West Nile Virus Infection

Fig. 11.1
(a) Red-free fundus photograph of the right eye of a diabetic 57-year-old woman with a recent history of WNV infection shows superotemporal linear clusterings of deep, chorioretinal lesions and associated faint intraretinal hemorrhages. Fluorescein angiography shows (b) early hypofluorescence and (c) late staining of the chorioretinal lesions


Fig. 11.2
(a) Red-free photograph of the left eye of a 64-year-old diabetic patient with serologically confirmed WNV infection shows multiple deep chorioretinal lesions, marked diffuse arterial sheathing, and diabetic macular edema. (b) Mid-phase fluorescein angiogram shows chorioretinal lesions with central hypofluorescence and peripheral hyperfluorescence and capillary leakage resulting from diabetic maculopathy. Several chorioretinal lesions extend superiorly and inferiorly in a linear pattern from the optic disc

Typical multifocal chorioretinitis, commonly associated with advanced age and/or diabetes, was found to be a specific marker of WNV infection, particularly in patients who present with meningoencephalitis [44, 49]. Other Ophthalmic Manifestations

Other ocular findings have been reported in association with WNV infection including iridocyclitis in the absence of chorioretinitis, retinitis, retinal hemorrhages, focal or diffuse vascular sheathing, vascular leakage, macular edema, occlusive vasculitis (Fig. 11.3), severe ischemic maculopathy, and segmental wedge-shaped zones of atrophy and mottling of the retinal pigment epithelium [29, 34, 37, 38, 48, 49]. WNV-associated optic nerve involvement may occur, including optic disc swelling, optic neuritis, neuroretinitis, papilledema (personal unpublished data), and optic disc staining on fluorescein angiography [29]. Other reported neuro-ophthalmic manifestations include ocular nerve palsy and nystagmus [29]. Congenital chorioretinal scarring secondary to intrauterine transmission of WNV infection has been reported [25].


Fig. 11.3
Fluorescein angiogram of the left eye of a 62-year-old patient with serologically confirmed WNV infection shows retinal hemorrhages with extensive areas of retinal capillary non-perfusion suggestive of occlusive vasculitis

11.5 Diagnosis

Diagnosis of WNV infection requires a high index of suspicion and specific laboratory testing. WNV should be strongly considered in patients who present with unexplained febrile illness, meningoencephalitis, or flaccid paralysis during mosquito season, particularly in endemic areas. The presence of mosquito bites on the skin will assist in diagnosis. The most common efficient diagnostic method is detection of WNV-specific IgM antibody in serum, cerebrospinal fluid, or both using the antibody-capture enzyme-linked immunosorbent assay (MAC-ELISA). This test is most accurate when performed within 8 to 21 days after the appearance of clinical symptoms [2, 24]. Since IgM antibody does not cross the blood-brain barrier, its presence in the cerebrospinal fluid strongly suggests infection of the central nervous system. Based on CDC guidelines (www.​cdc.​gov/​ncidod/​dvbid/​westnile/​resources/​ wnvguidelines-aug-2003.pdf), the diagnosis of WNV meningoencephalitis is confirmed if the IgM from cerebrospinal fluid is positive for WNV. A fourfold or greater increase serum antibody titer in serum samples collected 2–3 weeks apart can also be used to make a diagnosis of WNV infection. Serum IgM antibody to WNV can persist for six months or longer after onset of illness. Flaviviruses may exhibit antigenic cross-reactivity; therefore persons, who have recently been vaccinated with yellow fever or Japanese encephalitis vaccines or have infections with related flaviviruses, may generate a false-positive result in the serum. The plaque-reduction neutralization test can help distinguish false-positive results of MAC-ELISA or other assays as well as to help to distinguish serologic cross-reactions among the flaviviruses [2, 20].

Recently, PCR-based detection systems for the rapid detection of WNV infection in clinical specimens that are negative for virus isolation have been reported, suggesting that nucleic acid-based assays hold great promise for the detection of WNV infection [42]. In addition, other PCR-based methods, including real-time PCR (RT-PCR), reverse transcription loop-mediated isothermal gene amplification (RT-LAMP) assay, and qRT-PCR, have been developed for the detection of WNV RNA [42, 50, 51].

Cerebrospinal fluid generally shows normal glucose, elevated protein, and pleocytosis (>5 leukocytes/μL) [20]. The unique pattern of multifocal chorioretinitis can help establish an early diagnosis of the disease while serologic testing is pending [49].

11.6 Differential Diagnosis

The differential diagnosis of WNV systemic disease include other arthropod-borne viral encephalitides, enteroviral aseptic meningitis, herpesvirus encephalitis, encephalopathy from systemic illnesses (Legionnaires’ disease, rickettsiosis, Epstein-Barr virus infectious mononucleosis, and systemic lupus erythematosus), epidural abscess, hypertensive encephalopathy, and drug-induced meningitis. Many infectious and inflammatory conditions may present with chorioretinitis. The differential diagnosis includes syphilis, tuberculosis, histoplasmosis, sarcoidosis, and idiopathic multifocal chorioretinitis [6, 30]. WNV-associated chorioretinitis can be distinguished from these entities on the basis of history, systemic signs and symptoms, and particularly the unique pattern of chorioretinitis [30].

11.7 Management

There is, at present, no proven treatment for WNV infection. In cases of severe systemic disease, intensive supportive therapy is indicated, often involving hospitalization, intravenous fluids, respiratory support, prevention of secondary infections, and good nursing care [24].

Clinical trials of antiviral agents such as ribavirin interferon α -2b, interferon b, high-titer intravenous immunoglobulin, and pluripotent immunomodulator AS101 will allow new and more effective therapeutic approaches to emerge in future [5254].

Passively transferring anti-WNV immunoglobulin has been shown to be effective in animal models and may be helpful in patients [7].

Specific ophthalmic treatment may be required: topical steroids for anterior uveitis, peripheral retinal photocoagulation for neovascularization due to occlusive vasculitis, pars plana vitrectomy for non-clearing vitreous hemorrhage or tractional retinal detachment, and intravitreal injection of anti-vasoendothelial growth factor (anti-VEGF) agent for choroidal neovascularization or macular edema [35, 55].

Prevention is the mainstay of WNV infection control: measures to reduce the number of mosquitoes (draining standing water, larvicides) and personal protection (repellents, window screen, protective clothing). Vaccination, a possible long-term solution, is still in the research phase [56, 57]. Although the cost-effectiveness of WNV vaccination is uncertain, vaccination of populations at risk of developing severe WNV infection may reduce the number of fatalities due to WNV.

11.8 Prognosis

Prognosis of WNV systemic disease is good in most patients. Full recovery is the norm for patients with uncomplicated West Nile fever or meningitis; however, initial symptoms, particularly extreme fatigue, may be prolonged [20]. However, severe cases may result in neurologic sequelae or death, especially in patients who are elderly or debilitated [7, 20]. Advanced age is the most important risk factor for death, ranging from 0.8 % among those aged less than 40 years to 17 % among those aged at least 70 years [20]. Encephalitis with severe muscle weakness, changes in the level of consciousness, diabetes, cardiovascular disease, hepatitis C virus infection, and immunosuppression are possible risk factors for death [20].

Ocular involvement usually has a self-limited course. Active chorioretinal lesions at presentation evolved to the typical inactive stage [6, 30]. Some inactive lesions become more prominent on both ophthalmoscopy and fluorescein angiography. Visual acuity returns to baseline in most patients [30]. However, persistent visual impairment may occur due to a foveal chorioretinal scar, choroidal neovascularization, complicated occlusive retinal vasculitis (vitreous hemorrhage secondary to retinal neovascularization, severe ischemic maculopathy), optic atrophy, or retrogeniculate damage [35, 37, 38]. Recently, one case of reactivation of WNV infection-related chorioretinitis has been reported [45].


WNV infection is among the most important emergent and resurgent infections that are tending to expand worldwide, mainly due to climate changes and globalization. Most frequently, systemic disease is subclinical or manifest as a mild febrile illness, but a severe, potentially lethal systemic involvement with neurologic disease also can occur. Chorioretinal involvement, frequently asymptomatic and self-limited, is the most common finding in patients with WNV infection associated with neurologic disease. The unique pattern of multifocal chorioretinitis can help establish an early diagnosis of the disease while serologic testing is pending. Therefore, an ocular examination, including ophthalmoscopy and fluorescein angiography in selected cases, should be part of the routine evaluation of patients with clinically suspected WNV infection.

Core Messages

  • Systemic WNV disease: often subclinical, but may vary from mild febrile illness to very severe neurologic involvement

  • Ocular disease: typical bilateral multifocal chorioretinitis with linear clustering of chorioretinal lesions, retinal vasculitis, anterior uveitis, optic neuropathy

  • Fundus examination: useful diagnostic tool while serologic testing is pending in patients with suspected WNV neurologic disease

  • Laboratory diagnosis: serology (WNV-specific IgM), real-time polymerase chain reaction (PCR)

  • Management: mostly supportive

  • Prognosis:

    • Systemic disease: usually good, but potentially lethal in patients who are elderly or debilitated

    • Ocular disease: usually self-limiting, rarely persistent visual loss

  • Prevention: personal protection against tick bites, improvement of sanitary conditions



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Sep 25, 2017 | Posted by in OPHTHALMOLOGY | Comments Off on West Nile Virus Infection

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