Dengue hemorrhagic fever in an infant after primoinfection dengue fever

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CliniCal            Case

               Dengue hemorrhagic fever in an infant
                       after primoinfection
                 Jorge Alberto García-Campos1, Francisco Javier Guzmán-de la Garza1,3,
      Víctor Manuel Alejandro-Quiroga1, María del Carmen González-Ruiz2, Héctor Moreno-Sánchez1,
                                 Carlos Rodrigo Cámara-Lemarroy3

      Background. Dengue fever is an infectious disease caused by a flavivirus and transmitted by a vector. It causes
      dengue fever, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). When one of these last
      two conditions appears, treatment consists of intensive fluid balance control.
      Case report. A 4-month-old female infant presented fever. She was admitted to the hospital and later showed
      signs and symptoms of DHF followed by DSS. Serological diagnosis was confirmed, and appropriate treatment
      offered. The mother does not have evidence of prior infection.
      Discussion. One theory proposes that DHF occurs in infants when passively transferred maternal antibodies
      from a previous infection cause an enhanced immune response when the infant is infected by a different type
      of dengue virus. This theory does not explain the occurrence of DHF in our report. Factors not dependent on
      the host, such as virological factors, may be responsible.
      Key words: dengue hemorrhagic fever, infants, primoinfection, dengue.

Introduction                                                    occurs between 8 and 12 days, after which it can
Dengue is an acute infectious disease caused by                 infect other humans when feeding.
viral infection transmitted by Aedes mosquitoes.                  The spectrum of DV infection ranges from as-
The etiologic agent corresponds to a virus of the               ymptomatic undifferentiated fever, dengue fever
genus flavivirus of the Flaviviridae family. Transmis-          (DF), dengue hemorrhagic fever (DHF) or even
sion of dengue virus (DV) requires a vector and                 dengue shock syndrome (DSS).2
a host.1 The female mosquito becomes infected
                                                                  According to the World Health Organization
by biting a human in viremia phase, which lasts
                                                                (WHO), 30 million people are infected each year,
from 2 to 7 days. In the mosquito, viral replication
                                                                thousands die and two billion people are at risk of
                                                                becoming infected.3 In Mexico, dengue is a major
 Departamento de Pediatría, Clínica Cuauhtémoc y Famosa;
                                                                health problem. In the year 2008 (up to week 49),
                                                                31,154 cases of dengue were confirmed of which
Monterrey, Nuevo Leon, México; 2Hospital San José, ITESM,
Monterrey, Nuevo Leon, México; 3Departamento de Fisiología,     6114 corresponded to DHF (19.62%) and 24
Facultad de Medicina, Universidad Autónoma de Nuevo León,       deaths were associated with DHF. In Nuevo Leon,
Monterrey, Nuevo León, México.                                  during the same period, there were 646 confirmed
Received for publication: 11-13-08                              cases of dengue of which 54 corresponded to
Accepted for publication: 4-28-09                               DHF (8.36%), although no deaths were reported.

Vol. 67, July-August 2010                                                                                               355
                                                García CJA et al.

Isolated serotypes were DENV-1 in 52 cases and              amoxicillin and paracetamol. The fever persisted
DENV-2 in two cases.4                                       and at 24 h of treatment she became drowsy and
   DHF is characterized by hemoconcentration                refused oral feeding. Laboratory results showed
secondary to increased capillary permeability and           the following: hemoglobin 15.6 g/dL, hematocrit
bleeding tendency. DSS usually occurs during the            45.8%, leukocytes 6900 x mm3, lymphocytes
clinical course of DHF, usually between the third           68.8%, neutrophils 11.2%, platelets 36,000 x
and fifth day, but can appear 2 or 3 days im-               mm3, PTT 63 sec (control 24 sec), and PT 18.6 sec
mediately after DF and, exceptionally, in patients          (control 15.2 sec). Due to the inability to locate a
with asymptomatic or nonspecific febrile dengue.2           peripheral vein, a central jugular venous catheter
According to WHO, 90% of cases worldwide of                 was placed and crystalloids were administered.
DHF and DSS occur in the pediatric population.3             At 3 h she developed hypoperfusion, petechiae,
                                                            ecchymosis and active bleeding at venopuncture
   DV can be isolated from the blood and from               sites. In the intensive care unit she was managed
some tissues, especially of the immune system               with crystalloids, platelet concentrate, red blood
during the period of fever, which ranges from 2             cell transfusion and cryoprecipitate. Laboratory
to 7 days after symptom onset. There is a greater           tests reported hemoglobin 6.8 g/dL, hematocrit
probability of isolating DV in the first 5 days of          19.7%, leukocytes 7600 x mm3, lymphocytes
symptoms. After the fifth day, IgM antibodies are           62%, neutrophils 25%, platelets 73,000 x mm3.
increased;5 80% of patients have detectable levels          IgM antibodies against dengue were positive. The
of IgM antibodies up to the fifth day of illness and        patient improved hemodynamically after 24-h
up to 90% at 10 days. The highest titers were ob-           management and was discharged asymptomatic
served at 15 days and fell to undetectable levels           within 48 h. Maternal IgG and IgM antibodies
within 2 or 3 subsequent months.6 IgG titers begin          against dengue were negative.
to increase from the second week after infection.
In a secondary infection, IgG titers increase more.
Even in the acute phase, IgM antibodies decline             Discussion
rapidly.7,8                                                 We reported here of a case of DHF/DSS in an
   Treatment for dengue infection is symptom-               infant. DHF is rare in infants <1 year of age.10
atic because there are no drugs against DV. Fluid           In Latin America this presents with a bimodal
and electrolyte management, hemodynamic                     distribution with peaks at 4 and 6 months of
monitoring, identifying early signs of DHF and              age. Fever was reported in 100% of the cases,
DSS, and hospital management in the latter                  60% of patients had signs of external bleeding
two cases are essential for reducing mortality              and 50% of patients had thrombocytopenia with
in this disease.9                                           platelet counts <50,000 x mm3 and petechaie.11
                                                            In all these infants, seropositivity of the mother
                                                            is assumed. At present, the immunopathogen-
Case report                                                 esis of DHF/DSS in infants has been completely
We present the case of a 4-month-old female
patient without relevant prior medical history.
                                                            explained. It is accepted that in older children,
                                                            secondary infections by various viral serotypes may
The patient was the product of a normal term                explain the development of DHF and/or DSS.12
pregnancy. Five days prior to the initial visit the         Other risk factors for the development of DHF have
patient had a difficult-to-control fever of 39°C.           been proposed including viral strain, host genet-
She was diagnosed with upper respiratory tract              ics, age, pre-existence of an anti-DV antibody,
infection and prescribed appropriate doses of               previous infection, or in those <1 year of age the

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                               Dengue hemorrhagic fever in an infant after primoinfection

presence of maternal antibodies transmitted to                 Asian variants of serotype DENV-2 are considered
infants through the placenta.                                  more virulent than its American counterpart,23 and
    In 1967, Halstead proposed the immunopatho-                the introduction of these variants to the western
logical hypothesis that focuses on the phenom-                 hemisphere has been linked to increased cases of
enon of sequential DV infections.12 During the                 HDF/DSS.24 Although we believe that the DENV-2
first infection, antibodies that neutralize DV are             virus with genotype SEA of Asian origin has already
generated. During a second infection with a differ-            supplanted the American variant (genotype AM)
ent serotype, persistent antibodies are not capable            in southern Mexico, recent epidemics due to this
of neutralizing the virus and, conversely, cause a             variant in northern Mexico and southern Texas
hypersensitive response leading to activation of               border states suggest that this genotype has also
the complement and monocytes. These release,                   supplanted AM in this region.20,25,26 It is possible
in an exaggerated manner, vasoactive agents and                that, in our case, virologic factors are responsible
cytokines that promote endovascular fluid loss                 for the observed severity of the disease. Unfortu-
and, therefore, lead to shock.13,14                            nately, it was not possible to isolate the virus and
                                                               determine the serotype involved.
   The immunopathological hypothesis cannot
explain the cases of DHF infection during first                   For patients who are in a state of shock the im-
infection in infants.15 To explain these cases, the            mediate administration of IV fluids is essential in
presence of maternal anti-dengue antibodies                    order to expand plasma volume and, in case of
transmitted through the placenta during gestation              deep or continuous shock, plasma or substances
has been assumed and documented in infants.16-18.              to expand it, should be administered in order to
                                                               restore initial fluids until improvement in vital signs
This effect on the elaborado a primary infection
Este documento es severity of por Medigraphic
caused by transmission of maternal antibodies                  is seen.27 Aggressive hemodynamic management
is not seen in other viral infections in humans,               in our case allowed for the patient’s adequate
although animal models exist to confirm this                   recovery.
mechanism in the pathogenesis of coronavirus.16                   In conclusion, the case presented here cannot
   However, this pathophysiological mechanism                  be explained with the theory of antibody-depen-
does not explain the development of DHF/DSS in                 dent immunology alone. It is possible that other
our case, given that the mother had no antibod-                factors dependent on the virus play an important
ies to dengue or evidence of prior infection with              role in the severity of the disease presented by this
DV. Epidemiological studies have reported cases                patient. The interactions between host factors and
where sequential infections are not associated with            the infecting serotype are crucial to the clinical
DHF DSS,19 as well as cases where DHF occurs                   presentation of dengue syndromes.
after primary infection,20 although none of them
in infants. This suggests that both factors (host
and virologic) could be decisive in the develop-
                                                               Correspondence to: Dr. Carlos Rodrigo Cámara Lemarroy
ment of the disease. Accordingly, the existence of
                                                               Departamento de Fisiología, Facultad de Medicina
genotypic variations that make some strains more               Universidad Autónoma de Nuevo León
virulent and are associated with greater severity              Monterrey, Nuevo León, México
of illness have been proposed.21,22 For example,               E-mail:

Vol. 67, July-August 2010                                                                                        357
                                                              García CJA et al.

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