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Cases are described of chronic zoster encephalitis presenting with the leading progressive focal epilepsy syndrome. The clinical presentation of the trouble can include both general cerebral signs and those of the focal affection of the central nervous system only. The progressive course and duration of remission suggest to us a persisting infection manifesting against the background of immune deficiency.

An experimental model of herpetic hepatitis is developed, levels and time course of changes in transaminases, the main indicators of lipid metabolism, are characterized, and morphologic features of hepatocyte injury by herpes simplex virus are shown. Liver involvement in herpetic infection is described in detail.

A serological study of blood from 44 patients with acutely progressive forms of pulmonary tuberculosis revealed their rather common association with active forms of the following opportunistic infections, such as M. pneumonia, Pn. carinii, and herpes simplex virus.

Studies on the epidemiology of infections caused by Herpes simplex virus, cytomegalovirus and Epstein-Barr virus in different age groups of the population of the Republic of Belarus, carried out over the period of many years, are summarized. The frequency of clinical manifestations of different forms of herpetic viral pathology in newborns, children and adults in different regions of the republic was studied. More frequent cases of the most severe clinical forms of herpetic viral infections (encephalitides, generalized infection) were noted in persons having immunodeficient states of different etiology, as well as among the population residing on the territory with unfavorable radiation conditions as a consequence of the catastrophe in the Chernobyl nuclear electric power station. For further study of the specific features of the epidemiology of herpetic obligatory registration of all cases of herpetic viral infections, starting from January 1, 1996, was introduced.

9 lethal cases of progressive dementias were analysed, both psychical and neurological disturbances characteristics on different stages of herpetic dementias were presented, a number of clinical morphological criteria of diagnosis ascertaining was described. It was determined that progressive dementias turned out to be one of the clinical forms of chronic CNS herpetic infection which was conditioned by prolonged persistence and activation of herpes simplex virus in brain tissue.

Clinical (n = 137) and virological (n = 50) analysis of the course of herpetic stomatitis in children with acute lymphoblastic leukemia was carried out. 97.8 +/- 1.4% of cases were relapses of a chronic herpetic infection, 73.8 +/- 3.7% of cases ran a medium severe or severe course. Herpetic stomatitis in children suffering from acute lymphoblastic leukemia was characterized by the following features: 1) a high risk of infection generalization; 2) progressive necrosis of tissues in a state of leukopenia; 3) infiltration at the site of necrosis; 4) tissue anemia; and 5) risk of hemorrhage from necrotic sites.

A clinical picture of herpetic stomatitis was studied in 173 newborns, 122 of these preterm and 51 full-term ones, aged 2 to 43 days. Herpesvirus origin of the disease was proved in 68 out of 77 examinees with stomatitis (88.31 +/- 3.66%) by virological and immunofluorescent methods. The authors conclude that herpetic stomatitis in newborns is usually a result of ante- and perinatal infection, with intrauterine infection occurring in 37.57 +/- 3.68% cases.

The features of thymus involvement in pathologic process in different types of experimental herpetic infection in rabbits were studied using morphologic and immunologic analysis methods. Insignificant features of thymus pathology were revealed in animals with regional manifestations of the infection in the form of ophthalmoherpes, whereas the rabbits with generalized herpes simplex virus (HSV) infection by retrosternal administration showed pronounced structural-functional changes and the presence of virus antigens as well, which may indicate the possibility of HSV reproduction in thymus cells.

As a result of herpes simplex virus reactivation with holoxan in rabbit reconvalescents with acute primary herpetic keratoconjunctivitis, the ophthalmic herpes relapse was observed and it was characterized by a more severe and prolonged course with longterm viremia and generalization of the infection. In the survived animals the chronic, recurrent ophthalmic herpes was developed.

Basing on the evidence provided by clinicomorphological and immunobiological studies, three, patients with progressive epileptic seizures were found to have chronic herpetic inflammation in the brain. The seizures took serial pattern with development of status epilepticus.

The authors describe the course of herpetic encephalitis in 52 patients aged 16 to 64 years. Five types of the initial manifestations of herpetic infection of the CNS were revealed. In 44.3% of cases the disease started from the general cerebral symptomatology and consciousness disturbance; in 13.6% it started in a brain stroke-like manner followed by the development of the comatose status; in 13.6% of cases from memory disorder and unmotivated actions; in the same percentage of cases, the disease onset was marked by the dominance of dizziness, diplopia, ataxia and central hemiplegia ; in 15.9% the disease started from pains in the stomach, loin and lower limbs. Hemispheric and pseudotumorous stem encephalitides (48.1 and 13.6% respectively) were predominant; in 25% meningoencephalitides and in the remainder, encephalomyelitis running their course in the form of disseminated encephalomyelitis (5.7%), focal myelitis (5.7%) or opticomyelitis (1.9%). The data presented attest to the pleomorphism of the clinical picture of herpetic lesions of the CNS.

Based on analysis of 17 cases with chronic herpetic encephalitis and encephalomyelitis, the authors demonstrate the diversity of the clinical manifestations of the illnesses. A problem of the progredient forms of those neurologic infections is discussed.

Clinical, morphological, and virological characteristics of a model of herpes infection of the CNS with predominant involvement of the spinal cord, an acute ascending myelitis with primary demyelinization, are presented. The development of spinal cord lesions after HSV inoculation into the spleen was observed in different species of laboratory animals: mice, hamsters, guinea pigs, and rabbits; some animals (30%-70%) developed generalized infection with the involvement of the brain. The frequency of the spinal cord involvement was found to depend on the age of the animal and the dose of the virus-containing inoculum. Differences in the clinical and morphological manifestations of herpes infection were due to different mechanisms of herpes simplex virus spread in the body: either centripetally on the axons of the visceral nerves innervating the spleen into the thoracal cord, or hematogenic disseminations with virus penetration across the hematoencephalic barrier. The total duration of the disease was 3-12 days depending on the animal species.

The use of specific immunoglobulin in combination with conventional agents of pathogenetic and symptomatic therapy was over two times more potent in reducing the lethality due to herpetic encephalitis. The residual phenomena in the survivors were also less pronounced in those given specific immunoglobulin. A relationship has been discovered between the outcomes of herpetic encephalitis and the time since the treatment with specific immunoglobulin was instituted, the rate of coma development and its intensity at the moment of the therapy onset.

Methods aimed at the detection of causative agents in the CSF and peripheral blood lymphocytes are recommended for the use in intravital laboratory diagnosis of slow infections of the central nervous system. The results obtained enable recommending the biotest on guinea-pigs or indication of the causative agent of amyotrophic leukospongiosis (AL) in cell culture coupled with the punctate immunoenzyme assay for the diagnosis of AL. As to the diagnosis of Creutzfeldt-Jacob disease, it is suggested that the biotest on guinea-pigs and the punctate immunoenzyme assay may be used.

Uterine cervix biopsies from 450 patients with endocervicosis were studied morphologically. Giant cell metamorphosis, nuclei hypertrophy and hyperchromatism with intranuclear viral basophilic inclusions typical for herpes infection were found in 24 cases (5.3%). These cell alterations were mainly observed in squamous epithelium of the uterine cervix, columnar epithelium of the glands and to a lesser degree in the stromal fibroblasts and vascular endothelium. These morphological changes were confirmed in 6 of 10 cases by means of the fluorescent antibodies to the herpes simplex viral antigen.

Modelling of generalized herpetic infection of Guinea pigs is described. It took the course in the form of acute or subacute recurring process with either involvement of separate internal organs, or disseminated involvement of all visceral organs, or principal involvement of subcortical structures of the brain, or involvement of the brain and spinal marrow and marked vegetative failures. Signs of vasculitis; development of disseminated intravascular coagulation (DIC) syndrome and CNS demyelinization are detected in animals during the terminal period.

Specimens of mixed untreated saliva from 3 groups of children were tested for antibodies to herpes virus by the fluorescent antibody technique (33 children with acute herpes stomatitis, 64 with recurrent herpes stomatitis, and 30 in the control group). Herpes virus antibodies were found in the saliva in 27.2 +/- 7.7% of the cases at the peak of acute stomatitis and in 77.7 +/- 10.0% of cases in the period of epithelization, in 84.6 +/- 10.0% of the examined subjects the antibodies were detected 2-4 months after the disease. Examinations of 64 saliva specimens obtained from the children during one of the relapses of chronic stomatitis demonstrated antibodies more frequently (59.3 +/- 8.0%) than in children at the peak of acute stomatitis disease. A trend for increased antibody content in the saliva of children by the period of epithelization of lesions in the buccal cavity both in acute stomatitis and during relapses of chronic disease was observed. No herpes antibodies were found in saliva specimens from 30 children of the control group.

The study of the brain of a patients with amyotrophic leukospongiosis and the brain of squirrel monkeys with the experimentally induced disease has resulted in the isolation of an agent which, in accordance with its physicochemical and biological properties, can be classified with unconventional viruses. The results of the experimental reproduction of the disease in laboratory animals have confirmed its etiological role in the development of the disease.

The results of modelling of amyotrophic leukospongiosis, a new form of slow infection of the human central nervous system, on guinea-pigs are reported. The animals were injected retrobalbulary with the virus-containing suspension. 1.5-2.5 weeks after the injection 70% of animals revealed signs of retinopathy during ophthalmoscopy. Two months later 90% of animals died, 40% of them exhibiting manifestations of the infection. Experimental amyotrophic leukospongiosis was histologically confirmed in all the dead animals. This method of modelling made it possible to shorten the incubation period to 1.0-2.0 months, while in intracerebral and intramuscular ways of contamination it was 3.5-8.2 and 5.3-11.1 months, respectively. The results evidence the involvement of the peripheral visual analyzer in the pathogenesis of experimental leukospongiosis at the early stages of its development.

Biochemical blood serum tests at different stages of amyotrophic leukospongiosis have shown differences in lactate and pyruvate levels as well as in lactate dehydrogenase activity, indicative of the increased oxidative exchange in sick guinea-pigs. It is suggested that intensified glycolysis is a compensatory-adaptive reaction in response to hypoxia due to respiratory disorders (spinal type) and degeneration and death of motoneurons. Leukospongiosis was accompanied by the decline in the complement level in the blood serum and production of antibodies to nervous fiber proteins.

Four groups of herpetic affection of the central nervous system have been described: meningitis, meningoencephalitis, encephalitis and encephalomyelitis. Each condition has a variety of neurological manifestations. Clinico-pathogenic aspects of the problem are discussed.

Amyotrophic leukospongiosis (ALSP) was produced in laboratory animals: hamsters, rabbits, guinea pigs. Guinea pigs were found to be a most suitable laboratory model for the study of ALSP pathogenesis with the longest incubation period. The data are obtained verifying the role of previously isolated unconventional virus in the ALSP etiology.

The theoretical foundations of the laboratory diagnosis of Creutzfeldt-Jakob disease and amyotrophic leukospongiosis in living patients are discussed and practical diagnostic methods are proposed on the basis of the study of the biological properties of nonclassical viruses and the pathogenesis of slow infections of the central nervous system. The use of the retrobulbar method of infecting susceptible animals has permitted, besides a considerable decrease in the incubation period in modeling slow infections, the improvement of the in vivo biological test. Thus, as the result of the multiplication of non-classical viruses in the visual nerve and the retina, experimental animals develop retinopathy which can be detected 1.5-2.5 weeks after the animals are injected with the spinal fluid or blood taken from the patient under examination. To diagnose amyotrophic leukospongiosis, the in vitro biological test, based on the capacity of the causative agent for inducing a considerable (2- to 5-fold) increase in the mitotic activity of HEp-2 cells, has been developed. The comparative studies have shown the expediency of using the method for the detection of antibodies to nerve-fiber proteins as an additional test for the differential diagnosis of slow infections of the central nervous system.

The results of five years studies on the possibility of experimental induction of bovine leukemia with purified BLV and different BLV-containing materials demonstrated that inoculation of calves with purified BLV (structures of 1.14-1.17 g/ml density in 20-60% sucrose gradient) can induce oncornavirus infection and bovine leukemia. From 41 experimentally infected calves 9 showed evidence of bovine leukemia. 5 of these 9 animals were from a group of 22 calves inoculated with purified BLV. Diagnosis of bovine leukemia in these 9 animals was established by hematologic (3 animals) and histologic method (6 animals). BLV was isolated from leukocytes of all of them. It was shown also that before the development of bovine leukemia the development of oncornavirus infection takes place. But only a small part of the animals with oncornavirus infection and presence of antibodies became ill with typical forms of hemoblastosis. The investigation of the role of milk and blood cells in milk in bovine leukemia transmission was also carried out. The presence was demonstrated of oncornavirus structures antigenically identical with BLV in milk and reproduction of these structures in blood cells being present in milk. These results, and also the induction of bovine leukemia, in cattle by rearing with raw milk from cattle with leukemia, allow us to suppose the possible routes of bovine leukemia transmission in nature.

The paper describes isolation from the brain of a patient who died of amyotrophic leukospongiosis (ALSP) and from squirrel monkeys with experimentally induced disease of heretofore unknown agents whose reproduction in continuous cell lines (HEp-2, CV-1, Vero) was accompanied by a significant increase in the mitotic activity of cells and adsorption of human 0(1) and M. rhesus erythrocytes. The blood sera from patients with ALSP and a monkey with experimental disease were found to contain a factor specifically inhibiting the hemadsorption phenomenon and the increase of the mitotic activity in the infected cell cultures. Investigations of the properties of the isolates showed them to have a buoyant density of 1.18 g/cm3 in a 20-60% sucrose gradient, to incorporate radioactive precursors of RNA and protein synthesis, and to be highly resistant to the effect of some physical and chemical factors. The data obtained suggest that the isolates differ from all the presently known conventional viruses but have some similarity with etiological agents of slow infections and may be classified as unconventional viruses.

The results of parenteral (2 to 3 injections of 1.5 to 3 ml once on 3-rd to 4-th day) application of the prepared immunoglobulin with the titer of antiherpetic antibodies of 1:512 to 1:1024 in combined treatment of 2 groups of patients are summarized. In 34 children aged 2 to 12 years recurrent herpetic stomatitis was at its exacerbation. In 27 patients aged 1 to 3 an acute (primary) herpetic stomatitis was present and the group was considered, on grounds of the originally designed prognostic system, as being at high risk of transition into the chronic frequently exacerbating form of the disease. Positive immediate anti-recidive and preventive effect was obtained and confirmed in 12 to 24 months' follow-up.