West Nile virus is an acute infectious viral disease with predominantly transmissible human infection. Specific symptoms are damage to the central nervous system, blood vessels, and mucous membranes. Characterized by cephalgia, prolonged fever with terrific chills, severe muscle pain, arthralgia. Diagnosis involves the detection of the pathogen and antibodies to it in the blood and liquor of the patient. Specific etiotropic treatment has not been developed, symptomatic therapy is being carried out (antipyretics, infusion, oral detoxification, vasoprotectors, etc.).
A92.3 West Nile virus
West Nile virus is a pathology with a frequent asymptomatic course and inflammatory lesion of the membranes of the brain. Less often accompanied by meningoencephalitis. The discovery of the virus and the description of the disease date back to 1937, were the result of a study in Uganda. The seasonality of the disease is due to the time of hatching of vectors (mosquitoes and ticks), which falls at the end of July – October. There are no gender features. There is a tendency to greater susceptibility in children in endemic areas (Northeast Africa, Asia, Israel, Egypt), in adults – in areas with low prevalence (southern regions of Russia, Ukraine, Europe, USA).
The causative agent is an RNA-containing flavivirus of the same name. There are 7 types of virus, the first genotype is the most common. The sources and reservoirs of infection in nature are birds (ravens, passerines), less often mammals (rodents, ungulates). Carriers of the pathogen are blood-sucking mosquitoes of the genus Culex, Aedes, Ixodes and Argass mites. In the body of the carrier (usually a mosquito), the virus affects the nervous system and salivary glands, therefore, when bitten, it is transmitted along with saliva. Much less common is the hemocontact pathway of fever transmission associated with transfusion of infected blood, organ transplantation of an infected donor, work with virus culture in research laboratories, breastfeeding, joint use of non-sterile syringes for intravenous drug administration, butchering of carcasses of deceased animals.
The risk group for the disease (especially the development of meningitis) includes patients with deletion in the CCR5 gene, persons over 60 years old, patients with diabetes mellitus, hypertension, chronic viral hepatitis C, renal, cardiovascular pathology, HIV infection, undergoing chemotherapy for malignant neoplasms, alcohol abusers, recipients of donor organs. Potentially susceptible to infection professions include medical workers, laboratory technicians, veterinarians, slaughterhouse employees, rangers, farmers. The pathogen dies during boiling, exposure to conventional doses of disinfectants.
After the virus enters the body during a mosquito bite, the pathogen infects the dendritic skin cells, getting into the lymph nodes with them. With subsequent viremia, the flavivirus spreads into parenchymal organs (including the kidneys and spleen). After 6 days from the moment of infection, the infectious agent disappears from the peripheral blood and axonally penetrates through the blood-brain barrier into the nervous tissue of the brain. This phenomenon is not always observed, with the normal state of the immune system, viremia is stopped without damage to the central nervous system. The pathogen infects neurons, triggering the processes of apoptosis, resulting in the formation of necrosis sites. Reproduction and accumulation of the virus occurs mainly in the hippocampus, the trunk and cerebellum, the anterior horns of the motor neurons of the spinal cord.
It was found that mutations of the CCR5 gene of CD8+ lymphocytes lead to delayed migration of leukocytes to the affected areas of the central nervous system, since their directional movement is regulated by this chemokine receptor. In neurons devoid of interferon-alpha and beta receptors (antiviral protection proteins), apoptosis is triggered almost immediately after intracranial penetration of the virus. These factors in experiments on mice led to an increased probability of death. The virus shows a tropicity to the vascular endothelium, can persist in the body for 1-2 months or more.
Clinical systematization implies division into groups, taking into account the presence of certain manifestations of fever. There may be a three-wave course of the disease with a consistent predominance of brain and heart damage, inflammatory phenomena in the respiratory tract. It is believed that neuroinvasive forms account for up to 50% of clinically pronounced cases of infection. Of practical importance, taking into account the need for therapeutic measures, is the classification, which includes two forms:
- Asymptomatic. According to WHO, in 80% of cases, pathology proceeds without any manifestations, can only be detected retrospectively in the presence of antibodies to a certain strain of the pathogen.
- Manifest. It is divided into West Nile virus with the involvement of the Central nervous system (meningitis, meningoencephalitis) and a flu-like form. Among immunocompetent individuals, the latter prevails. Neuroinvasive symptoms may include chorioretinitis, occlusive vasculitis, and ocular neuritis.
West Nile virus symptoms
The incubation period is usually 3-16 days, but can be extended to 60-90 days. The disease begins acutely with a sharp rise in body temperature to 38.5 ° C or more, chills, aching muscles and joints, severe headache, localized mainly in the forehead, decreased appetite, pain in the left half of the chest, a feeling of “fading” of the heart. There is a tickling, dry throat, less often – nasal congestion and dry cough. In 5% of cases, a rash appears on the skin in the form of spots and bumps, the skin and mucous membranes become hyperemic. Patients complain of pain when moving in large joints, constipation, sometimes diarrheal syndrome, nausea and vomiting, diffuse abdominal pain.
The neuroinvasive form of fever is characterized by an increase in temperature and headache, gushing vomiting at the peak of pain, which does not bring relief, worsening disorders of consciousness, increased drowsiness or, conversely, agitation, photo- and phonophobia, convulsions, difficulty in contact with the patient, progressive muscle weakness (to the complete absence of voluntary movements with preserved sensitivity), choking on liquid food, asymmetry of the eye slits, double vision. Rash and catarrhal phenomena in this form are almost always absent.
The most common causes of complications are comorbid pathology and later seeking medical help. The main threatening conditions developing with fever are swelling and swelling of the brain, cerebral hemorrhages, acute cardiovascular insufficiency, hypostatic pneumonia and other secondary bacterial purulent complications. Active replication of the virus in the brain stem can lead to acute respiratory failure, cardiac arrest, uncontrolled hyperpyrexia. After the disease, ataxic phenomena may occur.
Consultation of an infectious disease specialist is required. In the presence of symptoms of central nervous system damage, a neurologist’s examination is indicated, with rashes – a dermatovenerologist. An essential role in the diagnosis is played by the collection of an epidemiological history with mandatory clarification of episodes of visits to endemic areas. Methods of laboratory and instrumental diagnosis of this fever include:
- Objective inspection. Hyperemia of the skin, rash, injection of sclera vessels, enlargement of lymph nodes, liver and spleen, granularity of the pharynx are physically determined. There may be a decrease in visual acuity, arterial hypotension, deafness of heart tones, meningeal symptoms (rigidity of the occipital muscles, symptoms of Kernig, Brudzinsky), scattered neurological symptoms (decreased tendon reflexes, horizontal nystagmus, proboscis reflex, etc.). In the presence of focal symptoms and signs of irritation of the meninges, a lumbar puncture is indicated with a macroscopic assessment of the transparency, color of the cerebrospinal fluid, and the rate of its leakage.
- Laboratory tests. In about 30% of cases, leukopenia is detected in the blood test, less often lymphopenia, thrombocytopenia. Biochemical parameters usually correspond to the norm, there may be a slight increase in the activity of AST, ALT, creatinine, urea. When examining the cerebrospinal fluid, the cerebrospinal fluid is transparent, colorless, marked lymphocytic pleocytosis, a slight increase in protein content. The level of glucose, chlorides remains within the normal range. There are no specific changes in the urine analysis, with prolonged fever, trace amounts of protein may be found.
- Identification of infectious agents. Isolation of the virus from the blood by PCR is possible as early as 4-9 days from the onset of the disease. In the cerebrospinal fluid, antibodies to pathogen antigens are determined using ELISA. The PCR method for searching for a virus in the cerebrospinal fluid is used less often due to low sensitivity, high specificity. There is a possibility of PCR-determination of the pathogen in the urine. ELISA for serological diagnosis is significant only when monitoring paired sera on 1-8 and 14-21 days of the disease and a simultaneous study for antibodies to other flaviviruses (in order to avoid cross-reactions). Genome sequencing is used to establish the strain of the virus, immunohistochemical analyses are prescribed for the study of sectional material.
- Radiation methods, ECG, EEG. For differential diagnosis, lung radiography, computer, magnetic resonance imaging of the brain with contrast, and, if necessary, PET-CT are performed. The ECG may show signs of myocardial hypoxia, a decrease in atrioventricular conduction. During EEG in 50-80% of cases, there is a decrease in the activity of the affected areas of the brain. Ultrasound of the abdominal cavity allows you to determine the increase in the size of the spleen, liver; examination of lymph nodes, thyroid gland, retroperitoneal space and pelvis is mandatory.
Differential diagnosis is carried out with a wide range of diseases:
- common infections: listeriosis, ARVI, influenza, tuberculosis, leptospirosis, ornithosis, herpes infection, enterovirus infection;
- other hemorrhagic fevers (yellow, Lassa, Ebola, chikungunya, Marburg, Rift Valley, Crimean, HFRS),
- brain damage: tick-borne encephalitis, cerebral toxoplasmosis, HIV encephalitis, meningococcal infection, acute lymphocytic choriomeningitis, Japanese encephalitis;
- prion diseases.
Possible causes of such a symptom complex can be oncological diseases of the blood, the debut of diffuse connective tissue diseases, thyrotoxicosis, head injuries, hemorrhagic strokes, cerebral infarctions, malignant neoplasms of the central nervous system.
West Nile virus treatment
Hospitalization is indicated for all patients with suspected of this disease. With the progression of neurological symptoms, treatment is carried out in the intensive care unit or in the intensive care unit. Strict bed rest is necessary until the steady disappearance of fever within 3-4 days, relief of acute neurological symptoms and the possibility of independent movement within the ward. The diet has not been developed, it is recommended to eat light nutritious meals, take a sufficient amount of liquid. With the threat of brain edema, the water regime is limited and carefully monitored.
There is no specific method of treating fever. In some studies, the use of alpha-interferon preparations, virus neutralizing monoclonal antibodies, has proven itself well. Ribavirin is not recommended for the treatment of infection, because during the outbreak in Israel, it was found that the mortality of patients with CNS damage in the group of people receiving ribavirin was higher than among the rest. Symptomatic therapy is prescribed. Antipyretics (paracetamol, celecoxib), vasoprotectors (rutoside), sedatives (barbiturates, diazepam), diuretics (furosemide) are used, infusion detoxification (glucose-salt, succinate-containing solutions) is carried out.
Prognosis and prevention
Timely treatment and treatment reduces the risks of complications and promotes full recovery within 10 days. In the presence of neurological lesions, the period of convalescence increases to 30 days or more. Mortality in neuroinvasive West Nile virus reaches 20%, usually associated with paralysis of the respiratory muscles. Long-term (over 1 year) depressive episodes have been described in 33% of patients who have had the disease. The period of preservation of asthenovegetative manifestations on average is 36 weeks, neurological symptoms – more than 8 months.
Specific prophylaxis for humans has not been developed, there is only an effective drug for vaccination of horses. One of the reasons for the lack of a human vaccine is the high variability of the virus; live attenuated and recombinant substances, as well as a DNA vaccine, are currently undergoing clinical trials. Methods of non-specific prevention of the disease include timely detection and isolation of patients, veterinary control over populations of wild birds and domestic animals, mosquito control (pest control, mosquito nets, overalls, repellents).