The death of a child in Kerala’s Malappuram district has drawn attention to the epidemiology of the little-known West Nile Virus in India. Though awareness is low, the virus is endemic to several States. However, official records do not reflect this, given the difficulty of diagnosing WNV in its acute phase. The alert is a welcome move; State health authorities will look harder for the disease.

1. WEST NILE VIRUS: A REVIEW
Dr. Mayank Gupta
Department Of Medicine
SMS Medical College
Jaipur

3. INTRODUCTION
 West Nile (WN) virus is an arthropod-borne
flavivirus, a member of the Japanese encephalitis
virus antigenic complex, transmitted by Culex
mosquitoes
 WNV is a neurotropic human pathogen that is the
causative agent of West Nile fever and
encephalitis
 This RNA virus was first isolated in a blood sample
in a patient from the West Nile province of Uganda
in 1937
 It emerged from obscurity in 1999 when the first
incursion of the virus into North America caused

4. INTRODUCTION
 Naturally maintained in an enzootic cycle between birds
and mosquitoes, with occasional epizootic spillover
causing disease in humans and horses
 WN virus Disease has a self limiting course, sometimes
associated with severe meningitis and encephalitis
 The vast majority of infections are not contagious from
person to person
 The WN virus' incubation period is about 2 to 14 days
after the bite of an infected mosquito
 Mostly asymptomatic; symptoms are seen in only about
20 to 40 percent of infected patients

5. EPIDEMIOLOGY
 Since its initial isolation in Uganda in 1937 through the
present, WNV has become an important cause of human
and animal disease worldwide
 WNV caused infrequent outbreaks typically associated
with mild febrile illnesses from the 1950s through the
1980s in Israel, Egypt, India, France, and South Africa
 The first outbreak of neuroinvasive disease caused by
WNV was reported among the elderly in Israel in 1957
 Since the mid-1990s, outbreaks of WN virus infection
associated with severe neurologic disease began to occur
in North Africa (Algeria [1994, 1997], Tunisia [1997],
Sudan [2002]); Europe (Romania [1996]); Russia (1999);
Israel (2000); North America (United States [1999],
Canada [2002]); and India (2011)

6. EPIDEMIOLOGY
 In the 77 years since its discovery, the virus has propagated to a vast
region of the globe and is now considered the most important causative
agent of viral encephalitis worldwide
 From 1999 to 2015, a total of 43,937 confirmed and probable cases of
WN virus disease, including 20,265 cases of neuroinvasive disease,
were reported to the CDC from 48 states and the District of Columbia
 In United States, the three largest outbreaks occurred in 2002 (2946
cases), 2003 (2866 cases), and 2012 (2873 cases)

8. WEST NILE VIRUS IN INDIA
 The death of a child in Kerala’s Malappuram district has drawn
attention to the epidemiology of the little-known West Nile Virus
in India
 The first sign of its presence came from positive antibody tests
among residents of Bombay in 1952
 Though awareness is low, the virus is endemic to several States
 The first documented WNV case in Kerala was in Alappuzha in
2011, with the numbers then growing
 However, official records do not reflect this, given the difficulty of
diagnosing WNV in its acute phase
 The alert is a welcome move; State health authorities will look
harder for the disease

9. VIRAL GENOME & STRUCTURE
 Genus Flavivirus, family Flaviviridae
 Member of the Japanese encephalitis serocomplex, which
also includes Japanese encephalitis virus, St. Louis
encephalitis virus, Rocio virus, and Murray Valley encephalitis
virus
 WNV has a single stranded positive-polarity icosahedral
envelope RNA genome

10. GENETIC CLASSIFICATION
 Genetically and geographically diverse virus
 Four or five distinct WNV genetic lineages have been proposed
 Lineages 1 and 2- associated with significant outbreaks in humans
 Lineage 1 is distributed widely throughout the world and consists of
three clades: 1a, 1b, 1c
 In 1999; this lineage 1a virus was exported, most likely from the Middle
East, to the Americas, where it spread over North America and then to
South America, making WNV a global public health problem
 Lineage 2 originated in Africa and was introduced into Europe, where it
became endemic
 Clade 1c of lineage 1, includes isolates from India from 1955 to the
present

11. TRANSMISSION OF WNV
WNV may be transmitted to humans via
the following-
 Bite of an infected mosquito
 Maternal-fetal transmission
 Blood product transfusion
 Organ transplantation
 Breast milk
 Occupational percutaneous exposure
 conjunctival exposure
 Unidentified means in a dialysis center

12. TRANSMISSION OF WNV
 Nearly all human infections with WN virus are due to mosquito bites
 Mosquitoes of the genus Culex have been reported as the most important
bridge vectors
 Birds are the primary amplifying hosts, and the virus is maintained in a bird-
mosquito-bird cycle

13. TRANSMISSION OF WNV
VECTOR BORNE
Through mosquito bites:
 Mosquitos transmitting
WNV are usually of the
Culex species, which vary
by geographic area
 The major mosquito vectors
in Africa and the Middle
East are Culex univittatus
and Culex pipiens
molestus, and in Asia,
Culex tritaeniorhynchus
Culex
tritaeniorhynchus

14. PATHOGENESIS
 Following mosquito
bite, virus laden saliva
is inoculated s.c. in the
host and disseminates
in three phases:
 Early phase
(replication in
keratinocytes,
dendritic cells &
Langerhans cells)
 Visceral-organ
dissemination phase
 Central nervous
system (CNS) phase
(invasion of the CNS)

15. WNV NEUROINVASIVE
MECHANISMS

16. RISK FACTORS FOR WNVD
West Nile Fever
 Increasing viral load
 Female gender
WNV Neuroinvasive Disease
 Advancing age
 Malignancy- particularly hematological
malignancies
 Organ transplant recipients
 Genetic factors- CCR5 deficiency increases the
risk of death due to neuroinvasive disease
 Others- Diabetes, hypertension, alcohol abuse,
renal disease, and male gender

17. WNV Human Infection “Iceberg”
 Incubation: 2
to 14 days
 Asymptomatic
(~80%)
 Two forms of
disease-
1. West Nile
fever
2. West Nile
neuroinvasiv
e disease

18. SIGNS AND SYMPTOMS
WEST NILE FEVER
(Mild self limiting illness)
Fever, Headache, Fatigue,
Body Aches, nausea,
vomiting, skin rash
West Nile Encephalitis
/Meningitis
High Fever, Severe
Headache, Stiff Neck,
Disorientation, Stupor, Coma,
Tremors, Convulsions, Muscle
weakness
ASYMPTOMATIC

19. WEST NILE FEVER
 Affects primarily in the late summer or early fall
 However, it can be transmitted year-round in the southern climates
where temperatures are milder
 Self limiting illness, typically last 3 to 10 days
 Abrupt onset of fever, headache, malaise, back pain, myalgias, and
anorexia
 Eye pain, pharyngitis, nausea, vomiting, diarrhea, and abdominal
pain can also occur
 Generalized lymphadenopathy- rare in contemporary outbreaks
 Most people recover completely, but fatigue and weakness can last
for weeks or months
RASH in WN Fever
 ~25 to 50 percent of patients
 Chest, back, and arms
 Morbilliform or maculopapular
 Accompanied by dysesthesia & pruritus
 Lasts for < 1 week
 Associated with a decreased risk of neuroinvasive disease and death

20. WEST NILE VIRUS
NEUROINVASIVE DISEASE
(1%)
 Presents as fever in conjunction with meningitis, encephalitis,
flaccid paralysis, or a mixed pattern of disease
 Encephalitis – Old age; 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
 Meningitis- Children; fever, headache, meningeal signs, and
photophobia
Persistent neurological dysfunction
 Occurs in 70% post encephalitis
 Fatigue, memory impairment, weakness, headache, and
balance problems persisting for years

21. WEST NILE NEUROINVASIVE
DISEASE
Ocular manifestations
 Chorioretinitis, retinal hemorrhages and vitreitis
 Chorioretinal lesions are multifocal with a "target-like"
appearance
Risk factors for death:
 Increasing age
 Male gender
 Encephalitis with severe muscle weakness
 Changes in the level of consciousness
 Diabetes
 Cardiovascular disease
 Hepatitis C virus infection
 Alcoholism
 Immunosuppression

22. RARE COMPLICATIONS OF WNVD
 Rhabdomyolysis
 Fatal hemorrhagic fever with multi-organ
failure and palpable purpura
 Hepatitis and pancreatitis
 Central diabetes insipidus
CONGENITAL INFECTION
 Most women infected with WNV during
pregnancy have delivered infants without
evidence of infection or clinical
abnormalities.

23. DIAGNOSIS OF WNV INFECTION
Based on high index of clinical suspicion and
obtaining specific laboratory tests-
 Consider WNV, or other arboviral diseases
such as Japanese encephalitis, (adults >50
yrs) with unexplained encephalitis or
meningitis (in summer or early fall)
 The local presence of WNV enzootic activity
or other human cases should further raise
suspicion

24. DIAGNOSIS OF WNV
INFECTION
A. Routine Investigations
B. Serology
 Serum or CSF
 IgM capture ELISA (MAC ELISA)- cross
reactivity
 Plaque reduction neutralization test
(PRNT)
C. Detection of virus, antigen, or nucleic
acids
 RT-PCR

25. CSF FINDINGS
 An elevated protein (<150 mg/dL)
 A moderate pleocytosis (<500 cells/microL) with a
predominance of lymphocytes
 However, neutrophils may predominate in early infection
 Cytology: plasmacytoid lymphocytes or large monocytic cells
resembling Mollaret cells
IMAGING
CT/MRI- findings are non differentiating from other viral causes
of neuroinvasive disease
EEG- shows generalized, continuous slowing; prominent in the
frontal or temporal regions

26. IgM capture ELISA (MAC ELISA)
 A positive test in CSF or serum is sufficient to make the
diagnosis in the vast majority
 IgM seroconversion develops between 4-10 days after
viremia
 If initial test is negative & WNV infection is still
suspected- repeat serum MAC-ELISA ~ 10 days later
 A negative convalescent phase serum R/O infection in
immunocompetent patients
 Detectable in serum for at least one to two months
following clinical resolution, but may persist for ≥12
months. Hence, can’t differentiate b/w acute v/s past
infection.

27. PLAQUE REDUCTION
NEUTRALIZATION TEST (PRNT)
PRNT should be performed-
a) If there is concern that the positive
MAC-ELISA is due to cross-reactivity
a) After recent vaccination for Japanese
encephalitis

29. PREVENTION & CONTROL

31. PRECAUTION & PREVENTION
 Human vaccines are unlikely to be available for
at least several years, as no phase three trials
are currently underway
 Individuals in areas with risk for transmission
should take measures including-
-Personal protection
-Environmental control measures
-Blood donor screening

32. MANAGEMENT
 There is no specific antiviral drug treatment for
WNV infection
 Management consists of rest and supportive
treatment including drinking fluids to prevent
dehydration and administration of Paracetamol to
relieve fever and pain
 Agents that have been considered in WN
neuroinvasive disease include:
a) Interferon alfa-2b
b) Ribavirin
c) Intravenous immunoglobulin

33. MANAGEMENT AND PREVENTION OF
INFECTION DURING PREGNANCY
 Pregnant women with meningitis, encephalitis,
acute flaccid paralysis, or unexplained fever in an
area of ongoing WN virus transmission should
have serum tested for antibody to WN virus
 Ultrasound examination of the fetus to screen for
abnormalities should be considered no sooner than
two to four weeks after onset of symptoms

34. CONCLUSION
 WNV, a mosquito-borne arboviral infection, little known
to Indian terrains, has shot to limelight because of the
unexpected death of a 7 year old child from
Malappuram district of Kerala
 Though awareness is low, WNV is endemic to several
states of India
 Untimely death in Kerala has led health authorities to
issue a nation wide advisory alert to watch out for WNV
infection
 Surveillance and preventive measures are an ongoing
need to reduce the public health impact of WNV in
areas with the potential for transmission

35. REFERENCES
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 Gerardi, Michael H., and Melvin C. Zimmerman. Wastewater Pathogens.
John Wiley & Sons, Inc. (US), 2005. eBook Collection (EBSCOhost).
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 Hoyle, Brian. "West Nile." Infectious Diseases: In Context. Ed. Brenda
Wilmoth Lerner and K. Lee Lerner. Vol. 2. Detroit: Gale, 2008. 899-905. Gale
Virtual Reference Library. Web.
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