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Introduction As of January 2021, rotavirus vaccination programs have been implemented in 109 countries and their use has resulted in a positive impact on rotavirus-related diarrheal hospitalizations and mortality in children below five years of age. Despite these successes, several countries in Africa and Asia where disease burden is high have not yet implemented rotavirus vaccination at all or at a scale sufficient enough to demonstrate impact. This could be, among other reasons, due to poor vaccine coverage and the modest levels of efficacy and effectiveness of the vaccines in these resource-limited settings. Areas covered We review various factors related to the human host (malnutrition, maternally-derived antibodies and breastfeeding, genetic factors, blood group and co-administration with oral polio vaccine), rotavirus pathogen (force of infection, strain diversity and coinfections) and the environment (related to the human microbiome) which reflect complex and interconnected processes leading to diminished vaccine performance in resource-limited settings. Expert opinion Addressing the limiting factors for vaccine efficacy is needed but likely to take a long time to be resolved. An immediate solution is to increase the immunization coverage to higher values generating an overall effect of adequate proportion of protected population to reduce the prevalence of rotavirus disease.

Introduction and Objectives Hepatitis E virus (HEV) is one of the most common causes of acute hepatitis. In recent years, its role in the development of chronic hepatitis and cirrhosis especially in immunosuppressed patients and its wide range of extrahepatic involvement have increased the amount of research on HEV. In this study we aimed to investigate the presence of HEV infection in individuals with cryptogenic cirrhosis. Materials and methods HEV antibodies were analysed using the Anti HEV enzyme-linked immunosorbent assay (ELISA) kit (anti-HEV ELISA; Diapro Prodiagnostic Bioprobes, Milan, Italy). HEV RNA was isolated with using QIAMP Viral RNA mini kit (QIAGEN, Hilden, Germany). The HEV RNA titre was detected with the Rotor Gene 3000 real time polymerase chain reaction (PCR) system using GenoSen's HEV (Rotor Gene) Quantitative Real Time PCR Kit (Genome Diagnostics Private Limited, the Netherlands). Results Our study included 21 healthy volunteers (12 males) and 35 cryptogenic cirrhosis patients (19 males). The ages of the patients and the controls were similar (46 ± 12.1 vs. 37.5 ± 9.7years). The mean Child–Pugh score was 8 ± 2.5. The anti HEV immunoglobulin G(IgG) positivity rate was 9.5% and 25.7% in the control and patient groups respectively (p > 0.05). HEV RNA positivity was not detected in the control group, but 3 cases (8.6%) in the patient group were positive (p > 0.05). The HEV RNA, aspartate aminotransferase (AST) and alanine aminotransferase(ALT) levels for these 3 cases were 326.461 copies/mL, 91 IU/L and 67 IU/L; 480 copies/mL, 68 IU/L and 36 IU/L and 72 copies/mL, 42 IU/L and 24 IU/L respectively. There were positive correlations between HEV RNA levels and AST and ALT levels (p Conclusions Anti HEVIgG and HEV RNA positivity rates are high in cryptogenic cirrhosis although it is not statistically significant and there is a positive correlation between HEV RNA and aminotransferases.

The diagnosis of influenza A virus is essential since it can be confused with influenza A like illness and lead to inaccurate drug prescription. In this study, the M2e peptide, a strategic antigen that is conserved in all virus subtypes, was used as a diagnostic marker of influenza A. For the first time, M2e-specific IgY antibody was covalently conjugated to alkaline phosphatase (ALP) enzyme in the presence of glutaraldehyde. The antibody-enzyme bioconjugate was characterized by fluorescence and Fourier-transform infrared spectroscopy. Subsequently, the diagnostic value of this bioconjugate was evaluated by direct sandwich ELISA using nasopharyngeal swab samples positive/negative for H1N1 and H3N2, which were previously analyzed by rRT-PCR for influenza. In conclusion, the M2e-specific IgY-ALP bioconjugate demonstrated positive results for Influenza A in samples that were diagnosed as Influenza A via the RT-PCR method.

Introduction: The aim of this study was to asses the surveillance of influenza A/other respiratory viruses and risk factors in hospitalized children with the symptoms of influenza-like illness during two consecutive influenza seasons. Methodology: All children hospitalized with adiagnosis of influenza-like illness had been investigated for Influenza A and other respiratory antigens in pharengeal/nasopharyngeal secretions. Results: A total of 132 hospitalized children between December 2013-May 2014 and December 2014-May 2015 were enrolled in this study. At least one respiratory virus was found to be positive by RT-PCR in 78 (59%) patients, influenza A (H3N2) was detected in only 8 (6%) patients. In 54 (41%) patients samples no respiratory viral pathogen was detected and in 70 (53%) patients, one non- influenza A virus was detected. The respiratory viral pathogens detected in decreasing rates were:RSV (n = 46, 35%), HCoV (n = 10, 7.5%), adenovirüs (n = 7, 5%), rhinovirüs (n = 6, 4.5%), HMPV (n = 5, 4%), Influenza B (n = 4, 3%) ve human Bocavirus (n = 2, 1.5%). In 10 patients, coinfection was detected, however none was with H3N2. In the H3N2 (+) group, the following risk factors were identified: age older than three years (p < 0.05), asthma history (p < 0.05) and chronic lung diseases (p < 0.05). Conclusion: Influenza A virus was detected in 6% of hospitalized patients with influenza-like illness. Viruses other then Influenza, especially RSV, can cause similar symptoms compatible with Influenza-like-illness.

The knowledge about the viral etiologies causing respiratory disease in adults is limited. Viral respiratory diseases may lead deterioration in certain patient populations. The aim of this study was to determine the viral etiologies of influenza-like illness among patients requiring hospitalization and to document the risk factors for mortality. This prospective study was performed in one of the 7 centers in Turkey in the context of influenza surveillance by the Global Influenza Hospital Surveillance Network. A 35-bed Adult Emergency Service and 10-bed Acute Care Unit were screened for consequent recruitment of eligible patients daily, on weekdays only. ICD-10 codes in the electronic health records and direct patient encounters were used to screen for the following eligibility diagnoses: acute respiratory tract infection, asthma, heart failure, pneumonia, influenza, chronic obstructive lung disease, dyspnea/respiratory abnormality, respiratory symptoms, cough and fever. A total of 334 patients who were admitted with the eligible ICD-10 codes within the 24th and 48th hours were screened during the study period and of those eligible ones, 106 consented and were swabbed. Nasal or nasopharyngeal swabs were collected using Virocult (Medical Wire & Equipment, UK) and sent to the central laboratory in 1-3 days. Swabs were collected and specimens were introduced to real-time polymerase chain reaction based multiplex kits, as well as, ABI 7500 platform with CDC primers and probes. A total of 106 patients were swabbed. Hospital mortality was 12.2%. More than one fourth of the patients needed a sort of mechanical ventilation support and at least one organ failure developed in one third of the patients. One or more viral pathogens were detected in 56 (52.8%) of the swabbed patients, with influenza H3N2 being the most prevalent one. Having a lower body mass index (OR, 0.845, p= 0.034) was associated with mortality. Chronic lung diseases were shown to confer a survival advantage (OR, 0.127, p= 0.009). Community acquired viral respiratory infections might lead to significant compromise in adult patients. Prevention of malnutrition might result in better outcomes in patients who need acute admission. The survival advantage of those with chronic lung diseases warrants further investigation.

Buyukkapu-Bay S, Kebudi R, Gorgun O, Mese S, Zulfikar B, Badur S. Respiratory viral infection`s frequency and clinical outcome in symptomatic children with cancer: A single center experience from a middle-income country. Turk J Pediatr 2018; 60: 653-659. In developing countries, acute respiratory tract infections are a significant cause of morbidity and mortality in children, particularly in pediatric cancer patients. A majority of these illnesses are precipitated by viral infections. In our country, studies were conducted on the single respiratory viral infection in a pediatric hematology-oncology unit; however, the analysis of respiratory viral infections in children with cancer is lacking. The present study aimed to provide analysis of multiple respiratory viral infections and clinical outcome in children with cancer who receive chemotherapy and show signs and symptoms of respiratory tract infections. During January, 2014 and January, 2015 children with cancer under treatment who presented with respiratory tract infections were assessed for viruses by using multiplex real-time reverse transcription polymerase chain reaction (rRT-PCR). Specimens were collected by nasal swabbing at in-patient and out-patient clinics. Overall, 72 samples of respiratory tract infection episodes, collected from children with cancer were evaluated with the simultaneous detection of 20 respiratory viruses. A respiratory viral pathogen was obtained in 56.9% samples. Rhinovirus (24.3%) and co-infection with two viruses (19.5%) were the most frequently isolated pathogens. There were four (9.6%) samples of severe pneumonia. Patients with febrile neutropenic episodes and pneumonia were hospitalized and treated with broad-spectrum antibiotics. Other non-neutropenic and mild respiratory tract infections were treated with supportive care as outpatient procedures. There were no deaths. Because there are no effective antiviral agents for certain respiratory viruses, infection control and early diagnosis are crucial in preventing the spread of infection. Clinical findings and serological results of viral respiratory tract infections help us to accurately determine the treatment approach and avoid the unnecessary use of antibiotics.

Rotavirus gastroenteritis imposes a heavy burden on low- and middle-income countries. The World Health Organization defines the Eastern Mediterranean region (WHO-EMRO) as a diverse area in terms of socioeconomic status and health indicators. Rotavirus vaccination has been introduced, at least partially, in 19 out of the 22 EM countries; however, vaccine coverage remains low, and data on rotavirus disease burden is scarce. Available data on rotavirus prevalence, seasonality, vaccination status, and genotype evolution was systematically compiled following a literature review that identified 165 relevant WHO-EMRO epidemiology studies published between 1990 and 2017. Although the infectious agents responsible for acute gastroenteritis vary over time, rotavirus remained the leading cause of acute gastroenteritis in children, as seen in 76.3% of reviewed publications. Younger children (

BACKGROUND The HBV core protein plays a major role in host immune response. Mutations occurring in the HBV core gene may cause alterations in the major epitopes being effective in the host immune response. Until now, the persistent effects of core gene mutations on HBV infections have not been fully understood. The aim of this study is to analyze the core gene mutations for epitopes in the T lymphocytes [T helper (Th) and cytotoxic (CTL)] and B cell and C terminal region in patients with chronic hepatitis using ultra-deep pyrosequencing (UDPS) method. METHODS Eleven patients with chronic hepatitis B infection were included in the study. Amplification of the core gene was performed by a conventional PCR method. Mutations in the epitopes for T lymphocytes (Th and CTL) and B cell and in the C terminal region of HBV core gene were screened by UDPS. These mutations were analyzed in HBeAg positive and negative patients. RESULTS The minimum percentages of amino acid substitutions were found with 0.9% in HBeAg positive patients and 1.2% in negative patients. The number of missense mutation was higher in patients with HBeAg positive than negative patients (p < 0.005). The number of amino acid substitutions in the region of aa49 - 69 in the Th epitopes was found to be the highest in both HBeAg positive and negative patients. The mutation frequency was higher in the C-terminal region of the core protein compared to the Th, CTL, and B cell regions and these were more common in subjects with high-grade fibrosis. Some types of mutations (V27I, R47H, Y132I, R174STOP, S181P, Q182K) were only detected in subjects with liver cirrhosis. CONCLUSIONS Unlike literature, our results show that there is no significant increase in number of mutations in the core gene of the virus during the anti-HBe positive period. The role of low abundance variants and mutations in the immune system can be understood using methods such as UDPS in the near future.

Human influenza is predominantly caused by influenza A virus (IAV) - A/H1N1 and/or A/H3N2 - and influenza B virus (IBV) - B/Victoria and/or B/Yamagata, which co-circulate each season. Influenza surveillance provides important information on seasonal disease burden and circulation, and vaccine content for the following season. To study the circulating influenza subtypes/lineages in western Turkey. Community-based sentinel surveillance results during 2003-2016 (weeks 40-20 each season; but week 21, 2009 through week 20, 2010 during the pandemic) were analyzed. Nasal/nasopharyngeal swabs from patients with influenza-like illness were tested for influenza virus and characterized as A/H1N1, A/H3N2, or IBV. A subset of IBV samples was further characterized as B/Victoria or B/Yamagata. Among 14,429 specimens (9,766 collected during interpandemic influenza seasons; 4,663 during the 2009-2010 pandemic), 3,927 (27.2%) were positive. Excluding the pandemic year (2009-2010), 645 (27.4%) samples were characterized as A/H1N1 or A/H1N1/pdm09, 958 (40.7%) as A/H3N2, and 752 (31.9%) as IBV, but the dominant subtype/lineage varied widely each season. During the pandemic year (2009-2010), 98.3% of cases were A/H1N1/pdm09. IBV accounted for 0-60.2% of positive samples each season. The IBV lineages in circulation matched the vaccine IBV lineage >50% in six seasons and

The potential antiviral resistance mutations within hepatitis B virus (HBV) reverse transcriptase (RT) region for nucleos(t)ide analogues (NA) are not well known. Especially, the effect of pre-existing antiviral drug resistance mutations in untreated patients in comparison to the resistance developed after treatment is not still clear. Sixteen naive chronic hepatitis B patients were studied. None of the patients had received NA treatment prior to the serum samples being collected. Forty-two potential NA resistance (NAr) mutation sites were screened by ultra-deep pyrosequencing (UDPS). After therapy, mutations conferring treatment resistance were detected by LiPA. Serum samples taken before treatment showed no classic primary or compensatory/secondary drug resistance mutations. However, NAr mutations found in 6 isolates (37.5%) involved 7 positions including rtL91I, rtT128I, rtQ215P, rtF221Y, rtN238D, rtC256S, and rtI266G. Substitutions at 3 NAr mutation sites (rtT128I, rtN238D, and rtC256S) were detected in 3 unresponsive patients developing drug resistance after NA treatment. One patient with rtI266G mutation also developed drug resistance after lamivudine (LAM) therapy. However, the relationship between rtI266G mutation and NA drug resistance was not previously reported. These results suggest that association of potential mutations besides the primary and secondary/compensatory resistance mutations should be investigated. Investigation of NAr mutations before treatment may be important for the success of the treatment.

Despite the effectiveness of nucleoside/nucleotide analogues in the treatment of chronic hepatitis B (CHB), their long-term administration is associated with the emergence of resistant hepatitis B virus (HBV) mutants. In this study, mutations resulting in antiviral resistance in HBV DNA samples isolated from 23 CHB patients (nine treatment naïve and 14 treated previously) were studied using a line probe assay (INNO-LiPA HBV DR; Innogenetics) and ultradeep pyrosequencing (UDPS) methods. Whilst the INNO-LiPA HBV DR showed no resistance mutations in HBV DNA samples from treatment-naive patients, mutations mediating lamivudine resistance were detected in three samples by UDPS. Among patients who were treated previously, 19 mutations were detected in eight samples using the INNO-LiPA HBV DR and 29 mutations were detected in 12 samples using UDPS. All mutations detected by the INNO-LiPA HBV DR were also detected by UDPS. There were no mutations that could be detected by INNO-LiPA HBV DR but not by UDPS. A total of ten mutations were detected by UDPS but not by INNO-LiPA HBV DR, and the mean frequency of these mutations was 14.7 %. It was concluded that, although INNO-LiPA HBV DR is a sensitive and practical method commonly used for the detection of resistance mutations in HBV infection, UDPS may significantly increase the detection rate of genotypic resistance in HBV at an early stage.

The aim of this study was to determine the frequency of respiratory viruses responsible for respiratory tract infections in Turkish children during the 2011-2012 influenza season. Nasal swabs were obtained from patients with symptoms suggestive of an influenza-like illness between December 2011 and April 2012. Samples were analyzed with multiplex real-time polymerase chain reaction (RT-PCR) to help identify the causative viral pathogen. A total of 200 patients were enrolled in the study. A respiratory virus was detected successfully in 102 (51%) children; influenza A (H3N2) in 39.2%, influenza B in 23.5%, RSV in 15.6%, rhinovirus in 13.7%, bocavirus in 2.9%, coronavirus in 2.9%, and metapneumovirus in 0.9% of patients. Only one patient was co-infected with bocavirus and influenza A virus. A statistically significant difference in the mean age of presentation was observed between the various viral pathogens (P

Background: Infections with influenza A virus cannot be clinically differentiated from infections caused by influenza B virus or other respiratory viruses. Additionally, although antiviral treatment is available for influenza A virus, it is not effective for the other viruses and must be initiated early in the course of disease for it to be effective. For these reasons, there is a need for a rapid, accurate diagnostic test for use in physicians' offices at the time patients are seen. We report the first field performance of BD Veritor™ System for Rapid Detection of Flu A+B test compared to real time PCR. The performance of this test was compared to real time PCR performed in the Istanbul University Influenza Reference Laboratory. Method: A single-blinded cross sectional study was conducted in nine different family medicine centers in Istanbul, Turkey between 01 November 2014 and 01 May 2015. For every patient, two specimens were collected, one for real time PCR and one for the Veritor test. Specimens for the Veritor test were immediately tested at the participating clinic according to the manufacturer's instructions. The specimens for real time PCR were transferred to the reference laboratory. Results: A total of 238 persons were included in the study: 72 (30 %) of the patients included in the study were below 19 years old and accepted as childhood group. Mean age of adults was 42.4 and children 10.2 years. A total of 122 patients out of 238 were positive for influenza. The clinical sensitivity and specificity of the Veritor test in all age groups was determined to be 80 and 94 %, respectively. Positive predictive value was 93 % and the negative one was 81 %. Conclusion: Field performance of the rapid influenza test was high and found to be useful with respect to rational antiviral use, avoiding unnecessary antibiotic usage and the management of cases by the family physicians. © 2016 The Author(s).

Erratum in - Correction: Temporal Patterns of Influenza A and B in Tropical and Temperate Countries: What Are the Lessons for Influenza Vaccination? PLoS One. 2016 May 2;11(5):e0155089. doi: 10.1371/journal.pone.0155089. Introduction: Determining the optimal time to vaccinate is important for influenza vaccination programmes. Here, we assessed the temporal characteristics of influenza epidemics in the Northern and Southern hemispheres and in the tropics, and discuss their implications for vaccination programmes. Methods: This was a retrospective analysis of surveillance data between 2000 and 2014 from the Global Influenza B Study database. The seasonal peak of influenza was defined as the week with the most reported cases (overall, A, and B) in the season. The duration of seasonal activity was assessed using the maximum proportion of influenza cases during three consecutive months and the minimum number of months with 80% of cases in the season. We also assessed whether co-circulation of A and B virus types affected the duration of influenza epidemics. Results: 212 influenza seasons and 571,907 cases were included from 30 countries. In tropical countries, the seasonal influenza activity lasted longer and the peaks of influenza A and B coincided less frequently than in temperate countries. Temporal characteristics of influenza epidemics were heterogeneous in the tropics, with distinct seasonal epidemics observed only in some countries. Seasons with co-circulation of influenza A and B were longer than influenza A seasons, especially in the tropics. Discussion: Our findings show that influenza seasonality is less well defined in the tropics than in temperate regions. This has important implications for vaccination programmes in these countries. High-quality influenza surveillance systems are needed in the tropics to enable decisions about when to vaccinate. The Global Influenza B Study is supported by an unrestricted research grant from Sanofi Pasteur. info:eu-repo/semantics/publishedVersion

Objective: The aim was to describe the clinical and epidemiologic characteristics of patients with lower res- piratory tract infection (LRTI) who were hospitalized to the Pediatric Infection Department in Istanbul due to respiratory viruses from October 2010 through May 2011. Material and Methods: Details of the 156 patients who were hospitalized were recorded. Respiratory viruses were con- firmed in specimens using real-time reverse transcriptase-polymerase-chain-reaction (RT PCR) assay. Results: Respiratory agents were detected in 48 (30.8%) of 156 children with LRTI. Fifty seven patients (36.5%) were female, 99 (63.5%) were male and the median age was 28.2 ±42.1 months. A single agent was identified in 41 (% 85) children, and multiple agents in 7 (%15). Influenza virus was the most common pathogen (31.2%), followed by rinovirus (20.8%), bocavi- rus (14.5%),coronavirus (10.4%), parainfluenza virus (8.3%), metapneumovirus (8.3%) and respiratory syncytial virus (6.2%). There were no statistically significant differences between the two groups (with isolated virus or no known viral etiology) with respect to symptoms, clinical findings, laboratory work-up, or radiological data except LDH level. Elevated levels of LDH in patients with respiratory virus were statistically significant. In addition, we showed a relationship between patients with the viral infection and peribronchial markings on chest X-ray (p = 0.017, OR 4071 CI :1.290-12, 843) and steroid therapy (p

Background: The aim of this study was to describe the clinical and epidemiological characteristics of pandemic influenza in hospitalized children. Methods: A total of 114 patients with suspected H1N1 virus infection were hospitalized, and nasal swabs were sent to National Influenza Reference Laboratory for confirmation of pandemic influenza A (H1N1) virus infection by rRT–PCR assay. Results: Forty-six female and 68 male patients were included in the study. Age of the patients ranged from 40 days to 16 years. Clinical and/or radiological pneumonia were detected in 96% of all. Sixteen patients required mechanical ventilation due to hypoxemia. Previously healthy children required mechanical ventilation and oxygen therapy more than patients with chronic diseases. Elevated levels of CRP and LDH in patients with respiratory distress and patients who required mechanical ventilation were statistically significant. Conclusion: Our study showed that progress of pandemic influenza infection in previously healthy children is as severe as their counterparts with chronic underlying diseases.

SUMMARYIn 2006 an outbreak of avian influenza A(H5N1) in Turkey caused 12 human infections, including four deaths. We conducted a serological survey to determine the extent of subclinical infection caused by the outbreak. Single serum samples were collected from five individuals with avian influenza whose nasopharyngeal swabs tested positive for H5 RNA by polymerase chain reaction, 28 family contacts of the cases, 95 poultry cullers, 75 individuals known to have had contact with diseased chickens and 81 individuals living in the region with no known contact with infected chickens and/or patients. Paired serum samples were collected from 97 healthcare workers. All sera were tested for the presence of neutralizing antibodies by enzyme-linked immunoassay, haemagglutination inhibition and microneutralization assays. Only one serum sample, from a parent of an avian influenza patient, tested positive for H5N1 by microneutralization assay. This survey shows that there was minimal subclinical H5N1 infection among contacts of human cases and infected poultry in Turkey in 2006. Further, the low rate of subclinical infection following contact with diseased poultry gave further support to the reported low infectivity of the virus.

Contains fulltext : 152751.PDF (Publisher’s version ) (Open Access) Influenza B represents a high proportion of influenza cases in some seasons (even over 50%). The Influenza B study in General Practice (IBGP) is a multicenter study providing information about the clinical, demographic and socio-economic characteristics of patients affected by lab-confirmed influenza A or B. Influenza B patients and age-matched influenza A patients were recruited within the sentinel surveillance networks of France and Turkey in 2010-11 and 2011-12 seasons. Data were collected for each patient at the swab test day, after 9+/-2 days and, if not recovered, after 28+/-5 days. It was related to patient's characteristics, symptoms at presentation, vaccination status, prescriptions of antibiotics and antivirals, duration of illness, follow-up consultations in general practice or emergency room. We performed descriptive analyses and developed a multiple regression model to investigate the effect of patients and disease characteristics on the duration of illness. Overall, 774 influenza cases were included in the study: 419 influenza B cases (209 in France and 210 in Turkey) and 355 influenza A cases (205 in France and 150 in Turkey). There were no differences between influenza A and B patients in terms of clinical presentation and number of consultations with a practitioner; however, the use of antivirals was higher among influenza B patients in both countries. The average (median) reported duration of illness in the age groups 0-14 years, 15-64 years and 65+ years was 7.4 (6), 8.7 (8) and 10.5 (9) days in France, and 6.3 (6), 8.2 (7) and 9.2 (6) days in Turkey; it increased with age but did not differ by virus type; increased duration of illness was associated with antibiotics prescription. In conclusion, our findings show that influenza B infection appears not to be milder disease than influenza A infection.

The clinical relevance of hepatitis B virus (HBV) genotypes are poorly understood and it is unclear if the prevalence of HBV genotypes differs with the various clinical features of HBV carriers. The aim of our study was to examine the prevalence of the HBV genotype in a group of patients with chronic hepatitis B, compared to a group with chronic inactive hepatitos B surface antigen (HbsAg) carriers.HBV genotypes were determined in 32 patients with chronic hepatitis B and in 12 chronic inactive HBsAg carriers. 35 males and nine females with a mean age of 33.95 +/- 13.04 were studied. Serum samples were examined for the presence of HBV DNA by polymerase chain reaction (PCR). Samples negative in first round PCR were further amplified with nested PCR. The PCR product was sequenced with the Cy5/5.5 dye primer kit on a Long Read Tower automated DNA sequencer.HBV DNA was detectable in 29 (66%) and 44 (100%) patients by the PCR with universal primers and nested-PCR, respectively. All patients were found to be infected with HBV genotype D. Genotype D was the only detected type found in different clinical forms of chronic HBV infection, in all hepatitis B e antigen (HbeAg)-positive and negative patients, in all patients who had elevated or normal alanine transaminase (ALT) levels and in all ages.In the present study we could not find any association between genotype D and distinct clinical phenotypes. Genotype D is the predominant type among hepatitis B carriers residing in our region and is not associated with more severe liver diseases. This genotype did not influence clinical manifestations in carriers with chronic hepatitis B virus infection. However, additional large-scale longitudinal studies are needed to find the relationship of HBV genotypes to liver disease severity and clinical outcomes.

Ulukol, Betul/0000-0001-8058-0911 WOS: 000173858300019 PubMed: 11818162 Chicken pox highly contagious and common throughout the world, is an infectious disease caused by varicella zoster virus (VZV). This study was conducted to determine the seroprevalence of VZV in a population under age 30 and to identify the relationship of VZV seroprevalence and several characteristics of the study subjects in nine provinces of Turkey. The sampling method of 30 clusters recommended for field studies was used for selecting subjects of a pre-determined number in the rural and urban areas in each province. For this, a total of 60 groups, 30 clusters in the rural and 30 in the urban areas were determined. It was planned that a total of 4800 subjects, including 600 subjects from five big provinces (Istanbul, Ankara, Izmir, Adana, Diyarbakir) and 450 subjects from the remaining smaller provinces (Samsun, Erzurum, Trabzon, Edirne), be included in the study. ELISA method was used to examine the blood samples for VZV seropositivity. Positive VZV seroprevalence was detected in 77.8% of 4387 subjects under age 30 in nine provinces of Turkey. There was no difference in seroprevalence rate between rural and urban areas. Seroprevalence was found to be 79.0% in urban areas and 76.3% in rural areas. Seroprevalence increased with age. Seroprevalence was 20% at the age of 1 year, subsequently increased to 40% at the age of 4 years, 60% at the age 6 years, 80% at the age of 8 years, 85% at the age of 10 years, and then remained at 85-90% in subjects over the age of 10 years. In order to develop vaccination protocols and take appropriate preventive health care measures against diseases in different countries, it is very important to know the seroprevalence of any disease for an individual country. (C) 2002 Elsevier Science Ltd. All rights reserved.

Background & Aims To evaluate the efficacy of tenofovir in chronic hepatitis B (CHB) patients with adefovir resistance (ADF-R) and suboptimal response to adefovir (ADF-S). Methods Nucleos(t)ide analogue (NA)-naive patients and patients with previous adefovir failure receiving tenofovir therapy for at least 6 months were included in the study. Biochemical and virological tests were obtained at baseline and 3-month intervals in the first year and every 6 months thereafter. The primary outcome measure was complete virological response (CVR) (HBVDNA

Background: The fatality attributed to pandemic influenza A H1N1 was not clear in the literature. We described the predictors for fatality related to pandemic influenza A H1N1 infection among hospitalized adult patients. Methods: This is a multicenter study performed during the pandemic influenza A H1N1 [A(H1N1) pdm09] outbreak which occurred in 2009 and 2010. Analysis was performed among laboratory confirmed patients. Multivariate analysis was performed for the predictors of fatality. Results: In the second wave of the pandemic, 848 adult patients were hospitalized because of suspected influenza, 45 out of 848 (5.3%) died, with 75% of fatalities occurring within the first 2 weeks of hospitalization. Among the 241 laboratory confirmed A(H1N1) pdm09 patients, the case fatality rate was 9%. In a multivariate logistic regression model that was performed for the fatalities within 14 days after admission, early use of neuraminidase inhibitors was found to be protective (Odds ratio: 0.17, confidence interval: 0.03-0.77, p = 0.022), nosocomial infections (OR: 5.7, CI: 1.84-18, p = 0.013), presence of malignant disease (OR: 3.8, CI: 0.66-22.01, p = 0.133) significantly increased the likelihood of fatality. Conclusions: Early detection of the infection, allowing opportunity for the early use of neuraminidase inhibitors, was found to be important for prevention of fatality. Nosocomial bacterial infections and underlying malignant diseases increased the rate of fatality.

This study was performed for evaluation of seroprevalence of hepatitis A, B, and E among children in Istanbul, Turkey. The study group included 909 children who were 6 months–15 years of age. The children were separated to three age groups: Group 1 (6 months–4.9 years; n = 321), Group 2 (5.0–9.9 years; n = 318), and Group 3 (10.0–15.0 years; n = 270). Group 1 was divided to two subgroups for evaluation of the maternal antibody sera (6 months–2 years and over 2 years). Serum IgG anti-HAV, anti-HBc, and anti-HEV were tested by commercial ELISA kits. The data were studied by multivariant analysis. In all subjects, seroprevalence of hepatitis A, B, and E were determined as 29, 15.9, and 2.1% respectively. The prevalence of hepatitis A increased with age (p 0.05). The seroprevalence of hepatitis E virus infection was higher in Group 1 (3.7%) than Group 3 (0.3%; p < 0.05). In Group 1 first subgroup, between 6 month and 2 year, antibody levels were 12.2, 17.3, and 4.8% respectively, for anti-HAV IgG, anti-HBc IgG and anti-HEV IgG. Hepatitis A and B infection is a community health problem, but hepatitis E infection is low in children in Istanbul, Turkey. The high positive rate in Group 1 for IgG anti-HEV may be due to maternal antibodies.

Background: Streptococcus pneumoniae, a common pathogen leading to pneumonia, is a cause of morbidity and mortality in immunosuppressed patients. Vaccination against this agent can be recommended for immunosuppressed patients, including those with chronic renal failure, nephrotic syndrome and renal transplant recipients: however, a diminished immune response and loss of protective antibodies have been observed. Patients and methods: In our prospective study, the efficacy and side effects of polyvalent pneumococcal vaccination were investigated in renal transplant recipients. A total of 21 patients (6 female. 15 male) with well-functioning renal allografts, who had transplant surgery at least 2 months before, were included in the study. The patients were stratified according to the immunosuppressive protocol and 8 received double, while 13 received triple, immunosuppresive agents. After obtaining basal serum samples, all cases were vaccinated with the 0.5 mL intramuscular administration of polyvalent polysaccharide pneumococcal vaccine (Pneumo 23 Pasteur Merieux. lot No: K 1131). Results: Following a mean of 6 wk in all patients and also a mean of 12 wk in 12 patients, serum samples were again obtained to measure pneumococcal antibodies. Antibody titers following 6 and 12 wk of vaccination were significantly higher, as compared with basal values in all patients, except one. These titers did not show any statistically significant difference between double and triple therapies. There was no significant difference between the 12th and 6th wk postvaccination antibody titers. No systemic or local adverse effects were observed Conclusion: Pneumococcal vaccination is safe and effective in patients with well-functioning renal allografts, at least in the short term. This vaccination policy may be useful for preventing invasive pneumococcal disease in immunosuppressed patients.

Background: Haemophilus influenzae infection is a mild and self-limited disease in the healthy population. However, it may show an aggressive course in the immunocompromised state which underlines the importance of vaccination against this agent. On the other hand, posttranplant immunosuppression may impair immune responses and thus the efficacy of the vaccination. Methods: Forty-three renal transplant recipients with well-functioning allografts were immunized with H. influenzae type b vaccine in order to investigate the immune response. The patients received a double or a triple immunosuppressive protocol. Seven healthy members of the dialysis unit served as controls. After obtaining basal serum samples, the patients and the control subjects were immunized with H. influenzae type b conjugate vaccine. After 6 and 12 weeks, serum samples obtained again to determine H. influenzae type b antibody titers. Results: The antibody titers 6 and 12 weeks after vaccination were significantly higher as compared with the basal values, similar to those of the control subjects. These titers did not show statistically significant differences between the double and triple immunosuppressive therapy groups. After 12 weeks of vaccination, the antibody titers did not show a statistically significant difference as compared with those obtained after 6 weeks. Conclusion: H. influenzae type b vaccination is safe and effective in patients with well-functioning renal allografts and should be recommended to renal transplant recipients who may have the risk of invasive disease on the basis of the immunosuppressive state.

Thirty-four out of 158 (22%) newborns to mothers chronically infected by the hepatitis B virus (HBV) did not produce antibodies (Ab) to HBsAg 1 month after the last injection of the HBV vaccine supplemented with HBV specific immunoglobulins. At birth the HBV genome was detected by polymerase chain reaction in the peripheral blood mononuclear cells (PBMC) of a large majority (28 out of 34) of these non-responder newborns but never in the other newborns who responded to the HBsAg vaccine. HBV genome was detected in serum, only in some cases (nine out of 34) and never in absence of HBV DNA in PBMC. For nine out of 14 followed newborns, the absence of response was transitory since anti-HBs Abs appeared after 15 months, without booster, while the HBV had disappeared. Unresponsiveness was specific of the HBV envelope protein since all late responders and 15 months non-responders to the HBsAg vaccine produced normal levels of Abs to the three poliovirus serotypes, to tetanus toxoid and to the pneumococcus polysaccharides. An in utero induced immune tolerance to low doses of HBsAg appears as the most plausible hypothesis to explain this unresponsiveness to HBV vaccine.

Recombinant human (rh) interferon alpha2a (IFN-α2a) therapy is successfully used for the treatment of Behcet’s disease (BD) uveitis refractory to conventional immunosuppressive treatment. Our aim in this study was to investigate the frequency and clinical significance of anti-IFN-α antibodies and autoantibodies during recombinant human rhIFN-α2a therapy in patients with BD uveitis. This comparative, cross-sectional, serological screening study included 30 BD patients treated with rhIFN-α2a (Group 1), 29 BD patients treated with conventional immunosuppressive agents (Group 2), 29 BD patients who received only colchicine (Group 3), and 30 healthy subjects (Group 4). Anti-IFN-α–binding antibodies and autoantibodies, including anti-nuclear antibody, anti-thyroid peroxidase antibody, and anti-cardiolipin antibody, were measured in serum samples. Antibody seropositivity was compared between study groups. Retrospective clinical data were compared between antibody-positive and antibody-negative patients. A significantly higher proportion of patients in Group 1 had anti-interferon-α (26.6 %) and autoantibody (30 %) seropositivity compared to the other groups. No correlation was found between seropositivity for anti-interferon-α and other autoantibodies. No significant difference was found in cumulative dose of IFN-α, duration of IFN-α therapy, time to first uveitis attack, or attack rate between anti-interferon-α antibody-positive and antibody-negative patients in Group 1. Uveitis attacks were observed in 22 % of autoantibody-positive and 71 % of autoantibody-negative patients in Group 1 (p = 0.018). Patients with BD uveitis develop anti-IFN-α–binding antibodies and autoantibodies during treatment with rhIFN-α2a. While the clinical relevance of anti-IFN-α–binding antibodies remains unclear in this study, induction of autoimmunity was found to be associated with a tendency for better therapeutic response.

Uyanikoglu, Ahmet/0000-0003-4881-5244; Baran, Bulent/0000-0001-7966-2346 WOS: 000326273700014 PubMed: 23665172 Background/Aim: To investigate the clinical features and treatment response in patients with hepatitis B (HBV) and hepatitis C virus (HCV) co-infection receiving anti-HCV therapy. Patients and method: Patients with HBV/HCV co-infection, who were eligible for anti-HCV therapy, were included in the study. Patients had detectable HBsAg for at least 6 months and detectable HCV-RNA before the initiation of therapy. Primary end-point was the proportion of patients achieving sustained virological response (SVR). HBV serology and HBV-DNA results obtained during the follow-up were assessed to determine HBV clearance or reactivation after anti-HCV therapy. Results: There were 612 patients in the HCV cohort and 52 (8.5%) of them were HBV/HCV co-infected. Twenty-eight patients (20 male, mean age: 47 +/- 12) received anti-HCV treatment and followed-up for a mean duration of 53 months (12-156). Fifteen patients received peginterferon/ ribavirin combination while the remaining patients received standard interferon/ribavirin combination (n = 6) or standard interferon monotherapy (n = 7). Patients receiving interferon monotherapy were under chronic hemodialysis therapy. SVR was achieved in 14 (50%) patients at the end of follow-up. The proportion of patients with SVR in three treatment arms were not significantly different (P = 0.78). Eight of 11 patients with detectable HBV-DNA cleared HBV-DNA during treatment. Seven (25%) patients experienced a rebound in HBV-DNA, and one patient experienced an acute hepatitis flare which was controlled by tenofovir therapy. Two (7%) patients cleared HBsAg and one of them was seroconverted to anti-HBs. Conclusion: Co-infection with HBV does not have a negative impact on the efficacy of anti-HCV treatment, but HBV-DNA should be monitored to overcome the risk of HBV exacerbation. (C) 2013 Published by Elsevier Masson SAS.

Objective To determine the frequency rate of C. pneumoniae, rhinovirus, respiratory syncytial virus (RSV), influenza virus, metapneumovirus, adenovirus’, parainfluenza virus and coronavirus in acute respiratory tract infections in children. Methods One hundred nine pediatric patients having respiratory tract infections were included in this study. Real time PCR, DFA and cell culture method were used for detection of C. pneumoniae, RSV antigen and influenza virus respectively. Multiplex PCR was used for detection of other viruses. Results No C. pneumoniae DNA was detected in the samples. Virus was detected in 43 cases from larynx swabs (43/109, 39.4 %). The frequency order of the viral agents detected were as follows; rhinoviruses 14.7 %, RSV B 7.3 %, influenza A 6.4 %, metapneumovirus 3.6 %, adenovirus 3.6 %, coronavirus 0.9 %, parainfluenzavirus type 3, 0.9 %, parainfluenzavirus type 4, 0.9 % and RSV A 0.9 %. Sensitivity of the PCR and DFA methods for the diagnosis of RSV infections were detected as 100 % and 100 %, respectively. Specificity of the PCR and DFA methods for RSV infections were detected as 97 % and 100 % respectively. Sensitivity of the PCR and cell culture methods for influenzavirus infections were detected as 100 % and 100 %, respectively. Specificity of the PCR and DFA methods for RSV infections were detected as 96 % and 100 % respectively. Conclusions Prevalence of viral agents was detected as 39.4 %. Influenza viruses and RSV were common. Metapneumovirus was also frequent (3.6 %). C. pneumoniae was not found to be a common agent for acute respiratory disease in children.

Hepatitis delta virus (HDV) is a subviral pathogen of humans, a satellite of hepatitis B virus (HBV) that induces severe acute and chronic liver diseases. The genus Deltavirus consists of eight clades or genotypes, with HDV1 being ubiquitous and frequently characterized. In Turkey, HDV1 infection is highly endemic among HBsAg carriers, especially in the southeastern region. In this study, we analyzed 34 samples from patients who were chronically infected with HBV/HDV, originating from 22 cities of rural regions in the central and eastern parts of Turkey, in order to determine the levels of viral replication and genetic diversity. HDV RNA levels ranged between 3.02 and 8.75 Log copies/mL, and HBV DNA was detected in 25 samples (73.5%), with values ranging from 2.53 to 5.30 Log copies/mL. Analysis of nucleotides 900-1280 of HDV genomes (n = 34) and full-length (n = 17) sequences indicated that all of the strains belonged to genotype HDV1. However, a high genetic diversity was observed among the isolates, with a mean full-length dissimilarity score of 13.05%. HDV sequences clustered with sequences from Western Europe (n = 11), Eastern Europe and Asia (n = 19) or Africa (n = 4). HDV1 isolates related to strains of African origin had a serine residue instead of an alanine at position 202 of the large delta protein. HBV preS1 sequences obtained for 34 isolates indicated an HBV/D genotype in all cases. Taken together, our results indicate that in Turkey, where HBV-HDV dual infection is highly endemic, both viruses have high levels of replication, and HDV strains exhibit wide genetic diversity, which might reflect ancient evolution and/or successive outbreaks.

Background/aims Hepatitis C virus transmission routes in chronic hepatitis C patients, the relationship between the viral genotype and the transmission routes were studied. Material and methods Genotyping was performed by using a commercial reverse hybridization method, Line Probe Assay. Results Genotyping of 108 HCV RNA positive patients revealed four different types (1, 2, 3, and 4) and some mixed types. Subtype 1b was the most common (n=82). Subtype 1a and 3a were detected in six patients, 2a/2c was detected in seven patients, and 4c/4d was detected in one patient respectively. Six subjects revealed mixed infections. Three of them were 1a+1b, two of them were 1b+4a, and one of them was 1b+2a/2c. Genotype 1b was most common in all groups. In 38.8% of the 108 patients with a history of blood or blood product transfusions, 16.6% of patients with a history of surgery, 15.7% of patients had an anamnesis of dental treatment and, 12.9% of patients receiving dialysis. Conclusion Before the routine screening of blood donor practices became mandatory, the most common route of HCV infection was blood transfusions. The other risk factors of transmission such as tattoos, piercings, iatrogenic infections and intravenous drug usage have not been recorded for any of these patients in our study. The patient with a history of surgery had the genotype 1b as the most common genotype. The genotype 1b was determined in 75.9% of the whole patient population of the study.

Background Chlamydia trachomatis and Neisseria gonorrhoeae are known to cause urethritis. However, only a small number of studies in Eastern European countries have investigated the causes of urethritis. Goals To determine the prevalence of C trachomatis and N gonorrhoeae among men with symptomatic urethritis in Istanbul, Turkey, and to determine whether contact with a commercial sex worker increased the likelihood of chlamydial infections. Study design Men with a diagnosis of urethritis at the Istanbul Faculty of Medicine were screened for C trachomatis and N gonorrhoeae by Abbott's ligase chain reaction (LCR) using either urethral swabs or first-void urine. N gonorrhoeae cultures were done on a subset of these patients. Results The study enrolled 813 men. All of the men denied condom use during their previous sexual exposures. The overall prevalence of C trachomatis, as determined by LCR, was 15.7%. Only 192 patients were screened for both organisms. N gonorrhoeae prevalence was 9.4%. There was no difference in the chlamydia prevalence between men who had contact with commercial sex workers (CSWs) and men who had no such contact (15.3% versus 17.2%). However, clients of foreign CSWs were more likely to have chlamydia than clients of registered Turkish CSWs. Conclusions C trachomatis and N gonorrhoeae are commonly found in Turkish men with urethritis. The findings did not show more chlamydial infection among men who had contact with CSWs than among men who had no such contact. The failure to use condoms among these men must be addressed.

The real-time reverse transcription polymerase chain reaction (rRT-PCR) technique has been used as the reference technique for the diagnosis of pandemic (H1N1)2009 virus infections. However, rapid influenza diagnostics tests (RIDTs) have been considered in the diagnosis of pandemic (H1N1)2009 by some healthcare institutions in Turkey due to their ease of use and generation of fast results. Nevertheless, their low sensitivity has caused concern during the control of the pandemic. This study aimed to determine the sensitivity of 4 different rapid tests available on the market in Turkey in the diagnosis of pandemic (H1N1)2009 infections compared to the reference rRT-PCR technique. One hundred and four patient samples that tested positive and 88 samples that tested negative for pandemic (H1N1)2009 by rRT-PCR were tested with RIDTs available on the market. The sensitivity of the rapid tests ranged from 31.7% to 50% depending on the brand of RIDT. Specificity ranged from 97.7% to 100%. Currently available RIDTs are not sensitive enough and could lead physicians to delay the treatment of patients, adversely affecting control efforts to mitigate the pandemic. Therefore, these tests should only be used for screening, and negative results should not rule out influenza. More sensitive and rapid point-of-care techniques are needed to meet the demands of point-of-care testing.

Monitoring the activity of influenza viruses is important for establishing the circulating types and for detection of the emergence of novel sub-types and antiviral resistant strains. This is the first report from Turkey on the surveillance and oseltamivir resistance of influenza viruses in 2007–2008. Five hundred twenty-four nasal swabs were tested from different geographical regions in Turkey during November 2007–April 2008. One hundred sixty-three (31%) samples were positive for influenza viruses of which 111 (68%) were influenza A, 52 (31%) influenza B using an immuno-capture ELISA. Forty isolates were selected at random from influenza A positive samples and grown in MDCK cell cultures. The supernatant of the cell cultures was used for RNA extraction followed by RT-PCR to detect the sub-types. Sub-typing revealed all samples as A/H1N1. The N1 gene segment of 30 A/H1N1 samples was sequenced in part, from the 201st to 365th residue, which included the critical region for oseltamivir resistance. Then resulting sequences were analyzed with oseltamivir sensitive and resistant strains obtained from National Center for Biotechnology Information (NCBI) GenBank by CLC Main Workbench Software. H275Y (H274Y according to N2 numbering) mutation, which is known to confer resistance to oseltamivir, was detected in 6 out of 30 (20%) H1N1 isolates from four cities (Istanbul, Bursa, Ankara, and Izmir). The D354G mutation was observed in all oseltamivir resistant H1N1 isolates but not in the oseltamivir sensitive isolates. Assay of neuraminidase activity revealed that these isolates were resistant to oseltamivir, but sensitive to zanamivir. J. Med. Virol. 81:1645–1651, 2009. © 2009 Wiley-Liss, Inc.

SUMMARY. The aims of the study were to investigate the efficacy of rescue therapy with lamivudine (LAM) and adefovir (ADV) combination for 6 months followed by ADV monotherapy in lamivudine-resistant chronic hepatitis B (LAM-R CHB) patients, and to analyze the frequency of ADV resistance mutant development in such patients. A total of 170 consecutive LAM-R CHB patients (male/female: 130/ 40, mean age: 42.9 ± 13.4 years) with viral breakthrough under LAM therapy were analyzed. A total of 68 had HBeAg-positive. Patients received rescue therapy with LAM [100 mg (qd)]+ADV [10 mg (qd)] for 6 months after which LAM was discontinued. HBV-DNA was assessed with the HBV-DNA 3.0 bDNA assay. ADV-resistant mutations were identified by sequencing the reverse transcriptase region. The median duration of rescue therapy was 24 months. Cumulative probability of becoming HBV-DNA undetectable was 33.8%, 59.6% and 68.2% after 24, 48 and 96 weeks of treatment, respectively. These figures were 43.2%, 58.0% and 73.1% for ALT normalization. Among 68 HBeAg-positive CHB patients, 10 patients had an e-antigen seroconversion. Low baseline HBV-DNA level (

Background: There is little information about the prevalence of occult hepatitis B virus infection (OHBVI). We have investigated the prevalence and virological features of OHBVI among female sex workers (FSWs) in Istanbul. Methods: Hepatitis B surface antigen (HBsAg) was tested in FSWs who work uncontrolled and were admitted to Venereal Diseases Hospital. HBV DNA and anti-HBs were investigated in all the HBsAg-negative cases. Hepatitis B envelope (HBe) antigen, anti-HBe, anti-hepatitis B core (HBc) antigen, HBV genotype, S gene and precore (PC)/basic core promoter (BCP) mutations were determined in HBV DNA-positive sera. Results: Two hundred and eighty-six volunteers were enrolled and 32.5% (n=93) of them had anti-HBs positivity. HBV DNA (range 30–209 copy/ml) was positive in 11 anti-HBs-negative and two anti-HBs-positive cases. The prevalence of OHBVI was 4.5% (13/286). Anti-HBc was positive in 77% (10/13) of those with OHBVI and anti-HBe positivity was 53.8% (7/13). Only genotype D was present in all occult HBV-infected cases. One PC (G1896A) and one BCP (T1762/A1764) mutation was found, but S gene mutation was not detected in any of the samples. Conclusion: In this population, OHBVI may have a negligible role in the horizontal transmission because of a very low viral load, and PC and core promoter mutations are very rare.

To evaluate whether the cytokine responses in liver and serum differ in chronic hepatitis C patients with normal and high alanine aminotransferase (ALT) levels.Thirty-three (16 with normal ALT level as group 1 and 17 with elevated ALT level as group 2) patients infected with genotype 1b hepatitis C virus (HCV) were examined. Liver infiltrating lymphomononuclear cells (LILMCs) were isolated from liver biopsy by collagenase type 1 and stimulated with phytohemagglutinin and interleukin 2 (IL-2). IL-10, IL-12, interferon gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) were determined in serum and LILMCs by ELISA.Serum cytokine levels were similar in both groups (P0.05). Stimulated IFN-gamma and TNF-alpha levels in LILMCs were increased in both groups. IL-12 and IL-10 levels stimulated with IL-2 were higher in group 1 than in group 2 (P = 0.023). Histological activity index (HAI) and stage had a negative correlation with TNF-alpha and IFN-gamma levels in group 2.Increased T-helper type 2 (Th2) cytokine response may regress inflammatory and biochemical activity. Progression of histological abnormalities in persons with elevated ALT probably depends on insufficient Th2 cytokine response, which does not balance Th1 cytokine response.

Increasing migration of sex workers across East European borders into Turkey has resulted in increased arrests of unregistered sex workers. There is concern regarding the prevalence of sexually transmitted diseases (STD) such as C. trachomatis in this unregulated group.To measure the prevalence of C. trachomatis infection and selected related demographic and behavioral factors among registered and unregistered sex workers in Istanbul, Turkey.In a cross-sectional study, the prevalence of C. trachomatis infection was studied by direct fluorescent antibody testing in 248 sex workers: 158 presented for routine medical screening and 90 who were arrested for lack of registration. All subjects were interviewed regarding demographic factors, sexual activity, and antibiotic and drug use.The overall C. trachomatis prevalence was 12.9% (12.0% registered and 14.4% unregistered). There was a strong association between never using condoms and chlamydia positivity (odds ratio 8.9 [95% confidence interval 3.7 to 21.6]).The high rate of C. trachomatis among all tested sex workers and the lack of regular condom use, particularly among unregistered sex workers, indicate that there is an urgent need for safe sex education and continued STD screening of unregistered sex workers.Accelerating migration of unregistered sex workers from Eastern European countries to Turkey has produced alarm about the potential for increased sexually transmitted disease (STD) transmission. Licensed sex workers are routinely screened for STDs and given medical examinations. However, in Turkey, women with foreign citizenship are ineligible for licensing. This cross-sectional study measured the prevalence of Chlamydia trachomatis in 248 sex workers in Istanbul in 1993. 158 sex workers were enrolled when they presented for routine medical screening, while 90 (from Rumania) were arrested for lack of registration. The overall C. trachomatis prevalence, as detected by direct fluorescent antibody testing, was 12.9% (12.0% among registered and 14.4% among unregistered women); however, the fact that almost half these women reported recent self-prescribed antibiotic use suggests these rates are underestimates. When the analysis was restricted to the 84 women without recent antibiotic use, the C. trachomatis prevalence was 36.9%. There was a significant association between never using condoms and chlamydia infection (odds ratio, 8.9; 95% confidence interval, 3.7-21.6). These findings suggest a need for safe sex education and continued STD screening of sex workers in Turkey. Eligibility for registration, regardless of nationality, should be reconsidered for public health reasons.

Summary Objectives: The occurrence of lamivudine resistance is often associated with the clinical breakthrough, which is characterised by the reappearance of hepatitis B virus (HBV) DNA in serum and the elevation of aminotransferases. We evaluated the efficacy of alpha interferon for clinical breakthrough in patients receiving lamivudine therapy. Patients: Six chronic hepatitis B patients receiving lamivudine were enrolled in the study. Results: Under lamivudine therapy, clinical breakthroughs occurred in between fifteenth and thirty-fourth month of lamivudine therapy. HBV DNA reappeared, and alanine aminotransferase was elevated. Genotypic analysis showed M552V, M552I and L528M mutations. After determining the clinical breakthrough, standard alpha interferon-2b was given for 6 months. Lamivudine was also maintained. In only one patient, HBV DNA became negative by polymerase chain reaction, and serum alanine transaminase level was normal at the end of therapy. Conclusion: Alpha interferon added to lamivudine is generally ineffective in the treatment of lamivudine resistance.

Background/Aims : End-stage renal disease patients on chronic hemodialysis are at risk for both hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. Although the prevalence is unknown in hemodialysis patients, occult HBV infection is frequent in subjects with chronic HCV infection. We aimed to investigate (1) the prevalence and clinical impact of occult HBV infection in hemodialysis patients with chronic HCV infection, and (2) the frequency of YMDD variants (tyrosine-methionine-aspartate-aspartate amino acid motif of HBV polymerase) in this setting. Methods : Thirty-three anti-HCV and HCV-RNA-positive, HBsAg-negative hemodialysis patients (mean age 36.9±10.4 years, 22 male) were admitted to this study. HBV-DNA (Innogenetics kit) and HCV-RNA (Cobas Amplicor HCV kit) were investigated by polymerase chain reaction technique (PCR). YMDD mutation was studied in all HBV-DNA-positive patients by the BOOM method. Results : HBV-DNA was detected in 12 of 33 patients (36.4%) by PCR. Their mean age was 33.0±9.0 years. Age, dialysis period (years) and biochemical parameters were not significantly different in patients with and without occult HBV infection. YMDD variants were identified in six of 12 (50%) patients with occult HBV infection. Conclusions : Occult HBV infection is frequent in hemodialysis patients with chronic HCV infection. YMDD variants are common in this setting.

Worldside viral hepatitis is still recognized as a mojor problem particularly in developing countries. During the past two decades there has been important progress in the field of viral hepatitis; the adapatation of molecular biology techniques to viral hepatitis has proven to be of great utility in the diagnosis of ‘classical’ hepatitis viruses, in monitoring during treatment, and also in learning more about the ‘new’ viruses. Here, the progress and pitfalls of serologic and molecular diagnosis techniques for viral hepatitis, unusual profiles and benefits of quantitative DNA/RNA tests will be discussed.

Patients who received multiple transfusions of blood and blood products are at high risk for blood transmittable diseases. The extent of this risk may vary in different communities. This study was planned to investigate the sero-prevalence of human immunodeficiency virus 1 (HIV-1) and hepatitis B virus (HBV) associated with blood transfusions in a group of multitransfused pediatric hematology and oncology patients in Istanbul, Turkey.

Background Children with cancer receiving intensive chemotherapy require multiple transfusions and are at increased risk for blood transmittable diseases such as hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) infections. Procedure Sera from 50 children (24 female, 26 male) admitted between January, 1994, and December, 1995, with solid tumors receiving intensive chemotherapy and multiple transfusions were investigated for HBsAg , anti-HBs, anti-HBc, anti-HCV, and anti-HIV by ELISA at diagnosis and at the end of therapy. Results HBsAg, HBV, HCV, and HIV seropositivities were 0%, 4%, 2% and 0% at diagnosis and 10%, 20%, 14% and 0% at the end of therapy, respectively. Conclusions The high seroprevalence of HCV may be due to the lack of anti-HCV screening of blood products in the blood banks during the study period. Although the HBV seroprevalance of 20% found in this study is much lower than the value of 56% found in a previous study conducted during 1986–1989 in a similar patient population and a similar setting, it is still high. Children infected with HBV during immunosuppressive therapy are at greater risk of becoming chronic carriers and precautions must be taken for immunization of these children. Med. Pediatr. Oncol. 34:102–105, 2000. © 2000 Wiley-Liss, Inc.

We report mutations in influenza A virus (H5N1) strains associated with 2 outbreaks in Turkey. Four novel amino acid changes (Q447L, N556K, and R46K in RNA polymerase and S133A in hemagglutinin) were detected in virus isolates from 2 siblings who died.

Thirty four out of 158 (22%) newborns to mothers chronically infected by the hepatitis B virus (HBV) did not produce antibodies (Ab) to HBsAg 1 month after the last injection of the HBV vaccine supplemented with HBV specific immunoglobulins. At birth, HBV genome was detected by polymerase chain reaction (PCR) in the peripheral blood mononuclear cells (PBMC) of a large majority (28 out of 34) of these non-responder newborns but never in the other newborns who responded to the HBsAg vaccine. HBV genome was detected in serum, only in some cases (nine out of 34) and never in the absence of HBV DNA in PBMC. For nine out of 14 followed newborns, the absence of response was transitory since anti-HBs Abs appeared after 15 months, without booster, while the HBV genome had disappeared. Unresponsiveness was specific to the HBV envelope protein since all late responders and 15-months-non-responders to the HBsAg vaccine produced normal levels of Abs to the three poliovirus serotypes, to tetanus toxoid and to the pneumococcus polysaccharides. An in utero induced immune tolerance to low doses of HBsAg appears as the most plausible hypothesis to explain this unresponsiveness to HBV vaccine.

In an uncontrolled study, the efficacy of azithromycin in the treatment of non-gonococcal urethritis was assessed in 41 male patients aged between 20 and 40 years with a mean age of 27 ± 5 years. Clinical and microbiological diagnosis confirmed that 28 men were found positive for Chlamydia trachomatis, 10 for Ureaplasma urealyticum and three for both C. trachomatis and U. urealyticum. All patients received 1 g azithromcyin orally (four 250 mg capsules). The length of time between the treatment and following visits were 7 – 10 days and 14 – 21 days for second and third visits, respectively. Complete eradication was achieved in 27 out of 41 patients. Of the remaining 14, six were found positive for C. trachomatis and were excluded as they did not return for the follow-up visit, one patient did not achieve complete eradication, one patient infected with both C. trachomatis and U. urealyticum failed to achieve complete eradication, and six patients infected with U. urealyticum failed to be completely cured. No adverse effects were reported in any patient. Single dose administration of 1 g azithromycin appears to be an effective and well-tolerated treatment for chlamydial urethritis and an advantage in terms of patient compliance.

Hepatitis C virus (HCV) and hepatitis E virus (HEV) are the principal causes of non-A, non-B hepatitis worldwide, and in Turkey one-third of the cases of acute hepatitis are non-A, non-B. To explore the epidemiology of HCV in Turkey (including the association of HCV with HEV), a seroprevalence study of HCV was conducted. Sera from residents from five distinct regions of the country were tested for antibodies to HCV (anti-HCV) and HEV (anti-HEV). Anti-HCV was detected in 21 (1.5%) of 1,374 persons and was more common in residents over 54 years of age (p = 0.02), with less than primary education (p = 0.013), more than two children (p = 0.003), and who lived in the regions of Ayvalik (p = 0.046) or Trabzon (p = 0.038) compared to Istanbul. Anti-HCV was marginally associated with anti-HEV, which was found in 5.9% of residents. However, this association was lost after controlling for age and education (p = 0.225). HCV infection occurs in all regions of Turkey and is more common in persons who are older and of low socioeconomic status. As resources permit, efforts to reduce the transmission of HCV in Turkey (such as screening blood donations for anti-HCV) are indicated.