Dynamics of viral load in Crimean Congo hemorrhagic fever.

Crimean Congo hemorrhagic fever (CCHF) is a viral zoonotic disease with high mortality rate. There are only a few studies on viral load in CCHF. In our study, we revealed the dynamics of viral load and its relationship with mortality in early phase of the disease. A total of 138 serum samples were collected from 23 patients. All patients had positive PCR for CCHF on admission. Serum samples were obtained daily from all patients for the first 6 days of hospitalization and stored at -80°C for viral load measurement. We found statistically significant difference between mean number of viremic serum samples of fatal and non-fatal patients. Furthermore, non-fatal cases' viral loads demonstrated statistically significant decreases over time; however, we could not observe a similar trend in viral loads of fatal cases. Limited number of studies on CCHF indicate that score of the contest between CCHF virus and immune system determines the survival in CCHF and viral load is found to be the most prognostic factor. In our study, we found that there is a notable decrease trend in viral loads of non-fatal patients over time and this clearance of CCHF virus is significantly related with survival.

Adherence to Nucleoside/Nucleotide Analogue Treatment in Patients with Chronic Hepatitis B.

BACKGROUND: Adherence to medication is an important aspect of preventing drug resistance and treatment failure in patients receiving nucleos(t)ide analogues for chronic hepatitis B. AIMS: To assess adherence to nucleoside/nucleotide analogues in chronic hepatitis B treatment and to determine factors associated with non-adherence. STUDY DESIGN: Cross-sectional study. METHODS: The study enrolled 85 chronic hepatitis B patients who had been receiving nucleoside/nucleotide analogues for ≥3 months. A questionnaire was completed by patients themselves, and adherence was evaluated based on patients' self-reporting. The use of at least 95% of the drugs in the previous month was considered as adequate adherence. RESULTS: Adherence was adequate in 82.4% of patients. Female gender (p=0.003), unemployment (p=0.041) and lower monthly family income (p=0.001) were related to lower adherence. Better adherence was significantly linked to adequate basic knowledge regarding chronic hepatitis B (p=0.049), longer treatment duration than 12 months (p<0.001), previous use of other medications for chronic hepatitis B (p=0.014) and regular follow-up by the same physician (p<0.001). CONCLUSION: Counselling patients about their disease state and the consequences of non-adherence is an important intervention for enhancing adherence. Naïve patients should be followed up more frequently to reinforce adherence.

A retrospective controlled study of thiol disulfide homeostasis as a novel marker in Crimean Congo hemorrhagic fever.

OBJECTIVES: Crimean Congo hemorrhagic fever (CCHF) is the second most common hemorrhagic fever worldwide. This study aimed to evaluate the oxidant-antioxidant balance of patients with CCHF by detecting dynamic thiol disulfide homeostasis (TDH), which is a novel oxidative stress marker, and other molecules, including paraoxonase (PON), arylesterase (ARES), ceruloplasmin (CLP), myeloperoxidase (MPO), and catalase. METHODS: This retrospective, cross-sectional, controlled study, which involved patients with CCHF and healthy volunteers, measured dynamic TDH using a novel automated method developed by Erel. RESULTS: We recruited 69 adult patients with CCHF (31 females, 38 males, median age 46 years). The case fatality rate was 1.49% (1/69). Increased disulfide/native thiol and disulfide/total thiol ratios, decreased total antioxidant status (TAS), and increased total oxidant status (TOS) were found in patients with CCHF. TAS, PON, and ARES values were found to be positively correlated with both native and total thiol levels, whereas TOS and CLP were negatively correlated with both, at a significant level. MPO activity was similar in both groups. DISCUSSION: This is the first study in the literature to evaluate dynamic TDH in CCHF. TDH shifts to the oxidative side in patients with CCHF, leading to an increase in TOS.

Risk factors for infection with colistin-resistant gram-negative microorganisms: a multicenter study.

BACKGROUND: Knowing risk factors for colistin resistance is important since colistin is the only remaining choice for the treatment of infections caused by multi-drug resistant microorganisms. OBJECTIVE: Evaluate risk factors associated with infection by colistin-resistant microorganisms. DESIGN: Retrospective study. SETTING: Tertiary healthcare centers. PATIENTS AND METHODS: An e-mail including the title and purpose of the study was sent to 1500 infec.tious disease specialists via a scientific and social web portal named "infeksiyon dunyasi (infection world)". Demographic and clinical data was requested from respondents. MAIN OUTCOME MEASURE(S): Colistin-resistance. RESULTS: Eighteen infectious disease specialists from twelve tertiary care centers responded to the invitation data was collected on 165 patients, 56 cases (39.9%) and 109 (66.0%) age- and sex-matched controls. The colistin-resistant microorganisms isolated from cases were 29 Acinetobacter baumannii (51.8%), 18 Pseudomonas aeruginosa (32.1%) and 9 Klebsiella spp. Colistin, carbapenem, and quinolone use in the last three months were risk factors for colistin resistance in the univariate analysis. Previous quinolone use in the last three months (P=.003; RR:3.2; 95% Ci:1.5-6,7) and previous colistin use in the last three months (P=.001; RR: 3.6; 95% CI: 1.63-7.99) were significant risk factors in the multivariate analysis. CONCLUSION: Clinicians should limit the use of quinolones and remain aware of the possibility of resistance developing during colistin use. LIMITATIONS: The lack of a heteroresistance analysis on the isolates. no data on use of a loading dose or the use of colistin in combination.

Crucial parameter of the outcome in Crimean Congo hemorrhagic fever: Viral load.

BACKGROUND: Crimean Congo hemorrhagic fever (CCHF) is a fatal disease with a mortality rate of 5-30%. CCHF can be asymptomatic or it may progress with bleeding and cause mortality. OBJECTIVES: To evaluate relation of viral load with mortality, clinical and laboratory findings in CCHF. STUDY DESIGN: A total of 126 CCHF patients were included. Serum samples obtained from all patients on admission for measurement of viral load. RESULTS: In our study, mortality rate was 11.1%. The most important prognostic factor was viral load. Mean viral load was 8.3×10(7)copy/ml and 4.6×10(9)copy/ml in survived and dead patients, respectively (p<0.005). Probability of survival is found to be significantly reduced where AST >1130U/l, ALT >490U/l, CPK >505U/l, LDH >980U/l, platelet count <23×10(3)/l, creatinine >1.4mg/dl, INR >1.3, d-dimer >7100ng/dl, and viral load >1.03×10(8)copy/ml. Patients with 10(8)copy/ml or higher viral load had diarrhea, headache, unconsciousness, bleeding, and seizure significantly more frequently (p<0.05). WBC, hemoglobin, platelet counts were significantly lower whereas AST, ALT, CPK, LDH, creatinine levels, PT and aPTT time, d-dimer levels, and INR were found to be significantly higher in these group. CONCLUSIONS: There are several severity criteria for prognosis of CCHF. In addition to these parameters, we introduce creatinine as a predictive factor for prognosis. Our study, which has the largest number of patients among studies that evaluate viral load on CCHF shows that viral load is the most effective parameter on mortality.

The Knowledge of the Physicians about Sepsis Bundles is Suboptimal: A Multicenter Survey.

OBJECTIVES: Sepsis is a severe condition with possible high mortality outcomes. A multicentre-survey to detect the knowledge of the physicians who are involved in sepsis management in daily work was conducted. MATERIALS AND METHODS: The study was held in October 2013. A questionnaire consisting of questions about sepsis bundles was prepared. Eight centers from different regions of the country were invited to join the survey. The questionnaires were introduced to physicians from infectious diseases, internal diseases, emergency (ER) and anaesthesiology departments. RESULTS: Two-hundred-and-twenty-three physicians from eight different centers were included. Of total 112 (50%) were male, median age was 30 years (24-59 years). Median working duration of participants was 5 years; 153 (69%) were residents, 70 (31%) were consultants. Of total 131 (59%) declared that they have enough knowledge on sepsis management. About the most important approach in sepsis, 151 (68%) voted for fluid replacement while 59 (26%) and 13 (6%) said early antibiotic use and inotropic support are the most important approaches respectively. Physicians from ER (56.5%) and anaesthesiology departments (55.4%) were more aware of the fluid replacement element of the bundle (30ml/kg, 3-hours bundle) in severe sepsis. The ID physicians, who routinely follow sepsis patients, were not aware of the fluid resuscitation (only 20% replied the element correctly) but almost all of them answered the question on early antibiotic use and blood culture sampling correctly. The knowledge of target CVP and MAP in severe sepsis were also below expectant among ID physicians. The overall knowledge of sepsis bundles of internal medicine physicians was poor. Almost all of the ER physicians knew that they have to measure lactate level upon admission but they were not aware of the threshold of the lactate level. CONCLUSION: The knowledge of the sepsis bundles of the physicians, who are in charge of sepsis patients in routine work, was suboptimal. Most of the participants were unaware of SSC and new bundles. Training of the physicians of all centers about sepsis bundles is suggested according to these results.

Colistin alone or combined with sulbactam or carbapenem against A. baumannii in ventilator-associated pneumonia.

INTRODUCTION: Colistin use has increased over the last ten years because of multidrug-resistant microorganisms. The aim of this study was to compare the clinical and microbiological efficacy of colistin alone or in combination with sulbactam or carbapenem in the treatment of ventilator-associated pneumonia (VAP) due to multidrug-resistant (MDR) and extremely drug-resistant (XDR) A. baumannii. METHODOLOGY: Cases treated for VAP because of MDR and XDR A. baumannii between January 2011 and January 2013 were included in the study. The primary and secondary outcome for colistin alone, colistin with sulbactam, and colistin with carbapenems were evaluated. The primary outcomes were clinical efficacy and microbiological efficacy; the secondary outcomes were nephrotoxicity, length of hospitalization, and mortality. RESULTS: A total of 70 VAP patients were evaluated. A total of 17 patients (24.3%) were administered colistin alone, 20 patients (28.6%) were administered colistin and sulbactam, and 33 patients (47.1%) were administered colistin and carbapenem. Clinical and microbiological response rates were higher in the carbapenem combination group (63.6% and 63.6% in both) than in the sulbactam combination group, which registered 55.0% and 60.0%, respectively. However, this did not represent a significant difference statistically (p > 0.05). There was also no significant difference between colistin alone and the combination groups regarding clinical and microbiological efficacy and mortality. CONCLUSIONS: Neither the administration of colistin alone nor colistin combined with either sulbactam or carbapenem had any noticeable advantage in the treatment of VAP in terms of clinical response, microbiological response, nephrotoxicity, length of hospitalization, and mortality.

Tularemia during pregnancy: three cases.

Limited knowledge is available regarding tularemia in pregnancy. A total of seven tularemia cases in pregnant women have been published in the literature. This report presents three new cases. Two of these cases improved without any treatment. The third case was treated with gentamicin. All three pregnancies reached full term without complication for either mother or child.

[P. falciparum malaria related with travel: four cases]. / Seyahat Iliskili P. falciparum Sitmasi: Dört Olgu.

Malaria is still an important public health problem in the world. Although the number of malaria cases in Turkey has been declining in recent years, the febrile patients with a history of travel to the endemic regions should raise the suspicion of malaria. P. vivax is the most common cause of malaria in Turkey; and those caused by other Plasmodium spp. are imported cases. Since P. falciparum malaria may cause fatal complications, urgent therapy is necessary. We hereby report four falciparum malaria cases with a history of travel to Sudan and Uganda.

Relationship between total thiol status and thrombocytopenia in patients with Crimean-Congo hemorrhagic fever.

The objective of this study was to investigate the relationship between serum total thiol level and total oxidant status (TOS) and thrombocytopenia among patients with Crimean-Congo hemorrhagic fever (CCHF). Eighty-three subjects and 56 controls were enrolled in the study. Thiol levels were measured with the DTNB method and TOS was measured with the Erel's method among subjects and controls. Thiol levels were lower in subjects than controls and TOS levels were higher in subjects than controls. There was a significant correlation between total thiol levels and platelet counts (r = 0.84, p < 0.0001) among subjects. Further investigations are needed into the link between total thiol level and TOS and the pathogenesis of hemorrhage in CCHF.

Correlation between intrahepatic hepatitis B virus cccDNA levels and other activity markers in patients with HBeAg-negative chronic hepatitis B infection.

OBJECTIVE: The aim of this study was to demonstrate the relation between intrahepatic (IH) hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) levels and the other HBV replicative intermediates and hepatocyte expression of HBV antigens. PATIENTS AND METHODS: Patients with hepatitis B surface antigen (HBsAg) positivity, hepatitis B early antigen negativity, serum HBV DNA levels 10 copies/ml or more, and constantly or intermittently increased alanine aminotransferase levels were included. RESULTS: Fifty-nine patients were included. There was a good correlation between the levels of IH HBV cccDNA and serum HBV DNA (P<0.001). Serum HBsAg levels were weakly correlated with IH HBV cccDNA levels and moderately correlated with serum HBV DNA (r=0.322, P=0.017; r=0.489, P=0.001, respectively). There were no significant correlation between serum HBsAg level and histologic activity index groups (P=0.691), but stage 0, 1, and greater than 2 fibrosis groups were positively correlated with serum HBsAg levels (P=0.019). IH cccDNA and serum HBV DNA were significantly different in hepatitis B core antigen staining groups (P=0.008 and <0.001, respectively) but there was no significant correlation between HBsAg staining groups and HBV replication markers. There was a weak correlation between serum HBsAg levels and IH HBsAg and hepatitis B core antigen levels (r=0.333, P=0.012; r=0.366, P=0.006, respectively). In multivariate analysis, alanine aminotransferase, age, fibrosis stage, and serum HBsAg quantitation were the most important factors predicting IH HBV cccDNA level. CONCLUSION: Histopathologic damage, serum HBV DNA levels, and IH HBV replication markers have a more complex and dynamic process. However, both serum and IH HBV replication markers provide important knowledge about the activity of the disease.

Crimean-Congo hemorrhagic fever in Eastern Turkey: clinical features, risk factors and efficacy of ribavirin therapy.

OBJECTIVES: This study described the clinical features, factors affecting the outcome of this disease, risk factors, and efficacy of ribavirin therapy for CCHF patients in Eastern Turkey. METHODS: Between 2002 and 2004, 60 cases admitted to our hospital were included in this study. The diagnosis was confirmed through detection of IgM by ELISA and/or genomic segment of virus by RT-PCR. RESULTS: In multivariate analysis, farming (OR, 11.4), living in a rural area (OR, 10.05) and being bitten by tick (OR, 6.75) were determined as risk factors for CCHF. The rates of fever during hospitalization, confusion, neck stiffness, bleeding from multiple sites, and presence of petechia/ecchymosis were higher in the patients who died than in surviving ones. Additionally, the mean values of ALT, AST, LHD, CK, PTT, INR and urea were also higher, and the mean PLT count was lower in the patients who died. Mean recovery time was shorter in the cases treated with ribavirin than those of control. But, the need for blood and blood product, mean hospitalization duration, fatality rates, and hospital expenditure values were not significantly different between the group of patients treated with ribavirin and control groups. CONCLUSIONS: In Eastern Turkey, clinical features, factors influencing outcome of the disease, and risk factors were similar to other outbreaks of CCHF. Further studies are needed for the evaluation of ribavirin therapy in CCHF.

Changes in antibiotic use, cost and consumption after an antibiotic restriction policy applied by infectious disease specialists.

The study was designed to compare antibiotic use, cost and consumption before and after an initiation of an antibiotic-restriction policy in our hospital. The policy was applied in 2003, and the prescription of two groups of antibiotics (intravenously used and expensive antibiotics) was restricted. A prescription for the restricted antibiotics could be obtained with approval by an infectious disease specialist (IDS). All the hospitalized patients who received antibiotics were evaluated by a cross-sectional study with standard criteria. The annual cost and consumption of antibiotics were evaluated. After restriction, the rate of antibiotic use decreased from 52.7 to 36.7% (P < 0.001), and the appropriate use increased from 55.5 to 66.4% (P < 0.05). Appropriate use was higher for restricted antibiotics (88.4%) than for unrestricted ones (58.2%) (P < 0.001), and higher in the presence of ID consultation (97.5%) than in the absence of consultation (55.7%) (P < 0.001). Culture-based treatment was increased, and appropriate use in such cases (93.0%) was higher than empirical treatment (33.3%) (P < 0.001). After the restriction policy, consumption of antibiotics belonging to the restricted groups was decreased by 44.8%. Total expenditure of all antibiotics was decreased by 18.5%, and the savings were US$332,000 per year. This restriction policy was effective in promoting rational antibiotic prescription and lowering antibiotic cost and consumption in our hospital.

[A transfusion-transmitted malaria case]. / Transfüzyonla bulasan bir sitma olgusu.

Malaria is a rare but potentially serious complication of blood transfusion. In this report a transfusion-transmitted malaria case has been presented. A 47-years-old woman admitted to our clinic with the complaints of striking fever with chills, diarrhea and vomiting. She had history of an operation and transfusion before 10 days of admission. On physical examination jaundice, splenomegaly and abdominal tenderness were detected. Laboratory results revealed anemia, and elevated LDH and bilirubin levels. Examination of thin blood films yielded Plasmodium vivax trophozoites. Chloroquine was initiated for therapy and the patient was successfully treated. On the other hand, informations about her blood donor indicated that he had been in the military service in Southeast Anatolia of Turkey where malaria is endemic. All the efforts to reach the donor, for his diagnosis and treatment, were failed. Since our region (Northeast Anatolia) is not an endemic area for malaria and the patient had no travel history to an endemic area, it has been considered that the transmission route of malaria in this case was blood transfusion. In conclusion, as there are no available approved tests for malaria screening of donations, the transfusion-transmitted malaria can only be prevented by careful questioning of the donors.

Crimean-Congo haemorrhagic fever outbreak in Middle Anatolia: a multicentre study of clinical features and outcome measures.

A Crimean-Congo haemorrhagic fever (CCHF) outbreak emerged from 2001 to 2003 in the Middle Anatolia region of Turkey. This study describes the clinical characteristics and outcome features of CCHF patients admitted to four tertiary care hospitals in Turkey. Definitive diagnosis was based on the detection of CCHF virus-specific IgM by ELISA or of genomic segments of the CCHF virus by RT-PCR. Related data were collected by a retrospective chart review. Hospital costs were extracted from the final discharge bills. Univariate and multivariate analyses were conducted to determine the independent predictors of mortality. CCHF virus-specific antibodies or genomic segments were detected in the sera of 99 cases. Seven cases that were treated with ribavirin were excluded from the study. Cases were mostly farmers (83 cases, 90 %), and 60 % had a tick-bite history before the onset of fever. Impaired consciousness and splenomegaly were independent predictors of a fatal outcome.

Anthrax during pregnancy: case reports and review.

We review, in detail, 2 cases of anthrax during pregnancy, its maternal and perinatal complications, and its management. Patient 1 was a 33-year-old woman at 32 weeks of gestation. She had a submandibular eschar; extensive edema on her face, neck, and upper thorax that inhibited respiratory function; and fever. The patient was treated with penicillin G and prednisolone after the diagnosis of anthrax. She recovered within 10 days but delivered a preterm baby. Patient 2 was a 29-year-old woman at 33 weeks of gestation. Her anthrax lesion was on her right elbow, and therapy consisted of procaine penicillin. She also delivered a preterm baby. These 2 cases show that anthrax during pregnancy can be successfully managed, but preterm delivery could be a complication.

Intrafamilial transmission of hepatitis B virus in the eastern Anatolian region of Turkey.

OBJECTIVE: To determine the possible route of hepatitis B virus (HBV) transmission throughout a family setting. METHOD: Two hundred and forty family members (42 spouses, 32 offspring, 34 mothers, 35 fathers and 97 siblings) of 84 HBsAg carriers attending the Ataturk University Medical Faculty Hospital between July 2000 and May 2001, and 384 first time blood donors (control group) were screened prospectively for markers of HBV by using an ELISA. The chi-squared and Fisher's exact tests were used for statistical analysis. RESULTS: The prevalence of HBsAg and HBV infection among the family members (29.6% and 43.8%, respectively) was significantly higher than in the control group (9.6%, and 29.7%), P < 0.001. Among family members, the highest prevalences of HBsAg and HBV infection were in the husbands (70.0% and 90.0%, respectively), offspring (66.7% and 100.0%) of female index cases, and siblings (40.2% and 49.5%, respectively) of all index cases. Transmission of HBV to offspring was high in cases where both the parents were positive, but there was no difference in cases where only the mother or father was positive. Despite a high prevalence of HBsAg in the offspring of female index cases, HBsAg and anti-HBs seroprevalences in the mothers of index cases were not higher than the control group (P < 0.05). Thus, it appears that mothers do not have an important role in the acquisition of HBV infection. CONCLUSION: In the area studied, in addition to the sexual route, both parents-to-child and sibling-to-sibling horizontal transmission might be the main route of intrafamilial spread of HBV infection.