Aynur Engin

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

OBJECTIVE The aim of this study was to evaluate the efficacy of oral ribavirin treatment in patients with Crimean-Congo haemorrhagic fever (CCHF). METHODS In 2004, all patients diagnosed with CCHF were treated with oral ribavirin, however in 2003 none of the CCHF patients had been given treatment due to lack of confirmatory diagnostic information at that time in Turkey. In this study, patients treated with ribavirin in 2004 (n=126) were compared with ribavirin-untreated CCHF patients (n=92) in 2003. Patients only with a definitive diagnosis of CCHF (clinical symptoms plus the presence of specific IgM antibodies against CCHF virus and presence of viral antigen) were included in this study. RESULTS There was no difference in the case-fatality rate between treated and untreated patients (7.1% vs. 11.9%; P>0.05). A Cox Proportional Hazards regression analysis revealed that altered sensorium and prolonged international normalized ratio were independent predictors of mortality. CONCLUSION Our results showed that oral ribavirin treatment did not improve the survival rate in CCHF patients. Ribavirin and supportive care are the only available choices for treatment of CCHF patients, but to ascertain the efficacy of ribavirin, more laboratory and observational studies are necessary and ultimately, to elucidate these conflicting results and evaluate the efficacy undoubtedly, a multicenter randomised controlled trial will be needed.

Crimean-Congo Hemorrhagic Fever Virus in High-Risk Population, Turkey

In the Tokat and Sivas provinces of Turkey, the overall Crimean-Congo hemorrhagic fever virus (CCHFV) seroprevalence was 12.8% among 782 members of a high-risk population. CCHFV seroprevalence was associated with history of tick bite or tick removal from animals, employment in animal husbandry or farming, and being >40 years of age.

MRSA genotypes in Turkey: Persistence over 10 years of a single clone of ST239

OBJECTIVES Methicillin-resistant Staphylococcus aureus (MRSA) is a significant cause of life-threatening human infections. The clinical impact of MRSA is mounting, not only due to the ever-increasing prevalence but also due to the occurrence of new, community-acquired MRSA strains. The aim of this prospective, multi-centre study was to determine the prevalence and genetic relatedness of clinically relevant MRSA isolates, in Turkey. METHODS During a 1-year period, data from 20 successive patients with invasive S. aureus infections were collected from eight university hospitals, geographically distributed over the six main regions of Turkey. Among these S. aureus isolates, the genetic association of MRSA isolates was investigated by pulsed-field gel electrophoresis (PFGE) and spa typing. A selected number of isolates were also analyzed by multilocus sequence typing (MLST). Furthermore, Panton Valentine leucocidin (PVL) genes were examined. RESULTS In this study, the rate of methicillin resistance in S. aureus in patients with apparent infections (sepsis, meningitis, lung abscess or septic arthritis) ranged from 12 to 75% within the seven participating centres. Typing by pulsed-field gel electrophoresis and spa typing revealed the presence of 22 closely related genotypes. According to the PFGE and spa typing results, 53 out of 54 MRSA isolates were closely related. These isolates were of spa type t030 or a related spa type, contain an SCC mec type III element and belong to sequence type ST239. None of the isolates contained the PVL genes. CONCLUSIONS Despite the broad surface area of Turkey, a single predominant clone of ST239 circulates in hospitals in different regions and only few new types of MRSA were introduced over the past years. These results place Turkey in the epicenter of ST239 prevalence.

Recommended precaution procedures protect healthcare workers from Crimean-Congo hemorrhagic fever virus☆

OBJECTIVES The Crimean-Congo hemorrhagic fever (CCHF) virus can spread from person to person and may cause nosocomial outbreaks among healthcare workers (HCWs). The US Centers for Disease Control and Prevention have recommended the use of personal protective equipment (PPE). We investigated the compliance of HCWs with PPE usage during the follow-up of patients, and also the number of risky contacts that occurred between patients and HCWs. We also aimed to determine the seroprevalence of CCHF virus in HCWs. METHODS This study was conducted at Cumhuriyet University Education and Research Hospital, a medical center located in a highly endemic area for CCHF where a total of 1284 confirmed CCHF patients were followed-up between 2002 and 2012. All HCWs who were at risk of CCHF virus contact and infection were included in the study. The compliance of the HCWs with PPE usage and the number of contacts that had occurred were recorded. HCW serum samples were analyzed for CCHF virus IgM and IgG by ELISA. RESULTS The total rates of PPE usage were 93.7% for gowns, 77.4% for gloves, and 38.9% for masks; the highest compliance was detected in the infectious diseases ward: 100%, 88.6%, and 82.9%, respectively. A total of four HCWs had a history of high-risk contact with contaminated material (two percutaneous exposure and two mucosal contacts), but the number of low-risk contacts was quite high. The total seroprevalence rate was only 0.53%. CONCLUSIONS Although the HCWs at our medical center have dealt with an extremely high number of CCHF patients during the last decade, the total seropositivity for CCHFV IgG was only 0.53%. This low rate may be a result of high compliance with PPE usage and also regular education programs.

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

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

Crimean-Congo hemorrhagic fever disease due to tick bite with very long incubation periods.

BACKGROUND Crimean-Congo hemorrhagic fever (CCHF) is a zoonotic viral disease with a high mortality rate, and is one of the viral hemorrhagic fever syndromes. The average mortality rate of CCHF is 3-30%. Research indicates that the longest incubation period after a tick bite is 12 days in CCHF disease. However, in clinical practice, we encounter patients with CCHF as a result of tick bites with much longer incubation periods (max. 53 days) than those reported in the literature. We present herein CCHF cases presumably infected through tick bites and having incubation periods longer than the upper limit reported in the literature. METHODS We analyzed the cases of the 825 CCHF patients admitted to our hospital from 2007 to 2010 and found that 312 of them had undoubtedly been bitten by a tick. We searched the patient records for information on the incubation period and found that 12 patients had experienced an incubation period of over 12 days, which is the longest incubation period stated in the literature for patients definitely bitten by a tick. RESULTS A total of 12 patients (eight males and four females, with a mean age of 45 years) were recruited into this study. Five (41.7%) of the 12 patients had positive CCHF virus-specific IgM antibodies, three (25%) had a positive reverse transcription polymerase chain reaction test for CCHF virus, and four (33.3%) had positive results in both tests during the acute and/or convalescent phase of the disease. In these cases, the interval between tick bite and the onset of symptoms was a mean of 23.6 days (range 13-53 days). CONCLUSION Physicians serving in endemic regions should be aware of these longer incubation periods after a tick bite. It is suggested that they perform more follow-ups on clinically and serologically highly suspected patients than they currently do.

Can the mild clinical course of crimean–congo hemorrhagic fever in children be explained by cytokine responses?

Cytokines are possibly one of the factors responsible for death due to Crimean–Congo hemorrhagic fever (CCHF). This study aimed to determine the differences between the cytokine levels in children and adult patients with CCHF; the influence of cytokines; and the severity of the course of the disease, which seems to be milder in children. Thirty‐four children and 36 adult patients diagnosed with CCHF between 2010 and 2011 were included in this study. Diagnosis was performed by serology or by the polymerase chain reaction for CCHF virus. Levels of IFN‐γ, TNF‐α, IL‐1β, IL‐2, IL‐4, IL‐5, IL‐6, IL‐9, IL‐10, IL‐12 p70, IL‐13, IL‐17A, and IL‐22 were measured in all serum samples. Although the disease had a fatal course in three adult patients, there were no deaths in children. Statistically significant differences were not observed between the cytokine concentrations in the adults and children. No differences were detected between the serum cytokine levels in the children with moderate and those with a severe clinical course of the disease. In the adult patients with fatal outcome, significantly higher serum levels of IL‐2, IL‐5, IL‐9, IL‐12 p70, and IL‐13 were detected as compared to the cytokine levels in patients who survived the infection. No differences were detected between the serum levels of IFN‐γ, IL‐1β, IL‐17A, IL‐22, IL‐10, IL‐6, IL‐4, and TNF‐α in the patients who died and those who survived. Thus, the milder clinical course in children with CCHF cannot be explained by the cytokine network alone. The incomplete maturation of the immune system and timing and scale of immune responses could change the outcome dramatically. J Med. Virol. 85:1955–1959, 2013.

Investigation of Crimean-Congo Hemorrhagic Fever Virus Transmission from Patients to Relatives: A Prospective Contact Tracing Study

We investigated the possibility of transmission of Crimean-Congo hemorrhagic fever (CCHF) virus through respiratory and physical contact. In this prospective study, we traced 116 close relatives of confirmed CCHF cases who were in close contact with the patients during the acute phase of the infection and evaluated the type of contact between patients and their relatives. These relatives were followed for clinical signs or symptoms indicative of CCHF disease, blood samples of those with and without clinical signs were analyzed for CCHF virus immunoglobulin M and G (IgM and IgG, respectively) by enzyme-linked immunosorbent assay. No close relatives developed any signs or symptoms of CCHF and were negative for CCHF virus IgM and IgG. The results suggest that CCHF virus is not easily transmitted from person to person through respiratory or physical contact.

Treatment failure of gentamicin in pediatric patients with oropharyngeal tularemia

Summary Background Tularemia is a zoonotic infection, and the causative agent is Francisella tularensis. A first-line therapy for treating tularemia is aminoglycosides (streptomycin or, more commonly, gentamicin), and treatment duration is typically 7 to 10 days, with longer courses for more severe cases. Material/Methods We evaluated 11 patients retrospectively. Failure of the therapy was defined by persistent or recurrent fever, increased size or appearance of new lymphadenopathies and persistence of the constitutional syndrome with elevation of the levels of the proteins associated with the acute phase of infection. Results We observed fluctuating size of lymph nodes of 4 patients who were on the 7th day of empirical therapy. The therapy was switched to streptomycin alone and continued for 14 days. The other 7 patients, who had no complications, were on cefazolin and gentamycin therapy until the serologic diagnosis. Then we evaluated them again and observed that none of their lymph nodes regressed. We also switched their therapy to 14 days of streptomycin. After the 14 days on streptomycin therapy, we observed all the lymph nodes had recovered or regressed. During a follow-up 3 weeks later, we observed that all their lymph nodes had regressed to the clinically non-significant dimensions (<1 cm). Conclusions All patients were first treated with gentamicin, but were than given streptomycin after failure of gentamicin. This treatment was successful in all patients. The results of our study suggest that streptomycin is an effective choice of first-line treatment for pediatric oropharyngeal tularemia patients.

Toll-like receptor 7 Gln11Leu, c.4-151A/G, and +1817G/T polymorphisms in Crimean Congo hemorrhagic fever

Crimean‐Congo hemorrhagic fever (CCHF) is a viral zoonosis. Toll‐like receptors (TLRs) initiate signaling cascades leading to the activation of the innate immune system following CCHF infection. In this study, TLR7 (Gln11Leu, c.4‐151A/G, and +1817G/T) polymorphisms were investigated in CCHF patients using polymerase chain reaction (PCR)‐based restriction fragment length polymorphism (RFLP). The study population comprised 149 CCHF patients and 171 controls. For the TLR7 Gln11Leu polymorphism, there was no significant difference between the case and control groups in allele (P = 0.144) and genotype frequencies (P = 0.219). In the TLR7 IVS1 +1817G/T polymorphism, a statistically significant difference was found in allele frequencies (P = 0.026), but there was no significant difference in the TLR7 c.4‐151A/G polymorphism (P = 0.310). There was a statistically significant difference in the distribution of the TLR7 c.4‐151GG genotypes frequencies between patients and controls (P = 0.042; OR = 2.23). Furthermore, there were statistically significant associations between the TLR7 c.4‐151A/G polymorphism and both severe disease and patient mortality (P < 0.001 and P = 0.047, respectively). The TLR7 IVS1 +1817TT genotype was also significantly associated with the case group but not the control group (P = 0.045). A strong positive linkage among TLR 7 variants was found using haplotype analysis. The incidence of two haplotypes, AGG and AGT, was determined to exhibit significant differences between the case and control groups (P < 0.001 and P < 0.001, respectively). These findings suggest that the TLR7 IVS1 +1817G/T and TLR7 c.4‐151A/G polymorphisms may be important in the susceptibility or clinical course of CCHF disease. J. Med. Virol. 87:1090–1095, 2015.