Serous meningitis. Serous lymphocytic choriomeningitis - Armstrong's disease. Lymphocytic choriomeningitis Cultivation and reproduction

Lymphocytic choriomeningitis(CHM) is a viral infection transmitted to humans from rodents and accompanied by primary damage to the meninges and choroid plexuses of the central nervous system.

It was identified as an independent nosological unit by Armstrong (S. Armstrong) and Lillie (R. D. Lillie) in 1933. In the structure of pathogens of neuroinfections, it accounts for about 10% [E. P. Dekonenko et al., 1986].

Etiology. The causative agent of LCM belongs to the arenavirus family (Arenaviridae). The spherical virions have a diameter from 110 to 130 nm, and are surrounded on the outside by closely adjacent villi 10 nm long. Inside the virions there are ribosome-like formations with a diameter of 20-25 nm, numbering from 10 to 16. The virus is sensitive to the action of detergents, ether, merthiolate, low pH values ​​and divalent cations. Virions contain single-stranded RNA consisting of two components. Virions contain three major proteins. The virus reproduces in most cell cultures tested, in chicken embryos, and macrophage cultures. Has a cytopathic effect.

Epidemiology. The main reservoir of the virus is gray house mice, which excrete the pathogen in nasal mucus, urine and feces. Human infection usually occurs due to consumption of food contaminated by mice. Infection through the respiratory tract and also transplacentally is possible. The disease is often sporadic, but epidemic outbreaks have also been described. The highest incidence occurs in the cold season, although isolated cases are also recorded in the summer. The FCM virus is distributed almost everywhere.

Pathogenesis. Once a virus enters the human body, it spreads hematogenously, penetrating the blood-brain barrier. The virus causes an inflammatory process in the membranes with exudation of lymphoid elements, as a result of which mainly lymphocytes appear in the cerebrospinal fluid. The inflammatory reaction of the membranes leads to increased production of cerebrospinal fluid, which, in turn, causes an increase in intracranial pressure and a number of symptoms associated with it. In some fatal cases, inflammatory phenomena were observed in the membrane, in the ependyma and choroid plexuses of the brain, characterized by lymphocytic infiltration. The changes are especially pronounced at the base of the brain. The vessels of the medulla, cortex and trunk, especially the bulbar region, are hyperemic to the point of stasis, the perivascular spaces are dilated; cellular elements are in a state of tirolysis. Inflammatory phenomena are also detected in the lungs, liver and kidneys.

It has been proven that reassortants of various strains of the virus, as a result of infection of newborn mice with them, cause the development of a slowly progressive disease characterized by growth retardation and death of animals, while parental strains and reciprocal reassortants do not cause such diseases. It is possible that the features of the pathogenesis of this disease are associated with the induction of interferon with a simultaneous pronounced increase in virus titers and subsequent liver necrosis.

In case of intrauterine infection of the fetus with the LCM virus, the pathogenesis of the slow form of the infectious process has not yet been sufficiently studied. It is only known that in this case the disease is characterized by meningoencephalitis, ependymatitis, plexitis, fusion of the meninges, fusion of the liquor ducts (hydrocephalus), pronounced lymphocellular infiltration and exceptionally high titers of antiviral antibodies in the cerebrospinal fluid, which may indicate the possibility of antibody synthesis in the central nervous system. Sometimes there is a picture of a slowly progressing proliferative process in the area of ​​the choroid plexus, subependyma, along the Sylvian aqueduct. In all cases, phenomena of encephalovasculitis and perivascular round cell infiltrates, as well as degenerative changes, are detected.

Symptoms and course. The disease can present with varying degrees of severity, ranging from asymptomatic to rare cases of systemic disease that can be fatal.

In the acute form of LCM, the incubation period ranges from 6 to 13 days. A prodromal period is possible (weakness, weakness, catarrh of the upper respiratory tract), after which the body temperature suddenly rises to 39-40°C, and within a few hours a pronounced meningeal syndrome develops with severe headaches, repeated vomiting and often confusion. The pulse and breathing are increased, but as neurological symptoms develop, tachycardia gives way to bradycardia. Among the neurological disorders, the most common are meningeal signs in the form of Kernig and Brudzinski symptoms, as well as stiff neck. The duration of existence of meningeal signs is on average 14 days. Objectively, mild disturbances of cranial innervation, mainly oculomotor, are also noted: sluggish reaction of the pupils to light, horizontal nystagmus, insufficiency of the abducens nerves, exophthalmos, weakness of convergence. Possible mildly expressed paresis of the facial nerve of the central type, mild cerebellar disorders in the form of unsteadiness of gait, instability in the Romberg position, and intention tremor. These deviations are temporary and usually smooth out after 3-4 weeks. Pathological reflexes (Babinsky, Rossolimo, Gordon, Oppenheim, etc.) can be expressed with varying intensity; they sometimes appear together, sometimes in isolation. Changes in the fundus (congestive atrophic pale nipple) are very characteristic. Swelling of the optic nerves appears already in the first days of the disease, but as recovery progresses, there is a tendency for congestion in the fundus to reverse.

Stagnant changes in the fundus indicate acute hypersecretory dropsy of the brain. In the first days of the disease, transient paresis of the eye and facial muscles is often observed.

Leukopenia is usually detected in the blood, although we cannot exclude slight leukocytosis and an increase in ESR. The cerebrospinal fluid is clear, the pressure is significantly increased. In the first days of the disease, pleocytosis is often observed within several hundred cells in 1 μl, usually mixed (70% lymphocytes, 30% neutrophils), later lymphocytic. The protein, sugar, and chloride content of the cerebrospinal fluid usually remains normal, although a slight increase in protein content and a decrease in sugar levels may occur.

Electrophysiological studies (electro-, echoencephalography) indicate mild diffuse changes in bioelectrical activity involving the midline formations of the brain and hypertensive-hydrocephalic phenomena. In some cases, “finger impressions” may be noted on radiographs of the skull.

The course of meningitis is usually favorable. Improvement in the condition and sanitization of the cerebrospinal fluid is observed in the 3-4th week. The average duration of inpatient treatment is 30-35 days. By discharge, residual asthenovegetative effects may persist.

Detailed clinical and virological studies of patients with LCM conducted by A. G. Panov, A. I. Shvarev and P. I. Remezov showed that influenza-like forms, syndromes of encephalitis, encephalomyelitis, polyradiculoneuritis and visceral manifestations of infection are not uncommon. The visceral and influenza-like phase of infection preceding the development of meningitis is very characteristic. The temperature curve has a two-wave character; the onset of the second wave coincides with the appearance of meningeal symptoms.

The slow form of LCM is also characterized by an acute onset, high fever, and the development of meningeal syndrome. Following the development of the acute stage of the disease, a visible improvement may occur with increasingly pronounced weakness, dizziness, the development of ataxia, and fatigue. This is accompanied by headaches, weakening of memory, mental depression, and changes in character. Signs of damage to the cranial nerves appear. Sometimes such a disease lasts several (up to 10) years, is accompanied by the development of paresis and paralysis of the limbs and ends in death.

In congenital LCM, the slowly progressive process is characterized by hydrocephalus, which can be detected already at birth, although in about half of cases hydrocephalus develops in the 1st to 9th week after birth. At the height of the development of the disease, children react little to the environment, almost do not come into contact, lie in a forced position with their arms brought to the body with clenched fists, legs extended and crossed. Sometimes, in the absence of obvious signs of hydrocephalus, signs of chorioretinitis or cerebral palsy may be observed, but in such cases latent internal hydrocephalus may be observed. In rare cases, microcephaly occurs. In approximately 80%, hydrocephalus syndrome is combined with chorioretinitis. Death can occur in the 2-3rd year of life.

Complications in acute forms of LCM, as a rule, are not observed.

Diagnosis and differential diagnosis. Clinically, the diagnosis of LCM is established on the basis of the following characteristic signs: acute onset of the disease with fever (more than 1/3 of patients have a two-wave fever), headache, vomiting, as well as moderate inflammation in the upper respiratory tract, meningeal signs, lymphocytic character pleocytosis in the cerebrospinal fluid, a slight increase in protein content and a decrease in sugar levels (with meningeal forms), often congestion in the fundus, a benign course of the disease and, as a rule, the absence of residual effects. Etiological diagnosis is carried out by isolating the virus, as well as detecting antibodies to it in neutralization reactions and complement fixation.

Specific therapy for viral serous meningitis is aimed directly at the virion, which is in the stage of active reproduction and lacks a protective shell.

The principles of therapy for serous meningitis, aimed at preventing or limiting the formation of irreversible cerebral disorders, are as follows: protective regimen, use of etiotropic drugs, reducing intracranial pressure, improving blood supply to the brain, normalizing brain metabolism.

Patients with meningitis should be on bed rest until complete recovery (until the cerebrospinal fluid is completely normalized), despite normal body temperature and the disappearance of pathological symptoms. Tiloron (a drug that has a direct antiviral effect on DNA and RNA viruses, 0.06-0.125 g once a day for 5 days, then every other day for up to 14 days), and recombinant interferons are used as etiotropic therapy. In severe cases, when vital functions are threatened, immunoglobulins are prescribed intravenously.

It is advisable to use antibiotics for serous viral meningitis only if bacterial complications develop. In the complex treatment of viral meningitis, a protective regime for 3-5 weeks is required. If necessary, detoxification and symptomatic therapy is prescribed. For intracranial hypertension (increased cerebrospinal fluid pressure >15 mm Hg), dehydration (furosemide, glycerol, acetazolamide) is used.

A unloading lumbar puncture is performed with slow removal of 5-8 ml of cerebrospinal fluid. In severe cases (complications of meningitis or encephalitis with cerebral edema), mannitol is used. The use of sodium polydihydroxyphenylene thiosulfonate (0.25 g 3 times a day for 2-4 weeks), an antioxidant and antihypoxant of the third generation, is highly effective. Due to the fact that sodium polydihydroxyphenylene thiosulfonate also stimulates the antiviral activity of monocytes and inhibits the process of primary fixation of the virus on the cell membrane, its early and combined use with antiviral drugs (tilorone) contributes not only to the rapid relief of inflammatory changes in the cerebrospinal fluid, but also prevents the formation of residual manifestations.

It is mandatory for serous meningitis to use drugs that improve neurometabolism: nootropics [pyritinol, gamma-hydroxybutyric acid (calcium salt), choline alfoscerate, hopantenic acid, etc.] in combination with vitamins. In the acute period, intravenous administration of ethylmethylhydroxypyridine succinate 0.2 ml/kg per day for children and 4-6 ml/day for adults is possible.

In the presence of focal symptoms, among neurometabolic drugs, preference should be given to the central cholinomimetic choline alfoscerate (prescribed at a dose of 1 ml/5 kg of body weight intravenously, 5-7 infusions, then orally at a dose of 50 mg/kg per day for up to 1 month).

After an acute period of serous meningitis or in the presence of residual manifestations, a course of treatment with polypeptides of the cerebral cortex of cattle is carried out at a dose of 10 mg/day intramuscularly, 10-20 injections 2 times a year, etc.

Inflammation of the pia mater of a serous nature, which can be caused by viruses (most often), bacteria, fungi, systemic diseases, tumors, cerebral cysts. In most cases, the disease is acute with fever, headache, meningeal symptom complex, and sometimes with damage to the cranial nerves. Diagnosis is based on epidemiological data, the results of a neurological examination, cerebrospinal fluid analysis, bacteriological and virological studies, EEG, and MRI of the brain. Therapy includes etiotropic treatment, dehydration, detoxification, antibiotic therapy, antipyretic, anticonvulsant, and neurometabolic drugs.

General information

Diagnosis of serous meningitis

Based on the characteristic clinical picture and the presence of a meningeal symptom complex (typical posture, rigidity of the posterior cervical muscles, positive Kerneg's symptoms, lower and upper Brudzinski's symptoms, in infants - Lesage's symptom), not only a neurologist, but also a local therapist or pediatrician can assume the presence of meningitis. A thorough study of the medical history (identifying contacts with sick individuals, determining the duration of the incubation period, the nature of the onset of the disease, etc.) and conducting additional examination methods are necessary to establish the type and etiology of meningitis.

Serous meningitis is accompanied by typical inflammatory changes in a clinical blood test, but usually the rise in ESR and leukocytosis are less pronounced than with purulent meningitis. To isolate the pathogen, bacterial culture of swabs from the throat and nose is carried out, and virological studies are carried out using PCR, RIF, and ELISA methods. In patients with immunodeficiency, immunological studies aimed at verifying the pathogen are not very informative, since they can give false results.

Serous meningitis can be confirmed by examining the cerebrospinal fluid. Serous inflammation of the soft cerebral membrane is characterized by slightly opalescent or transparent cerebrospinal fluid with a slightly increased protein content. Tuberculous and fungal meningitis are accompanied by a decrease in glucose levels. Cerebrospinal fluid leaks under increased pressure. In the first few days, neutrophilic leukocytosis may be observed, which resembles the picture of bacterial meningitis. Then lymphocytes begin to predominate in the cerebrospinal fluid, which is more typical for viral meningitis. Therefore, lumbar puncture must be repeated and the data from the study of cerebrospinal fluid must be compared at different periods of the disease.

With tuberculous and syphilistic etiology of meningitis, pathogens can be identified by microscopy of cerebrospinal fluid after special staining of smears. If serous meningitis is of viral origin, then the pathogen is not detected. If necessary, the following examinations may be additionally prescribed:

For the purpose of detoxification, infusion therapy is carried out, and to combat liquor-hypertensive syndrome - dehydration (administration of diuretics: furosemide, acetazolamide). For febrility, antipyretics are prescribed (ibuprofen, paracetamol), for convulsive syndrome - detomidine, diazepam, valproic acid. At the same time, neuroprotective and neurotropic therapy is carried out - nootropics are prescribed (gamma-aminobutyric acid, piracetam, glycine), B vitamins, pig brain hydrolyzate, etc.

Forecast and prevention of serous meningitis

In the vast majority of cases, with correct and timely treatment, serous meningitis has a favorable outcome. Usually the temperature begins to subside already on the 3-4th day; a repeated wave of febrility is rarely observed. On average, serous meningitis lasts about 10 days, with a maximum of 2 weeks. As a rule, it passes without leaving any consequences. In some cases, after meningitis, liquor-hypertension syndrome, frequent cephalgia, asthenia, emotional instability, memory impairment, and difficulty concentrating may persist. However, these residual effects disappear within a few weeks or months. Tuberculous meningitis has a serious prognosis; without the use of anti-tuberculosis pharmaceuticals, it leads to death on the 23-25th day of illness. With a late start of anti-tuberculosis treatment, the prognosis is serious - relapses and complications are possible.

The best prevention of meningitis of any etiology is a strong immune system, i.e. healthy diet, active lifestyle, hardening, etc. Preventive measures should also include timely treatment of acute infections, isolation of sick people, vaccination against tuberculosis, drinking only purified or boiled water, thoroughly wash vegetables and fruits, maintain personal hygiene.

In 1934, Armstrong, while studying St. Louis encephalitis, isolated a new virus that caused serous inflammation of the soft meninges and choroid plexuses in experimental animals and was accompanied by lymphocytic pleocytosis. Based on the main symptoms of the disease caused by this virus, the authors named it "lymphocytic choriomeningitis". Due to the fact that the etiology of many meningitis was not yet known at that time, all serous meningitis for a long time was associated with the lymphocytic choriomeningitis virus, which, according to A. G. Panov, introduced great confusion into the diagnosis of meningitis and complicated clinical study these diseases.

Isolation of causative agents of other meningitis and especially enteroviral ones showed that the lymphocytic choriomeningitis virus is not only not the only, but not even the most common causative agent of serous meningitis. Thus, according to A.I. Shvarev, in St. Petersburg over 10 years, diseases caused by this virus accounted for only 5% of all serous meningitis.

Epidemiology

The lymphocytic choriomeningitis virus is widespread and occurs in countries with different climates. In Russia, diseases of lymphocytic choriomeningitis have been described in a number of cities where laboratory diagnosis of this infection is used - in Kharkov, Moscow, St. Petersburg, Voronezh, Tomsk and many others. The disease is usually sporadic. Small outbreaks are occasionally observed. Lymphocytic choriomeningitis can occur at any time of the year, but is more common in winter. Adults are most often affected; children are rarely affected.

The main source of infection for humans are gray house mice, which infect each other and excrete the virus in urine, nasal mucus, and seminal fluid. Various methods of transmission of infection are possible - droplet, nutritional, transmission through the bite of arthropods. Etiological diagnosis is based on the isolation of the virus from the cerebrospinal fluid or blood in the early stages of the disease and on neutralization and complement fixation reactions. The latter method, according to A.I. Shvarev, plays the most important role in the diagnosis of lymphocytic choriomeningitis.

Pathomorphology

Pathomorphologically, lymphocytic choriomeningitis is characterized by a significant participation in the inflammatory process of the choroid plexuses, which, like the meninges, are edematous, hyperemic, with widespread lymphoid infiltration. The same lymphoid infiltration is found in the ependyma and subependymal layer of the ventricles of the brain, in which large amounts of fluid accumulate. The subarachnoid spaces are also filled with serous fluid. Lymphocytic choriomeningitis is a common infectious disease with a polymorphic clinical picture, in which lesions of the nervous system do not always play a leading role. The disease most often occurs acutely and ends after 1-2 months with complete recovery, but in some cases relapses and a chronic course are noted. The cause of the chronic course is not clear and, apparently, is associated with the properties of the pathogen and the reactivity of the macroorganism.

Most authors distinguish two phases during lymphocytic meningitis: influenza-like and meningeal. A.I. Shvarev believes that it is more correct to call the flu-like phase visceral. The presence of this phase shows that lesions of the nervous system in lymphocytic choriomeningitis cannot be considered primary. The influenza-like phase is characterized by fever, catarrh of the upper respiratory tract; Sometimes joint pain, abdominal pain, and gastrointestinal disorders are observed. In some cases, the disease may end in the first phase, but in most patients, after a few days, the second phase begins - the meningeal phase, characterized by a new rise in temperature, severe headache, vomiting and the appearance of meningeal symptoms. Meningeal syndrome in lymphocytic choriomeningitis is expressed much more sharply than in enteroviral meningitis, and the course of the disease resembles severe forms of mumps meningitis. The cerebrospinal fluid is inflammatoryly altered: lymphocytic cytosis is high and ranges from several hundred to 1-2 thousand or more formed elements per 1 mm 3; the protein content is normal or slightly increased.

With lymphocytic choriomeningitis, in addition to meningeal, other forms of damage to the nervous system are noted. Milser distinguished three clinical forms of this disease: influenza-like, meningeal and encephalomyelitis. Armstrong identified a fourth - asymptomatic form. A. G. Shvarev classifies the clinical forms of lymphocytic choriomeningitis based on the predominant syndrome, and distinguishes between meningeal, encephalitic, hypertensive-hydrocephalic, myelitic and radicular forms. In addition, the author identifies more erased and asymptomatic forms of the disease.

Clinical characteristics

The clinical symptom complex of lymphocytic choriomeningitis in most cases consists of the predominance of meningeal symptoms over all others. But along with this form of the disease, there are cases with a pronounced encephalitic component, occurring as meningoencephalitis. Rivers identifies the following clinical forms of lymphocytic choriomeningitis: aseptic meningitis, influenza-like form, meningo-encephalomyelitis and general acute febrile disease with a fatal outcome. Lymphocytic choriomeningitis can occur without clinical manifestations. However, the most common in the clinic are meningeal and influenza-like forms.

We observed in children, in addition to meningeal and encephalitic forms, mild spinal monoparesis and neuritis of the facial nerves caused by the lymphocytic choriomeningitis virus. Here are some examples.

Patient S., 10 years old, fell ill on January 20, 2008, the temperature rose to 39°, headache, vomiting, and abdominal pain appeared. On the 3rd day of illness he was admitted to the clinic in serious condition. Upon admission: the condition is serious, pale, lethargic, complaining of a headache. Severe meningeal syndrome: stiff neck, Kernig and Brudzinski symptoms; red dermographism. No focal symptoms of brain damage were found. Uniform tendon hyperreflexia.

Examination of the cerebrospinal fluid on the 4th day of illness: the fluid is clear, the pressure is increased, cytosis is 1800/3 (lymphocytes 84%, neutrophils 13%), protein 0.396%, sugar 63 mg, chlorides 685 mg. The high temperature lasted for 4 days. The general condition improved by the 5th day of the disease, meningeal symptoms gradually smoothed out and disappeared on the 10th day of the disease. The composition of the cerebrospinal fluid did not return to normal for a long time: on the 24th day of illness, cytosis was still 61/3, protein 0.33%; only on the 30th day of illness, cytosis - 18/3 - mononuclear cells, protein 0.165%, sugar 52 mg, chlorides 725 mg.

On the craniogram in the lateral projection there are pronounced digital impressions throughout the entire skull, more noticeable in the posterior half. Bone sutures are emphasized. EEG from 31/1 shows the absence of alpha rhythm, the predominance of slow oscillations of theta waves and delta waves, lack of reactivity to external stimuli. The EEG from 7/11 shows alpha-like oscillations, no delta waves, a predominance of theta waves, and reduced reactivity.

Tests for enteroviruses, mumps virus and respiratory pathogens gave negative results. Testing of paired patient sera obtained on the 5th and 32nd day of illness in the RSC with the LCM virus antigen revealed a 4-fold increase in antibody titer in the 2nd serum. After 1.5 months, the patient was discharged from the clinic in good condition without residual effects.

In this patient, the meningeal form of lymphocytic choriomeningitis was severe with pronounced inflammatory changes in the cerebrospinal fluid, which were observed for a long time. The EEG also showed significant changes that were not completely smoothed out by the time of clinical recovery.

Patient Ts., 14 years old, fell ill on May 6, 2008, and felt “numbness of the upper lip.” On April 8, a facial deformity was discovered. The temperature did not rise. Upon admission to the clinic, pronounced peripheral paresis of the left facial nerve was noted: the left palpebral fissure is wider than the right, the eyelids do not close completely; lacrimation on the left, the left corner of the mouth is drooping, the left superciliary and nasolabial folds are not formed. Paresthesia of the facial skin on the left. Tendon, periosteal and skin reflexes are uniform. ENT organs are normal. The cerebrospinal fluid is not changed. After 3 weeks of appropriate treatment, facial asymmetry almost completely disappeared. He was discharged with slight smoothness of the left nasolabial fold.

Virological and serological studies were carried out for enteroviruses, the respiratory group of viruses and MycoplasmaPneumonia with negative results.

A study of paired sera with the LCM antigen revealed a significant increase in the titer of antibodies to the LCM virus (4-fold increase).

In this patient, the lymphocytic choriomeningitis virus caused a typical neuritis of the facial nerve.

Thus, in children, in addition to the clinical syndromes of lymphocytic choriomeningitis described by many authors, there are forms included in the combined polyetiological group of so-called “poliomyelitis-like” diseases.

Classification of forms of lymphocytic choriomeningitis according to M. I. Levi

A. Asymptomatic infection.

B. Clinical infection.

Along the way, he divides choriomeningitis into:

I. Acute:

1) visceral (flu-like form);

2) generalized (visceral-septic form);

3) neural form: a) hypertension syndrome; b) meningeal syndrome and c) encephalomyelitis syndrome.

II. Chronic forms.

Lymphocytic choriomeningitis (LCM), or acute aseptic, serous, benign meningitis, Armstrong's disease, is one of the most pronounced forms of the clinical course of a zoonotic generalized viral infection in humans.

Diseases that occur in humans occur not only with symptoms of damage to the soft meninges and the central nervous system in the form of serous meningitis or meningoencephalitis, but also in the form of a general infectious process with clinical symptoms of influenza, pneumonia, myocarditis, mumps, otitis, orchitis, as well as in a subclinical or parasitic form .

Due to the fact that in experimental animals infected with the virus, the most pronounced pathomorphological inflammatory changes occurred in the choroid plexuses of the ventricles and pia mater of the brain with an increase in the number of lymphocytes in the CSF, this pathogen was named lymphocytic choriomeningitis virus. The etiological significance of the LCM virus in human pathology was confirmed after its isolation from the CSF of two adult patients with acute serous meningitis.

Lymphocytic choriomeningitis is widespread. The true incidence of LCM has not been studied, since sporadic cases are recorded relatively infrequently, and group cases are rare. It can be assumed that as modern virological and serological diagnostic methods are introduced into diagnostic practice, diseases will be detected in many territories of our country.

Etiology. The causative agent of LCM, isolated for the first time in 1933 by S. Armstrong and R. Lillie, belongs to the group of arenoviruses - a toxonomic association of viruses of a similar structure that are sensitive to lipid solvents. Contains RNA; The formation of mature virions occurs by budding from the plasma membrane of the cell. The size of the virus ranges from 50 to 200 nm or more. It is preserved in a 50% glycerin solution, and in a dried state it can be viable for more than a year. Sensitive to detergents, ether, etc., quickly inactivated at a temperature of 56 ° C. The LCM virus is cultivated on most cell cultures, chicken embryos, mouse macrophage cultures, as well as in cell cultures of chicken and mouse embryos. The virus causes diseases in humans and many animals (white mice, guinea pigs, house mice, rats, monkeys). Asymptomatic forms of infection are observed in dogs, rabbits, chickens, Syrian hamsters, and newborn mice.

Epidemiology. Lymphocytic choriomeningitis is a zooanthroponotic infection, in which the most common source of human infection is gray house mice. However, infection can also occur from other domestic and wild animals (white mice, guinea pigs, dogs, rats, hamsters, monkeys, etc.). Research by M.I. Levi (1964) showed the presence of natural foci of lymphocytic choriomeningitis, in which forest mice and voles can be the reservoir of the virus. In recent years, various clinical syndromes of the disease have increasingly begun to be recorded in adults and children, resulting from infection with the LCM virus from Syrian hamsters that are kept at home and carry a latent infection. The insufficient detection of diseases in people is most likely due to the polymorphism of the clinical symptoms of the disease, the lack of special information from doctors and the corresponding simple laboratory diagnostic methods.

The infectious process in animals occurs in a hidden, latent form, and the pathogen persists for up to 291 days or longer [Levi M.I., 1964]. From the body of animals, the virus is released into the external environment with feces, urine, nasal mucus and seminal fluid. Human infection occurs when the pathogen enters the mucous membranes of the respiratory tract and digestive tract with air and dust, or when food is contaminated. The introduction of the virus is possible through bites, scratches and other violations of the integrity of the skin. The pathogen can also be transmitted through bites from ticks, mosquitoes, mosquitoes, dung flies, bedbugs and body lice. The literature does not describe cases of human infection from patients with LCM.

Diseases occur more often in winter and early spring, but no strict seasonality is observed; mainly adults and older children suffer. Single sporadic cases are more often recorded in rural areas or on the outskirts of cities, but group outbreaks limited to a small number of individuals are possible. In the anamnesis of patients with LCM, as a rule, there is an indication of the presence of mice or other domestic animals in the living quarters. Infections are also possible when working with laboratory animals.

Pathological anatomy. The LCM virus, when infecting animals, causes serous inflammation of the pia mater with lymphocytic infiltration and significant changes in the choroid plexuses of the brain. Pathomorphological studies of rare cases that resulted in the death of patients revealed the most significant changes in the pia mater and brain matter. There is perivascular, and in some cases, diffuse infiltration of lymphocytes in the pia mater and brain tissue. The substance of the brain is swollen and congested. In the dilated cavities of the ventricles there is an accumulation of a large amount of clear fluid. In the protracted and chronic course of lymphocytic choriomeningitis, ending in death, obliteration of the subarachnoid space due to the proliferation of connective tissue, pronounced lymphocytic infiltration of the perivascular spaces, and gliosis in the cerebral cortex were noted. Changes were also found in the white matter of the brain in the form of local and diffuse demyelination. In severe cases of the disease, which ends in death, sections often reveal interstitial pneumonia, as well as inflammatory changes in the liver tissue.

Clinic. Clinical manifestations of LCM in children and adults are extremely diverse. The acute phase of the disease can occur with a clinical picture of influenza, myocarditis, pneumonia, mumps, orchitis, meningitis, meningoencephalitis, myelitis. The disease usually begins acutely, without prodromal symptoms. Initially, many patients experience chills or short-term chills, followed by an increase in body temperature to high numbers. A general infectious process develops, manifested by headache, weakness, and weakness. In cases accompanied by selective damage to the brain substance and its membranes, meningeal syndrome is expressed from the first day of the disease and is dominant in the entire clinical picture of the disease. Patients usually complain of persistent and very intense diffuse headache, nausea, and vomiting. Occasionally, an extremely serious condition develops, manifested initially by anxiety, agitation and hallucinations, followed by loss of consciousness. A constant symptom is repeated vomiting. Body temperature rises from the first day of illness and remains at high levels from 5-7 to 8-14 days, and then decreases to normal. Subsequently, low-grade fever is often observed for 5 to 7 days, in rare cases longer. The pulse is usually increased, blood pressure is slightly reduced, and heart sounds are muffled. There are no significant changes in the liver and spleen. The tongue is usually coated and dry; the mucous membranes of the pharynx are slightly hyperemic; tonsils are not enlarged. No pathology of the urinary system is detected.

Meningeal syndrome is manifested by rigidity of the neck muscles of varying severity, positive Brudzinsky and Kernig symptoms. In some patients, general cerebral symptoms are detected in the form of hand tremors, unstable focal lesions of the cranial nerves (usually the abducens and oculomotor nerves), less often - hemiparesis, and also in 20-50% of cases - blurring of the optic nerve nipples, dilatation of the veins of the fundus. Only hand tremors and some paresis persist for a longer time. Severe cases are often accompanied by blackouts, delirium and significant functional disorders of the cardiovascular system. If such a clinical picture of the disease occurs, deaths are possible as a result of the development of infectious-toxic shock.

Spinal puncture reveals hypertension, reaching 30 - 40 cm of water. Art. (3-4 kPa). As a rule, after puncture there is a subjective and objective improvement in the condition of patients. CSF is usually clear, in rare cases slightly opalescent, flowing through the needle in a stream or frequent drops. Laboratory testing reveals normal or increased protein content, positive Nonne-Apelt and Pandi tests; the content of sugar and chlorine ions does not change; a film in the form of a “cobweb” rarely falls out when the liquid is kept in the cold. Cytosis is often detected, reaching 0.1-0.3* 109/l and even 1.2-1.5 109/l. Microscopic examination of the CSF in the first 2-3 days of illness reveals predominantly lymphocytes and a small number of polynuclear cells, and subsequently lymphocytes predominate (up to 90-95%).

In the vast majority of cases, the disease is acute, ending with normalization of body temperature, disappearance of headache and gradual extinction of meningeal symptoms, as well as normalization of CSF. General cerebral symptoms decrease in severity, but persist for up to 2-3 weeks or longer. During the period of early convalescence, patients often experience attacks of severe headaches. In the peripheral blood, normocytosis or leukopenia, significant lymphocytosis and a slightly elevated ESR are observed. There are no significant changes in red blood.

Diseases caused by the LCM virus also occur with the development of the clinical symptom complex of influenza, acute respiratory infection, pneumonia, myocarditis, mumps, orchitis, or in erased and latent forms. Clinical manifestations of catarrh of the mucous membranes of the nose, pharynx and upper respiratory tract are very mild or completely absent. In some cases, a cough with serous sputum is associated, and unstable, scanty fine rales are heard over the lungs.

The disease can manifest itself as fever, tachycardia, muffled heart sounds, arterial hypotension and other symptoms of myocardial damage. It is also possible to develop focal inflammatory phenomena in the salivary glands or testes. Such variants of the course of the disease are manifested not only by swelling and an increase in the size of the salivary glands or testes, pain and tenderness when palpated, but also by a general reaction in the form of increased body temperature, headache, decreased appetite and other symptoms. The latent form occurs without disruption of general well-being or the appearance of any symptoms and is detected on the basis of epidemiological data and the increase in specific antibodies in blood serum. The mentioned clinical forms of the disease end in recovery, but in some cases they lead to the development of meningitis or encephalitis with all clinical manifestations.

Group diseases resulting from infection from hamsters were characterized by a variety of clinical forms - from asymptomatic and influenza-like infections to classic manifestations of meningitis and encephalitis.

Prevention. To prevent infection of people, it is necessary to take measures to protect residential premises, food warehouses and other places where food is stored from the penetration of mice, rats and other mouse-like rodents. You should also keep food and food products out of reach of mice. After feeding and caring for domestic and laboratory animals (cats, dogs, rabbits, guinea pigs, hamsters, etc.), you must thoroughly wash your hands with hot water and soap. It is necessary to avoid bites and scratches by domestic and laboratory animals (if the skin is damaged, it must be treated with a 5% alcohol solution of iodine), contact with insects on the skin, as well as bites from ticks, mosquitoes and other arthropods.