Oropharyngeal tularemia in father and son after consumption of under-cooked rabbit meat.

Tularemia has been recognized for more than 10 y in Serbia, since the first epidemic of tularemia occurred in Sokobanja region in 1999. We report 2 cases of oropharyngeal tularemia in a father and son after the consumption of under-cooked rabbit meat. Both presented with fever, unilateral tonsillopharyngitis and cervical lymphadenitis.

Boceprevir in genotype 1 chronic hepatitis C: first experiences in Serbia.

INTRODUCTION: The triple therapy which consists of one of the protease inhibitor plus pegylated interferon and ribavirin (P/R) is the standard of care for the treatment of chronic hepatitis C virus (HCV) genotype 1 (G1) infection both in treatment-naïve and experienced patients. OBJECTIVE: The aim of this study was to analyze the efficacy and tolerability of this regime in hospital practice in Serbia. METHODS: From July 2012 to October 2012, 20 previously treated patients with advanced fibrosis and HCV G1 infection were included in the triple antiviral regimen in six referral centers in Serbia. All patients were treated with response guide therapy (RGT) regime according to the boceprevir treatment protocol. During the 4-week lead-in period all patients received peginterferon plus ribavirin. After the lead-in pe- riod boceprevir was added in the dosage of 800 mg three times a day orally.The subsequent treatment varied according to virologic response and fibrosis. During the therapy HCV RNA level was measured at week 4, 8, 12, 24 of the treatment for the assessment of virologic response profile. All patients who completed therapy were assessed at the end of the treatment and at the end of an additional 24-week treatment-free period for a sustained virologic response (SVR). RESULTS: The total of 20 patients with advanced fibrosis was treated. Among patients with an undetectable HCV RNA level at week 8 the rate of SVR was 100%. No patient with decrease in the HCV RNA level < 1 log 10 IU/ml at treatment week 4 achieved SVR. The overall rate of SVR was 55%. The safety profile of the treatment regimen was good. Anemia was reported in 25% of patients. There was no life-threatening treatment adverse event. CONCLUSION: Boceprevir in combination with P/R achieved fairly good SVR rates in patients that were"most difficult to treat"who failed on dual therapy and was effective among patients with cirrhosis.

Anaphylactic shock due to unruptured hepatic hydatid cyst complicated by multiple intrahospital infections.

Anaphylactic shock due to unruptured hydatid cyst is a rare complication of hepatic echinococcosis. Here, we present an unusual case of unruptured hydatid cyst causing anaphylactic shock followed by appendicitis, ileus, and complicated by septic condition due to multiple intrahospital infections. Decision of the surgical cyst removal at the right moment and appropriate antimicrobial treatment are key factors for a positive outcome.

Hepatitis C viral infection among prisoners.

BACKGROUND/AIM: Hepatitis C virus (HCV) infection is an important sociomedical problem worldwide because the chronification of the disease is frequent and the occurance of liver cirrhosis and hepatocellular carcinoma can be expected. The aim of this study was to determine the way of infection, pathohistological changes of the liver, virus genotype presence and sustained virological response after pegylated interferon and ribavirin therapy in prison inmates. METHODS: The study included 52 patients with chronic HCV infection classified in two groups managed during 2008-2010. The first group consisted of prisoners (n = 22) and the second one of "non-prisoners" (n = 30). The patients from both groups underwent diagnostic preparation (biochemical analyses, liver biopsy, hepatitis virus detection and genotypisation using polymerase chain reaction issue). The treatment lasted for 24 weeks for virus genotypes 2 and 3, and 48 weeks for genotypes 1 and 4. RESULTS: All the patients were males, approximately the same age (35 +/- 4.1 and 31 +/- 7.6 years). Virus genotype 1 was significantly more frequent in the prisoners (p < 0.05), that demanded longer treatment (48 weeks). At the same time, statistically significant higher number of patients, "non-prisoners", achieved a sustained virological response (p < 0.01). CONCLUSION: Intravenous drug abuse and tattoos, separately or together, are the most frequent way of infection in prisoners. The dominant presence of virus genotype 1 resulted in lower number of patients with sustained virological response, probably regardless prison environment and regime.

[Side effects of antiviral therapy in patients with chronic hepatitis C infection].

INTRODUCTION: Chronic hepatitis C currently represents a global health problem, which is expected to be reduced by pegylated-interferon and ribavirin therapy. MATERIAL AND METHODS: We examined 88 patients with chronic hepatitis C, divided into three groups according to their comorbidity: the patients without comorbidity were in group I, group III included the patients on dialysis, and group III included the patients with hemophilia. RESULTS A significant difference was found in the percentage of achieved sustained virological response between the patients on dialysis and other patients, p < 0.05. Having analyzed the therapy adverse effects, we observed a significantly higher decrease of erythrocytes count, hemoglobin and hematocrit levels in dialysis patients compared to others (p < 0.01). The patients on hemodialysis predominantly had anemia and leukopenia, while thrombocytopenia was equally present in all groups. The dominant clinical side effect was flu-like syndrome, present in more than a half of patients. DISCUSSION: The therapy positive effect is usually accompanied with adverse effects. The lowest therapeutic response was recorded in group II, due to the virus genotype 1. A significant decrease in hematological parameters was determined in all patients. The most common clinical adverse effect was flu-like syndrome, later manifestations included: weight loss, alopecia, insomnia and irritability. Side effects like psychosis, thyroid gland dysfunction or psoriasis were not recorded. CONCLUSION: A significant decrease in the value of all these hematological parameters was found in all groups of patients. Clinical side effects were present in 60% of patients. Side effects did not lead to discontinuation of therapy, but only to modification of drug doses.

Antioxidant defense and oxidative stress in children with acute hepatitis A.

BACKGROUND AND OBJECTIVES: Published data on oxidative stress in children with acute hepatitis A are still very scarce. This study aims to evaluate the oxidant/antioxidant status of these patients. DESIGN AND SETTING: Prospective, case-control study, over 2.5 years in patients under hospitalized and ambulatory care. PATIENTS AND METHODS: The levels of a whole-blood antioxidant, reduced glutathione; and plasma antioxidants, ß-carotene, retinol, ascorbic acid, α-tocopherol; and the biomarker of oxidative stress, malondialdehyde, were evaluated in 50 pediatric patients (age range, 5-16 years; 29 males and 21 females) with acute hepatitis A and in 50 healthy children as control subjects (age range, 5-16 years; 25 males and 25 females). RESULTS: Plasma levels of reduced glutathione, ß-carotene, retinol, α-tocopherol and ascorbic acid were significantly lower, while malondialdehyde plasma levels were significantly increased in the patient group when compared to the controls (P<.0001 for all parameters). CONCLUSIONS: Our findings show that pediatric patients with acute hepatitis A were influenced by oxidative stress, resulting in significantly lower levels of plasma antioxidants and increased lipid peroxidation. In the absence of other therapeutic options, antioxidant vitamin supplements could be added to the therapy for these patients to help reestablish the oxidant status balance. Further investigations to confirm this suggestion are recommended.

Characteristics of chronic hepatitis C among intravenous drug users: a comparative analysis.

Hepatitis C virus (HCV) usually evades the host's immune system and persists as a chronic infection. Intravenous drug users (IVDU) represent the majority of patients infected with HCV. Combined therapy of chronic hepatitis C (CHC) with peginterferon alpha-2a and ribavirin can be successful even when patients continue the intravenous drug use. In this study, we compared the characteristics of age, gender, genotype, and stage of fibrosis and the therapy outcome among IVDU and patients with no history of drug use. The study included 69 patients diagnosed with chronic hepatitis C, evaluated and treated at the Clinic for infectious diseases in Nis from 2005 to 2009. HCV RNA was detected by a polymerase chain reaction and the determination of genotypes was undertaken. Liver biopsies were examined histopathologically. Patients received a combined treatment of peginterferon alfa-2a and ribavirin. Therapy efficiency was evaluated based on the achievement of the sustained virological response (SVR). A comparison of characteristics was performed with the use of Mann-Whitney U test, chi-square (chi2) test and logistic regression. IVDU were significantly younger than patients in the control group. Prevalence of stage 1 fibrosis was significantly higher among IVDU. The therapy outcome is influenced by the patient's age and HCV genotypes. Each year added to one patient decreased the therapy efficiency by 8.1%, while genotypes 2 and 3 experienced a therapy which was 2.08 times more efficient than in other cases. IVDU represent a specific population different from non-using patients. However, they can be treated effectively if an adequate patient-doctor relationship is established.

[Efficiency of a combined peginterferon alpha-2a and ribavarin therapy in intravenous opiate substances abusers with chronic hepatitis C].

BACKGROUND/AIM: The most important ethiology factor of chronic liver disease that progresses into terminal insufficiency is hepatitis C virus (HCV) infection. Intravenous (iv) drug abuse is the main cause for spreading HCV. Thus the therapy for such patients is of extreme importance in reducing the incidence of the disease. The aim of the study was to establish efficacy of a combined therapy with peginterferon alpha-2a and ribavirin in iv opiate substances abusers having chronic HCV infection in relation to sex, age, genotype and level of fibrosis and duration of HCV infection before the treatment. METHODS: Thirty one iv opiate substances abusers with chronic hepatitis C (HHC) were enrolled in the examination. The patients were divided according to the genotype into two groups. The patients with genotypes 1 and 4 (n = 18) were treated for 48 weeks, while those with genotypes 2 and 3 (n = 13) for 24 weeks. PCR HCV RNA, genotype determination and liver biopsy were done to each patient. RESULTS: A stabile virological response was achieved in 93.5% of the patients, so the therapy demonstrated statistically significant efficacy i. v. opiate substances abusers with HHC (p < 0.001). There was no statistically significant difference in therapeutic response among patient groups formed according to the genotype, sex, duration of the disease and level of fibrosis (p > 0.05). CONCLUSION: Therapy of of iv opiate substances abusers with HHC has its specificities, and these patients need special treatment. Efficacy of the therapy was equivalent in patient groups formed according to the sex, genotype, level of fibrosis and duration of HCV infection. A combined therapy with peginterferon alfa 2a and ribavirin has high level of success in the treatment of these patients.

[Efficacy of antiviral therapy in patients with hemophilia and hepatitis C virus infection].

INTRODUCTION: HCV infection was common cause of morbidity and mortality in patients with hemophilia before 1986. We wanted to investigate the effect of treatment with combination therapy in HCV positive patients with hemophilia. MATERIAL AND METHODS: The research included totally 13 persons afflicted with hemophilia and HCV infection out of 21 tested. The patients were submitted to laboratory and clinical tests as well as genotypization, whereby a different hepatitis C virus genetic adherence was observed. Parallel with this subcategory the other one was put into comparison, consisting of 12 patients afflicted with chronic C hepatitis, marked as non-hemophilics. The both subcategories were treated with combination antiviral therapy (peginterferon alpha-2a and ribavirin) during 48 weeks for genotype 1 and 4, in reference to 24 weeks for genotype 2 and 3. Within the treatment, clinical and laboratory side-effects were noticed, which did not require therapy interruption. A more frequent hemorrhage during the therapy was found within the hemophilics, rather than before initiliazing it. RESULTS: After the statistical processing of the results (Students' t-test), statistically significant difference among these two subcategories was noticed as values for ALT (***p<0.0001) after 24 weeks of therapy, red blood cells (*p<0.05), haemoglobin and haematocrite (***p<0.0001) 24 weeks after therapy completing By PCR examination of the patients, 6 months after the end of treatment, a sustained viral response (SVR) of the same percentage was registrated within both subcategories, which is even greater than what the other authors have described. DISCUSSION: Main results were without important difference between two subgroups, except for higher number of spontanuous bleeding in group with hemophilia, which was somewhat expected. Most importantly, we didn't find any difference in SVR rates between groups. CONCLUSION: HCV positive patients with hemophilia could be successfully treated with combination therapy of peginterferon alfa-2a and ribavirin.

[Liver damage caused by hepatitis C viral infection and ethyl alcohol consumption].

BACKGROUND/AIM: Hepatitis C virus infection (HCV) is a complex disease, most commonly chronicle (80-85%). The aim of this research was to determinate the level of the liver damage in the patients cansed by HCV in conjunction with consuming ethyl alcohol. METHODS: The research included 15 patients with chronic HCV infection supported by the misuse of ethyl alcohol, as well. The diagnosis of C infection hepatitis was proved using the ELISA test and PCR method. RESULTS: The results of the study showed the liver damage by both HCV infection and ethyl alcohol, which was verified by the presence of biochemical changes and patohystological processing of the patients (liver biopsy and prosection). Patohystological changes were at the level of liver cirrhosis and carcinoma (2 patients). There was a signficant difference between the two subgroups (p < 0.001) regarding the examined values gamma-GT, PLT and PTV. The basic therapeutic procedure was to introduce this category of patients into alcohol abstinence, and, in a few patients, to apply the antivirus therapy, as well. CONCLUSION: Based on the number of the examined patients (n = 15), we could conclude that a prolonged ethyl alcohol misuse with the presence of HCV infection was in a correlation with the liver disease progression.

[Histopathologic and immunocytochemical changes in the liver in patients with chronic hepatitis C]. / Histopatoloske i imunocitohemijske promene u jetri bolesnika sa hronicnim hepatitisom C.

BACKGROUND: The presence of lymphocytes within the liver parenchyma is related to immunologically mediated liver damage in chronic hepatitis C. The aim of the study was to make histological, histochemical, and immunocytochemical assessment of liver biopsy specimens in patients with chronic hepatitis C virus (HCV) infection. METHODS: Biopsy specimens of 20 patients with chronic HCV disease were analyzed, using standard staining procedures to verify histologic liver lesions, as well as immunoenzymatic staining with monoclonal antibodies to detect CD4+ T-lymphocytes, B-lymphocytes, and macrophages. RESULTS: Micromorphologic characteristics of chronic active viral hepatitis C were present in all the patients, differing, however, by the level of their activity. Dominant changes were found within the portal space, consisting of mononuclear lympho-plasmocytic infiltration and macrophages. Immunocytochemical investigation of mononuclear and macrophageal infiltration showed the correlation between micromorphological findings and the degree of the activity. CONCLUSION: The presence of lymphocytic and macrophageal infiltration within the hepatic tissue directly correlated with the intensity of the liver damage. Analysis of the population of cellular infiltrate in the liver together with the monitoring of viremia level and the level of hepatocyte necrosis, could be useful tools for elucidation of the pathogenesis of chronic hepatitis C.

[An epidemic of tularemia in the Nish area]. / Epidemija tularemije u Niskom okrugu.

Tularaemia, as a rare disease, surprised medical workers in 1999 and 2000 when it was detected and diagnosed in 31 patients. In 1999 patients were registered in villages of the Sokobanja community, and in 2000 also in other communities in the district of Nish. Patients were peasants, mostly housewives. Glandular form of the disease was dominant. The main clinical symptoms were: tonsillitis, pain in the region of enlarged lymphatic glands and temperature, Biohumoral syndrome presented accelerated sedimentation of erythrocytes and elevated fibrinogen values. Antibody titer of Francisella tularensis was extremely high in the majority of patients. The disease was cured in all patients: in 27 patients after the first therapy, in 4 subjects after recidivation and 5 patients were surgically treated.

[Soluble CD4 antigens in the cerebrospinal fluid as a marker of lymphocytic infiltration of the central nervous system]. / Solubilni CD4 antigeni u cerebrospinslnoj tecnosti kao marker limfocitne infiltracije centralnog nervnog sistema.

Early diagnosis of the central nervous system (CNS) infections is a precondition of their successful treatment. However, the essential standard examination of the cerebrospinal fluid (CSF) is sometimes neither specific enough to define their basic nature, nor sufficient to differentiate them from processes of non-infectious origin. Supposing that the released surface molecules of activated immunocompetent cells could better define the character of inflammatory reaction, the levels of soluble CD4 antigens (sCD4) were determined with enzyme-immunosorbent test in the CSF of the patients with various CNS diseases. In contrast to cerebrovascular insults, toxic-metabolic, and other conditions in control group, detectable sCD4 concentrations in acute encephalitis (24 +/- 11 U/ml) were verified at the beginning of the disease, being also present in cytologically diagnosed normal CSF findings. They were significantly higher (p<0.05) compared to acute serous meningitis (13.5 +/- 8 U/ml), while in purulent meningitis they were measurable only after the disease progression--in correlation with the disturbed brain system function. The obtained results suggested the significance of CD4 antigen levels in CSF as a sensitive and specific marker of lymphocytic infiltration of the brain parenchyma, the measurement of which could contribute to early identification of the CNS infections, better understanding of their pathogenesis, and the assessment of the actual level of the destruction of neurons.