An experience in the clinical use of specific immunoglobulin from horse blood serum for prophylaxis of Ebola haemorrhagic fever.

The aim of this work was to estimate the efficacy and safety of single intramuscular introduction of specific heterologous immunoglobulin as prophylactic drug against Ebola hemorrhagic fever. Materials and methods. The specific heterologous immunoglobulin was introduced as a special prophylactic drug to 28 patients in epidemic situations, after skin hurt with infectious materials or contact with infectious blood. Clinico-laboratory observation was performed in 24 subjects after single intramuscular introduction of heterologous immunoglobulin Ebola. The samples of blood serum were investigated for immunoglobulin Ebola and antibodies to horse gamma-globulin on the 30th and 60th days after prophylaxis. Results. None of the subjects of the study contracted Ebola fever. There were no anaphylactic reactions after special prophylaxis with specific heterologous immunoglobulin. Among the subjects with normal allergic state 31% responded with local reactions; 13%, with a general reaction (mild case of the serum disease). Almost no reaction was observed in patients with unfavorable allergic state subjected to desensitizing therapy; in the absence of desensitizing therapy, 50% of patients with unfavorable allergic state exhibited local reactions; 17%, mild cases of the serum disease; 33%, moderate cases of the serum disease. In summary, if the tactics of immunoglobulin application was right, the quantity of local allergic reactions was 28%; of wide spread reactions, 6%. Weak serum disease was observed in 11% of the subjects. The prognostic period of resistance to Ebola fever was less than 30 days. Conclusion. The prophylactic use of specific immunoglobulin from horse blood serum against hemorrhagic Ebola fever is effective and relatively safe in patients subjected to desensitizing therapy.

[Bolivian hemorrhagic fever].

Analysis of data of the available literature on epidemiology of Bolivian hemorrhagic fever, manifestations of human disease, biological properties of the causative agent and development carried out abroad of means and methods of diagnostics, prophylaxis and therapy of this infection that presents a potential threat for the population and economy of the Russian Federation in case of introduction of the causative agent is presented.

[Rift valley fever].

In the last quarter of century virus of Rift valley fever (RVF) sharply extended its distribution by moving from Africa to Asia and evolving from low- to high pathogenic for humans causing severe hemorrhagic disease, practically equaling in this respect with some members ofa group of extremely dangerous pathogens. Morbidity and epidemics of RVF are analyzed. Evolution of epidemic development of the infection is examined. Necessity of development of means and methods for diagnostics, prophylaxis and therapy of RVF is underlined.

[Hantapulmonary syndrome].

Features of hantavirus pulmonary syndrome are considered in the review - zoonosis natural focal polyetiological viral infection, that is characterized by lung injury. Etiology of the disease, main characteristics of the agents, epidemiology, contagiousness, pathogenesis, clinical presentation of this pathology are examined. Laboratory diagnostics, therapy and prophylaxis ofhantavirus pulmonary syndrome are described.

[Argentine hemorrhagic fever].

Features of the Argentine hemorrhagic fever are described in the review. Epidemiology, etiology, clinical presentation and pathogenesis of the disease are examined. Special consideration is given to the features of the pathological agent of Argentine hemorrhagic fever--the Junin virus. Features of the disease diagnostics are indicated--virological and serological studies, immunochemical and molecular-biological methods of identification of the pathological agent and antibodies against it. Approaches to etiotropic therapy of this disease and vaccination are examined. Based on the foreign experience perspective guidance for the creation of the system of protection of the population of the Russian Federation against Argentine hemorrhagic fever are presented.

[Stabilization of peroxidase conjugates used in enzyme immunoassay systems to detect Ebola and Marburg virus antigens].

The time course of changes in the activity of solutions of horseradish peroxidase conjugates with immunoglobulins against Ebola and Marburg fevers was studied in the presence of different components. The series of the conjugates of ELISA kits for the detection of Ebola and Marburg virus antigens, which were prepared on the basis of the designed stabilizing solution, preserved at less than 90% of its baseline activity during 10 months at a storage temperature of 2 to 8 degrees C.

[Chemotherapy for Bolivian hemorrhagic fever in experimentally infected guinea pigs].

The efficacy of the antiviral agents nucleoside analogues manufactured in Russia and foreign countries against Bolivian hemorrhagic fever in the treatment and rapid prevention regimens was studied in guinea pigs. In rapid prevention and treatment of guinea pigs, the intraperitoneal injection of 1/10 of the equivalent dose of vero-ribavirin for this animal species was ascertained to protect 70% of the animals infected with Machupo virus strain Carvallo in doses 8 and 10 LD50.

[Evaluation of the probability of the infection of medical personnel with Crimean-Congo hemorrhagic fever virus in cases of introduction of the infective agent to a non-endemic territory of Russia].

The data on the secondary cases of infection with Crimean-Congo hemorrhagic fever (CHF) virus during the period of 1960 - 2002 have been analyzed and the probability of the infection of medical personnel with this virus has been evaluated. The data obtained in this study may be used in the development of the mathematical model of CHF epidemics (outbreaks), taking into account not only the transmission of the infective agent, but also hospital infection, as well as for calculating the number medical personnel, necessary for the liquidation of CHF epidemics (outbreaks).

[Clinical studies of vaccine TEOVac under the conditions of remote revaccination].

In the clinical trials of vaccine TEOVac in lower and reglamented doses under the conditions of remote vaccination, carried out on 11 volunteers, local reactions in the form of hyperemia, gingival edema (1 vaccinee), faucial hyperemia, enlargement of submaxillary lymph nodes (2 vaccinees) were registered in some of the vaccines; in one vaccinee systemic postvaccinal reaction of medium gravity was observed. Revaccination produced no negative effect on the hematological and biochemical characteristics of the blood, as well as on the urine characteristics. The study of the sensitizing vaccine to the antigens of the accumulation substrate (chick embryo), as well as its influence on the development of autoimmune reactions, revealed the absence of the allergic action of the preparation and its influence on autoimmune processes in the vaccines. The trial of the smallpox vaccine in tablets under the conditions of the primary immunization of adults was the topical and most promising trend in the improvement of smallpox vaccination, as the preparation TEOVac proved to be safe, in contrast to the traditional smallpox vaccine introduced by the scarification method, for both vaccines and nonimmunized persons having contacts with them.

[The antiviral efficacy of ribamidil in an experimental infection of animals with the Venezuelan equine encephalomyelitis virus]. / Protivovirusnaia éffektivnost' ribamidila pri éksperimental'noi infektsii zhivotnykh, zarazhennykh virusom venesuél'skogo éntsefalomielita loshadei.

Considerable differences in antiviral efficacy of ribamydil were demonstrated in various animals experimentally infected with Venezuelan equine encephalomyelitis virus. The infection in baboons was quite similar to the manifestations of this disease in man as reported in the literature. With ribamydil used prophylactically, manifestations of the infection in monkeys were less marked.

[Comparative evaluation of test-systems for detection of Venezuelan equine encephalomyelitis virus and variola virus using dot immunoenzyme assay and solid-phase lanthanide immunofluorescent assay]. / Sravnitel'naia otsenka test-sistem dlia opredeleniia virusov venesuél'skogo éntsefalomielita loshadei i ospovaktsiny metodami tochechnogo immunofermentnogo analiza i tverdofaznogo lantanidnogo immunofliuorestsentnogo analiza.

The sensitivity and specificity of 4 experimental test systems for dot enzyme immunoassay (dot-EIA) and solid-phase lanthanide immunofluorescent analysis (SP LIFA) were studied with Venezuelan equine encephalomyelitis (VEE) and variolovaccinia viruses. Test systems for SP LIFA proved to be 25 times more sensitive than those for dot-EIA. The test systems were highly specific and did not react with the heterologous viruses and proteins. Diagnostic agent for detecting VEE virus in dot-EIA was false-positive with Sindbis virus in low dilutions. The first trials of the Russian test systems for dot-EIA and SP LIFA showed that these systems rapidly and reliably detect VEE and variolovaccinia viruses in liquid samples.

[Development of the immunoenzyme test-system for detection of Ebola virus antigen]. / Razrabotka immunofermentnoi test-sistemy dlia opredeleniia antigena virusa Ebola.

An enzyme immunoassay system has been developed for the detection of Ebola virus antigen. It permits a highly accurate and sensitive rapid detection of the antigen. Optimal dilutions of specific immunoglobulin (1:500, corresponding to protein concentration of 50 micrograms/ml) and conjugate were found. The resolving capacity of the new test system is 1.9 x 10(-7) g protein.

[Viral haemorrhagic fevers--evolution of the epidemic potential]. / Virusnye gemorragicheskie likhoradki--évoliutsiia épidemicheskogo potentsiala.

In this review modern data on dangerous and particularly dangerous viral haemorrhagic fevers caused by a group of viruses belonging to the families of phylo-, arena-, flavi-, bunya- and togaviruses are presented. Morbidity rates and epidemics caused by Marburg virus, Ebola fever virus, Lassa fever virus, Argentinian and Bolivian haemorrhagic fever viruses, dengue haemorrhagic fever virus, Crimean haemorrhagic fever virus, Hantaviruses are analyzed. Mechanisms of the evolution of the epidemic manifestation of these infections are considered. The importance of the development of tools and methods of diagnosis, rapid prevention and treatment of exotic haemorrhagic fevers is emphasized.

[Laboratory diagnostics of the outbreak of Crimean haemorrhagic fever in Southern Russia]. / Laboratornaia diagnostika vspyshki krymskoi gemorragicheskoi likhoradki na iuge Rossii.

The results of the serological analysis of blood sera taken from patients with Crimean haemorrhagic fever (CHF) and from persons suspected for this disease are presented. These results made it possible to confirm that during the period of April 16-September 04, 2000, the outbreak of CHF occurred on the territory of Southern Russia. In addition to the laboratory confirmation of the outbreak of CHF by means of the enzyme immunoassay and the indirect immunofluorescence test the diagnostic work was completed by the isolation, and subsequent identification, of 3 strains of CHF virus from the blood of patients and 1 strain from the pool of ticks Hyalomma marginatum.

[Isolation and identification of Crimean-Congo hemorrhagic fever virus in the Stavropol territory]. / Vydelenie i identifikatsiia virusa Krymskoi-Kongo gemorragicheskoi likhoradki v Stavropol'skom krae.

The results of the isolation and identification of the causative agent of a haemorrhagic fever outbreak in the Stavropol Territory are presented. The virus isolated from blood of haemorrhagic fever patients by virological methods was identified in serological and molecular tests as Crimean haemorrhagic fever virus. This epidemiological analysis testify to increased activity of the natural focus of Crimean-Congo haemorrhagic fever in this area due to a number of natural and other factors leading to intensification of its epidemic realization.

[Isolation and identification of the smallpox virus which caused iatrogenic vaccinia in children in the city of Vladivostok]. / Vydelenie i identifikatsiia virusa ospovaktsiny, vyzvavshego iatrogennuiu vaktsiniiu u detei v g. Vladivostoke.

The comparative study of the specimens of the morphological elements of exanthema obtained from 8 children with the clinical diagnosis of secondary exogenic vaccinia, dried smallpox vaccine and the cultures of other orthopoxviruses (rabbit pox, monkey pox and buffalo pox viruses) was made. The isolation and identification of the causative agents from the specimens was carried out with the use of modern virological, electron microscopic and molecular methods. The study proved the fact that 8 children had orthopoxvirus infection with its causative agent identified as vaccinia virus.

[Isolation and identification of the infective agent of severe acute respiratory syndrome (SARS) from a patient with atypical pneumonia]. / Vydelenie i identifikatsiia vozbuditelia tiazhelogo ostrogo respiratornogo sindroma (TORS) ot bol'nogo atipichnoi pnevmoniei.

The virological, morphological, molecular biological and immunochemical study of the infective agent isolated from the patient with the symptoms of atypical pneumonia, hospitalized in the infectious department of the clinical hospital in Blagoveshchensk, was carried out. Thus the fact of the appearance of SARS virus on the territory of Russia was proved. The isolated infective agent, identified as coronavirus strain CoD, was partly characterized and deposited to the virus collection of the Center of Special Laboratory Diagnostics and Treatment of Quarantine and Exotic Infectious Diseases.

[The laboratory diagnosis of an outbreak of hemorrhagic fever at Oblivskaya village, Rostov Province: proof of the etiological role of the Crimean-Congo hemorrhagic fever virus]. / Laboratornaia diagnostike vspyshki gemorragicheskoi likhoradki v stanitse Oblivskoi Rostovskoi oblasti: dokazatel'stva étiologicheskoi roli virusa krymskoi-kongo gemorragicheskoi likhoradki.

The results of the molecular biological detection of the etiologic agent of hemorrhagic fever in Rostov Province are presented. The role of the causative agents of Astrakhan rickettsial fever, hemorrhagic fever with the renal syndrome, Q fever, leptospirosis and listeriosis has been excluded by means of such immunochemical reactions as the direct and indirect immunofluorescent tests, the solid-phase immunoenzyme assay, the complement fixation test and the agglutination test. The relationship between the cases of hemorrhagic fever in the focus of the outbreak and Crimean-Congo hemorrhagic fever virus has been demonstrated due to the use of the polymerase chain reaction with preliminary reverse transcription.

[Crimean-Congo hemorrhagic fever in Rostov Province: the epidemiological characteristics of an outbreak]. / Krymskaia-Kongo gemorragicheskaia likhoradka v Rostovskoi oblasti: épidemiologicheskie osobennosti vspyshki.

The results of the epidemiological analysis of the outbreak of hemorrhagic fever which was caused by Crimean-Congo hemorrhagic fever virus and occurred during the period of July 3-19, 1999, in the Oblivskaya district of Rostov Province are presented. The specific epidemiological features of the outbreak have been determined. The possible versions of the appearance of the focus of infection and the role of Ixodes ticks in the circulation of the infective agent are discussed.