Evaluation of Dual Therapy in Real Life Setting in Treatment-Naïve Turkish Patients with HCV Infection: A Multicenter, Retrospective Study.

BACKGROUND: Before the introduction of direct-acting antivirals in the treatment of chronic hepatitis C patients, the combination of peginterferon alpha and ribavirin was the standard therapy. Observational studies that investigated sustained virological response (SVR) rates by these drugs yielded different outcomes. AIMS: The goal of the study was to demonstrate real life data concerning SVR rate achieved by peginterferon alpha plus ribavirin in patients who were treatment-naïve. STUDY DESIGN: A multicenter, retrospective observational study. METHODS: The study was conducted retrospectively on 1214 treatment naïve-patients, being treated with peginterferon alpha-2a or 2b plus ribavirin in respect of the current guidelines between 2005 and 2013. The patients' data were collected from 22 centers via a standard form, which has been prepared for this study. The data included demographic and clinical characteristics (gender, age, body weight, initial Hepatitis C virus RNA (HCV RNA) level, disease staging) as well as course of treatment (duration of treatment, outcomes, discontinuations and adverse events). Renal insufficiency, decompensated liver disease, history of transplantation, immunosuppressive therapy or autoimmune liver disease were exclusion criteria for the study. Treatment efficacy was assessed according to the patient's demographic characteristics, baseline viral load, genotype, and fibrosis scores. RESULTS: The mean age of the patients was 50.74 (±0.64) years. Most of them were infected with genotype 1 (91.8%). SVR was achieved in 761 (62.7%) patients. SVR rate was 59.1% in genotype 1, 89.4% in genotype 2, 93.8% in genotype 3, and 33.3% in genotype 4 patients. Patients with lower viral load yielded higher SVR (65.8% vs. 58.4%, p=0.09). SVR rates according to histologic severity were found to be 69.3%, 66.3%, 59.9%, 47.3%, and 45.5% in patients with fibrosis stage 0, 1, 2, 3 and 4, respectively. The predictors of SVR were male gender, genotype 2/3, age less than 45 years, low fibrosis stage, low baseline viral load and presence of early virological response. SVR rates to each peginterferon were found to be similar in genotype 1/4 although SVR rates were found to be higher for peginterferon alpha-2b in patients with genotype 2/3. The number of patients who failed to complete treatment due to adverse effects was 33 (2.7%). The number of patients failed to complete treatment due to adverse effects was 33 (2.7%). CONCLUSION: Our findings showed that the rate of SVR to dual therapy was higher in treatment-naïve Turkish patients than that reported in randomized controlled trials. Also peginterferon alpha-2a and alpha-2b were found to be similar in terms of SVR in genotype 1 patients.

Cutaneous anthrax in an unusual location: case report.

Cutaneous anthrax is well known, unlike anthrax of the lumbar region, which is not reported elsewhere. We present a case of anthrax of the lumbar region in a 50-year-old man. The infection was characterised by a wide, black eschar and oedema on an erythematous ground. After isolation of the Gram-positive bacilli from the skin lesions, prompt antibiotic treatment (intravenous sulbactam-ampicillin 1.5 g every six hours) was initiated. Following eradication of the bacilli after 14 days of antibiotic treatment, a split-thickness skin graft was applied. A diagnosis of anthrax depends on clinical suspicion. Early diagnosis, antibiotic and surgical treatment can facilitate the treatment and prevent development of complications.

Retreatment of Chronic Hepatitis C Infection with Telaprevir: Preliminary Results in Turkey.

BACKGROUND: The use of pegylated interferon alpha and ribavirin (PegIFN/RBV) for the retreatment of chronic hepatitis C virus (HCV) infection without a sustained virological response (SVR) prior to PegIFN/RBV treatment has resulted in low success rates. AIMS: To investigate the efficacy and safety of telaprevir (TVR) in combination with PegIFN/RBV in patients infected with HCV genotypes 1 and 4 who were previously treated with PegIFN/RBV and failed to achieve SVR. STUDY DESIGN: Multi-center, retrospective, cross-sectional study. METHODS: The study included 111 patients: 80 prior relapsers, 25 prior null responders, and six prior partial responders to PegIFN/RBV treatment. The patients were given TVR/PegIFN/RBV for 12 weeks, followed by a 12-week PegIFN/RBV treatment; virological response results were assessed at weeks 4, 12, and 24. Treatment was discontinued in patients with HCV RNA >1000 IU/mL at week 4 or with negative RNA results at week 4 but >1000 IU/mL at week 12. Rapid virological response (RVR), early virological response (EVR), extended rapid virological response (eRVR), and virological response at 24th week of treatment were evaluated. The side effects of combination therapy and the rates of treatment discontinuation were investigated. RESULTS: The mean age of the patients was 56.02±9.96 years and 45.9% were male. Ninety-one percent of the patients were infected with viral genotype 1, 69.6% with the interleukin (IL) 28B genotype CT and 20.2% were cirrhotic. The RVR rate was 86.3% in prior relapsers, 56% in prior null responders, and 50% in prior partial responders (p=0.002). EVR rates in those groups were 91.3%, 56%, and 83.3%, respectively (p<0.001). eRVR rates were 83.8% in prior relapsers, 48% in prior null responders, and 50% in prior partial responders (<0.001). The virological response at the 24th week of treatment was found to be the highest in prior relapsers (88.8%); it was 56% in prior null responders and 66.7% in prior partial responders (p<0.001). Common side effects were fatigue, headache, anorexia, malaise, anemia, pruritus, dry skin, rash, dyspepsia, nausea, pyrexia, stomachache, and anorectal discomfort. All treatments were discontinued due to side effects in 9.9% of patients. CONCLUSION: High virological response rates were obtained with TVR/PegIFN/RBV treatment. Although side effects were frequently observed, the discontinuation rate of combination therapy was low.

Assessment of Growth and Development in Children With Hepatitis B Positivity.

BACKGROUND: Chronic infections and liver diseases may influence the growth and development of children by leading to malnutrition. In this study, demographic characteristics, anthropometric measurements and laboratory findings for children with hepatitis B positivity were analyzed. METHODS: A total of 43 cases were admitted to our clinic between January 2012 and February 2013 and detected to have HBsAg positivity. RESULTS: Malnutrition was detected in 11 cases (25.6%) and obesity in three cases (6.9%). Aspartate aminotransferase (AST) levels were significantly higher in malnourished patients compared to those without malnutrition. The weight to height was significantly higher in patients with positive HBeAg compared to children with negative HBeAg. We found that the weight standard deviation scores (SDS) ratios dropped as alanine aminotransferase (ALT) and AST levels increased and height SDS ratios decreased. In addition, body mass index (BMI) decreased as AST and alpha feto protein (AFP) values increased. While a significant relationship was not detected between insulin-like growth factor binding protein-3 (IGFBP-3) and insulin-like growth factor-1 (IGF-1) and ALT, a significantly negative correlation was detected between IGFBP-3 and IGF-1 and AST. We found a malnutrition rate of 25.6% in children with HBsAg positivity. We also found that weight and height SDS rates decreased as ALT and AST levels increased. In addition, we detected that BMI decreased as AST and AFP values increased. CONCLUSION: We consider that hepatic inflammation is the factor that affects growth. Monitoring of growth and development during follow-up of children who are detected to have HBsAg positivity would be beneficial to determine the mechanism and causes of growth retardation.

Transmitted antiretroviral drug resistance mutations in newly diagnosed HIV-1 positive patients in Turkey.

INTRODUCTION: The objective of this study was to determine the transmitted drug resistance mutations (TDRMs) in newly diagnosed HIV-1 positive patients in Turkey. MATERIALS AND METHODS: The study was carried out between 2009 and 2014 and antiretroviral naïve 774 HIV-1 infected patients from 19 Infectious Diseases and Clinical Microbiology Departments in Turkey were included; gender: 664 (86%) male, median age: 37 (range; 1-77), median CD4+T-cell: 360 (range; 1-1320) count/mm(3), median HIV-RNA load: 2.10+E6 (range; 4.2+E2-7.41+E8) IU/mL. HIV-1 drug resistance mutations were detected by population based sequencing of the reverse transcriptase (codon 41-238) and protease (codon 1-99) domains of pol gene of HIV-1, and analyzed according to the criteria by the World Health Organization 2009 list of surveillance drug resistance mutations [1]. RESULTS: The patients had TDRMs to NRTIs (K65R, M184V), NNRTIs (K101E, K103N/S, G190A/E/S, Y181I/C, Y188H/L) and PIs (M46L, I54V, L76V, V82L/T, N83D, I84V, L90M). The prevalence of overall TDRMs was 6.7% (52/774). Resistance mutations were found to be 0.7% (6/774), 4.1% (32/774) and 2.1% (17/774) to NRTIs, NNRTIs and PIs drug groups, respectively. Three patients had NRTIs+NNRTs resistance mutations (M184V+K103N) as multi-class drug resistance. However, thymidine analogue resistance mutations (TAMs) determined two distinct genotypic profiles in the HIV-1 reverse transcriptase: TAM1: M41L, L210W and T215Y, and TAM2: D67N, K70R, K219E/Q, and T215F. The prevalence of TAM1 and TAM2 were 7.7% (60/774) and 4.3% (34/774), respectively. CONCLUSIONS: The TDRMs prevalence of antiretroviral naïve HIV-1 infected patients may be suggested current situation of Turkey. These long-term and large-scale results show that the resistance testing must be an integral part of the management of HIV infection in Turkey.

Prolidase and oxidative stress in chronic hepatitis C.

BACKGROUND: Hepatitis C infection represents a common healthcare issue worldwide. The present trial was designed to investigate the role of prolidase, an enzyme that is significantly involved in the biosynthesis of collagen, and of the oxidative stress that is considered to be involved in the pathogenesis of various diseases, in the chronic hepatitis C infection. The trial was performed to assess the serum prolidase enzyme level and the oxidative-antioxidative status and to determine the relation between the serum prolidase activity and the oxidative stress parameters. METHODS: A total of 95 individuals, including 55 patients with chronic hepatitis C infection (CHC) and 40 healthy adults, were enrolled in the trial. The values for prolidase, the total antioxidant status (TAS), the total oxidative stress (TOS), the oxidative stress index (OSI), sulfhydryl (SH), lipid peroxidation LOOH, catalase (CAT), and ceruloplasmin were measured and compared between the patient groups. RESULTS: The prolidase, TOS, LOOH, CAT, and the OSI values were higher in the chronic hepatitis C group compared to the control group (P < 0.001). The TAS, SH, and ceruloplasmin levels were lower in the CHC group relative to the control group (P < 0.001). CONCLUSION: We suppose that the values of prolidase and the oxidative stress are increased while the antioxidant levels are decreased in CHC. As a result, prolidase and the oxidative stress seem to be related with the progression of the disease.

Management of Brucella endocarditis: results of the Gulhane study.

Brucella endocarditis (BE) is a rare but life-threatening complication of human brucellosis. The aim of this study was to investigate the course of BE along with the therapeutic interrelations. A total of 53 patients with BE hospitalised in 19 health institutions between 2006 and 2011 were included in the Gulhane study. Diagnosis of brucellosis was established by either isolation of Brucella sp. or the presence of antibodies, and the definition of endocarditis was made according to Duke's criteria. There were four treatment groups: ceftriaxone combined with oral antibiotics (Group 1); aminoglycosides combined with oral antibiotics (Group 2); oral antibiotic combinations (Group 3); and aminoglycoside plus ceftriaxone combined with an oral antibiotic (Group 4). Involvement rates of the aortic, mitral and tricuspid valves were 49.1%, 43.4% and 5.7%, respectively. Thirty-two patients (60.4%) had an underlying cardiac valvular problem, including previous prosthetic valve replacement (n=18). Medical treatment was provided to 32 patients (60.4%), whilst concordant medical and surgical approaches were provided to 21 patients (39.6%). Mortality in Group 1 was 15% (3/20), whilst in Group 2 it was 5.3% (1/19). In Group 3, 25.0% (3/12) of the cases died, whereas none of the cases in Group 4 died. In conclusion, mortality increased 47-fold with pericardial effusion and 25-fold due to congestive heart failure that developed after BE. Although mortality was lower in the aminoglycoside-containing arm (Groups 2 and 4), statistical analysis could not be performed owing to the small number of patients.

Comparative analysis of cerebrospinal fluid adenosine deaminase activity in meningitis.

AIM: The purpose is to determine the cut-off value of adenosine deaminase (ADA) activity in cerebrospinal fluid (CSF) of patients with tuberculous and non-tuberculous meningitis, and to assess its value in differential diagnosis. MATERIAL AND METHODS: This study was conducted in 91 patients with meningitis in two university hospitals in Turkey. 24 patients had tuberculous meningitis (TBM), 25 purulent meningitis (PM), 25 aseptic meningitis (AM) and 17 neurobrucellosis (BM). ADA activity of CSF was quantified by colorimetry. RESULTS: In our study, mean ADA values in CSF were 28.34 ± 14.83 IU/L in TB cases, 8.71 ± 5.83 IU/L in BM, 6.18 ± 2.54 IU/L in PM and 3.43 ± 3.48 U/L in AM cases. If we accept for CSF ADA an activity cut-off value of 12.5 IU/L for differential diagnosis of TBM and BM, its sensitivity was 92% and specificity was 88%. If we accept 12.35 IU/L for differential diagnosis of TBM and PM, its sensitivity was 92% and specificity was 100%. If we accept 6.45 IU/L for differential diagnosis of TBM and AM, its sensitivity was 100% and specificity was 92%. Additionally, we examined the cases after dividing them into two groups, viz. TB and non-TB. If we accept an ADA activity cut-off level of 11 IU/L for differential diagnosis of TB and non-TB by applying ROC analysis, its sensitivity was 92% and specificity was 90%. CONCLUSION: The sensitivity and specificity for CSF ADA activity are markedly high in differential diagnosis of TB from non-TB. Hence CSF ADA activity may be used as a simple, cost-effective and reliable test for early differential diagnosis of TB.

Decreasing oxidative stress in response to treatment in patients with brucellosis: could it be used to monitor treatment?

OBJECTIVES: The aims of this study were to evaluate oxidant and antioxidant status in patients with acute brucellosis before and after therapy, and to determine whether this index could be used to monitor the treatment of brucellosis. METHODS: Thirty patients with a diagnosis of acute brucellosis and 37 healthy volunteers were enrolled in the study. Total antioxidant status (TAS) and total oxidant status (TOS) were measured in patients before and after therapy, and an oxidative stress index (OSI) was calculated. These measurements were also taken for the healthy control group and the values were compared. RESULTS: Plasma levels of TOS and OSI were significantly higher in patients with brucellosis before therapy as compared to the treated group (t: 11.19, p<0.000 and t: 9.91, p<0.000, respectively). After treatment, TOS and OSI levels were lower, whereas in contrast, TAS levels were significantly higher (t: -4.17, p<0.000). TOS and OSI levels were found to be significantly higher in the patients before treatment than in the control group (t: 15.01, p<0.000 and t: 15.00, p<0.000, respectively). TAS levels in patients before treatment were lower than in the controls and the difference was significant (t: -8.03, p<0.000). TOS and OSI levels were significantly higher in the treated group than in the control group (t: 4.58, p<0.000 and t: 9.91, p<0.000, respectively). TAS levels in the treated group were lower than in the control group and the difference was significant (t: -3.02, p<0.004). CONCLUSION: Reduced TAS capacity and elevated TOS levels may lead to considerable oxidative stress in brucellosis. Increased oxidative stress may cause severe oxidative damage in the body, and even though this damage ameliorates considerably with 6weeks of treatment, normal healthy levels are not attained. In addition, it appears possible that these oxidant and antioxidant parameters could be used to monitor treatment.

Where do we stand in the control of rabies? Knowledge and practices among physicians in a health district in Turkey.

OBJECTIVE: The aim of this study was to determine the level of knowledge of rabies transmission and control among physicians practicing in healthcare centers in Sanliurfa, Turkey where 2 cases of human rabies were reported in the past 12 months. Implementation issues regarding the current guidelines will also be discussed. METHODS: A cross-sectional study was conducted among 84 physicians practicing in healthcare centers in Sanliurfa, located in the Southeastern Anatolian region of Turkey. RESULTS: Among physicians, average duration of medical practice was 8.5 ± 6.7 years. The correct incubation period of rabies cases was known by 57.1% of the physicians. While 88.1% of physicians were aware of possible exposure routes, only 44.0% of them had the information that mucosal contact may also lead to transmission. While 96.4% of the physicians correctly indicated that cats and dogs can transmit the disease, the fact that foxes also have a role in transmission was known by only 48.8%. Post-exposure prophylaxis was correctly indicated by 65.5% of participants, but only 17.9% had correct information about pre-exposure prophylaxis. CONCLUSION: An important approach in rabies control is to increase community awareness, particularly among healthcare providers. It was found that basic management issues and insufficient awareness still exist despite the presence of legal regulations. To control rabies, the issue must be dealt with locally, through both economic and social means, by supporting rabies control efforts of local health and agricultural directorate managers and by encouraging collaboration with academics.

Increased liver mast cells in patients with chronic hepatitis C.

BACKGROUND AND AIM: The aim of the study was to investigate the mast cell (MC) concentration in the liver tissue of patients diagnosed with chronic hepatitis C and to determine whether there was a correlation with clinical and pathological characteristics of patients. MATERIALS AND METHODS: The study was conducted on liver biopsy samples from 60 patients with chronic hepatitis C. Clinical and laboratory data were obtained from follow-up records. Stained liver biopsies were examined. Immunohistochemical staining was performed by using an anti-c-kit antibody. Patients were divided into four groups (minimal, mild, moderate, and severe) based on the intensity of inflammation and their hepatic activity index scores and into two groups (no-mild, moderate-severe) according to fibrosis grade. RESULTS: Among patients enrolled, 60.0% (n=36) were men with a mean age of 48.3 ± 12.7 (range 18-64) years. The mean number of mast cells per portal area in the liver was 0.87 ± 0.86 (0-4.0). No correlation was found between alanine aminotransferase (ALT) and hepatitis C virus (HCV). Ribonucleic acid ( RNA ) levels and the degree of inflammation of cases with number of mast cells and liver steatosis (P>0.05). As the degree of fibrosis increased in the liver so did the number of mast cells in portal areas (P=0.001). On the other hand, no correlation was found between the degree of fibrosis and the number of MCs in the sinusoids and steatosis (P<0.05). The increase in the number of MCs in the portal areas correlated with an increase in liver steatosis (t: 0.02, P=0.04). CONCLUSION: In light of these findings, it appears possible that MC accumulation in chronic HCV patients may be used as an indicator of fibrosis and possibly be considered in the follow-up of these patients.

[A human rabies case with antemortem diagnosis]. / Yasarken tani konulan bir insan kuduz olgusu.

Rabies, which is an acute, progressive, fatal zoonotic infectious disease, is almost always caused by the bite of rabid animals containing rabies virus in their saliva. Since there is no established specific therapy for rabies, preventive and prophylactic measures are of critical importance. In this report a case of human rabies diagnosed antemortem, was presented. A 29 year old man was admitted to Harran University Hospital (in Sanliurfa province, located at southeastern Anatolia) emergency service with symptoms of high fever, general weakness, paresthesia of the right arm, hypersalivation and dysphagia. The patient with poor socioeconomical status was living in a rural area and his anamnesis revealed a history of dog bite about five months ago. It was learned that he refused vaccination against rabies after the bite event, despite the warnings of his relatives. Shortly after admission, the patient's neurological status severly deteriorated; he became increasingly agitated. Upon the development of progressive respiratory failure, the patient underwent ventilatory support and heavily sedated with presumptive diagnosis of rabies. A nuchal skin biopsy, cerebrospinal fluid, saliva and corneal smear were sent to the Ministry of Agriculture and Rural Affairs Etlik Central Veterinary Control and Research Institute Rabies Diagnosis Laboratory in Ankara. The corneal smear was positive for rabies virus antigen revealed by direct fluorescent antibody test and saliva sample was also positive for rabies virus RNA by reverse-transcriptase polymerase chain reaction assay. Thus, on the third day of the admission the diagnosis was confirmed and on day 11, the patient was deceased due to rabies encephalitis. This case report emphasizes the importance of public education particularly in low socio-economic and socio-cultural areas, about rabies transmission and preventive and prophylactic measures that should be taken after animal bite.

[A rare cause of nosocomial bacteremia: Sphingomonas paucimobilis]. / Sphingomonas paucimobilis: nadir bir hastane kaynakli bakteriyemi etkeni.

Sphingomonas paucimobilis, is a yellow-pigmented, aerobic, non-fermentative, non-spore-forming, gram-negative bacillus. Infections by S. paucimobilis which is widely found in nature and hospital environments are rarely serious or life threatening. In this report we present a case of hospital acquired bloodstream infection due to S. paucimobilis. The patient had a history of hydrocephalus diagnosed at sixth months of his birth and had experienced two ventriculoperitoneal shunt surgery. He was hospitalized and been treated for bronchopneumonia. On the 47th day of hospitalization, blood cultures (BACTEC, Becton Dickinson, USA) were taken because of a body temperature of 38.5 degrees C. One of the blood cultures was positive for gram-negative rods. After 48 h of incubation, the sub-cultures on blood agar medium yielded pure growth of a yellow, non-fermentative, gram-negative, rod-shaped bacterium. The microorganism was positive for oxidase, and esculin hydrolysis, while negative for urea and nitrate reduction and citrate utilisation. Motility was negative as well. The isolate has been identified as S. paucimobilis by using mini API (bioMerieux, France) system. The antibiotic susceptibility test was also performed with the same system and the strain was found susceptible to ceftazidime, ceftriaxone, cefoperazone, cefepime, cefotaxime, ciprofloxacin, imipenem, piperacillin-tazobactam, aztreonam, amikasin and gentamicin. Treatment with intravenous ceftriaxone (2 x 750 mg/day) was initiated. He responded well to the treatment and discharged on the tenth day. This case was reported to emphasize that S. paucimobilis should be kept in mind as a nosocomial infectious agent and the infections should be treated according to the sensitivity test results.

Three cases of anicteric leptospirosis from Turkey: mild to severe complications.

Leptospirosis is an acute generalized infectious disease, caused by spirochaetes, Leptospira interrogans. The severity of the disease ranges from an asymptomatic subclinical course to a fatal outcome. The three cases presented here were diagnosed serologically and had thrombocytopenia and acute renal failure as complication of anicteric leptospirosis. Our first case admitted with clinical presentation of pneumonia but clinical progress and laboratory findings made us to consider leptospirosis. The other two cases presented with aseptic meningitis were diagnosed as anicteric leptospirosis by the serological test results. One of the cases had fatal outcome but could not be strictly correlated with leptospirosis.

Juniper tar poisoning.

Juniper tar (cade oil) is distilled from the branches and wood of Juniperus oxycedrus. It contains etheric oils, triterpene and phenols, and is used for many purposes in folk medicine. A case is reported of a previously healthy man who ingested a spoonful of home-made extract of Juniperus oxycedrus. The poisoning caused fever, severe hypotension, renal failure, hepatotoxicity, and severe cutaneous burns on the face. After supportive and symptomatic treatment, the patient improved and was discharged in a good condition on the eleventh day.