Dengue Fever. Dengue virus Most prevalent vector- borne viral illness in the world Main mosquito...
-
Upload
myron-riley -
Category
Documents
-
view
220 -
download
0
Transcript of Dengue Fever. Dengue virus Most prevalent vector- borne viral illness in the world Main mosquito...
Dengue FeverDengue Fever
Dengue FeverDengue Fever
Dengue virusDengue virus Most prevalent vector-Most prevalent vector-
borne viral illness in the borne viral illness in the worldworld
Main mosquito vector is Main mosquito vector is Aedes aegypti,Aedes aegypti,
Year round Year round transmissiontransmission
Dengue FeverDengue Fever
WHO says some 2.5 billion people, two says some 2.5 billion people, two fifths of the world's population, are now at fifths of the world's population, are now at risk from dengue and estimates that there risk from dengue and estimates that there may be 50 million cases of dengue may be 50 million cases of dengue infection worldwide every year.infection worldwide every year.
epidemic in more than 100 countriesepidemic in more than 100 countries
Dengue feverDengue fever
genus genus Flavivirus, , family family Flaviviridae also known as also known as breakbone feverbreakbone fever..
((bonecrusher diseasebonecrusher disease) -Dandy Fever) -Dandy Fever Aedes aegypti - rarely the - rarely the
Aedes albopictus mosquito,,
DistributionDistribution
Endemic in more than Endemic in more than 100 tropical and 100 tropical and subtropical countries subtropical countries
Pandemic began in Pandemic began in Southeast Asia after WW Southeast Asia after WW II with subsequent global II with subsequent global spread spread
Several epidemics since Several epidemics since 1980s1980s
Distribution is comparable Distribution is comparable to malariato malaria
Manifestations of dengue virus infection:
ASYMPTOMATIC
SYMPTOMATIC
UndifferentiatedFever
Dengue Fever
DengueHaemorrhagicFever
Without haemorrhagic
With unusualhaemorrhagic
No shock
DSS
Virology Virology
Flavivirus familyFlavivirus family Small enveloped Small enveloped
viruses containing viruses containing single stranded single stranded positive RNA positive RNA
Four distinct viral Four distinct viral serotypes (Den-1, serotypes (Den-1, Den-2, Den-3, Den-4)Den-2, Den-3, Den-4)
DengueVirusesDengueViruses
Four closely related single-stranded RNA Dengue Four closely related single-stranded RNA Dengue
viruses (DEN-1, DEN-2, DEN-3 and DEN-4)viruses (DEN-1, DEN-2, DEN-3 and DEN-4)
Each serotype provides specific lifetime immunity, and Each serotype provides specific lifetime immunity, and
short-term cross-immunity (A person can be infected short-term cross-immunity (A person can be infected
as many as four times, once with each serotype)as many as four times, once with each serotype)
All serotypes can cause severe and fatal diseaseAll serotypes can cause severe and fatal disease
PathophysiologyPathophysiology
Transmitted by the Transmitted by the bite of Aedes bite of Aedes mosquito (Aedes mosquito (Aedes aegypti) aegypti)
Incubation 3-14 days Incubation 3-14 days Acute illness and Acute illness and
viremia 3-7 daysviremia 3-7 days Recovery or Recovery or
progression to progression to leakage phaseleakage phase
Dengue MosquitoDengue Mosquito
Aedes aegyptiAedes aegypti is the most important dengue mosquito is the most important dengue mosquito It breeds in collections of water close to dwellingsIt breeds in collections of water close to dwellings Common breeding sites are;Common breeding sites are;
-- Domestic water storage containers - tanks, Domestic water storage containers - tanks, jars, drums, flower vases with waterjars, drums, flower vases with water
-- Roof gutters /sun shadesRoof gutters /sun shades
-- Used tyres, discarded tins, cans, pots, yogurt Used tyres, discarded tins, cans, pots, yogurt cups, polythene bags, tree axils & cups, polythene bags, tree axils &
- - Many more places where rain watercollectsMany more places where rain watercollects
The most common epidemic vector of dengue in the world is the Aedes aegypti mosquito. It can be identified by the white bands or scale patterns on its legs and thorax.
Disease FactorsDisease Factors
Dengue-2 serotype most virulentDengue-2 serotype most virulent Increased severity with secondary infectionsIncreased severity with secondary infections Increased risk in children <15 years and elderly. Increased risk in children <15 years and elderly. Greatest risk of DHF in infants.Greatest risk of DHF in infants. More severe in femalesMore severe in females Increased mortality with comorbid conditions Increased mortality with comorbid conditions Less common in malnourished childrenLess common in malnourished children
Replication and TransmissionReplication and Transmissionof Dengue Virus (Part 1)of Dengue Virus (Part 1)
1. Virus transmitted to human in mosquito saliva
2. Virus replicateers in target organs localLymph nodes,liver
3. Virus infects white blood cells and lymphatic tissues
4. Virus released and circulates in blood
3
4
1
2
Replication and TransmissionReplication and Transmissionof Dengue Virus (Part 2)of Dengue Virus (Part 2)
5. Second mosquito ingests virus with blood
6. Virus replicates in mosquito midgut and other organs, infects salivary glands
7. Virus replicates in salivary glands
6
7
5
Dengue Clinical SyndromesDengue Clinical Syndromes
Undifferentiated feverUndifferentiated feverClassic dengue feverClassic dengue feverDengue hemorrhagic Dengue hemorrhagic
feverfeverDengue shock syndromeDengue shock syndrome
Undifferentiated FeverUndifferentiated Fever
May be the most common manifestation of May be the most common manifestation of denguedengue
Prospective study found that 87% of Prospective study found that 87% of students infected were either asymptomatic students infected were either asymptomatic or only mildly symptomaticor only mildly symptomatic
Other prospective studies including all age- Other prospective studies including all age- groups also demonstrate silent transmissiongroups also demonstrate silent transmission
Clinical CharacteristicsClinical Characteristicsof Dengue Feverof Dengue Fever
FeverFever HeadacheHeadache Muscle and joint painMuscle and joint pain Nausea/vomitingNausea/vomiting RashRash Hemorrhagic manifestationsHemorrhagic manifestations Retro orbital painRetro orbital pain
Hemorrhagic ManifestationsHemorrhagic Manifestationsof Dengueof Dengue
Skin hemorrhages: Skin hemorrhages: petechiae, purpura, ecchymosespetechiae, purpura, ecchymoses
Gingival bleedingGingival bleeding Nasal bleedingNasal bleeding Gastro-intestinal bleeding: Gastro-intestinal bleeding:
hematemesis, melena, hematemesis, melena, HematuriaHematuria Increased menstrual flowIncreased menstrual flow
Clinical Case Definition forClinical Case Definition forDengue Hemorrhagic FeverDengue Hemorrhagic Fever
Fever, or recent history of acute feverFever, or recent history of acute fever Hemorrhagic manifestationsHemorrhagic manifestations Low platelet count (100,000/mmLow platelet count (100,000/mm33 or less) or less) Objective evidence of “leaky capillaries:”Objective evidence of “leaky capillaries:”
elevated hematocrit (20% or more over elevated hematocrit (20% or more over baseline)baseline)
low albuminlow albumin pleural or other effusionspleural or other effusions
4 Necessary Criteria:4 Necessary Criteria:
Clinical Case Definition for Clinical Case Definition for Dengue Shock SyndromeDengue Shock Syndrome
4 4 criteria for DHFcriteria for DHF Evidence of circulatory failure manifested Evidence of circulatory failure manifested
indirectly by all of the following:indirectly by all of the following: Rapid and weak pulseRapid and weak pulse Narrow pulse pressure (Narrow pulse pressure ( 20 mm Hg) OR 20 mm Hg) OR
hypotension for agehypotension for age Cold, clammy skin and altered mental statusCold, clammy skin and altered mental status
Frank shock is direct evidence of circulatory Frank shock is direct evidence of circulatory failurefailure
Four Grades of DHFFour Grades of DHF
Grade 1Grade 1 Fever and nonspecific constitutional symptomsFever and nonspecific constitutional symptoms Positive tourniquet test is only hemorrhagic Positive tourniquet test is only hemorrhagic
manifestationmanifestation Grade 2Grade 2
Grade 1 manifestations + spontaneous bleedingGrade 1 manifestations + spontaneous bleeding Grade 3Grade 3
Signs of circulatory failure (rapid/weak pulse, narrow Signs of circulatory failure (rapid/weak pulse, narrow pulse pressure, hypotension, cold/clammy skin)pulse pressure, hypotension, cold/clammy skin)
Grade 4Grade 4 Profound shock (undetectable pulse and BP)Profound shock (undetectable pulse and BP)
Danger Signs inDanger Signs inDengue Hemorrhagic FeverDengue Hemorrhagic Fever
Abdominal pain - intense and Abdominal pain - intense and sustainedsustained
Persistent vomitingPersistent vomiting Abrupt change from fever to Abrupt change from fever to
hypothermia, with sweating and hypothermia, with sweating and prostrationprostration
Restlessness or somnolenceRestlessness or somnolence
Unusual PresentationsUnusual Presentationsof Severe Dengue Feverof Severe Dengue Fever
EncephalopathyEncephalopathy Hepatic damageHepatic damage CardiomyopathyCardiomyopathy Severe gastrointestinal Severe gastrointestinal
hemorrhagehemorrhage
Signs and Symptoms ofSigns and Symptoms ofEncephalitis/EncephalopathyEncephalitis/Encephalopathy
Associated with Acute Dengue Associated with Acute Dengue InfectionInfection
Decreased level of Decreased level of consciousness: lethargy, consciousness: lethargy, confusion, comaconfusion, coma
SeizuresSeizures Nuchal rigidityNuchal rigidity ParesisParesis
Physical ExamPhysical Exam
Nonspecific findingsNonspecific findings Conjunctival injection, Conjunctival injection,
pharyngeal erythema, pharyngeal erythema, lymphadenopathy, lymphadenopathy, hepatomegaly (20-hepatomegaly (20-50%)50%)
Macular or Macular or maculopapular rash maculopapular rash (50%)(50%)
Laboratory FindingsLaboratory Findings
LeukopeniaLeukopenia Thrombocytopenia (<100,000)Thrombocytopenia (<100,000) Modest liver enzyme elevation (2-5x nml)Modest liver enzyme elevation (2-5x nml) Serology:Serology:• Acute phase serum IgM (+6-90 days) ELISAAcute phase serum IgM (+6-90 days) ELISA• Acute and convalescent IgG (99% sens, 96% Acute and convalescent IgG (99% sens, 96%
spec) spec) • Hemagglutination inhibition assay (HI) is gold Hemagglutination inhibition assay (HI) is gold
standard. Paired acute and convalescent HI standard. Paired acute and convalescent HI assay, positive if >4 fold titer rise assay, positive if >4 fold titer rise
tourniquet testtourniquet test The tourniquet test is performed by inflating a blood The tourniquet test is performed by inflating a blood
pressure cuff to a point mid-way between the systolic pressure cuff to a point mid-way between the systolic andand
diastolic pressures for five minutes. A test is diastolic pressures for five minutes. A test is considered positive when 10 or more petechiae per considered positive when 10 or more petechiae per 2.5 cm2 (1 inch)2.5 cm2 (1 inch)
are observed. In DHF, the test usually gives a are observed. In DHF, the test usually gives a definite positive result (i.e. >20 petechiae). The test definite positive result (i.e. >20 petechiae). The test may bemay be
negative or mildly positive during the phase of negative or mildly positive during the phase of profound shock.profound shock.
DengueDengue is currently classified as an is currently classified as an emerging or re-emerging infectious emerging or re-emerging infectious diseasedisease
1.1. Overcrowded population.Overcrowded population.2.2. Unplanned & uncontrolled Unplanned & uncontrolled
urbanization.urbanization.3.3. Lack of effective mosquito control.Lack of effective mosquito control.4.4. Increased air travel.Increased air travel.5.5. Decay of public health measures.Decay of public health measures.
TreatmentTreatment
No specific therapyNo specific therapy Supportive measures:Supportive measures: adequate hydration adequate hydration acetaminophen (if no liver dysfunction)acetaminophen (if no liver dysfunction) avoid NSAIDs avoid NSAIDs DHF or DHF w/ shock:DHF or DHF w/ shock: IV fluid resuscitation and hospitalizationIV fluid resuscitation and hospitalization blood or platelet transfusion as neededblood or platelet transfusion as needed
TreatmentTreatment Treatment with corticosteroids shown not to Treatment with corticosteroids shown not to
reduce mortality with severe dengue shock reduce mortality with severe dengue shock • 2 studies of 63 and 92 pediatric DHF shock pts 2 studies of 63 and 92 pediatric DHF shock pts
treated w/ hydrocortisone 50mg/kg x1 or treated w/ hydrocortisone 50mg/kg x1 or methylprednisolone 30mg/kg x1 dose vs methylprednisolone 30mg/kg x1 dose vs placebo.placebo.
• Study of 95 pediatric DHF shock pts treated with Study of 95 pediatric DHF shock pts treated with carbazochrome sodium sulfate (AC-17) vs B carbazochrome sodium sulfate (AC-17) vs B vitamins for 3 daysvitamins for 3 days
Ribavirin very weak in vitro and in vivo activity Ribavirin very weak in vitro and in vivo activity against flavivirusesagainst flaviviruses
Traditional and emerging Traditional and emerging treatmentstreatments
Emerging evidence suggests that Emerging evidence suggests that mycophenolic acid and ribavirin inhibit mycophenolic acid and ribavirin inhibit dengue replication. dengue replication.
Brazilian traditional medicine,-cat's claw Brazilian traditional medicine,-cat's claw herbherb
Malaysia,-natural medicine. Mas Amirtha Malaysia,-natural medicine. Mas Amirtha and Semaluand Semalu
Philippines -tawa-tawa herbs and sweet Philippines -tawa-tawa herbs and sweet potato tops juicepotato tops juice
VaccinationVaccination
No current dengue vaccineNo current dengue vaccine Estimated availability in 5-10 yearsEstimated availability in 5-10 years Vaccine development is problematic as the Vaccine development is problematic as the
vaccine must provide immunity to all 4 serotypesvaccine must provide immunity to all 4 serotypes Lack of dengue animal modelLack of dengue animal model Live attenuated tetravalent vaccines under Live attenuated tetravalent vaccines under
phase 2 trials phase 2 trials New approaches include infectious clone DNA New approaches include infectious clone DNA
and naked DNA vaccinesand naked DNA vaccines
Mortality/MorbidityMortality/Morbidity
Treated DHF/DSS is associated with a 3% Treated DHF/DSS is associated with a 3% mortality rate.mortality rate.
Untreated DHF/DSS is associated with a Untreated DHF/DSS is associated with a 50% mortality rate.50% mortality rate.
Differential DiagnosesDifferential Diagnoses
HepatitisHepatitis Tick-Borne Diseases, Rocky Mountain Tick-Borne Diseases, Rocky Mountain
Spotted FeverSpotted Fever MalariaMalaria Yellow FeverYellow Fever MeningitisMeningitis Pediatrics, Bacteremia and SepsisPediatrics, Bacteremia and Sepsis Pediatrics, Meningitis and EncephalitisPediatrics, Meningitis and Encephalitis
PreventionPrevention
Biological: Biological: Target larval stage of Aedes in large water Target larval stage of Aedes in large water
storage containers storage containers Larvivorous fish (Gambusia), endotoxin Larvivorous fish (Gambusia), endotoxin
producing bacteria (Bacillus), copepod producing bacteria (Bacillus), copepod crustaceans (mesocyclops) crustaceans (mesocyclops)
Chemical: Chemical: Insecticide treatment of water containersInsecticide treatment of water containers Space spraying (thermal fogs)Space spraying (thermal fogs)
Public HealthPublic Health
Major and escalating global public health Major and escalating global public health problemproblem
Global demographic changes: urbanization and Global demographic changes: urbanization and population growth with substandard housing, population growth with substandard housing, water, and waster management systemswater, and waster management systems
Deteriorating public health infrastructure with Deteriorating public health infrastructure with limited resources resulting in “crisis limited resources resulting in “crisis management” not preventionmanagement” not prevention
Increased travel Increased travel Lack of effective mosquito control Lack of effective mosquito control
Mosquito control: Mosquito control: Options availableOptions available
“Mosquitoes take about 7 days to
complete life cycle.
The first three Stages: eggs,larva
and pupa are aquatic.
Therefore, the best way to
prevent mosquito breeding isto remove
stagnant clear water”
Common Misconceptions aboutCommon Misconceptions aboutDengue Hemorrhagic FeverDengue Hemorrhagic Fever
Dengue + bleeding = DHFDengue + bleeding = DHF
Need 4 WHO criteria & capillary permeabilityNeed 4 WHO criteria & capillary permeability
DHF kills only by hemorrhageDHF kills only by hemorrhage
Patient dies as a result of shockPatient dies as a result of shock
Poor management turns dengue into DHFPoor management turns dengue into DHF
Poorly managed dengue can be more severe, Poorly managed dengue can be more severe, butbut DHF is a distinct DHF is a distinct
condition, which even well-treated patients may developcondition, which even well-treated patients may develop
DHF is a pediatric diseaseDHF is a pediatric disease
All age groups are involvedAll age groups are involved
DHF is a problem of low income familiesDHF is a problem of low income families
All socioeconomic groups are affectedAll socioeconomic groups are affected
Important Instructions for Important Instructions for Treatment of DHFTreatment of DHF
Ø Cases of DHF should be observed every hour.Ø Cases of DHF should be observed every hour.
Ø Serial platelet and haematocrit determinations, drop Ø Serial platelet and haematocrit determinations, drop inin
plaelets and rise in haematocrits are essential for earlyplaelets and rise in haematocrits are essential for early
diagnosis of DHF.diagnosis of DHF.
Ø Timely intravenous therapy – isotonic crystalloid Ø Timely intravenous therapy – isotonic crystalloid solution –solution –
can prevent shock and/or lessen its severity.can prevent shock and/or lessen its severity.
Ø If the patient’s condition becomes worse despite Ø If the patient’s condition becomes worse despite givinggiving
20ml/kg/hr for one hour, replace crystalloid solution 20ml/kg/hr for one hour, replace crystalloid solution withwith
colloid solution such as Dextran or plasma. As soon ascolloid solution such as Dextran or plasma. As soon as
improvement occurs replace with crystalloid.improvement occurs replace with crystalloid.
Important Instructions for Important Instructions for Treatment of DHFTreatment of DHF
Ø In case of shock, give oxygen.Ø In case of shock, give oxygen.
Ø For correction of acidosis (sign: deep Ø For correction of acidosis (sign: deep breathing), use sodium bicarbonate.breathing), use sodium bicarbonate.
What not to doWhat not to do
Ø Do not give Aspirin or Brufen for treatment of fever.Ø Do not give Aspirin or Brufen for treatment of fever. Ø Avoid giving intravenous therapy before there is evidence ofØ Avoid giving intravenous therapy before there is evidence of haemorrhage and bleeding.haemorrhage and bleeding. Ø Avoid giving blood transfusion unless indicated, reduction inØ Avoid giving blood transfusion unless indicated, reduction in haematocrit or severe bleeding.haematocrit or severe bleeding. Ø Avoid giving steroids. They do not show any benefit.Ø Avoid giving steroids. They do not show any benefit. Ø Do not use antibioticsØ Do not use antibiotics Ø Do not change the speed of fluid rapidly, i.e. avoid rapidlyØ Do not change the speed of fluid rapidly, i.e. avoid rapidly increasing or rapidly slowing the speed of fluids.increasing or rapidly slowing the speed of fluids. Ø Insertion of nasogastric tube to determine concealedØ Insertion of nasogastric tube to determine concealed bleeding or to stop bleeding (by cold lavage) is bleeding or to stop bleeding (by cold lavage) is notnot recommended since it is hazardous.recommended since it is hazardous.
THANK YOU THANK YOU