Publications by authors named "Hakan Leblebicioglu"

122 Publications

COVID-19 pandemic and international travel: Turkey's experience.

Travel Med Infect Dis 2021 Mar-Apr;40:101972. Epub 2021 Jan 13.

Infectious Diseases Department, Samsun VM Medicalpark Hospital, Samsun, Turkey. Electronic address:

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http://dx.doi.org/10.1016/j.tmaid.2021.101972DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7803620PMC
April 2021

SARS-CoV-2/COVID-19 and advances in developing potential therapeutics and vaccines to counter this emerging pandemic.

Ann Clin Microbiol Antimicrob 2020 Sep 2;19(1):40. Epub 2020 Sep 2.

Department of Infectious Diseases, Samsun VM Medicalpark Hospital, Samsun, Turkey.

A novel coronavirus (SARS-CoV-2), causing an emerging coronavirus disease (COVID-19), first detected in Wuhan City, Hubei Province, China, which has taken a catastrophic turn with high toll rates in China and subsequently spreading across the globe. The rapid spread of this virus to more than 210 countries while affecting more than 25 million people and causing more than 843,000 human deaths, it has resulted in a pandemic situation in the world. The SARS-CoV-2 virus belongs to the genus Betacoronavirus, like MERS-CoV and SARS-CoV, all of which originated in bats. It is highly contagious, causing symptoms like fever, dyspnea, asthenia and pneumonia, thrombocytopenia, and the severely infected patients succumb to the disease. Coronaviruses (CoVs) among all known RNA viruses have the largest genomes ranging from 26 to 32 kb in length. Extensive research has been conducted to understand the molecular basis of the SARS-CoV-2 infection and evolution, develop effective therapeutics, antiviral drugs, and vaccines, and to design rapid and confirmatory viral diagnostics as well as adopt appropriate prevention and control strategies. To date, August 30, 2020, no effective, proven therapeutic antibodies or specific drugs, and vaccines have turned up. In this review article, we describe the underlying molecular organization and phylogenetic analysis of the coronaviruses, including the SARS-CoV-2, and recent advances in diagnosis and vaccine development in brief and focusing mainly on developing potential therapeutic options that can be explored to manage this pandemic virus infection, which would help in valid countering of COVID-19.
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http://dx.doi.org/10.1186/s12941-020-00384-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464065PMC
September 2020

An open call for influenza vaccination pending the new wave of COVID-19.

J Med Virol 2021 01 14;93(1):172-173. Epub 2020 Jul 14.

Infectious Diseases Department, Liv Hospital, Samsun, Turkey.

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http://dx.doi.org/10.1002/jmv.26272DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7361616PMC
January 2021

Six-year multicenter study on short-term peripheral venous catheters-related bloodstream infection rates in 246 intensive units of 83 hospitals in 52 cities of 14 countries of Middle East: Bahrain, Egypt, Iran, Jordan, Kingdom of Saudi Arabia, Kuwait, Lebanon, Morocco, Pakistan, Palestine, Sudan, Tunisia, Turkey, and United Arab Emirates-International Nosocomial Infection Control Consortium (INICC) findings.

J Infect Public Health 2020 Aug 12;13(8):1134-1141. Epub 2020 Apr 12.

Armed Forces Institute of Pathology, Rawalpindi, Pakistan.

Background: Short-term peripheral venous catheters-related bloodstream infections (PVCR-BSIs) rates have not been systematically studied, and data on their incidence by number of device-days is not available.

Methods: Prospective, surveillance study on PVCR-BSI conducted from September 1st, 2013 to 31st Mays, 2019 in 246 intensive care units (ICUs), members of the International Nosocomial Infection Control Consortium (INICC), from 83 hospitals in 52 cities of 14 countries in the Middle East (Bahrain, Egypt, Iran, Jordan, Kingdom of Saudi Arabia, Kuwait, Lebanon, Morocco, Pakistan, Palestine, Sudan, Tunisia, Turkey, and United Arab Emirates). We applied U.S.

Results: We followed 31,083 ICU patients for 189,834 bed-days and 202,375 short term peripheral venous catheter (PVC)-days. We identified 470 PVCR-BSIs, amounting to a rate of 2.32/1000 PVC-days. Mortality in patients with PVC but without PVCR-BSI was 10.38%, and 29.36% in patients with PVC and PVCR-BSI. The mean length of stay in patients with PVC but without PVCR-BSI was 5.94 days, and 16.84 days in patients with PVC and PVCR-BSI. The microorganism profile showed 55.2 % of gram-positive bacteria, with Coagulase-negative Staphylococci (31%) and Staphylococcus aureus (14%) being the predominant ones. Gram-negative bacteria accounted for 39% of cases, and included: Escherichia coli (7%), Klebsiella pneumoniae (8%), Pseudomonas aeruginosa (5%), Enterobacter spp. (3%), and others (29.9%), such as Serratia marcescens.

Conclusions: PVCR-BSI rates found in our ICUs were much higher than rates published from USA, Australia, and Italy. Infection prevention programs must be implemented to reduce the incidence of PVCR-BSIs.
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http://dx.doi.org/10.1016/j.jiph.2020.03.012DOI Listing
August 2020

Six-year multicenter study on short-term peripheral venous catheters-related bloodstream infection rates in 727 intensive care units of 268 hospitals in 141 cities of 42 countries of Africa, the Americas, Eastern Mediterranean, Europe, South East Asia, and Western Pacific Regions: International Nosocomial Infection Control Consortium (INICC) findings.

Infect Control Hosp Epidemiol 2020 05 18;41(5):553-563. Epub 2020 Mar 18.

Department of Anesthesiology and Intensive Therapy, Wroclaw Medical University, Wroclaw, Poland.

Background: Short-term peripheral venous catheter-related bloodstream infection (PVCR-BSI) rates have not been systematically studied in resource-limited countries, and data on their incidence by number of device days are not available.

Methods: Prospective, surveillance study on PVCR-BSI conducted from September 1, 2013, to May 31, 2019, in 727 intensive care units (ICUs), by members of the International Nosocomial Infection Control Consortium (INICC), from 268 hospitals in 141 cities of 42 countries of Africa, the Americas, Eastern Mediterranean, Europe, South East Asia, and Western Pacific regions. For this research, we applied definition and criteria of the CDC NHSN, methodology of the INICC, and software named INICC Surveillance Online System.

Results: We followed 149,609 ICU patients for 731,135 bed days and 743,508 short-term peripheral venous catheter (PVC) days. We identified 1,789 PVCR-BSIs for an overall rate of 2.41 per 1,000 PVC days. Mortality in patients with PVC but without PVCR-BSI was 6.67%, and mortality was 18% in patients with PVC and PVCR-BSI. The length of stay of patients with PVC but without PVCR-BSI was 4.83 days, and the length of stay was 9.85 days in patients with PVC and PVCR-BSI. Among these infections, the microorganism profile showed 58% gram-negative bacteria: Escherichia coli (16%), Klebsiella spp (11%), Pseudomonas aeruginosa (6%), Enterobacter spp (4%), and others (20%) including Serratia marcescens. Staphylococcus aureus were the predominant gram-positive bacteria (12%).

Conclusions: PVCR-BSI rates in INICC ICUs were much higher than rates published from industrialized countries. Infection prevention programs must be implemented to reduce the incidence of PVCR-BSIs in resource-limited countries.
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http://dx.doi.org/10.1017/ice.2020.20DOI Listing
May 2020

International Nosocomial Infection Control Consortium (INICC) report, data summary of 45 countries for 2012-2017: Device-associated module.

Am J Infect Control 2020 04 29;48(4):423-432. Epub 2019 Oct 29.

Hospital del Niño de Panama, Panama.

Background: We report the results of International Nosocomial Infection Control Consortium (INICC) surveillance study from January 2012 to December 2017 in 523 intensive care units (ICUs) in 45 countries from Latin America, Europe, Eastern Mediterranean, Southeast Asia, and Western Pacific.

Methods: During the 6-year study period, prospective data from 532,483 ICU patients hospitalized in 242 hospitals, for an aggregate of 2,197,304 patient days, were collected through the INICC Surveillance Online System (ISOS). The Centers for Disease Control and Prevention-National Healthcare Safety Network (CDC-NHSN) definitions for device-associated health care-associated infection (DA-HAI) were applied.

Results: Although device use in INICC ICUs was similar to that reported from CDC-NHSN ICUs, DA-HAI rates were higher in the INICC ICUs: in the medical-surgical ICUs, the pooled central line-associated bloodstream infection rate was higher (5.05 vs 0.8 per 1,000 central line-days); the ventilator-associated pneumonia rate was also higher (14.1 vs 0.9 per 1,000 ventilator-days,), as well as the rate of catheter-associated urinary tract infection (5.1 vs 1.7 per 1,000 catheter-days). From blood cultures samples, frequencies of resistance, such as of Pseudomonas aeruginosa to piperacillin-tazobactam (33.0% vs 18.3%), were also higher.

Conclusions: Despite a significant trend toward the reduction in INICC ICUs, DA-HAI rates are still much higher compared with CDC-NHSN's ICUs representing the developed world. It is INICC's main goal to provide basic and cost-effective resources, through the INICC Surveillance Online System to tackle the burden of DA-HAIs effectively.
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http://dx.doi.org/10.1016/j.ajic.2019.08.023DOI Listing
April 2020

Rotational thromboelastometry alongside conventional coagulation testing in patients with Crimean-Congo haemorrhagic fever: an observational cohort study.

Lancet Infect Dis 2019 08 28;19(8):862-871. Epub 2019 Jun 28.

Haemostasis Research Unit, Guy's and St Thomas' Foundation Trust, London, UK.

Background: Data describing the coagulopathy of Crimean-Congo haemorrhagic fever are scarce. We did rotational thromboelastometry (ROTEM) and conventional coagulation testing in patients with Crimean-Congo haemorrhagic fever to increase our understanding of the coagulopathy of this infectious disease.

Methods: We did a prospective observational cohort study of adults aged 18 years and older and admitted to hospitals with PCR-confirmed Crimean-Congo haemorrhagic fever in Samsun and Tokat, Turkey. Demographic, clinical, and laboratory data were collected and blood samples for ROTEM analysis and coagulation testing were drawn at admission and during hospital admission and convalescence (up to 30 days after onset of illness). For the ROTEM analysis we recorded the following extrinsically activated ROTEM (EXTEM S) variables, with normal ranges indicated: clotting time (38-79 s), clot formation time (34-159 s), amplitude at 10 min after clotting time (43-65 mm), maximum clot firmness (50-72 mm), and maximum lysis (>15% at 1 h). The following fibrin-specific ROTEM (FIBTEM S) variables were also recorded: amplitude at 10 min after clotting time (normal range 7-23 mm) and maximum clot firmness (9-25 mm). Disease severity was assessed by Swanepoel criteria, severity grading score (SGS), and the severity scoring index (SSI), with mild disease defined as meeting no Swanepoel criteria, graded mild by SSI, and graded low risk by SGS.

Findings: Between May 27, 2015, and Aug 2, 2015, 65 patients with confirmed Crimean-Congo haemorrhagic fever were recruited and had blood taken at 110 time points. Most were male (40 [62%] of 65) with mild disease (49 [75%] of 65). Haemorrhage occurred in 13 (20%; 95% CI 11·1-31·8) of 65 patients and 23 (35%) of 65 received blood products (15 received fresh frozen plasma and eight received red blood cell concentrates), and 21 patients received platelet transfusions. At admission, the following EXTEM S variables differed significantly between mild cases and moderate to severe cases: median clotting time 56 s (range 42-81; IQR 48-64) versus 69 s (range 48-164; IQR 54-75; p=0·01); mean amplitude at 10 min after clotting time 45·1 mm (SD 7·0) versus 33·9 mm (SD 8·6; p<0·0001); median clot formation time 147 s (range 72-255; IQR 101-171) versus 197 s (range 98-418; IQR 156-296; p=0·006); and maximum clot firmness 54·4 mm (SD 7·2) versus 45·1 mm (SD 12·5; p=0·003). The EXTEM S variables were compared at different time points; maximum clot firmness (p=0·024) and amplitude at 10 min after clotting time (p=0·090) were lowest on days 4-6 of illness. We found no significant differences in FIBTEM variables between mild and moderate to severe cases (median amplitude at 10 min, 13 mm [range 8-20; IQR 11-15] vs 12 mm [range 6-25; IQR 10-15; p=0·68]; and median maximum clot firmness, 15 mm [range 9-60; IQR 13-21] vs 17 mm [range 7-39; IQR 13-23; p=0·21]); and no hyperfibrinolysis (maximum lysis >15%).

Interpretation: Coagulopathy of Crimean-Congo haemorrhagic fever is related to defects in clot development and stabilisation that are more marked in severe disease than in mild disease. The combination of normal and slightly deranged coagulation screens and FIBTEM results with the absence of hyperfibrinolysis suggests that the coagulopathy of Crimean-Congo haemorrhagic fever relates to platelet dysfunction.

Funding: Wellcome Trust, UK Ministry of Defence, and National Institute for Health Research Health Protection Research Unit.
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http://dx.doi.org/10.1016/S1473-3099(19)30112-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7641897PMC
August 2019

Hepatitis E virus infection in Turkey: a systematic review.

Ann Clin Microbiol Antimicrob 2018 May 2;17(1):17. Epub 2018 May 2.

Medilife Hospital, Istanbul, Turkey.

Hepatitis E virus (HEV), a non-enveloped single stranded RNA virus causes sporadic cases of hepatitis or outbreaks. The disease is generally self-limited although it may cause fulminant hepatitis in pregnant women, elderly, those with underlying chronic hepatitis, immunosuppressed, and transplant recipients. It is transmitted through fecal-oral route and zoonotic transmission. Hepatitis is a main health care problem in Turkey; HBV and HCV prevalences are 4 and 1% respectively. Hepatitis D represents another considerable hepatitis etiology with a prevalence of 5-27%. The information about HEV is not clear. In this systematic review, we aimed to analyze HEV studies reported from Turkey, to determine the current situation of the disease in the country, to delineate the limits of the studies and to determine the future study areas. The prevalence of HEV ranged from 0 to 12.4%. Children had lower prevalence than the adults. The prevalence was determined as 7-8% in pregnant women, 13% in chronic HBV patients, 54% in chronic HCV patients, 13.9-20.6% in patients with chronic renal failure, and ≈ 35% in agriculture workers. Among individuals immigrating form Turkey to Europe, HEV seroprevalence was found 10.3% in Italy and 33.4% in the Netherlands. HEV prevalence seems high in certain risk groups. Although previous studies suggest that Turkey is among the endemic countries of HEV, there are some pitfalls for the analysis of data: the studies are not powered enough to represent the whole population; they did not include immunosuppressed patients and solid organ recipients; and the prevalence of non-A non-B hepatitis was not determined.
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http://dx.doi.org/10.1186/s12941-018-0269-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5930810PMC
May 2018

Recommendations for Management of Endemic Diseases and Travel Medicine in Solid-Organ Transplant Recipients and Donors: Latin America.

Transplantation 2018 02;102(2):193-208

Unit of Infectious Diseases, Hospital Universitario 12 de Octubre, Madrid, Spain.

The Recommendations for Management of Endemic Diseases and Travel Medicine in Solid-Organ Transplant Recipients and Donors: Latin America clinical practice guideline is intended to guide clinicians caring for solid-organ transplant (SOT) donors, candidates and recipients regarding infectious diseases (ID) issues related to this geographical region, mostly located in the tropics. These recommendations are based on both systematic reviews of relevant literature and expert opinion from both transplant ID and travel medicine specialists. The guidelines provide recommendations for risk evaluation and laboratory investigation, as well as management and prevention of infection of the most relevant endemic diseases of Latin America. This summary includes a brief description of the guideline recommendations but does not include the complete rationale and references for each recommendation, which is available in the online version of the article, published in this journal as a supplement. The supplement contains 10 reviews referring to endemic or travel diseases (eg, tuberculosis, Chagas disease [ChD], leishmaniasis, malaria, strongyloidiasis and schistosomiasis, travelers diarrhea, arboviruses, endemic fungal infections, viral hepatitis, and vaccines) and an illustrative section with maps (http://www.pmourao.com/map/). Contributors included experts from 13 countries (Brazil, Canada, Chile, Denmark, France, Italy, Peru, Spain, Switzerland, Turkey, United Kingdom, United States, and Uruguay) representing four continents (Asia, the Americas and Europe), along with scientific and medical societies.
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http://dx.doi.org/10.1097/TP.0000000000002027DOI Listing
February 2018

Viral Hepatitis Recommendations for Solid-Organ Transplant Recipients and Donors.

Transplantation 2018 02;102(2S Suppl 2):S66-S71

Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY USA.

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http://dx.doi.org/10.1097/TP.0000000000002013DOI Listing
February 2018

Availability of hepatitis C diagnostics and therapeutics in European and Eurasia countries.

Antiviral Res 2018 02 5;150:9-14. Epub 2017 Dec 5.

Infectious Diseases, Hôpitaux Universitaires Paris Centre, Université Paris Descartes, Paris, France.

Background: Treatment with direct acting antiviral agents (DAAs) has provided sustained virological response rates in >95% of patients with chronic hepatitis C virus (HCV) infection. However treatment is costly and market access, reimbursement and governmental restrictions differ among countries. We aimed to analyze these differences among European and Eurasian countries.

Methods: A survey including 20-item questionnaire was sent to experts in viral hepatitis. Countries were evaluated according to their income categories by the World Bank stratification.

Results: Experts from 26 countries responded to the survey. As of May 2016, HCV prevalence was reported as low (≤1%) in Croatia, Czech Republic, Denmark, France, Germany, Hungary, the Netherlands, Portugal, Slovenia, Spain, Sweden, UK; intermediate (1-4%) in Azerbaijan, Bosnia and Herzegovina, Italy, Kosovo, Greece, Kazakhstan, Romania, Russia, Serbia and high in Georgia (6.7%). All countries had national guidelines except Albania, Kosovo, Serbia, Tunisia, and UK. Transient elastography was available in all countries, but reimbursed in 61%. HCV-RNA was reimbursed in 81%. PegIFN/RBV was reimbursed in 54% of the countries. No DAAs were available in four countries: Kazakhstan, Kosovo, Serbia, and Tunisia. In others, at least one DAA combination with either PegIFN/RBV or another DAA was available. In Germany and the Netherlands all DAAs were reimbursed without restrictions: Sofosbuvir and sofosbuvir/ledipasvir were free of charge in Georgia.

Conclusion: Prevalence of HCV is relatively higher in lower-middle and upper-middle income countries. DAAs are not available or reimbursed in many Eurasia and European countries. Effective screening and access to care are essential for reducing liver-related morbidity and mortality.
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http://dx.doi.org/10.1016/j.antiviral.2017.12.001DOI Listing
February 2018

Infection prevention and control practice for Crimean-Congo hemorrhagic fever-A multi-center cross-sectional survey in Eurasia.

PLoS One 2017 8;12(9):e0182315. Epub 2017 Sep 8.

Department of Clinical Microbiology and Infectious Diseases, School of Medicine, Ondokuz Mayis University, Samsun, Turkey.

Background: Crimean Congo Hemorrhagic Fever (CCHF) is a life threatening acute viral infection that presents significant risk of nosocomial transmission to healthcare workers.

Aim: Evaluation of CCHF infection prevention and control (IP&C) practices in healthcare facilities that routinely manage CCHF cases in Eurasia.

Methods: A cross-sectional CCHF IP&C survey was designed and distributed to CCHF centers in 10 endemic Eurasian countries in 2016.

Results: Twenty-three responses were received from centers in Turkey, Pakistan, Russia, Georgia, Kosovo, Bulgaria, Oman, Iran, India and Kazakhstan. All units had dedicated isolation rooms for CCHF, with cohorting of confirmed cases in 15/23 centers and cohorting of suspect and confirmed cases in 9/23 centers. There was adequate personal protective equipment (PPE) in 22/23 facilities, with 21/23 facilities reporting routine use of PPE for CCHF patients. Adequate staffing levels to provide care reported in 14/23 locations. All centers reported having a high risk CCHFV nosocomial exposure in last five years, with 5 centers reporting more than 5 exposures. Education was provided annually in most centers (13/23), with additional training requested in PPE use (11/23), PPE donning/doffing (12/23), environmental disinfection (12/23) and waste management (14/23).

Conclusions: Staff and patient safety must be improved and healthcare associated CCHF exposure and transmission eliminated. Improvements are recommended in isolation capacity in healthcare facilities, use of PPE and maintenance of adequate staffing levels. We recommend further audit of IP&C practice at individual units in endemic areas, as part of national quality assurance programs.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0182315PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5590734PMC
October 2017

Enterococcus durans Endocarditis.

Am J Ther 2018 Nov/Dec;25(6):e663-e665

Departments of Infectious Diseases and.

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http://dx.doi.org/10.1097/MJT.0000000000000519DOI Listing
March 2019

Crimean-Congo hemorrhagic fever: A neglected infectious disease with potential nosocomial infection threat.

Am J Infect Control 2017 07 11;45(7):815-816. Epub 2017 Apr 11.

Department of Infectious Diseases and Clinical Microbiology, Ondokuz Mayis University, Medical School, Samsun, Turkey.

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http://dx.doi.org/10.1016/j.ajic.2016.05.039DOI Listing
July 2017

Infective endocarditis with atypical clinical feature and relapse by .

J Saudi Heart Assoc 2017 Apr 16;29(2):136-138. Epub 2016 Jun 16.

Department of Clinical Microbiology and Infectious Diseases, Ondokuz Mayis University School of Medicine, Samsun, aTurkey.

A case of infective endocarditis caused by an uncommon agent with atypical manifestations is presented. A 42-year-old woman previously had rheumatic heart disease, presented with the symptoms of fever and chills that resolved within 3 days under antibiotherapy. She was diagnosed with endocarditis due to . Despite culture-directed antibiotics being administered in the first admission, her symptoms and also blood culture growth relapsed 3 weeks later. She was successfully treated with antimicrobial therapy and surgical intervention including aorta and mitral valve replacement. This case demonstrates that should be considered as a causative organism of endocarditis particularly in the presence of atypical symptoms and should be followed up carefully in terms of relapses and complications.
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http://dx.doi.org/10.1016/j.jsha.2016.06.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5366814PMC
April 2017

Current status of Crimean-Congo haemorrhagic fever in the World Health Organization Eastern Mediterranean Region: issues, challenges, and future directions.

Int J Infect Dis 2017 May 1;58:82-89. Epub 2017 Mar 1.

Infectious Hazards Management, World Health Organization, Geneva, Switzerland.

Crimean-Congo haemorrhagic fever (CCHF) is the most widespread, tick-borne viral disease affecting humans. The disease is endemic in many regions, such as Africa, Asia, Eastern and Southern Europe, and Central Asia. Recently, the incidence of CCHF has increased rapidly in the countries of the World Health Organization Eastern Mediterranean Region (WHO EMR), with sporadic human cases and outbreaks of CCHF being reported from a number of countries in the region. Despite the rapidly growing incidence of the disease, there are currently no accurate data on the burden of the disease in the region due to the different surveillance systems used for CCHF in these countries. In an effort to increase our understanding of the epidemiology and risk factors for the transmission of the CCHF virus (CCHFV; a Nairovirus of the family Bunyaviridae) in the WHO EMR, and to identify the current knowledge gaps that are hindering effective control interventions, a sub-regional meeting was organized in Muscat, Oman, from December 7 to 9, 2015. This article summarizes the current knowledge of the disease in the region, identifies the knowledge gaps that present challenges for the prevention and control of CCHFV, and details a strategic framework for research and development activities that would be necessary to curb the ongoing and new threats posed by CCHFV.
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http://dx.doi.org/10.1016/j.ijid.2017.02.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7110796PMC
May 2017

Crimean-Congo hemorrhagic fever in pregnancy: A systematic review and case series from Russia, Kazakhstan and Turkey.

Int J Infect Dis 2017 May 27;58:58-64. Epub 2017 Feb 27.

Ondokuz Mayis University, Department of Infectious Diseases and Clinical Microbiology, Samsun, Turkey; Liverpool School of Tropical Medicine, Liverpool, United Kingdom. Electronic address:

Background: Crimean-Congo hemorrhagic fever (CCHF) is acute viral infection and a major emerging infectious diseases threat, affecting a large geographical area. There is no proven antiviral therapy and it has a case fatality rate of 4-30%. The natural history of disease and outcomes of CCHF in pregnant women is poorly understood.

Objectives: To systematically review the characteristics of CCHF in pregnancy, and report a case series of 8 CCHF cases in pregnant women from Russia, Kazakhstan and Turkey.

Methods: A systematic review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement protocol. PubMed, SCOPUS, Science Citation Index (SCI) were searched for reports published between January 1960 and June 2016. Two independent reviewers selected and reviewed studies and extracted data.

Results: Thirty-four cases of CCHF in pregnancy were identified, and combined with the case series data, 42 cases were analyzed. The majority of cases originated in Turkey (14), Iran (10) and Russia (6). There was a maternal mortality of 14/41(34%) and fetal/neonatal mortality of in 24/41 cases (58.5%). Hemorrhage was associated with maternal (p=0.009) and fetal/neonatal death (p<0.0001). There was nosocomial transmission to 38 cases from 6/37 index pregnant cases.

Conclusion: Cases of CCHF in pregnancy are rare, but associated with high rates of maternal and fetal mortality, and nosocomial transmission.
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http://dx.doi.org/10.1016/j.ijid.2017.02.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5421160PMC
May 2017

Risk factors and mortality in the Carbapenem-resistant Klebsiella pneumoniae infection: case control study.

Pathog Glob Health 2016 Oct - Dec;110(7-8):321-325. Epub 2016 Dec 1.

a Department of Clinical Microbiology and Infectious Diseases , School of Medicine, Ondokuz Mayis University , Samsun , Turkey.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) has been known as a nosocomial pathogen, both for the last 10 years in Turkey and for 20 years worldwide. Due to limited treatment options and high mortality rates, despite improvements in the field of medicine at the present time, CRKP is still a big threat for public health. This study was carried out between the dates of January 2010 and September 2014. Patients ≥18 who were hospitalized for at least 72 h and who also had CRKP growth were included in the study as a case group. In the same period patients, who were hospitalized in the same ward and did not have CRKP growth were selected as the control group. It was determined that no glycopeptides and steroids use nor tracheostomy as protective factors would be employed in terms of non-development of CRKP. Mechanical ventilation, tracheostomy, urinary catheter presence, central venous catheterization, nasogastric tube placement, advanced age, acute renal insufficiency, total parenteral nutrition, carbapenem, glycopeptide, and piperacillin tazobactam were all detected as risk factors in terms of CRKP infection development. As a result, rational usage of antibiotics for preventing infections developing with CRKP should be targeted.
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http://dx.doi.org/10.1080/20477724.2016.1254976DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5189867PMC
June 2017

Treating hepatitis B virus/hepatitis C virus coinfected patients with direct-acting hepatitis C virus antivirals only is not safe.

Hepatology 2016 11 24;64(5):1825-1827. Epub 2016 May 24.

Department of Infectious Diseases, Ondokuz Mayis University Medical School, Samsun, Turkey.

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http://dx.doi.org/10.1002/hep.28592DOI Listing
November 2016

International Nosocomial Infection Control Consortium report, data summary of 50 countries for 2010-2015: Device-associated module.

Am J Infect Control 2016 12 11;44(12):1495-1504. Epub 2016 Oct 11.

Clinical Center of Serbia, Belgrade, Serbia.

Background: We report the results of International Nosocomial Infection Control Consortium (INICC) surveillance study from January 2010-December 2015 in 703 intensive care units (ICUs) in Latin America, Europe, Eastern Mediterranean, Southeast Asia, and Western Pacific.

Methods: During the 6-year study period, using Centers for Disease Control and Prevention National Healthcare Safety Network (CDC-NHSN) definitions for device-associated health care-associated infection (DA-HAI), we collected prospective data from 861,284 patients hospitalized in INICC hospital ICUs for an aggregate of 3,506,562 days.

Results: Although device use in INICC ICUs was similar to that reported from CDC-NHSN ICUs, DA-HAI rates were higher in the INICC ICUs: in the INICC medical-surgical ICUs, the pooled rate of central line-associated bloodstream infection, 4.1 per 1,000 central line-days, was nearly 5-fold higher than the 0.8 per 1,000 central line-days reported from comparable US ICUs, the overall rate of ventilator-associated pneumonia was also higher, 13.1 versus 0.9 per 1,000 ventilator-days, as was the rate of catheter-associated urinary tract infection, 5.07 versus 1.7 per 1,000 catheter-days. From blood cultures samples, frequencies of resistance of Pseudomonas isolates to amikacin (29.87% vs 10%) and to imipenem (44.3% vs 26.1%), and of Klebsiella pneumoniae isolates to ceftazidime (73.2% vs 28.8%) and to imipenem (43.27% vs 12.8%) were also higher in the INICC ICUs compared with CDC-NHSN ICUs.

Conclusions: Although DA-HAIs in INICC ICU patients continue to be higher than the rates reported in CDC-NSHN ICUs representing the developed world, we have observed a significant trend toward the reduction of DA-HAI rates in INICC ICUs as shown in each international report. It is INICC's main goal to continue facilitating education, training, and basic and cost-effective tools and resources, such as standardized forms and an online platform, to tackle this problem effectively and systematically.
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http://dx.doi.org/10.1016/j.ajic.2016.08.007DOI Listing
December 2016

Medical Considerations before International Travel.

N Engl J Med 2016 10;375(15):e32

Ondokuz Mayis University, Samsun, Turkey.

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http://dx.doi.org/10.1056/NEJMc1610671DOI Listing
October 2016

Aetiology of PCR negative suspected Crimean-Congo hemorrhagic fever cases in an endemic area.

Pathog Glob Health 2016 Jun-Jul;110(4-5):173-7

a Department of Infectious Disease and Clinical Microbiology , Ondokuz Mayıs University, Medical School , Samsun , Turkey.

Crimean-Congo hemorrhagic fever (CCHF) is a potentially fatal tick-borne viral infection that is widely distributed worldwide. The diagnosis is frequently missed due to the non-specific initial symptoms and the differential diagnosis included many infectious and non-infectious causes. This retrospective study describes the clinical features and final diagnoses of 116 suspect CCHF cases that were admitted to a tertiary CCHF center in Turkey, and were CCHF IgM and PCR negative.
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http://dx.doi.org/10.1080/20477724.2016.1213958DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5072119PMC
April 2017

A case of endocarditis mimicking Crimean-Congo haemorrhagic fever.

Trop Doct 2017 Jan 2;47(1):71-72. Epub 2016 Aug 2.

Department of Infectious Disease and Clinical Microbiology, Ondokuz Mayıs University, Medical School, Samsun, Turkey.

Infective endocarditis (IE) is life-threatening condition with a highly variable clinical presentation. We report a case of acute IE with delayed diagnosis which resulted due to an initial misdiagnosis of Crimean Congo Hemorrhagic Fever (CCHF) in an endemic area. A case was due to Staphylococcus aureus and requiring valve replacement. They serve to emphasize the importance of careful history taking, physical examination and a broad range of different diagnostic techniques in the context of suspected viral hemorrhagic fever.
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http://dx.doi.org/10.1177/0049475516660465DOI Listing
January 2017

Multi-center prospective evaluation of discharge criteria for hospitalized patients with Crimean-Congo Hemorrhagic Fever.

Antiviral Res 2016 09 15;133:9-13. Epub 2016 Jul 15.

Department of Infectious Diseases and Clinical Microbiology, Istanbul University Cerrahpasa Medical School, Istanbul, Turkey.

Introduction: The information of discharge criteria in patients with Crimean-Congo Hemorrhagic Fever (CCHF) is limited. In this study, we aimed to determine the clinical and laboratory parameters used in discharging the patients by the experienced centers.

Materials And Methods: The study was done in 9 reference centers of CCHF from May 1, 2015 to December 1, 2015 and included laboratory-confirmed patients with CCHF. The study was prospective, observational and non-interventional.

Results: The study included 260 patients. Mean age was 51.3 ± 16.3 years; 158 (60.8%) were male. Mean hospital stay was 7 ± 2.6 days. The decision of discharging was taken considering clinical and laboratory findings. On discharge, no patients had fever or hemorrhage. The patients were followed-up clinically and a repeat CCHF PCR was not studied. All centers considered the following criteria for discharge: no fever and hemorrhage, improvement in clinical findings and laboratory studies. For all patients except one, platelet count was >50,000/mm(3) and had a tendency to increase. Prothrombin time and international normalized ratio (INR) were normal in 258 (99.6%) and 254 (98.1%) patients respectively. Alanine aminotransferase (ALT) was either normal or not higher than 10-fold and had a tendency to decrease in 259 (99.6%) patients. ALT and aspartate aminotransferase (AST) levels were not taken as discharge criteria with priority. During 30 days following the discharge, complication, relapse, or secondary transmission were not reported.

Conclusions: The discharging practice of the centers based on clinical and laboratory parameters seems safe considering no complications, relapses, or secondary infection thereafter. Current discharge practice of the centers composed of no fever and hemorrhage, improvement in clinical findings, platelet count of either >100,000/mm(3) or >50,000/mm(3) with a tendency to increase, and normal bleeding tests can be used as the criteria of discharge.
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http://dx.doi.org/10.1016/j.antiviral.2016.07.010DOI Listing
September 2016

Prognostic factors, pathophysiology and novel biomarkers in Crimean-Congo hemorrhagic fever.

Antiviral Res 2016 08 1;132:233-43. Epub 2016 Jul 1.

Department of Infectious Diseases and Clinical Microbiology, Ondokuz Mayis University Medical School, Samsun, Turkey. Electronic address:

Crimean-Congo hemorrhagic fever (CCHF) is a geographically widespread tick-borne zoonosis. The clinical spectrum of the illness varies from mild infection to severe disease and death. In severe cases, hemorrhagic manifestations develop, with fatality rates of 4-20%, depending on the geographic region and quality of the health care. Although vast majority of the CCHF cases were reported from Turkey, mortality rate is lower than the other regions, which is 5% on average. Prediction of the clinical course of the disease enables appropriate management planning by the physician and prompt transportation, if needed, of the patient to a tertiary care hospital for an intensive therapy. Thus, predicting the outcome of the disease may avert potential mortality. There are numerous studies investigating the prognostic factors of CCHF in the literature. Majority of them were reported from Turkey and included investigations on clinical and biochemical parameters, severity scoring systems and some novel biomarkers. Somnolence, bleeding, thrombocytopenia, elevated liver enzymes and prolonged bleeding times are the most frequently reported prognostic factors to predict the clinical course of the disease earlier. High viral load seems to be the strongest predictor to make a clinical decision about the patient outcome. The severity scoring systems based on clinically important mortality-related parameters are especially useful for clinicians working in the field to predict the course of the disease and to decide which patient should be referred to a tertiary care hospital for intensive care. In the light of the pathophysiological characteristics of CCHF, some new biomarkers of prognosis including cytokines, soluble adhesion molecules, genetic polymorphisms and coagulopathy parameters were also investigated. However most of these tests are not available to clinicians and they were obtained mostly for research purposes. In spite of the various studies about prognostic factors, they have several inherent limitations, including large variability in the results and confusing data that are not useful for clinicians in routine practice. In this paper, the results of diverse studies of the prediction of the prognosis in CCHF based on epidemiological, clinical and laboratory findings of the disease were summarized and suggestions for future studies are provided.
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http://dx.doi.org/10.1016/j.antiviral.2016.06.011DOI Listing
August 2016

Apoptosis-Related Gene Expression in an Adult Cohort with Crimean-Congo Hemorrhagic Fever.

PLoS One 2016 15;11(6):e0157247. Epub 2016 Jun 15.

Department of Clinical Microbiology and Infectious Diseases, School of Medicine, Ondokuz Mayis University, Samsun, Turkey.

Crimean-Congo Hemorrhagic Fever (CCHF) is a life threatening acute viral infection characterized by fever, bleeding, leukopenia and thrombocytopenia. It is a major emerging infectious diseases threat, but its pathogenesis remains poorly understood and few data exist for the role of apoptosis in acute infection. We aimed to assess apoptotic gene expression in leukocytes in a cross-sectional cohort study of adults with CCHF. Twenty participants with CCHF and 10 healthy controls were recruited at a tertiary CCHF unit in Turkey; at admission baseline blood tests were collected and total RNA was isolated. The RealTime ready Human Apoptosis Panel was used for real-time PCR, detecting differences in gene expression. Participants had CCHF severity grading scores (SGS) with low risk score (10 out of 20) and intermediate or high risk scores (10 out of 20) for mortality. Five of 20 participants had a fatal outcome. Gene expression analysis showed modulation of pro-apoptotic and anti-apoptotic genes that facilitate apoptosis in the CCHF patient group. Dominant extrinsic pathway activation, mostly related with TNF family members was observed. Severe and fatal cases suggest additional intrinsic pathway activation. The clinical significance of relative gene expression is not clear, and larger longitudinal studies with simultaneous measurement of host and viral factors are recommended.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0157247PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4909233PMC
July 2017

Management of infections in critically ill returning travellers in the intensive care unit-II: clinical syndromes and special considerations in immunocompromised patients.

Int J Infect Dis 2016 Jul 28;48:104-12. Epub 2016 Apr 28.

Infectious Disease Department, Ondokuz Mayis University Medical School, Samsun, Turkey.

This position paper is the second ESCMID Consensus Document on this subject and aims to provide intensivists, infectious disease specialists, and emergency physicians with a standardized approach to the management of serious travel-related infections in the intensive care unit (ICU) or the emergency department. This document is a cooperative effort between members of two European Society of Clinical Microbiology and Infectious Diseases (ESCMID) study groups and was coordinated by Hakan Leblebicioglu and Jordi Rello for ESGITM (ESCMID Study Group for Infections in Travellers and Migrants) and ESGCIP (ESCMID Study Group for Infections in Critically Ill Patients), respectively. A relevant expert on the subject of each section prepared the first draft which was then edited and approved by additional members from both ESCMID study groups. This article summarizes considerations regarding clinical syndromes requiring ICU admission in travellers, covering immunocompromised patients.
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http://dx.doi.org/10.1016/j.ijid.2016.04.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7110459PMC
July 2016

Management of infections in critically ill returning travellers in the intensive care unit-I: considerations on infection control and transmission of resistance.

Int J Infect Dis 2016 Jul 28;48:113-7. Epub 2016 Apr 28.

CIBERES, Vall Hebron Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain. Electronic address:

Depending on their destinations and activities, international travellers are at a significant risk of contracting both communicable and non-communicable diseases. On return to their home countries, such travellers may require intensive care. The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), and more recently Ebola haemorrhagic fever, has highlighted the risks. Other well-known communicable pathogens such as methicillin-resistant Staphylococcus aureus and carbapenemase-producing Enterobacteriaceae have been described previously. However, malaria remains by far the most important cause of death. The issues related to imported antibiotic resistance and protection from highly contagious diseases are reviewed here. Surveillance strategies based on epidemiological data (country visited, duration of travel, and time elapsed since return) and clinical syndromes, together with systematic search policies, are usually mandatory to limit the risk of an outbreak. Single-bed hospital rooms and isolation according to symptoms should be the rule while awaiting laboratory test results. Because person-to-person contact is the main route of transmission, healthcare workers should implement specific prevention strategies.
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http://dx.doi.org/10.1016/j.ijid.2016.04.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7110831PMC
July 2016

Barriers to access to hepatitis C treatment.

J Infect Dev Ctries 2016 Apr 28;10(4):308-16. Epub 2016 Apr 28.

Ondokuz Mayis University Medical Samsun, Turkey.

Hepatitis C virus (HCV) is a major cause of chronic liver disease worldwide. Only 1%-30% of patients in need of treatment may get it. In recent years, the availability of direct-acting antiviral agents (DAA) has been an important advancement in treating HCV infection. However, due to cost, it is not possible to receive these drugs in many countries where infection is endemic. In these low- and middle-income countries, the main barriers to controlling HCV infection are lack of knowledge about the infection, constraints on diagnostic testing and treatment, and lack of experts. Both national and international support are essential to overcoming these barriers. In low- and middle-income countries, interferon and ribavirin-based therapies still are the first choices due to their availability and to government payment support. In addition, in developed countries, efforts to provide lower-cost DAA drugs continue. Pharmaceutical companies continue to research manufacture of bio-equivalent drugs to reduce treatment costs. Considering the fake drug market, all developments need to be monitored closely by the institutions involved. This review focuses on barriers to hepatitis C treatment and ways to overcome those barriers.
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http://dx.doi.org/10.3855/jidc.7849DOI Listing
April 2016
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