We report that WNV infection can result in a protracted convalescent period with long-term physical, cognitive, and functional impairments lasting >18 months after acute illness. Approximately 40% of patients hospitalized in 1999 did not return to their own homes immediately after discharge, and physical therapy was required by 47% of patients after hospitalization. Comparing the prevalence of symptoms before illness with that at 12 months after WNV illness onset, physical, functional, and cognitive symptoms persisted. We estimate that 37% achieved full recovery by 12 months. Younger age (<65 years) was the only significant predictor of achieving a full recovery.
WNV is clinically, serologically, and epidemiologically similar to St. Louis encephalitis virus (SLEV) (14
), and recovery after WNV infection might be comparable to that of patients recovering from SLEV-associated encephalitis (SLE). Information on sequelae from SLE has been documented after U.S. outbreaks occurring from the 1930s to the 1970s. Various methods assessed recovery from SLE, including medical examinations (with neurologic assessments) and patient or proxy interviews (19
). Follow-up times varied from 6 months to 5 years after acute illness (15
). In general, studies of recovering patients with SLE have documented generalized susceptibility to fatigue, headaches, nervousness, inability to concentrate, depression, and problems with gait and balance throughout convalescent periods of 6 months to 3 years after acute SLEV infection; on average, ≈30% of case-patients were not fully recovered 1 year after acute illness (19
Different approaches to defining recovery were used by researchers who characterized the experience of patients after SLEV infection. After the first SLE epidemic in St. Louis in 1933, researchers defined overall recovery based on the ability to return to work. Of 331 patients, 141 (66%) reported that they felt completely recovered 12–18 months after acute illness, whereas 22 (6.7%) felt they were physically unable to return to their jobs. Although none of the patients <20 years of age was incapacitated, >10% of patients >20 years could not return to work (20
). After an SLE epidemic in Mississippi in 1975, researchers conducted follow-up interviews 6 months after illness onset. Of the 175 patients contacted, 87 (49.7 %) achieved full recovery, 24 (13.7%) reported minor symptoms, and 29 (16.6 %) reported that they resumed previous activities but not at the same level. SLE patients from the Tampa Bay, Florida, outbreaks occurring from 1959 to 1962 (N = 160) had more difficulty completing tests that evaluated balance and equilibrium than controls. In particular, SLE patients had difficulty walking in straight lines and widening their lateral base of support (25
). Predominant cognitive problems included nervousness, irritability, depression, and forgetfulness (15
Our findings are similar to those reported in these SLE studies. Regardless of acute clinical symptoms, WNV case-patients in this study continued to report difficulty walking, muscle weakness, fatigue, and insomnia, with >40% reporting a combination of these difficulties, and 30% continued to report persistence of memory loss, confusion, depression, and irritability at 18 months after acute illness. Eighteen months after illness, 30% of case-patients reported needing assistance with activities of daily living, mostly those requiring increased strength. Although average functional ability from 6 months to 1 year post-onset improved significantly, functional ability reached a plateau and did not improve further during the 12- to 18-month period.
Our results suggest that WNV has more severe long-term sequelae in older persons than in younger persons. These sequelae may be attributable to the severity of the patients' WNV infection, to the more general effects of serious illness and hospitalization, or to the aging process itself; regardless, WNV causes severe neurologic illness and might be associated with lasting sequelae in persons >65 years.
The presence of underlying disease at the time of onset of illness was not significantly associated with recovery at 12 months (RR = 1.4, 95% CI 0.58–3.3), even after adjusting for age (adjusted RR = 1.3, 95% CI 0.70–2.5). However, the lack of significance of this association could be a result of the small number of patients in our study or misclassification.
Several aspects of our investigation might limit the generalizability of these findings. Although participation was high, our estimates may be imprecise because of the small sample size. Furthermore, the ages of the study participants span a wide range (16–90 years), making adequate adjusting for age difficult. We used a structured interview questionnaire, the content and format of which, when possible, was similar across interviews to maximize comparability of data obtained over time. Proxies were used when case-patients could not be interviewed because of poor health, hearing difficulties, or a language barrier. Data were based on subjective report, either by the patient or their proxy. Subjective accounts provided by persons who are cognitively impaired might overattribute or underattribute certain dysfunctions to their WNV illness, and recall bias might have caused case-patients to selectively suppress or exaggerate information about their health status, either current or past.
Baseline information regarding physical, cognitive, and functional health before WNV disease was collected during the second follow-up interview at 1 year (i.e., by recall). Participants may have had problems recalling baseline health status over a 12-month period, limiting our ability to accurately ascertain actual baseline level of functioning. Sequelae could not be verified by objective physical examination, physician interview, or medical record review. Future studies of recovery in WNV patients should attempt to obtain more objective measurements of sequelae, such as provider interviews, medical chart review, or neurologic examination. As WNV continues to affect older age groups, further research should consider ways to control for declines in functioning associated with the aging process and to obtain objective data regarding baseline status. Finally, future studies should try to assess the baseline health status of WNV patients closer to the time of onset to reduce the impact of recall bias on long-term measures of recovery.
Our study documents that, in addition to causing severe acute illness, WNV meningitis or encephalitis likely results in a prolonged recuperation and rehabilitation period, especially in older persons. As WNV continues to establish itself as a national public health concern, these findings reinforce the need for local governments in affected areas to institute widespread public health measures to safeguard against WNV transmission and for persons—especially those age 65 and over—to take precautions to avoid exposure to mosquitoes and reduce mosquito breeding sites on their properties. More studies are needed to document the long-term sequelae of this increasingly common infection.