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

Outline

Dengue infection

Traditional means of diagnosis Bedside ultrasound – evidence so far

Dengue: Major Public Health

3.9 billion people in 128 countries at risk 390 million dengue infections per year

Dengue: Major Public Health

Average annual number of DF and DHF cases reported to WHO, and of countries reporting dengue, 1955-2007

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

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

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

Dengue: Course of Illness

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

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)

Dengue Infection: Diagnosis ���(CDC 2009)

Dengue Infection Classification: WHO 2009

Dengue Infection Classification:���WHO SEA (2010)

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

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)

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

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 Negl Trop Dis 2013

Dengue: Role of Ultrasound

Raise a possibility of this diagnosis in unsuspected cases:

Atypical presentation Limited resources in lab testing

Bertfish.com

Ultrasound Findings

Increased capillary permeability ! plasma leakage Pleural effusion Ascites

Pericardial effusion Organomegaly

Gallbladder wall edema/thickening

Elifesciences.org

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 I&II 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

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

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

GB Wall Edema/Thickening

>3 mm or >5 mm

Diffuse thickening Or focal at fundus

“Honeycomb” pattern

GB Wall Edema/Thickening

More common in 20 infection

Usually with free fluid (ascites) Resolved with clinical recovery

Ascites

Sensitivity 91%, NPV 84% to detect plasma leakage

Balasubramanian S, et al. Indian Pediatr 2006; 43:334

*   *  *  

Ascites

Positive correlation with GB wall thickening

*  

Pleural Effusion

Right or bilateral effusions

Very rarely (or non-existent?) isolated left effusion

Srikiatkhachorn, et al. Pediatr Infect Dis 2007; 26:283

*  

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

*  

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

Severity of Disease

Possible early prediction of disease severity

Mild disease – less % of US abnormalities Severe disease – US abnormalities very common

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

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

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

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

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