ﺑﺎﺯﮔﺸﺖ ﺑﻪ ﺻﻔﺤﻪ ﻗﺒﻠﯽ
خرید پکیج
تعداد آیتم قابل مشاهده باقیمانده : 3 مورد
نسخه الکترونیک
medimedia.ir

Clinical manifestations and diagnosis of West Nile virus infection

Clinical manifestations and diagnosis of West Nile virus infection
Literature review current through: Jan 2024.
This topic last updated: Aug 04, 2022.

INTRODUCTION — West Nile (WN) virus, a member of the Japanese encephalitis virus antigenic complex, can lead to a wide range of clinical symptoms from asymptomatic disease to severe meningitis and encephalitis.

The clinical manifestations and diagnosis of WN virus are discussed below. Topics that discuss the epidemiology and pathogenesis of this infection, as well as the treatment and prevention of WN virus, are found elsewhere. (See "Epidemiology and pathogenesis of West Nile virus infection" and "Treatment and prevention of West Nile virus infection".)

RISK FACTORS — Approximately 25 percent of those infected with West Nile (WN) virus develop WN fever, and 1 out of 150 to 250 develop neuroinvasive disease. Increasing viral load and female gender may increase the risk of developing WN fever [1].

There are several risk factors for developing neuroinvasive disease. These include:

Age – Advancing age is by far the most important risk factor for neuroinvasive disease, particularly encephalitis [2-4].

Malignancy – Case reports suggest that certain cancers, particularly hematological malignancies, increase the risk of severe disease after infection [5]. A case-control study showed that cancer and chemotherapy increased the risk of developing neuroinvasive disease by at least sixfold [6].

Organ transplantation – Persons infected through organ transplantation are at very high risk for developing neuroinvasive disease [7-9]. However, there are conflicting data about the risk of developing neuroinvasive disease among organ transplant recipients infected via mosquito bite [10,11]. (See "Epidemiology and pathogenesis of West Nile virus infection", section on 'Organ transplant'.)

Genetic factors – Host genetic factors, such as chemokine receptor CCR5 deficiency, may increase the risk of death due to neuroinvasive disease [12] but do not appear to be a risk factor for acquisition of infection [13].

Other studies suggest that diabetes, hypertension, alcohol abuse, renal disease, and male gender may also increase the risk of neuroinvasive disease [2,3,14,15]. Several case reports suggest that patients taking Rituximab may be at greater risk of developing neuroinvasive disease [16,17].

CLINICAL MANIFESTATIONS — Most persons infected with West Nile (WN) virus are asymptomatic; symptoms are seen in only about 20 to 40 percent of infected patients [1,18-20]. The typical incubation period for infection ranges from 2 to 14 days, although longer incubation periods have been observed among immunosuppressed hosts [8,21]. After the acute infection, many patients experience persistent symptoms, such as fatigue, memory impairment, weakness, headache, and balance problems [22-26]. Once a patient recovers, immunity to WN virus is thought to be lifelong; if reinfection occurs, it is very rare.

West Nile fever — The usual presentation of WN virus infection is a self-limited illness, called WN fever, which is indistinguishable from dengue fever and other viral syndromes. The illness is characterized by an abrupt onset of fever, headache, malaise, back pain, myalgias, and anorexia. Despite the name "West Nile fever," some patients report very low grade or no fever at all [19]. Eye pain, pharyngitis, nausea, vomiting, diarrhea, and abdominal pain can also occur [1]. Generalized lymphadenopathy, although commonly reported in the past, is rare in contemporary outbreaks. Acute symptoms typically last 3 to 10 days, but some patients with WN fever report a prolonged recovery to their previous baseline functioning.

Rash appears in approximately 25 to 50 percent of patients with WN fever [1,27]. The rash is typically found on the chest, back, and arms, is morbilliform or maculopapular, and is sometimes accompanied by complaints of dysesthesia and pruritus [28]. It often appears at the time of defervescence and generally lasts for less than one week (picture 1) [29]. In addition, rash may be associated with a decreased risk of neuroinvasive disease and death. As an example, in an analysis of two large-scale outbreaks of WN virus, age-adjusted risks were significantly decreased for encephalitis, meningitis, and/or death among those with rash. [30].

Neuroinvasive disease — WN virus neuroinvasive disease presents as fever in conjunction with meningitis, encephalitis, flaccid paralysis, or a mixed pattern of disease [31]. Encephalitis is more commonly reported than meningitis in older age groups, while meningitis occurs more commonly in children [2,32,33]. The mortality rate of patients with neuroinvasive disease is approximately 10 percent. Possible risk factors for death include increasing age, male gender, encephalitis with severe muscle weakness, changes in the level of consciousness, diabetes, cardiovascular disease, hepatitis C virus infection, alcohol misuse, and/or immunosuppression [5,26,29,34].

The clinical features of meningitis and encephalitis associated with WN virus infection are as follows:

The clinical manifestations of meningitis associated with WN virus are similar to those of other viral meningitis and include fever, headache, meningeal signs, and photophobia.

Encephalitis ranges in severity from a mild, self-limited confusional state to severe encephalopathy, coma, and death [35]. Extrapyramidal symptoms are common and suggest WN virus as an etiology of encephalitis, particularly during mosquito season in summer and early fall. Common neurological manifestations include coarse tremor and myoclonus, particularly in the upper extremities, as well as parkinsonian features such as rigidity, postural instability, and bradykinesia [36,37]. Patients report substantial functional and cognitive difficulties for up to a year following the acute infection [29].

WN virus infection can also cause an acute flaccid paralysis syndrome. Paralysis results from an anterior horn cell process suggestive of poliomyelitis [36,38-42]. Patients present with asymmetric weakness of the limbs that rapidly develops within the first 48 hours after symptom onset. Symptoms can occur with or without overt meningitis or encephalitis [36,38]. Approximately one-third of affected patients recover strength to near baseline, one-third modestly improve, and one-third fail to improve [43]. Recovery mostly occurs within the first six to eight months of illness. Quadriplegia and respiratory failure are associated with high morbidity and mortality; however, even patients with initially severe and profound paralysis may experience profound recovery [36].

Other manifestations of WN virus-associated neurologic disease include brachial plexopathy, demyelinating neuropathy, motor axonopathy, axonal polyneuropathy, involvement of ventral spinal roots, myasthenia gravis, acute transverse myelitis, and a disorder similar in character to Guillain-Barré syndrome [29,44-47]. Thus, it is imperative that appropriate diagnostic testing, including lumbar puncture, electromyography, and nerve conduction studies, be obtained before initiating therapies for Guillain-Barré syndrome or other inflammatory neuropathies. (See 'Approach to diagnosis' below.)

Less common neurologic manifestations of WN virus include cranial nerve palsies resulting in facial weakness, vertigo, dysarthria, seizures, cerebellar ataxia, and dysphagia [31,37,48,49].

Ocular manifestations — Common ocular manifestations include chorioretinitis, retinal hemorrhages, and vitreitis [50-56]. The chorioretinal lesions are multifocal with a "target-like" appearance. Other reported ocular findings include iridocyclitis [52], occlusive vasculitis [57], and uveitis [58]. Persistent and/or possibly permanent visual deficits are frequently caused by optic neuritis and occlusive vasculitis, which are less commonly observed lesions [55].

A prospective study of patients presenting to a hospital with WN virus infection in Tunisia found that 80 percent had multifocal chorioretinitis with a mild vitreous inflammatory reaction [54]. Most patients were asymptomatic, and findings were self-limited. In a cohort of patients evaluated a median of 6.8 years post-infection, 24 percent had evidence of WN virus-associated retinopathy, which was more frequent in older patients and those with diabetes mellitus or a history of encephalitis [59].

Other features — WN virus infection has been associated with many other less commonly reported complications including:

Rhabdomyolysis [60]

Fatal hemorrhagic fever with multi-organ failure and palpable purpura [61]

Hepatitis and pancreatitis [62,63]

Central diabetes insipidus [64]

Myocarditis [65]

Myositis and orchitis [66]

Congenital infection — Most women who have been infected with WN virus during pregnancy have delivered infants without evidence of infection or clinical abnormalities [67-69]. However, there is some evidence that transplacental transmission of WN virus can occur [67,70]. (See "Epidemiology and pathogenesis of West Nile virus infection", section on 'Transmission'.)

There have been a few reported cases of congenital WN infection:

There was one confirmed case of congenital WN infection [71]. This infant was born to a mother who developed WN virus encephalitis during week 27 of gestation. The infant presented with chorioretinitis and widespread brain damage seen on magnetic resonance imaging. Immunoglobulin M (IgM) antibodies to WN virus were found in cord blood and cerebrospinal fluid.

There were three possible cases of congenital infection reported among neonates born to women who developed symptomatic WN virus infection within the three weeks preceding delivery. These infants developed WN virus disease (encephalitis, meningitis, rash) shortly after birth [67]. Since cord blood or infant serum at the time of delivery was not available, it was unknown whether transplacental transmission occurred or whether the infants were infected at the time of delivery.

However, a follow-up study of 28 infants born to mothers with WN virus infection during pregnancy showed no differences in birth weight, length, head circumference, Apgar scores, and frequency of congenital anomalies compared with infants born to mothers without WN virus infection [69]. In addition, developmental testing at around 24 months was generally normal.

Persistent symptoms — After the acute infection, many patients with WN virus infection experience persistent symptoms, such as fatigue, memory impairment, weakness, headache, and balance problems, some of which can be documented by neurocognitive testing [6,22-27,72-74]. As an example, in a study of 157 patients with WN virus (most with neuroinvasive disease), 40 percent continued to experience symptoms possibly related to their infection (eg, fatigue, weakness, depression, neck/back pain) for up to eight years [72]. Patients with encephalitis, and those who were over 50 years of age, were significantly more likely to report continued symptoms. Among those with encephalitis, 70 percent were still reporting symptoms related to their infection five-and-a-half years after the initial diagnosis (95% CI 57.8 to 82.3 percent). A more detailed discussion on the long-term prognosis of patients with WN neuroinvasive disease is found elsewhere. (See "Treatment and prevention of West Nile virus infection", section on 'Prognosis'.)

LABORATORY FINDINGS — In general, routine clinical laboratory studies done on peripheral blood samples do not distinguish WN virus infection from other viral infections.

In cases with central nervous system (CNS) involvement, the cerebrospinal fluid (CSF) usually demonstrates an elevated protein (<150 mg/dL) and a moderate pleocytosis (<500 cells/microL) with a predominance of lymphocytes. However, neutrophils may predominate in early infection [29]. As an example, in a study of CSF samples from 334 patients with WN virus infection, the mean CSF nucleated cell count was similar for patients with meningitis and encephalitis (226 and 227 cells/microL, respectively) [75]. In addition, a neutrophilic predominance was present in approximately 40 percent. A small percentage of patients had normal CSF cell counts (3 and 5 percent of those with meningitis and encephalitis, respectively).

On cytologic examination of CSF, plasmacytoid lymphocytes or large monocytic cells resembling Mollaret cells may be present [76].

IMAGING — Among those with suspected West Nile (WN) neuroinvasive disease, computed tomography (CT) of the brain typically shows no evidence of acute disease. Abnormal findings can be observed on magnetic resonance imaging (MRI) [77-79], although findings may not appear for several weeks after illness onset, and in some cases (even in severe WN encephalitis), MRI findings may be normal [35].

When present, MRI findings can include: signal intensity abnormalities seen only on diffusion weighted images, or isolated restricted diffusion; increased signal intensity in the brain and brainstem on FLAIR imaging and T2 weighted imaging; meningeal involvement; and intraspinal abnormalities consisting of spinal cord, cauda equina, and nerve root involvement [79]. Hyperintensity on T2-weighted magnetic resonance images may be seen in regions such as the basal ganglia, thalami, caudate nuclei, brainstem, and spinal cord [77-79].

NEUROPHYSIOLOGIC STUDIES — Electroencephalography (EEG) in patients with meningitis or encephalitis typically shows generalized, continuous slowing, which is more prominent in the frontal or temporal regions [80,81]. Patients with acute flaccid paralysis have electrodiagnostic studies showing normal sensory nerve action potentials (SNAPs), normal nerve conduction velocities, widespread fibrillation potentials, and compound motor action potentials (CMAPs) that vary between normal and markedly decreased (depending upon the degree of paralysis) [40,82].

DIAGNOSIS — Identification of immunoglobulin M (IgM) antibodies in serum or CSF forms the cornerstone of diagnosis in most cases.

Indications for testing — West Nile (WN) virus should be considered in patients who have the onset of an unexplained febrile illness, encephalitis, meningitis, and/or flaccid paralysis during mosquito season. Evidence of WN virus enzootic activity or other human cases, either locally or in a region where the patient has traveled, should raise the index of suspicion. Year-round transmission is possible in warmer climates with continuous mosquito activity. (See 'Clinical manifestations' above and "Epidemiology and pathogenesis of West Nile virus infection".)

Approach to diagnosis — If WN virus infection is suspected, we first order a WN virus IgM antibody on serum using an enzyme-linked immunosorbent assay (MAC-ELISA). A lumbar puncture should be performed in patients with neurologic symptoms, and testing of the CSF for detection of IgM antibody should be done in addition to serum testing. (See 'Serologic tests' below.)

A positive MAC-ELISA test in CSF or serum is sufficient to make the diagnosis in the vast majority of patients. This is particularly true for those with a clinically compatible illness and epidemiologic risk factors for WN virus, such as presentation during an outbreak. (See 'MAC-ELISA' below.)

A plaque reduction neutralization test (PRNT) should only be performed to help confirm the diagnosis if there is concern that the positive MAC-ELISA is due to cross-reactivity from a different flavivirus infection (eg, dengue, yellow fever, St. Louis encephalitis, Zika, Japanese encephalitis viruses) or after recent vaccination for Japanese encephalitis. More detailed information about PRNT testing is discussed below. (See 'Plaque reduction neutralization test (PRNT)' below.)

If the initial MAC-ELISA test is negative and WN virus infection is still suspected, we obtain a repeat serum MAC-ELISA approximately 10 days later. A negative convalescent phase serum rules out infection in immunocompetent patients. Viral detection methods may also be helpful in confirming the diagnosis, especially in immunocompromised patients whose viremia may be prolonged and/or antibody development may be delayed or absent. (See 'Viral detection' below.)

While some commercial laboratories offer WN virus immunoglobulin G (IgG) testing, there is no role for IgG testing when making a diagnosis of acute WN virus infection. While a positive IgG test can indicate previous infection with WN virus, false positives are common.

The approach to diagnosis above describes what is done in most clinical settings. In addition, the United States Centers for Disease Control and Prevention (CDC) has established criteria for the laboratory diagnosis of WN virus infection that can be used for surveillance and clinical purposes (table 1) [83].

Serologic tests — Two types of serologic testing can be used when evaluating a patient with possible WN virus infection, an enzyme-linked immunosorbent assay (MAC-ELISA) and a plaque reduction neutralization test (PRNT). In most cases, a MAC-ELISA is sufficient; however, on occasion a PRNT test is used to confirm the diagnosis. (See 'Approach to diagnosis' above.)

MAC-ELISA — The IgM antibody-capture enzyme-linked immunosorbent assay (MAC-ELISA) is optimal for IgM detection because it is simple, sensitive, and applicable to serum and CSF samples. Testing of serum or CSF is available commercially and can also be obtained through local or state health departments. Because IgM antibody does not cross the blood-brain barrier, detection of IgM antibodies in CSF is highly indicative of WN virus neuroinvasive disease.

IgM seroconversion usually develops between 4 and 10 days after viremia is detected [84,85]. Although IgM antibodies may not be detectable at the time of clinical presentation in those with early disease, they are almost always detected in serum by the eighth day of illness in immunocompetent patients. CSF IgM antibodies may be detected before serum IgM antibodies. In our experience, patients with neuroinvasive disease are more likely than those with WN fever to have a positive MAC-ELISA test result at the time of clinical presentation. The approach to testing in a patient with a negative MAC-ELISA is discussed above. (See 'Approach to diagnosis' above.)

IgM antibodies usually remain detectable in serum for at least one to two months following clinical resolution, but may persist for ≥12 months [84,86-88]. Thus, patients from endemic areas may have detectable IgM antibody from a previous WN virus infection that is unrelated to their current clinical illness.

False-positive WN virus MAC-ELISA tests may occur because antibodies to other arthropod-borne flaviviruses cross-react with WN virus. A false-positive result can be due to recent immunization with flavivirus vaccines (yellow fever or Japanese encephalitis) or due to infections with other related flaviviruses (eg, St. Louis encephalitis, dengue, or Zika) [89]. The PRNT and/or polymerase chain reaction (PCR) testing may provide a definitive diagnosis of WN virus if the patient has risk factors for more than one of these infections (table 1). (See 'Plaque reduction neutralization test (PRNT)' below and 'Viral detection' below.)

Plaque reduction neutralization test (PRNT) — In patients with no previous flavivirus exposure, the PRNT is the most specific antibody test for the arthropod-borne flaviviruses. It may also help to determine whether a positive WN virus ELISA test is due to WN virus specific antibodies or serologic cross-reaction from another flavivirus infection (table 1). However, the test lacks specificity in patients with previous heterologous flavivirus exposure by natural infection or vaccination. As an example, a patient with WN infection and previous yellow fever or Japanese encephalitis vaccination may have higher neutralizing antibody titers to yellow fever or Japanese encephalitis than to WN virus [90].

Typically, neutralizing antibody titers are measured for several flaviviruses, depending upon the epidemiologic situation. In patients without previous flavivirus exposure, a sample is considered to have WN virus antibodies if neutralizing antibody titers to WN virus are at least fourfold greater than those for other tested flaviviruses:

A positive PRNT for WN virus in combination with a positive MAC-ELISA confirms the diagnosis.

A fourfold or greater change in virus-specific quantitative antibody titers (PRNT) in paired sera obtained at least 10 days apart also confirms WN infection, whereas a negative PRNT test or a lack of fourfold change in a convalescent-phase sample rules it out.

The PRNT test is not commercially available, but it is able to be performed by reference labs at the CDC and/or certain state health departments.

Viral detection — In general, we use PCR testing to help identify WN virus infection in the following groups:

Immunocompromised patients whose viremia may be prolonged and antibody development may be delayed or absent.

Patients requiring an urgent diagnosis.

Patients with previous flavivirus exposure whose serologic results may be ambiguous.

Blood donors, since patients who are viremic are often asymptomatic [91]. (See "Blood donor screening: Laboratory testing", section on 'West Nile virus'.)

Virus detection is highly specific, but is of limited value for routine diagnosis since viremia in humans is only found early in the course of disease (often before symptoms develop), is of low titer, and is short lived [85,92-94]. Among patients with neuroinvasive disease, the sensitivity of nucleic acid testing using the PCR is less than 15 percent for serum or plasma, and approximately 55 percent for CSF [18]. PCR testing may be more sensitive in patients with WN fever, with which patients present earlier in the course of disease.

In a study of 296 patients with early symptomatic WN virus infection, PCR, MAC-ELISA, or a combined approach identified 45, 58, and 94 percent of cases, respectively; although, the PCR methods used in this study may have had greater sensitivity than what is seen with commercial testing [95]. In patients with acute WN infection, the sensitivity of PCR is higher in whole blood and urine compared with serum; however, testing of these sample types is not routinely available in commercial laboratories [94,96].

Viral isolation through culture is less sensitive than nucleic acid amplification and is not routinely available or recommended for diagnosis. Detection of viral antigen may be useful for examining tissue samples, but this is usually performed post-mortem.

DIFFERENTIAL DIAGNOSIS — The differential diagnosis for a patient presenting in the late summer/early fall with a non-specific febrile illness, with or without neurologic manifestations, is broad and includes infections due to viruses, spirochetes, and other tickborne illnesses. It is important to obtain a recent travel and/or exposure history to help narrow the number of possible infectious organisms. These agents can usually be diagnosed through culture, serologic, and molecular techniques, though it may take weeks to obtain the results of some of these tests.

Viral infections — Viral etiologies of meningitis/encephalitis include a wide variety of possibilities. Clues to help distinguish between the likelihood of one virus over another include geographic area and the potential routes/vectors of exposure. A detailed discussion of viral encephalitis is discussed elsewhere. (See "Viral encephalitis in adults" and "Arthropod-borne encephalitides".)

WN virus infection should be suspected in patients who present with neurologic changes consistent with encephalitis, encephalitis with movement disorders, or asymmetrical flaccid paralysis (with or without encephalitis or meningitis). Development of a maculopapular rash on the trunk and extremities, although not specific for WN virus, should raise suspicion even further; however, the rash may not appear until the time of defervescence.

Suspicion of other viral encephalitides is based upon characteristic clinical features and/or recent travel history:

Grouped vesicles in a dermatomal pattern may suggest varicella-zoster virus (VZV), which can occasionally cause encephalitis; however the absence of rash does not eliminate VZV from consideration. (See "Epidemiology, clinical manifestations, and diagnosis of herpes zoster".)

Temporal lobe abnormalities on brain imaging suggest infection with herpes simplex virus in a patient with encephalitis. (See "Herpes simplex virus type 1 encephalitis".)

Headache associated with severe joint and bone pain should suggest infection with dengue virus in a patient with recent travel to an endemic area. (See "Dengue virus infection: Clinical manifestations and diagnosis" and "Dengue virus infection: Epidemiology".)

Patients with recent exposure to Ixodes scapularis ticks or Ixodes cookei ticks in the upper Midwest and Northeast United States should be suspected of being infected with Powassan virus, a related flavivirus. Although uncommon, Powassan virus appears to be increasing in frequency. (See "Arthropod-borne encephalitides".)

St. Louis encephalitis is epidemiologically and clinically similar to WN virus. Few cases of St. Louis encephalitis virus have been documented in recent years; this may be due in part to cross-reactivity of antibodies between the two viruses. (See "St. Louis encephalitis".)

Tickborne encephalitis should be suspected in patients with recent travel history to endemic areas in Europe and Russia. (See "Arthropod-borne encephalitides".)

Those with recent travel to endemic areas in Asia should be suspected of being infected with Japanese encephalitis virus. (See "Japanese encephalitis".)

Enteroviruses are also a common cause of meningitis and encephalitis during the summer months, particularly in infants. (See "Enterovirus and parechovirus infections: Clinical features, laboratory diagnosis, treatment, and prevention".)

Other tickborne diseases — A variety of tickborne pathogens (in addition to Powassan virus and tickborne encephalitis virus described above) can cause infections that present with fever and headache during summer and early fall. Rash may or may not be seen. These infections include Lyme disease, human ehrlichiosis and anaplasmosis, and Rocky Mountain spotted fever. The diagnosis is typically confirmed by serology. (See "Nervous system Lyme disease" and "Human ehrlichiosis and anaplasmosis" and "Clinical manifestations and diagnosis of Rocky Mountain spotted fever".)

Bacterial meningitis — Bacterial meningitis due to infection with pathogens such as meningococcus or pneumococcus must be considered in all patients presenting with fever and headache. It is important that this diagnosis be considered given the high morbidity and mortality in patients who are untreated. Unlike patients with CNS infection due to viral causes, patients with bacterial meningitis present with a high CSF white blood cell count with an elevated neutrophil count. The gram stain may reveal the presence of bacteria. (See "Clinical features and diagnosis of acute bacterial meningitis in adults".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Beyond the Basics topics (see "Patient education: West Nile virus infection (Beyond the Basics)")

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Infectious encephalitis".)

SUMMARY AND RECOMMENDATIONS

Most persons infected with the West Nile (WN) virus are asymptomatic; symptoms are seen in only about 20 to 40 percent of infected patients. The two most common manifestations of WN virus infection are fever and neuroinvasive disease. (See 'Clinical manifestations' above.)

WN fever is characterized by fever, headache, malaise, back pain, myalgias, and anorexia. A maculopapular rash appears in up to one-half of such patients. (See 'West Nile fever' above.)

WN neuroinvasive disease can present as encephalitis, meningitis, or an acute asymmetric flaccid paralysis. Encephalitis that is associated with muscle weakness and flaccid paralysis is particularly suggestive of WN virus infection. Other neurologic manifestations include tremor, myoclonus, and Parkinsonian features such as rigidity, postural instability, and bradykinesia. (See 'Neuroinvasive disease' above.)

After the acute infection, many patients with WN virus infection experience persistent symptoms, such as fatigue, memory impairment, weakness, headache, and balance problems. (See 'Persistent symptoms' above.)

In general, routine clinical laboratory studies done on peripheral blood samples do not distinguish WN virus infection from other viral infections. In cases with central nervous system involvement, the cerebrospinal fluid (CSF) usually demonstrates an elevated protein (<150 mg/dL) and a moderate pleocytosis (<500 cells/microL) with a predominance of lymphocytes. However, neutrophils may predominate in early infection. (See 'Laboratory findings' above.)

If WN virus infection is suspected, serologic testing for WN virus IgM antibody should be performed on serum using an enzyme-linked immunosorbent assay (MAC-ELISA). In patients with neurologic symptoms, a lumbar puncture should also be performed and testing of the CSF for detection of IgM antibody should be done in addition to serum testing. (See 'Indications for testing' above and 'Approach to diagnosis' above.)

In the vast majority of patients, a positive MAC-ELISA test on CSF or serum is sufficient to make the diagnosis. This is particularly true for those with a clinically compatible illness and epidemiologic risk factors for WN virus, such as presentation during an outbreak. A plaque reduction neutralization test (PRNT) should only be performed to confirm the diagnosis in select cases when it is important to distinguish serologic cross-reactions caused by recent immunization against or infection with other flaviviruses. (See 'Approach to diagnosis' above and 'Serologic tests' above.)

For patients with a clinically compatible illness whose initial IgM results are negative, repeat testing at least 10 days after symptom onset is warranted. Nucleic acid testing using the polymerase chain reaction (PCR) may also be helpful as an adjunct to IgM antibody testing in certain patients, such as those who are immunocompromised since viremia may be prolonged and/or development of IgM may be delayed or absent. (See 'Approach to diagnosis' above and 'Viral detection' above.)

The differential diagnosis for a patient presenting in the late summer/early fall with a non-specific febrile illness (with or without neurologic manifestation) is broad and includes infections due to viruses, spirochetes, and tickborne illnesses. It is important to obtain a recent travel and/or exposure history to help narrow the number of possible infectious organisms. (See 'Differential diagnosis' above.)

  1. Zou S, Foster GA, Dodd RY, et al. West Nile fever characteristics among viremic persons identified through blood donor screening. J Infect Dis 2010; 202:1354.
  2. Lindsey NP, Staples JE, Lehman JA, et al. Surveillance for human West Nile virus disease - United States, 1999-2008. MMWR Surveill Summ 2010; 59:1.
  3. Carson PJ, Borchardt SM, Custer B, et al. Neuroinvasive disease and West Nile virus infection, North Dakota, USA, 1999-2008. Emerg Infect Dis 2012; 18:684.
  4. Sutinen J, Fell DB, Sander B, Kulkarni MA. Comorbid conditions as risk factors for West Nile neuroinvasive disease in Ontario, Canada: a population-based cohort study. Epidemiol Infect 2022; 150:e103.
  5. Visentin A, Nasillo V, Marchetti M, et al. Clinical Characteristics and Outcome of West Nile Virus Infection in Patients with Lymphoid Neoplasms: An Italian Multicentre Study. Hemasphere 2020; 4:e395.
  6. Patnaik JL, Harmon H, Vogt RL. Follow-up of 2003 human West Nile virus infections, Denver, Colorado. Emerg Infect Dis 2006; 12:1129.
  7. Nett RJ, Kuehnert MJ, Ison MG, et al. Current practices and evaluation of screening solid organ donors for West Nile virus. Transpl Infect Dis 2012; 14:268.
  8. Winston DJ, Vikram HR, Rabe IB, et al. Donor-derived West Nile virus infection in solid organ transplant recipients: report of four additional cases and review of clinical, diagnostic, and therapeutic features. Transplantation 2014; 97:881.
  9. Soto RA, McDonald E, Annambhotla P, et al. West Nile Virus Transmission by Solid Organ Transplantation and Considerations for Organ Donor Screening Practices, United States. Emerg Infect Dis 2022; 28:403.
  10. Kumar D, Drebot MA, Wong SJ, et al. A seroprevalence study of West Nile virus infection in solid organ transplant recipients. Am J Transplant 2004; 4:1883.
  11. Freifeld AG, Meza J, Schweitzer B, et al. Seroprevalence of West Nile virus infection in solid organ transplant recipients. Transpl Infect Dis 2010; 12:120.
  12. Glass WG, McDermott DH, Lim JK, et al. CCR5 deficiency increases risk of symptomatic West Nile virus infection. J Exp Med 2006; 203:35.
  13. Lim JK, McDermott DH, Lisco A, et al. CCR5 deficiency is a risk factor for early clinical manifestations of West Nile virus infection but not for viral transmission. J Infect Dis 2010; 201:178.
  14. Murray K, Baraniuk S, Resnick M, et al. Risk factors for encephalitis and death from West Nile virus infection. Epidemiol Infect 2006; 134:1325.
  15. Bode AV, Sejvar JJ, Pape WJ, et al. West Nile virus disease: a descriptive study of 228 patients hospitalized in a 4-county region of Colorado in 2003. Clin Infect Dis 2006; 42:1234.
  16. Goates C, Tsuha S, Working S, et al. Seronegative West Nile Virus Infection in a Patient Treated with Rituximab for Rheumatoid Arthritis. Am J Med 2017; 130:e257.
  17. Owens M, Choe L, Rivera JE, Avila JD. West Nile virus neuroinvasive disease associated with rituximab therapy. J Neurovirol 2020; 26:611.
  18. Nash D, Mostashari F, Fine A, et al. The outbreak of West Nile virus infection in the New York City area in 1999. N Engl J Med 2001; 344:1807.
  19. Orton SL, Stramer SL, Dodd RY. Self-reported symptoms associated with West Nile virus infection in RNA-positive blood donors. Transfusion 2006; 46:272.
  20. Brown JA, Factor DL, Tkachenko N, et al. West Nile viremic blood donors and risk factors for subsequent West Nile fever. Vector Borne Zoonotic Dis 2007; 7:479.
  21. Pealer LN, Marfin AA, Petersen LR, et al. Transmission of West Nile virus through blood transfusion in the United States in 2002. N Engl J Med 2003; 349:1236.
  22. Murray K, Walker C, Herrington E, et al. Persistent infection with West Nile virus years after initial infection. J Infect Dis 2010; 201:2.
  23. Loeb M, Hanna S, Nicolle L, et al. Prognosis after West Nile virus infection. Ann Intern Med 2008; 149:232.
  24. Carson PJ, Konewko P, Wold KS, et al. Long-term clinical and neuropsychological outcomes of West Nile virus infection. Clin Infect Dis 2006; 43:723.
  25. Haaland KY, Sadek J, Pergam S, et al. Mental status after West Nile virus infection. Emerg Infect Dis 2006; 12:1260.
  26. Patel H, Sander B, Nelder MP. Long-term sequelae of West Nile virus-related illness: a systematic review. Lancet Infect Dis 2015; 15:951.
  27. Watson JT, Pertel PE, Jones RC, et al. Clinical characteristics and functional outcomes of West Nile Fever. Ann Intern Med 2004; 141:360.
  28. Ferguson DD, Gershman K, LeBailly A, Petersen LR. Characteristics of the rash associated with West Nile virus fever. Clin Infect Dis 2005; 41:1204.
  29. Petersen LR, Brault AC, Nasci RS. West Nile virus: review of the literature. JAMA 2013; 310:308.
  30. Huhn GD, Dworkin MS. Rash as a prognostic factor in West Nile virus disease. Clin Infect Dis 2006; 43:388.
  31. Davis LE, DeBiasi R, Goade DE, et al. West Nile virus neuroinvasive disease. Ann Neurol 2006; 60:286.
  32. Lindsey NP, Hayes EB, Staples JE, Fischer M. West Nile virus disease in children, United States, 1999-2007. Pediatrics 2009; 123:e1084.
  33. Gaensbauer JT, Lindsey NP, Messacar K, et al. Neuroinvasive arboviral disease in the United States: 2003 to 2012. Pediatrics 2014; 134:e642.
  34. Popescu CP, Florescu SA, Hasbun R, et al. Prediction of unfavorable outcomes in West Nile virus neuroinvasive infection - Result of a multinational ID-IRI study. J Clin Virol 2020; 122:104213.
  35. Sejvar JJ. Clinical manifestations and outcomes of West Nile virus infection. Viruses 2014; 6:606.
  36. Sejvar JJ, Haddad MB, Tierney BC, et al. Neurologic manifestations and outcome of West Nile virus infection. JAMA 2003; 290:511.
  37. Kramer LD, Li J, Shi PY. West Nile virus. Lancet Neurol 2007; 6:171.
  38. Sejvar JJ, Bode AV, Marfin AA, et al. West Nile virus-associated flaccid paralysis. Emerg Infect Dis 2005; 11:1021.
  39. Al-Shekhlee A, Katirji B. Electrodiagnostic features of acute paralytic poliomyelitis associated with West Nile virus infection. Muscle Nerve 2004; 29:376.
  40. Li J, Loeb JA, Shy ME, et al. Asymmetric flaccid paralysis: a neuromuscular presentation of West Nile virus infection. Ann Neurol 2003; 53:703.
  41. Jeha LE, Sila CA, Lederman RJ, et al. West Nile virus infection: a new acute paralytic illness. Neurology 2003; 61:55.
  42. Leis AA, Stokic DS, Webb RM, et al. Clinical spectrum of muscle weakness in human West Nile virus infection. Muscle Nerve 2003; 28:302.
  43. Sejvar JJ, Bode AV, Marfin AA, et al. West Nile Virus-associated flaccid paralysis outcome. Emerg Infect Dis 2006; 12:514.
  44. Ahmed S, Libman R, Wesson K, et al. Guillain-Barré syndrome: An unusual presentation of West Nile virus infection. Neurology 2000; 55:144.
  45. Park M, Hui JS, Bartt RE. Acute anterior radiculitis associated with West Nile virus infection. J Neurol Neurosurg Psychiatry 2003; 74:823.
  46. Almhanna K, Palanichamy N, Sharma M, et al. Unilateral brachial plexopathy associated with West Nile virus meningoencephalitis. Clin Infect Dis 2003; 36:1629.
  47. Jani C, Walker A, Al Omari O, et al. Acute transverse myelitis in West Nile Virus, a rare neurological presentation. IDCases 2021; 24:e01104.
  48. Pepperell C, Rau N, Krajden S, et al. West Nile virus infection in 2002: morbidity and mortality among patients admitted to hospital in southcentral Ontario. CMAJ 2003; 168:1399.
  49. Kanagarajan K, Ganesh S, Alakhras M, et al. West Nile virus infection presenting as cerebellar ataxia and fever: case report. South Med J 2003; 96:600.
  50. Garg S, Jampol LM. Systemic and intraocular manifestations of West Nile virus infection. Surv Ophthalmol 2005; 50:3.
  51. Bains HS, Jampol LM, Caughron MC, Parnell JR. Vitritis and chorioretinitis in a patient with West Nile virus infection. Arch Ophthalmol 2003; 121:205.
  52. Hershberger VS, Augsburger JJ, Hutchins RK, et al. Chorioretinal lesions in nonfatal cases of West Nile virus infection. Ophthalmology 2003; 110:1732.
  53. Vandenbelt S, Shaikh S, Capone A Jr, Williams GA. Multifocal choroiditis associated with West Nile virus encephalitis. Retina 2003; 23:97.
  54. Khairallah M, Ben Yahia S, Ladjimi A, et al. Chorioretinal involvement in patients with West Nile virus infection. Ophthalmology 2004; 111:2065.
  55. Chan CK, Limstrom SA, Tarasewicz DG, Lin SG. Ocular features of west nile virus infection in North America: a study of 14 eyes. Ophthalmology 2006; 113:1539.
  56. Rousseau A, Haigh O, Ksiaa I, et al. Ocular Manifestations of West Nile Virus. Vaccines (Basel) 2020; 8.
  57. Kaiser PK, Lee MS, Martin DA. Occlusive vasculitis in a patient with concomitant West Nile virus infection. Am J Ophthalmol 2003; 136:928.
  58. Kuchtey RW, Kosmorsky GS, Martin D, Lee MS. Uveitis associated with West Nile virus infection. Arch Ophthalmol 2003; 121:1648.
  59. Hasbun R, Garcia MN, Kellaway J, et al. West Nile Virus Retinopathy and Associations with Long Term Neurological and Neurocognitive Sequelae. PLoS One 2016; 11:e0148898.
  60. Montgomery SP, Chow CC, Smith SW, et al. Rhabdomyolysis in patients with west nile encephalitis and meningitis. Vector Borne Zoonotic Dis 2005; 5:252.
  61. Paddock CD, Nicholson WL, Bhatnagar J, et al. Fatal hemorrhagic fever caused by West Nile virus in the United States. Clin Infect Dis 2006; 42:1527.
  62. Georges AJ, Lesbordes JL, Georges-Courbot MC, et al. Fatal hepatitis from West Nile virus. Ann Inst Pasteur Virol 1988; 138:237.
  63. Perelman A, Stern J. Acute pancreatitis in West Nile Fever. Am J Trop Med Hyg 1974; 23:1150.
  64. Sherman-Weber S, Axelrod P. Central diabetes insipidus complicating West Nile encephalitis. Clin Infect Dis 2004; 38:1042.
  65. Pergam SA, DeLong CE, Echevarria L, et al. Myocarditis in West Nile Virus infection. Am J Trop Med Hyg 2006; 75:1232.
  66. Smith RD, Konoplev S, DeCourten-Myers G, Brown T. West Nile virus encephalitis with myositis and orchitis. Hum Pathol 2004; 35:254.
  67. O'Leary DR, Kuhn S, Kniss KL, et al. Birth outcomes following West Nile Virus infection of pregnant women in the United States: 2003-2004. Pediatrics 2006; 117:e537.
  68. Paisley JE, Hinckley AF, O'Leary DR, et al. West Nile virus infection among pregnant women in a northern Colorado community, 2003 to 2004. Pediatrics 2006; 117:814.
  69. Pridjian G, Sirois PA, McRae S, et al. Prospective study of pregnancy and newborn outcomes in mothers with West nile illness during pregnancy. Birth Defects Res A Clin Mol Teratol 2016; 106:716.
  70. Nguyen Q, Teran S, Snedeker J, et al. CNS sequelae in an infant with congenital West Nile virus infection. Infect Med 2005; 22:626.
  71. Alpert SG, Fergerson J, Noël LP. Intrauterine West Nile virus: ocular and systemic findings. Am J Ophthalmol 2003; 136:733.
  72. Murray KO, Garcia MN, Rahbar MH, et al. Survival analysis, long-term outcomes, and percentage of recovery up to 8 years post-infection among the Houston West Nile virus cohort. PLoS One 2014; 9:e102953.
  73. Hart J Jr, Tillman G, Kraut MA, et al. West Nile virus neuroinvasive disease: neurological manifestations and prospective longitudinal outcomes. BMC Infect Dis 2014; 14:248.
  74. Samaan Z, McDermid Vaz S, Bawor M, et al. Neuropsychological Impact of West Nile Virus Infection: An Extensive Neuropsychiatric Assessment of 49 Cases in Canada. PLoS One 2016; 11:e0158364.
  75. Tyler KL, Pape J, Goody RJ, et al. CSF findings in 250 patients with serologically confirmed West Nile virus meningitis and encephalitis. Neurology 2006; 66:361.
  76. Procop GW, Yen-Lieberman B, Prayson RA, Gordon SM. Mollaret-like cells in patients with West Nile virus infection. Emerg Infect Dis 2004; 10:753.
  77. Petropoulou KA, Gordon SM, Prayson RA, Ruggierri PM. West Nile virus meningoencephalitis: MR imaging findings. AJNR Am J Neuroradiol 2005; 26:1986.
  78. Zak IT, Altinok D, Merline JR, et al. West Nile virus infection. AJR Am J Roentgenol 2005; 184:957.
  79. Ali M, Safriel Y, Sohi J, et al. West Nile virus infection: MR imaging findings in the nervous system. AJNR Am J Neuroradiol 2005; 26:289.
  80. Gandelman-Marton R, Kimiagar I, Itzhaki A, et al. Electroencephalography findings in adult patients with West Nile virus-associated meningitis and meningoencephalitis. Clin Infect Dis 2003; 37:1573.
  81. Rodriguez AJ, Westmoreland BF. Electroencephalographic characteristics of patients infected with west nile virus. J Clin Neurophysiol 2007; 24:386.
  82. Flaherty ML, Wijdicks EF, Stevens JC, et al. Clinical and electrophysiologic patterns of flaccid paralysis due to West Nile virus. Mayo Clin Proc 2003; 78:1245.
  83. Arboviral Diseases, Neuroinvasive and Non-neuroinvasive 2015 Case Definition. Centers for Disease Control and Prevention. Available at: https://ndc.services.cdc.gov/case-definitions/arboviral-diseases-neuroinvasive-and-non-neuroinvasive-2015/. (Accessed on August 01, 2022).
  84. Prince HE, Tobler LH, Lapé-Nixon M, et al. Development and persistence of West Nile virus-specific immunoglobulin M (IgM), IgA, and IgG in viremic blood donors. J Clin Microbiol 2005; 43:4316.
  85. Busch MP, Kleinman SH, Tobler LH, et al. Virus and antibody dynamics in acute west nile virus infection. J Infect Dis 2008; 198:984.
  86. Roehrig JT, Nash D, Maldin B, et al. Persistence of virus-reactive serum immunoglobulin m antibody in confirmed west nile virus encephalitis cases. Emerg Infect Dis 2003; 9:376.
  87. Prince HE, Tobler LH, Yeh C, et al. Persistence of West Nile virus-specific antibodies in viremic blood donors. Clin Vaccine Immunol 2007; 14:1228.
  88. Staples JE, Gibney KB, Panella AJ, et al. Duration of West Nile Virus Immunoglobulin M Antibodies up to 81 Months Following West Nile Virus Disease Onset. Am J Trop Med Hyg 2022; 106:1721.
  89. Martin DA, Biggerstaff BJ, Allen B, et al. Use of immunoglobulin m cross-reactions in differential diagnosis of human flaviviral encephalitis infections in the United States. Clin Diagn Lab Immunol 2002; 9:544.
  90. Johnson BW, Kosoy O, Martin DA, et al. West Nile virus infection and serologic response among persons previously vaccinated against yellow fever and Japanese encephalitis viruses. Vector Borne Zoonotic Dis 2005; 5:137.
  91. Petersen LR, Busch MP. Transfusion-transmitted arboviruses. Vox Sang 2010; 98:495.
  92. Busch MP, Caglioti S, Robertson EF, et al. Screening the blood supply for West Nile virus RNA by nucleic acid amplification testing. N Engl J Med 2005; 353:460.
  93. Busch MP, Wright DJ, Custer B, et al. West Nile virus infections projected from blood donor screening data, United States, 2003. Emerg Infect Dis 2006; 12:395.
  94. Barzon L, Pacenti M, Ulbert S, Palù G. Latest developments and challenges in the diagnosis of human West Nile virus infection. Expert Rev Anti Infect Ther 2015; 13:327.
  95. Tilley PA, Fox JD, Jayaraman GC, Preiksaitis JK. Nucleic acid testing for west nile virus RNA in plasma enhances rapid diagnosis of acute infection in symptomatic patients. J Infect Dis 2006; 193:1361.
  96. Lustig Y, Mannasse B, Koren R, et al. Superiority of West Nile Virus RNA Detection in Whole Blood for Diagnosis of Acute Infection. J Clin Microbiol 2016; 54:2294.
Topic 1273 Version 22.0

References

آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟