Summer School DHF

7/27/2019 Summer School DHF

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Dengue

Dengue is a serious viral disease transmitted by thebite of the mosquito, Aedes aegypti.


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Dengue Virus

Causes dengue and dengue hemorrhagic fever

Is an arbovirus Transmitted by mosquitoes

Composed of single-stranded RNA

Has 4 serotypes (DEN-1, 2, 3, 4)


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Dengue Viruses

Each serotype provides specific lifetime immunity,

and short-term cross-immunity All serotypes can cause severe and fatal disease

Genetic variation within serotypes

Some genetic variants within each serotype appear

to be more virulent or have greater epidemicpotential


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Replication and Transmissionof Dengue Virus

Virus transmitted to human in mosquito saliva

Virus replicates in target organs

Virus infects white blood cells and lymphatic tissues Virus released and circulates in blood

Second mosquito ingests virus with blood

Virus replicates in mosquito midgut and other

organs, infects salivary glands

Virus replicates in salivary glands


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Aedes aegyptiMosquito


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Aedes aegypti

Dengue transmitted by infected female mosquito

Primarily a daytime feeder Lives around human habitation

Lays eggs and produces larvae preferentially in

artificial containers


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World Distribution of Dengue 1999

Areas infested with Aedes aegypti

Areas with Aedes aegyptiand recent epidemic dengue


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Jogjakarta ProvinceAverage of monthly incidence rate / 100,000

(1997-2006)

02

4

6

8

10

12

14

16

18

Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec


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Jogjakarta provinceDHF mortality rate (%)

0

0,5

1

1,5

2

2,5

3

3,5

4

1997 1998 1999 2000 2001 2002 2003 2004 2005 2006


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Risk Factors Reported for DHF

Virus strain

Pre-existing anti-dengue antibody

previous infection

maternal antibodies in infants Host genetics

Age

Higher risk in secondary infections

Higher risk in locations with two or more serotypes

circulating simultaneously at high levels

(hyperendemic transmission)


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Hypothesis on Pathogenesis of DHF

Persons who have experienced a dengue infection develop serum

antibodies that can neutralize the dengue virus of that same

(homologous) serotype

In a subsequent infection, the pre-existing heterologous antibodies

form complexes with the new infecting virus serotype, but do notneutralize the new virus

Antibody-dependent enhancement is the process in which certain

strains of dengue virus, complexed with non-neutralizing antibodies,

can enter a greater proportion of cells of the mononuclear lineage,

thus increasing virus production

Infected monocytes release vasoactive mediators, resulting in

increased vascular permeability and hemorrhagic manifestations that

characterize DHF and DSS


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Viral Risk Factorsfor DHF Pathogenesis

Virus strain (genotype) Epidemic potential: viremia level, infectivity

Virus serotype

DHF risk is greatest for DEN-2, followed by DEN-3,

DEN-4 and DEN-1


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Dengue Clinical Syndromes

Undifferentiated fever

Classic dengue fever

Dengue hemorrhagic fever

Dengue shock syndrome


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Undifferentiated Fever

May be the most common manifestation of dengue

Prospective study found that 87% of studentsinfected were either asymptomatic or only mildly

symptomatic

Other prospective studies including all age- groups

also demonstrate silent transmission


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Clinical Characteristicsof Dengue Fever

Fever

Headache Muscle and joint pain

Nausea/vomiting

Rash

Hemorrhagic manifestations


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Dengue Fever

is an acute febrile illness of 2-7 days duration (sometimes with

two peaks) with two or more of the following manifestations:

headache

retro-orbital pain

myalgia/arthralgia

rash

haemorrhagic manifestation (petechiae and positive tourniquettest) and,

leukopenia.


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Dengue Haemorrhagic Fever

is a probable case of dengue and haemorrhagic tendency evidencedby one or more of the following:

Positive tourniquet test

Petechiae, ecchymosis or purpura

Bleeding from mucosa (mostly epistaxis or bleeding from gums), injectionsites or other sites

Haematemesis or melena

Thrombocytopaenia (platelets 100,000/cu.mm or less) and

Evidence of plasma leakage due to increased capillary permeabilitymanifested by one or more of the following:

A >20% rise in haemotocrit for age and sex

A >20% drop in haemotocrit following treatment with fluids as compared tobaseline

Signs of plasma leakage (pleural effusion, ascites or hypoproteinaemia).


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Dengue Shock Syndrome (DSS)

All the above criteria of DHF plus signs of

circulatory failure manifested by rapid and weakpulse, narrow pulse pressure (< or equal to 20 mm

Hg); hypotension for age, cold and clammy skin

and restlessness.


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Petechiae


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Tourniquet Test

The tourniquet test is

performed by inflating a blood

pressure cuff to a point mid-

way between the systolic and

diastolic pressures for five

minutes. A test is consideredpositive when 10 or more

petechiae per 2.5 cm2 (1 inch)

are observed. In DHF, the test

usually gives a definite positive

result (i.e. >20 petechiae). The

test may be negative or mildly

positive during the phase of

profound shock.

Signs and Symptoms of


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Signs and Symptoms ofEncephalitis/Encephalopathy

Associated with Acute Dengue Infection

Decreased level of consciousness: lethargy,

confusion, coma Seizures

Nuchal rigidity

Paresis

H h i M if t ti


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Hemorrhagic Manifestationsof Dengue

Skin hemorrhages: petechiae, purpura, ecchymoses

Gingival bleeding

Nasal bleeding

Gastro-intestinal bleeding: hematemesis, melena, hematochezia

Hematuria

Increased menstrual flow

Cli i l C D fi iti f


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Clinical Case Definition forDengue Hemorrhagic Fever

Fever, or recent history of acute fever

Hemorrhagic manifestations

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

Objective evidence of leaky capillaries:

elevated hematocrit (20% or more over baseline)

low albumin

pleural or other effusions

4 Necessary Criteria:


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Cli i l C D fi iti f D


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Clinical Case Definition for DengueShock Syndrome

4 criteria for DHF

Evidence of circulatory failure manifestedindirectly by all of the following:

Rapid and weak pulse

Narrow pulse pressure ( 20 mm Hg) ORhypotension for age

Cold, clammy skin and altered mental status

Frank shock is direct evidence of circulatoryfailure


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Four Grades of DHF

Grade 1

Fever and nonspecific constitutional symptoms

Positive tourniquet test is only hemorrhagic manifestation

Grade 2

Grade 1 manifestations + spontaneous bleeding

Grade 3

Signs of circulatory failure (rapid/weak pulse, narrow pulse

pressure, hypotension, cold/clammy skin)

Grade 4

Profound shock (undetectable pulse and BP)


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WHO guidelines for the diagnosis of dengue haemorrhagic fever(DHF) and dengue shock syndrome (DSS).

Danger Signs in


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Danger Signs inDengue Hemorrhagic Fever

Abdominal pain - intense and sustained Persistent vomiting

Abrupt change from fever to hypothermia, with

sweating and prostration

Restlessness or somnolence

Martnez Torres E. Salud Pblica Mex 37 (supl):29-44, 1995.

Laboratory Tests


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Laboratory Testsin Dengue Fever

Clinical laboratory tests

CBC--WBC, platelets, hematocrit

Albumin

Liver function tests

Urine--check for microscopic hematuria

Dengue-specific tests

Virus isolation

Serology (IgM & IgG anti Den)

General Recommendations


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General Recommendationsfor Medical Care

Epidemiologic considerations

Season of year Travel history

Diagnosis

Treatment

Follow-up


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Differential Diagnosis of Dengue

Influenza

Measles

Rubella

Malaria Typhoid fever

Leptospirosis

Meningococcemia

Rickettsial infections

Bacterial sepsis Other viral hemorrhagic fevers


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Management of DF


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Management of DHF Grade I/II

V l R l t Fl Ch t f P ti t ith


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Volume Replacement Flow Chart for Patients withDHF Grades I and II


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V l R l t Fl Ch t f ti t ith


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Volume Replacement Flow Chart for patient withDHF Grades III and IV


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Clinical Evaluation in Dengue Fever

Blood pressure

Evidence of bleeding in skin or other sites Hydration status

Evidence of increased vascular permeability--

pleural effusions, ascites

Tourniquet test


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Important Instructions for Treatment of DHF

Cases of DHF should be observed every hour. Serial platelet and haematocrit determinations, drop in plaelets and rise in

haematocrits are essential for early diagnosis of DHF.

Timely intravenous therapy isotonic crystalloid solution can prevent shockand/or lessen its severity.

If the patients condition becomes worse despite giving 20ml/kg/hr for onehour, replace crystalloid solution with colloid solution such as Dextran or

plasma. As soon as improvement occurs replace with crystalloid. If improvement occurs, reduce the speed from 20 ml to 10 ml, then to 6 ml,

and finally to 3 ml/kg.

If haematocrit falls, give blood transfusion 10 ml/kg and then give crystalloidIV fluids at the rate of 10ml/kg/hr.

In case of severe bleeding, give fresh blood transfusion about 20 ml/kg fortwo hours. Then give crystalloid at 10 ml/kg/hr for a short time (30-60

minutes) and later reduce the speed. In case of shock, give oxygen.

For correction of acidosis (sign: deep breathing), use sodium bicarbonate7.


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Criteria for Discharging Patients

Absence of fever for at least 24 hours without the

use of anti-fever therapy

Return of appetite

Visible clinical improvement Good urine output

Minimum of three days after recovery from shock

No respiratory distress from pleural effusion and no

ascites Platelet count of more than 50,000/mm3

Prevention Elimination of mosquito


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Prevention - Elimination of mosquitobreeding places

Cover water containersTight covers on water storage containers,will prevent the mosquitos laying their eggs there. If the cover isloose, mosquitos can go in and out.

Septic tanks and soak-away pitsCover and seal these, so thatdengue mosquitos cannot breed there.

Removal of rubbishGarbage articles and other rubbish foundaround houses can collect rain water. They should be removed orsmashed and buried in the ground or burned, where this ispermissible.

Biological controlMosquito wigglers can be controlled by smalllarva-eating fish, such as guppies. These fish can be found instreams or ponds or obtained through pet shops. Bacterial pesticides

will also kill mosquito wigglers.

Chemical controlSafe and easily used larvicides such astemephos sand core granules can be placed in water containers tokill developing wigglers.


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Prevention - prevent mosquito bites

Mosquito coils and electric vapour matsSlow burning mosquito coils orelectric vapour mats are effective in the rainy season, just after sunrise and/orin the afternoon hours before sunset, when dengue mosquitos bite.

Mosquito netsNets placed over sleeping places can protect small childrenand others who may rest during the day. The effectiveness of such nets canbe improved by treating them with permethrin (a pyrethroid insecticide).Curtains (cloth or bamboo) can also be treated with insecticide and hung at

windows or doorways, to repel or kill mosquitos.

RepellentsMosquito repellents can be applied to exposed parts of thebody where mosquitos bite. Care should be taken in using repellents on smallchildren and the elderly.

ScreensScreens on windows and doorways are effective protectionagainst the entry of mosquitos in homes.

Protection of people sick with dengueMosquitos become infected whenthey bite people who are sick with dengue. Mosquito nets and mosquito coilswill effectively prevent mosquitos from biting sick people and help stop thespread of dengue.

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Summer School DHF

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