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2010 CPG Management of Dengue Infection in Adults (2nd Edition)

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Management of dengue infection in adults.
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CLINICAL PRACTICE GUIDELINES
MOH/P/PAK/209.10 (GU)
MINISTRY OF HEALTH MALAYSIA
ACADEMY OF MEDICINE MALAYSIA
1

These are Clinical Practice Guidelines on Management of Dengue
Infection in Adults (Revised 2nd Edition) 2010. The CPG supersede the
previous CPG on Management of Dengue Infection in Adults (2nd Edition) 2008.
These guidelines are meant to be guides for clinical practice,
based on the best available evidence at the time of develoment.
Adherence to these guidelines may not necessary guarantee
the best outcome in every case. Every healthcare provider is
responsible for the management of his/her unique patient
based on the clinical picture presented by the patient and
the management options available locally.
Review of the Guidelines
These guidelines were issued in 2010 and will be reviewed in
2014 or sooner if new evidence becomes available.
CPG Secretariat
Health Technology Assessment Section
Medical Development Division
Ministry of Health Malaysia
4th Floor, Block E1, Parcel E
62590 Putrajaya.
Electronic version available on the following websites :
http://www.moh.gov.my
http://www.acadmed.org.my
2

GUIDELINES DEVELOPMENT AND OBJECTIVE
GUIDELINES DEVELOPMENT

The development group for these guidelines consisted of a family medicine
specialist, an emergency medicine specialist, a general physician, infectious
disease physicians, intensivists, haematologists, public health physicians,
a virologist and a nursing sister from the Ministry of Health and Ministry of
Higher Education, Malaysia. During the process of development of these
guidelines, there was active involvement of a review committee.
The previous edition of CPG (2003) was used as the basis for the
development of these present guidelines.
These guidelines provide:
a. A detailed description of the clinical course of dengue illness which

reflects the dynamism and systemic nature of dengue that have crucial

bearing on the patient's management.
b. A detailed description of the basic pathophysiological changes of

severe dengue (i.e. plasma leakage and hypovolemia/shock) and

provide guidance on the recognition of these changes and appropriate

action of management.
c. A brief discussion on WHO Classification (1997) and its limitations.
d. Some useful guides on the differential diagnoses that can be confused

with dengue or vice versa; they were described according to the stage

of disease.
e. A more focused guide on the disease monitoring in accordance with

the dynamic changes as the disease progresses.
f. Emphasis on the importance of monitoring the plasma leakage (clinical

signs of plasma leakage and haematocrit (HCT) and haemodynamic

status of the patients.
g. Clearer algorithm on fluid management in severe dengue.
h. Emphasis on the importance of recognising or suspecting significant

occult bleed with some useful guides.
i. A more systematic approach on the recognition of signs of recovery.
Literature search was carried out at the following electronic databases:
International Health Technology Assessment Website, PUBMED, Cochrane
Database of Systemic Reviews (CDSR), Journal full text via OVID search
engine, Comprehensive; Database of Abstracts of Reviews of Effectiveness,
i

Cochrane Controlled Trials Registered, CINAHL via EBSCO search
engine. In addition, the reference lists of all relevant articles retrieved were
searched to identify further studies. Reference was also made to other
guidelines - WHO Dengue Haemorrhagic Fever: Diagnosis, Treatment,
Prevention and Control, WHO Geneva, 1997; Guidelines, Guidelines for
DHF Case Management, Bangkok, Thailand 2002; Guidelines on Clinical
Management Of Dengue Fever / Dengue Haemorrhagic Fever 2005 Sri
Lanka; WHO Regional Publication SEARO, 1999; Guidelines for Treatment
of Dengue Fever/Dengue Hemorrhagic Fever in Small Hospitals, WHO
Regional Office for SE Asia, New Delhi, 1999. There were very few studies
carried out on dengue patients in the adult population. Many of the studies
included in these guidelines are based upon the management of dengue
in children. The findings of these studies were then extrapolated on to the
adult population, taking into consideration our local practices.
The clinical questions were divided into major subgroups and members
of the development group were assigned individual topics within these
subgroups. The group members met a total of 15 times throughout the
development of the guidelines. All literature retrieved were appraised by
at least two members and presented in the form of evidence tables and
discussed during group meetings. All statements and recommendations
formulated were agreed by both the development group and review
committee. Where the evidence was insufficient the recommendations were
derived by consensus of the development group and review committee.
The articles were graded using the modified version of the criteria used
by the Catalonia Agency for Health Technology Assessment and Research
(CAHTAR) Spain, while the grading of recommendation in this guideline
was modified from the Scottish Intercollegiate Guidelines Network (SIGN).
The draft guidelines was posted on both the Ministry of Health Malaysia
and Academy of Medicine, Malaysia websites for comment and feedback.
These guidelines had also been presented to the Technical Advisory
Committee for Clinical Practice Guidelines, and the Health Technology
Assessment and Clinical Practice Guidelines Council, Ministry of Health
Malaysia for review and approval.

i i

OBJECTIVES
GENERAL OBJECTIVES
To provide evidence-based guidance in the management of dengue
infection in adult patients
SPECIFIC OBJECTIVES
* To improve recognition and diagnosis of dengue cases and provide
appropriate care to the patients
* To identify severe dengue and carry out more focused close monitoring
and prompt appropriate management
* To provide guidance on appropriate and timely fluid management and
the use of blood and blood products
* To improve on early and accurate notification of dengue cases for
prompt public health intervention
CLINICAL QUESTIONS
Please refer to Appendix 6
TARGET POPULATION
Adult patients with dengue fever, dengue haemorrhagic fever or dengue
shock syndrome and other forms of severe dengue.
TARGET GROUP/USER
These guidelines are applicable to primary care doctors, public health
personnel, nurses, assistant medical officers, physicians and critical care
providers involved in treating adult patients with dengue fever, dengue
haemorrhagic fever or dengue shock syndrome and other forms of severe
dengue.
HEALTHCARE SETTINGS
Both outpatient and inpatient settings
i i i

CLINICAL INDICATORS FOR QUALITy MANAGEMENT
PRIMARy INDICATORS
i. Case fatality rate (DF & DHF)

Numerator: No of DF & DHF/DSS death

Denominator: No of DF & DHF cases (clinically diagnosed)

National target (9th Malaysian Plan):< 0.2%
ii. DHF fatality rate

Numerator: No of DHF/ DSS death

Denominator: No of DHF/ DSS cases (clinically diagnosed)

National target (9th Malaysian Plan):<1.0%
SECONDARy INDICATORS
1. Appropriateness of usage of blood and blood components

(a) Numerator : No of DF/DHF cases received platelet concentrates

Denominator : No of DF/DHF cases with significant bleeding
(b) Numerator : No of DF/DHF cases received Fresh Frozen Plasma

Denominator : No of DF/DHF cases with significant bleeding
(c) Numerator :
No of DF/DHF cases received Whole blood/ Packed cel s

Denominator : No of DF/DHF cases with significant bleeding

Denominator : No of DF/DHF cases with no or insignificant bleeding
Note : Al dengue deaths should be audited at individual hospitals/state/national level
i v

GUIDELINES DEVELOPMENT GROUP
CHAIRPERSON
Dr. Mahiran Mustafa
Senior Consultant Infectious Disease Physician
Hospital Raja Perempuan Zainab II
Kota Bharu Kelantan
MEMBERS (alphabetical order)
Dr. Abdul Hamid Jaafar
Dr. Norita Ahmad
Assistant Director
Consultant Infectious Disease Physician
Communicable Disease Control Division
Hospital Raja Perempuan Zainab II
Ministry of Health
Kelantan
Dr. Ainul Nadziha Mohd. Hanafiah
Dr. Salmah Idris
Assistant Director
Consultant Pathologist
Health Technology Assessment Section
Hospital Sungai Buloh
Medical Development Division, MOH
Selangor
Dr. Chow Ting Soo
Dr. Sheamini Sivasampu
Consultant Infectious Disease Physician
Principal Assistant Director
Hospital Pulau Pinang
Health Technology Assessment Section
Pulau Pinang
Medical Development Division MOH
Dr. Faisal Salikin
Ms Sin Lian Thye
Emergency Medicine Specialist
Nursing Sister
Hospital Kuala Lumpur
Health Technology Assessment Section
Kuala Lumpur
Medical Development Division MOH
Dato' Dr. Faraizah Abdul Karim
Dato' Dr. K. Sree Raman
Deputy Director
Senior Consultant Physician
National Blood Centre Kuala Lumpur
Hospital Tuanku Ja'afar
Negeri Sembilan
Dr. Ho Bee Kiau
Dr. Suresh Kumar
Family Medicine Specialist
Consultant Infectious Disease Physician
Bukit Kuda Health Clinic
Hospital Sungai Buloh
Selangor
Selangor
Dr Mohamad Ikhsan Selamat
Dr. Tan Cheng Cheng
Principal Assistant Director
Senior Consultant Intensivist and
Communicable Disease Control Division
Anaesthesiologist
Ministry of Health
Hospital Sultanah Aminah Johor
Dr. Jameela Sathar
Dr. Tan Lian Huat
Senior Consultant Haematologist
Lecturer and Infectious Disease Physician
Hospital Ampang Selangor
University Malaya Medical Centre
Selangor
Dr. Lim Chew Har
Consultant Intensivist & Anaesthesiologist
Hospital Pulau Pinang
Pulau Pinang
v

REVIEW COMMITTEE (alphabetical order)
The draft guidelines was reviewed by a panel of independent expert referees
from both public and private sectors, who were asked to comment primarily
on the comprehensiveness and accuracy of interpretation of the evidence
supporting the recommendations in the guideline.
Dr. Christopher Lee
Senior Consultant Infectious Disease Physician
Hospital Sungai Buloh
Selangor
Professor Lucy Lum Chai See
Professor of Paediatrics
University Malaya Medical Centre
Selangor
Datin Paduka Dr. Santha Kumari
Senior Consultant Physician
Hospital Tengku Ampuan Rahimah
Selangor
Dr. Radhakrishnan Sothiratnam
Consultant Physician
Columbia Asia Medical Centre
Negeri Sembilan
Dr. Rudy yeoh Seok Ching
Consultant Haematologist
S. C. Yeoh Haemotology Consultancy Sdn Bhd
Kuala Lumpur
Datin Dr. Rugayah Bakri
Deputy Director
Health Technology Assessment Section
Medical Development Division
Ministry of Health
Dr. Tai Li Ling
Senior Consultant Intensivist & Anaesthesiologist
Hospital Kuala Lumpur
Kuala Lumpur
v i

EXTERNAL REVIEWERS (alphabetical order)
The following external reviewers provided feedback on the draft
Dr. Alan Teh
Dr. Maimunah Mahmud
Consultant Physician & Haematologist
Family Medicine Specialist
Subang Jaya Medical Centre
Klinik Kesihatan Jinjang
Selangor
Kuala Lumpur
Dr. Chua Kaw Beng
Dato' Dr. Ravindran Jegasothy
Consultant Virologist
Head of Department and Senior
National Public Health Laboratory
Consultant O&G
Ministry of Health
Hospital Kuala Lumpur
Sungai Buloh, Selangor
Kuala Lumpur
Dr. Jeyaram Menon
Dr. Rashidi Ahmad
Senior Consultant Gastroenterologist
Emergency Physician/Lecturer
& Head of Department
Hospital Universiti Sains Malaysia
Hospital Queen Elizabeth
Kelantan
Sabah
Dato' Dr. ST Kew
Assoc. Prof. Dr. Shaiful Bahari Ismail
Senior Consultant Physician
Lecturer and Family Medicine Specialist
International Medical University
Hospital Universiti Sains Malaysia
Kuala Lumpur
Kelantan
Dr. G. R. Letchuman Ramanathan
Dr. Tan It
Senior Consultant Physician
Consultant Anaesthetist
Hospital Taiping
Sunway Medical Centre
Perak
Selangor
Dato' Dr. Lim yu Hoe
Dr. S Visalachy Purushothaman
Senior Consultant Physician
Senior Consultant Haematologist
Hospital Pulau Pinang
Hospital Ampang
Pulau Pinang
Selangor
Dr. Mahathar Abdul Wahab
Dr. yoong Kar yaw
Emergency Medicine Specialist
Consultant Physician
Hospital Kuala Lumpur
Hospital Sultan Ismail
Kuala Lumpur
Johor
v i i

TABLE OF CONTENTS
GUIDELINES DEVELOPMENT AND OBJECTIVE
i
GUIDELINES DEVELOPMENT COMMITTEE
v
REVIEW COMMITTEE
vi
EXTERNAL REVIEWERS
vii
TABLE OF CONTENT
viii
1.
EPIDEMIOLOGY
1
2.
VIROLOGY
3
3.
CLINICAL MANIFESTATIONS AND PATHOPHYSIOLOGY
3
3.1 SPECTRUM OF DENGUE INFECTION
3
3.2 CLINICAL COURSE OF DENGUE INFECTION
4
i.Febrile Phase
4
ii.Critical Phase
4
iii.Recovery Phase
5
3.3 PATHOPHYSIOLOGY OF PLASMA LEAKAGE IN DENGUE
6
HAEMORRHAGIC FEVER (DHF) / DENGUE SHOCK SYNDROME (DSS)
3.4 TOURNIQUET TEST
8
3.5 WHO DENGUE CLASSIFICATION
8
3.5.1 Limitations of WHO classification
8
3.5.2 Suggested WHO Classification 2009
9
3.6 OTHER IMPORTANT MANIFESTATIONS
9
3.7 DIAGNOSTIC CHALLENGES
10
4.
DISEASE NOTIFICATION
11
5.
LABORATORY INVESTIGATIONS
12
5.1 DISEASE MONITORING LABORATORY TESTS
12
5.2 DIAGNOSTIC TESTS
13
5.2.1 Dengue Serology Tests
13
5.2.2 Virus Isolation
15
5.2.3 Polymerase Chain Reaction (PCR)
15
5.2.4 Non-structural Protein-1 (NS1 Antigen)
15
6.
INVESTIGATION OF POST MORTEM CASE
16
7.
MANAGEMENT OF DENGUE INFECTION
16
7.1 OUTPATIENT MANAGEMENT
16
7.2 PATIENT TRIAGING AT EMERGENCY AND
18
OUTPATIENT DEPARTMENTS
7.3 CRITERIA FOR HOSPITAL REFERRAL / ADMISSION
19
7.3.1 Referral from Primary Care Providers to Hospital
19
7.3.2 Referral from Hospitals Without Specialist to Hospital with 19
Specialists
v i i i

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