Historical epidemiology of hepatitis C virus (HCV) in selected countries.

Chronic infection with hepatitis C virus (HCV) is a leading indicator for liver disease. New treatment options are becoming available, and there is a need to characterize the epidemiology and disease burden of HCV. Data for prevalence, viremia, genotype, diagnosis and treatment were obtained through literature searches and expert consensus for 16 countries. For some countries, data from centralized registries were used to estimate diagnosis and treatment rates. Data for the number of liver transplants and the proportion attributable to HCV were obtained from centralized databases. Viremic prevalence estimates varied widely between countries, ranging from 0.3% in Austria, England and Germany to 8.5% in Egypt. The largest viremic populations were in Egypt, with 6,358,000 cases in 2008 and Brazil with 2,106,000 cases in 2007. The age distribution of cases differed between countries. In most countries, prevalence rates were higher among males, reflecting higher rates of injection drug use. Diagnosis, treatment and transplant levels also differed considerably between countries. Reliable estimates characterizing HCV-infected populations are critical for addressing HCV-related morbidity and mortality. There is a need to quantify the burden of chronic HCV infection at the national level.

Strategies to manage hepatitis C virus (HCV) disease burden.

The number of hepatitis C virus (HCV) infections is projected to decline while those with advanced liver disease will increase. A modeling approach was used to forecast two treatment scenarios: (i) the impact of increased treatment efficacy while keeping the number of treated patients constant and (ii) increasing efficacy and treatment rate. This analysis suggests that successful diagnosis and treatment of a small proportion of patients can contribute significantly to the reduction of disease burden in the countries studied. The largest reduction in HCV-related morbidity and mortality occurs when increased treatment is combined with higher efficacy therapies, generally in combination with increased diagnosis. With a treatment rate of approximately 10%, this analysis suggests it is possible to achieve elimination of HCV (defined as a >90% decline in total infections by 2030). However, for most countries presented, this will require a 3-5 fold increase in diagnosis and/or treatment. Thus, building the public health and clinical provider capacity for improved diagnosis and treatment will be critical.

The present and future disease burden of hepatitis C virus (HCV) infection with today's treatment paradigm.

The disease burden of hepatitis C virus (HCV) is expected to increase as the infected population ages. A modelling approach was used to estimate the total number of viremic infections, diagnosed, treated and new infections in 2013. In addition, the model was used to estimate the change in the total number of HCV infections, the disease progression and mortality in 2013-2030. Finally, expert panel consensus was used to capture current treatment practices in each country. Using today's treatment paradigm, the total number of HCV infections is projected to decline or remain flat in all countries studied. However, in the same time period, the number of individuals with late-stage liver disease is projected to increase. This study concluded that the current treatment rate and efficacy are not sufficient to manage the disease burden of HCV. Thus, alternative strategies are required to keep the number of HCV individuals with advanced liver disease and liver-related deaths from increasing.

Predictors of outcome in patients with tuberculous meningitis.

OBJECTIVE: To assess predictors of mortality and neurological sequelae in patients with tuberculous meningitis (TBM). METHODS: Patients with TBM treated at 12 university hospitals in Turkey between 1985 and 1997 were evaluated using a standardised protocol applied retrospectively. Variables associated with hospital mortality as well as with the presence of neurological sequelae at 6 months were determined using logistic regression models. RESULTS: Four hundred and thirty-four patients between the ages of 13 and 83 years (mean 33 years) were evaluated. Sixty-eight per cent of these patients presented with Medical Research Council Stage II or III. One hundred and one patients (23.3%) died and 67 (27%) of evaluable survivors had neurological sequelae. In multi-variable analysis, convulsion (OR 3.3, 95%CI 1.2-9.0, P = 0.02), comatose mental status (OR 6.0, 95%CI 3.6-10.2, P = 0.01), and delayed or interrupted treatment (OR 5.1, 95%CI 2.4-11.2, P = 0.01) were shown to be predictors for mortality. The presence of extra-meningeal tuberculosis (OR 2.1, 95%CI 1.1-4.2, P = 0.035), cranial nerve palsy (OR 2.6, 95%CI 1.4-4.2, P = 0.01), hemiparesia/focal weakness (OR 9.3, 95%CI 3.8-22.6, P = 0.01), hemiplegia/multiple neurological deficit (OR 7.1, 95%CI 2.14-23.38, P = 0.01) and drowsiness (OR 4.2, 95%CI 2.04-8.82, P = 0.01) were independent predictors of neurological sequelae at 6 months following hospital discharge. CONCLUSION: The results of this study emphasise the importance of prompt and uninterrupted anti-tuberculosis therapy for tuberculous meningitis. The presence of seizures or coma on admission to hospital are important predictors for mortality, while the presence of focal neurological signs is a predictor for persistent neurological sequelae in survivors.

Epidemiology and clinical outcome of hepatitis D virus infection in Turkey.

The prevalence, the epidemiology, the clinical and biochemical characteristics of hepatitis delta virus (HDV) infection were studied in patients with HBsAg-positive acute hepatitis, in those with chronic liver disease, and in apparently healthy carriers in Turkey. Fifty-eight of the 242 carriers of HBsAg (23.9%) and 31 of the 237 (13.1%) patients with acute HBsAg-positive hepatitis had serological evidence of HDV infection. Eleven of these individuals were HBsAg carriers with acute HDV superinfection. The prevalence of HDV infection was significantly (p less than 0.001) higher in patients with chronic liver disease (54/165; 32.7%) than in asymptomatic carriers of HBsAg (4/77; 5.2%). The highest prevalence (26/57; 45.6%) of HDV infection was found in patients at high risk of acquiring hepatitis virus infection (health care workers, hemodialysis patients, polytransfused patients) with chronic liver disease. Whereas the frequency of "severe" or fulminant hepatitis was similar in HBV infected patients (7.8%) and in HBV/HDV coinfected individuals (10%), the frequency of biphasic hepatitis was significantly (p less than 0.005) higher in the latter patients (30%) than in those with classical hepatitis B (7.8%). Chronic evolution of the disease was observed in 3.9% of the patients with classical hepatitis B and in 5% of those who had evidence of simultaneous HBV/HDV infection. The 10 carriers of HBsAg who survived the acute HDV superinfection developed chronic delta hepatitis. These findings indicate that HDV is endemic in Turkey and that its prevalence is highest among chronic HBsAg-positive hepatitis patients, implicating HDV as a major cause of liver disease among urban Turkis.

Widespread detection of PER-1-type extended-spectrum beta-lactamases among nosocomial Acinetobacter and Pseudomonas aeruginosa isolates in Turkey: a nationwide multicenter study.

We studied the prevalence and molecular epidemiology of PER-1-type beta-lactamases among Acinetobacter, Klebsiella, and Pseudomonas aeruginosa strains isolated over a 3-month period in eight university hospitals from distinct regions of Turkey. A total of 72, 92, and 367 Acinetobacter, Klebsiella, and P. aeruginosa isolates were studied, respectively. The presence of blaPER was determined by the colony hybridization method and later confirmed by isoelectric focusing. We detected PER-1-type beta-lactamases in 46% (33/72) of Acinetobacter strains and in 11% (40/367) of P. aeruginosa strains but not in Klebsiella strains. PER-1-type enzyme producers were highly resistant to ceftazidime and gentamicin, intermediately resistant to amikacin, and susceptible or moderately susceptible to imipenem and meropenem. Among PER-1-type-beta-lactamase-positive isolates, five Acinetobacter isolates and six P. aeruginosa isolates from different hospitals were selected for ribosomal DNA fingerprinting with EcoRI and SalI. The EcoRI-digested DNAs were later hybridized with a digoxigenin-labelled PER-1 probe. The ribotypes and the lengths of blaPER-carrying fragments were identical in four Acinetobacter strains. A single isolate (Ac3) harbored a PER gene on a different fragment (approximately 4.2 kbp) than the others (approximately 3.4 kbp) and showed a clearly distinguishable ribotype. Ribotypes of P. aeruginosa strains obtained with EcoRI showed three patterns. Similarly, in Pseudomonas strains two different EcoRI fragments harbored blaPER (approximately 4.2 kbp in five isolates and 3.4 kbp in one isolate). PER-1-type beta-lactamases appear to be restricted to Turkey. However, their clonal diversity and high prevalence indicate a high spreading potential.

Tuberculous meningitis in adults in Turkey: epidemiology, diagnosis, clinic and laboratory [corrected].

A retrospective study was performed to assess the epidemiology, diagnosis, clinic, and laboratory of the patients with tuberculous meningitis (TBM) in a multicentral study. The medical records of adult cases with TBM treated at 12 university hospitals throughout Turkey, between 1985 and 1998 were reviewed using a standardized protocol. The diagnosis of TMB was established with the clinical and laboratory findings and/or microbiological confirmation in cerebrospinal fluid (CSF). The non-microbiologically confirmed cases were diagnosed with five diagnostic sub-criteria which CSF findings, radiological findings, extra-neural tuberculosis, epidemiological findings and response to antituberculous therapy. A total of 469 patients were included in this study. Majority of the patients were from Southeast Anatolia (164 patients, 35.0%) and (108 patients, 23.0%) from East Anatolia regions. There was a close contact with a tuberculous patient in 88 of 341 patients (25.8%) and with a tuberculous family member in 53 of 288 patients (18.4%). BCG scar was positive in 161 of 392 patients (41.1%). Tuberculin skin test was done in 233 patients and was found to be negative in 75. Totally 115 patients died (24.5%) of whom 23 died in 24 hour after admittance. The diagnosis was confirmed with clinical findings and CSF culture and/or Ziehl-Nelson staining in 88 patients (18.8%). Besides clinical criteria, there were three or more diagnostic sub-criteria in 252 cases (53.7%), two diagnostic sub-criteria in 99 cases (21.1%), and any diagnostic sub-criteria in 30 patients (6.4%). Since TBM is a very critical disease, early diagnosis and treatment may reduce fatal outcome and morbidity.