[Role of host in spontaneous recovery from viral hepatitis C: the body's condition at the moment of infection].

The condition of the host at the moment of infection is that its immune competence largely determines the efficiency, kinetics, and profile (Thl/Th2) of a further specific immunity response and, accordingly, the outcome of penetration of hepatitis C virus (HCV) into the body and subsequent acute infection (if it occurs). The parameters determining immune competence may include age, traumatizing exposures (operations, burns, wounds, and fractures), immunosuppressive therapy, stresses, con-infections, and alcohol use. The highest rates of spontaneous convalescence from HCV infection are observed in children and adolescents. Other human conditions are much shorter, transient; their impact is difficult to determine in the retrospective review and therefore it has not been adequately studied. Previous operations, posttransplantation immune suppression, immune modulation after blood transfusion, alcohol-induced immune imbalance, drug and narcotic intoxication are poor predictors. Immunosuppression and immune imbalance caused by viral and parasitic infections are observed among the host's temporary conditions affecting the outcome of HCV infection. The authors have analyzed the sequels of superinfections in patients with chronic hepatitis C, other hepatotropic viruses and the common liver fluke Schistosoma mansoni. The interesting therapeutic activities against HCV and parasitic infection (contamination with Echinococcus granulosus in particular), which are shown in the treatment of co-infection patients with alpha-interferon preparations that ensure normalization of immune deficiency caused by each of the infections and their increased combination. A deeper insight into the correlation between the condition of the host and its ability to eliminate the virus may be one more step on the road to the prevention of the infection and to the designing an effective vaccine against HCV.

[Role of a host in spontaneous recovery from viral hepatitis C: genetic predetermined factors].

The impact of both congenital and specific human immune responses on the invasion of viruses is determined by a broad spectrum of genetically determined parameters. The review attempts to characterize the influence of genetic determinants on the outcome of human hepatitis C viral (HCV) infection. The increased rate of convalescence is associated with female sex and white ethnicity. Hereditary immune disorders/deficiency lead to the reduced probability of spontaneous convalescence and the complicated course of a chronic stage of the disease. The carriage of some HLA haplotypes and gene alleles, which determine the development of an immune response following the Th1 or Th2 type, is essential in predicting both the outcome of acute HCV infection and the course of chronic hepatitis C. Specifically, the higher elaboration of IFN-gamma and IL-12 which specify a Th1 immune response facilitates the good outcome of HCV infection. At the same time, the increased generation of Th2-orienting IL-6 and IL-10 predisposes to the chronic course of the disease. In recent studies, the outcome of the infection is also associated with the polymorphism of genes, encoding for low-density lipoproteins and complement type 1 receptors, with other genes determining the development of a congenital immune response and a specific one. The understanding of genetic predisposition of the outcome of HCV infection and the possibility of its prediction may make a considerable contribution to the definition of treatment policy for viral hepatic C.

[The organ pathology in the acute stage of tissue helminthiases: the role of eosinophilia of the blood and tissues, blood immunoglobulins E and G4 and immune response-inducing factors]. / Organnaia patologiia v ostroi stadii tkanevykh gel'mintozov: rol' éozinofilii krovi i tkanei, immunoglobulinemii E, G4 i faktorov, indutsiruiushchik immunnyi otvet.

The pathogenesis of organic lesions in the early phase of tissue-dwelling helminthic infections has been analyzed and discussed by taking into account the previous findings [8, 9, 12], the results of current clinical and immunological studies [10, 11, 60] in the light of a fundamental literature data review. The products secreted by invasive helminthic larvae and the substances expressed onto their cuticula tegument surface mimic nonspecific [34, 43] and specific [21, 28, 33, 42] modulators of host inflammatory processes or induce the latter directly [37, 30, 42, 70]. The development of severe visceral pathology at the very early stage of human toxocariasis [60] is associated with unbalanced overproduction of these modulators and directly acting substances by a zoonotic agent. Some of these substances provoke organic and systemic pathology in the nearest day-hours after massive human invasion with sylvatic Trichinella spiralis strains or with Paragonimus westermani ichunensis larvae with a fatal end in 2-2.5 weeks [8, 14]. Parasitic enzymes that mimic the host proteins [73, 42], perhaps recently revealed [30] parasitic myogenic proteins, human tissue epitopes normally unexpressed [71], i.e. autoantigens from the impaired tissues [16] have been regarded as the factors leading to immunopathological/autoimmunological processes [21, 73]. Experimental allergic myocarditis (EAM) with endo-, pericardial, and valvular damages was reproduced in the guinea pigs immunized with T. spiralis somatic antigen and myocardial tissue homogenate (without BCG) in lanoline and mineral oil [8]. The development of trichinellosis-induced EAM with its pathomorphological characteristics revealed the existence of a Th1-variant of myocarditis in trichinosis similar to that of myosin-induced myocarditis [69] and confirmed the unfavourable effect of Th1 population stimulated in tissue-dwelling helminthic infections [62, 66, 70]. Visceral pathology in 22 patients at the acute stage of trichinosis, Opisthorchis felineus infection and in the early phase of toxocariasis coincided with serum IgG4 hyperproduction, competitive with serum IgE production, or with hypereosinophilia in IL-4-independent allergic reaction [60]. The absence of visceral pathology in the examined patients with high blood eosinophilia and serum IgE content (without elevated IgG4 levels) confirmed the protective functions of these parameters of immune responses in helminthic infections. However, there were individual variations of responses in terms of these parameters: high levels of all 3 parameters in three patients and IL-4-independent allergic reaction in 4 patients, only 6 of them had no visceral pathology. These substantial individual variations of immune responses at the early stage of disease seem to reflect the susceptibility to infections [71].

[Organ pathology in chronic tissue-dwelling helminthic infections: role of blood and tissue eosinophilia, immunoglobulinemia E, G4, and immune response-inducing factors]. / Organnaia patologiia v khronicheskoi stadii tkanevykh gel'mintozov: rol' éozinofilii krovi i tkanei, immunoglobulinemii E, G4 i faktorov, indutsiruiushchikh immunnyi otvet.

The results of earlier clinical, pathomorphological, and immunological studies of organic visceral and tissue lesions in helminthic infections [2, 3, 8, 10, 11, 14, 46] and present clinical and immunological ones [4-6, 44, 45] were analyzed and discussed in the light of a fundamental literature data review. The chronic visceral pathology in tissue-dwelling helminthic infections is associated with super- and reinfections [1, 2, 16, 36], with an inadequate immune response of humans to the invasion of zoonotic agents [2, 6, 13, 20] and with an individual invalidity of an immune response to infections [1, 2, 6, 16, 54]. The persistent course of infections, especially zoonotic, leads to organic pathology, sometimes irreversible [2, 13, 15, 21, 34, 46] if an individual (population) does not respond by immunity or by acquired (inherited) tolerance of invasion [1, 2, 3, 11, 16, 20, 36]. Transplacental transfer of Opisthorchis felineus antigens in the hyperendemic foci of the infection does not prevent superinfections, but does prevent the acute phase of disease and significantly mitigates the organic lesions in the chronic phase in spite of a very high intensity of infection [7, 10, 11]. Paramyosines (Pmes), proteins expressed on the tegument of Schistosoma mansoni and S. japonicum, show their immunogenic effect [42]. Antibodies to PM of Lumbricoidea and to a cardiac muscle myosin peptide (alpha-mp), known to induce experimental allergic myosites [55], were revealed in the sera of 32 trichinellosis, toxocarosis, opisthorchiasis, and hydatid echinococcosis patients with organic visceral abnormalities. The levels of antibodies against alpha-mp correlated with the severity of pathology [44]. S. mansoni PM peptide smp97 is a homologue of alpha-mp [25]. This fact suggests that there is a relationship between the development of an immune response to Pmes immunological processes in helminthiases. The relationship between organic visceral pathology and a competitive with serum IgE serum IgG4 hyperproduction at the early [6] and late stages of the studied helminthic infections was revealed. One may resume that this balance of production of these isotypes is not beneficial for the development of disease as IgG4-antibody hyperproduction is not beneficial for reinfection resistance [26, 28, 54]. One of the mechanisms may be serum IgG4 blocking the antibody-dependent cytotoxic effect, as it was supposed for unspecific IgE hyperproduction [47]. The selected development of cardiomyopathy or obstructive fibrosis in the lung after trichinellosis [2, 6, 45], endomyocardiofibrosis in the foci of filariases [21, 31] suggests that their development like resistance or susceptibility to infections [54] should be programmed.

[Blood eosinophilia and immunoglobulin E: the characteristics of their regulation in helminthiases and allergic diseases]. / Eozinofiliia krovi i immunoglobulinemiia E: osobennosti reguliatsii pri gel'mintozakh i allergicheskikh bolezniakh.

Patients with eosinophilia (due to helminthic infections in 44 patients, to allergic diseases in 32, and to unknown causes in 37) were studied and followed up at the in- and outpatient departments of the E. I. Martsinovskii Institute. Conventional laboratory studies and several parasitological, serological and image techniques were used in each case. During surveillance made during 1994 and 9 months of 1995, 11 patients (8 with toxocariasis) of the last group were replaced in the first one, 9 patients were found to have atopic diseases, and 3 patients were diagnosed as having lymphoma or blood diseases. Yet, the origin of eosinophilia remained unclear in 14 patients, 12 of whom were studied at the inpatient department of the E. I. Martsinovskii Institute. The regulatory features of immune responses were analyzed in helminthic and allergic diseases by reviewing vast recent experimental data. Conceivably, comparative estimation of serum IgE/IgG4 ratios in these two groups of patients may be helpful in limiting the field of search and the time of an examination/analysis.

[The specific and biological action of chemical preparations and their combination with pathogenetic agents in trichinosis]. / Spetsificheskoe i biologicheskoe deistvie khimiopreparatov i ikh kombinatsii s patogeneticheskimi sredstvami pri trikhinelleze.

The hypersensitizing effect of benzimidazole carbamates (BC), the therapy for trichinellosis, especially in heavily infected patients, determines the necessity of simultaneous administration of glucocorticoids (GC) for the prevention of severe systemic and organ-specific complications. This combination delayed the convalescent period, in severe cases it provokes coagulopathic disorders, infrequently fatal haemorrhages. The combination of BC with nonsteroidal anti-inflammatory drugs (NSAIDs) significantly shortened the convalescent period in semisevere and moderate cases of the disease along with normalized PGF and PGE production. In experimental mice and guinea pigs, the inhibition of specific T-cell responses without inhibiting their response to FGA, and the high antibody mediated cytotoxic activity after BC and NSAID therapy were found. Thus, in severe cases of the disease GC should be applied very immediately, replaced later by NSAIDs. The possible role of the biological action of BC, as donors of imidazoles in the microenvironment of muscle larvae, favoured by the poor content of natural imidazoles is discussed.

[The mass treatment of opisthorchiasis with praziquantel from the viewpoints of the clinician and the epidemiologist]. / Massovoe lechenie opistorkhoza prazikvantelem s pozitsii klinitsista i épidemiologa.

About a 20-years period of chloxyl (hexaparaxylol) mass treatment of opisthorchiasis in hyper- and mesoendemic territories of Russia did not change the prevalence of the infection, reducing only by some degree its intensity. Morbidity and incapacity in treated patients and in cured ones paradoxically appeared to be higher than in untreated persons. High parasitocidal activity of praziquantel in trematode infections has tempted (20) to use the drug as a tool in improving the level of health of population of endemic areas. For areas with a moderate and with a high rates of the infection "radical" and "selective" treatment with praziquantel was proposed (6). The study of clinical and immunological parameters in aboriginal, settler and migrant population of hyperendemic area in the Ob-Irtysh basin--Khanty-Mansi Autonomous District revealed striking differences in the groups and their different responses to praziquantel treatment. The possibility of transplacental transmission of O. felineus antigens in aborigines and in a part of settlers leading to immunological tolerance was revealed. "Retreatment" with praziquantel can lead to the loss of the latter and can challenge higher morbidity in adults and unsafety of their progeny. Monitoring system, checking the results of "retreatment" with praziquantel is proposed.

[The level of the eosinophils in the blood, serum immunoglobulins and circulating immune complexes and interferon production in patients with unilocular echinococcosis depending on the location of the cysts]. / Soderzhanie éozinofilov v krovi, syvorotochnykh immunoglobulinov, tsirkuliruiushchikh immunnykh kompleksov i produktsiia interferonov u bol'nykh odnokamernym ékhinokokkozom v zavisimosti ot lokalizatsii kist.

The correlations between blood eosinophils, serum immunoglobulins (Ig), circulating immune complexes (CIC) content, alpha- and gamma-interferon (IFN) production and HLA class I antigens were analyzed in 33 patients with hydatid disease aged 37.5 +/- 1.5 years. Direct correlation between the activity of gamma-IFN production, blood eosinophils, IgG and specific IgE content was found in patients with multiple pulmonary damage. In this group the high level of CIC correlated with the high content of IgG and specific IgE. In patients with solitary and multiple cysts in the liver in spite of high alpha- and gamma-IFN production the levels of total and specific IgE were low, IgG and CIC contents were moderate and eosinophils percent was low. In patients with combined damage of the liver and multiple cysts in the abdominal cavity high CIC production correlated directly with high total IgE content. In the total group of patients percent of HLA B5 carriers was significantly higher than in controls: 36.6 and 14.7 respectively (R = 0.01 after Fischer) that correlated with comparatively active gamma-IFN production in patients with the pulmonary and the liver cysts. The possible explanation of the different immune response in patients with the different localisation of the parasite cysts are discussed.

[Differences in the dynamics of the eosinophilia, blood immunoglobulin E and the level of circulating immune complexes in patients with chronic opisthorchiasis treated with different doses of praziquantel]. / Razlichiia v dinamike éozinofilii krovi, immunoglobulinemii E i soderzhaniia tsirkuliruiushchikh immunnykh kompleksov u bol'nykh khronicheskim opistorkhozom, lechennykh raznymi dozami prazikvantelia.

Sixty patients with a chronic Opisthorchis felineus infection were administered one-day therapy with praziquantel in doses 25, 40, or 60-75 mg/kg b. m. The former two doses of the drug did not much improve the levels of the examined immunologic parameters. In patients treated with the highest dose of praziquantel a significant decrease of the total and specific IgE and CIC levels, reaching that in the reference groups, was observed in 6-8 months after the treatment, this indicating a 92% efficacy of the drug in this group of patients.

[Interleukin-1 production in patients with subacute and chronic opisthorchiasis]. / Produktsiia interleikina-1 u bol'nykh podostrym i khronicheskim opistorkhozom.

Interleukin-1 (IL-1) production by peripheral blood lymphocytes was studied in 3 patients with the subacute and in 28 patients with the chronic stage of the disease. Monocyte culture was obtained by the H. R. Recalde method, IL-1 activity was evaluated by the S. B. Mizel modification of the classic LAF-ASSAY. In the subacute stage of the disease IL-1 activity was 3.3 fold lower that in healthy controls and lower than in the total group of patients with chronic opisthorchiasis (Kact. 0.64 +/- 0.09, 2.12 +/- 0.17, 1.83 +/- 0.11, respectively, p < 0.01, p < 0.01). In those with the syndrome of chronic gastroduodenitis IL-1 production was lower than in patients with the syndrome of cholepathy (Kact. 1.55 +/- 0.18 and 2.03 +/- 0.16, p < 0.01). Immediately after praziquantel therapy IL-1 production fell from Kact. 1.82 +/- 0.13 to 1.18 +/- 0.06 (p < 0.01), but 5-6 months later the production of the cytokine normalized in convalescents.

[Interferon status and the HLA antigen system. 1. Unilocular echinococcosis]. / Interferonovyi status i antigeny sistemy HLA. 1. Odnokamernyi ékhinokokkoz.

In 26 patients with hydatid disease interferons (IFN) blood levels by titration method and HLA-antigens by lymphocyte cytotoxicity microtest were estimated. In total group B5 antigen frequency was significantly (p = 0.007 after Fischer) higher than in the control group of 155 practically healthy persons: 38.5% and 14.7% respectively. The determination of possible correlation between IFN-alpha and IFN-gamma production, HLA-antigens specificity and the localisation of Echinococcus granulosus cysts showed that in hydatid disease A2 and B5 antigens carriers are significantly stronger producers of the cytokines as compared with patients having A3 and B13 antigens. The highest titers of IFN-alpha was found in A2 antigen carriers with the liver cysts, the highest level of IFN-gamma had B5 antigen carriers with the lung damage. A3 and B13 antigens carriers had low IFN titers independently of the character of damaged organ. Relatively high IFN-gamma blood titers in B5 antigen carriers with the lung cysts, persons predisposed to hydatid disease, permit supposing the stimulation of the cytokine production by the parasite for cysts formation in the lungs.

[The interferon status in helminthiases. 3. Opisthorchiasis]. / Interferonovyi status pri gel'mintozakh. 3. Opistorkhoz.

In 23 patients with Opisthorchis felineus infection, 4 in subacute and 19 in chronic stages of the disease (7 subclinical, 8 with cholepathy and 4 with gastroduodenitis) the blood levels of alpha-interferon (IF-alpha) and IF-gamma were measured using vesical stomatitis virus culture. In patients with subacute opisthorchiasis the blood contents of IF-alpha and IF-gamma were the same as in control-30 practically healthy people (640-1280, log2 9.73 +/- 0.19, and 128-256, log2 7.75 +/- 0.25 against 640-1280, log2 10.04 +/- 0.12 and 128-256, log2 7.47 +/- 0.13 respectively). In patients with chronic opisthorchiasis the levels of IF-alpha and IF-gamma were lower than in control (320-640, log2 8.68 +/- 0.28 and 32-128, log2 6.0 +/- 0.58, p less than 0.01 and p less than 0.01 respectively). Among the ones with the subclinical course of the infection the content of IF-alpha was lower than in control (320-1280, log2 9.31 +/- 0.27, p less than 0.05). Patients with cholepathy had lower levels of IF-alpha and IF-gamma than those with subclinical course of the infection (160-640, log2 8.55 +/- 0.24 and 16-64, log2 5.0 +/- 0.26, p less than 0.01, p less than 0.01 respectively). That seemed to be a sign of immunodepression in the chronic stage of the disease some way more prominent in cases with cholepathy. Immediately after praziquantel therapy interferon levels remained unchanged.

[The effect of toluene and ammonia on the invasive process and immunological indices in experimental trichinelliasis in mice]. / Vliianie toluola i ammiaka na invazionnyi protsess i immunologicheskie pokazateli pri éksperimental'nom trikhinelleze u myshei.

Rap mice were exposed to toluene (T) inhalation for 10 days before invasion with 20 Trichinella spiralis larvae per g body weight (moderate infection). This resulted in diminished number of intestinal parasites in the presence of greater number of mast cells in the peritoneal exudate, higher IgE production, enhanced cell adhesion to trichinella larvae and of migration of splenic lymphocytes. Simultaneous inhalation of T and ammonia diminished the immune stimulating effect of the former. The number of intestinal trichinella was 1.5 times more but still twice less than in controls. Inhalation of T during the first 10 days of infection stimulated the immune response only in mice given 5 larvae per g. In those given 20 or 60 larvae per g, the immune response was suppressed and 40 and 100% of mice perished respectively. The exposure to T during 30-39 days of infection of mice given 35 larvae per g (the intensive infection) resulted in 50% death of the animals without significant changes in immune response. Simultaneous therapy with mebendazole (75 mg/kg) provided 100% survival in the presence of suppressed immune response. 100% of mice of the same group not exposed to T but treated with mebendazole died. The toxic and immunomodulating effects of T differ in intact and infected mice due to the dense, the stage of infection and to chemotherapy.

[The molecular bases of the pathogenesis of malaria and their potential uses in developing a combined therapy for the infection]. / Molekuliarnye osnovy patogeneza maliarii i vozmozhnosti ikh ispol'zovaniia v razrabotke kompleksnoi terapii infektsii.

Molecular mimicry of a host is essential malaria parasite invasion and spreading in a host and it makes self-advantage for the parasite affecting vital organs and systems of the latter. It is tempting to assume that monoclonal antibody (MA) blocking specific (such as IMAM-I or CD36) and some unspecific (such as C3b) receptors of the blood stages of P. falciparum may prevent the malignant course of the infection. In our experience pyrazolone derivative not only suppressed schizont P. vivax infection but parasitemia too. After ceasing the drug administration, fever and parasitemia reappeared. It is of interest to study whether MA to the parasite hsp75 kD are able to suppress blood schizogony in P. falciparum infection. The prevention with MA to IFN-u the development of experimental cerebral malaria has been reported. Principally new approach in advancing the therapy of malignant malaria might be inducing agents of TNF inhibitors production. The suppressing of the parasite activity by blocking its receptors in a host seems to be perspective in the therapy of malignant malaria.

[The comparative characteristics of the clinico-immunological indices in different contingents of opisthorchiasis patients in a hyperendemic focus. 4. The transplacental transmission of Opisthorchis felineus antigens]. / Sravnitel'naia kharakteristika kliniko-immunologicheskikh pokazatelei raznykh kontingentov bol'nykh opistorkhozom v giperéndemichnom ochage. Soobshchenie 4. Transplatsentarnaia peredacha antigenov Opisthorchis felineus.

25 women in labour with chronic opisthorchiasis have been examined. They were representatives of native (7), local (8) and migrated population of the focus. Control group comprised 10 women from the local population free of invasion. Their immune status was assessed by the level of IgA, IgG, IgM, circulating immune complexes (CIC) and specific antibodies in the serum obtained from peripheral and funic veins, as determined by enzyme immunoassay (ELISA). To detect opisthorchis antigens in the serum modified radial immunodiffusion test was used. Antibody titres in ELISA, IgG and CIC levels were the highest in migrated women. Antibody titres in ELISA and IgG level in the newborn of migrated women were also considerably higher than in other newborn. Serum IgM level in all groups of newborn was considerably lower than in their mothers and IgA was altogether undetectable. In 3 native and 2 local women the results of immunodiffusion test were positive. It is suggested that transplacental migration of opisthorchis throughout the neonatal period may lead to tolerance formation.