Abstract.
West Nile virus is a single-stranded RNA virus of the Flaviviridae family
which is maintained in an enzootic cycle between mosquitoes and birds,
whereas humans and other mammals are accidental hosts. The majority of human
infections (80%) are asymptomatic while 20% exhibit clinical disease which
may be manifested by mild febrile condition to severe neurological disease.
Since there are no vaccines or effective medication, the precautionary
measures are particularly important.
1. Epidemiology.
The epidemiology of West Nile virus
(WNV) is continuously changing. It was first isolated in Uganda in 1937 [1].
From there, the virus was spread to Africa and areas of the Middle East [2].
In the 50's, the virus was found in Israel, in the 60's in France and since
the mid 1990's many epidemics occurred in Europe. In August of 1999, 62
patients with meningoencephalitis in New York signaled the entry of the
virus in North America [3]. Currently, the geographical distribution of the
virus extends from Canada to South America [4], Caribbean, Europe, Africa
and Asia.
The virus is amplified in birds from
which different mosquito species, but mainly the Culex species, may become
infected and transmit the virus to humans through bites. Human is considered
a "dead end" host in this cycle since the viral burden which is developed is
insufficient to infect a mosquito. Transmission of the virus to humans in
other ways, through blood transfusion, transplantation, intrauterine
transmission and breastfeeding, has been reported [5,6,7,8].
The peak incidence of infection
occurs during the months of August and September. Most vulnerable are
elderly people undergoing the seventh or eighth decade of their life and
with a male / female ratio, 3 / 1 [9].
2.
Pathogenesis.
Given the large number of
asymptomatic or subclinical infections and the relatively small number of
the laboratory confirmed infections, our knowledge on the pathogenesis of
the virus mainly comes from animal models.
A WNV-infected mosquito transmits
the virus through bites and WNV is deposited in the skin tissues and the
blood. A few days later, the virus is amplified in the skin tissues and
moves to the regional lymph nodes [10], causing a low-level viremia that
typically wanes with the production of specific antibodies [11]. After this
initial reproduction phase which is transient, a second viraemia phase is
presented with central nervous system (CNS) insult [12].
The virus entry in the CNS can occur
without disruption of the blood-brain barrier (BBB) [13]. The high viremia,
however, may lead to brain infection by both capillary leakage and increased
permeability of the BBB [14]. However, neither the increased permeability of
BBB in infected Hamsters indicates an increased mortality nor the fatal
infection requires increased BBB permeability in all mice strains [15].
In low viremia cases, where the
disruption of the BBB is unlikely, the virus can enter the CNS via infected
peripheral nerves [16]. In any case, the exact mechanism of the brain insult
requires further investigation.
3. Clinical picture.
The incubation period of the virus
varies from 2 to 15 days [17]. The symptomatic infections – i.e. 20% of
infected individuals - exhibit a febrile illness with fatigue, myalgias,
nausea, vomiting and abdominal pain [18,19]. The duration of the disease is
generally less than 7 days.
Approximately 5% of symptomatic
patients will develop neurological disease. Symptoms include rapid onset of
headache, photophobia, altered consciousness, focal weakness and continued
fever [20,21].
Headache, fever, myalgias, back
pain, photophobia at a rate of 20-25% and a stiff neck, suggest aseptic
meningitis [22]. It preferably occurs in younger patients and usually
resolves without consequences. Brain insult as well (meningoencephalitis) is
manifested by irritability, confusion, disorientation, tremor, ataxia, focal
weakness and hyperreflexia unless myelitis coexists when there is a loss of
reflexes [9,22].
In about one half of patients with
WNV CNS infection, focal weakness, often asymmetrical and rapidly evolving
is developed [23,24]. Clinically, it consists of flaccid quadriparesis,
asymmetrical paraparesis, or monoparesis. If the focal weakness occurs
outside of meningoencephalitis context, it may cause diagnostic confusion.
Respiratory muscles weakness may require prolonged mechanical ventilation
[9].
4.
Diagnosis.
In endemic areas of the disease,
febrile patients with headache, myalgias or other signs of CNS infection
should be investigated for possible WNV infection.
The peripheral blood image is
usually normal although lymphopenia may be observed [25]. Many patients
develop hyponatremia [22]. On CNS infection (image 1), in the cerebrospinal
fluid (CSF) elevated proteins and elevated numbers of white blood cells
(median 171 cells / ml) are observed, which first present
polymorphonuclearic and then lymphocytic type.
The serological tests provide
definite diagnosis either by isolating the virus itself or by detecting
specific IgM antibodies in CSF or serum samples.
In brain MRI, abnormalities appear
in the meninges whereas in the brain the basal ganglia, the thalami, the
brainstem and the ventral horns are most commonly affected.
5.
Conclusion.
Given that a significant proportion
of patients with WNV infection will develop severe neurological disease,
information and awareness of the medical community is required for the early
diagnosis of the disease. Due to lack, to date, of targeted effective
therapies, prevention remains vital.
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