Complicated Ulceroglandular Tularemia.

A 52-year-old woman presented with a tender swelling in the right axilla, fever, a headache, nausea, and general weakness. On examination, she was found to have lymphangitis on the right arm and red papules on the 1st and 2nd fingers of the right hand. She had had prepared wild rabbit stew 5 days before disease onset. Serology and an ultrasound of the right axilla confirmed the diagnosis of ulceroglandular tularemia. The lymphadenitis did not resolve after streptomycin treatment so an incision was made and 30 cc of purulent fluid drained. Over the course of the next 3 months, the fluid continued to drain. A radiographic fistulography was performed and it revealed a short main channel with a few long channels of varying caliber branching out from it, all terminating in a conglomerate of necrotic axillary lymph nodes. The lesions healed spontaneously and completely over the following 12 months without additional antibiotic therapy. Radiographic fistulography can help plot the course of the fistula/fistulas and demonstrate the anatomic features of the lesion in resource poor settings.

Helicobacter pylori infection rates in dyspeptic Serbian HIV-infected patients compared to HIV-negative controls.

Helicobacter pylori infection does not belong to the spectrum of opportunistic infections in people living with HIV (PLHIV). To evaluate the Helicobacter pylori infection prevalence rate trends in HIV co-infected individuals in comparison to the HIV-negative population, we compared histopathological findings of H. pylori positive gastritis (gastritis topography and histopathology) between 303 PLHIV and 2642 HIV-negative patients who underwent esophagogastroduodenoscopy (EGD) between 1993 and 2014 due to dyspeptic symptoms. The prevalence of H. pylori infection was significantly higher in HIV-negative controls than in PLHIV (50.2% vs. 28.1%). A significantly positive linear trend of H. pylori co-infection in PLHIV was revealed in the observed period (b = 0.030, SE = 0.011, p = 0.013), while this trend was significantly negative in HIV-negative patients (b = - 0.027, SE = 0.003, p < 0.001). Patients with HIV/H. pylori co-infection had significantly higher CD4+ T cell counts and more often had undetectable HIV viremia, due to successful anti-retroviral therapy (ART). Stomach histopathological findings differed between HIV co-infected and H. pylori mono-infected patients. Our findings confirm that the ART has changed the progression of HIV infection, leading to a significant increase in the prevalence of H. pylori infection in dyspeptic PLHIV over time. Our data also suggests that a functional immune system may be needed for H. pylori-induced human gastric mucosa inflammation.

Successful treatment of chronic hepatitis C in a hemodialysis.

We present the first case of successful direct acting antiviral therapy of chronic hepatitis C in a hemodialysis patient in Serbia. The patient infected with genotype 1a has been successfully treated with Paritaprevir/Ritonavir/Ombitasvir/Dasabuvir and Ribavirin. There are only a few real world reports regarding this therapeutic option in hemodialysis patients.

The prevalence and the risk factors for hepatitis C virus infection in Serbia.

INTRODUCTION: The epidemiological characteristics of the hepatitis C virus (HCV) infection in Republic of Serbia have not been studied sufficiently so far. The aim of this study was to estimate the prevalence of anti-HCV positivity in the general population of Serbia and determine the risk factors for this infection. METHODOLOGY: Estimation of the prevalence was done using the median ratio method with data from several regional countries to a previously determined prevalence of anti-HCV positivity among volunteer blood donors of 0.19%. In order to determine the risk factors a matched case-control study was conducted of 106 subjects with confirmed HCV infection from the Clinic for Infectious and Tropical Diseases, Clinical Center of Serbia and the same number of hospital controls matched by sex and age. RESULTS: The estimated prevalence of anti-HCV positivity in the general population of Serbia was 1.13% (95% CI: 1.0-1.26%). The most important predictive risk factors of HCV infection were: intravenous drug use (OR = 31.0; 95% CI: 3.7-259.6), blood transfusions (OR = 3.7; 95% CI: 1.6-8.7), invasive dental treatment (OR = 3.1; 95% CI: 1.4-6.8), and low level of education (OR = 2.2; 95% CI:1.1-4.7). A total of 91.5% of the persons with hepatitis C had at least one of the significant risk factors. CONCLUSION: The prevalence of anti-HCV positivity ranks Serbia in the range of mid-endemic European countries. Preventive measures should be directed at preventing drug use, on education about getting the infection, creating safe conditions for blood transfusions, and strict adherence to adopted practices in dentistry.

FIB-4 and APRI scores for predicting severe fibrosis in chronic hepatitis C - a developing country's perspective in DAA era.

INTRODUCTION: Chronic Hepatitis C Virus (HCV) infection leads to progressive fibrosis making fibrosis staging necessary in the evaluation of such patients. Different fibrosis scores are emerging as possible non-invasive alternatives for liver biopsy. The Fibrosis-4 Index (FIB-4) and AST to Platelet Ratio Index (APRI) scores are the most widely used and the most extensively tested. This study aims to determine if it was possible to accurately use these to identify patients that are unlikely to have severe fibrosis. METHODOLOGY: One hundred and forty-two patients with chronic hepatitis C infection who underwent liver biopsy since January 1st 2014 until May 31st 2017 at the Hospital for Infectious and Tropical Diseases in Belgrade were analyzed. The FIB-4 and APRI scores were calculated for each patient and compared to histologically determined fibrosis stage. RESULTS: A comprehensive statistical analysis was conducted in order to compare patients with and without severe fibrosis and to evaluate the accuracy of the fibrosis scores. Patients with non-severe fibrosis were younger, had higher platelet counts and lower transaminase levels. FIB-4 had an AUC of 0.875 and the APRI score had an AUC of 0.861. No patients with severe fibrosis or cirrhosis had a FIB-4 lower than 1.08. FIB-4 was superior to APRI in identifying patients with severe fibrosis in the study cohort. CONCLUSION: FIB-4 was superior to APRI in the recognition of severe fibrosis. FIB-4 may prove very useful in identifying patients without advanced liver disease, especially if other non-invasive methods are inaccessible.

The increasing prevalence of HIV/Helicobacter pylori co-infection over time, along with the evolution of antiretroviral therapy (ART).

Helicobacter pylori (H. pylori) is one of the most common human bacterial infections with prevalence rates between 10-80% depending upon geographical location, age and socioeconomic status. H. pylori is commonly found in patients complaining of dyspepsia and is a common cause of gastritis. During the course of their infection, people living with HIV (PLHIV) often have a variety of gastrointestinal symptoms including dyspepsia and while previous studies have reported HIV and H. pylori co-infection, there has been little data clarifying the factors influencing this. The aim of this case-control study was to document the prevalence of H. pylori co-infection within the HIV community as well as to describe endoscopic findings, gastritis topography and histology, along with patient demographic characteristics across three different periods of time during which antiretroviral therapy (ART) has evolved, from pre- highly active antiretroviral therapy (HAART) to early and modern HAART eras. These data were compared to well-matched HIV negative controls. Two hundred and twelve PLHIV were compared with 1,617 controls who underwent their first esophagogastroduodenoscopy (EGD) to investigate dyspepsia. The prevalence of H. pylori co-infection among PLHIV was significantly higher in the early (30.2%) and modern HAART period (34.4%) compared with those with coinfection from the pre-HAART period (18.2%). The higher rates seen in patients from the HAART eras were similar to those observed among HIV negative controls (38.5%). This prevalence increase among co-infected patients was in contrast to the fall in prevalence observed among controls, from 60.7% in the early period to 52.9% in the second observed period. The three PLHIV co-infected subgroups differed regarding gastritis topography, morphology and pathology. This study suggests that ART has an important impact on the endoscopic and histological features of gastritis among HIV/H. pylori co-infected individuals, raising the possibility that H. pylori-induced gastritis could be an immune restoration disease.

Intravenous drug use - an independent predictor for HCV genotypes 3 and 4 infection among HIV/HCV co-infected patients.

INTRODUCTION: About one quarter of human immunodeficiency virus (HIV) infected persons in Serbia have also been found to be hepatitis C virus (HCV) co-infected. In the general population, HCV genotype 1 has been shown to be the most prevalent one. Here, we present the first study on the distribution of HCV genotypes among HIV/HCV co-infected patients in Serbia, in relation to epidemiological and clinical features. MATERIAL AND METHODS: The study included HIV/HCV co-infected and a group of HCV mono-infected patients in the period 1998-2012, with collection of epidemiological, clinical, and behavioral data using a standardized questionnaire. The HCV genotyping to the level of pure genotype was performed by reverse hybridization. RESULTS: Intravenous drug use (IDU) was found to be significantly more prevalent among the co-infected patients (p < 0.01). HCV genotype 1 was detected in 87% of patients with mono-infection, compared to 46.3% of patients with co-infection (p < 0.01); genotypes 3 and 4 were significantly more common among co-infected patients (6% and 5%, vs. 27% and 25%, respectively). Multivariate logistic regression confirmed IDU, infection with non-1 HCV genotype and HCV viral load over 5 log to be predictors of HIV co-infection. CONCLUSIONS: The HCV genotypes 3 and 4 were found to be significantly more prevalent among HIV/HCV co-infected patients in Serbia, compared to HCV mono-infected patients, but also more prevalent compared to the European HIV/HCV co-infected cohort. History of IDU represents an independent predictor of HCV genotypes 3 and 4 infection, with important implications for treatment.

Human case of fasciolosis in Serbia treated with triclabendazole.

INTRODUCTION: The number of humans infected by Fasciola hepatica is increasing worldwide. Humans can become accidental hosts by ingesting drinking water or plants contaminated with metacercariae. CASE REPORT: We reported a case of a 68-year-old Serbian woman, in which the diagnosis of acute fasciolosis had been established after serious diagnostic concerns. Based on clinical picture (episodic right upper quadrant abdominal pain, febrility and generalized body pain) and biochemical analyses (high eosinophilia and high activity of alkaline phosphatase), she was appointed as suspected to the acute fasciolosis. Stool and duodenal aspirate exams were negative for Fasciola ova. In the absence of adequate serologic diagnostic for fasciolosis in Serbia, the diagnosis was confirmed using enzyme immunoassays and immunoblot at the Institute for Tropical Diseases in Hamburg, Germany. Soon after triclabendazole was administered, the symptoms disappeared and biochemical values returned to normal. CONCLUSION: The diagnosis of human fasciolosis may be problematic and delayed, especially in non endemic areas, because physicians rarely encounter this disease and a long list of other diseases must be considered in the differential diagnosis. The syndrome of eosinophilia, fever, and right upper quadrant abdominal pain suggest acute fasciolosis. Unclear source does not rule out fasciolosis.

[Diagnosis and treatment of esophageal diseases in patients with acquired immunodeficiency syndrome in Serbia].

INTRODUCTION: Gastrointestinal complications are common manifestations of acquired immune deficiency syndrome. The aim of this study was to establish the type and frequency of esophageal disease, the influence of antiretroviral therapy on it and the most adequate approach to this group of patients. MATERIALS AND METHODS: This study included 146 patients with acquired immune deficiency syndrome treated at the Institute of Infectious and Tropical Diseases of Clinical Centre in Serbia from 1991-2001. The statistical data processing was done by the Statistical Package for the Social Sciences for Windows version 10.0. The level of statistical significance was defined to be p < or = 0.05 and p < or = 0.01. The diagnosis was made upon endoscopic exams, pathohistological findings and isolation of causative agents. RESULTS: Esophagitis was found in 78 (53.41%) patients. These patients complained mostly of odynophagia and dysphagia. The most common was Candida esophagitis. It was diagnosed in 59 (40.41%) patients; 5 patients (3.42%) had cytomegalovirus esophagitis; 2 patients (1.37%) had herpes simplex virus esophagitis, and one -patient (0.68%) had a mixed Candida and herpes simplex virus infection of esophagus. Idiopathic esophageal ulcer was diagnosed in one (0.68%) patient. CONCLUSION: Seventy-eight (53.41%) patients with acquired immune deficiency syndrome had esophagitis. Candida (40.41%) was the most common cause of esophagitis. Viral esophagitis was less common: cytomegalovirus in 5 patients (3.42%); herpes simplex virus in 2 patients (1.37%), and idiopathic esophageal ulcer in 1 patient (0.68%)). These patients complained mostly of odynophagia and dysphagia. Modern antiretroviral therapy reduces the frequency of esophagitis and therefore changes symptomatology in patients with acquired immune deficiency syndrome.

The prognosis of late presenters in the era of highly active antiretroviral therapy in serbia.

To examine the prognosis of patients who present with very advanced HIV-induced immunodeficiency, and their response to highly active antiretroviral therapy (HAART), a series of 101 treatment naïve patients from the Serbian cohort of HIV infected patients, who presented with a CD4 count of

Activated liver stellate cells in chronic viral C hepatitis: histopathological and immunohistochemical study.

BACKGROUND: There is positive correlation between the number of activated hepatic stellate cells and necroinflammatory activity and/or the stage of liver fibrosis in viral hepatitis. No study has investigated such a relationship with regard to the activated hepatic cells within specified zones of liver tissue in chronic C hepatitis. The aim of the present study was to correlate the level of activated hepatic stellate cells within perivenular, intermediate, periportal, and portal tracts area and fibrous septa with stages of liver fibrosis and necroinflammatory activity in patients with chronic C hepatitis. METHODS: This retrospective study included 20 liver biopsy samples from patients with chronic C hepatitis and 10 normal liver biopsies. Biopsy specimens were processed routinely and stained with haematoxylin-eosin, periodic acid-Schiff, Masson;s trichrome, aldechide fuchsin, reticulin and iron (Pearls). Activated hepatic stellate cells were identified immunohistochemically using antibody to alpha-smooth muscle actin. Assessment of immunoreactivity was performed using a semiquantitative method. RESULTS: In chronic C hepatitis, a positive correlation between the stage of fibrosis and the number of activated hepatic stellate cells within portal spaces and fibrous septa was found. These cells were increased in number in other areas of liver tissue as well, but without statistical significance. There was no correlation between either the stage of fibrosis and necroinflammatory activity or the number of activated hepatic stellate cells and necroinflammatory activity. CONCLUSION: An increased number of activated hepatic stellate cells within portal spaces and fibrous septa may be a useful prognostic marker for the development of advanced fibrosis and cirrhosis in chronic C hepatitis.

The prognosis of pediatric AIDS in serbia.

To determine the outcome of HIV infection in children in a resource-limited setting, a retrospective analysis of a series of 51 pediatric cases from the Serbian cohort of HIV infected patients was performed. Twenty seven patients died in the pre-HAART era, but mono/dual antiretroviral treatment had significantly (p=0.046) prolonged survival. Of the total of 24 HAART-treated patients, 10 had clinical AIDS before HAART initiation. The mean baseline CD4 cell count was 193.9 +/- 170.0/mm(3). After a mean follow-up of 72.6 +/- 44 months, a favorable response was recorded in 62.5%, treatment failure (defined as non-achievement of undetectable viremia) in 20.8%, and a discrepant virological and immunological response (achievement of undetectable viremia but without a rise in CD4 cell counts adequate for age) in 16.7% patients. No patients died, and there were only three hospital admissions after commencing HAART. Five immune restoration inflammatory syndrome episodes were recorded, of which four were due to BCG-osis. Lipodystrophy and hyperlipidemia occurred in 18.2% and 26.3% patients, respectively. We conclude that even in suboptimal facilities, the prognosis of HIV disease among children on HAART may be rather good. The metabolic syndrome seems to emerge as an important issue among long-term surviving children on HAART.

Diagnostic esophago-gastro-duodenoscopy (EGD) in patients with AIDS-related upper gastrointestinal abnormalities.

BACKGROUND/AIMS: Gastrointestinal (GI) diseases are common among patients infected with human immunodeficiency virus (HIV), and may involve the entire GI tract. The aim of the article is to investigate the prevalence of various upper gastrointestinal abnormalities in patients with AIDS. METHODOLOGY: Diagnostic esophago-gastro-duodenoscopy (EGD) was performed in cohort of AIDS patients (total 186) including non-ART, mono and/or dual ART and HAART treated subgroups. Clinical presentation, level of immunosupression and presence of H. pylori infection was also considered. RESULTS: Endoscopic findings included normal (29), esophageal candidiasis (22), esophageal erosions (16), gastritis/duodenitis (135), gastric/duodenal ulcers (7), erosions (6) and infiltration/tumor in the stomach (5). Thirty-nine patients (20.4%) had opportunistic infections/tumors including candida esophagitis, CMV esophagitis, CMV gastritis, gastric non-Hodgkin's lymphoma (NHL) and gastric cryptosporidiosis. H. pylori infection was present in 25.8% of patients, and majority (89.6%) had chronic non-atrophic gastritis. These patients had a higher mean CD4 count compared with H. pylori negative patients (403.5 vs. 226.9 CD4+ cells/microL, p = 0.001). Patients who received HAART had significantly higher frequency of H. pylori infection then non-ART treated patients (p = 0.048). CONCLUSION: Candidiasis was the marker of advanced immunodeficiency, and H. pylori was more common in patients with higher CD4 cell counts on ART, which may suggest that this infection could be an unusual presentation of immune restoration inflammatory syndrome.

[Disseminated BCG infection in patients with urinary bladder carcinoma].

INTRODUCTION: Bacillus Calmette-Guërin--a live, attenuated strain of Mycobacterium bovis has been used in immunotherapy of patients with superficial urinary bladder carcinoma. Some patients develop complications after intravesical instillation of BCG: high temperature followed by hematuria or granulomatous prostatits, epidydimoorchitis, urethral obstruction, and less than 1% have a systemic disease followed by dissemination of bacteria into other organs. CASE REPORT: A 50-year-old man underwent transurethral resection of a bladder tumor. One month after the operation BCG intravesical installations were administered for three weeks. After the fourth installation, our patient developed high fever, fatigue, vomiting, dark urine, light stools, and jaundice. On admission he was jaundiced with a high fever, enlarged liver and spleen and laboratory findings which included high erythrocyte sedimentation rate, pancytopenia, elevated liver enzymes, especially alkaline phosphatase and aminotranspherases. The bone-marrow biopsy showed granulomatous inflamation suggesting mycobacterial spread in the bone marrow, liver and spleen and sepsis. The patient was initially treated with antituberculous therapy, but his state did not improve until corticosteroids were added to the antituberculous treatment regimen. CONCLUSION: Although dissemination of BCG is a rare complication of intravesical BCG treatment of the bladder carcinoma, it may result in prolonged fever and granulomatous inflamation of the liver, spleen, lungs, bone marrow and BCG sepsis. Antituberclous agents in combination with corticosteroids comprise the treatment of choice for disseminated BCG infection.

Liver enlargement associated with opportunistic infections in patients with human immunodeficiency virus infection.

BACKGROUND AND AIM: Liver disease is commonly present in human immunodeficiency virus (HIV) infection. The aim was to determine the frequency of liver enlargement and its association with opportunistic infections in patients with HIV infection. PATIENTS AND METHODS: A total of 400 HIV-infected patients were investigated. Commercial kits (Ortho EIA; BioRad, ELISA) were used for detection of serum specific antibodies to HIV, hepatitis C virus, surface antigen of hepatitis B virus, and cytomegalovirus. Liver tissues were stained for various microorganisms. The electronic data base SPSS for Windows (version 10.0) was used for statistical analysis. A p <0.05 was considered significant. RESULTS: Ultrasonographic screening revealed liver enlargement in 63.75% of HIV patients. In 40.7% the right lobe size varied from 140 mm to 160 mm. Of those with hepatomegaly, 60.7% had AIDS. Hepatitis C and B viruses and Mycobacterium tuberculosis were detected in 50%, 29% and 18% of patients, respectively. Histological changes were mostly non-specific. Liver pathology depended on the degree of cellular immune deficiency, particularly in patients with HBV co-infection. In a minority of patients (32.5%), the histology revealed granulomatous hepatitis. Liver function tests were abnormal in 46%. CONCLUSION: Liver enlargement is common in HIV-infected patients mostly in association with hepatitis C and B viruses and Mycobacterium tuberculosis.