INFECTIONS OF DENGUE VIRUSES

Dr.Nuchin MD,MBA.

District Surveillance Officer, Belgaum Venue of presentation- DHO Office Belgaum

Audience-Medical Officers of Belgaum District

Date-14-07-2009

Dengue fever

An acute febrile disease.

Dengue is the fastest emerging and most common Arboviral infection in the world

Most rapidly spreading vector borne disease

Dengue is found in tropical and sub-tropical climates worldwide, mostly in urban and semi-urban areas.(WHO)

Problem statement- World

At present 100 countries are affected 2.5billion people are at risk(2/5) The maximum burden is borne by countries of the

Asia Pacific Region. Mortality is highest during the initial period of the

outbreak or epidemic. (The geographical spread includes northern Australia and northern Argentina, and the entire Singapore, Malaysia, Taiwan, Thailand,

Vietnam, Indonesia, Honduras, Costa Rica, Philippines, Pakistan, India, Sri Lanka, Bangladesh, Mexico, Suriname, Puerto Rico, Jamaica, Bolivia, Brazil, Guyana, Venezuela, Barbados, Trinidad and Samoa)

Contnd…

New infections annually: 50-100 million Deaths: 30,000 annually People at risk: 2.5-3 billion Hospitalized (DHF) cases: 500 000/year (90% of those affected are children) Disease burden: 465,000 Disability Adjusted Life Years (DALY)

Global burden

Prevalent from centuries Highly prevalent now

Burden in SEAR (SEA- HF)

All the countries are reporting the diseaseA leading cause of hospitalization and death among children next only to ADDs and ARIs (First in I,M,T)

30 million DF cases and 2 lakh DHF cases with 15000 deaths occur annually

BURDEN OF DISEASE IN S.E.ASIA

A. CATEGORY-A - INDONESIA,MYANMAR,AND THAILAND

- Major PHP, leading cause of hospitalization and deaths among children, multiple virus serotype circulating and Aedes aegypty is the main epdemic vector and role of Aedes albopictus uncertain, disease spreading to rural environment

A. CATEGORY-B - INDIA,BANGALADESH,MALDIVES,AND SRILANKA- DHF an emerging disease, cyclical epidemics becoming more frequent, multiple virus serotype circulating ,expanding geographically within the country Aedes aegypty is the main epdemic vector and role of Aedes albopictus uncertain,

A. CATEGORY-C -BHUTAN, NEPAL- No reported cases and endemicity uncertain

B. CTEGORY-D - DPR KOREA- non-endemic

Problem statement- India In India first outbreak of dengue was recorded in 1780

Virus was first isolated in Calcutta in1945

A dengue hemorrhagic fever epidemic occurred in India for the first time in Calcutta between July 1963 & March 1964

A major outbreak in New Delhi, occurred in 1996 with 10252 cases and 423 deaths.

Major outbreaks In India 1963 Kolkata

1964 Vishakapattanam & Chennai

1968 Pondicherry

1998 Various places in North India

1996 Delhi

12

State wise distribution of cases

Dengue in India since 1996Year Cases Deaths

1996 10500 440

1997 1177 36

1998 707 18

1999 944 17

2000 650 7

2001 3306 53

2002 1926 33

2003 12754 215

2004 4153 45

2005 11928 156

Problem statement- India

Karnataka

Dengue incidence is on rise

Belgaum district

Year Cases Deaths

2005 3 __________

2006 5 __________

2007 9 __________

2008 5 ___________

2009 52

History The exact origins of the disease are not clearIt is said that it originated in Africa and was

spread worldwide with the slave trade. The name dengue is derived from the Swahili "Ka-

Dinga pepo" that describes the disease as a sudden cramp like disease caused by an evil spirit.

In the wild- The virus has a life cycle very similar to that of yellow fever involving passing between primates living in the jungle canopy and mosquitoes that feed on them.

It is believed that the virus was transferred to man by the bite of the tiger-striped mosquito (Aedes albopticus) as man began clearing the jungle and building settlements.

The commonest vector is now the closely-related mosquito Aedes aegypti which is African in origin but has spread throughout the tropics in the Old and New Worlds.

Contnd..The earliest reports of a dengue-like disease are from

Chin Dynasty China (265-420 AD).

The illness was called “water poison” and known to be associated with flying insects near water

The first recognized Dengue epidemics occurred almost simultaneously in Asia, Africa, and North America in the 1780s (when the disease was first described), shortly after the identification and naming of the disease in 1779.

Epidemics occurred in • Cairo and Alexandria (Egypt, 1799);

• Jakarta (then called Batavia, Indonesia, 1799);

• Philadelphia (United States, 1780);

• Madras (India, 1780).

• Outbreaks have occurred throughout the temperate and tropical climes since then.

Population movements during World War II spread the disease globally.

A pandemic of dengue began in Southeast Asia after World War II and has spread around the globe since then (1950)

The DHF was first recognized in Philippines in 1953

Chronology

1950s A pandemic began in Southeast Asia

by 1975 DHF had become a leading cause of death among children in the SEAR.

By 1980s Dengue epidemics- became more common

By the late 1990s dengue became the most important mosquito-borne disease affecting humans after malaria

Epidemiology

Inter play of three factors

Host

The Virus Environment

Mosquito

Interaction

The Virus

Dengue Virus

Dengue Virus

Electron Micrograms

Virology

An Arbovirus

Single stranded positive sense enveloped RNA viruses

50-60 nm Four serotypes are there (DEN-1, 2, 3, 4)

Family Flaviviridae

Genus Flavivirus

Serotypes Den1,2,3 &4

Dengue Virus

The virus was isolated by Sabin in 1944

By 1956, all the four serotypes of the virus were identified

Each serotype provides specific lifetime immunity, and short-term cross-immunity

All serotypes can cause severe and fatal disease

Second, third and possibly four infections are possible.

Reservoir- Both Man and Mosquito. The transmission cycle is “Man-Mosquito-Man”

Incubation period- Intrinsic IP- 3-14 days average 5-8 days

Extrinsic IP- 8-12 days

Period of communicability- Few hours to one day prior to the onset of symptoms to 5 days

Immunity Infection with one serotype confers lifelong immunity

to that serotype and only temporary and transient protection to other three

Sequential infection increases the risk of DHF/DSS Significant outbreaks of dengue fever tend to occur

every five or six months. The cyclical rise and fall in numbers of dengue cases is

thought to be the result of seasonal cycles interacting with a short-lived cross-immunity for all four strains in people who have had dengue

Immunity-Contnd…

When the cross-immunity wears off the population is more susceptible to transmission whenever the next seasonal peak occurs.

Thus over time there remain large numbers of susceptible people in affected populations despite previous outbreaks due to the four different serotypes of dengue virus and the presence of unexposed individuals from childbirth or immigration.

Mode of transmission

Dengue is transmitted by bite of infected Aedes mosquitoes, particularly A. aegypti and A.albopictus.

Dengue may also be transmitted via infected blood products (blood transfusions, plasma, and platelets), but the scale of this problem is unknown.

Transovarian transmission of viruses-

1. Mosquitoes transmitdengue to human dendriticcells

2. Dengue targets areaswith high WBC counts(liver, spleen, lymph nodes, bone marrow, andglands)

3. Dengue enters

WBCs & lymphatic

tissue

4. Dengue enters bloodcirculation

3

4

1

2

http://phil.cdc.gov/PHIL_Images/08051999/00004/dengue_phf/sld006.htm

3

HOW DENGUE SPREADS

Then, within the mosquito, the virus replicates during an extrinsic incubation period of 8-12 days.

After which it becomes infective to man during its whole life time

Pathogenesis

Pathogenesis of DHF- decides the course of disease Not clearly understood

Many theories have been put forward

A new hypothesis of immunopathogenesis (ADE) is proposed for the development of the DHF/DSS.

According to it , in order to clear the virus in the

body, there occurs

An aberrant over activation of immune system

Overproduction of cytokines (that affect monocytes, endothelial cells, and hepatocytes)

The abnormal production of autoantibodies to platelet and endothelial cells.

A molecular mimicry occurs between platelets/endothelial cells and dengue virus antigens

viral entry , viral replication , rate of cell infection - increased

Manifestation Of Dengue Virus Infections

Infection with any serotype can be asymptomatic or lead to one of the four clinical scenarios of increasing severity: undifferentiated fever, dengue fever, DHF, and DSS Synonym/Breakbone fever

SynonymsDandy fever Duengero fever Saddle back fever Seven day fever

40

Central Peripheral

Bone marrow suppression

Utilization-Excessive used for platelet aggravation-Consumptive coagulopathy

Platelet destruction

MECHANISM OF THROMBOCYTOPENIA

A) ASYMPTOMATICA) ASYMPTOMATIC

DSS (Grade III & IV)

B) SYMPTOMATICB) SYMPTOMATIC

Without haemorrhage

With unusual haemorrhage

No shock (Grade I & II)

Undifferentiated Fever

Dengue Fever

DengueHaemorrhagicFever

Asymptomatic (Subclinical infections)

About 30% of the total infections

They sensitize the immune system

Symptomatic

1) Undifferentiated Fever Definition- a group of illnesses

resulting from infection by any of the arboviruses pathogenic to humans, in which the only constant manifestation is fever

May be the most common manifestation of dengue

It was found in a prospective study that 87% of students infected were either asymptomatic or only mildly symptomatic

Other prospective studies including all age- groups also demonstrate silent transmissionDS Burke, et al. A prospective study of dengue infectionsin Bangkok. Am J Trop Med Hyg 1988; 38:172-80.

2) Dengue Fever without haemorrhage ( Classical dengue fever)

is an acute febrile illness of 2-7 days duration (Fever is in most of the cases is followed by a remission of 2hours- 2days-biphasic curve - with two peaks) with two or more of the following manifestations:

1.Headache2.Muscle and joint pain (severe-break-bone fever)-

>78%3.Nausea/vomiting

4. Retro orbital pain

5. Rash (Day 2-5)-Rashes appear in remission period or in second febrile period which lasts for 1-2 days. The rash is accompanied by similar but milder symptoms

(Rash- During the first half of the febrile period- diffuse flushing, mottling or fleeting pin-point eruptions on the face, neck and chest

It becomes maculopapular or scarletiniform on 3rd -4th day- It starts on the chest and trunk and spreads to extremities and rarely spreads to face. It may be accompanied by itching and hyperaesthesia. The rash lasts for 2 hours to several days and may be followed by desquamation.)

4. Hemorrhagic manifestations (petichiae and positive tourniquet test) and, leucopenia.

Tourniquet TestInflate blood pressure cuff to a point

midway between systolic and diastolic pressure for 5 minutes

Positive test: 20 or more petechiae per 1 inch2 (6.25 cm2)

Pan American Health Organization: Dengue and Dengue Hemorrhagic Fever: Guidelines for Prevention and Control. PAHO: Washington, D.C., 1994: 12.

Positive Tourniquet Test

2.5 cm

Hepatomegaly

Low blood pressure

All the primary infections result in this type of dengue fever

In children, DF is usually mild

“Dengue triad”: fever, rash, and headache (Carson-DeWitt 2004).

DENGUE -MACULO-PAPULAR RASH.

fever.

Petechiae

http://www.cdc.gov/ncidod/dvbid/dengue/slideset/set1/images/petechiae2-small.jpg

P E T E C H I A E

Subconjunctival haemorrhage

Other common symptoms include- Extreme weaknessAnorexiaConstipationAltered taste sensationColicky pain and abdominal tendernessDragging pain in inguinal regionSore throatGeneral depression

What is the end result?

Complete recovery is the rule Severe weakness many persist for many

days after the fever leaves us Death occurs very rarely

4) Dengue Fever with unusual haemorrhage Occasionally variable degrees of thrombocytopenia

and cutaneous hemorrhage are observed.

Infrequently, DF may be accompanied by unusual bleeding complications that may cause death .

Unusual Presentations of Dengue Fever1)Encephalopathy :(Den2 and den3 are neurovirulent,

2-3% of total cases)- Decreased level of consciousness-lethargy, confusion and coma

Seizures Nuchal rigidity Paresis 2)Hepatic damage3) Cardiomyopathy4)Severe gastrointestinal hemorrhage

Dengue Hemorrhagic Fever-

A severe form of the disease Occurs in persons already sensitized ( secondary)

The first infection sensitizes the patient, while second produces an immunological catastrophe

Begins abruptly with high fever accompanied by facial flushing and headache

Anorexia, vomiting, epigastric discomfort, tenderness at the right costal margin and generalised abdominal pain are common

During the first few days the illness usually resembles classical DF, but after a few days the patient becomes irritable, restless, and sweaty. These symptoms are followed by a shock -like state

Rash may appear early or late in the course of illness

Febrile convulsions may occur in infantsThere may be bleeding under the skin (purpura), from the gums and from the gastrointestinal tract.

Hemorrhagic Manifestationsof DHF Skin hemorrhages: petechiae, purpura,

ecchymoses Gingival bleeding Nasal bleeding Gastro-intestinal bleeding: haematemesis,

melena, haematochezia Hematuria Increased menstrual flow

1. Fever, or recent history of acute fever

2. Hemorrhagic manifestations

3. Low platelet count (100,000/mm3 or less)

4. Objective evidence of “leaky capillaries:”elevated hematocrit (20% or more over baseline)low albuminpleural or other effusions

4 Necessary Criteria:

Four Grades of DHF Grade 1

Fever and nonspecific constitutional symptomsPositive tourniquet test is only hemorrhagic manifestation

Grade 2Grade 1 manifestations + spontaneous bleeding

Grade 3Signs of circulatory failure (rapid/weak pulse, narrow pulse pressure, hypotension, cold/clammy skin)

Grade 4Profound shock (undetectable pulse and BP)

DENGUE GRADATIONDENGUE GRADATION

http://w3.whosea.org/en/Section10/Section332/Section554_2564.htm

DISEASE SPECTRUM DISEASE SPECTRUM MILD SEVEREMILD SEVERE

DF DHFDF DHF+ Thrombocytopenia +++ Thrombocytopenia+ Thrombocytopenia +++ Thrombocytopenia

Hidden Vasc. PermHidden Vasc. Perm11? Overt Vasc. Perm.? Overt Vasc. Perm.

11. Wills BA et al J Infect Dis 190:810-818, 2004 . Wills BA et al J Infect Dis 190:810-818, 2004

68

-Fever

-Flushed face

-Headache

-Retro-orbital pain

-Myalgia

-Arthralgia

-Rash

-Haemorrhagic

manifestation

-Leucopenia

Thrombocytopenia*

Hepatomegaly

capillary

permeability

Serous

effusion

(pleural, ascite)

Hypoprotidemia

Hypovolemia

(haemoconcentration)

Shock

DIC

Intestinal

haemorrhage

Acidosis

Anoxia

Dead

DFDHF

DSS

*Trombocytopenia is not constant in DF

DENGUE PATHOGENESIS

Ag-Ab-complement complex

Danger Signs in DHF that predict progression to DSS

Abdominal pain - intense and sustainedPersistent vomitingAbrupt change from fever to hypothermia, with sweating and prostrationRestlessness or somnolence

This thermometer illustrates the developments in the illness that are progressive warning signs that DSS may occur.The initial evaluation is made by determining how many days have passed since the onset of symptoms. Most patients who develop DSS do so 3-6 days after onset of symptoms. Therefore, if a patient is seven days into the illness, it is likely that the worst is over. If the fever goes between three and six days after the symptoms began, this is a warning signal that the patient must be closely observed, as shock often occurs at or around the disappearance of fever.

Other early warning signs to be alert for include a drop in platelets, an increase in hematocrit, or other signs of plasma leakage. If you document hemoconcentration and thrombocytopenia and other signs of DHF and the patient meets the criteria for DHF, the prognosis and the patient's risk category have changed. Though dengue fever does not often cause fatalities, a greater proportion of DHF cases are fatal. The next concern would be observation of the danger signs—severe abdominal pain, change in mental status, vomiting and abrupt change from fever to hypothermia. These often herald the onset of DSS. The goal of treatment is to prevent shock. The plasma leakage syndrome is self-limited. If you can support the patient through the plasma leakage phase and provide sufficient fluids to prevent shock, the illness will resolve itself.

P U R P U R A

http://www.pediatrics.wisc.edu/education/derm/tutb/85m.jpg

http://www-medlib.med.utah.edu/WebPath/ATHHTML/ATH036.html

E C C H Y M O S I S

http://www.cgste.mq/brainstorm/dengue/image/hemo.gif

NASAL HEMORRHAGING

Criteria for clinical diagnosis of Dengue Shock Syndrome

1. 4 criteria for DHF

2. Evidence of circulatory failure manifested indirectly by all of the following:

Rapid and weak pulseNarrow pulse pressure ( 20 mm Hg) OR hypotension for ageCold, clammy skin and altered mental status

It is sometimes not easy to categorize the disease, mixed presentations can also be seen

Adequate treatment and prompt referral saves the patient's life

Early signs of shock include restlessness, cold clammy skin, rapid weak pulse, narrowing of pulse pressure, and hypotension.DHF patients may rapidly progress into dengue shock syndrome (DSS), which, if not treated correctly, can lead to profound shock and death.Most patients who develop DSS do so 3-6days after onset of symptoms.If a patient is 7 days into the illness, it is likely

that the worst is over

Risk Factors Reported for DHF Virus strain- strain 2 is more virulent followed by 3,1

and 4

Pre-existing anti-dengue antibody

previous infection

maternal antibodies in infants ( dengue infection in pregnant mother may result in passive transfer of anti-dengue IgG to the foetus (or congenital infection)

Risk Factors for DHF (continued) Higher risk in secondary infections ( Hyperendemic regions) Higher risk in locations with two or more

serotypes circulating simultaneously at high levels (hyper endemic regions)

Host genetics—for example, race seems to be a factor: data from Cuba suggest that whites may be at greater risk, and blacks at lower risk. And Age—in Southeast Asia, children are most affected, though in the Americas, all age- groups are affected.

Dengue Infection in Pregnancy

Limited information Vertical transmission Dengue infection may be associated with:

Spontaneous abortion and fetal death Premature births

1. Chye, 1997; 2. Boussemart, 2001;1. Chye, 1997; 2. Boussemart, 2001; 3. Carles, 1999; 4. 2000

Infection and Pregnancy

10-25% of fetal loss caused by maternal or fetal infection

Due to: High maternal fever Reduced blood flow from infected placenta Fetal infection and damage of vital organs

Clinical Evaluation in Dengue Fever

Blood pressureEvidence of bleeding in skin or other

sitesHydration statusEvidence of increased vascular

permeability-- pleural effusions, ascites

Tourniquet test

Population

Infection

Clinical Cases

DHF/DSS

AsymptomaticInfection

DF(non-DHF)

survive Death

5%

24%

6%

0.8%

76%

94%

99.2%

Rates in dengue model

by Shepard et al. Vaccine. 2004, 22:1275-1280.

Dengue + bleeding = DHF Need 4 WHO criteria, capillary permeability

DHF kills only by hemorrhage Patient dies as a result of shock

Poor management turns dengue into DHF Poorly managed dengue can be more severe, but

DHF is a distinct condition, which even well-treated patients may developPositive tourniquet test = DHF

Tourniquet test is a nonspecific indicator of capillary fragility

Differential diagnosisInfluenzaMeaslesRubellaMalariaTyphoid feverLeptospirosisMeningococcemiaRickettsial infectionsBacterial sepsisOther viral hemorrhagic fevers

Vaughn DW, Green S, Kalayanarooj S, et al. Dengue in the early febrilephase: viremia and antibody responses. J Infect Dis 1997; 176:322-30.

A

B

PEI = A/B x 100

Pleural Effusion IndexPleural Effusion Index

Laboratory diagnosis

Laboratory diagnosis is essential for confirmation of dengue virus infections.

Routine lab tests

1) CBC- WBC, Platelets, Haematocrit (Adults: Females 0.36 - 0.44 Males 0.39 - 0.50)

2) Albumin3) Liver function test4) Urine- for microscopic hematuria

Dengue specific tests

Virus isolationPCR

Serology ( IgM or rising IgG titre)-

MAC ELISA IgM capture test is done at DSU- Belgaum

Temperature, Virus Positivity and Anti-Dengue IgM , by Fever Day

Dengue IgMMean Max. Temperature Virus

Fever Day

0

20

40

60

80

100

Per

cen

t V

iru

s P

osit

ive

-4 -3 -2 -1 0 1 2 3 4 5 6

39.5

39.0

38.5

38.0

37.5

37.0

Tem

per

atu

re (

deg

rees

Cel

siu

s)

Den

gue

IgM

(E

IA u

nit

s)300

150

0

75

225

Adapted from Figure 1 in Vaughn et al.,J Infect Dis, 1997; 176:322-30.

Primary Infection

IgM antibodies appear approximately 5 days after onset of symptoms and rise for the next 1-3 weeks 

IgM antibodies detectable for up to 6 months

IgG are detectable at approximately 14 days after onset of symptoms and are maintained for life

Secondary InfectionApproximately 5% patients do not produce detectable levels of specific IgM

IgM titre can be slower to rise in secondary infection

IgG appears approximately 2 days after symptoms appear

IgG titre significantly higher in secondary infection

ManagementNo specific treatment for dengue fever.

With appropriate intensive supportive therapy, mortality may be reduced to less than 1%.

Maintenance of the circulating fluid volume is the mainstay of managing patients with DHF

Outpatient triage

No hemorrhagic manifestations and the patient is well hydrated- Home treatmentHemorrhagic manifestations or hydration is borderline (Grade I & Grade II) –Outpatient observation or hospitalizationWith warning signs (even without profound shock) Grade III & Grade IV- Hospitalize

Management of dengue fever is symptomatic and supportiveBed rest – during the acute febrile phaseA rise in hematocrit value- significant plasma loss-indicates the parenteral therapy- hospitalizationVolume replacement therapy

Lost plasma should be replaced early with an electrolyte solution, plasma, or plasma expanders to prevent or treat reduced blood volume (hypovolemic) shock. Patients with mild dengue hemorrhagic fever can usually be rehydrated orally.

Fluids Rest Antipyretics (avoid aspirin and non-steroidal anti-inflammatory drugs) Monitor blood pressure, hematocrit, platelet count, level of consciousness

Signs of recoveryAbsence of fever for 24 hours (without anti-fever therapy) and return of appetiteVisible improvement in clinical pictureStable hematocrit3 days after recovery from shockPlatelets 50,000/mmNo respiratory distress from pleural effusions/ascites

99

MANAGEMENT OF DF

100

MANAGEMENT OF DHF

101

MANAGEMENT OF DHF

The manifestations and management of DHF during the febrile phase are the same as DF.

102

MENAGEMENT OF DHFGRADE I & II

103

Type of IV fluids Crystalloid solutions

- 5%D/NSS- 5%D/N/2* (only for < 1 year of age)- 5%DLR- 5%DAR

Colloid solutions - 10% Dextran 40- 10% Haes-Sterile

D= Dextrose, NSS= Normal Saline Solution, AR= Acetate Ringer, LR= Lactate Ringer

104

Start IV fluid 3ml/kg/h crystalloid solutions over 1 – 3h

No improvement, stationary (2)

Continue with the same IV Continue with the same IV fluid for another 1 – 3hfluid for another 1 – 3h

Reevaluation VS hourly

Improvement (1)

IV fluid 3 ml/kg/h another 3h

Further Improvement

IV fluid therapy for DHF grade I & II

Improvement aggravation (3)

Reevaluation Ht, VS hourly

↓IV fluid to 1.5 ml/kg/h over 3h

Still improvement

IV fluid 1.5 ml/kg/h over 24 – 48h and stop

IV fluid to 6 ml/kg/h 1 – 3h

More aggravation (4)

See DHF grade III or IV

105

1. Improvement:↓ Ht, stable pulse & Blood Pressure, ↑ urine diuresis

2. No improvement, stationary:Pulse and BP not changed and still having oliguria

3. Aggravation: pulse faster and oliguria

4. More aggravation: weak and rapid pulse or not detectable, narrow pulse pressure, hypotension or not measurable blood pressure

106

MANAGEMENT OF DHF GRADE III

107 Crystalloid solutions:

- 5%D/NSS- 5%DLR*- 5%D/AR

Colloid solution: - Dextran 40- Fresh whole blood (FWB)

Type of solutions

* * Lactate Ringer solutions are contra-indicated Lactate Ringer solutions are contra-indicated in case of acidosis.in case of acidosis. NSS or Acetate Ringer should be used instead of LR NSS or Acetate Ringer should be used instead of LR in case of shockin case of shock

108

Ht immediately, IV fluid 10ml/kg/h crystalloid solutions over 1 – 2h + oxygen

No improvementImprovement

↓ IV to 6 ml/kg/h over 3h

Further Improvement

IV fluid therapy for DHF grade III

Ht

↓IV to 3 ml/kg/h over 6h

Always improvement

↓IV to 1.5 ml/kg/h over 24 –

48h and stop

Control Ht

Ht

Dextran 40 10ml/kg/h and repeated if

necessary (not exceed 30ml/kg/day)

FWB 10ml/kg/h

Improvement

↓ IV fluid of crystalloid from 10 → 6 → 3 → 1.5 ml/kg/h

No improvement

ASCB* see complications

guideline

109 A – Acidosis (Bicarbonate Na 8.4% 1ml/kg/dose) S – Blood sugar (<60mg%) →

D10% 5ml/kg/dose. C – Calcemia ( Ca gluconate 10%

1ml/kg/dose Max: 1 ampoule B - Bleeding → Blood Transfusion,

Platelet Transfusion

110

If shock: oxygen (nasal prongs) - Infant < 1 year = 1L/min - Children > 1 year = 2L/min

OXYGEN USED IN SHOCK CASES

111 MANAGEMENT OF DHF GRADE IV (PROFOUND SHOCK)

112

Crystalloid solutions:- NSS- AR

Colloid solution: - Dextran 40- Fresh Whole Blood

Type of solutions

113

IV fluid therapy for DHF grade IV

NSS or AR 10ml/kg bolus

Improvement No improvement

NSS/AR 10ml/kg bolus5%NSS/DAR 10ml/kg 1 – 2h

Improvement No improvementNo improvementImprovement

Lab: Hct, blood gas, ionogram, Ca, LFT, BUN, creatinin, glucose

Hct ↑ Hct ↓

FWB 10ml/kg/hDextran 40 10ml/kg/h and repeated if necessary

Improvement

↓ IV 10 → 6 → 3 → 1.5 ml/kg/h discontinue IV after 24 – 48h

No improvementImprovement

ASCB and see complications guideline

114

Fluid Overload The common causes:

Early IV fluid therapy in the early febrile phase Use of hypotonic solution Do not reduce the rate of IV fluid and do not

discontinue IV fluid when entering convalescence period

Do not use colloidal solution when indicates Do not give blood transfusion when there is concealed

bleeding and continue giving crystaloid and colloidal solutions

Do not calculate the amount of IV fluid according to ideal body weight in obese/overweight patients

115

Note for Overweight Patients

Use ideal body weight (weight for age) to calculate the IV fluid in overweight/obese patients

Maximum weight for IV calculation is 50 kg (for adult and overweight patients)

Weight (kg) = 2 (Age + 4)

(Child aged between 1-10 years)

116

Management of Patient with Fluid Overload

Change IV fluid to Dextran 40 Insert urinary catheter with special precaution Furosemide 1mg/kg/dose IV. Vital signs should be

monitored every 15 min for at least 1 hour after furosemide and observe clinical signs of shock

Shock: Colloidal solution: Dextran 40 10ml/kg/h IV over 10-15 minutes or until the patient has stable vital signs, usually not more than 30 min and then switch to crystalloid solution.

Prevention and Control

IVCM-Integrated Vector control Management

VaccinesNo licensed vaccine at present

Effective vaccine must be tetravalent, otherwise protection against only one or two dengue viruses

could increase the risk of more serious disease.

Field testing of an attenuated tetravalent vaccine currently underway

Effective, safe and affordable vaccine will not be available in the immediate future

Thank You !