Genotypic analysis of S segment of Crimean-Congo hemorrhagic fever virus in Turkey.

The Crimean-Congo hemorrhagic fever (CCHF) virus (CCHFV) is a tick-borne virus, whose viral RNA consists of S, L, and M segments. The virus is migrating through the ticks with animals and migratory birds and the geographical distribution can be investigated based on genetic analysis. To better understand the connection between the seropositivity and the mortality rate, the key factor could be the temporal and spatial analysis of the different strains. In this study, serum samples (n = 26) were selected from CCHFV RNA-positive patients and subjected to sequence analysis of the gene regions encoding the S segments. According to the neighbor-joining analysis, the obtained partial sequences were linked to the European strain. The strains were closely related to Turkey-Kelkit06, Turkey 200310849 viruses, and viruses from Russia and Kosovo. The comparison with previously analyzed isolates from the GenBank showed 95%-99% sequence similarity. The isolates in phylogenetic branches were divided into two groups. AST, platelet, and APTT levels were found significantly higher in Group 2 compared to Group 1. Nucleotide differences can be prognostic factor in CCHF disease. Increasing CCHF cases not originating from local isolates were circulating strains imported from different neighboring countries of Turkey. The results show new evidence to the emerging threat of the CCHF disease.

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

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.

Secondary infections after cytotoxic chemotherapy in patient with hematological malignancies.

INTRODUCTION: This study was initiated to investigate the risk factors of secondary infections in febrile neutropenic patients following chemotherapy, and to evaluate the clinical, microbiological, and mortality outcomes of these infections. METHODOLOGY: An evaluation was done on all patients with hematological malignancy who developed a febrile neutropenic episode (FNE) after cytotoxic chemotherapy in the Department of Hematology, Akdeniz University Faculty of Medicine, between January 2007 and December 2008. RESULTS: A total of 294 primary FNEs that responded to the initial empirical or targeted treatment were included in the study, and secondary infections developed after 72 (24.5%) of 294 primary FNEs. Risk factors for secondary infections were determined as acute leukemia as the underlying disease, salvage chemotherapy for refractory/relapse diseases, prolonged neutropenia (10 days and over), Multinational Association of Supportive Care in Cancer (MASSC) score < 21, and fungal infection during the primary episode. The mortality rate of patients who developed secondary infections was significantly higher compared to patients without secondary infections (27.8% and 5.4%, respectively; p = 0.001). CONCLUSIONS: The development of secondary infections in patients with hematological malignancy was not very rare. Greater concern should be shown for these infections to increase patient survival rates.

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

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.