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West Nile virus (WNV)

Etiology: - West Nile virus Epidemiology: 1) spread by [5] a) mosquitoes b) blood transfusions c) organ transplantation d) breast feeding e) vertical transmission, mother to infant 2) birds are the main reservoir [11] 3) sporadic outbreaks - epidemic transmission in Africa & throughout the world 5) most cases in August & September 7) fatal infections in birds, from Arkansas to Maine 8) horses only non-human mammal with documented infection 9) older adults & immunocompromised are high risk [11] 10) cases reported in USA - cases reported in New York City (62 in 1999) - 1/2 of these patients > 70 years of age - 66 deaths; most in New York, New Jersey, Florida - 4200 cases in 2002; 25 from blood transfusions [6] - at least 3 deaths in Louisiana 2002 - 4000 cases in US (2003); 284 deaths [5] - cases up in 2012 [12] - 2600 as of Jan 1 - Sept 13 2012, with 118 deaths - 50% of cases in Texas [15] - epidemic in Dallas, Texas 2012 precipitated by a high mosquito infection rate & mild weather during preceding winter [18] - virus detected in people, birds, or mosquitoes in every state except Alaska & Hawaii [15] - 286 deaths in the U.S. in 2012 - 2911 cases in 2021 [25] - median age, 65; 60% male; 72% hospitalized, 8% mortality - 1140 cases reported in Arizona - 69% of cases neuroinvasive - most commonly reported arbovirus infection in U.S, [25] 11) sentinel chickens used in Los Angeles county as one of the 1st lines of defense against West Nile virus [23] 6) spreading of disease in Europe Pathology: - meningitis, encephalitis, myelitis (< 1%) [11] - renal disease, cancer, alcohol abuse, diabetes, & hypertension associated with severe West Nile virus infection [12] - diabetes & hypertension may increase permeability of the blood-brain barrier, facilitating viral entry into the CNS [12] Genetics: - variations in CCR5 are associated with susceptibility to West Nile virus Clinical manifestations: 1) majority of infected individuals (80%) are asymptomatic [7] 2) 20% of infected individuals get flu-like symptoms 3) symptoms develop 3-14 days after infection (mosquitoe bite) 4) illness may be mild & transient 5) in endemic areas, infection generally results in mild febrile illness 6) fever 7) headache 8) rash (19%) 9) focal muscle weakness characteristic [11] (27%) 10) myalgias 11) hyporeflexia (32%) 12) diffuse or asymmetric flaccid paralysis (10%) 13) multifocal chorioretinitis [9] 14) encephalitis (1%) a) severe neurologic disease b) brainstem, cranial nerve, cerebellar dysfunction c) basal ganglia involvement can account for tremors, myoclonus, parkinsonism d) persistent vegetative state 15) meningitis 16) myelitis 17) absence of sensory deficits [] Laboratory: 1) complete blood count (CBC) a) lymphpenia b) anemia c) thrombocytopenia 2) serum Na+: hyponatremia may be observed 3) routine laboratories are otherwise generally unremarkable 4) West Nile virus serology: - West Nile virus Ab in serum - West Nile virus IgM in serum* - West Nile virus Ab in CSF - antibodies to WNV in other body fluids - West Nile virus IgM in CSF* positive in > 90% of patients with neuroinvasive WNV (within 1 week of symptom onset) [11] - diagnostic test of choice [11] 5) West Nile virus antigen 6) RT-PCR for West Nile virus RNA - viremia generally cleared by the time of presentation 7) viral culture (no corresponding Loinc found) 8) CSF examination: a) consistent with viral meningitis/encephalitis b) does NOT establish prognosis [10] * initial diagnostic tests of choice [11] Special laboratory: - electromyography (EMG) & or nerve conduction study for flaccid paralysis [11] Radiology: - magnetic resonance imaging (MRI) - exclude Herpes simplex virus (HSV) encephalitis - neuroimaging generally normal; thalamus, basal ganglia, & spinal cord abnormalities most common [11] Management: (based on 1999 NY city population) 1) 59 of 62 required hospitalization a) supportive care (no specific treatment) [5] b) 10 patients required mechanical ventilation c) mean length of stay: 15 days 2) all case fatality 12% 3) risk factors for severe or fatal infection a) age > 75 years b) diabetes mellitus 4) treat patients with acyclovir until HSV is excluded [11] 5) ophthalmologic examination of symptomatic patients [9] 6) prophylaxis: - insect repellants [7] - no vaccine available (2021) [11] 7) screening of blood supply by RT-PCR began 2003 [5,6] Comparative biology: - WNV infection of neurons triggers activation of the complement cascade within the hippocampus of mice [22] - microglia then trim presynaptic terminals in response to complement activation (neurons remain viable)

General

encephalitis virus flaviviridae

Properties

KINGDOM: virus GENOME-TYPE: RNA SINGLE-STRANDED NEGATIVE-STRAND GENOME-SIZE: 10 kB ENVELOPE: PRESENT CAPSID-SYMMETRY: ICOSAHEDRAL

Database Correlations

OMIM 610379

References

  1. Journal Watch 21(1):12, 2001
  2. Centers for Disease Control and Prevention (CDC). Update: West Nile Virus activity--Eastern United States, 2000. MMWR Morb Mortal Wkly Rep. 2000 Nov 24;49(46):1044-7. PMID: 11105767
  3. Journal Watch 21(14):116, 2001 Nash D et al The outbreak of West Nile virus infection in the New York City area in 1999. N Engl J Med 344:1807, 2001 PMID: 11407341
  4. Journal Watch 22(14):111, 2002
  5. Prescriber's Letter 10(7):39 2003
  6. Journal Watch 23(22):180, 2003 Pealer LN et al Transmission of West Nile virus through blood transfusion in the United States in 2002. N Engl J Med 349:1236, 2003 PMID: 14500806 - Centers for Disease Control and Prevention (CDC). Update: Detection of West Nile virus in blood donations- United States, 2003. PMID: 14515874 MMWR Morb Mortal Wkly Rep 52:916, 2003 http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5238a6.htm Erratum to: MMWR Morb Mortal Wkly Rep 52:916, 2003 http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5239a8.htm
  7. Prescriber's Letter 12(6): 2005 Keeping Safe From West Nile Virus Detail-Document#: 210601 (subscription needed) http://www.prescribersletter.com
  8. Busch MP, Caglioti S, Robertson EF, McAuley JD, Tobler LH, Kamel H, Linnen JM, Shyamala V, Tomasulo P, Kleinman SH. Screening the blood supply for West Nile virus RNA by nucleic acid amplification testing. N Engl J Med. 2005 Aug 4;353(5):460-7. PMID: 16079369 - Stramer SL, Fang CT, Foster GA, Wagner AG, Brodsky JP, Dodd RY. West Nile virus among blood donors in the United States, 2003 and 2004. N Engl J Med. 2005 Aug 4;353(5):451-9. PMID: 16079368 - Petersen LR, Epstein JS. Problem solved? West Nile virus and transfusion safety. N Engl J Med. 2005 Aug 4;353(5):516-7. No abstract available. PMID: 16079376
  9. Abroug F et al, A cluster of predictors of severe West Nile virus infection Mayo Clinc 2006; 81:12 PMID: 16438473
  10. Tyler KL, Pape J, Goody RJ, Corkill M, Kleinschmidt-DeMasters BK. CSF findings in 250 patients with serologically confirmed West Nile virus meningitis and encephalitis. Neurology. 2006 Feb 14;66(3):361-5. Epub 2005 Dec 28. PMID: 16382032
  11. Medical Knowledge Self Assessment Program (MKSAP) 14, 16, 17, 19. American College of Physicians, Philadelphia 2006, 2012, 2015, 2021. - Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022
  12. Lindsey NP et al Medical risk factors for severe west nile virus disease, United States, 2008-2010. Am J Trop Med Hyg. 2012 Jul;87(1):179-84. PMID: 22764311
  13. Centers for Disease Control and Prevention Press Release: August 1, 2012 West Nile virus disease cases up this year http://www.cdc.gov/media/releases/2012/p0801_west_nile.html
  14. Dallas mayor declares emergency over West Nile virus Reuters, August 15, 2012 http://www.reuters.com/article/2012/08/15/us-usa-health-westnile-idUSBRE87E0ZO20120815
  15. Prescriber's Letter 19(10): 2012 COMMENTARY: The Facts About West Nile Virus Detail-Document#: 281025 (subscription needed) http://www.prescribersletter.com
  16. Sejvar JJ, Bode AV, Marfin AA et al West Nile virus-associated flaccid paralysis. Emerg Infect Dis. 2005 Jul;11(7):1021-7 PMID: 16022775
  17. Murray KO, Walker C, Gould E. The virology, epidemiology, and clinical impact of West Nile virus: a decade of advancements in research since its introduction into the Western Hemisphere. Epidemiol Infect. 2011 Jun;139(6):807-17 PMID: 21342610
  18. Chung WM et al. The 2012 West Nile encephalitis epidemic in Dallas, Texas. JAMA 2013 Jul 17; 310:297. PMID: 23860988 - Ostroff SM. West Nile virus: Too important to forget. JAMA 2013 Jul 17; 310:267. PMID: 23860984
  19. Lindsey NP et al West Nile Virus and Other Arboviral Diseases, United States 2013 MMWR. June 20, 2014 / 63(24);521-526 http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6324a1.htm
  20. Petersen LR, Brault AC, Nasci RS. West Nile virus: review of the literature. JAMA. 2013 Jul 17;310(3):308-15. Review. PMID: 23860989 Free PMC Article
  21. Hart J Jr, Tillman G, Kraut MA et al West Nile virus neuroinvasive disease: neurological manifestations and prospective longitudinal outcomes. BMC Infect Dis. 2014 May 9;14:248. PMID: 24884681 Free PMC Article
  22. Vasek MJ, Garber C, Dorsey D et al A complement-microglial axis drives synapse loss during virus- induced memory impairment. Nature. 2016 Jun 22;534(7608):538-43. PMID: 27337340
  23. McFarling UL Chickens a Sentinel Species for West Nile. Researchers in California using domesticated fowl to track viral spread. MedPage Today. Sept 30, 2017 https://www.medpagetoday.com/InfectiousDisease/GeneralInfectiousDisease/68233
  24. NEJM Knowledge+ Neurology
  25. Fagre AC, Lyons S, Staples JE, Lindsey N. West Nile virus and other nationally notifiable arboviral diseases - United States, 2021. MMWR Morb Mortal Wkly Rep 2023 Aug 25; 72:901. PMID: 37616182 PMCID: PMC10468221 Free PMC article https://www.cdc.gov/mmwr/volumes/72/wr/mm7234a1.htm
  26. Centers for Disease Control and Prevention West Nile Virus http://www.cdc.gov/ncidod/dvbid/westnile/index.htm