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Transactions of the Royal Society of Tropical Medicine and Hygiene 105 (2011) 601– 603

Contents lists available at ScienceDirect

Transactions of the Royal Society ofTropical Medicine and Hygiene

j ourna l ho me pag e: ht t p: / /www.e lsev ier .com/ locate / t rs tmh

hort Communication

haracteristics of children hospitalized with dengue fever in anutbreak in Rio de Janeiro, Brazil

iana Giraldoa, Clemax Sant’Annab, André Reynaldo Santos Périsséa,aria de Fatima Pombo Marchb, Ana Paula Souzab, Analucia Mendesb,arcia Bonfimb, Cristina B. Hoferc,∗

Escola Nacional de Saude Publica / Fundac ão Osvaldo Cruz, Rio de Janeiro, BrazilInstituto de Puericultura e Pediatria Martagão Gesteira – Universidade Federal do Rio de Janeiro, Rio de Janeiro, BrazilPreventive Medicine Department, School of Medicine – Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

r t i c l e i n f o

rticle history:eceived 17 June 2010eceived in revised form 13 July 2011ccepted 13 July 2011vailable online 19 August 2011

a b s t r a c t

During a dengue epidemic in Rio de Janeiro in 2007–2008 the Instituto de Puericulturae Pediatria Martagão Gesteira Hospital was a reference for admitted children. The WorldHealth Organization (WHO) considered several manifestations as warning signs of severedengue This is a retrospective cohort study of all children admitted with dengue fever.Clinical variables considered warning signs by WHO were evaluated in the multivariate

eywords:enguehildrenrazilbdominal painethargy

analysis, to investigate if they were independently associated with severe dengue.One hundred and eighty one children were admitted, aged from 4 months to 15 years; 30

were classified as severe dengue. Abdominal pain (OR = 2.63, 95% CI1.06–6.53) and lethargy(OR = 3.40, 95% CI 1.45–7.99) were independently associated with severe dengue.

© 2011 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.

. Introduction

In 2009, the World Health Organization (WHO) pro-osed a classification system for dengue fever (DF).engue fever was categorized as with or without warning

igns (abdominal pain or tenderness, persistent vomiting,linical fluid accumulation, mucosal bleed, lethargy, rest-essness, liver enlargement >2 cm, increase in hematocrit

ith rapid decrease in platelet count); or severe dengue:f the patient presented plasma leakage, leading to shockr respiratory distress due to fluid accumulation; severe

leeding; and/or severe organ involvement.1

In 2008 there was a large epidemic of DF in Rio deaneiro, Brazil,2 so the aim of this paper is to describe the

∗ Corresponding author. Present address: Rua Lopes Quintas 340/106,ardim Botanico, Rio de Janeiro, Brazil, 22460-010. Tel.: +55 21 22744731;ax: +55 21 22744731.

E-mail address: cbhofer@hucff.ufrj.br (C.B. Hofer).

035-9203/$ – see front matter © 2011 Royal Society of Tropical Medicine and Hoi:10.1016/j.trstmh.2011.07.007

clinical characteristics of children who were admitted tothe Instituto de Puericultura e Pediatria Martagao Gesteira(IPPMG) during this epidemic, from November 2007 toApril 2008, with DF, and to evaluate whether the clini-cal signs and symptoms cited by WHO as warning signspredicted severe dengue in this population.

2. Methods

This is a retrospective cohort study of all children whowere admitted with a diagnosis of DF to the IPPMG fromNovember 2007 to April 2008. The IPPMG is a paediatrichospital in Rio de Janeiro, with 80 beds and eight paediatricintensive care unit (PICU) beds. There was a reference andcounter-reference service organized at this hospital and

the communities’ clinics around it during the epidemic. Allfebrile children with signs and symptoms of DF, as definedby the Brazilian Ministry of Health (BMH), who requiredadmission were referred to the IPPMG, and patients who

ygiene. Published by Elsevier Ltd. All rights reserved.

602 D. Giraldo et al. / Transactions of the Royal Society of Tropical Medicine and Hygiene 105 (2011) 601– 603

Table 1Baseline clinical manifestations of dengue fever

Clinical manifestation Severe denguen = 30

Dengue fevern = 151

RR 95% CI P–value Adjusted OR (95% CI)

Chronic disease 7 44 0.77 0.36–1.70 0.52 (NS)Gender–female 14 74 0.92 0.48–1.78 0. 81 (NS)Age (mean), months 104 104 0.99 (NS)Fever 29 146 0.99 0.16–6.13 0.99 (NS)Headache 17 92 0.86 0.45–1.67 0.66 (NS)Lethargy 20 54 2.89 1.44–5.82 0.002 3.40 (1.45–7.99)Vomiting 23 96 1.68 0.77–3.70 0.18 (NS) 1.72 (0.66–4.53)Abdominal tenderness 22 78 2.23 1.05–4.74 0.03 2.63 (1.06–6.53)Diarrhea 5 29 0.86 0.35–2.08 0.75 (NS)Fluid accumulation 3 21 0.73 0.24–2.21 0.55 (NS) 0.52 (0.13–2.07)Hepatomegaly 7 27 1.32 0.62–2.81 0.48 (NS) 0.99 (0.34–2.91)Bleeding manifestations 14 51 1.56 0.82–2.99 0.18 (NS) 1.57 (0.68–3.67)

Retro orbital pain 4 18

Skin rash 16 63

RR: Relative risk; OR: Odds ratio; NS: Not significant.

were evaluated and did not needed to be admitted or weredischarged were referred to community clinics.3 The BMHdefinition of DF was fever up to seven days, with at least twoof the following signs/symptoms: headache, retro-orbitalpain, myalgia, arthralgia, lethargy or rash (with or withoutbleeding).3

Children who required admission were those withwarning signs, also defined by BMH: abdominal pain,persistent vomiting, postural hypotension, painful hep-atomegaly, bleeding manifestations, drowsiness or irri-tability, decreased urine volume, hypothermia, increasedhematocrit, decreased platelet count, respiratory distress.3

Patients without those signs but with a chronic dis-ease, such as malignancy, HIV, asthma, sickle cell disease,diabetes, immune deficiency, previous prematurity, renal,cardiac or liver disease were also admitted.

The patients’ charts were reviewed by a paediatric res-ident, who collected all clinical data. Dengue fever wasclassified either as dengue or severe dengue by the PICUor the ward staff during patients’ admittance.

This study was reviewed and approved by the IPPMGEthical Research Committee.

2.1. Statistical analysis

All the information collected was processed in STATAversion 9.0 statistical software (Stata Corp., College Sta-tion, TX, USA). Bivariate analysis was performed usingWilcoxon two-sample test or Fisher’s exact test (forcategorical variables).

Variables with a P-value < 0.15 and/or variables thatwere cited as warning signs by WHO were included in themultivariate analysis.

A main-effects logistic regression model was fittedusing the stepwise maximum likelihood estimation tech-nique. The level of significance for removal of a variable inbackward regression was 0.10. The Pearson’s �2 goodnessof fit test, as well as the Hosmer-Lemeshow test were usedto evaluate fitness of the model.

3. Results

One hundred-eighty-one patients with DF were admit-ted to the IPPMG from November 2007 to April 2008.

1.11 0.43–2.89 0.83 (NS)1.48 0.77–2.84 0.24 (NS)

They were aged from 4 months to 15 years (median 8.7years old); 93 (51.4%) were male. Thirty patients (16.6%)were classified as having severe dengue, and 27 (14.9%)presented with haemodynamic instability or shock. Therewere no deaths among these patients.

The presence of shock among our study participantsranged from 9–59%, but the case-fatality rate in otherpaediatric studies, and in the Rio de Janeiro population,was higher than in ours (0.7–9.3%).2,4,5 We believe that wedid not have any fatalities due to the referral system builtin to our community.

We were able to perform serology in only 47 patients(IgM qualitative) during their admittance; 85% werepositive (41/47). This test was performed just once, andsome before the fifth day of disease, consequently serologytest negativity did not necessarily rule out dengue. Thisalso reflects an epidemic situation when, due to logisticreasons, the serology could not be performed to all thepopulation, and the definition of a dengue case used waslinked to the occurrence of other cases in the same locationand time.3

The frequency of any clinical manifestation was thesame between patients who had the dengue serology testand those that did not.

The crude and adjusted comparisons of the baselineclinical manifestations between patients with and with-out severe dengue are shown in Table 1. In line with otherpaediatric studies, lethargy (OR = 3.40, P-value < 0.01) andabdominal pain (OR = 2.63, P-value = 0.03) were more fre-quent in severe dengue patients.5

A prognostic study in Thailand demonstrated thatbleeding, secondary dengue infection, and haemoconcen-tration were associated with severe dengue in children.6 Inthis population, epistaxis, oliguria, and liver enlargementwere also associated with dengue severity in 231 cases.7

However, both studies used a population approach, and webelieve that a hospital based study, would better demon-strate the prognostic value of this clinical manifestations,since this is the setting where the decision to admit (or refer

the patient to the PICU), must be made.

Among the paediatric population, abdominal pain is afrequent and non-specific complaint, and the use of it as awarning sign, such as in adults, could be a mistake. In this

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differences of clinical manifestations and laboratory findings in chil-

D. Giraldo et al. / Transactions of the Royal Societ

tudy, we were able to validate this sign as a warning signn the paediatric population, even adjusting for age.

We believe that this study is an important description ofhe clinical manifestations of dengue in paediatric patientsuring an epidemic in a large urban area in a developingountry.

uthors’ contributions: DG and APS: study conceptionnd design, data collection, draft and final review; CS andFPM: study conception and design, data collection super-

ision, draft and final review; ARSP: data analysis, draftnd final review; AM and MB: study design, draft and finaleview; CBH: study conception, data analysis and draft andnal writing. Guarantor of the paper: Cristina B Hofer.

cknowledgements: Mrs Andrea Fiorani for the Englisheview.

unding: None

onflicts of interest: None declared.

thical approval: This study was approved by Instituto deuericultura e Pediatria Martagao Gesteira – UFRJ ethicalommittee.

ical Medicine and Hygiene 105 (2011) 601– 603 603

References

1. WHO. Dengue: guidelines for diagnosis, treatment, prevention and con-trol. A joint publication of the World Health Organization (WHO) andthe Special Programme for Research and Training in Tropical Diseases(TDR). New ed. Geneva: Switzerland; 2009.

2. Health Municipality Secretary, Rio de Janeiro. Number of denguecases monthly, by planned areas, administrative regions and coun-ties [in Portuguese]. http://www.saude.rio.rj.gov.br/saude/pubsms/media/tab incidengue2008, [accessed 15 October 2008].

3. Ministerio da Saude do Brasil. Dengue, diagnosis and clinicalmanagement- children and adults [in Portuguese]. 3rd ed. Rio deJaneiro: Brazilian Ministry of Health; 2007.

4. Phuong CX, Nhan NT, Kneen R, Thuy PT, van Thien C, Nga NT, et al.Clinical diagnosis and assessment of severity of confirmed dengueinfections in Vietnamese children: is the World Health Organiza-tion classification system helpful? Am J Trop Med Hyg 2004;70:172–9.

5. Chacko B, Subramanian G, Chacko B, Subramanian G. Clinical, lab-oratory and radiological parameters in children with dengue feverand predictive factors for dengue shock syndrome. J Trop Pediatr2008;54:137–40.

6. Tantracheewathorn T, Tantracheewathorn S. Risk factors ofdengue shock syndrome in children. J Med Assoc Thai 2007;90:

dren and adults with dengue virus infection. J Clin Virol 2007;39:76–81.