Patient number (%) Young patients, n = 162
Final diagnosis at discharge DHF 4 (2.5) DSS 1 (0.6) Serotype of dengue a DENV-1 133 (82.1) DENV-3 29 (17.9) Duration of hospitalization (h), mean ± SD Length of hospital stay (d) 3.4 ± 4.0 Length of ICU stay (d) 0.3 ± 3.0 14-d crude mortality rate 1 (0.6)
that nonspecific febrile presentations in the elderly render diagnosis by ED clinicians difficult with respect to differentiation between dengue and bacterial infections.
P values
5. Limitations
The elderly, n = 31 4 (12.9) 0 (0)
0.02 1.00 0.31
23 (74.2) 8 (25.8) 7.4 ± 5.8 0.7 ± 2.8 0 (0)
b0.001 0.47 1.00
Data are expressed as case numbers (percentages), unless indicated specifically. a DENV indicates dengue virus.
Moreover, the serotype distribution of dengue virus, DENV-1 or DENV-3, was not different. 4. Discussion The current study compares the clinical characteristics of dengue between elderly patients and young adults. More cases of DHF, a longer length of ED and hospital stay, a higher severity of disease, and more comorbidities were discovered in the elderly. As for clinical presentations of dengue in the ED, isolated fever and atypical presentations were often present in the elderly. However, the 14day mortality rate was similar in both groups. Several previous investigations that have emphasized the differences in the clinical manifestations of dengue due to age were limited to comparisons of adults and children [15–17] or adolescents and adults [24]. Although there has been one report that old age is risk factor of DHF/DSS [25] and another report emphasized that a higher age at viral infection resulted in higher risk of clinical attack [26], the present study is the only report that has discussed the differences in clinical presentation between young adults and elderly patients. For various infections in elderly patients, atypical presentations and increased mortality and morbidity are well known [8–11]. However, for elderly patients with dengue fever, one study reported that a longer hospitalization but a similar mortality rate were observed in the elderly [19], whereas another investigation, which focused on the difference in DHF outcome between elderly and nonelderly adults, revealed a high fatality rate in the elderly adults [20]. It is possible that a similar outcome between our young adults and elderly patients may be due to a very limited proportion of DHF. In addition, skin rashes were less often noted in elderly patients in the ED. Such a finding is likely to be related to the earlier visits to the ED in the elderly, at 2.3 days after the onset of relevant symptoms, whereas young adults visited the ED later after symptom onset. Typically, adults with dengue develop febrile syndromes and severe headache, myalgia, arthralgia, retroorbital pain, and maculopapular rash; however, patients sometimes develop nonspecific symptoms, such as nausea, vomiting, cough, dizziness, and diarrhea [1]. Currently, ED overcrowding is a common issue in many hospitals in the United States and Taiwan [27,28]. Overcrowding at the ED is a common problem that creates a high-risk environment for medical errors, including contamination of blood culture sampling, delays in diagnosis, as well as inappropriate management, and may be related to poor patient outcomes [29,30]. Therefore, to assist the ED clinicians’ practice of using a “simple and convenient” rule, instead of nonspecific symptoms of dengue, the “typical presentation” of dengue was defined and used in the present study. In addition, the elderly had more blood cultures sampled and more empirical antimicrobial therapies prescribed, further supporting the practice
We interpreted our data in light of several limitations inherent in the study design. First, the clinical setting was an outbreak period because 72.6% of adults with suspected dengue were proved to have dengue. High diagnostic yield of our patients may indicate the presence of certain clinical characteristics that ED clinicians were familiar with these clinical clues for dengue disease. Therefore, our finding may not generalize to other areas of low incidence of dengue. Second, as a previous report in Taiwan [2], the major serotype of dengue virus in the study period is serotype one. There had been clinical reports suggestive of different clinical presentations in patients with dengue fever due to different serotypes of dengue virus [31]. Our findings cannot be generalized to other areas or periods. Finally, with respect to typical presentations of dengue, maculopapular rash usually developed after the febrile period. Although the time factor, such as the period between fever onset and ED arrival, was not included in the analyses, the major issue emphasized in our study was frequent episodes of isolated fever in the elderly. 6. Conclusions This study demonstrated that the clinical features of dengue in elderly patients and young adults varied in their initial presentations. Further investigation and education for ED clinicians to improve the recognition of atypical presentations of dengue in the elderly should be encouraged. References [1] Halstead SB. Dengue. Lancet 2007;370:1644–52. [2] Lin CC, Huang YH, Shu PY, Wu HS, Lin YS, Yeh TM, et al. Characteristic of dengue disease in Taiwan: 2002-2007. Am J Trop Med Hyg 2010;82:731–9. [3] Centers for Disease Control ROCT. Statistics of communicable diseases and surveillance report in Taiwan area, 2004. Taiwan: Centers for Disease Control. http://www.cdc.gov.tw (accessed 7 July 2012). [4] McCaig LFBC. National Hospital Ambulatory Medical Care Survey: 2003 emergency department summary: advance data from vital and health statistics: no. 358. Hyattsville, MD: National Center for Health, Statistics; 2005. [5] Grubeck-Loebenstein B, Wick G. The aging of the immune system. Adv Immunol 2002;80:243–84. [6] Opal SM, Girard TD, Ely EW. The immunopathogenesis of sepsis in elderly patients. Clin Infect Dis 2005;41(Suppl 7):S504–12. [7] Martin GS, Mannino DM, Moss M. The effect of age on the development and outcome of adult sepsis. Crit Care Med 2006;34:15–21. [8] Gavazzi G, Krause KH. Ageing and infection. Lancet Infect Dis 2002;2:659–66. [9] Chassagne P, Perol MB, Doucet J, Trivalle C, Menard JF, Manchon ND, et al. Is presentation of bacteremia in the elderly the same as in younger patients? Am J Med 1996;100:65–70. [10] Cooper GS, Shlaes DM, Salata RA. Intraabdominal infection: differences in presentation and outcome between younger patients and the elderly. Clin Infect Dis 1994;19:146–8. [11] Norman DC, Toledo SD. Infections in elderly persons. An altered clinical presentation. Clin Geriatr Med 1992;8:713–9. [12] Strange GR, Chen EH, Sanders AB. Use of emergency departments by elderly patients: projections from a multicenter data base. Ann Emerg Med 1992;21: 819–24. [13] Sikdar KC, Dowden J, Alaghehbandan R, MacDonald D, Peter P, Gadag V. Adverse drug reactions in elderly hospitalized patients: a 12-year population-based retrospective cohort study. Ann Pharmacother 2012;46:960–71. [14] Burke DS, Nisalak A, Johnson DE, Scott RM. A prospective study of dengue infections in Bangkok. Am J Trop Med Hyg 1988;38:172–80. [15] Trung DT, Thao le TT, Dung NM, Ngoc TV, Hien TT, Chau NV, et al. Clinical features of dengue in a large Vietnamese cohort: intrinsically lower platelet counts and greater risk for bleeding in adults than children. PLoS Negl Trop Dis 2012;6: e1679. [16] Kittigul L, Pitakarnjanakul P, Sujirarat D, Siripanichgon K. The differences of clinical manifestations and laboratory findings in children and adults with dengue virus infection. J Clin Virol 2007;39:76–81. [17] Hammond SN, Balmaseda A, Perez L, Tellez Y, Saborio SI, Mercado JC, et al. Differences in dengue severity in infants, children, and adults in a 3-year hospitalbased study in Nicaragua. Am J Trop Med Hyg 2005;73:1063–70.
C.-C. Lee et al. / American Journal of Emergency Medicine 31 (2013) 783–787 [18] Hanafusa S, Chanyasanha C, Sujirarat D, Khuankhunsathid I, Yaguchi A, Suzuki T. Clinical features and differences between child and adult dengue infections in Rayong province, southeast Thailand. Southeast Asian J Trop Med Public Health 2008;39:252–9. [19] Garcia-Rivera EJ, Rigau-Perez JG. Dengue severity in the elderly in Puerto Rico. Rev Panam Salud Publica 2003;13:362–8. [20] Lee IK, Liu JW, Yang KD. Clinical and laboratory characteristics and risk factors for fatality in elderly patients with dengue hemorrhagic fever. Am J Trop Med Hyg 2008;79:149–53. [21] Schellevis FG, van der Velden J, van de Lisdonk E, van Eijk JT, van Weel C. Comorbidity of chronic diseases in general practice. J Clin Epidemiol 1993;46: 469–73. [22] WHO. Dengue hemorrhage fever:diagnosis, treatment, prevention and control. 2nd ed. Geneva: World Health Organization; 1997. [23] Le Gall JR, Lemeshow S, Saulnier F. A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter study. JAMA 1993;270: 2957–63. [24] Tantawichien T. Dengue fever and dengue haemorrhagic fever in adolescents and adults. Paediatr Int Child Health 2012;32(Suppl 1):22–7.
787
[25] Lee MS, Hwang KP, Chen TC, Lu PL, Chen TP. Clinical characteristics of dengue and dengue hemorrhagic fever in a medical center of southern Taiwan during the 2002 epidemic. J Microbiol Immunol Infect 2006;39:121–9. [26] Thai KT, Nishiura H, Hoang PL, Tran NT, Phan GT, Le HQ, et al. Age-specificity of clinical dengue during primary and secondary infections. PLoS Negl Trop Dis 2011;5:e1180. [27] Shih FY, Ma MH, Chen SC, Wang HP, Fang CC, Shyu RS, et al. ED overcrowding in Taiwan: facts and strategies. Am J Emerg Med 1999;17:198–202. [28] Trzeciak S, Rivers EP. Emergency department overcrowding in the United States: an emerging threat to patient safety and public health. Emerg Med J 2003;20: 402–5. [29] Cowan RM, Trzeciak S. Clinical review: emergency department overcrowding and the potential impact on the critically ill. Crit Care 2005;9:291–5. [30] Lee CC, Lee NY, Chuang MC, Chen PL, Chang CM, Ko WC. The impact of overcrowding on the bacterial contamination of blood cultures in the ED. Am J Emerg Med 2012;30:839–45. [31] Tsai JJ, Chan KS, Chang JS, Chang K, Lin CC, Huang JH, et al. Effect of serotypes on clinical manifestations of dengue fever in adults. J Microbiol Immunol Infect 2009;42:471–8.
Contents lists available at SciVerse ScienceDirect
American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajem
Original Contribution
Atypical presentations of dengue disease in the elderly visiting the ED Ching-Chi Lee MD a, Hsiang-Chin Hsu MD b, Chia-Ming Chang MD a, Ming-Yuan Hong MD b, Wen-Chien Ko MD a, c,⁎ a b c
Department of Internal Medicine, National Cheng Kung University Hospital, Tainan 704, Taiwan Department of Emergency Medicine, National Cheng Kung University Hospital, Tainan 704, Taiwan Department of Medicine, National Cheng Kung University Medical College, Tainan 704, Taiwan
a r t i c l e
i n f o
Article history: Received 30 October 2012 Received in revised form 12 January 2013 Accepted 13 January 2013
a b s t r a c t Objective: The objective was to compare the clinical characteristics of elderly and young adult patients with dengue in the emergency department (ED). Methods: Demographic characteristics, clinical presentation, disease severity, laboratory characteristics, and outcomes were analyzed prospectively as a case-control study. Results: Of the 193 adults with serologically confirmed dengue disease in 2007, 31 (16.1%) were elderly patients (aged ≥65) and 162 were young adults (aged b 65). More dengue hemorrhagic fever (12.9% vs 2.5%, P = .02), a longer ED stay (13.3 vs 8.6 hours, P = .004), a longer hospital stay (7.4 vs 3.4 days, P b .001), a higher Simplified Acute Physiology Score II in the ED (29.7 vs 17.4, P b .001), and a higher rate of at least 1 comorbidity (61.8 vs 22.8%, P b .001) were found in the elderly. However, the length of the intensive care unit stay (elderly 0.7 vs young adults 0.3 day, P = .47) and the 14-day mortality rate (0% vs 0.6%, P = 1.00) were similar. Of note, in terms of clinical presentations of dengue in the ED, there were more elderly patients with isolated fever (41.9% vs 17.9%, P = .003) and fewer with typical presentation (41.9% vs 75.9%, P = b .001) than there were young adults. Conclusions: The present study found a higher number of atypical presentations, a longer hospitalization, and a higher degree of clinical illness in elderly patients with dengue. © 2013 Elsevier Inc. All rights reserved.
1. Introduction Dengue is an important arboviral disease of humans; and it has emerged as a global public health problem, especially in tropical and subtropical areas [1]. The dengue case burden and the number of countries reporting outbreaks have increased 10-fold in the last 30 years. In southern Taiwan, several outbreaks of dengue fever have been reported in recent years [1,2]. In a previous study conducted between 2002 and 2007, a common pattern of dengue transmission was noted. Every year, the epidemic was initiated by the importation of the virus from abroad in the summer, spread in southern Taiwan, and came to an end of the epidemic in the winter. Most of the affected patients were adults, mainly those aged between 50 and 54 [2]. In 2007, 2179 symptomatic cases of dengue were reported in Taiwan, resulting in an incidence of 0.0095%; and most (1888, 86.6%) patients were adults [3].
⁎ Corresponding author. Department of Internal Medicine, National Cheng Kung University Hospital, Tainan 70403, Taiwan. Tel.: +886 6 2353535x3596; fax: +886 6 2752038. E-mail address: [email protected] (W.-C. Ko). 0735-6757/$ – see front matter © 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.ajem.2013.01.011
Dengue fever is characterized by a sudden onset of high-grade fever and often associated with nonspecific constitutional symptoms [1]. Fever has been found to be the third leading reason for visiting the emergency department (ED) and the chief concern in 5% of all ED visits [4]. Therefore, for adult visitors, dengue fever should be put into the list of differential diagnosis of febrile illness. However, aging is associated with significant changes in the adaptive humoral and cellmediated immunity [5]. Poor cytokine responses to sepsis have been discovered in the elderly [6], which lead to atypical clinical presentation and the well-recognized increase in mortality among the elderly due to various infections [7–11]. Moreover, the increased prevalence of chronic, degenerative diseases; frequent prescription of immunosuppressive or antineoplastic drugs in the elderly; and the susceptibility of the elderly to frequent exacerbations of preexisting conditions result in the elderly becoming frequent visitors of the ED [12,13]. Because primary dengue infections are observed in young children and travelers immunologically naive to dengue virus exhibit the same symptoms of dengue infection as the initial infection observed in children, symptomatic dengue generally occurs during secondary dengue infections in adults and city residents [1,14]. This conclusion was compatible with a study in Taiwan [2], in which most cases of symptomatic dengue were adults. Several investigations have
784
C.-C. Lee et al. / American Journal of Emergency Medicine 31 (2013) 783–787
discussed the differences of clinical manifestations of dengue diseases between children and adults [15–18]. However, there were few investigations focusing on dengue diseases in the elderly [19,20]. In the English literature, no study addressing their presentation in the ED has been found. Thus, we conducted this study to describe the clinical presentation and the outcome of dengue in elderly patients by a comparison with dengue infections in young adults in the ED. 2. Materials and methods 2.1. Study design and population A prospective case-control study was conducted between January 2007 and December 2007 at a medical center of approximately 1000 beds in southern Taiwan; and 64,345 annual visits to the ED were recorded during the study period. The local institutional review board approved this study. The analysis included the records of adults who visited the ED during the study period and had suspected dengue as determined by ED clinicians. Demographic information and clinical characteristics, severity scores, comorbidities, and laboratory data of adults suspected to have dengue were prospectively collected in a predetermined record form immediately after their arrival at the ED. However, the study excluded those with a serologically negative result of dengue disease. For the eligible adults, elderly patients (≧ 65 years) were regarded as the case group; and young adults (b65 years) were regarded as control patients. The medical records were reviewed for hospital course and clinical outcome by 2 of the authors, an ED clinician and an internist. If any discrepancy was found, the medical records were inspected by these 2 authors together. The primary outcome was the overall mortality in the 14 days immediately after visiting the ED. If the patients were discharged within 14 days after ED arrival and not followed up at our hospital, their outcome information was obtained by a telephone call. The patients not reached by the telephone were excluded. 2.2. Dengue reporting system and diagnosis According to the guideline of the Taiwan Centers for Disease Control Taiwan, dengue is a category II notifiable infectious disease; and physicians are obliged to report any suspected dengue cases to the health department within 24 hours of clinical diagnosis. All sera were tested in the Kaohsiung laboratory. Routine diagnosis includes molecular analysis by real-time transcriptase-polymerase chain reaction, serologic testing using captured immunoglobulin (Ig) M/ IgG enzyme-linked immunosorbent assay (ELISA), and viral isolation by cell culture. Dengue viral infection is defined as one of the following: a positive IgM antibody detection by ELISA, a positive real-time transcriptase-polymerase chain reaction for dengue virus, or at least a 4-fold increase in dengue-specific hemagglutination inhibition titers in convalescent serum compared with those in acute-phase serum [2,3]. However, as previously described [3], patients diagnosed by a dengue-specific IgM ELISA in the acute phase must also be concomitantly serologically negative for the specific IgM for Japanese encephalitis virus. 2.3. Definitions Elderly patients were defined as patients 65 years or older, whereas those aged less than 65 years were considered as young adults. Underlying malignancies included hematological malignancies or solid tumors, and the definitions of comorbidities were previously described [21]. The hemorrhage phenomena of dengue included a positive tourniquet test result, petechiae, ecchymosis, epistaxis, gingival bleeding, gastrointestinal bleeding, hematuria, hypermenorrhea, or vaginal bleeding, whereas conscious disturbance, intracranial hemorrhage, vessel occlusion, or cerebral anoxia was considered to be
its neurologic signs. The typical presentation of dengue diseases in the adults included fever plus at least 1 of the following: bone pain, myalgia, arthralgia, retroorbital pain, headache, and maculopapular rash [1]. In patients with a serological confirmation of dengue, a diagnosis of dengue hemorrhage fever (DHF) was made based on World Health Organization criteria, that is, the presence of fever, hemorrhagic phenomena, thrombocytopenia, and the existence of hemoconcentration (≥20% rise in hematocrit above the baseline value or the presence of pleural effusion or ascites) [22]. Moreover, the severity of DHF was categorized into grades I to IV according to the World Health Organization criteria: DHF grade III was defined as circulatory failure manifested by a rapid and weak pulse, with narrowing pulse pressure (less than 20 mm Hg); DHF grade IV was defined as profound shock, with undetectable pulse or blood pressures; and DHF grades III and IV were collectively grouped as dengue shock syndrome (DDS). The severity of dengue was also graded by a Simplified Acute Physiology Score II (SAPS II) [23]. 2.4. Data analysis Statistical analyses were performed using the Statistical Package for the Social Sciences for Windows, Version 15.0 (SPSS, Chicago, IL). Continuous variables were expressed as the means ± standard deviations (SDs) and compared using Student t test. Categorical variables, expressed as numbers and percentages, were compared using a χ 2 test or Fisher exact test. A P value of less than .05 was considered significant. 3. Results 3.1. Demographics and clinical characteristics of all dengue patients During the 1-year period, of the total 64,345 ED visits, 266 adults had suspected dengue; and their sera were examined by the Taiwan Centers for Disease Control laboratory. A total of 193 adults had a dengue virus infection, whereas 58 were not infected with dengue virus. The results of 15 patients were undetermined because of a lack of convalescent serum. Moreover, no patients were excluded because of the loss of follow-up within 14 days after ED arrival. Of the 193 eligible adults, elderly patients accounted for 16.1% (31 patients); and 91 patients (47.2%) were male, as shown in Fig. Most patients (179, 92.7%) visited the ED from the community, but 14 (7.3%) were transferred from other hospitals. Only one (0.5%) had been hospitalized within 28 days before the ED visit. Common comorbidities included hypertension (36 patients, 18.7%), diabetes mellitus (22, 11.4%), coronary artery disease (10, 5.2%), chronic renal insufficiency (5, 2.6%), malignancy (4, 2.1%), chronic obstructive pulmonary disease (4, 2.1%), liver cirrhosis (3, 1.6%), and old stroke (3, 1.6%); and no comorbidity was identified in 129 (66.8%) of the patients. Most patients (136, 70.5%) were admitted to general wards, 4 (2.1%) were admitted to intensive care units (ICUs), and 57 (29.5%) were discharged from the ED. Eight (4.1%) patients evolved into DHF at discharge, whereas 1 patient (0.5%) with DDS died. No patients died during the ED stay or within 14 days of their ED arrival. Therefore, the overall 14-day mortality rate was 0.5%. 3.2. Clinical characteristics and presentation in the case and control patients Clinical variables of the elderly patients and young adults in the ED, including demographics, severity, comorbidities, and laboratory data, are compared in Table 1. Longer ED stay, more blood cultures sampled, more antibiotics prescribed, more admission through the ED, higher SAPS scores, and more comorbidities, including hypertension, diabetes mellitus, malignancy, and coronary artery diseases, were present in the elderly, whereas no comorbidity was noted more
C.-C. Lee et al. / American Journal of Emergency Medicine 31 (2013) 783–787
785
Fig. Patient flowchart.
often in young adults. With respect to laboratory data, fewer cases of leukopenia or normal serum levels of C-reactive protein were observed in the elderly, whereas fewer young adults exhibited elevated levels of blood urea nitrogen (N20 mg/dL) or serum creatinine (N 1.5 mg/dL).
Table 1 Clinical characteristics and laboratory data of elderly patients (aged ≥65) and young adults (aged b65) with dengue virus infection in an ED Clinical characters
Male Comorbidity None ≥1 Comorbidity ≥2 Comorbidities Hypertension Diabetes mellitus Coronary artery diseases Chronic renal insufficiency Chronic obstructive pulmonary disease Liver cirrhosis Malignancy Old stroke Events in the ED Length of stay (h), mean ± SD Blood culture sampling Antimicrobial agents prescription Severity of illness in the ED SAPS II, mean ± SD Ward admission through the ED ICU admission through the ED Laboratory data in the ED Leukocyte b4000/mm3 Bandemia (≥10% bands) Hemoglobulin b10 mg/dL Platelet b100,000/mm3 C-reactive protein b7 mg/Lb Blood urea nitrogen N20 mg/dL Serum creatinine N1.5 mg/dL ALT or AST N3×c
Patient number (%)a
P values
Young patients, n = 162
Elderly patients, n = 31
76 (46.9)
15 (48.4)
1.00
120 (74.1) 37 (22.8) 14 (8.6) 25 (15.4) 14 (8.6) 6 (3.7) 4 (2.5) 3 (1.9)
9 (29.0) 19 (61.8) 10 (32.3) 11 (35.3) 8 (25.8) 4 (12.9) 1 (3.2) 1 (3.2)
b.001 b.001 .001 .009 .01 .05 .59 .51
2 (1.2) 1 (0.6) 1 (0.6)
1 (3.2) 3 (9.7) 2 (6.50)
.41 .01 .07
8.6 ± 8.3 119 (73.5) 35 (21.6)
13.3 ± 8.7 30 (96.8) 19 (61.3)
.004 .005 b.001
17.4 ± 6.7 107 (66.0) 2 (1.2)
29.7 ± 10.7 29 (93.5) 2 (6.5)
b.001 .002 .12
122 (75.3) 46 (28.4) 2 (1.9) 76 (46.9) 77 (47.5) 5/151 (3.3) 6/154 (3.9) 55 (34.0)
17 (54.8) 12 (38.7) 3 (6.5) 18 (58.1) 7 (22.6) 6 (19.4) 5 (16.1) 12 (38.7)
.02 .25 .18 .26 .01 .004 .02 .61
ALT, alanine aminotransferase; AST; aspartate aminotransferase. a Data are expressed as case numbers (percentages), unless indicated specifically. b Within the reference range. c More than 3 times the upper limit of the reference range.
The differences in clinical presentations between elderly patients and young adults are listed in Table 2. A shorter period between symptom onset and ED arrival, more patients with isolated fever, and fewer patients with typical presentations of dengue were observed among elderly patients during their ED stay. With respect to the clinical symptoms/signs between the 2 groups, fewer cases with maculopapular rash were observed in the elderly. 3.3. Clinical outcome, hospital stay, and serotype of dengue in elderly patients and young adults More patients with DHF and a longer hospital stay were observed among the elderly; but the 14-day crude mortality rate and the length of ICU stay were similar in the 2 groups, as shown in Table 3.
Table 2 Clinical presentation and duration of dengue in elderly patients (aged ≥65) and young adults (aged b65) in an ED Clinical variable
Patient number (%)a Young patients, n = 162
The period between symptoms 3.9 ± 2.4 onset and ED arrival, mean ± SD Symptom/signs of dengue during the ED stay Isolated fever 29 (17.9) 123 (75.9) Typical presentations of dengueb Detailed symptom/signs Fever 160 (98.8) Maculopapular rash 60 (37.5) Headache 50 (30.9) Myalgia 41 (25.3) General malaise 38 (23.5) Bone pain 36 (22.2) Hemorrhagec 34 (21.0) Retroorbital pain 7 (4.3) Arthralgia 6 (3.7) d Neurologic abnormality 1 (0.6) a
P values
Elderly patients, n = 31 2.3 ± 1.8
.001
13 (41.9) 13 (41.9)
.003 b.001
29 (93.5) 2 (6.5) 7 (22.6) 6 (19.4) 8 (25.8) 4 (12.9) 6 (19.4) 0 (0) 1 (3.2) 1 (3.2)
.12 .001 .35 .48 .78 .24 1.00 .60 1.00 .30
Data are expressed as case numbers (percentages), unless indicated specifically. Fever plus at least 1 of following symptoms: bone pain, myalgia, arthralgia, retroorbital pain, headache, and maculopapular rash. c Includes positive tourniquet test result, petechiae, ecchymosis, epistaxis, gingival bleeding, gastrointestinal bleeding, hematuria, hypermenorrhea, or vaginal bleeding. d Includes consciousness disturbance, intracranial hemorrhage, vessel occlusion, or cerebral anoxia. b
786
C.-C. Lee et al. / American Journal of Emergency Medicine 31 (2013) 783–787
Table 3 Clinical outcome, serotype, and hospitalization of dengue in elderly patients (aged ≥65) and young adults (aged b65) in an ED Clinical variables
Patient number (%) Young patients, n = 162
Final diagnosis at discharge DHF 4 (2.5) DSS 1 (0.6) Serotype of dengue a DENV-1 133 (82.1) DENV-3 29 (17.9) Duration of hospitalization (h), mean ± SD Length of hospital stay (d) 3.4 ± 4.0 Length of ICU stay (d) 0.3 ± 3.0 14-d crude mortality rate 1 (0.6)
that nonspecific febrile presentations in the elderly render diagnosis by ED clinicians difficult with respect to differentiation between dengue and bacterial infections.
P values
5. Limitations
The elderly, n = 31 4 (12.9) 0 (0)
0.02 1.00 0.31
23 (74.2) 8 (25.8) 7.4 ± 5.8 0.7 ± 2.8 0 (0)
b0.001 0.47 1.00
Data are expressed as case numbers (percentages), unless indicated specifically. a DENV indicates dengue virus.
Moreover, the serotype distribution of dengue virus, DENV-1 or DENV-3, was not different. 4. Discussion The current study compares the clinical characteristics of dengue between elderly patients and young adults. More cases of DHF, a longer length of ED and hospital stay, a higher severity of disease, and more comorbidities were discovered in the elderly. As for clinical presentations of dengue in the ED, isolated fever and atypical presentations were often present in the elderly. However, the 14day mortality rate was similar in both groups. Several previous investigations that have emphasized the differences in the clinical manifestations of dengue due to age were limited to comparisons of adults and children [15–17] or adolescents and adults [24]. Although there has been one report that old age is risk factor of DHF/DSS [25] and another report emphasized that a higher age at viral infection resulted in higher risk of clinical attack [26], the present study is the only report that has discussed the differences in clinical presentation between young adults and elderly patients. For various infections in elderly patients, atypical presentations and increased mortality and morbidity are well known [8–11]. However, for elderly patients with dengue fever, one study reported that a longer hospitalization but a similar mortality rate were observed in the elderly [19], whereas another investigation, which focused on the difference in DHF outcome between elderly and nonelderly adults, revealed a high fatality rate in the elderly adults [20]. It is possible that a similar outcome between our young adults and elderly patients may be due to a very limited proportion of DHF. In addition, skin rashes were less often noted in elderly patients in the ED. Such a finding is likely to be related to the earlier visits to the ED in the elderly, at 2.3 days after the onset of relevant symptoms, whereas young adults visited the ED later after symptom onset. Typically, adults with dengue develop febrile syndromes and severe headache, myalgia, arthralgia, retroorbital pain, and maculopapular rash; however, patients sometimes develop nonspecific symptoms, such as nausea, vomiting, cough, dizziness, and diarrhea [1]. Currently, ED overcrowding is a common issue in many hospitals in the United States and Taiwan [27,28]. Overcrowding at the ED is a common problem that creates a high-risk environment for medical errors, including contamination of blood culture sampling, delays in diagnosis, as well as inappropriate management, and may be related to poor patient outcomes [29,30]. Therefore, to assist the ED clinicians’ practice of using a “simple and convenient” rule, instead of nonspecific symptoms of dengue, the “typical presentation” of dengue was defined and used in the present study. In addition, the elderly had more blood cultures sampled and more empirical antimicrobial therapies prescribed, further supporting the practice
We interpreted our data in light of several limitations inherent in the study design. First, the clinical setting was an outbreak period because 72.6% of adults with suspected dengue were proved to have dengue. High diagnostic yield of our patients may indicate the presence of certain clinical characteristics that ED clinicians were familiar with these clinical clues for dengue disease. Therefore, our finding may not generalize to other areas of low incidence of dengue. Second, as a previous report in Taiwan [2], the major serotype of dengue virus in the study period is serotype one. There had been clinical reports suggestive of different clinical presentations in patients with dengue fever due to different serotypes of dengue virus [31]. Our findings cannot be generalized to other areas or periods. Finally, with respect to typical presentations of dengue, maculopapular rash usually developed after the febrile period. Although the time factor, such as the period between fever onset and ED arrival, was not included in the analyses, the major issue emphasized in our study was frequent episodes of isolated fever in the elderly. 6. Conclusions This study demonstrated that the clinical features of dengue in elderly patients and young adults varied in their initial presentations. Further investigation and education for ED clinicians to improve the recognition of atypical presentations of dengue in the elderly should be encouraged. References [1] Halstead SB. Dengue. Lancet 2007;370:1644–52. [2] Lin CC, Huang YH, Shu PY, Wu HS, Lin YS, Yeh TM, et al. Characteristic of dengue disease in Taiwan: 2002-2007. Am J Trop Med Hyg 2010;82:731–9. [3] Centers for Disease Control ROCT. Statistics of communicable diseases and surveillance report in Taiwan area, 2004. Taiwan: Centers for Disease Control. http://www.cdc.gov.tw (accessed 7 July 2012). [4] McCaig LFBC. National Hospital Ambulatory Medical Care Survey: 2003 emergency department summary: advance data from vital and health statistics: no. 358. Hyattsville, MD: National Center for Health, Statistics; 2005. [5] Grubeck-Loebenstein B, Wick G. The aging of the immune system. Adv Immunol 2002;80:243–84. [6] Opal SM, Girard TD, Ely EW. The immunopathogenesis of sepsis in elderly patients. Clin Infect Dis 2005;41(Suppl 7):S504–12. [7] Martin GS, Mannino DM, Moss M. The effect of age on the development and outcome of adult sepsis. Crit Care Med 2006;34:15–21. [8] Gavazzi G, Krause KH. Ageing and infection. Lancet Infect Dis 2002;2:659–66. [9] Chassagne P, Perol MB, Doucet J, Trivalle C, Menard JF, Manchon ND, et al. Is presentation of bacteremia in the elderly the same as in younger patients? Am J Med 1996;100:65–70. [10] Cooper GS, Shlaes DM, Salata RA. Intraabdominal infection: differences in presentation and outcome between younger patients and the elderly. Clin Infect Dis 1994;19:146–8. [11] Norman DC, Toledo SD. Infections in elderly persons. An altered clinical presentation. Clin Geriatr Med 1992;8:713–9. [12] Strange GR, Chen EH, Sanders AB. Use of emergency departments by elderly patients: projections from a multicenter data base. Ann Emerg Med 1992;21: 819–24. [13] Sikdar KC, Dowden J, Alaghehbandan R, MacDonald D, Peter P, Gadag V. Adverse drug reactions in elderly hospitalized patients: a 12-year population-based retrospective cohort study. Ann Pharmacother 2012;46:960–71. [14] Burke DS, Nisalak A, Johnson DE, Scott RM. A prospective study of dengue infections in Bangkok. Am J Trop Med Hyg 1988;38:172–80. [15] Trung DT, Thao le TT, Dung NM, Ngoc TV, Hien TT, Chau NV, et al. Clinical features of dengue in a large Vietnamese cohort: intrinsically lower platelet counts and greater risk for bleeding in adults than children. PLoS Negl Trop Dis 2012;6: e1679. [16] Kittigul L, Pitakarnjanakul P, Sujirarat D, Siripanichgon K. The differences of clinical manifestations and laboratory findings in children and adults with dengue virus infection. J Clin Virol 2007;39:76–81. [17] Hammond SN, Balmaseda A, Perez L, Tellez Y, Saborio SI, Mercado JC, et al. Differences in dengue severity in infants, children, and adults in a 3-year hospitalbased study in Nicaragua. Am J Trop Med Hyg 2005;73:1063–70.
C.-C. Lee et al. / American Journal of Emergency Medicine 31 (2013) 783–787 [18] Hanafusa S, Chanyasanha C, Sujirarat D, Khuankhunsathid I, Yaguchi A, Suzuki T. Clinical features and differences between child and adult dengue infections in Rayong province, southeast Thailand. Southeast Asian J Trop Med Public Health 2008;39:252–9. [19] Garcia-Rivera EJ, Rigau-Perez JG. Dengue severity in the elderly in Puerto Rico. Rev Panam Salud Publica 2003;13:362–8. [20] Lee IK, Liu JW, Yang KD. Clinical and laboratory characteristics and risk factors for fatality in elderly patients with dengue hemorrhagic fever. Am J Trop Med Hyg 2008;79:149–53. [21] Schellevis FG, van der Velden J, van de Lisdonk E, van Eijk JT, van Weel C. Comorbidity of chronic diseases in general practice. J Clin Epidemiol 1993;46: 469–73. [22] WHO. Dengue hemorrhage fever:diagnosis, treatment, prevention and control. 2nd ed. Geneva: World Health Organization; 1997. [23] Le Gall JR, Lemeshow S, Saulnier F. A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter study. JAMA 1993;270: 2957–63. [24] Tantawichien T. Dengue fever and dengue haemorrhagic fever in adolescents and adults. Paediatr Int Child Health 2012;32(Suppl 1):22–7.
787
[25] Lee MS, Hwang KP, Chen TC, Lu PL, Chen TP. Clinical characteristics of dengue and dengue hemorrhagic fever in a medical center of southern Taiwan during the 2002 epidemic. J Microbiol Immunol Infect 2006;39:121–9. [26] Thai KT, Nishiura H, Hoang PL, Tran NT, Phan GT, Le HQ, et al. Age-specificity of clinical dengue during primary and secondary infections. PLoS Negl Trop Dis 2011;5:e1180. [27] Shih FY, Ma MH, Chen SC, Wang HP, Fang CC, Shyu RS, et al. ED overcrowding in Taiwan: facts and strategies. Am J Emerg Med 1999;17:198–202. [28] Trzeciak S, Rivers EP. Emergency department overcrowding in the United States: an emerging threat to patient safety and public health. Emerg Med J 2003;20: 402–5. [29] Cowan RM, Trzeciak S. Clinical review: emergency department overcrowding and the potential impact on the critically ill. Crit Care 2005;9:291–5. [30] Lee CC, Lee NY, Chuang MC, Chen PL, Chang CM, Ko WC. The impact of overcrowding on the bacterial contamination of blood cultures in the ED. Am J Emerg Med 2012;30:839–45. [31] Tsai JJ, Chan KS, Chang JS, Chang K, Lin CC, Huang JH, et al. Effect of serotypes on clinical manifestations of dengue fever in adults. J Microbiol Immunol Infect 2009;42:471–8.