b r a z j i n f e c t d i s .

2 0 1 3;1 7(1):27–31

The Brazilian Journal of

INFECTIOUS DISEASES
www.elsevier.com/locate/bjid

Original article

Comparison of clinical and laboratory characteristics

between children and adults with dengue

Luiz José de Souza a,b,c,∗ , Laís Bastos Pessanha a,b,c , Laura Carvalho Mansur a,b,c ,
Luiza Assed de Souza a,b,c , Mariana Barbosa Tâmega Ribeiro a,b,c ,
Monique do Vale da Silveira a,b,c , João Tadeu Damian Souto Filho c
a Reference Center for Dengue, Campos dos Goytacazes, Rio de Janeiro, RJ, Brazil
b Hospital dos Plantadores de Cana, Campos dos Goytacazes, Rio de Janeiro, RJ, Brazil
c Faculdade de Medicina de Campos, Campos dos Goytacazes, Rio de Janeiro, RJ, Brazil

a r t i c l e i n f o a b s t r a c t

Article history: Over the past several years, the epidemiological profile of dengue has been changing
Received 10 July 2012 progressively and is currently characterized by an increase in the number of cases in
Accepted 19 August 2012 children under 15 years of age. This study was aimed at comparing the clinical and lab-
Available online 11 January 2013 oratory features between adults and children with dengue; therefore, we performed a
cross-sectional analysis of 5686 individuals with laboratory-confirmed dengue who sought
Keywords: treatment at a healthcare facility in Rio de Janeiro, Brazil from 2010 to 2011. A multi-
Dengue variate analysis indicated that myalgia (OR = 2.58; CI 95% = 2.08–3.18), retro-orbital pain
Dengue fever (OR = 1.36; CI 95% = 1.15–1.62), nausea (OR = 1.92; CI 95% = 1.60–2.30), and arthralgia (OR = 3.64;
Clinical spectra CI 95% = 2.72–4.89) were the most frequent clinical symptoms in adults, whereas vomiting
Epidemiology (OR = 0.52; CI 95% = 0.43–0.61) and skin rash (OR = 0.46; CI 95% = 0.25–0.85) were the most
prevalent symptoms in children. Adults exhibited a higher hemoconcentration (OR = 3.04;
CI 95% = 2.53–3.65), thrombocytopenia (OR = 2.17; CI 95% = 1.80–2.60), increased erythro-
cyte sedimentation rate (OR = 1.81; CI 95% = 1.53–2.14), and increased ALT (OR = 3.13; CI
95% = 2.44–4.02) than did children. In addition, adults exhibited a higher frequency of the
severe forms of the disease (OR = 1.74; CI 95% = 1.12–2.72) and hospitalization (OR = 2.21; CI
95% = 1.59–3.06) relative to children. Based on these results, this study demonstrated signif-
icant differences in the clinical and laboratory presentations and disease severity between
adults and children affected by dengue.
© 2013 Elsevier Editora Ltda. All rights reserved.

Flaviviridae family and the Flavivirus genus and has four

Introduction serotypes. Dengue is the most common arthropod-borne
viral disease and is one of the most significant diseases
Dengue is an acute febrile disease. The etiologic agent of because it is associated with high rates of morbidity and
dengue is the dengue virus (DENV), which belongs to the mortality.1–3

∗
Corresponding author at: Av. Alberto Torres, 205, Centro, Campos dos Goytacazes, RJ, 28030-582, Brazil.
E-mail addresses: luizjosedes@gmail.com, sbcmrj@gmail.com (L.J. de Souza).
1413-8670/$ – see front matter © 2013 Elsevier Editora Ltda. All rights reserved.
http://dx.doi.org/10.1016/j.bjid.2012.08.020
28 b r a z j i n f e c t d i s . 2 0 1 3;1 7(1):27–31

This disease currently represents a major public health Following the current WHO guidelines, suspected cases
issue, especially in tropical and subtropical countries, where were classified as severe and nonsevere. Severe cases were
environmental conditions enable the development and prolif- defined as the following: severe plasma extravasation that led
eration of the mosquito Aedes aegypti, which is the main vector to dengue shock syndrome (DSS) or liquid accumulation with
of DENV.4,5 respiratory discomfort; severe hemorrhage that was evaluated
Dengue epidemiology has been changing in Brazil, with a by the physician; severe commitment of tissues, such as ≥1000
shift being observed in the age group of the affected popula- aminotransferases; and commitment of the central nervous
tion. Currently, at least 25% of notified dengue cases occur in system, heart, and other organs.11
children who are 15 years of age or younger.6,7
The clinical manifestations of dengue vary from a non-
Laboratory methods
specific febrile disease to a more severe form with bleeding,
thrombocytopenia, and plasma extravasation, which can
In the first medical visit, individuals who presented with
result in death. In children, dengue can be asymptomatic
the clinical and epidemiological indications for dengue were
or polysymptomatic, which may hinder the differential
referred to the laboratory for peripheral blood collection and
diagnosis.8,9
the following laboratory tests: complete blood count (CBC),
An early clinical diagnosis of dengue hemorrhagic fever
erythrocyte sedimentation rate (ESR), aspartate aminotrans-
is difficult because the criteria that were established by the
ferase (AST), and alanine aminotransferase (ALT). To minimize
World Health Organization (WHO) may be present only in the
bias, the tests were performed at a laboratory that was associ-
initial phase of the acute form of the disease.4 Thus, laboratory
ated with the CRD. The hematocrit (Ht) parameters that were
tests combined with a guided clinical examination, especially
used to evaluate hemoconcentration included an adult man
in endemic areas, are crucial to confirm a diagnosis, identify,
with a Ht > 45%, an adult woman with a Ht > 40%, and children
and prevent outbreaks and provide early treatment for the
with a Ht > 38%. Leukopenia was defined as a leukocyte count
severe forms of the disease and complications.9
of <4000/␮L, and thrombocytopenia was defined as a platelet
There are few reports on the clinical and laboratory differ-
count of <150,000/␮L. An ESR result >20 mm/h, an AST result
ences in children (0–14 years of age) and adults with dengue.10
>50 U/L, and an ALT result >50 U/L were considered to be high.
Thus, this study aimed to determine the differences among
All of the dengue cases were confirmed in the laboratory
individuals with dengue who were admitted to the Reference
by the following: (1) serological tests using an immunoenzyme
Center for Dengue (Centro de Referência da Dengue, CRD) in
assay (PANBIO® Indirect ELISA for anti-DENV IgM) for the cap-
Campos dos Goytacazes, Rio de Janeiro.
ture of anti-dengue IgM with blood that was collected between
days 5–10 after the first fever symptoms; and (2) detection
of the NS1 antigen of DENV using an immunoenzyme assay
Material and methods (BIORAD® Platelia Dengue NS1 AssayTM ) with samples that
were collected between days 1–4 after the first fever symp-
Study design and subjects toms.

This study was a cross-sectional, retrospective analysis that

was conducted at the Reference Center for Dengue (Centro Treatment
de Referência da Dengue, CRD), which is located at Campos
dos Goytacazes city, Rio de Janeiro, Brazil. The medical records Severe cases were admitted to the CRD support hospital (Hos-
of all of the individuals who were admitted to the CRD from pital dos Plantadores de Cana) to receive proper clinical and
January 2010 to September 2011 were evaluated. The CRD Eval- laboratory treatment. The nonsevere cases with no alarming
uation Protocol was used as a tool for data collection, which clinical signs were admitted to the CRD ambulatory clinic. The
consists of a questionnaire on the epidemiological, clinical, nonsevere cases who presented with alarming clinical signs
and laboratory data that were collected during the first med- were treated individually, and clinical support was provided
ical visit. Individuals with a dengue diagnosis that was based at either the hospital or ambulatory clinic according to the
on clinical and serological criteria were included in the study. severity of each case.

Definitions Statistical analysis

Suspected cases of dengue were defined as individuals who A statistical analysis was performed to evaluate the differ-
were living in or traveled to dengue-endemic areas within the ences in the clinical and laboratory manifestations among
previous 15 days and who presented with fever combined with individuals with dengue from the two age groups: adults and
at least two of the following symptoms: nausea, vomiting, skin children. For the univariate analysis, a chi-square analysis or
rash, myalgia, arthralgia, positive tourniquet test, leucopenia, Fisher’s exact test were performed for the categorical vari-
and any other warning sign. The latter symptoms of suspected ables. Variables with a p-value lower than 0.10 were used for
cases included the following: pain or abdominal discomfort, a multivariate logistic regression model. p-Values lower than
persistent vomiting, serositis, mucosal bleeding, lethargy, agi- 0.05 were considered to be significant. A data analysis was
tation, hepatomegaly >2 cm, and an increase in the hematocrit performed with the software program SPSS 13.0 for Windows
with a simultaneous decrease in platelets.11 (Statistical Package for the Social Sciences, Chicago, IL, USA).
 b r a z j i n f e c t d i s . 2 0 1 3;1 7(1):27–31 29

Table 1 – Univariate and multivariate comparative analysis of initial symptoms/signs, laboratory data and dengue
severity in adults and children with dengue.
Characteristics Adults Children Univariate Multivariate

n = 4817 n = 869 OR CI 95% p OR CI 95% p

Demographic data
Male [n (%)] 1977 (41.0) 440 (50.6)
Age (years) (mean ± SD) 37.2 ± 15.4 9.2 ± 3.6

Initial symptoms/signs [n (%)]

Fever 4494 (93.3) 815 (93.8) 0.92 0.69–1.24 0.592
Headache 4283 (88.9) 697 (80.2) 1.98 1.64–2.39 <0.001* – – NS
Myalgia 4254 (88.3) 620 (71.3) 3.04 2.56–3.61 <0.001* 2.58 2.08–3.18 <0.001
Retro-orbital pain 2531 (52.5) 353 (40.6) 1.62 1.40–1.88 <0.001* 1.36 1.15–1.62 0.001
Prostation 2277 (47.3) 378 (43.5) 1.17 1.01–1.35 0.040* – – NS
Nausea 2187 (45.4) 216 (24.9) 2.52 2.14–2.96 <0.001* 1.92 1.60–2.30 <0.001
Vomiting 2052 (42.6) 445 (51.2) 0.71 0.61–0.82 <0.001* 0.52 0.43–0.61 <0.001
Anorexia 1428 (29.6) 152 (17.5) 1.99 1.65–2.39 <0.001* – – NS
Arthralgia 1205 (25.0) 58 (6.7) 4.67 3.55–6.14 <0.001* 3.64 2.72–4.89 <0.001
Rash 724 (15.0) 127 (14.6) 1.03 0.84–1.27 0.750
Abdominal pain 491 (10.2) 59 (6.8) 1.56 1.18–2.06 0.002* – – NS
Bleeding 134 (2.8) 9 (1.0) 2.74 1.39–5.39 0.004* – – NS
Itch 75 (1.6) 15 (1.7) 0.90 0.52–1.58 0.713
Petechiae 74 (1.5) 22 (2.5) 0.60 0.37–0.97 0.038* 0.46 0.25–0.85 0.013
Hypotension 47 (1.0) 9 (1.0) 0.94 0.46–1.93 0.870
Diarrhea 33 (0.7) 11 (1.3) 0.54 0.27–1.07 0.077
Plasma leakage 22 (0.5) 5 (0.6) 0.79 0.30–2.10 0.640

Initial laboratory data [n (%)]

Hemoconcentrationa 2350 (48.8) 206 (23.7) 3.07 2.60–3.62 <0.001* 3.04 2.53–3.65 <0.001
Thrombocytopeniab 2507 (52.0) 283 (32.6) 2.25 1.93–2.62 <0.001* 2.17 1.80–2.60 <0.001
Leucopeniac 2498 (51.9) 412 (47.4) 1.19 1.03–1.38 0.016* – – NS
High ESRd 1610 (33.4) 188 (21.6) 1.82 1.15–1.54 <0.001* 1.81 1.53–2.14 <0.001
High ASTe 1915 (39.8) 306 (35.2) 1.22 1.05–1.42 0.010* – – NS
High ALTf 1638 (34.0) 147 (16.9) 2.54 2.11–3.07 <0.001* 3.13 2.44–4.02 <0.001

Severity [n (%)]
Severe dengue 366 (7.6) 30 (3.5) 2.29 1.57–3.35 <0.001* 1.74 1.12–2.72 <0.001
Hospitalization 696 (14.4) 55 (6.3) 2.50 1.88–3.32 <0.001* 2.21 1.59–3.06 <0.001

OR, odds ratio; CI 95%, 95% confidence interval; ESR, erythrocyte sedimentation rate; AST, aspartate aminotransferase; ALT, alanine amino-
transferase; DHF, dengue hemorrhagic fever; NS, not significant.
∗
Variables with a p-value <0.05 by univariate analysis included in multivariate analysis.
a
Hemoconcentration: hematocrit >45% in men, >40% in women and >38% in children.
b
Thrombocytopenia: platelets <150,000/␮L.
c
Leucopenia: leukocytes <4000/␮L.
d
High ESR: ESR >20 mm/h.
e
High AST: AST >50 U/L.
f
High ALT: ALT >50 U/L.

A comparison among age groups revealed that the fre-

Results quency of clinical signs and symptoms was significantly
A total of 5686 individuals with confirmed dengue were evalu- different between adults and children. The univariate analysis
ated: 4817 were adults (84.7%), and 869 were children (15.2%). indicated that headache, myalgia, anorexia, retro-orbital pain,
The majority of adults were female, who represented 59.0% abdominal pain, nausea, arthralgia, prostration, and bleed-
(2840) of adults and 49.4% (429) of children. The average adult ing were present more frequently in adults than in children.
age was 37.2 years, and the average child age was 9.2 years However, the multivariate analysis indicated that only myal-
(Table 1). Adults who were 15–19 years of age and children gia (OR = 2.58; CI 95% = 2.08–3.18), retro-orbital pain (OR = 1.36;
who were 10–14 years of age were the most affected groups CI 95% = 1.15–1.62), nausea (OR = 1.92; CI 95% = 1.60–2.30), and
(Fig. 1). arthralgia (OR = 3.64; CI 95% = 2.72–4.89) were significantly
Regarding the signs and symptoms that were identified in associated with adults with dengue. Vomiting (OR = 0.52; CI
the first evaluation at the CRD, classical signs, such as fever, 95% = 0.43–0.61) and rash (OR = 0.46; CI 95% = 0.25–0.85) were
headache, and myalgia, were present in over 70% of adults the correlated symptoms in children in both the univariate
and children with dengue (Table 1). Common clinical mani- and multivariate analyses.
festations, such as retro-orbital pain, prostration, nausea, and Regarding the laboratory evaluations, all of the alterations
vomiting, were observed in 40–50% of adults and children. (hemoconcentration, thrombocytopenia, leukopenia, and
30 b r a z j i n f e c t d i s . 2 0 1 3;1 7(1):27–31

A 700 maybe because of the anatomo-physiological differences of

the organs affected by dengue according to age.10
600
There were more hemorrhagic manifestations in adults. It
500 is believed that the primary infection acts as a protective fac-
No. of cases

400 tor against the hemorrhagic forms in children since repeated

infections by different serotypes of the DENV, results in more
300
severe manifestations.10
200 We found a higher prevalence of petechiae and vomiting in
100 children, as opposed to other studies.12
As reported in the literature, on Dengue’s Fever, leukope-
0
0-1 1-4 5-9 10-14 15-19 20-24 25-29 30-34 35-39 40-44 45-49 50-54
nia and thrombocytopenia were the most prevalent laboratory
Age group (yrs) findings.10,16,17 The induced viral destruction or the inhibition
B 250 of myeloid progenitor cells causes leukopenia and peripheral
destruction of platelets or destruction of megakaryocytes of
200 the bone marrow by the virus, resulting in decreased produc-
tion of platelets. There were no clinical correlation between
No. of cases

150 thrombocytopenia and severity of Dengue.16

The literature on dengue infection indicates that an
100 increase in aminotransferases is a relevant laboratory
result.1,16,18 In this study, we observed that increased ALT and
50
AST levels were frequent; however, there was no correlation
between these results and the severe forms of dengue.16,19
0
1-2 3-4 5-6 7-8 9-10 11-12 13-14
The laboratories alterations such as thrombocytopenia and
elevation of ALT were more severe in adults, like published
Age group (yrs)
before.10 It is noteworthy that we also did not find respiratory
Fig. 1 – (A) Age distribution of study cohort. (B) Age and renal involvement in any of the cases studied.
distribution of study participants 0–14 years of age. Several studies have suggested that adults who have been
previously primed with DENV have a favorable prognosis;
however, subsequent infections by distinct DENV serotypes
may result in severe forms of the disease. Primary infection
increases in ESR, AST and ALT) were more frequent in adults could be a protective factor against the severe forms of dengue
than in children. However, the multivariate analysis demon- in children, which may explain the higher incidence of the
strated significant differences between adults and children severe forms of the disease and hospitalization in adults.10
only for the hemoconcentration (OR = 3.04; CI 95% = 2.53–3.65), In this study, a low prevalence of severe cases (7.0%) and
thrombocytopenia (OR = 2.17; CI 95% = 1.80–2.60), increased hospitalization (13.2%) was observed. We ascribe these find-
ESR (OR = 1.81; CI 95% = 1.53–2.14), and increased ALT ings to the efficacy of the CRD Protocol, which advises patients
(OR = 3.13; CI 95% = 2.44–4.02) (Table 1). to seek medical assistance immediately after the onset of
Adults had a higher risk for severe dengue (7.6% vs. 3.5%) clinical manifestations and recommends that a diagnosis be
and a higher frequency of hospitalization (14.4% vs. 6.3%) than based on the clinical evolution of the disease, thereby reduc-
did children (Table 1). The differences were significant in both ing the risk of disease development to the severe forms, such
the univariate and multivariate analyses for severe dengue as DSS.20
(OR = 1.74; CI 95% = 1.12–2.72) and hospitalization (OR = 2.21; CI According to the Notifiable Diseases Information System
95% = 1.59–3.06) (Table 1). (Sistema de Informação de Agravos de Notificação – SINAN)
of the Ministry of Health of Brazil, Campos dos Goytacazes
(where CRD is located) has the lowest mortality rate (1.3%)
Discussion in Rio de Janeiro, whereas the capital has a rate of 4.8%, and
other cities may reach a mortality rate of 10% among severe
In this study, we detected a higher prevalence of women who cases. These findings reinforce the need to standardize pro-
were infected with dengue than of men. These data are similar grams for the early diagnosis and treatment of dengue, such
to those reported by a study in Nicaragua3 and different from as the programs conducted at the CRD.
other studies.10,13,14,15 We did not observe a significant differ-
ence in gender when it was correlated with the age groups.
The children with age between 10 and 14 years old and Conclusion
adults between 15 and 19 years old were the age groups most
prevalent affected, similar to the data reported previously.13 The present study detected the presence of classic signs and
In contrast to some studies,3 we found a higher preva- symptoms (fever, headache and myalgia) in 70% of the adults
lence of headache, myalgia, arthralgia, retro-orbital pain in and the children with this dengue. Many signs and symp-
adults. These findings may be related to the difficulty in iden- toms of dengue manifest differently in adults and children.
tifying these signs and symptoms by the parents and the Adult patients with dengue typically present symptoms of
children. Abdominal pain is also more common in adults, myalgia, retro-orbital pain, nausea and arthralgia. Children
 b r a z j i n f e c t d i s . 2 0 1 3;1 7(1):27–31 31

manifests mainly with vomiting and petechiae. There were no 3. Hammond NS, Balmaseda A, Perez Leonel, et al. Differences
differences between these two age groups about the presence in dengue severity in infants, children, and adults in a 3-year
of fever, rash, itch, hypotension and diarrhea. Hemoconcen- hospital-based study in Nicaragua. Am J Trop Med Hyg.
2005;73:1063–70.
tration, thrombocytopenia, ALT and ESR elevation occurred
4. Carlos CC, Oishi K, Cinco MTDD, Mapua CA, et al. Comparison
predominantly among adults. Adult patients also had a higher of clinical features and hematologic abnormalities between
risk of severe dengue and an increased frequency of hospital- dengue fever and dengue hemorrhagic fever among children
ization. in the Philippines. Am Soc Trop Med Hyg. 2005;73:435–40.
5. Souza LJ, Nogueira RMR, Soares LC, et al. The impact of
dengue on liver function as evaluated by aminotransferase
Authors’ contributions levels. Braz J Infect Dis. 2007;11:407–10.
6. Rocha LA, Tauil PL. Dengue in children: clinical and
LCM, LAS, MBTR, LBP, MVS, LJS and JTDSF were involved with epidemiological characteristics, Manaus, State of Amazonas,
conception and design of the study. LJS coordinated the study. 2006 and 2007. Rev Soc Bras Med Trop. 2009;42:18–22 [in
LCM, LAS, MBTR, LBP and MVS collected clinical and epidemi- Portuguese].
ological data. JTDSF did the analysis and interpret the data. 7. Ministry of Health, Brazil. Dengue-diagnosis and clinical
management. 3rd ed. Brasília: Ministério da Saúde; 2007 [in
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Portuguese].
All authors reviewed the manuscript critically, improved the 8. Potts JA, Gibbons RV, Rothman AL. Prediction of dengue
intellectual content, and approved the final version. LJS is the severity among pediatric Thai patients using clinical
guarantor of this paper. laboratory indicators. Negl Trop Dis. 2010;4:1–7.
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laboratory characteristics and disease severity between
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This study was conducted in accordance with the Declaration
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of Helsinki, the International Conference on Harmonisation
of clinical manifestations and laboratory findings in children
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