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REVISITING DENGUE FEVER
AND LEPTOSPIROSIS
DR FATHIYAH BINTI MAZLAN
MEDICAL OFFICER ED HOSPITAL KULIM
DENGUE FEVER
Introduction and epidemiology
• Dengue infection is caused by dengue virus which is a mosquito-
borne flavivirus. It is transmitted by Aedes aegypti and Aedes
albopictus. There are four distinct serotypes, DENV-1,2,3 and 4.
• The incubation period for dengue infection is 4-7 days. It may be
asymptomatic or may result in a spectrum of illness ranging from
undifferentiated mild febrile illness to severe disease, with or without
plasma leakage and organ impairment.
CLINICAL COURSE OF DENGUE INFECTION
5
Incubation period : 4 - 7 days (range 3 -
14 days)
After the incubation period, the illness
begins abruptly.
Febrile phase : 2 - 7 days. Commences at
symptom onset
Critical phase : Usually after D3 of fever
(maybe earlier). Commences around time
of defervescence*. Coincides with
increase in capillary permeability. Lasts
24 - 48 hours.
* Definition : Body temperature <38
degrees & remains below this level.
Recovery phase : Reabsorption of
extravascular fluid.
FEBRILE PHASE
6
Viraemia : Fever, headache, N&V,
flushing, myalgia, joint pain, rash,
retro-orbital pain, mild haemorrhage
(petechial, mucosal bleed)
Progressive decrease in total white
cell count followed by platelet
reduction
Haematocrit
male < 60 years – 46%
male > 60 years – 42%
female (all age groups) – 40%
Increase vascular permeability:
third space loss, organ
dysfunction
*Leukopenia with relative
lymphocytosis
*Haemoconcentration
*Thrombocytopenia
Prolonged APTT
AST > ALT
CRITICAL PHASE
7
The primary pathophysiological abnormality seen in dengue infection is an acute increase in
vascular permeability that leads to plasma leakage, resulting in haemoconcentration and
hypovolaemia or shock.
Hypovolaemia leads to reflex tachycardia and generalised vasoconstriction due to increased
sympathetic output. Clinical manifestations of vasoconstriction in various systems are as
follows:
• Skin - coolness, pallor and delayed capillary refill time
• Cardiovascular system - raised diastolic blood pressure and narrowing of pulse pressure
• Renal system - reducing urine output
• Gastrointestinal system - persistent vomiting, persistent diarrhoea andabdominal pain
• Central nervous system – lethargy, restlessness, apprehension,reduced level of consciousness
• Respiratory system – tachypnoea (respiratory rate >20/min)
Inadequate perfusion of the tissue leads to increased anaerobic glycolys is and lactic acidosis.
If the hypovolaemia is not corrected promptly, the patient will progress to a refractory shock
state. By then, the tissue perfusion would not respond to vasopressor drugs, even if the
bloodpressure and intravascular volume were to be restored and cardiac output would remain
depressed. The resultant lactic acidosis further depresses the myocardium and worsens the
hypotension.
The common late complications of prolonged shock are massive bleeding , disseminated
intravascular coagulopathy (DIC) and multi-organ failure which are often fatal.
Classical rash of “isles of
white in the sea of red” with
generalised pruritus
*HCT level stabilises and
drops further due to
haemodilution
*Recovery of white cell
count (WCC).
* Recovery of platelet count
RECOVERY PHASE
9
ARNING SIGNS
TRIAGING AT EMERGENCY
CLINICAL HISTORY
Date of onset of fever
Assess warning signs (last BO/Vomit)
*Oral intake : quantity and quality ? >1.5L/day
*Urine output : frequency, volume & time of
most recent voiding (last PU)? <6hours
What activities could do patient do during the
febrile illness ? ADL independent, no MC
Change in mental state/seizure/dizziness
Other important relevant histories :
Family or neighbourhood history of dengue or travel to dengue
endemic area
Jungle trekking and swimming in waterfall ( DD:
leptospirosis/malaria/typhus)
Recent unprotected sexual or IVDU (DD : acute HIV
seroconversion illness)
Co-morbidities (DD : sepsis particularly in diabetes mellitus)
Medications : *anticoagulants/antiplatelet NSAIDS,
OTC/traditional meds/IM injections/anti-HPT/all meds with last
time taken
*Risk factors: pregnancy, obesity, diabetes mellitus,
hypertension, IHD, coagulopathy, renal failure, CLD, COPD.
Age>65yo.
*Social factors that limit follow up blood ix
12
CLINICAL EXAMINATION
Assess consciousness GCS
Assess hydration: eye, lip, tongue, skin turgor
Assess haemodynamic:
 CCTVR
 BP
 Pulse pressure (>20mmHg)
 Urine output (>0.5ml/kg/hr, not concentrated)
Look for tachypnoea / acidotic breathing / pleural
effusion
Check for abdominal tenderness / hepatomegaly /
ascites
 Abdominal pain in febrile phase: omentum
ischaemia due to dehydration
 Abdominal pain in critical phase: acute stretch of
liver capsule
 Abdominal pain in recovery phase: ascites
Examine for bleeding tendency
 Petechiae
 Purpura
 Ecchymoses
 Malaena
 Bleeding gingiva
 Epistaxis
13
Tourniquet
test
INVESTIGATIONS
Disease monitoring tests
FBC: Thrombocytopenia, leucopenia, inc HCT
Coagulation profile
RP/ LFT
Lactate
Blood gases
Special test: CK
Diagnostic test
rapid combo test
dengue antigen and serology test by ELISA
NS1 antigen & IgM/IgG antibodies
Dengue viral RNA detection
DIAGNOSTIC INVESTIGATION
Dengue NS1 antigen test and rapid
combo tests (NS1 antigen and
dengue IgM/IgG antibodies)
 Interpret within 15-20 minutes
 Invalid after 20 minutes
 sensitivity 93.9%; specificity 92%
Dengue Viral RNA Detection (Real
time RT PCR)
 Determine Dengue serotype
Virus isolation
- NS1 Antigen : sensitivity drop day
4-5. In defervescence, usually non-
detectable. If present >D5, predict
severe dengue.
False positive in Yellow Fever.
- IgM : >D5 of illness, peaks about
2/52 then wanes down over 1 hour.
-IgG : after Day 7. Check titre. If 1 :
2560, indicate of secondary dengue
False positive in JE, malaria,
leptospirosis, toxoplasmosis,
syphilis, RA 17
DISEASE MONITORING INVESTIGATION
Identify phase of dengue
TWC, HCT, Platelet
Markers of plasma leakage
and hypovoleamia
HCT (haemoconcentration),
VBG (metabolic acidosis),
lactate (adaequate<2
mmol/L)
Complication (when in suspect severe dengue)
Hepatitis: AST or ALT >=1000 (AST>ALT)
Coagulopathy: Coagulation profile (prolonged
APTT)
Acute renal failure: UFEME, Renal profile (RP)
Myocarditis: Troponin and Creatine Kinase (CK),
Echo, ECG
Myositis: CK
Pleural effusion: CXR, US Thorax
Ascites / gallbladder wall edema: US Abdomen
Neurological (Encephalopathy/encephalitis): CT
Brain, Lumbar puncture
18
Diagnosis: Dengue fever D? of illness (point taken @time date), in ? Phase with/without warning
signs of ?, currently hemodynamically stable/resolved compensated shock. 19
CRITERIA FOR HOSPITAL ADMISSION AND REFERRAL
!! Decision for referral and admission must not be basesd on a single clinical parameter but should depend on the
TOTAL ASSESSMENT of the patient.
SYMPTOMS
a.Warning signs
b.Bleeding manifestations
c.Inability to tolerate oral fluids
d.Reduced urine output
e.Seizure
SIGNS
a.Dehydration
b.Shock
c.Bleeding
d.Any organ failure
SPECIAL SITUATION
a.Patients with comorbidities as diabetes, HPT, IHD, Coagulopathy, Morbid Obesity, Renal Failure, Chronic Liver
disease , COPD
b.Elderly mor than 65 years old
c.Patients who are on anti platelet and anti coagulant.
d.Pregnancy
e.Social factors that limit follow up as living far from health facility, no transport or living alone.
LAB CRITERIA
a.Rising HCT with reduced platelet count
FLUID MANAGEMENT
1. Is the haemodynamic status stable or compromised?
2. Which phase of disease?
3. Can the patient tolerate orally well?
4. Is there a warning sign?
5. What is the aim for fluid therapy?
22
Common pitfalls in fluid therapy:warning signs as the sole parameter without considering other
clinical parameters.
Treating patients with unnecessary fluid boluses based on raised HCT or
Excessive and prolonged fixed fluid regime in stable patients.
Infrequent monitoring and adjustment of infusion rate.
Continuation of intravenous fluid during the recovery phase.
Excessive fluid therapy in patients with co-morbidities (such as heart disease and renal
disease)
NON SHOCK STABLE
PATIENT
23
• Encourage oral fluid intake
• 2-3L daily, and 1.2-1.5 times the normal
maintenance during the critical phase for
dengue patient without comorbidities).
• IV fluid (0.9% saline is recommended) is
indicated for(asmaintainancefluid)
• increasing HCT with evidence of ongoing
plasma leakage, despite increased oral
intake
• Vomiting, unable to tolerate oral fluid,
severe diarrhoea
• Review infusion rate within 2-4 hours (IO
chart monitoring)
PATIENT WITH PERSISTENT WARNING
SIGNS WITH INCREASING OR
PERSISTENTLY HIGH HCT
Graded bolus fluid regime
Frequent monitoring of
clinical and laboratory
parameters every 2-4 hours
until patients improve.
Aim for urine output of 0.5-
1.0 ml/kg/hr.
24
FLUID RESPONSIVENESS
PARAMETERS
GRADE OF DENGUE SHOCK
SYNDROME
⚫ Grade l : Fever accompanied by non-specific constitutional
symptoms; the only haemorrhagic manifestation is a positive
tourniquet test and / or easy bruising.
⚫ Grade ll : Spontaneous bleeding, in addition to the manifestations
of Grade l patients, usually in the form of skin or other
haemorrhages.
⚫ Grade lll : Circulatory Failure manifested by a rapid, weak pulse
and narrowing of pulse pressure or hypotension with the presence
of cold, clammy skin and restlessness.
⚫ Grade lV: Profound shock with undetectable blood pressure or
pulse.
PATIENT IN
SHOCK
Bolus fluid regime
Shock can happen in any phases
of dengue.
27
NON RESPONDER TO INITIAL
RESUSCITATION
If the first two cycles off fluid resuscitation (40cc/kg) fails to establish stable
haemodynamically and HCT remains high the 3rd cycle colloid should be
considered.
If the repeated HCT drops but clinically patient still in shock we must suspect of
significant bleed (occultbleed).
Other possible causes of persistent shockare:
-sepsis , cardiogenic shock (due to myocarditis ,RV / LV dysfuction , pericardial
effusion or cardiac ischaemia ) , cytokine storm , liver failure with lactic acidosis.
29
30
31
MANAGEMENT OF SIGNIFICANT OCCULT BLEEDING
⚫ Transfuse blood (5-10 ml/kg of packed red cells) and
observe the clinical response. Consider blood
components if required
⚫ Consider repeating the blood transfusion if there is
further blood loss or no appropriate rise in HCT acter
blood transfusion
⚫ Endoscopy by trained surgeon or gastroenterologist is
indicated if these patients have persistent bleeding
despite optimum medical therapy
DISCHARGE CRITERIA
⚫ Afebrile for 48 hours
⚫ Improved general condition
⚫ Improved apetite
⚫ Stable hematocrit
⚫ Rising platlet count
⚫ No dyspnoea or respiratory distress from
plural effusion or ascites
⚫ Resolve bleeding episodes
⚫ Resolution or recovery of organ dysfunction

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REVISITING DENGUE FEVER AND LEPTOSPIROSIS

  • 1. REVISITING DENGUE FEVER AND LEPTOSPIROSIS DR FATHIYAH BINTI MAZLAN MEDICAL OFFICER ED HOSPITAL KULIM
  • 3. Introduction and epidemiology • Dengue infection is caused by dengue virus which is a mosquito- borne flavivirus. It is transmitted by Aedes aegypti and Aedes albopictus. There are four distinct serotypes, DENV-1,2,3 and 4. • The incubation period for dengue infection is 4-7 days. It may be asymptomatic or may result in a spectrum of illness ranging from undifferentiated mild febrile illness to severe disease, with or without plasma leakage and organ impairment.
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  • 5. CLINICAL COURSE OF DENGUE INFECTION 5 Incubation period : 4 - 7 days (range 3 - 14 days) After the incubation period, the illness begins abruptly. Febrile phase : 2 - 7 days. Commences at symptom onset Critical phase : Usually after D3 of fever (maybe earlier). Commences around time of defervescence*. Coincides with increase in capillary permeability. Lasts 24 - 48 hours. * Definition : Body temperature <38 degrees & remains below this level. Recovery phase : Reabsorption of extravascular fluid.
  • 6. FEBRILE PHASE 6 Viraemia : Fever, headache, N&V, flushing, myalgia, joint pain, rash, retro-orbital pain, mild haemorrhage (petechial, mucosal bleed) Progressive decrease in total white cell count followed by platelet reduction Haematocrit male < 60 years – 46% male > 60 years – 42% female (all age groups) – 40%
  • 7. Increase vascular permeability: third space loss, organ dysfunction *Leukopenia with relative lymphocytosis *Haemoconcentration *Thrombocytopenia Prolonged APTT AST > ALT CRITICAL PHASE 7
  • 8. The primary pathophysiological abnormality seen in dengue infection is an acute increase in vascular permeability that leads to plasma leakage, resulting in haemoconcentration and hypovolaemia or shock. Hypovolaemia leads to reflex tachycardia and generalised vasoconstriction due to increased sympathetic output. Clinical manifestations of vasoconstriction in various systems are as follows: • Skin - coolness, pallor and delayed capillary refill time • Cardiovascular system - raised diastolic blood pressure and narrowing of pulse pressure • Renal system - reducing urine output • Gastrointestinal system - persistent vomiting, persistent diarrhoea andabdominal pain • Central nervous system – lethargy, restlessness, apprehension,reduced level of consciousness • Respiratory system – tachypnoea (respiratory rate >20/min) Inadequate perfusion of the tissue leads to increased anaerobic glycolys is and lactic acidosis. If the hypovolaemia is not corrected promptly, the patient will progress to a refractory shock state. By then, the tissue perfusion would not respond to vasopressor drugs, even if the bloodpressure and intravascular volume were to be restored and cardiac output would remain depressed. The resultant lactic acidosis further depresses the myocardium and worsens the hypotension. The common late complications of prolonged shock are massive bleeding , disseminated intravascular coagulopathy (DIC) and multi-organ failure which are often fatal.
  • 9. Classical rash of “isles of white in the sea of red” with generalised pruritus *HCT level stabilises and drops further due to haemodilution *Recovery of white cell count (WCC). * Recovery of platelet count RECOVERY PHASE 9
  • 12. CLINICAL HISTORY Date of onset of fever Assess warning signs (last BO/Vomit) *Oral intake : quantity and quality ? >1.5L/day *Urine output : frequency, volume & time of most recent voiding (last PU)? <6hours What activities could do patient do during the febrile illness ? ADL independent, no MC Change in mental state/seizure/dizziness Other important relevant histories : Family or neighbourhood history of dengue or travel to dengue endemic area Jungle trekking and swimming in waterfall ( DD: leptospirosis/malaria/typhus) Recent unprotected sexual or IVDU (DD : acute HIV seroconversion illness) Co-morbidities (DD : sepsis particularly in diabetes mellitus) Medications : *anticoagulants/antiplatelet NSAIDS, OTC/traditional meds/IM injections/anti-HPT/all meds with last time taken *Risk factors: pregnancy, obesity, diabetes mellitus, hypertension, IHD, coagulopathy, renal failure, CLD, COPD. Age>65yo. *Social factors that limit follow up blood ix 12
  • 13. CLINICAL EXAMINATION Assess consciousness GCS Assess hydration: eye, lip, tongue, skin turgor Assess haemodynamic:  CCTVR  BP  Pulse pressure (>20mmHg)  Urine output (>0.5ml/kg/hr, not concentrated) Look for tachypnoea / acidotic breathing / pleural effusion Check for abdominal tenderness / hepatomegaly / ascites  Abdominal pain in febrile phase: omentum ischaemia due to dehydration  Abdominal pain in critical phase: acute stretch of liver capsule  Abdominal pain in recovery phase: ascites Examine for bleeding tendency  Petechiae  Purpura  Ecchymoses  Malaena  Bleeding gingiva  Epistaxis 13 Tourniquet test
  • 14. INVESTIGATIONS Disease monitoring tests FBC: Thrombocytopenia, leucopenia, inc HCT Coagulation profile RP/ LFT Lactate Blood gases Special test: CK Diagnostic test rapid combo test dengue antigen and serology test by ELISA NS1 antigen & IgM/IgG antibodies Dengue viral RNA detection
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  • 17. DIAGNOSTIC INVESTIGATION Dengue NS1 antigen test and rapid combo tests (NS1 antigen and dengue IgM/IgG antibodies)  Interpret within 15-20 minutes  Invalid after 20 minutes  sensitivity 93.9%; specificity 92% Dengue Viral RNA Detection (Real time RT PCR)  Determine Dengue serotype Virus isolation - NS1 Antigen : sensitivity drop day 4-5. In defervescence, usually non- detectable. If present >D5, predict severe dengue. False positive in Yellow Fever. - IgM : >D5 of illness, peaks about 2/52 then wanes down over 1 hour. -IgG : after Day 7. Check titre. If 1 : 2560, indicate of secondary dengue False positive in JE, malaria, leptospirosis, toxoplasmosis, syphilis, RA 17
  • 18. DISEASE MONITORING INVESTIGATION Identify phase of dengue TWC, HCT, Platelet Markers of plasma leakage and hypovoleamia HCT (haemoconcentration), VBG (metabolic acidosis), lactate (adaequate<2 mmol/L) Complication (when in suspect severe dengue) Hepatitis: AST or ALT >=1000 (AST>ALT) Coagulopathy: Coagulation profile (prolonged APTT) Acute renal failure: UFEME, Renal profile (RP) Myocarditis: Troponin and Creatine Kinase (CK), Echo, ECG Myositis: CK Pleural effusion: CXR, US Thorax Ascites / gallbladder wall edema: US Abdomen Neurological (Encephalopathy/encephalitis): CT Brain, Lumbar puncture 18
  • 19. Diagnosis: Dengue fever D? of illness (point taken @time date), in ? Phase with/without warning signs of ?, currently hemodynamically stable/resolved compensated shock. 19
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  • 21. CRITERIA FOR HOSPITAL ADMISSION AND REFERRAL !! Decision for referral and admission must not be basesd on a single clinical parameter but should depend on the TOTAL ASSESSMENT of the patient. SYMPTOMS a.Warning signs b.Bleeding manifestations c.Inability to tolerate oral fluids d.Reduced urine output e.Seizure SIGNS a.Dehydration b.Shock c.Bleeding d.Any organ failure SPECIAL SITUATION a.Patients with comorbidities as diabetes, HPT, IHD, Coagulopathy, Morbid Obesity, Renal Failure, Chronic Liver disease , COPD b.Elderly mor than 65 years old c.Patients who are on anti platelet and anti coagulant. d.Pregnancy e.Social factors that limit follow up as living far from health facility, no transport or living alone. LAB CRITERIA a.Rising HCT with reduced platelet count
  • 22. FLUID MANAGEMENT 1. Is the haemodynamic status stable or compromised? 2. Which phase of disease? 3. Can the patient tolerate orally well? 4. Is there a warning sign? 5. What is the aim for fluid therapy? 22 Common pitfalls in fluid therapy:warning signs as the sole parameter without considering other clinical parameters. Treating patients with unnecessary fluid boluses based on raised HCT or Excessive and prolonged fixed fluid regime in stable patients. Infrequent monitoring and adjustment of infusion rate. Continuation of intravenous fluid during the recovery phase. Excessive fluid therapy in patients with co-morbidities (such as heart disease and renal disease)
  • 23. NON SHOCK STABLE PATIENT 23 • Encourage oral fluid intake • 2-3L daily, and 1.2-1.5 times the normal maintenance during the critical phase for dengue patient without comorbidities). • IV fluid (0.9% saline is recommended) is indicated for(asmaintainancefluid) • increasing HCT with evidence of ongoing plasma leakage, despite increased oral intake • Vomiting, unable to tolerate oral fluid, severe diarrhoea • Review infusion rate within 2-4 hours (IO chart monitoring)
  • 24. PATIENT WITH PERSISTENT WARNING SIGNS WITH INCREASING OR PERSISTENTLY HIGH HCT Graded bolus fluid regime Frequent monitoring of clinical and laboratory parameters every 2-4 hours until patients improve. Aim for urine output of 0.5- 1.0 ml/kg/hr. 24
  • 26. GRADE OF DENGUE SHOCK SYNDROME ⚫ Grade l : Fever accompanied by non-specific constitutional symptoms; the only haemorrhagic manifestation is a positive tourniquet test and / or easy bruising. ⚫ Grade ll : Spontaneous bleeding, in addition to the manifestations of Grade l patients, usually in the form of skin or other haemorrhages. ⚫ Grade lll : Circulatory Failure manifested by a rapid, weak pulse and narrowing of pulse pressure or hypotension with the presence of cold, clammy skin and restlessness. ⚫ Grade lV: Profound shock with undetectable blood pressure or pulse.
  • 27. PATIENT IN SHOCK Bolus fluid regime Shock can happen in any phases of dengue. 27
  • 28. NON RESPONDER TO INITIAL RESUSCITATION If the first two cycles off fluid resuscitation (40cc/kg) fails to establish stable haemodynamically and HCT remains high the 3rd cycle colloid should be considered. If the repeated HCT drops but clinically patient still in shock we must suspect of significant bleed (occultbleed). Other possible causes of persistent shockare: -sepsis , cardiogenic shock (due to myocarditis ,RV / LV dysfuction , pericardial effusion or cardiac ischaemia ) , cytokine storm , liver failure with lactic acidosis.
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  • 32. MANAGEMENT OF SIGNIFICANT OCCULT BLEEDING ⚫ Transfuse blood (5-10 ml/kg of packed red cells) and observe the clinical response. Consider blood components if required ⚫ Consider repeating the blood transfusion if there is further blood loss or no appropriate rise in HCT acter blood transfusion ⚫ Endoscopy by trained surgeon or gastroenterologist is indicated if these patients have persistent bleeding despite optimum medical therapy
  • 33. DISCHARGE CRITERIA ⚫ Afebrile for 48 hours ⚫ Improved general condition ⚫ Improved apetite ⚫ Stable hematocrit ⚫ Rising platlet count ⚫ No dyspnoea or respiratory distress from plural effusion or ascites ⚫ Resolve bleeding episodes ⚫ Resolution or recovery of organ dysfunction