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Dengue fever,WHAT IS DENGUE FEVER?,An acute ,self-limited, febrile disease . Dengue virus are maintained in a cycle that involves humans and Aedes aegypti primarily a disease of the tropics OCCURS IN two forms: Dengue fever(DF) Dengue haemorrhagic fever(DHF),Clinical manifestations,DF: fever, headache, myalgias, bone pain.Lymphadenopathy, skin rash. Leukopenia DHF: high fever, haemorrhage, hepatomegaly evidences of “leaky capillaries” signs of circulatory failure(dengue shock syndrome,DSS.),Why should we learn it ?,2500 million at risk from dengue per year. Epidemic in more than 100 countries in Africa, America, Eastern Mediterranean, South east Asia and the Western pacific. The global prevalence of DHF grown dramatically in recent decades: 1970/1995:4 fold increase. The most important mosquito-transmitted viral disease in term of mortality and morbidity.,Etiology,Dengue virus: enveloped RNA virus Classified : family of Flaviviridae. Serum type:1-4 causes closely related illness, severe and fatal disease but antigenically distinct homotypic immunity: lifelong heterotypic immunity :short period but cross-response may worsen the second infection by a another serum type.,How DF transmitted?,Sources of infection: patients and anyone who with Covert infection Transmitted vectors: Aedes aegypti is the most common vectors other Aedes mosquitos are less effiecitent : Ae.albopictus,Ae.polynesiesis Primarily a daytime feeder Lives around human habitation The host: all susceptible if never came across dengue fever.,How dengue virus cause the disease? (pathogenesis and clinical presentations),Dengue virus,Blood stream,Mononuclear-phagocyte system,second viremia,Antigen antibody complexes,complement system,incubation,Lymphadenopathy,hepatomegly,Bone marrow depress,Vascular permeability,Rash, haemarrhagic,fever Bone pains,etc,Imfllamatory materials,risk factors for DHF,Important risk factors for DHF include Virus factors: the serotype :2 is the predominating the strain: virulent strain Host factors: genetic predisposition the age Children : experienced a precious dengue infection Infants with waning levels of maternal dengue antibody. immune status: if there are enhancing Ab.,Enchancing antibody,A mechanism of DHF/DSS is heterotypic antibodies enhancement of virus replication in macrophages worsen the condition,Neutralizing antibody to Dengue 1 virus,Dengue 1 virus,Homologous Antibodies(同型抗体) Form Non-infectious Complexes,Non-neutralizing antibody,Complex formed by neutralizing antibody and virus,Heterologous (异型的)Complexes Enter More Monocytes, Where Virus Replicates,Non-neutralizing antibody,Dengue 2 virus,Complex formed by non-neutralizing antibody and Dengue 2 virus,First infection,heterotypic antibodies,fail to neutralize virus of the other serum type infection,the number of infected monocytes,activation of cytotoxic lymphocytes,rapid release of cytokines,plasma leakage,viral uptake and the replication in the mononuclear phagocytes.,haemorrhage,Haemoconcentrationor shock,pathophysiological changes occur in DHF/DSS:,Increased vascular permeability haemoconcentration(Hct20%) low pulse pressure other signs of shock. Disorder in haemostaisis : vascular changes thrombocytopenia coagulopathy.,CLINICAL PRESENTATIONS,Incubation: 5-8 days Clinical features depend on the age of the patient: Infants and young children undifferentiated febrile disease, with maculapapular rash. Older children and adults either a mild febrile syndrome or the classic disease.,Manifestation Of Dengue Virus Infections,Undifferentiated Fever,the most common manifestation of dengue 87% of students infected were either asymptomatic or mildly symptomatic studies including all age- groups also demonstrate silent transmission,Dengue fever (DF),1. fever,Abrupt onset, rising to 39.5-41.4 C Accompanied by frontal or retro-orbital headache Pain behind the eyes chillness Last 1-7 days Biphasic: defervesce for 1-2 days recurring with second rash but :T not as high,2. Bone pains,break bone fever is the another name of DF After onset of fever May last several weeks Increase in severity Most common in legs, joints, and lumbar spine; With muscular and joint pains.,3. Rash,first rash: first 1-2 days of fever, transient, generalized, macular and blanching; Second rash 3-6 days. morbilliforms , maculopapular , rubella type Involving the trunk first, spreading to the face and extremities, sparing palms and soles. other rash: petechiae,4. Hemorrhage,Skin hemorrhages: petechiae, purpura Gingival bleeding Nasal bleeding GI bleeding: hematemesis, melena, hematochezia Hematuria Increased menstrual flow,Physical exams(1),Fever Conjunctival injection, pharyngeal erythema Rash: Measles-like rash over chest and upper limbs Generalized lymphadenopathy,Physical exams(2) : Tourniquet Test,Method: 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),Clinical forms of DF(china),Mild type Typical type Severe type: Unusual bleedings meningoencephalitis,DHF/DSS(1),high fever: remains 39 for 2-7days hepatomegaly : varies in size common haemorrhage bleeding at venepuncture sites (coagulopathy) GI bleeding Evidence of plasma leakage: a rise in hematocrit (Hct):=20% pleural effusion ,ascites , hypoproteinemia a distinctive laboratory finding : Moderate to marked thrombocytopenia with concurrent haemoconcentration,DSS(2)=DHF+SHOCK,at the end of the febrile phase signs of circulatory disturbance sweat, cool extremities restless rapid ,weak pulse hypotension varying severity less severe: transient recover spontaneously more severe: uncorrected Shock ensues: metabolic acidosis, severe bleeding Patient may dies or recovers within 12-24hours,finding DF DHF,(+1-25%,+26-50%,+51-75%,+76-100%) Fever + + Petechiae + + Lymphadenopathy + + GI bleeding + +,finding DF DHF,Maculopapular rash + + Myalgia/arthralgia + + Leukopenia + + Thrombocytopenia + + Positive tourniquet test + + Hepatomegaly 0 + Shock 0 +,Lab tests(1),Clinical laboratory tests CBC- Leukopenia is typical; thrombocytopenia , hematocrit Liver function tests : Albumin Urine-check for microscopic hematuria,Lab tests(2) :Dengue-specific tests,serologic tests: Antibody assay useful for documenting: IgM and complement fixing (CF)Ab : short lived Fourfold increase in titer between acute and convalescent sera Viral antigen or viral RNA by PCR : prove the diagnosis Virus isolation: grown in vertebrate and mosquito cell lines Virus is best isolated from serum: febrile patients. but are difficult and dangerous to isolate.,ELISA Test for Serologic Diagnosis,Virus Isolation: Cell Culture,Virus Isolation: Mosquito Inoculation,Virus Isolation: Fluorescent Antibody Test,Diagnosis of DF,Epidemiological evidences Clinical presentations Lab tests: Routine test: for monitoring the severity serologic tests: for clinical diagnosis Virus isolate: to distinguish the serum types.,four criteria for DHF,Fever , last for 2-7days at least one of Hemorrhage evidences Thrombocytopenia :PLT=20% pleural effusion ,ascites and hypoprotinemia,Diagnosis criteria for DSS,four criteria for DHF Evidence of shock sweat, restless, cool extremities rapid ,weak pulse narrowing of pulse pressure2.7kpa hypotension,Differencial diagnosis,Include a wide spectrum of viral bacterial Parasitic infections,prognosis,Self-limit disease Convalescence may be prolonged with weakness and mental depression Continued bone pains, bradycardia Survival is related to early hospitalization aggressive supportive care,Treatment of DF,complicated, no specific trx Fluid replacement: adequate hydration Bed Rest Antipyretics acetaminophen (if no liver dysfunction) No aspirin(association with Reye syndrome ), steroids, avoid NSAIDS(anticoagulant properties).,Continuous Monitoring of,VS Diuresis,mental status Evidence of bleeding Hydration status Evidence of increased vascular permeability hematocrit, platelet count(manual),Management for DHF,Prevent and Treatment of shock: mild to moderate isotonic dehydration (5%-8% deficit) Iv crystalloids ; colloids; central line Correct electrolyte abnormalities and acidemia Monitor the vital signs: avoid hypovolemia or fluid overload. therapy for DIC: if indicated Unknown effective = steroid ,immune globulin platelet transfusions,Discharge criteria,afebrile for 24 h appetite clinical improvement 3 days post shock Stable Hct Platelets 50,000/mm3 Eupnea: No respiratory distress from pleural effusions/ascites,prevention,Three operations must be conducted isolation of patients. emergency mosquito control simultaneously Personal protection,vaccine,no vaccine currently available research is underway for the development of a vaccine. vaccine will not available for 5 to 10 years. as it must provide immunity to all 4 serotypes Lack of dengue animal model,Personal protection,remain in well-screened or completely enclosed, air-conditioned areas; wear light-colored clothing with full-length pant legs and sleeves; use insect repellent on exposed skin. Use netting when sleeping,thanks!,Common Misconceptions about DHF,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,Rehydrating Patients Over 40 kg,Volume required: twice the recommended maintenance volume Formula for calculating maintenance volume: 1500 + 20 x (weight in kg - 20) For example 55 kg patient: maintenance volume : 1500 + 20 x (55-20) = 2200 ml For this patient, the rehydration volume would be 2 x 2200, or 4400 ml,Dengue virus infection,Asymptomatic,symptomatic,Undifferentiated fever (viral syndrome),dengue hemorrhagic fever (plasma leakage),dengue fever syndrome,no shock,DSS,Without hemorrhage,with unusual hemorrhage,DF,DHF,Fever,tournigeut test(+),Increased vascular permeability,heptomegaly,thrombocytopenia,Dengue infection,Other haemorrhagic manifestations,Leakage of plasma,Rising haematocrit Hypoproteinaemia Serous effusion,coapulopathy,hypovolaemia,shock,DIC,Severe bleeding,death,Antiinflamatory agents Monitor vital sings q2h Provide oral hydration,Same as above + type and cross match Determine PT AND PTT,Same as above+ iv isotonic fluids, monitor q30mins, follow urine output,Same as above+ Iv colloids or plasma Provide critical care support,1.Four Criteria for DHF,1+spontaneaous bleeding,1+Sings of shock: hypotention,1+undetectalbe pulse and blood pressure,Grade 1,Grade 2,Grade 3,Grade 4,Multiple choice of dengue,1.Which of following have high frequency of leukopenia with thrombocytopenia? a. dengue fever b. hemorragic fever with renal failure c. typhoid fever(malaria) d. scrub typhoid e. leptospirosis,2.Dengue fever,which is not common seen? a.Enlargement of liver and spleen or haemoconcentration b.Fever c. GI bleeding d.Rash e.myalgia/arthialgia,3.which of following is the feature of rash in dengue infection? a.less than 10 in number b.typical rash occur in 3-6days after the onset. c.more common seen in DHF d.Begin from the face e.Can spread all over the body.,4.the criteria for diagnosis DHFexcept? a.Fever b. thrombocytopenia c.Haemorrage tendency or evidence of bleedings d. Haemocrit elevation more than 20% e.lymphadenopathy.,5. Shock in dengue shock syndrome ,which is not correct? a.Hypovolemic shock b.sweat,cool extremities,rapid weak pulse. c.In severe case,the duration will be prolonged to 7-10days. d. with severe bleedings e.The critical stage is at the end of the febribe phase.,6. Bone pains in dengue a. Occur right after the onset of fever. b. May last several weeks. c. Most common in legs,joints and lumber spine. d. With myalgia and arthialgia e. Similar frequency in DF and DHF.,7.Which is not correct? a. DF is accute self-limited febrile disease. b. DV is tranmitted by mosqitor c. Primiarily a disease of the tropics. d. Mainly occur from may to october. e. Only children are vulnerable during the epidemic.,8.Which is correct for dengue fever?,After infection, there may have heterotypic immunity which can last lifelong. DF is the most important mosquito transmitted disease. Main different of DF and DHF is that DHF with haemorragic or DHF is always more severe than DF. The onset of