Dr. Sachin Verma is a young, diligent and dynamic physician. He did his graduation from IGMC Shimla and MD in Internal Medicine from GSVM Medical College Kanpur. Then he did his Fellowship in Intensive Care Medicine (FICM) from Apollo Hospital Delhi. He has done fellowship in infectious diseases by Infectious Disease Society of America (IDSA). He has also done FCCS course and is certified Advance Cardiac Life support (ACLS) and Basic Life Support (BLS) provider by American Heart Association. He has also done a course in Cardiology by American College of Cardiology and a course in Diabetology by International Diabetes Centre. He specializes in the management of Infections, Multiorgan Dysfunctions and Critically ill patients and has many publications and presentations in various national conferences under his belt. He is currently working in NABH Approved Ivy super-specialty Hospital Mohali as Consultant Intensivists and Physician.

1. Dr. Sachin Verma MD, FICM, FCCS, ICFC
Fellowship in Intensive Care Medicine
Infection Control Fellows Course
Consultant Internal Medicine and Critical Care
Web:- http://www.medicinedoctorinchandigarh.com
Mob:- +91-7508677495
References;
1. Harrison´s principle of internal medicine -16th ed
2. Park´s textbook of preventive and social medicine -17th ed
3. www.cdc.org

2. DENGUE

3. Virus vector and transmission
Dengue Virus
Causes dengue and dengue hemorrhagic fever
Is an arbovirus
Transmitted by mosquitoes
Composed of single-stranded RNA
Has 4 serotypes (DEN-1, 2, 3, 4)

4. Dengue Viruses
Each serotype provides specific lifetime
immunity, and short-term cross-immunity
All serotypes can cause severe and fatal
disease
Genetic variation within serotypes
Some genetic variants within each serotype
appear to be more virulent or have greater
epidemic potential

5. Aedes aegypti
Dengue transmitted by
infected female mosquito
Primarily a daytime feeder
Lives around human
habitation
Lays eggs and produces
larvae preferentially in
artificial containers.
Diseases- yellow fever, filaria
dengue, chikungunya fever,
rift valley fever.

6. Aedes aegypti:
Distribution
throughout the world

7. Model of baseline transmission
potential (1961-1990 climate)

8. Model of future transmission
potential (2080s climate)

9. Population at % of total
risk (billions) population
Population increase only
2050s 3.2 34
2080s 3.5 35
Population increase plus
climate change (HADCM2)
2050s 4.1 44
2080s 5.2 52

10. Replication and Transmission
of Dengue Virus
1. Virus transmitted 1
to human in mosquito
saliva
2
2. Virus replicates 4
in target organs
3. Virus infects white 3
blood cells and
lymphatic tissues
4. Virus released and
circulates in blood

11. Replication and Transmission
of Dengue Virus
5. Second mosquito 6
ingests virus with blood
6. Virus replicates
in mosquito midgut 7
and other organs,
infects salivary
glands 5
7. Virus replicates
in salivary glands

12. Transmission of Dengue Virus
by Aedes aegypti
Mosquito feeds / Mosquito refeeds /
acquires virus transmits virus
Extrinsic Intrinsic
incubation incubation
period period
Viremia Viremia
0 5 8 12 16 20 24 28
DAYS
Illness Illness
Human #1 Human #2

13. Clinical Manifestations of Dengue and
Dengue Hemorrhagic Fever
Undifferentiated fever
Classic dengue fever
Dengue hemorrhagic fever
Dengue shock syndrome

14. Undifferentiated Fever
May be the most common manifestation of
dengue
Prospective study found that 87% of patients
infected were either asymptomatic or only mildly
symptomatic
Other prospective studies including all age-
groups also demonstrate silent transmission.

15. Clinical Characteristics
of Dengue Fever
Fever
Headache
Muscle and joint pain
Nausea/vomiting
Rash
Hemorrhagic manifestations

16. Hemorrhagic Manifestations
of Dengue
Skin hemorrhages: petechiae, purpura,
ecchymoses
Gingival bleeding
Nasal bleeding
Gastro-intestinal bleeding:
hematemesis, melena, hematochezia
Hematuria
Increased menstrual flow

17. Signs and Symptoms of
Encephalitis/Encephalopathy
Associated with Acute Dengue
Infection
Decreased level of consciousness:
lethargy, confusion, coma
Seizures
Nuchal rigidity
Paresis

18. Clinical Case Definition for
Dengue Hemorrhagic Fever
4 Necessary Criteria:
Fever, or recent history of acute fever
Hemorrhagic manifestations
Low platelet count (100,000/mm 3 or less)
Objective evidence of “leaky capillaries:”
– elevated hematocrit (20% or more over
baseline)
– low albumin
– pleural or other effusions

19. Four Grades of DHF
Grade 1
– Fever and nonspecific constitutional symptoms
– Positive tourniquet test is only hemorrhagic
manifestation
Grade 2
– Grade 1 manifestations + spontaneous bleeding
Grade 3
– Signs of circulatory failure (rapid/weak pulse, narrow
pulse pressure, hypotension, cold/clammy skin)
Grade 4
– Profound shock (undetectable pulse and BP)

20. Danger Signs in
Dengue Hemorrhagic Fever
Abdominal pain - intense and sustained
Persistent vomiting
Abrupt change from fever to
hypothermia, with sweating and
prostration
Restlessness or somnolence

21. Clinical Case Definition for Dengue
Shock Syndrome
4 criteria for DHF
Evidence of circulatory failure manifested
indirectly by all of the following:
– Rapid and weak pulse
– Narrow pulse pressure (≤ 20 mm Hg) OR
(
hypotension for age
– Cold, clammy skin and altered mental
status
Frank shock is direct evidence of circulatory
failure

22. Risk Factors Reported for DHF
Virus strain :DHF risk is greatest for DEN-2, followed
by DEN-3, DEN-4 and DEN-1
Pre-existing anti-dengue antibody
– previous infection
– maternal antibodies in infants
Host genetics-females more affected,
malnutrition protective.
Age(<12)

23. Unusual Presentations
of Severe Dengue Fever
Encephalopathy
Hepatic damage
Cardiomyopathy
Severe gastrointestinal hemorrhage

24. Increased Probability of DHF
Hyperendemicity
Increased circulation Increased probability
of viruses of secondary infection
Increased probability of Increased probability of
occurrence of virulent strains immune enhancement
Increased probability of DHF

25. Pathogenesis of DHF
STEP 1- Homologous Antibodies Form Non-
infectious Complexes
1
1
1
1
Dengue 1 virus
Neutralizing antibody to Dengue 1 virus
Non-neutralizing antibody
1 Complex formed by neutralizing antibody and virus

26. STEP2- Heterologous Antibodies of first
serotype infection form Infectious Complexes
with second serotype
2
2 2
2
2
Dengue 2 virus
Non-neutralizing antibody to Dengue 1 virus
2
Complex formed by non-neutralizing antibody
and virus

27. STEP3 - Heterologous Complexes Enter More
Monocytes, Where Virus Replicates
2
2
2
2
2
2
2 2
2
2
2 Dengue 2 virus
Non-neutralizing antibody
2 Complex formed by non-neutralizing
antibody and Dengue 2 virus

28. STEP4 –DHF pathogenesis
Infected monocytes release vasoactive
mediators, resulting in increased vascular
permeability and hemorrhagic manifestations
that characterize DHF and DSS

29. Clinical Evaluation in Dengue Fever
Blood pressure
Evidence of bleeding in skin or other sites
Hydration status
Evidence of increased vascular
permeability-- pleural effusions, ascites
Tourniquet test

30. Petechiae

31. Tourniquet Test
Inflate blood pressure
cuff to a point midway
between systolic and
diastolic pressure for 5
minutes
Positive test: 20 or more
petechiae per 1 inch2
(6.25 cm2)

32. Laboratory Tests
in Dengue Fever
Clinical laboratory tests
– CBC--WBC, platelets, hematocrit
– Albumin
– Liver function tests
– Urine--check for microscopic hematuria
Dengue-specific tests
– Virus isolation
– Serology

33. Laboratory Methods for Dengue Diagnosis-
Virus isolation to determine serotype of
the infecting virus
IgM ELISA test for serologic diagnosis

34. Virus isolation: cell culture, mosquito inoculation&
fluroscent antibody test

35. ELISA Plate

36. Collection and Processing of
Samples for Laboratory
Diagnosis
Type of Time of Type of
Specimen Collection Analysis
Acute-phase When patient presents; Virus isolation
blood collect second sample and/or serology
(0-5 days after onset) during convalescence
Convalescent-phase Between days 6 and 21 Serology
blood after onset
(≥ 6 days after onset)

37. Temperature, Virus Positivity
and Anti-Dengue IgM , by
Fever Day
Temperature (degrees Celsius)
100
Dengue IgM (EIA units)
300
39.5
Percent Virus Positive
80
39.0 225
38.5 60
150
38.0 40
37.5 20 75
37.0
0 0
-4 -3 -2 -1 0 1 2 3 4 5 6
Fever Day
Mean Max. Temperature Virus Dengue IgM

38. Management of dengue fever
Outpatient Triage
No hemorrhagic manifestations and patient is
well-hydrated: home treatment
Hemorrhagic manifestations or hydration
borderline: outpatient observation center or
hospitalization
Warning signs (even without profound shock) or
DSS: hospitalize

39. Warning Signs for Dengue Shock
Alarm Signals:
Alarm Signals:
•• Severe abdominal pain
Severe abdominal pain
•• Prolonged vomiting
Prolonged vomiting
Four Criteria for DHF:
Four Criteria for DHF: •• Abrupt change from fever
Abrupt change from fever
•• Fever
Fever
•• Hemorrhagic manifestations
Hemorrhagic manifestations
•• Excessive capillary permeability
Excessive capillary permeability
••≤ 100,000/mm33platelets
≤ 100,000/mm platelets
to
to
hypothermia
hypothermia
Initial Warning Signals:
Initial Warning Signals: • Change in level of
Change in level of
•• Disappearance of fever •WhenPatients Develop DSS:
When Patients Develop DSS:
Disappearance of fever consciousness (irritability
consciousness (irritability
•• Drop in platelets
Drop in platelets •• 3 to 6 days after onset of
3 to 6 days after onset of
•• Increase in hematocrit
Increase in hematocrit
or
or
symptoms
symptoms
somnolence)

40. Treatment of Dengue Fever
Fluids
Rest
Antipyretics (avoid aspirin and non-
steroidal anti-inflammatory drugs)
Monitor blood pressure, hematocrit,
platelet count, level of consciousness

41. Treatment of Dengue Fever
Continue monitoring after defervescence
If any doubt, provide intravenous fluids, guided
by serial hematocrits, blood pressure, and urine
output
The volume of fluid needed is similar to the
treatment of diarrhea with mild to moderate
isotonic dehydration (5%-8% deficit)

42. Rehydrating Patients Over 40 kg
Volume required for rehydration is twice the
recommended maintenance requirement
Formula for calculating maintenance volume:
1500 + 20 x (weight in kg - 20)
For example, maintenance volume for 55 kg
patient is: 1500 + 20 x (55-20) = 2200 ml
For this patient, the rehydration volume would
be 2 x 2200, or 4400 ml.

43. Treatment of Dengue Fever
Avoid invasive procedures when
possible
Unknown if the use of steroids,
intravenous immune globulin, or platelet
transfusions to shorten the duration or
decrease the severity of
thrombocytopenia is effective
Patients in shock may require treatment
in an intensive care unit

44. Indications for Hospital
Discharge
Absence of fever for 24 hours (without
anti-fever therapy) and return of appetite
Visible improvement in clinical picture
Stable hematocrit
3 days after recovery from shock
Platelets ≥ 50,000/mm3
No respiratory distress from pleural
effusions/ascites

45. Common Misconceptions about
Dengue Hemorrhagic Fever
Dengue + bleeding = DHF
Need 4 WHO criteria, capillary permeability
DHF kills only by hemorrhage
Patient dies as a result of shock
Poor management turns dengue into DHF
Poorly managed dengue can be more severe, but DHF is a
distinct condition, which even well-treated patients may
develop
Positive tourniquet test = DHF
Tourniquet test is a nonspecific indicator of capillary
fragility

46. DHF is a pediatric disease
All age groups are involved in the
Americas
DHF is a problem of low income
families
All socioeconomic groups are affected
Tourists will certainly get DHF with a
second infection
Tourists are at low risk to acquire DHF

47. Vector Control Methods:
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

48. Vector Control Methods:
Biological and Environmental
Control
Biological control
– Largely experimental
– Option: place fish in containers to eat
larvae
Environmental control
– Elimination of larval habitats
– Most likely method to be effective in the
long term

49. Purpose of Control
Reduce female vector density to a level
below which epidemic vector
transmission will not occur
Based on the assumption that
eliminating or reducing the number of
larval habitats in the domestic
environment will control the vector
The minimum vector density to prevent
epidemic transmission is unknown