The causative agents of slow viral infections are prions. Slow infections. What is this infection
Slow infections, penetrating into the human body, may not manifest themselves for many years, and when they do, it causes serious health problems. The origin of many of them has not yet been studied. What is it, what are the symptoms of the disease and how to recognize it on early stages Let's try to figure it out further.
What is this infection?
It happens that viruses of an unusual nature enter the human body, which, taking root in it, do not appear immediately, and sometimes for several years. The infection progresses very slowly in a living organism, which is why it is called "slow".Such an infection causes great harm human body, destroying individual bodies especially the central nervous system is affected. In frequent cases, it leads to death.
causative agents of slow infection
The causative agents are considered to be two groups of viruses:Prion viruses
They have a protein composition, and the molecular weight is 23-35 kDa. The composition of prions does not include nucleic acid, so this virus exhibits unusual properties, these include:- resistance to ultraviolet radiation;
- resistance to formaldehyde and ultrasound;
- the ability to withstand heating temperatures from 80 to 100 degrees Celsius.
One more distinctive feature of these viruses is that the coding gene is located in the cell, and not in the composition of the prion.
The prion protein, affecting the body, starts the activation of the gene, and the synthesis of the same protein occurs. As a result, such viruses very quickly adapt to the new environment, increasing their concentration. They are very difficult to predict, as they differ in that they have different strains, they can clone.
Despite the fact that the virus is classified as an unusual protein, it has the classic properties of viruses. So, it has the ability to pass through filters designed for bacteria. It cannot be propagated in specially created environments for experimental work.
Viruses-virions
Another group related to the causative agents of a slow viral infection are virion viruses. These are full-fledged viruses containing a nucleic acid and an envelope, which includes protein and lipids. The virus particle is located outside the living cell.Infection with these viruses can be the beginning of a large number of diseases. These include kuru disease, Creutzfeldt-Jakob disease, amyotrophic leukospongiosis, and others.
There are also a number of diseases that have an unexplained cause of occurrence, but they are classified as infections that develop slowly, as they have completely similar symptoms and a long period of development without any special symptoms. These are multiple sclerosis, Parkinson's disease, amyotrophic lateral sclerosis, etc.
How is the infection transmitted?
Factors affecting the penetration of this infection are still being studied. It has been observed that pathogenic viruses settle in the body with weak immunity, that is, there is a reduced reaction of the body to the production of antibodies that neutralize these viruses.People infected with these viruses pose a danger to others. In addition, animals are also carriers, since some of their diseases can pass to humans, including scrapie, anemia of an infectious nature in horses, Aleutian mink disease.
The disease can be transmitted in several ways:
- during contact with a sick person and animal;
- through the placenta;
- when inhaling.
Pathogenic effects on the body and symptoms
When falling into the body, the virus begins to multiply, harm, disrupt the activity of important organs and vital processes. Most often, the central nervous system undergoes degeneration. These pathologies do not have pronounced symptoms and changes in well-being, but some of them can be recognized with progression:
- Parkinson's disease has symptoms in the form of impaired coordination of movements, which is reflected in a change in a person's gait, then paralysis of the limbs may develop;
- kuru and can be identified by trembling limbs;
- in the presence of chickenpox or rubella, passed from mother to fetus, the child has a developmental delay, small stature and body weight.
Therapy of diseases and preventive measures
A person who has unusual viruses in his body cannot be cured. No new technologies and developments provide an answer to the question of the treatment of slow infections that kill a person. In the presence of an infection, as well as its detection, it is necessary to contact an infectious disease specialist.TO preventive measures can be attributed:
- intake of food rich in vitamins and minerals;
17.3. Slow viral infections and prion diseases
Slow viral infections are characterized by the following features:
unusually long incubation period(months, years);
a kind of damage to organs and tissues, mainly the central nervous system;
slow steady progression of the disease;
inevitable death.
Slow viral infections can be caused by viruses known to cause acute viral infections. For example, measles virus sometimes causes SSPE (see section 17.1.7.3), rubella virus sometimes causes progressive congenital rubella and rubella panencephalitis (Table 17.10).
A typical slow viral infection in animals is caused by the Madi/Vysna virus, which is a retrovirus. It is the causative agent of a slow viral infection and progressive pneumonia in sheep.
Diseases similar in terms of signs of slow viral infections cause prions - the causative agents of prion infections.
prions- protein infectious particles (transliteration from abbr. English. proteinacous infection particles). The prion protein is referred to as RgR(English prion protein), it can be in two isoforms: cellular, normal (RgR from ) and altered, pathological (PrP sc). Previously, pathological prions were attributed to the causative agents of slow viral infections, now it is more correct to attribute them to the causative agents of conformational diseases 1 that cause I dysproteinosis (Table 17.11).
Prions are non-canonical pathogens that cause transmissible spongiform encephalopathies: in humans (kuru, Creutzfeldt-Jakob disease, Gerstmann-Streussler-Scheinker syndrome, familial fatal insomnia, amyotrophic leukospongiosis); animals (sheep and goat scrapie, transmissible encephalopathy
|
Table 17.10. The causative agents of some slow human viral infections |
|
|
Pathogen | |
|
measles virus |
Subacute sclerosing panencephalitis |
|
rubella virus |
Progressive congenital rubella, progressive rubella panencephalitis |
|
tick-borne encephalitis virus |
Progressive form of tick-borne encephalitis |
|
herpes simplex virus |
Subacute herpetic encephalitis |
|
AIDS virus |
HIV, AIDS infection |
|
T cell lymphoma |
|
|
Poliomavirus JC |
Progressive multifocal leukoencephalopathy |
|
Prion Properties |
|
|
PrP c (cellular prion protein) |
PrP sc (scrapie prion protein) |
|
PrP c(cellular prion protein) - cellular, normal isoform of prion protein with molecular weight 33-35 kDa, is determined by the prion protein gene (the prion gene - PrNP - is located on the short arm of the 20th human chromosome). Normal RgR from appears on the cell surface (anchored to the membrane by a glycoprotein molecule), is sensitive to protease. It regulates the transmission of nerve impulses, circadian rhythms (daily) cycles, is involved in the metabolism of copper in the central nervous system |
PrP sc (scrapie prion protein - from the name of scrapie prion disease - scrapie) and others, for example, PgP * (in Creutzfeldt-Jakob disease) are pathological prion protein isoforms with a molecular weight of 27-30 kDa, altered by prion modifications. Such prions are resistant to proteolysis (to protease K), to radiation, high temperature, formaldehyde, glutaraldehyde, beta-propiolactone; do not cause inflammation and immune response. Differ in the ability to aggregate into amyloid fibrils, hydrophobicity and secondary structure as a result of an increased content of beta-sheet structures (more than 40% compared to 3% in PrP c ). PrP sc accumulates in plasma vesicles of the cell |
The scheme of prion proliferation is shown in fig. 17.18.
mink, chronic wasting disease of captive deer and elk, large spongiform encephalopathy cattle, feline spongiform encephalopathy).
Pathogenesis and clinic. Prion infections are characterized by spongiform brain changes (transmissible spongiform encephalopathies). At the same time, cerebral amyloidosis (extracellular dysproteinosis, characterized by the deposition of amyloid with the development of tissue atrophy and sclerosis) and astrocytosis (proliferation of astrocytic neuroglia, hyperproduction of glial fibers) develop. Fibrils, aggregates of protein or amyloid are formed. Immunity to prions does not exist.
Kuru - prion disease, previously common among the Papuans (in translation means trembling or trembling) on about. New Guinea as a result of ritual cannibalism - eating insufficiently thermally processed prion-infected brains of dead relatives. As a result of damage to the central nervous system, coordination of movements, gait are disturbed, chills, euphoria appear ("laughing death"). Death occurs within a year. The infectious properties of the disease were proved by K. Gaidushek.
Creutzfeldt-Jakob disease - prion disease (incubation period - up to
20 years), occurring in the form of dementia, visual and cerebellar disorders and motor disorders with a fatal outcome after 9 months from the onset of the disease. There are various ways of infection and the causes of the development of the disease: 1) when using insufficiently thermally processed products of animal origin, such as meat, brain of cows, patients with bovine spongiform encephalopathy, as well as; 2) when transplanting tissues, for example, the cornea of the eye, when using hormones and other biologically active substances of animal origin, when using contaminated or insufficiently sterilized surgical instruments, during prosector manipulations; 3) with overproduction of PrP and other conditions that stimulate the process of transformation of PrP c into PrP sc. The disease can develop as a result of a mutation or insertion in the region of the prion gene. The familial nature of the disease is common as a result of a genetic predisposition to this disease.
Gerstmann-Streussler Syndrome- Shainker - prion disease with hereditary pathology (family disease), occurring with dementia, hypotension, swallowing disorders, dysarthria. It often has a family character. The incubation period is from 5 to 30 years. Fatal outcome
occurs 4-5 years after the onset of the disease.
fatal familial insomnia - an autosomal dominant disease with progressive insomnia, sympathetic hyperreactivity (hypertension, hyperthermia, hyperhidrosis, tachycardia), tremor, ataxia, myoclonus, hallucinations. Circadian rhythms are disrupted. Death - with the progression of cardiovascular insufficiency.
scrapie (from English. scrape - scrape) - "scabies", a prion disease of sheep and goats, characterized by severe skin itching, damage to the central nervous system, progressive impairment of coordination of movements and the inevitable death of the animal.
spongiform encephalopathy of the large horn that cattle - prion disease of cattle, characterized by damage to the central nervous system, impaired coordination of movements and
inevitable death of the animal. Animals are most infected with the head, spinal cord and eyeballs.
With pri-on pathology, sponge-like changes in the brain, astrocytosis (gliosis), and the absence of inflammatory infiltrates are characteristic; coloring. The brain is stained for amyloid. Protein markers of prion reactions are detected in the cerebrospinal fluid. brain disorders(using ELISA, IB with monoclonal antibodies). Genetic analysis of the prion gene is carried out; PCR to detect RgR.
Prevention. Introduction of restrictions on the use of medicinal products of animal origin. Cessation of the production of pituitary hormones of animal origin. Restriction of solid transplantation meninges. Use of rubber gloves when handling body fluids of patients.
17.4. Acute respiratory pathogensviral infections
SARS- this is a group of clinically similar, acute infectious human viral diseases that are transmitted predominantly aerogenically and are characterized by lesions respiratory organs and moderate intoxication.
Relevance. SARS are among the most common human diseases. Despite the usually benign course and favorable outcome, these infections are dangerous due to their complications (eg, secondary infections). ARVI, which affects millions of people every year, causes significant damage to the economy (up to 40% of working time is lost). In our country alone, about 15 billion rubles are spent every year to pay for medical insurance, medicines and means of preventing acute respiratory infections.
Etiology. Acute infectious diseases in which the human respiratory tract is affected can be caused by bacteria, fungi, protozoa, and viruses. Various viruses can be transmitted aerogenically and cause symptoms characteristic of the respiratory tract (for example, measles viruses, mumps, herpes viruses, some enteroviruses, etc.). However, ARVI pathogens are considered to be only those viruses in which primary reproduction occurs exclusively in the epithelium of the respiratory tract. More than 200 antigenic varieties of viruses have been registered as causative agents of SARS. They belong to different taxa, each of which has its own characteristics.
Taxonomy. Most pathogens were first isolated from humans and typed in the 1950s and 1960s. The most common pathogens of SARS are representatives of the families shown in Table. 17.12.
General comparative characteristics of the excitationditel. Most ARVI pathogens are RNA-containing viruses, only adenoviruses contain DNA. The genome of viruses is represented by: double-stranded linear DNA - in
adenoviruses, single-stranded linear plus-RNA in rhino- and coronaviruses, single-stranded linear minus-RNA in paramyxoviruses, and in reoviruses, RNA is double-stranded and segmented. Many ARVI pathogens are genetically stable. Although RNA, especially segmented, predisposes to the readiness of genetic recombinations in viruses and, as a result, to a change in the antigenic structure. The genome encodes the synthesis of structural and non-structural viral proteins.
Among the ARVI viruses, there are simple (ade-no-, rhino- and reoviruses) and complex enveloped (paramyxoviruses and coronaviruses). Complex viruses are sensitive to ether. In complex viruses, the nucleocapsid has a helical type of symmetry and the shape of the virion is spherical. Simple viruses have a cubic type of symmetry of the nucleocapsid and the virion has the shape of an icosahedron. Many viruses have an additional protein coat covering the nucleocapsid (in adeno-, ortho-myxo-, corona- and reoviruses). The size of virions in most viruses is average (60-160 nm). The smallest are rhinoviruses (20 nm); the largest are paramyxoviruses (200 nm).
The antigenic structure of SARS viruses is complex. Viruses of each kind, as a rule, have common antigens; in addition, viruses also have type-specific antigens, which can be used to identify pathogens with serotype determination. Each group of ARVI viruses includes a different number of serotypes and serovariants. Most ARVI viruses have hemagglutinating ability (except for PC- and rhinoviruses), although not all of them have hemagglutinins proper. This determines the use of RTGA for the diagnosis of many SARS. The reaction is based on blocking the activity of hemagglutinins of the virus with specific antibodies.
Reproduction of viruses occurs: a) entirely in the cell nucleus (in adenoviruses); b) entirely in the cytoplasm of the cell (in the rest). These features are important for diagnosis, as they determine the localization and nature of intracellular inclusions. Such inclusions are "factories"
|
Table 17.12. The most common causative agents of SARS |
||
|
Family | ||
|
Human parainfluenza viruses, serotypes 1.3 |
||
|
PC virus, 3 serotiia |
||
|
Human parainfluenza viruses, serotypes 2, 4a, 4b, epidemic virusmumps, etc. * |
||
|
Measles virus, etc.* |
||
|
Coronaviruses, 11 serotypes |
||
|
Rhinoviruses (more than 113 serotypes) |
||
|
respiratory reoviruses, 3 serotypes |
||
|
adenoviruses, more often serotypes 3, 4, 7 (outbreaks caused by types 12, 21 are known) |
||
*Infections are independent nosological forms and are usually not included in the SARS group itself.
for the production of viruses and usually contain a large number of viral components "unused" in the assembly of viral particles. The release of viral particles from the cell can occur in two ways: for simple viruses, by an “explosive” mechanism with the destruction of the host cell, and for complex viruses, by “budding”. In this case, complex viruses receive their shell from the host cell.
The cultivation of most SARS viruses is quite easy (the exception is coronaviruses). The optimal laboratory model for culturing these viruses is cell cultures. For each group of viruses, the most sensitive cells were selected (for adenoviruses - HeLa cells, embryonic kidney cells; for coronaviruses - embryonic and tracheal cells, etc.). In infected cells, viruses cause CPE, but these changes are not pathognomonic for most ARVI pathogens and usually do not allow identification of viruses. Cell cultures are also used in the identification of pathogens with cytolytic activity (for example, adenoviruses). For this, the so-called biological neutralization reaction of viruses in cell culture (RBN or PH of viruses) is used. It is based on the neutralization of the cytolytic action of viruses by type-specific antibodies.
Epidemiology. Respiratory viruses are ubiquitous. The source of infection is a sick person. The main mechanism of infection transmission is aerogenic, the ways are airborne (when coughing, sneezing), less often - airborne. It has also been proven that some pathogens of SARS can be transmitted by contact (adeno-, rhino- and PC-viruses). In the environment, the resistance of respiratory viruses is average, infectivity is especially well preserved at low temperatures. There is a seasonality of most acute respiratory viral infections, which often occur in the cold season. The incidence is higher among the urban population. Predisposing and aggravating factors are passive and active smoking, respiratory diseases, physiological stress, a decrease in the overall resistance of the body, immunodeficiency states and non-communicable diseases in which they are observed.
Both children and adults get sick, but more often children. In developed countries, the majority of preschool children attending kindergartens and nurseries get ARVI 6-8 times a year, and usually these are infections caused by rhinoviruses. natural passive immunity and breast-feeding form protection against SARS in newborns (up to 6-11 months).
Pathogenesis. The entry gate of infection is the upper respiratory tract. Respiratory viruses infect cells by attaching their active centers to specific receptors. For example, in almost all rhinoviruses, capsid proteins bind to ICAM-1 adhesion receptor molecules in order to then enter fibroblasts and other sensitive cells. In parainfluenza viruses, supercapsid proteins attach to glycosides on the cell surface, in coronaviruses, attachment is carried out by binding to cell glycoprotein receptors, adenoviruses interact with cellular integrins, etc.
Most respiratory viruses replicate locally in the cells of the respiratory tract and therefore cause only short-term viremia. Local manifestations of ARVI are mostly caused by the action of inflammatory mediators, in particular, bradykinins. Rhinoviruses usually cause minor damage to the epithelium of the nasal mucosa, but the PC virus is much more destructive and can cause necrosis of the epithelium of the respiratory tract. Some adenoviruses are cytotoxic and rapidly cytopathic and reject infected cells, although the virus itself usually does not spread beyond the regional lymph nodes. Edema, cell infiltration and desquamation of the surface epithelium at the site of pathogens are also characteristic of other SARS. All this creates conditions for the attachment of secondary bacterial infections.
Clinic. With ARVI of various etiologies, the clinical picture may be similar. The course of the disease can vary significantly between children and adults. ARVI is characterized by a short incubation period. Diseases, as a rule, are short-term, intoxication is weak or moderate. Often, SARS even occur without any significant rise in temperature. Characteristic symptoms are catarrh of the upper respiratory tract (laryngitis, pharyngitis, tracheitis), rhinitis and rhinorrhea (with rhinovirus infection, isolated rhinitis and dry cough often occur). At hell-
pharyngoconjunctivitis, lymphadenopathy can join a novirus infection. Children usually have a severe infection with PC viruses. In this case, the lower respiratory tract is affected, bronchiolitis, acute pneumonia and asthmatic syndrome occur. With ARVI, sensitization of the body often develops.
Nevertheless, the majority of uncomplicated ARVI in practically healthy individuals is not severe and ends within a week with a complete recovery of the patient, even without any intensive treatment.
The course of acute respiratory viral infections is often complicated, since secondary bacterial infections (for example, sinusitis, bronchitis, otitis media, etc.) occur against the background of post-infectious immunodeficiency, which significantly aggravate the course of the disease and increase its duration. The most severe "respiratory" complication is acute pneumonia (viral-bacterial pneumonia is severe, often leading to the death of the patient due to massive destruction of the epithelium). respiratory tract, hemorrhages, abscess formation in the lungs). In addition, the course of SARS can be complicated by neurological disorders, dysfunction of the heart, liver and kidneys, as well as symptoms of gastrointestinal damage. This may be due to the action of both the viruses themselves and the toxic effects of the decay products of infected cells.
Immunity. The most important role in protection against repeated diseases, of course, is played by the state of local immunity. In ARVI, the virus-neutralizing specific IgA (provide local immunity) and cellular immunity have the greatest protective functions in the body. Antibodies are usually produced too slowly to be effective protective factors during illness. Another important factor in protecting the body from ARVI viruses is the local production of al-interferon, the appearance of which in the nasal discharge leads to a significant decrease in the number of viruses. An important feature of SARS is the formation of secondary immunodeficiency.
Post-infectious immunity in most acute respiratory viral infections is unstable, short-lived and type-specific. An exception is adenovirus infection, which is accompanied by the formation of a sufficiently strong, but also type-specific immunity. A large number of serotypes, a large number and variety of the viruses themselves explain the high frequency of recurrent ARVI infections.
Microbiological diagnostics. The material for the study is nasopharyngeal mucus, smears-imprints and swabs from the pharynx and nose.
Express diagnostics. Detect viral antigens in infected cells. RIF is used (direct and indirect methods) using specific antibodies labeled with fluorochromes, as well as ELISA. For difficult-to-cultivate viruses, a genetic method is used (PCR).
Virological method. IN For a long time, infection of cell cultures with the secrets of the respiratory tract for the cultivation of viruses was the main direction in the diagnosis of acute respiratory viral infections. Indication of viruses in infected laboratory models is carried out by CPE, as well as RHA and hemadsorption (for viruses with hemagglutinating activity), by the formation of inclusions (intranuclear inclusions in adenovirus infection, cytoplasmic inclusions in the perinuclear zone in reovirus infection, etc.), as well as by the formation of "plaques", and "color test". Viruses are identified by antigenic structure in RSK, RPHA, ELISA, RTGA, RBN viruses.
Serological method. Antiviral antibodies are examined in paired patient sera obtained at intervals of 10-14 days. The diagnosis is made by increasing the antibody titer by at least 4 times. This determines the level of IgG in such reactions as RBN viruses, RSK, RPHA, RTGA, etc. Since the duration of the disease often does not exceed 5-7 days, a serological study usually serves for retrospective diagnosis and epidemiological studies.
Treatment. There is currently no effective etiotropic treatment for ARVI (according to
attempts to create drugs that act on ARVI viruses are carried out in two directions: preventing the "undressing" of viral RNA and blocking cell receptors). A-interferon, the preparations of which are used intranasally, has a nonspecific antiviral effect. Extracellular forms of adeno-, rhino- and myxoviruses are inactivated by oxolin, which is used as eye drops or ointments intranasally. Only with the development of a secondary bacterial infection, antibiotics are prescribed. The main treatment is pathogenetic / symptomatic (includes detoxification, plenty of warm drink, antipyretic drugs, vitamin C, etc.). Antihistamines can be used for treatment. Of great importance is the increase in the general and local resistance of the body.
Prevention. Non-specific prophylaxis consists in anti-epidemic measures that limit the spread and transmission of viruses by aerogenic and contact. In the epidemiological season, it is necessary to take measures aimed at increasing the general and local resistance of the body.
Specific prevention of most acute respiratory viral infections is not effective. For the prevention of adenovirus infection, oral live trivalent vaccines (from strains of types 3, 4 and 7; administered orally, in capsules) have been developed, which are used according to epidemiological indications.
Slow viral infections are diseases that are caused by prions. These are special pathogens of infectious diseases, consisting exclusively of one protein. Unlike other agents, they do not contain nucleic acids. Slow viral infections primarily affect the central nervous system. Symptoms of diseases caused by prions:
- Memory impairment.
- Impaired coordination.
- Insomnia/sleep disturbance.
- Heat.
- Speech disorder.
- Tremor.
- Seizures.
The concept of disease
Slow viral infections (prion diseases) are pathologies affecting humans and animals. They are accompanied by a specific lesion nervous system. Diseases are characterized by a very long incubation period (the time from the pathogen entering the human body until the first signs of the disease appear).
This group of diseases includes:
- Creutzfeldt-Jakob disease.
- Kuru is a disease found in New Guinea.
Prion diseases affect animals. They were first discovered by examining a sick sheep.
Etiology and transmission of the disease
The etiological factor of slow viral infections is prions. These proteins were studied not so long ago and are of great scientific interest. Without their own nucleic acids, prions reproduce in a peculiar way. They bind to normal proteins in the human body and turn them into their own kind.
Prion is a pathological protein (photo: www.studentoriy.ru)
There are several ways of transmission of pathogens of slow neuroinfections:
- Alimentary (food) - prions are not destroyed by the action of enzymes released in the human digestive tract. Penetrating through the intestinal wall, pathogens spread throughout the body and reach the nervous system.
- Parenteral route - through the injection of drugs into the human body. For example, when using pituitary hormone preparations to treat dwarfism.
There is evidence of the possibility of infection during neurosurgical operations, since prions are resistant to existing methods of disinfection and sterilization.
Disease classification
All slow viral infections are divided into two large groups: those affecting people and animals. The first option includes:
- Subacute sclerosing panencephalitis.
- Progressive multifocal leukoplakia.
- Creutzfeldt-Jakob disease.
- Kuru.
The most common prion disease in animals is skrep (a disease of sheep).
Clinical picture of the disease
Prion diseases are distinguished by their long incubation period. In humans, it lasts from several to decades. In this case, the patient does not have any symptoms, and he is unaware of his disease. The clinical picture of the disease occurs when the number of dead neurons reaches a critical level. Symptoms of prion diseases both have common features and differences, depending on the type of disease. They are presented in the table:
|
Disease |
Symptoms |
|
Subacute sclerosing panencephalitis |
The disease begins with pathological forgetfulness, insomnia, fatigue. With progression, mental faculties and speech are impaired. In the terminal stages - impaired coordination, speech, persistent fever, pulse disorders and blood pressure |
|
Progressive multifocal leukoplakia |
At the beginning of the disease - mono- and hemiparesis (disturbances in movement in a single or several limbs). As the disease progresses, the symptoms are accompanied by impaired coordination, blindness, epileptic seizures. |
|
Creutzfeldt-Jakob disease |
All patients with this disease have impaired attention, memory. In the later stages - myoclonic convulsions, hallucinations |
|
The first symptoms are walking disorders, after which there are tremors of the limbs, speech disorders, muscle weakness. characteristic clinical feature kuru - causeless euphoria |
Important! All slow viral infections are nearly 100% fatal
Complications, consequences and prognosis
The consequences and prognosis of prion diseases are, as a rule, disappointing. Almost all cases of diseases end in death.
Which doctors are involved in the diagnosis and treatment of the disease
Since slow viral infections affect the nervous system, the main specialists who are involved in the diagnosis and treatment of the disease are neuropathologists and infectious disease specialists.
Doctor's advice. In case of unreasonable occurrence of symptoms of neurological disorders, consult a neurologist for advice
Diagnosis of prion infections
In the diagnosis of prion diseases, two large groups of research methods are used: laboratory and instrumental. Laboratory methods include:
- Study cerebrospinal fluid- determination of its cellular composition, the amount of protein, glucose and electrolytes.
- Immune blotting is one of the types of enzyme immunoassay (ELISA).
- Molecular genetic methods.
Of the instrumental methods, those that provide neuroimaging are used:
- Electroencephalography - recording of biopotentials of the brain.
- A brain biopsy is an intravital taking of a piece of the brain for microscopic examination.
- Computed tomography (CT) and magnetic resonance imaging (MRI) - the study of nerve structures in layers.
The World Health Organization (WHO) recommends a biological method for diagnosing prion diseases. It includes infection biological material transgenic mice.
Basic principles of treatment
Etiological and pathogenetic methods of treatment aimed at the pathogen and the mechanisms of its effect on the human body have not been developed. Symptomatic principles are used in the treatment of slow viral infections. Anticonvulsant drugs, neuroprotectors, drugs that improve memory and coordination are used.
Prevention of slow viral infections
Prevention of prion diseases consists in the appropriate processing of reusable medical instruments. Most disinfection and sterilization methods are ineffective against prions. WHO recommends using the following instrument processing algorithm:
- Autoclaving at a temperature of 130-140⁰ C for 18 minutes.
- Chemical treatment with alkali (NaOH) and hydrochloric acid.
Emergency prevention and vaccination of prion diseases has not been developed.
Chronic, slow, latent viral infections are quite difficult, they are associated with damage to the central nervous system.
Viruses evolve towards a balance between the viral and human genomes. If all viruses were highly virulent, then a biological impasse would be created associated with the death of the hosts. There is an opinion that highly virulent ones are needed for viruses to multiply, and latent ones - for viruses to persist. There are virulent and non-virulent phages.
Types of interaction of viruses with a macroorganism:
short-lived type. This type includes 1. Acute infection 2. Inapparent infection (asymptomatic infection with a short stay of the virus in the body, as we learn from the seroconversion of specific antibodies in the serum.
Long stay of the virus in the body (persistence).
Classification of forms of interaction of the virus with the body.
Latent infection - characterized by a long stay of the virus in the body, not accompanied by symptoms. In this case, the accumulation of viruses occurs. The virus can persist in an incomplete form (in the form of subviral particles), so the diagnosis of latent infections is very difficult. Under the influence of external influences, the virus comes out, manifests itself.
chronic infection. persistence is manifested by the appearance of one or more symptoms of the disease. The pathological process is long, the course is accompanied by remissions.
Slow infections. In slow infections, the interaction of viruses with organisms has a number of features. Despite the development of the pathological process, the incubation period is very long (from 1 to 10 years), then a fatal outcome is observed. The number of slow infections is increasing all the time. Now more than 30 are known.
Causative agents of slow infections: the causative agents of slow infections include common viruses, retroviruses, satellite viruses (these include the delta virus, which reproduces in hepatocytes, and the supercapsid is supplied by the hepatitis B virus), defective infectious particles arising from natural or artificial mutation purem, prions, viroids , plasmids (may also be found in eukaryotes), transposons (“jumping genes”), prions are self-replicating proteins.
Professor Umansky emphasized the important ecological role of viruses in his work “The Presumption of Innocence of Viruses”. In his opinion, viruses are needed in order for information to be exchanged horizontally and vertically.
Slow infections are subacute sclerosing panencephalitis (SSPE) . PSPE affects children and adolescents. The central nervous system is affected, slow destruction of the intellect, motor disorders, always fatal. Found in blood high level antibodies to the measles virus. The causative agents of measles were found in the brain tissue. The disease manifests itself first in malaise, loss of memory, then speech disorders, aphasia, writing disorders appear - agraphia, double vision, impaired coordination of movements - ataxia; then hyperkinesis develops, spastic paralysis, the patient ceases to recognize objects. Then comes the exhaustion of the patient falls into a coma. With PSPE, degenerative changes in neurons are observed, in microglial cells - eosinophilic inclusions. In pathogenesis, a breakthrough of the persistent measles virus in the central nervous system through the blood-brain barrier occurs. The incidence of SSPE is 1 case per million. Diagnosis - with the help of EEG, the tyr of anti-measles antibodies is also determined. Prevention of measles is also the prevention of SSPE. In those vaccinated against measles, the incidence of SSPE is 20 times less. Treated with interferon, but without much success.
CONGENITAL RUBELLA.
The disease is characterized by intrauterine infection of the fetus, its organs are infected. The disease progresses slowly, leading to malformations and (or) death of the fetus.
The virus was discovered in 1962. Belongs to the family togaviridae, genus ribovirio. The virus has a cytopathogenic effect, hemagglutinating properties, and is capable of aggregating platelets. Rubella is characterized by calcification of mucoproteins in the system blood vessels. The virus crosses the placenta. Rubella often causes heart damage, deafness, cataracts. Prevention - 8-9 year old girls are vaccinated (in the USA). Using killed and live vaccines.
Laboratory diagnostics: use hemagglucination inhibition reaction, fluorescent antibodies, complement fixation test for serological diagnostics (looking for class M immunoglobulins).
PROGRESSIVE MULTIFOCIAL LEUKOENCEPHALOPATHY.
This is a slow infection that develops with immunosuppression and is characterized by the appearance of lesions in the central nervous system. Palavaviruses of three strains (JC, BK, SV-40) were isolated from the brain tissue of the diseased.
CLINIC. The disease is observed with immune depression. Diffuse damage to the brain tissue occurs: the white matter of the brain stem, the cerebellum is damaged. The infection caused by SV-40 affects many animals.
Diagnostics. Fluorescent antibody method. Prevention, treatment - not developed.
PROGRADIENT FORM OF TIC-BASED ENCEPHALITIS.
Slow infection which is characterized by pathology of astrocytic glia. There is spongy degeneration, gliosclerosis. Characterized by a gradual (progradient) increase in symptoms, which eventually leads to death. The causative agent is a tick-borne encephalitis virus that has passed into persistence. The disease develops after tick-borne encephalitis or when infected with small doses (in endemic foci). The activation of the virus occurs under the influence of immunosuppressants.
Epidemiology. Carriers are ixodid ticks infected with the virus. Diagnosis includes the search for antiviral antibodies. Treatment - immunostimulating vaccination, corrective therapy (immunocorrection).
ABORTIVE TYPE OF RABIES.
After an incubation period, symptoms of rabies develop, but the disease is not fatal. One case is described when a child with rabies survived and after 3 months was even discharged from the hospital. Viruses in the brain did not multiply. Antibodies were found. This type of rabies has been described in dogs.
LYMPHOCYTIC CHOREOMENINGITIS.
This is an infection in which the central nervous system is affected, in mice the kidneys, liver. The causative agent belongs to arenaviruses. Sick except for humans Guinea pigs, mice, hamsters. The disease develops in 2 forms - fast and slow. With a fast form, chills are observed, headache, fever, nausea, vomiting, delirium, then death occurs. The slow form is characterized by the development of meningeal symptoms. Infiltration of the meninges and vessel walls occurs. Impregnation of vascular walls with macrophages. Anthropozoonosis is a latent infection in hamsters. Prevention - deratization.
DISEASES CAUSED BY PRIONOMI.
KURU. In translation, Kuru means “laughing death”. Kuru is an endemic slow infection found in New Guinea. Kuru discovered Gajdushek in 1963. The disease has a long incubation period - an average of 8.5 years. The infectious onset has been found in the brains of people with kuru. Some monkeys also get sick. CLINIC. The disease manifests itself in ataxia, dysarthria, increased excitability, causeless laughter, after which death occurs. Kuru is characterized by spongiform encephalopathy, cerebellar damage, degenerative fusion of neurons.
Kuru was found in tribes that ate the brains of their ancestors without heat treatment. 10 8 prion particles are found in the brain tissue.
CREUTZFELD-JACOB DISEASE. Slow prion infection characterized by dementia, damage to the pyramidal and extrapyramidal pathways. The causative agent is heat-resistant, stored at a temperature of 70 0 C. CLINIC. Dementia, thinning of the cortex, a decrease in the white matter of the brain, death occurs. The absence of immune shifts is characteristic. PATHOGENESIS. There is an autosomal gene that regulates both sensitivity and reproduction of the prion, which depresses it. Genetic predisposition in 1 person per million. Elderly men are sick. DIAGNOSTICS. It is carried out on the basis of clinical manifestations and pathoanatomical picture. PREVENTION. In neurology, instruments must undergo special processing.
GEROTHNER-STREUSPER DISEASE. The infectious nature of the disease has been proven by infection of monkeys. With this infection, cerebellar disorders are observed, amyloid plaques in the brain tissue. The disease has a longer duration than Creutufeld-Jakob disease. Epidemiology, treatment, prevention have not been developed.
AMIOTROPHIC LEUCOSPONGIOSIS. With this slow infection, atrophic paresis of the muscles is observed. lower limb, followed by death. There is a disease in Belarus. The incubation period lasts for years. EPIDEMIOLOGY. in the spread of the disease there is a hereditary predisposition, perhaps food rituals. Possibly the causative agent is related to cattle diseases in England.
It has been proven that a common disease in sheep, scrapie, is also caused by prions. Suggest a role for retroviruses in etiology multiple sclerosis, influenza virus - in the etiology of Parkinson's disease. Herpes virus - in the development of atherosclerosis. The prion nature of schizophrenia, myopathy in humans is assumed.
There is an opinion that viruses and prions have great importance in the process of aging, which occurs when the immune system is weakened.
Slow infections - group infectious diseases, predominantly affecting the central nervous system, characterized by a long incubation period and a slow, over several months or years, increase movement disorders And mental disorders usually with inevitable death.
Slow infections are caused by viruses (subacute sclerosing panencephalitis, progressive rubella panencephalitis, progressive multifocal leukoencephalopathy) or prions (eg, Creutzfeldt-Jakob disease). Slow viral infections of the CNS can also include the previously discussed chronic form tick-borne encephalitis and HIV encephalopathy, as well as tropical spastic paraparesis.
In the ICD-10, slow CNS infections are coded under A81 (“Slow viral infections of the central nervous system”). It should be emphasized that, according to modern concepts, the classification of prion diseases as viral infections is erroneous. A prion (from the English Pro(etaseoi8 1pGesIou8 par-Ice - letters, a protein infectious particle) is a protein molecule (prion protein) and, unlike viruses and other infectious particles, does not contain nucleic acid. Prion protein is normally found in cells of the central nervous system, especially the brain.The pathological prion protein differs from the normal one in its altered structure and resistance to enzymes that break down proteins - proteases.After entering the cell, the prion comes into contact with the normal prion protein, changing its structure and turning it into a pathological one.
A whole group of neurodegenerative diseases is associated with the accumulation of abnormal prion protein in the brain (see below). The accumulation of prion protein in nerve and glial cells in most prion diseases is accompanied by the appearance of numerous microscopic vacuoles in them, which give the tissue a characteristic spongy (spongioform) appearance, so the morphological substrate of prion diseases is defined as spongioform encephalopathy.
Human prion diseases include:
1. Creutzfeldt-Jakob disease:
a) sporadic (idiopathic);
b) family;
c) iatrogenic;
d) a variant of Creutzfeldt-Jakob disease.
2. Gerstmann-Straussler-Scheinker disease.
3. Fatal insomnia:
a) family;
b) sporadic;
Most cases of prion disease are patients with sporadic Creutzfeldt-Jakob disease, the origin of which remains unclear. In some cases, prion diseases are hereditary and are associated with a mutation of the gene encoding the prion protein (Gerstmann-Straussler disease).
Scheinker, familial Creutzfeldt-Jakob disease, familial fatal insomnia). Only in a small proportion of cases, prion diseases are clearly infectious in nature and are associated with the transmission of prions from sick people or, in the strict sense of the word, are slow infections. Infection can occur when eating products, primarily brain tissue containing a large amount of prions (kuru and some cases of Creutzfeldt-Jakob disease), as well as during a number of medical procedures - transplantation of the dura mater or cornea from patients, the introduction of a growth hormone preparation obtained from pituitary gland patients, blood transfusion (iatrogenic Creutzfeldt-Jakob disease).
But even in these cases, hereditary predisposition is now of great importance.
A81.0 Creutzfeldt's disease- OFD. Same as in ICD-10
Jacob PRFD. Sporadic (idiopathic)
Subacute spongiform) Creutzfeldt's disease
Jacob's encephalopathy, extrapyramidal form with
development of severe dementia, akinetic-rigid syndrome, multifocal cortical myoclonus, kinetic mutism
Note. Creutzfeldt-Jakob disease is diagnosed in the presence of a characteristic clinical picture(onset in middle and old age, rapidly developing - often within 6 months - dementia, cerebellar, extrapyramidal and pyramidal disorders, myoclonus, visual disturbances), characteristic EEG changes (triphasic and polyphasic complexes of sharp waves against the background of EEG flattening), increased signal intensity from the basal ganglia and thalamus on T2-weighted MRI images of the brain and the exclusion of other diseases. Clinical diagnosis can be confirmed by brain biopsy. When formulating a diagnosis, it should be clarified whether the disease is sporadic (idiopathic), familial, iatrogenic (indicating the source of infection). In patients with sporadic disease, if possible, indicate the clinical forms:
1. Occipital (Heidenhain) with a predominant lesion of the posterior sections of the cerebral cortex and the early development of cortical blindness.
2. Ataxic (Brownell-Oppenheimer) with a primary lesion of the cerebellum and trunk and early development of cerebellar ataxia.
3. Extrapyramidal (Stern-Garcia) with a predominant lesion of the basal ganglia and thalamus and the early development of parkinsonism and other extrapyramidal syndromes.
4. Frontal (frontopyramidal) (Jakob) with a predominant lesion of the frontal cortex.
5. Amyotrophic with a predominant lesion of the neurons of the anterior horns.
6. Panencephalopathic (Mizutani) with diffuse lesions of both the gray and white matter of the cerebral hemispheres.
Criteria for the sporadic form of Creutzfeldt-Jakob disease and the variant Creutzfeldt-Jakob disease associated with the consumption of foods containing abnormal prion protein are presented in the Appendix.
A81.1 Subacute sclerosing OFD. The same as in ICD-10.
panencephalitis PRFD. Subacute sclerosing
generalized panencephalitis, rapidly progressive course with the development of dementia, multifocal reflex myoclonus, generalized seizures, spastic tetraparesis
Note. Subacute sclerosing panencephalitis (syn. Dawson's encephalitis, inclusion encephalitis, Van Bogart's leukoencephalitis) is associated with the persistence of an altered measles virus in brain cells. The diagnosis is established in the presence of: 1) a typical clinical picture (increasing dementia, myoclonus, cerebellar ataxia, pyramidal and extrapyramidal syndromes); 2) debut at a young age (5-25 years); 3) periodic complexes on the EEG (high-amplitude biphasic, triphasic or polyphasic waves lasting 2-3 s, repeating every 4-12 s and synchronous with myoclonic jerks); 4) increased titer of anti-measles antibodies in CSF;
5) multifocal white matter changes and cortical atrophy on CT or MRI When formulating a diagnosis, the stage of the disease is indicated:
Stage 1: asthenia, personality changes, apathy or irritability, mild neurological symptoms are possible (dysarthria, incoordination, change in handwriting, trembling, muscle twitching); duration - no more than a few weeks or months.
2nd stage: increase in ataxia, appearance and increase of myoclonus, decrease in intelligence, addition of epileptic seizures, hyperkinesis (like choreoathetosis or dystonia), ataxia, pyramidal disorders
| 1 | 2 | 3 |
| speech disorders, disorders of praxis and visuo-spatial functions, visual impairment due to chorioretinitis, atrophy of the optic nerves, cortical blindness. Stage 3: the patient is bedridden, contact is sharply limited, patients are only able to turn their heads to sound or light, decerebrate rigidity, autonomic instability with a tendency to hyperthermia, impaired sweating, tachycardia, respiratory disorders, uncontrollable hiccups. 4th (terminal) stage: contact with the patient is impossible, limbs are fixed in the position of flexion, mutism, wandering eye movements, the gradual development of a vegetative state and coma |
||
| A81.2 | Progressive multifocal leukoencephalopathy Multifocal leukoencephalopathy NOS | OFD. Progressive multifocal leukoencephalopathy PRFD. Progressive multifocal leukoencephalopathy, rapidly progressive course with the development of severe pseudo-bulbar syndrome, spastic tetraparesis, dementia |
| Note. Progressive multifocal leukoencephalopathy most often occurs in immunodeficient states and is associated with persistence in the brain cells of papovaviruses. On CT and MRI of the brain, multiple foci are detected in the white matter of the brain, brainstem and cerebellum | ||
| A81.8 | Other slow viral infections of the central nervous system | OFD - see note |
| Note. The subcategory includes other slow infections of the central nervous system caused by viruses or prions (progressive rubella panencephalitis, kuru, fatal insomnia, Gerstmann-Schaatrussler-Scheinker disease) | ||
| A81.9 | Slow viral infections of the central nervous system, unspecified Slow viral infections NOS | Code for statistical reporting of unspecified cases with a presumptive diagnosis of “slow CNS infection” |
