Ilyas Dokmetas

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.

The relation between serum leptin levels and body fat mass in patients with active lung tuberculosis.

The relationship of leptin to diminished appetite and weight loss has been investigated in many diseases. Diminished appetite and weight loss are the most apparent characteristics of patients with active lung tuberculosis and in this study the relation of leptin to such diminished appetite and weight loss has been investigated in patients with active lung tuberculosis before and after treatment. Twenty‐five patients (7 female, 18 male) with active tuberculosis having an age range of 18–70 years (mean 47.48 ± 15.36 y) and 25 normal individuals (9 female, 16 male) having an age range of 25–71 years (mean 44.60 ± 13.80 y) were included in this study. Leptin levels, body mass index (BMI), body fat ratio (BFR), and waist hip ratio (WHR) were measured before and after 6 months of antituberculosis treatment. The same measurements were also made in the control group and the results were compared. While the pretreatment BMI (22.02 ± 4.31 kg/m2) and BFR (16.60% ± 9.30%) values in the patient group were significantly lower than in the control group, we found no difference in their pretreatment WHR values. Pretreatment leptin levels (3.49 ± 3.34 µg/L) were significantly higher in patients with tuberculosis than in the control group (2.33 ± 1.10 µg/L). Leptin levels were found to be significantly increased at the 6th month of antituberculosis treatment (5.65 ± 5.41 µg/L) than the pretreatment values (p < 0.05). We observed an evident increase in BMI (24.10 ± 4.87 kg/m2) and BFR (17.51% ± 9.25%) due to antituberculosis treatment (p < 0.05). This study suggests that leptin has a role in the diminished appetite and weight loss symptoms in patients with active lung tuberculosis.

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.

Antimicrobial Susceptibility of Bacillus anthracis in an Endemic Area

We aimed to test the antimicrobial susceptibility of 28 Bacillus anthracis strains isolated from cutaneous anthrax cases to various antimicrobial agents using the Sceptor automatic system in an anthrax endemic area. All strains tested were susceptible to penicillin (MIC ≤⃒ 0.03 μg/ml). Piperacillin-tazobactam and carbapenems showed good activity towards all strains. Trimethoprim-sulfamethoxazole and cefepime had no activity. Strains were also tested with other antimicrobials.

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.

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.

Miliary tuberculosis: Epidemiologicaland clinical analysis of large-case series from moderate to low tuberculosis endemic Country

Abstract The aim of this study was to determine the clinical features, and outcome of the patients with miliary tuberculosis (TB). We retrospectively evaluated 263 patients (142 male, 121 female, mean age: 44 years, range: 16–89 years) with miliary TB. Criteria for the diagnosis of miliary TB were at least one of the followings in the presence of clinical presentation suggestive of miliary TB such as prolonged fever, night sweats, anorexia, weight loss: radiologic criterion and pathological criterion and/or microbiological criterion; pathological criterion and/or microbiological criterion. The miliary pattern was seen in 88% of the patients. Predisposing factors were found in 41% of the patients. Most frequent clinical features and laboratory findings were fever (100%), fatigue (91%), anorexia (85%), weight loss (66%), hepatomegaly (20%), splenomegaly (19%), choroid tubercules (8%), anemia (86%), pancytopenia (12%), and accelerated erythrocyte sedimentation rate (89%). Tuberculin skin test was positive in 29% of cases. Fifty percent of the patients met the criteria for fever of unknown origin. Acid-fast bacilli were demonstrated in 41% of patients (81/195), and cultures for Mycobacterium tuberculosis were positive in 51% (148/292) of tested specimens (predominantly sputum, CSF, and bronchial lavage). Blood cultures were positive in 20% (19/97). Granulomas in tissue samples of liver, lung, and bone marrow were present in 100% (21/21), 95% (18/19), and 82% (23/28), respectively. A total of 223 patients (85%) were given a quadruple anti-TB treatment. Forty-four (17%) patients died within 1 year after diagnosis established. Age, serum albumin, presence of military pattern, presence of mental changes, and hemoglobin concentration were found as independent predictors of mortality. Fever resolved within first 21 days in the majority (90%) of the cases. Miliary infiltrates on chest X-ray should raise the possibility of miliary TB especially in countries where TB is endemic. Although biopsy of the lungs and liver may have higher yield rate of organ involvement histopathologicaly, less invasive procedures including a bone marrow biopsy and blood cultures should be preferred owing to low complication rates.

Treatment of Tuberculous Meningitis in Adults with a Combination of Isoniazid, Rifampicin and Streptomycin: A Prospective Study

15 patients with tuberculous meningitis were treated with isoniazid, streptomycin and rifampicin and 14 with isoniazid, streptomycin and ethambutol for 12 months. Both groups received prednisolone at the beginning of treatment. The two groups were compared with regard to clinical improvement, presence of neurological sequelae and mortality. No difference in recovery rate between the groups was observed. 6 patients (21%) died (5 in group I and 1 in group II). Residual sequelae developed in 9 cases (5 in group I and 4 in group II; 31%). The difference between the groups was not significant. The regimen including rifampicin for tuberculous meningitis did not result in any superiority compared to standard therapy.

Relationship between IFNA1, IFNA5, IFNA10, and IFNA17 gene polymorphisms and Crimean-Congo hemorrhagic fever prognosis in a Turkish population range.

Crimean‐Congo hemorrhagic fever (CCHF) is a fatal emerging acute viral infection. Not much is known regarding the pathogenic mechanisms and the reasons behind severe or mild disease courses in CCHF. IFN‐alpha (IFNA) is one of the essential cytokines in the immune system. Existence of single nucleotide gene polymorphisms (SNPs) in cytokines can cause susceptibility or resistance to viral agents and different clinical courses. Hence, the relationship between SNPs in genes encoding cytokines (IFNA1 ‐1823G/A (rs1332190), IFNA5 ‐2529T/A (rs758236), IFNA10 Cys20stop (rs10119910), and IFNA17 Ile184Arg (rs9298814) SNPs and disease susceptibility were investigated. The associations between SNPs and CCHF prognosis were also studied. Total 150 patients with CCHF and 170 healthy individuals were enrolled. Genotyping was performed by PCR‐RFLP methods. The frequency of IFNA1 ‐1823 (rs1332190) GG genotype was significantly higher in control subjects than CCHF patients (20% vs. 8%; P = 0.01). For IFNA17 Ile184Arg (rs9298814) polymorphism, CCHF patients having TG genotype had a higher frequency than the control subjects (38% vs. 32.4%; P = 0.039). The distribution of TT + TG genotype frequencies was also significantly higher in CCHF group than the controls (97.3% vs. 91.8%; P = 0.049). Genotype and allele frequencies for IFNA subtypes between fatal and survivors were the same (P > 0.05). Genotype and allele frequencies between severe and mild/moderate CCHF patients were also the same (P > 0.05). The results show that IFNA1 rs1332190 and IFNA17 rs9298814 SNPs may play an important role in CCHF susceptibility. Determining the existence of other connections for IFNA SNPs and CCHF severity and fatality requires further investigations. J. Med. Virol. 88:1159–1167, 2016.