Publications (14)89.82 Total impact
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Article: Genotyping of mumps virus circulating in Turkey in the 2006-2007 winter season.
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ABSTRACT: In the winter of 2006-2007, several parotitis cases were reported in different provinces of Turkey. Serological and virological studies were undertaken to investigate these cases with the aim of determining the genotype of the mumps virus (MuV) circulating in Turkey. Samples from 23 cases-Ankara (n:5), Kirklareli (n:4), Mugla (n:10), Isparta (n:3), Trabzon (n:1)-with a diagnosis of clinical parotitis were investigated. Serum samples were tested against mumps IgM and IgG, nested PCR amplification of a 639-bp fragment encompassing the entire SH gene was performed using buccal swabs, and PCR products were sequenced. Of 18 serum samples, 16 (88.9%) were positive for mumps IgM. Seven (30.4%) of 23 buccal swab samples were positive by PCR. In five PCR-positive cases, the sample was also positive for mumps IgM, and serum samples were not available from two of the PCR-positive cases. There was 98% identity between the different sequences, and all were identified as genotype H. The sequences were most similar to sequences identified in Spain, Japan, Switzerland and the UK, and less closely related to the H strains identified in Belarus, Korea and Russia. This is the first report of the mumps virus genotypes circulating in Turkey. Turkey is, geographically, a bridge between Europe and Asia, and therefore, a better understanding of the molecular epidemiology of MuV in Turkey may led to improved tracking of the circulation of strains between the two continents. Moreover, there is a need to further investigate the existence of other genotypes in Turkey.Archives of Virology 10/2009; 154(11):1807-12. · 2.11 Impact Factor -
Article: Efficacy of oral ribavirin treatment in Crimean-Congo haemorrhagic fever: a quasi-experimental study from Turkey.
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ABSTRACT: The aim of this study was to evaluate the efficacy of oral ribavirin treatment in patients with Crimean-Congo haemorrhagic fever (CCHF). In 2004, all patients diagnosed with CCHF were treated with oral ribavirin, however in 2003 none of the CCHF patients had been given treatment due to lack of confirmatory diagnostic information at that time in Turkey. In this study, patients treated with ribavirin in 2004 (n=126) were compared with ribavirin-untreated CCHF patients (n=92) in 2003. Patients only with a definitive diagnosis of CCHF (clinical symptoms plus the presence of specific IgM antibodies against CCHF virus and presence of viral antigen) were included in this study. There was no difference in the case-fatality rate between treated and untreated patients (7.1% vs. 11.9%; P>0.05). A Cox Proportional Hazards regression analysis revealed that altered sensorium and prolonged international normalized ratio were independent predictors of mortality. Our results showed that oral ribavirin treatment did not improve the survival rate in CCHF patients. Ribavirin and supportive care are the only available choices for treatment of CCHF patients, but to ascertain the efficacy of ribavirin, more laboratory and observational studies are necessary and ultimately, to elucidate these conflicting results and evaluate the efficacy undoubtedly, a multicenter randomised controlled trial will be needed.The Journal of infection 02/2009; 58(3):238-44. · 4.13 Impact Factor -
Article: Genotyping of mumps virus circulating in Turkey in the 2006–2007 winter season
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ABSTRACT: In the winter of 2006–2007, several parotitis cases were reported in different provinces of Turkey. Serological and virological studies were undertaken to investigate these cases with the aim of determining the genotype of the mumps virus (MuV) circulating in Turkey. Samples from 23 cases—Ankara (n:5), Kırklareli (n:4), Mugla (n:10), Isparta (n:3), Trabzon (n:1)—with a diagnosis of clinical parotitis were investigated. Serum samples were tested against mumps IgM and IgG, nested PCR amplification of a 639-bp fragment encompassing the entire SH gene was performed using buccal swabs, and PCR products were sequenced. Of 18 serum samples, 16 (88.9%) were positive for mumps IgM. Seven (30.4%) of 23 buccal swab samples were positive by PCR. In five PCR-positive cases, the sample was also positive for mumps IgM, and serum samples were not available from two of the PCR-positive cases. There was 98% identity between the different sequences, and all were identified as genotype H. The sequences were most similar to sequences identified in Spain, Japan, Switzerland and the UK, and less closely related to the H strains identified in Belarus, Korea and Russia. This is the first report of the mumps virus genotypes circulating in Turkey. Turkey is, geographically, a bridge between Europe and Asia, and therefore, a better understanding of the molecular epidemiology of MuV in Turkey may led to improved tracking of the circulation of strains between the two continents. Moreover, there is a need to further investigate the existence of other genotypes in Turkey.Archives of Virology - ARCH VIROL. 01/2009; 154(11):1807-1812. -
Article: Oseltamivir-ribavirin combination therapy for highly pathogenic H5N1 influenza virus infection in mice.
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ABSTRACT: We studied the effects of a neuraminidase inhibitor (oseltamivir) and an inhibitor of influenza virus polymerases (ribavirin) against two highly pathogenic H5N1 influenza viruses. In vitro, A/Vietnam/1203/04 virus (clade 1) was highly susceptible to oseltamivir carboxylate (50% inhibitory concentration [IC(50)] = 0.3 nM), whereas A/Turkey/15/06 virus (clade 2.2) had reduced susceptibility (IC(50) = 5.5 nM). In vivo, BALB/c mice were treated with oseltamivir (1, 10, 50, or 100 mg/kg of body weight/day), ribavirin (37.5, 55, or 75 mg/kg/day), or the combination of both drugs for 8 days, starting 4 h before virus inoculation. Monotherapy produced a dose-dependent antiviral effect against the two H5N1 viruses in vivo. Three-dimensional analysis of the drug-drug interactions revealed that oseltamivir and ribavirin interacted principally in an additive manner, with several exceptions of marginal synergy or marginal antagonism at some concentrations. The combination of ribavirin at 37.5 mg/kg/day and oseltamivir at 1 mg/kg/day and the combination of ribavirin at 37.5 mg/kg/day and oseltamivir at 10 mg/kg/day were synergistic against A/Vietnam/1203/04 and A/Turkey/15/06 viruses, respectively. These optimal oseltamivir-ribavirin combinations significantly inhibited virus replication in mouse organs, prevented the spread of H5N1 viruses beyond the respiratory tract, and abrogated the cytokine response (P < 0.01). Importantly, we observed clear differences between the efficacies of the drug combinations against two H5N1 viruses: higher doses were required for the protection of mice against A/Turkey/15/06 virus than for the protection of mice against A/Vietnam/1203/04 virus. Our preliminary results suggest that oseltamivir-ribavirin combinations can have a greater or lesser antiviral effect than monotherapy, depending on the H5N1 virus and the concentrations used.Antimicrobial Agents and Chemotherapy 09/2008; 52(11):3889-97. · 4.84 Impact Factor -
Chapter: Transmission and Pathogenicity of H5N1 Influenza Viruses
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ABSTRACT: The interaction between multiple viral and host factors determine the pathogenicity and transmissibility of H5N1 influenza viruses. The viral surface glycoprotein haemagglutinin (HA) plays a crucial role in attachment to the host-cell sialic acid (SA) receptor and in viral growth and tissue tropism. Other viral factors known as host range or virulence determinants include viral polymerase, particularly residue 627 in the PB2 protein, and the ability to evade the host immune response through the viral NS1 protein. Applying plasmid-based reverse genetics, we have provided a good model system to study the molecular basis for pathogenicity. Differences in the pathogenicity in mammalian species were previously observed between human (A/Vietnam/1203/04) and chicken (A/Chicken/Vietnam/C58/04) H5N1 isolates. Detailed molecular characterization by plasmid-based reverse genetics showed that the polymerase subunits PB1 and PB2 contribute to the lethality of A/Vietnam/1203/04. The polymerase complex possessed significantly higher transcription/ replication activity than the A/Chicken/Vietnam/C58/04 polymerase complex. Our results suggest that high polymerase activity acts as a molecular determinant for virulence in mammalian species. We also evaluated the transmissibility and pathogenicity of H5N1 viruses isolated from humans during the years 2003- 2006 using a ferret contact model comprising one inoculated and two contact ferrets. This animal model has been shown to support efficient transmission of seasonal human influenza viruses. At 103 TCID50, A/Vietnam/1203/04 and A/ Vietnam/JP36-2/05 viruses, which have ‘avian-like’ α2,3-linked SA receptor affinity, caused neurological symptoms and death in ferrets. A/HongKong/213/03 and A/Turkey/65-596/06 viruses, which have affinity for both ‘human-like’ (α2,6- linked) and ‘avian-like’ SA receptors, caused mild clinical symptoms and were not lethal to ferrets. No transmission of A/Vietnam/1203/04 and A/Turkey/65-596/06 viruses was detected, and transmission of A/HongKong/213/03 and A/Vietnam/ JP36-2/05 viruses was inefficient. These results demonstrate that despite their receptor binding affinity, circulating H5N1 viruses retain molecular determinants that restrict their spread among mammals.05/2008: pages 128 - 140; , ISBN: 9780470770672 -
Article: [Short communication: The sensitivity of measles diagnosis by physicians and families during an intraepidemic period in Edirne: implications for measles surveillance].
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ABSTRACT: Measles is still a leading cause of death among young children, despite the availability of a safe and effective vaccine for the past 40 years. EURO Region of World Health Organisation including Turkey has targeted elimination of measles by the year 2010. It is concluded that there must be a sensitive surveillance system to investigate all suspicious measles cases, and diagnosis should be based on both standardized case definition and laboratory confirmation. Standardized case definition based notification has started in 2005 in Turkey. This study was carried out to determine the sensitivity and specificity of clinical measles diagnosis by physicians and families during a measles epidemic affecting 597 cases in Edirne province in 1997. Blood samples and data were collected by trained teams consisting of one physician and one nurse. Thirty clusters sampling method was used for sampling and 210 blood samples were taken from the children. The sera were then sent to Refik Saydam Hygiene Institute, Ankara, for the detection of measles specific IgG and IgM antibodies. Positive results for IgM were considered as acute measles during epidemics, and positive results for IgG were considered as acquired immunity due to vaccination or passed infection. Of 210 children, 19 were found to have recent infection (IgM+, IgG-), 101 were found immune (IgM-, IgG+), 67 were found in convalescence phase after infection (IgM+, IgG+), and 23 were found susceptible (IgM-, IgG-) to measles. The overall IgM seropositivity was detected as 40.9% in the study group. Only half of confirmed cases (43/86) were diagnosed as measles clinically by the physicians. The sensitivity, specificity, positive and negative predictive values (PPV and NPV, respectively) of clinical diagnosis by physicians were estimated as 33%, 89%, 67% and 86%, respectively. Validity measures for measles diagnosis by the families were as follows; 8% sensitivity, 96% specificity, 6% PPV and 60% NPV. It is concluded that, all required measures should be taken for the availability of laboratory confirmation of all suspicious measles cases and field investigation via structured case investigation forms, is necessary for the success of measles surveillance system in our country.Mikrobiyoloji bülteni 02/2008; 42(1):143-8. · 0.40 Impact Factor -
Article: Assessment of the immune response to trivalent split influenza vaccine in children with solid tumors.
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ABSTRACT: To assess the immune response to influenza vaccine in children with solid tumors receiving chemotherapy or under the influence of chemotherapy. Forty-five children (aged 1-18) with solid tumors on chemotherapy or within 6 months of completion of chemotherapy were included in the study. The children received two doses of intramuscular trivalent split influenza vaccine with 1 month apart in November-December 2003 (children <4 age 0.25 ml; >4 age 0.5 ml). Antibody titer was detected in the pre-vaccination and 4-week post-vaccination sera by hemagglutination inhibition (HI) method. Immune responses were measured as protective, geometric mean titers (GMT), and fourfold rises in HI titers. We revealed that the post-vaccination GMT for each of the three antigens in patients with solid tumors has increased significantly (P < 0.05). A fourfold rise in the percentage of post-vaccination antibody titers has been detected as 84.4% for H(1)N(1), 77.8% for H(3)N(2), 60% for B. Stratification of patients as on active chemotherapy or being within 6 months of completion of chemotherapy in terms of fourfold rise in antibody titers exposed a statistically significant difference for only B (P = 0.34). Post-vaccination protective rates were between 86 and 97%. Due to the interruptions in treatment caused by influenza infections, and economic benefits of the vaccine, we suggest that inactivated influenza vaccine should be applied as two doses annually in patients with solid tumor.Pediatric Blood & Cancer 12/2007; 49(7):914-7. · 1.89 Impact Factor -
Article: Inefficient transmission of H5N1 influenza viruses in a ferret contact model.
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ABSTRACT: The abilities to infect and transmit efficiently among humans are essential for a novel influenza A virus to cause a pandemic. To evaluate the pandemic potential of widely disseminated H5N1 influenza viruses, a ferret contact model using experimental groups comprised of one inoculated ferret and two contact ferrets was used to study the transmissibility of four human H5N1 viruses isolated from 2003 to 2006. The effects of viral pathogenicity and receptor binding specificity (affinity to synthetic sialosaccharides with alpha2,3 or alpha2,6 linkages) on transmissibility were assessed. A/Vietnam/1203/04 and A/Vietnam/JP36-2/05 viruses, which possess "avian-like" alpha2,3-linked sialic acid (SA) receptor specificity, caused neurological symptoms and death in ferrets inoculated with 10(3) 50% tissue culture infectious doses. A/Hong Kong/213/03 and A/Turkey/65-596/06 viruses, which show binding affinity for "human-like" alpha2,6-linked SA receptors in addition to their affinity for alpha2,3-linked SA receptors, caused mild clinical symptoms and were not lethal to the ferrets. No transmission of A/Vietnam/1203/04 or A/Turkey/65-596/06 virus was detected. One contact ferret developed neutralizing antibodies to A/Hong Kong/213/03 but did not exhibit any clinical signs or detectable virus shedding. In two groups, one of two naïve contact ferrets had detectable virus after 6 to 8 days when housed together with the A/Vietnam/JP36-2/05 virus-inoculated ferrets. Infected contact ferrets showed severe clinical signs, although little or no virus was detected in nasal washes. This limited virus shedding explained the absence of secondary transmission from the infected contact ferret to the other naïve ferret that were housed together. Our results suggest that despite their receptor binding affinity, circulating H5N1 viruses retain molecular determinants that restrict their spread among mammalian species.Journal of Virology 08/2007; 81(13):6890-8. · 5.40 Impact Factor -
Article: Efficacy of oseltamivir therapy in ferrets inoculated with different clades of H5N1 influenza virus.
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ABSTRACT: Highly pathogenic H5N1 influenza viruses have infected an increasing number of humans in Asia, with high mortality rates and the emergence of multiple distinguishable clades. It is not known whether antiviral drugs that are effective against contemporary human influenza viruses will be effective against systemically replicating viruses, such as these pathogens. Therefore, we evaluated the use of the neuraminidase (NA) inhibitor oseltamivir for early postexposure prophylaxis and for treatment in ferrets exposed to representatives of two clades of H5N1 virus with markedly different pathogenicities in ferrets. Ferrets were protected from lethal infection with the A/Vietnam/1203/04 (H5N1) virus by oseltamivir (5 mg/kg of body weight/day) given 4 h after virus inoculation, but higher daily doses (25 mg/kg) were required for treatment when it was initiated 24 h after virus inoculation. For the treatment of ferrets inoculated with the less pathogenic A/Turkey/15/06 (H5N1) virus, 10 mg/kg/day of oseltamivir was sufficient to reduce the lethargy of the animals, significantly inhibit inflammation in the upper respiratory tract, and block virus spread to the internal organs. Importantly, all ferrets that survived the initial infection were rechallenged with homologous virus after 21 days and were completely protected from infection. Direct sequencing of the NA or HA1 gene segments in viruses isolated from ferret after treatment showed no amino acid substitutions known to cause drug resistance in conserved residues. Thus, early oseltamivir treatment is crucial for protection against highly pathogenic H5N1 viruses and the higher dose may be needed for the treatment of more virulent viruses.Antimicrobial Agents and Chemotherapy 05/2007; 51(4):1414-24. · 4.84 Impact Factor -
Article: Avian influenza A (H5N1) infection in eastern Turkey in 2006.
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ABSTRACT: An outbreak of highly pathogenic avian influenza A (H5N1) that had previously been detected throughout Asia, with major economic and health repercussions, extended to eastern Turkey in late December 2005 and early January 2006. We documented the epidemiologic, clinical, and radiologic features of all cases of confirmed H5N1 virus infection in patients who were admitted to Yuzuncu Yil University Hospital in Van, Turkey, between December 31, 2005, and January 10, 2006. H5N1 virus infection was diagnosed in eight patients. The patients were 5 to 15 years of age, and all eight had a history of close contact with diseased or dead chickens. The mean (+/-SD) time between exposure and the onset of illness was 5.0+/-1.3 days. All the patients had fever, and seven had clinical and radiologic evidence of pneumonia at presentation; four patients died. Results of enzyme-linked immunosorbent assay and rapid influenza tests were negative in all patients, and the diagnosis was made by means of a polymerase-chain-reaction assay. H5N1, which causes a spectrum of illnesses in humans, including severe and fatal respiratory disease, can be difficult to diagnose.New England Journal of Medicine 12/2006; 355(21):2179-85. · 53.30 Impact Factor -
Article: Serum adenosine deaminase enzyme and plasma platelet factor 4 activities in active pulmonary tuberculosis, HIV-seropositive subjects and cancer patients.
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ABSTRACT: The aim of this study was to determine the serum adenosine deaminase (ADA) and plasma platelet factor (PF-4) activities in patients with active pulmonary tuberculosis, HIV seropositive subjects, cancer patients (acute and chronic type lymphoblastic leukaemia) and to compare them with the results of healthy individuals. Eighty-eight subjects were enrolled in this study, 24 patients with active pulmonary tuberculosis, 20 patients with HIV seropositive subjects, 24 patients with cancer, 12 patients with acute type lymphoblastic leukaemia, 12 patients with chronic type lymphoblastic leukaemia) patients and 20 healthy individuals. ADA activity was determined in serum samples using colorimetric method and plasma PF4 activity was measured by using a sandwich-type enzyme immunoassay. When all study groups were compared with the control group, mean serum ADA activities were found to be significantly (p<0.01) higher in the sera of patients with active pulmonary tuberculosis (median, range: 39 IU/l), HIV seropositive subjects (median, range: 31 IU/l) than in the sera of cancer patients (median, range: 15) and healthy controls (median, range: 32 IU/l). Plasma PF-4 activities in active pulmonary tuberculosis patients (median, range: 84 IU/ml) were found to be significantly elevated when compared to HIV seropositive subjects (median, range: 59 IU/ml), cancer patients (median, range 55 IU/ml) and healthy individuals (median, range: 56 IU/ml) (p<0.01). Serum ADA and plasma PF-4 activities showed significant alteration in patients with active pulmonary tuberculosis compared to patients with HIV seropositive subjects, cancer patients and healthy individuals. In conclusion, we suggest that serum ADA and PF-4 activities can be used in the diagnosis of tuberculosis as an supplementary laboratory test in combination with clinical and laboratory findings. Further controlled studies are necessary to determine the importance of the PF-4 and ADA activities in patients with active pulmonary tuberculosis, HIV seropositive subjects and cancer patients.The Journal of infection 04/2006; 52(4):264-8. · 4.13 Impact Factor -
Article: Crimean-Congo hemorrhagic fever in Eastern Turkey: clinical features, risk factors and efficacy of ribavirin therapy.
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ABSTRACT: This study described the clinical features, factors affecting the outcome of this disease, risk factors, and efficacy of ribavirin therapy for CCHF patients in Eastern Turkey. Between 2002 and 2004, 60 cases admitted to our hospital were included in this study. The diagnosis was confirmed through detection of IgM by ELISA and/or genomic segment of virus by RT-PCR. In multivariate analysis, farming (OR, 11.4), living in a rural area (OR, 10.05) and being bitten by tick (OR, 6.75) were determined as risk factors for CCHF. The rates of fever during hospitalization, confusion, neck stiffness, bleeding from multiple sites, and presence of petechia/ecchymosis were higher in the patients who died than in surviving ones. Additionally, the mean values of ALT, AST, LHD, CK, PTT, INR and urea were also higher, and the mean PLT count was lower in the patients who died. Mean recovery time was shorter in the cases treated with ribavirin than those of control. But, the need for blood and blood product, mean hospitalization duration, fatality rates, and hospital expenditure values were not significantly different between the group of patients treated with ribavirin and control groups. In Eastern Turkey, clinical features, factors influencing outcome of the disease, and risk factors were similar to other outbreaks of CCHF. Further studies are needed for the evaluation of ribavirin therapy in CCHF.The Journal of infection 04/2006; 52(3):207-15. · 4.13 Impact Factor -
Article: Measles seroepidemiology in 3 cities in Turkey.
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ABSTRACT: To evaluate immunity against measles and its relation with some variables among healthy subjects in 3 cities in Turkey. We carried out a cross-sectional study on measles antibody titers in the serum samples of 712 people from Antalya, 696 from Diyarbakir and 667 from Samsun, Turkey using particle agglutination test between February 2000 and October 2001. The study groups, informed and asked for their consent by midwives, consisted of randomly selected subjects of all ages older than 6 months. We implemented the study in 3 steps: physical examination, interview and blood collection. We considered titers of > or = 1:16 as positive and we observed lower seropositivity in Diyarbakir (90.8%) than Antalya (95.9%), and Samsun (94.9%) (p=0.040). We also observed that seropositivity was lower among preschool group than older groups (p=0.006). The number of doses of measles vaccine (p=0.001) and measles infection history (p=0.003) were found as a factor increasing the seropositivity ratio. There was no statistically significant between age groups (p=0.219), gender (p=0.148), residence (p=0.537), and number per household (p=0.983) among the provinces. Based on the findings, measles infection still has a high incidence in Turkey and the second dose of measles vaccine is extremely important in the prevention of measles transmission among school children and the community. Furthermore, we must improve our regional differences in routine vaccination services.Saudi medical journal 12/2005; 26(12):1971-7. · 0.52 Impact Factor -
Article: Serum copper and zinc concentrations in patients with chronic hepatitis C.
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ABSTRACT: The aim of this study was to measure the alterations in serum trace elements, including zinc and copper in patients with chronic hepatitis C and to compare them with the results of healthy individuals. Seventeen patients with chronic hepatitis C and 17 healthy individuals were included in this study. Serum zinc and cooper concentrations were measured by using atomic absorption spectrophotometer of patients with chronic hepatitis C and the results were statistically compared with those of healthy individuals. Serum zinc concentrations were 105.6+/-22.8 microg/dl in patients with chronic hepatitis C and 94.41+/-19 microg/dl in healthy controls, respectively. Serum copper concentrations were 103.17+/-20.8 microg/dl in patients with chronic hepatitis C and 90.8+/-14.3 microg/dl in healthy subjects, respectively. Serum zinc and copper concentrations were not found statistically different in patients with chronic hepatitis C compared with those of healthy individuals (p>0.05). In conclusion, serum trace element concentrations did not show statistical alterations in patients with chronic hepatitis C compared to healthy subjects.Journal of Infection 07/2005; 51(1):35-7. · 4.13 Impact Factor
