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VIRUSES
Dr.Nuchin MD,MBA.
2005 3 __________
2006 5 __________
2007 9 __________
2008 5 ___________
2009 52
History
The exact origins of the disease are not clear
It is said that it originated in Africa and was spread
worldwide with the slave trade.
The name dengue is derived from the Swahili "Ka-
Dinga pepo" that describes the disease as a sudden
cramp like disease caused by an evil spirit.
In the wild- The virus has a life cycle very similar to
that of yellow fever involving passing between
primates living in the jungle canopy and mosquitoes
that feed on them.
It is believed that the virus was transferred to
man by the bite of the tiger-striped mosquito
(Aedes albopticus) as man began clearing the
jungle and building settlements.
The commonest vector is now the closely-
related mosquito Aedes aegypti which is
African in origin but has spread throughout the
tropics in the Old and New Worlds.
Contnd..
The earliest reports of a dengue-like disease are
from Chin Dynasty China (265-420 AD).
gy
Inter play of three factors
Host
Interaction
Family Flaviviridae
Genus Flavivirus
Serotypes Den1,2,3 &4
Single stranded positive sense enveloped
RNA viruses
50-60 nm
Four serotypes are there (DEN-1, 2, 3, 4)
The virus was isolated by Sabin in 1944
3. Dengue enters
WBCs & lymphatic
tissue
4. Dengue enters blood
circulation http://phil.cdc.gov/PHIL_Images/08051999/00004/dengue_phf/sld0
Then, within the mosquito, the virus replicates
during an extrinsic incubation period of 8-12 days.
Central Peripheral
Undifferentiated
Fever
Without haemorrhage
With unusual
haemorrhage
1.Headache
2.Muscle and joint pain (severe-break-bone
fever)- >78%
3.Nausea/vomiting
4. Retro orbital pain
(Rash- During the first half of the febrile period- diffuse flushing, mottling or fleeting pin-point
eruptions on the face, neck and chest
It becomes maculopapular or scarletiniform on 3rd -4th day- It starts on the chest and trunk and
spreads to extremities and rarely spreads to face. It may be accompanied by itching and
hyperaesthesia. The rash lasts for 2 hours to several days and may be followed by
desquamation.)
2.5
cm
Hepatomegaly
http://www.cdc.gov/ncidod/dvbid/dengue/slideset/set1/images/petechiae2-small.jpg
Subconjunctival
haemorrhage
Other common symptoms include-
Extreme weakness
Anorexia
Constipation
Altered taste sensation
Colicky pain and abdominal tenderness
Dragging pain in inguinal region
Sore throat
General depression
What is the end result?
Nasal bleeding
Gastro-intestinal bleeding:
haematemesis, melena,
haematochezia
Hematuria
2. Hemorrhagic manifestations
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)
DENGUE GRADATION
http://w3.whosea.org/en/Section10/Section332/Section554_25
DISEASE SPECTRUM
MILD SEVERE
DF DHF
+ Thrombocytopenia +++
Thrombocytopenia
Hidden Vasc. Perm1?
Overt Vasc. Perm.
DF DENGUE PATHOGENESIS
DHF
DSS
Ag-Ab-complement complex
Serous
-Fever
effusion
-Flushed face Hepatomegaly Dead
(pleural, ascite)
-Headache
-Retro-orbital Hypoprotidemia Acidosi
pain s
-Myalgia ↑ capillary Hypovolemia
Shock Anoxia
-Arthralgia permeability (haemoconcentratio
n)
-Rash
Thrombocytopenia* DIC
- Intestinal
Haemorrhagi
c haemorrhag
e
manifestation
*Trombocytopenia is not constant in 68
-Leucopenia DF
Danger Signs in DHF that
predict progression to DSS
Abdominal pain - intense
and sustained
Persistent vomiting
Abrupt change from fever
to hypothermia, with
sweating and prostration
Restlessness or somnolence
This thermometer illustrates the developments in the
illness that are progressive warning signs that DSS may
occur.
The initial evaluation is made by determining how many
days have passed since the onset of symptoms.
Most patients who develop DSS do so 3-6 days after onset
of symptoms. Therefore, if a patient is seven days into the
illness, it is likely that the worst is over.
If the fever goes between three and six days after the
symptoms began, this is a warning signal that the patient
must be closely observed, as shock often occurs at or
around the disappearance of fever.
Other early warning signs to be alert for include a drop in
platelets, an increase in hematocrit, or other signs of plasma
leakage.
If you document hemoconcentration and thrombocytopenia
and other signs of DHF and the patient meets the criteria for
DHF, the prognosis and the patient's risk category have
changed. Though dengue fever does not often cause
fatalities, a greater proportion of DHF cases are fatal.
The next concern would be observation of the danger signs—
severe abdominal pain, change in mental status, vomiting
and abrupt change from fever to hypothermia. These often
herald the onset of DSS.
The goal of treatment is to prevent shock. The plasma
leakage syndrome is self-limited. If you can support the
patient through the plasma leakage phase and provide
sufficient fluids to prevent shock, the illness will resolve
itself.
PURPURA
http://www.pediatrics.wisc.edu/education/derm/tutb/85m.jpg
ECCHYMOSIS
http://www-medlib.med.utah.edu/WebPath/ATHHTML/ATH036.html
NASAL HEMORRHAGING
http://www.cgste.mq/brainstorm/dengue/image/hemo.gif
Criteria for clinical diagnosis
of Dengue Shock Syndrome
1. 4 criteria for DHF
previous infection
Infection 24%
76%
Asymptomatic Clinical Cases 6%
Infection 94%
DF DHF/DSS
(non-DHF) 0.8%
99.2%
survive Death
B
A
Vaughn DW, Green S, Kalayanarooj S, et al. Dengue in the early febrile
phase: viremia and antibody responses. J Infect Dis 1997; 176:322-30.
Laboratory diagnosis
Laboratory diagnosis is essential for confirmation of
dengue virus infections.
Routine lab tests
1)CBC- WBC, Platelets, Haematocrit
(Adults: Females 0.36 - 0.44 Males 0.39 - 0.50)
2)Albumin
3)Liver function test
4)Urine- for microscopic hematuria
Dengue specific tests
Virus isolation
PCR
Serology ( IgM or
rising IgG titre)-
MAC ELISA IgM
capture test is done
at DSU- Belgaum
Temperature, Virus Positivity and
Anti-Dengue IgM , by Fever Day
Temperature (degrees Celsius)
100
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
Adapted from Figure 1 in Vaughn et al.,
J Infect Dis, 1997; 176:322-30.
Primary Infection
MANAGEMENT OF DF
100
MANAGEMENT OF
DHF
MANAGEMENT OF DHF
101
MENAGEMENT OF
DHF
GRADE I & II
Type of IV fluids
103
Crystalloid solutions
- 5%D/NSS
- 5%D/N/2* (only for < 1 year of age)
- 5%DLR
- 5%DAR
Colloid solutions
- 10% Dextran 40
- 10% Haes-Sterile
2. No improvement, stationary:
Pulse and BP not changed and still having
oliguria
4. More aggravation:
weak and rapid pulse or not detectable,
narrow pulse pressure, hypotension or not
measurable blood pressure
106
MANAGEMENT OF DHF
GRADE III
Type of solutions
107
Crystalloid solutions:
- 5%D/NSS
- 5%DLR*
- 5%D/AR
Colloid solution:
- Dextran 40
- Fresh whole blood
(FWB)
* Lactate Ringer solutions are contra-indicated
in case of acidosis.
NSS or Acetate Ringer should be used instead of LR
in case of shock
IV fluid therapy for DHF grade III
Ht immediately, IV fluid 10ml/kg/h
crystalloid solutions over 1 – 2h +
108
oxygen
Improvement No improvement
Control Ht
↓ IV to 6 ml/kg/h
over 3h Ht ↑ Ht ↓
Further Improvement Dextran 40 10ml/kg/h FWB 10ml/kg/h
↓IV to 3 ml/kg/h and repeated if
over 6h necessary (not exceed
30ml/kg/day)
Always
improvement
No improvement Improvement
↓IV to 1.5 ml/kg/h ↓ IV fluid of crystalloid
ASCB* see
over 24 – from 10 → 6 →
complications
48h and 3 → 1.5 ml/kg/h
guideline
stop
109 A – Acidosis (Bicarbonate Na 8.4%
1ml/kg/dose)
S – Blood sugar (<60mg%) →
D10% 5ml/kg/dose.
C – Calcemia ( Ca gluconate 10%
1ml/kg/dose Max: 1 ampoule
B- Bleeding → Blood Transfusion,
Platelet Transfusion
OXYGEN USED IN SHOCK
110
CASES
If shock: oxygen (nasal
prongs)
- Infant < 1 year = 1L/min
- Children > 1 year = 2L/min
111
MANAGEMENT OF DHF
GRADE IV
(PROFOUND SHOCK)
112
Type of solutions
Crystalloid solutions:
- NSS
- AR
Colloid solution:
- Dextran 40
- Fresh Whole Blood
IV fluid therapy for DHF grade IV
NSS or AR 10ml/kg bolus
113
Improvement No improvement