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RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES
KARNATAKA, BANGALORE
ANNEXURE II
PROFORMA FOR REGISTRATION OF SUBJECTS FOR
DISSERTATION
1.
NAME OF THE
CANDIDATE & ADDRESS
DR. PRABHAVATI JINAGOUDA PATIL
POST GRADUATE STUDENT
MD PATHOLOGY
SDM COLLEGE OF MEDICAL SCIENCES
AND HOSPITAL, DHARWAD - 580009
NAME OF THE
INSTITUTION
SDM COLLEGE OF MEDICAL SCIENCES
AND HOSPITAL, DHARWAD – 580009
3.
COURSE OF STUDY AND
SUBJECT
MD PATHOLOGY
4.
DATE OF ADMISSION TO
THE COURSE
3RD MAY 2010
5.
TITLE OF TOPIC
DENGUE: A CLINICOHEMATOLOGICAL
PROFILE.
6.
BRIEF RESUME OF THE INTENDED WORK:
6.1 Need for study:
Dengue is the most rapidly spreading mosquito-borne viral disease in the
world. In the last 50 years, incidence has increased 30-fold with increasing
geographic expansion to new countries and, in the present decade, from urban to
rural settings. An estimated 50 million dengue infections occur annually and
approximately 2.5 billion people live in dengue endemic countries. In India dengue
has seen resurgence in recent times. Reported case fatality rates in India are 3-5 %.1
It can range from a nonspecific febrile illness to severe disease i.e. dengue
hemorrhagic fever and dengue shock syndrome in which patients develop
hematological complications.2
Since the death in these patients is due to hematological complications, the
study of hematological changes would have a substantial impact on reducing the
mortality and morbidity associated with dengue.
Hence the present study is planned to analyze the hematological findings in
dengue illness and to correlate the same with clinical course.
2.
6.2 REVIEW OF LITERATURE:
Dengue fever is caused by a single stranded RNA virus of flaviviridae
family. The WHO estimates that 50 – 100 million cases of dengue infection occur
each year. It causes 24,000 deaths per year. Dengue virus infection is transmitted
by Aedes aegypti and Aedes albopticus mosquitoes.3
Dengue viruses, of which there are 4 serotypes, cause a variable spectrum of
disease that changes from an undifferentiated fever to dengue fever (DF) through
to more severe syndromes called dengue hemorrhagic fever (DHF) and dengue
shock syndrome (DSS).3
Infection with one serotype confers immunity to only that serotype and
temporary immunity to other serotypes. Sequential infections are possible after a
short time.3
DHF and DSS are typically confined to children who have experienced
dengue infection previously and infants with weaning levels of maternal
antibodies. The mechanism involved in development of DHF and DSS is
enhanced virus replication in macrophages leading to increased vascular
permeability and plasma leakage resulting in signs of shock. There will also be a
haemostatic disorder characterized by thrombocytopenia and coagulopathy.1
The clinical manifestations of dengue infection are:
1. Dengue fever: characterized by flue like illness
2. DHF: characterized by high fever, hemorrhagic phenomena, and circulatory
failure
3. DSS: characterized by shock4
In a study of 34 cases from Mumbai, patients ranged in the age group from
6 months to 11 years. Most common clinical manifestation was fever seen in all.
19 (55.9%) patients had hypotension, 17 (50%) patients had vomiting and
hepatomegaly was seen in 16 (47.1%) patients.4
Another study by Banerjee et al3 of 50 clinically suspected cases of
dengue, showed age range between 4 to 62 years of which 13(26%) were females
and 37(74%) males. Fever with rash was the commonest clinical presentation,
seen in 35(70%) cases.3
In primary dengue infection IgM antibodies increase by 5-10 days and
persist for 6 months. IgG antibodies increase by 14 days and persist for life. NS1
antigen assay becomes positive from 0-9th day after the onset of symptoms and
persist for 15 days.3 In secondary infections, the levels of IgM increase by 4-5
days, and IgG levels raise rapidly within 2 days. Thus the presence of high titres
of IgG early in the course of disease is criteria for secondary infection.1
Commercially available assays that detect the dengue virus protein NS1 in
the plasma or serum of the patients offers the possibility of early, rapid and
specific diagnosis. The combination of NS1 and IgM detection in samples
collected in first few days of fever increased the overall dengue diagnostic
sensitivity.5
The hematological effects observed are changes in blood counts, hemoconcentration due to plasma leakage, leucopenia because of decreased
neutrophils near the end of the febrile phase, presence of atypical lymphocytes
and relative lymphocytosis before shock, thrombocytopenia and changes in blood
hemostasis with frequent presence of hemorrhagic manifestations.1
Hematological analysis of 34 cases in Mumbai revealed thrombocytopenia
in 27(79.4%) patients, hemoconcentration in17(50%) patients and leucopenia in
16(47%) patients.4 In a study by Banerjee et al3 thrombocytopenia was seen in
19% of patients. The platelet count in these patients ranged between 44,000 to
1,00,000/mm3. Normocytic normochromic anemia was observed in 11% of
patients. Leukopenia was not observed in their study.3
The time course relation between drop in platelet count and increase in
hematocrit is unique for dengue hemorrhagic fever, before the onset of shock.
These all changes are related to disease severity and indicate the need for
appropriate therapeutic intervention.1
6.3 Objectives of study:
1. To evaluate hematological changes in patients suffering from clinical
manifestations of dengue with serological confirmation.
2. To study the age and sex distribution, and clinical features of dengue illness
3. To correlate hematological findings with different stages of serology
4. To correlate hematological findings with the clinical outcome
7.
MATERIALS AND METHODS:
7.1 Source of data:
It is a prospective study from September 2010 to September 2011, done in
SDM College of Medical sciences and hospital, Dharwad. Clinically suspected cases
of dengue with serological confirmation of either dengue specific NS1 antigen assay
and/or IgM and/or IgG antibodies detection are selected. Evaluation of
hematological parameters and peripheral smear study are carried out.
.
Inclusion Criteria:
All the blood samples sent to the department of pathology, which are found to
be positive by serology (Dengue NS1 antigen / IgM antibody / IgG antibody), are
included.
Exclusion Criteria:
 Suspected dengue cases in which serology is found to be negative
 Serologically positive cases of dengue which are also positive for other
coexistant infections Eg. Malaria, typhoid, are excluded from the study.
7.2 Methods of collection of data:
 Patients’ clinical data will be collected from the medical records.

Serology derived from a venous blood sample collected from the patients
presenting with symptoms suggestive of dengue and placed in a sterile glass
bottle and transported to the laboratory immediately. A commercially
available Dengue NS1 Ag & Ab combi-card test kit is used to detect NS1
antigen and IgM and IgG antibodies. The test results are expressed as
positives/negatives for antigen and both antibodies.

Evaluation of hematological parameters is done by collecting 2 ml of sample
on EDTA prefilled bottles and transporting it to the laboratory immediately.
The analysis is done by the automated analyzer SYSMEX XT 1800i.
Peripheral smears are studied after staining with Leishman’s stain.
The data is collected in a specially designed proforma for the study. It is
transformed to a master chart which will then be subjected to analysis.
7.3 Does the study require any investigation to be conducted on patients or
animals? If so please describe briefly.
Yes. The study involves the study of serology, hematological parameters and
peripheral smear as described in 7.2. An informed consent is taken from the patients
during admission for all the investigations.
7.4 Has ethical clearances been obtained from ethical committee of your
institution in case of 7.3?
Yes. Ethical clearance has been obtained from the Institutional Ethical
Committee. SDM Medical college, Dharwad.
Ref: SDMIEC: 027 : 2010
8.
LIST OF REFERENCES:
1. WHO. Dengue hemorrhagic fever: Diagnosis, treatment, prevention and control.
Geneva: WHO press; 2009. p. 3-106.
2. Oliveira EC, Pontes ER, Cunha RV, Fróes IB, Nascimento D. Hematological
changes in patients with dengue. Revista da Sociedade Brasileira de Medicina
Tropical. 2009 Dec;42(6):682-85.
3.Banerjee M, Chatterjee T, Choudhary GS, Srinivas V, Kataria VK. Dengue: A
Clinico-hematological profile. MJAFI. 2008;64(4):333-6.
4. Shah I, Katira B. Clinical and Laboratory Abnormalities due to Dengue in
Hospitalized Children in Mumbai in 2004. Dengue Bulletin. 2005;29:90-96.
5. Guzman MG, Jaenisch T, Gaczkowski R, Hang VT, Sekaran SD, et al. MultiCountry Evaluation of the Sensitivity and Specificity of Two CommerciallyAvailable NS1 ELISA Assays for Dengue Diagnosis. PLoS Neglected Tropical
Diseases. 2010 Aug;4(8):1-10.
9.
Signature of the Candidate
10.
Remarks of the Guide
11.
NAME & DESIGNATION
11.1 GUIDE
Planned study is very relevant and
timely. It addresses a major recent health
problem seen in this region. Findings
will be very important and will have a
definite impact on patient care
DR. DEEPAK R. KANABUR MD
PROFESSOR,
DEPARTMENT OF PATHOLOGY,
SDMCMSH, DHARWAD
11.2 SIGNATURE
11.3 CO-GUIDE
11.4 SIGNATURE
11.5 HEAD OF THE DEPARTMENT
11.6 SIGNATURE
12.
12.1 REMARKS OF CHAIRMAN
AND PRINCIPAL
12.2 SIGNATURE
DR. RAVIKALA RAO MD
PROFESSOR & HEAD,
DEPARTMENT OF PATHOLOGY,
SDMCMSH, DHARWAD.