Dengue 2019
Dengue 2019
Ministry of Health
2018
National guideline
for Clinical Management
of Dengue
N AT I O N A L C E N T R E F O R PA R A S I TO L O G Y ,
ENTOMOLOGY AND MAL ARIA CONTROL 1
2018
National guideline
for Clinical Management
of Dengue
Foreword
This authoritative document should be used in all levels of health care provision in
Cambodia for the management of dengue and dengue hemorrhagic fever patients.
I am sure this document will help in further strengthening the case management
and ultimately reduce the number of cases and significantly bring down the deaths
due to dengue.
2
Preface
Dengue fever (DF), Dengue hemorrhagic fever (DHF), Dengue shock syndrome (DSS)
and its complications are serious global health problems.Approximately two fifths of
the world’s population are at risk, and more than 100 countries have experienced
for DF/DHF outbreaks. The annual incidence of dengue is up to 50 million cases per
year, in which with 500,000 cases were hospitalized and 20,000 dies.
Cambodia is one of the highest dengue burdened countries inSouth-East Asia. The
regular dengue epidemic occur every 3 to 5 years in pattern such as 1985, 1990,
1995,1998, 2003, 2007, and 2012. Dengue outbreaks have occurred not only at
urban or dense populated areas, it also has started to spread into very remote
localities in almost 22 among 25 provinces, due to improvement of accessibility and
greater population movement. Since year 2001- 2007, due to better improvement
of dengue surveillance system, the average dengue cases admitted at Public Health
Facilities and reported every year were 12,000 cases, which with around one
hundred cases or more died. From 2008 - 2010, the annual dengue case fatality
rate has dropped to less than 1% (0.68% in year 2008, 0.32% in year 2009 and
0.30% in year 2010).
The global strategy for control of dengue and dengue hemorrhagicfever, has
emphasized on surveillance system, 2 rounds of pre-emptive strike larvicide
application a year, Improvement of clinical management and nursing care,
community and school-based health education, emergency and rapid of integrated
of vector management response. The ultimate goal of the National Dengue Control
Program is to reduce dengue case fatality rate due to DHF and DSS to less than
0.1% by the year 2020.
This clinical management guideline of DF/DHF has been revised based on the WHO
SEAR guideline of 2011, old national dengue guideline 2004 and fit with the actual
and practical practice of our clinicians at central and provincial referral hospitals.
The clinical sub-clinical committee wishes to congratulate its expert members, the
National Dengue Control Program, National Center of Parasitology, Entomology
and Malaria Control, Ministry of Health for the great achievement and success to
come-out with this guideline to be used by all medical doctors at the referral and
operational district hospitals.
December 2017
3
Acknowledgements
4
Acronyms and abbreviations
Increase
Decrease
Ab Anti-body
Ag Antigen
AR Acetate Ringer
BP Blood Pressure
BS Blood Sugar
BT Bleeding Time
BW Body Weight
C Celsius
CT Clotting Time
Cr Creatinine
D5% 5% Dextrose
5
ACRONYMS AND ABBREVIATIONS
DF Dengue Fever
IgG Immunoglobulin G
IgM Immunoglobulin M
IV Intravenous
gm Gram
Hct Hematocrit
H Hour
6
HMIS Health Management information System
kg kilogram
LV Left Ventricle
Plt Platelet
PR Pulse Rate
mg milligram
ml milliliter
RL Ringer Lactate
RI Regular Insulin
RR Respiratory Rate
RV Right Ventricle
PT Prothrombin Time
TT Thrombin Time
WS Warning Signs
7
NATIONAL GUIDELINE
Clinical Management of Dengue
2018
Table of content
Forword 2
Preface 3
Acknowledgements 4
Part 1 Introduction 10
Part 3 Pathogenesis 16
8
Part 6 Management of Dengue Illnesses 34
1. Febrile phase 35
1.1 Fever 35
1.2 Vomiting 35
1.3 Intense abdominal pain 36
1.4 Convulsion 36
1.5 Food and ORS 36
1.6 Home management and message to the parents/family 36
1.7 Follow up with clinical and CBC indicators 37
1.8 Warning signs 37
1.9 OPD Triage 38
1.10 Indicators for admission 39
1.11 High-risk patients who need special attention 39
2. Leakage/Critical phase of DHF/DSS 40
2.1 Monitoring 40
2.2 Management of DHF without shock (DHF grade I and II) 40
2.3 Management on DHF grade III and IV 42
3. Convalescent Phase 47
3.1 Indication for discharge 47
3.2 Indication for transfer 48
Tables 66
Figures 67
References 68
Annexures 70
Participants list 74
9
Part 1
Introduction
11
Part 2
Epidemiology
of Dengue in Cambodia
Dengue virus was first detected in
Cambodia way back in 1963. Dengue
fever has been reported through
passive surveillance since 1980.
Disease is considered endemic,
reported mainly among children, and
the country has been affected by a
number of dengue epidemics over the
10 last years.
06
In Cambodia, dengue is a major health 2002 - 2007 (Figure 1). All 4 dengue virus
problem. The National surveillance reported serotypes have circulated in Cambodia with
on average 103 cases per 100,000 population however a predominance of DENV2 and DENV3
with C.F.R less than 1% annually during the past since 2002. Since 2002, the cycles of epidemic
5 years. Of all the reported cases in children seems to be less marked with a same pattern
under 16, most (79%) cases were aged 9 years appearing each year during 2002 - 2006. The
and younger. The highest age specific incidence seasonal epidemics have occurred (April – May),
rate was in the 5 to 9 years age group followed peaked (July – August) and waned off (October
by the 0 to 4 years age group. – November) consistently during the same
months over the past 5 years. Noticeably, the
These patterns have been consistent since magnitude of the 2007 and 2012 epidemic was
2002. No differences in gender were observed dramatically high with 39,851 dengue cases and
overall and annually for the past five years. 407 deaths (CFR=1.2%) and in year 2012, up to
Incidence and case fatality rates vary widely 42,362 cases, in which with 189 deaths ( CFR=
by province. Among the hospitalized reported 0.46%), reported to the National surveillance.
cases, the percentage of DHF and DSS This epidemic also began earlier in February -
increased steadily from 30% to 60% during March and peaked during June and July.
13
02. EPIDEMIOLOGY OF DENGUE IN CAMBODIA
FIGURE 1:
DHF DF
45K
40K
35K
30K
25K
20K
15K
10K
5K
0
2002 2003 2004 2005 2006 2007 2008 2009
14
D DSS Deaths
1800
1600
1400
1200
1000
800
600
400
200
0
2010 2011 2012 2013 2014 2015 2016
15
Part 3
Pathogenesis
17
Part 4
Pathophysiology
of DHF
a . Pla sm a le a kag e :
The plasma leakage is due to the increased vascular permeability. The evidence of plasma leakage
includes hemoconcentration, pleural effusion, ascites and hypoproteinemia lead to shock and
profound shock if not properly managed with fluids. The rising hematocrit may not be evidenced
because of either severe bleeding or early IV fluid replacement.
b. A b no rm a l h e m os ta s i s
The bleeding diathesis is caused by vasculopathy, platelet alteration (thrombocytopenia and platelet
dysfunction) and coagulopathy.
(1) Vasculopathy
A positive tourniquet test indicating the increased capillary fragility is found in the early febrile
stage. It may be a direct effect of dengue virus as it appear in the first few days of illness during the
viremic phase (Halstead SB 1988).
Platelet defects may be both quantitative (thrombocytopenia) and qualitative (platelet dysfunction).
a. Thrombocytopenia
Patients with DHF usually have platelet count < 100 000 cells/mm3 during the critical stage.
The pathogenesis of thrombocytopenia involves two major mechanisms, a decreased platelet
production by bone marrow suppression and an increased peripheral destruction and increased
utilization of platelets (Srichaikul T and Nimmannitya S 2000).
Subsequently, the number of platelets is increased in the convalescent stage and reaches the
normal level within 7 – 10 days after defervescence (Funahara Y et al., 1987).
b. Platelet dysfunction
The platelet dysfunction as evidenced by the absence of adenosine disphosphate (ADP) was found
in both shock and non-shock dengue patients. The majority of the patients had normal platelet
aggregation response to ADP 2 – 3 weeks later (Srichaikul T et al., 2000).
(3) Coagulopathy
During the acute febrile stage, plasma clotting time revealed a prolonged prothrombin time (PT)
and a partial thromboplastin time (PTT), as well as reduced fibrinogen levels. Variable reductions
in the activities of several coagulation factors, including prothrombin, factors V, VII, VIII, IX and X,
antithrombin and Fibrin degradation product (FDP) slightly elevated (Suvatte V et al., 1973).
19
Part 5
Clinical presentations
of dengue infections
All four dengue viruses (DEN 1, 2, 3
and 4) Infection may be asymptomatic
or may lead to undifferentiated
fever, dengue fever (DF) or dengue
haemorrhagic fever (DHF) with
plasma leakage that may lead to
hypovolaemic shock, dengue shock
syndrome (DSS).
FIGURE 2: Manifestation of dengue virus infections:
Asymptomacic
Undifferentiated fever
Without haemorrhage
No shock (DHF)
Dengue haemorrhagic
fever
With shock (DSS)
Dengue is suspected in patients with acute high fever 2 – 7 days in dengue endemo-epidemic areas
with 2 or more of the followings:
-- Headache
-- Retro-orbital pain
-- Myalgia
-- Arthralgia
-- Severe body pain
-- Anorexia, nausea, vomiting, diarrhea
-- Rash
-- Bleeding manifestations: positive tourniquet test*, petechiae, epistaxis, gum bleeding,
hematemesis or melena.
-- Leucopenia* (WBC < 5000 cells/cumm)
-- Rising hematocrit 10 – 20%
-- Platelet count < 150, 000cells/cumm
* Recommended practical diagnosis of dengue infection is: Positive tourniquet test (or petechiae)
plus leucopenia.
Tourniquet test:
The tourniquet test is performed by inflating a blood pressure cuff to a point midway between the
systolic and diastolic pressures for five minutes.
The test is considered positive when 10 or more petechiae per sq. inches areobserved.
In DHF, the test usually gives a definite positive result with 20 petechiae or more. The test may be
negative or only mildly positive in obese patients and
during the phase of profound shock. It usually becomes positive, sometimes strongly positive after
recovery from shock.
21
05. CLINICAL PRESENTATIONS OF DENGUE INFECTIONS
1 . 1 D e ng u e feve r ( D F )
-- Infants and small children infected with the dengue virus for the first time usually develop a
simple fever syndrome.
-- Children and adults may have a mild febrile syndrome, or the classic dengue syndrome
with high fever of abrupt onset, sometimes with two peaks, severe headache, nausea
and vomiting, pain behind the eyes, joints and bones pain. Rash varies from redness to
cutaneous erythema and maculopapular rash.
-- After an average intrinsic incubation period of 4–6 days (range 3–14 days), various non-
specific constitutional symptoms and headache, backache and general malaise may
develop. Typically, the onset of DF is sudden with a sharp rise in temperature and is
frequently associated with a flushed face36 and headache. Occasionally, chills accompany
the sudden rise in temperature. Thereafter, there may be retro-orbital pain on eye
movement or eye pressure, photophobia, backache, and pain in the muscles and joints/
bones. The other common symptoms include anorexia and altered taste sensation.
Fever: The bodytemperature is usually between 39 °C and 40 °C, and the fever may be biphasic,
lasting 5–7 days in the majority of cases. Most patients will have high continuous fever for 2-7
days.
Ache and Pain: Severe headache, retro-orbital pain, myalgia and arthralgia.
Rash: Diffuse flushing or fleeting eruptions may be observed on the face, neck and chest
during the first two to three days, and a conspicuous rash that may be maculopapular or
rubelliform appears on approximately the third or fourth day. Towards the end of the febrile
period or immediately after defervescence, the generalized rash fades and localized clusters of
petechiae may appear over the dorsum of the feet, on the legs, and on the hands and arms. This
convalescent rash is characterized by confluent petechiae surrounding scattered pale, round
areas of normal skin. Skin itching may be observed.
22
In some epidemics, DF may be accompanied by haemorrhagic complications such as epistaxis,
gingival bleeding, gastro-intestinal bleeding, haematuria and menorrhagia. In those cases, it is
important to differentiate DF with unusual bleeding from DSS and DHF:
-- In case of DF, there is no aggravation of symptoms during the afebrile phase, but rather an
improvement.
-- DF is generally a mild disease. Recovery (convalescence rash) with or without itching may
be observed. Convalescence may be short and uneventful. Bradycardia is common during
convalescence.
It should be noted that the use of medications such as analgesics, antipyretics, anti-emetics and
antibiotics can interfere with liver function and blood clotting.
Laboratory findings:
-- Platelets count may be normal or mildly to moderately decreased (rarely could be very low <
50,000per mm3)
2. Clinical presentations
In dengue endemic areas, positive tourniquet test and leukopenia (WBC ≤5000 cells/mm3) help
in making early diagnosis of dengue infection with a positive predictive value of 70%–80%.The
laboratory findings during an acute DF episode of illness are as follows:
-- Total WBC is usually normal at the onset of fever; then leucopenia develops with decreasing
neutrophils and lasts throughout the febrile period.
-- Mild haematocrit rise (≈10%) may be found as a consequence of dehydration associated with
high fever, vomiting, anorexia and poor oral intake.
-- Platelet counts are usually normal, as are other components of the blood clotting mechanism.
Mild thrombocytopenia (≤150 000 cells/mm3) is common and dengue fever DF patients may
have platelet count below 100 000 cells/mm3; but severe thrombocytopenia (<50 000 cells/
mm3) is rare.
23
05. CLINICAL PRESENTATIONS OF DENGUE INFECTIONS
FIGURE 3:
• Fever
• Retro-orbital pain
• Myalgia/arthralgia
• Rash
Release of chemical
• Bleeding manifestation mediators and
Megaly
Vascular
permeability
Thrombocytopenia *
24
DSS (Dengue Shock Syndrome)
Hypovolemia
(Haemoconcentration)
DIC
25
05. CLINICAL PRESENTATIONS OF DENGUE INFECTIONS
Towards the end of febrile phase there is a drop in the total number of WBC as well as in the
number of polymorphonuclear cells, a relative lymphocytosis with more than 15% atypical
lymphocytes.
-- Serum biochemistry is usually normal but liver enzymes and aspartate amino transferase (AST)
levels is usually elevated (Not more than 200 UI) in majority of dengue cases.
a. D e ng u e Feve r ( D F )
DF is different from DHF/DSS in that there is no plasma leakage. More than half of DF patients may
have thrombocytopenia.
b. De ng u e He m or r h ag i c Feve r (D HF)
In the first few days of DHF patients will have signs and symptoms similar to that of DF, however in
DHF usually beyond day 3 will develop feature of plasma leakage. Early detection of plasma leakage
with proper fluid intervention will prevent shock.
D1 D2 D3 D4 D5 D6 D7 D8
Pleural
Fever effusion
ascites
26
(1) Febrile phase
During 2 to 7 days in 1 or 2 peaks (usually 3-4 days). Patients with high continuous fever, aches
and pain (headache, retro-orbital pain, myalgia, arthralgia), bleeding manifestation and rash
are highly suspicious to have dengue infections. Some patients may have a sore throat, an
injected pharynx, and conjunctival injection. Anorexia, nausea and vomiting are common. The
earliest abnormality in the full blood count is a progressive decrease in total white cell count,
which should alert the physician to a high probability of dengue. Platelet count also decreases
progressively but remains above 100,000/mm3 during this phase. In addition to these somatic
symptoms, with the onset of fever patients may suffer an acute and progressive loss in their
ability to perform daily functions.
During the transition from the febrile to afebrile phase, patients without an increase in capillary
permeability (Dengue fever) will improve without going through the critical phase.Patients who
have plasma leakage may experience warning sign and become worse when the temperature
decrease (without antipyretic). The duration of critical phase of DHF without shock is 24 to 48
hours, but for DHF with shock is 24hours. Progressive leukopenia followed by a rapid decrease
in platelet count usually precedes plasma leakage. An increasing haematocrit above the baseline
may be one of the earliest additional signs. The period of clinically significant plasma leakage
usually lasts 24-48 hours. The degree of plasma leakage varies. A rising haematocrit precedes
changes in blood pressure (BP) and pulse volume.
The degree of haemoconcentration above the baseline haematocrit reflects the severity of
plasma leakage; however, this may be reduced by early intravenous fluid therapy. Pleural
effusion and ascites are usually only clinically detectable after intravenous fluid therapy,unless
plasma leakage is significant. A right lateral decubitus chest radiograph, ultrasound detection of
free fluid in the chest or abdomen, or gall bladder wall oedema may precede clinical detection. In
addition to the plasma leakage, hemorrhagic manifestations such as easy bruising and bleeding
at venipuncture sites occur frequently.
Warning signs usually precede the manifestations of shock and appear towards the end of the
febrile phase, usually between days 3-7 of illness. Persistent vomiting and severe abdominal pain
are early indications of plasma leakage and become increasingly worse as the patient progresses
to the shock state. The patient becomes increasingly lethargic but usually remains mentally alert.
These symptoms may persist into the shock stage. Weakness, dizziness or postural hypotension
occur during the shock state. Spontaneous mucosal bleeding or bleeding at previous
venipuncture sites are important hemorrhagic manifestations. Increasing liver size and a tender
liver is frequently observed. However, clinical fluid accumulation may only be detected if plasma
loss is significant or after treatment with intravenous fluids. A rapid and progressive decrease
in platelet count ≤100 000 cells/mm3 and a rising hematocrit above the baseline may be the
earliest sign of plasma leakage. This is usually preceded by leukopenia (≤ 5000 cells/mm3).
Substantial number of DSS patient will not have warning signs at all.
27
05. CLINICAL PRESENTATIONS OF DENGUE INFECTIONS
The duration of convalescent phase lasts 3 to 7 days, generally 3-4 days after critical phase.
Reabsorption phase (ascites and pleural effusion is returned to the intravascular space) is to be
recognized by clinicians, especially in cases with signs and symptoms of fluid overload.
Equilbrium Reabsorption
Start Stop
Hct
28
Grading the severity of DHF
DHF is classified into four grades of severity, where grades III and IV are considered to be DSS. The
presence of thrombocytopenia with concurrent hemoconcentration differentiates grades I and II
DHF from DF. Evidence of plasma leakage is the most important finding in the diagnosis of DHF,
even without other evidence like thrombocytopenia or bleeding which may not be available at that
time.
Grade I
Grade II
Spontaneous bleeding in addition to the manifestations of grade I patient, usually in the forms of
skin or other haemorrhages.
Grade III
Circulation failure manifested by a rapid, weak pulse and narrowing of pulse pressure
(compensated shock), with the presence of cold, clammy skin and lethargy.
Grade IV
-- Evidence of plasma leakage due to increased vascular permeability, manifested by at least one
of the following:
• A rise in the hematocrit equal to or greater than 20% of baseline (see appendix);
• Signs of plasma leakage such as pleural effusion, ascites and hypo-albuminemia
≤3.5gm% (Normal ≤4gm% in obese patient)
29
05. CLINICAL PRESENTATIONS OF DENGUE INFECTIONS
c. De ng u e S h oc k Syn dro me (D SS )
All the above four criteria for DHF must be present, plus evidence of circulatory failure manifested by:
Note: Presentation of shock by narrowing of pulse pressure is usually due to plasma leakage
while presentation with hypotension/ fainting is usually due to bleeding. Other causes of shock
in dengue infected patients are possible due to hypoglycemia, severe vomiting and co-infections
(septic shock)
30
3. High-risk dengue patients
a. Fe b rile p h a s e
Dengue is commonly misdiagnosed as with other febrile illnesses such as viral infections, acute
pharyngitis, acute tonsillitis and acute gastroenteritis. Zika and Chikgungunya viruses are also in the
differential diagnosis of dengue.
-- Measles
Very high fever at 39-40°C with conjunctivitis,Koplik spots, nasal and bronchial catarrh. Maculo-
papular rash appears on the 4th– 5th day of disease and persistent fever during the rash.
-- Typhoid fever
Fever progressively increasing up to 39-40°C and persistent after the 7th day, coated tongue,
and rumbling of the right iliac fossa.
-- Malaria:
Fever with thrombocytopenia often associated with history of travel or living in a malaria
endemic zone. The fever persists over 7 days.
31
05. CLINICAL PRESENTATIONS OF DENGUE INFECTIONS
b. S ho c k p h as e
-- Meningococcemia
The shock with thrombocytopenia, caused by the meningococcemia before the appearance
of a necrotic purpura, can simulate DSS.
DSS is often misdiagnosed as septic shock and cause more prolonged shock with serious
complications of organs failure. Disseminated Intravascular Coagulation (DIC) is present in both
DSS and septic shock.
The differential diagnosis between DSS and Septic shock are in Table 1 below:
T A B L E 1 : SHO CK WI T H F E V E R - D I F F E RE N TI A L D I A G N O S I S B E TW E E N D S S A N D S E P TI C S H O C K
D SS SEPTIC SHOCK
32
Differenting dengue from surgical acute abdomen
Do CBC and ultrasound to differentiate this to conditions. DHF will have rising Hct and
thrombocytopenia and pleural effusion/ascites.
33
Part 6
Management of
Dengue illnesses
06
If any patient suspected to have dengue infection that presents
with any of the following symptoms is admitted:
1. Febrile phase
1 . 1 Fever
Management of fever we use two of the following methods:
-- Tepid sponge:
Tepid sponge is indicated.
-- Antipyretic:
Paracetamol 10mg/kg/dose 6 hourly (not more than 4 times per day) is used to reduce the
fever if temperature is greater than 38.5 °C.
1. Over-dosage of Paracetamol may cause liver impairment and then renal dysfunction.
2. Aspirin and Ibuprofen are contraindicated because they may provoke massive gastro-
intestinal bleeding. Furthermore aspirin may cause acidosis and Reye’s syndrome (severe
encephalopathy).
1 . 2 Vo m it i n g
In case of repeated vomiting, Domperidone 0.3mg/kg/dose (2 – 3 times per day) is considered.
35
06. MANAGEMENT OF DENGUE ILLNESSES
1 . 3 I nten s e ab d o m i n al p a i n
Management of severe abdomen of dengue is as the following:
1 . 4 C o nv u l s i o n s
Diazepam 0.5 mg/kg/dose per rectal route (Max: 10mg/dose)
Check glucose, electrolytes and calcium levels and correct accordingly
1 . 5 Fo o d a n d O R S
-- Fruit juice rice water, coconut water, oral rehydration solution
-- Soft and balanced nutrition is preferred.
Remark
-- Intravenous fluid therapy is not necessary, except in dengue patient with severe
dehydration and inability to drink (repeated vomiting or lethargy)
-- Inappropriate IV fluid therapy in the febrile phase may cause fluid overload which
may lead to death because of respiratory failure and congestive heart failure
1 .6 Ho m e m an ag e m e nt an d me s s a ge to th e p a re nts / fa mi ly
The parents should take their children to the hospital immediately in case as following:
36
-- Cold, clammy skin and extremities
-- Decreased urine output or no urine for 4 – 6 hours
1 .7 Fo llow u p wi t h c l i n i c al a n d CB C i n d i cato rs
Clinical sign and symptom and laboratory finding often precede entering critical phase:
a. Clinical indicator
Patient in the febrile phase should be followed up for the following signs and symptoms every 4 - 6
hours, but every to 2 – 4 hours if near to critical period.
2. Severe vomiting
4. Dehydration
7. Consciousness
b. Lab indicator
1 . 8 Wa rn i n g s i g n s
No clinical improvement or worsening of the situation just before or during the transition to afebrile
phase or as the disease progresses.
-- Giddiness
-- Pale, cold and clammy hands and feet
-- Less/no urine output for 4–6 hours
37
06. MANAGEMENT OF DENGUE ILLNESSES
1 . 9 O P D Tr i ag e
Fever Shock
WS + WS - WS + WS - WS + WS - WS + WS -
38
1 . 10 I nd i c ato r s for ad m i s si o n
All patients suspected of dengue infection with any of the following signs should be admitted:
1 . 11 H i g h- r i s k p at i e nt s wh o n e e d s p e ci a l atte nti o n
Infants < 1 year:
Complications: liver dysfunction, overfilling (found more often than by older children or adults)
Overweight/Obesity:
-- Compared with malnourished or normal-weight children, obese children are more prone to
severe forms of DHF
-- Difficulties making IV fluid, especially in the critical period. Dextran is indicated earlier than in
normal children
39
06. MANAGEMENT OF DENGUE ILLNESSES
Prolonged shock:
-- Thalassemia, Hemophilia
-- G-6-PD deficiency
-- Congenital heart disease etc.
-- Referred patients
DHF grad IV or prolonged shock,
2. 1 Mo n itor i n g ( refe r an n ex u re 1: Mo n i to ri n g Ch a rt fo r
D e ng u e p at i e nt s )
> Monitor the vital signs (temperature, pulse rate and volume, capillary refill time, blood
pressure, respiratory rate every 1 - 2 hours and urine outputevery 4 - 6 hours.
2. 2 Ma n a g e m e nt of D H F w i th o ut s h o ck (D HF gra d e I a n d II
To compensate the plasma leakage, the administered volume should not be more than required
to maintain an efficient circulation during the critical phase. Inappropriate IV fluid therapy will
cause respiratory distress by massive pleural effusion or pulmonary edema.
-- For children >6months: 5%D/NSS or 5%DAR or 5%DLR at 1.5-3 ml/kg/h over 1 to 3 hours
> When improvement, continue the infusion at the same dose of IVF for another 3
hours. Recheck the vital signs; if the vital signs keep improving, reduce the infusion to 1.5
ml/kg/h for another 3 to 6 hours. If the vital signs keep improving, continue the infusion at
1.5 ml/kg/h for another 24 to 48 hours while controlling the vital signs every 3 hours and
then stop the infusion. The duration of IV fluid should not be > 48-60hours
Check ABCS: Hct, blood gases(A), blood sugar (S), bleeding test (B), calcemia (C) and see the
management of complicated cases. Calcium gluconate 10% and vitamin K1 can be given without
waiting for the laboratory results. Glucose can be given immediately when rapid blood sugar test
(DTX) is less than 70mg/dL.
40
> When no improvement:
1. When the situation worsens (pulse rapid and weak, decrease urine output):
increase the IV infusion to 3-6 ml/kg/h for 1 to 3 hours. according to the degree of
rising Hct.
2. If still worsening, determine hematocrit and increase the rate of the IV infusion
to 10 ml/kg/h. See scheme for the treatment of DHF degree III and IVF therapy.
Amount of IVF
10ml/kg/h
8ml/kg/h
6ml/kg/h
3ml/kg/h
1.5ml/kg/h
Time
The amount of fluid (both oral + IV) expected that the DHF Grade I & II patients should
receive depends on 2 parameters
1. Degree of thrombocytopenia: first day of plasma leakage the platelet count is usually
between 50,000 – 100,000 cells/cumm; second day of plasma leakage, platelet count is
usually < 50,000 cells/cumm.
2. Degree of plasma leakage: first day we expect rising Hct to be 10-20%; if Hct> 20%,
probably it is the second day of plasma leakage and we have to aware of possible
shock
If we can make clinical diagnosis of DHF in patients with poor appetite and cannot drink
ORS, i.e. rising Hct> 20%, the recommended IV fluid is about maintenance (3 ml/kg/hr).
If the rising Hct is < 20%, the fluid recommended fluid is < maintenance (1.5 ml/kg/hr). If
patients can drink some ORS, the IV fluid should be less.
41
06. MANAGEMENT OF DENGUE ILLNESSES
T A B L E 2 : R AT E O F I V FL U I D I N A D U L T C O M P A RE TO C H I L D RE N
NOT E C H I LD R E N A D U LT
M + 6% Deficit 3 100-120
M + 8% Deficit 8 120-150
2. 3 Ma n a g e m e nt on D H F gra d e III a n d IV
-- aside from crystalloid solutions, there is the need for oxygen, 10% Dextran 40 in NSS, fresh
frozen plasma or fresh whole blood, bicarbonate solution 10% Dextrose, Vitamin K1
-- testing of liver function (ASAT, ALAT), kidney function (creatinine, uremia), electrolytes,
calcaemia, glycemia, blood gasses, coagulation tests (PT, PTT)
-- Do immediately Hct and blood sugar (DTX). If blood glucose more than 6 mmol/L (110mg/dL)
start infusion of NSS, AR or LR at 10ml/kg/h during 1-2h + Oxygen.
-- If blood glucose less than 6 mmol/L (110 mg/dL) start infusion of crystalloid solutions (5% D /
NSS; 5%DAR or 5% DLR) at 10ml/kg/h during 1-2h + Oxygen.
-- Monitor vital signs, especially the BP and the radial pulse every 15 - 30 minutes until they are
stable (usually not exceed 1 hour), then every 1 hour. Maintain glucose level between 70mg/
dL to 120mg/dL
42
• If the patient’s condition improves within 1-2hours, reduce the rate from10 -> 6 ml/kg/h during
3 hours and monitor vital signs every 1-3 hours.
• If further improvement, reduce the rate from 6->3 ml/kg/h during 6-12 hours. Monitor vital
signs every1- 3 hours.
• If still improvement reduce the rate to 1.5 ml / kg / h and maintained during 24-30hours. The
duration of fluid should not exceed 36 hours
• If the vital signs are not stable (BP is lowered, narrow pulse pressure, pulse rapid and weak,
urine decrease) check the Hct.
1. If the Hct is increased change crystalloid to colloid solution preferably Dextran 40%
10ml/kg/h, After Dextran, swithch IV fluid to crystalloid and repeat Dextran if necessary
(not exceeding 30ml/kg/24h) if Hct progressively rises to again. Monitor vital signs every
30 minutes.
• If no improvement: check Hct, blood gases(A), blood sugar (S), bleeding test (B), calcemia (C)
and see the management of complicated cases. Calcium gluconate 10% and vitamin K1 can
be given without waiting for the laboratory results. Glucose can be given immediately when
rapid blood sugar test (DTX) is less than 70mg/dL.
• If improvement, continue with a crystalloid solution at a rate appropriate for the timing after
shock (see figure below). The duration of IV fluid is 24 hours.
2. If Hct decreased, transfuse fresh whole blood 10ml/kg/h or fresh packed cells 5ml/kg/h
for 1 hour:
• If no improvement: check Hct and ABCS and see the management of complicated cases.
If the rate of IV fluid cannot be reduce according to the above diagram, check ABCS (page ???) and
correct the abnormalities.
-- Oxygen;
• If the patient was not received IV fluid before admission, begin the infusion with
crystalloid solution without dextrose (check blood sugar, if low, immediate infuse 10%
glucose). Maintain glucose level 70 to 120mg/dL.
• If the patient was already received IV fluid, choose the colloid solution (Dextran40)
43
06. MANAGEMENT OF DENGUE ILLNESSES
Improvement No Improvement
HCT HCT
Improvement
No Improvement
44
FIGURE 9: The rate of IVF in non-shock DHF according
to the time of plasma leakage
Amount of IVF
10ml/kg/h
8ml/kg/h
6ml/kg/h
3ml/kg/h
1.5ml/kg/h
KVO
0h 6h 12h 18h 24h
If improvement:
3
See schema Dengue grade III
If unresponsive and persistent SHOCK, if it is likely that the patient already has multiple organ failure
and the prognosis is grave:
-- Management of pre-hepatic coma may be necessary.
-- Plan for more sophisticated technique: plasmapheresis , hemodialysis, peritoneal dialysis, CVVH,
CAVH or other renal replacement therapy, if no urine obtained
-- Maintain airway and good oxygenation, may need intubation.
-- Hct check is necessary
-- Complications usually found and have to correct, are:
• Hyponatremia,
• Hypocalcemia,
• Hypoglycemia and
• Metabolic acidosis.
> Gastrointestinal bleeding is frequently internal, and may not be recognize early. Fresh whole
blood transfusion should be urgent.
> If the above situation is not recognized and managed urgently, then fluid overload will occur.
45
06. MANAGEMENT OF DENGUE ILLNESSES
Improvement No Improvement
Repeat 2 nd Bolus of IVF
Give NHCO3 1-2mEq/kg
Change IVF to 5%D/NSS: (OR 50-100ml in adults)
10ml/kg/hr for 1-2 hr
(in adults 500ml/hr)
No Improvement
46
3. Convalescent phase
The beginning of convalescence is often characterized by the appearance of a pruritic rash on the
extremities with confluent erythema and sometimes petechial lesions.Be aware of reabsorption
phase when extravasated plasma is reabsorbed into the circulation, especially in cases with signs and
symptoms of fluid overload because the patients may suddenly develop acute pulmonary edema or
heart failure.
-- Normal temperature
-- Return of appetite
-- No vomiting
-- Stable hematocrit
Note:
During the convalescent phase, sinus bradycardia can occur.
Hepatalgia and thrombocytopenia can last a few more days.
The following criteria should be met before patients recovering from DHF/DSS are discharged:
-- Absence of fever for at least 24 hours without the use of anti-pyretic therapy
-- Return of appetite
-- Stable haematocrit
47
06. MANAGEMENT OF DENGUE ILLNESSES
3 . 2 I n d i c at i o n fo r t ran s fe r
1. All patients suspected to dengue infection must be transferred from Health Center to
referral hospital ;
-- Heart disease
• No respond to IV fluid 10ml/kg/h for 2 – 3 hours of shock (in case that there is no colloidal
solution).
• After one dose of colloid and the patient is still has high Ht.
-- Patient with DHF with signs of fluid overload: massive pleural effusion, very tense and
distended abdomen with respiratory difficulty.
NB:
48
49
Part 7
Complications and
management
1. Common complications in leakage phase (ABCS)
-- Electrolyte imbalance
-- Fluid overload
-- Prolonged shock
-- Massive bleeding
-- Other problems:
-- Encephalopathy/encephalitis
-- Hepatic failure
-- Renal failure
-- Dual infection
51
07. COMPLICATIONS AND MANAGEMENT
2. 1 F lui d ove r lo ad
> Signs of fluid overload:
-- Puffy eye lids/ very distended abdomen
-- Dyspnea/ Tachypnoea
-- Positive lung signs
• But some patients (Critical phase and early convalescence, not yet in reabsorption phase :
stable BP or shock; narrow pulse pressure, poor tissue perfusion (CRT > 2 sec)
-- Change IV fluid to colloid solution such as 10% Dextran 40 in NSS at the rate 10ml/kg/h
(500ml/hr in adults), give furosemide 1mg/kg/dose (40mg in adults) after 30 minute
(midway) of 10% Dextran 40 in NSS.
-- Oxygen Mask or NCPAP(see appendix)
-- Insert urinary catheter and record the amount of urine output in ml/kg/h
-- Check Urine (ml), Blood Pressure, Pulse rate, Capillary Refill Time, Respiratory Rate and
SaO2 q15mn
52
-- Check ABCS (if available):
A : Acidosis (Bicarbonate Na 8.4% 1ml/kg/dose)
B : Bleeding › BT, CT, PT and APTT(see massive bleeding complication)
C : Calcemia (if hypocalcemiaàCagluconate 10% 1ml/kg/dose (Max: 1 ampoule) very slowly
IV(>15mn)
S : Blood sugar (<60mg%) › D10% 5ml/kg/dose.
-- After finish Dextran infusion, switch IV fluid to crystalloid at the rate minimal to keep urine
output to 0.5 ml/kg/hr (25-30ml/hr in adults) or according to the time after shock or leakage
of individual patients. If severe respiratory distress, IV fluid may be reduced to 1 ml/kg/hr and
monitor urine output every hour.
Improvement
With good urine output >1 ml/kg/hr HCT <10 HCT <10 points
(>50ml/hr in adults) points or below baseline
• Stop iv fluid and follow up vital signs FWB 10ml/kg (OR 1 unit in adults)
+amount of urine output
• Repeat Furosemide if signs/ symptoms of
fluid overload persist No Improvement
With no urine output, still
dyspnoea/tachypnoea
53
07. COMPLICATIONS AND MANAGEMENT
2. 2 Ma ssi ve b le e d i n g
• Early massive bleeding is usually due to underlying peptic ulcer or drug induced gastritis
(Aspirin, NSAIDs, steroids)
• Usually occur after prolonged shock in patients with advanced disseminated intravascular
coagulopathy (DIC) and liver failure.
Signs:
Bleeding in DHF is mostly concealed but can have gastro-intestinal bleeding (Hematemesis or
melena). Hypermenorrhea and haemoglobinuria are also common.
Treatment:
-- Transfuse blood when estimated blood loss is >10% of the total blood volume (6-8ml/kg in
children OR 300ml in adults)
-- If the patient has no signs of fluid overload, give Fresh whole blood 10ml/kg/dose (1 unit in
adults),
-- If the patient has signs of fluid overload, give Pack Red cells 5ml/kg/dose (1 unit in adults), and
-- Start transfusion when Hct is between 40-45%, don’t wait it to drop <30 OR when patient
develop shock; However, when Hct is>45% always bring it down by Dextran bolus before
blood transfusion
2. 3 En c e p h a lop at hy
The patient usually presents with changes of consciousness as restlessness, irritable or coma.
Neurological examination may reveal hyper-reflexia, extensor plantar response (Babinski sign).
Causes:
54
Management with hepatic encephalopathy:
-- Consider Furosemide and /or Dexamethasone in patients with signs increase intracranial
pressure.
-- Reduce the ammonia production by giving lactulose (for loosen stool) and local antibiotic –
neomycin (no need if systemic antibiotics are already given)
Multi-organ dysfunction is a result of prolong and profound DSS. It would comprise of Liver
failure, Renal failure and Respiratory failure. Therefore, the management of such patient is in
line with the management of hepatic encephalopathy, renal replacement therapy and ventilation
(preferably CPAP ventilation).
55
Part 8
Management of
high-risk patients
1. Infancy
Infants with DHF manifest differently from diarrhea. Expect every clinician to look at CBC
older children and adult with DHF. They usually first before doing the spinal tapping in those
present with unusual presentations. The 2 with convulsion and also in those patients
most common presentations are convulsion who present with diarrhea before consider
and diarrhea which often make clinicians hypotonic salt solution to them. Detection of
misdiagnose them as meningitis or acute plasma leakage is sometimes missed because
diarrhea. inexperience/young doctors do not recognize
hemoconcentration in infants. Hct of 36-38%
For convulsion, they usually have subtle is quite high for infants, i.e. probably 20%
form of seizure and the onset of seizure is hemoconcentration because their baseline is
a few days after high fever especially when only 28-32%.
the temperature is coming down. Electrolyte
disturbance (hypocalcemia and hyponatremia) The course of leakage in infants is much
and minute bleeding in the CNS is suggested shorter than in older children and adults.
to be the causes of this subtle form of seizure. The duration of leakage is only 12 – 24 hours
If the febrile infants do not have flank watery compare to 24 – 48 hours in older patients.
diarrhea, especially after a few day of high IV fluid in the leakage phase for infants > 6
fever, it is possible that they may have dengue months old is recommended to be NSS as
infections. in older children and even in < 6 months
Infants with DSS are very difficult to diagnose old if they are in shock. If they are under
because non-stop crying may be the only sign 6 months old with no shock, 5%D/N/2 is
of shock. Blood pressure is very difficult to recommended. Shorter duration of IV fluid for
measure especially in irritable, crying infants. infants, probably 12-24 hrs is recommended
Delayed capillary refill time may help in in shock cases. Urine output needs to
diagnosis of shock in infants. monitored closely for the decision to reduce
and discontinue early before they got signs
Frequent follow up of CBC daily or twice a of fluid overload. Infants have limited lung
day will help in infant management properly, expansion and develop acute pulmonary
especially those who come with convulsion and edema early and rapidly.
57
08. MANAGEMENT OF HIGH-RISK PATIENTS
2. Obesity
Obese DHF/DSS patients (infants and pregnancy patients as well) have limited capacity of lung
expansion according to their basic physiology, so IV fluid management is strict than in other patients. IV
fluid administer has to be as minimal as possible to maintain intravascular volume. Urine output (UOP)
is the good indicator for adequate intravascular volume. UOP has to be monitored to be 0.5 ml/kg/hr.
When these obese patients complain of abdominal or respiratory discomfort, we have to pay
more attention and furosemide with or without dextran-40 are to be considered.
3. Pregnancy
The guidelines for management of dengue infections in pregnancy are not available right now. We need
multi-disciplinary team to discuss about the management. The team includes obstetrician, Pediatrician,
internal medicine doctor, surgeon and families from each side to discuss and have consensus on
individual case management.
It is preferably make an early clinical/confirmed diagnosis of dengue with NS1Ag and early admission
and observe pregnant dengue patients in a referral hospital with all those subspecialties doctor
mentioned above.
• If the gestation is > 28-32 weeks and that pregnant woman are in febrile phase, we recommend
to do early Caesarian section and takes the rather mature baby out to be taken care so that we can
manage only mother which may be easier.
• If the gestation is 24-28 weeks, Dexamethazone is preferably given to the mother at least 2 days
before the operation (if possible).
• If the gestation is < 24 weeks, recommend to on pregnancy and observe mother closely with
early detection of plasma leakage with proper IV fluid therapy. Keep IV as minimal to maintain
intravascular volume because they have limited respiratory reserve.
If the pregnant mothers are in the critical period, i.e. platelet count ≤ 100,000 cells/cumm., we need to
have a serious discussion between multi-disciplinary doctors and families from both sides.
58
4. Other co-morbidities
These patients usually have problems with hemolysis of RBC when encounter with viruses, especially
dengue viruses infections. History of dark-colored urine is important. If they have dark-colored urine,
it is very important to transfuse PRC as soon as possible to prevent organ hypoxia which may lead
to organ injury/failure. These DHF cases with hemoglobinuria are often confused to most doctors
because from CBC, they will have definitely hemoconcentration (rising Hct) without thrombocytopenia.
The automate CBC machines that we use have the disadvantage for they do not recognize fragmented
RBC, instead they count them as platelets so we do not see low platelets.
There is also no need to give a large amount of IV fluid or to alkalinized urine as in other infections with
hemoglobinuria because we will give proper amount of IV according to the degree of leakage and these
patients naturally have mild respiratory alkalosis due to slight tachypnea with pleural effusion and
ascites.
Diabetes Mellitus
These patients IV fluid management is the same except that if there BS is > 300 IU, they need RI to
control their sugar level and the IV fluid should not contain 5%Dextrose. Only when their blood sugar
is < 200 mg% that 5%Dextrose in IV is to be considered. Urine sugar may not be reliable if the urine
sugar is > 3+-4+, for it will cause osmotic diuresis. Differential diagnosis with diabetic keto-acidosis is
important because the management is different.
Hypertension
History and baseline BP is important among these patients for proper detection of shock and IV
management. Clinical signs of shock, capillary refilled time is used in patients with hypertension to
detect shock because we do not usually know their baseline BP.
59
Part 9
Outbreak
preparedness
in hospitals
In any part of Cambodia there could
be a sudden reporting of dengue
patients. Therefore, having a hospital
emergency response plan for dengue
outbreaks will help in early diagnosis
and appropriate clinical management
of patients to minimize complications
and deaths.
Hospital response plan should include the following key elements:
During an impending outbreak situation, as the first step, hospitals should develop and strengthen
the capacity to screen and triage suspected dengue patients at the out-patient department.
Hospital staff including doctors, nurses and other categories should be trained and assigned
appropriate duties in case of an outbreak. It is essential to conduct regular training for medical
staff based on the updated guidelines on clinical management of dengue fever and dengue
haemorrhagic fever.
61
09. OUTBREAK PREPAREDNESS IN HOSPITALS
Medicines:
• Paracetamol
• IV Fluids
• Vit K1
• Calcium Gluconate
• KCl solution
• Na bicarbonate
• Thermometers
• Sphygmomanometers
• Iv access sets
62
Laboratory support:
• Laboratories should be equipped round the clock for basic tests such as – Complete blood count
(CBC), haematocrit, platelet count, white blood count (WBC), and differential count.
• More complicated patients will need blood sugar, liver function test (AST/ ALT), renal function test,
electrolyte (including serum calcium), blood gases, coagulogram, chest x-rays, untrasonography.
Blood Bank:
• Fresh whole blood, packed red cells and other blood products should be available on demand.
63
Part 10
Reporting
dengue
65
Tables
Shock with fever - differential diagnosis between DSS
1 32
and Septic Shock
66
Figures
Proportion of Dengue Cases by Severity, Cambodia,
1 14
2002 – 2016
5 Convalescent Phase 28
67
References
Malasit P. Complement and dengue hemorrhagic fever/dengue shock syndrome.
1
Southeast Asian Trop Med Pub Health 1987; 18:316-20
Kurane I, Innis BL, Nimmannitya S, Nisalak A, Rothman AL, Livingstone PG, et al. Human
2
immune response to dengue viruses. Southeast Asian J Trop Med Public Health 1990;
21:658-62
WHO Dengue hemorrhagic fever guideline for Diagnosis, Treatment, Prevention and
8
Control. Second edition in Geneva 1997, pp: 21.
68
Kalayanarooj S and Nimmanitya S. Guinelines for DENGUE HEMORRHAGIC FEVER CASE
10
MANAGEMENT 2004.
WHO Guidelines for Treatment of Dengue fever/ Dengue Hemorrhagic Fever in Small
11
Hospital, New Delhi 1999.
WHO SEARO. Comprehensive Guideline for the Prevention and Control of Dengue and
17
Dengue Hemorrhagic Fever. 2011. Revise and Expanded Edition.
69
Annexures
71
2. Classification of Dengue for reporting
Suspected Dengue:
(ICD10-A91.2) very high fever at 39-40°C of 2 to 7 days duration (usually 3-4 days), with 2
or more following signs:
• flushed face
• headache
• retro-orbital pain
• myalgia / arthralgia
• rash cutaneous
• haemorrhagic signs (petechiae, positive tourniquet test)
• leucopenia
Probable Dengue:
(ICD10-A91.3)very high fever at 39-40°C of 2 to 7 days duration (usually 3-4 days), with 2 or
more following signs:
• flushed face
• headache
• retro-orbital pain
• myalgia / arthralgia
• rash cutaneous
• haemorrhagic signs (petechiae, positive tourniquet test)
• leucopenia
and
or
Case occurred in the region where the dengue case has been confirmed
> Pay a particular attention to a patient with tourniquet test positive (petechiae)
+ leukopenia (WBC ≤ 5,000 cells per mm3)
Confirmed Case:
Significant (4-folds or greater) rise in specific antibodies between acute-phase and convalescence-
phase serum samples by haemagglutination-inhibition (HI), compliment fixation (CF), neutralization
test (NT), IgM-capture enzyme-linked immunosorbant assay (MAC-ELISA), or indirect IgG ELISA.
72
3. Calculation of the amount of drops per minute
Remark
The relationship between body temperature, heart rate and respiratory rate in children.
• In the assessment of the hot and unwell child, to determine whether any tachycardia or
tachypnoea is caused solely by fever, or whether there may be an element of concurrent shock.
• Body temperature an independent determinant of HR
• Increase of ~ 10 beats/minute/degree centigrade.
Derivation and validation of age and temperature specific reference values and centile
charts to predict lower respiratory tract infection in children with fever.
• An increase in respiratory rate of > 2.5 breaths/minute/1°C rise predicts LRTI
PARAMETE R S FE B R IL E DENGUE WA R M S E P T I C CO LD S E P T I C
R ES PO NS E SHOCK SHOCK SHOCK
High fever
Temperature High fever Normal/below High fever
(Hypothermic)
Tachycardia
More trhan Tachycardia
Heart Rate proportional to the Tachycardia
temperature rise (Bradycardia)
fever
Peripheral
Vasodilation Vasoconstriction due
vasoconstriction
Peripheral in response to to inadequate fluid
Physiology to conserve
vasoconstriction cytokines, high resuscitation, poor
heat, to generate
cardiac output cardiac output
temperature
Increased/
Normal, Normal, decreased Poor LV and RV
Myocardium Decreased LV and
hyperdynamic LV size function
RV function
Dr. Huy Rekol, Director National Center for Parasitology, Entomology and Malaria Control.
Dr. Leang Rithea, Director of Health Research and Head of the National Program of fight
Dengue Strategic National Center for Parasitology , Entomology and Malaria Guidelines
Prof. Ung Sophal, Pediatrician, Chief of infections Department, Vice chief of BT NPH and Director
of the clinical sub-committee of the NDCP
Associated Prof Duch Moniboth, chief of BT NPH and Vice chief of the clinical sub-committee
of the NDCP
Dr.Te Vantha, Pediatrician, Vice- Director of Takeo Provincial Hospital and Chief of Pediatric ward,
Dr.Norng Sokra, Senior dengue officer and Chief clinical management of National Dengue
Control Program
Asst.Prof. Chroeung Norith, Pediatrician, Kg Cham Provincial Hospital and Chief of Pediatric Ward
74
Dr. Chao Vannarong Senior dengue officer, National Dengue Control Program
Dr. Phok Born Senior dengue officer, National Dengue Control Program
Dr. Som Leakhan chief department monitoring and evaluation planning stastistic and health
information system national pediatric hospital
Mr. Srun Vechaboth, Senior dengue officer, National Dengue Control Program
I N T E R N AT I O N A L
Miss Alexa Wharton-Smith, PhD student dengue, London School of Hugiene+ Tropical
Medicine
Prof. Siripen Kalayanarooj, MD.Director, WHO Collaborating Centre for case management of
Dengue/DHF/DSS. Queen Sirikit National Institute of Child Health(QSNICH).
Dr. Hasitha A. Tissera, M.B.B.S, MSc, MD Consultant Epidemiologist National coordinator for
Dengue Prevention and control Ministry of Health-srilanka.
75
National guideline
for Clinical Management of Dengue
2018
77