Lymphocytic choriomeningitis is an acute viral infectious disease of the central nervous system. Pathognomonic symptoms are meningeal signs, general cerebral symptoms, less often lesions of the upper respiratory tract. Fever, general intoxication manifestations are also characteristic. Pathology is diagnosed by PCR, biopsy on rodents to isolate the pathogen, serological methods – to find antibodies. Specific etiotropic treatment of the disease has not been developed, pathogenetic, symptomatic measures are widely used.
ICD 10
A87.2 Lymphocytic choriomeningitis
General information
Lymphocytic choriomeningitis (acute Armstrong serous meningitis) is a viral nosology with a predominant lesion of the meninges. The pathogen was first described by American bacteriologists Armstrong and Lilly (1933), reports of patients with similar symptoms have been recorded since the 70s of the twentieth century. Pathology is widespread everywhere, the infection rate of domestic rodents reaches 9%. Adults and adolescents are most often affected, sometimes in small groups (family foci); there is no clear seasonality, but the incidence increases in winter and spring.
Causes
The causative agent of the disease is the arenavirus of the same name. The source and reservoir of infection are monkeys, mice, rats, guinea pigs, dogs, rabbits, chickens. The virus is released into the external environment with feces, saliva. Transmission routes: airborne, transplacental, alimentary (when food and water are infected), sometimes contact – during a violation of the integrity of the skin, and transmissible, when bitten by mosquitoes, bedbugs, mosquitoes, ticks and lice.
The main risk factors are professions related to the extermination of vectors, the care of decorative rodents (hamsters), in dusty conditions, granaries, virological laboratories, living in agricultural areas. For clinical infectology, lymphocytic choriomeningitis is relevant in that the prevalence among the human population reaches 5%; this means a high probability of asymptomatic course and congenital infectious pathology.
Pathogenesis
The pathogenesis has not been fully studied; studies have been conducted mainly on animals. Penetrating into the body, arenavirus does not leave a primary affect, but is lymphogenically transferred to regional accumulations of lymphoid tissue, where its replication and accumulation occurs. In the future, the pathogen with the blood flow spreads through the organs, multiplying in the cells of the reticular-endothelial system, is tropic to the membrane and substance of the brain.
At the same time, there is a long-term persistence of circulating immune complexes. Pathohistologically, inflammatory changes are detected in the membrane, ependyma and vascular plexuses of the brain, marked lymphocytic infiltration is characteristic. In the chronic course of lymphocytic chiriomeningitis, signs of obliteration of the subarachnoid space with infiltration of the meninges and gray matter are found.
Symptoms
The incubation period of lymphocytic choriomeningitis is 6-14 days. A pronounced prodromal period is characteristic – a prolonged feeling of weakness, lethargy, weakness, decreased performance, moderate headaches without a rise in body temperature. Often this condition is accompanied by symptoms of inflammation of the upper respiratory tract – nasal congestion, cough, sore throat, less often pain when swallowing.
Fever begins with high numbers (over 39 ° C), prolonged chills, severe pain in the joints, muscles. Photophobia occurs, severe headache with vomiting at the peak of sensations, the inability to bend the head to the body in a supine position, paralysis, decreased visual acuity, sometimes convulsions. After a while – from a few days to a month – the body temperature normalizes, but after a day or two there is a second wave of feverish symptoms.
Complications
The most common complications of lymphocytic choriomeningitis are progressive intracranial hypertension, cerebral edema, myocarditis, purulent secondary infections: orchitis, otitis, mumps. With intrauterine infection, there is a high probability of complications such as miscarriage, fetopathy of the nervous system (hydrocephalus, microcephaly, cerebellar hypoplasia), including cerebral palsy and chorioretinitis.
Progressive slow infection of the brain leads to diffuse demyelination, gliosis of gray and white matter, manifested by symptoms of dementia, mental deviations and disorders of cortical functions. Over time, paralysis and paresis of the extremities develop; without treatment, the life expectancy of patients with a similar course of nosology rarely exceeds 10 years.
Diagnostics
Verification of the diagnosis of viral infection and treatment is carried out jointly by infectious disease specialists and neurologists. Other medical specialists are involved according to indications. It is important to collect an epidemiological history, including the specifics of the patient’s residence and profession. The main clinical, instrumental and laboratory signs of lymphocytic choriomengitis:
- Physical data. Objective examination of patients determines meningeal syndrome, complaints of visual impairment, rarely hyperemia of the throat, dry wheezing in the lungs, hepatosplenomegaly. Ophthalmoscopy in 20-50% of patients with lymphocytic choriomeningitis reveals signs of congestion of the optic disc, dilation and tortuosity of the veins.
- Laboratory tests. A general clinical blood test reveals leukocytosis, a shift of the formula to the left, acceleration of ESR. In the general analysis of urine, there may be traces of protein, red blood cells. Liquorogram for this choriomeningitis: lymphocytic pleocytosis, increased protein content, decreased glucose concentration, sharply positive Pandi test.
- Identification of infectious agents. Verification of the diagnosis is carried out using the PCR method (urine, blood, cerebrospinal fluid), less often by a biopsy on mice. Serological examination (ELISA, RSC) is carried out twice, with an interval of 10-14 days, it is necessary to increase the titer of antibodies by at least 4 times.
- Instrumental methods. Radiography of the chest and skull organs is performed with lymphocytic choriomeningitis for the purpose of differential diagnosis. EEG – signs of hypertension, diffuse disturbances of bioelectric activity. On an ECG, it is possible to detect symptoms of myocarditis.
Differential diagnosis
Differential diagnosis is carried out with poliomyelitis, meningitis caused by tick-borne encephalitis viruses, Coxsackie, adenoviruses, mumps. In these conditions, there are changes not only in the function of the central nervous system. For tuberculous meningitis, a primary focus of mycobacterial lesion is needed. The differences in the clinical course of meningococcal and secondary purulent meningitis are that the symptoms increase at lightning speed, specific changes in the cerebrospinal fluid are detected.
Treatment
Patients with symptoms of the disease are subject to mandatory hospitalization in an infectious hospital; in case of severe CNS damage, treatment in the intensive care unit is recommended, sometimes a ventilator is required. Patients with immunodeficiency of any genesis need immediate treatment – most of the fatal cases are accounted for by these patients.
Bed rest is prescribed until the normalization of the cerebrospinal fluid, on average, for up to 2-3 weeks, even at normal body temperature. With meningeal symptoms, it is necessary to ensure peace, the absence of sharp noises, bright light. The diet consists in limiting heavy, hard-to-digest food, alcohol. The drinking regime is increased due to water and other liquids, comparing it with the clinic of brain damage.
Conservative therapy
There are currently no standardized protocols for the treatment of patients with lymphocytic choriomeningitis clinic; new etiotropic antiviral formulas are being developed. Most often, clinical improvement occurs after 3-5 days; in uncomplicated cases, treatment is limited to symptomatic measures. Most often , the disease is treated with the following drugs:
- Etiotropic. Ribavirin is considered as a possible antiviral agent for the treatment of lymphocytic choriomeningitis, but it does not have a convincing evidence base. It is proved that when used in sub-inhibitory concentrations, the drug is able to cause mutations of the pathogen and enhance its replicative activity.
- Pathogenetic. Detoxification with intravenous infusions of chlosol, succinate-containing, glucose-salt solutions plays an important role. Corticosteroids are used only to a limited extent, as they increase the likelihood of relapses.Sedatives, diuretics, anticonvulsants, antipyretics, antihypoxants are also used.
- Symptomatic. For the relief of emerging symptoms, means that improve microcirculation, local antiseptic sprays, antitussive, antiemetic drugs are used. With proven secondary bacterial infection, antibiotics are selected taking into account the sensitivity of the flora. In cases of severe cephalgia, repeated lumbar punctures are performed.
Due to the persistence of the pathogen in the bone marrow, depletion of the CD8+ T-lymphocyte pool, excessive secretion of tumor necrosis factor and other pro-inflammatory cytokines, some patients experience symptoms of aplastic anemia. For correction, the use of recombinant erythropoietin, monoclonal T-lymphocytes is proposed, transfusion of blood components is often necessary.
Experimental treatment
According to a number of studies, the combined use of some cardiac glycosides contributes to limiting the entry into target cells of the pathogen of lymphocytic choriomeningitis, probably due to inhibition of Na+/K+-ATPase. The substance PF-429242 is a reversible competitive inhibitor of aminopyrrolidinamide S1P, in experiments in vitro and in animal models showed a significant decrease in virus replication.
The studied drug favipiravir (T-705) showed high activity against arenaviruses of lymphocytic choriomeningitis, Machupo, Junin and Guanarito in experiments on hamsters. Its virusocidal ability is based on the suppression of transcription and replication of the pathogen due to inhibition of RNA-dependent viral polymerase. It is important that the pharmaceutical, unlike ribavirin, does not have cellular toxicity.
Prognosis and prevention
The prognosis with timely diagnosis and treatment is favorable. Mortality among patients with lymphocytic choriomeningitis is 0.13%. Regression of neurological symptoms may take more than 3 weeks; during this time, patients report paroxysmal headaches. Subfebrility persists for about a week after recovery, asthenic symptoms – up to several months.
No specific prevention has been developed. Some researchers consider the use of vector vaccines against adenovirus, rabies, and influenza to form cellular immunity to lymphocytic choriomeningitis promising. The main importance is given to non-specific measures: deratization, protection of drinking sources, products from rodents, compliance with the rules of working with viruses in laboratories, personal and professional hygiene.