ADENOVIRAL DISEASES — the diseases of the adenoviral nature arising preferential at children and proceeding with symptoms of damage of a mucous membrane of respiratory tract, an eye, intestines and also an adenoid tissue.
The following forms of adenoviral diseases of the person are known; acute Qatar of upper respiratory tracts, viral pneumonia, infectious cold, conjunctival fever, Sander's disease, acute follicular and filmy conjunctivitis, gastroenterocolites.
Activators A. are adenoviruses (see).
Value of different serotypes of adenoviruses in pathology is unequal, (tab. 1). Diseases of a respiratory organs cause 3, 4 and 7 serotypes more often, 2, 5, 8, 14 and 21 serotypes are more rare. Faringo-konjyunktivalnaya fever and feverish pharyngitis etiologically are connected with 3 and 7, is more rare with 4 and 14 serotypes. According to R. S. Dreyzin, etc. (1959), at the children sick with acute Qatar of respiratory tracts which is followed by a filmy konjyuktivit adenoviruses of two were allocated, is more often than three serotypes and their etiological value at this form of a disease is proved.
The same adenovirus can cause different farms of diseases that 3 serotypes are especially characteristic of viruses. At the same time different serotypes of adenoviruses can cause the same disease. The serological researches conducted among the population of the USA, Holland, Hungary, Congo, Japan and the USSR confirmed that adenoviruses extend among children of early age, and antibodies to 1, 2, and then to 3 and 5 serotypes are found more often. To five-year age practically all children are infected at least with a virus of one type and 50% of children — not less than four.
ADENOVIRAL DISEASES occupy rather big specific weight among respiratory diseases of a virus etiology (tab. 2).
Apparently from the table, number of laboratory confirmed cases And. considerably exceeds number of cases of all other combined infections (excepting it is mixed ny and, apparently, rinovirusny which in the table are absent); they are on the second place after flu. However, unlike the last, And. are not the reason of widespread epidemics, not to mention pandemics. Most often they meet in the form of the localized flashes, the family centers and individual diseases. In blood had And. specific antibodies collect. Products of antibodies are observed also at an asymptomatic infection. A considerable part of newborn children has oroimmunity which is lost by the end of the sixth month of life of the child that is in relative compliance with the greatest susceptibility to And. also is more senior than children aged from 6 months. By 5 years most of children has antibodies and together with it incidence sharply decreases And. Rather rare incidence of adults, most likely, is explained by earlier postponed infection and the acquired postpremunition.
Children of preschool age are most susceptible to adenoviruses. L. A. Sigayev, etc. (1971) was described by two outbreaks of an adenoviral infection of the 5th serotin among children. The adults who were in continuous and close contact with sick children remained healthy, and the virologic researches conducted at them yielded negative takes. At adults epidemic flashes quite often arise among the people arriving from different areas and for the first time having among themselves close contact (exchange, or mutual, infection), e.g. at the young people who are called up for military service. Mufson (1967) reported observations over 9197 recruits, hl. obr. in army of the USA, the ached acute respiratory infections, among which And. made from 0,5 to 52%.
Seasonality the frequency of diseases has no crucial importance, but in cold season And. increases, excluding faringo-conjunctival fever (see), edges meets in the summer. Mechanism of transmission of infection airborne. However on epidemiological classification of infectious diseases And. it is impossible to carry only to respiratory infections. It is necessary to consider that in patients and carriers adenoviruses the longest time are found in contents of intestines (fig.), in limf, nodes to-rogo there is their reproduction. Therefore it must be assumed that the mechanism of transfer of adenoviruses is carried out both as respiratory, and as intestinal infections.
Sick people and carriers are a source of an infection. Treat the last recovered at which the virus remains up to 50 days, and it is possible, and longer time, and also healthy. It is necessary to consider also the frequency of detection of the adenoviruses similar with human, at animals, including house — cows, pigs, dogs. The interrelation of adenoviruses of the person and animals still demands studying and makes one of the most important problems of epidemiology And.
Adenoviruses quite often define diseases of the mixed etiology. Deserve attention of a research of Pereira and Kandeyas (M. of S. Pereira, J. A. Candelas, 1971), shown that at patients with whooping cough (136 children are inspected) in 30% of cases adenoviruses are allocated, and V. is revealed by pertussis in 22%. Authors conclude that clinical symptoms of whooping cough can be caused not only V. by pertussis, but also other activators, in particular adenoviruses.
Adenoviruses cause the diseases similar on a clinical picture to katara of upper respiratory tracts, pneumonia, gastrointestinal frustration, conjunctivitis. Therefore methods of laboratory diagnosis have crucial importance. They share on virologic (allocation and identification of a virus) and retrospective (the serological researches indicating an etiology of the postponed disease). Allocate a virus from the material received from patients (or virus carriers), by capture of slime with a tampon from a mucous membrane of a throat and a conjunctiva. It is possible to investigate pharyngeal washouts for what the throat is carefully rinsed by 20 ml of buffered saline solution. Kal for a research collect in sterile ware; for capture of material from a mucous membrane of a rectum use also a tampon.
To the taken material (except washout) add 5 ml of saline buffered solution (by immersion of tampons to in advance prepared test tubes) and antibiotics (penicillin, streptomycin and nystatin). After keeping within an hour at the room temperature of a test tube quickly cool in mix of dry ice and alcohol, inventions keep in the refrigerator at a temperature not above — 12 °. The material taken from the patient can be used also without freezing on condition of urgent transportation in laboratory and an immediate research.
Prior to a research it is necessary to homogenize and centrifuge material 30 min. at 3000 rpm for sedimentation of a fabric detritis. Nadosadochny liquid is used for infection of fabric cultures and control crops on bacteriological mediums.
Allocation of adenoviruses is made on the intertwined epithelial cells of HeLa, KV, HEp-2 and other similar lines received from tumoral and normal tissues of the person. Mediums are applied to cultivation of cells according to the copy-books developed for this purpose (see. Cultures of fabrics ), however at transfer of culture in the supporting solutions (before infection) it is not necessary to use serums of people and animals, considering frequent presence at them of adenoviral antibodies.
The infected cultures of cells subject incubations at t ° 37 ° within 14 days, systematically looking through test tubes and comparing them to the control, not infected cultures of the same cells. At good shape of cells in control test tubes duration of an incubation can be increased. Emergence of a visible degeneration demands further passages on fresh cells. In the absence of a degeneration make 2 — 4 «blind» passages directed to accumulation of a virus. In the course of reproduction adenoviruses remain localized in cells and, unlike intestinal viruses, poorly come to a liquid phase of culture, to nutrient solution. Therefore apply the suspension of cells besieged in the centrifuge and processed to passages or crushing in the device like the blender, or repeated snap-freezing and thawing.
The degeneration of cells indicates a positive take of experience. The allocated virus is subject to identification which is carried out by means of reaction of binding complement for definition of group antigen and a neutralization test with specific serums for typing. To reaction of binding complement apply serum of previously immunizirovanny Guinea pigs, to a neutralization test — serum of immunizirovanny rabbits. For immunization of animals producers of serum use prototype strains of the known adenoviruses (see above).
At identification of the strain allocated from solo it is necessary to define its etiological value since it is possible latent And. It is reached by definition of a gain of antibodies in the blood serum taken from the patient at the beginning of a disease and at recovery. Increase in an antiserum capacity not less than by 4 times validates laboratory diagnosis. Along with serological experiences study biological properties of a virus and conduct an elektronnomikroskopichesky research.
Retrospective diagnosis is based on serological tests in which group fixators to the known antigen are defined. Apply a neutralization test and delays of hemagglutination with prototype strains of adenoviruses to detection of standard antibodies.
For diagnosis of adenoviruses in experimental conditions the method of immune fluorescence is used (tsvetn. the tab. of fig. 4 — 7), at Krom fluorescent dyes is found a specific antigen (see. Immunofluorestsention ).
A clinical picture
ADENOVIRAL DISEASES, as a rule, proceed in the form of faringo-conjunctival fever, Qatar of upper respiratory tracts, an intestinal form. The isolated damages of a throat, a conjunctiva, mezenterialny limf are less often observed. nodes.
Adenoviral Qatar of respiratory tracts — a frequent and easiest form A. It is shown by fever (lasting average 3 — 6 days), moderate or easy disturbance of the general condition of the patient and the expressed symptoms of Qatar of respiratory tracts: rhinitis, tracheobronchitis. Occasionally (in 3 — 4% of cases) development of an asthmatic syndrome and laryngitis is possible. Frequent displays of a disease are pharyngitis with the expressed granularity of a mucous membrane and swelling cervical and submaxillary limf. nodes. Vomiting and the speeded-up liquid chair is sometimes noted.
Conjunctivitis — frequent and characteristic display of a disease. In the beginning he is usually unilateral; the second eye can be surprised later. Distinguish catarral, follicular and filmy conjunctivitis. The last form is especially typical for And. The conjunctiva is hyperemic a century, a zernist and a little bulked up; not plentiful allocation of a secret is noted. In 1 — 3 day on a conjunctiva a century, sometimes and transitional folds, gentle filmy plaques of white or grayish-white color appear. The frequent symptom — swelled a century, is sometimes sharply expressed, soft to the touch. Defeat of a cornea (an adenoviral keratoconjunctivitis) occurs at children of early age very seldom.
Faringo-konjyunktivalnaya fever — typiform And., shown a combination of Qatar of respiratory tracts, pharyngitis and conjunctivitis.
Pneumonia it is observed preferential at children of the first year of life. Changes in lungs are connected with specific action of adenovirus, but in developing of pneumonia the main role is played by a secondary bacterial flora. Late pneumonia is caused by hl. obr. bacterial infection. Pneumonia is often combined with Qatar of respiratory tracts or faringo-conjunctival fever. It has intersticial, melkoochagovy, macrofocal or drain, polysegmented character and is usually shown by the expressed symptoms — plentiful mixed rattles and a clear dullness. Short wind, cyanosis, the phenomena of the general intoxication is noted. Convulsive attacks can be observed. Quite often there are vomiting and a diarrhea. Temperature has the wrong character. The disease, especially at children of chest age, tends to a long recurrent current and can come to an end with death.
Intestinal form (adenoviral diarrhea) it is observed preferential at children of the first year of life and characterized by moderately speeded up liquid chair, sometimes with impurity of slime, disorder of appetite; vomiting is occasionally observed. Temperature is increased; the phenomena of Qatar of respiratory tracts are very frequent.
Mesadenitis — rare manifestation And.; it is observed or against the background of other its manifestations or as the main syndrome. It is characterized by sharply arising strong, pristupoobrazny abdominal pains (it is preferential in its bottom, it is frequent in the right ileal area), a feverish state, nausea and sometimes vomiting. The phenomena of irritation of a peritoneum are absent or are expressed poorly. Appendicitis is quite often mistakenly diagnosed, and patients are subjected by operations. Cases of a complication of a mesadenitis are described by invagination of guts.
At newborns some features of a current are noted And.: subfebrile temperature, frequency of dispeptic frustration and pneumonia and, on the contrary, rarity of filmy conjunctivitis and increase limf. nodes. At premature children the disease usually proceeds at a standard or reduced temperature.
Complications: otitises, sinusitis, quinsies and pneumonia — are caused by accession of a bacterial infection. And. can be the cause of an aggravation various hron. inflammatory processes and education hron. tonsillitis.
At diagnosis And. it is necessary to consider its idiosyncrasies: katara of respiratory tracts with the expressed exudative phenomena, moderate intoxication, a frequent combination of various syndromes which consecutive developing is followed by new rises in temperature, the frequency of conjunctivitis. In conditions epid. flashes in children's collective the clinical diagnosis is considerably facilitated.
Treatment of most of patients is carried out in house conditions. Hospitalization (in the boxed departments) are subject patients with a severe form of a disease, in the presence of complications, associated diseases, and also on epid. to indications (e.g., patients from the closed child care facilities). In the feverish period the bed rest is necessary. Food shall be full and vitamin-rich; in the feverish period dominance of milk and carbohydrate food is desirable.
Specific therapy is in a stage of studying. Reviews of efficiency of use of interferon are contradictory. Use of a deoxyribonuclease — an instillation of 0,05% of solution of drug every 3 hour within 2 — 3 days in a nose (on 3 — 4 drops) and in a conjunctival sac is offered (on 1 — 2 drops). Also intramuscular administration of gamma-globulin of the directed action i.e. containing specific antibodies in a considerable caption is recommended. Antibiotics are shown only at pneumonia and other complications of the bacterial nature. Pathogenetic and symptomatic therapy is carried out generally as well as at other respiratory viral infections. In the presence of a hyperthermia — antibiotics, acetilsalicylic to - that, pyramidon inside or intramusculary, a bubble with ice on the head, cold drink; the seriously ill patient appoints drop introduction to a rectum of the cooled ringerovsky solution. For the purpose of desintoxication — intravenous injection of plasma, hypertonic salt solutions of glucose. At the expressed katara of respiratory tracts apply an instillation in a nose of solutions of ephedrine, sanorin, expectorant; at an asthmatic syndrome — ephedrine, antihistaminic drugs, the distracting therapy (mustard plasters, hot foot baths). At cardiovascular weakness appoint Cordiaminum, caffeine, ephedrine, an oxygenotherapy. Treatment pneumonia is carried out by the general rules accepted in pediatrics (see. Pneumonia , at children).
Prevention And. it is developed in the direction of receiving vaccines of three types: inactivated, live and associated. Due to the existence of a set of types of adenoviruses introduction to a vaccine of many antigens is necessary. But since it is the most frequent And. cause adenoviruses of 3, 4 and 7 ssrotip, they also are components of the adenoviral inactivated vaccine. For an inactivation of adenoviruses use formalin, and for strengthening of an immunogenicity — dopolnitel in the form of mineral oil [G. Meiklejohn, 1961]. Formalin and formol-oil vaccines are applied subcutaneously and intramusculary. R. S. Dreyzin and V. M. Zhdanov (1962) consider that vaccination only against adenoviruses is inexpedient in view of a large number of respiratory viral and bacterial infections, so frequent at children. Therefore they speak in favor of virusnobakterialny vaccines from the killed antigens adsorbed on aluminum hydroxide.
Vaccination by a live peroral vaccine is offered by Huebner. Tropism of adenoviruses to an adenoid tissue and their ability not only it is long to remain in intestines, but also to breed in it allow to assume efficiency of such vaccination. First observations of Kaush (R. Century of Couch), etc. (1962) showed that the strains of adenoviruses of 4 and 7 types entered through a mouth in gelatin capsules to adult volunteers caused in them products of antibodies which were more expressed than at introduction of the inactivated vaccine. The competition of two antigens in intestines was not observed. Op a dignity a number of experiments on infection of volunteers with adenoviruses through upper respiratory tracts therefore increase in specific antibodies in blood at vaccinated was observed. Similar experiment was made by A. A. Smorodintsev and A. A. Selivanov (1959). Authors showed that live adenoviruses of 4, 5 and 7 serotypes after 4 — 6 passages on tissue of kidneys of monkeys cause in volunteers slight feverish reaction without the catarral phenomena with the subsequent development of immunity. Use of a live adenoviral vaccine was not beyond a limited experiment yet.
In the USA preventive vaccination against And. it was repeatedly carried out among soldiers of the first year of service who as showed statistical data, are most susceptible to acute respiratory diseases. For this purpose the vaccine inactivated at t ° 37 ° by formalin in cultivation 1 was used: 4000 in a dose of 1 ml subcutaneously or intramusculary. Most often the vaccine consisted of three types of adenoviruses: 3, 4 and 7. Besides, the live attenuirovanny enteral vaccine was applied. As antigen also other types of adenoviruses were used. In controlled group decrease in diseases of the respiratory infections caused by 4 and 7 types of adenoviruses was noted.
However these researches, despite positive takes, did not receive practical implementation, in particular for the vaccination put. The reason of it is that adenoviruses in an experiment have cancerogenic properties, stimulating malignant regeneration of cells of in vitro, and cause tumors in an experiment in young animals (in more detail — see. Adenoviruses ). Therefore the enteral vaccine prepared from the adenovirus 4 types deprived of oncogenous properties was tested more widely. According to Chanok (R. M of Chanock, 1967), such vaccine is checked for 23015 servicemen recruits. It was harmless, did not cause side reactions, but, as one would expect, the vaccine of a tipospetsifichn also has protective properties only to And. 4 types. The general decrease in incidence at vaccinated made 59%.
Usual measures of prevention: airing of the room, uv radiation of rooms at absence in them of people, washing of surfaces solution of drugs of chlorine, boiling of the contaminated clothes and linen.
See also Respiratory viral diseases .
The table 1 TYPES of ADENOVIRUSES, VYDELENNYH V of the USSR AT VARIOUS DISEASES (according to R. S. Dreyzin and V. M. Zhdanov. 1962)
The table 2 RATIO of VARIOUS GROUPS of VIRUSES, ALLOCATED AT INSPECTION of PATIENTS with RESPIRATORY DISEASES (on I. V. Antonova and L. Ya. Zakstelskaya's materials, 1972)
* Researches are conducted in the different regions of the USSR.
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