Brucellosis in pregnancy and its response to the changing immunoglobulin A: A prospective controlled study.

Objective: This study aimed to define the rare Brucella infection in pregnancy and its effects on immunoglobulins (Ig). Materials and Methods: This prospective study has conducted Brucella screening using the Rose Bengal test on pregnant and non-pregnant outpatients who did not show any specific Brucella symptoms. The immunoglobulin levels were measured using the enzyme-linked immunosorbent assay. The study group consisted of pregnant women who were at 20 weeks or below gestation and applied to our hospital outpatient clinic for routine check-ups. The control group consisted of healthy patients who applied for routine controls. Results: This study included a total of 584 participants, 293 of whom were controls and 291 were the study (pregnant) participants. The study revealed a 1.5% incidence of Brucella during pregnancy. In acute and chronic Brucella infection, lower levels of IgA response were observed in pregnant cases compared to the control group. Conclusion: Brucella infection is a disease that can cause fetal problems, especially in endemic areas. The role of the altered IgA response in pathologies that are associated with Brucella infection stands out as a new target for disease pathophysiology.

Consensus Report on Diagnosis, Treatment and Prevention of Infective Endocarditis by Turkish Society of Cardiovascular Surgery (TSCVS), Turkish Society of Clinical Microbiology and Infectious Diseases (KLIMIK), Turkish Society of Cardiology (TSC), Turkish Society of Nuclear Medicine (TSNM), Turkish Society of Radiology (TSR), Turkish Dental Association (TDA) and Federation of Turkish Pathology Societies (TURKPATH) Cardiovascular System Study Group.

Infective endocarditis (IE) is rare, but associated with significant morbidity and mortality rates. Estimates of the incidence of IE in Turkey are compromised by the absence of population-based prospective studies. Due to the frequent presence of predisposing cardiac conditions and higher rates of nosocomial bacteremia in highrisk groups, the incidence of IE is expected to be higher in Turkey. Additionally, while IE generally affects older people in developed countries, it still affects young people in Turkey. In order to reduce the mortality and morbidity, it is critical to diagnose the IE to determine the causative agent and to start treatment rapidly. However, most of the patients cannot be diagnosed in their first visits, about half of them can be diagnosed after three months, and the disease often goes unnoticed. In patients diagnosed with IE, the rate of identification of causative organisms is significantly lower in Turkey than in developed countries. Furthermore, most of the centers do not perform some essential microbiological diagnostic tests as a routine practice. Some antimicrobials that are recommended as the first-line of treatment for IE, particularly antistaphylococcal penicillins, are not available in Turkey. These problems necessitate reviewing the epidemiological, laboratory, and clinical characteristics of IE in our country, as well as the current information about its diagnosis, treatment, and prevention together with local data. Physicians can follow patients with IE in many specialties. Diagnosis and treatment processes of IE should be standardized at every stage so that management of IE, a setting in which many physicians are involved, can always be in line with current recommendations. Study Group for Infective Endocarditis and Other Cardiovascular Infections of the Turkish Society of Clinical Microbiology and Infectious Diseases has called for collaboration of the relevant specialist organizations to establish a consensus report on the diagnosis, treatment, and prevention of IE in the light of current information and local data in Turkey.

Evaluation of Endometrial Receptivity by Measuring HOXA-10, HOXA-11, and Leukemia Inhibitory Factor Expression in Patients with Polycystic Ovary Syndrome.

CONTEXT: Polycystic ovary syndrome (PCOS) is an important cause of infertility. In women with PCOS have increased rate of spontaneous abortion and reduced rate of conception. HOXA-10 and HOXA-11 are proteinous products of homeobox gene group and play an important role during implantation. AIMS: The aim of this study was to evaluate endometrial receptivity by measuring HOXA-10, HOXA-11, and leukemia inhibitory factor (LIF) gene expressions in women with PCOS. SETTINGS AND DESIGN: A tertiary referral center. MATERIALS AND METHODS: This study was conducted on reproductive age women with abnormal uterine bleeding without sonographically proven anatomical reason. Endometrial sampling procedures were done in proliferative phase using low-pressure endometrial suction device to exclude endometrial pathology. HOXA-10, HOXA-11, and LIF gene expressions were measured from endometrial sampling material. Blood sample was taken to measure serum estradiol level on the day of endometrial sampling. STATISTICAL ANALYSIS USED: Statistical analysis was performed using SPSS software version 17 (SPSS Inc., Chicago, IL, USA). Mann-Whitney U-test was used to compare the variables. RESULTS: A total of 53 patients were included in this study. Study group consisted of 33 patients with PCOS. Gene expressions of HOXA-10, HOXA-11, and LIF were significantly lower in patients with PCOS (P < 0.05). CONCLUSIONS: This study results showed that in patients with PCOS have decreased gene expression of HOXA-10, HOXA-11, and LIF which might contribute PCOS-related infertility.

Decreased expression of LIF mRNA in patients withmyoma uteri.

OBJECTIVE: The aim of this study was to evaluate endometrial receptivity by measuring HOXA-10, HOXA-11, and LIF gene expressions in women with polycystic ovary syndrome. METHODS: A total of 48 women were included in this clinical study. Thepatients were allocated to two groups: study group consisted of 28 patients with myoma uteri and control group consisted of 20 patients without myoma uteri. Endometrial sampling was performed during the proliferative phase. The biopsies obtained from the patients with myoma uteri were taken from the place where the fibroids were localized. HOXA-10, HOXA-11, and LIF expressions were measured in the endometrial sampling material. Demographic data of the patients such as age, obstetric and gynecologic history, medical conditions, medications, surgical history, last menstrual period were recorded. Also, the number, size, localization, and type of the myoma were registered. RESULTS: The mean age of the patients was 42.07 and 38.17, respectively. HOXA-11 levels in the study and control groups were 0.004 ± 0.001 and 0.010 ± 0.001, respectively ( P < 0.90). Paradoxically, HOXA-10 levels were found to be higher in the study group than the control group, but the difference was not statistically significant ( P < 0.25). LIF levels were significantly lower in the study group ( P < 0.05). CONCLUSION: Our results showed that myoma uteri might lead to a decrease in implantation rate by diminishing LIF gene expressions. However, there were no differences between the two groups in terms of HOXA-10 and HOXA-11 levels.

Polymorphisms in the Growth Differentiation Factor 5 (GDF 5) Gene in Knee Osteoarthritis.

OBJECTIVE: To identify the frequency of the rs143383 SNPin the GDF5 gene, which is located in the 5'-untranslated region of Turkish population with knee osteoarthritis (OA). STUDY DESIGN: Acase-control study. PLACE AND DURATION OF STUDY: Orthopedics and Traumatology Department, Bozok University Medical Faculty, Yozgat, Turkey, from 2012 to 2014. METHODOLOGY: Patients diagnosed with OA(n=94) and patients who did not have joint complaints (n=279) were enrolled in this study. Patients diagnosed with osteoarthritis according to the 1986 American College of Rheumatology osteoarthritis criteria and Kellgren and Lawrence scores were investigated, based on age, gender, and X-ray findings. Blood samples were taken for the identification of GDF5 (rs143383) SNPs by PCR/RFLP, according to a standard protocol. RESULTS: This study included 373 patients. The OAgroup (25.2%; n=94) was characterized by specific genotypes: TT (39.4%; n=37); heterozygotes (TC; 45.7%; n=43); and homozygotes (CC; 14.9%; n=14). The control group (74.8%; n=279) was comprised of TT(26.5%; n=74), TC (54.8%; n=153), and CC (18.6%; n=52) genotypes. An analysis of rs143383 SNP of the GDF5 gene polymorphism revealed that the rs143383 TTgenotype had a higher risk for OA(crude OR=1.798, 95% CI=1.010-2.941, p=0.021). CONCLUSION: This study demonstrated that there is a correlation of +104T/C polymorphism in the 5'-UTR of GDF5 with knee OAin a Turkish population.

Promoter polymorphism (T-1486C) of TLR-9 gene is associated with knee osteoarthritis in a Turkish population.

In this study, we aimed to determine whether TLR-9 T-1486C SNP was associated with susceptibility to OA in the Turkish population. The study group comprised 272 patients with Grade 2-3-4 knee OA according to the Kellgren-Lawrence scoring system and the control group was formed of 296 individuals with Grade 0-1. The TLR-9 genotype were assessed by real-time polymerase chain reaction. An analysis of TLR-9 promoter -1486T/C polymorphism revealed that the -1486CC genotype appeared to have a higher risk for OA and -1486TT and -1486CT genotypes have a protective effect against the development of OA (crude OR = 0.473, 95% CI = 0.297-0.754, p = 0.002, adjusted OR = 0.531, 95% CI = 0.326-0.864, p = 0.011). This study indicate that there is a correlation of TLR-9 T-1486C gene polymorphism with advanced knee OA in a Turkish population. Changed in TLR expression due to different allelles may cause osteoarthrith development outcome cartilage degeneration. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2484-2489, 2017.

In Vitro Efficacy of the Ankaferd Galenic Hemostatic Extract as a Germicidal Agent.

BACKGROUND: Hydatid cysts are encountered frequently in regions endemic with livestock. The basic treatment for a hydatid cyst is total surgical removal of the cyst and its inner contents. Hypertonic NaCl or diluted betadine solution are used as germicidal agents for most hydatid surgeries. However, the germicidal efficacy of the Ankaferd Blood Stopper® (ABS) has not been investigated. Thus, we compared the efficacy of ABS for hydatid cysts with that of other germicidal agents. METHODS: Lung and liver tissues containing hydatid cyst liquid were collected from slaughterhouses. Six samples of each cyst were randomly allocated into different groups as follows: 20% hypertonic NaCl, betadine solution, ABS, 20% liquefied Andazole solution, 0.1% eosin, and distilled water. All groups were examined microscopically at 5, 10, and 15 min after treatment began to determine protoscolece viability rates. RESULTS: The most efficacious germicidal agent at 5 min was ABS, and betadine and hypertonic NaCl had similar efficacies. Betadine, ABS, and hypertonic NaCl showed similar efficacies at 15 min. CONCLUSION: ABS was an effective germicidal agent to treat hydatid cysts.

Sequential determination of serum viral titers, virus-specific IgG antibodies, and TNF-α, IL-6, IL-10, and IFN-γ levels in patients with Crimean-Congo hemorrhagic fever.

BACKGROUND: Although there have been a number of studies on the pathogenesis of Crimean-Congo hemorrhagic fever (CCHF) recently, knowledge on this topic is still insufficient. This study aims to reveal the kinetics of serum CCHF virus (CCHFV) titers, serum levels of anti-CCHFV immunoglobulin (Ig)G, tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10, and interferon (IFN)-γ in CCHF patients. METHODS: In total, 31 CCHF cases (11 fatal) were studied. Serum samples were obtained daily from all patients from the time of admission and continued for a 7-day hospitalization period for serologic (ELISA), virologic (real-time PCR), and cytokine (ELISA) analysis. RESULTS: The mean serum CCHFV titer at admission was 5.5E + 09 copies/mL in fatal cases and 5.7E + 08 copies/mL in survivors (p < 0.001). Compared to survivors, both the mean serum levels of IL-6 and TNF-α at admission were found to be significantly increased in fatal cases. The serum levels of IL-6, TNF-α and serum CCHFV titer at admission were significantly and positively correlated with disseminated intravascular coagulation (DIC) scores (r = 0.626, p = 0.0002; r = 0.461, p = 0.009; and r = 0.625, p = 0.003, respectively). When the data obtained from the sequential determination of CCHFV titer and levels of anti-CCHFV IgG, IL-6, TNF-α, IL-10 and IFN-γ were grouped according to the days of illness, the initial serum CCHFV titer of a fatal patient was 5.5E + 09 (copies/mL) and it was 6.1E + 09 (copies/mL) in a survivor on the 2 day of illness. While significant alterations were observed in all cytokines during the monitoring period, IL-6 levels remained consistently higher in fatal cases and TNF-α levels increased in both in fatal and non-fatal CCHF cases. CONCLUSIONS: The increased CCHFV load and higher concentrations of IL-6 and TNF-α, the presence of DIC, and the absence of CCHFV specific immunity are strongly associated with death in CCHF.

The Serum S100B Level as a Biomarker of Enteroglial Activation in Patients with Ulcerative Colitis.

Objective. Recent studies have demonstrated that enteric glial cells (EGC) participate in the homeostasis of the gastrointestinal tract. This study investigated whether enteroglial markers, including S100B protein and glial fibrillary acidic protein (GFAP), can serve as noninvasive indicators of EGC activation and disease activity in UC patients. Methods. This clinical prospective study included 35 patients with UC and 40 age- and sex-matched controls. The diagnosis of UC was based on standard clinical, radiological, endoscopic, and histological criteria. Clinical disease activity was evaluated using the Modified Truelove-Witts Severity Index. Serum samples were analyzed for human GFAP and S100B using commercial enzyme-linked immunosorbent assay kits. Results. GFAP was not detected in the serum of either UC patients or controls (P > 0.05). However, we found a significant (P < 0.001) decrease in the serum S100B levels in the UC patients. No correlation between the serum S100B level and the disease activity or duration was observed (P > 0.05). The serum S100B levels did not differ between UC patients with active disease (24 patients, 68.6%) or in remission (11 patients, 31.4%) (P > 0.05). Conclusions. Ulcerative colitis patients had significantly lower serum S100B levels, while GFAP was of no diagnostic value in UC patients.

Elevated neurofilament light chain (NFL) mRNA levels in prediabetic peripheral neuropathy.

Evidence suggests that peripheral nerve injury occurs during the early stages of disease with mild glycemic dysregulation. Two proteins, neuron-specific enolase (NSE) and neurofilament light chain (NFL), have been examined previously as possible markers of neuronal damage in the pathophysiology of neuropathies. Herein, we aimed to determine the potential value of circulatory NSE and NFL mRNA levels in prediabetic patients and in those with peripheral neuropathy. This prospective clinical study included 45 prediabetic patients and 30 age- and sex-matched controls. All prediabetic patients were assessed with respect to diabetes-related microvascular complications, such as peripheral neuropathy, retinopathy and nephropathy. mRNA levels of NSE and NFL were determined in the blood by real-time polymerase chain reaction. NSE mRNA levels were similar between prediabetic and control groups (p > 0.05), whereas NFL mRNA levels were significantly higher in prediabetics than in controls (p < 0.001). NSE mRNA levels did not significantly differ between prediabetic patients with and without peripheral neuropathy (p > 0.05), while NFL mRNA levels were significantly higher in prediabetics with peripheral neuropathy than in those without (p = 0.038). According to correlation analysis, NFL mRNA levels were positively correlated with the Douleur Neuropathique 4 questionnaire score in prediabetic patients (r = 0.302, p = 0.044). This is the first study to suggest blood NFL mRNA as a surrogate marker for early prediction of prediabetic peripheral neuropathy, while NSE mRNA levels may be of no diagnostic value in prediabetic patients.

Is serum S100B protein an useful biomarker in migraine?

Experimental data have demonstrated a role for S100B protein through the release of proinflammatory cytokines, following trigeminal nerve activation, implicated in the pathology of migraine. We investigated serum levels of S100B protein, as a peripheral glial biomarker, in patients with migraine. In total, 49 migraineurs and 35 age- and gender-matched controls were enrolled in this prospective clinical study. The migraine diagnosis was made according to the International Classification of Headache Disorders II diagnostic criteria. Serum samples were obtained for the measurement of S100B levels from all participants and were analyzed using commercial enzyme-linked immunosorbent assay kits. Serum S100B levels were significantly lower in migraineurs than controls (p < 0.001). S100B levels did not significantly differ in migraineurs with or without aura (p > 0.05). In addition, there was no correlation between serum S100B levels and headache characteristics, including attack severity, frequency and duration, and disease duration (p > 0.05). These findings suggest that serum S100B levels were significantly decreased in migraine patients, but further research is needed to ascertain the contribution of S100B in the clinical evaluation of migraine.

S100B as a glial cell marker in diabetic peripheral neuropathy.

Evidence suggests that acute and chronic hyperglycemia can cause oxidative stress in the peripheral nervous system which, in turn, can promote the development of diabetic neuropathy. Recent studies have found increased expression of glial fibrillary acidic protein (GFAP) and S100B, both of which are indicators of glial reactivity, in the neural and retinal tissues of diabetic rats. For the first time in the literature, the serum levels of GFAP and S100B were assessed in patients with diabetes to evaluate the potential of these factors to serve as peripheral glial biomarkers of diabetes and to investigate their relationship to diabetic peripheral neuropathy. This prospective clinical study included 72 patients with type 2 diabetes mellitus and 50 age- and sex-matched control subjects. All diabetic patients were assessed with respect to diabetes-related microvascular complications, such as peripheral neuropathy, retinopathy, and nephropathy. Serum samples were analyzed for human GFAP and S100B using a commercially available Enzyme-linked Immuno Sorbent Assay kit. GFAP was not detected in the serum samples of either diabetic or control patients (p>0.05). However, we found a statistically significant decrease in S100B serum levels in patients with diabetes compared with control participants (p<0.001). No associations between serum S100B levels and the presence of diabetic peripheral neuropathy or other microvascular complications were observed (p>0.05). The findings of markedly decreased serum levels of S100B may possibly indicate a neuroprotective effect of S100B, whereas GFAP may be of no diagnostic value in human patients with diabetes.

Preoperative medical treatment in patients undergoing diabetic foot surgery with a Wagner Grade-3 or higher ulcer: a retrospective analysis of 52 patients.

Diabetic foot ulcers (DFU) are one of the most important complications in people with diabetes mellitus. The present study was aimed to retrospectively review the efficacy of at least 1-week medical treatment before any surgical intervention in patients with Grade-3 and higher DFU according to Wagner's classification. A total of 52 patients (36 males and 16 females) hospitalized and treated between June 2006 and February 2009 and had initially received therapeutic treatment (local wound care, antibiotic therapy and blood glucose regulation) for a period of at least 1 week were included in the study. The level of amputation, rates of reulceration and mortality in both groups were recorded in the following period of 2 years. Group 1 (did not respond to preoperative medical intervention) included 16 patients where a surgical debridement, flap or skin graft surgery was performed in 2 (12.5%) patients, major amputation was performed in another 2 (12.5%) patients and minor amputation was performed in the remaining 12 (75%) patients. Of 36 patients in Group 2 (did respond to preoperative medical intervention), 5 (13.9%) patients underwent the surgical debridement, flap or skin graft surgery, 8 (22.2%) patients had a major amputation and the remaining 23 (63.9%) patients lead to a minor amputation. The ulcer recurrence and mortality rates were obtained as 2 (12.5%) and 2 (12.5%) in Group 1 and 2 (5.6%) and 1 (2.8%) in Group 2, respectively. Despite the lower rates of ulcer recurrence and mortality in patients having adequate responses to initial treatment before surgical procedures were performed, no statistically significant difference was observed between the 2 groups. In addition, there was no statistically significant difference between the levels of amputation in both groups.

Genotyping of mumps virus circulating in Turkey in the 2006-2007 winter season.

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.

Efficacy of oral ribavirin treatment in Crimean-Congo haemorrhagic fever: a quasi-experimental study from Turkey.

OBJECTIVE: The aim of this study was to evaluate the efficacy of oral ribavirin treatment in patients with Crimean-Congo haemorrhagic fever (CCHF). METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Oseltamivir-ribavirin combination therapy for highly pathogenic H5N1 influenza virus infection in mice.

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.

[Short communication: The sensitivity of measles diagnosis by physicians and families during an intraepidemic period in Edirne: implications for measles surveillance]. / Kisa bildiri: Edirne'de bir kizamik salgini sirasinda hekimlerin ve ailelerin koydugu kizamik tanilarinin duyarliligi: kizamik sürveyansi için oneriler.

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.

Inefficient transmission of H5N1 influenza viruses in a ferret contact model.

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.

Efficacy of oseltamivir therapy in ferrets inoculated with different clades of H5N1 influenza virus.

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.