Clinical Management of Dengue

SIIDC 2017 Singapore

Prof (Dr) Yee-Sin LEO

Executive Director National Centre of Infectious Disease NCID

Clinical Director Communicable Disease Centre

Director Institute of Infectious Disease and Epidemiology

Tan Tock Seng Hospital

Communicable Disease Centre

Communicable

Disease Centre 2

Self-contained

No of Beds: 94

Communicable

Disease Centre

No of Beds: 211

Communicable

Disease Centre 1

80 Isolation Rooms

Built in 1907 In the middle of

SARS

Near end of SARS

Interim enhancement of isolation

facilities

Centralised outbreak management centre

1907 1960s 2018 2000s

1907 Smallpox, plaque

1938 Typhoid

1945-46 Polio outbreak

1957 Asian Flu

1958 Polio

1959 Smallpox

1961 Diphtheria

1963 Cholera

1964 Typhoid

1999 Nipah Outbreak

2003 SARS

2005 Worst dengue epidemic

2008 Chikungunya

2009 H1N1

2013 Worst dengue epidemic

2106 Zika

1985 Merged with TTSH

1992 Dept ID formed1907 Isolation camp

1920 Middleton Hospital

National Centre

for Infectious

Diseases (NCID)2012 Formed IIDE

H7N9

EBOLA

MERS CoV

National Centre for Infectious Diseases NCID

Dengue in Singapore

Despite vector

control, low

breeding index,

Singapore faces

successive waves

of dengue epidemic

Predominantly

adult dengue and

increasingly more

senior adults

Increasing

recognition of

atypical dengue

2.5 billion people -40% of world population – are at risk of dengue

100 million dengue virus infections worldwide every year

Half a million with severe dengue

Expect the unexpected

“Atypical” presentations

Dengue epidemic

Are admission and iv fluid necessary?

Primary Care

• Early recognition / suspicion of dengue

POCT / rapid combined Ag/Abs

Daily monitoring

•Early recognition of warning signs

Febrile phase

Secondary Care Hospitalization

Critical phase

• Adequate trained staff

• Lab support

• Adequate consumables

Tertiary Care ICU

Final Outcome

Recovery

Dengue management

WHO 2009

Specialized dengue care unit

Hospitalisation

Fluid management

Enhance care at community

Admission criteria

Early predictors

Early diagnosis

Emphasis on early

diagnosis and identify

early predictors to

effectively manage the

entire course of

dengue illness

Day 8 illness, afebrile

Simple cheap clinical and or laboratory tools are needed to

better diagnose dengue and able to diagnose dengue early

WHO 2012

Dengue diagnostics - Use the

right tool at the right time

Dengue diagnosis in 20 minutes

246 patients at TTSH Over 8 months

NS1 only Sen 82%, Spec 98% NS1/IgM,IgG Sen 94%, Spec 92%

Either WHO 1997 or 2009 is sensitive (>90%) but not specific (20-26%)

Straits Time 22nd Nov 2012 Reaching out to community

ST 13th June 2013

5th ASEAN Dengue Day Seminar - 2015

13 Jun 2015:Attended by over 140 general practitioners, physicians, researchers, nurses, pharmacists, and other healthcare professionals

Engaging Primary Care

June – Oct 2011

2 hospitals + reference lab

162 enrolled, 157 analysed

85 confirmed, 41 probable

(32DF, 84DHF, 8DSS)

31 negativeK 0.96, 98.1% agreement

K 0.55, 68.8% agreement

Dengue duo NS1/IgM/IgG

Hospital labs: 85.7% Sn,

83.9% Sp, PPV 95.6%,

NPV 59.1%

Reference lab:94.4% Sn,

90% Sp, PPV 97.5%,

NPV77.1%

NS1

Sn 45%,Spc 97%

WHO 2009

PLOS NTD 2013;7:e2023

NPV 0.96 in the

absence of any WS

> 3 WS specific

but not sensitive

Predicting DHF

Mucosal bleeding the most common WS

NPV for severe disease in the absence of any WS was 100%

Majority had WS 1 day prior to onset of severe illness

Considerable within-patient variation

Higher UACR values in dengue cases

Peak UACR values for dengue cases observed around day 5

PADS prospective study

168 dengue cases

34 DHF

WHO 2009

WHO 1997

Dengue Fever

Dengue Hemorrhagic fever

Dengue Shock Syndrome

WHO 1997

Capillary permeability, age and DHF

Bethell CID 2001; 32: 243-53Gamble Clin Science 2000; 98: 211-16

Age and DHF in SingaporeOoi IJID 2003; 7: 231

Increasing DHF with younger patients; 0.3 in 1997 to 0.07 in 2000

Adult dengue

Pleural effusion

Typically right side

Pediatric Dengue

Severe plasma leakage

39, Female designer, history of Thalassemia, Prolapsed intervertebral

disc,

No recent travel for the past 2 weeks before illness onset

Consulted GP twice (D1 and D3 illness-> referred to ED)

1st ED presentation at D3 Illness 14:00: T 39.6 C, lowest BP recorded 86/50, HR

91/min

1.5 L NS given, advised admission but patient requested AMA (personal

commitment) BP 94/58, HR 90/min upon ED discharge

2nd ED presentation D3 illness 21:26: returned for admission, BP 78/58, HR

99/min, total 2 L IV NS given, IV dopamine 5 10 mcg/kg/min

Fever and hypotension

ECG: D3 4:20 PM

ECG D4 1:35 PM

ECG D5 8:30 AM

ECG D7 9:16 AM

Proposed Viral and Immune Mechanisms

in the Cardiac Manifestations of Dengue

WHO 2012

No all hypotension

are due to

hypovolemia

No one size fit all

Study on optimal

fluid management

Bleeding in dengue fever

DHF – age in 2o Infection, 1981 Cuba Outbreak

Guzman IJID 2002;6:118

Age distribution of adult dengue deaths Singapore 2004-2008

0

2

4

6

8

10

12

15-24 25-34 35-44 45-54 55-64 >65

Age group (years)

Fa

taliti

es

Older adults with dengue have more atypical presentations, more organ involvement, more

pre-existing comorbidities, higher mortality, require higher index of suspicion to diagnose,

closer monitoring and careful management

Dengue (DHF) in the elderly

Dengue in the elderly

Co-morbidity, ARF, Pleural effusion, fatality

Severe

Dengue with warning signs

Dengue Fever

Death

4 basements with 850 car park lots

Food and retail outlets

NCID14-storey clinical

building330 beds

CHI9-storey educational and training building

DEVELOPMENT DATA

NCID –

functionally go-

live in April 2018

Building ready in

2018-2019

Welcome to NCID

Singapore