RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES BANGALORE, KARNATAKA ANNEXURE II

Proforma for Registration of Subjects for Dissertation

1. NAME OF THE CANDIDATE AND ADDRESS : DR. SHABBEER. S. BATAKURKI POST GRADUATE IN PEDIATRICS, ROOM NO 44, BMC PG HOSTEL FOR MEN, CHAMARAJPET BANGALORE 560 018. 2. NAME OF THE INSTITUTION : BANGALORE MEDICAL COLLEGE AND RESEARCH INSTITUTE, BANGALORE. 3. COURSE OF STUDY AND SUBJECT 4. DATE OF ADMISSION TO THE COURSE 5. TITLE OF THE TOPIC : CORRELATION OF CLINICAL, HEMATOLOGICAL AND BIOCHEMICAL PARAMETERS IN EARLY DIAGNOSIS OF DENGUE VIRAL ILLNESS. : 09-04-2008 : M.D. IN PEDIATRICS.

6. BRIEF RESUME OF THE INTENDED WORK: 6.1 NEED FOR THE STUDY :
Dengue fever/Dengue hemorrhagic fever (DF/DHF) is a reemerging disease throughout the tropical world. The disease is caused by four closely related Dengue

viruses, which are transmitted by the Aedes mosquitoes, principally Aedes aegypti. DHF and Dengue shock syndrome (DSS) represent the severe end of the disease spectrum, which if not properly manage would result in significant mortality.1 The pathophysiology of severe DHF and DSS is characterized by plasma leakage as a result of alteration in microvascular permeability. There is as yet no vaccine or specific antiviral therapy for DF/DHF and management of cases remains largely supportive. Dengue illness is often confused with other viral febrile states, confounding both clinical management and disease surveillance for viral transmission prevention. This difficulty is especially striking during the early phase of illness, where nonspecific clinical symptoms and signs accompany the febrile illness. More definitive symptoms, such as retro-orbital pain and clinical signs, such as petechiae do not appear until the later stages of illness.1 Definitive early Dengue diagnosis requires laboratory tests and those suitable for use at this stage of illness are either costly, such as RT-PCR for Dengue; not sufficiently rapid, such as virus isolation; or undergoing field trials, such as ELISA for NS1 protein of Dengue virus.1 Hence there is a need for simple laboratory tests like hematological and biochemical tests for early diagnosis of Dengue viral illness which will be useful for case management and preventing mortality and morbidity.1
.

6.2 REVIEW OF LITERATURE:

Jien-Wei Liu, Boon-Siang Khor, Chen-Hsiang Lee, Ing-Kit Lee, Rong-Fu Chen et.al. in their Study about Dengue Hemorrhagic fever in Taiwan in 2001 found certain abnormal laboratory findings, including atypical lymphocytosis, prolonged activated partial thromboplastin time (APTT) and elevated aspartate

aminotransferase, and alanine aminotransferase were found in patients with DHF than those with DF.2

Faridi M. M. A, Agarwal Anju, Kumar Monish, Sarfazul Abedin, in their study on Clinical and biochemical profile of Dengue hemorrhagic fever in children in Delhi in 2003 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, serum glutamic pyruvate transaminase (SGPT) >40 IU/L, alkaline phosphatase (ALP) >400 IU/L and serum bilirubin >1 mg%. IgM Dengue serology was positive and they concluded that hepatic dysfunction with increased levels of serum enzymes was common in DHF.3 Wahid S.F, Sanusi S, Zawawi M.M, Ali RA in their study on A comparison of pattern of liver involvement in Dengue hemorrhagic fever with classic Dengue fever 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.4

Luis Jose Desouza, Rita Maria Ribeiro, Nogueira Leandro cordeiro Soares, Carlos Eduardo Cordeiro Soares, Bruno Fernandes Ribas et.al. In there study on Impact of Dengue on liver function as evaluated by aminotransferase levels. In a total of 336 patients, Dengue was confirmed in 169 cases by both immuno-enzymatic tests, of these, 97 patients (57.4%) were female and 72 (42.6%) were male. Mean age of patients was 34.5 years (range 7-78 years). A total of 127 cases (75.1%) were classified as classic Dengue and 42 (24.9%) as DHF. DENV-3 was isolated in 3 cases, 2 of which were classified as classic Dengue and 1 as DHF. In 34.9% of the population studied, no changes in aminotransferases were detected (Grade A), whereas aminotransferase levels were high in 65.1% of patients, 48.5% classified as Grade B, 14.8% as Grade C and 1.8% as Grade D. In the cases classified as classic

Dengue, aminotransferases were high in 61.4%, while in cases of DHF, aminotransferases were abnormal in 76.2% of cases.5 Larreal Y, Valero N, Estevez J, Reyes I, Maldonado M, Espina L M.et.al. In their study on Hepatic alterations in patients with Dengue. Laboratory test findings showed leucopenia in 72.5% in both forms of Dengue, and of patients with DHF severe thrombocytopenia (< 50,000/mm3platelets), prolonged PT and APPT was found in 70.9%, 23.0% and 42.3% respectively. 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.6 W.Petdachai in his study titled Hepatic dysfunction in children with Dengue shock syndrome 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.7 Nazish Butt, Amanullah Abbasi, S.M Munir, S.Masroor Ahmad and Qurban Hussain Sheikh, in their study about Hematological and biochemical indicators for early diagnosis of Dengue viral infection 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.8

6.3 OBJECTIVES OF THE STUDY:

Role of hematological and biochemical parameters for early diagnosis of Dengue viral illness.

To compare clinical, hematological and biochemical parameters in Dengue

viral illness.

7 MATERIALS AND METHODS:

Study Design:- Hospital based prospective study.

7.1 SOURCE OF DATA:

Children admitted in Vanivilas Children hospital, Bowring and lady Curzon hospital attached to Bangalore Medical College and Research Institute during 2009-10 will be taken for study.

7.2 METHOD OF COLLECTION OF DATA:

Definition of Study Subjects- 50 cases of suspected Dengue children who fulfill the following inclusion criteria will be selected. Pretest counseling will be given to parents / guardian. After taking written consent from parents ,blood samples will be collected from children with suspected Dengue infection for complete blood count, haematocrit, liver function tests, prothrombin time, activated partial thromboplastin time, Dengue viral IgG & IgM, and other relevant investigations who are admitted to Vanivilas Children hospital, Bowring

and lady Curzon hospital attached to Bangalore medical college and research institute. Statistical methods used for the analysis of the data collected will be Chi-squares test.

7.3 INCLUSION CRITERIA:

All children with fever less than 2 weeks duration with or without body rashes, flushing and with or without bleeding manifestations and clinically suspected of Dengue illness according to WHO criteria are included.

7.4 EXCLUSIONCRITERIA:
Children with fever more than 2 weeks duration, other liver diseases like hepatitis, other causes of thrombocytopenia and bleeding manifestation, are excluded.

7.5 Does the study require any investigation or interventions to be conducted on patients ? YES
Blood tests for Dengue IgG & IgM, Liver function tests, Prothrombin time and Partial thromboplastin time, complete blood count and haematocrit.

7.6

Has the ethical committee clearance been obtained for this study from your institution ? YES

8. LIST OF REFERENCES:

1) Tanner L, Schreiber M, Low JGH, Ong A, Tolfvenstam T, Cameroon P. et.al. Decision Tree Algorithms Predict the Diagnosis and Outcome of Dengue Fever in the Early Phase of Illness. Journal of Trop Dis2008 March; 2(3):196-201. 2) Jien-Wei Liu, Boon-Siang Khor, Chen-Hsiang Lee, Ing-Kit Lee, Rong-Fu Chen Kuender D Yang. Dengue Hemorrhagic fever in Taiwan in 2001.WHO Dengue bulletin 2003; (27):23-27 3) 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. 4) Wahid SF,Sanusi S, Zawawi MM, Ali RA. A comparison of pattern of liver involvement in Dengue hemorrhagic fever with classic J Southeast Asian J Trop Med Public Health 2000; 31(2):259-63. 5) 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 Infect Dis Aug2007; 11(4). 6) 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. 7) Petdachai W. Hepatic dysfunction in children with Dengue shock Dengue fever.

syndrome.Dengue bulletin 2005; (29):112-118.

8) Butt N, Abbasi A, Munir S M, Masroor Ahmad S, Sheikh Q H. Hematological and Biochemical indicators for early diagnosis of Dengue viral infection. Journal of the college of Physicians and Surgeons Pakistan 2008; 18(5):282-285.

9.

SIGNATURE OF THE CANDIDATE REMARKS OF THE GUIDE

: DR.SHABBEER . S . BATAKURKI : THIS STUDY HELPS IN EARLY DIAGNOSIS AND PROGNOSIS OF DENGUE VIRAL ILLNESS THUS PREVENTING MORTALITY IN CHILDREN.

NAME & DESIGNATION OF GUIDE 11.1 GUIDE : DR. S. PUSHPALATHA . PROFESSOR DEPARTMENT OF PEDIATRICS, BOWRING AND LADY CURZON HOSPITAL, BANGALORE MEDICAL COLLEGE & RESEARCH INSTITUTE, BANGALORE

11.2 SIGNATURE

11.3 CO-GUIDE

11.4 SIGNATURE

11.5 HEAD OF THE DEPARTMENT

: DR. GANGADHAR .B. BELAVADI. PROF. AND HOD, DEPARTMENT OF PEDIATRICS, VANIVILAS HOSPITAL, BANGALORE MEDICAL COLLEGE & RESEARCH INSTITUTE, BANGALORE :

11.6 SIGNATURE

12.1 REMARKS OF THE CHAIRMAN & DEAN

12.2 SIGNATURE