SERUM IgE LEVEL IN CHILDREN WITH DENGUE INFECTION AND ITS CORRELATION WITH THE
SEVERITY OF ILLNESS
fever (DF) is currently a huge epidemiological and clinicopathological
challenge, not only in our country but also all over the world1.
caused by an RNA arbovirus belonging to the Flaviviridae family which is
transmitted by the female Aedes aegypti mosquito and leads usually to a
passing flu-like illness but sometimes (in 10-15% of cases) progresses to severe
disease with its potentially lethal complications of the dengue haemorrhagic
(DHF) and shock syndromes (DSS)2,3.
the last 6-7 years of managing children with DF in this institution, we have
noted that adolescents develop more serious symptoms, more severe disease and
complications more often than younger children significantly endangering their
lives. Consequently, these children are noted to require more intense
monitoring and therapy leading to extended hospital stay and unacceptable
morbidity and mortality. The commonest explanation for this phenomenon is said
to be a robust immune reaction to dengue viremia in adolescents and
its role in enhancing the vascular leak characteristic of the disease4,5.
this aspect of the pathogenesis has neither been studied adequately. The Serum
IgE level is one of the more easily available marker for quantifying immune
response to any antigen entering the body and challenging the immune system6,7,8,9.
have undertaken this study to assess whether the adolescents serologically
diagnosed with DF have higher levels of IgE during the course of their illness
as compared to younger children and correlate the same with the severity of
illness as determined by the degree of thrombocytopenia, requirement of
component transfusion, need for inotropic support, duration of hospital stay
and mortality (if any).
this does indeed correlate, the exciting prospect of using anti-inflammatory
agents (steroids, anti-histamines, intravenous immunoglobulin therapy, etc.) as
adjuvants to standard therapy in this subgroup of children may be explored
which may then result in saving precious lives10,11.
assess the serum levels of IgE in two groups of children (pre – adolescent and
adolescent) serologically diagnosed with dengue and to correlate the same with
the haematological recovery, progression to severe disease duration of hospital
stay and mortality (if any) in these children.
Hypothesis- Based on a study done by Koraka P et al.6 who concluded that serum
IgE levels can be used as a prognostic marker for the progression to severe
dengue, we postulated that adolescent children may mount an exaggerated immune
response to the dengue virus as compared to pre-adolescent subjects due to
their possessing a well-developed and robust immune system. This in turn may
lead to severe disease and complications as it is universally known that most
of the complications of severe DF occur because of a immunological storm ‘the cytokine tsunami’12 that causes a significant
and severe vascular leak resulting in the loss of platelets and coagulant
factors into the third space. In addition, due to the loss of plasma, the blood
pressure falls and the child goes into shock. Thus, we intend to correlate the
serum IgE levels (a reliable marker of immune response) with the severity of the disease in adolescents.
period: 2 months
NS1 or IgM positive patients presenting within the first 3 days of fever.
5 – 15 years.
below 5 years of age.
with history of known allergies / asthma / atopy / urticaria / angioneuritic
with confirmed helminthic infestations.
with an increased Absolute Eosinophil count.
with prior haematological conditions associated with thrombocytopenia
with haematological malignancies.
The Hammond et al study has observed that children formed 35% of the population
that was severely affected by Dengue. In the present study expecting similar
results in the 5-10 year age group and a 22% difference in the 11-15 year age
group with 80% power and 95% confidence level, the study requires a minimum of
46 subjects in each age group3.
description of procedure:
written informed consent will be obtained from the parents of the participants
who are admitted to the Tertiary care Teaching Hospital fulfilling the
inclusion criteria. These participants will be divided into two groups – Group
1 (age: 5-10 years) and Group 2 (age: 11-15 years). The first serum sample for IgE titre will be collected on the 1st
day of fever (or upon admission) and the second serum sample will be collected
24 to 36 hours after defervescence (or 72-96 hours after the collection of the
first sample). Both these samples will be collected along with routine blood
samples collected daily to monitor the progress of the patient. The samples
for IgE titre will be stored at -800C for collective analysis on a
counts will be followed up serially. The day of reversal of the downward trend
will be noted and thereafter normalization of platelet count would be recorded
to have occurred when the platelet count exceeds 1,00,000 cells / mm3.
will be clinically followed up to assess progression to severe disease, use of
component therapy, inotropic requirement along with duration of hospital stay
and mortality (if any)
risks and benefits:
blood samples for serum IgE will be collected as a part of the routine
investigations for dengue as required for monitoring and management. Hence
there is no additional risk to the patient.
conducting this study, we intend to provide justification for further studies
on the use of anti-inflammatory agents as adjuvants to standard therapy in a
particular sub group of children with DF (adolescents) with an aim to reduce
the morbidity and mortality often associated with severe disease.
materials needed with quantity:
blood will be collected with due aseptic precautions in plain vacutainer tubes
and the serum separated and stored at a temperature of -800C till
further collective analysis for IgE levels by the ELISA method in the central
research laboratory. (Reference range: 0-160 IU/ml)
Investigations: as mentioned earlier
The day of reversal of platelet trend and the
day of normalization of platelet count.
b. Progression to
complications / severe disease –
ii. Development of DHF and
Duration of hospital stay.
e. Mortality (if any)
(i) Independent t test would be used to
compare IgE levels between the 2 groups.
(ii) Descriptive statistics of IgE will be analysed and summarized
in terms of mean with standard deviation.
(iii) Chi-square test would be used to compare the progression of
subjects of each group to severe disease and the odds ratio would be estimated.
· Ethical considerations: A written consent from the parents of
the participants would be obtained before enrolment. The parents will also be
informed about the procedure before collection of the blood sample.
determine the possible role of anti-inflammatory agents as an addition to the
standard of care in the management of dengue illness in adolescent children
with a view to reduce the morbidity and mortality from the disease.