今日の臨床サポート

ウエストナイルウイルス感染症(脳炎など)

著者: 上田晃弘 東海大学医学部付属病院 総合内科

監修: 具芳明 東京医科歯科大学大学院医歯学総合研究科 統合臨床感染症学分野

著者校正/監修レビュー済:2016/06/30
患者向け説明資料

概要・推奨   

疾患のポイント:
  1. ウエストナイルウイルス感染症とは、フラビウイルス科フラビウイルス属に属するウエストナイルウイルスによる感染症である。感染症法では4類感染症に属し、直ちに最寄りの保健所に届け出る必要がある。発熱、頭痛、筋肉痛、全身倦怠感、皮疹、けいれん、麻痺、意識障害などの症状を来す。
  1. 20165月時点で日本に存在しないとされるが、海外からの輸入例はある。また、日本にいるコガタアカイエカ(Culex tritaeniorhynchus)やヤマトヤブカ(Aedes japonicus)などが媒介し得るため、ウイルスの侵入により感染が拡大、定着する可能性がある
  1. 潜伏期は、一般に2~14日とわれるが、免疫抑制者ではこれよりも長くなる可能性がある。
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臨床のポイント:
  1. 流行地滞在後、潜伏期間内の全身症状や神経症状をみたらウエストナイルウイルス感染症を鑑別疾患に加える
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薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
上田晃弘 : 特に申告事項無し[2021年]
監修:具芳明 : 特に申告事項無し[2021年]

病態・疫学・診察

疾患情報(疫学・病態)  
  1. ウエストナイルウイルスは、日本脳炎ウイルスと同じフラビウイルス属に属する。鳥と蚊の間で感染サイクルが成立しているが、蚊を介して人間に感染し、脳炎などさまざまな疾患の原因となる[1]
  1. 20165月時点でウエストナイルウイルスは日本に存在しないとされるが、海外からの輸入例はある[2]。また、日本にいるコガタアカイエカ(Culex tritaeniorhynchus)やヤマトヤブカ(Aedes japonicus)などが媒介し得るため、ウイルスの侵入により感染が拡大、定着する可能性がある[3]。事実、米国では1999年まで存在しなかったこのウイルスが流行により全米に広がり、毎年多くの感染者を出すようになった(Culex pipiens, Cx. tarsalisとカラスなどの野鳥を介して感染拡大)[4]
  1. 臨床症状は多彩で、非特異的な発熱、頭痛、筋肉痛、皮疹といった急性ウイルス感染的症状、脳炎、髄膜炎、ギラン・バレー症候群のような神経症状がみられることがある。脈絡網膜炎、肝炎、心筋炎が生じることもある。流行地からの帰国者では本疾患を鑑別に入れることが大切である。なお、80%は不顕性感染である。
  1. 本疾患に特異的な治療法は存在せず、対症療法となる。また、ヒトに有効なワクチンも開発されていないため、予防は流行地で蚊に刺されないことで行われる。
  1. 初発患者(index case)を見逃すと、日本全体に一気に広がり、定着してしまうおそれがあるため、公衆衛生的にもきわめて重要な感染症である。
問診・診察のポイント  
  1. 流行地への渡航歴が最も重要である。流行地はアフリカ、ユーラシア大陸、オーストラリア、北米(カナダ、米国)、中米など多彩である[5]

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文献 

著者: D Nash, F Mostashari, A Fine, J Miller, D O'Leary, K Murray, A Huang, A Rosenberg, A Greenberg, M Sherman, S Wong, M Layton, 1999 West Nile Outbreak Response Working Group
雑誌名: N Engl J Med. 2001 Jun 14;344(24):1807-14. doi: 10.1056/NEJM200106143442401.
Abstract/Text BACKGROUND: In late August 1999, an unusual cluster of cases of meningoencephalitis associated with muscle weakness was reported to the New York City Department of Health. The initial epidemiologic and environmental investigations suggested an arboviral cause.
METHODS: Active surveillance was implemented to identify patients hospitalized with viral encephalitis and meningitis. Cerebrospinal fluid, serum, and tissue specimens from patients with suspected cases underwent serologic and viral testing for evidence of arboviral infection.
RESULTS: Outbreak surveillance identified 59 patients who were hospitalized with West Nile virus infection in the New York City area during August and September of 1999. The median age of these patients was 71 years (range, 5 to 95). The overall attack rate of clinical West Nile virus infection was at least 6.5 cases per million population, and it increased sharply with age. Most of the patients (63 percent) had clinical signs of encephalitis; seven patients died (12 percent). Muscle weakness was documented in 27 percent of the patients and flaccid paralysis in 10 percent; in all of the latter, nerve conduction studies indicated an axonal polyneuropathy in 14 percent. An age of 75 years or older was an independent risk factor for death (relative risk adjusted for the presence or absence of diabetes mellitus, 8.5; 95 percent confidence interval, 1.2 to 59.1), as was the presence of diabetes mellitus (age-adjusted relative risk, 5.1; 95 percent confidence interval, 1.5 to 17.3).
CONCLUSIONS: This outbreak of West Nile meningoencephalitis in the New York City metropolitan area represents the first time this virus has been detected in the Western Hemisphere. Given the subsequent rapid spread of the virus, physicians along the eastern seaboard of the United States should consider West Nile virus infection in the differential diagnosis of encephalitis and viral meningitis during the summer months, especially in older patients and in those with muscle weakness.

PMID 11407341  N Engl J Med. 2001 Jun 14;344(24):1807-14. doi: 10.1056・・・
伊藤美佳子:ウエストナイル熱/ウエストナイル脳炎とは, 国立感染症研究所[last viewed Jan 19, 2016]
著者: Roland Brilla, Margo Block, Glen Geremia, Melvin Wichter
雑誌名: J Neurol Sci. 2004 May 15;220(1-2):37-40. doi: 10.1016/j.jns.2004.01.013.
Abstract/Text BACKGROUND: West Nile Virus (WNV) is a flavivirus WNV that has spread westwards across North America in recent years. It can cause a febrile illness and infection of the central nervous system, which is associated with poor outcome.
METHODS: We retrospectively studied the clinical and neuroradiologic features of 39 consecutive patients admitted during summer of 2002 that had IgM in the cerebrospinal fluid positive for WNV.
RESULTS: Fever, headache and altered mentation were predominant clinical features. Clinically significant involvement of lower motor neurons was seen in few cases. Magnetic resonance imaging (MRI) of the brain did not show changes attributable to meningitis or encephalitis except for one case of subcortical signal abnormalities. Unfavorable prognostic factors are old age, decreased level of alertness and elevated serum creatinine.
CONCLUSIONS: Encephalopathic presentations, with or without additional neurological focality, dominated this series. Fever and meningitic signs are often absent. Involvement of lower motor neurons was uncommon. Given the paucity of positive findings, the value of MRI to support the diagnosis of WNV-meningoencephalitis is limited.

PMID 15140603  J Neurol Sci. 2004 May 15;220(1-2):37-40. doi: 10.1016/・・・
著者: Muhammad Ali, Yair Safriel, Jaideep Sohi, Alfred Llave, Susan Weathers
雑誌名: AJNR Am J Neuroradiol. 2005 Feb;26(2):289-97.
Abstract/Text BACKGROUND AND PURPOSE: West Nile virus (WNV) infection is an ongoing seasonal epidemic. We correlated the MR imaging findings with the clinical presentations and outcomes of WNV infection.
METHODS: We reviewed 14 brain and three spinal MR images: nonenhanced and contrast-enhanced T1-weighted images (T1WIs) and T2-weighted images (T2WIs), nonenhanced fluid-attenuated inversion recovery (FLAIR) images (11 patients) and enhanced FLAIR images (three patients), with diffusion-weighted (DW) images and apparent diffusion coefficient maps. WNV infection was diagnosed by means of enzyme-linked immunosorbent assay with a plaque reduction neutralization test. We also correlated the MR findings with the clinical presentation, course, and outcome to determine their prognostic importance.
RESULTS: MR imaging findings included: 1) normal (five patients); 2) DW imaging-only abnormalities in the white matter, corona radiata, and internal capsule (four patients); 3) hyperintensity on FLAIR images and T2WIs in the lobar gray and white matter, cerebellum, basal ganglia, thalamus and internal capsule, pons and midbrain (three patients); 4) meningeal involvement (two patients); and 5) spinal cord, cauda equina, and nerve root involvement (three patients). All patients with finding 1 and all but one with finding 2 recovered completely. Two patients with finding 3 died. Those with finding 4 or 5 had residual neurologic deficits that were severe or moderate to severe, respectively.
CONCLUSION: Patients with normal MR images or abnormalities on only DW images had the best prognosis, while those with abnormal signal intensity on T2WI and FLAIR images had the worst outcomes. No definite predilection for any specific area of the brain parenchyma was noted.

PMID 15709126  AJNR Am J Neuroradiol. 2005 Feb;26(2):289-97.
著者: Kalliopi A Petropoulou, Steven M Gordon, Richard A Prayson, Paul M Ruggierri
雑誌名: AJNR Am J Neuroradiol. 2005 Sep;26(8):1986-95.
Abstract/Text BACKGROUND AND PURPOSE: Reports of MR imaging in West Nile virus (WNV) meningoencephalomyelitis are few and the described findings limited. The purpose of this study was to review the spectrum of MR imaging findings for WNV meningoencephalomyelitis and investigate whether any of the findings correlates with clinical presentation of flaccid paralysis.
METHODS: We reviewed the MR imaging findings of 17 patients with confirmed WNV encephalitis and/or myelitis. MR imaging brain studies were evaluated for location of signal intensity abnormalities, edema, hydrocephalus, or abnormal enhancement. MR imaging spine studies were evaluated for signal intensity abnormalities in cord and/or enhancement.
RESULTS: Retrospective review of the MR imaging studies of 17 patients was performed by 2 neuroradiologists. Eleven of 16 brain MR images demonstrated abnormalities. Eight (50%) patients had abnormal studies related to meningoencephalitis. All 8 patients had abnormal findings in the deep gray matter and/or brain stem; 2 had additional white matter abnormalities. Three patients with abnormal MR studies of the spine had extremity weakness on examination. The imaging findings included abnormal signal intensity more pronounced in the ventral horns and/or enhancement around the conus medullaris and cauda equina. One patient had additional abnormalities in the pons.
CONCLUSION: Abnormal MR imaging findings in patients with WNV meningoencephalomyelitis are nonspecific but not uncommon. Anatomic areas commonly affected are basal ganglia, thalami, mesial temporal structures, brain stem, and cerebellum. Extremity weakness or flaccid paralysis corresponds to spinal cord/cauda equina abnormalities.

PMID 16155147  AJNR Am J Neuroradiol. 2005 Sep;26(8):1986-95.
著者: Daniel R O'Leary, Anthony A Marfin, Susan P Montgomery, Aaron M Kipp, Jennifer A Lehman, Brad J Biggerstaff, Veronica L Elko, Peggy D Collins, John E Jones, Grant L Campbell
雑誌名: Vector Borne Zoonotic Dis. 2004 Spring;4(1):61-70. doi: 10.1089/153036604773083004.
Abstract/Text Since 1999, health officials have documented the spread of West Nile virus across the eastern and southern states and into the central United States. In 2002, a large, multi-state, epidemic of neuroinvasive West Nile illness occurred. Using standardized guidelines, health departments conducted surveillance for West Nile virus illness in humans, and West Nile virus infection and illness in non-human species. Illnesses were reported to the Centers for Disease Control and Prevention (CDC) through the ArboNET system. In 2002, 39 states and the District of Columbia reported 4,156 human West Nile virus illness cases. Of these, 2,942 (71%) were neuroinvasive illnesses (i.e., meningitis, encephalitis, or meningoencephalitis) with onset dates from May 19 through December 14; 1,157 (28%) were uncomplicated West Nile fever cases, and 47 (1%) were clinically unspecified. Over 80% of neuroinvasive illnesses occurred in the central United States. Among meningitis cases, median age was 46 years (range, 3 months to 91 years), and the fatality-to-case ratio was 2%; for encephalitis cases (with or without meningitis), median age was 64 years (range, 1 month to 99 years) and the fatality-to-case ratio was 12%. Neuroinvasive illness incidence and mortality, respectively, were significantly associated with advanced age (p = 0.02; p = 0.01) and being male (p < 0.001; p = 0.002). In 89% of counties reporting neuroinvasive human illnesses, West Nile virus infections were first noted in non-human species, but no human illnesses were reported from 77% of counties in which non-human infections were detected. In 2002, West Nile virus caused the largest recognized epidemic of neuroinvasive arboviral illness in the Western Hemisphere and the largest epidemic of neuroinvasive West Nile virus ever recorded. It is unknown why males appeared to have higher risk of severe illness and death, but possibilities include higher prevalence of co-morbid conditions or behavioral factors leading to increased infection rates. Several observations, including major, multi-state West Nile virus epidemics in 2002 and 2003, suggest that major epidemics may annually reoccur in the United States. Non-human surveillance can warn of early West Nile virus activity and needs continued emphasis, along with control of Culex mosquitoes.

PMID 15018774  Vector Borne Zoonotic Dis. 2004 Spring;4(1):61-70. doi:・・・
著者: Hetal Patel, Beate Sander, Mark P Nelder
雑誌名: Lancet Infect Dis. 2015 Aug;15(8):951-9. doi: 10.1016/S1473-3099(15)00134-6. Epub 2015 Jul 7.
Abstract/Text We systematically reviewed the clinical outlook of West Nile virus (WNV)-related illness in North America and western Europe. As of March, 2015, more than 45 000 cases of WNV-related illness have been reported in North America. Unlike acute morbidity and mortality, the long-term physical, cognitive, and functional sequelae associated with WNV-related illness are not well characterised. An understanding of WNV-related sequelae and their prognostic factors can support physicians with early diagnosis and tertiary prevention efforts. We searched Ovid Medline, Embase, Scopus, and Environment Complete for studies published between 1999 and 2015. We included 67 studies in our Review. Although muscle weakness, memory loss, and difficulties with activities of daily living were among the most common physical, cognitive, and functional sequelae, respectively, some population groups were reported to be at greater risk of severe neurological disease or death (ie, older men with underlying illnesses such as cardiovascular disease or cancer). A high level of heterogeneity was reported among studies included in this Review, suggesting a need for consistent methods for collecting data and reporting findings. Further, more than half of the studies reporting sequelae relied exclusively on subjective assessment and only two studies used matched control groups. Therefore, opportunities exist for more robust primary studies in future research.

Copyright © 2015 Elsevier Ltd. All rights reserved.
PMID 26163373  Lancet Infect Dis. 2015 Aug;15(8):951-9. doi: 10.1016/S・・・
著者: James J Sejvar, Amy V Bode, Anthony A Marfin, Grant L Campbell, John Pape, Brad J Biggerstaff, Lyle R Petersen
雑誌名: Emerg Infect Dis. 2006 Mar;12(3):514-6. doi: 10.3201/eid1205.050643.
Abstract/Text We report 1-year follow-up data from a longitudinal prospective cohort study of patients with West Nile virus-associated paralysis. As in the 4-month follow-up, a variety of recovery patterns were observed, but persistent weakness was frequent. Respiratory involvement was associated with considerable illness and death.

PMID 16704798  Emerg Infect Dis. 2006 Mar;12(3):514-6. doi: 10.3201/ei・・・
著者: Allan R Tunkel, Carol A Glaser, Karen C Bloch, James J Sejvar, Christina M Marra, Karen L Roos, Barry J Hartman, Sheldon L Kaplan, W Michael Scheld, Richard J Whitley, Infectious Diseases Society of America
雑誌名: Clin Infect Dis. 2008 Aug 1;47(3):303-27. doi: 10.1086/589747.
Abstract/Text Guidelines for the diagnosis and treatment of patients with encephalitis were prepared by an Expert Panel of the Infectious Diseases Society of America. The guidelines are intended for use by health care providers who care for patients with encephalitis. The guideline includes data on the epidemiology, clinical features, diagnosis, and treatment of many viral, bacterial, fungal, protozoal, and helminthic etiologies of encephalitis and provides information on when specific etiologic agents should be considered in individual patients with encephalitis.

PMID 18582201  Clin Infect Dis. 2008 Aug 1;47(3):303-27. doi: 10.1086/・・・

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