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