Benign West Nile Infection May Mask Long-Term Trouble

GRAND FORKS, N.D., Aug. 22 -- Long-term effects of West Nile virus infection may emerge irrespective of the severity of initial acute symptoms, according to investigators here.

West Nile fever caused just as much long-term fatigue, depression, motor impairment, and even tremor as West Nile meningitis, encephalitis, or acute flaccid paralysis, according to a small, retrospective study reported in Clinical Infectious Diseases.

"This might suggest that West Nile fever is not a self-limited benign illness, as previously thought, and may, in fact, be a subclinical encephalitis," wrote Paul J. Carson, M.D., of the University of North Dakota here, and colleagues.

None of the multiple risk factors examined, including severity of initial illness, predicted which patients would have long-term adverse outcomes.

Most West Nile infection is asymptomatic, but about 20% of patients develop West Nile fever and up to 1% develop meningitis, encephalitis, or acute flaccid paralysis.

In the study, one year after the initial infection, patients whose infection was not severe enough to warrant hospitalization were 10.67 times more likely to report fatigue and 6.5 times more likely to report word-finding difficulties than those who had been hospitalized with West Nile infection.

Fatigue was the most common symptom at one year of follow-up. More than 80% of the 49 patients reported persistent fatigue. Clinically, half of the cohort had fatigue scores similar to what is seen with moderate-to-severe multiple sclerosis on the Modified Fatigue Impact Scale.

Half of the patients scored low on the physical component of the quality of life SF12 version two questionnaire. A third scored low on the mental component. A quarter scored in the range of moderate-to-severe depression on the Beck Depression Inventory II, though 10% had a prior history of depression well-controlled with treatment.

Executive function tests revealed mild-to-moderate cognitive impairment in 7% to 36% of the patients depending on the test. Motor function tests indicated severe motor speed abnormalities in 43%.

Physical examination revealed tremor in six patients while another four reported having intermittent tremor. One patient continued to have acute flaccid paralysis that was severe and disabling in the legs.

Of all the outcomes, only disability differed between the 15 patients who had more severe cases requiring hospitalization and the 34 who were treated as outpatients. Surprisingly, it was the outpatient West Nile fever patients who had more long-term disability (mean score 99.7 versus 97 on the Barthel Index, P=0.022).

Still, "most patients returned to a reasonable level of functioning and independence despite their ongoing symptoms," Dr. Carson and colleagues wrote.

Most of the "constellation of clinical and neuropsychological abnormalities" seen in these patients cannot be explained solely by fatigue, the researchers concluded.

Rather, "these abnormalities could all be potentially explained by subtle damage to the frontal-subcortical structures" even in the patients without overt clinical encephalitis, they suggested.

The investigators made contact with patients with laboratory-confirmed West Nile virus infection identified from state surveillance programs and their own institutions. Participants underwent a thorough neurological exam and completed questionnaires for quality of life, functional ability, fatigue, and depression. Patients with a history of a confounding mental or physical condition or who had developed one since initial infection were excluded.

Less than half of the patients contacted participated in the study, which the authors noted may have introduced selection bias. They noted that short of a multicenter cooperative trial it would be difficult to do such extensive testing in a much larger cohort of patients.

Since the introduction of mosquito-borne West Nile virus to North America in 1999, it has continued to be a major public health threat. It caused more than 9,000 human infections and 264 deaths in 2003 alone.

"Effective therapies for patients with acute infection are greatly needed," the researchers said.