Dengue fever is a mosquito-borne viral disease transmitted by Aedes aegypti and Aedes albopictus mosquitoes. It is caused by the dengue virus, of which there are four serotypes. The disease places a large burden globally, with most cases occurring in Asia. Clinical manifestations range from a self-limiting flu-like illness to severe dengue, which can be fatal if not properly treated. Diagnosis involves virus detection, antigen testing, or serology. There is no vaccine or specific antiviral treatment, so management focuses on fluid replacement and symptom relief. Complications include bleeding, organ impairment, and fluid imbalance.
1. Dengue Fever
Dinoosh De Livera, 6th Year
Foreign Students’ Training Faculty
Vitebsk State Medical University
Department of Infectious Diseases
Tropical Diseases
2. Contents
1. What is ‘’Dengue’’ ?
2. Epidemiology
3. Vector
4. Virus
5. Pathogenesis of the disease
6. Classification
7. Clinical signs & symptoms
8. Diagnosis
9. Main principles of Management & Complications
10. Prevention
3. (1)What is Dengue?
A vector-borne disease: Transmitted by Aedes aegypti, Aedes albopictus & Aedes polynesiensis.
Breeds in relatively fresh water, Day time biting, Limited flight range, Urbanized populations most affected.
Dengue virus, Genus Flavivirus, Family Flaviviridae, Four serotypes (1-4).
The most rapidly spreading mosquito-borne viral disease in the world.
Incubation period : 4-7 days (range 3-14)
Primary Dengue Infection – Self Limited
May also progress to severe dengue (DHF/DSS)
(normally children, elderly & immunocompromised)
4. (2) Epidemiology:
World Situation:
Most common arboviral disease worldwide
75% of global disease burden in Asia-Pacific region
Yearly 50 to 100 million infections
500,000 DHF cases
22,000 deaths, mostly among children.
“In the last 50 years, 30 fold rise 2.5 billion or 40% of the world, live in dengue
endemic countries.” - WHO (2009).Dengue: guidelines for diagnosis, treatment, prevention and control -- New edition
5. Reasons for incidence increase by 30-fold in last 50 years :
Inadequate closed drainage
Insecticide resistance in mosquito
vector population
Can also be considered reasons
for increased incidence.
7. (2) Epidemiology continued...
Sri Lankan Situation:
First serologically confirmed case - 1962
First documented dengue outbreak - 1965- 1966
First epidemic of DHF/ Dengue Shock Syndrome -
1989 – 1990.
Year 2014, 46584 suspected dengue cases
55.26% of dengue cases from the Western province.
10. (3) Vector:
Biological vector – Female Mosquitoes
In Sri Lanka: Aedes albopictus and Aedes aegypti
Aedes aegypti is the main species.
11. (4) Virus-
Genus – Flavi virus
Family – Flaviviridae
Virus – Dengue virus (DEN)
Serotypes – 4 serotypes:
DEN 1 to 4
13. Pathogenesis:
1.The virus is inoculated into humans with the mosquito saliva.
2.The virus localizes and replicates in various target organs, for example, local lymph nodes and the liver.
3.The virus is then released from these tissues and spreads through the blood to infect white blood cells and
other lymphatic tissues.
4.The virus is then released from these tissues and circulates in the blood. This secondary viremia is
responsible for the signs and symptoms of dengue fever
1) Primary dengue infection: First time viral infection, with any of the 4 virus types.
2) Secondary dengue infection: Any dengue infection, except the primary infection virus type. (NOT
necessarily the ‘’second’’ dengue infection)
14. Pathogenesis of Secondary infection:
Primary Infection - host develops a Life-long protective immunity to the homologous (same) serotype
Secondary Infection (caused by other 3 serotype) - host shows only partial and transient protection. High
risk of Dengue Hemorragic Fever development.
“Antibody dependent enhancement mechanism”
Infection by virus of another serotype
Production of non-neutralizing antibodies
Facilitate entry of virus to monocytes
15. Dengue virus never spreads from person to person directly. It is transmitted only by
the bite of an infected mosquito.
16. Moreover , the time between the bite of a mosquito carrying dengue virus and the start
of symptoms averages (INCUBATION PERIOD) 4 to 6 days, with a range of 1 to 7
days . And an infected person can be a source of dengue virus for mosquitos for about
6 days
17. Risk Factors for development of DHF/DSS:
(Harrison’s textbook of internal medicine, 17th edition,2008)
Presence of enhancing and non neutralising antibodies
Age : susceptibility to DHF/DSS drops significantly after 12 yrs of age
Sex : females more often affected than males
Race : Caucasians more often affected than blacks
Nutritional status : malnutrition is protective
Sequence of infection : example, serotype 1 followed by serotype 2 is more dangerous than serotype 4 followed
by serotype 2
Infecting serotype : type 2 more dangerous than others
Infecting genotype : Asian type 2 causes DHF/DSS while American type is not responsible for the illness
19. Pathogenesis of Bleeding in DSS:
Vasculopathy
Thrombocytopenia (due to virus induced reduction in hematopoeitic progenitor cell
growth and a subsequent decrease in thrombopoeisis)
Platelet dysfunction (due to interaction of virus with platelets through IgM
antiplatelet antibody)
Disseminated intravascular clotting (d-dimer, a marker for DIC is significantly
correlated with dengue disease severity)
22. Earlier(in 2005), WHO grouped symptomatic dengue virus infection into 3
categories:
1. Undifferentiated fever
2. Dengue fever
3. Dengue hemorrhagic fever
(which was further classified into four severity grades)
Currently, the classification into DF/DHF/DSS continues to be widely used
24. According to WHO, “dengue is one disease entity with different clinical
presentations and often with unpredictable clinical evolution and outcome”;
The classification into levels of severity has a high potential for being of practical
use in the clinicians’ decision as to where and how intensively the patient should be
observed and treated (i.e. triage, which is particularly useful in outbreaks)
Hence, the rationale for following case classification of dengue (New Classification)
26. Clinical manifestations of DHF:
1. Undifferentiated fever
2. Classic dengue fever
3. Dengue hemorrhagic fever
4. Dengue shock syndrome
Criteria for Diagnosis:
1. Fever, or recent history of acute fever
2. Hemorrhagic manifestations
3. Low platelet count (100,000/mm3 or less)
4. Objective evidence of “leaky capillaries:”
● elevated hematocrit (20% or more over
● baseline)
● low albumin
● pleural or other effusions
Hemorrhagic manifestations:
● Skin hemorrhages: petechiae,
purpura,
● ecchymoses
● Gingival bleeding
● Nasal bleeding
● Gastro-intestinal bleeding:
● hematemesis, melena, hematochezia
● Hematuria
● Increased menstrual flow
27. Classical Presentation:
Sudden onset of fever, headache, retro-orbital pain, and back pain
Severe myalgia (hence the colloquial designation “break bone fever”)
Macular rash on the first day
Adenopathy, palatal vesicles, scleral injection
Epistaxis and scattered petechiae may be seen and pre-existing gastrointestinal lesions
may bleed
At the time of defervescence, a maculopapular rash may be seen (beginning on the trunk
and spreading to the extremities and face) along with mild grade fever (hence the
designation “biphasic fever”)
28. Dengue Fever (DF):
2 – 7 days of illness + high grade fever
Headache
Retro – orbital pain
Myalgia
Arthralgia
Rash & haemorrhagic manifestations
Positive tourniquet test
Petechiae
29. 1) Classic Dengue – Break Bone fever
● Incubation period is 4 – 6 days ( range 3 -14)
● Abrupt onset of fever, chills, headache, retro orbital
● pain and backache
● Fever is 39 – 40◦ C; remission of 2days followed by
● Second febrile phase for 1 -2 d.
● Biphasic curve or saddle back fever.
● Fever lasts for 5- 7 days
● Transient generalized erythematous rash – first 24 – 48hrs. This morbilliform rash appears on trunk,
spreads to face and limbs sparing palms and soles. It lasts for 1- 5 days.
● Generalised myalgias, arthralgia and constitutional symptoms like anorexia, nausea, vomiting and
dysgeusia
● Relative bradycardia and generalised lymphadenopathy
● Marked leucopenia and thrombocytopenia.
● ↓ Platelets is due to impaired megakaryocyte production & ↑ platelet destruction.
30. Signs & Symptoms of DHF:
Signs & symptoms + Plasma leakage
Criteria (4)
1. Fever or h/o fever lasting 2-7 days
2. Hemorrhagic tendency
● +ve tourniquet test
● Petechae, ecchymosis, purpura
● Bleeding per mucosa, GIT , etc.
● Hematemesis, Malena
1. Thrombocytopenia, Platelets < 100,000/mm3
2. Plasma leakage
● rise in hematocrit > 20%
● fall in hematocrit > 20% after i/v fluids
● Pleural effusion, ascites, hypoalbuminemia.
31. Dengue haemorrhagic fever is a dynamic disease:
1. Febrile phase
2. Critical phase
3. Convalescent phase
32. DSS symptomatology according to phases &
1. Leaky phase : -
a. Circulatory failure
b. Oliguria
c. Postural hypotension
2. Congestive phase :
a. Fast and bounding pulse
b. Wider pulse pressure
c. Improved urinary output
3. Convalescence:
a. Bradycardia
b. Arrhythmia
c. Confluent petechial rash
33. Definition of DSS - Dengue Shock Syndrome (WHO, 2005)
DHF (following must all be present )
● Fever
● Hemorrhagic tendencies
● Thrombocytopenia
● Plasma leakage
plus
EVIDENCE OF CIRCULATORY FAILURE (manifested as)
● Narrow pulse pressure / hypotension for age
● Rapid and weak pulse
● Cold clammy extremities
34. Grading of severity of DSS & DHF:
Grade I : fever & constitutional signs and symptoms plus haemorrhagic
manifestation (positive TT and/or easy bruising)
Grade II : grade I plus spontaneous bleeding
Grade III : grade II plus circulatory failure
Grade IV : grade III plus shock with undetectable blood pressure or pulse.
(Grades III and IV define DSS)
35. (8) Diagnosis & Work-up of Dengue patient:
1) Laboratory diagnosis
● Virus isolation (cultured mosquito cells / mammalian cells - “Gold Standard” - low sensitivity & long
duration)
● Genome detection (RT-PCR, NASBA Assay)
● Antigen detection (E/M Antigen, NS I Antigen)
● Serological diagnosis (IgM & IgG Antibody detection)
2) Supportive investigations
● Tourniquette test
● Hematocrit & platelet count
● Time bound relationship between rise in hematocrit & fall in platelets: Represents pathophysiological
hallmark of disease: capillary permeability & abnormal haemostasis
● Fall in hematocrit during shock
● Progressive leukopenia
● Chest X-Rays
38. Markers for Severe Disease:
Increased urinary levels of heparan sulphate
Increased plasma levels of pentraxin 3
Decreased serum albumin
Increased levels of vascular endothelial growth factor (VEGF)
Increased levels of soluble vascular cell adhesion molecule – 1 (VCAM-1)
39. Differential Diagnosis:
Dengue-like diseases [including Chikungunya fever , West Nile fever (with rash) &
Colorado tick fever, sandfly fever, Rift Valley fever, and Ross River fever (without
rash)]
Early stages of malaria
Mild yellow fever
Viral hepatitis
Leptospirosis
Viral respiratory and influenza like diseases
40. (9) Main principles of Management:
Out-patient Management:
● Advise bed rest
● Encourage plenty of oral fluid intake (of oral rehydration solution (ORS), fruit
juice and other fluids containing electrolytes and sugar), avoid plain water.
● Give paracetamol for high fever if the patient is uncomfortable (10-15mg/kg/dose)
● Inform the patient about the warning signs
● Anti-emetics and H2 RB.
● NO NSAIDs or STEROIDs
● Review with FBC , 1st after 3 days of onset
● Advice to return immediately for review if Indications for hospitalization (Next
slide)
41. Indications for hospitalization:
● Suspect severe dengue and the need for hospitalisation when patient develops :
● Feeling of giddiness
● Cooler extremities compared to trunk & extremities
● Oliguria with dark urine
● Right hypochondriac pain or severe abdominal pain
● Bleeding from any site
● Persistent vomiting
● Lethatgy or irritability/restlessness
also
● Infants
● Obese
● Major co-morbidities
● Adverse social circumstances
49. Indicators for end of Critical Phase:
Stable vital signs
HCT becomes normal
Clinically improvement
Diuresis
50. 3. Convalescent Phase Management:
Lasts for 2-5 days
Steps in Management:
1. Change over to hypotonic fluid
2. Decrease infusion rate to 3-5 ml/kg BW/hr
3. Diuretics & digitalisation needed in patients with cardiac overload due to regurgitant fluid
Reabsorption of the extravasated fluid.
Complications
1. Fluid overload
2. Hypocalaemia
3. Nosocomial infections
52. Dos & Dont’s:Dos:
1. Avoid IM injections
2. Administer paracetamol for high fever
3. Use isotonic intravenous fluids for severe dengue
4. Give intravenous fluid volume just sufficient to maintain effective circulation
during period of plasma leakage for severe dengue
5. Tight glycemic control
Dont’s:
1. Administer aspirin or ibuprofen for fever
2. Use hypotonic intravenous fluids for severe dengue
3. Excessive or prolonged intravenous fluid during severe dengue
4. Unaware of effect of hyperglycemia on osmotic diuresis and hypovolemia
53. Primary causes of death in DHF:
Prolonged shock
1. >4 hrs organ failure
2. Liver failure 50% prognosis
3. Liver + Renal 10% prognosis
4. 3 organs(+ respiratory) very bad
Fluid overload
Features :-
1. Early- puffy eye lids, distended abdomen
2. (ascites), tachypnoea, mild dyspnoea
3. Late – Respiratory distress, SOB, &
4. wheezing
54. Patients with high risk for Complications:
1. Infants
2. Obese
3. Bleeding
4. Encephalopathy
5. Underline diseases
6. Pregnancy
Complications according to stage:
1- Febrile phase - Dehydration
2- Critical phase - Shock from plasma leakage: severe haemorrhage / organ impairment = DSS
3- Recovery phase - Hypervolaemia
55. Other Complications & Management:
A – Acidosis: NaHCO3 1ml/kg slow bolus (max 50ml) Diluted in equal volume of Normal Saline
B – Bleeding: Use Packed Red Cells 5ml/kg once
C – Calcium (hypocalcaemia): 1ml/kg of 10% Ca Gluconate,(max 10ml) Slow IV bolus over 15-20 mins,
Diluted in equal volume of NS Repeat 6 hourly,
S – Sugar (hypoglycaemia): Dextrose saline (0.9% NaCl with 5% Dextrose): Add 50ml 50% Dextrose to
450ml of 0.9% NaCl.
Hyponatremia: 3% NaCl is 3-5ml/kg Slow IV Through a larger vein; mostly a central vein
Encephalopathy: Mainly - Hepatic encephalopathy
56. Prognosis:Poor prognostic indicators include :
1. Early & profound shock with no detectable diastolic pressure or unrecordable BP
2. Delayed admission to hospital
3. DSS with gastrointestinal hemorrhage
Causes of death in a case of DHF/DSS :
1. Failing to recognise that a patient is in shock
2. Hemorrhages
3. Failing to recognise that patient has entered congestive phase
Sequelae:
1. Bradycardia & ventricular extra-systoles during convalescent stage
2. Profound asthenia with or without mental depression
57. Criteria that should be met before discharge:
No fever 24 hrs, without antipyretics
At least 2 days after recovery from shock
Generally good & Increasing appetite
Normal HCT for age. [baseline around 38-40% when not known]
No distress from pleural effusion or ascites
Rising platelet count & >50,000/mm3
No other complication
58. Signs of Recovery:
Stable pulse, BP & breathing rate
Normal temperature
No evidence of external/internal bleeding
Return of appetite
No vomiting
Good urinary output
Stable hematocrit
Convalescent confluent petechial rash
59. (10) Control and Prevention:
1. Vector Control (Insecticides, destroying breeding sites and larvae)
2. Individual Measures (Mosquito repellants & sprays, avoiding high risk areas,
using mosquito nets at night & wearing clothes that cover body)
3. Immunization (Sanofi Dengvaxia for all 4 serotypes)
60. Vector Control Methods:
1. Chemical Control
● Larvicides (organophosphorus compounds – fenthion ,abate) may be used to kill immature aquatic
stages
● Ultra-low volume fumigation ineffective against adult mosquitoes
● Mosquitoes may have resistance to commercial aerosol sprays
2. Biological control
● Largely experimental
● Option: place fish in containers to eat larvae
3. Environmental control
● Elimination of larval habitats
● Most likely method to be effective in the long term