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September 25, 2011 9th HelMedica Issue  Article 3rd

HELLENIC CENTRE FOR DISEASE CONTROL AND PREVENTION (KE.EL.P.NO).
Title : GUIDELINES FOR HEALTH PROFESSIONALS, ON THE DIAGNOSIS AND TREATMENT
OF THE WEST NILE VIRUS INFECTION.

  

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

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          Highlights

The virus is spread by an infected mosquito bites and is not transmitted directly from person to person.

More than 80 percent of people who are infected with West Nile virus (WNV) do not exhibit any symptoms and approximately only 20% exhibit a mild self-limited disease resembling flu-like symptoms. Less than 1% of people, who become infected, develop a serious disease that affects the central nervous system (encephalitis / meningitis or acute flaccid paralysis).
There is currently neither a vaccine available for humans, nor a specific treatment for West Nile virus infection.
The diagnosis of human cases is confirmed by the Reference Center for arboviruses and haemorrhagic fever at the Aristotle University of Thessaloniki or the Immunology of Infectious Diseases Unit of the Clinical Microbiology Laboratory, Medical School of Athens University.
The criterion for sending the sample to the reference laboratory is the appearance of encephalitis / meningitis with no determined cause, whereas the WNV-induced encephalitis / meningitis usually occur in elderly people (> 50 years old).
A reporting of the cases with a positive laboratory diagnosis to KE.EL.P.NO is required.

           1. The West Nile virus

          The West Nile virus (WNV) is an RNA virus and it belongs to the flaviviridae family. It is closely related to Japanese encephalitis virus, St. Louis encephalitis and to other similar viruses that cause encephalitis. It was first isolated in the West Nile province of Uganda in 1937, from where it got its name.

 

           2. Epidemiology

           2.1 Outbreaks among animals

           Outbreaks of WNV infection have been reported in many animal species:

           • Wild birds (especially crows and magpies): In the U.S.A., birds exhibit substantial mortality from the infection, and birds’ deaths have been used as early detection systems of the virus circulation in a region. However, in Europe, an increased mortality in birds has not been observed.

           • Horses: horses also exhibit encephalitis resulting in death in approximately 40% of the cases. Horses, like humans, are occasional hosts of the virus and do not transmit the virus.

           • Domestic animals (dogs, cats): become infected the same way that humans become infected through the bite of an infected common mosquito. They are also occasional hosts.

           • Other wild mammals (squirrels, bats, hares, rabbits) are less frequently infected.

           2.2 Outbreaks in humans

           Outbreaks in humans have been reported in Africa, the Middle East, Europe, Australia and Asia. In Israel, human cases are reported each year from summer to autumn.

           In 1999, the virus was first detected in New York and then it was tramsmitted to all of the U.S. states and Canada. Since then, thousands of cases are reported every year in North America, where the disease is considered endemic, whereas, since 1999, 1065 deaths have been recorded.

           In Europe, the first outbreak occurred in 1996 in Romania, while sporadic cases in humans have been recorded in Portugal, Spain, France, Czech Republic and Hungary. Confluence of WNV infections with encephalitis manifestations appear in Europe since 2008, in regions of Italy, Hungary and Romania. In 2010, probable cases have so far been reported by Portugal.

           In Greece, an outbreak of WNV infection was first appeared between summer -Autumn of 2010, focusing on areas of Central Macedonia. However, earlier sero-epidemiological studies (decade of 1980, 2007) have revealed the presence of antibodies against WNV in about 1% of the healthy population from specific areas of Central Macedonia.

 

           3. Primary Transmission Modes

           • The main hosts of the virus are wild birds and mosquitoes. After viremia, lasting 1-4 days, the bird, if survives, acquires immunity.

           • Humans become primarily infected through the common mosquito bite (Culex spp.). Mosquitoes become infected when they feed on infected birds.

           • It is not precisely known how the virus survives the dry periods during the winter months. One of the known mechanisms is the virus survival in infected female Culex mosquitos, which fall into hibernation.

           • The infection of humans, horses and other mammals is not common, and these species do not develop high levels of viraemia. For this reason, the virus does not spread further from them.

           • Aside from the case of a common mosquito bite, WNV transmission from infected animals to humans has not been reported.

 

           4. Other Ways Of Transmission

           Additional ways of WNV transmission have also been described:

           • Transmission through transplanted organs

           • Transmission through transfusion of infected blood (isolated cases)

           • Vertical transmission from mother to fetus (isolated cases)

           • Transmission through breastfeeding (isolated cases)

           • Occupational exposure of microbiology laboratory workers (isolated cases).

 

           5. Clinical picture and Treatment in humans

           5.1 West Nile Virus Infection 

           The majority of people who are infected with West Nile Virus remain asymptomatic. Their rate, according to data provided by epidemics in the Northern Hemisphere, is about 80%.
           Approximately 20% of people who are infected with West Nile Virus exhibit a mild form of the disease, which is usually characterized by the term "West Nile Fever.
           Less than 1% of people who become infected develop serious disease affecting the central nervous system (encephalitis / meningitis or acute flaccid paralysis).
           The incubation time of the disease ranges from 2-14 days, although longer incubation times have been reported in immunocompromised patients.

           5.2 Clinical symptoms and signs of mild infection caused by West Nile Virus

           Fever
           Headache
           Malaise
           Maculopapular rash on the trunk (less often)
           Swollen lymph nodes (less often)
           Retrobulbar pain (less often)

           5.3 West Nile virus Infection with Central Nervous System complications (CNS)

          •  When the CNS is affected, patients may develop symptoms of encephalitis and / or aseptic meningitis, with a clinical picture similar to that caused by other viruses.
          •  Headache is a common symptom of the mild disease and does not constitute a specific finding which implies the CNS involvement.
          •  60-75% of patients who exhibit symptoms from the CNS develop encephalitis or meningoencephalitis, which includes both impaired consciousness and occurrence of focal neurological findings.
          •  25-35% of patients who exhibit symptoms from the CNS develop meningitis without concomitant encephalitis.
          •  Meningitis caused by West Nile Virus manifests with fever, headache and meningism as well as increased leukocytes in the cerebrospinal fluid (CSF). A mild, usually, impaired consciousness may coexist.
          •  West Nile Virus encephalitis is the most serious form of the CNS complication and is manifested by fever, headache, impaired consciousness ranging from lethargy to coma. It may also be accompanied by focal neurological findings such as peripheral or cranial nerves paresis. Tremor, impaired gait and other movement disorders have also been recorded.
          •  Finally, flaccid paralysis (poliomyelitis manifestations) by West Nile Virus has also
been described, but it occurs more rarely than encephalitis and meningitis. This syndrome usually manifests as sudden asymmetric accommodative paresis or paralysis of limbs, without loss of sensation. Pain may precede paralysis in the affected limbs, although the syndrome may occur without an accompanying fever, headache or the other common symptoms of the disease. The involvement of the respiratory muscles may lead to respiratory failure.
          •  Long-term disturbances may persist after recovery from the acute phase (tremor, chronic fatigue, depression).

           5.4. Clinical symptoms and signs of West Nile Virus infection with CNS complications

        Fever
        Gastrointestinal symptoms
        Ataxia and extrapyramidal signs
        Optic neuritis
        Spasms
        Weakness
        Disorders of consciousness
        Myelitis and radiculitis
        Maculopapular rash on the neck, trunk and limbs (rarely)
        Acute flaccid paralysis
        Myocarditis, pancreatitis and hepatitis have also been described

 

           6. Risk factors

           So far, age is the only risk factor associated with the development of CNS complications. The mean age of patients who develop encephalitis ranges between 62-64 years old, whereas the average age of death ranges between 78-80 years old.

 

           7. Laboratory findings in severe disease

        Peripheral leukocytosis, with an increase of lymphocytes
        Hyponatremia, usually in patients with encephalitis
        CSF: white blood cells increase, usually lymphocytosis, elevated proteins, normal values of glucose.
        The CT scan is not helpful in diagnosis, but it may exclude other causes of meningoencephalitis.
        The MRI is usually normal, indicates nonspecific findings in only 25-35% of the patients, such as leptomeningeal enhancement with the intravenous contrast and brain parenchyma signal-intensity changes.

 

           8. Laboratory diagnosis

           • Serological testing for specific IgM and IgG antibodies

in both serum and CSF. The presence of IgM antibodies in the CSF suggests the CNS involvement in the infection, as this group of antibodies does not cross the blood-brain barrier.
Significant increase in specific antibodies titer between serum samples from the acute phase and the remission phase is also diagnostic of an acute infection.
Patients that are likely vaccinated within the immediate preceding period with vaccines against other Flaviviruses (eg yellow fever or Japanese encephalitis) or have become sick by them may exhibit a false positive result due to a cross- reactive immune response.

           Polymerase chain reaction (PCR): is also used to diagnose the infection, but its usefulness in detecting the viral genetic material in the serum is limited by the short period of viraemia.

           Cultivation of the virus: from blood, CSF or autopsy material from the brain or solid organs. It is considered as the test of choice, but it is rarely positive. Autopsy material may also be examined by immunohistochemistry techniques.

 

           9. Sampling and sample shipment

           The virus diagnosis in Greece is achieved in the following laboratories:

           1) Reference Laboratory for arboviruses and haemorrhagic fever, Aristotle University of Thessaloniki
Address and Contact Person:

Associate Professor Ms. Anna Pappa
A΄ Microbiology Laboratory
School Of Medicine
Aristotle University of Thessaloniki
54124, Thessaloniki
Tel: 2310-999 006, 2310-999 151
Mobile: 6945 708 450

           2) Immunology of Infectious Diseases Unit, Microbiology Laboratory, Medical School - National & Kapodistrian University of Athens.

Address and Contact Person:
Professor Mr. Athanasios Tsakris
Microbiology Laboratory
School Of Medicine
University of Athens
M. Asias 75, 115 27
Athens
Tel.:210-746 2011, 210-746-2133

           The criterion for sending the sample to the reference laboratory is the appearance of encephalitis / meningitis or acute flaccid paralysis without a specified cause, considering that West Nile virus encephalitis / meningitis usually occurs in elderly people (> 50 years old).

           In order to facilitate the diagnosis it is required to send all of the following samples:

          whole blood (with EDTA) - minimum quantity 1 ml
          serum (separated after centrifugation) - minimum quantity 1ml
          CSF (if lumbar puncture is performed) - minimum quantity 0,5 ml

          • The samples are sent to the laboratory after an arrangement.
          • The transport vials must be properly closed with a stopper, so that the material does not leak during the sample transportation.
          • Then the vial is placed in a specific transport container (triple pack) for biological samples.
          • On all the samples a label is placed, where the patient's details, the date of the sample collection and the hospital from which the sample was obtained are recorded.
          • The samples are ALWAYS accompanied by the specific "Accompanying shipping note for a clinical sample" of KE.EL.P.NO—Warning!: not wrapped around the sample.

 

           10. Therapeutic confrontation

          • There is no specific treatment for the WNV infection. Treatment is supportive and there are no specific antiviral drugs or vaccine available.
          • In cases of severe disease, treatment mainly consists in providing supportive care via hospitalization, providing fluids, respiratory support and prevention of secondary infections.
          • Clinical studies on the use of different pharmaceutical agents are ongoing. Interferon α-2β has been used to treat the neurological effects of the disease, with controversial results. This treatment is not approved by the EMA (European Medicines Agency) in Europe, or by the FDA in USA.1
          • A particular attention is recommended for patients with collagen diseases treated with monoclonal antibodies (INFLIXIMAB) for the occurrence of severe WNV neurological manifestations.2

 

           11. Prevention Measures

          • There is currently no vaccine available against WNV for humans.
          • The preventive measures are primarily aimed at obtaining information on personal protection measures against mosquitoes and reducing exposure to mosquitoes. (See KE.EL.P.NO- Guidelines for Protection from Mosquito Bites)

 

           12. Health Professionals’ Protection

           • West Nile virus infection is not transmitted from person to person.
           • However, as always, the use of basic safety precautions is required. More specifically, for the treatment of patients infected with the West Nile virus:

          Hospitalization in specialized centers is not required in order to treat West Nile virus infection. Admission to a general-care ward of a General Hospital is sufficient.
          Isolation of patients (suspected or confirmed cases) with WNV infection is not required, or specific measures to avoid contact other than those recommended for all hospitalized patients are required.
          The need for hospitalization in the intensive care unit (ICU) is clearly dictated by
the clinical picture of the patient. In such a case, a specialized hospital or specific measures for isolation and protection of the nursing staff are not required.
          Even in case of an occupational accident (eg needle stick) there is no transmission risk.
          West Nile virus is destroyed by sunlight, heat and drought conditions. No specific measures are required for the disinfection and sterilization of instruments and medical equipment. Their disinfection and sterilization should be performed according to standard hospital sterilization procedures and according to the manufacturers' instructions.
          The infection risk from handling dead bodies of patients who died from West Nile virus infection is very small. However, the usual precautions when handling dead bodies must be taken.

 

           13. Case reporting to KE.EL.P.NO

           Simultaneously with the clinical sample shipping, the physicians must fill and send to KE.EL.P.NO the specific bulletin of WNV infection declaration (see bulletin of WNV infection declaration). It will be faxed to:

Department of Epidemiological Surveillance and Intervention of the Hellenic Center for Disease Control and Prevention (KE.EL.P.NO).
Tel: 210.8899.000, Fax: 210.8818868, 210.8842.011
For further information, see guidelines for diagnosis, sample shipping and case reporting.

 

 

Further Information
1. ECDC, Health Topics, West Nile:
http://www.ecdc.europa.eu/en/healthtopics/Pages/West_Nile_Fever.aspx 
2. CDC – USA: http://www.cdc.gov/ncidod/dvbid/westnile/index.htm

         

 

 

 

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