CLINICAL & LABORATORY PROFILE OF DENGUE IN CHILDREN ADMITTED AT THENI MEDICAL COLLEGE

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DISSERTATION ON

CLINICAL & LABORATORY PROFILE OF DENGUE IN CHILDREN ADMITTED AT THENI MEDICAL COLLEGE

HOSPITAL

Dissertation submitted to

THE TAMILNADU DR. M. G. R. MEDICAL UNIVERSITY In partial fulfillment of the regulations for the award of the

degree of

M.D. DEGREE IN PEDIATRIC MEDICINE BRANCH – VII Reg.No.201717654

GOVERNMENT THENI MEDICAL COLLEGE THENI – 635531

THE TAMILNADU DR. M. G. R. MEDICAL UNIVERSITY CHENNAI – 32

MAY 2020

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Government Theni Medical College Hospital

DECLARATION BY THE CANDIDATE

I hereby declare that this dissertation titled “CLINICAL & LABORATORY PROFILE OF DENGUE IN CHILDREN ADMITTED AT THENI MEDICAL COLLEGE HOSPITAL” is a bonafide and genuine research work carried out by me under the guidance of Prof. DR. D.SIVAKUMARAN, M.D., Professor, Department of Paediatrics, Government Theni Medical College Hospital, Theni.

Place : Theni Signature of the Candidate

Date : DR. KAMESH . D

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Government Theni Medical College Hospital

CERTIFICATE BY THE GUIDE

This is to certify that this dissertation titled “CLINICAL & LABORATORY PROFILE OF DENGUE IN CHILDREN ADMITTED AT THENI MEDICAL COLLEGE HOSPITAL” is a bonafide work done by Dr. KAMESH D in partial fulfillment of the requirement for the degree of M. D. in Paediatrics, examination to be held in May 2020.

Signature of the Guide

Prof. Dr. D. SIVAKUMARAN, M.D.,

Place: Theni

Professor

Date :

Department of Paediatrics

Government Theni Medical College Theni.

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Government Theni Medical College Hospital

ENDORSEMENT BY THE HEAD OF DEPARTMENT

This is to certify that this dissertation titled “CLINICAL & LABORATORY PROFILE OF DENGUE IN CHILDREN ADMITTED AT THENI MEDICAL COLLEGE HOSPITAL” is a bonafide work done by Dr. KAMESH D under overall guidance and supervision of Dr. R. SELVAKUMAR, M.D., Professor & HOD of Department of Paediatrics, Government Theni Medical College Hospital, in partial fulfillment of the requirement for the degree of M. D. in Paediatrics, examination to be held in May 2020.

Seal & Signature of the HOD Prof. Dr. R.SELVAKUMAR, M.D.,

Place: Theni

Professor & Head

Date:

Department of Paediatrics

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Government Theni Medical College Hospital

ENDORSEMENT BY THE DEAN OF THE INSTITUTION

This is to certify that this dissertation titled “CLINICAL & LABORATORY PROFILE OF DENGUE IN CHILDREN ADMITTED AT THENI MEDICAL COLLEGE HOSPITAL” is abonafide work done by Dr.KAMESH D under overall guidance and supervision of Prof. Dr. R.SELVAKUMAR, M.D., Professor, Department of Paediatrics, Government Theni Medical College Hospital, in partial fulfillment of the requirement for the degree of M. D. in Paediatrics, examination to be held in May 2020.

Seal & Signature of the of the Dean

Place : Theni Prof.Dr.K.RAJENDRAN, M.S(Gen).,D.ORTHO Date : Dean

Govt. Theni Medical College Theni.

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Government Theni Medical College Hospital

COPY RIGHT

I hereby declare that THE TAMILNADU DR. M. G. R. MEDICAL UNIVERSITY, CHENNAI, TamilNadu, India, shall have the rights to preserve, use and disseminate this dissertation / thesis in print or electronic format for academic / research purpose.

Place: Theni Signature of the Candidate

Date : DR. KAMESH D

© THE TAMILNADU DR. M. G. R. MEDICAL UNIVERSITY, CHENNAI, Tamil Nadu, India.

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ACKNOWLEDGEMENT

I express my gratitude to the Dean, Prof. Dr. K. RAJENDRAN, M.S(Gen)., D.ORTHO., for allowing me to pursue this Dissertation work in Government Theni Medical college Hospital.

I would like to express my humble gratitude and sincere thanks to Prof. Dr. R. SELVAKUMAR, M.D., Head of the Department of Pediatrics,

Govt. Theni College and Hospital, Theni for his excellent guidance and encouragement during this study.

I sincerely thank our Professor Dr. D. SIVAKUMARAN M.D., for their invaluable guidance to complete this dissertation.

I am grateful to Dr. P.MURUGALATHA, M.D., Associate Professor of Pediatrics for her valuable advice during this study.

I extend my sincere and heartfelt thanks to my Assistant Professors Dr. P. REGHUPATHY, M.D., D.C.H., Dr. (MAJOR). R. ILANGOVAN,

M.D., Dr.M.KRITHIGA, M.D., Dr.C.VASANTHAMALAR, M.D., Dr.A.VIDHYADEVI, M.D., Dr.D.VIDJEADEVAN, M.D., DCH.,

Dr.KARTHIKEYAN, M.D., Dr.A.SUGANTHI, DCH., and Dr.R.GOPINATHAN, M.D. and for their valuable support and guidance.

I express my sincere thanks to post graduate colleagues and friends who have helped me in preparing this dissertation.

I am greatly indebted to all my patients and their mothers for their co-operation in spite of pain and suffering from disease without whom this study would have been impossible.

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PLAGIARISM CERTIFICATE

This is to certify that this dissertation work titled “CLINICAL &

LABORATORY PROFILE OF DENGUE IN CHILDREN ADMITTED AT THENI MEDICAL COLLEGE HOSPITAL” of the candidate DR.KAMESH D with registration Number 201717653 for the award of M.D. DEGREE IN PAEDIATRICS, BRANCH VII. I personally verified the urkund.com website for the purpose of plagiarism Check. I found that the uploaded thesis file contains from introduction to conclusion pages and result shows 1 percentage of plagiarism in the dissertation

.

Guide & Supervisor sign with Seal

Prof. Dr. D. SIVAKUMARAN, M.D.,

Place: Theni Professor

Date: Department of Paediatrics

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Dengue is the most rapidly spreading mosquito-borne disease of mankind, with a 30-times increase in global incidence over the last five decades. Dengue is a major public health problem throughout the tropical and subtropical regions of the world. Half the world's population almost lives in countries where dengue is endemic.

According to WHO, about 50–100 million new infections are estimated to occur annually in more than hundred endemic countries, with a intense increase in the number of countries reporting the disease.¹

A very large proportion (≈ 90%) of them are children aged less than five years. About 2.5% of those affected die. During epidemic, infection rate among those who have not been previously encountered to the virus are often 40 to 50 % but can also reach 80 to 90 percent. Aedes aegypti is the primary epidemic vector. Primarily an urban disease, dengue and DHF are now spreading to rural areas worldwide.

Generally, Dengue is an acute febrile illness, and sometimes biphasic fever with severe myalgia, headache, arthralgia, rashes, thrombocytopenia and leucopenia may also be observed. Dengue haemorragic fever is characterized by the acute onset of high fever and with associated signs and symptoms similar to dengue fever in the early febrile phase. There were common haemorrhagic manifestation such as positive tourniquet test (TT), petechiae, easy bruising and/or GI haemorrhage in severe cases. By the end of the pyrexic phase, there is a tendency to develop hypotensive shock (DSS) due to plasma leakage. The presence of preceding warning signs such as lethargy or restlessness or irritability, persistent vomiting, oliguria and abdominal pain are important for intervention to prevent shock.

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Plasma leakage and abnormal haemostasis are the main pathophysiological hallmarks of Dengue haemorragic fever. Rising haematocrit/ haemoconcentration and Thrombocytopenia are constant findings before the cessation of fever/ onset of shock.

Dengue haemorragic fever occurs most commonly in children with secondary dengue infection. DHF has also been documented in primary infections with Dengue Virus 1 and 3 as well as in infants. We live in a country with resource limited settings add on by public ignorance about the disease and poor access to health care. Severity is high in paediatric age group.

No vaccine is available for preventing this dengue fever at present.

Chandrakanta et al² describe the varied manifestations of dengue viral infection as seen in hospitalized children in northern India. Manjunath J. Kulkarni et al³ in their study describe various clinical manifestations.

The demographic pattern and the trend of disease are largely changing every year through the past decade. South India and especially South Tamil nadu had witness several dengue fever epidemic outbreaks during the past few years. Additional studies about the disease can lead to change in guidelines and alterations in public health programs. Early recognition and prompt initiation of appropriate management is vital.

Here, I have made an attempt to study the clinical & laboratory profile and outcome of dengue viral infection the time period from March 2018 to September 2019.

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LITERATURE REVIEW

EPIDEMIOLOGY

Dengue fever ranks as the most important, rapidly emerged mosquito-borne viral fever in recent years and is endemic in all continents. It has shown an increase due to various reasons – lifestyle changes, construction activities, improper water storage, deficient water management, stagnation of rain water in containers lying outside and practices leading to proliferation of vector breeding sites in all areas.

The epidemiology of dengue is an complex phenomenon which depends upon an intricate relationship between epidemiological factors like man and mosquito (host), virus (agent) and the abiotic and biotic factors (environment).

The complexity of relationship among all these factors finally determines the level of endemicity in an area. During inter-epidemic periods, the transmission of dengue remains low due to extremes of temperature with low relative humidity, but during monsoons the environment becomes suitable for vectors. Temperatures in the range of 25^oC ± 5 ⁰C, relative humidity around 80% and innumerable small water collections result in high vector density.

Dengue virus

The agent of dengue, i.e. dengue viruses, are categorized under the genus Flavivirus. It contain single stranded RNA and in size 50 nm. There are 4 dengue virus serotypes viz, Dengue virus-1, Dengue virus-2, Dengue virus-3 and Dengue virus-4.

Infection with any 1 serotype confers lifelong immunity to the virus serotype.

Although all 4 serotypes are antigenically similar, dengue virus are different enough to elicit cross-immunity only for a few months after infection by any one of them.

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Fig.1. Dengue virus

Molecular bioiology

The 4 dengue virus types Dengue virus-1–4, called dengue virus serotypes. It forms a phylogenetic group & differ in nucleotide sequence from each other. These serotypes are closely related to one another rather than to other flaviviruses. It forms an antigenic complex of their own. Based on their the envelope gene, the following subtypes or genotypes are also detected within each serotype^4,5.

• DENV-1: three

• DENV-2: two (one non-human primate)

• DENV-3: four

• DENV-4: four (one non-human primate)

The immunity to 1 serotype does not afford protection from the infection by a other serotype, hence the 4 dengue virus serotypes can co-circulate in the endemic areas. Individual variations occur in antiglobulin responses to the DENV.

Secondary infections are associated with increased risks of severe disease outcomes. Primary and secondary infections are differentiated based on their antibody responses. The ability of all Dengue virus serotypes to utilize past

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infection heterotypic flavivirus antiglobulin to enhance infection is a unique feature of Dengue virus which distinguishes it from all other flaviviruses. It is considered to be the primary basis of Dengue virus pathogenesis. All 4 serotypes are reported from India.

The DENV genome is composed of 3 structural protein genes encoding the envelope protein-E, membrane associated protein M, nucleocapsid of core protein

& NS5. The functions for all the individual non-structural proteins are not well characterized. However, non-structural protein1 had shown to interact with the host immunity, and known to evoke T cell immune responses. In DENV infection, patients have measurable levels of non-structural protein1 protein in the blood.

These are utilized as a diagnostic marker of the infection.

Dengue viral infection is mostly asymptomatic. The exact causes of severity among some patients when there is interaction between agent and host are still not clearly understood. Infected people play a major role in introducing the dengue virus by their movement to newer areas.

Vector

Dengue viruses are transmitted from one person to others by the bite of the female Aedes mosquito. Ae. aegypti is the main vector in most urban areas of india, however, Ae. albopictus is also involved in many states. Ae. polynesiensis and Ae.

niveus have also been incriminated as secondary vectors in other countries.

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The female mosquito deposits eggs singly on damp surfaces. Under suitable conditions, the adult emerges in seven days, after the aquatic stages in the life cycle of Ae. aegypti. It may take several weeks to emerge at low temperatures.

The eggs can withstand drying for more than a year and emerge within 1 day once it comes in contact with water. It is also a major problem in prevention and control of dengue.

The life cycle, breeding and longevity of vectors and thus transmission of the disease depends on climatic conditions, particularly temperature and rainfall.

The average survival of Ae. aegypti is thirty days and Ae. albopictus is about 8 weeks. The risk of virus transmission is greater during the rainy season. It is a daytime feeder and can fly up to a 400 metres distance. Vector control is very important in preventing disease transmission, in the non-availability of any specific drug or vaccine for DENV.

Aedes breeds almost entirely in domestic man-made water sources found in and around households, overhead tanks, desert coolers, unused tyres, coconut shells, water storage containers, industrial and domestic junk, construction sites, water reservoirs, disposable cups, unused grinding stones, etc. Ae. albopictus prefers natural larval habitats which include bamboo stumps, leaf axils, tree holes, coconut shells, latex collecting cups in rubber plantations. Recently, its breeding has been reported in domestic habitats as well.

Environmental factor

The Ae. aegypti population fluctuates with water storage and rainfall. Ae.

aegypti lifespan is influenced by temperature and humidity. It is highly

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humidity of 60–80% and temperature of 16 ^oC and 30^oC. Altitude is also a limiting factor for the distribution. It is restricted to between sea level and upto sea level of 1000 ft... The rural spread of Ae. aegypti is a relatively recent occurrence associated with the societal and lifestyle changes in rural areas and also with developmental activities, improved transport systems, etc. Ae. albopictus has posed a serious threat of dengue transmission in certain geographical regions endowed with a sylvatic environment, particularly in peninsular and northeastern states.

Host factor

The DENV infects humans and several species of lower primates. It affects all ages and both genders. Secondary dengue infection is a risk factor for Dengue haemorrhagic fever, including passively acquired antibodies in infants. The most important risk factor is travel to dengue endemic areas. However, if the patient develops fever more than two weeks after travel, it is unlikely to be dengue infection. Migration of infected person during viremia to a non-endemic area may introduce dengue virus into that area. The geographical spread of virus had report to occur mainly by people moving from endemic areas to non-endemic areas.

Transmission cycle

The female Ae. aegypti usually becomes infected with the dengue virus when it takes a blood meal from a person during the viremia (acute febrile) phase of dengue fever. The mosquito becomes infected, after an extrinsic incubation period of 8 to 10 days. It is transmitted when the infected female mosquito bites. The cycle of dengue continues by this process. Dengue fever begins abruptly after an intrinsic incubation period of 4 to 7 days (range 3–14 days). The vertical transmission of

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dengue virus from infected female mosquitoes to the next generation is also observed.

The transmission of dengue through blood transfusion and organ transplantation are also reported.¹⁰ the congenital dengue infections in newborns born to mothers infected very late in pregnancy also reported.

CLINICAL MANIFESTATION OF DENGUE/DENGUE HAEMARROHAGIC FEVER

Immuno-pathogenesis

In the pathogenesis of Dengue Fever, host immune responses play an important role. The exact pathological mechanism for variable clinical manifestations of dengue is still not clearly understand. Various mechanisms are proposed to explain signs and symptoms such as T-cell mediated antibodies cross reactivity with vascular endothelium, complement and its products, complex immune mechanism, enhancing antibodies and various soluble mediators including chemokines & cytokines.

The ultimate target of whatever the mechanisms are are vascular endothelium, platelets and various organs leading to coagulopathy & vasculopathy. It is responsible for the development of haemorrhage and shock. The most accepted mechanism are virus strains enhancing antiglobulins and memory T-cells in a 2⁰ infection resulting in

‘Cytokine Tsunami’.

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DF/DHF Patho-physiology

Fig. 2. Dengue fever Pathophysiology

Capillary leakage and shock

More commonly, hypotension is caused by plasma leakage. Capillary leakage may be mild and temporary or progress to full blown shock with un recordable pulse and blood pressure. A transient disturbance in the endothelial glycocalyx layer function may be related during dengue and alter temporarily the

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features of the fibre matrix of the endothelium. Anti-non-structural protein-1 antibody acts as autoantibodies that cross-react with platelets and non-infected endothelial cells which trigger the intracellular signaling leading to disturbances in capillary permeability. Plasma leakage is caused by diffuse increase in capillary permeability and manifest as any combination of haemoconcentration, pleural effusion or Ascites.^4,6. It usually becomes evident on 3^rd to 7^th day of illness and patients may be afebrile during this time. It is likely that both dengue virus infected monocytes and activated specific T lymphocytes are responsible for increased level of cytokines especially in DHF/DSS.

Coagulopathy in dengue

Coagulopathy associated with DF is well observed but unfortunately underlying pathogenesis still remain unclear. An increase in aPTT and reduction in fibrinogen concentrations are fairly associated findings. Release of heparin sulphate or chondroitin sulphate (molecules similar in structure to heparin that can mimic in function as an anticoagulant) from the glycocalyx also contribute to coagulopathy.

Thrombocytopenia associated with coagulopathy increases the severity of haemorrhage.

Thrombocytopenia Causes:

ü Bone marrow suppression in early stage

ü Destruction of platelet (antiplatelet antibodies) ü Peripheral sequestration of Platelets

ü DIC

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Causes of Bleeding in DF/DHF

• Abnormal coagulogram • Decrease fibrinogen level

• Thrombocytopenia • Increase level of fibrinogen degradation

• Platelet dysfunction product (FDP)

• Prothombin complex deficiency • Increase level of D-Dimer secondary to Liver involvement •

Consumptive coagulopathy (activation of

• Endothelial injury

mononuclear phagocytes)

• DIC and Prolong aPTT

• Sequestration of platelets

Clinical manifestations of DF/ DHF

Dengue patients may be asymptomatic or symptomatic. Clinical manifestations vary from undifferentiated fever to DHF & DSS.^6,7,8,9. The clinical manifestations depend on various factors such as the virus strain, immune status of the host, age, and primary or secondary infection. Infection with 1 serotype gives lifelong immunity to that particular dengue serotype.

UDF - Undifferentiated dengue Fever

In primary dengue patients may develop mild to moderate fever. It is often difficult to distinguish from other viral infections. Maculopapular rash may or may not appear during fever or convalescence. The symptoms of Dengue fever may not be well distinguished. Signs of bleeding or capillary leakage may be absent.

Fig. 3. Dengue patient with Fig. 4. Impression mark on skin Maculopapular rash of a dengue patient

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Severe dengue

Most of the dengue virus infected persons are asymptomatic but symptomatic patients may present with undifferentiated fever, non-severe and severe manifestation. Some patients with dengue virus infection present with severe manifestations like shock, plasma leakage, and bleeding and organ involvement.

Based on thrombocyte count, haematocrit, evidence of capillary leakage, bleeding and hypotension. DHF has been divided into four grades^11. Non severe cases may be DF and DHF grade I and II without significant bleeding. Severe dengue may be DHF III and IV with or without significant bleeding. DHF grade I and II may be severe when they present with significant bleeding or with metabolic and electrolyte abnormalities. Sometimes DF may present with life threatening significant bleeding without evidence of capillary leakage or haemoconcentration.

Some dengue Fever patients may also present with multiple organ involvement without bleeding and shock. In some patient there may be unusual atypical presentation also.

High morbidity and mortality in Dengue fever/Dengue Haemorrhagic Fever is due to involvement of the following organs,

ü Cardiac ü CNS ü Hepatic ü Pulmonary ü Renal

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Dengue Fever with warning signs and symptoms:

The following signs and symptoms are useful as indicators of disease progression and severity of DF/DHF/DSS:

ü Recurrent vomiting

ü Abdominal pain or discomfort ü Palpitation, breathlessness

ü Pleural effusion/ ascites/ gall bladder oedema on imaging ü Hepatic dysfunction or hepatomegaly

ü Decrease urinary output

ü Minor bleeding from different sites ü Narrow pulse pressure

ü Rapid pulse ü Hypotension ü High HCT (>45%) ü Cold clammy extremities ü Rapid fall in platelet count

High Risk group

The following high risk groups may have severe manifestations or complications with DF/DHF, therefore this group of patients should be closely monitored for the development of severity:

Ø Elderly Ø Obesity Ø Pregnancy Ø Infant

Ø Peptic ulcer diseases

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Ø G6PD deficiency

Ø Chronic diseases: diabetes, COPD, bronchial asthma, hypertension Ø Thalassemia

Ø Patients on steroid, antiplatelet, anticoagulant drugs Ø Coronary Artery Disease

Ø HIV infected persons/ Immuno-compromised persons

EDS (Expanded dengue Syndrome)

Unusual manifestations of Dengue Fever/Dengue Haemorrhagic fever are commonly associated with co-morbidities and co-infections. Clinical manifestations observed in expanded dengue Syndrome are as follows:

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Dengue infection in paediatric age groups:

Dengue infection occurs in all age groups of human population and paediatric age group was found to have mostly affected. Paediatric age groups are also at high risk for morbidity and mortality. In the recent past it has been observed that there is a paradigm shift of high incidence of dengue infection from paediatric age group to adolescent and adult.

Vertical transmission and neonatal dengue infection:

Vertical dengue transmission from pregnant women to their foetus had reported in different studies from 1.6 - 64%.⁸ Effect of dengue infection on pregnant women, foetus and new born should be carefully examined to access capillary leakage and bleeding tendency. Fever, thrombocytopenia, petechial rash and hepatomegaly to severe illness with gastric bleeding, pleural effusion, circulatory failure, massive intracerebral haemorrhage are manifested ini nfected neonates. Clinical presentation in the newborn infant does not appear to be associated with maternal disease severity or dengue immune status or mode of delivery. However, timing of maternal infection may be important; peripartum maternal infection may increase the incidence of symptomatic infection in the newborn. Passive transfer of maternal dengue antibodies to the foetus influences the occurrence of a severe development of the disease.

Antibodies to the DENV in the dengue infected mother can cross the placenta and can cause severe dengue in newborn infants. Initial presentation may be confused with bacterial sepsis, birth trauma and other neonatal illnesses.

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Dengue in infants:

DENV can cause a spectrum of outcomes in infants. It ranges from asymptomatic infection to mild or clinically significant severe disease like older children. The severe dengue occurs predominantly in infants 4–9 months of age.⁸

Manifestations of dengue in infants:

As in older children, infants with dengue typically have high fever that usually lasts 2–7 days. Compared to older children upper respiratory tract symptoms (cough, nasal congestion, runny nose, dyspnoea), gastrointestinal symptoms (vomiting, diarrhoea), and febrile convulsions are more common in infants with dengue. It is often not possible to differentiate between dengue and other common infections in infants such as pneumonia, meningoencephalitis, measles, rotavirus infections, etc. at the febrile stage. Around the time of defervescence (which usually falls on days 3–6 of illness), an increase in capillary permeability, in parallel with increasing haematocrit levels become apparent in the majority of dengue infants. The period of clinical plasma leakage lasts 24–48 hours. Clinical features and laboratory findings of infant infected with dengue become more prominent during this critical phase. Skin bleeding such as petechiae, mucosal membrane bleeding (e.g. of the nose and gums), and gastrointestinal bleeding may occur. Hepatomegaly is usually noted and Splenomegaly is seen in almost 10% of dengue infants. Shock occurs when a significant amount of volume of plasma is lost through leakage. The body temperature may be subnormal when shock occurs.

However, a differential diagnosis of septic shock should be kept in mind in infants who have fever at the onset of shock. The degree of increase above the baseline haematocrit often reflects the severity of plasma leakage. However, rise of haematocrit may not be sometimes detectable because the normal value of haematocrit in infants 2-12 months

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of age is relatively low and may be even lower in iron deficiency anaemia.

Thrombocytopenia and leukopenia are often observed in this phase. Liver involvement is found more frequently in infants compared to children. Progression of infants with dengue is the same as that of children and adults during the recovery phase.

Clinical Criteria for DF / DHF/ DSS Clinical Features of DF:

An acute febrile illness of 2-7 days duration with two or more of the following manifestations:

Headache, retro-orbital pain, myalgia, arthralgia, rash, haemorrhagic manifestations.

Dengue Haemorrhagic Fever (DHF):

a).A case with clinical criteria of dengue Fever plus

b).Haemorrhagic tendencies evidenced by one or more of the following 1. Positive tourniquet test

2. Petechiae, ecchymoses or purpura

3. Bleeding from mucosa, gastrointestinal tract, injection sites or other sites Plus

c). Thrombocytopenia (<100 000 cells per cumm) plus

d).Evidence of plasma leakage due to increased vascular permeability, manifested by one or more of the following:

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1. A rise in average haematocrit for age and sex > 20%

2. A more than 20% drop in haematocrit following volume replacement treatment compared to baseline

3. Signs of plasma leakage (pleural effusion, ascites, hypoproteinemia)

Dengue Shock Syndrome (DSS):

All the above criteria for DHF with evidence of circulatory failure manifested by rapid and weak pulse and narrow pulse pressure (< 20 % mm Hg) or hypotension for age, cold and clammy skin and restlessness.

Tourniquet test:

The tourniquet test is performed by inflating a blood pressure cuff to a midpoint between the systolic and diastolic pressure and maintain for five minutes.

The test is considered positive when 10 or more petechiae per one square inch area over forearm are observed.¹³ In DHF, the test usually gives a definite positive test with 20 petechiae or more. The test may be negative or only mildly positive during the phase of profound shock (DSS).

Case Definition

Probable DF/DHF:

• A case compatible with clinical description of dengue Fever during outbreak. OR

• Non-ELISA based NS1 antigen/ IgM positive.

(A positive test by RDT will be considered as probable due to poor sensitivity and Specificity of currently available RDTs.)

Confirmed dengue Fever:

A case compatible with the clinical description of dengue fever with at least one of the following

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•Isolation of the dengue virus (Virus culture +VE) from serum, plasma, leucocytes.

•Demonstration of IgM antibody titre by ELISA positive in single serum sample.

•Demonstration of dengue virus antigen in serum sample by NS1-ELISA.

•IgG seroconversion in paired sera after 2 weeks with Four fold increase of IgG titre.

•Detection of viral nucleic acid by polymerase chain reaction (PCR).

Natural course of dengue Infection

The clinical course of illness passes through the following three phases:

• Febrile phase

• Critical phase

• Convalescent phase

Febrile phase

The onset of dengue fever is usually with sudden rise in temperature which may be biphasic, lasting 2-7 days and commonly associated with headache, flushing and rash. There may be pain in retro-orbital area, muscles, joint or bone. Rash may be maculopapular or rubelliform and usually appear after 3^rd or 4^th day of fever and commonly seen in face, neck and other part of the body which generally fades away in the later part of the febrile phase. Localized cluster of petechiae may appear over upper and lower limbs. Dengue Fever with unusual haemorrhagic manifestation may be seen rarely in case with co-morbid illness.

Critical phase (Leakage phase)

DF/DHF patients usually go to critical phase after 3 to 4 days of onset of fever.

During this critical phase plasma leakage and high haemoconcentration are documented and patients may develop hypotension. Abnormal haemostasis and

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leakage of plasma leads to shock, bleeding, accumulation of fluid in pleural and abdominal cavity. High morbidity and mortality in DHF/DSS are commonly associated with various organ involvements and metabolic derangement. The period of plasma leakage usually persists for 36-48 hrs.

Convalescent phase (recovery phase)

During the recovery phase the extracellular fluid which was lost due to capillary leakage returns to the circulatory system and signs and symptoms improve. This phase usually after 6-7 days of fever and last for 2-3 days. Longer convalescence may be expected in some of the patients with severe shock, organ involvement and other complications which may require specific treatment. Patient may develop pulmonary oedema due to fluid overload if the fluid replacement is not optimized carefully.

Fig.5. COURSE OF DENGUE ILLNESS

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Fig. 6. Dengue Case classification

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Differential Diagnosis of DF/DHF

• Malaria

• Enteric fever

• Pharyngitis

• Tonsillitis

• Influenza

• Leptospirosis

• Meningococcal infection

• Chikungunya fever

• Epidemic typhus/ scrub typhus

• Crimean-Congo haemorrhagic fever

• Ebola haemorrhagic fever

Grading of DF/DHF

DF: Fever of 2-7 days with two or more of following;

Headache, Retro orbital pain, Myalgia, Arthralgia with or without leukopenia, thrombocytopenia and no evidence of plasma leakage.

DHFI: Above criteria plus positive tourniquet test and evidence of plasma leakage.

Thrombocytopenia with platelet count less than 100000/ cu.mm and Hct rise more than 20% over baseline.

DHFII: Above plus some evidence of spontaneous bleeding in skin or other organs (black tarry stool, epistaxis, gum bleeds) and abdominal pain. Thrombocytopenia

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with platelet count less than 100000/ cu.mm and Hct rise more than 20% over baseline.

DHFIII (DSS): Above plus circulatory failure (weak rapid pulse, narrow pulse pressure < 20 mm Hg, Hypotension, cold clammy skin, restlessness).

DHFIV (DSS): Profound shock with undetectable blood pressure or pulse.

LABORATORY DIAGNOSIS

Laboratory diagnosis can be carried out by one or more of the following tests.

ELISA-based NS1 antigen tests

Dengue NS1 antigen, a highly conserved glycoprotein which is produced in both membrane-associated and secretion forms, is abundant in the serum of patients during the early stages of DENV infection. It has been found to be useful as a tool for the diagnosis of acute dengue infections. It is a simple test that is more specific and shows high sensitivity.

NS1 enables detection of the cases early, i.e. in the viremic stage, which has epidemiological significance for containing the transmission. The NS1 ELISA- based antigen assay is commercially available for DENV and many investigators have evaluated this assay for sensitivity and specificity. The NS1 assay may also be useful for differential diagnostics between flaviviruses because of the specificity of the assay.

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IgM-capture enzyme-linked immunosorbent assay (MAC-ELISA)

MAC-ELISA has been widely used in the past few years. It is a simple test that requires very little sophisticated equipment. MAC-ELISA is based on detecting the dengue-specific IgM antibodies in the test serum by capturing them using anti- human IgM that was previously bound to the solid phase. This is followed by addition of dengue antigen if the IgM antibody from the patient's serum is anti- dengue, it will bind to the dengue antigen. An enzyme-substrate is added to give a colour reaction for easy detection.

The anti-dengue IgM antibody develops a little faster than IgG and is usually detectable by day 5 of the illness. However, the rapidity with which IgM develops varies considerably among patients. Some patients have detectable IgM on days 2 to 4 after the onset of illness, while others may not develop IgM for seven to eight days after the onset. In some primary infections, detectable IgM may persist for more than 90 days, but in most patients it wanes to an undetectable level by 60 days. It is reasonably certain, however, that the person had a dengue infection sometime in the past two to three months. MAC-ELISA has become an invaluable tool for surveillance of DF/DHF. In areas where dengue is not endemic, it can be used in clinical surveillance for viral illness or for random, population-based serosurveys, with the certainty that any positives detected are recent infections. It is especially useful for hospitalized patients, who are generally admitted late in the illness after detectable IgM is already present in the blood.

Isolation of dengue virus

Isolation of most strains of dengue virus from clinical specimens can be accomplished in the majority of cases, provided that the sample is taken in the first five days of illness and processed without delay. Specimens that may be suitable for

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virus isolation include acute phase serum, plasma or washed buffy coat from the patient, autopsy tissues from fatal cases, especially liver, spleen, lymph nodes and thymus and mosquitoes collected in nature. Isolation of the virus takes 7–10 days;

hence it may not be very useful for starting the management of patients with DF/DHF.

Polymerase chain reaction (PCR)

Molecular diagnosis based on reverse transcription polymerase chain reaction (RT-PCR), such as one-step or nested RT-PCR, nucleic acid sequence-based amplification (NASBA) or real-time RT-PCR has gradually replaced the virus isolation method as the new standard for the detection of dengue virus in acute-phase serum samples.

IgG-ELISA

An IgG-ELISA has been developed that compares well to the hemagglutination-inhibition (HI) test. This test can also be used to differentiate primary and secondary dengue infections. The test is simple and easy to perform but not considered as a diagnostic test as it indicates past infections only.

Serological tests

Besides MAC-ELISA and IgG-ELISA, there are a few serological tests available for the diagnosis of dengue infection such as HI, complement fixation (CF) and neutralization test (NT). These are not commonly used due to various technical problems.

RAPID DIAGNOSTICS TESTS

A number of commercial RDT kits for anti-dengue IgM/IgG antibodies and NS1 antigen are commercially available, which give the results within 15 to 25

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not yet been properly validated. Some of the RDTs have been independently evaluated. The results showed a high rate of false positives compared to standard tests, while some others have agreed closely with standard tests. The sensitivity and specificity of some RDTs are also found to vary from batch to batch. According to WHO guidelines, these kits should not be used in clinical settings to guide management of DF/DHF cases because many serum samples taken in the first five days after the onset of illness will not have detectable IgM antibodies. The tests would thus give a false negative result. Reliance on such tests to guide clinical management could, therefore, result in an increase in the case–fatality ratio. Hence, use of RDT is not recommended under the programme.

Collection of samples

Laboratory diagnosis of dengue depends on proper collection, processing, storage and shipment of the specimens. While collecting blood for serological studies from suspected DF/DHF cases, all universal precautions should be taken.

While sending the samples for lab confirmation, the day of onset of fever and day of sample collection should be mentioned to guide the laboratory for the type of test to be performed (NS1 for samples collected from day 1 to day 5 and IgM after day 5).

CLINICAL MANAGEMENT

Clinical management of DF may vary depending on severity of illness.

The child who have simple fever without any danger signs / complications can be managed with symptomatic treatment. Child have warning signs and symptoms should be closely monitored and watch for progression of disease. The child with dengue haemorrhagic fever III & IV / significant bleeding or multi organs involvement require aggressive treatment to reduce morbidity and mortality. Child

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may develop complications during later stage of afebrile phase, where we should be careful to watch for danger signs and signs of fluid overload.

Dengue Fever (DF) Management

Management of DF is symptomatic and supportive

1. Antipyretics may be used to lower the body temperature. Aspirin/NSAIDS like Ibuprofen, etc should be avoided. Paracetamol is preferable

2. Use cold/tepid sponging to keep temperature below 38.5 ⁰ C.

3. Bed rest is advisable during the acute phase

4. Oral fluid and electrolyte therapy is recommended for child with excessive sweating or vomiting.

5. Patients should be monitored for 1 to 2 days after they become afebrile for development of complications.

Management during Febrile Phase

Adequate fluid should be advised orally as much as the patient tolerates.

Paracetamol is recommended to keep the temperature below 39^oC. ORS (Oral rehydration solution), such as those used for the treatment of ADD / fruit juices are preferable to plain water. If the patient is vomiting persistently or refusing to feed, IV fluid should be administered.

Child should be monitored closely for the early signs of shock. The critical period is during the transition from the febrile to the afebrile stage. It usually occurs after the third day of illness. Sometimes serial haematocrit determinations are essential to guide treatment plan, since they reflect the degree of plasma leakage and need for intravenous administration of fluids. Haematocrit should be determined daily specially from the third day until the temperature remains normal for one or two days.

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Management of DHF Grade I and II

Any person who has dengue fever with thrombocytopenia, high haemoconcentration and presents with abdominal pain, black tarry stools, epistaxis, bleeding from the gums etc. needs to be hospitalized. All these patients should be observed for signs of shock. The critical period for development of shock is during transition from febrile to abferile phase of illness, which usually occurs after third day of illness. Rise of haemoconcentration indicates plasma leakage and loss of volume for which proper fluid management plays an important role. Despite the treatment, if the patient develops fall in BP, decrease in urine output or other features of shock, the management for Grade III/IV DHF/DSS should be instituted.

Oral rehydration should be given along with antipyretics like Paracetamol, sponging, etc. as described above. The algorithm for fluid replacement therapy in case of DHF Grade I and II is given in Chart 1.

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Notes: * Improvement: Hct falls, pulse rate and blood pressure stable, urine output rises

**No Improvement: Hct or pulse rate rises, pulse pressure falls below 20 mmHg, urine output falls

Management of Shock (DHF Grade III / IV)

Immediately after hospitalization, the haematocrit, platelet count and vital signs should be examined to assess the patient's condition and intravenous fluid therapy should be started. The patient requires regular and continuous monitoring. If the patient has already received about 1000 ml of intravenous fluid, it should be

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changed to colloidal solution preferably Dextran40 or if haematocrit further decreases fresh whole blood transfusion 10-20ml/kg/dose should be given.

However, in case of persistent shock even after initial fluid replacement and resuscitation with plasma or plasma expanders, the haematocrit continues to decline, internal bleeding should be suspected. It may be difficult to recognize and estimate the degree of internal blood loss in the presence of haemoconcentration. It is thus recommended to give whole blood in small volumes of 10ml/kg/hour for all patients in shock as a routine precaution. Oxygen should be given to all patients in shock. Treatment algorithm for patients with DHF Grades III and IV is given in Chart 2 and 3.

Management of severe bleeding

In case of severe bleeding, patient should be admitted in the hospital and investigated to look for the cause and site of bleeding and immediately attempt should be made to stop the bleeding. Internal bleeding like GI bleeding may be sometime severe and difficult to locate. Patients may also have severe epistaxis and haemoptysis and may present with profound shock. Urgent blood transfusion is life saving in this condition. However, if blood is not available shock may be managed with proper IV fluid or plasma expander.. If the patient has thrombocytopenia with active bleeding, it should be treated with blood transfusion and then if required platelet transfusion. In case of massive haemorrhage blood should be tested to rule out coagulopathy by testing for prothrombin time (PT) and aPTT. Patients of severe bleeding may have liver dysfunction and in such case, liver function test should also be performed. In rare circumstances, intracranial bleed may also occur in some

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Management of DF/ DHF with co-morbid illness

Different co-morbid illness like hypertension, diabetes, thyroid diseases, hepatitis, heart diseases and renal diseases may contribute in the development of severe manifestations in DF/DHF.

Viral hepatitis in Dengue: Liver function test impairment due to dengue viral infection is seen in some patients. In some patients the SGOT/SGPT level may be very high and Prothrombin time may be prolonged. Pre-existing conditions like chronic viral hepatitis, cirrhosis of liver and hepatomegaly due to some other cause is commonly associated with Hepatic involvement. Patient may also develop hepatic encephalopathy due to acute liver failure. Severe DHF and bleeding may be associated with Low albumin due to chronic liver disease. Gastrointestinal bleeding is common in these condition. If Prothrombin time is prolonged IV vitamin K1 may be initiated in such conditions. Patient may go to severe Dengue shock syndrome and they should be treated carefully with hepatic failure regimen with blood transfusion and appropriate fluid.

Myocarditis in Dengue: DF may rarely cause acute myocarditis.²⁰ It is also may contribute for the development of Dengue shock syndrome. Cardiac complications may be seen in presence of hypertension, diabetic Coronary artery disease, and VHD. Treatment of shock with intravenous fluid is sometime difficult due to myocardial dysfunction. Cardiac patients on Aspirin and other drug also contribute for severe bleeding unless these are stopped during infection. Patients may develop pulmonary oedema due to improper fluid management.

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Renal involvement in DF: ATN (Acute Tubular Necrosis) may develop during Dengue shock Syndome. It may complicate to AKI (acute kidney injury), If fluid therapy is not initiated in time. It may be reversible, if shock is corrected early.

Output monitoring and Microscopic-macroscopic Haematuria should be examined in Dengue haemorrhagic patients and also blood urea, electrolytes, creatinine, GFR, ABG should be performed.

CNS involvement in DF: hypoglycemia, shock (DSS), fluid overload, hepatic encephalopathy, electrolyte imbalance and also due to involvement of CNS by dengue virus cause altered sensorium in dengue patient. Severe dengue may cause acute encephalopathy or encephalitis. It may be difficult to clinically exclude cerebral Malaria and enteric encephalopathy. Dengue IgM in CSF may help to confirm dengue encephalopathy/encephalitis.

Management of DF with co-infections:

Management of DF with co-infections is sometimes difficult to manage DF with co- infections like HIV, TB, malaria, chikungunya, enteric fever and leptospira as mostly clinical presentations are severe in presence of these co-infections.

Tuberculosis: If patient has Dengue fever in presence of Tuberculosis and is on Antituberculosis drug, then should be closely monitored. Child may develop breathlessness and massive haemoptysis in Pulmonary TB. Tuberculosis patients may also develop Acute Respiratory Distress Syndrome and moderate to massive pleural effusion.

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Malaria: Malaria should be excluded without delay as it has specific management.

It is also a common co-infection in dengue because, it is prevalent across India and transmission also coincides during the same season. Antimalarial treatment should be started as soon as possible.

HIV: Outcome of Dengue fever is poor amongst AIDS patients with opportunistic infection and very low CD4 count. Patients may have severe complications like significant bleeding Dengue Haemorrhagic Fever, Dengue Shock Syndrome,, and organ involvement among HIV and AIDS patients. Multi-organ involvement may be common in Dengue fever. It is responsible for high mortality. Management of Dengue fever with HIV and AIDS should be done with consultation of HIV specialist

Typhoid Fever: During monsoon season, when dengue infection is reported in large number Typhoid fever and gastroenteritis are also common. In the initial phase DF, child may be more complicated with enteric fever if antibiotic treatment is started late. Widal test may not be positive before second weeks of fever. Hence, In high suspected cases enteric culture should be sent to confirm the diagnosis.

Chikungunya: In some geographical area both Dengue and chikungunya infections are prevalent at the same period. In case of predominant joint involvement in a DF child, Chikungunya should be investigated. Proper treatment to be carried out accordingly .Acute complications are sometimes severe in Dengue fever in presence of Chikungunya..

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Neonatal dengue Management: History of febrile illness during pregnancy is important. It may help to diagnose DSS among neonates and infants. After delivery, the newborn may go into shock. It may be confused with septic shock or birth trauma.

Symptomatic and supportive treatment and close observation are the mainstay of management.

Dengue among infants without warning signs Management

Oral intake should be encouraged with ORS (oral rehydration solution), fruit juice and other fluids containing electrolytes and sugar, together with breastfeeding or formula feeding. Parents should be instructed about fever control with tepid sponging and paracetamol. If the infant has any of the warning signs, they should be advised to bring the infant back to the hospital immediately.

Dengue among infants with warning signs Management

Intravenous fluid therapy is indicated,when the infant has dengue with warning signs. Judicious volume replacement by IV therapy may change the course and severity of the illness in the early stage. Initially 0.9% saline, Ringer's lactate or Ringer's acetate solution should be used. The critical phase resolves spontaneously after 1-2 days in most of the patients.

Infants with severe dengue/shock management

Volume replacement should be done promptly during the period of defervescence. It is very challenging in infants with dengue shock. Each and every case should be critically analyzed separately.

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Admission Criteria

• Dengue patients with warning signs and symptoms

• persistent high grade fever

• rapid fall of platelet count

• significant bleeding from any site

• sudden drop in temperature

• signs of hypotension

• evidence of organ involvement

Discharge Criteria

Patients who have recovered from acute dengue infection with

• no fever for at least 24 hours,

• no respiratory distress,

• adequate urine output,

• normal blood pressure &

• persistent platelet count >50,000/cu.mm should be discharged from hospital.

Platelet transfusion Indication

1. Platelet count less than 10000/cu.mm in absence of bleeding manifestations (Prophylactic platelet transfusion).

2. Haemorrhage with or without thrombocytopenia.

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Packed cell transfusion/FFP along with platelets may be required in cases of severe bleeding with coagulopathy. Whole fresh blood transfusion doesn't have any role in managing thrombocytopenia.

DENGUE VACCINE

There is no licensed vaccine available against dengue till now. In the world, several trials are ongoing for the development of dengue fever vaccine. A recombinant, live attenuated tetravalent dengue vaccine-CYD-TDV has completed phase III trials in children of Five Asian countries which may be promising in preventing dengue infection in near future.¹⁴

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AIM OF THE STUDY

To study the clinical and laboratory profile of the dengue in children and to evaluate the outcomes of dengue infection at the paediatrics department of tertiary care hospital.

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METHODOLOGY

Type of Study: Cross Sectional Study.

Study Period: The study was conducted from March 2018 to September 2019.

Settings: Children less than 12 years of age with clinical signs and symptoms of Dengue- any acute febrile illness with two of the following:

• head ache,

• myalgia,

• retro- orbital pain,

• bleeding,

• low platelet count

• shock or

• altered sensorium

Admitted at paediatric ward of Theni Medical College Hospital during the study period were observed for the study. Informed consent from parents was obtained and detailed history and examination were done. For all suspected dengue fever, the Ig M ELISA qualitative test was done at our hospital. Children positive for Ig M dengue were taken up for study and followed up for clinical profile.

Sample Size: From March 2018 to september 2019, there were totally 83 cases according to the inclusion and exclusion criteria.

Inclusion Criteria:

Children < 12 years of age with acute febrile illness with 2 of the following:

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Ø Headache Ø Myalgia Ø Rash Ø Arthralgia

Ø Bleeding manifestation Ø Shock

Ø low platelet count Ø Retro orbital pain Ø Altered sensorium Exclusion Criteria:

• Fever with other serology positive cases.

Tools used:

Using Proforma the Clinical signs & symptoms were collected. Lab investigations carried out in these patients include CBC, Haemoglobin, renal function test, Liver function test and Dengue IgM serology,. Chest X ray was taken to demonstrate pleural effusion.

Outcome Measures: Children positive for IgM were followed up for the clinical profile and outcome. The number of children included based on the above criteria was 83. Children who were seropositive were classified on the basis of National guideline for dengue fever 2014 as follows:

Ø Mild dengue

• Undifferentiated Dengue Fever

• Fever without complication like hypotension, bleeding and organ involvement

• Without evidence of capillary leakage

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Ø Moderate dengue

• DF with high risk & comorbid conditions

• Dengue Fever with warning signs and symptoms

• Dengue haemorrhagic fever I & II with minor bleeds Ø Severe dengue

• Dengue fever/Dengue haemorrhagic fever with significant haemorrhage

• Dengue haemorrhagic fever with shock (DHF III & IV-DSS)

• Severe organ involvement (Expanded dengue syndrome)

• Severe metabolic disorder

Data Analysis:

Descriptive analysis was carried out by mean and standard deviation for quantitative variables, frequency and proportion for categorical variables. Non normally distributed quantitative variables were summarized by median and interquartile range (IQR). Data was also represented using appropriate diagrams like bar diagram, pie diagram and box plots.

All Quantitative variables were checked for normal distribution within each category of explanatory variable by using visual inspection of histograms and normality Q-Q plots. Shapiro- wilk test was also conducted to assess normal distribution. Shapiro wilk test p value of >0.05 was considered as normal distribution.

For normally distributed Quantitative parameters the mean values were compared between study groups using ANOVA (>2 groups). For non-normally

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distributed Quantitative parameters, Medians and Interquartile range (IQR) were compared between study groups using Kruskal Wallis test (> 2 groups).

Categorical outcomes were compared between study groups using Chi square test /Fisher's Exact test (If the overall sample size was < 20 or if the expected number in any one of the cells is < 5, Fisher's exact test was used.)

P value < 0.05 was considered statistically significant. IBM SPSS version 22 was used for statistical analysis.(1)

1. IBM Corp. Released 2013. IBM SPSS Statistics for Windows, Version 22.0.

Armonk, NY: IBM Corp.

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RESULTS

A total of 83 subjects were included in the final analysis.

1. Mild Dengue fever: 42 (50.6%) 2. Moderate Dengue fever: 26 (31.3%)

• Dengue Fever with warning signs: 20 (24.1%)

• Dengue haemorrhagic fever I & II: 6 (7.2%)

3. Severe Dengue fever: 15 (18.1%)

• Dengue haemorrhagic fever III (DHF III): 11 (13.3%)

• Dengue haemorrhagic fever IV (DHF IV): 4 (4.8%)

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Table 1: Comparison of age group across diagnosis (N=83)

Parameter

Total (N= 83)

Mild dengue (N=42)

Dengue Fever

With Warning

Sign (N=20)

DHF I

& II (N=6)

DHF III (N=11)

DHFIV (N=4)

Chi Square

P value

< 1 Year 9(10.8%) 6

(14.29%) 1 (5%) 1

(16.67%) 1

(9.09%) 0 (0%)

5.323 0.723 1-5 Years 20(24.1%) 11

(26.19%) 3 (15%) 2

(33.33%) 2

(18.18%) 2 (50%) 6-12 Years 54(65.1%) 25

(59.52%) 16 (80%) 3 (50%) 8

(72.73%) 2 (50%)

The larger number of cases are in 6 to 12 years. In all subgroups also the more affected is 6 – 12 age groups. But it was statistically not significant (P=0.732).

Infants comprised 10.8% of total study group. 24.1% were children between 1 and 5 years of age. 65.1% were children between 6 and 12 years.

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6 1 1 1 0

11 3

2 2 2

25 16

3 8 2

0 5 10 15 20 25 30 35 40 45

Mild dengue Dengue Fever With Warning Sign (N=20) Moderate Dengue DHF I & II (N=6) Severe Dengue DHF III (N=11) DHFIV (N=4)

FIG.6.AGE GROUP AMONG STUDY GROUPS

< 1 Year 1-5 Years 6-12 Years

Table 2: Comparison of Mean age among study groups (N=83)

Parameter Mild dengue (N=42)

Sign (N=20)

DHF I

& II (N=6)

DHF III (N=11)

DHFIV (N=4)

F value

P value

Mean Age

6.7 6.4 7.4 5.1 7.4

0.86 0.492

SD 3.1 3.5 2.9 3.1 1.9

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The age group of the affected children was between 5 months to 12 years.

(Mean 6.7 year, standard deviation 3.1).

Table 3: Comparison of Gender among study groups (N=83)

Parameter Total (N= 83)

Mild dengue (N=42)

Sign (N=20)

DHF I

& II (N=6)

DHF III (N=11)

DHFIV (N=4)

Chi Square

P value

Male

46

(55.4%) 24

(57.14%) 12 (60%) 4 (66.67%)

4 (36.36%)

2 (50%)

2.192 0.701 Female

37

(44.6%) 18

(42.86%) 8 (40%) 2

(33.33%) 7

(63.64%) 2 (50%)

0 1 2 3 4 5 6 7 8

(N= 83) (N=42)

Total Mild dengue Dengue Fever With Warning Sign (N=20)

DHF I & II (N=6) DHF III (N=11) DHFIV (N=4)

FIG.7.MEAN AGE

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Males were affected slightly more than females in total and also in subgroups except in DHF III. It was not significant (P=0.70).

Table 4: Comparison of symptoms across diagnosis (N=83)

Mild dengue (N=42)

Sign (N=20)

DHF I

& II (N=6)

DHF III (N=11)

DHFIV (N=4)

Chi Square

P value

Fever 83

(100)

42

(50%) 20 (50%) 6 (50%) 11 (50%) 4

(50%) 0.000 1.000 Mean

duration of

fever 6.11

6.31 6.15 6 5.909 5.25 0.14 0.967

Headache 12(14.5) 4

(9.52%) 1 (5%) 0 (0%) 4 (36.36%)

3

(75%) * **

Myalgia 9(10.8) 4

(9.52%) 0 (0%) 1 (16.67%)

3 (27.27%)

1

(25%) * **

Arthralgia

rash 3(3.6) 3

(7.14%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) * **

0 24

12

4 4

2 18

8

2

7

2 0

5 10 15 20 25 30

Mild dengue Dengue Fever With Warning Sign (N=20)

Moderate Dengue DHF I

& II (N=6)

Severe Dengue

DHF III (N=11) DHFIV (N=4)

FIG.8. GENDER DISTRIBUTION AMONG STUDY GROUPS

Male Female

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The mean duration of fever was 6.11. There is no much variation among subgroups, which is not statistically significant. The headache was present in 14.5 % of patient. The myalgia and arthralgia were 10.8 % and 3.6 % respectively.

0 1 2 3 4 5 6 7

(N=42)

Mild dengue Dengue Fever With

Warning Sign (N=20) DHF I & II (N=6) DHF III (N=11) DHFIV (N=4)

FIG.9. SYMPTOMS ACROSS STUDY GROUPS

Mean duration of Fever Headache Myalgia Arthralgia rash

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Table 5: Comparison of abdominal symptoms across diagnosis (N=83)

Mild dengue (N=42)

Sign (N=20)

DHF I

& II (N=6)

DHF III (N=11)

DHFIV (N=4)

Chi Square

P value

Vomiting 50(60.2) 18

(42.86%) 15 (75%) 6 (100%) 8 (72.73%)

3

(75%) * **

Diarrhoea 8(9.6) 4

(9.52%) 3 (15%) 1

(16.67%) 0 (0%) 0 (0%) * **

Abdominal

pain 46(55.4) 15

(35.71%) 16 (80%) 5

(83.33%) 6

(54.55%) 4

(100%) * **

Abdominal

distension 2(2.4) 0 (0%) 0 (0%) 1

(16.67%) 0 (0%) 1

(25%) * **

The vomiting was the most common symptom followed by abdominal pain.

The vomiting was 60.2 %. 9.6 % of patients had diarrhoea.

The incidence of Abdominal pain was 55.4 % of cases. The abdominal distension was seen in 2.4 % of cases.

CLINICAL & LABORATORY PROFILE OF DENGUE IN CHILDREN ADMITTED AT THENI MEDICAL COLLEGE

DISSERTATION ON