[Seasonal Trends and Interactions of Viral Pathogens in Children Presenting with Acute Respiratory Tract Infections in the Advancing Periods of SARS-CoV-2 Pandemic]. / SARS-CoV-2 Pandemisinin Ilerleyen Dönemlerinde Akut Solunum Yolu Enfeksiyonu ile Basvuran Çocuklarda Viral Patojenlerin Mevsimsel Egilimleri ve Etkilesimleri.

Although various bacteria and viruses have been identified in the etiology of acute respiratory tract infections (ARI), 90% of acute ARIs that develop in children are of viral origin. The aim of this study was to investigate the seasonal trends and interactions between infectious agents and to determine the risk factors associated with ARI in children aged 1-15 years admitted to the Pediatric Emergency Department of Manisa Celal Bayar University Hospital in the advancing periods of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic. To determine the bacterial and viral agents, samples were taken from 314 patients attending to the hospital with symptoms suggestive for ARI, between 06/01/2021 and 05/31/2022. Viral and bacterial agents were identified by multiplex polymerase chain reaction (PCR) and automated identification system, respectively. Demographic data of the participants and possible risk factors for ARI were recorded in the questionnaires. In the study, viral agents were detected in 77.3% of the children, and the most common infectious agent was rhinovirus/enterovirus (RV/EV) (36.3%), followed by influenza viruses (11.2%), and SARS-CoV-2 (10.5%). While RV/EV positivity was found to be higher in children with moderate and below average (p< 0.001) hand hygiene, influenza positivity was found higher in those attending school/preschool institution (p< 0.001) and whose mothers working full-time (p< 0.001). Respiratory syncytial virus positivity was associated with maternal smoking (p= 0.013) and home overcrowding (p= 0.014). Bacterial colonization was detected in 33 (11.6%) of 284 children whose swabs were taken for both bacterial and viral agents and the most frequently detected agents were Staphylococcus aureus (60.6%) and Pseudomonas aeruginosa (15.2%). Having siblings (p= 0.008) and maternal smoking (p= 0.012) were found to be associated with the detection of bacterial agents. In this study, in the advanced period of the pandemic, the most detected agents and seasonal characteristics were found to be similar to the pre-pandemic period. It is thought that knowing the regional etiology and risk factors will contribute to taking the necessary local control and protective measures.

Evaluation of Clinical Features and Olfactory Functions in COVID-19: A Multicentre Study.

Introduction Coronavirus Disease-2019 (COVID-19) causes olfactory loss one of the initial diagnostic criteria. The brief smell identification test (BSIT) is an objective test frequently used in olfactory dysfunction. This study aimed to observe the changes in olfactory functions and clinical features in a short time in COVID-19. Methods In this prospective study involving 64 patients, the BSIT was performed at two different times; at the time of first application and on the 14th day. Demographic features, laboratory findings, body mass index (BMI), blood oxygen saturation values (SpO2), complaints at first admission, fever, follow-up place, and treatment schemes were noted. Results There was a significant difference between the BSIT scores at the first admission and when the polymerase chain reaction (PCR) became negative on the 14th day (p<0.001). Low oxygen saturation values at first admission were associated with low BSIT scores. No relationship was found between olfactory functions and complaints at admission, fever, follow-up place, and treatment schemes. Conclusion As a result, negative effects of COVID-19 on olfactory functions have been demonstrated even in the short follow-up period. In addition, low saturation values at first admission were associated with low BSIT scores.

[Efficacy of Homologous and Heterologous Vaccine Applications on SARS-CoV-2 Omicron Variant: Cohort of Manisa Celal Bayar University Healthcare Workers]. / Homolog ve Heterolog Asi Uygulamalarinin SARS-CoV-2 Omicron Varyanti Üzerindeki Etkililigi: Manisa Celal Bayar Üniversitesi Saglik Çalisanlari Kohordu.

This study was aimed to determine the efficacy of homologous (only CoronaVac or only Pfizer-BioNTech) and heterologous (CoronaVac and Pfizer-BioNTech) vaccines during the period when the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) Omicron variant was dominant in Türkiye. Coronavirus disease-2019 (COVID-2019) infection was confirmed by reverse transcriptase polymerase chain reaction and data on vaccination status against COVID-19 were evaluated during the period of 15 January 2022-1 May 2022 when the SARS-CoV-2 Omicron variant was dominant among 1854 employees followed in the SARS-CoV-2 Vaccine Cohort of Manisa Celal Bayar University (MCBU) Hospital Health Workers. Two separate reference groups were used in the evaluation of vaccine efficacy: those who were never vaccinated and those who received only two doses of CoronaVac. The efficacy of homologous and heterologous vaccine models was evaluated with relative risks and attributable risk percentages. MS Excel, SPSS 23.0 and STATA 14.1 package programs were used for statistical analysis. The mean age of the participants was 36.6 ± 10.0. During the period from January 15th to May 1st 2022, 372 hospital workers were infected with COVID-19. Taking the never vaccinated as the reference group, the most effective model was found to be only the three or more doses of the Pfizer-BioNTech primary vaccination model (85.8%, 95% CI= 40.7-96.6). Models consisting of a single dose of CoronaVac (6.5%, 95% CI= -56.3-44.2) or a single dose of Pfizer-BioNTech (17.7%, 95% CI= -30.2-48.0) booster dose administered after two doses of primary CoronaVac vaccination was not found to be effective against the SARS-CoV-2 Omicron variant. When only two doses of primary CoronaVac vaccination model was taken as the reference group, the model consisting of two doses CoronaVac followed by two Pfizer-BioNTech booster doses was effective as 38.4% (95% CI= 15.4-55.3), whereas three doses of Pfizer-BioNTech booster model was effective as 56.4% (95% CI= 33.9-71.3). To conclude, none of the models other than the homologous or heterologous vaccine models containing at least three doses of Pfizer-BioNTech vaccine were effective compared to those unvaccinated. Compared with those who received only two doses of primary Coronavac, models with at least three doses of Pfizer-BioNTech reminder doses were more effective against the Omicron variant than other models.

The effect of COVID-19 vaccinations on menstrual cycle and serum anti-Mullerian hormone levels in reproductive age women.

The aim of this prospective cohort study was to investigate the effect of coronavirus disease 2019 (COVID-19) vaccinations on menstrual cycle and ovarian reserve in reproductive aged-women. Health care providers (n = 258) vaccinated with inactivated (CoronaVac) and mRNA based (Pfizer-BioNTech®) COVID-19 vaccines were included. All subjects completed a gynaecological and menstrual history questionnaire and Anti-Mullerian Hormone (AMH) levels were measured in serum samples collected before first vaccination and at 1st, 3rd, 6th and 9th months. The prevalence of new-onset menstrual dysregulation following vaccination was 20.6% and it was statistically significant compared to baseline (p = 0.001). Menstrual pattern turned back to normal in 59.6% of vaccinated women. Serum AMH levels gradually decreased until 6th month of follow-up compared to baseline (p < 0.001). A significant increase in serum AMH level was observed at 9th month of follow-up compared to 6th month follow-up levels (p < 0.001). The decrease in serum AMH level was statistically significant regardless of serum anti SARS-CoV-2 antibody levels, subgroups of age, occupation, menstrual dysregulation following vaccination and presence of gynaecological diseases. In conclusion, vaccination against SARS-CoV-2 causes a transient decrease on serum AMH levels and moderate irregularities in menstrual pattern increasing with age and is mostly reversible.

Factors affecting the serologic response to SARS-CoV-2 vaccination in patients with solid tumors: A prospective study.

OBJECTIVE: To evaluate the factors affecting seropositivity and antibody levels after SARS-CoV-2 vaccines in patients with cancer because they were excluded from clinical studies of SARS-CoV-2 vaccines. METHODS: This prospective, observational, single-center study included 290 patients with solid tumors followed up in our medical oncology clinic between March 2021 and August 2021. SARS-CoV-2 antibody status was determined before the first dose of vaccine. Fifty-one patients with positive prevaccine baseline antibody tests were excluded from the study, regardless of whether they had previously confirmed SARS-CoV-2 PCR positivity. To determine the quantitative IgG antibody response of the vaccines, blood samples were collected at least 28 days after each dose of vaccine. Quantitative IgG levels against virus spike protein receptor binding domain (RBD) were measured using chemiluminescent enzyme immunoassay (CLIA). Demographic and clinical features affecting seropositivity were analyzed. RESULTS: One hundred and fifty-one (69.3%) patients were vaccinated with two doses of CoronaVac followed by one dose of BNT162b2 (Biontech) (group 1). Sixty-seven (30.7%) patients were vaccinated with three doses of BNT162b2 (group 2). The proportion of patients who developed seropositivity was significantly higher in group 2 (78.6% vs. 54.9%, p < 0.012). Antibody response increased significantly after the second dose of vaccine in both groups. Female sex, being younger than 65 years, and chemotherapy status were significantly related to higher anti-SARS-CoV-2 S antibody levels (p = 0.033, p = 0.036, and p = 0.047, respectively). Antibody levels were significantly higher in patients who had previously received chemotherapy than in patients receiving active chemotherapy (p = 0.042). CONCLUSIONS: Our study is the first to evaluate basal SARS-CoV-2 IgG levels before the first dose of vaccine and after three doses in patients with solid tumors. The rate of development of seropositivity with two doses of mRNA vaccine was found to be higher than with two doses of inactivated SARS-CoV-2 vaccine. More attention should be paid to preventive measures in addition to vaccination in patients aged over 65 years and men with cancer diagnoses.

[Antibody Sustainability in SARS-CoV-2 Healthcare Professionals' Patient Cohort]. / Saglik Çalisanlari SARS-CoV-2 Hasta Kohordunda Antikor Sürdürülebilirligi.

In this study, it was aimed to evaluate one-year follow-up of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) specific antibodies formed against the virus binding site, in a coronavirus disease-2019 (COVID-19) positive case cohort (n= 413) between the period March 2020 to December 2020 in Manisa Celal Bayar University Hospital, until July 2021. SARS-CoV-2 antibodies were determined by the chemiluminescent enzyme immunoassay (CLIA) method. Values of 1.0 and above were considered positive. Chi-square tests and Joinpoint regression analysis (version 4.7.0) were used in the statistical analyses. The mean age of the participants was 34.9 ± 9.3 and 60.2% of them were women. Between 21-30 days after the diagnosis of COVID-19, total antibody level was above the threshold value in 72.2% (n= 126) of the participants, while this rate increased to 79.1% (n= 240) in 31-60 day interval. In the following period, this rate decreased to 38.8% (n= 108) in days 211st to 240th. Antibody response could not be detected in 76 (20.7%) of 367 employees who have initially been followed up. The percentage of total antibody positivity prevalence ranged from 98.9% to 96.1% in the 31-210th day after diagnosis, in the follow-up of 291 employees whose total antibody positivity was detected after diagnosis. According to the results of the Joinpoint regression analysis, after the diagnosis of COVID-19, the curve showing the percentage of antibody positivity was broken at two points: The first breaking point was observed in 181-210th days (6-7 months) (p= 0.069), and the second breaking point was in 271-300th days (9-10 months) (p< 0.001). As a result, the highest antibody positivity rates were detected after the 30th day of the disease onset and antibody positivity was maintained in the first seven months after diagnosis; the antibody positivity rate decreased to 25% at the end of the first year.

[Factors Affecting Side Effects, Seroconversion Rates and Antibody Response After Inactivated SARS-CoV-2 Vaccination in Healthcare Workers]. / Saglik Çalisanlarinda Inaktif SARS-CoV-2 Asilamasi Sonrasi Yan Etkiler, Serokonversiyon Oranlari ve Antikor Yanitini Etkileyen Faktörler.

In this study, it was aimed to prospectively evaluate the efficacy, side effects and seroconversion data of inactive severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), CoronaVac® (Sinovac, China) vaccine in healthcare workers. A total of 1053 healthcare workers who were initially seronegative (COV2T® SARS-CoV-2 Total Siemens, USA) and vaccinated with inactivated SARS-CoV-2 were included in the study. Quantitative IgG antibodies (ADVIA Centaur® SARS-CoV-2 IgG, Siemens, USA) were investigated 28 days after the first vaccine (n= 939) and the second vaccine (n= 771). In addition, neutralizing antibodies were evaluated via "enzyme linked immunosorbent assay (ELISA)" test (ACE2-RBD Neutralization Assay, Dia-Pro, Italy) 28 days after the first vaccine. Antibody response of the vaccine was evaluated statistically by univariate (Chi-square, Fisher's exact test, Student's t test, Mann-Whitney U, one-way ANOVA and Kruskall Wallis ANOVA tests) analysis and linear regression models. The consistency between quantitative IgG test and neutralizing antibody test was also evaluated in blood samples taken 28 days after second vaccination. Statistical analysis was determined in logarithmically transformed data with statistical analysis with SPSS 23.0 and Stata, and type 1 error level was accepted as 0.05. At least one side effect was reported by 31.3% and 26.8% of the participants after the first and second vaccine, respectively. The most frequent side effect was pain at the injection site with a frequency of 20.4% vs 21.7%. The frequency of applying to a health center due to side effects was 1.0% after the first vaccine and 0.8% after the second vaccine. The percentage of those who produced sufficient quantitative IgG was found as 25.3% (95% CI= 22.5-28.1) 28 days after the first vaccine and 97.9% (95% CI= 96.91- 98.93) after the second vaccine. Neutralizing test antibody positivity was found as 97.7% 28 days after the second vaccine. In univariate analysis, the characteristics that significantly increased the quantitative IgG response against inactivated SARS-CoV-2 vaccine were young age (p<0.01), female gender (p<0.01), being a non smoker (p<0.001), not having a chronic disease (p= 0.019), having had the flu vaccine this year (p= 0.012), not being overweight or obese (p= 0.020), and having a SARS-CoV2 infection prior to vaccination (p<0.001). In addition, allied health personnel showed significantly lower antibody responses than the other workers (p<0.001). Multiple linear regression models revealed that, female gender, younger age, smoking and previous COVID-19 polymerase chain reaction test positivity significantly affected the quantitative IgG response after vaccination. A 99% agreement was found between the ELISA-based neutralizing antibody test and the quantitative IgG test (Kappa p= 0.783) performed on the 28th day after the second vaccination. CoronaVac® provides adequate antibody response in 25% of healthcare workers aged 18-64, after 28 days from a single vaccine, and 97% after 28 days from the second vaccine. Antibody response was significantly higher in younger ages, women, non-smokers, and those who had previously encountered SARS-CoV-2. Phase 3 and phase 4 results are needed to Show effectiveness of this vaccine in real life.

Evaluation of the pol/S Gene Overlapping Mutations in Chronic Hepatitis B Patients in Northern Cyprus.

Mutations associated with the pol and the S gene can emerge as a consequence of the high replication capacity and proofreading deficiencies of hepatitis B virus during replication. The current study was constructed to evaluate primary, partial, compensatory and the escape mutations in chronic hepatitis B patients in Northern Cyprus. The samples of HBsAg positive treatment naïve 100 patients were involved in this study. HBV pol gene region was sequenced, amplified and HBV pol/S gene mutations were determined. The samples of thirty-two patients were excluded because of their low viral load (HBV < 1000 iu/ml). Among the sequenced 68 samples, there was a partial mutation (1.5%) and 36.7% displayed a resistance profile to lamivudine, adevofir, and telbivudine. Immune response escape, vaccine escape, HBIg and diagnosis escape mutations were determined in 24%, 10%, 6%, and 4% samples of the patients, respectively. Additionally, there were six different combined mutations. These data underscored that there is no concern for primary mutations in Northern Cyprus, however, we have identified a compensatory mutation (rtV173M) that may have primary mutation characteristics by combining with other mutation patterns. Additionally, HBsAg escape mutants demonstrated that detection of the S gene together with the pol gene mutations might be beneficial and important to monitor the surveillance of S variants.Mutations associated with the pol and the S gene can emerge as a consequence of the high replication capacity and proofreading deficiencies of hepatitis B virus during replication. The current study was constructed to evaluate primary, partial, compensatory and the escape mutations in chronic hepatitis B patients in Northern Cyprus. The samples of HBsAg positive treatment naïve 100 patients were involved in this study. HBV pol gene region was sequenced, amplified and HBV pol/S gene mutations were determined. The samples of thirty-two patients were excluded because of their low viral load (HBV < 1000 iu/ml). Among the sequenced 68 samples, there was a partial mutation (1.5%) and 36.7% displayed a resistance profile to lamivudine, adevofir, and telbivudine. Immune response escape, vaccine escape, HBIg and diagnosis escape mutations were determined in 24%, 10%, 6%, and 4% samples of the patients, respectively. Additionally, there were six different combined mutations. These data underscored that there is no concern for primary mutations in Northern Cyprus, however, we have identified a compensatory mutation (rtV173M) that may have primary mutation characteristics by combining with other mutation patterns. Additionally, HBsAg escape mutants demonstrated that detection of the S gene together with the pol gene mutations might be beneficial and important to monitor the surveillance of S variants.

[Determination of drug resistance mutations of NS3 inhibitors in chronic hepatitis C patients infected with genotype 1]. / Genotip 1 ile enfekte kronik hepatit C hastalarinda NS3 inhibitörü ilaçlarin direnç mutasyonlarinin belirlenmesi.

Direct-acting antiviral agents (DAA) such as NS3 protease inhibitors is the first class of drugs used for chronic hepatitis C (CHC) treatment. NS3 inhibitors (PI) with low genetic barrier have been approved to be used in the CHC genotype 1 infections, and in the treatment of compensated liver disease including cirrhosis together with pegile interferon and ribavirin. Consequently, the development of drug resistance during DAA treatment of CHC is a major problem. NS3 resistant variants can be detected before treatment as they can occurnaturally. The aim of this study was to investigate new and old generation NS3 inhibitors resistance mutations before DAA treatment in hepatitis C virus (HCV) that were isolated from CHC. The present study was conducted in 2015 and included 97 naive DAA patients infected with HCV genotype 1, who were diagnosed in Manisa and Kocaeli cities of Turkey. Magnetic particle based HCV RNA extraction and than RNA detection and quantification were performed using commercial real-time PCR assay QIASypmhony + Rotorgene Q/ArtusHCV QS-RGQ and COBAS Ampliprep/COBAS TaqMan HCV Tests. HCV NS3 viral protease genome region was amplified with PCR and mutation analysis was performed by Sanger dideoxy sequencing technique of NS3 protease codons (codon 32-185). HCV NS3 protease inhibitors; asunaprevir, boceprevir, faldaprevir, grazoprevir, pariteprevir, simeprevir and telaprevir were analysed for resistant mutations by Geno2pheno-HCV resistance tool. HCV was genotyped in all patients and 88 patients (n= 88/97, 91%) had genotype 1. Eight (n= 8/97, 8.2%) and 80 (n= 80/97, 82.4%) HCC patients were subgenotyped as 1a and 1b, respectively. Many aminoacid substitutions and resistance mutations were determined in 39/88 (44%) patients in the study group. Q80L, S122C/N, S138W were defined as potential substitutions (6/88 patients; 7%); R109K, R117C, S122G, I132V, I170V, N174S were described as potential resistance (34/88 patients; 39%); V36L, T54S, V55A, Q80H were characterized as resistance (7/88 patients; 8%) and Q80K, A156S were defined as high resistance (3/88 patients; 3%) mutations. Based on resistance and high resistance mutations, clinically significant mutations were defined in 10/88 (11%) of the patients. Our study shows that it is essential to analyse HCV NS3 protease inhibitors drug resistance before DAA treatment of CHC patients. On the other hand, our results pointed out that analysis of NS5A and NS5B genome region mutations may also be required in the near future.

[Investigation of the correlation between anti-HCV levels (S/Co) with HCV-RNA in the diagnosis of hepatitis C virus (HCV) infection]. / Hepatit C virus (HCV) enfeksiyonunun tanisinda anti-HCV düzeyi (S/Co) ile HCV-RNA arasindaki korelasyonun arastirilmasi.

Detection of borderline and/or low positive anti-HCV results by enzyme immunoassay (EIA) leads to severe problems in routine laboratories and needs confirmation with nucleic acid amplification tests which can increase the cost. In EIA tests, if the ratio of sample to cut-off (S/Co) is ≥ 1, the sample is accepted as positive according to the manufacturers' instructions. Although over the last decade the application of S/Co values have also applied to HCV-RNA readings, the current study aims to determine whether the S/Co value is adequate and applicable for the anti-HCV EIA test, and to determine whether a correlation exists between HCV-RNA and HCV infections. A total of 658 cases (402 female, 256 male; mean age: 49.4 ± 17.0 years) who were found anti-HCV positive between January 2011-July 2013 were included in the study. Anti-HCV tests were performed by chemiluminescent EIA (Architect i2000SR, Abbott, USA and LiaisonXL Murex, DiaSorin, Italy) and HCV-RNA by real-time PCR (Cobas Ampliprep/Cobas TaqMan HCV, Roche, USA). The mean S/Co value of the cases was 7.3 ± 4.8 (range: 1.00-17.59) and mean HCV-RNA value was 2.3x105 ± 2.1x106 copies/ml. When the anti-HCV S/Co value of varying ranges was compared with HCV-RNA readings a particular trend was noted. In the anti-HCV S/Co values of 1.0-4.0; 4.1-7.0; 7.1-10.0; 10.1-13.0; 13.1-16.0 and ³16.1, HCV-RNA positivity rates were detected as 1.9%, 24.7%,37.1%, 46.7%, 56.4% and 75%, respectively. Statistical analysis indicated an intermediate positive correlation (r= 0.454) between anti-HCV ve HCV-RNA readings (p= 0.000). An adequate S/Co value was accepted as 5.0 based on the ROC analysis, and this value gave a performance confidence level of 95.6% when determining whether a patient is HCV positive. Based on the data of this study it became evident that further EIA testing is not required if the S/Co value is ≥ 5.0, however if the S/Co value is less than 5.0, then further clinical analysis and revaluation of the patient is required.

[Molecular epidemiology of hepatitis B virus in Northern Cyprus]. / Kuzey Kibris'ta hepatit B virusunun moleküler epidemiyolojisi.

Identification of hepatitis B virus (HBV) strains and understanding of molecular epidemiological characteristics are important for the effective surveillance of HBV infections. Genotype D is dominant in studies performed in Turkey but it is known that cases infected with genotypes A, E, G and H also exists. In contrast, there are no data regarding the molecular epidemiologic characteristics of the HBV in Northern Cyprus. The aim of this study was to determine the distribution of genotypes and subgenotypes of HBV among the people living, educating and working in Northern Cyprus. A total of 160 cases (1.2%) who were HBsAg seropositive out of 13.892 subjects admitted to Nicosia, Near East University Hospital microbiology laboratory for the routine control and to blood center for donor screening tests between November 2011 to September 2014, were included in the study. HBV-DNA levels in the HBsAg positive cases were detected by real-time polymerase chain reaction and genotypes/subgenotypes were determined by sequence analysis of the viral pol gene (reverse transcriptase [rt] region, between 80-250. aminoacids). Sixty samples (60/160, 37.5%) were excluded from sequencing analysis due to negative and/or very low (< 30 IU/ml) HBV-DNA levels, so 100 samples were included in sequence analysis. Ninety-six of those cases (13 female, 87 male; mean age: 35.51 ± 12.88 years) were anti-HBc IgG, 95 were anti-HBe and five were HBeAg positive, with a mean HBV-DNA level of 5.36 x 10(6) ± 3.58 x 10(7) IU/ml. As 32 (32%) samples yielded HBV-DNA level below the threshold of 1000 IU/ml, sequence analyses were unsuccesful, eventually 68 (68/160, 42.5%) samples could be phylogenetically analyzed. The distribution of HBV genotypes/subgenotypes were found as follows: 48 were (70.6%) D/D1; four were (5.9%) D/D2; one was (1.5%) D/D3, five were (7.4%) A/A1, two were (2.9%) A/A2 and eight were (11.8%) genotype E. Among the most frequent D1 strains, 60.4% (29/48) cases were from Turkish; single D/D3 strain from Benguela (Angola) and all eight genotype E strains were from Nigerian national cases. According to the data of this first study performed in TRNC on this subject, genotype D is dominant (53/68, 78%) in Northern Cyprus and consistent with the subgenotype distribution that is similar to Turkey and mediterranean basin. The prevalences of genotype A (7/68, 10.3%) and E (8/68, 11.8%) were also remarkable. In conclusion, although Northern Cyprus is an island country the heterogeneous distribution of HBV genotype/subgenotype may be contributed to the cosmopolitan characteristics of various populations from different countries who have come here for education, work or touristic purposes.

[Hepatitis B virus genotype E infection in Turkey: the detection of the first case]. / Türkiye'de ilk kez saptanan hepatit B virus genotip E enfeksiyonu.

Hepatitis B virus (HBV) infection is a global major health problem. Currently, 10 genotypes (A-J) of hepatitis B virus (HBV) are identified based on the nucleic acid sequence heterogeneity, and these genotypes have been shown to have distinct geographic distribution. Reports of the previous studies indicated that the genotype D is the predominant type among hepatitis B patients in different regions of Turkey. However, recent studies indicated that other HBV genotypes are also seen with an increasing rate. Although epidemiological and clinical information on genotype E infection is currently limited, it is known that genotype E infection is common in West and Central Africa. In this report, the first case of HBV genotype E infection in Turkey was presented. A 22-year-old Nigerian male employee who resided in Manisa for five years was admitted to Celal Bayar University Hospital Manisa, Turkey, for his routine check-up. Since HBsAg was found positive, other HBV markers were tested with a repeated serum sample. Laboratory findings were as follows; HBsAg (+), anti-HBs (-), HBeAg (-), anti-HBe (+), anti-HBc (+), anti-HCV (-), anti-HIV (-), ALT: 44 U/L and AST: 45 U/L. HBV-DNA level was detected as 700 IU/ml by real-time PCR (Artus HBV QS RGQ Qiagen, Germany). HBV-DNA isolated from the serum sample of the patient was amplified by PCR and polymerase gene segment of HBV was directly sequenced. UPGMA method was used for phylogenetic analysis and Inno-LIPA HBV genotyping method (Innogenetics, Belgium) was performed to determine multiple HBV genotype infection. On the basis of those methods the genotype of the virus was identified as genotype E. The partial sequences of the HBV polymerase gene were loaded to the international DNA data bank (GenBank) for contribution to the global HBV surveillance. This report emphasized that besides genotype D the other HBV genotypes could be found in Turkey. Since the patient was an inactive HBsAg carrier before his residence in Turkey, this case was regarded as an imported HBV genotype E case. In conclusion, detection of different HBV genotypes, their epidemiology and molecular characteristics are important for both national and global HBV surveillance and better clinical approach.

Are human adenovirus-5 and 36 associated with obesity in children?

OBJECTIVES: The aims of this study were to determine the association between adenovirus-5- and adenovirus-36-specific antibodies and obesity in children and to investigate their relationship with serum lipid and leptin levels. METHODS: A cross-sectional study was performed on a total of 120 children who were divided into subgroups according to body mass index percentile as obese (≥ 95th percentile) or nonobese (<95th percentile). The presence of adenovirus-36 and adenovirus-5-neutralizing antibodies was investigated by using the serum neutralization assay. Serum leptin levels were determined by microenzyme immonoassay; high-density lipoprotein, low-density lipoprotein, triglyceride, and cholesterol levels were measured by chemiluminescence method. RESULTS: The presence of adenovirus-5-specific antibodies was 28.3% and 6.6% in the obese children and in non-obese children, respectively (P = 0.02). The frequency of adenovirus-36-specific antibodies was significantly greater (P = 0.018) in the obese children (26.6%) than in the non-obese children (10.0%). Serum leptin level of the obese group were significantly higher than that of the non-obese group (P = 0.000). CONCLUSIONS: Our data support the association between obesity and the presence of specific antibodies to adenovirus-36 and adenovirus-5 in children. Our research has the feature of being the first national study to indicate the relationship between adenovirus-36 and human obesity as well as the first international study to indicate the relationship between adenovirus-5 and human obesity.

Human papilloma virus frequency and genotype distribution in a Turkish population.

OBJECTIVES: To determine human papillomavirus (HPV) frequency, genotypes and the relation between cervical smear results, risk factors and types in women living in Manisa, Turkey. MATERIALS AND METHODS: A total of 410 women were included in the study. Cervical specimens were obtained for linear array HPV genotyping and pathological testing. Conventional Pap test and Bethesda system were used for evaluation of cytology specimens. RESULTS: A total of 410 women with a mean age of 34.9 years were tested. A positive result of any HPV was found in 35 patients (8.5%). Among them, 26 different serotypes of HPV were identified and the most frequent type was HPV 16 (28.5%) followed by type 45 and 53 (11.4%). Patients were infected by 65.7% high risk, 11.4% probable high risk and 22.9% low risk HPV types. Multiple HPV positive results were found in 13 patients (37.1%). Patients with single partner, history of abnormal smear or condyloma had positive HPV results and this was statistically significant (p<0.05). Correlation analysis showed a statistically weak relation between positive HPV and abnormal smear results (r=0.120). CONCLUSIONS: Determining HPV types of genital HPV infections is important for epidemiological studies. We have found the rate of positive HPV as 8.5% which implies the need for extended screening programs in order to diagnose oncogenic HPV at an early stage.

[Molecular typing of adenoviruses isolated from clinical specimens by PCR and DNA sequencing methods]. / Klinik Örneklerden Izole Edilen Adenoviruslarin PCR ve DNA Dizi Analizi Yöntemiyle Tiplendirilmesi.

Adenoviruses are responsible for a broad spectrum of diseases, including upper and lower respiratory tract infections (URTIs and LRTIs, respectively), conjunctivitis, gastroenteritis, and hemorrhagic cystitis. The aim of this study was to determine the adenovirus (AdV) types isolated from clinical specimens by polymerase chain reaction (PCR) and DNA sequencing methods. A total of 22 AdV strains isolated between January 1st 2011 to May 31th 2011, from various samples (295 nasopharyngeal swabs, 42 conjunctival swabs, 13 stool) sent to our routine virology laboratory were included in the study. Of the 22 patients whose samples yielded adenovirus positivity, 8 were adult (4 were male; median age: 32.5 years) and 14 (7 were male; median age: 1 year) were children. Those specimens (14 nasopharyngeal swabs, 7 conjunctival swabs, 1 stool) were obtained from patients with URTIs (n= 6), LRTIs (n= 8), conjunctivitis (n= 7) and gastroenteritis (n= 1). For the isolation and identification of adenoviruses, rapid (shell vial) cell culture and direct immunofluorescence antibody methods were used, respectively. Molecular typing of adenoviruses were performed by PCR and sequencing of a partial region (hipervariable region 1-6) of the hexon gene. PCR primers (Adhex F1, Adhex R1) used for DNA amplification were from those described by Lu and Erdman, previously. If insufficient DNA was amplified from the first reaction for sequencing, a nested PCR was performed using Adhex F2 and Adhex R2 primers. Sequencing was performed using the amplification primers and Sequence Reagent Mix-DYEnamic ET Terminator Cycle Sequencing Kit (Amersham Pharmacia Biotech Inc, USA) on ABI PRISM 310 Genetic Analyzer (Applied Biosystems, USA). Obtained adenovirus sequences were typed by BLAST analysis and three AdV types namely type 3, 4, and 8 were identified. In our study, AdV type 3 was detected in a gastroenteritis case and six cases with URTIs and LRTIs (n= 7, 31.8%). AdV type 8 was identified as the cause of conjunctivitis in seven patients and of URTIs and LRTIs in five patients (n= 12, 54.5%). AdV type 4 was found to be associated with URTI in one, and LRTIs in two patients (n= 3; 13.7%). Our data indicated that AdV type 8 was the most prevalent type in patients with conjunctivitis and URTIs, while AdV type 3 was the most prevalent type in patients with LRTI. BLAST analysis was thought to be useful for the molecular typing of adenoviruses. In conclusion, advanced studies with large number of specimens are necessary to achive a reliable, detailed national adenovirus database.

Evaluation of serological tests for diagnosis of brucellosis.

The aim of the present study was to compare serological tests (Rose Bengal [RB]; standard agglutination test [SAT]; enzyme immunoassay [EIA] for detection of IgM, IgA, and IgG; and 2-mercaptoethanol [2-ME] test) that are routinely used in patients prediagnosed with different clinical types of brucellosis (acute, subacute, or chronic), and to evaluate the results of the IgG avidity test. Ninety-two patients having titers≥1/160 as measured by SAT were included in the study. The IgG avidity test was performed in 78 patients who had positive EIA-IgG results. RB test results were positive in 88 (95.7%) patients. A statistically significant correlation was found between a positive EIA-IgM result and the diagnosis of acute brucellosis. When compared to the results of the SAT, the 2-ME test showed a lower titer in 55 (59.8%) patients, and the agreement between the 2-ME test and EIA-IgG was calculated as 84.8%. No statistical difference was found between the 40% avidity index used in the IgG avidity test and avidity maturation time (6 months). From our study, we concluded that (i) the RB and SAT tests are appropriate and reliable tests for the serological diagnosis of brucellosis; (ii) IgM can be used as a marker of acute brucellosis; (iii) the 2-ME test, similar to EIA, can be used to determine IgM levels; and (iv) the IgG avidity test should be standardized.

Impact of hemostatic gene single point mutations in patients with non-diabetic coronary artery disease.

Single point mutations in the genes coding for hemostatic factors were shown to be major inherited predisposing factors for venous thromboembolism. However, their contribution in the development of non-diabetic coronary artery disease [nDCAD] remains controversial. Angiographically demonstrated nDCAD patients (n = 86) and healthy controls (n = 90) were included in the study. Genotype analysis of hemostatic gene polymorphisms were assessed by using CVD strip assay, based on allele specific oligonucleotide probes. The carrier frequency of factor V (FV) H1299R, prothrombin G20210A, glycoprotein (Gp) IIIa L33P, plasminogen activator inhibitor-I (PAI-1) 4G/5G, 4G/4G, 5G/5G, methylenetetrahydrofolate reductase (MTHFR) A1298C and beta-fibrinogen -455 G > A were similar between patients and controls. In contrast, frequency of FV Leiden was significantly higher among patients (12.5%) than controls (5%, OR: 7.94; 95%CI: 1.9-49.6) and FXIII V34L was significantly lower among patients (23.7%) than controls (40%, OR: 0.24; 95%CI: 0.1-0.89). In addition, the frequency of the MTHFR C677T polymorphism was 32.5% among patients compared with 42.5% in controls, of which the T/T genotype was significantly lower among patients (5%) than controls (17.5%, OR: 0.06; 95%CI: 0.01-0.58). No difference was observed in prevalence of prothrombin G20210A, FV H1299R, Gp IIIa L33P, PAI-1 4G5G, MTHFR A1298C, beta fibrinogen 455 G > A mutations between patients and controls. However, lower frequency of FXIII Val34Leu and MTHFR C677T polymorphisms may decrease, while FV Leiden polymorphism may increase development of nDCAD.

[Distribution of hepatitis C virus genotypes in Manisa region, Turkey]. / Manisa bölgesinde hepatit C virus genotiplerinin dagilimi.

The duration of hepatitis C virus (HCV) infection and the response to the standard therapy is strongly related to the HCV genotypes. In addition, the geographical distribution of HCV genotypes is important for the epidemiological studies in terms of distribution and possible risk groups. The aim of this retrospective study was to investigate the distribution of HCV genotypes in Manisa region (located at the Aegean part of Turkey). A total of 100 anti-HCV (microparticle EIA; Abbott Laboratories, USA) and HCV-RNA (real time RT-PCR; Applied Biosystems, USA) positive patients (53 female, 47 male; mean age: 44.4 +/- 10.4 years), who were admitted to Celal Bayar University Medical School Hospital between 2002-2005, were included to the study. Quantitative HCV-RNA levels of the patients were between 10(4)-10(8) copies/ml. Complementary DNAs obtained from HCV-RNAs isolated by Invitek RTP DNA/RNA Virus Mini Kit were used for genotyping with selected primers [primer 11 (5'-AGG TCT CTG AGA CCG TGC ACC ATG AGC AC-3') and primer 13 (5'-CTG TGA GGA ACT ACT GTC TT-3') for the first PCR; primer 12 (5'-ACT GCC TGA TAG GGT GCT TGC GAG TG-3') and primer 14 (5'-CAC GCA GAA AGC GTC TAG-3') for the second PCR]. The RT-PCR products were purified with Invisorb Spin PCRapid Kit and sequenced by BigDye Terminator v3.1 Cycle Sequencing Kit in ABI Prism 310 Genetic Analyzer. Genotype 1 was found in 92% of the patients (92%) and genotypes 2 and 4 were found in 7% of the patients, while HCV genotype could not be identified in one patient (1%). When evaluating the subtypes, genotype 1b was determined in 90 patients (90%), genotype 4a in five patients (5%), genotype 1a in two patients (2%) and genotype 2a in two patients (2%). In conclusion, 1b was found to be the most common HCV genotype in Manisa region in concordance with the previous data obtained in Turkey, followed by genotype 4a, although a rare one. The data of this study is noteworthy especially for the arrangement of treatment and follow-up of HCV infected patients.

[Common viral etiologies of community acquired lower respiratory tract infections in young children and their relationship with long term complications]. / Küçük çocuklarda toplum kökenli viral alt solunum yolu enfeksiyonu etkenlerinin sikligi ve uzun dönem komplikasyonu ile iliskileri.

Viral lower respiratory tract infections (LRTIs) and their late complications are important causes of morbidity and mortality in childhood. The aims of this study were the detection of viral agents that cause community-acquired LRTIs in young children and investigation of the relationship between viral etiology and bronchiolitis obliterans (BO) which is one of the late complications of LRTIs. A total of 151 children (86 male, 65 female; mean age: 2.9 +/- 1.9 years) who were diagnosed to have LRTIs between the period of 2002-2004, at Pediatric Allergy and Pulmonology Department of a University Hospital in Manisa (located in the Aegean region of Turkey) were included to the study. The presence of respiratory viruses [respiratory syncytial virus (RSV), influenza virus type A and B, parainfluenza virus types 1, 2 and 3, adenovirus] in the nasopharyngeal aspirate specimens collected from children have been searched by direct fluorescence antibody test (Biotrin, Ireland). Respiratory viruses were detected in 25.2% (38/151) of the patients with LRTIs, while this rate was 46.8% (22/47) for 2002 period, 13.3% (8/60) for 2003 period and 18.2% (8/44) for 2004 period. RSV and adenoviruses both detected with a frequency of 31.5% (n= 12/38); were the most common agents encountered, and followed by parainfluenza (10/38, 26.3%) and influenza (9/38, 23.6%) viruses. Postinfectious BO have been diagnosed in 7.3% (11/151) of the patients; seven in 2002, one in 2003 and three in 2004 periods. Viral etiology were present in all of the patients who developed BO in 2002, while viral infection was detected in one of the patients who developed BO in 2003-2004 periods. Adenoviruses were the most frequently detected agents (n= 5) in BO cases with viral etology (n= 8). Viral agents were found positive in 72.7% (8/11) and 21.4% (30/140) of the patients with and without BO development, respectively, and this difference was found statistically significant (p= 0.02). Besides, BO development was detected in 21.1% (8/38) and 2.6% (3/113) of LRTI patients with and without viral etiology, respectively, and this difference was also significant (p< 0.05). In conclusion, the long term follow-up is important in young children with viral LRTIs for the early diagnosis of complications. Thus the identification of viruses might aid in estimation of prognosis.

[Comparison of interferon-gamma whole blood assay with tuberculin skin test for the diagnosis of tuberculosis infection in tuberculosis contacts]. / Temaslilarda tüberküloz enfeksiyonunun tanisi için interferon-gama tam kan testi ile tüberkülin deri testinin karsilastirilmasi.

Tuberculin skin test which is used for the detection of latent tuberculosis (TB), has many disadvantages such as false positivities due to cross reactions between environmental mycobacteria and BCG strain, false negativities due to immunosuppression and malpractice, and also difficulties in application and evaluation. Recently a new diagnostic test which measures the production of interferon (IFN)-gamma in whole blood upon stimulation with specific ESAT-6 and CFP-10 antigens of Mycobacterium tuberculosis has been introduced. Since most of the mycobacteria other than tuberculosis and BCG strain do not contain these antigens, the detection of IFN-gamma levels indicates the specific T-cell response against M. tuberculosis. The aim of the study was to compare the tuberculin skin test and whole blood IFN-gamma assay (QuantiFERON-TB Gold, Cellestis Ltd, Carnegie, Victoria, Australia) for the identification of latent TB infection in the contacts with active TB patients. The tests results were evaluated by using Kappa (K) analysis, and K coefficients of < 0.4, 0.4-0.75 and > 0.75 were accepted as poor, moderate and excellent agreements, respectively. A total of 233 subjects from three risk groups were included to the study. Group 1 included the household members (n = 133) who had contact with smear positive index cases, Group 2 included the subjects from community (n = 46) who had contact with smear positive index cases, and Group 3 included health care workers (n = 74) who had contact with TB patients or their specimens. The positivity rates of tuberculin skin test and IFN-gamma assay in the cases were found as 37% and 42%, respectively. There were no significant differences among the three patient groups with regard to the results of the tuberculin skin test (p > 0.05). However, the positive result of the IFN-gamma assay in Group 1 was found statistically higher than the other groups (51.3%, p = 0.013). A poor agreement between the two tests was detected in the results taken from 233 subjects (65.7%, K = 0.28), while agreement was moderate in unvaccinated group (72.7%, K = 0.44). Evaluation of agreement rates of the tests according to the risk groups yielded 64.6% (K = 0.3) for Group 1, 71.7% (K = 0.32) for Group 2, and 63.5% (K = 0.21) for Group 3, which all coefficients showed poor agreement. Although IFN-gamma blood assay has many advantages such as objective and quantitative results, no interference with vaccination due to the use of specific antigens and being practical, the high cost and the need for well-equipped laboratory are its disadvantages. As a result it was concluded that, IFN-gamma blood assay has limited value for the detection of latent TB infection in our country, since the prevalence of TB infection and BCG vaccination rates are high in Turkey.