Short review on diagnosis of Dengue infection and use of ultrasound

1. Dengue and Bedside US:
What Could Help You More
Than Blood Test
Rathachai Kaewlai, MD
Division of Emergency Radiology, Dept of Radiology
Ramathibodi Hospital, Bangkok,Thailand
WINFOCUS Ultrasound Enhanced Life Support,
Chulalongkorn Hospital University, 10 Jan 2016

2. Outline
Dengue infection
Traditional means of diagnosis
Bedside ultrasound – evidence so far

3. Dengue: Major Public Health
3.9 billion people in 128 countries at risk
390 million dengue infections per year

4. Dengue: Major Public Health
Average annual number of DF and DHF cases reported to WHO,
and of countries reporting dengue, 1955-2007

5. Dengue Infection
Flavivirus infection
Four serotypes: DEN-1, DEN-2, DEN-3, DEN-4
Several possible vectors:Aedes aegypti,Aedes albopictus
Incubation period 3-14 days (average 4-7 days)
Most severe infections = co-infection of two different
serotypes
Images from ucanr.edu and virology.wisc.edu

6. Dengue Infection:
Primary or Secondary
Primary: infection with any serotype inducing immune
response protecting re-infection by that serotype
Mostly children
Secondary: infection by another serotype
Mostly adults or elderly
A/W significant morbidity and occasional death

7. Dengue Infection
Wide spectrum of clinical presentations
Often unpredictable clinical evolution and outcome
Infection may be asymptomatic, self-limiting febrile
illness or
Small number of cases – severe/life-threatening
characterized by plasma leakage w/wo hemorrhage

8. Dengue: Course of Illness

9. WHO:
Focus on First Level of Care
Recognize that the febrile patient could have dengue
Notify public health authorities
Manage patients in early febrile phase
Recognize early stage of plasma leakage or critical phase
and initiate fluid therapy
Recognize patients with warning signs needing referral
or admission
Recognize and manage severe plasma leakage and shock

10. Dengue Infection: Diagnosis
Clinical features
Blood picture
Serology:
Antibody- IgG, IgM
Antigen- non-structural 1 (NS1) antigen
Viral genome: PCR (80-90% sensitive, 95% specific)

11. Dengue Infection: Diagnosis
(CDC 2009)

12. Dengue Infection Classification:
WHO 2009

13. Dengue Infection Classification:
WHO SEA (2010)

14. Dengue: Confusing With
Classification?
Think of it as the same disease of different severity
Asymptomatic ! Mild ! Severe ! Lethal
Fever ! Leakage/hemorrhage
Viral syndrome ! DF ! DHF ! DSS (WHO SEAsia)
Dengue wo warning ! w warning ! Severe (WHO)
Symptomatic Rx ! Admission ! ICU

15. Dengue: Beware
Even dengue patients without warning signs may develop
severe dengue (“DHF is not a continuum of DF”)
Expanded dengue syndrome
Unusual or atypical manifestations
Uncommon but increasing reports
Neurological, hepatic, renal and other isolated organ
involvement (complications of severe profound shock
or a/w underlying host diseases)

16. Dengue: Role of Ultrasound
Detect plasma leakage
Ascites
Pleural effusion
Gallbladder wall edema is a/w plasma leakage and may
precede clinical detection of plasma leakage
Helpful for diagnosis of severe dengue/DHF in patients
with anemia, severe hemorrhage, no baseline Hct or
rise in Hct 20% because of early IV therapy

17. Dengue: Role of Ultrasound
Identify patients at risk of progression to severe dengue
Detect subclinical plasma leakage by daily US
Ascites and/or pleural effusion found in 27/66 cases:
31% in non-severe dengue vs 91% in severe dengue
PPV 35%, NPV 90%
Thickened GB wall for predicting severe dengue
PPV 21%, NPV 91%
Michels M, et al. PLoS NeglTrop Dis 2013

18. Dengue: Role of Ultrasound
Raise a possibility of this diagnosis in unsuspected cases:
Atypical presentation
Limited resources in lab testing
Bertfish.com

19. Ultrasound Findings
Increased capillary permeability ! plasma leakage
Pleural effusion
Ascites
Pericardial effusion
Organomegaly
Gallbladder wall edema/thickening
Elifesciences.org

20. US Findings in Proven Dengue Cases
US Findings
%
Hepatomegaly
88
Pericholecystic edema
83
GB wall thickening
83
Ascites
77
Pleural effusion*
- Right sided only
- Bilateral
46
21
Splenomegaly
35
96 pediatric patients
80 grade III
13 grade III, 3 grade IV
No mortality
US Day3-4 of fever
*Effusion seen on CXR in only 26% of cases
Chatterjee R, et al. Pediatr Infect Dis 2012; 4:107

21. US Findings in Proven Dengue Cases
US Findings
%
GB wall thickening
- Honeycomb pattern
- Other patterns
95
5
Ascites
75
Pleural effusion
- Right-sided only
- Bilateral
50
20
Splenomegaly
40
20 adult patients
All with abdominal pain/
discomfort
No mortality
US Day3-7 of fever
F/U US: most GB wall
thickenings resolved on
Day7
Sachar S, et al. Arch Clin Exp Surg 2013; 2:38

22. US Findings in Proven Dengue Cases
US Findings
Non-
severe (%)
Severe
(%)
GB wall thickening
87
100
Pericholecystic fluid
44
60
Hepatomegaly
27
60
Splenomegaly
22
40
Effusion
- Right
- Left
9
-
60
20
Ascites
18
60
Pericardial effusion
4
20
50 patients (6-59 years)
45 non-severe
5 severe (2 deaths)
GB wall 5 mm
No Murphy sign
Mehdi SA, et al. Ann Punjab Med Coll 2012; 6:32

23. GB Wall Edema/Thickening
3 mm or 5 mm
Diffuse thickening
Or focal at fundus
“Honeycomb” pattern

24. GB Wall Edema/Thickening
More common in 20 infection
Usually with free fluid (ascites)
Resolved with clinical recovery

25. Ascites
Sensitivity 91%, NPV 84% to detect plasma leakage
Balasubramanian S, et al. Indian Pediatr 2006; 43:334
*
*
*

26. Ascites
Positive correlation with GB wall thickening
*

27. Pleural Effusion
Right or bilateral effusions
Very rarely (or non-
existent?) isolated left
effusion
Srikiatkhachorn, et al. Pediatr Infect Dis 2007; 26:283
*

28. Pleural Effusion
Time of performance of US
may influence its presence
Common US evidence of
plasma leakage, starting 2
days before defervescence
(decrease of body temp)
Srikiatkhachorn, et al. Pediatr Infect Dis 2007; 26:283
Day 3 of fever
*

29. Pericardial Effusion
8% of patients with DHF had small pericardial effusion*
US at Day5-8 from onset of fever ! 28% had this**
0 out of 32 patients US Day2-3 had this**
3 out of 12 volunteers inoculated with dengue virus
developed small pericardial effusion btw Day10-20
Cardiac tamponade possible but very rare (case reports)
*Setiawan MW, et al. J Clin Ultrasound 1998; 23:357
**Venkata Sai PM, et al. Br J Radiol 2005; 78:416

30. Severity of Disease
Possible early prediction of disease severity
Mild disease – less % of US abnormalities
Severe disease – US abnormalities very common

31. US Differential Diagnosis
Acute cholecystitis:
GB distension
Gallstones (acalculous – uncommon in ER)
Wall thickening not marked
Ascites, pleural effusion, pericardial eff not common
Murphy may not be that helpful

32. US: Limitations
Findings of plasma leakage are seen in both mild and
severe disease, primary as well as secondary
infections
Findings possibly related to time of onset
Can findings be reflective of treatment?
Nonspecific US findings when stand-alone

33. Summary (I)
Spectrum of plasma leakage a/w dengue is broad.With
improved techniques of identification – minor
leakage will become more apparent
Ascites, pleural effusion, pericardial effusion, GB wall
thickening and hepatosplenomegaly are US signs of
plasma leakage

34. Summary (II)
Unsuspected case – US performed for other reasons
Suspected case, limited hospital resources – US helps
making diagnosis or narrowing DDx
Suspected/confirm case – US helps detecting subclinical
plasma leakage
Serial US may help identify patients whom disease
might progress

35. Suggested Readings
2010