I

A STUDY ON CLINICAL PROFILE IN CORRELATION WITH LABORATORY INVESTIGATIONS AND RADIOLOGICAL

FINDINGS IN DENGUE FEVER.

By

Dr. LAKSHMI.V M.B.B.S,

Dissertation submitted to the

Rajiv Gandhi University of Health Sciences, Bangalore, Karnataka

In partial fulfillment of the requirements for the degree of

DOCTOR OF MEDICINE

IN

PAEDIATRICS

Under the Guidance of

Dr. CHANDRAKALA.P. M.D., Associate Professor

DEPARTMENT OF PAEDIATRICS

KEMPEGOWDA INSTITUTE OF MEDICAL SCIENCES K.R.ROAD, BANGALORE, KARNATAKA

2013

  II

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,

BANGALORE, KARNATAKA

DECLARATION BY THE CANDIDATE

I hereby declare that this dissertation/thesis entitled “A STUDY ON CLINICAL

PROFILE IN CORRELATION WITH LABORATORY

INVESTIGATIONS AND RADIOLOGICAL FINDINGS IN DENGUE

FEVER” is a bonafide and genuine research work carried out by me under the

guidance of Dr.CHANDRAKALA.P M.D, Associate Professor of Paediatrics,

KIMS, Bangalore.

Date:

Place: Bangalore Dr. LAKSHMI.V

 

  III

CERTIFICATE BY THE GUIDE

This is to certify that the dissertation entitled “A STUDY ON CLINICAL

PROFILE IN CORRELATION WITH LABORATORY

INVESTIGATIONS AND RADIOLOGICAL FINDINGS IN DENGUE

FEVER ” is a bonafide research work done by Dr. LAKSHMI.V, Postgraduate

student, Department of Pediatrics, Kempegowda Institute of Medical Sciences,

Bangalore, in partial fulfillment of the requirement for the degree of DOCTOR

OF MEDICINE IN PAEDIATRICS.

Dr. CHANDRAKALA.P. M.D,

Associate Professor of Paediatrics Kempegowda Institute of Medical

Sciences and Research Centre

Date: Bangalore

Place: Bangalore

  IV

ENDORSEMENT BY THE HOD, PRINCIPAL/HEAD OF THE

INSTITUTION

This is to certify that the dissertation entitled “A STUDY ON CLINICAL

PROFILE IN CORRELATION WITH LABORATORY

INVESTIGATIONS AND RADIOLOGICAL FINDINGS IN DENGUE

FEVER” is a bonafide research work done by Dr. LAKSHMI.V Postgraduate

Student in Pediatrics, Kempegowda Institute Of Medical Sciences, Bangalore,

under the guidance of Dr. CHANDRAKALA.P M.D, Associate Professor of

Paediatrics, Kempegowda Institute of Medical Sciences and Research Centre ,

Bangalore

Signature and Seal of HOD Signature and Seal of Dean

Dr. A.C.RAMESH M.B.B.S., M.D.,DCH Dr. M.K. SUDARSHAN M.D (BHU), FAMS

Professor and Head of Department Dean And Principal

Department of Paediatrics Kempegowda Institute of Medical Sciences

Kempegowda Institute of Medical Sciences and Research Centre

and Research Centre Bangalore.

Bangalore.

Date : Date :

Place : Bangalore Place : Bangalore

  V

COPYRIGHT

DECLARATION BY THE CANDIDATE

I hereby declare that the Rajiv Gandhi University of Health Sciences,

Karnataka shall have the rights to preserve, use and disseminate this dissertation /

thesis in print or electronic format for academic / research purpose.

Date:

Place: Bangalore Dr. LAKSHMI.V

© Rajiv Gandhi University of Health Sciences, Karnataka

  VI

ACKNOWLEDGMENT

I consider it my utmost privilege and honour to owe my immense gratitude

and respect to my mentor and guide Dr. CHANDRAKALA.P, Associate

Professor of Paediatrics, Kempegowda Institute of Medical Sciences and

Research Centre, Bangalore, who has long and steadfastly encouraged, constantly

guided and supported me. Her efforts, wise expertise and counsel have had an

indelible impact on me throughout my post-graduate course and on the final form

and quality of this dissertation.

I am extremely thankful to Dr. M. K. SUDARSHAN, Dean, Principal

and Professor of Community Medicine, Kempegowda Institute of Medical

Sciences, Bangalore for giving me an opportunity to conduct this study.

I immensely thank our beloved Head of Department of Pediatrics,

Dr.A.C.RAMESH who has been a friend, philosopher and a guide throughout

my course for his valuable support.

I thank Dr. SURESH., Medical Superintendent, Dr.(Capt.)

G.S.VENKATESH, Medical Director and Dr. VEERANNA, AMO, for allowing

me to conduct this study in this Institute and for their valuable support during the

study period.

It is with a humble sense of gratitude that I express my heartfelt thanks to

Dr. NISARGA.R, Dr. S.R. KESHAVAMURTHY, Dr. SRINIVASA.S,

Dr.YASHODHA.H.T, Professors in department of Paediatrics for their help and

guidance throughout my course.

  VII

I also thank Dr. MURALI.B.H, Dr. POORNIMA SHANKAR,

Associate Professors in department of Paediatrics for their professional guidance

and encouragement during my post-graduate course.

I am immensely thankful to Dr.MADHU.G.N, Dr.H.S.RAMYA,

Dr.HARISH.J, Dr.SIVASHARANAPPA, Dr.GIRISH and Dr.SUSHANTH,

Assistant Professors in department of Paediatrics for their kind guidance during

the course.

I thank Dr.MOHAN KUMAR, Dr.DEEPASHRI, Dr.TANVIR AND

Dr.SHYLAJA, Senior residents in the department of Paediatrics for their

valuable support.

I thank Dr.NARESH, Dr.JAYAPRAKASH, Dr.SNEHA,

Dr.ARCHANA and all my other Post graduate colleagues for their wholehearted

support.

On a personal note, special thanks to my Husband MR. KARTHIK.J.

LINGAM , a dear friend, for his endless patience, constant encouragement and

unconditional moral support in this process of learning.

My most regardful thanks and I am ever grateful to my Father Mr.

S.VENKATESHA, my Mother Mrs. VIBHA.V, my Brother Mr. NAVEEN

KUMAR.V and my IN-LAWS, who have been a constant motive force and

support behind everything I do in my life. It is their love, prayers and sacrifice

that has made my education possible.

My sincere thanks to all the patients and their parents who have

participated in this study, without whose valuable time and co-operation, this

study would have been just a dream.

  VIII

I also thank the Nursing staff, Dept Steno Mr. BABU and Dept Attender

Mr. PURANDAR for their help and encouragement during my PG course.

I thank M/s CYBER GARDEN for their meticulous typing and styling of

this script.

Above all, I thank the Almighty for showering me with His love and for

having blessed me to pursue the PG course in the most noble subject of the most

noble profession i.e. Paediatrics.

Date:

Place: Bangalore Dr. LAKSHMI.V

  IX

ABSTRACT 

Background: Dengue is the most important emerging tropical viral disease of

humans in the world today. It is estimated that there are between 50 and 100

million cases of dengue fever (DF) and about 500,000 cases of dengue

hemorrhagic fever (DHF) each year which require hospitalization. Over the last

10-15 years, DF/DHF has become a leading cause of hospitalization and death

among children in the South-East Asia Region of WHO, following diarrhoeal

diseases and acute respiratory infections. Earlier it was prevalent in those areas

with humid atmosphere and plenty of rains with changing monsoon pattern this

disease becoming prevalent in deccan land scape including Karnataka. Dengue is

a mosquito-borne disease, caused by serologically related but antigenically

distinct single-strand positive sense RNA viruses; the viruses have been grouped

into four serotypes (DENV-1 through DENV-4) belonging to the genus Flavivirus

(family Flaviviridae). Aedes aegypti is the primary mosquito vector; however,

other species from the genus Aedes ,such as Aedes albopictus , can also be

vectors of dengue virus transmission. It is important to recognise the clinical

signs and symptoms, alterations in the biochemical parameters, radiological

findings and the multi system involvement pattern to manage dengue cases

effectively. The current study is undertaken to study the various clinical

presentation , laboratory parameters and radiological features of Dengue Fever

and to evaluate common modes of clinical presentation and complications of

dengue in our hospital and to correlate these features with lab findings and the

various factors affecting the prognosis which may help us in early diagnosis and

better case management.

  X

Aim: To assess various clinical manifestations of Dengue fever, to describe the

atypical presentation and complications, to establish the diagnosis of dengue fever

based on dengue antigen (NS 1) and antibody (IgM , IgG) and to find the

association between the clinical findings with laboratory investigations and

radiological findings.

Methods: 100 cases of suspected cases of dengue infection i.e. children below 18

yrs of age with clinical features suggestive of Dengue infection and children

presenting with fever of acute onset (<2wks), pain abdomen, vomiting, rash,

flushed appearance and bleeding manifestation admitted to KIMS, Bangalore

between December 2010 to April 2012 were studied. A detailed clinical history

and physical examination was done and baseline investigations were performed .

The cases were followed-up daily for the clinical and laboratory parameters.

WHO classification and case definition was used to classify Dengue Fever,

Dengue Hemorrhagic Fever and Dengue Shock Syndrome. And were treated

according to WHO guidelines. The data related to each of these cases was

collected, compiled and analysed.

Results: Out of 100 children in this study 36% cases belongs to DF, 33% cases

belongs to DHF, 15% cases belongs to DSS group and 16% cases belongs to DLI.

Conclusion: The clinical manifestation, examination finding, laboratory

parameters and radiological evidences in this study was similar to other Indian

studies.

In our present study classical dengue fever was most common presentation

followed by DHF and DSS.

  XI

In children importance should be given to symptoms like, fever, vomiting,

abdominal pain, retro orbital pain, bleeding, musculoskeletal pain and flushing

during an epidemic of dengue fever.

If these associated with positive tourniquet test, hepatomegaly, elevated liver

enzymes, elevated PTT, thickened gall bladder on USG abdomen, pleural effusion

on chest X-ray, a strong possibility of dengue fever should be considered.

Platelet count does not correlate with severity of the disease.

During epidemics, differential diagnosis of dengue fever to be strongly considered

in a child with fever.

A focused history , detailed clinical examination and appropriate relevant

investigations can aid for early diagnosis and treatment. Proper evaluation of the

progress of the disease is a key in the management of disease.

Keywords : Dengue fever; Dengue Hemorrhagic Fever; Dengue Shock

Syndrome; Thrombocytopenia; Epistaxis; Liver enzymes; Shock; Bleeding;

WHO; Tourniquet test; Hematocrit.

 

  XII

LIST OF ABBREVIATIONS USED

+ / - Present or absent

ADE Antibody-dependent enhancement

ARDS Acute Respiratory Distress Syndrome

ALT Alanine transaminase

ALK Alkaline phosphatase

APTT Activated partial thromboplastin time

ARBO Arthropod-borne

AST Aspartate transaminase

BT Bleeding time

C Complement

CD Cluster of Differentiation

CMV Cytomegalovirus

CNS Central nervous system

CT Clotting time

CVS Cardiovascular System

Cu.mm Cubic millimeter

CXR Chest X-ray

DEN Dengue

DF Dengue fever

DHF Dengue hemorrhagic fever

DIC Disseminated intravascular coagulation

DNA Deoxyribose Nucleic Acid

DSS Dengue shock syndrome

  XIII

EBV Epstein Barr Virus

ELISA Enzyme linked immunosorbent assay

GB Guillain Barre Syndrome

GIT Gastrointestinal Tract

Hb Haemoglobin

HCT Hematocrit

HLA Human Leucocyte Antigen

IFN Interferon

IgM/IgG Immunoglobulin M/Immunoglobulin G

IL Interleukin

JEV Japanese encephalitis virus

KD Kilo Dalton

LN Lymphadenopathy

LFT Liver function test

MAC ELISA IgM Antibody Capture Enzyme linked immunosorbent assay

MRI Magnetic resonance imaging

NS Nonstructural protein

NSAIDs Non steroidal anti inflammatory drugs

ORS Oral Rehydration Solution

PCR Polymerase chain reaction

PT Prothrombin time

RBC Red blood corpuscles

RNA Ribo nucleic acid

ROP Retro orbital pain

RR Respiratory Rate

  XIV

RS Respiratory system

SA Serum Albumin

SGOT Serum glutamate oxaloacetate transaminase

SGPT Serum glutamate pyruvate transaminase

SLEV Saint Louis encephalitis virus

TC/TLC Total leucocyte count

TNF Tumour necrosis factor

USG Ultra sonography

WBC White blood corpuscles

WHO World health organization

WNV West Nile virus

YFV Yellow fever virus

  XV

TABLE OF CONTENTS

SI No. PARTICULARS Page No.

1 INTRODUCTION 1

2 OBJECTIVES 2

3 REVIEW OF LITERATURE 3 - 54

3.1 INTRODUCTION 3

3.2 HISTORY 3

3.3 EPIDEMIOLOGY 8

3.4 PATHOLOGY 20

3.5 PATHOGENESIS 23

3.6 CLINICAL FEATURES 30

3.7 DIAGNOSIS 44

3.8 MANAGEMENT 47

3.9 VECTOR SURVEILLANCE AND CONTROL 52

4 METHODS AND MATERIALS 55 - 58

4.1 SOURCE OF DATA 55

4.2 METHODS OF COLLECTION OF DATA 55

4.3 SAMPLE SIZE AND DESIGN 55

4.4 METHODOLOGY 56

5 RESULTS 59 - 95

6 DISCUSSION 96 - 107

7 CONCLUSION 108 - 109

  XVI

8 SUMMARY 110 - 111

9 BIBLIOGRAPHY 112 - 124

10 ANNEXURES

10.1 ETHICAL CLEARANCE FOR DISSERTATION STUDY 125

10.2 CLINICAL PHOTOGRAPHS 126

10.3 PROFORMA 127

10.4 KEY TO MASTER CHART 133

10.5 MASTER CHART  

 

 

 

 

 

 

 

  XVII

LIST OF TABLES

SI

N

o. TABLE

PAGE

NO

1 DIAGNOSIS – CLINICAL SPECTRUM OF

CASES 59

2 AGE DISTRIBUTION OF PATIENTS 60

3 AGE DISTRIBUTION OF PATIENTS

ACCORDING TO CLINICAL SPECTRUM 61

4 GENDER DISTRIBUTION OF PATIENTS 62

5 GENDER DISTRIBUTION OF CASES

ACCORDING TO CLINICAL SPECTRUM 63

6 SYMPTOMATOLOGY OF CASES 64

7 ANALYSIS OF SYMPTOMATOLOGY 65

8 SIGNS IN PATIENTS 67

9 TEMPERATURE 68

10 DISTRIBUTION OF SIGNS ACCORDING

TO CLINICAL SPECTRUM 69

11 RESPIRATORY SYSTEM EXAMINATION 70

12

DISTRIBUTION OF AIR ENTRY

(RESPIRATORY SYSTEM)

ACCORDING TO CLINICAL SPECTRUM OF

CASES

71

13 RELATIONSHIP BETWEEN VARIOUS SITES

OF BLEEDING AND DENGUE FEVER 72

14 RELATIONSHIP BETWEEN VARIOUS SITES

OF

BLEEDING AND DENGUE FEVER

73

  XVIII

ACCORDING

TO CLINICAL SPECTRUM

15 TYPES OF SKIN RASHES 74

16 DISTRIBUTION OF TYPES OF SKIN RASHES

ACCORDING TO CLINICAL SPECTRUM 75

17 TOURNIQUET TEST 76

18 ANALYSIS OF TOURNIQUET TEST RESULTS

ACCORDING TO CLINICAL SPECTRUM 77

19 PLATELET COUNT 78

20 PLATELET COUNT 78

21 HAEMOGLOBIN LEVELS ACCORDING TO

CLINICAL SPECTRUM OF CASES 79

22 HAEMOGLOBIN LEVELS (Hb g%) 79

23 HEMATOCRIT (PACKED CELL VOLUME)

ACCORDING TO CLINICAL SPECTRUM OF

CASES

80

24 HEMATOCRIT (PCV%) 80

25 TOTAL LEUCOCYTE COUNT ACCORDING

TO CLINICAL SPECTRUM OF CASES 81

26 TOTAL LEUCOCYTE COUNT (TLC in cells/cu

mm) 81

27 PROTHROMBIN TIME ACCORDING TO

CLINICAL

SPECTRUM OF CASES

82

28 PROTHROMBIN TIME (PT in seconds) 82

29 ACTIVATED PARTIAL THROMBOPLASTIN

TIME ACCORDING TO CLINICAL SPECTRUM

OF CASES

83

30 ACTIVATED PARTIAL THROMBOPLASTIN

TIME 83

  XIX

(APTT in seconds)

31 BLOOD UREA ACCORDING TO CLINICAL

SPECTRUM OF CASES 84

32 BLOOD UREA 84

33 SERUM CREATININE ACCORDING TO

CLINICAL

SPECTRUM OF CASES

85

34 SERUM CREATININE 85

35 LIVER FUNCTION TESTS- SERUM

GLUTAMATE OXALOACETATE

TRANSAMINASE (SGOT)

87

36 SERUM GLUTAMATE PYRUVATE

TRANSAMINASE (SGPT) 87

37 SERUM ALBUMIN ACCORDING TO

CLINICAL SPECTRUM OF CASES 88

38 SERUM ALBUMIN (g/dl) 88

39 SERUM ELECTROLYTES 89

40 DENGUE SEROLOGY 90

41 DENGUE SEROLOGY ACCORDING TO

CLINICAL

SPECTRUM OF CASES

91

42 CHEST X-RAY 92

43 CHEST X-RAY FINDINGS ACCORDING TO

CLINICAL SPECTRUM 93

44 ULTRASONOGRAPHY 94

45 ULTRASONOGRAPHY FINDINGS

ACCORDING TO CLINICAL SPECTRUM 95

  XX

LIST OF FIGURES

SI No. FIGURES PAGE

NO

1 ANNUAL WORLDWIDE INCIDENCE OF DENGUE FEVER 5

2 WORLD WIDE DISTRIBUTION OF DENGUE FEVER 6

3 EMERGENCE OF DEN/DHF 6

4 FLAVIVIRUS VIRION STRUCTURE 10

5 DENGUE VIRUS 11

6 FLAVIVIRUS GENOME 12

7 AEDES AEGYPTI MOSQUITO 13

8 LIFE CYCLE OF AEDES AEGYPTI MOSQUITO 14

9 TRANSMISSION OF DENGUE VIRUS 20

10 MECHANISM OF ACTION OF DENGUE VIRUS 28

11 COURSE OF DENGUE ILLNESS 34

12 COMPARISON OF DIAGNOSTIC TESTS 44

13 PRIMARY & SECONDARY DENGUE INFECTION 44

14 RASH IN CASE OF A DENGUE FEVER 126

15 RIGHT SIDED PLEURAL EFFUSION IN CASE OF DENGUE FEVER 126

  1

INTRODUCTION

Dengue fever is an arthropod borne viral fever. It is acquiring epidemic

proportion in this part of the world.

The geographical distribution has greatly expanded over the last 30 years,

because of increased potential for breeding of Aedes aegypti. This has been prompted

by demographic explosion, rapid growth of urban centers with strain on public

services, such as potable water and rainwater harvesting. Dengue fever (DF) with its

severe manifestations such as Dengue Hemorrhagic Fever (DHF) and Dengue Shock

syndrome (DSS) has emerged as a major public health problem of international

concern.1

Today, Dengue ranks as one of the most important mosquito-borne viral

disease in the world. In the past 50 years, its incidence has increased 30-fold with

significant outbreaks occurring in five of six WHO regions. Current estimates report

that, atleast 112 countries are endemic for Dengue and about 40% of the world

populations (2.5-3 billion people) are at risk in tropics and sub-tropics. Estimates

suggest that annually 100 million cases of dengue fever and half a million cases of

dengue haemorrhagic fever (DHF) occur in the world with a case fatality in Asian

countries of 0.5%–3.5%. 90% of DHF subjects are less than 15 years of age. Early

recognition and prompt initiation of treatment are vital if disease related morbidity

and mortality are to be controlled.2

Dengue fever is caused by an RNA virus of the family Flaviviridae;

genus Flavivirus. It has 4 closely related serotypes DEN 1 ,DEN 2 , DEN 3 , DEN4

which bear partial cross reactivity with each other. The viruses are transmitted to man

by the bite of infective mosquitoes, mainly Aedes aegypti.

  2

OBJECTIVES

1. To assess various clinical manifestations of Dengue fever.

2. To describe the atypical presentation and complications.

3. To establish the diagnosis of dengue fever based on dengue antigen (NS 1)

and antibody ( IgM , IgG )

4. To find the association between the clinical findings with laboratory

investigations and radiological findings.

  3

REVIEW OF LITERATURE

3.1 INTRODUCTION

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 50-100 million dengue infections occur annually and approximately 2.5

billion people live in dengue endemic countries.

3.2 HISTORY OF DENGUE

Dengue fever (DF) is an old disease; the first record of a case of probable

dengue fever is in a Chinese medical encyclopedia from the Jin Dynasty (265–420

AD) which referred to a “water poison” associated with flying insects.6 As the global

shipping industry expanded in the 18th and 19th centuries, port cities grew and

became more urbanized, creating ideal conditions for the principal mosquito vector,

Aedes aegypti. Both the mosquitoes and the viruses were thus spread to new

geographic areas causing major epidemics. Because dispersal was by sailing ship,

however, there were long intervals (10-40 years) between epidemics. In the aftermath

of World War II, rapid urbanization in Southeast Asia led to increased transmission

and hyperendemicity. The first major epidemics of the severe and fatal form of

disease, dengue haemorrhagic fever (DHF), occurred in Southeast Asia as a direct

result of this changing ecology.

In the last 25 years of the 20th century, a dramatic global geographic

expansion of epidemic DF/DHF occurred, facilitated by unplanned urbanization in

tropical developing countries, modern transportation, lack of effective mosquito

control and globalization. As we go into the 21st century, epidemic DF/DHF is one of

  4

the most important infectious diseases affecting tropical urban areas. Each year there

are an estimated 50-100 million dengue infections, 500000 cases of DHF that must be

hospitalized and 20000-25000 deaths, mainly in children. Epidemic DF/DHF has an

economic impact on the community of the same order of magnitude as malaria and

other important infectious diseases. There are currently no vaccines nor antiviral

drugs available for dengue viruses; the only effective way to prevent epidemic

DF/DHF is to control the mosquito vector, Aedes aegypti.3

The first definite clinical report of Dengue is attributed to Benjamin Rush in 1789.4

Since the geographical distribution of Dengue fever is world-wide, involving

nearly all tropical and subtropical countries, it has many names like-dandy fever,

Denguero, denga, dunga,break-bone fever, bouguet, seven day fever, bonon,

chapenonada, Knieueble, Tokkive-ana, Mal de genoux, homa mguu, and coup-d-

barre.5

The origins of the word dengue are not clear, but one theory is that it is

derived from the Swahili phrase "Ka-dinga pepo", meaning "cramp-like seizure

caused by an evil spirit". The Swahili word "dinga" may possibly have its origin in

the Spanish word "dengue" meaning fastidious or careful, which would describe the

gait of a person suffering the bone pain of dengue fever . Alternatively, the use of the

Spanish word may derive from the similar-sounding Swahili. Slaves in the West

Indies who contracted dengue were said to have the posture and gait of a dandy, and

the disease was known as "Dandy Fever".

The first recognized Dengue epidemics occurred almost simultaneously in

Asia, Africa, and North America in the 1780s, after the identification and naming of

the disease in 1779.

  5

Benjamin Rush coined the term "breakbone fever" because of the symptoms

of myalgia and arthralgia. The viral etiology and the transmission by mosquitoes

were only deciphered in the 20th century. Nowadays, about 2.5 billion people, or 40%

of the world’s population, live in areas where there is a risk of dengue transmission .

Dengue spread to more than 100 countries in Asia, the Pacific, the Americas, Africa,

and the Caribbean.

Fig 1: ANNUAL WORLDWIDE INCIDENCE OF DENGUE FEVER.

The appellation of break-bone fever for dengue is attributed to the popular

name given to the disease in the first described epidemic of an illness that is clinically

compatible with dengue in Philadelphia in 1780.6

Dengue hemorrhagic fever has been recognized as a separate disease entity

from classical dengue fever since the second half of twentieth century with the first

out break called “Philippine Hemorrhagic fever” in 1953. This was followed by out

break in Thailand in 1958, which was referred to as “Thai hemorrhagic fever”.The

term Dengue shock syndrome was coined to describe the cases of DHF with shock.

  6

The clinical studies indicated that it was caused by increased vascular permeability

and resultant intravascular hypovolemia.7

MAGNITUDE OF THE PROBLEM : WORLD SCENARIO

Fig 2 : WORLD WIDE DISTRIBUTION OF DENGUE FEVER

Fig 3 : EMERGENCE OF DEN/DHF

Dengue and dengue haemorrhagic fever are present in urban and suburban

areas in the Americas, South-East Asia, the Eastern Mediterranean and the Western

Pacific and dengue fever is present mainly in rural areas in Africa.

  7

Several factors have combined to produce epidemiological conditions in

developing countries in the tropics and subtropics that favour viral transmission by the

main mosquito vector, Aedes aegypti:

rapid population growth,

rural-urban migration,

inadequate basic urban infrastructure (eg. unreliable water supply

leading householders to store water in containers close to homes),

increase in volume of solid waste, such as discarded plastic containers

and other abandoned items which provide larval habitats in urban

areas.

Geographical expansion of the mosquito has been aided by

international commercial trade particularly in used tyres which easily

accumulate rainwater.

Increased air travel and breakdown of vector control measures have

also contributed greatly to the global burden of dengue and DHF.8

WHO has reported that a temperature rise of 1–2⁰ C could result in an increase

of the risk population by several hundred million, with 20,000– 30,000 more fatal

cases annually.9

MAGNITUDE OF THE PROBLEM : INDIAN SCENARIO

India is one of the seven identified countries in the South-East Asia region

regularly reporting incidence of DF/DHF outbreaks and may soon transform into a

major niche for dengue infection in the near future.10

The first recorded outbreak of dengue fever in India was in 1812.5

The dengue virus was isolated for the first time almost simultaneously in

Japan and Calcutta in 1963.12 After the first virologically proved epidemic of dengue

  8

fever along the East Coast of India in 1963-1964, it spread to all over the country.

DEN-2 virus strains were isolated from patients with severe haemorrhagic

manifestations . Further outbreaks occurred in 1965, 1967 and 1968. All four

serotypes of Dengue viruses have been isolated form various parts of India. New

Delhi, reported outbreaks of Dengue fever in 1967, 1970 and 1982,1996,2003. DEN-

2 were isolated during the 1970 epidemic. An explosive outbreak of Dengue fever

occurred between August and October 1982.15 The first full-blown epidemic of the

severe form of the illness,the dengue haemorrhagic fever/dengue shock syndrome

occurred in North India in 1996.11

DHF was first reported in Calcutta (Kolkata), West Bengal in 1963 , again in

1964 . Since then, there are numerous studies from the Indian subcontinent

investigating DHF in various parts of the country.13

In 1960, DEN-1 was isolated in Vellore, in the south, without any association

with hemorrhagic diathesis.14

3.3 EPIDEMIOLOGY

DHF first emerged as a public health problem in 1954, when the first epidemic

occurred in Manila. This gradually spread to other countries in the region. Major

epidemics occurred in other regions of the world in the 1980s and 1990s and were

caused by all four dengue viral serotypes. While the predominant serotype in the

1980s and the early 1990s was DEN-2, in recent years it has changed to the DEN-3

serotype. In 1998, a pandemic of dengue viral infections occurred, where 1.2 million

cases of dengue fever and DHF were reported from 56 countries worldwide. The

world population was exposed to a new subtype of the DEN-3 virus (subtype III),

which originated in the Indian subcontinent and later spread to involve other

  9

continents. Exposure of a non-immune population to this new subtype of DEN-3 may

have been the cause of this pandemic. A situation of comparable magnitude was also

seen in 2001–02.

Microevolution of the dengue virus may have also contributed to the spread of

more virulent strains around the world. In fact there is evidence that the more virulent

genotypes of the virus are replacing the less virulent genotypes, which may explain

the global emergence of dengue infections.

EPIDEMIOLOGICAL TRENDS IN SOUTH ASIA

The first major epidemic of DHF occurred in Sri Lanka in 1989. Since then

regular epidemics have been occurring in Sri Lanka. As yet, no cases of DHF have

been reported from Nepal or Bhutan, endemicity is uncertain.2

AGENT – THE DENGUE VIRUS

DEN-II was isolated by Sabin and his co workers in 1944.15 In 1956 Hammon

and coworkers isolated two new serotypes of Dengue virus, designated DEN-3 and

DEN-4, as well as the previously recognized DEN-1 and DEN-2 during epidemics of

severe hemorrhagic in the Philippines.16

STRUCTURE OF DENGUE VIRUS:

Dengue virus belong to a larger, heterogeneous group of viruses called

arboviruses. This is an ecological classification, which implies that transmission

between vertebrate hosts including humans is dependent upon haematophagous

(blood-sucking) arthropod vectors.

The known natural hosts for Dengue virus are man, lower primates, and

mosquitoes.17

Dengue virus (DENV) is a member of the genus Flavivirus in the

family Flaviviridae.18

  10

Flaviviridae are enveloped viruses with positive-strand RNAgenomes that

have been grouped into three genera, Hepacivirus, Pestivirus, and Flavivirus.19

There are over 70 antigenically related viruses in the genus Flavivirus,

including the type species, Yellow fever virus. The genus includes several antigenic

complexes, including the dengue complex, the Japanese encephalitis complex and the

tick-borne encephalitis complex. The Japanese encephalitis complex includes several

well known disease pathogens of humans, including Japanese encephalitis, Murray

Valley encephalitis, St Louis encephalitis, West Nile, Kunjin, Zika and other viruses,

all of which are transmitted by mosquitoes. The tick-borne flaviviruses include Tick-

borne encephalitis, Omsk haemorrhagic fever and Kyasanur Forest disease viruses.20

Fig 4: FLAVIVIRUS VIRION STRUCTURE

  11

Fig 5: DENGUE VIRUS

The structural proteins are included in mature virion, whereas the NS proteins

play various roles in virus replication and polypeptide processing.

NS1 – a glycoprotein is detected in high titres in patients with secondary dengue

infection. Its function is unknown.

NS2 – codes for 2 proteins (NS2A and NS2B), which play a role in polyprotein

processing.

NS3 – the viral proteinase functions in the cytosol.

NS4 – this region codes for two small hydrophobic proteins involved in the

membrane bound RNA replication complex establishment.

NS5 – most conserved flavivirus protein. This protein is assumed to be the virus

encoded RNA dependent RNA polymerase.

NS6 and NS7 – function yet to be found.

  12

Fig 6: FLAVIVIRUS GENOME

Infection with one serotype is thought to produce lifelong immunity to that

serotype but only a few months immunity of the others. Humans and mosquitoes

(aedes aegypti) are the principal hosts of Dengue virus; the mosquito remains infected

for life, but the viruses are only known to cause illness in humans. In forest and

enzootic cycles in Africa and Asia, the virus is probably sustained through vertical

(transovarial) transmission in the mosquito with periodic amplification in non-human

primates.21

  13

VECTOR : MOSQUITO

Fig 7: AEDES AEGYPTI MOSQUITO

  14

Fig 8: LIFE CYCLE OF AEDES AEGYPTI MOSQUITO

Transmission by Aedes aegypti which belongs to Stegomyia family, first

described by Bancroft in 1906, was later proved by Silver et al and Simmons et al.22

Aedes aegypti, considered the most effective vector, originated in the forests

of Africa and is found in between 35 degrees north and 35 degrees south latitude.

The characteristic features of the Aedes aegypti are:

It is highly susceptible to Dengue virus.

It feeds preferentially on human blood.

Rest indoor, maximizes man- vector contact.

It is a daytime feeder.

Its bite is almost imperceptible.

It is a container breeder like flower vases, uncovered barrels, buckets, and

discarded tyres, but the most dangerous areas are wet shower floors and toilet

tanks.

  15

It is restless mosquito as the slightest movement interrupts feeding, thus

several people may be bitten in a short period for one blood meal.

The female mosquito feeds during the daytime, with peak activity in the

mornings and late afternoons.

Flight range studies suggest that most female Ae. aegypti may spend their lifetime

in or around the houses where they emerge as adults and they usually fly an average

of 400 metres. This means that people, rather than mosquitoes, rapidly move the virus

within and between communities and places.

Unlike most mosquitoes, A aegypti takes more than one blood meal during a

gonotropic cycle—that is, before the eggs are laid. In many areas, dengue epidemics

occur during the warm, humid, rainy seasons, which favour abundant mosquitoes and

shorten the extrinsic incubation period.23

Dengue transmission is largely confined to tropical and subtropical regions

because

freezing temperatures kill overwintering larvae and eggs of Ae. aegypti mosquitoes .

Also, temperature strongly affects pathogen replication, maturation, and period of

infectivity, as laboratory data suggest that the extrinsic incubation period (or viral

development rate) shortens nonlinearly with higher temperatures, increasing the

proportion of mosquitoes that become infectious at a given time . Also, elevated

temperatures can shorten insect survival time or disrupt pathogen development.24

The average lifespan of an Aedes mosquito in Nature is 2 weeks

The mosquito can lay eggs about 3 times in its lifetime, and about 100 eggs

are produced each time.

The eggs can lie dormant in dry conditions for up to about 9 months, after

which they can hatch if exposed to favourable conditions, i.e. water and food

  16

After feeding on a viraemic individual, the mosquito may transmit the

virus directly by change of host, or after 8 to 10 days during this time the virus

multiplies in the salivary glands. The infected mosquito then remains capable

of transmission for its entire life. Transovarian transmission of Dengue virus

has been documented and A.aegypti eggs are highly resistant to desiccation

and can survive for extended periods.25

Aedes albopictus is indigenous to Southeast Asia, feeds during the day and has

been shown to have a higher biting frequency than A.aegypti. It was introduced into

Nigeria, Europe and the United States, probably by shipments of used automobile

tyres.

Aedes aegypti Index is the ratio expressed as percentage of the number of houses

in a well defined limited area in surrounding of which breeding places of Aedes

aegypti has been identified to the total number of houses surveyed in that area.

Breteau Index: Number of positive containers per 100 houses inspected.

Container Index : Percentage of water holding containers infested with larvae or

pupae.

House (premise) index : This is the percentage of houses infested with Aedes

aegypti larvae and/or pupae.

THE HOST: HUMAN

After an incubation period of 4--10 days, infection by any of the four virus

serotypes can produce a wide spectrum of illness, although most infections are

asymptomatic or subclinical . Primary infection is thought to induce lifelong

protective immunity to the infecting serotype . Individuals suffering an infection are

protected from clinical illness with a different serotype within 2--3 months of the

primary infection but with no long-term cross-protective immunity.

  17

Individual risk factors determine the severity of disease and include secondary

infection, age, ethnicity and possibly chronic diseases (bronchial asthma, sickle cell

anaemia and diabetes mellitus). Young children in particular may be less able than

adults to compensate for capillary leakage and are consequently at greater risk of

dengue shock.26

The high prevalence, lack of an effective vaccine, and absence of specific

treatment conspire to make dengue fever a global public health threat.27

Air travel has enabled infected humans import viruses. These factors can

change a region form non-endemic (no virus present) to hypoendemic (one serotype

present) to hyperendemic (multiple serotypes present).17

In South East Asia the mean number of annual cases of Dengue haemorrhagic

fever has increased to more than twenty fold in the past forty years. The same pattern

is now unfolding in the Americas.28 The numbers of reported cases of imported

Dengue in countries outside

the tropics have also been increasing.29,30

ENVIRONMENTAL CONDITIONS

Population growth in the tropics provides many susceptible hosts.

Uncontrolled urbanization leads to inadequate management of water and waste,

providing a range of large water stores and disposable, non-biodegradable containers

that become habitats for the larvae. Few control programmes are effective against the

mosquitoes.31

The monsoon and post-monsoon surge of the disease is very well documented,

largely due to an effective breeding opportunity for the mosquito vector.5 The

incidence increases from the monsoon season, reaches a peak in the post-monsoon

season before declining. The reasons for dramatic global emergence of Dengue fever

  18

or DHF as a major public health problem are complex and not very well understood.

However, several important factors can be identified.

Major global demographic changes have occurred, the most important of

which have been uncontrolled urbanization and concurrent population growth.

These demographic changes have resulted in substandard housing and

inadequate water, sewage, and waste management systems, all of which

increase A.aegypti population densities and facilitate transmission of

A.aegypti borne disease.

Effective mosquito control is virtually nonexistent in most Dengue endemic

countries. Considerable emphasis for the past 25 years has been placed on

ultra-low-volume insecticide space sprays for adult mosquito control, a

relatively ineffective approach for controlling A.aegypti.

Increased travel by airplane provides the ideal mechanism for transporting

Dengue virus between population centers of the tropics, resulting in a constant

exchange of Dengue virus and other pathogens.

In most countries the public health infrastructure has deteriorated.

Limited financial and human resources and competing priorities have resulted

in a “crisis mentality” with emphasis on implementing so-called emergency control

methods in response to epidemics rather than on developing programmes to prevent

epidemic transmission. This approach has been particularly detrimental to Dengue

control, because in most countries, surveillance is very inadequate; the system to

detect increased transmission normally relies on reports by local physicians who often

do not consider Dengue in their differential diagnoses.17 As a result, an epidemic has

often reached or passed transmission before it is detected.

  19

Dengue has been linked to urbanization, explaining its maximum incidence in

middle class. The immediate microenvironment of the patient, consisting of artificial

collections of water within the house (as in flower vases, decorative plant pots within

the house), forms a fertile breeding place for the mosquito vector. This leads to

exposure to the mosquito bites and spread of Dengue.

Finally, international commercial trade has aided geographical expansion of

the mosquito, particularly in used tyres, in which rainwater easily accumulates.

Increased air travel and breakdown of vector control measures have also contributed

greatly to the global burden of Dengue fever. 32

ECONOMIC IMPACT OF DENGUE

Few studies on the economic impact of DF, DHF and DSS have been

conducted. For children suffering from dengue fever average hospital stays will be

about 5 – 10 days. Intensive care is required for severely ill patients, including

intravenous fluids, blood or plasma transfusion and medicines. Adults miss work in

order to attend to their children’s illness. Consequently, there are both direct and

indirect costs for each Dengue patient, ranging from inconvenience due to a sick child

with uncomplicated Dengue, to substantial costs for hospitalization and significant

disruption of earning potential. In addition, burden to local municipalities for vector

control activities, and often revenue is lost through reduced tourism. While the exact

cost of each epidemic is difficult to calculate, it is clear that Dengue and DHF/DSS

represent a significant economic burden on the society.33

  20

TRANSMISSION OF DENGUE VIRUS:

Dengue viruses are transmitted to humans through bite of infected female

Aedes Aegypti mosquitoes. Once infected, a mosquito remains infected for life

transmitting viruses to susceptible individuals during probing and feeding. Infected

female mosquito may also pass virus to next generation of mosquitoes by transovarian

transmission but this occurs infrequently and probably does not contribute

significantly to human transmission. Humans are main amplifying host of virus .The

virus circulates in blood of infected human at approximately time that they have

fever.34

Fig 9: TRANSMISSION OF DENGUE VIRUS

3.4 PATHOLOGY

First attack of dengue virus in non immune individuals causes Classic Dengue.

Symptoms begin after 5 to 10 days of incubation period .The severe forms like DHF

and DSS usually occurs during a secondary Dengue infection in persons with pre-

existing, acquired immunity to a heterologous Dengue virus serotype .Illness begins

abruptly with a febrile episode of 2-4 days duration followed by rapid deterioration. 35

, 36

  21

After inoculation, virus reaches the regional lymph nodes and disseminates to

the reticulo endothelial system where it multiples and enters the blood. The

pathological findings include endothelial swelling, Perivascular edema and

infilteration with mononuclear cells. Extensive extravasation of blood without

appreciable inflammatory reaction was observed in petechiae. Hemorrhages found in

skin and subcutaneous tissue, in mucosa of GIT, heart , liver. GI Hemorrhage may be

severe, but subarachnoid or cerebral hemorrhage is rarely seen. Serous effusion with a

high protein content (mostly albumin) commonly present in pleural and abdominal

cavity, pericardial cavity. In most severe cases, lymphocyte tissue shows an increased

activity of B lymphocyte system, with active proliferation of plasma cells and

lymphoblastoid cells and active germinal centres. 37

Pathological finding in other organ system:

LIVER: In liver, there is a focal necrosis of hepatic cells, swelling appearance of

Councillman bodies and hyaline necrosis and kupfer cells. Proliferation of

mononuclear leukocytes and less frequently polymorphonuclear leukocytes occurs in

sinusoids and occasionally in the portal areas.

At autopsy, dengue virus antigen has been found predominantly in liver,

spleen, lymph node and lung cells. The virus has also been isolated at autopsy from

bone marrow, brain, heart, kidney, liver, lungs, lymphnodes and GIT.38

BONE MARROW: In bone marrow, depression of all haemopoetic cell is observed

which could rapidly improve as fever subsides.

KIDNEY: Studies in kidney has a mild immune-complex type of glomerulonephritis,

which could resolve after about 3 weeks with no residual change.

  22

SKIN: Biopsies of skin rashes have revealed perivascular oedema of

microvasculature of dermal papillae and infilteration of lymphocytes and monocytes.

Antigen bearing mononuclear phagocytes has been found in viscinity of this oedema.

Deposition of serum complements, immunoglobulin & fibrinogen on vessel walls has

been described.

The target cells include dendritic reticulum cells, monocytes, lymphocytes,

hepatocytes, and vascular endothelial cells.39

Dengue hemorrhagic fever is distinguished from dengue by the presence of

increased vascular permeability, not by the presence of hemorrhage. Patients with

dengue may have severe hemorrhage without meeting WHO criteria for dengue

hemorrhagic fever. In these cases the pathogenesis probably derives from

thrombocytopenia or a consumptive co-agulopathy, not from the vascular leak

syndrome seen in dengue hemorrhagic fever. Dengue hemorrhagic fever may (grades

III and IV) or may not (grades I and II) include clinical shock, referred to as dengue

shock syndrome.

In primary and secondary infections, higher viral titres are associated with

more severe disease. Higher titres may result in an amplified cascade of cytokines and

complement activation causing endothelial dysfunction, platelet destruction, and

consumption of coagulation factors, which result in plasma leakage and hemorrhagic

manifestations.23

All four serotypes have been associated with DHF . Variations in virus strains

within and between the four serotypes may influence disease severity. Secondary

infections (particularly with DEN-2) are more likely to result in severe disease and

dengue hemorrhagic fever.

  23

The theory of immune enhancement, developed extensively by Halstead.40 The

increased severity seen in secondary infections is due to antibody - dependent

enhancement (ADE) leading to increased replication in Fc receptor-bearing cells 41,

42,43 , where by cross reactive but non-neutralising antibodies from a previous

infection bind to the new infecting serotype and facilitate virus entry into cells

resulting in higher peak viral titres.

3.5 PATHOGENESIS OF DENGUE FEVER / DHF / DSS

These severe forms are characterized by

1) Increased vascular permeability that give rise to loss of plasma from vascular

compartment. This results in haemoconcentration, low pulse pressure and other signs

of shock.

2) Disorders in haemostasis involving vascular changes, thrombocytopenia and

coagulopathy.

After the bite of an infected mosquito, the dengue virus enters the body and

replicates within cells of the mononuclear phagocyte lineage (macrophages,

monocytes, and B cells). Additionally, infection of mast cells, dendritic cells, and

endothelial cells are known to occur. The incubation period of dengue infections is 7–

10 days. A viraemic phase follows where the patient becomes febrile and infective.

Thereafter, the patient may either recover or progress to the leakage phase, leading to

DHF and/or dengue shock syndrome.

The mechanism of bleeding in dengue hemorrhagic fever is not known, but a

mild degree of disseminated intravascular coagulation, liver damage, and

thrombocytopenia may operate synergistically. Capillary damage allows fluid,

electrolytes, small proteins, and, in some instances, red cells to leak into extra

  24

vascular spaces. This internal redistribution of fluid, together with deficits caused by

fasting, thirsting, and vomiting, results in haemoconcentration, hypovolemia,

increased cardiac work, tissue hypoxia, metabolic acidosis, and hyponatremia.

Antibody dependent enhancement is found to occur only in the presence of

subneutralising concentrations of dengue antibodies. DEN-1 immune sera at 1:250

dilution (subneutralising titre), but not at 1:10 dilution, enhances DEN-2 infection of

mononuclear leucocytes, in turn resulting in increased lymphocyte proliferation and

decreased interferon-c (IFN-c) production.

After primary dengue infection, antibodies form against both structural and

non-structural viral proteins. Although, the precise role of these different antibodies is

not known, antibodies against viral NS1 have been shown to induce endothelial cell

apoptosis in a caspase dependent manner.

Varying degrees of thrombocytopenia are common in DHF. Some of the

mechanisms responsible for this include: IgM type of antiplatelet antibodies, dengue

viral specific antibodies, bone marrow hypocellularity (leading to increases in

defective megakaryocytes), or destruction of platelets in the liver and spleen.

Immune complexes have been described in DHF but their role is not yet clear.

16 , 35

Dengue virus infected monocytes, B-lymphocytes, and mast cells produce

different cytokines. At present there is disagreement about the predominant cytokines

produced during dengue fever and DHF. According to Chaturvedi et al serum

concentrations of tumour necrosis factor-a (TNF-a), interleukin (IL)-2, IL-6, and IFN-

c are highest in the first three days of illness whereas IL-10, IL-5, and IL-4 tend to

appear later. IL-2 and IFN-c are Th1 and IL-5 and IL-4 Th2 type cytokines. Thus, it

has been suggested that Th1 responses are seen during the first 3 days and Th2

  25

responses occur later. Increased levels of IL-13 and IL-18 have also been reported

during severe dengue infections, with highest levels seen in patients with grade IV

DHF. Serum IL-12 levels are highest in patients with dengue fever, but undetectable

in patients with grade III and IV DHF.44 DHF patients have higher levels of TNF-a,

IL-6, IL-13, IL- 18, and cytotoxic factor compared with DF patients. These cytokines

have been implicated in causing increased vascular permeability and shock during

dengue infections. Moreover, cytotoxic factor, produced by CD4+ T-cells, induces

macrophages to produce the pro inflammatory cytokines IL- 1a, TNF-a, and IL-8.

Levels of cytotoxic factor correlate with disease severity (being highest in patients

with grade IV DHF). Serum IL-6 concentrations are higher in patients with DHF and

dengue shock syndrome. IL-6 is produced mainly by mast cells and endothelial cells.

It is an endogenous pyrogen that also increases endothelial cell permeability.

Endothelial cells also produced IL-8, having potent proinflammatory and

chemoattractant activity. Levels of IL-8 are higher during severe dengue infections

and highest in those who died. Activated neutrophils release proteinases such as

elastase, which may facilitate neutrophil mediated endothelial injury, and activate the

complement, coagulation, and fibrinolytic systems. Since increased serum IL-8 and

elastase are found in patients with severe infections, they may have an important role

in pathogenesis of dengue infections.

The simultaneous activation of proteolytic enzymes of complement,

coagulation and possibly the Kinin systems may be expected to consume plasma

enzyme inhibitors. Partial depletion of these inhibitors may result in an imbalance

between activated enzymes and inhibitors and thus produce increased vascular

permeability and shock.36 , 45

  26

Dengue virus infected lymphocytes produce both IFN-a and IFN-c ; levels of

the former being higher than the latter. IFN-a inhibits infection of monocytes by the

dengue virus and hence is important in controlling primary dengue infections. IFN-c

is produced early in the course of infection. Peak levels occur on or before the day of

deferverscence and coincide with disappearance of viraemia.

Dengue virus infected dendritic cells produce high levels of TNF-a and IFN-a,

but low levels of IL-12.46 TNF-a prolongs dendritic cell survival by up regulating

antiapoptotic factors within it. Prolonged survival of dengue virus infected dendritic

cells may contribute towards producing severe dengue infections. Serum

concentrations of serum TNF-a, IFN-c, IL-10, and soluble TNF receptor (sTNF-R )

are significantly higher in patients compared with normal controls. Increased levels of

TNF-a and IL-10 correlate with haemorrhagic manifestations and platelet decay

respectively. IL-10 may also down-regulate platelet function and thus contribute to

platelet defects associated with dengue infections. TNF-alpha and NO are produced

primarily by infected monocytes/macrophages and activate endothelial cells, which

can contribute to increased vascular permeability.47 , 48

The dengue virus can infect both CD4+ and CD8+ T-cells.36 Dengue

infections are associated with decreased numbers of CD4+ T-cells, CD8+ T-cells, and

natural killer cells. Reversal of CD4:CD8 ratios tend to occur around the sixth to 10th

day after the onset of fever, being seen more frequently in patients with DHF.

Generalised bone marrow suppression known to occur in dengue infections

may contribute to the absolute lymphopenia.

Early in the acute stage of secondary dengue infections, there is rapid

activation of the complement system. C1q, C3, C4, C5-C8, and C3 proactivators are

depressed, and C3 catabolic rates are elevated. These factors may interact at the

  27

endothelial cell to produce increased vascular permeability through the nitric oxide

final pathway. The blood clotting and fibrinolytic systems are activated, and levels of

factor XII (Hageman factor) are depressed.

The model of “original antigenic sin” involving memory T-cell responses

postulates an inappropriate immune response to a secondary infection due to clonal

expansion of cross reactive memory T cells specific for the previous rather than a

current infection, resulting in delayed viral clearance and/or increased cytokine

secretion. There is evidence that this may occur during secondary DENV infections.

An imbalance in the regulation of coagulation and fibrinolysis, as in the

disseminated intravascular coagulation syndrome (DIC), in conjunction with the

characteristic thrombocytopenia may contribute to the bleeding tendency in DHF.49

  28

Fig 10 : MECHANISM OF ACTION OF DENGUE VIRUS

  29

PLATELET DYSFUNCTION

Platelet defects may be both quantitative or qualitative,i.e in some circulating

platelet during acute phase of DHF may be exhausted (in capable of normal

function).Therefore even a patient with patients count greater than 1,00,000 / cu mm

may still have prolonged bleeding time.

Evidence for activation of blood coagulation system, occurrence of

intravascular coagulation is indicated by low fibrinogen level, decreased platelet

count and high proportion of considerable amount of fibrin and fibrinogen split

products. Further more activation of complement may affect platelet activation and

initiate blood coagulation. 5

Several hypotheses have emerged to explain why DHF occurs in some

individuals who are infected with Dengue virus. These include changes or differences

in viral virulence between serotypes and/or between strains within serotypes.50

Interactions of Dengue virus with other environmental or infectious agent.

Age : usually children are more susceptible to develop DHF.2

Sex : DHF is also reported to be more severe among females.2

DHF tends to be commoner among patients suffering from other chronic

illnesses.2

Differences in genetic susceptibility - Several human HLA class I and II

alleles are associated with development of DHF .Polymorphism in the tumor

necrosis factor alpha, Fc receptor, vitamin D receptor, CTLA-4, and

transforming growth factor genes has been associated with development of

DHF/DSS and certain host factors, such as glucose-6-phosphate

dehydrogenase (G6PD) deficiency, may also contribute to increased

replication of DENV in monocytes.51

  30

The immunologic enhancement of Dengue infection by antibody acquired

from a previous infection with a different Dengue serotype.

Generally malnutrition predisposes to many infectious diseases (for example,

measles or tuberculosis) and tends to correlate positively with severity of disease.

However, malnutrition appears to be significantly uncommon among patients with

DHF, compared with patients with other infectious diseases or healthy children.2

Entry of Dengue virus into mononuclear phagocytes, resulting in the increased

activation of complement and kinins and the release of mediators of vascular

permeability. This proposed mechanism has been supported by laboratory

investigation and several studies have shown that during outbreaks a majority of DHF

patients show secondary immune response patterns.52

However, cases of DHF have been described in patients with primary Dengue

infection.53

3.6 CLINICAL FEATURES

The clinical features of dengue vary with the age of the patient and in addition

to clinically inapparent infections, can be classified into five presentation:

Non-specific febrile illness,

Classic Dengue,

Dengue haemorrhagic fever,

Dengue haemorrhagic fever with Dengue shock syndrome,

Other unusual syndromes such as encephalopathy and fulminant liver

failure.

Three to Ten days after the bite of an infective mosquito, the patient typically

suffers sudden onset of headache, fever, retro-orbital pain, backache, bone and joint

  31

pain, weakness, depression and malaise. Young children with Dengue often have an

undifferentiated febrile illness with a maculopapular rash. Upper respiratory

infections, especially pharyngitis are common. Classic Dengue is more commonly

seen among older children, adolescents, and adults. They are less likely to be

asymptomatic.54

Dengue is abrupt in onset, typically with high fever accompanied by severe

headache, incapacitating myalgias and arthralgias, nausea and vomiting, sore throat,

cough, groin pain, hyperesthesia, dizziness, photophobia, eye pain and rash. The

decline in fever may be followed by 1 to 3 days later by a resurgence of fever and

symptoms, giving a “saddleback” appearance to the temperature curve.55

The characteristic exanthem of DF is estimated to occur in 50-82% of patients

with DF. In DF, the initial rash is a transient flushing erythema of face that typically

occurs shortly before or within the first 24-48 hours of the onset of symptoms and is

thought to be the result of capillary dilatation. Some patients have an evanescent rash

over the thorax and joint flexures. There may be taste aberrations, anorexia and

abdominal pain.

Lymphadenopahty and hepatomegaly may occur but splenomegaly is

infrequent. Fever and associated symptoms may subside after 3 or 4 days and the

patient may recover completely. Recovery may be prolonged and include depression.

Dengue hemorrhagic fever is primarily a disease of children under 15 year of

age. Black populations may be at decreased risk. If major plasma leakage occurs, it

usually develops 24 hours before to 24 hours after defervescence. Patients may

develop effusions and ascites with a variable amount of bleeding. Enlargement and

tenderness of the liver has been reported in up to 40% of patients. As the fever begins

to drop around day 3 to 5, circulatory instability may develop with signs of decreased

  32

peripheral perfusion. Profound shock may follow. Disseminated intravascular

coagulation and severe gastrointestinal hemorrhage have been described. Mortality

can be as high as 10-20% (over 40% if shock occurs) without early appropriate

treatment, but it is as low as 0.2% in hospitals with staff experienced in the disease.

Warning signs that Dengue shock syndrome is impending include:

Sustained abdominal pain.

Persistent vomiting,

Change in level of consciousness (irritability or somnolence),

Sudden change from fever to hypothermia,

Sudden decrease in platelet counts.

The second rash usually occurs 3-6 days after the onset of fever and it is

characterized by asymptomatic maculopapular or morbilliform eruption. In some

cases, individual lesions may coalesce and are then seen as generalized confluent

erythema with petechiae and rounded islands of sparing-“white islands in a sea of

red” and is thought to be due to an immune response to the virus. The generalized

rash characteristically starts on the dorsum of the hands and feet and spreads to the

arms, legs, and torso and it lasts for several days. The morbilliform, maculopapular

rash usually spares palms and soles. Severe itching, especially of the hands and feet,

may accompany this rash, which is sometimes followed by desquamation.

Hemorrhagic manifestations on the skin such as petechiae , purpura, or ecchymosis

are commonly seen in DHF and DSS and rarely in DF. Mucosal involvement is

estimated to occur in 15% to 30% of patients with dengue viral infections and more

commonly in patients with DHF than with DF. The mucosal manifestations noted in

dengue viral infections are conjunctival and scleral injection , small vesicles on the

soft palate, erythema and crusting of lips and tongue.56

  33

During the course of the illness there is often a relative or paradoxical

bradycardia in the face of increased temperature. Patients may have hemorrhagic

manifestations such as epistaxis or menorrhagia. Jaundice is rare. Convulsions may

occur with the onset of fever. The spinal fluid is almost always clear with no elevation

of cell count but the pressure may be increased. Depression, weakness and blurred

vision may resolve slowly during convalescence. Patients may take several weeks to

recover completely. Although these symptoms characterize “classical” Dengue fever,

Dengue virus infection may also manifest a nonspecific febrile illness which can be

confused with influenza, measles or any nonspecific viral syndrome.

Significant Thrombocytopenia may occur in both DHF and “classical”

Dengue. A fall in platelet count associated with a rising hematorit may suggest the

development of DHF.57

A negative tourniquet test may not be sufficient to exclude a diagnosis of DHF in a

febrile patient.58

  34

Fig 11 : COURSE OF DENGUE ILLNESS

3.7 DIAGNOSIS : 59

WHO has laid down the following criteria for the diagnosis of Dengue fever.

Diagnosis of Dengue fever and dengue haemorrhagic fever :

Dengue fever

Acute illness with two or more of :

• Headache;

• Retro-orbital pain;

• Myalgia;

• Arthralgia;

• Rash;

• Haemorrhagic manifestations;

• Leucopenia.

  35

Dengue haemorrhagic fever

All of following criteria must be present :

• Fever, high degree and continuous of 2-7 days duration and occasionally

biphasic.

• Haemorrhagic manifestations (shown by positive tourniquet test, petechiae,

ecchymoses or purpura, or bleeding from mucosa- epistaxis or bleeding from

gums , gastrointestinal tract- hematemesis or melena , injection sites, or other

locations)

• Platelet count <100,000 /mm3

• Objective evidence of plasma leakage due to increased vascular permeability

shown by either fluctuation of packed cell i.e.,

- A rise in Haematocrit equal to or greater than 20% above average for age, sex

and population;

- A drop in Haematocrit following volume replacement treatment equal to or

greater than 20% of baseline ,during the course of illness and recovery or

clinical signs of plasma leakage such as pleural effusion, ascites, or

hypoproteinaemia.

Other clinical manifestations suggestive of DHF are :

• Hepatomegaly (which may be tender)

• Circulatory disturbances (restlessness, cool extremities, capillary refill time >3 sec.,

tachycardia)

• A fall in haematocrit following volume replacement

  36

Dengue shock syndrome

All of the above four criteria for DHF must be present, plus evidence of

circulatory failure manifested by

• Rapid and weak pulse, and Narrow pulse pressure «20 mmHg (2.7 kpa) or

manifested by:

• Hypotension for age(defined as systolic pressure <80 mm Hg for those aged

<5 years or <90 mm Hg for those aged >5 years) and

• Cold, clammy skin and restlessness.

Who grading of dengue haemorrhagic fever :

• Grade I : In the presence of haemoconcentration, fever and non-specific

constitutional symptoms, a positive tourniquet test is the only haemorrhagic

manifestation.

• Grade II : Spontaneous bleeding in addition to the manifestation of Grade I

• Grade III : Circulatory failure, pulse pressure less than 20 mm Hg but

systolic pressure is still normal plus manifestations of Grade II

• Grade IV : Profound shock, hypotension or unrecordable blood pressure.

(Grades III and IV are classified as Dengue shock Syndrome (DSS)).23 , 60

  37

CRITERIA FOR DENGUE ± WARNING SIGNS

CRITERIA FOR

SEVERE DENGUE

Probable Dengue Warning signs

live in /travel to dengue

endemic area.

Fever and 2 of the

following criteria:

• Nausea, vomiting

• Rash

• Aches and pains

• Tourniquet test

positive

• Leukopenia

• Any warning sign

Laboratory-confirmed

Dengue (important when

no sign of plasma leakage)

Abdominal pain or

tenderness

• Persistent vomiting

• Clinical fluid

accumulation

• Mucosal bleed

• Lethargy, restlessness

• Liver enlargment >2 cm

• Laboratory: increase in

HCT

concurrent with rapid

decrease

in platelet count

Severe plasma leakage

leading to:

• Shock (DSS)

• Fluid accumulation with

respiratory

distress

Severe bleeding

as evaluated by clinician

Severe organ involvement

• Liver: AST or ALT

>=1000

• CNS: Impaired

consciousness

• Heart and other organs

DIAGNOSTIC CLASSIFICATION:73

Probable diagnosis An acute febrile illness with two or more of the following manifestations

• Headache

• Retro - orbital pain

• Myalgia

• Arthralgia

  38

• Rash

• Haemorrhagic manifestations

• Leukopenia

• thrombocytopenia (platelet count <100 000 cells/mm3),

• rising haematocrit (5 – 10%);

And

Supportive serology (a reciprocal haemagglutination-inhibition antibody titre

>1280, a comparable IgG enzyme-linked immunosorbent assay (ELISA) titre or a

positive IgM antibody test on a late acute or convalescent-phase serum specimen); OR

- Occurrence at the same location and time as other combined cases of dengue fever.

• Confirmed-a case confirmed by laboratory criteria (see below).

• Reportable-any probable or confirmed case should be reported

Occurrence at same location and time as confirmed cases of Dengue fever.

Confirmed diagnosis :

Atleast one of following :

• Isolation of dengue virus from serum , CSF or autopsy samples.

• Fourfold or greater increase in serum IgG (by haemagglutination inhibition test) or

increase in IgM antibody specific to Dengue virus.

• Detection of Dengue virus in tissue, serum or cerebrospinal fluid by

immunohistochemistry, immunofluorescence, or enzyme linked immunosorbent

assay.

• Detection of Dengue virus genomic sequences by reverse transcription polymerase

chain reaction.

  39

REPORTABLE CASES OF DHF OR DSS:

Patients with provisional diagnosis of DHF or DSS should be reported to the

health Authorities as case of DHF or DSS if there is:

• Virological or serological evidence of acute dengue infection,or

• History of exposure in dengue endemic or epidemic area( during a period of

epidemic transmission ,or significant levels of endemic transmission, it is unlikely

that many cases will have laboratory confirmation).

CASE DEFINITION FOR DENGUE FEVER:

The clinical diagnosis must be supported by laboratory tests .

LABORATORY CRITERIA FOR CONFIRMATION OF DENGUE FEVER

ARE:

• Isolation of the dengue virus from serum

• Demonstration of a four fold or greater change m reciprocal IgG or IgM antibody

titres to one or more dengue virus antigens in paired serum samples ; or

Demonstration of dengue virus antigen in autopsy tissue, serum or cerebrospinal fluid

samples by polymerase chain reaction(PCR).

Atypical variants :

Rare and unusual presentations of Dengue are protean. The atypical variants have

been encountered in various studies. To quote a few,

Acute abdominal pains, diarrhoea, severe gastrointestinal haemorrhage,

Irregular pulse and heart rate, acute renal failure, haemolytic uraemic

syndrome.61

Severe headache, convulsions, altered sensorium, Encephalitic signs

associated with or without intracranial haemorrhage.62

  40

Fulminant hepatic failure, obstructive jaundice, raised liver enzymes,

Reye’s syndrome

Disseminated intravascular coagulation.63

Respiratory distress.64

Vertical transmission in newborns.65

Dengue virus has been isolated from CSF suggesting direct involvement of

the brain.66

Multisystem involvement is increasingly being documented during the last

10 years.

Transient reverse in the CD4/CD8 ratio occurred at days 6-10 after the

onset of fever. These changes in immune parameters indicate aberrant

immune activation during Dengue virus infection.67

The haemophagocytic syndrome is characterized by systemic proliferation

of non-neoplastic histiocytes showing haemophagocytosis resulting in

blood cytopenia. Bone marrow aspirations showed that platelets, red and

white blood cells were phagocyted by histiocytes.68

Rare presentations of infection include severe haemorrhage, jaundice,

parotitis, cardiomyopathy and non-specific ECG changes like ST

elevations, premature ventricular complexes and bradycardia.68

Unusual neurological presentations include mononeuropathies,

polyneuropathies, encephalitis, and transverse myelitis.

Guillain-Barre syndrome has been associated with Dengue.

Encephalopathy occurs occasionally and may result from cerebral edema,

cerebral haemorrahge, liver failure or electrolyte imbalances.`23

  41

Lymphoreticular/bone marrow: Infection associated haemophagocytic

syndrome (IAHS) or Haemophagocytic lymphohistiocytosis (HLH),

idiopathic thrombocytopenic purura , Spontaneous splenic rupture, Lymph

node infarction.74

COMPLICATIONS AND UNUSUAL MANIFESTATIONS

CNS :

Peripheral nerve involvement occur in the form of mononeuritis. The patients

with encephalopathy progressing to the death.

The pathogenesis of dengue encephalopathy include cerebral edema, anoxia, micro

vascular or frank haemorrhages, hyponatraemia and fulminant hepatic failure (DEN 2

and DEN 3 frequently reported as cause of neurological disease) which may a part of

reye like syndrome.69 , 70 , 35

Few patients may develop coma. Encephalopathy and Encephalitis can occur.

Hemorrhagic encephalopathy in DSS caused by type 3 Dengue virus.

GIT , AND LIVER

Hepatitis/fulminant hepatic failure, Acalculous cholecystitis, Acute

pancreatitis, Hyperplasia of Peyer’s patches, Acute parotitis are some of the

manifestations .Dengue fever may present with lower GI bleeding and colonoscopic

features of Acute inflammatory colitis, acute liver failure which may completely

recovers with supportive management, acute abdominal pain, diarrhoea, obstructive

jaundice, Reye's syndrome. 35 , 71

Liver involvement is in the form of hepatitis secondary to either direct viral

invasion or due to consequence of inflammatory reaction . Patient may develop

jaundice , with elevation of liver enzymes . Few cases may progress to fulminant

hepatic failure and lead to hepatic encephalopathy. Typical features of fever , upper

  42

quadrant abdominal pain, abnormality of liver function tests, thickened GB wall

without stones and positive Murphy's sign and sonographic evidence can establish a

diagnosis of Acute acalculus cholecystitis.72 Acalculus cholecystitis may be seen in

patients with DHF.

RESPIRATORY SYSTEM:

The increased permeability of alveolar capillary membrane may result in

Edema in alveoli and interstitial spaces and pulmonary hemorrhage which leads to a

deterioration in pulmonary function.69

Dengue shock syndrome is reported to be third leading causes of ARDS in

pediatric intensive care setting in endemic area. There are two important implication

for this manifestation. First , Early restoration of adequate tissue perfusion is critical

to prevent progression of dengue shock syndrome to ARDS. However equal care must

be exercised to avoid excessive fluid infusion after adequate volume replacement

because fluid over load may result in ARDS. Second, this manifestation in children

requires early recognition and appropriate treatment by means of intermittent positive

pressure ventilation with positive end expiratory pressure.

OCULAR MANIFESTATIONS :

The ophthalmologic findings mainly included retinal hemorrhage as a sign of

increased vascular permeability and breakdown of inner blood retinal barrier and

cotton wool spots representing micro infarction of nerve fibre layer due to occulusion

of pre capillary arterioles.37

Pan ophthalmitis is also seen. Optic neuritis is consistent with colour vision

impairment, in cases of severe exudative maculopathy, the visual recovery may be

prolonged or may remain visually impaired.

  43

RENAL SYSTEM :

Acute renal failure and haemolytic uremic syndrome are the complications.

MUSCULOSKELETAL SYSTEM :

Myositis with raised creatine phosphokinase (CPK) and Rhabdomyolysis.

Individuals with DENV-3 had a higher prevalence of musculoskeletal and

gastrointestinal manifestations, whereas individuals with DENV-4 infection had a

higher prevalence of cutaneous and respiratory manifestations. The higher prevalence

of malaise with DENV-2 and DENV-3 compared with the other DENV serotypes was

also a novel finding. a higher pleural effusion index was found in DENV-2 compared

with DENV-1. DENV serotypes showed a common respiratory endpoint (combining

cough, rhinorrhea, nasal stuffiness, or sore throat) was more prevalent in DENV-3

than DENV-2. An increased prevalence of rhinorrhea with DENV-1 infection and an

increased prevalence of pharyngeal congestion with DENV-4 infection. The DENV-2

period tended to be more associated with mucosal or internal bleeding (e.g.,

hematemesis, melena, menorrhagia, gingival bleeding, and epistaxis), whereas the

milder signs, such as a positive torniquet test and petequiae, were significantly more

associated with the DENV-1 period .75

DIFFERENTIAL DIAGNOSIS OF DENGUE.23

• Arboviruses - Chikungunya virus (this has often been mistaken for dengue in South

East Asia)

• Viral diseases - Hantavirus; measles; rubella; enteroviruses; influenza; hepatitis A

• Bacterial diseases - Meningococcaemia; scarlet fever; typhoid

• Parasitic diseases - Leptospirosis; rickettsial diseases; malaria

  44

3.7 DIAGNOSIS:

Fig 12 : COMPARISON OF DIAGNOSTIC TESTS

Fig 13 : PRIMARY & SECONDARY DENGUE INFECTION

  45

COMMON LABORATORY FINDINGS

Increased Hematocrit (due to hemoconcentration)

Thrombocytopenia – platelet count below 1,00,000 / cu mm, usually observed

in the period between day 3 and day 8 following the onset of illness.57 , 76 , 77 , 79

Lymphocytosis with reactive lymphocytes

Leucopenia.78

Elevated liver enzymes. 80

Increased capillary permeability and the presence of thrombocytopenia with

hemoconcentration differentiate DHF from classical dengue fever.57 , 75 , 81

DIAGNOSIS OF DENGUE

Virus isolation : Detection of dengue virus by culture is definite diagnostic,

but practical consideration limits its use. During the febrile phase, dengue viruses can

be isolated from serum, plasma, or leucocytes. Ideally, blood should be collected

during the febrile period, preferably before the fifth day of illness (that is, before

formation of neutralising antibodies). And as noted above dengue virus is generally

heat labile and special precaution must be taken against thermal inactivation of

specimen. It takes two weeks to read the results and lastly virus culture is expensive.

The immunofluorescence assay is cheaper and provides results faster (24–48 hours).

Molecular detection : The sensitivity, specificity, and rapid detection of

minute quantities of dengue viral material i.e. Dengue RNA in the patient’s serum

makes RT-PCR amplication assay useful for the detection of dengue infection early in

the disease when antibodies are not detected. RT-PCR is more sensitive than virus

isolation, allows for rapid detection of dengue infections (results are usually available

in 24 hours) and easier identification of the circulating serotype . Dengue RNA may

also be identified in individuals, Using In situ hybridization or immunocytochemistry.

  46

Dengue virus antigen detection by immuno cytochemisty is simple and can be used

for routine diagnostic purpose.

Serological diagnosis : It involves detection of antibodies in patients serum.

Methods used for serological diagnosis of dengue infections include:

haemagglutination inhibition tests, enzyme linked immunosorbent assay (ELISA),

complement fixation test and neutralisation tests. The timing of specimen collection

can be more flexible because anti dengue antibody response lasts for at least several

weeks after onset of illness. Immunoglobulins are not easily inactivated by harsh

treatment of specimens.

Dengue specific IgM and IgG ELISA is widely used, as it is relatively

inexpensive, has good sensitivity, and is quick and simple to perform. Most patients

have measurable IgM antibodies by the fifth day of infection. On average, they

become undetectable 30–60 days after the onset of illness. The sensitivity of IgM

ELISA range from 83.9%–98.4% with a specificity of 100%.

The ability of dengue viruses to agglutinate goose erythrocytes is used in the

haemagglutination inhibition test. A fourfold or greater rise in antibody titres is

suggestive of a flavivirus infection (and not diagnostic of dengue infections).

However, a single antibody titre 1:2560 is accepted as indicating secondary dengue

infection if supported by a clinical history suggestive of dengue.

On other hand, serological tests may produce false positive results which may

be due to polyclonal B cell activation or cross reactive antibodies, antibodies elicited

by other flavi virus (eg. Japanese Encephalitis) may cross react with dengue virus.

In summary serological diagnosis is in general less specific than diagnosis by

culture. The serological diagnosis of dengue in population exposed to other

  47

flavivirusis are the challenges. Some degree of uncertainly is inevitable. MAC ELISA

and Hemagglutination inhibition test improve quality of lab diagnosis.

Future challenges in the study of dengue and DHF include the application of

modern techniques such as nucleic acid chips, protein chips and now biomarkers to

avoid cross reaction among different serotypes of dengue virus and other

flavivirus. Plans are development for internationally standardized guidelines to

improve quality assurance of those advanced Laboratory tests.74

A triad of thrombocytopenia, raised hematocrit and elevated liver enzymes can be

used for early diagnosis of Dengue.80

3.8 MANAGEMENT

There is no specific treatment that exist for Dengue. Steroids, antivirals and

(which decreases capillary permeability) have no proven role. Assessment of the

patient's condition includes investigations such as haemoglobin, packed cell volume,

platelet count, liver function tests, prothrombin time, partial thromboplastin time,

electrolytes, and blood gas analysis , renal function tests , chest radiograph and

abdominal ultrasound. Tests may also be done to rule out other causes of acute febrile

illness prevalent in that particular geographic location such as malaria, enteric fever,

chikungunya, hepatitis A etc.

Oral hydration solution should be started early, since the disease can lead to

increased vascular permeability and shock. Paracetamol (aspirin and other non-

steroidal anti-inflammatory drugs should be avoided owing to Reye's syndrome and

haemorrahge) can be used for fever and analgesia. Volume replacement and

transfusion of blood products are essential in patients with shock and severe

haematological abnormalities. The choice of crystalloid or colloid solutions in

  48

Dengue shock syndrome is under debate. The patient's clinical condition should be

monitored until at least 24 hours after defervescence because of the risk of shock.

Management of a child with suspected Dengue infection :

A child with continuous fever for 3 or more days with no focus of infection

identified. Criteria for admission (any of the following) in the presence of

suspicion of Dengue fever:

• Restlessness or lethargy

• Cold extremities or circumoral cyanosis

• Bleeding in any form

• Oliguria or reluctance to drink fluids

• Rapid and weak pulse

• Narrowing of pulse pressure (< 20 mm Hg or hypotension)

• Haematrocrit of 40 or rising

• Platelet count of less than 100,000/mm3

• Acute abdominal pain

• Evidence of plasma leakage, e.g., pleural effusion, ascites

If patient refuses admission, parent should be advised to:

• Encourage child to drink fluids

• Observe for coldness / blueness of extremities

• Administer paracetamol for fever 10-15 m/kg/dose 4-6 hourly (limit to 5 doses in 24

hours)

• Tepid sponging as necessary

  49

Parents must bring the child back immediately to the nearest hospital in the

presence of any one of the following situations:

• Not drinking / feeding poorly

• Passing less urine than usual

• Abdominal pain

• Bleeding in any form

• In older children, inability to sit up, giddiness

• Irritability, drowsiness, restlessness

• Child continues to be unwell

Following are the criterias to consider a patient for hospitalization in case of

significant dehydration (> 10% of normal body weight) has occurred . Signs of

significant dehydration include:

• Increasedcapillary refill time (>2s)

• Tachycardia

• Cool,mottled or pale skin

• Diminished peripheral pulses

• Changes in mental status

• Oliguria

• Sudden rise in haematocrit or continuously elevated haematocrit

• Narrowing of pulse pressure «20mmHg (2.7kPa))

• Hypotension (a late finding representing uncorrected shock).82

Pointers for early diagnosis of DHF:

• Frequent vomiting during first one or two days of febrile illness

• Leucopenia on day 2

  50

Management of grades I and II DHF :

• All cases are to be admitted

• Encourage patient to drink fluids, ORS, fruit-juices

• Start intravenous fluid (1/5 dextrose saline initially) for those with poor oral intake.

• Paracetamol for high fever

• Daily capillary haematocrit determination

• Rise in haematocrit of 20% or more reflects a significant plasma loss and also

indicates need for intravenous fluid therapy

• Monitor urine output, vital signs.

Management of Dengue shock syndrome (Grades III and IV DHF) :

Infuse 0.9% saline or Ringer’s lactate at 10-20ml/kg boluses as rapidly as

possible until vital signs return to normal. 2-3 boluses may be needed in profound

shock. When vital signs improve, change IV fluids to dextrose 5% and 0.45% saline

at a reduced rate, 1-2 times maintenance (3-6 ml/kg/hour), guided by haematocrit,

urine output and vital signs.

If there is not definite improvement in vital signs and if haematocrit remains

high, use plasma or plasma expanders. If there is no definite improvement in vital

signs and if haematocrit is low or has decreased, transfuse blood because this signifies

hemorrhage, occult or obvious. Sudden drop in haemoglobin level is also an indicator

of occult hemorrhage.

Continue replacement of further plasma losses with Dextrose 5% and 0.45%

saline over a period of 24-48 hours. Reduce or discontinue intravenous fluids between

24-48 hours after the onset of shock if vital signs are stable. Reduce intravenous fluids

earlier if patient has good urine output. (Pulmonary edema and massive pleural

effusion will occur if excessive intravenous fluids are given after this stage).

  51

Hyponatraemia and acidosis occur commonly in DSS. These will correct with

fluid resuscitation with 0.9% saline. Periodic arterial blood gases and electrolytes

should be measured.

Blood transfusion :

• Blood transfusion is indicated in significant clinical bleeding, most often

haematemesis and melena.

• Persistent shock with rapidly declining haematocrit level despite adequate volume

replacement, indicates significant clinical bleeding which requires prompt treatment

with blood transfusion.

• It may be difficult to estimate and recognize the degree of internal blood loss in the

presence of haemoconcentration.

• Blood products like fresh frozen plasma, platelet concentrate, and cryoprecipitate

may be indicated in some cases, especially with consumptive coagulopathy causing

significant bleeding.

• In the presence of disseminated intravascular coagulation (DIC), supportive therapy

consisting of maintaining circulatory volume, correcting acidosis with sodium

bicarbonate and hypoxia with oxygen are required in addition to the use of blood

products. Cryoprecipitate (1 unit per 5 kg body weight) followed by platelets of 10-20

ml/kg within one hour and fresh frozen plasma (FFP 10 to 20 ml/kg). Frequent

clinical assessment and regular coagulation profile (PT, PTT, fibrinogen, platelet and

FDP) are mandatory as indicated. The administration of heparin may need to be

considered in patients who develop DIC.

  52

Signs of Recovery:

Stable pulse, blood pressure and breathing rate

Normal temperature

No evidence of external or internal bleeding

Return of appetite

No vomiting

Good urinary output

Stable haematocrit

Convalescent confluent petechiae rash

Criteria for Discharging Patients:

Absence of fever for at least 24 hours without the use of antipyretics

Return of appetite

Visible clinical improvement

Good urine output

Stable haematocrit

Minimum of three days after recovery from shock

No respiratory distress from pleural effusion and no ascites

Platelet count of more than 50,000/mm3

Based on case-definitions, all suspected, probable and confirmed cases of

DF/DHF should be reported to the District Health Officer.82

3.9 VECTOR SURVEILLANCE AND CONTROL:

The most important vector of dengue virus is mosquito which should be the main

target of surveillance and control activities.

  53

Vector Surveillance:

Entomological surveillance is used to determining changes in geographical

distribution and density of vector, obtain relative measurements of the vector

population over time , evaluate control programmes, and facilitate appropriate and

timely decision regarding interventions. Special attention should be given to

surveillance of sea ports, air ports, other points of entry,

Vector control:

1. Environmental control methods : include: reducing vector breeding sites,

solid waste management, modification of man made breeding sites, and

improvements in house design. Environmental management methods to

control Aedes Aegyptus, Aedes Albopticus include the improvement of water

supply and storage, solid waste management and modification of man made

larval habits. Naturally occurring repellents (citronella oil, lemon grass) or

chemical repellents (DEET) are available.

Emergency control measures are based primarily on applications of

insecticides and it is essential to monitor periodically vector's susceptibility to

insecticides. Most widely used are temephos, malathion, fenthion, and

fenithrothion.

2. Biological control of the vector : These methods are targeted against the

larval stages of the dengue vector. They include the use of larvivorous fish

such as Gambusia affinis and Poecilia reticulate, endotoxin producing bacteria

(Bacillus thuringiensis serotype H-14 and Bacillus sphaericus are currently

used), and copepod crustaceans.

  54

3. Chemical control : This includes the application of larvicidal insecticides or

space spraying. Larvicidal or focal control of Aedes Aegypti is usually limited

to containers Maintained for domestic use that can't be eliminated. The

larvicidal agents most commonly used are 1% Temphos sand granules,Insect

growth regulator methoprene.

Dengue Vaccines:

The importance of critical subjects like pathogenesis of dengue haemorrhagic

fever and inadequacy of animal model adversely affected dengue vaccine

development. The efficacy and safety of some of new vaccines candidates have been

evaluated and proven in human preclinical or clinical trials.

A tetravalent vaccine should simultaneously immunize against all four dengue

virus (DENV) serotypes in order to reduce the theoretical risk of dengue hemorrhagic

fever from subsequent wild-type DENV infections.108Two live attenuated tetravalent

vaccine candidates are in Phase 2 clinical trials in DENV endemic regions. Numerous

other vaccine candidates including inactivated whole virus, recombinant subunit

protein, DNA and virus-vectored vaccines are also under development. There are

possibilities that non-structural components of Dengue virion, such as NS1 could

serve as protective antigens in addition to structural ones such as E antigen. Anti-

idiotypic vaccine is also a hypothetical candidate. The advantage of having

recombinant genes for protective epitopes packed into a single carrier is apparent. The

candidate carriers may include , l7D yellow fever vaccine and JE vaccine. The DEN-2

candidate vaccine may also serve as the carrier for such a recombinant. The aim is to

obtain information on gene sequencing of different strains and types of Dengue virus

and to perform epitope mapping of these viruses using monoclonal antibodies.

  55

METHODS AND MATERIALS

4.1 Source of Data: Suspected cases of Dengue fever in Outpatients and admitted as

Inpatient in Kempegowda Institute of Medical Sciences and Research Centre ,

Bangalore.

4.2 Method of collection of data: Definition of Study Subjects- 100 cases of

suspected Dengue fever children who fulfilled the inclusion criteria were selected.

Pretest counseling was given to parents / guardian. After taking written informed

consent from parents ,case was enrolled ,data was collected in a predesigned semi-

structured questionnaire .Blood samples were collected from children with suspected

Dengue infection for complete blood count, haematocrit , liver function tests,

prothrombin time, activated partial thromboplastin time, Dengue viral Ag, IgG &

IgM, and other relevant investigations who are admitted to Kempegowda Institute of

medical sciences as inpatient and also as Out-patients .WHO classification and case

definition was used to classify Dengue Fever, Dengue Hemorrhagic Fever, Dengue

Shock Syndrome and Dengue like illness.

4.3 Sample size : 100

4.3 Study design : Hospital based descriptive study.

Duration of study : one and a half year.

Inclusion criteria:

1. All children below 18 yrs of age with clinical features suggestive of Dengue

infection admitted as inpatients and outpatients in Kempegowda Institute of

Medical Sciences, Bangalore.

2. Child presenting with fever of acute onset (<2wks), pain abdomen, vomiting,

rash, flushed appearance and bleeding manifestation.

  56

Exclusion criteria:

1. Febrile illness of >2wks duration.

2. Patients with any identified specific infection like Malaria, Typhoid, UTI,

etc…..

4.4 Methodology :

The present study was conducted at Kempegowda Institute of Medical

Sciences hospital, Bangalore , a tertiary care pediatric hospital.

An alarmingly increasing epidemic of dengue was noticed in this part of state, with

more number of admissions in the pediatric age group. Hence the following study was

conducted to find out the early clinical manifestation and its outcome in dengue fever.

Hundred children in the paediatric age group (<18yrs) presenting with symptoms and

signs suggestive of dengue fever as per WHO criteria were included in the study,

between December 2010 to April 2012.

Written consent was taken from parents before enrolling in study. A detailed

demographic data, clinical history, physical examination and relevant baseline

investigations were undertaken as per the proforma. Patients with an identified

bacterial focus or any other identified specific infection were excluded during the

Study. Serum samples were obtained on an average of 5 to 7 days after DF symptoms

had appeared. The cases were followed-up daily for the clinical and laboratory

parameters. The patients were treated with IV fluids, paracetamol ,antacids, blood

products and inotropics as per WHO criteria for treatment of dengue. These cases

were stratified based on the presence or absence of complications like shock and

haemorrhage in to various dengue types. The frequency of various signs and

symptoms and the values of laboratory tests were compared. The results were

tabulated and correlated. The outcome was recorded in every subject. The criteria

  57

defined by WHO as mentioned previously, were followed for the inclusion of subjects

in to the study.

Investigations :

1. Complete blood count,

2. Blood test (Serology) for Dengue fever,

3. Urine routine,

4. Serum electrolytes,

5. Random blood sugar,

6. QBC for MP,

7. WIDAL/ Blood culture,

8. Liver enzymes- SGOT, SGPT, Serum albumin,

9. Chest x ray,

10. Ultrasound abdomen,

11. PT, APTT.

If necessary-

12. Blood urea, serum creatinine,

13. CSF analysis,

14. 2D echo,

15. CT scan brain/MRI.

  All the hundred children registered in the study were treated at KIMS,

Bangalore as per the WHO algorithm on dengue fever. 

  58

Method of Statistical Analysis:

The following methods of statistical analysis have been used in this study. The Excel

and SPSS (SPSS Inc, Chicago) software packages were used for data entry and

analysis.

The results were presented in numbers and percentage for categorical data in

Table and Figure.

1) Proportions were compared using Chi-square test of significance

Chi-Square (χ2) test for (r x c tables)

a,b…..h are the observed numbers. N is the Grand Total

χ2 = ⎥⎦

⎤⎢⎣

⎡−+++ ∑ ∑∑ 11.................11

1 1

21

21

1 2

21

1

c c

iri

c

i nh

tnb

tna

tN

DF=(r-1)*(c-1), where r=rows and c=columns

DF= Degrees of Freedom (Number of observation that are free to vary after

certain . Restriction have been placed on the data)

2) One way analyses of variance were used to test the difference between groups.

When comparing more than two means, an ANOVA F-test tells you whether the

means are significantly different from each other. Comparison of Two variance Sa2

and Sb2 , estimated for two group Na and Nb subjects respectively. Uses F test

2

2

SbSaF =

with Na-1 and Nb-1 degrees of freedom.

In the above test a “p” value of less than 0.05 was accepted as indicating

statistical significance.

  59

RESULTS

Out of the 100 children the study group, the following characteristics

were noted.

1. DIAGNOSIS – CLINICAL SPECTRUM OF CASES.

Diagnosis Frequency(N=100) Percentage

DF 36 36.0

DHF 33 33.0

DLI 16 16.0

DSS 15 15.0

Total 100 100.0

Out of total 100 cases studied, 36 children met WHO specified criteria for DF, 33

children with DHF, 15 children with DSS and 16 children with DLI.

  60

2. AGE DISTRIBUTION OF PATIENTS.

Age groups Frequency(N=100) Percentage

<1 yr 3 3.0

1-4 yrs 16 16.0

5-8 yrs 31 31.0

9-12 yrs 26 26.0

>12 yrs 24 24.0

Total 100 100.0

In the present study highest number of cases were found in age group of 5 to 8yrs

(31% ), followed by in age group of 9-12yrs (26%).

  61

3. AGE DISTRIBUTION OF PATIENTS ACCORDING TO CLINICAL

SPECTRUM.

Age distribution of patients

<1 yr

1-4 yrs

5-8 yrs

9-12 yrs

>12 yrs

Total χ2

value

‘p’

value

DF 1 7 6 12 10 36

DHF 1 2 15 5 10 33

DLI 0 4 6 3 3 16

DSS 1 3 4 6 1 15

3 16 31 26 24 100 Total

3.0% 16.0% 31.0% 26.0% 24.0% 100.0%

15.856 0.198

In the present study highest number of cases were found in age group of 5 to 8yrs

(31% ), followed by in age group of 9-12yrs (26%).

  62

4. GENDER DISTRIBUTION OF PATIENTS.

Gender Frequency( N=100) Percentage

Male 66 66.0

Female 34 34.0

Total 100 100.0

Out of the 100 children 66 were male and 34 were female. The ratio M:F =1.94:1.

  63

5. GENDER DISTRIBUTION OF CASES ACCORDING TO CLINICAL SPECTRUM.

Gender distribution

Male Female

Total χ2

value

‘p’

value

28 8 36 DF

77.8% 22.2% 100.0%

19 14 33 DHF

57.6% 42.4% 100.0%

11 5 16 DLI

68.8% 31.3% 100.0%

8 7 15 DSS

53.3% 46.7% 100.0%

66 34 100 Total

66.0% 34.0% 100.0%

4.395 0.222

Out of the 100 children 66 were male and 34 were female. The ratio M:F =1.94:1.

  64

6. SYMPTOMATOLOGY OF CASES.

Symptomatology Present

Fever 96

Abdominal pain 42

Vomiting 49

Headache 12

Myalgia 7

Joint pain 4

Edema 3

R O Pain 1

Diarrhea 7

Cold 3

Cough 10

Convulsion 2

Menorrhagia 1

Symptomatology

96

42

49

12

7

4

3

1

7

3

10

2

1

0 20 40 60 80 100

Fever

Abdominal pain

Vomiting

Headache

Myalgia

Joint pain

Edema

R O Pain

Diarrhea

Cold

Cough

Convulsion

Menorrhagia

MenorrhagiaConvulsionCoughColdDiarrheaR O PainEdemaJoint painMyalgiaHeadacheVomitingAbdominal painFever

96 (96%) children presented with fever as the predominant complaint.

  65

7. ANALYSIS OF SYMPTOMATOLOGY.

DF(N=36) DHF

(N=33) DLI (N=16)

DSS (N=15) Symptoms

n % n % n % n %

χ2

value

‘p’

value

Fever 35 97.2% 33 100.0% 14 87.5% 14 93.3% 4.803 0.187

Abdominal Pain

14 38.9% 13 39.4% 9 56.3% 6 40.0% 1.593 0.661

Vomiting 20 55.6% 16 48.5% 7 43.8% 6 40.0% 1.285 0.733

Headache 3 8.3% 3 9.1% 3 18.8% 3 20.0% 2.322 0.508

Myalgia 4 11.1% 2 6.1% 1 6.3% 0 0.0% 2.122 0.547

Joint Pain 1 2.8% 1 3.0% 2 12.5% 0 0.0% 3.856 0.277

Edema 1 2.8% 1 3.0% 1 6.3% 0 0.0% 1.051 0.789

Retro Orbital Pain

0 0.0% 0 0.0% 0 0.0% 1 6.7% 5.724 0.126

Diarrhea 2 5.6% 3 9.1% 0 0.0% 2 13.3% 2.466 0.482

Cold 1 2.8% 2 6.1% 0 0.0% 0 0.0% 2.027 0.567

Cough 5 13.9% 3 9.1% 1 6.3% 1 6.7% 1.070 0.784

Convulsion 0 0.0% 1 3.0% 0 0.0% 1 6.7% 2.907 0.406

Menorrhagia 0 0.0% 1 3.0% 0 0.0% 0 0.0% 2.051 0.562

  66

96 (96%) children presented with fever as the predominant complaint followed

by vomiting 49 (49%), Abdominal pain 42 (42%), Headache 12 (12%), Cough 10

(10%), Diarrhea 7 (7%), Myalgia 7 (7%), Joint pain 4 (4%), Edema 3 (3%), Cold

3 ( 3%), Convulsion 2 (2%), Retro orbital pain 1 (1%), Menorrhagia 1 (1%).

  67

8. SIGNS IN PATIENTS.

Signs Present Absent

Conjunctival congestion 18 82

Facial puffiness 28 72

Pedal edema 21 79

Hepatomegaly 53 47

Splenomegaly 8 92

Ascites 13 87

The most common signs were Hepatomegaly(53%), followed by Facial

puffiness(28%), Pedal edema(21%), Conjunctival congestion(18%),

Ascites(13%), Splenomegaly (8%).

  68

9. TEMPERATURE

Temperature Frequency

Febrile 12

Afebrile 88

12% of children in the study group had fever.

  69

10. DISTRIBUTION OF SIGNS ACCORDING TO CLINICAL

SPECTRUM.

DF(N=36) DHF (N=33)

DLI (N=16)

DSS (N=15) Signs

n % n % n % n %

χ2

value

‘p’

value

Conjunctival congestion

3 8.3% 8 24.2% 1 6.3% 6 40.0% 9.566 0.023

Facial Puffiness

2 5.6% 14 42.4% 1 6.3% 11 73.3% 31.447 <0.001

Pedal edema 1 2.8% 11 33.3% 1 6.3% 8 53.3% 21.782 <0.001

Temp (Febrile) 6 16.7% 0 0.0% 4 25.0% 2 13.3% 7.828 0.050

Hepatomegaly 13 36.1% 25 75.8% 5 31.3% 10 66.7% 15.147 0.002

Splenomegaly 3 8.3% 3 9.1% 1 6.3% 1 6.7% 0.162 0.984

Ascites 1 2.8% 7 21.2% 1 6.3% 4 26.7% 8.415 0.038

The most common sign was Hepatomegaly (53%).

  70

11. RESPIRATORY SYSTEM EXAMINATION.

Air entry Frequency

Normal 73

Decreased 27

On respiratory system examination , 27% of cases were observed to have

decreased air entry.

  71

12. DISTRIBUTION OF AIR ENTRY (RESPIRATORY SYSTEM)

ACCORDING TO CLINICAL SPECTRUM OF CASES.

DF(N=36) DHF (N=33)

DLI (N=16)

DSS (N=15)

Air entry n % n % n % n %

χ2

value

‘p’

value

Normal 32 88.9% 19 57.6% 15 93.8% 7 46.7%

Decreased 4 11.1% 14 42.4% 1 6.3% 8 53.3% 17.367 0.001

On respiratory system examination , 27% of cases were observed to have

decreased air entry.

  72

13. RELATIONSHIP BETWEEN VARIOUS SITES OF BLEEDING AND DENGUE FEVER.

Site of bleeding Present Absent

Rashes 12 88

Melaena 0 100

Hematuria 2 98

Hematemesis 4 96

Epistaxis 4 96

Gum bleeds 2 98

Bleeding was noted in 24% of total number of cases. The skin bleeds were the

most common manifestation noted in 12 cases (12%) followed by GIT bleeding

like hematemesis 4 cases (4%) followed by epistaxis 4 cases (4%) ,hematuria 2

cases (2%) and gumbleeds 2 cases (2%). The bleeding manifestations were more

in DHF, DSS group than DF group.

  73

14. RELATIONSHIP BETWEEN VARIOUS SITES OF BLEEDING AND DENGUE FEVER ACCORDING TO CLINICAL SPECTRUM.

DF(N=36)DHF (N=33)

DLI (N=16)

DSS (N=15) Site of

Bleeding n % n % n % n %

χ2

value

‘p’

value

Rashes 0 0.0% 8 24.2% 0 0.0% 4 26.7% 14.830 0.002

Melaena 0 0.0% 0 0.0% 0 0.0% 0 0.0%

Hematuria 0 0.0% 2 6.1% 0 0.0% 0 0.0% 4.143 0.246

Hematemesis 0 0.0% 4 12.1% 0 0.0% 0 0.0% 8.460 0.037

Epistaxis 1 2.8% 3 9.1% 0 0.0% 0 0.0% 3.659 0.301

Gum Bleeds 0 0.0% 2 6.1% 0 0.0% 0 0.0% 4.143 0.246

Bleeding was noted in 24% of total number of cases. The skin bleeds were the

most common manifestation noted in 12 cases (12%) followed by GIT bleeding

like hematemesis 4 cases (4%) followed by epistaxis 4 cases (4%) ,hematuria 2

cases (2%) and gumbleeds 2 cases (2%). The bleeding manifestations were more

in DHF, DSS group than DF group.

  74

15. TYPES OF SKIN RASHES

Skin rashes Present Absent

Flushing 54 46

Macular rash 21 79

Petechiae 33 67

Ecchymosis 11 89

Most common type of skin rash observed in the present study was Flushing 54%,

followed by Petechiae 33% , Macular rash 21% and Ecchymosis in 11% of cases.

  75

16. DISTRIBUTION OF TYPES OF SKIN RASHES ACCORDING TO

CLINICAL SPECTRUM.

DF(N=36) DHF (N=33)

DLI (N=16)

DSS (N=15) Skin rashes

n % n % n % n %

χ2

value

‘p’

value

Flushing 15 41.7% 22 66.7% 6 37.5% 11 73.3% 8.347 0.039

Macular rash

0 .0% 14 42.4% 0 .0% 7 46.7% 28.909 <0.001

Petechiae 0 .0% 23 69.7% 0 .0% 10 66.7% 53.401 <0.001

Ecchymosis 0 .0% 4 12.1% 0 .0% 7 46.7% 25.960 <0.001

Most common type of skin rash observed in the present study was Flushing 54%,

followed by Petechiae 33% , Macular rash 21% and Ecchymosis in 11% of cases.

  76

17. TOURNIQUET TEST.

Tourniquet test Frequency

Positive 43

Negative 57

Tourniquet test (Hess capillary resistance test) was performed by placing the

sphygmomanometer cuff around the upper arm and raising the pressure midway

between systolic and diastolic pressure for 5 – 7 minutes. The test was considered

positive when more than 20 petechiae developed in an area of 1 sq. inch on the flexor

aspect of forearm. Tourniquet test is performed by inflating a blood pressure cuff on

the upper aspect of arm to a point midway between systolic and diastolic pressures for

5 minutes. The test is considered positive when >20 petechiae/2.5 cm2 are observed.

Hemorrhagic manifestations usually appear 4-5 days after the onset of fever. This test

is a very useful screening test in suspected cases of Dengue fever.

The tourniquet test was positive in 43% of cases.

  77

18. ANALYSIS OF TOURNIQUET TEST RESULTS ACCORDING TO

CLINICAL SPECTRUM.

DF(N=36) DHF (N=33)

DLI (N=16)

DSS (N=15) Hess

Test n % n % n % n %

χ2

value

‘p’

value

Positive 0 0.0% 30 90.9% 1 6.3% 12 80.0%

Negative 30 100.0% 3 9.1% 15 93.8% 3 20.0%75.256 <0.001

The tourniquet test was positive in 43% of cases.

  78

19. PLATELET COUNT.

DF(N=36) DHF (N=33) DLI (N=16) DSS (N=15) Platelet Count

(cells/cu mm) n % N % n % n %

<20000 2 5.6% 18 50.0% 16 44.4% 0 0.0%

20000-50000 12 36.4% 12 36.4% 8 24.2% 1 3.0%

500001-100000 1 6.3% 8 50.0% 7 43.8% 0 0.0%

>100000 7 46.7% 6 40.0% 2 13.3% 0 0.0%

20. PLATELET COUNT.

Parameter Platelet count

(cells/cu mm)

Mean 41870

SD 31459.98

A mean value of Platelet count was 41870 cells/cu mm. The WHO criteria of

low platelet count of < 1,00,000 cells/cu mm was seen in most of the cases (85%).

With maximum number of cases having platelet count in the range of <20000 cells/cu

mm in DHF and DLI groups.

  79

21. HAEMOGLOBIN LEVELS ACCORDING TO CLINICAL SPECTRUM OF CASES.

DF(N=36) DHF (N=33)

DLI (N=16)

DSS (N=15)

n % n % n % n %

χ2

value

‘p’

value

Hb(g%) <=15 31 86.1% 24 72.7% 16 100.0% 13 86.7%

>15 5 13.9% 9 27.3% 0 0.0% 2 13.3% 6.366 0.095

22. HAEMOGLOBIN LEVELS (Hb g%).

N Mean SD Min. Max. ‘f’ value

‘p’ value

DF 36 12.831 1.6570 9.3 15.9

DHF 33 13.158 2.5024 6.8 18.9

DLI 16 11.956 1.4339 9.3 14.3 Hb

DSS 15 12.313 2.7823 6.5 15.4

1.364 0.258

TOTAL 100 12.721 2.14 6.5 18.9

The hemoglobin level ranges from 6.5–18.9 gm%, with a mean level of 12.721 gm%.

  80

23. HEMATOCRIT (PACKED CELL VOLUME) ACCORDING TO CLINICAL SPECTRUM OF CASES.

DF(N=36) DHF (N=33)

DLI (N=16)

DSS (N=15)

n % n % n % n %

χ2

value

‘p’

value

<=45 34 94.4% 28 84.8% 16 100.0% 13 86.7% PCV (%) >45 2 5.6% 5 15.2% 0 0.0% 2 13.3%

3.973 0.264

24. HEMATOCRIT (PCV%)

N Mean SD Min. Max. ‘f’ value

‘p’ value

DF 36 38.147 4.4575 27.9 48.0

DHF 33 38.739 6.9912 19.2 54.2

DLI 16 36.550 4.0678 27.2 40.4 PCV

DSS 15 36.653 7.8856 18.7 45.7

0.737 0.533

TOTAL 100 37.86 5.91 18.7 54.2

The hematocrit ranged from 18.7 – 54.2% with a mean value of 37.86%.

  81

25. TOTAL LEUCOCYTE COUNT ACCORDING TO CLINICAL SPECTRUM OF CASES.

DF(N=36) DHF (N=33)

DLI (N=16)

DSS (N=15)

n % n % N % n %

χ2

value

‘p’

value

<4000 13 36.1% 15 45.5% 2 12.5% 6 40.0%

4000-11000

21 58.3% 14 42.4% 13 81.3% 7 46.7%

Total count

(cells/cu

>11000 2 5.6% 4 12.1% 1 6.3% 2 13.3%

7.835 0.250

26. TOTAL LEUCOCYTE COUNT (TLC in cells/cu mm)

N Mean SD Min. Max. ‘f’

value

‘p’ value

DF 36 5786.11 3377.417 1600 19200

DHF 33 5778.79 4286.079 1400 18900

DLI 16 6362.50 3019.023 3400 15700 TLC

DSS 15 6710.00 5097.766 2400 22000

0.278 0.841

TOTAL 100 6014.5 3893.197 1400 22000

Normal : 4000 – 11000 cells/cu mm.

The range of total leukocyte count varied from 1400 – 22000 cells/cumm with a mean

count of 6014.5 cells/cu mm.36 (36%) patients had leucopenia i.e. <4000 cells/cu

mm.

  82

27. PROTHROMBIN TIME ACCORDING TO CLINICAL SPECTRUM

OF CASES.

DF(N=36) DHF (N=33)

DLI (N=16)

DSS (N=15)

n % n % n % n %

χ2

value

‘p’

value

10-13

0 .0% 7 21.2% 0 0.0% 1 6.7%

>13 1 2.8% 25 75.8% 1 6.3% 14 93.3% PT (in seconds)

ND 35 97.2% 1 3.6% 15 93.5% 0 0.0%

92.032 <0.001

28. PROTHROMBIN TIME (PT in seconds)

N Mean SD Min. Max. ‘f’ value

‘p’ value

DF 1 24.000 . 24.0 24.0

DHF 32 17.856 4.8536 11.6 32.1

DLI 1 13.600 . 13.6 13.6 PT

DSS 15 21.063 10.1666 12.5 54.0

1.096 0.361

TOTAL 49 18.88 6.98 11.6 54.0

PT - Normal 10-13 sec.

The prothrombin time ranged from 11.6-54 sec with a mean of 18.88 sec.

  83

29. ACTIVATED PARTIAL THROMBOPLASTIN TIME ACCORDING TO CLINICAL SPECTRUM OF CASES.

DF(N=36) DHF (N=33)

DLI (N=16)

DSS (N=15)

n % n % n % n %

χ2

value

‘p’

value

26-36

1 2.8% 8 24.2% 0 0.0% 3 20.0%

>36 0 0.0% 24 72.7% 1 6.3% 11 73.3%

APTT (in seconds)

ND 35 97.2% 1 3.0% 15 93.8% 1 6.7%

85.127 <0.001

30. ACTIVATED PARTIAL THROMBOPLASTIN TIME (APTT in

seconds)

N Mean SD Min. Max. ‘f’ value

‘p’ value

DF 1 35.700 . 35.7 35.7

DHF 32 43.366 8.5671 28.2 60.4

DLI 1 47.000 . 47.0 47.0 APTT

DSS 15 45.336 11.1144 31.0 69.0

0.434 0.730

TOTAL 49 43.86 9.22 28.2 69.0

APTT – Normal 26-36 sec.

The activated partial thromboplastin time ranged from 28.2-69.0 sec with a

mean of 43.86 sec.

  84

31. BLOOD UREA ACCORDING TO CLINICAL SPECTRUM OF CASES.

DF(N=36) DHF (N=33)

DLI (N=16)

DSS (N=15)

N % n % n % n %

χ2

value

‘p’

value

5-18 0 0.0% 0 0.0% 1 0.0% 0 0.0%

>18 2 5.6% 7 21.2% 1 6.3% 9 60.0% B.Urea (in mg/dl)

ND 34 94.4% 26 78.8% 14 87.5% 6 40.0%

27.457 <0.001

32. BLOOD UREA.

N Mean SD Min. Max. ‘f’

value ‘p’ value

DF 2 35.00 5.657 31 39

DHF 7 49.71 40.194 25 136

DLI 2 26.50 17.678 14 39

B.Urea (mg/dl)

DSS 9 43.00 32.592 19 114

0.284 0.836

TOTAL 20 42.9 32.056 14 136

The range for Blood urea was 14-136 mg/dl with a mean of 42.9 mg/dl.

  85

33. SERUM CREATININE ACCORDING TO CLINICAL SPECTRUM OF CASES.

DF(N=36) DHF (N=33)

DLI (N=16)

DSS (N=15)

N % n % n % n %

χ2

value

‘p’

value

0.3-0.7

1 2.8% 4 12.1% 1 6.3% 7 46.7%

>0.7 1 2.8% 3 9.1% 1 6.3% 2 13.3% S.Creatinine (in mg/dl)

ND 34 94.4% 26 78.8% 14 87.5% 6 40.0%

22.605 0.001

34. SERUM CREATININE.

N Mean SD Min. Max. ‘f’

value

‘p’ value

DF 2 0.750 0.0707 0.7 0.8

DHF 7 0.700 0.1633 0.4 0.9

DLI 2 0.650 0.3536 0.4 0.9

S.Creatinine (mg/dl)

DSS 9 0.778 0.4147 0.4 1.8

0.128 0.942

TOTAL 20 0.735 0.299 0.4 1.8

The range for Serum creatinine was 0.4 – 1.8 mg/dl with a mean of 0.735 mg/dl.

  86

Distribution of Lab parameter values

86.1%

13.9%

94.4%

5.6%

36.1%

58.3%

5.6%

0.0% 2.8%

97.2%

2.8%

0.0%

97.2%

72.7%

27.3%

84.8%

15.2%

45.5%

42.4%

12.1% 21

.2%

75.8%

3.6%

24.2%

72.7%

3.0%

100.0%

0.0%

100.0%

0.0%

12.5%

81.3%

6.3%

0.0% 6.

3%

93.5%

0.0% 6.

3%

93.8%

86.7%

13.3%

86.7%

13.3%

40.0% 46.7%

13.3%

6.7%

93.3%

0.0%

20.0%

73.3%

6.7%

0.0%

20.0%

40.0%

60.0%

80.0%

100.0%

120.0%

<=15 >15

<=45 >45

<400

0

4000

‐110

00

>110

00

10‐13

>13

ND

26‐36

>36

ND

Hb(%) PCV (%) Total count  (cells/cu mm) PT (in seconds) PTT (in seconds)

DF(N=36)

DHF (N=33)

DLI (N=16)

DSS (N=15)

  87

LIVER FUNCTION TESTS

35. SERUM GLUTAMATE OXALOACETATE TRANSAMINASE (SGOT). N Mean SD Min. Max. ‘f’

value ‘p’ value

DF 36 122.81 111.275 10 596

DHF 31 144.39 60.918 50 298

DLI 16 84.50 81.310 12 298

SGOT (IU/L)

DSS 15 340.47 324.793 35 1072

9.397 <0.001

TOTAL 98 156.69 168.58 10 1072

SGOT - Normal 1-55 IU/lt.

The range for SGOT was 10-1072 IU/lt with a mean of 168.58 IU/lt.

36. SERUM GLUTAMATE PYRUVATE TRANSAMINASE (SGPT).

N Mean SD Min. Max. ‘f’ value

‘p’ value

DF 36 60.11 62.910 7 268

DHF 33 112.48 121.982 23 481

DLI 16 73.81 49.872 6 200

SGPT (IU/L)

DSS 15 188.33 245.011 24 829

4.080 0.009

TOTAL 100 98.82 130.37 6 829

SGPT - Normal 5-45 IU/lt.

The range for SGOT was 6-829 IU/lt with a mean of 98.82 IU/lt.

  88

37. SERUM ALBUMIN ACCORDING TO CLINICAL SPECTRUM OF CASES .

DF(N=36) DHF (N=33)

DLI (N=16)

DSS (N=15)

n % n % n % n %

χ2

value

‘p’

value

<3.4 14 38.9% 26 78.8% 8 50.0% 14 93.3%

3.4-5.4

22 61.1% 4 12.1% 8 50.0% 1 6.7% S.Albumin (g/dl)

ND 0 0.0% 3 9.1% 0 0.0% 0 0.0%

29.856 <0.001

38. SERUM ALBUMIN (g/dl) .

N Mean SD Min. Max. ‘f’ value

‘p’ value

DF 36 3.381 0.5019 2.2 4.2

DHF 30 2.883 0.4160 1.9 3.6

DLI 16 3.056 0.6511 1.9 3.8 S.Alb

DSS 15 2.620 0.6405 1.0 3.5

9.017 <0.001

TOTAL 97 3.066 0.58 1.0 4.2

SA – Normal 3.4 – 5.4 gm%. The range for serum albumin was 1.0 – 4.2 gm% with a

mean of 3.066 gm%. Serum albumin of <3.4 gm% was seen in 62% of children,

more in DHF and DSS group. It is statistically significant. (χ2 = 29.856, P =

<0.001).

  89

39. SERUM ELECTROLYTES

N Mean SD Min. Max. ‘f’ value ‘p’ value

DF 2 132.00 2.828 130 134

DHF 8 135.25 6.497 122 144

DLI 2 134.00 1.414 133 135

DSS 8 135.38 6.116 130 148

0.199 0.896

Na

TOTAL 20 134.85 5.57 122 148

DF 2 4.200 0.4243 3.9 4.5

DHF 8 4.525 0.8481 3.7 6.3

DLI 2 4.850 1.2021 4.0 5.7

DSS 8 4.075 0.7146 2.8 4.8

0.727 0.551

K

TOTAL 20 4.35 0.78 2.8 6.3

DF 2 98.00 2.828 96 100

DHF 8 100.38 6.116 91 107

DLI 2 98.00 0.000 98 98

DSS 8 97.00 4.629 90 102

0.598 0.626

Cl

TOTAL 20 98.55 4.96 90 107

Na – Normal 136-146 meq/l. The range for serum sodium was 122-148 meq/l

with a mean of 134.85 meq/l. K – Normal 3.5-5.0 meq/l. The range for serum

potassium was 2.8-6.3 meq/l with a mean of 4.35 meq/l. Cl – Normal 98-106 meq/l.

The range for serum chloride was 90-107 meq/l with a mean of 98.55 meq/l.

  90

40. DENGUE SEROLOGY.

Test component Frequency

Antigen 43

IgM 58

IgG 22

Dengue Ag was positive in 43 cases (43%), IgM was positive in 58 cases (58%)

and IgG was positive in 22 cases (22%) in this study.

  91

41. DENGUE SEROLOGY ACCORDING TO CLINICAL SPECTRUM OF

CASES .

DF(N=36) DHF (N=33)

DLI (N=16)

DSS (N=15)

Test component

n % n % n % n %

χ2

value

‘p’

value

Positive. 16 44.4% 21 63.6% 0 0.0% 6 40.0% Antigen

Negative. 20 55.6% 12 36.4% 16 100.0% 9 60.0% 17.890 <0.001

Positive. 24 66.7% 21 63.6% 0 0.0% 13 86.7% IgM

Negative. 12 33.3% 12 36.4% 16 100.0% 2 13.3% 28.696 <0.001

Positive. 9 25.0% 8 24.2% 0 0.0% 5 33.3% IgG

Negative. 27 75.0% 25 75.8% 16 100.0% 10 66.7% 5.921 0.116

Dengue Ag was positive in 43 cases (43%), IgM was positive in 58 cases (58%)

and IgG was positive in 22 cases (22%) in this study.

  92

42. CHEST X-RAY.

Chest x-ray Frequency

Normal 62

Effusion 38

Chest x-ray was done in all the 100 cases, in 38 children (38%) there was pleural

effusion.

  93

43. CHEST X-RAY FINDINGS ACCORDING TO CLINICAL SPECTRUM.

DF(N=36) DHF (N=33)

DLI (N=16)

DSS (N=15)

Chest X-

ray

Findings n % n % n % n %

χ2

value

‘p’

value

Normal 29 80.6% 15 45.5% 14 87.5% 4 26.7%

Effusion 7 19.4% 18 54.5% 2 12.5% 11 73.3% 21.460 <0.001

Chest x-ray was done in all the 100 cases, in 38 children (38%) there was pleural

effusion.

In the DHF and DSS group the number of cases were more compare to DF and

DLI group. ( χ2 = 21.460 , P<0.001) It was statistically significant.

  94

44. ULTRASONOGRAPHY.

Ultra sonography Frequency

Normal 47

Gall bladder wall thickening 33

Acalculous cholecystitis 14

Pleural effusion 37

Ascites 32

Hepatomegaly 8

Splenomegaly 12

About 33 patients had gall bladder wall thickening, 37 patients had

pleuraleffusion, 32 patients had ascites, 14 patients had acalculous cholecystitis.

  95

45. ULTRASONOGRAPHY FINDINGS ACCORDING TO CLINICAL

SPECTRUM.

DF(N=36) DHF (N=33)

DLI (N=16) DSS (N=15)

Diagnosis n % n % n % n %

Normal 26 14.4% 5 3.0% 14 17.5% 2 2.7%

Gall bladder wall thickening

8 4.4% 16 9.7% 1 1.3% 8 10.7%

Acalculous Cholecystitis

2 1.1% 8 4.8% 0 0.0% 4 5.3%

Pleural Effusion 7 3.9% 18 10.9% 2 2.5% 10 13.3%

Ascites 4 2.2% 20 12.1% 0 0.0% 8 10.7%

Hepatomegaly 0 0.0% 5 3.0% 0 0.0% 3 4.0%

Splenomegaly 1 .6% 7 4.2% 1 1.3% 3 4.0%

About 33 patients had gall bladder wall thickening, 37 patients had

pleuraleffusion, 32 patients had ascites, 14 patients had acalculous cholecystitis.

  96

DISCUSSION

Dengue fever is the most important arboviral infection of humans and has

become a major global public health problem. It is one of the most important tropical

infectious disease in the world.

In India, epidemics are becoming more frequent. Involvement of younger age

group and increasing in the frequency of epidemics are indicators of higher incidence

of infection. Classical dengue fever is an acute febrile illness but in a small percentage

of Dengue infection, a more severe form of disease known as DHF occurs. Early

recognition and meticulous management are very important to save precious lives

from this killer disease.

INCIDENCE

In the present study of 100 cases - 36% cases belongs to DF, 33% cases

belongs to DHF, 15% cases belongs to DSS group and 16% cases belongs to DLI.

AGE DISTRIBUTION

Although high incidence of degree has been described in children, very few

studies have been exclusively studied on them. The 5-11 year age group dominated

the Present study, accounting for 54% of the total.

The present study correlate with the previous studies in the age incidence.

Among the subgroup, there is a tendency for DSS to occur at younger age.

However previous studies have not noted any difference in age between dengue with

or without shock. The youngest child in the present study was 8 months old.

  97

The following table gives incidence in the age group of 5 –11 years among other

studies.

Sl. No. Study Place Year %

1 WHO meta

analysis28

SEAR 1978-88 54

2 Narayanan et al83 Chennai 2002 45

3 Gomber et al84 Delhi 2001 78.9

4 Present study Bangalore 2010-12 54

GENDER DISTRIBUTION :

The incidence of male children that were affected is slightly more in our study,

the ratio being 1.94:1. Similar observation were made by others also showed

increased preponderance among boys as in WHO study in 1999 due to increased

outdoor activities of male children.

Sl. No. Study Year No. of

cases

Place M:F ratio

1 Chandrakanta et

al85

2008 80 Lucknow 1.6:1

2 Cam et al86 2001 27 Denmark 1.7:1

3 Pancharoen et al87 2001 80 Thailand 1.1:1

4 Gurdeep S.D et

al88

2008 81 North India 1.89:1

5 Kumar et al74 2002-08 466 Karnataka 1.8:1

6 Sajid et al89 2011 35 Pakistan 1.33:1

7 Present study 2010-12 100 Bangalore 1.94:1

  98

SYMPTOMATOLOGY

In the present study fever (96%) was the predominant symptoms followed by

vomiting (49%), abdominal pain (42%%), bleeding (24%), Rashes (24, retro-orbital

pain (28%).

The following pattern of symptoms have been observed in other studies.

SI

No.

Study No of

cases

Fever Vomiti

ng

Abd

Pain

Headac

he

Bleeding ROP

1 Narayana

n et al83

59 98.3% 83% 23.7% 28.8% 66.1% 11.9%

2 Anuradh

a et al90

515 100% 8% 10.2% - 52.6% -

3 Misra et

al91

17 100% 58% - 52.5% - -

4 Kankira

watana

et al92

8 100% 62.5% - 62.5% - -

5 Solomon

et al66

9 100% 45% - 55% - -

6 Kumar et

al46

466 99.1% 47.6% 37.6% 47.6% 21.7% -

7 Sajid et

al89

35 100% 34% 51% - - -

8 Present

study

100 96% 49% 42% 12% 24% 1%

  99

EPIDEMIOLOGICAL CHARACTERISTICS :

The evaluation of immediate micro and macroenvironments of the patients

habitat revealed following observations.

• Storage of water in containers was present.

• Artificial storage of water as in flower vases, plant pots and ceiling hung

plants, coconut shell were also noticed.

• The scope for mosquito breeding was present. Those children got infected in

the immediate monsoon or post monsoon months, being responsible for the

increase in the number of cases in that period.

Efforts were made to educate parents about disease from which their children

was suffering and the possible modes of spread, the environmental factors that might

have been responsible, the ways and means to prevent spread of disease, like keeping

surrounding clean using mosquito curtain etc, as a long term measures.

CLINICAL EXAMINATION :

Of the 100 children in the study 96% children had fever and no child was in

category of hyperpyrexia.

BLEEDING :

In the present study bleeding manifestations were found in 24% of cases.

Apart from petechiae, which usually associated with bleeding manifestations,

Hematemesis and epistaxis were the predominant modes of bleeding. Hematemesis

was the most common bleeding manifestation reported in other Indian studies.

  100

Other studies have noted following pattern of bleeding.

SI. No. Study Place Year Bleeding Type

1 Kumar et

al94

Lucknow 2000 31.2% Hematemesis

2 Anuradha et

al90

New Delhi 1998 52.6% Epistaxis

3 Rahman et

al95

Bangladesh 2002 46% Maelena

4 Present

study

Bangalore 2010-12 24% Hematemesis

TOURNIQUET TEST :

The platelet count and tourniquet test did not consistently correlate with each

other. The tourniquet test was positive in 43% of cases. Other studies have noted

varying results in this test.

Tourniquet test is not a reliable test for diagnosis as observed in many other

Indian studies.

SI No. Study Place Year Test positive

1 Kabra et al96 New Delhi 1999 40%

2 Nimmannitya et

al97

SEAR 1969 83.9%

3 Gomber et al84 New Delhi 2001 25%

4 Present study Bangalore 2010-12 43%

  101

SYSTEMIC EXAMINATION :

The systemic examination revealed non specific signs, as like any other viral

illness. Hepatomegaly was been in 53 children (53%) in the present study. Other

studies also reported hepatomegaly in significant percentage.

SI. No. Study Place Year Hepatomegaly

1 Narayanan et

al83

Chennai 2002 52.5%

2 Nimmannitya et

al97

SEAR 1969 90%

3 Mohan et al98 New Delhi 2000 74%

4 Jagadish kumar

et al99

Mysore 2008-10 79%

5 Present Study Bangalore 2010-12 53%

INVESTIGATIONS :

The mean hemoglobin and hematocrit in the present study were 12.721 gm%

and 37.86 % respectively.

In a study done by Gurdeep S.D et al; the mean hematocrit value was 35.5 % .88

There was no significant statistical correlation between hematocrit and

severity of disease among the clinical subgroups of dengue.83

Narayanan et al reported the same to be 10.8 gm% and 33.2% respectively.

The classical description of > 20% rise in the hematocrit is difficult to

establish, as the reference standards have not been established for Indian children.

Hence the rise in hematocrit was not taken as a diagnostic criteria.

  102

Leucopoenia has been reported in a number of studies, the present study had

36 (36%) patients with leucopenia i.e. <4000 cells/cu mm.and mean total leukocyte

count of 6014.5 cells/cumm. The highest and lowest TLC was 22000 and 1400

cells/cu mm respectively.

Nazish Butt et al, in their series found that, out of 104 patients ,55 (52.8%) had

leucopenia. The mean leucoycte count was 5200 cells/cu.mm , which almost correlates

with the present study.80

Thrombocytopenia and dysfunctional platelets remains a central hallmark of

dengue fever, surprisingly little is known about the interaction of dengue virus with

platelets.100

Platelets counts carry one of the most important key for diagnosis. On taking

the WHO limit of < 100000/cmm for low platelet count, 85 % had thrombocytopenia

in the present study.

The mean platelet in the present study was 41870 cells/cmm. The platelet

counts at the admission was neither an indicator of prognosis nor of bleeding

tendencies or progression of the disease. This suggest that other factors like platelet

dysfunction or disseminated intravascualr coagulation may have role in bleeding in

dengue fever cases. However studies which include only DHF cases shows correlation

between low platelet count and bleeding manifestations.101

The studies by Gomber et al and Narayanan et al have documented the same

opinion.83 , 84

A study done in Hong-Kong during 1998-2005 among 126 patients with 123

(98%) being dengue fever and 3 (2%) had dengue hemorrhagic fever,

thrombocytopenia, was present in 86%of patients.78

  103

But platelet count provides a very useful means of diagnosis at the screening

level. Hence the platelet count was a sensitive indicator for diagnosis but it did not

correlated with the outcome. Bleeding manifestations are more frequent with low

platelet count.

Nazish Butt et al study found that history, clinical examination and triad of

thrombocytopenia, haematocrit and elevated liver enzymes useful in early diagnosis

of Dengue hemorrhagic fever without waiting for Dengue serology..In Nazish Butt et

al study, 100% of the patients had thrombocytopenia. 80

In Larreal et al study, laboratory test findings showed leucopenia in 72.5% in

both forms of dengue, and of patients with DHF severe thrombocytopenia (<

50,000/mm3platelets) in 70.9% .102

Faridi et al study found that children presented with fever and hepatomegaly,

had a platelet count of between 20,000 /mm3 and 50,000/mm3, bleeding

manifestations were not related to platelet count.103

The present study findings concurred with the previous studies and we found

that thrombocytopenia was the most commonly associated finding.

PROTHROMBIN TIME AND ACTIVATED PARTIAL THROMBOPLASTIN

TIME :

Few studies have documented utility of PTT as a diagnostic indicator.

PT is a sensitive indicator of synthetic function of liver. The prolonged APTT in the

acute phase may be due to hepatic injury and a low grade disseminated intravascular

coagulation.

  104

Larreal et al study found that laboratory test findings showed prolonged PT and APPT

in 23.0% and 42.3% respectively.102

TRANSAMINASES :

Although transaminases are said to be non specific for infections and stress, a

significant more than four fold rise was documented in some cases in this study. They

are not of any prognostic value, but serve as useful masker for diagnosis. Many

studies have noted high transaminases levels. Kalayanarooj’s et al in 1997 in their

study at Bangkok reported higher levels of SGPT in patients of DHF than in DF.1

The present study did not demonstrate a significant difference in the LFT’s

between the clinical subgroup of dengue.

In epidemic or endemic areas, dengue fever infection should be considered in

the differential diagnosis of anicteric hepatitis. The high incidence of vomiting,

hepatomagaly and elevated liver enzymes can score as markers of suspicion of dengue

during an epidemic.

SI. No. Study Place Year No. of

cases

SGPT

levels

SGOT

levels

1 Chandrakanta

et al85

Lucknow 2008 80 78 98

2 Kumar et al94 Lucknow 2008 39 129 116

3 Pancharoen

et al87

Thailand 2001 80 1503 597

4 Present study Bangalore 2010-12 100 98.82 168.58

  105

Wahid et al study noted that ALT levels were significantly different in grade 2

or 4 DHF cases, indicating that the liver function derangement is related to the

severity of Dengue viral infection. DHF patients in the present study with

spontaneous hemorrhage had significantly higher ALT and ALP levels than those

without hemorrhage, suggests that DHF patients who bled had more severe

hepatocellular damage. Concluded that the liver is commonly involved in Dengue

viral infection, the presence of spontaneous bleeding may be useful in predicting the

extent of the hepatocellular damage observed in DHF.104

Itha S et al study showed transaminases values being increased in 96% of

cases.105

Larreal et al study showed that laboratory test findings showed Transaminase

values five fold higher than the normal values (p < 0.005) were observed in 36.8%

and 74.4% of patients with CD and DHF respectively, AST was predominant in both

groups as their results suggest liver damage during the course of Dengue.102

W.Petdachai in his study found that in children with Dengue shock syndrome,

AST levels were elevated in all cases and were more than ALT levels. Hepatic

dysfunction is common in Dengue infection and aminotransferase levels were useful

in predicting the occurrence of hepatic dysfunction.106

Jagadish kumar et al found a rise in AST in 93% and ALT in 78% of the

cases.99

Luis et.al. In there study on “Impact of Dengue on liver function as evaluated

by aminotransferase levels” found that aminotransferase levels were high in

65.1% of patients.107

  106

Faridi et al study found that children had serum glutamic pyruvate

transaminase (SGPT) >40 IU/L and they concluded that hepatic dysfunction with

increased levels of serum enzymes was common in DHF.103

SERUM ALBUMIN :

SI. No. Study Place Year No. Of cases

Test Positivity

1 Itha S, et al105

Uttar Pradesh 2005 45 76%

2 Jagadish kumar et al99

Mysore 2008-10 110 66%

3 Present study Bangalore 2010-12 100 64%

Plasma leakage, which indicates that dengue causes hypoalbuminemia, is an

indicator of severity. In our study, albuminemia lesser than 3.4 g/dL was associated

with higher incidence of DHF. Usually high values of albuminemia may reflect the

integrity of the vascular endothelium, whereas albumin levels less than 3.4 g/dL may

be an early indicator of vascular permeability alteration. Therefore, this parameter

may be an early indicator of plasma leakage and a useful prognostic marker.

CHEST RADIOGRAPHY :

Out of 100 children in the study 38 (38%) showed evidence of right sided

pleural effusion, out of them 2 had bilateral effusion.

WHO has mentioned pleural effusion, especially on right side, as a consistent finding

of dengue. According to WHO, pleural effusion is a supporting evidence of plasma

leakage, the distinguishing feature of DHF. It also mentions that extent of pleural

  107

effusion correlates with the severity of the disease and bilateral pleural effusion is

common in shock.

USG ABDOMEN :

The most striking USG-Abdomen finding in our study population was GB

wall thickening /edema that was seen in 33% of the patients. Splenomegaly,

hepatomegaly and ascites were also seen.

P M Venkata sai, R Krishnan, in their study on role of Ultrasound in Dengue

fever found that ultrasound of abdomen is an important adjunct to clinical profile in

diagnosing DF and may help direct further confirmatory investigations and during an

epidemic , ultrasound features of thickened GB wall, pleural effusion and ascites

strongly favour the diagnosis of Dengue fever.108

Jagadish kumar et al , in their study have demonstrated abnormal USG

abdomen findings in 65% of cases which included Gall bladder wall thickening.99

DENGUE SEROLOGY:

The dengue Ag was positive in 43 children, IgM was tested positive in 58 children ,

IgG was positive in 22 cases in the study.

FINAL DIAGNOSIS:

The present study had DF 36 (36%), DHF 33 (33%), DSS 15 (15%) and DLI 16

(16%) cases among total of 100 cases.

  108

CONCLUSION

Dengue is a major public health problem in Bangalore and surrounding

districts in the state of Karnataka in South India.

The present study had an objective of studying early clinical manifestation and

complications, hematological and hepatic dysfunction associated with the disease and

to correlate with other laboratory investigations and radiological findings in Dengue

fever.

In our present study classical dengue fever was most common presentation

followed by other complicated forms such as dengue hemorrhagic fever and dengue

shock syndrome.

Most of the patients presented with classical features such as fever, vomiting,

abdominal pain, headache, myalgia, arthralgia, oedema, low back ache, retro orbital

pain, rashes, bleeding manifestations. However few patients presented with atypical

presentations such as cough, diarrhoea, sore throat (cold).

Hypotension, hemorrhagic spots , positive tourniquet test , jaundice , pleural

effusion , ascites , neck stiffness are the common findings on examination associated

with complicated forms of dengue.

Bleeding , shock , hepatitis, polyserositis , meningitis, pneumonia are the

complications seen in severe forms.

On investigation Deranged liver function test, renal function test, secondary

dengue infection, thickened gall bladder wall , hepatosplenomegaly on ultrasound

abdomen, pleural effusion on chest radiogram are associated with DHF and DSS.

Platelet count does not correlate with severity of the disease.

  109

In children, importance should be given to symptoms like fever, vomiting,

bleeding, musculoskeletal pain flushing and abdominal pain. If these are associated

with hepatomegaly, positive tourniquet test, low platelet count , elevated PTT and

elevated liver enzymes, a strong possibility of dengue to be considered, especially

during epidemic.

A positive torniquet test should prompt close observation and early hospital

referral, but a negative test does not excluded dengue infection.

During epidemic, dengue should be considered on the differential diagnosis of

any child presenting with fever.

Tourniquet test, low platelet count and chest radiograph for pleural effusion

are useful guides at primary health care level. Blood pressure should be monitered for

evaluating the progress of the disease. Bleeding tendencies should be closely watched.

Any evidence of disease progressing towards dengue hemorrhagic fever or dengue

shock syndrome, should be immediately referred to nearby referral centres.

A focused history , detailed clinical examination and appropriate relevant

investigations will aid for early diagnosis. The treatment of dengue is mainly

supportive, but early institution and meticulous monitoring are the corner stone for

positive outcome.

  110

SUMMARY

The present study was undertaken to study various clinical manifestations and

acute complications of Dengue fever, including its complicated forms such as

DSS and DHF.

It involved prospective analysis of 100 cases of suspected cases of dengue

fever who were admitted at KIMS Hospital Bangalore from December 2010 to

April 2012 i.e. during the study period.

It was observed that the disease was common in age group of 5-11 yr (54%).

Most of the patients were male (66%) with an M: F ratio of 1.94:1.

The common presenting symptoms were fever(96%), vomiting(49%),

abdominal pain(42%), headache(12%), myalgia(7%), arthralgia(4%), retro

orbital pain(1%).

But few patients had unusual symptoms such as vomiting, diarrhoea, cough,

sore throat, breathlessness.

General physical examination revealed presence of hypotension, tachycardia,

rashes, facial puffiness (28%), pedal oedema (21%), and conjunctival

congestion (18%).

Tourniquet test was positive in 43 cases.

The skin bleeding was the most common manifestation noted in 12 cases

(12%) followed by GIT bleeding like hematemesis 4 cases (4%) followed by

epistaxis 4 cases (4%), hematuria 2 cases (2%) and gum bleeds 2 cases (2%).

On Systemic examination patients were found to have Hepatomegaly (53%),

Ascites (13%), Splenomegaly (8%), and pleural effusion (27%).

The mean hemoglobin and hematocrit in the present study were 12.721 gm%

and 37.86 % respectively.

  111

36 (36%) patients in the study had leucopenia and mean total leukocyte count

of 6014.5 cells/cu mm. The highest and lowest TLC was 22000 and 1400

cells/cu mm respectively.

85 % cases had thrombocytopenia in the present study. The mean platelet in

the present study was 41870 cells/cu mm.

Elevated liver enzymes and elevated serum creatinine was found in

complicated forms of disease.

Out of total 100 cases studied 36 were classified as classical dengue fever, 33

as DHF, 15 as DSS, 16 as DLI.

  112

BIBLIOGRAPHY

1. Kalayanarooj S, Vaughn DW, Nimmannitya S, Green S, Suntayakorn S et

al., Early clinical and laboratory indicators of acute Dengue illness. J Infect

Dis 1997; 176: 313-21.

2. Malavige GN, Fernando S, Fernando DJ, Seneviratne SL. Dengue viral

infections. Postgrad Med J 2004; 80:588-601.

3. Gubler DJ. Dengue/dengue haemorrhagic fever: history and current status.

Novartis Found Symp. 2006; 277:3-16; discussion 16-22, 71-3, 251-3.

4. Perez JGR, Clark GG, Gubler DJ, Reiter P, Sanders EJ, Vorndam AV.

Dengue and Dengue hemorrhagic fever. Lancet 1998; 352: 971-977.

5. World Health Organization, Dengue Hemorrhagic Fever: Diagnosis,

Treatment and Control. Geneva: WHO, 1986.

6. Rigau-Pérez JG. The early use of break-bone fever (Quebranta huesos,

1771) and dengue (1801) in Spanish. Am J Trop Med Hyg. 1998 Aug;

59(2):272-4.

7. Cohen S.N. Halsread SB. Shock associated with Dengue infection. J Pediatr

1966; 68: 448-56.

8. WHO. Dengue and Dengue Hemorrhagic Fever, Impact of Dengue, Global

Alert and Response (GAR), Geneva, World Health Organization, 2009

9. Maria G Guzmán , Gustavo Kouri. Dengue: an update. The Lancet Infectious

Diseases Jan 2002 ; 2(1) : 33 – 42.

10. Ashwini Kumar, Chythra R Rao, Vinay Pandit, Seema shetty,

Chanaveerappa Bammigatti, Charmaine Minoli Samarasingh ,et al. Clinical

  113

manifestations and trend of dengue cases admitted in a tertiary care hospital,

Udupi district, Karnataka Indian J Community Med 2010;35:386-90

11. Chaturvedi UC, Nagar R. Dengue and dengue haemorrhagic fever: Indian

perspective. J Biosci. 2008 Nov; 33(4):429-41.

12. CVR Mohan Rao. Dengue fever in India (Annotational). The Indian

Journal of Pediatrics 1987; 54(1):11-14

13. Arindam Sarkar, Debjani Taraphdar, and Shyamalendu Chatterjee.

Molecular Typing of Dengue Virus Circulating in Kolkata, India in 2010. J

Trop Med; 2012 (2012): Article ID 960329, 5 pages

14. Carey DE, Myers RM, Reuben R, Rodrigues FM. Studies on dengue in

Vellore, South India. Am J Trop Med Hyg. 1966 Jul;15(4):580–587

15. Hammon WMcD. Dengue hemorrhagic fever: do we know its cause? Am J

Trop Med Hyg 1973; 22: 82-91.

16. Naseem Salahuddin, Farheen Ali, Muhammad Ali and Fauzia Rashid.

Dengue Fever Outbreak in Karachi, 2005—A Clinical Experience. Infect dis

J of Pakistan Oct - Dec 2005;14(4):115-7.

17. Gubler DJ. Dengue and Dengue Hemorrhagic Fever. Clin. Microbiol. Rev.

1998; 11(3):480-496

18. Marcelo M. Samsa, Juan A. Mondotte, Julio J. Caramelo, Andrea V.

Gamarnik. Uncoupling cis-Acting RNA Elements from Coding Sequences

Revealed a Requirement of the N-Terminal Region of Dengue Virus Capsid

Protein in Virus Particle Formation. J Virol. 2012 January; 86(2): 1046–

1058.

19. Thai Leong Yap, Ting Xu, Yen-Liang Chen, Helene Malet, Marie-Pierre

Egloff, Bruno Canard, et al. Crystal Structure of the Dengue Virus RNA-

  114

Dependent RNA Polymerase Catalytic Domain at 1.85-Angstrom

Resolution. J Virol. 2007 May; 81(9): 4753–4765.

20. Duane J Gubler. Dengue Fever Viruses. Encyclopedia of life sciences 2001

Nature Publishing Group / www.els.net

21. Soila Sukupolvi-Petty, S. Kyle Austin, Michael Engle, James D. Brien,

Kimberly A. Dowd, Katherine L. Williams, et al . Structure and Function

Analysis of Therapeutic Monoclonal Antibodies against Dengue Virus Type

2. J Virol. 2010 September; 84(18): 9227–9239.

22. Communicable disease surveillance and response, WHO 2002,

http://www.who.int/entity/csr/disease/Dengue

23. Gibbons RV, Vaughn DW. Dengue: an escalating problem. BMJ, 2002; 324:

1563-1566.

24. Jonathan A. Patz, Willem J.M. Martens, Dana A. Focks, and Theo H.

Jettend. Dengue Fever Epidemic Potential as Projected by General

Circulation Models of Global Climate Change. Environmental Health

Perspectives Mar 1998 ; 106(3):147-53.

25. Cheong LL. The vectors of Dengue and Dengue haemorrhagic fever in

Malaysia. In: Rudnick A, Lin TW, editors. Dengue fever studies in

Malaysia, bulletin 23. Kuala Lumpur, Malaysia : Institute of Medical

Research. 1986

26. World Health Organization. Prevention and Control of Dengue and Dengue

Hemorrhagic Fever. WHO SEARO Publication No.29, New Delhi 1999.

  115

27. October M. Sessions, Nicholas J. Barrows , Jayme A. Souza-Neto , Timothy

J. Robinson , Christine L. Hershey, Mary A. Rodgers , et al. Discovery of

insect and human dengue virus host factors. Nature April 2009; 458: 1047-

1050.

28. World Health Organization. Dengue and dengue haemorrhagic fever.

Factsheet. No. 117, 2002. revised May 2008. Geneva, World Health

Organization, 2008. Available from :

http://www.who.int/mediacentre/factsheets/fs117/en/ [last accessed on 2012-

09-25].

29. Kurane, Takasaki T, Yamada K. Trends in flavivirus infections in Japan.

Emerg Infect Dis 2000; 6: 569-571.

30. From the Centers for Disease Control and Prevention. Imported Dengue-

United States, 1997 and 1998. JAMA 2000; 283: 1953-1954.

31. Gubler DJ. Aedes aegypti and Aedes aegypti-borne disease control in the

1990s: top down or bottom up? Charles Franklin Craig Lecture. Am J Trop

Med Hyg 1989; 40: 571-578.

32. Burke DS, Nisalak A, Johnson DE. Scott RM. A prospective study of

Dengue infections in Bangkok. Am J Trop Med Hyg 1988; 38: 172-180.

33. Communicable disease surveillance and response, WHO 2002,

http://www.who.int/entity/csr/disease/Dengue

34. Donald E.Carey, Ruth M.Myers.Studies on Dengue in Vellore, South India.

Am J Trop Med Hyg 1966;15(4):580-87.

35. Rachel Daniel, Rajamohanan and Aby Zachariah Philip. A Study of

Clinical Profile of Dengue Fever in Kollam, Kerala, India, Dengue bulletin

2007; 29: 197-203

  116

36. Anitha chakravarthi, Rajni kumaria. Eco-epidemiological analysis of

Dengue infection during an outbreak of Dengue fever ,India. Virology

journal 2005; 2: 232.

37. Acharya SK, Buch P. Out break of Dengue fever In Delhi. Lancet 1998 ;2:

I485-6.

38. Halstead SB. Dengue hemorrhagic fever: a public health problem and a field

for research. Bull WHO 1980;58:1-21.

39. Leong AS, Wong KT, Leong TY, Tan PH, Wannakrairot P. The pathology

of dengue hemorrhagic fever. Semin Diagn Pathol. 2007 Nov; 24(4):227-36.

40. Halstead SB. The pathogenesis of Dengue: The Alexander D.Langmuir

Lecture. Am J Trop Med Hyg 1981; 114: 632-48.

41. Thaneeya Duangchinda , Wanwisa Dejnirattisai , Sirijit Vasanawathana ,

Wannee Limpitikul ,Nattaya Tangthawornchaikul , Prida Malasit, et al.

Immunodominant T-cell responses to dengue virus NS3 are associated with

DHF. PNAS September 28, 2010; 107(39): 16922-16927.

42. Wanwisa Dejnirattisai, Amonrat Jumnainsong, Naruthai Onsirisakul,

Patricia Fitton, Sirijitt Vasanawathana, Wannee Limpitikul, et al. Cross-

Reacting Antibodies Enhance Dengue Virus Infection in Humans. Science 7

May 2010; 328(5979) :745-748.

43. Tikki Pang , Mary Jane Cardosa and Maria G Guzman. Of cascades and

perfect storms: the immunopathogenesis of dengue haemorrhagic fever-

dengue shock syndrome (DHF/DSS). Immunology and Cell Biology (2007)

;85: 43–45

  117

44. Raghunath D, Rao Durga C (Ed); Prida Malaist ; Immunopathogenisis of

DHF;Arthropod Borne Viral infections- Current status and Research ; Vol 8,

Tata Mc Graw Hill, New Delhi,;2008: 137.

45. Harrington LC, Edman JD, Scott TW. Why do female Aedes aegypti

(Diptera: Culicidae) feed preferentially and frequently on human blood. J

Med Entomol 2001;38:411-422

46. Raghunath D, Rao Durga C (Ed); Prida Malaist ; Immunopathogenisis of

DHF;Arthropod Borne Viral infections- Current status and Research ; Vol 8,

Tata Mc Graw Hill, New Delhi,;2008: 137.

47. Byron E. E. Martina, Penelope Koraka and Albert D. M. E. Osterhaus.

Dengue Virus Pathogenesis: an Integrated view. Clin. Microbiol.

Rev. October 2009 ; 22(4): 564-581.

48. Karen Clyde, Jennifer L. Kyle and Eva Harris. Recent Advances in

Deciphering Viral and Host Determinants of Dengue Virus Replication and

Pathogenesis. J. Virol. 2006, 80(23):11418-11431.

49. Eric C. M. Van Gorp , Monique C. Minnema, Catharina Suharti, Albert T.

A. Mairuhu, Dees P. M. Brandjes, Hugo Ten Cate , et al. Activation of

coagulation factor XI, without detectable contact activation in dengue

haemorrhagic fever. British Journal of Haematology April 2001;

113(1): 94–99.

50. Sumarmo. The role of steroids in Dengue shock syndrome. Southeast Asian

J Trop Med Public Health 1987; 18: 383-389.

51. Nimmanitya S. Dengue hemorrhagic fever with unusual clinical

manifestations. Southeast Asian J Trop Med Public Health 1987; 18: 398-

406.

  118

52. Sangkawahibha N, Rojanasuphot S, Ahandrik S ,et al. Risk factors in

Dengueshock syndrome: a prospective epidemiologic study in Rayong,

Thailand. Am J Epidemiol 1984; 120: 653-69.

53. Gubler DJ. Dengue. In: Monath TP, ed. The arbovirus: Epidemiology and

ecology. Boca Raton, FLA: CRC Press, 1988: 223-60

54. Sharp TW, Wallace MR, Hayes CG, Sanchez JL, DeFraites RF, Arthur RR,

et al. Dengue fever in US troops during Operation Restore Hope, Somalia,

1992-1993. Am J Trop Med Hyg 1995; 53: 89-94.

55. Waterman SH, Gubler DJ. Dengue fever. Clin Dermatol 1989; 7: 117-122

56. Emy Abi Thomas, Mary John, and Bimal Kanish. Mucocutaneous

manifestations of dengue fever. Indian J Dermatol. 2010 Jan-Mar; 55(1):

79–85.

57. World Health Organization, Dengue guideline for diagnosis, treatment,

prevention and control: Geneva; WHO, 2009.

58. Wali J.P, Biswas A; Validity of tourniquet test in Dengue hemorrhagic

fever; Journal of associate physicians of India; 1999; 47:203-204

59. Janak Kishore , Jagdeep Singh, T.N. Dhole and A. Ayyagari. Clinical and

Serological Study of First Large Epidemic of Dengue in and around

Lucknow, India . Dengue bulletin 2006. 30, 72-80

60. World Health Organization- Technical Guides for Diagnosis, Treatment,

Surveillance, Prevention and Control of Dengue Haemorrhagic fever.

Geneva: WHO, 1975.

61. George R, Liam CK, Chua CT, Lam SK, Pang T, Geethan R, Foo LS.

Unusual clinical manifestations of Dengue virus infection. Southeast Asian J

Trop Med Public Health. 1998; 19: 585-590.

  119

62. Lum LCS, Lam SK, Choy YS, George R, Harun F. Dengue Encephalitis: a

true entity ? Am J Trop Med Hyg. 1996; 54: 256-259.

63. Lum LCS, Lam SK, George R and Devi S. Fulminant hepatitis in Dengue

infection. Southeast Asiaan J Trop Med Public Health. 1993; 24: 467-471.

64. Lum LCS, Thong MK, Cheah YK and Lam SK Dengue-associated adult

respiratory distress syndrome. Ann Trop Paediatrics. 1995; 15: 335-339.

65. Chye JK, Lim CT, Ng KB, Lim JMH, George R, Lam SK, et al. Vertical

transmission of Dengue Clin Inf Dis. 1997; 25: 1374-1377.

66. Solomon T, Dung NM, Vaughn DW, Kneen R, Thao LT, Raengsakulrach B,

et al. Neurological manifestations of Dengue infection. Lancet 2000; 355:

1053-1059.

67. Liu CC, Huang KJ, Lin YS, Yeh TM, Liu HS, Lei HY, et al. Transient

CD4/CD8 ratio inversion and aberrant immune activation during Dengue

virus infection. J Med Virol. 2002 Oct; 68(2): 241-52.

68. Burke DS, Nisalak A, Johnson DE. Scott RM. A prospective study of

Dengue infections in Bangkok. Am J Trop Med Hyg 1988; 38: 172-180.

69. Anitha chakravarthi, Rajni kumaria. Circulating levels of tumor necrosis

factor alfa in patients with Dengue and Dengue hemorrhagic fever during an

outbreak. Indian J med Res 2006; 123:25-30.

70. Ibrahim NM" Cehong . Dengue hemorrhagic fever at Kualalampur hospital:

retrospective study of 102 cases. Br J Clin Pract 1995;49: 189-91.

71. Dengue: clinical and public health aspects-Transmission of Dengue virus by

Aedes aegypti,Centre for disease contro1.435-36.

72. Robert F. Pulmonary hemorrhage syndrome associated with an autochtonous

case of Dengue hemorrhagic fever. South med J 2004; 97(7):688-91.

  120

73. Naseem Salahuddin, Farheen Ali, Muhammad Ali and Fauzia Rashid.

Dengue Fever Outbreak in Karachi, 2005—A Clinical Experience. Infect dis

J of Pakistan Oct - Dec 2005;14(4):115-7.

74. Gulati S., Maheshwari A. Atypical manifestations of dengue. Trop Med Int

Health. 2007 Sep.; 12(9):1087 – 95.

75. Angel balmaseda, samantha n. Hammond, leonel pérez, yolanda tellez, saira

indirasaborío, juan carlos mercado, et al. Serotype-specific differences in

clinical manifestations of dengue. Am. J. Trop. Med. Hyg., 2006; 74(3):

449–456.

76. Curtis G.H, Corazon R.M, Dengue infections in the Philippines: Clinical and

virological findings in 517 hospitalized patients; Am .J Trop. Med. Hyg.

1988; 39(1) : 110-116.

77. Dengue fever outbreak: A clinical management experience; J.coll.

Physicians Surg. Pak. 2008; 18(1):8-12 (Abstract).

78. Chuang W.V, Wong Y.T, Leung Y.H; Review Of Dengue fever cases in

Hong Kong during 1998 to 2005. Hong Kong Medical Journal 2008;

14(30):170-177.

79. Abrol .A, Dewan A; A clinico-Epidemological profile of Dengue fever cases

in periurban area of Chandigarh; The Internet Journal of epidemiology 2007;

5(1).

80. Butt N, Abbassi A, Munir S.M, Ahmad S.M, Sheikh Q.H. Haematological

and Biochemical indicators for early diagnosis of Dengue viral infections.

Journal of the college of physicians and Surgeons Pakistan 2008;18:282-

285.

  121

81. De Gruchy G.C (Ed); The hemorrhagic disorders vascular and platelet

defects; clinical hematology in medical practice, 3rd edition, Alden press,

Oxford, 1970: 616- 617.

82. Songee L Branch,Paul N Levetti. Evaluation of four methods for detection

of immunoglobulin M antibodies to Dengue virus. Clinical and diagnostic

laboratory immunology July 1999:555-57.

83. Narayanan M, Arvind MA, Thilothammal N, Prema R, Sargunam Rex CS et

al. Dengue Fever Epidemic in Chennai – A Study of Clinical Profile and

Outcome. Indian Pediatr 2002; 39: 1027-1033.

84. Gomber S, Ramachandran VG, Kumar S, Agarwal, Gupta P, Gupta P et al.

Hematological observations as diagnostic markers in dengue hemorrhagic

fever – a reappraisal. Indian Pediatr 2001; 38: 477-481.

85. Chandrakanta, Kumar R, Garima, Agarwal J, Jain A, Nagar R, et al.

Changing clinical manifestations of dengue infection in north India.! Dengue

Bulletin 2008;32: 118-125.

86. Cam BV, Fonsmark L, Hue NB, Phoung NT, Poulsen A, Heegaard ED, et al.

Prospective case control study of encephalopathy in children with dengue

hemorragic fever . Am J Trop Med Hyg 2001;65: 848-51.

87. Panchareon C, Thisyakorn U. Neurological manifestations in dengue

patients. Southeast Asian J Trop Med Public Health 2001; 32(2): 341-5

88. Gurdeep S.D, Deepak B; Clinical profile and outcome in children of dengue

hemorrhagic fever in North India. Iran Journal of pediatrics 2008; 18(No: 3)

:222-228.

  122

89. Aisha Sajid, Asim Ikram, Mubashir Ahmed. Dengue fever outbreak 2011:

clinical profile of children presenting at madina teaching hospital faisalabad.

JUMDC Jan-Jun 2012; 3(1) : 42-47.

90. Anuradha S, Singh NP, Rizvi SN, Agarwal SK, Gur R, Mathur MD, et al.

The 1996 outbreak of dengue hemorrhagic fever in Delhi, India. Southeast

Asian J Trop Med Public Health. 1998 Sep ; 29(3): 503-6.

91. Misra UK, Kalita J, Syam UK, Dhole TN. Neurological Manifestation of

dengue viral infection. J Neurol Sci 2006 ;244(1-2):117-22.

92. Kankirawatana P, Chokephaibolkit K, Yoksan S , Pathavathana P. Dengue

infection presenting with central nervous system manifestation. J Child

Neurol 2000;(8):544-7.

93. Solomon T, Dung NM, Vaughn DW, Kneen R, Thao LT, Raengsakulrach B,

et al. Neurological manifestations of Dengue infection. Lancet 2000; 355:

1053-1059.

94. Kumar ND, Tomar V, Singh B, Kela K. Platelet transfusion practice during

Dengue fever epidemic. Indian J Pathol Microbiol. 2000; 43: 55-60.

95. Rahman M, Rahman K, Siddque AK, Shoma S, Kamal AH, Ali KS et al.

First outbreak of Dengue hemorrhagic fever, Bangladesh. Emerg Infect Dis.

2002; 8: 738-40.

96. Kabra SK, Jain Y, Pandey RM, Madhulika, Singhal T, Tripathi P, et al.

Dengue haemorrhagic fever in children in the 1996 Delhi epidemic. Trans R

Soc Trop Med Hyg. 1999; 93: 294-8.

97. Nimmannitya S. Dengue and Dengue Hemorrhagic fever in the South-East

Asian Regions. Am J Trop Med Hyg. 1969; 18: 954-971.

  123

98. Mohan B, Patwari AK, Anand VK. Hepatic dysfunction in childhood

Dengue infection. J Trop Pediatr. 2000; 46: 40-3.

99. Kalenahalli Jagadishkumar, Puja Jain, Vaddambal G. Manjunath, Lingappa

Umesh . Hepatic Involvement in Dengue Fever in Children. Iran J Pediatr

Jun 2012 ; 22 ( 2):231-36.

100. Raghunath D, Rao Durga C (Ed); Atana Basu ;Dengue interaction with

platelets; Clinical feature and management ;Current status and Research ,

Vol 8, Tata Mc Graw Hill, New Delhi, 2008: 147-151.

101. Aggarwal A, Chandra J, Aneja S, Patwari AK, Dutta AK. An epidemic of

Dengue hemorrhagic fever and Dengue shock syndrome in children in Delhi.

Indian Pediatr 1998; 35: 727-732.

102. Larreal Y, Valero N, Estevez J, Reyes I, Maldonado M, Espina L. M. et.al.

Hepatic alterations in patients with Dengue. Invest Clin 2005 Jun; 46(2):169-

78.

103. Faridi M. M. A, Agarwal Anju, Kumar Monish, Sarfazul Abedin. Clinical

and Biochemical profile of Dengue Hemorrhagic fever in children in Delhi.

Tropical doctor 2008; (38):28-30.

104. Wahid SF,Sanusi S, Zawawi MM, Ali RA. A comparison of pattern of liver

involvement in Dengue hemorrhagic fever with classic Dengue fever. J

Southeast Asian J Trop Med Public Health 2000; 31(2):259-63.

105. Itha S, Kashyap R, Krishnani N, Saraswat VA, Choudhuri G, Aggarwal R:

Profile of liver involvement in dengue virus infection. Natl Med J India

2005, 18:127-30.

  124

106. Petdachai W. Hepatic dysfunction in children with Dengue shock syndrome.

Dengue bulletin 2005; (29):112-118.

107. Desouza L J, Ribeiro Rita M, Cordeiro Soares N L, Cordeiro Soares C E,

Bruno Fernandes, Ribas et.al. Impact of Dengue on liver function as

evaluated by aminotransferase levels. Braz J Dis Aug 2007; 11(4).

108. P M Venkata sai, R Krishnan. Role of ultrasound in Dengue fever. The

British Journal of Radiology; 78(2005), 416-418.

  125

10.1 ETHICAL CLEARANCE FOR DISSERTATION STUDY

  126

10.2 CLINICAL PHOTOGRAPHS

Fig 14 : RASH IN CASE OF A DENGUE FEVER.

Fig 15 : RIGHT SIDED PLEURAL EFFUSION IN CASE OF DENGUE FEVER.

  127

10.3 PROFORMA FOR A CASE OF DENGUE FEVER

SECTION A

1. NAME OF THE INSTITUTE : KEMPEGOWDA INSTITUTE OF

MEDICAL SCIENCES AND RESEARCH CENTRE, B’LORE.

2. CASE INVESTIGATION No. :

3. NAME OF THE PATIENT :

4. AGE :

5. SEX : MALE / FEMALE

6. ADDRESS :

7. OCCUPATION :

8. RELIGION : HINDU /MUSLIM /CHRISTIAN /OTHERS

9. INFORMANT :

10. DATE OF ADMISSION :

11. DATE OF DISCHARGE :

12. IP / OP No. :

SECTION B

SYMPTOMS :

IF YES, DURATION:

1. Fever : Yes / No

2. Abdominal Pain : Yes / No

3. Vomiting : Yes / No

4. Headache : Yes / No

5. Myalgia : Yes / No

6. Joint Pains : Yes / No

7. Rashes : Yes / No

  128

8. Petechiae : Yes / No

9. Ecchymosis : Yes / No

10. Melaena : Yes / No

11. Hematuria : Yes / No

12. Hematemesis : Yes / No

13. Epistaxis : Yes / No

14. Gum Bleeds : Yes / No

15. Edema : Yes / No

16. Retro Orbital Pain : Yes / No

17. Diarrhea : Yes / No

18. Constipation : Yes / No

19. Cold : Yes / No

20. Cough : Yes / No

21. Hurried Respiration : Yes / No

22. Convulsions : Yes / No

23. Altered Sensorium : Yes / No

24. Transient Weakness : Yes / No

25. H/O Recent Travel : Yes / No

  129

GENERAL PHYSICAL EXAMINATION

General condition : Stable / Critical

Temperature :

Pulse Rate :

Blood Pressure :

Respiratory Rate :

Pulse pressure :

Tourniquet Test : Positive / Negative

Anthropometry :

PARAMETERS

OBSERVED

EXPECTED

REMARKS

Weight

Height / Length

Head Circumference

Chest Circumference

Mid Arm Circumference

SYSTEMIC EXAMINATION

PER ABDOMEN :

RESPIRATORY SYSTEM :

CARDIOVASCULAR SYSTEM :

CENTRAL NERVOUS SYSTEM:

DIAGNOSIS :

1. Dengue like illness :

2. Dengue Fever :

3. Dengue Hemorragic Fever Grade :

4. Dengue shock syndrome :

  130

SECTION C

INVESTIGATIONS :

1. Date & Time

Hb (g/dl)

PCV (%)

Platelet

count(/cu mm)

2. Total count (TC) :

3. Differential Count (DC) :

4. ESR :

5. Peripheral Smear (PS) :

6. Urine Routine : Albumin -

Sugar -

Pus cells -

Epi cells –

7. SGPT :

8. SGOT :

9. PT : INR:

10.aPTT :

11. Sr. Albumin :

12. Dengue Serology : Ag –

Ig M –

Ig G –

13. RBS :

14. QBC For MP :

  131

15. Widal Test /Blood c/s :

16. Chest X-Ray :

17. Ultrasound Abdomen :

OTHERS / IF NECESSARY :

18. Blood urea :

19. Serum Creatinine :

20. Serum Electrolytes :

21. ECG :

22. 2D ECHO :

23. CSF Analysis :

24. CT Scan Brain/MRI :

TREATMENT:

1. Supportive :

Fluid Therapy

10 ml/kg/hr : Yes / No

7 ml/kg/hr : Yes / No

5 ml/kg/hr : Yes / No

3 ml/kg/hr : Yes / No

2. FFP Transfusion : Yes / No

3.Platelet Transfusion : Yes / No

4. Packed RBC Transfusion : Yes / No

5. Whole Blood Transfusion : Yes / No

6. Inotropes :

Dopamine –

Dobutamine –

  132

7. Antibiotics : Yes / No

8. Ventilator Support : Yes / No

FINAL DIAGNOSIS :

OUTCOME OF THE PATIENT :

SIGN OF THE CANDIDATE / SIGN OF THE GUIDE :

INVESTIGATOR : DATE :

DATE :

  133

10.4 KEY TO MASTER CHART

M Male

F Female

P Present

A Absent

Abd Pain Abdominal Pain

R O Pain Retro-orbital Pain

1 Positive

2 Negative

3 Dengue Antigen Positive

4 Dengue IgM Positive

5 Dengue IgG Positive

6 Gall bladder wall thickened

7 Acalculous Cholecystitis

8 Pleural Effusion

9 Ascites

10 Hepatomegaly

11 Splenomegaly

N Normal

F Febrile

D Decreased

Na Sodium

K Potassium

Cl Chloride

SI 

No.

IP 

No.

Na

me

Ag

e  Sex

Fev

er d  mit

ady

algi

nt 

hes

lae

ma

ma p sta

m 

em Pai

rrh

Col

d ug nv nor

ss 

shi

cul

ech

hy nju

nct

ial 

dal 

mp

Pul

se BP RR pat p en ites

ent

Hb

PC V Plt 

co unt

TC ES R SG OT

SG PT PT PT T IN R S.A

D.S

ero 

CX R US

G 

ab d B.U

rea

S.C

rea

Na

K Cl Dia

gn

1 24488/10 Syed Muthaiyab 5 yrs M P P P A A A A A A P A A A A A A A A A 1 A A A A A A A N 86 98/70 24 P A A N 15.3 43.9 20000 18900 6 366 17.7 36.8 1.19 4, 5 N 6, 8, 9, 10 DHF

2 24580/10 Archana 12 Yrs F P P A A A A A A A A A P A A A A A A A 2 A A P A A A A N 88 82/64 28 A A A N 13.5 40 9000 2600 4 38 22 40 1.5 3 N 6, 8, 9, 10 DHF

3 24609/10 Chandana 11 yrs F P P A A A A A A A A A A A A A A P A A 2 A A A A A A A N 80 104/70 28 A A A N 11.5 32 35000 4900 12 298 200 2  ‐  N N DLI

4 24647/10 Harish 11 yrs 10mM P A P A A A A A A A P A A A A A A A A 1 P A P A A A A N 82 96/56 28 P A A N 13.3 37.2 7000 3800 12 50 49 16 42.5 1.11 5 N N DHF

5 24730/10 Dhanush 4 yrs M P P A A A A A A A A A A A A A A A A A 2 A A A A A A A N 78 100/60 24 P A A N 9.5 29 100000 15700 44 247 147 1.9  ‐  N N DLI

6 24988/10 Gagana 10 yrs F P A A A A A A A A A A A A A A A A A A 1 A A P A A A A N 96 100/64 28 P A P D 14.6 39.8 9000 4300 4 203 92 32.1 60.4 2.22 2.6 3, 4 E 7, 8, 9 DHF

7 25077/10 Arif Pasha 13 yrs M P P P A A A A A A A A A A A A A A A A 1 P A A A A A A N 72 106/68 22 P A P D 18.9 54.2 6000 13300 20 255 379 28 50.5 1.93 2.9 3 E 7, 10, 11 DHF

8 25209/10 Prajwal 6 yrs M P P A A A A A A A A A A A A A A A A A 1 A A P A A A A N 110 94/54 28 P A A N 12.4 37.2 52000 4500 20 298 90 20.3 43.1 1.37 3.2 3 N N DHF

9 25474/10 Md Mannan 11 yrs M P P P P P A A A A A A A A A A A A A A 1 A A P A A A A N 68 100/70 26 A A A N 12.1 36.1 54000 2700 7 102 98 20.2 40.2 1.37 2.9 3, 4 N N DHF

10 25479/10 Dil Nawaz 6 yrs M P A A A A A A A A A A A A A A A A A A 1 P A A A A A A N 98 90/60 40 A A A N 11.4 35 33000 3700 13 139 38 20.9 45 1.47 3.6  ‐  N 6, 7, 8 DHF

11 25522/10 Roshan 11 yrs M P A A A A A A A A A A A A A A A A A A 1 A A A A A P A N 98 80/64 28 A A A N 14.7 43 17000 3400 6 36 24 21 40 1.39 2.6  ‐  E 6, 8, 9 DSS

12 26499/10 Ranjitha 8 yrs F P P P A A A A A A A A A A A A A A A A 1 P P P P P P A N 108 80/64 22 P A A N 13.3 38 5000 3400 2 226 43 21 40.5 1.45 2.7 3, 4, 5 N N DSS

13 1666/11 Nadish k 8yrs M P A A A A A P A A A A P A A A A P A A 1 P P A A A P P N 104 98/72 22 P A A N 9.9 28.9 5000 11000 12 112 23 14.1 33.2 1.15 2.5 3, 4 E 6, 9 DHF

14 2134/11 Walahith 4 yrs M P P A A A A A A A A A A A A A A A A A 2 P A A A A A A F 108 96/66 24 P A A N 12.6 40.2 48000 6200 7 62 78 2.9 4 N N DF

15 2334/11 Harshitha 7 yrs F P A A A A A A A A A A A A A A A A A A 2 P A A A A A A N 92 98/68 20 A A A N 10.3 38.3 48000 3400 10 117 119 2.3  ‐  N N DLI

16 3834/11 Moulya 1.8 yrs F P A A A A A A A A A A A A A A A A A A 2 A A A A A A A F 98 90/64 22 P P A A 13.6 39.6 25000 9600 12 84 44 3.2 3 N N DF

17 4431/11 Syed Salauddin 16 yrs M P P A A P A A A A A A A A A A A A A A 2 A A A A A A A N 90 104/64 20 P A A N 13.5 40.1 26000 2500 5 454 267 2.7 3, 4, 5 E 7 DF

18 4596/11 Hoysala 7 yrs M P P P A A A A A A A A A A A A A A A A 2 A A A A A A A N 78 100/70 18 A A A N 13.2 40.4 53000 6000 5 38 42 3.5  ‐  N N DLI

19 4860/11 Raghu 14 yrs M P A A A A A A A A A A A A A A A P A A 2 A A A A A A A N 68 100/70 20 A A A N 11.9 34.8 99000 8300 24 102 32 4 4 N N DF

20 4957/11 Hema 13 yrs F P A A P P A A A A A A A A A A A A A A 1 P P P A P P A N 98 104/78 26 P A A N 16.1 49.9 13000 2600 5 81 33 17 52 1.15 3.1 4, 5 E 7, 9, 10, 11 28 0.7 138 4.9 107 DHF

21 4988/11 Syed Salauddin 16 yrs M P P A P A A A A A A A A A A A A A A A 1 P P P P A P A N 108 80/66 18 P A A N 13.5 40.1 26000 2500 5 454 267 18 42.5 1.02 2.7 3, 4, 5 E 7 28 0.7 DSS

22 5392/11 Gracy 8 yrs F P A A A A P A A A A A A P A A A A A A 2 P A A A A A A N 82 94/64 18 A A A N 12.6 40 52000 4200 10 45 42 3.4  ‐  N N DLI

23 6227/11 Rekha 15 yrs F P P P A A A A A A A A A A A A A A A A 1 P P P A A P A N 100 100/76 24 A A A N 15.5 43.2 13000 3700 4 107 71 17.7 55.4 1.2 3.6 4, 5 N 7, 9 DHF

24 6917/11 Thasmias 10 yrs F P A P A A A A A A A A A A A A A A A A 2 P A A A A A A N 90 104/72 22 P A A N 11.6 34.7 65000 2100 24 101 61 4.2 3, 4, 5 N N DF

25 7155/11 Moheen khan 8 months M P A P A A A A A A A A A A A P A A P A 2 A A A A A P A N 120 90/60 30 P A A N 10.1 30.6 12000 4700 3 218 101 17.1 57.7 1.15 2.3 3, 4 N 6, 8 51 0.8 140 4.2 103 DHF

26 8007/11 Rizwana 14 yrs F P A P A A A A A A A A A A A P A A A P 1 P A P A A A A N 92 100/70 20 P A A N 6.8 19.2 8000 1400 6 120 65 20 47.9 1.43 3 3 E 6, 8, 9, 11 25 0.9 144 3.7 106 DHF

27 8043/11 Md Roshan 6 yrs M P P P A A A A A A A A A A A A A A A A 2 A A A A A A A N 86 100/60 20 A A A N 15.5 43.8 48000 10000 32 112 32 2.6 4, 5 E 6, 8 DF

28 8107/11 Anirudh 2.6 yrs M P P P A A A A A A A A A A A A A A A A 2 P A A A A A A F 104 90/62 18 P A A N 12.6 38.4 75000 4800 8 77 42 3.3  ‐  N N DLI

29 9180/11 Waseem 6 yrs M P P P A A A P A P A A A A A A A A A A 1 P P P A P P P N 92 90/64 20 P P P D 15.8 45 43000 4100 9 146 48 23 39.6 1.49 3.2 4 E 6, 8 DHF

30 9633/11 Arbiya 8 yrs F P P A A A A A A A P A A A A A A A A A 1 A A A A A P P N 96 90/70 24 P A P D 14.9 43.4 34000 6700 12 173 82 18 54 1.2 3.2 4, 5 E 8, 9 134 5 104 DHF

31 10277/11 Punitha 1 yrs F P A A A A A A A A A A A A A P A A A A 1 A A P A P P P N 86 70/54 34 P A P D 6.5 18.7 32000 2400 15 309 127 54 69 4.9 1.6 4 E 7, 8, 10, 11 19 0.7 130 4.3 92 DSS

32 10527/11 Vinod 2 yrs M P A A A A A A A A A A A A A A A A A A 2 A A A A A A A F 96 98/68 22 A A A N 13.2 35.7 75000 7800 7 44 46 3.4  ‐  N N DLI

33 10823/11 Rithesh 5 yrs M A P P A A A A A A A A A A A A A A A A 2 A A A A A A A N 70 98/68 20 A A A N 10.4 35.4 32000 3800 10 40 78 3.5  ‐  N N DLI

34 11587/11 Jabeer k 11 months M P A P A A A A A A A A A A A P A A A A 2 A A A A A A P N 90 90/70 28 P A A D 10.7 32.1 25000 8500 5 119 60 2.8 4 N 6, 9 DF

35 11816/11 Nandini 12 yrs F P A A A A A A A A A A A A A A A A A A 2 A A A A A A A F 114 110/70 26 P P P D 13.2 42.5 75000 2800 5 42 46 3.7 4 E 6, 8, 9 DF

36 13056/11 Somashekhar 14 yrs M P A A A A A P A A A A A A A A A A A A 1 P P P A A A A N 100 98/68 20 P A A D 15.8 45.7 42000 3300 8 228 43 24 42.5 1.42 2.6 3 N 6, 8, 9 DHF

37 13677/11 Yashas 8 yrs M P A P A A A A A A P A A A A A A A A A 1 P P P A A A P N 76 90/66 24 A A A D 14.4 39.5 31000 2600 10 101 42 12.5 32.5 0.88 2.99 3 E 6, 8, 9 DHF

38 14130/11 Sowmya 9 yrs F P A A A A A A A A A A A A A A A A A A 2 A A A A A A A N 72 100/70 26 P A A N 12.4 36.2 50000 3500 4 42 38 2.6 4 N N DF

39 15051/11 Devika 7 yrs F A P A P P A A A A A A A A A A A A A A 2 A A A A A A A N 72 110/74 22 A A A N 12.6 38.7 67000 4200 7 56 43 2.9  ‐  N N DLI

40 15140/11 Harshalam 8 yrs M P A A A A A A A A A A A A A A A A A A 1 A A A A A A A N 70 100/70 18 P P A N 11.8 36.5 59000 5100 10 188 62 13.6 50.4 0.97 3 4, 5 E 6, 8, 9 DHF

41 15630/11 Amit Gowda 9 yrs M P P A A A A A A A A A A A A A A A A A 2 A A A A A A A N 72 110/60 18 A A A N 12.6 38.4 82000 6200 12 48 45 3.8 4 N N DF

42 16142/11 Vijay k 13 yrs M P A P A A A A A A A A A A A A A A A A 2 P A A A A A A N 92 108/70 20 P A A N 11.5 32.6 36000 7500 35 207 175 24 35.7 1.18 2.2 3 N N DF

43 16447/11 Suhas 16 yrs M P A A A A A A A A A A A A A A A A A A 2 A A A A A A A N 80 110/70 22 P A A D 13.3 38 27000 3800 15 150 66 2.9 4, 5 E 6, 8 DF

44 16550/11 Rashmitha 14 yrs F P P P A A A A A A A A A A A A A A A A 1 P A A A A A A N 92 102/68 20 P A A N 11.7 34.1 47000 5200 8 185 183 14.2 45.9 1.02 2.8 4 N 9, 11 DHF

45 16553/11 Bindushree 11 yrs F P A P P A A A A A A A A A A A A A A A 1 P A A A A A A N 94 104/64 22 P P A N 11.1 31.3 30000 11400 62 114 133 19.1 37.2 1.44 2.3 3, 4 N N DHF

46 17946/11 Yashwanth 14 yrs M P A P A A A A A A A A A P A A A A A A 2 A A A A A A A N 90 106/72 22 P A A N 12.3 35.4 90000 7300 5 86 79 3.8 4 N 6, 8, 11 DF

47 18062/11 Akhil 4 yrs M A P P P P P A A A A A A A A A A A A A 2 P A A A A A A N 74 96/68 18 A A A N 11.4 37.4 78000 3500 7 164 44 3.2 3 N N DF

48 18092/11 Manasa 9 yrs F P P P A A A A A A A A A A A A A A A A 1 P A A A A P P N 98 88/64 26 A A A N 12.6 37.3 15000 4800 14 122 98 30 45 1.45 3 4 N 8 DSS

49 18138/11 Tamim 6 yrs M P A A A A A P A A A A A A A A A P A A 1 P A P P A A A N 102 70/52 30 P A A D 11.3 33 50000 7500 20 725 694 15.15 33.6 1.09 2.7 4, 5 E 6 DSS

50 18770/11 Praveena 12 yrs M P P P P A A P A A A A A A P A A A A A 1 P P P A A P P N 110 80/66 30 P A P D 15.4 45.7 6000 2850 3 280 75 16.2 50.3 1.28 3.2 4, 5 E 6, 8, 9 29 0.9 132 4.8 102 DSS

51 20062/11 Sangeetha 11 yrs F P A P A A A A A A A A A A A A A A A A 2 P A A A A A A F 110 120/70 24 A A A N 9.3 27.9 60000 5200 28 112 40 3.4 4 N N DF

52 21819/11 Praneeth 14 yrs M P A P P A A A A A A A A A A A A A A A 2 A A A A A A A N 120 110/70 28 A A A N 15.3 44.7 14000 2900 8 82 60 2.9 4 N N DF

53 21998/11 Kousar 5 yrs F P P A A A A A A A A A A A A A A A A A 2 P A A A A A A N 120 64 26 P A A N 13.5 44 13000 2700 8 82 36 22 40.2 1.3 2.9 3, 4 E 6, 8, 9 26 0.7 136 3.6 102 DSS

54 21999/11 Yasin 4 yrs F P P P A A A A A A A A A A A A A A A A 2 P A A A A A A N 88 110/80 22 P A A N 11.7 38.2 14000 7300 10 110 35 3.5  ‐  N N DLI

55 22181/11 Advitha 1 yrs F P A A A A A P A A A A A A A A P A A A 1 P P P A A A A N 120 90/60 30 P A A N 15.9 45.8 43000 3400 8 226 43 24 40.5 1.45 2.6 3, 4 N 6, 8, 9 DHF

56 22685/11 Heena Khanum 10 yrs F P P P A A A A A A A A A A A A A A A A 2 P A A A A A A A 90 110/70 20 A A A N 14.3 42.8 26000 5200 2 20 60 2.9 3 N N DF

57 22728/11 Kiran K 3 yrs M P A P A A A A A A A A A A A A A A A A 2 A A A A P P A N 116 96/60 28 A A A N 10.6 32.5 96000 3800 25 60 28 3.5 3, 4 N N DF

58 22830/11 Venkatesh 5 yrs M P A P A A A A A A A A A A A A A A A A 2 P A A A A A A N 124 100/60 26 A A A N 11.6 37.5 39000 8800 5 114 31 3.2 4, 5 E 6 DF

59 22980/11 Noor Ahmed 15 Yrs M P A P P A A A A A A A A A A A A A A A 2 A A A A A A A F 120 120/80 40 P A A D 11.9 39.6 22000 7800 14 30 78 2.9 E 8 39 0.9 135 5.7 98 DLI

60 23142/11 Syed Ismail 11 yrs M P A A P A A A A A A A A A A A A A A A 2 A A A A A A A F 96 110/70 20 A A A N 12.4 39.8 42000 6500 7 78 44 3.6 N N DLI

61 23143/11 Syed Rehman 10 yrs M P P P A A A A A A A A A A A A A A A A 2 P A A A p A A F 90 100/70 22 P A A N 14.8 42.5 32000 3900 6 10 47 4 3 N 6, 8, 9 DF

62 23460/11 Vijay N 10 yrs M P A A P A A A A A A A A A A A A A A A 2 P A A A p P P N 92 70 28 A A A D 14.9 42.1 9000 11100 2 35 110 18.3 31 1.37 1 4, 5 E 7, 8, 9, 10, 1 28 0.7 131 4.8 90 DSS

63 23497/11 Thammanna 7 yrs M P P P A A A A A A A A A A A A A A A A 1 P A A A p P P N 98 80/60 26 P A P N 9.3 27.2 47000 9700 18 117 119 13.6 47 0.97 2  ‐  E 6, 8, 11 14 0.4 133 4 98 DLI

64 23609/11 Ajay 14 yrs M P A P A A A A A A A A A A A A A A A A 2 A A A A A A A N 92 120/80 22 A A A N 14.9 41.2 59000 3600 7 153 268 3.4 4, 5 N 6, 8 DF

65 23760/11 Saniya Kousar 6 yrs F P A A A A A A A A A P A A A A A A A A 1 P P P P A P A N 100 104/80 30 P A A N 12.3 39.5 50000 2600 12 112 38 12.8 35 0.91 3.2 4 N 6, 9 DHF

66 23978/11 Bhaskar 16 yrs M P P A A A A A A A A A A A A P A A A A 1 A A P A P A A N 94 110/70 28 P A P D 17.6 49.6 6000 5300 2 92 33 19 35 0.99 3.4 3, 4 E 6, 8, 9, 10, 11 DHF

67 24279/11 Bharath K 14 yrs M P P P A A A A A A A A A A A A A A A A 2 A A A A A A A N 64 98/68 22 A A A N 13.4 37.4 45000 5000 7 12 78 3.2  ‐  N N DLI

68 24809/11 Zahid K 2.2 Yrs M P P P A A A A A A A A A A A A P P A A 2 A A A A P P A N 96 96/62 24 A A A N 15.9 48 52000 19200 5 89 26 3.4 4 N N DF

69 25772/11 Inchara 6 yrs F P A A A A A A A A A A A A A A A A A A 1 P A P A A A A N 98 104/80 30 P A A N 12.4 39.5 50000 2700 10 116 38 12.8 35 0.921 3.4 4 N 6 DHF

70 25860/11 Abhishek 15 Yrs M P A P A P A A A A A A A A A A A A A A 2 A A A A A A A N 60 110/72 20 A A A N 15.2 46.8 54000 5200 10 163 40 3.9 4 N N DF

71 25865/11 Pankaj 1 yr M P A A A A A A A A A A A A A A A A A A 2 P A A A A A A F 126 90/64 26 A A A N 11.2 38.4 49000 7700 9 48 42 3.6 3 N N DF

72 26504/11 Pavan 10 yrs M P A P A A A A A A A A A A A A A A A A 2 A A A A A A A N 110 80/66 34 A A A N 15.3 45.7 50000 6700 3 275 75 16.1 50.3 1.18 3.1 4, 5 N N 130 4.6 97 DSS

73 26819/11 Hemanth K 4 yrs M P P P A A A A A A A A A A A A A A A A 2 A A A A A A A N 92 92/62 20 P A A N 14.1 40.8 14000 4400 3 596 183 3.4 3 N N DF

74 27275/11 Uma 9 yrs F P A P A A A A A A A A A A A A A A A A 1 P P P P A P P N 120 80/60 28 A A A N 13.4 39.2 27000 10200 5 49 31 14.5 55.5 1.09 2.6 3 N 6, 8 DSS

75 27432/11 Aliya Anjum 1 yr F A A A A A A A A A A A A A A A A A P A 1 A A P A A A A N 120 84/66 40 P A A D 7.7 26.1 28000 22000 10 1072 829 25 42 1.7 3.5 4 E 6, 9 28 0.7 138 3.5 101 DSS

76 28834/11 Mohan 10 yrs M P A P A A A A A A A A A A A A A A A A 2 A A A A A A A N 80 120/78 20 A A A N 15.3 39.2 51000 6500 3 40 13 4.2 4 N N DF

77 29696/11 Sandhya 11 yrs F P P P P A A A A A A A A A A A A A A A 2 P A A A A A A N 90 110/70 20 P P A N 11.4 35.6 65000 11800 20 56 37 4 4, 5 N N DF

78 1165/12 Mayamma 13 yrs F P A P A A A A A A A A A A A A A A A A 1 A A P A A A A N 74 96/70 34 A A A N 11.4 34.7 79000 6200 4 112 90 2.5 3, 4, 5 N N DHF

79 1712/12 Karuna 13 yrs M P A A A A P A A A A A A A A A A A A A 2 A A A A A A A N 90 86/60 32 A P A N 12.4 34.3 67000 5500 35 21 6 3.8  ‐  N N DLI

80 2166/12 Uday K 2 yrs M P A A A A A P A A A A A P A A A P A A 1 P P P P P P P N 120 90/60 30 P A A D 10.6 30.8 74000 17900 10 77 68 16.3 40.7 1.1 2.2 3, 5 E 6, 8, 9 26 0.4 132 4.1 98 DHF

81 4057/12 Ravi 10 yrs M P A A A A A A A A A A A A A A A A A A 2 P A A A A A A N 94 104/74 20 A A A N 14.3 40.4 25000 5200 2 22 62 3.7  ‐  N N DLI

82 5949/12 Rashmi 10 yrs F P A A A A A A A A A A A A A A A A A A 2 A A A A A A A N 90 100/70 20 A A A N 13.6 35.4 20000 6000 10 56 15 3.2 3 N N DF

83 7240/12 Aishwarya 7 yrs F P A A A A A A A A A A A A A A A A A A 1 P P P A P P P N 110 90/70 26 P A P D 15.3 43.9 19000 7100 6 220 52 16.5 54.7 1.21 1.89 4 E 8, 9 56 0.8 122 6.3 91 DHF

84 8977/12 Prashanth 8 yrs M P A P A A A A A A A A A A A A A A A A 1 A A P A A P P N 102 88/72 24 A A A D 12.3 38 43000 7000 20 115 43 12.1 53.2 0.84 3 3, 4, 5 E 11 136 0.7 136 4 102 DHF

85 10274/12 Md Fardeen 13 yrs M P A P A P A A A A A P A A A A A P A A 2 P A A A A A A N 86 110/70 20 A A A D 12.4 37 22000 1600 14 112 35 3.5 3 E N DF

86 10294/12 Harish 5 yrs M P P A A A A A A A A A A A A A A A A A 2 P A A A A A A N 94 94/64 18 A A A N 12.6 37.1 36000 5600 12 170 12 4 4, 5 E N DF

87 10564/12 B/O Ramya 9 months M P A A A A A A A A A A A A A P A A A A 1 P P P P P P P F 124 56 30 P P P D 8.4 26.5 9000 5500 10 285 90 16 >3 min 1.25 2 3, 4 E 7, 8, 9, 10, 1 114 1.8 148 2.8 94 DSS

88 12041/12 Santhosh 7 yrs M P P A A A A A A A A A A A A A A P A A 2 A A A A A A A N 88 94/68 24 A A A N 12.9 37.1 86000 4600 8 114 14 3.4 3, 4, 5 N N DF

89 12616/12 Chandana 3.6 yrs F P A A A A A P A A A A A A A A A A A A 1 P P P P P P P F 122 70 28 P A P D 11.4 33.2 26000 8600 7 937 256 12.5 32.5 0.88 2.9 4 E 6, 8, 9 32 0.4 138 4.2 98 DSS

90 12878/12 Syed Gouse 10 yrs M P P A A A A A A A A A A A A A A A A A 2 A A A A A A A N 88 104/74 20 A A A N 10.6 31.8 32000 4600 6 131 38 2.8 5 N N DF

91 13522/12 Vasanth Kumar 13 yrs M P P P A A P P A P A P A A A A A A A A 1 P P P A P P P N 110 70/52 18 P A A D 11.9 37.7 17000 2200 7 79 241 11.9 52.8 0.77 2.5 3 E 7, 8, 11 DHF

92 13531/12 Jaswanth 8 yrs M P P P A A A A A A A A A A A A A A A A 1 P P P P P P P N 92 80/50 20 P A A D 12.5 41.8 78000 2900 7 127 481 11.6 38 0.8 2.8 3, 4 E 7, 8 DHF

93 13560/12 Krishna 5 yrs M P A A A A A A A A A A A A A A A A A A 2 P A A A A A A N 90 94/64 18 A A A N 12.6 37.1 38000 6600 12 170 12 3.5 3, 4 N N DF

94 13594/12 Nayeem Pasha 14 yrs M P A A A A A A A A A A A A A A P P A A 1 P A A A A A A N 90 110/72 18 A A A D 13.8 42.1 30000 3600 2 125 418 12.7 28.2 0.89 3 3, 4, 5 E 9 DHF

95 13798/12 Amar 5 yrs M P P P A A A P A A A A A A A A A A A A 1 P P P P P P P N 110 70/52 20 P A A D 12.8 37.2 20000 7000 4 220 70 16.2 62.3 1.19 2.8 3, 4, 5 E 6, 8, 9 83 0.4 DSS

96 14094/12 Dilip 14 yrs M P A A A A A A A A A A A A A A A P A A 2 P A A A A A A N 94 120/80 18 A A A N 13 40.7 36000 4800 17 170 53 3.4 3 N N 39 0.7 134 4.5 100 DF

97 14419/12 Sudeep 7 yrs M P A A A A A A A A A A A A A A A A A A 2 A A A A A A A N 94 90/60 20 A A A N 10.3 31.6 34000 2200 6 112 36 3.6 4 N 7, 8, 9 DF

98 14678/12 Suhas 6 yrs M P A A A A A P A A A A A A A A A A A A 1 P P P A A P P N 90 90/60 20 P A A D 10.3 30.6 245000 5100 17 74 70 19 34 1.01 3.2 3 E 6, 9 DHF

99 14695/12 Shivananda 10 yrs M P P P A A A A A A A A A A A P A A A A 2 P A A A A A A N 78 100/70 20 A A A N 13.9 41.8 72000 2300 6 70 7 3.9 3, 4, 5 N N 31 0.8 130 3.9 96 DF

100 14845/12 Harini 7 yrs F P P P A A A P A A P A A A A A A A A A 2 P P P P P P P N 96 100/72 20 P A P D 12.5 33.7 33000 9100 5 181 61 15.2 33.8 1.1 3 3, 5 E 7 , 8 , 9 26 0.6 136 4 92 DHF