Browsing by Author "Gündüz C."
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Item Leishmaniasis in Turkey: Determination of Leishmania species by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS)(Tehran University of Medical Sciences (TUMS), 2014) Culha G.; Akyar I.; Yildiz Zeyrek F.; Kurt Ö.; Gündüz C.; Özensoy Töz S.; Östan I.; Cavus I.; Gülkan B.; Kocagöz T.; Özbel Y.; Özbilgin A.Background: Cutaneous leishmaniasis (CL) is endemic in Southeastern Anatolia, mainly in Sanliurfa and Hatay provinces, and the causative agents are mostly Leishmania tropica and less frequently L. infantum. Here, we report the first MALDI-TOF analyses of Leishmania promastigotes obtained from the cultures of two CL cases from Osmaniye and Hatay provinces who were initially diagnosed by microscopy, culture and identified as L. infantum with Real-Time PCR (RT-PCR). Methods: Samples obtained from the skin lesions of patients were initially stained with Giemsa and cultivated in NNN medium. Examination of the smears and cultures revealed Leishmania amastigotes and promastigotes, respectively. The promastigotes (MHOM/TR/2012/CBU15 and MHOM/TR/2012/MK05) obtained from the cultures of both patients were used for RT-PCR targeting the ITS-1 region in the SSU of rRNA. The reference strains of four Leishmania species (L. infantum, L. donovani, L. tropica and L. major) were initially assessed with MALDI-TOF and their data were added to MALDI-TOF Biotyper Library. Results: Both RT-PCR and MALDI-TOF analyses indicated that the causative agent in both patient samples was L. infantum. Conclusion: Despite disadvantages such as requirement of culture fluid with nothing but promastigotes and high cost, MALDI-TOF analysis may be a fast, sensitive and specific diagnostic tool in especially large-scale research studies, where the cost declines, relatively.Item COMET, TUNEL, and TEM analysis of an infertile male with short tail sperm(AVES Ibrahim Kara, 2015) Durmaz A.; Mıçılı S.C.; Vatansever S.; Gündüz C.; Bağrıyanık H.A.; Dikmen N.; Tavmergen Göker E.N.; Tavmergen E.Male infertility is correlated with sperm morphology and sperm DNA damage, which are completely different from that of fertile individuals. An accurate sperm DNA damage analysis and ultrastructural examination of the ejaculate provide important support in the clinical evaluation. It is supposed that in the near future, the fertilization rate, pregnancy rate, and miscarriages could be predicted using the combination of these types of tests in assisted reproductive technologies (ARTs). For this purpose, we report a very rare case of an infertile man having short tail sperm. The infertile man and his wife underwent in vitro fertilization (IVF) with intracytoplasmic sperm injection (ICSI). During this process, we examined the ultrastructure of the ejaculated sperm with transmission electron microscopy (TEM) and calculated the sperm DNA damage with terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and COMET assays. Then, we evaluated the association between sperm DNA damage and embryo quality. © 2015 by the Turkish-German Gynecological Education and Research Foundation.Item Serum procalcitonin and C-reactive protein kinetics as indicators of treatment outcome in hospitalized patients with community-acquired pneumonia(Turkiye Klinikleri Journal of Medical Sciences, 2016) Taşbakan M.S.; Gündüz C.; Sayiner A.; Çilli A.; Çelenk Karaboğa B.; Şakar Çoşkun A.; Durmaz Yaman F.; Kilinç O.; Kiliç Soylar Ö.Background/aim: There has been growing interest in the use of serum procalcitonin (PCT) and C-reactive protein (CRP) in patients with community-acquired pneumonia (CAP). The aim of this study was to investigate whether an assessment of fever, leukocyte count, and serum CRP and PCT levels on admission and during follow-up (day 3) provides any information about the clinical outcome in hospitalized patients with CAP. Materials and methods: Patients with a diagnosis of CAP who were admitted to and followed at four university hospitals were evaluated retrospectively using the Turkish Thoracic Society Pneumonia Database. Results: A total of 103 hospitalized CAP patients (57 males, mean age: 61.5 ± 16.7 years) were enrolled in the study. Treatment failure (TF) was observed in 20 patients (19.4%). Pneumonia Severity Index scores, serum CRP levels, and PCT levels on admission were significantly higher in the TF group. There were significant decreases in CRP and PCT levels between admission day and day 3 in the treatment success group. Conclusion: In patients with CAP, the body temperature and leukocyte count on admission do not predict outcome. Monitoring levels of CRP and PCT may be useful as a predictor of treatment outcome. © TÜBİTAK.Item The first monkey malaria in Turkey: A case of plasmodium knowlesi; [Tiirkiye'deki ilk Maymun Sitmasi: Bir Plasmodium knowlesi Olgusu](Ankara Microbiology Society, 2016) Özbilgin A.; Çavuş I.; Yildirim A.; Gündüz C.Plasmodium knowlesi is now added to the known four Plasmodium species (P.vivax, P.falciparum, P.malariae, P.ovale) as a cause of malaria in humans because of the recent increasing rate of cases reported from countries of southeastern Asia. P.knowlesi which infects macaque monkeys (Macaca fascicufaris and M.nemestrina) is transmitted to humans especially by Anopheles leucosphyrus and An.hackeri mosquitos. First human cases of P.knowlesi malaria have been detected in Malaysia which have reached high numbers in recent years and also have been reported from countries of Southeast Asia such as Thailand, Philippines, Myanmar, Singapore and Vietnam. However the number of cases reported from western countries are rare and limited only within voyagers. This report is the first presentation of an imported case of P.knowlesi malaria in Turkey and aims to draw attention to the point that it could also be detected in future. A 33-year-old male patient from Myanmar who has migrated to Turkey as a refugee, was admitted to a health center with the complaints of fever with a periodicity of 24 hours, headache, fatigue, cough, sore throat, anorexia, myalgia and arthralgia. He was prediagnosed as upper respiratory tract infection, however because of his periodical fever and background in Myanmar, thick and thin blood films were prepared and sent to our laboratory for further examinations. Microscopic examination of the thin blood films revealed erythrocytic stages compatible with P.knowlesi (three large early trophozoites in an erythrocyte, three late trophozoites with compact view, and three late band-form trophozoites). Upon this, both real-Time polymerase chain reaction (Rt-PCR) targeting the small subunit ribosomal RNA (SSU-rRNA) genes of Plasmodium genus and DNA sequence analysis targeting P.knowlesi rRNA gene were performed. As a result, the suspected identification of P.knowlesi by microscopy was confirmed by Rt-PCR and DNA sequencing. The patient was treated with chloroquine and primaquine combination and in the follow-up on the seventh day after the treatment, his parasitemia and symptoms had ceased. Although there were some previous reports concerning about imported patients infected with different Plasmodium species in our country, no cases of P.knowlesi have been reported. This first case presented here emphasizes the occurence of P.knowlesi malaria in Turkey hereinafter due to the increasing number of refugees.Item Leishmaniasis in Turkey: First clinical isolation of Leishmania major from 18 autochthonous cases of cutaneous leishmaniasis in four geographical regions(Blackwell Publishing Ltd, 2016) Özbilgin A.; Çulha G.; Uzun S.; Harman M.; Topal S.G.; Okudan F.; Zeyrek F.; Gündüz C.; Östan I.; Karakuş M.; Töz S.; Kurt Ö.; Akyar I.; Erat A.; Güngör D.; Kayabaşi Ç.; Çavuş I.; Bastien P.; Pratlong F.; Kocagöz T.; Özbel Y.Objective: To report isolation of Leishmania major strains obtained from 18 Turkish autochthonous cutaneous leishmaniasis (CL) patients infected with L. major between 2011 and 2014. Methods: Initial diagnosis relied on microscopy and culture in enriched medium, prepared by adding specific amounts of liver extract, protein and lipid sources to NNN medium. Promastigotes were then transferred to RPMI medium including 10% of foetal calf serum for mass culture. Species-specific real-time PCR targeting ITS1 region of Leishmania spp. was performed using both lesion aspiration samples and cultured promastigotes. Two of 18 isolates were identified by isoenzyme analysis in the Leishmaniasis Reference Center in Montpellier, France. Each isolate was inoculated into the footpads of six mice to observe the pathogenicity of L. major. Developing lesions were observed, and the thickening of footpads was measured weekly. Results: Melting curve analyses of 18 isolates showed a peak concordant with L. major, and two of them were confirmed by isoenzyme analyses as L. major zymodeme MON103. In the mouse model, acute lesions seen on day 21 were accepted as an indication of heavy infection. Severe impairments were observed on all mouse footpads over 3 weeks, which even progressed to extremity amputation. Conclusion: Cutaneous leishmaniasis-causing L. major was recently identified in Adana province in southern Turkey, with PCR. Our study shows that such CL cases are not limited to Adana but currently present from western to Southeastern Anatolia, and along the Mediterranean coast. The role of small mammals, the main reservoirs of L. major in Anatolia, needs to be elucidated, as do the underlying factors that cause severe clinical manifestations in L. major infections in Turkey, contrary to the infections in neighbouring countries. © 2016 John Wiley & Sons Ltd.Item Clinical characteristics and outcome of healthcare associated pneumonia in Turkey; [Türkiye’de sağlık bakımı ile ilişkili pnömoni olgularının klinik özellikleri ve sonuçları](Ankara University, 2016) Gündüz C.; Taşbakan M.S.; Sayiner A.; Çıllı A.; Kilinç O.; Şakar Coşkun A.Introduction: Pneumonia in cases with preceding hospitalization, hemodialysis, intravenous therapy, wound care, or chemotherapy within the prior 30 days and residence in nursing homes are defined as healthcare associated pneumonia (HCAP). The aim of this study was to compare the demographic and laboratory data, isolated causative agents and prognosis of patients with communityacquired pneumonia (CAP) and HCAP in a large population in Turkey. Materials and Methods: The data of 785 cases (average age 65.3 ± 16.4, 530 male) registered to Turkish Thoracic Society Respiratory Infections Study Group CAP database (TURCAP) were examined. The demographic data, clinical history, pneumonia severity scores (PSI), laboratory and radiologic findings of the CAP and HCAP patients were compared. Results: Out of 785 cases, 207 (26.4%) were diagnosed with HCAP and 578 (73.6%) with CAP. Among HCAP cases, 140/207 (67.6%) had preceding hospitalization in the last 90 days, 28/207 (13.5%) were on a hemodialysis program during the previous 30 days and 22/207 (10.6%) were staying in nursing homes. Patients with HCAP more frequently had comorbidities (93.2% vs. 81.6%; p= 0.001) and higher PSI scores (103.9 ± 37.2 vs. 94.6 ± 35.4; p= 0.002) compared to patients with CAP. A causative microorganism was isolated in only 12.1% (70/578) of CAP and 14.5% (30/207) of HCAP patients. The length of stay in hospital was higher in HCAP than CAP (8.6 ± 5.5 vs. 7.5 ± 6.1 days, p= 0.03); however the rates of treatment failure, intensive care unit admission and mortality were similar. Conclusion: In comparison to CAP, HCAP patients tend to have more severe disease, despite have no difference in mortality. The current criteria for HCAP do not predict worse clinical outcomes. Further work is required to define local risk factors for multidrug resistant pathogens. © 2016, Ankara University. All rights reserved.Item Factors affecting treatment success in community-acquired pneumonia(Turkiye Klinikleri Journal of Medical Sciences, 2016) Gündüz C.; Taşbakan M.S.; Sayiner A.; Çilli A.; Kilinç O.; Şakar Coşkun A.Background/aim: Treatment failure in hospitalized patients with community-acquired pneumonia is a major cause of mortality. The aim of this study was to evaluate the factors affecting treatment success in community-acquired pneumonia. Materials and methods: A total of 537 patients (mean age: 66.1 ± 15.8 years, 365 males) registered to the Turkish Thoracic Society Pneumonia Database were analyzed. Of these, clinical improvement or cure, defined as treatment success, was achieved in 477, whereas 60 patients had treatment failure and/or died. Results: Lower numbers of neutrophils (5989.9 ± 6237.3 vs. 8495.6 ± 7279.5/mm3), higher blood urea levels (66.1 ± 42.1 vs. 51.2 ± 38.2 mg/dL), higher Pneumonia Severity Index (PSI) scores (123.3 ± 42.6 vs. 96.3 ± 32.9), higher CURB-65 scores (2.7 ± 1.2 vs. 2.2 ± 0.9), lower PaO2/FiO2 ratios (216.3 ± 86.8 vs. 269.9 ± 65.6), and the presence of multilobar (33.3% vs. 16.4%) and bilateral (41.7% vs. 18.9%) radiologic infiltrates were related to treatment failure. The PSI score and PaO2/FiO2 ratio were independent parameters affecting treatment results in multivariate linear regression analysis (P < 0.001). Conclusion: The risk of treatment failure is high in patients with severe pneumonia and with respiratory failure. Effective treatment and close monitoring are required for these cases. © TÜBİTAK.Item Leishmaniasis in Turkey: Visceral and cutaneous leishmaniasis caused by Leishmania donovani in Turkey(Elsevier B.V., 2017) Özbilgin A.; Harman M.; Karakuş M.; Bart A.; Töz S.; Kurt Ö.; Çavuş İ.; Polat E.; Gündüz C.; Van Gool T.; Özbel Y.In Turkey, the main causative agents are Leishmania tropica (L. tropica) and Leishmania infantum (L. infantum) for cutaneous leishmaniasis (CL) and L. infantum for visceral leishmaniasis (VL). In this study, we investigated leishmaniasis cases caused by L. donovani and established animal models for understanding its tropism in in vivo conditions. Clinical samples (lesion aspirations and bone marrow) obtained from CL/VL patients were investigated using parasitological (smear/NNN) and DNA-based techniques. For species identification, a real time ITS1-PCR was performed using isolates and results were confirmed by hsp70 PCR-N/sequencing and cpb gene PCR/sequencing in order to reveal Leishmania donovani and Leishmania infantum discrimination. Clinical materials from CL and VL patients were also inoculated into two experimental groups (Group CL and Group VL) of Balb/C mice intraperitoneally for creating clinical picture of Turkish L. donovani strains. After 45 days, the samples from visible sores of the skin were taken, and spleens and livers were removed. Measurements of the internal organs were done and touch preparations were prepared for checking the presence of amastigotes. The strains were isolated from all patients and amastigotes were seen in all smears of the patients, and then isolates were immediately stored in liquid nitrogen. In real time ITS1-PCR, the melting temperatures of all samples were out of range of L. infantum, L. tropica and L. major. Sequencing of hsp70 PCR-N showed that all isolates highly identical to previously submitted L. donovani sequences in GenBank, and cpb gene sequencing showed five isolates had longer cpbF allele, whereas one isolate contained a mixed sequence of both cpbF and cpbE. All mice in both experimental groups became infected. Compared to controls, the length and width of both liver and spleen were significantly elevated (p < 0.001) in both groups of mice. However, the weight of the liver increased significantly in all mice whereas the weight of spleen increased only in VL group. Amastigotes were also seen in all touch preparations prepared from skin sores, spleen and liver. L. donovani strain was isolated from autocutaneous a VL patient first time in Turkey. Animal models using clinical samples were successfully established and important clinical differences of the isolated strains were observed. © 2017 Elsevier B.V.Item Do the rodents have a role in transmission of cutaneous leishmaniasis in Turkey?; [Türkiye’de kutanöz leyşmanyaziste kemiricilerin rolü var mı?](Ankara Microbiology Society, 2018) Özbi̇Lgi̇n A.; Çavuş İ.; Yildirim A.; Gündüz C.Leishmaniasis is a zoonotic/anthroponotic vector borne parasitic infection which is caused by Leishmania species and transmitted by sand flies (Phlebotomus spp.) The reservoirs of Leishmania species in nature are various wild and domestic carnivores, rodents and human. The aim of this study was to investigate whether the rodents in genera Meriones, Mesocricetus, Rattus and Mus which inhabit in the natural habitat of our country could be natural reservoirs of Leishmania tropica, Leishmania infantum, Leishmania major and Leishmania donovani for cutaneous Leishmaniasis (CL)., The rodents Mus musculus (Balb/C mouse), Mesocricetus auratus (hamster), Meriones unguiculatus (gerbil) and Rattus norvegicus (rat) which are part of the natural habitat in Turkey were used in the study. L.tropica, L.infantum, L.major and L.donovani promastigote isolates obtained from CL patients and cultured in enriched media were injected in the footpads of the animals intradermally using the density of 108 promastigote/ml. The scale of the lesions on the footpads of the animals were measured for 12 weeks. At the end of the experiment, the animals were sacrificed and “touch preparations” were prepared using footpad, liver, spleen and testicles of the sacrified animals and were examined using Giemsa stained slides following culturing in enriched NNN medium. Leishmania amastigotes were seen in the slides prepared from the footpads of the all experimental animals and all cultures were positive for promastigotes prepared from the same clinical material. But not all the experiment groups were positive for the liver, spleen and testicle preparations. According to these results it was concluded that while all rodents in the experiment groups were positive for CL, only a part of the experiment groups were positive for internal organ involvement. Accordingly, (a) All Leishmania strains caused both CL and internal organ involvement in M.unguiculatus and M.musculus, (b) only L.tropica caused CL and internal organ involvement in R.norvegicus, while other Leishmania strains only caused CL in this group, (c) in M.auratus only L.donovani caused CL while other strains caused both CL and internal organ involvement. In our study, it was determined that the rodents Meriones, Mesocricetus, Rattus and Mus genera which are part of our country’s natural habitat could serve as natural reservoirs of L.tropica, L.infantum, L.major and L.donovani, thus having the potential for the spreading of Leishmaniasis in our country and important information were gathered concerning the clinical aspects of the infection caused by Leishmania species in their potential reservoir hosts. © 2018 Ankara Microbiology Society. All rights reserved.Item Investigation of Dientamoeba fragilis Prevalence and Evaluation of Sociodemographic and Clinical Features in Patients with Gastrointestinal Symptoms(Springer, 2019) Aykur M.; Calıskan Kurt C.; Dirim Erdogan D.; Biray Avcı C.; Vardar R.; Aydemir S.; Girginkardeşler N.; Gündüz C.; Dagci H.Background: Dientamoeba fragilis is a protozoan parasite of the human gastrointestinal tract and still controversial in association with gastrointestinal symptoms. Purpose: We present cross-sectional study of the prevalence of D. fragilis, and sociodemographic and clinical features in the patients with gastrointestinal symptoms. Methods: A total of 490 fecal specimens were collected from outpatients with gastrointestinal symptoms in the Department of Parasitology, Faculty of Medicine, Ege University and Celal Bayar University, Turkey. Fecal specimens were examined with microscopy and inoculated in Robinson medium. D. fragilis-positive samples were examined for the presence of other intestinal parasites using enzyme immunoassay. Real-time PCR analysis was performed on all samples. Results: Of the 490 stool specimens examined by real-time PCR, 59 patients were positive for D. fragilis infection with prevalence rate of 12.04%. Forty-four of positive patients (74.5%) were found to be infected with only D. fragilis, while 23.7% were co-infected with Blastocystis and 1.7% were co-infected with Rotavirus. No statistically significant difference was found in all the examined patients in terms of D. fragilis positivity for all sociodemographic parameters. Loose stool consistency was associated with the presence of D. fragilis, with 18.3% (P = 0.001). When the clinical symptoms of all the patients participating in this study were examined, diarrhea was statistically more significant in patients with the presence of D. fragilis (16.3%; P = 0.001). The rate of diarrhea in D. fragilis-positive patients (84.09%; P = 0.0005) was higher than that of D. fragilis-negative patients and it was statistically significant. Conclusion: This study is important for assessing the prevalence of D. fragilis and its association with other factors in symptomatic patients in a large sample group in Turkey, as well as investigating the relationship of identified symptoms with the D. fragilis pathogenicity. It is suggested that D. fragilis in this case is not a commensal parasite but a pathogenic parasite and that the most common clinical symptom is diarrhea. © 2019, Witold Stefański Institute of Parasitology, Polish Academy of Sciences.Item The current clinical and geographical situation of cutaneous leishmaniasis based on species identification in Turkey(Elsevier B.V., 2019) Özbilgin A.; Töz S.; Harman M.; Günaştı Topal S.; Uzun S.; Okudan F.; Güngör D.; Erat A.; Ertabaklar H.; Ertuğ S.; Gündüz C.; Çavuş İ.; Karakuş M.; Östan Ural İ.; Ölgen M.K.; Kayabaşı Ç.; Kurt Ö.; Özbel Y.Leishmaniases are a group of vector-borne diseases caused by the members of Leishmania genus, and there are three main clinical forms of the infection as visceral, cutaneous, and mucocutaneous. Cutaneous leishmaniasis is a growing public health problem in Turkey due to increasing detection of autochthonous cases caused by L. major and L. donovani in some regions in addition to Syrian imported cases. For this reason, we aimed to evaluate the current epidemiological situation of CL in the view of causative agents and their geographical distribution throughout Turkey. The samples were collected from 356 CL patients admitted to different centers in 18 provinces between January 2013 and December 2016. Direct microscopy, culture (regular and enriched NNN) and molecular techniques (real-time ITS1 PCR and hsp70 PCR/sequencing) were performed. By molecular techniques, 299, 28, 19 and 10 isolates/clinical samples were identified as L. tropica, L. major, L. infantum and L. donovani, respectively. Most of the patients (65.73%) had one lesion usually on their face/head. Dry-nodular type lesions (n = 291) were mainly associated with L. tropica while L. major was mainly found related to wet-ulcerative ones. Leishmaniasis recidivans was also detected in 2.52% among 356 patients. L. tropica was detected as most widespread species causing CL in Turkey. L. infantum and L. major was also found in one third of the provinces. Enriched NNN culture was worked well for isolating the parasite and 346 isolates were successfully grown and stored in liquid nitrogen. The comparison of all diagnostic techniques showed that the parasitological positivity rate could increase if the combination of direct microscopy and real-time ITS1 PCR is used. Besides well-known anthroponotic L. tropica cases, the increasing detection of CL cases caused by zoonotic species, L. infantum and L. major, is one of the most important findings in the present study. In our opinion to ensure timely and accurate diagnosis, proper treatment and countrywide effective control of CL in Turkey a systematic approach is needed on the base of information about characteristics of lesions and patients and epidemiological features of the disease. © 2018 Elsevier B.V.Item First Report and in Silico Analysis of Leishmania virus (LRV2) identified in an autochthonous Leishmania major isolate in Turkey(Luigi Ponzio e figlio Editori, 2019) Kurt Ö.; Mansur N.; Çavuş I.; Özcan O.; Burak Batir M.; Gündüz C.; Sezerman U.; Özbilgın A.Leishmania virus (LRV) has previously been identified in different Leishmania species. Host-LRV interaction is associated with exacerbated clinical manifestations of cutaneous leishmaniasis (CL) and may cause poor therapeutic response. CL cases due to L. major with large skin lesions resistant to routine therapy were recently identified in Turkey. Here, we report the first autochthonous case of cutaneous leishmaniasis caused by LRV-positive Leishmania major, using conventional PCR targeting the viral capsid protein of LRV. The lesion of the case was 6 months old, relatively large (4 cm), and did not recover despite three consecutive intralesional applications of glucantime. Assessment of LRV’s influence on prognosis and clinical outcomes of leishmaniasis, based on additional studies, is required. ©2019 by EDIMES - Edizioni Internazionali Srl. All rights reservedItem The effect of inhaled corticosteroids in the outcomes of community-acquired pneumonia: ICCAP study (TURKCAP Database)(Blackwell Publishing Ltd, 2020) Baha A.; Kokturk N.; Bahcecioglu S.N.; Yapar D.; Aksakal N.; Gündüz C.; Tasbakan S.; Sayiner A.; Coskun A.S.; Durmaz F.; Cilli A.; Celenk B.; Kılınc O.; Salman S.; Hazar A.; Tokgoz F.Objective: We aimed to investigate the effect of inhaled corticosteroids (ICS) in the outcomes of community-acquired pneumonia (CAP), as well as to determine if ICS usage is exist among the risk factors for mortality in those patients. Materials and Methods: In this retrospective cross-sectional multicentre study, 1069 hospitalised CAP patients were investigated using CAP Database of Turkish Thoracic Society (TURKCAP Database). The patients were divided into two groups, depending on their ICS use. The data were analysed by appropriate statistical methods. Results: 172 (75.8%) of the 227 patients who were on ICS had COPD and 37 (16.3%) had asthma. There were fewer patients with fever among ICS-users compared to non-ICS users (P = 0.013), and less muscle pain (P = 0.015) and fewer GIS symptoms (P = 0.022). No statistically significant difference was found between ICS use/ type of ICS and the duration of hospitalisation (P = 0.286). The multivariate regression analysis showed that patients using ICS had lower body temperature and, less crackles/bronchial sound. In the multivariate logistic regression model lung cancer (OR: 6.75), glucose (OR: 1.01) and CURB-65 (OR: 1.72) were significantly associated with mortality in the CAP patients. ICS usage were not found to be associated with mortality. Conclusion: The use of ICS by the patients with CAP admitted to the hospital is not independently related with any radiological pattern, hospitalisation duration and mortality. ICS usage may diminish fever response and may suppress the findings of crackles and/or bronchial sounds. This needs further confirmation. © 2020 John Wiley & Sons LtdItem Refugees at the Crossroads of Continents: A Molecular Approach for Cutaneous Leishmaniasis Among Refugees in Turkey(Springer, 2020) Özbilgin A.; Gencoglan G.; Tunali V.; Çavuş İ.; Yıldırım A.; Gündüz C.; Harman M.Purpose: Due to mass population movements driven by internal conflicts and wars, cutaneous leishmaniasis (CL) is becoming increasingly important in Turkey. This study is aimed at determining the clinical aspects, diagnosis and genotyping of CL patients coming to Turkey from abroad. Methods: In our study, the clinical materials obtained from the patients or sent for diagnostic purposes from other centers to our laboratory between years 2012 and 2016 were assessed retrospectively. In total, there were 38 patients from Syria, Iraq, Afghanistan, Iran, and Turkmenistan. Results: 29 (76%), 28 (73%) and 33 (87%) samples were positive by light microscopy, Novy-McNeal-Nicolle(NNN), and enriched medium, respectively. By ITS-1 gene region PCR, 31 (81%) of the cases were positive. 35 of the patients were tested positive by at least one of the diagnostic methods. By genotyping, 21 Leishmania tropica, 8 Leishmania major, 3 Leismania infantum, 2 Leishmania donovani, and 1 Leishmania aethopica were detected. Conclusion: This study is aimed at informing the clinicians working in the field for the import CL cases and recording the changing epidemiological features of CL in the region as well as discussing the possible focus for L. aethiopica infection which has not been shown in the region before. © 2019, Witold Stefański Institute of Parasitology, Polish Academy of Sciences.Item Diversity of leishmania strains isolated from cutaneous leishmaniasis patients in Turkey and its reflection to clinics in mice model; [Türkiye’de kutanöz leyşmanyazis hastalarından elde edilen leishmania İzolatlarındaki farklılıklar ve bunların fare modeline klinik yansıması](Ankara Microbiology Society, 2021) Özbilgin A.; Çulha G.; Güray M.Z.; Zeyrek F.Y.; Akyar I.; Töz S.; Östan Ural İ.; Kurt Ö.; Kocagöz T.; Çavuş I.; Gündüz C.Although asexual reproduction has been attributed to Leishmania species, genetic exchange has recently been demonstrated, which helped emerging of hybrid isolates. Situated on the crossroads between three continents, Leishmania hybrids may be present in Turkey. In Turkey, visceral leishmaniasis caused by Leishmania infantum is less common, while cutaneous leishmaniasis (CL) caused by Leishmania tropica and L.infantum could reach 2500 reported cases a year. Our aim was to investigate genetic variability of local Leishmania species and presence of hybrid Leishmania strains in Turkey. Twenty CL patients from Sanliurfa and Hatay, where only L.tropica and both L.tropica and L.infantum cause CL, respectively, were registered equally. All isolates were assessed with real-time polymerase chain reaction (Rt-PCR), isoenzyme analysis, gene sequencing, two-dimensional gel electrophoresis (2D-PAGE) and MALDI-TOF/TOFMS followed by in vivo analyses on mouse model. Identification of differentially expressed proteins was performed. These proteins were confirmed by sequence analysis. All isolates from Sanliurfa were found to be L.tropica which caused cutaneous infection in mice. However, one of 10 isolates from Hatay was found as Leishmania major which caused cutaneous infection. Five isolates were found as L.tropica with Rt-PCR and gene sequencing, one of which had one different protein from the reference L.tropica strain and caused cutaneous infection. Four of the five isolates had five different proteins compared to reference strain and caused both cutaneous and visceral infections. Remaining four isolates showed double melting curves in Rt-PCR, which were concordant with L.tropica and L.infantum. Their sequencing and isoenzyme analyses indicated them as L.infantum. They had six different proteins compared to reference L.infantum strain and caused cutaneous and visceral infections. It is concluded that the isolates with different proteins were hybrid Leishmania species. In the present study, outcomes of the proteomics, genomics, clinical manifestations and tissue tropism on animal models were evaluated together for the first time. In addition to L.tropica and L.infantum, L.major was identified as a causative agent for CL and hybrids of L.infantum/tropica were also shown to be present. © 2020 Ankara Microbiology Society. All rights reserved.Item Determination of antimony resistance mechanism of leishmania tropica causing cutaneous leishmaniasis in Turkey; [Türkiye’de kutanöz leyşmanyazis etkeni leishmania tropica’da antimon direnç mekanizmasının belirlenmesi](Ankara Microbiology Society, 2021) Özbilgin A.; Zeyrek F.Y.; Güray M.Z.; Çulha G.; Akyar I.; Harman M.; Özbel Y.; Ertabaklar H.; Çavuş İ.; Gündüz C.World Health Organization reported that approximately one billion people are at risk in endemic areas, one million cases of cutaneous leishmaniasis (CL) and approximately 300,000 cases of visceral leishmaniasis (VL) were reported per year in the last five years. The number of deaths due to VL is reported to be approximately 20,000 per year. Approximately 2500 cases/year have been reported as CL, caused by Leishmania tropica and Leishmania infantum, in Turkey. The significant increase observed in many cities mainly in the provinces of Mediterranean and Aegean regions in cases and foci in recent years, suggests that there may be an increase in this infections in the following years as well. In Turkey, the causative agent of CL is L.tropica and meglumine antimoniate is used in the treatment of CL. We aimed to determine antimony resistance genes specific for L.tropica by comparing the gene and protein expressions of antimony-resistant and non-resistant L.tropica strains. L.tropica isolates obtained from 3 CL patients without antimonate resistance from Aegean, Mediterranean and Southeastern regions of Turkey were provided to transform into 3 resistant isolates against meglumine antimony in the laboratory conditions. Gene expression alterations by microarray method; protein profiles by two-dimensional gel electrophoresis (2D-PAGE) and relevant proteins by MALDI-TOF/TOF MS of these isolates were accomplished and compared. L.tropica isolates from 10 CL patients who did not respond to antimony therapy were analyzed for resistance to antimonial compounds and quantitative real-time polymerase chain reaction was performed to detect the expression of genes responsible for resistance development. Moreover, differences in protein expression levels in isolates with and without antimony resistance were determined by comparing protein profiles and identification of proteins with different expression levels was carried out. Enolase, elongation factor-2, heat shock protein 70, tripanthione reductase, protein kinase C and metallo-peptidase proteins have been shown to play roles in L.tropica isolates developing resistance to antimonial compounds and similar expression changes have also been demonstrated in naturally resistant isolates from patients. In conclusion, it was revealed that L.tropica strains in our country may gain resistance to meglumine antimoniate in a short time. It is foreseen that if the patients living in our country or entering the country are treated inadequately and incompletely, there may be new, resistant leishmaniasis foci that may increase the number of resistant strains and cases rapidly. © 2020 Ankara Microbiology Society. All rights reserved.Item Overcoming the Challenge; In Vivo Efficacy of Miltefosine for Chronic Cutaneous Leishmaniasis(Springer Science and Business Media Deutschland GmbH, 2021) Tunalı V.; Harman M.; Çavuş İ.; Gündüz C.; Özbilgin A.; Turgay N.Background: Cutaneous Leishmaniasis (CL) is the most common form of leishmaniasis. CL can be divided into two major groups: acute CL (ACL) and chronic CL (CCL). The aim of this study is to compare the efficacy of miltefosin and pentavalent antimony compounds in vivo with the CCL patient samples. Materials: Three study groups were formed, each consisting of five male Mus musculus (Balb/C) mice. In this model, promastigotes from the culture of a CCL patient were utilized. 100 μL L. tropica promastigote suspension with a density of 108 promastigotes/ml were injected into the hint-right footpad of each experimental animal intradermally. Footpads of the mice were measured every two weeks until 24th week. From the 13th week, miltefosin 50 mg/kg/day was administered orally using gavage for 21 days, Meglumin antimoniate (MA) was administered by intramuscular (IM) injection daily for 21 days at 50 mg/kg/day and saline was administered IM for 21 days for the miltefosine, MA and control group, respectively. Results: The footpad measurements of the miltefosine group were lower than the control group statistically. Between the MA group and the miltefosine group and MA group and the control group, there was no statistically significant difference. Giemsa stained slides revealed amastigotes in one, two and all of the slides for the miltefosine, MA and control group, respectively. Molecular tests were performed with the Rotor-Gene device and L. tropica consistent peaks were obtained in one of the miltefosine group, four in the MA group and all mice in the control group. Conclusions: Demonstration of both clinical and laboratory improvement in four of the five experimental animals provides strong evidence that miltefosine is an effective drug in the treatment of CCL. In the literature, no clinical or laboratory studies using miltefosine have been performed with CCL patients only. © 2020, Witold Stefański Institute of Parasitology, Polish Academy of Sciences.Item Autochthonous transmission of Leishmania donovani and Leishmania major with all the components of infection cycle at Europe's doorstep(Elsevier B.V., 2022) Özbilgin A.; Tunalı V.; Akar Ş.Ş.; Yıldırım A.; Şen S.; Çavuş I.; Zorbozan O.; Gündüz C.; Turgay N.; İnanır I.Objectives: Leishmaniasis is a vector-borne disease and dogs may act as urban reservoirs. Turkey and most of the Mediterranean basin countries are endemic for leishmaniasis. In this study, it is aimed to report the autochthonous leishmaniasis cases, with all the components of the infection cycle (reservoir, vector, and the host) in a region close to Europe. Methods: Nine human and four canine autochthonous leishmaniasis cases were included in the study. Direct microscopy, culture methods, serological, and molecular tests were applied to the samples obtained from the cases. Results: VL and CL patients consisted of 2 L.infantum, 1 L. donovani, 2 L. tropica, and 2 L. tropica,1 L. major,1 L. infantum infected patients respectively. CanL cases were infected with L. infantum, L. donovani, L. tropica, and L. major. Conclusions: All the cases were autochthonous cases located in Manisa province. As Greece and all the Mediterranean basin countries in Europe share competent vectors, it is concluded that the detection of all 4 species of Leishmania parasites in such proximity to Europe poses an important public health threat for Europe. This study reports all four species of Leishmania spp., including L. major and L.donovani in close proximity to continental Europe. © 2022 Elsevier B.V.Item Investigation of the Anti-Leishmanial Effects of Prangos ferulacea and Ferula orientalis Extracts Collected from Şırnak Province Against Leishmania tropica İsolated in Turkey; [Şırnak İli ve Çevresinden Toplanan Prangos ferulacea ve Ferula orientalis Ekstrelerinin Türkiye’den İzole Edilmiş Leishmania tropica’ya Karşı Anti-Leishmanial Etkilerinin Araştırılması](Ankara Microbiology Society, 2022) Babat S.Ö.; Çavuş I.; Özbilgin A.; Kayalar H.; Gündüz C.; Ceylan Ş.S.; Girginkardeşler N.Leishmaniasis is a vector-borne disease that is caused by the protozoa of Leishmania genus. Leishmaniasis is endemic in tropical, subtropical, and large areas of the Mediterranean basin, and covers a total of 98 countries worldwide. It is estimated, according to the World Health Organization (WHO) data, that approximately 350 million people are at risk in these areas, and approximately 12 million people are infected. Increased drug resistance has been documented lately, in the treatment of leishmaniasis which causes almost 1.2 million new cases annually. Thus, interest in plant-derived active substances has increased in recent years, and new anti-leishmanial agents are investigated with in vitro studies. The aim of the present study was to investigate the anti-leishmanial effects of Prangos ferulacea and Ferula orientalis plant extracts collected from the rural areas of Şırnak province against Leishmania tropica. The water, chloroform, and ethanol extracts of the roots, stems, and fruits of P.ferulaceae and F.orientalis plants were obtained, and the cytotoxic activity tests of the extracts were performed. L.tropica isolate obtained from the Parasite Bank in Manisa Celal Bayar University in Turkey (MHOM/TR/2012/CBCL-LT) was grown on NNN and RPMI 1640 broth medium. The cytotoxicity of each extract on the L.tropica isolate was evaluated with the XTT test. Amphotericin B (AmpB) was used as the positive control, and the IC50 values were determined. The lowest IC50 values of the plant extracts were found to be as follows: P.ferulaceae root chloroform extract 36 µg/ml and fruit chloroform extract 20 µg/ml, F.orientalis root ethanol extract 2.5 µg/ml, and fruit ethanol extract 48 µg/ml, stem chloroform extract 24 µg/ml, and fruit chloroform extract 3.1 µg/ml. It was also determined in our study that only P.ferulaceae root ethanol extract showed cytotoxic activity on the WI-38 fetal lung fibroblast cell line at 65.19 µg/ml at 72 hours. This is the first study that assessed the anti-leishmanial activities of P.ferulaceae and F.orientalis plants that grow in high altitude areas of our country. It was determined that P.ferulaceae root ethanol extract and fruit chloroform extract had the lowest IC50 values among the 18 plant extracts that we examined for their anti-leishmanial activities. The outcomes of this study will be useful in further studies for the determination of active compounds in P.ferulaceae and F.orientalis plant extracts. © 2022 Ankara Microbiology Society. All rights reserved.Item Visceral Leishmaniasis Caused by Leishmania Tropica(Springer Science and Business Media Deutschland GmbH, 2023) Özbilgin A.; Tunalı V.; Çavuş İ.; Tetik A.V.; Dinç M.; Yalçın T.; Gündüz C.; Beyaz M.; Köse Ş.Purpose: In Turkey, the main causative agent of visceral leishmaniasis (VL) is Leishmania. infantum and the main causative agent of cutaneous leishmaniasis (CL) is Leishmania tropica. In this study, we aimed to discuss the possible mechanisms, clinical aspects, and threat of visceralizing L. tropica. Methods: This study includes seven cases of VL caused by L. tropica.Five patients were male (71%) and four were adults (57%). Results: All the VL patients complained of fever and splenomegaly. Fatigue, pancytopenia, and hepatomegaly were present in six patients each (86%), while weight loss and gastrointestinal system (GIS) symptoms were present in 5 patients (71%). Conclusions: In this study, we have evaluated seven cases of visceralized L. tropica (VLT) in the context of the changing leishmaniasis epidemiology in Turkey. We have evaluated the possible mechanisms of visceralization; inter- and intraspecies genetic exchange with all the old world leishmaniasis agents present in the region, stress induced by inappropriate use of drugs, and possible ongoing adaptation mechanisms of Leishmania spp. The threat posed by VLT is significant as L. tropica is the most widespread and most common cause of leishmaniasis in Turkey. We do not know the vectorial capacity of the sand flies for the transmission of VLT strains or if these strains are in circulation in Turkey. Future studies should be carried out to investigate these issues as the transition of L. tropica from a mild disease-causing agent to a mortal one poses a significant public health concern for Turkey and Europe. © 2023, The Author(s) under exclusive licence to Witold Stefański Institute of Parasitology, Polish Academy of Sciences.