1、Dengue fever 報告者:PGY 學員吳明政醫師 指導醫師:吳冠達醫師 台灣登革熱流行史台灣登革熱流行史 台灣登革熱流行史台灣登革熱流行史 典型登革熱其學名 Dengue fever，俗名天狗熱或斷骨熱，係由埃及斑蚊及白線斑蚊 兩種病媒蚊傳播的急性病毒性熱疾，依血清抗原性分為 1、2、3、4型，均具感染致病力。病毒必須藉由病媒蚊叮咬才能從人傳給人。造成登革熱/登革出血熱/登革休克症候群。蟲媒病毒，由黃病毒科Flaviviridae黃病毒屬Flavivirus中的登革病毒亞屬所引起。登革熱簡介 病患從開始發燒的前一天直到退燒，此期間都具有病毒傳染力，此為登革熱病患之病毒血症期(virem
2、ia)。病媒蚊叮咬登革熱病患815天後，則具有終生傳染病毒的能力。再次感染不同型別再次感染不同型別登革病毒，可能發生登革病毒，可能發生較嚴重的登革出血熱。較嚴重的登革出血熱。登革熱簡介 登革熱臨床症狀登革熱臨床症狀 臨床症狀 有些人感染到登革熱病毒並不會生病，稱為不顯性或無症狀感染，有些人僅有發燒等輕微症狀，有些人則出現較嚴重的典型症狀，包括發燒、紅疹、眼窩或發燒、紅疹、眼窩或骨頭酸痛，甚至出血現象骨頭酸痛，甚至出血現象。由於個人感染後表現之症狀有很大的差異，必須由醫師診斷或實驗室檢驗，因此懷疑感染疾病時就必須就診。一、典型登革熱 1.潛伏期：58天(314天)2.前驅症狀：在發熱數小時至12
3、小時前，可能有頭痛、厭食、僵硬、違和、臉部潮紅。3.發熱：體溫驟然昇高至 3940，而後持續56天。4.疼痛：在首24小時內，四肢酸痛、關節痛、肌肉痛、背痛、後眼窩痛、畏光。5.發疹：第3或第4病日，出現疹子，先發生在胸部、軀幹再擴散至四肢及臉部，有時會引起全身發癢。臨床症狀 登革出血熱 1.有發燒等典型病癥。2.出血性癥候：如止血帶試驗陽性，輕微或嚴重出血現象。3.血小板減少：血小板數目105 /mm3。4.血液濃縮：血比容上升超過正常時20%，出現血管通透性明顯增加的證據，如低蛋白血症，胸膜或腹膜積水。1.有出血性登革熱病癥。2.低血壓，脈搏微弱至幾乎測不到，脈搏壓20mmHg。登革休克症
4、候群 History Fever Abrupt onset,rising to 39.5-41.4 C Accompanied by frontal or retro-orbital headache Lasts 1-7 days,then defervesces for 1-2 days Biphasic,recurring with second rash but not as high Rash Initial rash transient,generalized,macular,and blanching;occurs in first 1-2 days of fever Second
5、 rash occurring within 1-2 days of defervescence,lasting 1-5 days Second rash morbilliform,maculopapular,sparing palms and soles Occasionally desquamates Bone pain Absent in dengue hemorrhagic fever(DHF)/dengue shock syndrome(DSS)After onset of fever Increases in severity Not associated with fractur
6、es May last several weeks Most common in legs,joints,and lumbar spine Miscellaneous symptoms Nausea and vomiting Cutaneous hyperesthesia Taste aberrations Anorexia Abdominal pain(severe in DHF/DSS)Physical Fever is present.Rash is described as follows:Up to half of patients with dengue fever develop
7、 a characteristic rash.The rash is variable and may be maculopapular or macular.Petechiae and purpura may develop as hemorrhagic manifestations.Conjunctival injection develops in approximately one third of patients with dengue hemorrhagic fever.Pharyngeal injection develops in almost 97%of patients
8、with dengue hemorrhagic fever.Generalized lymphadenopathy is observed.Hepatomegaly is present more often in dengue shock syndrome than in milder cases.Hepatic transaminase levels may be mildly elevated.Hemorrhagic manifestations include the following Petechiae and bleeding at venipuncture sites are
9、most common.Results from a tourniquet test are often positive.This test is performed by inflating a blood pressure cuff on the upper arm to midway between diastolic and systolic blood pressures for 5 minutes.The results are considered positive if more than 20 petechiae per square inch are observed o
10、n the skin of the arm.Other hemorrhagic manifestations include nasal or gingival bleeding,melena,hematemesis,and menorrhagia.Duration of illness The period of maximum risk for shock is between the third and seventh day of illness.This tends to coincide with resolution of fever.Plasma leakage general
11、ly first becomes evident between 24 hours before and 24 hours after defervescence.Alarm signs Severe abdominal pain,persistent vomiting,abrupt change from fever to hypothermia,or abnormal mental status,such as disorientation,are noted in a minority of patients.Hematocrit An elevation of the hematocr
12、it is an indication that plasma leakage has already occurred and that fluid repletion is urgently required.Platelet count Severe thrombocytopenia(100,000/mm3)is one of the clinical criteria for DHF and usually precedes overt plasma leakage.Serum aspartate transaminase(AST)Mild elevations in serum tr
13、ansaminases are common in both dengue fever and DHF.However,levels are significantly higher in patients with DHF,and elevated AST levels are noted earlier in illness than the other signs listed above.In one study conducted in Thailand,a normal AST level was a strong negative predictor of DHF(negativ
14、e predictive value 0.96)even in the first three days of illness 1.傳染方式Mode of transmission 人被帶有登革病毒的病媒蚊叮吮而受到感染。台灣重要的病媒蚊為埃及斑蚊Aedes aegypti及白線斑蚊Aedes albopictus。病媒蚊經叮咬病毒血症期viremia的病患812天後，則具有終生傳染病毒的能力，其時期可能長達幾個月 可傳染期Period of communicability 登革熱之傳播須經由具有感染之媒蚊叮咬，人不會直接傳染給人。病人在發病前一天及發病後約5天內，血液裡就會有病毒，此時期假设
15、蚊蟲吸取病人的血液，病毒會在蚊體內繁殖，經812日後蚊蟲才有感染力。此後其終生皆具傳染力。病媒蚊如在氣溫攝氏18度以下，吸取含有病毒之血液時，病毒並不會在蚊體內繁殖，故不具感染性。在高溫下已具有感染力之蚊蟲，如置於溫度攝氏18度以下，將會喪失感染，但如再度置於高溫時會恢復傳染性。登革熱病媒蚊登革熱病媒蚊 埃及斑蚊埃及斑蚊(Aedes aegypti)嘉義以南嘉義以南 白線斑蚊白線斑蚊(Aedes albopictus)全台全台 感受性及抵抗力 人對於典型登革熱的感受性並沒有年齡及性別的差異，但大體上小孩子的罹患率相對的低於成人，症狀以及經過亦較成人輕微且不太典型，老人的罹患率也比較低。這一點與
16、登革出血熱DHF或者登革休克症候群DSS迥然不同，後者的罹患率以未滿1歲78個月的嬰兒以及28歲的小孩最高。性別的差異不多。典型登革熱症狀雖然劇烈，但其致死率幾乎是零，而登革出血熱DHF或登革休克症候群DSS致命率高達4050，但如經適當的醫療照護，致死率5。康復後對同一型之登革病毒具有終生的免疫力。但是對其他三型病毒，則免疫力有效期極短，通常約29個月之間。嚴重併發症之致病機轉嚴重併發症之致病機轉 抗體依賴性免疫加強反應抗體依賴性免疫加強反應 (antibody dependent enhancement,ADE)(antibody dependent enhancement,ADE)第一次感染登革熱病毒後體內自然產生的抗體第一次感染登革熱病毒後體內自然產生的抗體 其它型登革熱病毒其它型登革熱病毒再次再次侵入時可被抗體辨識，侵入時可被抗體辨識，結合成抗原結合成抗原-抗體複合體，進入到巨噬細胞複製繁殖抗體複合體，進入到巨噬細胞複製繁殖 記憶型記憶型T細胞活化細胞活化 釋放淋巴細胞激素釋放淋巴細胞激素(cytokines)(cytokines)，引起過敏性反應，引起過敏性反應 血管通透性