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Long-term prognosis for clinical West Nile virus infection.


Relatively little is known about the long-term prognosis for patients with clinical West Nile virus West Nile virus, microorganism and the infection resulting from it, which typically produces no symptoms or a flulike condition. The virus is a flavivirus and is related to a number of viruses that cause encephalitis.  (WNV WNV West Nile Virus
WNV World Net Visions
) infection. We conducted a study to describe the recovery of New York City New York City: see New York, city.
New York City

City (pop., 2000: 8,008,278), southeastern New York, at the mouth of the Hudson River. The largest city in the U.S.
 residents infected during the 1999 WNV encephalitis encephalitis (ĕnsĕf'əlī`təs), general term used to describe a diffuse inflammation of the brain and spinal cord, usually of viral origin, often transmitted by mosquitoes, in contrast to a bacterial infection of the meninges  outbreak. Patients were interviewed by telephone on self-perceived health outcomes 6, 12, and 18 months after WNV illness onset. At 12 months, the prevalence of physical, functional, and cognitive symptoms was significantly higher than that at baseline, including muscle weakness, loss of concentration, confusion, and lightheadedness. Only 37% achieved a full recovery by 1 year. Younger age at infection was the only significant predictor of recovery. Efforts aimed at preventing WNV infection should focus on elderly populations who are at increased risk for neurologic neurologic /neu·ro·log·ic/ (-loj´ik) pertaining to neurology or to the nervous system.
Neurologic
Having to do with the nervous system.
 manifestations and more likely to experience long-term sequelae sequelae Clinical medicine The consequences of a particular condition or therapeutic intervention  of WNV illness. More studies are needed to document the long-term sequelae of this increasingly common infection.

**********

West Nile virus (WNV, family Flaviviridae, genus Flavivirus) has become endemic throughout much of the United States United States, officially United States of America, republic (2005 est. pop. 295,734,000), 3,539,227 sq mi (9,166,598 sq km), North America. The United States is the world's third largest country in population and the fourth largest country in area.  since its introduction in 1999 (1). In 2003, a total of 2,866 laboratory-confirmed human cases of neuroinvasive illness and 264 deaths were caused by WNV infection (2). Older persons are at substantially increased risk for severe WNV disease, a hallmark of which is profound muscle weakness (1), often with acute flaccid paralysis Flaccid paralysis
Paralysis characterized by limp, unresponsive muscles.

Mentioned in: Botulism

flaccid paralysis Neurology Paralysis characterized by complete loss of muscle tone and tendon reflexes. Cf Spastic paralysis.
 or other motor disorder (2-4).

Investigators of the first WNV disease outbreak in North America North America, third largest continent (1990 est. pop. 365,000,000), c.9,400,000 sq mi (24,346,000 sq km), the northern of the two continents of the Western Hemisphere.  in 1999 documented that older persons and persons with diabetes are at increased risk for death after WNV infection (1,5-7) However, few epidemiologic studies epidemiologic study A study that compares 2 groups of people who are alike except for one factor, such as exposure to a chemical or the presence of a health effect; the investigators try to determine if any factor is associated with the health effect  have examined the sequelae or time course of recovery from WNV meningitis or encephalitis in survivors. A recent investigation of neurologic manifestations of WNV infections showed persistent symptoms at 8 months after infection, particularly in those patients who experienced flaccid paralysis (8).

We conducted an 18-month follow-up study on a cohort of New York City (NYC NYC
abbr.
New York City


NYC New York City
) case-patients identified as being ill with WNV infection in 1999 (1). The investigation had the following objectives: 1) to describe the physical, cognitive, and functional outcomes in patients recovering from WNV meningitis or encephalitis over the 18 months after acute illness and 2) to determine whether the severity of the initial clinical syndrome, the patient's age, and the patient's underlying illness affected the likelihood of recovery.

Methods

The medical records of all patients hospitalized with WNV infections were reviewed by using a standard form to abstract chart information. Follow-up interviews were conducted and blood was collected at approximately 6-month intervals from laboratory confirmed case-patients whose WNV infections were diagnosed in 1999. Three distinct health outcome areas--physical, cognitive, and functional health status--were each assessed at 6, 12, and 18 months after illness onset. Baseline health status was assessed by recall at the 12-month interview. Physical and cognitive health status outcomes were assessed at each interview by asking about the frequency of selected symptoms (Table 1). Functional ability was evaluated by administering the Instrumental Activities of Daily Living instrumental activities of daily living A series of life functions necessary for maintaining a person's immediate environment–eg, obtaining food, cooking, laundering, housecleaning, managing one's medications, phone use; IADL measures a  Scale (IADLS IADLS Interoperable Airborne Data Link Subsystem ) (9) to assess daily functioning before and after WNV illness. The prevalence of physical, cognitive, and functional symptoms Functional symptom is sometimes used in medicine to describe symptoms that have no current visible organic basis, e.g. if they are a result of psychological or perceptual dysfunction.  at baseline (by recall at 12 months) and at the 6-, 12-, and 18-month interviews was calculated. Underlying illness and initial clinical syndrome were ascertained from the medical chart.

The initial clinical syndrome was classified as WNV encephalitis, indicated by fever and altered mental status or other cortical cor·ti·cal
adj.
1. Of, relating to, derived from, or consisting of cortex.

2. Of, relating to, associated with, or depending on the cerebral cortex.
 signs (e.g., seizures) and cerebrospinal fluid cerebrospinal fluid (CSF)

Clear, colourless liquid that surrounds the brain and spinal cord and fills the spaces in them. It helps support the brain, acts as a lubricant, maintains pressure in the skull, and cushions shocks.
 (CSF Cerebrospinal Fluid (CSF) Analysis Definition

Cerebrospinal fluid (CSF) analysis is a laboratory test to examine a sample of the fluid surrounding the brain and spinal cord.
) suggestive of suggestive of Decision making adjective Referring to a pattern by LM or imaging, that the interpreter associates with a particular–usually malignant lesion. See Aunt Millie approach, Defensive medicine.  viral infection viral infection,
n an infection by a pathogenic virus. A virus acts on the cell nucleus, taking over the genetic material within the nucleus and replicating itself.
; WNV meningitis, indicated by fever, meningeal signs meningeal sign Neurology Any clinical sign that indicates meningeal irritation; of the 3 signs–Brudzinski's signs–chin to chest evokes hip flexion, Kerdnig's sign–resistance to knee extension evokes pain in hamstrings, and nuchal rigidity, the  (documentation of Kemig sign, Brudzinski sign Brudzinski sign Neurology A physical sign of meningitis, which is evoked by either passive flexion of one leg resulting in a similar movement on the opposite side, or if the neck is passively flexed, flexion occurring in the legs , or nuchal nuchal (nyōōˑ·kl),
adj pertaining to the posterior or nape of the neck.
 rigidity), and CSF suggestive of viral infection; or WNV fever with headache. CSF suggestive of viral infection was defined as a negative bacterial stain and culture, with elevated leukocyte count leukocyte count see White cell count  ([greater than or equal to] 5 cells/[mm.sup.3]) or elevated protein (>4.5 g/L). Proxy interviews were conducted when case-patients could not be interviewed because of poor health, hearing difficulties, or a language barrier.

Laboratory Methods

Laboratory evidence for recent WNV infection (10) was confirmed in all patients and defined by any of the following test results: 1) isolation of WNV by culture or amplification of WNV RNA RNA: see nucleic acid.
RNA
 in full ribonucleic acid

One of the two main types of nucleic acid (the other being DNA), which functions in cellular protein synthesis in all living cells and replaces DNA as the carrier of genetic
 by reverse transcriptase Reverse transcriptase

Any of the deoxyribonucleic acid (DNA) polymerases present in particles of retroviruses which are able to carry out DNA synthesis using an RNA template.
 polymerase chain reaction polymerase chain reaction (pŏl`ĭmərās') (PCR), laboratory process in which a particular DNA segment from a mixture of DNA chains is rapidly replicated, producing a large, readily analyzed sample of a piece of DNA; the process is  testing from human tissue specimens; 2) demonstration of immunoglobulin immunoglobulin: see antibody; immunity; immunology.
Immunoglobulin

Any of the glycoproteins in the blood serum that are induced in response to invasion by foreign antigens and that protect the host by eradicating pathogens.
 (Ig) M antibody to WNV in CSF by IgM-capture enzyme-linked immunosorbent assay enzyme-linked immunosorbent assay
n.
ELISA.


Enzyme-linked immunosorbent assay (ELISA)
A diagnostic blood test used to screen patients for AIDS or other viruses.
 (ELISA ELISA (e-li´sah) Enzyme-Linked Immuno-Sorbent Assay; any enzyme immunoassay using an enzyme-labeled immunoreactant and an immunosorbent.

ELISA
n.
); 3) greater than fourfold fourfold
Adjective

1. having four times as many or as much

2. composed of four parts

Adverb

by four times as many or as much

Adj. 1.
 serial change in WNV-specific neutralizing antibody neu·tral·iz·ing antibody
n.
An antibody that reacts with an infectious agent, usually a virus, and destroys or inhibits its infectiveness and virulence.
 as measured by the plaque-reduction neutralization test neutralization test
n.
See protection test.
 (PRNT) in paired, appropriately timed serum samples; or 4) demonstration of both WNV-specific IgM (by ELISA) and IgG (screened by ELISA and confirmed by PRNT) in a single serum specimen. Patients with WNV-specific IgM in a single serum sample were classified as having a probable recent infection. Patients with anti-WNV IgG only in a single serum specimen were also classified as having a probable WNV infection if the antibodies were found to be WNV-specific by PRNT and the patient had no history of travel to an area outside the United States where WNV infection is endemic.

Blood specimens were obtained at 6-month intervals starting at 6 months through 18 months alter illness onset, until WNV-specific IgM, indicative of recent infection, was undetectable. Serum samples were tested for anti-WNV IgM (capture ELISA) and IgG (indirect ELISA) (11,12). Results from the ELISA testing were expressed as a WNV-positive to WNV-negative control (P/N (Part/Number) Common shorthand for part number. ) ratio of observed A450 nm (MAC-ELISA) or A405 nm (IgG ELISA IgG ELISA,
n.pr a diagnostic test for identifying reactive substances that provoke delayed hypersensitivity of the immune system. A solid-phase immunoassay that uses enzymes to test for IgG subclass reactions.
) as described. In these tests, P/N ratios >3.0 were considered positive and P/N ratios >2.0 and <3.0 were considered equivocal EQUIVOCAL. What has a double sense.
     2. In the construction of contracts, it is a general rule that when an expression may be taken in two senses, that shall be preferred which gives it effect. Vide Ambiguity; Construction; Interpretation; and Dig.
. Detailed information on WNV serologic se·rol·o·gy  
n. pl. se·rol·o·gies
1. The science that deals with the properties and reactions of serums, especially blood serum.

2.
 features in this cohort study A cohort study is a form of longitudinal study used in medicine and social science. It is one type of study design.

In medicine, it is usually undertaken to obtain evidence to try to refute the existence of a suspected association between cause and disease; failure to refute
 has been previously published (13).

Study Population

Of the 59 surviving patients hospitalized with WNV infection in 1999, 40 were NYC residents and eligible for inclusion in the follow-up study. During the course of the study, two additional patients with laboratory-confirmed WNV infection who had fever and headache were identified and enrolled. Thirty-eight (90.5%) of the 42 case-patients completed the first interview (6 months postonset), 35 (83.3%) participated in the second interview (12 months postonset), and 36 (85.7%) participated in the third interview (18 months postonset). Forty (95%) case-patients participated in at least one of the three interviews; 32 (76%) completed all three interviews. The proportion of interviews that were completed by proxy was 39% at the first interview to 25% at the third interview.

Recovery Assessment at 12 Months After Infection

A recovery assessment was completed for the 35 case-patients who participated in the 12-month interview. At the 12-month interview, patients responded to questions on the frequency of occurrence (never, sometimes, or often) of selected symptoms during the month before the interview and during the month before illness onset (baseline). A symptom was counted as being present if it was experienced sometimes or often. Current and baseline composite scores were calculated within each health status domain by tabulating the responses for each outcome in that domain. Difficulty walking was weighted double in computing the physical health domain score, because it appears to be a very specific symptom of severe WNV infection (1,3,4). If a response of not applicable or unknown was given for a particular outcome, then that outcome was not included in calculating that case-patient's baseline or 12-month composite score.

Within each health status domain, the ratio of the 12-month composite score to the baseline composite score was calculated and used as a measure of recovery for that domain. Persons with a 12-month composite score [greater than or equal to] 85% of baseline for a given health status domain were considered to be recovered in that domain. Those persons with 12-month composite [greater than or equal to] 85% of baseline in all three health status domains were considered fully recovered.

Statistical Methods

Prevalence ratios were calculated for all outcomes at each interval relative to baseline; p values associated with prevalence ratios were calculated by using a matched analysis with McNemar test for correlated proportions. Crude and adjusted relative risks (RRs) were calculated to examine the relationships of clinical syndrome (i.e., encephalitis, meningitis, and mild illness), age, and underlying medical conditions See carpal tunnel syndrome, computer vision syndrome, dry eyes and deep vein thrombosis.  with recovery in each health status domain at 12 months postonset. RRs were adjusted by using the method of Mantel and Haenszel. Data were analyzed by using the SPSS A statistical package from SPSS, Inc., Chicago (www.spss.com) that runs on PCs, most mainframes and minis and is used extensively in marketing research. It provides over 50 statistical processes, including regression analysis, correlation and analysis of variance.  System for Windows, version 10.0 and SAS (1) (SAS Institute Inc., Cary, NC, www.sas.com) A software company that specializes in data warehousing and decision support software based on the SAS System. Founded in 1976, SAS is one of the world's largest privately held software companies. See SAS System.  Version 8 (SAS Institute SAS Institute Inc., headquartered in Cary, North Carolina, USA, has been a major producer of software since it was founded in 1976 by Anthony Barr, James Goodnight, John Sall and Jane Helwig. , Cary, NC).

Consent and Human Subjects Review

Verbal consent was obtained from participants during telephone interviews, and written consent was obtained before each follow-up blood specimen collection. The study protocol underwent human subjects review and was approved by institutional review boards of both the New York City Department of Health and Centers for Disease Control and Prevention Centers for Disease Control and Prevention (CDC), agency of the U.S. Public Health Service since 1973, with headquarters in Atlanta; it was established in 1946 as the Communicable Disease Center. .

Results

Table 2 shows the patients who were ill with WNV infection in 1999 (N = 59) and the 40 surviving NYC residents who were eligible for participation in the follow-up study, plus 2 additional patients with West Nile virus disease who were not hospitalized. Of the 40 surviving NYC case-patients participating in one or more interviews, the median age of the participants at illness onset was 68 years (range: 16 to 90 years), and all patients resided in their own homes before illness. At the time of diagnosis, 22 (55%) patients had encephalitis, 11 (27.5%) had meningitis, and 7 (17.5%) had illness characterized by fever and headache. Of 33 hospitalized patients with known disposition at discharge, those who had diagnoses of encephalitis were more likely to have discharge placements outside their homes (p < 0.05) and more likely to be >65 years of age (p < 0.001).

Physical, Cognitive, and Functional Health Status

Table 3 shows the prevalence of physical, cognitive, and functional sequelae reported at 6, 12, and 18 months postonset. At the 12-month interview, patients were also asked to recall the prevalence of those symptoms before illness onset. All participants interviewed with a clinical diagnosis of encephalitis with weakness (n = 10) reported difficulty walking 6 months after illness. Those who had an initial diagnosis of encephalitis were more likely to require a wheelchair at the first follow-up interview than those with meningitis or mild illness.

The prevalence of cognitive symptoms was higher 1 year after illness compared with baseline for all cognitive outcomes. All cognitive symptoms were more common after illness onset in case-patients at intervals coming or happening with intervals between; now and then.

See also: Interval
 extending up to 18 months after acute illness (Table 3), and some symptoms did not diminish over time. Prevalence ratios of functional disabilities were also significantly elevated compared with baseline.

Analysis of Recovery Outcomes

The mean domain-specific health status score was significantly lower at 12 months compared with baseline for all three domains (data not shown). Overall, 54%, 59%, and 57% of patients were physically, cognitively, or functionally recovered, respectively (Table 4). Case-patients [greater than or equal to] 65 years achieved recovery rates of 50%, 52%, and 45% in the respective domains of physical recovery, cognitive recovery, and functional recovery (Table 5). Only 37% of patients were considered fully recovered. Diagnosis (encephalitis versus meningitis or other mild illness) was not predictive of physical or cognitive recovery (Table 4), even after adjusting for age. Age was a positive predictor of recovery in each domain, with younger persons more likely to achieve physical, cognitive, and functional recovery (Table 5). The absence of an underlying health condition was associated with an increased likelihood of recovery in all domains (Table 6). After adjusting for baseline clinical status (Mantel-Haenszel method), younger persons (<65 years) were significantly more likely to achieve a full recovery than older persons ([greater than or equal to] 65 years) (relative risk [RR] = 3.3, 95% confidence interval confidence interval,
n a statistical device used to determine the range within which an acceptable datum would fall. Confidence intervals are usually expressed in percentages, typically 95% or 99%.
 [CI] 1.1-9.9). After adjusting for underlying illness, younger persons were also more likely to recover fully than older persons (RR = 2.3, 95% CI 0.97-5.5).

Discussion

We report that WNV infection can result in a protracted pro·tract  
tr.v. pro·tract·ed, pro·tract·ing, pro·tracts
1. To draw out or lengthen in time; prolong: disputants who needlessly protracted the negotiations.

2.
 convalescent con·va·les·cent
adj.
Relating to convalescence.

n.
A person who is recovering from an illness, an injury, or a surgical operation.



convalescent

1. pertaining to or characterized by convalescence.

2.
 period with long-term physical, cognitive, and functional impairments lasting [greater than or equal to] 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 hospitalization /hos·pi·tal·iza·tion/ (hos?pi-t'l-i-za´shun)
1. the placing of a patient in a hospital for treatment.

2. the term of confinement in a hospital.
. 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 St. Louis encephalitis

see St. Louis encephalitis.
 virus (SLEV SLEV Saint Louis Encephalitis Virus
SLEV Surround Level
) (14-18), and recovery after WNV infection might be comparable to that of patients recovering from SLEV-associated encephalitis (SLE SLE systemic lupus erythematosus.

SLE
abbr.
systemic lupus erythematosus


Systemic lupus erythematosus (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 (15-23). 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, [approximately equal to] 30% of case patients were not fully recovered 1 year after acute illness (19,20,24).

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 in·ca·pac·i·tate  
tr.v. in·ca·pac·i·tat·ed, in·ca·pac·i·tat·ing, in·ca·pac·i·tates
1. To deprive of strength or ability; disable.

2. To make legally ineligible; disqualify.
, >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 Tampa Bay, inlet of the Gulf of Mexico, 25 mi (40 km) long and 7 to 12 mi (11.3–19 km) wide, W Fla., separated from the Gulf by numerous small islands; it receives the Hillsborough River. St. , 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 irritability /ir·ri·ta·bil·i·ty/ (ir?i-tah-bil´i-te) the quality of being irritable.

myotatic irritability  the ability of a muscle to contract in response to stretching.
, depression, and forgetfulness Forgetfulness
See also Carelessness.

Absent-Minded Beggar, The

ballad of forgetful soldiers who fought in the Boer War. [Br. Lit.: “The Absent-Minded Beg-gars” in Payton, 3]

absent-minded professor
 (15-23).

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 insomnia, abnormal wakefulness or inability to sleep. The condition may result from illness or physical discomfort, or it may be caused by stimulants such as coffee or drugs. However, frequently some psychological factor, such as worry or tension, is the cause. , 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 longterm 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 [greater than or equal to] 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 im·pre·cise  
adj.
Not precise.



impre·cisely adv.
 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 neurologic examination A battery of clinical tests that evaluates a person's physiologic function and mental status, as well as the presence of any structural–organic lesions that may cause changes in neurologic function. Cf Psychiatric 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 obtaining 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 longterm measures of recovery.

Our study documents that, in addition to causing severe acute illness, WNV meningitis ore ncephalitis results in a prolonged recuperation recuperation /re·cu·per·a·tion/ (-koo?per-a´shun) recovery of health and strength.
recuperation,
n the process of recovering health, strength, and mental and emotional vigor.
 and rehabilitation rehabilitation: see physical therapy.  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.
Table 1. Health outcomes assessed during follow-up telephone
interviews of New York residents with clinical West Nile virus
infection in 1999 (a),(b)

Physical health            Cognitive health       Functional health

Difficulty walking (c)         Confusion             Heavy chores
Fatigue                       Depression               Laundry
Headache                     Irritability         Light housekeeping
Insomnia                    Lightheadedness      Managing medications
Joint pain               Loss of concentration      Managing money
Muscle pain                 Loss of memory         Meal preparation
Muscle weakness                                        Shopping
Seizures                                             Telephoning
Stiff neck                                          Transportation

(a) At 12 months post -onset, baseline status for each outcome was
assessed: for each outcome, patients were asked to report the degree
to which they experienced the signs and symptoms at baseline
(by recall) and at 12 months postonset.

(b) Each outcome w as scored 0-2 according to the following scale:
always = 2, sometimes = 1, never = 0. Functional health was scored
according to how frequently the patient had difficulty performing
the task. Recovery was calculated as the sum of the baseline score
in each category, divided by the sum of the 12-month score.

(c) Difficulty walking was given twice the weight as other outcomes
in the recovery score calculation.

Table 2. Characteristics of participating and nonparticipating
patients who survived clinical West Nile virus infection New York
City, 1999

                                  All hospitalized    Enrolled
                                     patients,        patients,
Characteristic                       N = 59 (%)      N = 42 (%)

Age
  <65                                 23 (39)          16 (38)
  [greater than or equal to] 65       36 (61)          26 (62)
Sex
  Female                              28 (47)          20 (48)
  Male                                31 (53)          22 (52)
Underlying illness before
    infection
  Hypertension                        25 (42)          17 (40)
  Diabetes                            12 (20)           6 (14)
  Hypertension or diabetes            31 (53)          19 (45)
Clinical syndrome
  Encephalitis                        37 (63)          22 (52)
  Meningitis or milder illness        22 (37)          20 (48)
Discharge status (a)
  Dead                                 7 (12)            NA
  Home                                22 (37)        20 (50) (b)
  Home of family or friend             3 (5)          3 (8) (b)
  Skilled nursing facility             4 (7)          4 (10) (b)
  Rehabilitation                       6 (10)         6 (15) (b)
  Unknown but alive                   17 (29)         7 (18) (b)
Required physical therapy                NA              NA

                                  Participants   Nonparticipants
                                  in 12-month      in 12-month
                                   interview,      interview,
Characteristic                     N = 35 (%)       N = 7 (%)

Age
  <65                               13 (37)          3 (43)
  [greater than or equal to] 65     22 (63)          4 (57)
Sex
  Female                            18 (51)          2 (29)
  Male                              17 (49)          5 (71)
Underlying illness before
    infection
  Hypertension                      14 (40)          3 (43)
  Diabetes                           5 (14)          1 (14)
  Hypertension or diabetes          16 (46)          3 (43)
Clinical syndrome
  Encephalitis                      19 (54)          3 (43)
  Meningitis or milder illness      16 (45)          4 (57)
Discharge status (a)
  Dead                                 NA              NA
  Home                            20 (50) (c)          NA
  Home of family or friend         3 (9) (c)           NA
  Skilled nursing facility         4 (12) (c)          NA
  Rehabilitation                   6 (18) (c)          NA
  Unknown but alive                    0             7 (100)
Required physical therapy           18 (51)            NA

(a) Includes hospitalized patients only.

(b) N = 40 for these calculations.

(c) N = 33 for these calculations.

Table 3. Prevalence of signs and symptoms at intervals of
follow-up in patients with clinical West Nile virus infection,
New York City, 1999

                            Before illness
                               onset (a)            Interview 1
Sign or symptom           (baseline), n/N (%)   (6 months), n/N (%)

Physical sequelae
  Difficulty walking          7/35 (20.0)           30/38 (78.9)
  Muscle weakness             4/35 (11.5)           25/38 (65.8)
  Fatigue                    12/35 (34.3)           20/37 (54.1)
  Insomnia                    7/35 (20.0)           17/38 (44.7)
  Muscle pain                12/35 (34.3)           14/37 (37.8)
  Headache                    9/35 (25.7)           13/37 (35.1)
  Joint pain                  7/35 (20.0)           12/38 (31.6)
Cognitive symptoms
  Memory loss                 7/35 (20.0)           21/38 (55.3)
  Loss of concentration       3/35 (8.6)            16/37 (42.2)
  Depressed                   5/35 (14.3)           15/38 (39.5)
  Irritable                   8/35 (22.9)           14/38 (36.8)
  Lightheaded                 4/35 (11.5)           13/38 (34.2)
  Confusion                   2/35 (5.7)            17/38 (44.8)
Functional sequelae
  Shopping                    4/33 (12.1)           17/36 (47.2)
  Meal preparation            2/32 (6.3)            22/31 (71.0)
  Laundry                     1/25 (4.0)            14/29 (48.3)
  Light housekeeping          1/28 (3.6)            19/35 (54.3)
  Heavy chores                5/30 (11.9)           19/33 (57.6)
  Transportation              3/29 (10.3)           23/37 (62.2)

                              Interview 2           Interview 3
Sign or symptom           (12 months) n/N (%)   (18 months) n/N (%)

Physical sequelae
  Difficulty walking          17/35 (48.6)          15/36 (41.6)
  Muscle weakness             15/34 (44.1)          20/36 (55.5)
  Fatigue                     22/33 (66.7)          23/36 (63.8)
  Insomnia                    16/34 (47.1)          17/36 (47.2)
  Muscle pain                 19/34 (55.9)          14/36 (38.8)
  Headache                    15/34 (44.1)          13/36 (36.1)
  Joint pain                  11/34 (32.3)          11/36 (30.6)
Cognitive symptoms
  Memory loss                 17/34 (50.0)          16/36 (44.5)
  Loss of concentration       14/34 (41.2)          12/36 (33.3)
  Depressed                   13/34 (38.2)          16/36 (44.4)
  Irritable                   14/34 (41.2)          14/36 (38.9)
  Lightheaded                 17/33 (51.5)          13/35 (37.1)
  Confusion                    9/34 (26.5)          11/36 (30.6)
Functional sequelae
  Shopping                    14/33 (42.4)          14/35 (40.0)
  Meal preparation            12/32 (37.5)          12/34 (35.3)
  Laundry                     10/25 (40.0)          10/33 (30.3)
  Light housekeeping          12/28 (42.9)          12/35 (34.3)
  Heavy chores                19/30 (63.3)          19/34 (55.9)
  Transportation              10/28 (35.7)          14/36 (38.9)

                          p value for 12
                            months vs.
Sign or symptom            baseline (b)

Physical sequelae
  Difficulty walking           0.002
  Muscle weakness            < 0.001
  Fatigue                      0.002
  Insomnia                     0.007
  Muscle pain                  0.035
  Headache                     0.014
  Joint pain                   0.157
Cognitive symptoms
  Memory loss                  0.002
  Loss of concentration      < 0.001
  Depressed                    0.005
  Irritable                    0.008
  Lightheaded                < 0.001
  Confusion                    0.008
Functional sequelae
  Shopping                     0.002
  Meal preparation           < 0.001
  Laundry                      0.003
  Light housekeeping         < 0.001
  Heavy chores                 0.003
  Transportation               0.008

(a) Assessed by recall at the 12-month follow-up interview.

(b) Based on McNemar's test for agreement in a matched analysis.

Table 4. Recovery at 12 months post-onset by health status domain and
clinical syndrome at diagnosis in patients with clinical West Nile
virus infection New York City, 1999

                                       Recovered,   Not recovered,
Recovery                       Total   n (%) (a)       n (%) (a)

Physical recovery
  Meningitis or mild illness    16      8 (50.0)       8 (50.0)
  Encephalitis                  19     11 (57.9)       8 (42.1)
  Total                         35     19 (54.3)      16 (45.7)
Cognitive recovery
  Meningitis or mild illness    16     10 (62.5)       6 (37.5)
  Encephalitis                  18     10 (55.5)       8 (44.4)
  Total                         34     20 (58.8)      14 (41.2)
Functional recovery
  Meningitis or mild illness    16     10 (62.6)       6 (37.5)
  Encephalitis                  19     10 (52.6)       9 (47.4)
  Total                         35     20 (57.1)      15 (42.9)
Total recovery
  Meningitis or mild illness    16      7 (43.8)       9 (56.3)
  Encephalitis                  19      6 (61.6)      13 (68.4)
  Total                         35     13 (37.1)      22 (62.9)

Recovery                       Risk ratio   95% confidence interval

Physical recovery
  Meningitis or mild illness      0.86             0.46-1.6
  Encephalitis                  Referent
  Total
Cognitive recovery
  Meningitis or mild illness      1.1              0.64-2.0
  Encephalitis                  Referent
  Total
Functional recovery
  Meningitis or mild illness      1.2              0.67-2.1
  Encephalitis                  Referent
  Total
Total recovery
  Meningitis or mild illness      1.4              0.58-3.3
  Encephalitis                  Referent
  Total

(a) Due to rounding, not all values add up to 100%.

Table 5. Recovery at 12 months post-onset by health status domain and
age at illness onset in patients with clinical West Nile virus
infection, New York City, 1999

                                          Recovered,   Not recovered,
Recovery                          Total   n (%) (a)      n (%) (a)

Physical recovery
  <65                              13      8 (61.5)       5 (38.5)
  [greater than or equal to] 65    22     11 (50.0)      11 (50.0)
  Total                            35     19 (54.3)      16 (45.7)
Cognitive recovery
  <65                              13      9 (69.2)       4 (30.8)
  [greater than or equal to] 65    21     11 (52.4)      10 (47.6)
  Total                            34     20 (58.8)      14 (41.2)
Functional recovery
  <65                              13     10 (76.9)       3 (23.1)
  [greater than or equal to] 65    22     10 (45.5)      12 (54.5)
  Total                            35     20 (57.1)      15 (42.9)
Total recovery
  <65                              13      8 (61.5)       5 (38.5)
  [greater than or equal to] 65    22      5 (22.7)      17 (77.3)
  Total                            35     13 (37.1)      22 (62.9)

                                               95% confidence
Recovery                          Risk ratio      interval

Physical recovery
  <65                                1.2          0.68-2.2
  [greater than or equal to] 65    Referent
  Total
Cognitive recovery
  <65                                1.3          0.77-2.3
  [greater than or equal to] 65    Referent
  Total
Functional recovery
  <65                                1.7          0.98-2.9
  [greater than or equal to] 65    Referent
  Total
Total recovery
  <65                                2.7          1.1-6.5
  [greater than or equal to] 65    Referent
  Total

(a) Due to rounding, not all values add up to 100%.

Table 6. Recovery at 12 months postonset by health status domain and
underlying health condition in patients with clinical West Nile virus
infection, New York City, 1999

                                     Recovered,   Not recovered,
Recovery                     Total   n (%) (a)      n (%) (a)

Physical recovery
  No underlying condition     18     11 (61.1)       7 (38.9)
  Hypertension or diabetes    17      8 (47.1)       9 (52.9)
  Total                       35     19 (54.3)      16 (45.7)
Cognitive recovery
  No underlying condition     17     11 (64.7)       6 (35.3)
  Hypertension or diabetes    17      9 (52.9)       8 (47.1)
  Total                       34     20 (58.8)      14 (41.2)
Functional recovery
  No underlying condition     18     12 (66.7)       6 (33.3)
  Hypertension or diabetes    17      8 (47.1)       9 (52.9)
  Total                       35     20 (57.1)      15 (42.9)
Total recovery
  No underlying condition     18      9 (50.0)       9 (50.0)
  Hypertension or diabetes    17      4 (23.5)      13 (76.5)
  Total                       35     13 (37.1)      22 (62.9)

                                          95% confidence
Recovery                     Risk ratio     inte rval

Physical recovery
  No underlying condition       1.3          0.70-2.4
  Hypertension or diabetes    Referent
  Total
Cognitive recovery
  No underlying condition       1.2          0.70-2.2
  Hypertension or diabetes    Referent
  Total
Functional recovery
  No underlying condition       1.4          0.78-2.6
  Hypertension or diabetes    Referent
  Total
Total recovery
  No underlying condition       2.1          0.80-5.6
  Hypertension or diabetes    Referent
  Total

(a) Due to rounding, not all values add up to 100%


Acknowledgments

We are indebted to our colleagues at the Centers for Disease Control and Prevention in Fort Collins, Colorado The City of Fort Collins, a home rule municipality situated on the Cache la Poudre River along the Colorado Front Range, is the county seat and most populous city in Larimer County, Colorado. , and the 1999 New York City West Nile Virus Outbreak Response Working Group fur their contributions. We are especially grateful to the recovering patients who graciously agreed to participate in this investigation to further our understanding of the long-term sequelae of West Nile virus infection.

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See : Easter
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(20.) Bredeck J, Broun G, Hemplemann T, McFaddden J, Specter H. Follow-up studies of the 1933 St. Louis epidemic of encephalitis. JAMA. 1938;111:15-8.

(21.) Azar CA Bond J, Chappel G, Lawton A. Follow-up studies of St. Louis encephalitis in Florida: sensorimotor sensorimotor /sen·so·ri·mo·tor/ (sen?sor-e-mo´ter) both sensory and motor.

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(23.) Powell KE, Blakey DL. St. Louis encephalitis: the 1975 epidemic in Mississippi. JAMA. 1977;237:2294-8.

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[Short for alongshore.]
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(25.) Azar CA Bond J, Lawton A. St. Louis encephalitis: age aspects of 1962 epidemic in Pinellas County, Florida Pinellas County is a county located in the state of Florida. Its county seat is Clearwater, Florida6, and its largest city is St. Petersburg. The county is contained entirely within area code (727), except for sections of Oldsmar, which has area code 813. . J Am Geriatr Soc. 1966;14:326-33.

Dr. Labowitz Klee worked on this study while she was an epidemiologist at the New York City Department of Health and completing her graduate work in clinical health psychology. She is the clinical director of the Psychosocial psychosocial /psy·cho·so·cial/ (si?ko-so´shul) pertaining to or involving both psychic and social aspects.

psy·cho·so·cial
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Involving aspects of both social and psychological behavior.
 Rehabilitation Fellowship Program at the Errera Community Care Center of the Veterans Administration. Her professional interests include psychiatric services, specifically those involving recovery from severe mental illnesses, and housing for chronically homeless populations.

Address for correspondence: Denis Denis, king of Portugal: see Diniz.  Nash, New York Academy of Medicine The New York Academy of Medicine was founded in 1847 by a group of leading New York City metropolitan area physicians as a voice for the medical profession in medical practice and public health reform. , Center for Urban Epidemiologic Studies, 1216 Fifth Ave., New York, NY 10029, USA; fax: 212-876-6220; email: dnash@nyam.org

Anne Labowitz Klee, * (1) Beth Maldin, * Barbara Edwin, * Iqbal Poshni, * Farzad Mostashari, * Annie Fine, * Marcelle Layton, * and Denis Nash * ([dagger]) (2)

* New York City Department of Health, New York City, New York, USA; and ([dagger]) Centers for Disease Control and Prevention, Atlanta, Georgia, USA

(1) Current affiliation: U.S. Department of Veteran Affairs, West Haven, Connecticut
"West Haven" redirects here. For other uses, see West Haven (disambiguation)
West Haven is a city in New Haven County, Connecticut, United States. According to 2006 Census Bureau estimates, the population of the city is 52,721.
, USA2

(2) Current affiliation: New York Academy of Medicine, New York, New York, USA
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