Professional Documents
Culture Documents
4
Replication and transmission
of dengue virus (Part 1)
1. Virus transmitted 1
to human in mosquito
saliva
2
2. Virus replicates
4
in target organs
6. Virus replicates
in mosquito midgut
and other organs,
infects salivary
7
glands
7. Virus replicates
5
in salivary glands
6
Pathophysiology
7
PATHOPHYSIOLOGY
Dengue Infection
Antibody Formation
Re-infection
Serotype cross-
reactive Ab
Virions + non-
neutralizing Ab
T cells activation
Cytokines +
complements
activation
Capillary Leak
(Rothman, 2004) 9
DHF is not a continuum of DF
Dengue
Self-limited
Viral direct effect Fever
Dengue Virus
infection
Dengue Life-threatening
Secondary infection + Haemorrhagic
Enhanced antibodies DHF is not
Fever
DF plus bleeding
10
Manifestation of dengue virus infection
Dengue virus infection
Asymtomatic Symtomatic
Hemokonsentrasi
Dehidrasi
Hipoproteinemia Kebocoran Plasma I
Perdarahan masif : IV
perdarahan saluran
cerna (tersembunyi),
Kematian perdarahan otak, dll
DBD/SSD
13
Demam Dengue
Course of dengue illness
Shock/Bleeding
Dengue: Guidelines for diagnosis, treatment, prevention and control, TDR-WH0 2009
14
Febrile phase
Febrile phase
• Facial flushing • (+) TT increases the
• Skin erythema probability of dengue
• Generalized body ache • (+) hemorrhagic
• Myalgia and arthralgia manifestations
• Headache • Enlarged and tender liver
• Sorethroat, injected pharynx, • Abnormality: progressive
and conjunctival injection decrease in total wbc
• Anorexia, nausea and
vomiting
Dengue: Guidelines for diagnosis, treatment, prevention and control, TDR-WH0 2009
15
Critical phase
Critical phase
• Temp drops to 37.5-38 • if (-) increase in • Shock: critical volume
(days 3-7) capillary permeability of plasma is lost
• (+) increase in capillary improve • Temperature may be
permeability with • if (+) increase in subnormal
increasing hematocrit
levels capillary permeability • Prolonged shock
• Significant plasma pleural effusion and organ hypoperfusion
leakage lasts for 24-48 ascites organ impairment,
hours • Degree of increase metabolic acidosis,
• Progressive leukopenia above the baseline and DIC severe
followed by rapid hematocrit reflects the hemorrhage
decrease in platelet severity of plasma • Severe hepatitis,
precedes plasma leakage encephalitis or
leakage myocarditis
Dengue: Guidelines for diagnosis, treatment, prevention and control, TDR-WH0 2009
16
Recovery phase
Recovery phase
• Gradual reabsorption of • Hematocrit stabilizes or may be
extravascular compartment fluid (48- lower due to dilutional effect of
72 hours) reabsorbed fluid
• General well-being improves, • Wbc starts to rise
appetite returns, GI symptoms abate, • Recovery of platelet count occurs
hemodynamic status stabilizes and later
diuresis ensues
• (+) rash: “isles of white in the sea of
red”
Dengue: Guidelines for diagnosis, treatment, prevention and control, TDR-WH0 2009
17
Pemeriksaan penunjang
• Pemeriksaan darah serta serologi
• DL, LFT, RFT, BG, Coagulation profile, BGA, Electrolyte, lactate, NS1,
Igm/IgG anti-dengue
• EKG
• Pemeriksaan Radiologis
• Foto Thoraks
• USG
• Penunjang lainnya sesuai indikasi
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Diagnosis of dengue
• Antibody detection
• Hemagglutination Inhibition
(HAI)
• IgM & IgG
• Antigen detection
• NS1
• RNA detection
• RT-PCR
• Viral isolation
19
Approximate timeline of primary and secondary dengue virus infections and
the diagnostic methods that can be used to detect infection
NS1 detection
Virus isolation
RNA detection
Viraemia
O.D
IgM primary
IgM secondary
HIA
>25
IgG secondary
O.D 60
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WHO Guidelines on dengue
2009
1997 2011
22
Criteria for clinical diagnosis of
DHF (2011)
• Clinical manifestations
• Fever: acute onset, high and continuous, lasting two to
seven days in most cases
• Any of the following haemorrhagic manifestations
including a positive tourniquet test (the most common),
petechiae, purpura, ecchymosis, epistaxis, gum
bleeding, and haematemesis and/or melena
• Laboratory findings
• Thrombocytopenia (100 000 cells per mm 3 or less)
• Haemoconcentration; haematocrit increase of ≥20%
from the baseline, plasma leakage : pleura effusion,
ascites, hypoproteinemia / hypoalbuminemia
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Classifications
1997 2009 2011
Dengue Fever Dengue without warning signs Dengue Fever
DHF grade I
DHF grade I
Dengue with warning signs
DHF grade II
DHF grade II
EXPANDED DENGUE
SYNDROME
WHO 2011 Classification of Dengue Infections
and Grading of Severity of DHF
DF/DHF Grade Symptoms Laboratory
DF Fever with two of the following: Leucopenia (wbc ≤5000
Headache, etro-orbital pain, Myalgia, cells/mm 3 ), Thrombocytopenia
Arthtralgia/bone pain, (Platelet count <150 000
Rash,Haemorrhagic manifestations, No cells/mm 3 ), Rising haematocrit
evidence of plasma leakage. (5% – 10% ),
No evidence of plasma loss
DHF I Fever and haemorrhagic manifestation Thrombocytopenia
(positive tourniquet test) and evidence of <100,000, Hct rise >20%
plasma leakage
DHF II As in Grade I plus Thrombocytopenia
Spontaneous bleeding. <100,000, Hct rise >20%
DHF III As in Grade I or II plus Thrombocytopenia
Circulatory Failure (weak pulse, narrow <100,000, Hct rise >20%
pulse pressure(≤20 mmHg),
hypotension,restlessness).
DHF IV As in Grade III plus profound shock Thrombocytopenia
with undetectable BP and pulse <100,000, Hct rise >20%
25 25
Expanded dengue syndrome
NEUROLOGICAL
Febrile seizures in young children. CARDIAC
Encephalopathy. Conduction abnormalities.
Encephalitis/aseptic meningitis. Myocarditis.
Intracranial haemorrhages/thrombosis. Pericarditis.
Subdural effusions.
Mononeuropathies/polyneuropathies/GBS
Transverse myelitis.
RESPIRATORY
GASTROINTESTINAL/HEPATIC Acute respiratory distress
Hepatitis/fulminant hepatic failure. syndrome.
Acalculous cholecystitis. Pulmonary haemorrhage.
Acute pancreatitis.
Hyperplasia of Peyer’s patches.
OTHERS
Acute parotitis.
MUSCULOSKELETAL
RENAL Myositis with raise CPK
Acute renal failure. Rabdomyolysis
Hemolytic uremic syndrome.
Maheshwari A. Atypical manifestations of dengue. Trop Med Int Health. 2007 Sep.; 12(9):1087 – 95 26
Warning signs (2009)
• Abdominal pain or tenderness
• Persistent vomiting
• Clinical fluid accumulation
• Mucosal bleed
• Lethargy, restlessness
• Liver enlargment >2 cm
• Laboratory: increase in HCT concurrent with rapid
decrease in platelet count
27
High-risk patients (2011)
The following host factors contribute to more severe disease and
its complications:
•Infants and the elderly
•Obesity
•Pregnant women
•Peptic ulcer disease
•Women who have menstruation or abnormal vaginal bleeding
•Haemolytic diseases
•Thalassemia and other haemoglobinopathies
•Congenital heart disease
•Chronic diseases such as diabetes mellitus, hypertension, asthma,
ischaemic heart disease
•Chronic renal failure, liver cirrhosis
•Patients on steroid or NSAID treatment
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Clinical management
• Complex pathogenesis and manifestations BUT,
relatively simple and inexpensive treatment
• No spesific treatment rely on fluid management
• The most effective way to reduce incidence and
morbidity vector control
• Potential manegement: vaccine and anti-viral
drugs
29
DF & DHF in Febrile Phase
• Parcetamole
• Physical methods of controlling fever
• Don’t use Aspirin and NSAID
• Fluid to maintain nutrition and hydration
Recognize the Time of Entry to the Critical Phase
( when blood vessels become leaky)
• Dropping platelet count below 100 000/dl
• Rising HCT & Evidence of plasma leakage
30
Choice of fluids
Crystalloid Colloid
Ringer’s lactate Dextran 40 in saline
Ringer’s acetate Hydroxyethyl strach (HES)
0.9% saline Gelatin solutions
5% dextrose 0,9%
5% dextrose 1/2 saline
32
Fluid management in DHF gr I & II
Kalayanarooj S. and Nimmannitya S. In: Guidelines for Dengue and Dengue Haemorrhagic Fever Management. Bangkok
Medical Publisher, Bangkok 2003.
33
Fluid management in DHF gr III Dengue: Guidelines for diagnosis,
treatment, prevention and control,
(systolic pressure maintained + signs of reduced perfusion) TDR-WH0 2009
36
Fluid management in DSS
Fluid bolus 10- 20 ml/kg crystalloid/ 15 mt
NO IMPROVEMENT IMPROVEMENT DHF gr III
Hypotensive shock
Fluid resuscitation with 20ml/kg isotonic crystaloid or colloid
over 15 minutes
Try to obtain a HCT level before fluid resuscitation
IMPROVEMENT
No
Yes
Review 1st HCT
Crystaloid/colloid 10 ml/kg/hr for 1 HCT or High HCT
hour, then continue with :
In cristaloid 5-7 ml/kg/hr for 1-2 hours Administer 2nd bolus fluid (colloid) Consider significant occult/overt bleed
Reduce to 3-5 ml/kg/hr for 2-4 hours 10-20 ml/kg over 1/2 hour Initiate transfusion with fresh whole
Reduce to 2-3 ml/kg/hr for 2-4 hours blood
IMPROVEMENT
No
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Yes Repeat 3sd HCT
Fluid management in DSS IV Adjust on shock grade III, IV
Name…………………..BW……………….kg. M=………….CC/days………..cc/hr M+5%=……….….CC/days………..cc/hr
10 6 hrs…….cc
9 10-5 ml/kg/hr
(200-120 ml/hr)
8
7 8 hrs…….cc
IV Transfusion
(ml/kg/hr)
6 5-3 ml/kg/hr
5 (120-80 ml/hr) 18 hrs…….cc
4 3-1.5 ml/kg/hr
3 (80-40 ml/hr) 24 hrs…….cc
2 1.5 ml/kg/hr-KVO
(40 ml/hr-KVO)
1
0
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
shock Rate of KV fluid for children (Rate for adults) hour
Hour 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
1
Time
Type IV
Intake
Urine (mL)
Hct (%)
Kalayanarooj S. and Nimmannitya S. In: Guidelines for Dengue and Dengue Haemorrhagic Fever Management. 39
Bangkok Medical Publisher, Bangkok 2003.79
Tatalaksana perdarahan masif
• Sumber pedarahan diidentifikasi, mis : epitaxis
dikontrol dgn nasal packing
• Perdarahan saluran cerna diberikan H-2 antagonis
atau PPI, monitor HCT
• Tranfusi darah segera diberikan, 10 ml/kg WB atau
PRC
• Trombosit konsentrat / fresh frozen plasma (FFP)
meningkatkan resiko kelebihan cairan
40
Fase pemulihan
• Perbaikan parameter klinis serta hemodinamik
• HCT kembali ke base line atau lebih rendah
• Cairan intravena dihentikan cegah overload
• Pada pasien dengan efusi masif dan ascites,
hypervolemia dapat terjadi dan terapi diuretik
dapat dipertimbang untuk mencegah edema paru
41
Criteria for transfer IGD Soetomo
• Early presentation with shock (on days 2 or 3 of
illness)
• Severe plasma leakage and/or shock
• Undetectable pulse and blood pressure
• Severe bleeding
• Fluid overload
• Organ impairment (such as hepatic damage,
cardiomyopathy, encephalopathy, encephalitis and
other unusual complications) Expanded dengue
syndrome
42
Kriteria KRS
• Tidak ada demam dalam 24 jam terakhir, tanpa
antipiretik
• Kembalinya nafsu makan
• Perbaikan klinis yang nyata
• Produksi urin yang baik
• Setidaknya 2-3 hari setelah sembuh dari syok
• Tidak ada distres nafas
• Tidak ada asites
• Trombosit lebih dari 50000 sel/mm3
43
Key message
44
TERIMA KASIH
Jalur triase untuk infeksi dengue
Demam dengan dugaan manifestasi perdarahan akibat dengue, sakit kepala,
nyeri retro orbital, mialgia, atralgia/nyeri tulang, ruam kulit
Uji torniquet
Source: Holiday M.A., Segar W.E.. Maintenance need for water in parenteral fluid therapy. Pediatrics 1957;19: 823.78
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