West Nile Virus

Slide 1 · West Nile Virus

Pathogenesis, neuroinvasive disease, and neuropathology

An integrated clinicopathologic lecture

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning objectives

Trace mosquito-borne transmission through skin, lymph nodes, and blood to the CNS.

Distinguish febrile disease from neuroinvasive syndromes and their outcomes.

Recognize characteristic neuropathologic reactions and diagnostic approaches.

Slide 3 · Two clinical trajectories

Mild / self-limited

Usually silent infection

Symptomatic illness may be febrile

Recovery without neuroinvasion

Neuroinvasive

Meningitis, encephalitis, or both

Potential spinal-cord involvement

Long-term cognitive and neurologic effects

Clinical breadth is a defining feature of West Nile virus infection.

Slide 4 · Etiologic identity

West Nile virus is an arthropod-borne virus (arbovirus).

It belongs to the flavivirus group.

The pathogen causes an acute systemic viral infection; CNS disease develops in a minority.

Slide 5 · Flavivirus context

Flavivirus group

West Nile virus

Dengue viruses

Yellow fever virus

Shared viral grouping is not evidence of identical clinical syndromes.

Slide 6 · Geographic distribution

A broad geographic range.

Regions named include Africa, the Middle East, Europe, Southeast Asia, and Australia.

Geographic familiarity matters when interpreting a compatible febrile or neurologic syndrome.

Slide 7 · United States: Emergence and spread

1999

First detected in New York City

Spread across the United States

Historical emergence; Not a current surveillance update.

Slide 8 · Reported burden

Approximately 1,000–3,000 U.S. Cases per year since 2013.

This is a historical textbook characterization, not a live incidence estimate.

Reported cases are distinct from all infections, because many infections are asymptomatic.

Slide 9 · Reservoir and vector are distinct

Birds: Reservoir

Infected birds develop prolonged viremia.

Birds are the major reservoir for West Nile virus.

Mosquitoes: Vector

Transmit virus to birds and mammals.

A bite is the usual acquisition route in humans.

Slide 10 · Humans are incidental hosts

The mosquito–bird cycle maintains virus in nature.

Humans become infected incidentally rather than serving as the major reservoir.

Epidemiologic exposure is therefore informative without establishing disease.

Slide 11 · Mosquito-borne acquisition

Infected mosquito

Bite and inoculation

Human infection

Most affected patients acquire West Nile virus through a mosquito bite.

Slide 12 · Less common transmission routes

Route

Mechanism named by Robbins

Blood products

Transfusion

Donated organ

Transplantation

Maternal–child

Transplacental spread

Breastfeeding

Milk-associated transmission

These routes are less common than mosquito-borne acquisition.

Slide 13 · Ecologic transmission schematic

Infected birds

Major reservoir

Mosquito vector

Incidental human host

Bird–mosquito cycle maintains transmission; Human infection is incidental.

Slide 14 · Transmission is not synonymous with severity

Exposure route describes acquisition, not the resulting clinical phenotype.

After infection, the spectrum extends from silent infection to meningoencephalitis.

Host factors and neuroinvasion are relevant to severe outcomes.

Slide 15 · Pathogenesis: Route from skin to neuron

Skin after bite

Dendritic cells

Lymph nodes

Bloodstream

CNS neurons

The sequence follows the core mechanism, Chapter 8.

Slide 16 · Initial site: Mosquito inoculation

Mosquito bite

Viral entry into skin

Local replication begins

Inoculation is the initiating event in the usual human infection route.

The skin is not merely an entry site: It is an early replication compartment.

Slide 17 · Skin dendritic cells amplify infection

Virus replicates in skin dendritic cells.

Skin at inoculation site

Dendritic cell

Clinical / pathologic meaning

Dendritic cells participate in an early stage of infection.

Their subsequent migration links local infection to regional lymphoid tissue.

Slide 18 · Migration to draining lymph nodes

Infected skin dendritic cell

Migration

Regional lymph node

The pathogen exploits cell trafficking to reach a new replication compartment.

Slide 19 · Lymph nodes provide additional replication

West Nile virus replicates further within lymph nodes.

Lymph node

Clinical / pathologic meaning

Lymph-node replication occurs after movement from the inoculation site.

This precedes entry of virus into the circulation.

Slide 20 · Viremia connects local and systemic disease

Skin

Lymphatic tissue

Bloodstream

Systemic infection

Viremia is a mechanistic bridge between local replication and dissemination.

Slide 21 · Crossing the blood–brain barrier

In some infected persons, virus crosses the blood–brain barrier.

Blood

CNS compartment

Viral entry

Clinical / pathologic meaning

Neuroinvasion occurs after systemic dissemination.

This distinguishes ordinary systemic infection from direct CNS infection.

Slide 22 · Neuronal infection defines neuroinvasion

Blood-borne virus

Blood–brain barrier

CNS neuron infected

The textbook specifically identifies neurons as infected CNS cells.

Slide 23 · Pathogenesis: The integrated sequence

Mosquito inoculation

Skin dendritic-cell replication

Lymph-node amplification

Bloodstream

Blood–brain barrier crossing

Neuronal infection

Pathogenic sequence; Neuroinvasion occurs only in some infected persons.

Slide 24 · Neuroinvasion is uncommon

Most

Infections asymptomatic

~20%

Symptomatic febrile illness

~1 in 150

CNS complications

The three categories are not equivalent denominators; Do not add the proportions.

Slide 25 · Host and disease course are not identical

Infection events

Mosquito acquisition

Early tissue replication

Viremia

Clinical outcomes

Asymptomatic infection

Febrile systemic illness

Rare neuroinvasive disease

Slide 26 · Asymptomatic infection predominates

Most infections do not produce a recognized clinical syndrome.

Absence of symptoms does not negate infection.

Symptom-based clinical series do not enumerate all infected individuals.

Slide 27 · The acute febrile illness

About 20% of infected persons develop symptoms.

Fever and headache commonly frame the illness.

Myalgia and fatigue add systemic symptoms without requiring CNS infection.

Slide 28 · Systemic and gastrointestinal manifestations

Constitutional

Gastrointestinal

Fever

Anorexia

Headache

Vomiting

Myalgia / fatigue

Diarrhea

These symptoms are listed for symptomatic West Nile virus infection.

Slide 29 · Maculopapular rash

A maculopapular rash occurs in approximately half of symptomatic cases.

Schematic: Maculopapular eruption

Clinical / pathologic meaning

The denominator is symptomatic infections—not all infections.

The rash is a clue within a compatible systemic illness, not a standalone etiologic diagnosis.

Slide 30 · Interpreting the febrile phenotype

Constitutional, gastrointestinal, and cutaneous features may coexist.

These symptoms do not, by themselves, establish neuroinvasive disease.

Progression to meningeal or cerebral dysfunction changes the clinical category.

Slide 31 · Forms of neuroinvasive disease

CNS complications

Meningitis

Encephalitis

Meningoencephalitis

These categories are explicitly listed.

Slide 32 · Meningitis: Meningeal compartment

Meningitis primarily denotes inflammation of the leptomeninges and CSF space.

Leptomeningeal boundary (schematic)

Clinical / pathologic meaning

West Nile virus can present with CNS meningitis.

A meningeal syndrome is not equivalent to parenchymal encephalitis.

Slide 33 · Encephalitis: Brain parenchyma

Viral encephalitis denotes infection and inflammation of brain parenchyma.

Parenchymal involvement (schematic)

Clinical / pathologic meaning

Confusion, delirium, seizures, or reduced consciousness may indicate encephalitic involvement.

Meningeal inflammation commonly accompanies viral encephalitis.

Slide 34 · Meningoencephalitis: Two compartments

Meningeal component

Leptomeningeal inflammation

CSF inflammatory response

Parenchymal component

Neuronal injury

Microglial response and focal necrosis

Combined disease has consequences beyond isolated meningeal irritation.

Slide 35 · Neurologic deficits in arboviral encephalitis

Generalized

Focal

Confusion / delirium

Reflex asymmetry

Seizures

Ocular palsies

Stupor or coma

Localizing neurologic abnormalities

Chapter 28 describes these across arthropod-borne viral encephalitides; Not all findings occur in every WNV patient.

Slide 36 · Spinal-cord involvement produces paralysis

West Nile neuroinvasion

Spinal-cord involvement

Polio-like paralysis

The Chapter 28 CNS discussion explicitly links WNV spinal-cord involvement to a polio-like syndrome.

Slide 37 · CNS disease spans several compartments

Leptomeninges

Brain parenchyma

Spinal cord

Meningitis, encephalitis, and WNV-related spinal disease are distinct but potentially overlapping sites.

Slide 38 · Who is at greater risk of severe disease?

Older adults are at greater risk.

Immunosuppressed individuals are also at greater risk.

These risk associations concern severe disease, not exclusive susceptibility to infection.

Slide 39 · Uncommon extracerebral complications

Organ

Rare complication named

Liver

Hepatitis

Heart

Myocarditis

Pancreas

Pancreatitis

Do not overstate the frequency of these complications.

Slide 40 · Meningoencephalitis can be fatal

~10%

Mortality among meningoencephalitis cases

~1 in 150

CNS disease among all infections

The 10% estimate and 1-in-150 frequency use different denominators.

Slide 41 · Long-term neurologic consequences

Many survivors of meningoencephalitis have persistent sequelae.

Cognitive impairment is specifically described.

Other neurologic impairment can persist after the acute phase.

Slide 42 · Clinical probability: Mind the denominator

Textbook statement

Population being counted

20% symptomatic

All infected persons

Rash in ~half

Symptomatic persons

CNS disease ~1 in 150

All infections

Meningoencephalitis mortality ~10%

Patients with meningoencephalitis

Do not combine these conditional probabilities as though they use the same denominator.

Slide 43 · CSF profile in arboviral encephalitis

Appearance and pressure

Usually colorless fluid

Pressure may be slightly elevated

Chemistry and cells

Protein elevated; Glucose normal

Early neutrophils shift to lymphocytes

Slide 44 · CSF cell pattern evolves with time

Early: Neutrophilic pleocytosis

Transition

Later: Lymphocytosis

Time of lumbar puncture affects the cytologic impression in arboviral encephalitis.

Slide 45 · Protein and glucose in arboviral CSF

Parameter

Typical textbook pattern

Protein

Elevated

Glucose

Normal

Pressure

Slightly elevated

Appearance

Usually colorless

Pattern supports but does not uniquely identify an arboviral cause.

Slide 46 · The characteristic tissue reaction

Virus-associated neuronal injury

Lymphocytic inflammation

Microglial response

Neuronophagia

Summary of characteristic WNV and broader arboviral encephalitis morphology.

Slide 47 · Perivascular inflammation

Lymphocytic perivascular cuff

Schematic — not a histologic specimen

Interpretation

Lymphocytes accumulate around vessels in brain parenchyma.

This is a characteristic pattern in arthropod-borne viral encephalitis.

Distribution and severity vary among cases.

Slide 48 · Leptomeningeal inflammation

Leptomeninges

Adjacent CNS tissue

Schematic — not a histologic specimen

Interpretation

West Nile autopsies show leptomeningeal chronic inflammation.

Inflammation can coexist with a parenchymal viral encephalitis.

Interpret with other sites and cell types in the CNS.

Slide 49 · Microglial nodules

Focal aggregate of microglia

Schematic — not a histologic specimen

Interpretation

Microglia form discrete cellular aggregates.

These nodules are a stereotypic reaction to neuronal injury.

Their presence alone does not prove which virus is responsible.

Slide 50 · Neuronophagia

Injured neuron with adjacent phagocytes

Schematic — not a histologic specimen

Interpretation

Injured or dead neurons are phagocytosed by microglial cells.

The process signifies neuronal damage in the infected CNS.

It may occur in gray and white matter foci of arboviral disease.

Slide 51 · Anatomic distribution in fatal West Nile infection

Reported regions

Recorded changes

Temporal lobes

Inflammation, microglial nodules, neuronophagia

Brainstem

Inflammation, microglial nodules, neuronophagia

WNV-specific morphology from Chapter 8; Wording is “predominantly involving” these sites.

Slide 52 · Arboviral encephalitis: Tissue necrosis

Multiple foci of necrosis may involve gray and white matter.

Schematic tissue injury foci

Clinical / pathologic meaning

Single-neuron necrosis with neuronophagia is emphasized.

Extent and severity vary across arboviral encephalitides.

Slide 53 · Severe cases may show vascular injury

Necrotizing vasculitis with focal hemorrhage may occur in severe arboviral encephalitis.

Vessel injury with focal hemorrhage: Schematic

Clinical / pathologic meaning

This is described as a severe-pattern feature.

It is not a required finding for West Nile virus diagnosis.

Slide 54 · Neuropathology and spinal signs

Anatomic substrate

West Nile may involve the spinal cord.

CNS infection can injure neuronal structures.

Clinical correlate

A polio-like paralytic syndrome may follow.

Do not equate all paralysis with poliovirus infection.

Slide 55 · Why morphology does not identify the virus

What histology shows

Perivascular lymphocytes

Microglial nodules

Neuronophagia / tissue necrosis

What it cannot establish alone

Unique etiologic identity

Specific arbovirus classification

Virologic confirmation

Slide 56 · When tissue is examined

Method named

Diagnostic role

Immunohistochemistry

Detection/identification of viral antigens

Molecular methods

Identification of viral nucleic acid

Ultrastructural methods

Viral characterization in tissue

Chapter 28 lists a combination of methods for tissue identification; Their performance varies by context.

Slide 57 · Serologic diagnosis: Virus-specific IgM

Compatible illness

Serum or CSF specimen

WNV-specific IgM detection

Robbins Chapter 8 identifies virus-specific IgM in serum or CSF as the usual diagnostic approach.

Slide 58 · Serum and CSF are different specimens

Serum IgM

Supports recent virus-specific immune response.

Must be interpreted with the illness and exposure context.

CSF IgM

Used when neuroinvasive infection is suspected.

Interpret in the context of neurologic signs and CSF findings.

Slide 59 · Alternative virologic methods

Method

What the test seeks

PCR-based assay

Viral nucleic acid

Viral culture

Recoverable virus

Both are named as additional diagnostic modalities by Robbins; The source does not provide sensitivity estimates.

Slide 60 · Integrate history, syndrome, and laboratory

Compatible exposure

Clinical syndrome

Serum/CSF IgM

Consider virologic tests

Illustrative diagnostic framework, not an externally validated clinical guideline.

Slide 61 · West Nile and other arboviruses

Shared pattern

West Nile-specific clue from source

Mosquito/arthropod vector

Bird reservoir; Humans incidental

Meningoencephalitis

Risk of spinal-cord polio-like syndrome

Perivascular inflammation

Temporal-lobe/brainstem changes described at autopsy

No single listed feature is presented as pathognomonic.

Slide 62 · West Nile versus HSV-1 encephalitis

West Nile

Arthropod-borne, bird reservoir

WNV can cause spinal paralysis

Microglial nodules / neuronophagia

HSV-1

Distinct viral etiology

Classically necrotizing encephalitis

Temporal-lobe involvement described

Slide 63 · Case 1: Acute febrile illness

Illustrative case — not patient data

A patient develops fever, headache, myalgia, vomiting, and a maculopapular rash after probable mosquito exposure. No new neurologic deficits are described.

Which clinical category is most consistent, and what additional change would suggest neuroinvasion?

Slide 64 · Case 1: Interpretation

The described syndrome is compatible with symptomatic systemic infection.

Rash is supportive context, not an etiologic proof.

Meningeal symptoms or altered cerebral function would shift concern toward CNS disease.

Slide 65 · Case 2: Acute altered consciousness

Illustrative case — not patient data

An older adult with a compatible febrile illness develops confusion and seizures. Cerebrospinal fluid shows elevated protein with normal glucose.

What syndrome is suggested, and which laboratory approach does Robbins emphasize?

Slide 66 · Case 2: Interpretation

Parenchymal neurologic dysfunction raises concern for encephalitis or meningoencephalitis.

Age increases concern for severe West Nile virus disease.

WNV-specific IgM in serum or CSF is the usual diagnostic method described.

Slide 67 · Case 3: Acute paralysis

Illustrative case — not patient data

A patient with suspected arboviral encephalitis develops limb paralysis. The syndrome resembles poliomyelitis clinically.

What anatomic extension of West Nile infection can account for this presentation?

Slide 68 · Case 3: Interpretation

Spinal-cord involvement in West Nile encephalitis can produce polio-like paralysis.

The syndrome is a clinicopathologic correlate of neuroinvasive infection.

Clinical similarity to poliomyelitis does not establish poliovirus etiology.

Slide 69 · Integrated clinicopathologic conclusions

Reservoir birds and mosquito vectors explain usual acquisition.

Skin → lymph nodes → blood → CNS provides the pathogenic sequence.

Neuroinvasive disease is uncommon but may cause death or lasting neurologic injury.

Lymphocytic inflammation, microglial nodules, and neuronophagia support an encephalitic process.

Slide 70 · Textbook sources

Robbins, Cotran & Kumar: Pathologic Basis of Disease. 11th edition (2026). Chapter 8, “West Nile Virus,” p. 318.

Same textbook, Chapter 28, “Viral Meningoencephalitis” and “Arthropod-Borne Viral Encephalitis,” pp. 1150–1151.