< Presentation of Case >
This 33-year-old man had been healthy before traveling to Soloman Islands during 2nd Nov and 16th Nov, 2013, and to Philippines during 25th Nov and 3rd Dec, 2013 for geographic study. He did not take any chemoprophylaxis for malaria or vaccination for yellow fever during or before the trip. He started to develop severe arthralgias of the bilateral knees and ankles on the next day when he returned to Taiwan (4th Nov, 2013). Fever, rigors, headache, and myalgias were noted over the following days, for which he sought medical attention at the travel medicine out-patient clinic at the National Taiwan University Hospital and was referred to the Emergency Department on 6th Nov, 2013.
On examination, the blood pressure was 137/76 mmHg, the heart rate 109 beats per minute, the respiratory rate 18 breaths per min and the temperature 39℃. Physical examination showed injection of the bilateral bulbar conjunctiva and tenderness of the bilateral knees and ankles without swelling. The remainder of the examination was unremarkable. Laboratory examination revealed a hemoglobin level of 14.8 g/dL, platelet count 191 K/μL and white-cell count 7.87 × K/μL, with 77.9% neutrophils, 11.9% lymphocytes, 7.1% monocytes, 2.8% eosinophils, 0.3% basophils, and no atypical lymphocytes. Blood biochemistry examination showed mildly elevated aspartate aminotransferase level (42 U/L) but the alanine aminotransferase (34 U/L) and total bilirubin level (0.86mg/dL) were both within normal limits; the serum creatinine level was 1.1 mg/dL, BUN level 13.7 mg/dL, serum sodium 132 mmol/L, and potassium 4.2 mmol/L. The creatinine kinase level was elevated (502 U/L). A chest radiograph on admission showed no abnormal finding.
Thick blood smears for detection of Plasmodium in the next five consecutive days all showed negative findings. A screening test for influenza A+B showed negative findings, either. A diagnosis of travel-related viral infections was made and the patient's serum and whole blood samples were sent to the reference laboratory of the Taiwan Centers for Disease Control for further enzyme-linked immunosorbent assay methods and reverse-transcriptase polymerase-chain reaction (PCR) assays to detect specific IgM antibodies and viral RNA. Supportive care was instituted without any antimicrobial therapy. Generalized erythematous maculopapular skin rash with some confluence over the torso, four extremities, and neck developed on the 5th day after the disease onset (9th Nov,2013) (Figure 1), which were not itching or scaling. A blood test for measles virus IgM antibody was negative. On the 6th day after the disease onset (10th Nov, 2013), a positive result for Chikungunya virus infection was confirmed with reverse-transcriptase PCR by the reference laboratory of the Taiwan Centers for Disease Control. The skin rash started to resolve gradually 2 days after they appeared (11th Nov, 2013). There was no more fever since the 7th day after the disease onset (11th Nov, 2013). The patient was discharged on the 9th day after the disease onset (13th Nov, 2013) with partial improvement of the polyarthralgias.
< 討論 >
本案例為一境外移入之屈弓熱(Chikungunya fever)個案，並具有典型的臨床病程及症狀。
屈弓熱病毒(Chikungunya virus)為一單股RNA病毒，其歸屬於披膜病毒科(Togaviridae)中的甲病毒屬(Alphavirus genus)1。屈弓(Chikungunya)之名源自斯瓦希里(Swahili)及馬孔德(Makonde)語中形容“成為扭曲的”(“to become contorted”) 及“彎曲的”(“that which bends up”)，用來形容屈弓病毒及屈弓熱。屈弓熱病毒於西元1952-1953年在坦尚尼亞(Tanzania)南方省份的一位發燒病人首次被分離出2。流行病學上，屈弓熱病毒分佈於非洲、印度洋群島、南亞及東南亞。屈弓熱流行疫情於西元2000年後頻率增加，推測跟病毒演化適應蚊子媒介有關3；近年來較大流行爆發疫情包括西元2000年於剛果共和國(Democratic Republic of the Congo)的Kinshasa、西元2001-2003年於印尼(Indonesia)、西元2004年於肯亞(Kenya)的Lamu及Mombasa、西元2005年於大葛摩島(Grande Comore)、賽席爾(Seychelles)及模里西斯(Mauritius)、西元2005-06年於留尼旺島(Reunion)、西元2006-2007年於印度(India)、及西元2007年於義大利(Italy)的Ravenna ( Figure 2)4。屈弓熱主要的傳播媒介為斑蚊(Aedes mosquitoes)，其中埃及斑蚊(Aedes aegypti)及白線斑蚊(Aedes albopictus)為造成亞洲都會區中流行的主要媒介。在台灣，白線斑蚊及埃及斑蚊分別分布於全島及台灣南部平地及高度1500公尺以下山區，因此地區性的傳播是有可能發生的。
屈弓熱與登革熱(Dengue fever)在臨床表現上有許多相似之處。屈弓病毒感染潛伏期為1到12天不等，平均為2到4天。病人在感染潛伏期後會發生屈弓熱；其症狀包括突發性高燒、嚴重關節疼痛及皮膚疹，合併症狀還包括有頭痛、畏光、疲勞及肌肉疼痛的產生。極少數的人會有無症狀的感染5。屈弓熱的多發性關節疼痛大多為對稱性，且好發於手指、手腕、腳踝、膝蓋、腳趾，局部常見腫脹但無其他發炎症狀。大多關節疼痛症狀於1至2周內會有部分或完全恢復，但很多病人會有持續性關節疼痛長達數月到數年6。屈弓熱所引起的皮膚疹在約50%的病人會發生，其皮膚疹為丘疹斑塊狀紅疹(maculopapular rash)，有時會伴隨搔癢感，通常分布於病人的驅幹、四肢、及臉部，持續時間大多只有2到3天；其他皮膚表現，包括口瘡狀潰瘍(aphthous-like ulcers)、水泡狀病灶伴隨脫落(vesiculobullous lesions with desquamation)、血管炎病灶(vasculitic lesions)也曾被報告過7-9。屈弓熱病毒一般認為不會侵犯神經，但近年於留尼旺島(Reunion)及印度(India)的流行皆有報告屈弓熱的神經併發症，其臨床表現包括腦膜腦炎(meningoencephalitis)及急性無力肢體麻痺(acute flaccid paralysis)等10-12。其他急性屈弓病毒感染的症狀還可能有腹瀉、嘔吐、肚痛、及結膜炎等4。
屈弓熱的診斷需倚賴臨床、流行病學、及實驗室的診斷。若病患有急性發燒、臨床上無法以其他醫學診斷解釋的嚴重關節疼痛、又居住或最近造訪過屈弓熱流行地區，即可懷疑可能有屈弓熱的感染；但臨床上要與登革熱、其他甲病毒感染、其他關節炎、及瘧疾(malaria)做區分，仍須倚靠實驗室的診斷。實驗室診斷包括偵測血清中病毒核酸的反轉錄聚合(西每)鏈鎖反應(reverse-transcriptase PCR)，利用細胞培養分離病毒，或利用間接免疫螢光法(indirect immunofluorescence)或酵素免疫吸附分析法(ELISA)偵測屈弓熱病毒IgM及IgG抗體。反轉錄聚合(西每)鏈鎖反應可在臨床症狀產生前一天到症狀產生後第七天之間偵測到病毒核酸。通常屈弓熱病毒IgM抗體可在發燒後第二到七天被測得，並於人體維持三到四個月可測得的血清濃度；屈弓熱病毒IgG抗體通常在發燒後第五到六天被測得，其可維持數年之久13。
目前對於屈弓熱病毒感染所引起的關節疼痛治療只有非類固醇抗發炎藥物(non-steroidal anti-inflammatory drugs)。其他治療包括屈弓熱病毒單株抗體(CHIKV antibodies)、ribavirin、及chloroquine皆有在動物及細胞實驗研究顯示有抗屈弓病毒效果，但尚無足夠證據於臨床上使用。根據2005年的流行病學資料，屈弓病毒感染的死亡率(case fatality rate)大約為千分之一4。屈弓病毒感染過後，病患可產生終生對於屈弓病毒感染保護的免疫力，但目前臨床上尚無可用之屈弓病毒疫苗。
屈弓病毒感染在台灣最早於民國56年有研究記載14，往後直到民國95年才有境外移入病例再被報告15，近幾年來屈弓熱境外移入案例逐年上升16。屈弓熱屬於第二類傳染病，需於24小時內通報。當病患有急性發燒且有嚴重關節炎或關節痛，無法以其他醫學診斷解釋者，且與確定病例有流行病學上的相關性或有屈公病流行地區相關旅遊史時，即需通報16。
< References >
- Solignat M, Gay B, Higgs S, Briant L, Devaux C. Replication cycle of chikungunya: A re-emerging arbovirus. Virology 2009; 393: 183–197.
- Robinson MC. An epidemic of virus disease in Southern Province, Tanganyika Territory, in 1952-53—1: Clinical features. Trans R Soc Trop Med Hyg 1955; 49: 28.
- Tsetsarkin KA, Vanlandingham DL, McGee CE, Higgs S. A single mutation in chikungunya virus aff ects vector specifi city and epidemic potential. PLoS Pathog 2007; 3: 1895–906.
- Burt FJ, Micheal RS, Rulli NE, Mahalingam S, Heise MT.Chikungunya: a re-emerging virus. Lancet 2012; 379: 662–71
- Queyriaux B, Simon F, Grandadam M, Michel R, Tolou H, Boutin JP. Clinical burden of chikungunya virus infection. Lancet Infect Dis 2008; 8: 2–3.
- Sissoko D, Malvy D, Ezzedine K, et al. Post-epidemic Chikungunya disease on Reunion Island: course of rheumatic manifestations and associated factors over a 15-month period. PLoS Negl Trop Dis 2009;3: e389.
- Robin S, Ramful D, Zettor J, et al. Severe bullous skin lesions associated with Chikungunya virus infection in small infants. Eur J Pediatr 2010; 169: 67–72.
- Inamadar AC, Palit A, Sampagavi VV, et al. Cutaneous manifestations of chikungunya fever: observations made during a recent outbreak in south India. Int J Dermatol 2008; 47: 154–59.
- Bandyopadhyay D, Ghosh SK. Mucocutaneous features of Chikungunya fever: a study from an outbreak in West Bengal, India. Int J Dermatol 2008; 47: 1148–52.
- Rampal M, Sharda M, Meena H. Neurological complications in Chikungunya fever. J Assoc Physicians India 2007; 55: 765–69.
- Singh SS, Manimunda SP, Sugunan AP, Sahina, Vijayachari P. Four cases of acute flaccid paralysis associated with chikungunya virus infection. Epidemiol Infect 2008; 136: 1277–80.
- Economopoulou A, Dominguez M, Helynck B, et al. Atypical Chikungunya virus infections: clinical manifestations, mortality and risk factors for severe disease during the 2005–2006 outbreak on Reunion. Epidemiol Infect 2009; 137: 534–41.
- Panning M, Grywna K, van Esbroeck M, Emmerich P, Drosten C. Chikungunya fever in travelers returning from the Indian Ocean Region, 2006. Emerg Infect Dis 2008; 14: 416–22.
- Clarke EJ Jr, Suitor EC Jr, Jenkin HM. A serologic survey for arbovirus antibodies in inhabitants of asouthwest Taiwan village. Trop Geogr Med 1967; 19: 326–32.
- Shu PY, Yang CF, Su CL, et al. Two imported chikungunya cases, Taiwan. Emerg Infect Dis 2008; 14:1326–7.
- 台灣衛生福利部疾病管制署網站，疾病介紹：屈弓熱
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