Case report Arch Argent Pediatr 2024;122(2):e202310144

Dengue fever in a 32-day-old patient. A rare case report

Carolina G. Goldberga , Alejandra F. López Alarcóna, María L. Salochaa, María F. Oteroa,

Mairena Jiméneza, Andrea Medinaa, Rubén de Sousa Serroa

ABSTRACT
Dengue fever is a viral disease transmitted by the Aedes aegypti mosquitoes.
In Argentina, dengue fever is an epidemic disease; most cases are reported during the hot months.
Until epidemiological week (EW) 20/2023, 106 672 cases were reported across 18 of the 24 provinces
of Argentina. Children younger than 2 years are among the main groups at risk. Recognizing signs and
symptoms and identifying risk factors is fundamental for the management of cases at a higher risk of
severity.
Here we describe the case of a 32-day-old female patient who was hospitalized due to febrile syndrome
without a source, who had a differential diagnosis of viral meningitis and sepsis and progressed to
leukocytosis, thrombocytopenia, hypoalbuminemia in association with rash and edema. The diagnosis
of dengue fever was established based on clinical, epidemiological, and positive IgM data.

Keywords: dengue; fever of unknown origin; sepsis; viral meningitis; dengue vaccine.

doi: http://dx.doi.org/10.5546/aap.2023-10144.eng

To cite: Goldberg CG, López Alarcón AF, Salocha ML, Otero MF, et al. Dengue fever in a 32-day-old patient. A rare case report. Arch Argent Pediatr
2024;122(2):e202310144.

a
Hospital General de Agudos Dr. Cosme Argerich, City of Buenos Aires, Argentina.

Correspondence to Carolina G. Goldberg: [email protected]

Funding: None.

Conflict of interest: None.

Received: 7-10-2023
Accepted: 8-18-2023

This is an open access article under the Creative Commons Attribution–Noncommercial–Noderivatives license 4.0 International.
Attribution - Allows reusers to copy and distribute the material in any medium or format so long as attribution is given to the
creator. Noncommercial – Only noncommercial uses of the work are permitted. Noderivatives - No derivatives or adaptations
of the work are permitted.

1
 Case report / Arch Argent Pediatr 2024;122(2):e202310144

INTRODUCTION done to look for enterovirus or herpes virus.

Dengue fever is caused by an arbovirus RNA of The patient’s cytochemical panel was positive,
the Flaviviridae family, with 4 serotypes (DENV-1, so her condition was deemed as viral meningitis
DENV-2, DENV-3, and DENV-4) distributed and an empirical antibiotic therapy with ampicillin
across the Americas. Dengue fever is a systemic and ceftriaxone was started. Her antigen test and
and dynamic infectious disease with a broad COVID-19 PCR were negative. Her urine test was
spectrum of manifestations.1 The risk of severe normal. Her virological test of nasopharyngeal
dengue is associated with different factors, secretions was negative. Lab test results are
including age younger than 2 years and infection shown in Table 1.
with a serotype followed by infection with a On day 2, she had fever, tachycardia with
different serotype. According to a report by the distal peripheral cyanosis, and generalized
Pan American Health Organization (PAHO), reticulation and required supplemental oxygen
the number of cases and deaths due to dengue and volume expansion with intravenous fluids,
fever increased in 2022. The 4 countries with an adequate response. Due to suspected
with the greatest incidence were Bolivia sepsis, new lab tests and 2 blood cultures were
(552.78 cases/100 000 inhabitants), Nicaragua done. The antibiotic therapy continued.
(260.30 cases/100 000 inhabitants), Belize Abdominal distension was observed on day 3.
(145.58 cases/100 000 inhabitants), and Brazil The oral route was interrupted and fluid intake
(166.8 cases/100 000 inhabitants).2 and output were controlled. The abdominal
In Argentina, dengue fever is an epidemic ultrasound showed hepatomegaly; perivesicular
disease; most cases are reported during the hot fluid; splenomegaly; and free fluid around the
months (November through May).2 liver, among the loops, and in the pelvis. The
Until epidemiological week (EW) 20/2023, pleural ultrasound showed mild right pleural
106 672 cases were reported in our country. effusion. The patient’s leukocyte count increased
The following jurisdictions confirmed endemic and thrombocytopenia and hematocrit values
circulation of dengue fever: Central region decreased from admission, which was deemed
(Buenos Aires, the City of Buenos Aires, Córdoba, as secondary to the management of the internal
Entre Ríos, and Santa Fe); Northwest region milieu in a severe patient with fluid extravasation.
(Catamarca, Jujuy, La Rioja, Salta, Santiago Dengue fever was suspected, so a serology test
del Estero, and Tucumán); Northeast region was performed, which showed a positive IgM and
(Chaco, Corrientes, and Formosa), except for a negative NS1 antigen.
Misiones; San Luis and Mendoza in the Cuyo On day 4, the patient developed a generalized,
region; and La Pampa in the South region. confluent macular erythematous rash that left
Reported dengue serotypes depend on the parts of healthy interposed skin in islets with
epidemiological moment; between 2022 and no pruritus. She developed leukocytosis, which
2023, DENV-2 (81.16%), DENV-1 (18.79%), and was deemed as an inflammatory response, and
DENV-3 (0.05%) prevailed in Argentina.3 Here we thrombocytopenia. Her cultures were negative.
describe the case of a 32-day-old female patient The patient was referred for consultation to
who was admitted due to fever without a source the Department of Infectious Diseases and
who developed signs consistent with dengue Hematology. The antibiotic therapy was
fever over the hours. discontinued. The probable diagnosis was
assumed to be dengue fever (Figure 1).
CASE REPORT On day 5, she developed generalized edema
A 32-day-old female infant, with no relevant with negative Godet’s sign. She began testing for
perinatal history, consulted due to fever for the tolerance to oral feeding.
past 12 hours. She was admitted with suspected On day 6, she had no fever, her edema
sepsis for diagnosis and treatment. Her father had resolved, she had a good attitude and oral
was experiencing upper airway disease, but tolerance, and her rash had reduced. A large
no history of travel, sick relatives or neighbors increase in leukocyte count, a rising platelet
was reported. The family lived in Moreno, in the count, and an improved albumin level were
province of Buenos Aires. observed.
Two blood cultures, a urine culture, and a On day 7, the patient did not have any edema.
cerebrospinal fluid (CSF) culture were performed. Her white blood cell count was going down. The
No CSF polymerase chain reaction (PCR) was serology test for dengue fever was repeated

2
 Case report / Arch Argent Pediatr 2024;122(2):e202310144

Table 1. Progress of most relevant lab tests

Test Day 1 Day 2 Day 3 Day 4 Day 5 Day 6 Day 7

Hct (%) 43 37.4 31 33.9 34.4 30 29

Hb (g/dL) 14.7 13 11.7 12 12 11 10.7
WBC (cells/mm3) 8590 10 100 17 700 22 400 55 700 76 400 46 800
N/L/M (%) 46/32.1/11.5 57/25/8 61/24/5 43/28/18 18/60/9 5/75/13 9/76/7
PLT (cells/mm3) 301 000 139 000 97 000 115 000 119 000 134 000 194 000
U/C 16/0.4 10/0.17 3/021
Albumin (g/dL) 2.6 3.1
PRO (ng/mL) 0.28
PCR (mg/dL) 42.6 65
Na/K/Cl (mEq/L) 129/4/95 136/4/104

CSF Colorless,
slightly
xanthochromic
PROT (mg/dL) 66
GLU (mg/dL) 59
GLU (mg/dL) 91
LEU 110/mm3
MO 80%

Dengue fever R
IgM Positive
NS1 antigen Negative NR
Viral genome UND

Hct: hematocrit. Hb: hemoglobin. WBC: white blood cells. N/L/M: neutrophils/lymphocytes/monocytes. PLT: platelets. U/C: urea/
creatinine. PCR: polymerase chain reaction. NA/K/Cl: sodium/potassium/chloride. PRO: procalcitonin (normal range: 0.5–2.4).
Serology for dengue IgM, sample 1 collected on day 3: MAC-ELISA technique to detect IgM, and sample 2 collected on day 7:
commercial ELISA technique to detect IgM.
NS1 antigen, sample 1 collected on day 3: immunochromatography technique; NS1 antigen, sample 2 collected on day 7:
ELISA technique to detect NS1.
NR: non-reactive. R: reactive.
Viral genome: RT-qPCR technique.
UND: undetectable
CSF: cerebrospinal fluid. PROT: CSF protein level. GLU: CSF glucose level. LEU: leukocytes. MO: mononuclear. Glu: blood
glucose level.

and showed positive IgM. The diagnosis was In April 2023, the National Drug, Food
confirmed. It was not possible to establish the and Technology Administration of Argentina
serotype. (Administración Nacional de Medicamentos,
On day 9, the patient was discharged. Alimentos y Tecnología Médica, ANMAT)
approved the use of a dengue vaccine developed
DISCUSSION by Japanese pharmaceutical company Takeda,
Dengue fever is a growing global public health for individuals aged 4 years and older, whether or
problem due to climate change, population not they suffered from dengue fever before. The
growth in urban areas, insufficient water supply, vaccine is called TAK-003.6 However, no vaccine
inadequate waste collection, containers that serve can block an outbreak of dengue fever. For all
as mosquito breeding sites, increased travel and age groups, the best prevention strategy is still the
migration, and failures in vector control.4 control and elimination of mosquito breeding sites,
Dengue fever is a notifiable disease. the avoidance of mosquito bites, and the use of
Prevention is based on immunization and vector vector isolation methods (repellents, mosquito
control, with proper disposal of solid waste and coils, mosquito nets, etc.).7,8 In endemic areas,
improved water storage practices to prevent it is important to keep in mind the possibility of
female mosquitoes from laying eggs.5 mother-to-child transmission, mainly in babies

3
 Case report / Arch Argent Pediatr 2024;122(2):e202310144

Figure 1. Physical examination on day 4

Generalized, confluent macular erythematous rash that leaves parts of healthy interposed skin with clear islets in between.
Edema in both lower extremities.

born to mothers with peripartum febrile symptoms, (transaminases above 1000 units); encephalitis;
rash, hepatomegaly, and thrombocytopenia, with myocarditis.10–12
or without clinical signs of sepsis during the first Rash first develops on day 3–4. The critical
2 weeks of life.2 phase starts between day 3 and 7. Increased
Dengue is a self-limited febrile disease with hematocrit level, hypoalbuminemia, perivesicular
an incubation period of 4 to 10 days. The febrile effusion, pleural effusion, ascites, and generalized
phase of 2 to 7 days marks the onset of the edema may be observed. Such capillary leakage
sudden onset disease that usually remits on the may cause dengue shock syndrome. The
third day with leukopenia, mild thrombocytopenia, recovery phase lasts 2 to 3 days, with a rapid
and a moderate increase in transaminases. recovery of thrombocytopenia. The alteration of
In children, the early signs and symptoms of vascular permeability lasts 48–72 hours, with a
the disease are non-specific and undifferentiated rapid clinical improvement.9
from other acute febrile illnesses. 9 Dengue Thrombocytopenia (68.46%) is the most
fever with warning signs is characterized by 1 frequent finding. Enzyme-linked immunosorbent
or more of the following: severe and sustained assay (ELISA) and reverse transcriptase
abdominal pain, persistent vomiting, serous polymerase chain reaction (RT-PCR) are the
effusion, mucosal bleeding, change in mental main laboratory diagnostic modalities to detect
status, hepatomegaly, increased hematocrit nonstructural protein 1 (NS1) antigen, IgG, and
level, decreased platelet count. Severe dengue is IgM in the late phases.13 The detection of viral
characterized by 1 or more of the following: severe antigens (NS1 Ag) (viremia) is the method of
plasma extravasation, expressed by hypovolemic choice in the first 5 days of disease; whereas
shock or respiratory distress due to excess serological tests are used as of day 5–6.
fluid in the lung; severe bleeding; severe hepatitis Leukocytosis may be observed, as in our

4
 Case report / Arch Argent Pediatr 2024;122(2):e202310144

patient,14 and an increased hematocrit level is 2. Berberian G, Fariña D, Rosanova M, Hidalgo S, et al.
a sign of hemoconcentration secondary to fluid Dengue perinatal. Arch Argent Pediatr. 2011;109(3):232-6.
3. Argentina. Ministerio de Salud. Boletin Epidemiológico
transfer and hypovolemia. The World Health Semanal. 2023;8 SE 20 (354). [Accessed on:
Organization considers a variation equal to or August 18th, 2023]. Available at: https://buenosaires.gob.
greater than 20% in the hematocrit level, either ar/salud/boletines-epidemiologicos-semanales-2023
an increase from baseline or a decrease during 4. Enfermedades infecciosas. Dengue: Diagnóstico de
Dengue. Guia para el equipo de salud. 4.a ed. Buenos
the convalescent phase from the critical phase, to Aires: MINSAL; 2015. [Accessed on: August 18th, 2023].
be diagnostic of dehydration. But such changes Available at: https://bancos.salud. gob.ar/sites/default/
are not observed if hypovolemia is managed in files/2018-10/0000000062cnt-guia- dengue-2016.pdf
an early manner.15 In our patient, a progressive 5. Arteaga-Livias K, Bonilla-Crispin A, Panduro-Correa V,
Martínez-Enríquez C, Dámaso-Mata B. Dengue en un
decrease was observed. She was offered early neonato. Rev Chil Infectol. 2017;34(5):494-8.
supportive treatment with adequate hydration, 6. ClinicalTrials.gov. Efficacy, Safety, and Immunogenicity of
especially after the resolution of fever.9 Takeda’s Tetravalent Dengue Vaccine (TDV) in Healthy
Other recommendations include rest, not Children (TIDES). 2017. Retrieved August 2018. [Accessed
on: August 18th, 2023]. Available at: https://classic.
using aspirin or NSAIDs, using repellents, and clinicaltrials.gov/ct2/show/NCT02747927
implementing environmental control measures to 7. Argentina. Ministerio de Salud. Comunicado de Prensa:
prevent mosquito bites during the febrile phase La ANMAT aprobó el uso de la vacuna del laboratorio
and to prevent transmission at the hospital or at Takeda contra el dengue. [Accessed on: August 18th, 2023].
Available at: https://www.argentina.gob.ar/noticias/la-anmat-
home.2 aprobo-el-uso-de-la-vacuna- del-laboratorio-takeda-contra-
The final diagnosis in our 32-day-old patient el-dengue
was severe dengue. The differential diagnoses 8. Torres-Flores JM, Reyes-Sandoval A, Salazar MI. Dengue
included viral meningitis, sepsis, and dengue Vaccines: An Update. BioDrugs. 2022;36(3):325-36.
9. Pavlicich V. Dengue: revisión y experiencia en pediatría. Arch
shock syndrome. The early identification of signs Pediatr Urug. 2016;87(2):143-56.
and symptoms serves as a window of opportunity 10. Cazes CI, Carballo CM, Praino ML, Ferolla FM, et al.
for effective treatment. n Brote epidémico de dengue en la Ciudad de Buenos
Aires, 2016: características clínicas y hematológicas de la
infección en una población pediátrica. Arch Argent Pediatr.
Acknowledgments 2019;117(1):e63-7.
We would like to thank Viviana Aguirre, M.D. 11. Berberian G, Pérez G, Mangano A, Borgnia D, et al. Dengue
and head of the Department of Promotion and más allá del trópico: estudio de series temporales 2015-2016
Protection of Hospital General de Agudos versus 2019-2020 en un hospital pediátrico de la Ciudad de
Buenos Aries. Arch Argent Pediatr. 2022;120(6):384-90.
Dr. Cosme Argerich. 12. Aurpibul L, Khumlue P, Issaranggoon na ayuthaya S,
And also to Silvina Pedrouzo, M.D. and Oberdorfer P. Dengue shock syndrome in an infant. BMJ
member of the Committee of Outpatient Pediatrics Case Rep. 2014;2014:bcr2014205621.
and of the Sub-Committee of Information and 13. Uthraraj NS, Sriraam LM, Hiriyur Prakash M, Kumar M,
et al. Predictive Factors for the Complications of Dengue
Communication Technologies of the Sociedad Fever in Children: A Retrospective Analysis. Cureus.
Argentina de Pediatría. 2022;14(12):e33027.
14. Méndez-Domínguez N, Achach-Medina K, Morales-
REFERENCES Gual YM, Gómez-Carro S. Dengue, presentación inusual
1. López Herminio O. Dengue. In Sociedad Argentina de en un lactante: Reporte de un caso. Rev Chil Pediatr.
Pediatría PRONAP. 2021;1(Módulo 2):15-36. 2017;88(2):275-9.
15. Pizarro D. Dengue, Dengue hemorrágico. Acta Pediátr
Costarric. 2009;21(1):8-17.