Dengue 1
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Transcript of Dengue 1
DENGUEDENGUEAlso known as Also known as breakbone fever. breakbone fever. is an infectious is an infectious tropical disease. tropical disease. caused by the dengue virus.caused by the dengue virus.There are four strains of the virus, There are four strains of the virus, which are called serotypes, and these which are called serotypes, and these are referred to as DENV-1, DENV-2, are referred to as DENV-1, DENV-2, DENV-3 and DENV-4. DENV-3 and DENV-4.
All four serotypes can cause the full All four serotypes can cause the full spectrum of disease.Infection with one spectrum of disease.Infection with one serotype is believed to produce lifelong serotype is believed to produce lifelong immunity to that serotype but only short immunity to that serotype but only short term protection against the others.term protection against the others.
The severe complications on secondary The severe complications on secondary infection occurs particularly if someone infection occurs particularly if someone previously exposed to one serotype then previously exposed to one serotype then contracts other serotype. contracts other serotype.
Dengue virus is primarily Dengue virus is primarily transmitted by transmitted by AedesAedes mosquitoes, mosquitoes, particularly particularly A. aegypti.A. aegypti.
Other Other Aedes Aedes species that transmit species that transmit the disease include the disease include A. albopictusA. albopictus, , A. A. polynesiensis polynesiensis and and A. scutellaris.A. scutellaris.
Humans are the primary host of the Humans are the primary host of the virus, but it also circulates in virus, but it also circulates in nonhuman primates. nonhuman primates.
The VectorThe Vector AedesAedes aegypti aegypti mosquitomosquito
Distinct feature is Distinct feature is black and white black and white stripes on its stripes on its body and legsbody and legs
Bites during the day.Bites during the day.
Lays its eggs in Lays its eggs in clean, stagnant clean, stagnant water.water.
Potential breeding Potential breeding groundsgrounds
Replication and Transmission Replication and Transmission of Dengue Virusof Dengue Virus
1.1. Transmitted in salivaTransmitted in saliva
2.2. Replicates in white Replicates in white blood cells and blood cells and lymphatic tissueslymphatic tissues
3.3. Circulates in bloodCirculates in blood
4.4. Second mosquito Second mosquito ingests virus with bloodingests virus with blood
5.5. Replicates in mosquito Replicates in mosquito midgut, infects and midgut, infects and replicates in salivary replicates in salivary glandsglands
Factors responsible for Factors responsible for resurgence of Dengueresurgence of Dengue
Population growth Population growth
Unplanned and uncontrolled Unplanned and uncontrolled urbanization urbanization
Inadequate & Interrupted water Inadequate & Interrupted water
supply- leading to storage of watersupply- leading to storage of water
Deficient waste water managementDeficient waste water management
Failure of effective mosquito control Failure of effective mosquito control measuresmeasures
Pathophysiology of DHF Pathophysiology of DHF and DSSand DSS
2 main pathophysiological 2 main pathophysiological changes: changes:
Increased vascular permeability Increased vascular permeability Haemostatic Disorder: Haemostatic Disorder:
Vascular ChangesVascular ChangesThrombocytopeniaThrombocytopeniaCoagulopathyCoagulopathy
Infected monocytesInfected monocytes
Vasoactive mediatorsVasoactive mediators
Increased vascular permeabilityIncreased vascular permeability
Hemorrhagic manifestations DHF, Hemorrhagic manifestations DHF, DSS DSS
Increased Vascular Permeability
ThrombocytopeniaThrombocytopenia
Infection of human haematopoietic Infection of human haematopoietic cellscells megakaryocytopoieses megakaryocytopoieses
Increased peripheral destruction of Increased peripheral destruction of antibody coated plateletsantibody coated platelets
Platelet destruction in the liver and Platelet destruction in the liver and spleen.spleen.
Platelet dysfunction(Qualitative Platelet dysfunction(Qualitative defect)defect)
Hemorrhage in Dengue Hemorrhage in Dengue
VasculopathyVasculopathyThrombocytopeniaThrombocytopeniaPlatelet dysfunction Platelet dysfunction DICDICCoagulopathyCoagulopathy
Clinical Manifestations of Clinical Manifestations of Dengue Virus InfectionDengue Virus Infection
Classic Dengue FeverClassic Dengue Fever is Dengue fever is Dengue fever without warning signswithout warning signs
Dengue Fever with unusual hemorrhageDengue Fever with unusual hemorrhage Dengue fever with warning signs Dengue fever with warning signs
DHF is Dengue fever with warning signs DHF is Dengue fever with warning signs DSS is Severe DengueDSS is Severe Dengue
But rather than separate entities, Now it But rather than separate entities, Now it is a continuum of the diseaseis a continuum of the disease
Dengue FeverDengue Fever is an acute febrile illness of is an acute febrile illness of 2-7 days duration(sometimes with two 2-7 days duration(sometimes with two peaks) with two or more of the following peaks) with two or more of the following manifestations:manifestations:
headacheheadache retro-orbital painretro-orbital pain myalgia/arthralgiamyalgia/arthralgia rashrash haemorrhagic manifestation (petechiae haemorrhagic manifestation (petechiae
and positive tourniquet test) and,and positive tourniquet test) and, leukopenialeukopenia
Dengue Haemorrhagic FeverDengue Haemorrhagic Fever is a is a probable case of dengue and probable case of dengue and haemorrhagic tendency evidenced by haemorrhagic tendency evidenced by one or more of the following:one or more of the following:
Positive tourniquet testPositive tourniquet test Petechiae, ecchymosis or purpuraPetechiae, ecchymosis or purpura Bleeding from mucosa (mostly Bleeding from mucosa (mostly
epistaxis or bleeding from gums), epistaxis or bleeding from gums), injection sites or other sitesinjection sites or other sites
Haematemesis or melenaHaematemesis or melena
Thrombocytopaenia (platelets 100,000/cu.mm Thrombocytopaenia (platelets 100,000/cu.mm or less) and or less) and
Evidence of plasma leakage due to increased Evidence of plasma leakage due to increased capillarycapillary
permeability manifested by one or more of permeability manifested by one or more of the following:the following:
– – A >20% rise in haemotocrit for age and sex A >20% rise in haemotocrit for age and sex – – A >20% drop in haemotocrit following A >20% drop in haemotocrit following
treatment with treatment with fluids as compared to baselinefluids as compared to baseline – – Signs of plasma leakage (pleural effusion, Signs of plasma leakage (pleural effusion,
ascites orascites or hypoproteinaemia).hypoproteinaemia).
Dengue Shock SyndromeDengue Shock Syndrome (DSS) All (DSS) All the above criteria of DHF plus signs the above criteria of DHF plus signs of circulatory failure manifested by;of circulatory failure manifested by;
rapid and weak pulse, rapid and weak pulse, narrow pulse pressure (< or equal to narrow pulse pressure (< or equal to
20 mm Hg);20 mm Hg); hypotension for age, hypotension for age, cold and clammy skin andcold and clammy skin and restlessnessrestlessness
Grading Of DHF/DSSGrading Of DHF/DSS Grade IGrade I:: Fever accompanied by non-specific constitutional Fever accompanied by non-specific constitutional
symptoms; the only haemorrhagic manifestation is a symptoms; the only haemorrhagic manifestation is a positive tourniquet test and/or easy bruising.positive tourniquet test and/or easy bruising.
Grade IIGrade II: : Spontaneous bleeding in addition to the Spontaneous bleeding in addition to the manifestations of Grade I patients, usually in the forms of manifestations of Grade I patients, usually in the forms of skin or other haemorrhages.skin or other haemorrhages.
Grade IIIGrade III: : Circulatory failure manifested by a rapid, weak Circulatory failure manifested by a rapid, weak pulse and narrowing of pulse pressure or hypotension, pulse and narrowing of pulse pressure or hypotension, with the presence of cold, clammy skin and restlessness.with the presence of cold, clammy skin and restlessness.
Grade IVGrade IV:: Profound shock with undetectable blood Profound shock with undetectable blood pressure or pulse.pressure or pulse.
Clinical courseClinical course
Disease CourseDisease Course Febrile phase Febrile phase lasts 2-7 days lasts 2-7 days
Look for warning signs Look for warning signs Mild hemorrhagic manifestations may occurMild hemorrhagic manifestations may occur
Critical phaseCritical phase Begins after the fever improvesBegins after the fever improves
usually on days 3–7 of illnessusually on days 3–7 of illness lasts 24–48 hourslasts 24–48 hours Progressive leucopenia , thrombocytopenia Progressive leucopenia , thrombocytopenia
and plasma leakageand plasma leakage Recovery phaseRecovery phase: :
Gradual reabsorption of fluid in 48-72hrsGradual reabsorption of fluid in 48-72hrs
The course of infection is divided The course of infection is divided into three phases: febrile, critical, into three phases: febrile, critical, and recovery and recovery
The febrile phase involves high The febrile phase involves high fever, often over 40 °C (104 °F), and fever, often over 40 °C (104 °F), and is associated with generalized pain is associated with generalized pain and a headache; this usually lasts and a headache; this usually lasts two to seven days two to seven days
The disease proceeds to a critical phase, The disease proceeds to a critical phase, which follows the resolution of the high which follows the resolution of the high fever and typically lasts one to two days. fever and typically lasts one to two days.
During this phase there may be significant During this phase there may be significant fluidaccumulation in thefluidaccumulation in the chest and chest and abdominal cavity due to increased abdominal cavity due to increased capillary permeability and leakage. This capillary permeability and leakage. This leads to depletion of fluid from the leads to depletion of fluid from the circulation and decreased blood supply to circulation and decreased blood supply to vital organs.During this phase, organ vital organs.During this phase, organ dysfunction and severe bleeding, typically dysfunction and severe bleeding, typically from the gastrointestinal tract, may from the gastrointestinal tract, may occur. occur.
The recovery phase occurs next, with The recovery phase occurs next, with resorption of the leaked fluid into the resorption of the leaked fluid into the bloodstream bloodstream
This usually lasts two to three days This usually lasts two to three days During this stage, a fluid overload state During this stage, a fluid overload state
may occur; if it affects the brain, it may may occur; if it affects the brain, it may cause a reduced level of consciousness cause a reduced level of consciousness or seizures.A feeling of fatigue may last or seizures.A feeling of fatigue may last for weeks afterwards.for weeks afterwards.
Unusual Manifestations Unusual Manifestations of Dengueof Dengue
Acute liver failure and Acute liver failure and encephalopathy which may be encephalopathy which may be present even in the absence of present even in the absence of plasma leakageplasma leakage
Cardiomyopathy and myocarditis Cardiomyopathy and myocarditis Encephalitis and rarely AIDPEncephalitis and rarely AIDP Severe gastrointestinal Severe gastrointestinal
hemorrhagehemorrhage
Clinical Evaluation in Clinical Evaluation in Dengue FeverDengue Fever
Blood Pressure including pulse Blood Pressure including pulse pressurepressure
Pulse ratePulse rate Hydration statusHydration status Capillary refill time Capillary refill time E/O petechiae, purpura and echymosisE/O petechiae, purpura and echymosis E/O increased vascular permeabilityE/O increased vascular permeability
Pleural effusion, ascitesPleural effusion, ascitesTourniquet testTourniquet test
Differential Diagnosis: Differential Diagnosis: Conditions that Conditions that mimic the febrile phase of dengue mimic the febrile phase of dengue
infectioninfectionFlu-like syndromesFlu-like syndromes Influenza, measles, Influenza, measles,
Chikungunya, infectious Chikungunya, infectious mononucleosis , HIV mononucleosis , HIV seroconversion illnessseroconversion illness
Illnesses with a rashIllnesses with a rash Rubella, measles, scarlet Rubella, measles, scarlet fever, meningococcal fever, meningococcal infection, Leptospirosis, infection, Leptospirosis, Chikungunya, drug Chikungunya, drug reactionsreactions
Diarrhoeal diseasesDiarrhoeal diseases Rotavirus, other enteric Rotavirus, other enteric infectionsinfections
Illnesses with Illnesses with neurological neurological manifestationsmanifestations
Meningo/encephalitisMeningo/encephalitisFebrile seizuresFebrile seizures
Differential Diagnosis: Conditions Differential Diagnosis: Conditions that mimic the critical phase of that mimic the critical phase of
dengue infectiondengue infectionInfectiousInfectious Acute gastroenteritis, Acute gastroenteritis,
malaria, leptospirosis, malaria, leptospirosis, typhoid, typhus, viral typhoid, typhus, viral hepatitis, acute HIV hepatitis, acute HIV seroconversion illness, seroconversion illness, bacterial sepsis, septic bacterial sepsis, septic shockshock
Other ConditionsOther Conditions Acute abdomenAcute abdomenDiabetic ketoacidosisDiabetic ketoacidosisPlatelet disordersPlatelet disordersRenal failureRenal failure
Laboratory Laboratory Manifestations Manifestations
Hematocrit/ Packed cell volume:Hematocrit/ Packed cell volume: Crude estimated Hb× 3Crude estimated Hb× 3 May be altered by bleeding/volume May be altered by bleeding/volume
replacementreplacement
Increase in Hct by 20% Increase in Hct by 20% DHF or plasma DHF or plasma leakageleakage
When previous value NAWhen previous value NA > 45% is > 45% is significantsignificant
Other Manifestations Other Manifestations
Peripheral Smear and TLCPeripheral Smear and TLC Normal, LeukocytosisNormal, Leukocytosis
Leukopenia Leukopenia Lymphocytosis and Atypical Lymphocytosis and Atypical
lymphocyteslymphocytes Thrombocytopenia Thrombocytopenia
Other Manifestations Other Manifestations
Hypoalbuminemia Hypoalbuminemia Hyponatremia Hyponatremia Mild increase in AST, ALT upto 200-250Mild increase in AST, ALT upto 200-250
> 250> 250 Hepatic involvement and severe Hepatic involvement and severe DengueDengue
↑ ↑ PT, APTTPT, APTT ↑ ↑ BUNBUN Mild albuminuria Mild albuminuria Reduced Serum Complement Reduced Serum Complement
Laboratory criteria for Laboratory criteria for confirmation of dengue confirmation of dengue
feverfever Isolation of the dengue virus from Isolation of the dengue virus from
serum or autopsy samplesserum or autopsy samples Demonstration of a fourfold or Demonstration of a fourfold or
greater change in reciprocal IgG or greater change in reciprocal IgG or IgM antibody titres to one or more IgM antibody titres to one or more dengue virus antigens in paired dengue virus antigens in paired serum samplesserum samples
Dengue NS-1 Antigen Dengue NS-1 Antigen NS-1 is a non structural protein NS-1 is a non structural protein
associated with intracellular organalles associated with intracellular organalles and transported to the surface by and transported to the surface by secretory pathways.secretory pathways.
Soluble hexameric form found to Soluble hexameric form found to circulate in the blood of patients with circulate in the blood of patients with acute dengueacute dengue
ELISA has been developed for specific ELISA has been developed for specific detection of Dengue Type NS-1 detection of Dengue Type NS-1 AntigenAntigen. .
TreatmentTreatment Management is relatively simple, inexpensive Management is relatively simple, inexpensive
and very effective in saving lives so long as and very effective in saving lives so long as correct and timely interventions are instituted.correct and timely interventions are instituted.
Main Pathological Abnormality Main Pathological Abnormality is LOSS OF is LOSS OF PLASMA VOLUME FROM THE VASCULAR PLASMA VOLUME FROM THE VASCULAR COMPARTMENTCOMPARTMENT because of increased because of increased capillary permeability. capillary permeability.
Loss of plasma volume varies = 5-20%Loss of plasma volume varies = 5-20% Early and effective replacement of plasma Early and effective replacement of plasma
losses with plasma expander or fluid and losses with plasma expander or fluid and electrolyte solution results in a favorable electrolyte solution results in a favorable outcome in most casesoutcome in most cases
Management Decisions Management Decisions
Depending on the clinical Depending on the clinical manifestations and other manifestations and other circumstances, patients may be circumstances, patients may be sentsent
Group A : Sent Home Group A : Sent Home Group B: In-hospital managementGroup B: In-hospital management Group C: Require emergency Group C: Require emergency
treatment treatment
Group AGroup A Outpatient treatment Outpatient treatment
Who?Who?
Able to take orallyAble to take orally
Pass urine adequately once every 6 hrsPass urine adequately once every 6 hrs
No warning signs particularly atdefervescence of No warning signs particularly atdefervescence of feverfever
What to doWhat to do
Review daily for disease progression ( TLC, Hct Review daily for disease progression ( TLC, Hct and warning signs)and warning signs)
ORS, juice and other fluidsORS, juice and other fluids
Paracetamol ( max 4/day)Paracetamol ( max 4/day)
Instruct to come back in case of warning signs or Instruct to come back in case of warning signs or decreasing urine outputdecreasing urine output
Group BGroup B In hospital In hospital
managementmanagement Warning SignsWarning Signs
Abdominal pain or Abdominal pain or tendernesstenderness
Persistent vomitingPersistent vomiting Clinical fluid Clinical fluid
accumulation: PE, ascitesaccumulation: PE, ascites Mucosal bleedMucosal bleed Lethargy, restlessnessLethargy, restlessness Liver enlargement >2 cmLiver enlargement >2 cm
Co-existing ConditionsCo-existing Conditions Pregnancy, Diabetes, Pregnancy, Diabetes,
renal failure, renal failure, infancy, old infancy, old age, obesity, chronic age, obesity, chronic haemolytic diseaseshaemolytic diseases
Social CircumstancesSocial Circumstances
Dengue without warning Dengue without warning signssigns
Encourage oral fluids
Start NS or RL at maintenance rate
If not tolerated
Give minimum volume required to maintain good perfusion
and urine output
IV fluids for few hrs switch to oral fluids as
soon as possibleContinue IV fluid
No warning signs patient improving
Warning signs or î Hct
3–5 ml/kg/hr for 2–4 hr
isotonic solutions such as NS or RL
5–7 ml/kg/hr for 1-2 hrs
Obtain Hct
2–3 ml/kg/hr
Obtain Hct and reassess clinically
Hct same or rising minimally
2–3 ml/kg/hr for 2-4 hrs
minimum IVF required to maintain good perfusion and urine output =0.5 ml/kg/hr.
Reduce IV fluid as Hct decreases and patient improves IV Fluid for 24-48hrs
Vital signs worseningHct rising
MonitoringMonitoring Vital signs and peripheral perfusionVital signs and peripheral perfusion 1–4 1–4
hourlyhourly
Urine outputUrine output 4–6 hourly 4–6 hourly Hematocrit Hematocrit before and after fluid before and after fluid
replacement, then 6–12 hourlyreplacement, then 6–12 hourly
Blood glucose, and other organ functions as Blood glucose, and other organ functions as
indicatedindicated
Till the patient is out of critical periodTill the patient is out of critical period
Group C: require urgent Group C: require urgent treatment in a treatment in a high dependency high dependency
unitunit Early presentation with shock (on days 2 Early presentation with shock (on days 2
or 3 of illness)or 3 of illness) Severe plasma leakage and/or shockSevere plasma leakage and/or shock Undetectable pulse and blood pressureUndetectable pulse and blood pressure Severe bleedingSevere bleeding Fluid overloadFluid overload Organ impairment (such as hepatic Organ impairment (such as hepatic
damage, cardiomyopathy, damage, cardiomyopathy, encephalopathy, encephalitis)encephalopathy, encephalitis)
Compensated vs hypotensive Compensated vs hypotensive shockshock
ParameterParameter Compensated Compensated shockshock
Hypotensive shockHypotensive shock
Fluid lossFluid loss 10-15%10-15% >15-20%>15-20%
Mental statusMental status Clear and lucidClear and lucid Change of mental stateChange of mental state
Capillary refill Capillary refill timetime
Prolonged (>2 Prolonged (>2 sec)sec)
Very prolonged, Very prolonged, mottled skinmottled skin
ExtremitiesExtremities Cool peripheriesCool peripheries Cold, clammy Cold, clammy extremitiesextremities
Pulse volumePulse volume Weak and Weak and threadythready
Feeble or absentFeeble or absent
Heart rateHeart rate 100-120100-120 >120>120
Blood Blood pressurepressure
SBP=N, DBP î, PP SBP=N, DBP î, PP decreased, decreased, Postural Postural hypotensionhypotension
Hypotension, Hypotension, Unrecordable blood Unrecordable blood pressure, Pulse pressure, Pulse Pressure<20mmHgPressure<20mmHg
Respiratory Respiratory raterate
20-3020-30 >30>30
IV Isotonic Crystalloid @10ml/kg/hr for 1 hr
Reassess vitals, CRT, Hct, urine output
improvementYes
IV crystalloid 5–7ml/kg/hr for 1–2hrs3–5 ml/kg/hr for 2–4hrs2–3 ml/kg/hr for 2–4hrs
Hct î fluid
bolusesHct decreases consider BT
Patient improves, Hct stable,↓IVF to maintenance level stop after 48hrs
No
Hct↑ or > 50%
10–20 ml/kg/hr for 1
hrimprovement
Yes
NoHct low (<45 in males, <40 in females or ↓ from baseline
Consider occult/ significant bleed BT
Management plan of Management plan of compensated shockcompensated shock
Hypotensive Shock
isotonic crystalloid or colloid 20 ml/kg for 15 min
Clinical ImprovementYES
Crystalloid/colloid 10 ml/kg/hr for 1 hour
IV crystalloid 5–7ml/kg/hr for 1–2hrs3–5 ml/kg/hr for 2–4hrs2–3 ml/kg/hr for 2–4hrs
Patient improves, Hct stable,↓IVF to maintenance level stop after 48hrs
Monitor Hct 6 hrly
NO
Review 1st HCT
HCT ↑or high
2nd Bolus: Colloid 10-20ml/kg over 1hr
Improvement
NO
Repeat 2nd HCT
HCT ↑or high
3rd Bolus: Colloid 10-20ml/kg over 1hr
Consider occult/ significant bleed BT
HCT ↓
HCT ↓
Repeat Hct
NO
Criteria for Platelet Criteria for Platelet Transfusion Transfusion
Platelet counts of dengue patients Platelet counts of dengue patients fluctuate in an unpredictable manner fluctuate in an unpredictable manner despite platelet transfusiondespite platelet transfusion
Stable patients with Platelet Count Stable patients with Platelet Count <10000/cc<10000/cc
Patients with Platelet Count < 20000/cc with Patients with Platelet Count < 20000/cc with minor bleedingminor bleeding
Patients with Platelet Count < 50000/cc with Patients with Platelet Count < 50000/cc with significant bleedingsignificant bleeding
Role of FFP in Dengue Role of FFP in Dengue associated thrombocytopeniaassociated thrombocytopenia
Antibody concentrates in FFPAntibody concentrates in FFP
block immune mediated platelet destructionblock immune mediated platelet destruction
reduction in peripheral platelet destructionreduction in peripheral platelet destruction
an increase in the platelet countan increase in the platelet counto Thrombopoeitin activator in FFP directly Thrombopoeitin activator in FFP directly
stimulates thrombopoeitin in BMstimulates thrombopoeitin in BM
Criteria for discharging inpatientsCriteria for discharging inpatients Absence of fever for at least 24 hours without the use Absence of fever for at least 24 hours without the use
of antifever therapyof antifever therapy Return of appetite·Return of appetite· Visible clinical improvementVisible clinical improvement Good urine outputGood urine output Stable haematocritStable haematocrit Passing of at least 2 days after recovery from shockPassing of at least 2 days after recovery from shock No respiratory distress from pleural effusion or ascitesNo respiratory distress from pleural effusion or ascites Platelet count >50 000 per mm3.Platelet count >50 000 per mm3.