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University of Thessaly-Medical Department

University of Thessaly-Medical School
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September 25, 2011 9th HelMedica Issue  Article 6th

Author : Tsintou Magdalini*
Department : Medical School, University of Thessaly
*Editor in Chief, reviewer, webmaster.

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          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.

Image 1: Illustration of the pathologic changes after CNS insult by WNV infection [26].


          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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