1、Dengue fever,WHAT IS DENGUE FEVER?,An acute ,self-limited, febrile disease .Dengue virus are maintained in a cycle that involves humans and Aedes aegyptiprimarily a disease of the tropicsOCCURS IN two forms:Dengue fever(DF)Dengue haemorrhagic fever(DHF),Clinical manifestations,DF: fever, headache, m
2、yalgias, bone pain.Lymphadenopathy, skin rash.Leukopenia DHF: high fever, haemorrhage,hepatomegalyevidences 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
3、, 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
4、Classified : family of Flaviviridae. Serum type:1-4 causes closely related illness, severe and fatal disease but antigenically distincthomotypic immunity: lifelongheterotypic immunity :short periodbut cross-response may worsen the second infection by a another serum type.,How DF transmitted?,Sources
5、 of infection: patients and anyone who with Covert infectionTransmitted vectors:Aedes aegypti is the most common vectorsother Aedes mosquitos are less effiecitent :Ae.albopictus,Ae.polynesiesisPrimarily a daytime feederLives around human habitationThe host: all susceptible if never came across dengu
6、e 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
7、,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
8、 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)
9、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,h
10、eterotypic 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,patho
11、physiological changes occur in DHF/DSS:,Increased vascular permeabilityhaemoconcentration(Hct20%)low pulse pressure other signs of shock. Disorder in haemostaisis :vascular changesthrombocytopenia coagulopathy.,CLINICAL PRESENTATIONS,Incubation: 5-8 daysClinical features depend on the age of the pat
12、ient: Infants and young children undifferentiated febrile disease,with maculapapular rash. Older children and adults eithera mild febrile syndrome or the classic disease.,Manifestation Of Dengue Virus Infections,Undifferentiated Fever,the most common manifestation of dengue87% of students infected w
13、ere either asymptomatic or mildly symptomaticstudies 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 headachePain behind the eyes chillness Last 1-7 days Biphasic:defervesce for 1-2
14、days recurring with second rash but :T not as high,2. Bone pains,break bone fever is the another name of DFAfter 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, trans
15、ient, 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 bleed
16、ing GI bleeding: hematemesis, melena, hematochezia Hematuria Increased menstrual flow,Physical exams(1),FeverConjunctival injection, pharyngeal erythemaRash: Measles-like rash over chest and upper limbsGeneralized lymphadenopathy,Physical exams(2) : Tourniquet Test,Method:Inflate blood pressure cuff
17、 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 typeTypical typeSevere type:Unusual bleedingsmeningoencephalitis,DHF/DSS(1),high fever: remains 39 for 2-7days hepatomegaly : varies i
18、n sizecommon 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)=DH
19、F+SHOCK,at the end of the febrile phasesigns of circulatory disturbancesweat, 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
20、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
21、laboratory testsCBC- Leukopenia is typical; thrombocytopenia , hematocrit Liver function tests : AlbuminUrine-check for microscopic hematuria,Lab tests(2) :Dengue-specific tests,serologic tests: Antibody assayuseful for documenting:IgM and complement fixing (CF)Ab : short livedFourfold increase in t
22、iter between acute and convalescent seraViral antigen or viral RNA by PCR : prove the diagnosis Virus isolation: grown in vertebrate and mosquito cell linesVirus is best isolated from serum: febrile patients.but are difficult and dangerous to isolate.,ELISA Test for Serologic Diagnosis,Virus Isolati
23、on: 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 type
24、s.,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 press
25、ure2.7kpahypotension,Differencial diagnosis,Include a wide spectrum of viralbacterial 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 support
26、ive 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 E
27、vidence 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 lineCorrect electrolyte abnormalities and ac
28、idemiaMonitor the vital signs: avoid hypovolemia or fluid overload. therapy for DIC: if indicatedUnknown effective = steroid ,immune globulinplatelet transfusions,Discharge criteria,afebrile for 24 h appetite clinical improvement 3 days post shockStable Hct Platelets 50,000/mm3 Eupnea: No respirator
29、y distress from pleural effusions/ascites,prevention,Three operations must be conductedisolation 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
30、 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 s
31、leeping,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 ev
32、en 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)
33、For example55 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,
34、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,shoc
35、k,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
36、 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 failur
37、ec. typhoid fever(malaria) d. scrub typhoide. leptospirosis,2.Dengue fever,which is not common seen?a.Enlargement of liver and spleen or haemoconcentrationb.Feverc. GI bleedingd.Rashe.myalgia/arthialgia,3.which of following is the feature of rash in dengue infection?a.less than 10 in numberb.typical
38、 rash occur in 3-6days after the onset.c.more common seen in DHFd.Begin from the facee.Can spread all over the body.,4.the criteria for diagnosis DHFexcept?a.Fever b. thrombocytopeniac.Haemorrage tendency or evidence of bleedingsd. Haemocrit elevation more than 20%e.lymphadenopathy.,5. Shock in deng
39、ue shock syndrome ,which is not correct?a.Hypovolemic shockb.sweat,cool extremities,rapid weak pulse.c.In severe case,the duration will be prolonged to 7-10days.d. with severe bleedingse.The critical stage is at the end of the febribe phase.,6. Bone pains in denguea. Occur right after the onset of f
40、ever.b. May last several weeks.c. Most common in legs,joints and lumber spine.d. With myalgia and arthialgiae. Similar frequency in DF and DHF.,7.Which is not correct?a. DF is accute self-limited febrile disease.b. DV is tranmitted by mosqitorc. Primiarily a disease of the tropics.d. Mainly occur fr
41、om 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 o
42、r DHF is always more severe than DF. The onset of fever is usually slow. Fever last less than one week.,9.The main transmitted vectors for DF Ae.albopicters. Ae.polynesiesis Aedes aegyptic Chigger anopheles,10.For diagnosis of DF,which is less important?,a.Coming from epicemic area.b.Tranvelling his
43、tory one month agoc.The disease occur in rainy season.d.History of DF 10 months ago.e.Familay member have similar disease.,11.Management of DFa. No specific antivirus therapy available.b. Anti-inflammatory agents can be used to relieve the symptoms.c.Monitoring daily is not needed as the disease is
44、benign.d. Aspirin should be avoided to avoid GI bleeding.e. Avoid fluid overload.,12.Management of DHF, which is not true?a. Iv crystalloids, colloids.b. corticosteroids are helpfulc. Correct electrolyte abnormalities and academiad. Monitor the vital signse. Implement therapy for DIC if indicated,13
45、.which is the most important measure for prevent DFa. Isolation of patients.b. Emergency mosquito controlc.Vaccinationd. Use insect repellent on exposed skine. Remain in enclosed air-conditioned areas.,14.Which is not correct?a. DV is a DNA virus.b. Main pathophysilogical changes in DHF are increased vascular permeability and disorder in homeostasisc. DF is a benign disease with mortality less than 1%.d. Serotype 2 is the predominating serotype in DHF.e. Patients with DSS can die or recovery in one day,
