Basak Dokuzoguz

Characteristics of Patients with Crimean-Congo Hemorrhagic Fever in a Recent Outbreak in Turkey and Impact of Oral Ribavirin Therapy

We describe the epidemiological, clinical, and laboratory findings and the role of ribavirin therapy for 35 patients who received a diagnosis of Crimean-Congo hemorrhagic fever (CCHF). All patients had immunoglobulin M antibodies and/or PCR results positive for CCHF virus in blood or tissue specimens. Eighty-six percent of the patients were considered to have severe cases of CCHF. The overall case-fatality rate was 2.8%. Eight patients were given ribavirin, and all 8 survived. We suggest using ribavirin to treat patients with CCHF, particularly those with severe cases.

Evaluation of Serum Levels of Interleukin (IL)–6, IL-10, and Tumor Necrosis Factor–α in Patients with Crimean-Congo Hemorrhagic Fever

We investigated the role played by cytokines in the mortality of patients with Crimean-Congo hemorrhagic fever (CCHF). Serum levels of several cytokines were measured in 3 patients with fatal CCHF and in 27 patients with nonfatal CCHF. Levels of interleukin (IL)-6 (P< or = .001) and tumor necrosis factor (TNF)-alpha (P = .004) were significantly higher in patients with fatal CCHF than in patients with nonfatal CCHF, whereas levels of IL-10 were not significantly different between the 2 groups (P = .937). Disseminated intravascular coagulation (DIC) scores were also higher in the patients with fatal CCHF (P = .023). Levels of IL-6 and TNF-alpha were positively correlated with DIC scores, whereas levels of IL-10 were negatively correlated with DIC scores. In conclusion, these findings demonstrate that proinflammatory cytokines play a major role in the mortality of patients with CCHF.

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.

Neurobrucellosis: Clinical and Diagnostic Features

BACKGROUND We describe the neurological involvement in brucellosis and revisited diagnostic criteria for neurobrucellosis. METHODS Patients with laboratory-confirmed brucellosis who were consequently hospitalized were observed prospectively in a brucellosis-endemic region. The neurobrucellosis was diagnosed by any one of the following criteria: (1) symptoms and signs consistent with neurobrucellosis; (2) isolation of Brucella species from cerebrospinal fluid (CSF) and/or presence of anti-Brucella antibodies in CSF; (3) the presence of lymphocytosis, increased protein, and decreased glucose levels in CSF; or (4) diagnostic findings in cranial magnetic resonance imaging or CT. RESULTS Lumbar puncture was performed in 128 laboratory-confirmed brucellosis cases who had neurological symptoms and signs, and 48 (37.5%) were diagnosed as neurobrucellosis. The sensitivity of tube agglutination (TA) in CSF was 0.94, specificity 0.96, positive predictive value 0.94, and negative predictive value 0.96. Brucella bacteria were isolated from CSF in 7 of 48 patients (15%). The mean age of 48 neurobrucellosis patients was 42 years (SD, 19 years), and 16 (33%) were female. The most common neurological findings were agitation (25%), behavioral disorders (25%), muscle weakness (23%), disorientation (21%), and neck rigidity (17%). Cranial nerves were involved in 9 of 48 patients (19%). One patient was left with a sequela of peripheral facial paralysis and 2 patients with sensorineural hearing loss. CONCLUSIONS Patients with severe and persistent headache and other neurologic symptoms and signs should be considered for neurobrucellosis in endemic regions and to possibly receive longer therapy than 6 weeks. Brucella TA with Coombs test in CSF is sensitive and specific by using a cutoff of ≥1:8.

Case Management and Supportive Treatment for Patients with Crimean-Congo Hemorrhagic Fever

Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne infection which has been increasing in Turkey and European countries since the year 2000. The disease is particularly endemic in the Middle East and in some African countries. It is also seen in European countries as a travel infection. Patients with confirmed diagnosis are usually hospitalized for monitoring, while patients with good overall condition may be monitored on an outpatient basis. Hospitals that manage CCHF should have easy access to a blood bank, and tertiary care hospitals must have a well-equipped intensive care unit. Strict blood and body fluid control precautions should be started on admission to limit CCHF exposure. The follow-up period for each patient is determined based on individual clinical status and laboratory values. Since there is no specific antiviral treatment for CCHF, supportive treatment is essential. This review highlights some of the major features of case monitoring and supportive treatment in CCHF.

Severity Scoring Index for Crimean-Congo Hemorrhagic Fever and the Impact of Ribavirin and Corticosteroids on Fatality

BACKGROUND Patients infected with Crimean-Congo hemorrhagic fever (CCHF) virus present with a wide clinical spectrum. In observational studies, the effects of therapeutic agents are confounded by severity. We describe use of a clinical severity scoring index (SSI) for CCHF patients and assess the effect of ribavirin and corticosteroid therapy on the case-fatality rate, stratified by SSI. METHODS The study group included hospitalized patients who received a diagnosis of CCHF at the Infectious Diseases and Clinical Microbiology Clinic of Ankara Numune Education and Research Hospital between 2004 and 2011. The SSI included platelet count, bleeding, fibrinogen level, activated partial thromboplastin time, and somnolence. The effects of ribavirin and corticosteroid on the case-fatality rate were studied by univariate and multivariate analysis, stratified by SSI. RESULTS Two hundred eighty-one confirmed cases of CCHF were included in the study. Of 281 patients, 23 (8%) died. The mean age (±SD) of the patients was 47 ± 16 years. Forty-nine percent were female. The mean duration of stay at our clinic after onset of symptoms was 4.4 days, with a range of 1-14 days. In multivariate analysis of factors for the prediction of death, the SSI (odds ratio [OR], 3.27; 95% confidence interval [CI], 2.09-5.13) and ribavirin use (OR, 0.04; 95% CI, .004-.48) were found to be statistically significant factors. CONCLUSION The SSI is an accurate predictor of death and will therefore be a useful tool for case management and for drug-assessment studies. After stratification of cases by SSI, ribavirin was found to be effective in reducing the case-fatality rate, especially among moderately ill patients, whereas steroids were found to be beneficial particularly among patients with severe disease.

Efficacy and Tolerability of Antibiotic Combinations in Neurobrucellosis: Results of the Istanbul Study

ABSTRACT No data on whether brucellar meningitis or meningoencephalitis can be treated with oral antibiotics or whether an intravenous extended-spectrum cephalosporin, namely, ceftriaxone, which does not accumulate in phagocytes, should be added to the regimen exist in the literature. The aim of a study conducted in Istanbul, Turkey, was to compare the efficacy and tolerability of ceftriaxone-based antibiotic treatment regimens with those of an oral treatment protocol in patients with these conditions. This retrospective study enrolled 215 adult patients in 28 health care institutions from four different countries. The first protocol (P1) comprised ceftriaxone, rifampin, and doxycycline. The second protocol (P2) consisted of trimethoprim-sulfamethoxazole, rifampin, and doxycycline. In the third protocol (P3), the patients started with P1 and transferred to P2 when ceftriaxone was stopped. The treatment period was shorter with the regimens which included ceftriaxone (4.40 ± 2.47 months in P1, 6.52 ± 4.15 months in P2, and 5.18 ± 2.27 months in P3) (P = 0.002). In seven patients, therapy was modified due to antibiotic side effects. When these cases were excluded, therapeutic failure did not differ significantly between ceftriaxone-based regimens (n = 5/166, 3.0%) and the oral therapy (n = 4/42, 9.5%) (P = 0.084). The efficacy of the ceftriaxone-based regimens was found to be better (n = 6/166 [3.6%] versus n = 6/42 [14.3%]; P = 0.017) when a composite negative outcome (CNO; relapse plus therapeutic failure) was considered. Accordingly, CNO was greatest in P2 (14.3%, n = 6/42) compared to P1 (2.6%, n = 3/117) and P3 (6.1%, n = 3/49) (P = 0.020). Seemingly, ceftriaxone-based regimens are more successful and require shorter therapy than the oral treatment protocol.

Crimean-Congo Hemorrhagic Fever among Health Care Workers, Turkey

We investigated 9 cases of Crimean-Congo hemorrhagic fever (1 fatal, 2 asymptomatic) among health care workers in Turkey. Needlestick injuries were reported for 4 workers. Eight received ribavirin. In addition to standard precautions, airborne infection isolation precautions are essential during aerosol-generating procedures. For postexposure prophylaxis and therapy, ribavirin should be given.

Risk of tuberculous infection among healthcare workers in a tertiary-care hospital in Ankara, Turkey

OBJECTIVE To determine risk factors for tuberculin skin test (TST) positivity among healthcare workers (HCWs). DESIGN Two-step TST was performed in 2002. SETTING Tertiary-care hospital in Ankara, Turkey. PARTICIPANTS A sample of 491 hospital HCWs were included. Information related to demographics, profession, work duration, department, and individual and family history of tuberculosis (TB) was obtained by a structured questionnaire. RESULTS Four hundred eight (83%) had two-step TST positivity. On multivariate analysis, male physicians (relative risk [RR], 1.5; 95% confidence interval [CI95], 1.23-1.69; P = .001), nurses (RR, 1.5; CI95, 1.29-1.66; P = .005), radiology technicians (RR, 1.7; CI95, 1.35-1.73; P = .002), laboratory technicians (RR, 1.6; CI95, 1.3-1.74; P = .007), and male housekeepers (RR, 1.6; (HCWs). CI95, 1.38-1.7; P < .001) had a higher risk than did female physicians. Among laboratory technicians, radiology technicians had the highest TST positivity (85%). HCWs working for less than 1 year (RR, 0.8; CI95, 0.72-0.98; P = .027) had a lower risk of infection. The HCWs having bacille Calmette-Guerin vaccination (RR, 1.12; CI95, 1.08-1.45) had higher TST positivity. CONCLUSION Male physicians, nurses, and laboratory technicians had increased risk of Mycobacterium tuberculosis infection in this setting, but community exposure likely accounted for most infections.

Pregnancy and Crimean-Congo haemorrhagic fever

Crimean-Congo Hemorrhagic fever (CCHF) is a potentially fatal viral infection with reported case fatality rates of 5-30%. Humans become infected through tick bites, by contact with a patient with CCHF during the acute phase of infection, or by contact with blood or tissues from viraemic livestock. In this first report in the literature, we present the characteristics of three pregnant women with CCHF infection and the outcome of their babies. Transmission of the CCHF infection could be either intrauterine or perinatal. In endemic regions, CCHF infection should be considered in the differential diagnosis of HELLP syndrome (haemolytic anaemia, elevated liver enzymes, low platelet count), and obstetricians should be familiar with the characteristics of CCHF infection. In the aetiology of necrotising enterocolitis, CCHF should be considered.