Rubella seroprevalence among healthy individuals in Izmir, Turkey.

In order to assess immunity to rubella in Izmir, Turkey, a total of 600 persons of 1-70 years of age were selected with cluster sampling. Of the 597 subjects, 120(20.1%) was susceptible to the rubella according to their serum antibody levels. Of children 1 to 6 years of age, 50.9% was found to be serologically susceptible to rubella. Rubella protection rates showed a age-related increase, reaching maximum in the 15-19 age group, in which 98.1% of these subjects had antibody titre above the full protective level. Of the 126 females in the reproductive age group, only 4(3.1%) were found to be serologically susceptible to rubella. Logistic regression analysis showed that among the several independent variables, only age (p< 0.001) was significantly associated with rubella protective antibody levels. Epidemiological studies should continue as the epidemiological characteristics of the disease may change depending on the uptake of MMR vaccination.

The relationship between HBV-DNA level and histology in patients with naive chronic HBV infection.

BACKGROUND: In patients with chronic hepatitis B (CHB) infection, precise definition of the hepatic fibrosis stage is the most important parameter to assess the risk of disease progression. Correlation between the prognosis of the CHB and the level of hepatitis-B virus DNA (HBV-DNA) is well considered in recent years. AIMS: The aim of this study is to investigate the relationship between serum HBV-DNA level and histology of the liver. We also wanted to determine a threshold level of HBV-DNA for differentiation of low and high risk patients for progression. METHODS: Two-hundred-fifty-nine patients with serum HBV-DNA level > 2000 copies/mL, determined by polymerase chain reaction (PCR), and biopsy proven naïve CHB infection were evaluated. Liver biopsies were evaluated histopathologically according to the Ishak scoring system. Laboratory values such as aspartate aminotransferase (AST), alanine aminotransferase ratio (ALT) were tested every 3 months and the highest value of each patient was evaluated. RESULTS: Mean age was 40 +/- 11 and 60% (155/259) of the patients were male. Mean laboratory values were as follows: AST: 52 +/- 46 U/L, ALT: 93 +/- 133 U/L, PLT: 224 +/- 60 1093)/l HBV DNA: 5.9 +/- 1.5 log copies/mL. In histological evaluation, mean inflammatory score was 4.34 +/- 2.72 and fibrosis score was 1.38 +/- 1.46. The fibrosis score was 0 or 1 in 63.3% (164/259) of the patients. The relationship between HBV-DNA level and histologic grade/stage was investigated and 15.000 copies/mL HBV DNA level was found as the threshold level to describe the activity of the disease. Fibrosis score was < 2 and/or grade < or = 5 in the patients who have HBV-DNA value below that level. CONCLUSION: In patients who have serum HBV-DNA level < or = 15000/copies/mL, histological activity was almost always low, and it seems that these patients do not need a liver biopsy regardless of hepatitis-B-e antigen (HBeAg) status.

Seroprevalence of hepatitis B infection in the Turkish population in Northern Cyprus.

This study was conducted to determine the seroprevalence of hepatitis B virus (HBV) infection in the Turkish population in Northern Cyprus. The secondary aim of this study was to assess the impact of the universal infant hepatitis B vaccination program, which started in 1998. A total of 600 persons 1- to 30-years-old were selected for the study with cluster sampling. The information on sociodemographic characteristics was gathered for each participant and in 585 of them, hepatitis B surface antigen (HBsAg), anti-hepatitis B surface antigen antibody (anti-HBs) and anticore antibody (anti-HBc) were tested. The overall prevalence of anti-HBc and HBsAg carriage was 13.2% and 0.85%, respectively. Old age and low parental educational level were the major independent risk factors for HBV transmission. Seroprevalence of both anti-HBc and anti-HBs antibodies was similar in children 1-7 years of age. After 8 years of age, anti-HBc seroprevalence increased significantly with age, while anti-HBs prevalence decreased (p<0.001). Anti-HBc prevalence increased from 7.0% in children aged 1-7 years to 17.9% in persons aged 16-20 years. None of the children under 12 years of age were HBsAg-positive, while 1.9% of persons aged 16-20 years were HBsAg carriers. Anti-HBs seroprevalence exceeding 90% was found in the cohorts targeted by the routine hepatitis B vaccination program, whereas 36.4% of young adults aged 21-30 years were anti-HBs-positive. The study shows that universal infant hepatitis B immunization has a substantial impact on the immunity in children. However, prevalence of HBV infection is still high in adolescent and young adults in Northern Cyprus. Therefore, catch-up immunization for these groups will help to reduce hepatitis B transmission.

Distribution of hepatitis C virus genotypes in patients with chronic hepatitis C infection in Western Turkey.

OBJECTIVE: The primary aim of this study was to determine the recent distribution of various genotypes of hepatitis C virus (HCV) in patients with chronic HCV infection in Western Turkey. Additional objectives were to determine whether there are any associations of genotype with gender and age, and to determine the nucleotide similarities and risk factors of non-1 HCV genotypes. METHODS: Serum samples from 345 patients (176 male, 169 female; mean age 53.3+/-12.7 years, range 10-81 years) with chronic HCV infection were analyzed in this study. Viral genotypes were determined by a restriction fragment length polymorphism (RFLP)-based in-house assay. To confirm genotypes for the samples with band patterns other than genotype 1, the 5' UTR was amplified and sequenced. RESULTS: Genotype 1 was observed in 335 of the 345 patients (97.1%). Of these, 34 patients showed infection with subtype 1a (9.9%) and 301 with subtype 1b (87.2%). Genotypes 2, 3, and 4 were determined in 0.9%, 1.4%, and 0.6% of the patients, respectively. Patients infected with type 1 were significantly older than patients infected with non-1 genotypes; however no significant differences were recorded in gender distribution. CONCLUSIONS: Genotypes other than genotype 1 are quite rare; these are possibly acquired in other countries. Turkish patients with chronic hepatitis C still represent a rather homogenous group with genotypic diversity encountered rarely.

Restriction fragment length polymorphism analysis and direct sequencing for determination of HBV genotypes in a Turkish population.

The aim of this study was to analyze the restriction fragment length polymorphism and direct sequencing results in genotyping of hepatitis B virus from a Turkish population in a clinical virology laboratory. Serum samples of 54 chronic hepatitis B patients attending the Ege University Hospital were studied. Sequences of partial S gene PCR products were analysed and RFLP was performed. Fifty-three isolates could be identified by direct sequencing as genotype D. One sample needed to be cloned and determined as genotype D. Forty-two isolates were genotyped as D with RFLP according to published determinative patterns. Twelve isolates had undefined patterns. Eight of them suggested a mixture of isolates with different patterns and cloning of these samples confirmed the presence of heterogeneous isolates. Four isolates with undefined pattern were determined as genotype D by direct sequencing. All the studied isolates were genotype D. The results of this studied population suggest that RFLP is suitable for HBV genotyping in a routine clinical virology laboratory setting. However sequence analysis and even cloning may be needed to clarify indeterminate results.

Hepatitis delta virus (HDV) genotypes in patients with chronic hepatitis: molecular epidemiology of HDV in Turkey.

OBJECTIVE: Analysis of hepatitis delta virus (HDV) isolates from around the world has indicated that there are at least three phylogenetically distinct genotypes with different geographic distributions. The aim of this study was to determine the distribution of HDV genotypes by direct sequencing in patients with chronic delta hepatitis in Izmir, Turkey. DESIGN AND METHODS: Serum samples from 32 chronic hepatitis patients (21 males, 11 females; mean age 44.2 years, range 23-70 years) with anti-delta positivity were analyzed for hepatitis B and C serologies. After reverse transcription, cDNA of partial delta antigen was amplified by in-house nested PCR. The products of the HDV PCR were bidirectionally sequenced with internal primers using Big Dye Terminator DNA Sequencing Kit (Applied Biosystems, CA, USA) and ABI Prism 310 Genetic Analyzer (Perkin Elmer, USA). Nucleotide sequences of HDV were compared with previously reported sequences and aligned by using ClustalW (1.82). RESULTS: HDV-RNA was positive in 26 (81.3%) of 32 anti-delta positive samples. Comparison of the HDV sequences with published sequences of HDV genotypes I, II, and III indicated that all were closely related to HDV genotype I isolates. Similarity among isolated sequences ranged from 84% to 96%. CONCLUSION: HDV genotyping was successfully performed by direct sequencing of the amplicons obtained from routine HDV-RNA screening PCR tests. All of the HDV isolates from the chronic delta hepatitis patients included in this study were found to be genotype I.

Low-dose hepatitis B immune globulin and higher-dose lamivudine combination to prevent hepatitis B virus recurrence after liver transplantation.

Post-transplant prevention of hepatitis B virus (HBV) infection is based on treatment with lamivudine and/or hepatitis B immune globulin (HBIG). However, optimum doses and duration for these drugs are not yet clear. We tested high doses of lamivudine (300 mg/day) in combination with low doses of HBIG (200-400 IU/2-4 weeks). Eighty patients who had post-transplant prophylaxis of lamivudine and HBIG were included in the study. Of those, 20 had hepatitis D virus co-infection and eight were HBV DNA-positive at the time of transplantation. Ten HBV DNA-positive patients were treated with lamivudine (150 mg/day) before transplantation; all were HBV DNA-negative after lamivudine treatment. All patients in the anhepatic phase were given 4000 IU of HBIG. Following this, 400 or 800 IU HBIG was administered intramuscularly daily for 5-10 days post-transplantation and 2-4 times weekly thereafter, according to serum titre of antibodies to hepatitis B surface antigen (anti-HBs). Lamivudine was maintained or initiated at the time of transplantation and was continued indefinitely. Median follow-up was 21 months (range 3-73 months). Recurrence of hepatitis B surface antigen (HBsAg)-positivity occurred in only three out of 78 (4%) patients; two of these three were HBV DNA-positive. Median anti-HBs titre at the final follow-up was 68 IU. Patient and graft survival was 85% at 1 year. In conclusion, a combination of lamivudine 300 mg/day and low-dose HBIG prevents post-transplantation recurrence of hepatitis B, even in the presence of viral replication in the pre-transplant period.

[Human herpesvirus 6 infections in kidney and bone marrow/stem cell transplant recipients]. / Böbrek ve kemik iligi/kök hücre alicilarinda insan herpesvirus 6 enfeksiyonunun arastirilmasi.

In this study, active human herpesvirus (HHV)-6 infection were investigated in 39 renal and 9 bone marrow/stem cell transplant recipients. For this purpose, the presence of HHV-6 DNA in patients sera have been searched by nested polymerase chain reaction (nPCR). In addition, HHV-6 IgM and IgG antibodies were performed by micro-enzyme immunoassay (EIA) to detect seronegative patients before transplantation and IgM response in active or primary HHV-6 infection. Active infection with HHV-6 DNA positivity was detected in 5.3% of renal and 22.2% of bone marrow/stem cell transplant recipients. Active HHV-6 infection was found to be related with asymptomatic reactivation, graft disfunction and cytomegalovirus disease in renal transplant recipients, and, fever and graft versus host disease in bone marrow/stem cell transplant recipients. It has been concluded that, the investigation of HHV-6 DNA by nPCR in the transplant sera, was a practical and useful method for the laboratories, in order to diagnose active HHV-6 infection, while HHV-6 IgG antibody detection was also useful for the differential diagnosis of primary infection or reactivation/reinfection, but HHV-6 IgM antibodies has low value to detect active HHV-6 infection.

[Polymerase chain reaction for Chlamydia trachomatis in urine specimens from patients with mucopurulent genital discharge]. / Mukopürülan genital akintisi olan hastalarin idrar örneklerinde Chlamydia trachomatis'in polimeraz zincir reaksiyonu ile arastirilmasi.

The aim of this study was to investigate the DNA of Chlamydia trachomatis by polymerase chain reaction (PCR) in the first-void urine samples of patients with mucopurulent genital discharge and to compare the results with the urethral/endocervical swab culture method. First-void urine samples from 56 patients (46 female, 14 male) and urethral swab samples from 14 male patients were tested by PCR. Additionally, shell-vial culture method was performed for the urethral/endocervical swab samples which were collected from 46 female and 14 male patients. Four (2 females, 2 males) of the patients (7.1%) showed positive results by both of the methods. In five (8.9%) of the urine samples, internal control tests were found negative, indicating the presence of amplification inhibitors, and the culture results of these patients were also negative. Since the PCR method (Cobas Amplicor CT, Roche Diagnostic Systems, NJ, USA) which was used in the study included internal control programme to identify inhibitors in urine, the sensitivity was improved. As a result, the perfect (100%) correlation between culture and PCR methods, lead to the conclusion that PCR is a rapid and reliable method for the detection of C. trachomatis in urine samples, however more detailed studies are necessary related to the sensitivity and specificity of PCR method.

Chlamydial infections in term and preterm neonates.

The aim of this study was to evaluate the incidence and morbidities of Chlamydia trachomatis infections in newborn infants. Tissue culture and direct immunofluorescence (DIF) tests were used to detect the presence of nasopharyngeal C. trachomatis infection in 35 preterm and 21 healthy term neonates. All infants were followed up clinically for 3 months, and enzyme-linked immunosorbent assay analysis for serum antichlamydial IgG and IgM was performed on day 15 and week 6. Tissue culture and/or DIF studies showed that 10 of the preterm infants (28.57%), but none of the term infants, were C. trachomatis-positive. The sensitivities of DIF and tissue culture were 40% and 70%, respectively, demonstrating the diagnostic superiority of tissue culture tests for detecting C. trachomatis. Only one asymptomatic preterm infant was found to be positive for antichlamydial antibodies at the 6th week. All C. trachomatis-positive infants were given macrolide antibiotics for 14 days. The study showed that male infants were more frequently infected, but types of delivery, mean gestational ages, mean birth weights, and the need for mechanical ventilation were similar in C. trachomatis-infected and uninfected preterm infants. However, the duration of oxygen treatment was longer in infected preterm infants. Clinical conjunctivitis was more frequent in C. trachomatis-infected infants (60%) than in uninfected infants (24%). C. trachomatis-positive infants had pneumonia more frequently; however, all patients with pneumonia were negative for antichlamydial IgM and IgG antibodies. Macrolide treatment for 2 weeks for nasopharyngeal C. trachomatis positivity may have prevented C. trachomatis related pneumonia, but it may not have significantly influenced the risk of pneumonia caused by other agents. Chlamydial infections may lead to early and late respiratory problems in preterm infants. Nasopharyngeal screening may help physicians detect C. trachomatis infections and provide a means of early diagnosis in this vulnerable patient group.

Varicella seroprevalence in Turkish population in Cyprus.

AIM: This study was conducted to determine the age-specific seroprevalence of varicella zoster virus (VZV) infection in Turkish population in Cyprus. METHODS: A total of 600 unvaccinated individuals aged 1-30 years were selected for the study with cluster sampling. Information on socio-demographic characteristics was gathered for each participant and, anti-VZV antibodies were assayed by using enzyme immune assay. RESULTS: Of the 578 assayed samples, 486 (84.1%) were seropositive. Varicella seroprevalence increased sharply with age from 25% for the 2-3 year olds to 55, 78 and 85% for 4-5, 6-7 and 8-9 year olds, respectively. More than 90% of individuals >16 years of age were seropositive. Varicella seroprevalence was higher in large families with five and more members (91.2%) than in small families with four or fewer members (80.2%). CONCLUSION: The majority of varicella-zoster virus infections occur during preschool period and at the first years of schooling. Therefore, routine varicella vaccination of children would be logical in Northern Cyprus, as is currently recommended by the European Working Group on Varicella.

Adefovir dipivoxil therapy in liver transplant recipients for recurrence of hepatitis B virus infection despite lamivudine plus hepatitis B immunoglobulin prophylaxis.

BACKGROUND: Treatment of post-transplantation recurrence of hepatitis B virus (HBV) infection despite prophylaxis with hepatitis B immunoglobulin (HBIG) and lamivudine combination therapy is not easy. Because HBV reinfection has a severe course and could result in graft failure in liver transplant recipients, prompt medication is essential. Herein is reported the authors' experience with adefovir dipivoxil (AD) therapy in 11 liver transplant recipients who had HBV reinfection despite the administration of lamivudine and HBIG. METHOD: Two-hundred and nine patients underwent liver transplantation (100 deceased donor liver transplantations [DDLT], 109 living donor liver transplantation [LDLT]) due to chronic hepatitis B infection between April 1997 and May 2005 in Ege University Medical School, Liver Transplantation Unit. Patients had prophylaxis with lamivudine and low-dose HBIG combination after liver transplantation. Treatment of recurrence consisted of AD 10 mg once a day and lamivudine 300 mg/daily and HBIG was discontinued in those patients. RESULTS: In total there were 11 HBV recurrences: five occurred in DDLT recipients and six in LDLT recipients, at a median follow up of 18 months (range, 6-48 months). In one of 11 patients, pretransplant HBV-DNA and HBeAg were positive. Three patients had a severe course and one patient had fibrosing cholestatic hepatitis. After AD treatment, HBV-DNA level decreased in all patients and became negative in seven patients. Two patients died due to hepatocellular carcinoma recurrence after 12 and 14 months of follow up. Serum creatinine level increased mildly in one patient and no other side-effect was observed, and all patients continued therapy. CONCLUSION: Adefovir dipivoxil is a safe, effective treatment option for post-transplant HBV recurrence even among patients with fibrosing cholestatic hepatitis caused by lamivudine-resistant HBV.

Living donor liver transplantation for hepatitis B cirrhosis.

BACKGROUND AND AIM: Living donor liver transplantation (LDLT) has particular advantages for Turkey where hepatitis B virus (HBV) infection is the most common cause of cirrhosis, both because LDLT circumvents the difficulties encountered in the emerging world in providing deceased donor organs, and because it allows preemptive antiviral therapy. The aim of this study was to review one institution's experience with LDLT in patients with chronic HBV infection. METHODS: A total of 109 patients with chronic HBV infection underwent LDLT between September 1999 and June 2005, of whom 40 were coinfected with hepatitis D virus and 23 had hepatocellular carcinoma. Antiviral prophylaxis was attempted in all, beginning prior to transplantation with lamivudine or adefovir, and continuing after transplantation with low dose intramuscular hyperimmune B immunoglobulin (HBIg) plus lamivudine or adefovir. RESULTS: In a median follow up of 20 months (range 1-66 months), there was no donor mortality. One-year recipient survival was 90%, and in total 16 recipients died. None of the deaths was related to HBV. Recurrence of HBV infection was detected by reappearance of serum hepatitis B surface antigen in six patients (5.5%) at 5, 8, 12, 17, 34 and 46 months after transplantation, respectively. There was no influence of donor hepatitis B core antibody status on the likelihood of recurrence of HBV in the allograft. CONCLUSION: The results indicate that LDLT with antiviral treatment and low dose HBIg provides excellent results for donors and recipients.

A two-dose schedule for combined hepatitis A and B vaccination in children aged 6-15 years.

A combined hepatitis A and B vaccine, Twinrix, in a paediatric formulation for ages 1-15 years and in an adult formulation for those ages 16 years and older, became commercially available in Turkey as well as in many countries. It is administered according to a three-dose schedule (0, 1 and 6 months). A reduction in the number of doses would improve the compliance rate and reduce administration costs. Therefore, we planned a trial evaluation of the immunogenicity, safety and reactogenicity profile of a high-dose combined hepatitis A and B vaccine, administered in two doses, compared with the profile of a paediatric-dose combined vaccine, administered in three doses, in healthy children aged 6-15 years. One hundred children were randomly attributed to the two study groups. The first group (paediatric-dose vaccine group) received the licensed Twinrix Paediatric, at months 0, 1 and 6; the second group (high-dose vaccine group) received the high-dose vaccine, following a 0, 6 months schedule. The reactogenicity was assessed after each vaccine dose. The immunogenicity was evaluated by testing for anti-HBs and anti-HAV antibodies. Seroconversion rates and geometric mean titres (GMTs) were compared. Both formulations of the combined vaccine were well tolerated. The high-dose combined vaccine administered in two doses, elicits satisfactory immunogenicity profiles, similar to those elicited by the paediatric vaccine administered in three doses. On completion of the vaccination schedule in the two groups all children were protected against hepatitis B and immune for hepatitis A. Anti-HAV GMTs after completion of the vaccination schedule were 7163 mlU/ml in the paediatric-dose group, 8241 mlU/ml in the high-dose group; anti-HBs GMTs were 8679 and 4583 mlU/ml, respectively. These results indicate that a two-dose schedule, compared with the standard three-dose schedule, offers fewer injections for satisfactory protection against the two infections. This means fewer clinic visits, lower administration costs, better compliance, and higher coverage rate. Therefore, this two-dose schedule can be considered an appropriate regimen for the immunization of children and adolescents against hepatitis A and B infection, in the context of school-based immunization programmes.

Assessment of Chlamydia trachomatis prevalence by cell culture and transcription-mediated amplification in symptomatic women.

OBJECTIVE: The frequency of Chlamydia trachomatis in women with mucopurulent discharge was determined by a cell culture technique and a transcription-mediated amplification (TMA) assay in endocervical swab specimens. SUBJECTS AND METHODS: Endocervical swab specimens were obtained from 116 symptomatic patients with genitourinary complaints or abdominal pain. All of the women were married, with an age range of between 19 and 44 (median 29) years. The cell culture assay was used in all specimens. For 75 specimens the TMA assay was also performed. RESULTS: Positive cell culture test results were obtained in 6 (5.2%) patients. Among 75 specimens, 2 were positive by both TMA and culture assays, while 1 specimen was positive only by the culture assay. Of those positive for C. trachomatis, 5 were in the 19- to 25-year age group, and 1 was in the >25-year age group. All of the patients with positive results were of low socioeconomic status. CONCLUSIONS: This study revealed a relatively low rate of C. trachomatis infections in symptomatic married women in Turkey. A commercial TMA assay failed to identify all positive patients, in contrast to a 'gold standard' culture assay used in patients having such infections.