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DENGUE FEVER
Prepared by :
Dr.Radheshyam sah
FCPS medicine resident
INTRODUCTION
Dengue is a mosquito borne viral disease that has
rapidly spread in many countries worldwide in
recent years.
In nepal,dengue is a rapidly emerging disease.
Endemic across most provinces,dengue incidence
has increased in recent years largely due to
expansion of the vector Aedes aegypti and Aedes
albopictus,as well as the movement of people and
the introduction of imported cases. All 4 dengue
serotypes exist in nepal,wt DENV1 historically
contributing the highest burden.
EPIDEMIOLOGY
• It is estimated to infect 390 million people
annually of which 96 million manifest
clinically
• One study on prevalence of dengue estimates
that 3.9 billion people in 128 countries are at
risk of infection wt dengue viruses. Before
1970,only 9 countries had experienced severe
dengue epidemics ,today the disease is
endemics in more than 100 countries.
In nepal
• Dengue has been identified as one of the
youngest emerging infectious disease in nepal.
The first case of dengue was reported in 2004.
in 2006,large no. of probable cases and 32 lab
confirmed cases were reported across
hospitals in central and western terai as well
as kathmandu.most cases were confirmed the
presence of all 4 serotypes. Sincethan no. of
outbreaks reported each year in many
districts.
Transmission
1. VIRUS –DENV is a small ss RNA virus comprising four distinct
serotypes (DENV1-DENV4).The virus belong to the genus
Flavivirus,family Flaviviridae.They encodes three structural
proteins (capsid c,membrane M,and envelope E) and seven
nonstructural proteins (NS1,NS2a,NS2b,NS3,
NS4a,NS4b,NS5).The NS1protein can be detected in the early
stages of infection and mark virus replication.
2. VECTOR-Aedes aegypti>Aedes albopictus.
3. HOST-humans are the main carriers and multipliers of the virus.
4. TRANSMISSION-the virus circulating in the blood of viraemic
humans is ingested by female mosquitoes during feeding .after
virus incubation for 8-10 days,an infected mosquito is capable
of transmitting the virus for the rest of life.
Natural course of dengue illness
1. Febrile phase
2. Critical phase
3. Recovery phase
Febrile phase(3-7 days)
• Sudden high grade fever usually lasts 3-7 days
• Headache
• Retro orbital pain
• Myalgia/arthalgia
• Facial flushing
• Skin erythema
• Anorexia/nausea and vomiting
• Positive tourniquet test
• Mild hemorrhagic like petechiae and nose ,gums bleed
• Rash generally occur two to five days after onset of fever,typically macular
or maculopapular and may occur over face,thorax,abdomen and
extremities ,a/w pruritus.
• The liver is often enlarged and tender after few days of fever
• CBC-progressive leucopenia and thrombocytopenia
Continue..
• Serum aspartate transaminase (AST) level are
frequently elevated (2 to 5 times the upper
limit of normal value ),occasionaly marked
elevation (5 to 15 times the upper limit value)
• Elevated aPTT and decrease fibrinogen
• Physical examination may demonstrate
conjunctival injection,pharyngeal
erythema,lymphadenopathy,hepatomegaly .
DENGUE RASH
TORNIQUET TEST
CRITICAL PHASE(24-48 hrs)
• The vast majority of infections that progress to critical
phase result from second DENV infection that occur
more than 18 months after resolved first infection.
• Moderate to severe thrombocytopenia , nadir platelet
count <20,000 cells/mm3
• Plasma leakage –eg pleuraleffusion, ascities
• Hemorrhagic manifestations –bruising,bleed
• Shock-organ hypoperfusion lead to progressive organ
impairement,metabolic acidosis
• Severe organ impairement-hepatitis, encephalitis or
myocarditis etc
Recovery phase
• During the recovery phase ,plasma leakage and
hemorrhage resolve,vital signs stabilize and
accumulated fluids are resorbed.
• An additional rash( a confluent ,erythematous
eruption with small islands of unaffected skin
that is often pruritic) may appear during the
recovery phase within 1 to 2 days of
deferervescence and lasting 1 to 5 days
• Recovery phase typically lasts 2 to 4 days ,adult
may have profound fatigue for days to weeks
after recovery .
WHO 1997 CLASSIFICATION
1. Dengue fever
2. Also known as break-bone fever
3. It defined by the presence of fever and two or more
of the following:
4. Headache,retroorbital pain,myalgia,bone
pain,arthralgia,rash,leukopenia
Dengue hemorrhagic fever
fever or h/c of acute fever lasting 2 to 7
days,occasionally biphasic
The cardinal feature of DHF is plasma leakage
d/t increased vascular permeability as
evidenced by hemoconcentration (>20% rise in
hematocrit above baseline),pleural effusion
,ascites.
Petechiae,ecchymoses,purpura, hematemesis or
melena,thrombocytopenia
Dengue shock syndrome
• DSS is DHF with marked plasma leakage that
leads to circulatory collapse (shock)as
evidence by narrowing pulse pressure or
hypotension .
WHO 2009 classification of dengue
1.Dengue without warning sign
 The person lived or travelledin an area of dengue transmission
in the last 14 days,has a sudden high fevertypically of 2 to 7
duration and presents two or more of the following:
manifestations
nausea,vomiting
Exanthem/rash
Myalgia/arthalgia
Headache/retroorbital pain
Peteciae or tourniquet test positive
leucopenia
Dengue with warning sign
• Abdominal pain or tenderness
• Persistent vomiting
• Fluid accumulation(ascities,pleural effusion)
• Mucosal bleeding
• Lethargy,restlessness
• Liver enargement>2cm
• Lab-increase in hematocrit,decrease in paltelet
Severe dengue
 DENGUE wt atleast 1 of the following
• Severe plasma leakage leading to shock(dss)or fluid
accumulation wt respi distress
• Severe bleeding
• Severe organ involvement(ie AST or ALT 1000 or greater,
impaired consciousness,organ failure)
Differential diagnosis
flu like syndromes-influenza,infectious mononucleosis
Illness wt rash-scarlet fever,meningococcal infection,
Chikungunya fever,zika virus infection,malaria,parvovirusB19
Diarrheal disease
AGE
Typhoid
Leptospirosis
Septic shock
Viral hepatitis
Scrub typhus
Diagnosis
• During the early stage of the disease virus
isolation, nucleic acid or antigen detection can
be used. At the end of the acute phase of
infection ,serology is the method of choice .
• Note-NS1 test is positive when pt have fever.
The sensitivity of the test is the highest in the
first day of fever(90%), then declines as fever
days.by day 5 of fever the test is less sensitive
and may b negative from day6.
Dengue diagnostic methods
A. Direct diagnostic methods
Virus isolation
Nucleic acid detection
Viral antigen detection
B.Indirect diagnostic methods
Igm antibodies
IgG antibodies
Virological and serological markers in
realtion of dengue infection
• An incubation period of 4-10 days occurs after mosquito bites
resulting in an asymptomatic or symptomatic dengue infection.
During this period the virus replicates and an antibody response is
developed.
• In general viraemia is detectable in most cases at the same time
when symptoms appear, and is no longer detectable at the time of
defervescence.the development of Igm antibody is coincident wt
disappearnce of fever and viraemia.
 Accordingly dengue infection is
• A.primary dengue infection-affects individuals wtout prior
flavivirus exposure
• B.secondary infection-occurs mainly in individuals previously
infected by any of the remaining virus serotypes .
Case management
Depending on the clinical manifestations and
other circumstances pt may either
1.Be sent home(group A)-dengue wtout
warning sign
2.Be referred for in hospital
management(group B)-dengue wt warning sign
3.Require emergency treatment and urgent
referral(group C)-severe dengue
Group A management
• Advice for -
1.Adequate bed rest
2.Adequate fluid intake
3.PCM 4gm max,per day
4.Monitor daily a.wbc b.defervescence c.warning signs
5.Advice for immediate return to hospital if
development of any warning signs
6.Avoid aspirin,NSAIDS
Group B management
• Treatment
• Encourage oral fluids. If not tolerated start iv fluid therapy 0.9% saline or ringer lactate at
maintenance rate.
• Obtain reference Hct before fluid therapy
• Give isotonic solutions 0.9% saline or RL start wt 5-7 ml/kg/hr for 1-2 hrs
then reduce to 3-5 ml/kg/hr for 2-4 hrs then reduce to 2-3 ml/kg/hr or
less based on clinical response
• Reasses clinical status and repeat Hct
• If hct remains same or rises only minimally continue wt 2-3ml/kg/hr for
another 2-4 hrs.
• If worsening of vital signs and rapidly rising hct increase rate 5-10ml/kg/hr
for 1-2 hrs.
• Reasses clinical status repeat hct and review fluid infusion rates
accordingly
• Reduce iv fluids gradually when the rate of plasma leakage decreases
towards the end of the critical phase.
• This is indicated bya.adequate urine output and/or fluid intakeb.hct decreases below
baseline in a stable pt.
• Monitoring-vitals,I/O chart,warning signs,hct,wbc,platelet
• Blood glucose,rft,lft.
Group c management
1.Treatment shock
Start iv fluid at 5-10 ml/kg/hr over 1hr
If pt improves than reduce gradually ie 5-7 ml/kg/hr for 1-2
hrs then 3-5ml/kg/hr for 2-4 hr then 2-3ml/kg/hrfor 2-4
hrs then reduced depending on hemodynamic status
Iv fluid can be maintained for upto 24-48 hrs
If pt still unstable check hct after first bolus –if hct increases
/still high(>50%)then repeat second bolus at 10-20 ml/kg/hr
for 1 hr
Hct decreases indicates bleeding and need to crossmatch
and blood transfuse
Management of bleeding
• Gastrointestinal bleeding ,epistaxis, heavy
menstrual bleeding may be severe enough to
warrant blood transfusion .
• Significant internal bleeding should be suspected
in patients with sign of intravascular hypovolemia
without evelation of hematocrit.
• Platelet transfusion has not been shown to be
effective at preventing or controlling hemorrhage
but may be warranted in patient with severe
thrombocytopenia (<10000/mm3)and active
bleeding
• Administration of iv vitamin K is warranted for
patient with severe liver dysfunction or
prolonged PT.
Discharge criteria
• No fever for 48 hrs
• Improve in clinical status
• Increasing trend of platelet count
• Stable hct wtout iv fluids
• No respi distress
Vector control
• 1.anti larval measures-biological larvicides,chemical control
• 2.Reducing breeding site
• 3.anti adult –spray chemical
• 4. personal protection-mosquito net,repellants,protective
clothing
• 5. community engagement
• 6.active mosquito and virus surveillance
• 7.CYD-TDV(Dengavaxia) vaccine –in 2018, CYD-TDV vaccine
was approved by European authorities and recommended
by the WHO for persons aged 9 to 45 years with confirmed
previous dengue infection who live in endemic area.
Risk factors
• Previous infection wt DENV increases the risk of
the individual developing severe dengue
• Previous infection wt DENV1 followed by
infection wt DENV2 is more fatal than infection
wt DENV4 followed by infection wt DENV2.
• Unplanned urbanization
• Community risk to dengue due to lack of
knowledge,attitude and poor control of vector.
SAGE journals on vaccine
• Vector control has achieved only limited success
in reducing the transmission of dengue and there
are currently no licensed antivirals to treat
dengue.
• The most effective way to control dengue in future
include the use of safe and effective vaccine.
• Although no licensed dengue vaccine is yet available,
several vaccine are under development including live
attenuated virus vaccine,live chimeric virus vaccine,
inactivated virus vaccine,live recombinant.
• The live chimeric virus vaccine is undergoing a phase 3
clinical trial.
References
• WHO journal for dengue and severe dengue
• National guidelines on dengue 2019 nepal
• Davidsons23rd
• Medscape
• UPTODATE
•
• THANK YOU

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DENGUE FEVER BY DR.RADHE.pptx CIVIL HOSPITAL NEPAL

  • 1. DENGUE FEVER Prepared by : Dr.Radheshyam sah FCPS medicine resident
  • 2. INTRODUCTION Dengue is a mosquito borne viral disease that has rapidly spread in many countries worldwide in recent years. In nepal,dengue is a rapidly emerging disease. Endemic across most provinces,dengue incidence has increased in recent years largely due to expansion of the vector Aedes aegypti and Aedes albopictus,as well as the movement of people and the introduction of imported cases. All 4 dengue serotypes exist in nepal,wt DENV1 historically contributing the highest burden.
  • 3.
  • 4. EPIDEMIOLOGY • It is estimated to infect 390 million people annually of which 96 million manifest clinically • One study on prevalence of dengue estimates that 3.9 billion people in 128 countries are at risk of infection wt dengue viruses. Before 1970,only 9 countries had experienced severe dengue epidemics ,today the disease is endemics in more than 100 countries.
  • 5. In nepal • Dengue has been identified as one of the youngest emerging infectious disease in nepal. The first case of dengue was reported in 2004. in 2006,large no. of probable cases and 32 lab confirmed cases were reported across hospitals in central and western terai as well as kathmandu.most cases were confirmed the presence of all 4 serotypes. Sincethan no. of outbreaks reported each year in many districts.
  • 6. Transmission 1. VIRUS –DENV is a small ss RNA virus comprising four distinct serotypes (DENV1-DENV4).The virus belong to the genus Flavivirus,family Flaviviridae.They encodes three structural proteins (capsid c,membrane M,and envelope E) and seven nonstructural proteins (NS1,NS2a,NS2b,NS3, NS4a,NS4b,NS5).The NS1protein can be detected in the early stages of infection and mark virus replication. 2. VECTOR-Aedes aegypti>Aedes albopictus. 3. HOST-humans are the main carriers and multipliers of the virus. 4. TRANSMISSION-the virus circulating in the blood of viraemic humans is ingested by female mosquitoes during feeding .after virus incubation for 8-10 days,an infected mosquito is capable of transmitting the virus for the rest of life.
  • 7.
  • 8. Natural course of dengue illness 1. Febrile phase 2. Critical phase 3. Recovery phase
  • 9. Febrile phase(3-7 days) • Sudden high grade fever usually lasts 3-7 days • Headache • Retro orbital pain • Myalgia/arthalgia • Facial flushing • Skin erythema • Anorexia/nausea and vomiting • Positive tourniquet test • Mild hemorrhagic like petechiae and nose ,gums bleed • Rash generally occur two to five days after onset of fever,typically macular or maculopapular and may occur over face,thorax,abdomen and extremities ,a/w pruritus. • The liver is often enlarged and tender after few days of fever • CBC-progressive leucopenia and thrombocytopenia
  • 10. Continue.. • Serum aspartate transaminase (AST) level are frequently elevated (2 to 5 times the upper limit of normal value ),occasionaly marked elevation (5 to 15 times the upper limit value) • Elevated aPTT and decrease fibrinogen • Physical examination may demonstrate conjunctival injection,pharyngeal erythema,lymphadenopathy,hepatomegaly .
  • 11.
  • 14. CRITICAL PHASE(24-48 hrs) • The vast majority of infections that progress to critical phase result from second DENV infection that occur more than 18 months after resolved first infection. • Moderate to severe thrombocytopenia , nadir platelet count <20,000 cells/mm3 • Plasma leakage –eg pleuraleffusion, ascities • Hemorrhagic manifestations –bruising,bleed • Shock-organ hypoperfusion lead to progressive organ impairement,metabolic acidosis • Severe organ impairement-hepatitis, encephalitis or myocarditis etc
  • 15. Recovery phase • During the recovery phase ,plasma leakage and hemorrhage resolve,vital signs stabilize and accumulated fluids are resorbed. • An additional rash( a confluent ,erythematous eruption with small islands of unaffected skin that is often pruritic) may appear during the recovery phase within 1 to 2 days of deferervescence and lasting 1 to 5 days • Recovery phase typically lasts 2 to 4 days ,adult may have profound fatigue for days to weeks after recovery .
  • 16. WHO 1997 CLASSIFICATION 1. Dengue fever 2. Also known as break-bone fever 3. It defined by the presence of fever and two or more of the following: 4. Headache,retroorbital pain,myalgia,bone pain,arthralgia,rash,leukopenia
  • 17. Dengue hemorrhagic fever fever or h/c of acute fever lasting 2 to 7 days,occasionally biphasic The cardinal feature of DHF is plasma leakage d/t increased vascular permeability as evidenced by hemoconcentration (>20% rise in hematocrit above baseline),pleural effusion ,ascites. Petechiae,ecchymoses,purpura, hematemesis or melena,thrombocytopenia
  • 18. Dengue shock syndrome • DSS is DHF with marked plasma leakage that leads to circulatory collapse (shock)as evidence by narrowing pulse pressure or hypotension .
  • 19. WHO 2009 classification of dengue 1.Dengue without warning sign  The person lived or travelledin an area of dengue transmission in the last 14 days,has a sudden high fevertypically of 2 to 7 duration and presents two or more of the following: manifestations nausea,vomiting Exanthem/rash Myalgia/arthalgia Headache/retroorbital pain Peteciae or tourniquet test positive leucopenia
  • 20. Dengue with warning sign • Abdominal pain or tenderness • Persistent vomiting • Fluid accumulation(ascities,pleural effusion) • Mucosal bleeding • Lethargy,restlessness • Liver enargement>2cm • Lab-increase in hematocrit,decrease in paltelet
  • 21. Severe dengue  DENGUE wt atleast 1 of the following • Severe plasma leakage leading to shock(dss)or fluid accumulation wt respi distress • Severe bleeding • Severe organ involvement(ie AST or ALT 1000 or greater, impaired consciousness,organ failure)
  • 22. Differential diagnosis flu like syndromes-influenza,infectious mononucleosis Illness wt rash-scarlet fever,meningococcal infection, Chikungunya fever,zika virus infection,malaria,parvovirusB19 Diarrheal disease AGE Typhoid Leptospirosis Septic shock Viral hepatitis Scrub typhus
  • 23.
  • 24. Diagnosis • During the early stage of the disease virus isolation, nucleic acid or antigen detection can be used. At the end of the acute phase of infection ,serology is the method of choice . • Note-NS1 test is positive when pt have fever. The sensitivity of the test is the highest in the first day of fever(90%), then declines as fever days.by day 5 of fever the test is less sensitive and may b negative from day6.
  • 25. Dengue diagnostic methods A. Direct diagnostic methods Virus isolation Nucleic acid detection Viral antigen detection B.Indirect diagnostic methods Igm antibodies IgG antibodies
  • 26. Virological and serological markers in realtion of dengue infection • An incubation period of 4-10 days occurs after mosquito bites resulting in an asymptomatic or symptomatic dengue infection. During this period the virus replicates and an antibody response is developed. • In general viraemia is detectable in most cases at the same time when symptoms appear, and is no longer detectable at the time of defervescence.the development of Igm antibody is coincident wt disappearnce of fever and viraemia.  Accordingly dengue infection is • A.primary dengue infection-affects individuals wtout prior flavivirus exposure • B.secondary infection-occurs mainly in individuals previously infected by any of the remaining virus serotypes .
  • 27.
  • 28. Case management Depending on the clinical manifestations and other circumstances pt may either 1.Be sent home(group A)-dengue wtout warning sign 2.Be referred for in hospital management(group B)-dengue wt warning sign 3.Require emergency treatment and urgent referral(group C)-severe dengue
  • 29. Group A management • Advice for - 1.Adequate bed rest 2.Adequate fluid intake 3.PCM 4gm max,per day 4.Monitor daily a.wbc b.defervescence c.warning signs 5.Advice for immediate return to hospital if development of any warning signs 6.Avoid aspirin,NSAIDS
  • 30. Group B management • Treatment • Encourage oral fluids. If not tolerated start iv fluid therapy 0.9% saline or ringer lactate at maintenance rate. • Obtain reference Hct before fluid therapy • Give isotonic solutions 0.9% saline or RL start wt 5-7 ml/kg/hr for 1-2 hrs then reduce to 3-5 ml/kg/hr for 2-4 hrs then reduce to 2-3 ml/kg/hr or less based on clinical response • Reasses clinical status and repeat Hct • If hct remains same or rises only minimally continue wt 2-3ml/kg/hr for another 2-4 hrs. • If worsening of vital signs and rapidly rising hct increase rate 5-10ml/kg/hr for 1-2 hrs. • Reasses clinical status repeat hct and review fluid infusion rates accordingly • Reduce iv fluids gradually when the rate of plasma leakage decreases towards the end of the critical phase. • This is indicated bya.adequate urine output and/or fluid intakeb.hct decreases below baseline in a stable pt. • Monitoring-vitals,I/O chart,warning signs,hct,wbc,platelet • Blood glucose,rft,lft.
  • 31. Group c management 1.Treatment shock Start iv fluid at 5-10 ml/kg/hr over 1hr If pt improves than reduce gradually ie 5-7 ml/kg/hr for 1-2 hrs then 3-5ml/kg/hr for 2-4 hr then 2-3ml/kg/hrfor 2-4 hrs then reduced depending on hemodynamic status Iv fluid can be maintained for upto 24-48 hrs If pt still unstable check hct after first bolus –if hct increases /still high(>50%)then repeat second bolus at 10-20 ml/kg/hr for 1 hr Hct decreases indicates bleeding and need to crossmatch and blood transfuse
  • 32. Management of bleeding • Gastrointestinal bleeding ,epistaxis, heavy menstrual bleeding may be severe enough to warrant blood transfusion . • Significant internal bleeding should be suspected in patients with sign of intravascular hypovolemia without evelation of hematocrit. • Platelet transfusion has not been shown to be effective at preventing or controlling hemorrhage but may be warranted in patient with severe thrombocytopenia (<10000/mm3)and active bleeding • Administration of iv vitamin K is warranted for patient with severe liver dysfunction or prolonged PT.
  • 33. Discharge criteria • No fever for 48 hrs • Improve in clinical status • Increasing trend of platelet count • Stable hct wtout iv fluids • No respi distress
  • 34. Vector control • 1.anti larval measures-biological larvicides,chemical control • 2.Reducing breeding site • 3.anti adult –spray chemical • 4. personal protection-mosquito net,repellants,protective clothing • 5. community engagement • 6.active mosquito and virus surveillance • 7.CYD-TDV(Dengavaxia) vaccine –in 2018, CYD-TDV vaccine was approved by European authorities and recommended by the WHO for persons aged 9 to 45 years with confirmed previous dengue infection who live in endemic area.
  • 35.
  • 36. Risk factors • Previous infection wt DENV increases the risk of the individual developing severe dengue • Previous infection wt DENV1 followed by infection wt DENV2 is more fatal than infection wt DENV4 followed by infection wt DENV2. • Unplanned urbanization • Community risk to dengue due to lack of knowledge,attitude and poor control of vector.
  • 37. SAGE journals on vaccine • Vector control has achieved only limited success in reducing the transmission of dengue and there are currently no licensed antivirals to treat dengue. • The most effective way to control dengue in future include the use of safe and effective vaccine. • Although no licensed dengue vaccine is yet available, several vaccine are under development including live attenuated virus vaccine,live chimeric virus vaccine, inactivated virus vaccine,live recombinant. • The live chimeric virus vaccine is undergoing a phase 3 clinical trial.
  • 38. References • WHO journal for dengue and severe dengue • National guidelines on dengue 2019 nepal • Davidsons23rd • Medscape • UPTODATE