Mandell：Bennett JE, Dolin R, Blaser MJ. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases 9th ed. Elsevier health sciences, 2019.
米国疾病対策予防センター（Centers for Disease Control and Prevention: CDC）：West Nile virus（2022年5月29日閲覧）.
Lyle R Petersen, Aaron C Brault, Roger S Nasci
West Nile virus: review of the literature.
JAMA. 2013 Jul 17;310(3):308-15. doi: 10.1001/jama.2013.8042.
Abstract/Text
IMPORTANCE: Since its introduction in North America in 1999, West Nile virus has produced the 3 largest arboviral neuroinvasive disease outbreaks ever recorded in the United States.
OBJECTIVE: To review the ecology, virology, epidemiology, clinical characteristics, diagnosis, prevention, and control of West Nile virus, with an emphasis on North America.
EVIDENCE REVIEW: PubMed electronic database was searched through February 5, 2013. United States national surveillance data were gathered from the Centers for Disease Control and Prevention.
FINDINGS: West Nile virus is now endemic throughout the contiguous United States, with 16,196 human neuroinvasive disease cases and 1549 deaths reported since 1999. More than 780,000 illnesses have likely occurred. To date, incidence is highest in the Midwest from mid-July to early September. West Nile fever develops in approximately 25% of those infected, varies greatly in clinical severity, and symptoms may be prolonged. Neuroinvasive disease (meningitis, encephalitis, acute flaccid paralysis) develops in less than 1% but carries a fatality rate of approximately 10%. Encephalitis has a highly variable clinical course but often is associated with considerable long-term morbidity. Approximately two-thirds of those with paralysis remain with significant weakness in affected limbs. Diagnosis usually rests on detection of IgM antibody in serum or cerebrospinal fluid. Treatment is supportive; no licensed human vaccine exists. Prevention uses an integrated pest management approach, which focuses on surveillance, elimination of mosquito breeding sites, and larval and adult mosquito management using pesticides to keep mosquito populations low. During outbreaks or impending outbreaks, emphasis shifts to aggressive adult mosquito control to reduce the abundance of infected, biting mosquitoes. Pesticide exposure and adverse human health events following adult mosquito control operations for West Nile virus appear negligible.
CONCLUSIONS AND RELEVANCE: In North America, West Nile virus has and will remain a formidable clinical and public health problem for years to come.
Caren Chancey, Andriyan Grinev, Evgeniya Volkova, Maria Rios
The global ecology and epidemiology of West Nile virus.
Biomed Res Int. 2015;2015:376230. doi: 10.1155/2015/376230. Epub 2015 Mar 19.
Abstract/Text
Since its initial isolation in Uganda in 1937 through the present, West Nile virus (WNV) has become an important cause of human and animal disease worldwide. WNV, an enveloped virus of the genus Flavivirus, is naturally maintained in an enzootic cycle between birds and mosquitoes, with occasional epizootic spillover causing disease in humans and horses. The mosquito vectors for WNV are widely distributed worldwide, and the known geographic range of WNV transmission and disease has continued to increase over the past 77 years. While most human infections with WNV are asymptomatic, severe neurological disease may develop resulting in long-term sequelae or death. Surveillance and preventive measures are an ongoing need to reduce the public health impact of WNV in areas with the potential for transmission.
Kalliopi A Petropoulou, Steven M Gordon, Richard A Prayson, Paul M Ruggierri
West Nile virus meningoencephalitis: MR imaging findings.
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.
Muhammad Ali, Yair Safriel, Jaideep Sohi, Alfred Llave, Susan Weathers
West Nile virus infection: MR imaging findings in the nervous system.
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.
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
The outbreak of West Nile virus infection in the New York City area in 1999.
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.
伊藤美佳子：感染症の話 ウエストナイル熱／ウエストナイル脳炎 国立感染症研究所感染症発生動向調査週報（IDWR） vol. 27, 2002.
Peter A G Tilley, Julie D Fox, Gayatri C Jayaraman, Jutta K Preiksaitis
Nucleic acid testing for west nile virus RNA in plasma enhances rapid diagnosis of acute infection in symptomatic patients.
J Infect Dis. 2006 May 15;193(10):1361-4. doi: 10.1086/503577. Epub 2006 Apr 4.
Abstract/Text
Although nucleic acid amplification testing (NAAT) for West Nile virus (WNV) is useful in screening blood donors, such methods have not been studied in symptomatic patients. For diagnosis of WNV infection, 1.0 mL of plasma was tested by NAAT, and WNV-specific immunoglobulin M was assayed. Of 276 WNV cases, 191 were tested by both serology and NAAT. Of these, 86 (45.0%), 111 (58.1%), and 180 (94.2%) were detected by NAAT, serology, and combined NAAT and serology, respectively. NAAT-based screening was most useful within 8 days of the onset of symptoms. Viremia is common in early symptomatic WNV infection, and NAAT enhances diagnostic yield.
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
The epidemic of West Nile virus in the United States, 2002.
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.
Hetal Patel, Beate Sander, Mark P Nelder
Long-term sequelae of West Nile virus-related illness: a systematic review.
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.
Fang Tang, Jiu-Song Zhang, Wei Liu, Qui-Min Zhao, Fang Zhang, Xiao-Ming Wu, Hong Yang, Hinh Ly, Wu-Chun Cao
Failure of Japanese encephalitis vaccine and infection in inducing neutralizing antibodies against West Nile virus, People's Republic of China.
Am J Trop Med Hyg. 2008 Jun;78(6):999-1001.
Abstract/Text
We examined whether live attenuated Japanese encephalitis (JE) vaccine is effective in preventing West Nile virus (WNV) infection in the People's Republic of China. Three groups were recruited into the study: patients with Japanese encephalitis (JE), healthy controls vaccinated with live attenuated 2 SA14-14-vaccine against JE virus (JEV), and unvaccinated healthy controls. Serum samples were collected and screened for IgG antibodies against JEV by an indirect immunofluorescence assay. Positive samples were then analyzed for levels of antibodies against JEV and neutralizing antibodies against West Nile virus (WNV) by a plaque-reduction neutralization test (PRNT). Although most persons had medium to high levels of JEV-reactive IgG and neutralizing antibodies, only 2 of the 82 unvaccinated control samples were positive for the WNV-reactive antibodies. These findings suggest that previous JEV infection or vaccination did not induce adequate levels of WNV-reactive antibodies in the population studied. However, how these persons would respond to a secondary flavivirus infection and whether their prior experience with wild-type or attenuated JE vaccine will provide some cross-protection against WNV disease still warrants further investigation.
