Sequential determination of viral load, humoral responses and phylogenetic analysis in fatal and non-fatal cases of Crimean-Congo hemorrhagic fever patients from Gujarat, India, 2019.

BACKGROUND: Thirty-four CCHF cases (17 fatal; 17 survived) were confirmed from Gujarat state, India during the year 2019. We aimed to find out the viral load, antibody kinetics, cytokine profile and phylogenetic analysis between fatal and non- fatal cases. METHODS: Thirty four cases were included in this study. Blood and urine samples were collected from all the cases on the day of admission to hospital. Non-fatal cases were followed weekly for understanding the profile of viral kinetics, anti-CCHFV IgM and IgG antibodies. We also quantified the cytokines in both fatal and non-fatal cases. For epidemiological correlation, livestock were screened for anti-CCHF IgG antibodies and the tick pool specimens were tested by real time RT-PCR. Virus isolation was attempted on tick pools and human specimens and phylogenetic analysis performed on human and ticks complete genome sequences. RESULTS: CCHF cases were detected throughout year in 2019 with the peak in August. Out of 34 cases, eight secondary CCHF cases were reported. Cases were predominantly detected in males and in 19-45 years age group (55.88%). The persistence of viremia was observed till 76th POD (post onset date) in one case whereas anti-CCHFV IgM and IgG was detected amongst these cases from the 2nd and 20th POD respectively. Positivity observed amongst livestock and tick pools were was 21.57% and 7.4% respectively. The cytokine analysis revealed a significant increase in the level of serum IL-6, IL-10 and IFN-γ during the acute phase of the infection, but interestingly IL-10 lowered to normal upon clearance of the virus in the clinically recovered case. Fatal cases had high viral RNA copy numbers. Bleeding from one or two mucosal sites was significantly associated with fatality (OR-16.47;p-0.0034 at 95% CI). We could do CCHF virus isolation from two cases. Phylogenetic analysis revealed circulation of re-assortment of Asian-West African genotypes in humans and ticks. CONCLUSIONS: The persistence of CCHF viral RNA was detected till 76th POD in one of the survivors. The circulation of a re-assortment Asian-West African genotype in a CCHF case is also reported first time from India.

Therapeutic plasma exchange for envenomation: Is it reasonable?

BACKGROUND AND OBJECTIVES: The incidence of poisoning due to snakebite and Crimean Congo Hemorrhagic Fever (CCHF), referred to as 'envenomation', varies according to the region, and many deaths occur every year. Therapeutic plasma exchange (TPE) is a method of extracorporeal blood purification that clears toxins and virus load from the circulation. Therefore, its use has been increasing recently in envenomation cases. However, there are a limited number of studies on poisoning due to snakebite and CCHF. In the present study, we share our TPE experience retrospectively in patients diagnosed with poisoning due to snakebite and CCHF between 2010 and 2019. MATERIALS AND METHODS: A total of 26 patiens, including 20 patients with poisoning due to snakebite and 6 CCHF patients were treated with TPE. Demographic data, clinical status, and outcomes of patients were recorded. Routine biochemical and hematologic laboratory parameters were analyzed before and after TPE. TPE was performed by using centrifugation technology via a central venous catheter. Fresh frozen plasma was used as replacement fluid. RESULTS: An average of 3.95 (1-11) apheresis sessions were applied to patients poisoned due to snakebite, and 19 patients (95 %) were discharged in an average of 8.3 (1-17) days without any complications. None of the patients enrolled in the study lost their limbs. Only one patient died due to disseminated intravascular coagulopathy. Six patients with CCHF who received 5 sessions of TPE on average were discharged successfully after an average of 6.5 days. No adverse events or complications were observed in any patient after TPE. CONCLUSIONS: TPE is a good alternative and a reliable method in treating envenomation cases who are refractory to supportive measures. TPE should be performed without delay in cases of poisoning due to snakebite and CCHF.

Development of double antibody sandwich ELISA as potential diagnostic tool for rapid detection of Crimean-Congo hemorrhagic fever virus.

Crimean-Congo hemorrhagic fever (CCHF) virus, a highly pathogenic viral agent is responsible for severe fatal hemorrhagic infections in many parts of the world. The early diagnosis of CCHF infection is important for successful clinical management and epidemiological control. The nucleoprotein (NP) of CCHFV being highly conserved and immunogenic is used as early diagnostic marker. In this study, we report a rapid and sensitive double antibody based antigen capture ELISA to detect Crimean-Congo hemorrhagic fever virus (CCHFV). Highly specific polyclonal and monoclonal antibody against NP has been generated and used as capture and detector antibody respectively. The assay was able to detect viral nucleoprotein in different matrices including human serum, ticks and culture supernatant. The detection limit of the developed sandwich ELISA assay was 25 ng of purified antigen. Comparison with a real time RT-PCR revealed its detection limit to be 1000 genome equivalents of CCHFV. Further the assay was comparatively evaluated with a commercial kit employing gamma irradiated CCHFV, revealing a sensitivity and specificity of 100%. This newly developed sandwich ELISA (sELISA) with high sensitivity and specificity could be used as an efficient method for the detection of CCHF virus in humans, ticks and culture supernatant. The assay will be useful as alternate tool for diagnosis of acute infection and is amenable for screening of large scale samples in resource limited settings.

Serologic and molecular evidence for circulation of Crimean-Congo hemorrhagic fever virus in ticks and cattle in Zambia.

Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne zoonosis with a high case fatality rate in humans. Although the disease is widely found in Africa, Europe, and Asia, the distribution and genetic diversity of CCHF virus (CCHFV) are poorly understood in African countries. To assess the risks of CCHF in Zambia, where CCHF has never been reported, epidemiologic studies in cattle and ticks were conducted. Through an indirect immunofluorescence assay, CCHFV nucleoprotein-specific serum IgG was detected in 8.4% (88/1,047) of cattle. Among 290 Hyalomma ticks, the principal vector of CCHFV, the viral genome was detected in 11 ticks. Phylogenetic analyses of the CCHFV S and M genome segments revealed that one of the detected viruses was a genetic reassortant between African and Asian strains. This study provides compelling evidence for the presence of CCHFV in Zambia and its transmission to vertebrate hosts.

Evaluation of neutrophil to lymphocyte ratio in predicting the prognosis of Crimean-Congo haemorrhagic fever.

Crimean-Congo haemorrhagic fever (CCHF) is a severe form of haemorrhagic fever identified in parts of Africa, Asia, Eastern Europe and the Middle East. CCHF continues to be a justifiable cause of concern for people in rural areas where the disease is endemic. A total of 151 patients, diagnosed with CCHF, were evaluated retrospectively. The demographic characteristics of these patients and the relationship between the neutrophil-lymphocyte ratio (NLR) at admission and survival were examined. There were 21 (13.9%) deaths. There was no relationship between age, gender and mortality, but elevated neutrophil-lymphocyte ratio (NLR) on admission was statistically associated with mortality. NLR is a laboratory marker that can be studied even in medical centres with limited facilities and may be helpful in predicting the clinical course of the disease.

Purification of Crimean-Congo hemorrhagic fever virus nucleoprotein and its utility for serological diagnosis.

Crimean-Congo hemorrhagic fever virus (CCHFV) causes a zoonotic disease, Crimean-Congo hemorrhagic fever (CCHF) endemic in Africa, Asia, the Middle East, and Southeastern Europe. However, the prevalence of CCHF is not monitored in most of the endemic countries due to limited availability of diagnostic assays and biosafety regulations required for handling infectious CCHFV. In this study, we established a protocol to purify the recombinant CCHFV nucleoprotein (NP), which is antigenically highly conserved among multiple lineages/clades of CCHFVs and investigated its utility in an enzyme-linked immunosorbent assay (ELISA) to detect CCHFV-specific antibodies. The NP gene was cloned into the pCAGGS mammalian expression plasmid and human embryonic kidney 293 T cells were transfected with the plasmid. The expressed NP molecule was purified from the cell lysate using cesium-chloride gradient centrifugation. Purified NP was used as the antigen for the ELISA to detect anti-CCHFV IgG. Using the CCHFV NP-based ELISA, we efficiently detected CCHFV-specific IgG in anti-NP rabbit antiserum and CCHFV-infected monkey serum. When compared to the commercially available Blackbox CCHFV IgG ELISA kit, our assay showed equivalent performance in detecting CCHFV-specific IgG in human sera. These results demonstrate the usefulness of our CCHFV NP-based ELISA for seroepidemiological studies.

Investigation of NEAT1, IFNG-AS1, and NRIR expression in Crimean-Congo hemorrhagic fever.

Crimean-Congo hemorrhagic fever (CCHF), whose causative agent is CCHF orthonairovirus (CCHFV), demonstrates different symptoms in patients. Long noncoding RNAs (lncRNAs) take part in various pathological processes of viral diseases. They are prominent regulators of antiviral immune responses. To our knowledge, this study is the first study to investigate nuclear paraspeckle assembly transcript 1 (NEAT1), interferon (IFN) gamma antisense RNA 1 (IFNG-AS1), and negative regulator of IFN response (NRIR) expression in CCHF in the literature. We selected these lncRNAs because they are related to IFN signal or IFN-stimulated genes. We investigated NEAT1, IFNG-AS1, and NRIR gene expression in patients with CCHF. Total RNA was extracted from blood samples of 100 volunteers and NEAT1, IFNG-AS1, and NRIR expression were measured using a quantitative real-time polymerase chain reaction. NRIR expression was statistically significant in cases versus controls (p < .001), fatals versus controls (p < .001), and fatals versus nonfatals (p = .01). Furthermore, NRIR was found statistically significant at some clinical parameters including alanine aminotransferase (p = .03), international normalized ratio (p = .03), prothrombin time (p = .02), and active partial thromboplastin time (p = .01) in CCHF cases. NEAT1 and IFNG-AS1 expression were downregulated in the case and fatal groups which were compared with controls. Our results demonstrate that NRIR may be important in CCHF pathogenesis and the target of CCHF treatment.

Identification of a novel lineage of Crimean-Congo haemorrhagic fever virus in dromedary camels, United Arab Emirates.

Crimean-Congo haemorrhagic fever virus (CCHFV) is a tick-borne virus causing Crimean-Congo haemorrhagic fever (CCHF), a disease reported to have a high fatality rate in numerous countries. The virus is geographically widespread due to its vector, and numerous wild and domestic animals can develop asymptomatic infection. Serological and limited molecular evidence of CCHFV has previously been reported in Camelus dromedarius (the dromedary, or one-humped camel) in the United Arab Emirates (UAE). In this study, 238 camel samples were screened for CCHFV RNA where 16 camel samples were positive for CCHFV by RT-PCR. Analysis of full-length CCHFV genome sequences revealed a novel lineage in camels from the UAE, and potential reassortment of the M segment of the genome.

Seroprevalence of Crimean-Congo Hemorrhagic Fever in Domesticated Animals in Northwestern Senegal.

Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne disease that can be contracted by direct contact with viremic animals or humans. In West Africa, recurrent CCHF outbreaks have been constantly observed in Mauritania and Senegal. Moreover, acquisition and epidemiology of the infection in humans are correlated with the occurrence and the seroprevalence of the virus in livestock. The main objective of this study is to provide updated information on the local spread of CCHF in animals in the northern region of Senegal. Out of a total of 283 animal sera collected, CCHF-specific antibodies were identified in 92 (32.5%; confidence interval [CI]95% 27.1-38.3) sera by double antigen sandwich enzyme-linked immunosorbent assay (ELISA) test. The prevalence of CCHF virus (CCHFV) infection among horses, cattle, sheep, dogs, donkeys, and goats was 70.3% (45/64), 57.1% (8/14), 22.1% (30/136), 18.2% (2/11), 17.2% (5/29), and 6.9% (2/29), respectively. The antibody titers were found significantly affected by age (p < 0.0001) and gender (p < 0.05). High tick infestation by Rhipicephalus spp. and Hyalomma spp. was recorded on horses. The high seroprevalence to CCHFV among animals in the northern region of Senegal observed in this study indicates the permanent presence of the infection in the northern region of the country suggesting the need to strengthen surveillance plans for CCHF in Senegal.

Descriptive epidemiology of Crimean-Congo Hemorrhagic Fever (CCHF) in Afghanistan: Reported cases to National Surveillance System, 2016-2018.

OBJECTIVE: This study aims to provide descriptive epidemiology of human CCHF cases in Afghanistan by demographic, geographical, and seasonal characteristics. METHODOLOGY: This paper's findings are based on the retrospective analysis of the National Surveillance System's collected data from 2016 to 2018. Weekly cases exceeding the 90th percentile of the expected number of cases were considered to be exceptional and above normal. RESULTS: The National Surveillance System detected 1,284 CCHF cases from 2007 to 2018, of which 163 cases were in 2016, 245 cases in 2017 and 483 cases in 2018. A total of 891 suspected and confirmed cases were reported between 2016 and 2018, 293 (33%) of these cases were confirmed by detecting IgM antibody using ELISA and RT-PCR. Among confirmed cases, the three-year case fatality ratio (CFR) was 43.3%. Among the reported cases, 68.5% were males and 31.5% females. The frequent reported occupational groups were housewives (15%), health staff (13%), shepherds (11%), butchers (6%), students (6%), animal dealers and farmers (both 2%) respectively, 19% were unemployed, and occupation was not recorded for 26% of cases. CONCLUSION: Recently, CCHF has significantly increased in Afghanistan. Despite the increased frequency of cases, the laboratory capacity to test specimens and overall knowledge of CCHF management remains limited.

The relationship with clinical course and prognosis of serum endothelin-1, angiopoietin-2, and tie-2 levels in Crimean-Congo hemorrhagic fever

Background/aim: Crimean-Congo hemorrhagic fever (CCHF) is a serious illness characterized by fever and hemorrhage. Endothelin-1 (ET-1), angiopoietin-2 (Ang-2), and endothelial cell-specific receptor tyrosine kinase (Tie-2) are believed to be important markers of the pathogenesis, clinical course, and prognosis of the disease. The aim of this study was to determine ET-1, Ang-2, and Tie-2 levels in adults with CCHF and investigate the associations between these markers and pathogenesis and disease course. Materials and methods: Sixty CCHF patients were included in the study. The patients were classified according to disease severity criteria and Ang-2, Tie-2, and ET-1 levels were compared. Results: Mean serum ET-1 level was 36.62 ± 27.99 pg/mL in the patient group and 3.70 ± 4.71 pg/mL in the control group (P = 0.001). Mean serum Ang-2 levels were 2511.18 ± 1018.64 pg/mL in the patient group and 3570.76 ± 209.52 pg/mL in the control group (P = 0.001). Mean serum Tie-2 levels were 7.35 ± 7.75 ng/mL in the patient group and 0.67 ± 1.26 ng/mL in the control group (P = 0.001). Conclusion: Elevated ET-1 and Tie-2 levels were associated with more severe disease course, while Ang-2 level was negatively correlated with severity in adult CCHF patients. ET-1, Tie-2, and Ang-2 levels are important prognostic parameters in CCHF and may contribute significantly to treatment and follow-up.

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.

Identification of potential microRNA markers related to Crimean-Congo hemorrhagic fever disease.

Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne disease caused by the arbovirus Crimean-Congo hemorrhagic fever virus (CCHFV). The CCHFV has a single-stranded RNA genome of negative sense. MicroRNAs (miRNAs) are key players in virus-host interactions and viral pathogenesis. We investigated the miRNA gene expression profiles in patients with CCHF using microarray for the first time in the world. Microarray analysis was performed using mirBase Ver 21 (Agilent Technologies, Santa Clara, CA). All statistical analyses were performed across the case-control, fatal-control, and fatal-nonfatal case groups using Genespring (Ver 3.0). Fifteen miRNAs were statistical significant in patients with CCHF compared with the controls (5 were upregulated, 10 were downregulated). Seventy-five and sixty-six miRNAs are in fatal compared with control and nonfatal case, respectively (fold change ([FC] ≥50) were statistically significant. In this study, the target genes of important miRNAs were identified and Gene Ontology analyses were performed across all groups. As a result of this study, we propose that the detection of miRNAs in patients with CCHF will allow the determination of therapeutic targets in diseases. CCHF is an important public health problem that can often be fatal. In this study, we investigated miRNA expression in case-control, fatal-control, and fatal-nonfatal case groups. Significant miRNAs associated with fatality were detected in CCHF. This study will serve as a source of data for the development of an antagomir-based therapy against CCHF using miRNAs in the future.

Crimean-Congo hemorrhagic fever (CCHF) seroprevalence: A systematic review and meta-analysis.

Crimean-Congo haemorrhagic fever (CCHF) is the most widespread, tick-borne viral disease affecting humans and therefore this paper performed a meta-analysis to highlight seroprevalence features of CCHF in a global context. After a preliminary review of the 396 papers representing areas throughout the world, 206 were selected for detailed meta-analysis. In general the total means of CCHF seroprevalence were, respectively 4.7 and 24.6% for humans and animals; and 17.1, 18.9, 24.3, 29.3 and 27.1% for camels, cattle, goats, sheep and livestock. Statistical analysis revealed a significant difference in seroprevalence between humans and camels (P = 0.043), cattle (P = 0.010), goats (P = 0.015), sheep (P = 0.005) and livestock (P = 0.017). Regionally, there also was a difference between humans, and goats (P = 0.0001), sheep (P = 0.007) and livestock (P = 0.002). Globally, CCHF seroprevalence in at-risk professionals was 7.5 fold greater than in normal humans, while CCHF seroprevalence was 5 fold greater in animals, camels, cattle, goats, sheep and livestock than normal humans. Animal contact, animal husbandry, farming, tick bite history and secretion exposure were the most frequently reported CCHF seropositivity risk factors. This study serves as an important resource for epidemiological discussions related to CCHF and CCHF seroprevalence features, providing specific information in understanding human and animal mean and trend CCHF seroprevalence for different regions of the world and on an aggregate global scale; seroprevalence in at-risk professionals; and total mean and trend CCHF seropositivity involving risk factors.

Crimean Congo Hemorrhagic Fever in Eastern Turkey: Epidemiological and Clinical Evaluation

Objective: The present study aimed to evaluate Crimean-Congo Haemorrhagic Fever (CCHF) in patients hospitalized in our hospital. Methods: A total of 61 adult patients who were diagnosed as having CCHF between January 2011 and August 2018, in whom the diagnosis was confirmed by detecting virus-specific IgM by ELISA and/or by showing viral RNA by RT-PCR and who were managed at our clinic were evaluated retrospectively for their epidemiological and clinical findings, treatment and prognosis. Results: Of the 61 cases, 41 (67.2%) were male and 20 (32.8%) female. The mean age of the patients was 45.31±2.12 years. Sixty (98.4%) patients were living in rural area. Forty four patients (72.1 %) had a tick-bite history. According to months, most of the cases were seen in June, July and May, respectively. Fever, weakness and loss of appetite were the most common complaints of the patients. Treatment of ribavirin was started on the day of admission in all patients. One patient who was admitted in the late period died. The other 60 patients were discharged after being healed. Conclusions: Especially during summers when the disease is seen frequently, the history of tick contact should be questioned and tick should be searched in the examination in the patients with suspected clinical findings. A significant number of the patients do not have a known tick contact. Therefore, training meetings should be organized about the symptoms and findings of the disease in the endemic areas and awareness should be raised among the community and the doctors working in emergency services and primary care.

Elevated Human Crimean-Congo Hemorrhagic Fever Virus Seroprevalence in Khashm el Girba, Eastern Sudan.

Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne disease that can evolve into deadly hemorrhagic fever and that is endemic in many parts of Europe, Middle East, Central Asia, and Africa. Because of several reports about CCHF outbreaks in the south of Sudan during the last years, we examined in this study if unrecognized CCHF-V infections also occurred in the eastern and central parts of the country. The study examined the seroprevalence of CCHF virus infection in 464 sera from three regions of Sudan without previous reports of CCHF infection. The total CCHF virus seroprevalence was 2.6% (12 sera). The percentage was significantly elevated (7.5%) in sera from Khashm el Girba in eastern Sudan. The population in this area should be educated about the risk of disease transmission and how to avoid the infection. Health-care providers should be informed about the disease to identify possible cases and to prevent nosocomial transmission.

Effects of platelet function on the haemorrhagic manifestations and mortality in Crimean-Congo haemorrhagic fever.

Crimean-Congo haemorrhagic fever (CCHF) is a viral zoonotic disease which can lead to life-threatening with haemorrhagic manifestations. We aimed here in this study was to evaluate the effect of the platelet count and volume-related indices, such as the mean platelet volume (MPV), platelet distribution width (PDW) which is a measure of platelet anisocytosis and plateletcrit, in the haemorrhagic manifestations and mortality seen in CCHF cases. We retrospectively examined data derived from 173 patients. The age, gender, alanine transaminase (ALT), aspartate transaminase (AST), platelet counts and MPV, PDW and PCT values upon admission (MPV1, PDW1 and PCT1) and those values measured at the time when the PLT was at the lowest level (MPV2, PDW2 and PCT2), haemorrhagic manifestations and the mortality status of patients diagnosed with CCHF were recorded. ALT and AST values were higher among the haemorrhagic patients when compared with the others (p<0.001), while platelet 1 (PLT1), platelet 2 (PLT2), plateletcrit 1 (PCT1), plateletcrit 2 (PCT2) and platelet distribution width 2 (PDW2) values were significantly lower (p=0.001, p<0.001, p=0.002, p<0.001 and p=0.003, respectively). A negative correlation was documented between haemorrhage and the PLT1, PLT2, PCT1, PCT2 and PDW2 (r=-0.255, r=-0.415, r=-0.241, r=-0.377, r=-0.223, respectively); however, there was a positive correlation between haemorrhage and mortality (r=0.34). This was the first study evaluating the platelet functions in CCHF, such as the PLT, PDW and PCT, in CCHF correlated with the mortality and haemorrhagic manifestations. The platelet functions contribute as much to the prediction of haemorrhage and mortality as the PLT. The present study suggests that the PCT and PDW values could be beneficial in anticipating the inclination toward haemorrhage and mortality.

Crimean-Congo hemorrhagic fever with hepatic impairment and vaginal hemorrhage: a case report.

BACKGROUND: Crimean-Congo hemorrhagic fever is a tick-borne disease described in more than 30 countries in Europe, Asia, and Africa. Albania is located in the southwestern part of the Balkan Peninsula. In 1986, the first case of Crimean-Congo hemorrhagic fever was registered, and cases of patients with hemorrhagic fever are rising, and most of them present in a serious condition, when the mortality rate is very high. In districts like Mirdite, Lezhe, Gjirokaster, Skrapar, Erseke, and Kukes, there is delineated human-to-human transmission. CASE PRESENTATION: We report the case of a 32 year-old Albanian woman from a rural area of Albania. She was hospitalized at the Infectious Diseases Service, for a severe influenza-like illness of 4 days duration. Our patient had been bitten by a tick while working in her garden. She presented with nausea, vomiting, headache and muscle pain. A physical examination found a high fever of 40 °C, an enlarged liver, petechia, and vaginal bleeding; flapping tremor and fetor hepaticus were found as a sign for hepatic encephalopathy; and confusion and disorientation were observed in her neurological examination. Her platelet and white blood cell counts were very low, while her aspartate aminotransferase and alanine aminotransferase levels were very high. She was transferred to the intensive care unit because of her worsening condition. Serological and C-reactive protein test results for Crimean-Congo hemorrhagic fever were positive. She was treated with oral ribavirin and discharged with normal parameters. CONCLUSIONS: People in high-risk professions in the endemic areas should be informed and trained on the risk of Crimean-Congo hemorrhagic fever as a matter of urgency. Vaginal bleeding is not always a gynecological problem. In Albania, these places are the mountainous areas, so people who have traveled to these areas and who have symptoms after a tick bite are advised to contact their doctors.

The protective effect and diagnostic performance of NOX-5 in Crimean-Congo haemorrhagic fever patients.

INTRODUCTION: Crimean-Congo haemorrhagic fever (CCHF) is an acute viral haemorrhagic disease. Reactive oxygen species that are mainly generated by the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) enzyme family have a pivotal role in the pathophysiology of many diseases. The serum levels of NOX isoforms in patients with CCHF have yet to be assessed. METHODS: This prospective study was conducted at Cumhuriyet University, Turkey. Only patients with CCHF confirmed by the National Reference Virology Laboratory were enrolled in the study. The study subjects comprised 67 CCHF patients and 70 healthy control subjects. The quantitative sandwich ELISA technique was used for the determination of serum NOX 1, 2, 4 and 5. RESULTS: Higher median median NOX-1 (P=0.001) and NOX-5 (P<0.001) levels were found in patients compared to the control group. Higher median serum NOX-5 levels were found in the low-grade disease group compared to the intermediate-high disease group according to two different severity scores (P=0.003). Negative correlations were also found between the serum NOX-5 levels and the severity scores [(P<0.05, r=-0.259), (P<0.01, r=-0.417)]. The area under the curve (AUC) values for the NOX-1 and NOX-5 were 0.67 (confidence interval: 0.58-0.75) and 0.99 (confidence interval: 0.95-1.00), respectively. Lower NOX-5 levels were found in patients receiving thrombocyte suspension (P=0.004)Conclusions. NOX-5 may have a protective effect on CCHF patients and the measurement of serum NOX-5 levels may be used as a novel biochemical test in the diagnosis of CCHF.

Carbonic anhydrase I-II autoantibodies and oxidative status in long-term follow-up of patients with Crimean-Congo haemorrhagic fever.

CONTEXT: Crimean-Congo haemorrhagic fever (CCHF) is a life-threatening acute febrile haemorrhagic disease. OBJECTIVE: This study was to measure levels of the oxidative stress biomarkers malondialdehyde (MDA), total oxidant status (TOS), total antioxidant status (TAS) and oxidative stress index (OSI) and of CA I-II autoantibodies as biomarkers for autoimmunity and course of disease in patients with CCHF. METHODS: Seventy CCHF patients and 39 healthy control volunteers were included in the study. RESULTS: Serum MDA and TAS levels were significantly higher (p < .0001) and serum TOS and OSI levels were significantly lower (p < .0001) in both the acute period and at 6th-month follow-up in the CCHF patients compared to the healthy volunteers. CA II levels were significantly higher in the acute period compared to the healthy volunteers (p < .005) and were significantly lower at 6th-month follow-up (p < .05). CONCLUSION: Serum MDA and CA II autoantibodies appear to reflect oxidative stress status and disease progression in CCHF and may be used as biomarkers for oxidative stress and disease progression.