utility of sonography in clinically suspected dengue

5
Utility of sonography in clinically suspected Dengue Rajib Chatterjee * , Amulya Mysore, Kunal Ahya, Dhananjay Shrikhande, Dhiraj Shedabale ABSTRACT Aim: Sonographic ndings can be used as early diagnostic modality even before serological results (IgM/IgG anti- bodies) 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 conrmed Dengue. OUTCOME MEASURES: Sonographic ndings 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 ndings: 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 sugges- tive of Dengue, serological conrmation, 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 ndings of hepatomegaly, pericholecys- tic oedema, thickened gall bladder wall, ascites, pleural effusion (right sided or both sided) and splenomegaly are early and signicant markers of dengue, conrmed by serology later on. 4,5 This study has been undertaken to emphasize the useful- ness 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 Pediatric Infectious Disease 2012 JulyeSeptember Volume 4, Number 3; pp. 107e111 Original Article

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Pediatric Infectious Disease 2012 JulyeSeptemberVolume 4, Number 3; pp. 107e111 Original Article

Utility of sonography in clinically suspected Dengue

Rajib Chatterjee*, Amulya Mysore, Kunal Ahya, Dhananjay Shrikhande, Dhiraj Shedabale

Pravar*CorreReceivCopyrihttp://d

ABSTRACT

Aim: Sonographic findings can be used as early diagnostic modality even before serological results (IgM/IgG anti-bodies) 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, USGshowed 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 testingis 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 thelast decade and it remains a health problem with endemicityboth in urban and rural areas which are infested with Aedesaegypti mosquito.1 There can be fatal complications of thisdisease such as Dengue Haemorrhagic Fever (DHF),Dengue Shock Syndrome (DSS).2,3

The present communication documents the value ofearly diagnosis by sonography in clinically suspectedpatients much before the serology (IgG and IgM antibodies)becomes positive. This helps in improving outcome in thesepotentially fatal cases of Dengue.

a Institute of Medical Sciences, Loni, Maharashtra 413736, India.sponding author. email: [email protected]

ed: 21.5.2012; Accepted: 15.7.2012; Available online: 5.9.2012ght � 2012, Indian Academy of Pediatrics, Infectious Disease Chaptx.doi.org/10.1016/j.pid.2012.07.006

In endemic area, when clinical manifestations are sugges-tive of Dengue, serological confirmation, except NS1 antigenassay, can only be obtained after 5 days. With the availabilityof sonography, diagnostic conclusion of dengue can be madeas early as the third day which could be life saving.

The sonography findings of hepatomegaly, pericholecys-tic oedema, thickened gall bladder wall, ascites, pleuraleffusion (right sided or both sided) and splenomegaly areearly and significant markers of dengue, confirmed byserology later on.4,5

This study has been undertaken to emphasize the useful-ness of ultrasonography in the early diagnosis of denguefever.

er. All rights reserved.

108 Pediatric Infectious Disease 2012 JulyeSeptember; Vol. 4, No. 3 Chatterjee et al.

AIMS

1. To determine the predominant early sonographic find-ings in clinically suspected Dengue cases.

2. To correlate the sonographic findings to serologicallyproven Dengue.

Table 1 Age and sex wise distribution of the 96 cases ofDengue.

Age in years No. of boys (%) No. of girls (%) Total (%)

<1 1 (1.04) 1 (1.04) 2 (2.08)1e5 12 (12.5) 5 (5.2) 17 (17.71)5e10 16 (16.67) 14 (14.52) 30 (31.25)>10 36 (37.5) 11 (11.45) 47 (48.96)Total 65 (67.71) 31 (32.29) 96

METHODS

A prospective study was done on 96 patients with Dengueserology positive (IgG-39, both IgG and IgM-57) from 1stJune to 31st Sept 2009 in Pravara Rural Hospital, Loni,Maharashtra, a tertiary care teaching hospital, to study thediagnostic value of sonography in clinically suspectedDengue patients. Study was conducted after approval byethical committee of the institute. Due informed writtenconsent was taken from parents for the study.

96 Serological positive Dengue patients admittedbetween age group 6 months and 12 years were studied.The patients were grouped based on age and sex. The clin-ical presentations of these patients included fever, abdom-inal pain, vomiting, malaena, petechiae, body ache,headache, oedema, hypotension, retro-orbital pain, epistaxisand CNS involvement.6,7

Petechia was checked by Diascopy method. Diascopy isa test for blanchability performed by applying pressure witha finger on glass slide placed over the skin and observingcolour changes. It is used to determine whether lesion isvascular or nonvascular or hemorrhagic. Hemorrhagiclesions and nonvascular lesions do not blanch, inflamma-tory 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 dilu-tion of 1:100. This solution haemolyses RBCs and WBCswithout destroying any of the platelets, which is put ina Neubauer chamber in a petridish. After 15 min the plate-lets can be observed and counted through a microscopewithout 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 collect-ing tube. The kit is placed on a flat surface which has a Testline “G”, Test line “M” and a Control line “C”. With a 10 mldisposable dropper, 10 ml of whole blood specimen isadded into a square sample well marked “S”. 3e4 drops

of assay diluent (100 mM Phosphate buffer: 5 ml, SodiumAzide: 0.01%w\w) is added into the assay diluents wellwhich 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 Dengueinfection.

(c) IgG positive e control line (C) and IgG line (G) arevisible. This is indicative of secondary or previousDengue infection.

(d) IgG, IgM positive e control line (C), IgM line (M) andIgG line (G) are visible. This is indicative of lateprimary or early secondary Dengue infection. Inprimary Dengue infection IgM levels are detectableafter 5th day of fever whereas in secondary infectionIgG rise after 2 days followed by a rise in IgM after20 days. The sensitivity of this test is 95.8% witha specificity of >99%.

X-ray imaging done for Pleural effusion. For this theexposure in <5 years age is 50e60 kv and for childrenbetween 5 and 12 years is 55e65 kv.

Ultrasonography was performed with LOGIQ-400 bya curvilinear probe of 3.5 MHz. Sonography was done after6 h of fasting.

Statistical method applied was Chi-Square test, where pvalue was calculated.

RESULTS

96 patients with Dengue serology positive were studied. Outof them 39 were IgG and 57 were both IgG and IgM positive.Theywere thengroupedaccording toageandsexas inTable1.The clinical spectrum of Dengue cases is shown in Fig. 1.

After assessing the clinical symptoms, laboratory inves-tigations were done and they are depicted in Table 2.

Liver function tests showed an elevation in serum trans-aminases (SGOT >> SGPT rise).

On chest X-ray, Pleural effusion was seen in 15 patientson right side i.e. 15.62% and in 10 patients bilaterallyi.e.10.42%.

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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 isa highly significant difference between proportions of clinical features in Dengue cases (i.e. p < 0.01).

Sonography in Dengue Original Article 109

The ultrasound findings were then studied which wasdone on the 3rd & 4th day of fever and the findings areshown in Table 3 and Fig. 2.

DISCUSSION

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

Table 2 Haematological parameters of the 96 cases of Dengue.

Parameter

Hb (11.92 � 2.47)No. of cases

<8 8e102 18

PCV (33.85 � 7.21)No. of cases

<25 25e308 16

Platelet count (39,000 � 34,289)No. of cases

<20,000 20,000e50,00011 50

of suspicion for Dengue if a patient has an abrupt onset offever, abdominal pain, vomiting, malaena, petechiae whichmay be associatedwith body ache, retro-orbital pain, hypoten-sion and in few cases CNS involvement.6,7,10,11 This alongwith laboratory findings of thrombocytopaenia, haemocon-centration and an elevation of transaminases should mandatefor an ultrasound study. The combination of clinical, labora-tory and ultrasound findings essentially suggests Dengue.4,5

Range of valuesDistribution of cases

10e12 12e14 >1430 30 1630e35 35e40 >4020 24 2850,000e80,000 80,000e120,000 120,000e150,00031 2 2

Table 3 Sonography findings in serologically proven Denguecases.

Findings Yes Percentage(%)

No Percentage(%)

Hepatomegaly 84 87.5 12 12.5Pericholecystic oedema 80 83.33 16 16.66Gall bladder wall thickening 80 83.33 16 16.66Ascites 74 77.08 22 22.91Pleural effusion (rt. sided) 44 45.83 52 54.16Splenomegaly 34 35.41 62 64.58Pleural effusion (bilateral) 20 20.83 74 79.16

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

110 Pediatric Infectious Disease 2012 JulyeSeptember; Vol. 4, No. 3 Chatterjee et al.

In this study we had patients in Grade I e 36, Grade II e44, Grade III e 13, and Grade IV e 3. Grade I: Patientswith fever, nonspecific constitutional symptoms, with orwithout easy bruising, associated with tachycardia andnormal blood pressure. Grade II: Patients with fever withnonspecific constitutional symptoms with spontaneousbleeding such as skin bleeds or other bleeds, associatedwith tachycardia and normal blood pressure. Grade III(DSS): Patients with features of Grade I/Grade II associatedwith cold peripheries, spontaneous bleeding and with signsof hypotension. Grade IV: Patients with features of Grade I/Grade II along with spontaneous bleeding and symptoms ofprofound shock.6,11,12

Thus early diagnosis is necessary to reduce the mortalityand morbidity associated with this disease and hencea combination of clinical, laboratory and sonography find-ings help us in arriving at a conclusion of Dengue.11,12

Dengue can be confirmed by serological detection ofvirus or antiviral antibodies but the results are obtained

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Fig. 2 Sonographic findings in serologically proven Dengue cases.

late to be of clinical benefit. The sonography findingsalthough nonspecific for Dengue are obtained as early asthe third day, whereas the serological results are reliableafter the fifth day of onset of fever. Hence sonographyhas a definite advantage over a serological test.4,5 The find-ings of hepatomegaly, pericholecystic oedema, gall bladderwall thickening, ascites, pleural effusion (right sided andbilateral) are present in a patient with Dengue.6,12 This isuseful especially in areas where Dengue NS1 antigen assaytesting is not available.

Sonographic evaluation in our study showed 77.08%ascites, 83.33% pericholecystic oedema, 83.33% gallbladder thickening, 87.5% hepatomegaly, 35.4% spleno-megaly, pleural effusion Right sided e 45.83%, Bilaterale 20.83%.

In the present study serological evaluation showed that39 cases had definite secondary dengue infection and 57had either late primary or early secondary dengue infection.There was a mortality of 3 cases (3.12%), all of which werein Grade IV, who expired within 72 h of admission.

The limitation of the study was serotyping could not bedone and hence inability in correlating specific sonographicfindings to a specific serotype.

A study in Taiwan in 2004 showed ascites (37%), Thick-ened gall bladder (59%) Splenomegaly (34%) and PleuralEffusion (32%: Right e 54%, Left e 51%). The virusconfirmed was Dengue type 2 virus.4 Our study couldn’tgive serological typing for specific virus and hence prob-ably the result differed.

A study was done in, Sri Ramachandra Medical College& Research Institute (DU), Porur, Chennai in May 2005. Ofthe 88 serologically positive cases, 32 patients underwentultrasound on second to third day. All showed gall bladderwall thickening and pericholecystic fluid, 21% had hepato-megaly, 6.25% had splenomegaly and right minimal pleural

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Sonography in Dengue Original Article 111

effusion. Follow-up ultrasound on fifth to seventh dayrevealed ascites in 53%, left pleural effusion in 22% andpericardial effusion in 28%.13

Thus the present study aims to put forth, that in clinicallysuspected dengue patients residing in an endemic area, ifabove sonography findings are present the diagnosis ofDengue lies first in the list of differential diagnosis (Menin-gococcemia, malaria, typhoid).

Hence necessary supportive intervention can be initiatedearlier on a firm footing enabling greater salvage witha better outcome.4,13

AUTHORS’ CONTRIBUTION

RC and AM conceived and designed the study and revisedthe manuscript for important intellectual content. RC willact as guarantor of the study. KA and SD collected data,drafted the paper and interpreted the laboratory tests. KAand DYS analyzed the data and helped in manuscriptwriting. The final manuscript was approved by all authors.

ETHICAL APPROVAL

Study was conducted after approval by ethical committee ofthe institute. Due informed written consent was taken fromparents for the study.

CONFLICTS OF INTEREST

All authors have none to declare.

ACKNOWLEDGEMENTS

Dr. H. Pawar, Associate Professor, Department of MedicalInformatics, Rural Medical College, Loni for Statisticalanalysis and Dr. Aironi, Associate Professor, Departmentof Imaging and Radiology for ultrasonography inter-pretation.

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2. Aggarwal A, Chandra J, Aneja S, Patwari AK, Dutta AK. Anepidemic of dengue hemorrhagic fever and dengue shocksyndrome inchildren inDelhi. IndianPediatr. 1998;35:727e732.

3. Narayanan M, Arvind MA, Thisothammal N, Prema R, RexSargonam CS, Ramamurty Nalini. Dengue Fever epidemicin Chennai e a study of clinical profile and outcome. IndianPediatr. 2002;39:1027e1033.

4. Wu KL, Changchien C, Kuo CH, et al. Early abdominal sono-graphic findings in patients with dengue fever. J Clin Ultra-sound. 2004;32:386e388.

5. Quiroz-Moreno R, Mendez GF, Ovendo-Rivera KM. Clinicalutility of ultrasound in the identification of dengue haemor-rhagic fever. Rev Med IMSS. 2006;44(3):243e248.

6. Ghai OP, Paul VK, Bagga A. Ghai’s Essential Paediatrics. 7thed.NewDelhi: CBSPublishers andDistributors; 2009:196e202.

7. Kapse AS. Dengue illness. In: Parthasarathy A, Menon PSN,Agarwal RK, Choudhury P, Thacker NC, Ugra D, et al., eds.IAP Textbook of Pediatrics. 4th ed. New Delhi: JaypeePublishers; 2009:396e403.

8. Vajayee N, Graham S, Bem S. Basic examination of blood andbone marrow. In: Mcpheson RA, Pincus MR, eds. Henry’sClinical Diagnosis and Management by Laboratory Methods.21st ed. New Delhi: Elsevier Publishers; 2007:480e487.

9. Raphall SS. Practice of haematology. In: Shoin I, ed. Lynch’sMedical Laboratory Technology. 4th ed. Japan: SaundersPublishers; 1983:672e713.

10. Gupta E, Das L, Narang P, Shrivastava VK, Broor S. Serodi-agnosis of Dengue on outbreak at a tertiary care hospital inDelhi. Indian J Med Res. 2005 Jan;121:36e38.

11. World Health Organization. Dengue Hemorrhagic Fever:Diagnosis, Treatment, Prevention and Control. 2nd ed.Geneva: World Health Organization; 1997.

12. Halstead SB. Dengue fever and dengue haemorrhagic fever.In: Kliegman RM, Behrman RE, Jenson HB, Stanton BF,eds. Nelson Textbook of Pediatrics. 18th ed. vol. 1. 2007:1412e1414.

13. Venkata Sai PM, Dev B, Krishnan R. Role of ultrasound indengue fever. Br J Radiol. 2005 May;78(929):416e418.