Dengue fever
Transcript of Dengue fever
DENGUE FEVER
Dr. Anita LamichhaneDeptt. Of pediatrics
Shaikh Zayed Hospital
Etiological AgentEtiological Agent
Dengue virus Dengue virus • Single stranded RNA virus,Arbovirus belonging to flaviviridae
family
• 4 antigenically distinct serotypes-DEN 1, 2,3, 4.
• DEN-1, DEN-2 were prevalent until 1980s
• DEN-3 is predominant in recent outbreak
• DEN-4 primarily detected in secondary dengue infections
• Serotype provides specific life time immunity and short term
cross immunity
Dengue virus transmission • Two general patterns
• Epidemic Dengue – dengue virus is introduced into a region
as an isolated event that involves a single viral
strain(Asia,Africa,America)
• Hyperendemic Dengue-continuous circulation of multiple
viral serotypes in an area where a large pool of susceptible
hosts & a competent vector are constantly
present,predominant pattern of global transmission.
The vector-Aedes aegypti
• Transmitted by the infected female Aedes aegypti
• Can be identified by the white bands or scale patterns on its legs and thorax
• Primarily a daytime feeder• Found in tropical & subtropical
region• Lives around human habitation• Lays egg & produces larvae
preferentially in artificial containers
Vector & its transmission
0 5 8 12 16 20 24 28 DAYS
Illness Illness Human #1 Human #2
Mosquito feeds/acquires virus
Mosquito refeeds/transmits
virus
Viremia Viremia
Intrinsic incubation
period
Intrinsic incubation
period
Extrinsic incubation
period
Extrinsic incubation
periodViremia
Replication & transmission of Dengue virus
• Virus inoculated into a human being with mosquito saliva
• The virus localizes and replicates in various target organs-
local lymph nodes & liver released spreads through
the blood infect the WBCs & reticuloendothelial
system(dendritic cells,hepatocytes,endothelial cells)
• The mosquito ingests blood containing the viruses (on
biting an infective person)
• Virus replicates in the midgut,ovaries,nerve tissue, fat body
of the mosquito
• It then escapes into the body cavity and later on infects the
salivary glands
• In the salivary glands, the virus replicates
• When the mosquito bites another human ,the life cycle
continues
• Humans are the primary reservoir of infection
Vector
• Aedes aegypti/Aedes albopictusAedes aegypti/Aedes albopictus
• The female mosquito feeds on blood ( they need the
protein found in blood to produce eggs)
• Male mosquitoes feed only on plant nectar.
• The mosquito is attracted by the body odours, carbon
dioxide and heat emitted from the animal or humans.
Aedes aegypti Mosquito life cycle
• Eggs are laid on the walls of water-filled containers in the
house and patio.
• The eggs can survive for months and hatch when
submerged in water.
• Female mosquitoes lay dozens of eggs up to 5 times
during their life time.
• The mosquito life cycle, takes 8 days and occurs in water.
Adult mosquitoes live for one month.
• Adult mosquitoes “usually” rest indoors in dark areas (closets, under beds, behind curtains); only female mosquitoes bite humans.
• The dengue mosquito can fly several hundred yards looking for water-filled containers to lay their eggs.
• The dengue mosquito does not lay eggs in ditches, drainages, canals, wetlands, rivers or lakes
Aedes aegypti
Aedes albopictus
PATHOPHYSIOLOGY
• Rapid activation of the complement system
• Blood level of soluble TNF receptor, interferon-
gamma,& IL-2 are
• C1q,C3,C4,C5-8 & C3 proactivators are
• These factors interact at the endothelial cell to
produce vascular permeability through the nitric
oxide final pathway
• The blood clotting & fibrinolytic system are & levels of
factor XII are
• Capillary damage allows fluid, electrolytes & small
proteins ,red cells to leak into extravascular spaces
• This internal redistribution of fluid together with deficits
caused by fasting, thirst,vomiting results in
hemoconcentration,hypovolaemia, increase cardiac work,
tissue hypoxia, metabolic acidosis & hyponatremia
CLINICAL MANIFESTATIONSCLINICAL MANIFESTATIONS
Four dengue clinical syndrome
• Undifferentiated fever
• Classic dengue fever
• Dengue hemorrhagic fever(DHF)
• Dengue Shock Syndrome (DSS)- a severe form of
DHF
Undifferentiated fever
• Most common presentation
• Silent transmission
• Incubation period of 3-14 days(average 4-7 days)
• Sudden onset of fever, biphasic
• Severe headache(retro-orbital)
• Myalgias & arthalgias that may be severe
• Nausea & vomiting
• Rash may be present at the different stages of
illness- maculpapular, petechial, erythematous
• Hemorrhagic manifestations
DENGUE HEMORRHAGICDENGUE HEMORRHAGIC FEVERFEVER
Dengue Hemorrhagic Fever
• Usually develops around 3rd -7th day of illness
• There is rapid onset of plasma leakage, altered hemostasis,
and damage to the liver, resulting in severe fluid losses and
bleeding
• Skin hemorrhage-petechiae, purpura, ecchymosis
• Gingival & nasal bleeding,Hematuria
• GI bleeding- haetamesis,melena,haematochezia
• Plasma leakage is due to increased capillary
permeability ;manifest as hemoconcentration, pleural
effusion & ascites.
• Bleeding due to capillary fragility & thrombocytopenia
• Liver damage manifests as increases in levels liver
enzymes, low albumin levels, and deranged coagulation
parameters(PT,PTT)
3 phases of DHF
• Febrile phase : 2-7 days Sudden onset fever
Severe headache
Epigastric discomfort,anorexia, vomiting
Arthralgia, myalgia
Flushing
Tender hepatomegaly, splenomegaly
Maculopapular rash
Leakage phase
• 1ST 24-48 HOURS• Pleural effusion• Ascities• Pericardial effusion• Haemorrhagic menifestation• Haematemesis,malena ,epistaxis & menorrhagia
Convalescent phase
Short & uneventful
• Short & uneventful• Return of appetite• Bradycardia• Recovery rash• Severe itching on palms & soles• of appetiteBradycardiaRecovery z
Criteria to label Dengue Criteria to label Dengue Hemorrhagic FeverHemorrhagic Fever
WHO case definition of DHF• Fever-sudden onset 2-7 days
• Hemorrhagic manifestations with positive tourniquet test
• Low platelet count(1,00,000/mm3 or less)
• Objective evidence of plasma leak syndrome
– Hematocrit ≥ 20% above baseline
– Low albumin
– Pleural/pericardial effusions
Four grades of DHF
• Grade I- Fever & non-specific constitutional symptoms
Positive tourniquet test is only hemorrhagic manifestations
• Grade II- Grade I manifestations + spontaneous bleeding
• Grade III-signs of circulatory failure• Grade IV- profound shock (undetectable pulse &
BP)
Danger signs in Dengue Hemorrhagic Fever
• Abdominal pain-intense & sustained
• Persistent vomiting
• Abrupt change from fever to hypothermia, with
sweating
• Change in mental status of the patient
Unusual presentation of Severe Dengue Fever
• Encephalopathy
• Liver failure or fulminant hepatitis
• Demonstrated by Increase aminotransferas,
increase bilirubin, incresae PT,APTT
• Cardiomyopathy-conduction defects, myocarditis
• Severe GI hemorrhage
Risk Factors
• Age: all groups are affected
• Pre-existing anti –dengue antibody,either caused by
previous infection or to maternal antibodies passed to
infants
• Higher risk in secondary infections
• Higher risk inlocations with two or more seroypes
circulating simultaneously at high levels
TOURNIQUET TESTTOURNIQUET TEST
• Inflate BP cuff to a point midway between SBP & DBP
for 5 minute
• After deflating the cuff, wait for the skin to return to its
normal colour ,then count the number of petechiae
visible in one inch-square area on the ventral surface of
the forearm
• Positive test:Positive test:20 0r more petechiae per one inch2
Positive Tourniquet Test• A typical positive result from a tourniquet test may look like. This patient has more than 20 petechiae per square inches.
Dengue Shock Dengue Shock SyndromeSyndrome
Four criteria • Evidence of circulatory failure, manifested indirectly by all
of the following
– Rapid & weak pulse
– Narrow pulse pressure (≤ 20 mm Hg or hypotension for
age)
– Cold, clammy skin & altered mental status
– Frank shock
Laboratory tests in Dengue Fever
• Complete blood count:– WBC-leucopenia,lymphocytosis– Platelets-thrombocytopenia– Hematocrit:≥20% of the baseline
• Liver function tests:– serum aminotransferases:deranged– Serum bilirubin:increased– serum albumin:low
• Coagulation studies –PT,APTT:prolongrd
• Serum electrolytes:deranged
• Blood gases:metabolic acidosis
• Tourniquet test:positive
• Complement levels:low
• Blood urea:raised
• Chest X-ray- for effusions
• ECG- sinus bradycardia, prolonged PR interval
• Serological diagnosiso ELISA Anti dengue IgM & IgG Ab Sensitivity 84-98% Specificity 100%o Haemagglutination inhibition testo Complement fixation test
• Virus isolation• Molecular detection - PCR
Treatment
• Mainly Supportive
• No hemorrhagic manifestations & well hydrated:
patient sent home with instructions for “follow up”
• If hemorrhagic manifestations/hydration status
borderline-patient observed in hospitals
• If warning signs are present even without evidence
of shock or if DSS present-hospitalized
• Intravenous fluids with Electrolyte balance
• Antipyretics-acetaminophen(aspirin and NSAIDS should be
avoided as they interfere with platelet function)
• H2 blockers,antiemetics(Domperidone)
• Platelet and FFP transfusion when needed
• Monitoring of BP, urine output, platelet count and
hematocrit
• Soft,balanced nutritious diet
Mosquito barrier
• Needed until fever subsides(to prevent Aedes
aegypti mosquito from biting patients &
acquiring virus)
• Patients should be kept ideally in screened room
or under mosquito net
Treatment of DHF & DSS• A medical emergency
• Admit in ICU
• Keep the patient in supine position
• Immediate evaluation of vital signs & degrees of
hemoconcentration, dehydration & electrolyte imbalance
• Rapid I/v replacement with wide bore cannula –N/S ideal
fluid of choice
• Monitor CBC, LFTs, S/E, PT/APTT
• When pulse pressure is ≤ 10 mmHg or when elevation of
Hct persists after replacement of fluids; plasma or colloids
are indicated
• FFP & platelets for bleeding
• No role of corticosteroids
• Look for evidence of complications
• Avoid hypervolaemia
Complications
• Fluid & electrolyte losses• Myocarditis • Hepatic dysfunction• Febrile convulsions• Residual brain damage• Encephalopathy • Disseminated Intravascular coagulation• Dengue shock syndrome
Indications for hospital discharge
• Absence of fever for 24 hours(without anti-fever
therapy) & return of appetite
• Visible improvement in clnical picture
• Stable haematocrit
• 3 das after recovery from shock
• platelets ≥ 50,000/mm3
• No respiratory distress from pleural effusion/ascites
Return IMMEDIATELY to clinic or emergency department if
any of the following warning signs appear:
• Severe abdominal pain or persistent vomiting
• Red spots or patches on the skin
• Bleeding from nose or gums , Vomiting blood
• Black, tarry stools
• Drowsiness or irritability
• Pale, cold, or clammy skin
• Difficulty breathing
Dengue Vaccine
• No licensed vaccine at present• Effective vaccine must be tetravalent
• Field testing of an attenuated tetravalent
vaccine currently underway
PREVENTION PREVENTION
Vector control
• Chemical control-
– Larvicides may be used to kill the immature aquatic stages
– Ultra-low volume fumigation is effective against adult mosquitoes
– Mosquitoes may have resistance to commercial aerosols spray
• Biological controlBiological control-largely experimental-Placing fish in containers to eat the larvae
• Environmental controlEnvironmental control– Elimination of larval habitats– Most likely method to be effective in the long
term
Prophylaxis • Avoiding mosquito bites– Use of insecticides– Repellents– Body covering with clothing– Screening of house– Destruction of the vector breeding sites– Using mosquito nets
• If storage is mandatory, a tight fitting lid or a thin layer of oil may prevent egg laying or hatching
• A larvicide (Abate) available as a 1% sand –
granule formations may be added safely to
drinking water
Why to control??/Purpose of control
• Reduce female vector density to a level below
which epidemic vector transmission will not
occur
• The minimum vector density to prevent epidemic
transmission is unknown
Program to minimize the impact of epidemic
• Teaching the medical community how to
diagnose and mange DHF
• Educating the general public to encourage &
enable them to carry out vector control in their
home and neighborhood
Common containers in which eggsdevelop into adult dengue
mosquitoes:
Recent advances
• Gene-modified mosquitos could stop dengue fever : genetically modified mosquitoes wee released last year at sites in Malaysia and the Cayman Islands.
Key MessageKey MessageDengue infection is preventable diseaseNo direct person to person transmissionPrevent Man – Mosquito contact to
prevent the disease