Utility of sonography in clinically suspected Dengue

Utility of sonography in clinically suspected Dengue

Pediatric Infectious Disease 2012 JulyeSeptember Volume 4, Number 3; pp. 107e111 Original Article Utility of sonography in clinically suspected Deng...

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Pediatric Infectious Disease 2012 JulyeSeptember Volume 4, Number 3; pp. 107e111

Original Article

Utility of sonography in clinically suspected Dengue Rajib Chatterjee*, Amulya Mysore, Kunal Ahya, Dhananjay Shrikhande, Dhiraj Shedabale

ABSTRACT Aim: Sonographic findings can be used as early diagnostic modality even before serological results (IgM/IgG antibodies) become positive in Dengue. Materials & methods: DESIGN: Prospective cross-sectional study in a paediatric teaching hospital in rural area. PARTICIPANTS: Children 6 monthse12 years with serologically confirmed Dengue. OUTCOME MEASURES: Sonographic findings in clinically suspected and laboratory proved Dengue. Results: 96 patients with Dengue serology positive presented with fever (100%), abdominal pain (62.5%), vomiting (56.25%), malaena (55.20%), petechiae (41.67%), body ache (37.5%), headache (31.25%), oedema (23.96%), hypotension (16.67%), retro-orbital pain (8.33%), epistaxis (3.13%) and CNS involvement (3.02%). Laboratory findings: Hb (11.92  2.47), PCV (33.85  7.21), PC (39,000  34,289). On 3rd day of fever, USG showed hepatomegaly (87.5%), pericholecystic oedema (83.33%), gall bladder wall thickening (83.33%), ascites (77.08), pleural effusion (45.83% right, 20.83% both), splenomegaly (35.41%) which has a positive correlation (p < 0.05) with Serology. Conclusion: Sonography in clinically suspected cases of dengue is a good tool to aid in early diagnosis of dengue, even before the Dengue antibodies become detectable. This is useful especially in areas where Dengue NS1 testing is not available. Copyright © 2012, Indian Academy of Pediatrics, Infectious Disease Chapter. All rights reserved. Keywords: Dengue, Hepatomegaly, Pericholecystic oedema, Serology, Sonography

BACKGROUND Epidemics of Dengue have hit several Indian cities in the last decade and it remains a health problem with endemicity both in urban and rural areas which are infested with Aedes aegypti mosquito.1 There can be fatal complications of this disease such as Dengue Haemorrhagic Fever (DHF), Dengue Shock Syndrome (DSS).2,3 The present communication documents the value of early diagnosis by sonography in clinically suspected patients much before the serology (IgG and IgM antibodies) becomes positive. This helps in improving outcome in these potentially fatal cases of Dengue.

In endemic area, when clinical manifestations are suggestive of Dengue, serological confirmation, except NS1 antigen assay, can only be obtained after 5 days. With the availability of sonography, diagnostic conclusion of dengue can be made as early as the third day which could be life saving. The sonography findings of hepatomegaly, pericholecystic oedema, thickened gall bladder wall, ascites, pleural effusion (right sided or both sided) and splenomegaly are early and significant markers of dengue, confirmed by serology later on.4,5 This study has been undertaken to emphasize the usefulness of ultrasonography in the early diagnosis of dengue fever.

Pravara Institute of Medical Sciences, Loni, Maharashtra 413736, India. * Corresponding author. email: [email protected] Received: 21.5.2012; Accepted: 15.7.2012; Available online: 5.9.2012 Copyright Ó 2012, Indian Academy of Pediatrics, Infectious Disease Chapter. All rights reserved. http://dx.doi.org/10.1016/j.pid.2012.07.006

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AIMS 1. To determine the predominant early sonographic findings in clinically suspected Dengue cases. 2. To correlate the sonographic findings to serologically proven Dengue.

METHODS A prospective study was done on 96 patients with Dengue serology positive (IgG-39, both IgG and IgM-57) from 1st June to 31st Sept 2009 in Pravara Rural Hospital, Loni, Maharashtra, a tertiary care teaching hospital, to study the diagnostic value of sonography in clinically suspected Dengue patients. Study was conducted after approval by ethical committee of the institute. Due informed written consent was taken from parents for the study. 96 Serological positive Dengue patients admitted between age group 6 months and 12 years were studied. The patients were grouped based on age and sex. The clinical presentations of these patients included fever, abdominal pain, vomiting, malaena, petechiae, body ache, headache, oedema, hypotension, retro-orbital pain, epistaxis and CNS involvement.6,7 Petechia was checked by Diascopy method. Diascopy is a test for blanchability performed by applying pressure with a finger on glass slide placed over the skin and observing colour changes. It is used to determine whether lesion is vascular or nonvascular or hemorrhagic. Hemorrhagic lesions and nonvascular lesions do not blanch, inflammatory lesions do. Blood pressure was measured to detect Hypotension. Hb, PCV was measured by automatic cell counter which required 12 ml of whole blood. Platelet count was estimated by Rees Ecker method which is a manual method of slide examination. In this, 2 ml of blood is diluted with 1% ammonium oxalate in dilution of 1:100. This solution haemolyses RBCs and WBCs without destroying any of the platelets, which is put in a Neubauer chamber in a petridish. After 15 min the platelets can be observed and counted through a microscope without being masked by larger cells.8,9 Biochemical studies included estimation of SGOT, SGPT levels.3 Serological tests included Dengue serology for IgG, IgM which was done by Erba-Den-G0 (TRANSASIA) IgG\IgM kit.10 In this 1 ml of blood is collected in a collecting tube. The kit is placed on a flat surface which has a Test line “G”, Test line “M” and a Control line “C”. With a 10 ml disposable dropper, 10 ml of whole blood specimen is added into a square sample well marked “S”. 3e4 drops

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of assay diluent (100 mM Phosphate buffer: 5 ml, Sodium Azide: 0.01%w\w) is added into the assay diluents well which is round. Results are interpreted in 15e20 min. Interpretation of test: (a) Negative e only control line (C) is visible. (b) IgM positive e the control line (C) and IgM line (M) are visible. This is indication of primary Dengue infection. (c) IgG positive e control line (C) and IgG line (G) are visible. This is indicative of secondary or previous Dengue infection. (d) IgG, IgM positive e control line (C), IgM line (M) and IgG line (G) are visible. This is indicative of late primary or early secondary Dengue infection. In primary Dengue infection IgM levels are detectable after 5th day of fever whereas in secondary infection IgG rise after 2 days followed by a rise in IgM after 20 days. The sensitivity of this test is 95.8% with a specificity of >99%. X-ray imaging done for Pleural effusion. For this the exposure in <5 years age is 50e60 kv and for children between 5 and 12 years is 55e65 kv. Ultrasonography was performed with LOGIQ-400 by a curvilinear probe of 3.5 MHz. Sonography was done after 6 h of fasting. Statistical method applied was Chi-Square test, where p value was calculated.

RESULTS 96 patients with Dengue serology positive were studied. Out of them 39 were IgG and 57 were both IgG and IgM positive. They were then grouped according to age and sex as in Table 1. The clinical spectrum of Dengue cases is shown in Fig. 1. After assessing the clinical symptoms, laboratory investigations were done and they are depicted in Table 2. Liver function tests showed an elevation in serum transaminases (SGOT >> SGPT rise). On chest X-ray, Pleural effusion was seen in 15 patients on right side i.e. 15.62% and in 10 patients bilaterally i.e.10.42%. Table 1 Age and sex wise distribution of the 96 cases of Dengue. Age in years <1 1e5 5e10 >10 Total

No. of boys (%) 1 12 16 36 65

(1.04) (12.5) (16.67) (37.5) (67.71)

No. of girls (%) 1 5 14 11 31

(1.04) (5.2) (14.52) (11.45) (32.29)

Total (%) 2 17 30 47 96

(2.08) (17.71) (31.25) (48.96)

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Clinical spectrum of dengue cases 96

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Fig. 1 Clinical spectrum of dengue cases. For the above figure by applying Z test for difference between two proportions, there is a highly significant difference between proportions of clinical features in Dengue cases (i.e. p < 0.01).

The ultrasound findings were then studied which was done on the 3rd & 4th day of fever and the findings are shown in Table 3 and Fig. 2.

DISCUSSION Dengue is an escalating health problem in the tropics and subtropics. This study shows that there should be a high index

of suspicion for Dengue if a patient has an abrupt onset of fever, abdominal pain, vomiting, malaena, petechiae which may be associated with body ache, retro-orbital pain, hypotension and in few cases CNS involvement.6,7,10,11 This along with laboratory findings of thrombocytopaenia, haemoconcentration and an elevation of transaminases should mandate for an ultrasound study. The combination of clinical, laboratory and ultrasound findings essentially suggests Dengue.4,5

Table 2 Haematological parameters of the 96 cases of Dengue. Parameter Hb (11.92  2.47) No. of cases PCV (33.85  7.21) No. of cases Platelet count (39,000  34,289) No. of cases

Range of values Distribution of cases <8 2 <25 8 <20,000 11

8e10 18 25e30 16 20,000e50,000 50

10e12 30 30e35 20 50,000e80,000 31

12e14 30 35e40 24 80,000e120,000 2

>14 16 >40 28 120,000e150,000 2

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late to be of clinical benefit. The sonography findings although nonspecific for Dengue are obtained as early as the third day, whereas the serological results are reliable after the fifth day of onset of fever. Hence sonography has a definite advantage over a serological test.4,5 The findings of hepatomegaly, pericholecystic oedema, gall bladder wall thickening, ascites, pleural effusion (right sided and bilateral) are present in a patient with Dengue.6,12 This is useful especially in areas where Dengue NS1 antigen assay testing is not available. Sonographic evaluation in our study showed 77.08% ascites, 83.33% pericholecystic oedema, 83.33% gall bladder thickening, 87.5% hepatomegaly, 35.4% splenomegaly, pleural effusion Right sided e 45.83%, Bilateral e 20.83%. In the present study serological evaluation showed that 39 cases had definite secondary dengue infection and 57 had either late primary or early secondary dengue infection. There was a mortality of 3 cases (3.12%), all of which were in Grade IV, who expired within 72 h of admission. The limitation of the study was serotyping could not be done and hence inability in correlating specific sonographic findings to a specific serotype. A study in Taiwan in 2004 showed ascites (37%), Thickened gall bladder (59%) Splenomegaly (34%) and Pleural Effusion (32%: Right e 54%, Left e 51%). The virus confirmed was Dengue type 2 virus.4 Our study couldn’t give serological typing for specific virus and hence probably the result differed. A study was done in, Sri Ramachandra Medical College & Research Institute (DU), Porur, Chennai in May 2005. Of the 88 serologically positive cases, 32 patients underwent ultrasound on second to third day. All showed gall bladder wall thickening and pericholecystic fluid, 21% had hepatomegaly, 6.25% had splenomegaly and right minimal pleural

Table 3 Sonography findings in serologically proven Dengue cases. Findings

Yes Percentage No Percentage (%) (%)

Hepatomegaly Pericholecystic oedema Gall bladder wall thickening Ascites Pleural effusion (rt. sided) Splenomegaly Pleural effusion (bilateral)

84 80 80 74 44 34 20

87.5 83.33 83.33 77.08 45.83 35.41 20.83

12 16 16 22 52 62 74

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12.5 16.66 16.66 22.91 54.16 64.58 79.16

For the above table by applying Z test for difference between two proportions, there is a highly significant difference between proportions of Sonography findings in dengue cases (i.e. p < 0.01).

In this study we had patients in Grade I e 36, Grade II e 44, Grade III e 13, and Grade IV e 3. Grade I: Patients with fever, nonspecific constitutional symptoms, with or without easy bruising, associated with tachycardia and normal blood pressure. Grade II: Patients with fever with nonspecific constitutional symptoms with spontaneous bleeding such as skin bleeds or other bleeds, associated with tachycardia and normal blood pressure. Grade III (DSS): Patients with features of Grade I/Grade II associated with cold peripheries, spontaneous bleeding and with signs of hypotension. Grade IV: Patients with features of Grade I/ Grade II along with spontaneous bleeding and symptoms of profound shock.6,11,12 Thus early diagnosis is necessary to reduce the mortality and morbidity associated with this disease and hence a combination of clinical, laboratory and sonography findings help us in arriving at a conclusion of Dengue.11,12 Dengue can be confirmed by serological detection of virus or antiviral antibodies but the results are obtained 100% 80% 60% 40% 20%

Fig. 2 Sonographic findings in serologically proven Dengue cases.

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Sonography in Dengue

effusion. Follow-up ultrasound on fifth to seventh day revealed ascites in 53%, left pleural effusion in 22% and pericardial effusion in 28%.13 Thus the present study aims to put forth, that in clinically suspected dengue patients residing in an endemic area, if above sonography findings are present the diagnosis of Dengue lies first in the list of differential diagnosis (Meningococcemia, malaria, typhoid). Hence necessary supportive intervention can be initiated earlier on a firm footing enabling greater salvage with a better outcome.4,13

AUTHORS’ CONTRIBUTION RC and AM conceived and designed the study and revised the manuscript for important intellectual content. RC will act as guarantor of the study. KA and SD collected data, drafted the paper and interpreted the laboratory tests. KA and DYS analyzed the data and helped in manuscript writing. The final manuscript was approved by all authors.

ETHICAL APPROVAL Study was conducted after approval by ethical committee of the institute. Due informed written consent was taken from parents for the study.

CONFLICTS OF INTEREST All authors have none to declare. ACKNOWLEDGEMENTS Dr. H. Pawar, Associate Professor, Department of Medical Informatics, Rural Medical College, Loni for Statistical analysis and Dr. Aironi, Associate Professor, Department of Imaging and Radiology for ultrasonography interpretation.

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