Depression after infection with West Nile Virus

Emerging Infectious Diseases, March, 2007 by Kristy O. Murray, Melissa Resnick, Vicki Miller

Previous reports have noted depression after West Nile virus (WNV) infection. We further measured this outcome and found that 31% of patients reported new-onset depression and 75% of these had Center for Epidemiologic Studies Depression scores indicative of mild-to-severe depression. Physicians should be aware of neuropsychiatric consequences of WNV in patients.

**********

West Nile virus (WNV) was identified for the first time in the Western Hemisphere in New York City in 1999; since then, a dramatic westward and southward spread of WNV activity has occurred in the United States (1,2). In 2002, WNV was identified in the Houston, Texas, metropolitan area, resulting in 105 human cases (3).

Long-term clinical sequelae after infection are still being defined. A year after the outbreak of WNV in New York City, 38% of patients subjectively reported depression (4). Another 1-year follow-up in Colorado noted that 23% of patients reported anxiety and depression (5). In Houston, we have been conducting a prospective study that involves both subjective and objective measurements of physical, neurologic, and cognitive functioning of patients identified with symptomatic WNV infections. We describe the subjective and objective evaluations of depression in these patients.

The Study

Clinical WNV patients, confirmed by immunoglobulin M ELISA and identified through local surveillance in the Houston metropolitan area from 2002 through 2004, were invited to participate in a study to determine long-term clinical sequelae. Those consenting to participate were interviewed. No patient was denied participation on the basis of age, sex, race, or ethnicity. Excluded patients included those who were residing outside of the Houston area, deceased, or lost to follow-up. This study was reviewed and approved by the University of Texas Health Science Center Institutional Review Board (HSC-SPH-03-039).

Initial interviews were conducted after hospitalization, and follow-up interviews were conducted every 6 months until the patient reported being back to pre-WNV infection functioning. For the 1-year follow-up, interviews were conducted during each December at the end of transmission season. Interviews were mainly conducted over the telephone, but a small proportion were conducted in person. In all of these interviews, a higher than expected proportion of patients reported depression immediately after their illness. To better assess this quantitatively, we incorporated the Center for Epidemiologic Studies Depression (CES-D) scale (6) into both initial and follow-up interviews. This scale is a commonly used method for objective measurement of clinical depression. The tool is composed of 20 questions focused on self-report of depressive moods and behavioral changes experienced by the patient during 1 week. The resulting scores were interpreted as follows: 1) <15, the patient is not experiencing depression; 2) 15-21, the patient may be experiencing mild-to-moderate depression; 3) [greater than or equal to] 22-60, the patient may be experiencing major depression. In addition to the objective measurement using the CES-D scale, we also asked patients if they were experiencing depression since their illness and if they had a previous history of depression, with yes/no responses elicited. Barthel Index scores were used to quantitatively evaluate level of physical functioning and disability in patients; a score of 100 points indicated no physical disability. Because patients also commonly reported a change in personality immediately after WNV infection, we assessed this finding subjectively and asked those reporting a change to describe what they were experiencing.

Data were analyzed by using NCSS statistical software (Kaysville, UT, USA). With the Kruskal-Wallis 1-way analysis of variance on ranks, we analyzed CES-D scores and WNV outcome; CES-D scores and sex, age, and depression (CES-D score of [greater than or equal to] 15); and physical functioning (Barthel Index) and depression.

A total of 65 patients were interviewed; 38 (58%) cases had encephalitis when initially evaluated, 19 (29%) had meningitis, and 8 (12%) had fever. The mean age of patients was 55 years (range 12-86 years). Most

patients were white, non-Hispanic (80%), followed by black (11%) and white, Hispanic (9%).

One year after infection with WNV, 26 patients reported experiencing depression. Of these, 6 reported a history of depression before infection. Of the 20 patients considered to have new-onset depression, 13 (65%) had a clinical diagnosis of WNV encephalitis (Table), and 10 (50%) were male. The mean CES-D scores for those who reported no depression was 5.5 (range 0-19) compared with a mean score of 22 (range 0-44) for those who reported depression. There was no statistical difference in CES-D scores between those who had encephalitis and those who had meningitis or fever (p = 0.19) or between those with West Nile neuroinvasive disease (encephalitis or meningitis) compared with those with fever (p = 0.55). On the basis of CES-D scores for those self-reporting depression since their illness with WNV, 5 (25%) patients were classified by CES-D as not depressed, 6 (30%) were classified as having mild-to-moderate depression, and 9 (45%) were classified as having major depression. Of the 39 patients who self-reported that they had not had depression since their WNV illness, 4 had a CES-D score of [greater than or equal to] 15. No statistically significant associations were found between loss of physical functioning (Barthel index scores <100; p = 0.39), sex (p = 0.89), or age (p = 0.47) and depression (CES-D scores of [greater than or equal to] 15).