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Clinical Characteristics and Functional Outcomes of West Nile Fever

John T. Watson, MD, MSc; Peter E. Pertel, MD, MPH; Roderick C. Jones, MPH; Alicia M. Siston, MPH; William S. Paul, MD, MPH; Constance C. Austin, DVM, PhD, MPH; and Susan I. Gerber, MD
[+] Article, Author, and Disclosure Information

From Chicago Department of Public Health, Chicago, and Illinois Department of Public Health, Springfield, Illinois; and Centers for Disease Control and Prevention, Atlanta, Georgia.

Potential Financial Conflicts of Interest: None disclosed.

Corresponding Author: John T. Watson, MD, Chicago Department of Public Health, 2160 West Ogden, Chicago, IL 60612; e-mail, watson_john@cdph.org.

Current Author Addresses: Drs. Watson, Paul, and Gerber, Mr. Jones, and Ms. Siston: Chicago Department of Public Health, 2160 West Ogden, Chicago, IL 60612.

Dr. Pertel: Bayer Pharmaceuticals, 400 Morgan Lane, West Haven, CT 06516.

Dr. Austin: Illinois Department of Public Health, 525 West Jefferson Street, Springfield, IL 62761.

Author Contributions: Conception and design: J.T. Watson, P.E. Pertel, R.C. Jones, W.S. Paul, S.I. Gerber.

Analysis and interpretation of the data: J.T. Watson, P.E. Pertel, R.C. Jones, A.M. Siston, S.I. Gerber.

Drafting of the article: J.T. Watson, P.E. Pertel, R.C. Jones.

Critical revision of the article for important intellectual content: J.T. Watson, P.E. Pertel, R.C. Jones, A.M. Siston, W.S. Paul, C.C. Austin, S.I. Gerber.

Final approval of the article: J.T. Watson, P.E. Pertel, R.C. Jones, A.M. Siston, W.S. Paul, C.C. Austin, S.I. Gerber.

Provision of study materials or patients: C.C. Austin.

Statistical expertise: R.C. Jones, A.M. Siston.

Collection and assembly of data: J.T. Watson, P.E. Pertel.

Ann Intern Med. 2004;141(5):360-365. doi:10.7326/0003-4819-141-5-200409070-00010
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In 2002, 331 West Nile virus infections reported in Illinois residents met the case definition for West Nile fever. Of these, 140 persons (42%) lived in jurisdictions of participating local health departments and were eligible for inclusion in the study. No information was obtained on 191 individuals (58%) who lived in jurisdictions of nonparticipating health departments. Of the 140 persons eligible for inclusion, 29 were not interviewed because of incorrect telephone numbers; 9 could not be reached in at least 3 attempts; 3 were unwilling or unable to participate; and 1, who was 3 years of age, was not evaluated. The remaining 98 patients, who did not report having a lumbar puncture and had no record of submission of cerebrospinal fluid for laboratory testing, were enrolled in the study.

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A Plea for Clinical Clarity: If West Nile Encephalitis is Caused by West Nile Virus, then what is WN
Posted on October 27, 2004
Burke A. Cunha
Winthrop-University Hospital
Conflict of Interest: None Declared

TO THE EDITOR: I read with interest the recent Annals article by Dr. Watson, et al describing West Nile Fever. (1)

In their article, the authors review the clinical features and outcomes of patients with infection due to West Nile Virus (WNV). The article's main point is that the use of the term West Nile Fever (WNF) WNV would permit a better mapping of the geographical distribution of WNV. The introduction of a separate term WNF for WNV infection seems unnecessary and serves no useful epidemiologic or clinical purpose. Seroepidemiology surveys mapping the extent of the disease are based upon positive serological tests against the etiological agent WNV. The authors suggest that WNF is worthy of a separate term is based on the self- reporting of 98 patients with WNV infection. While fever was a common finding in their data (81%), headache was present in 71%, and myalgias in 62% were also present. In a group of 98 respondents, 55% had neck pain or stiffness suggesting meningeal involvement and importantly, 53% reported difficulty concentrating suggesting a some degree of encephalitis. Therefore, the cohort that they described of 98 patients with WNF, in fact, had a spectrum of neurological manifestations associated with WNV and not just fevers. The validity of the group's responses can be questioned since 57% reported a rash, which has been common in WNE cases in Europe but not in the United States experience. (2)

Clinicians are constantly deluged with confusing terms and in my view, the term WNF does not add anything helpful in a public health or clinical sense. WNE is the proper term for the main clinical manifestation of WNV. Physicians understand that WNV infection represents a spectrum of disease including aseptic meningitis, meningoencephalitis, or WNE. Any of these variants may or may not be accompanied by flaccid paralysis. Other manifestations of WNE have also been described including ophthalmologic manifestations. If the current terminology is maintained, i.e., WNV is the term used to indicate the spectrum of WNV infection then everyone understands the spectrum of clinical expression of WNV. (3 "“ 10)

To state that a viral infection causes fever, makes little sense since fever is a cardinal manifestation of a wide variety of infectious and non-infectious disorders. The patients the authors described did not have only fever, but in fact, had neurological and systemic manifestations associated with WNE. Besides WNE, other flavivirus cause encephalitis, e.g., Murray Valley encephalitis (MVE), Japanese encephalitis (JE). Both MVE and JE also have a wide spectrum of clinical manifestations including fever as well as non-encephalopathic manifestations. The clinical usefulness of the terms MVE and JE are time tested, unambiguous and retain their usefulness epidemiologically and clinically. No one should suggest renaming JE Japanese fever (JF) or hemorrhagic Japanese fever (HJF) since these terms would add nothing and be confusing. The same is true with the other arthropod bourne causes of encephalitis, i.e., Eastern Equine encephalitis (EEE), Western Equine encephalitis (WEE), Venezuelan Equine encephalitis (VE), St. Louis encephalitis (SLE), California encephalitis (CE), etc. No epidemiologic or clinical purpose would be served by adding new terms, i.e., Eastern Equine fever, Western Equine fever, Venezuelan Equine fever, etc. Physicians realize these causes of viral encephalitis have a clinical spectrum like WNV which, varies and all are accompanied by fever. (3, 7, 10)

Therefore, I think that the clinical term WNV should represent the entire clinical spectrum of infection, i.e., aseptic meningitis, meningoencephalitis, or WNE with or without muscle weakness/paralysis. Fever accompanies WNV infections. The presence of fever, per se, does not warrant a special term or diagnostic category. The term WNF should be abandoned in my view since fever is rarely, if ever, the sole manifestation of WNV and regularly accompanies the clinical spectrum of WNV ranging from aseptic meningitis to meningoencephalitis or encephalitis. (2 "“ 5) The large number of viral causes of encephalitis and systemic disorders with encephalopathy as a component, are difficult enough for clinicians to keep straight and recognize their differential diagnostic features. In endemic areas, febrile patients with neurological manifestations should certainly be serologically tested for WNV. The clinical classification of WNV depends on the clinical manifestations. I would strongly urge clinicians to continue to use the clinical and epidemiologically useful terms WNE and WNV and not use the unhelpful term of WNF. I agree with the authors that WNV infection should be a reportable, which would determine the actual geographical distribution of WNV infection. However, WNF should not be a reportable illness. That WNV causes WNE is sufficient and WNF is unnecessary. This is an additional term, e.g., WNF can only confuse physicians when they could best benefit from more rather than less clinical clarity.

Burke A. Cunha, MD Infectious Disease Division Winthrop-University Hospital Mineola, New York and State University of New York School of Medicine Stony Brook, New York

References 1. Watson JT, Pertel PE, Jones RC, Siston AM, Paul WS, Austin CC, Gerber SI. Clinical characteristics and function outcomes of West Nile fever. Ann Intern Med. 2004;141:360-365.

2. Asnis DS, Conetta R, Teixeira AA, et al. The West Nile virus outbreak of 1999 in New York: The Flushing Hospital Experience. Clin Infect Dis 2000; 30:413-418.

3. Cunha BA. West Nile Encephalitis. Infectious Disease Practice 1999;23:85-90.

4. Mostashari F, Bunning ML, Kitsutani PT, Singer DA, Nash D, Cooper MJ, et al. Epidemic West Nile encephalitis, New York, 1999: results of a household-based seroepidemiological survey. Lancet. 2001;358:261-264.

5. Klein NC, Johnson DH, Cunha BA, Minniganti V, Hansen E. West Nile Encephalitis: The Long Island Experience. Infect Dis Clin Pract 2000;9:303-308.

6. Gea-Banacloche J, Johnson RT, Bagic A, et al. West Nile virus: pathogenesis and therapeutic options. Ann Intern Med 2004;140:545-553.

7. Solomon T. Exotic and emerging viral encephalitides. Curr Opin Neurol 2003; 16:411-418.

8. Sejvar JJ, Leis AA, Stokic DS, et al. Acute flaccid paralysis and West Nile virus infection. Emerg Infect Dis 2003;9:788-793.

9. Sejvar JJ, Haddad MB, Tierney BC, Campbell GL, Marfin AA, Van Gerpe JA, et al. Neurologic manifestations and outcome of West Nile virus infection. JAMA. 2003;290:511-515.

10. Cunha BA. Differential diagnosis of West Nile encephalitis. Curr Opin Infect Dis. 2004;17:413-420..

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Summary for Patients

Clinical Characteristics and Consequences of West Nile Fever

The summary below is from the full report titled “Clinical Characteristics and Functional Outcomes of West Nile Fever.” It is in the 7 September 2004 issue of Annals of Internal Medicine (volume 141, pages 360-365). The authors are J.T. Watson, P.E. Pertel, R.C. Jones, A.M. Siston, W.S. Paul, C.C. Austin, and S.I. Gerber.


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