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  • DENGUE

    50-100 10,000 RNA family Flaviviridae 4 serotype DEN1 DEN2 DEN3 DEN4 serotype serotype (homotypic immunity) serotype (heterotypic immunity) serotype Aedes aegypti 7-10 28-35 C 3-15 5-6 1 1-3 (dengue hemorrhagic fever, DHF) hyperendemic area DHF ..2497 (dengue fever, DF) ..2501

  • 4

    5 3-4 6 seroconversion dengue antibody 4.7 7 DF DHF8-11 DHF serotype DEN-2 12

    20 50-150 100,000 200-300 100,000 0.15 5-9 15-25 20-30

  • DF DHF (dengue shock syndrome , DSS)4,13

    serotype serotype 14 serotype 2 15

    6-9 dengue antibody (non-neutralizing antibody) enhancing antibody Antibody dependent enhancement serotype enhancing antibody serotype monocyte15,16 17 T B cells chemokines T cell autoantibody vasculopathy autoantibody Lei HY cytokines monocytes endothelial cell 1-3,15,18

  • aspartate aminotrans ferase (AST) alanine aminotransferase (ALT) AST ALT albumin globulin partial prothrombin time (PTT) prothrombin time (PT) alkaline phosphatase (AP) bilirubin albumin globulin AST/ALT PTT DHF DF2,19

    6 2 20 21 1-3,20,21 90 3 22 1. Undifferentiated fever viral syndrome maculopapular 2. DF break bone fever tourniquet

  • 3. DHF plasma plasma hematocrit pleural effusion ascites plasma 24-48 tourniquet coagulopathy DHF 3 1. (febrile stage) 39-41 C 2-7 17 7 (flushing) tourniquet 80-85 2. (shock or hemorrhagic stage) plasma plasma pulse pressure 3. (convalescent stage) plasma petechial rash convalescent rash

    4 grade grade 1 tourniquet grade 2 grade 3 pulse pressue grade 4 DHF grade 3 4 DSS23

    Dengue infection: A new classification

  • New classification Dengue infection 24

    () serotype

  • 6-9 dengue antibody (neutralizing antibody) enhancing antibody serotype 1-3

    .. 2513 (ARDS) serum amylase (co-infection, dual infection) 1-3

    ..2530 DF DHF 25,26 virus infection retrospective study viral hemorrhagic fever 2 ..1997-1998 722 140 serology27,28 rapid colloidal gold-based immunochromatography specificity 8829,30 hemaglutination-inhibiton test (HI)22 DHF 23 DF 89 DHF 51 15-67 26 40

  • retrospective study 90 30 31 leukopenia thrombocytopenia serious bacterial infection typhus malaria serology 30-40

    serology DF DHF break bone fever DF DHF DF DF specificity 50 touniquet test serology DF DHF DF DF peptic ulcer NSIADS ( DF with unusual bleeding) DHF DF hemoconcentration plasma hematocrit hemoconcentration pleural effusion ascites

    ( 1) DF DHF 80 5 7 27,28,32 9 9 1023 9 1 (dual infection) biphasic fever

  • 25 5 23,27,28,33 2-5 (flush face) petechiae 1-2 DF (break bone fever) muscle enzyme CPK DF rhabdomyolysis 1 (DF, DHF) (..1997-98) 27,28

    Dengue severity DF (n=89)

    DHF (n=51)

    Age: mean+SD (years) range (years) Total duration of fever : mean+SD (days) range (days) Fever Nausea/vomiting Headache Diarrhea Myalgia Abdominal pain Hemorrhagic manifestations Petechiae Epistaxis Gum bleeding Hematemesis

    28.6+13.2 15-67

    5.2+1.10

    2-8 100% 40.4% 38.2% 33.3% 25.8% 12.3% 24.7% 14.6% 4.4% 5.5% 0%

    23.4+7.6 15-44

    5.2+1.0

    3-8 100% 58.8% 37.3% 21.2% 25.6% 43.1% 54.9% 35.2% 14.3% 10.2% 5.9%

  • Vaginal bleeding (female only) Bleeding > 2 sites Rash (convalescence) Hypotension/pulse pressure < 20 mmHg Jaundice Epigastrium or right upper quandrant tenderness Hepatomegaly Splenomegaly (by ultrasonography) Ascites (by ultrasonography) Pleural effusion (by chest x-ray)

    21% 6.7%

    31.5% 0% 0%

    10.1% 11.2%

    0% 0% 0%

    31.6% 19.6% 21.6% 5.8% 1.9%

    29.4% 39.2% 5.9% 9.8%

    29.4%

    5-8 50,000 20,000/mm3 AST, ALT PT/PTT DHF disseminated intravascular coagulopathy (DIC) coagulopathy DHF PTT (petechial hemorrhage) 1 4 9-20 5.6 27,28,31,34,35 32

  • DHF 2 DF27,28,33 DF 36,37 hypotension shock (gastric, duodenal ulcer) gastritis H2 blocker aspirin NSAIDs peptic ulcer DHF DF DF27,28 DHF shock DIC

    intracranial bleeding, pulmonary hemorrhage, splenic rupture DHF DHF DHF DF DHF 47,200 22,800/mm3 ( 2) DHF 20,000/mm3 50 grade III IV 23,27,28 (hemolysis) hemoglobinopathy HbH disease, thalassemia (mild unconjugated hyperbilirubinemia) (platelet concentration) 20,000/mm3 38 (active bleeding)

  • 48-72 1

    narrowing of pulse pressure 6 DHF 23,27,28 DHF hypotension 20 DHF plasma hematocrit pleural effusion ascites urine specific gravity hematocrit prolonged shock sinus tachycardia sinus bradycardia relative bradycardia 1-2 EKG abnormalities 40-60 bradycardia conduction defects 1st 2nd degree A-V block premature ventricular contraction (PVC) non-specific ST-T change13,39 echocardiogram ejection fraction myocarditis congestive heart failure congestive heart failure congestive heart failure reabsorption extracellular fluid 2 DHF pleural effusion adult respiratory distress syndrome

    / 40-58 25 ( 1) 23,27,285 (co-infection)

  • salmonella gastroenteritis amoebiasis 1-2 43 DHF 12 DF ( 1)27,28 DHF 5-8 jaundice hepatobiliary tract sulfonamide phynetoin dapsone unconjugated hyperbilirubinemia hemolysis thalassemia, hemoglobinopathy HbH disease jaundice conjugated hyperbilirubinemia (acalculus cholecystitis) bacteremia, malaria 10-30 DF 5-90 DHF DHF 1-2 1-2 liver transaminase 90 ALT AST DF DHF DHF liver transaminase DF DF AlT/AST = 258/184 IU/ml DHF ALT/AST = 399/261 IU/ml DF ALT/AST 23,27,28,40,41 jaundice liver enzyme ALT/AST 48 ALT/AST 7-9 2-3 40 liver transaminase / hepatitis fulminant hepatic failure severe jaundice ascites prolonged PT/PTT alteration of consciousness liver injury direct invasion viral antigen hepatocyte13 acetaminophen 5-7

  • ALT/AST acetaminophen encephalopathy NSAIDs ALT/AST 400 IU/ml hypotension DIC renal failure DHF liver injury Reyes syndrome DHF liver injury pre-existing hepatic disease liver failure thalassemia hemoglobinopathy chronic liver disease encephalopathy, severe bleeding, DIC, jaundice, bacterial sepsis fulminant hepatic failure blood exchange transfusion 23 DHF thickening gallbladder wall42,43 acalculus cholecystitis DHF ultrasound bacterial infection DHF ascites DHF 42 plasma leakage acute pancreatitis hyperglycemia serum lipase edema 44 dengue 5 acute appendicitis measles, CMV, HIV DF/DHF serology 5 appendectomy acute appendicitis 1-2 right lower quadrant WBC 10,000/mm3 post-operative bleeding WBC leukocytosis neutrophilia acute appendicitis

  • DF20-80 DHF (flush face) maculopapular rash 2-6 morbilliform maculopapules, scarlatiniform eruptions, urticaria 1-2 convalescent rash confluent petechial rash petechial rash 1-2

    DF DHF 3

    1. delirium, restlessness, mental irritability depression, fatigue, insomnia, irritability

    2. (alteration of consciousness coma) (focal or generalized seizure) encephalopathy encephalitis meningoencephalitis meningism (stiff neck) DEN-3 coma 4.2 (encephalitis) 23,27,28,45,46 2 1 serology dengue encephalopathy DHF grade III IV CSF inflammatory reaction CSF EEG encephalopathy encephalitis shock electrolyte imbalance (hepatic encephalopathy) (encephalitis) dengue IgM

  • 13,47-49

    3. acute polyneuritis, acute polyradiculopathy, optic neuritis immunologic process post-infectious

    placenta teratogenic effect, abortion, intrauterine growth retardation50-52 neural tube defects 1st trimaster (peripartum period) 1 20,50-52 20

    (dual infection) dual infection 3 27,28 9-10 predictors bacteremia co-infection 5 53 10,000/mm3 shift to the left neutrophil band form enteric fever, malaria, infective diarrhea, parasitic infection urinary tract infection, bacteremia, catheter-related infection non-infectious causes

  • stress ulcer plasma Reye-like syndrome lymphoid hyperplasia antigen interstitial infiltration pleural effusion rapid test 8,9

    PMN lymphocyte atypical lymphocyte 100,000/.. hematocrit plasma aspartate transaminase (AST) alanine transaminase (ALT)

  • enzyme-linked immunosorbent assay (ELISA) hemagglutination inhibition (HI) PCR serology serotype serology HI 5-14 ELISA rapid test sepsis PCR serotype PCR serotype

    2 CBC hematocrit 20 hematocrit plasma leakage hematocrit hemolysis hematocrit DHF stage II 2-4 1-4 / (WBC) ( 5,000/mm3) WBC 1,000-1,500/mm3 neutrophil lymphocyte (neutrophil 70) band form neutorphil atypical lymphocyte 5 2 malaria, enteric fever, typhus

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