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The paper demonstrates it possible to work out a phosphorescence analysis (PHOSPHAN) microplate technology-based microarray for concurrently examining human sera and detection of their specific IgG antibodies against two heterological West Nile and Crimean-Congo hemorrhagic fever viruses. The sensitivity and specificity of the microarray were comparable with those of enzyme immunoassay with separate sample testing. The advantages of PHOSPHAN were associated with the microplate format of an immunoassay and its enhanced multiplexity, which may contribute to the lower cost of clinical sample testing.

The study aimed at estimating the pharmacotherapeutic efficacy of medications possessed of antiviral activity, such as ribavirin, cycloferon solution and tablets, in 410 patients with Crimean hemorrhagic fever: The early beginning of therapy (days 1-4 after the onset of the disease) with these drugs reduced the number of severe cases and manifestations of hemorrhagic syndrome. The duration of the disease decreased, the occurrence of intoxication syndrome reduced to a minimum, hemorrhagic rash rapidly disappeared, and the frequency of complications decreased. Adverse events were documented in 5.2% of the patients (n = 15); most of them developed on day 2 after using the drugs, their duration did not exceed 2.2 days. There were no cases of drug withdrawal.

Background Crimean-Congo Haemorrhagic Fever (CCHF) is a zoonotic viral disease transmitted by ixodid tick bites, mainly of Hyalomma spp., or through contact with blood/tissues from infected people or animals. CCHF is endemic in the Balkan area, including Bulgaria, where it causes both sporadic cases and community outbreaks. Methods We described trends of CCHF in Bulgaria between 1997 and 2009 and investigated the associations between CCHF incidence and a selection of environmental factors using a zero-inflated modelling approach. Results A total of 159 CCHF cases (38 women and 121 men) were identified between 1997 and 2009. The incidence was 0.13 cases per 100,000 population/year with a fatality rate of 26%. An epidemic peak was detected close to the Turkish border in the summer of 2002. Most cases were reported between April and September. Increasing mean temperature, Normalized Difference Vegetation Index (NDVI), savannah-type land coverage or habitat fragmentation increased significantly the incidence of CCHF in the CCHF-affected areas. Similar to that observed in Turkey, we found that areas with warmer temperatures in the autumn prior to the case-reporting year had an increased probability of reporting zero CCHF cases. Conclusions We identified environmental correlates of CCHF incidence in Bulgaria that may support the prospective implementation of public health interventions.

WOS: 000340311300009, PubMed ID: 24499853, Background & objectives: Crimean-Congo haemorrhagic fever (CCHF) can be fatal with bleeding, shock and disseminated intravascular coagulopathy (DIC). Although similar genetic strains have been defined, the causes of the clinical differences between the cases are yet to be found. We aimed to demonstrate the balance between oxidant and antioxidant system in CCHF. Methods: In this study, the patient group consisted of 72 cases with a positive diagnosis of CCHF according to PCR/ELISA outcome among the patients referred to Cumhuriyet University, Medical Faculty in 2010. A total of 74 volunteers who were not having any viral or metabolic disease, non-smokers and age and sex matched with the patients group were enrolled as the control group. Both in the controls and the patients, individuals aged under 16 yr were defined as group 1 and the individuals aged over 16 yr as group 2. The serum samples were stored at -80 degrees C until the study was carried out. All the samples were simultaneously thawed. In these cases, total antioxidant capacity (TAC), total oxidative status (TOS), oxidative stress index (OSI), lipid peroxide (LPO), paraoxonase (PON) and arylesterase were analyzed with the ELISA method. OSI was calculated. Results: Levels of TOS, OSI and LPO were found significantly higher in CCHF patients in both the groups (p

The authors remind, what are the viral haemorrhagic fevers, and explain the situation in Madagascar. The viruses of Crimée-Congo haemorrhagic fever, Rift valley fever and haemorrhagic fever with renal syndrome are present in Madagascar. There is no real proof about the presence of Dengue viruses. The yellow fever viruses have never been stown off. It seems that there was not diagnosed outbreak of haemorrhagic fever, since the beginning of our century.

The clinico-epidemiological analysis of morbidity in Crimean haemorrhagic fever in the Stavropol Territory is presented. Information on the clinical features, epidemiological characteristics and diagnostic criteria of the disease, as well as trends in its treatment, is given.

Sera samples from patients suspected of Crimean-Congo hemorrhagic fever (CCHF) taken during epidemic outbreak at the territory of Sarysusky and Moiynkumsky districts of the Zhambyl region in Kazakhstan, in 2000, were analysed by means of reverse transcription-polymerase chain reaction (RT-PCR) and sequencing of virus genome fragments. Genome RNA of CCHF virus was found in 2 assays. Analysis of nucleotide sequences of fragments of S-segment of viral genome revealed in the Sarysusky districts circulation of CCHF virus, genetically resembled to close phylogenetically to CCHF virus strains from China.

The results of the serological analysis of blood sera taken from patients with Crimean haemorrhagic fever (CHF) and from persons suspected for this disease are presented. These results made it possible to confirm that during the period of April 16-September 04, 2000, the outbreak of CHF occurred on the territory of Southern Russia. In addition to the laboratory confirmation of the outbreak of CHF by means of the enzyme immunoassay and the indirect immunofluorescence test the diagnostic work was completed by the isolation, and subsequent identification, of 3 strains of CHF virus from the blood of patients and 1 strain from the pool of ticks Hyalomma marginatum.

A patient with fever, and haemorrhagic symptoms was admitted to a hospital in Glasgow on 2 October 2012. Since he had returned from Afghanistan, serum samples were sent for diagnosis at the Rare and Imported Pathogens Laboratory, where a real-time reverse transcriptase-PCR diagnosis of Crimean – Congo haemorrhagic fever was made within 3 hrs after receipt of the sample. Hereafter the patient was transferred to a high-security infectious diseases unit in London but died on 6 October.

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.

Background Crimean-Congo Haemorrhagic Fever Virus (CCHFV) is a zoonotic virus transmitted by Ixodid ticks and causes Crimean-Congo hemorrhagic fever (CCHF) disease in humans with up to 50 % mortality rate. Methods Freshly slaughtered livestock at the Kumasi abattoir in the Ashanti Region of Ghana were examined for the presence of ticks once a month over a 6-month period from May to November 2011. The ticks were grouped into pools by species, sex, and animal source. CCHFV was detected in the ticks using reverse transcription PCR. Blood samples were collected from enrolled abattoir workers at initiation, and from those who reported fever in a preceding 30-day period during monthly visits 2–5 months after initiation. Six months after initiation, all participants who provided baseline samples were invited to provide blood samples. Serology was performed using enzyme linked immunosorbent assay (ELISA). Demographic and epidemiological data was also obtained from enrolled participants using a structured questionnaire. Results Of 428 freshly slaughtered animals comprising 130 sheep, 149 cattle, and 149 goats examined, 144 ticks belonging to the genera Ambylomma, Hyalomma and Boophilus were identified from 57 (13.3 %): 52 (34.9 %), 4 (3.1 %) and 1 (0.7 %) cattle, sheep and goat respectively. Of 97 tick pools tested, 5 pools comprising 1 pool of Hyalomma excavatum and 4 pools of Ambylomma variegatum, collected from cattle, were positive for CCHFV. Of 188 human serum samples collected from 108 abattoir workers, 7 (3.7 %) samples from 6 persons were anti-CCHF IgG positive with one of them also being CCHF IgM positive. The seroprevalence of CCHFV identified in this study was 5.7 %. Conclusions This study detected human exposure to CCHF virus in slaughterhouse workers and also identified the CCHF virus in proven vectors (ticks) of Crimean Congo hemorrhagic fever in Ghana. The CCHFV was detected only in ticks collected from cattle, one of the livestock known to play a role in the amplification of the CCHF virus.

Crimean-Congo haemorrhagic fever (CCHF) is an infectious viral disease that has (re-)emerged in the last decade in south-eastern Europe, and there is a risk for further geographical expansion to western Europe. Here we report the results of a survey covering 28 countries, conducted in 2012 among the member laboratories of the European Network for Diagnostics of 'Imported' Viral Diseases (ENIVD) to assess laboratory preparedness and response capacities for CCHF. The answers of 31 laboratories of the European region regarding CCHF case definition, training necessity, biosafety, quality assurance and diagnostic tests are presented. In addition, we identified the lack of a Regional Reference Expert Laboratory in or near endemic areas. Moreover, a comprehensive review of the biosafety level suitable to the reality of endemic areas is needed. These issues are challenges that should be addressed by European public health authorities. However, all respondent laboratories have suitable diagnostic capacities for the current situation., peer-reviewed

A rare case of Crimean haemorrhagic fever in a pregnant woman during the sixth month of gestation is described. The typical clinical course of the disease is present with positive anamnesis and visible locus from tick bite. After several days, fever and local lymphadenitis appear, followed by severe toxicoinfectious and haemorrhagic syndromes. The disease is proved virologically and serologically. The outcome is favourable for the pregnant woman. She is discharged home after 16-day hospital treatment. During the illness no complications of the fetus are documented. The pregnancy terminates with a normal-term delivery of a healthy newborn baby with birthweight of 3350g. The clinical and laboratory follow up of the baby showed no abnormalities. The case is of interest because of the rarely and often severe course of the disease during pregnancy. In this case the outcome is favourable for both the mother and the newborn child.

A serological serosurvey was made in different ethnic groups of Mauritania in 1985. A very high prevalence of hepatitis B markers was found with more than 20% of HBs antigen carriers. Treponema specific antibodies in low-age classes observed is a reflect of endemic syphilis. The seroprevalence of antibody against HIV and viral haemorrhagic fever viruses (Rift Valley fever, Crimean-Congo haemorrhagic fever and haemorrhagic fever with renal syndrome) was very low.A serological survey in Mauritania in 1985-86 provided data on certain viral and bacterial markers whose frequency has been well established in countries neighboring this gateway between North Africa and subSaharan Africa. Blood samples from 1230 male blood donors and 983 pregnant women at the hospital in Nouakchott were analyzed for treponema infection, hepatitis B, HIV, and for antibodies to certain viruses causing hemorrhagic fever. Positive results for treponema specific antibodies using the Kline reaction were obtained in 76 of 2213 serums examined. High positive rates in young age groups reflect endemic nonvenereal treponematosis. 16 of 218 persons aged 10-19 tested positive compared to 10 of 593 aged 30-39 and 2 of 133 aged over 40. Observed differences between ethnic groups were highly significant. Infection rates were higher among males except among the Poulars. A very high prevalence of hepatitis B markers was found with more than 20% of hepatitis B surface antigen carriers among the 766 samples studied. 88.68% of the 813 subjects studied had been infected with the hepatitis B virus. The results suggest that nomadism, or the hygienic conditions of nomadism, favor contamination by the hepatitis B virus. 3 of the 510 samples examined were positive for HIV. Only 1 of the positive samples was from a Mauritanian, a 28-year-old male Poular. The other 2 positive results were obtained from foreigners temporarily residing at Nouakchott. The prevalence of antibodies against the viruses responsible for hemorrhagic fever was very low: 1/965 for the Crimee-Congo, 2/965 for the Rift Valley fever virus, and 3/965 for the Hantaan virus.

Background Pakistan is considered as an endemic country for Crimean-Congo Hemorrhagic fever with numerous outbreaks and sporadic cases reported during the past two decades. Majority of cases are reported from Baluchistan province with subsequent transmissions to non-endemic regions mainly through infected animals directly or via infested ticks. We hereby describe the molecular investigations of CCHF cases reported during 2008 in Quetta city of Baluchistan province. Methods Serum Samples from 44 patients, with clinical signs of hemorrhagic fever attending a tertiary care hospital in Quetta city, were collected and tested for CCHF virus antigen and genomic RNA, using capture IgM EIA kit and standard RT-PCR assay, respectively. The partial S-gene fragments were directly sequenced to get information related to the prevailing CCHFV genotypes and their molecular epidemiology in Pakistan. Results Out of the total forty four, sixteen (36%) samples were found positive for CCHF IgM. Similarly, viral RNA was detected in six (16%) samples. Phylogenetic analysis revealed that all study viruses belong to genotype Asia-1 with closest similarity (99-100%) to the previously reported strains from Pakistan, Afghanistan and Iran. Conclusion We conclude that CCHF virus remains endemic within Baluchistan and its neighboring regions of Afghanistan warranting a need of incessant surveillance activities.

Crimean-Congo hemorrhagic fever (CCHF), caused by infection with CCHF virus (CCHFV), is viral hemorrhagic fever with high case fatality rate. CCHFV is classified to Family Bunyaviridae, Genus Nairovirus. CCHF is endemic to Africa, Eastern Europe, the Middle East, central Asia, and southern Asia. CCHFV is maintained in nature in several spe- cies of ticks (Hyalomma and Ixodes species) and mammals. Humans are infected with CCHFV by tick-bite or direct contact with viremic animals such as sheep. The CCHF-endemic re- gions are relatively economically disadvantaged areas, therefore CCHF is considered to be one of the neglected infectious diseases. The pathophysiology has not yet been clarified fully. It is necessary to clarify the pathophysiology of CCHF and to develop specific antiviral drug- based therapy and vaccines, which might be effective in confering protection against CCHFV infections in the near future, because CCHF outbreaks continue to occur in the endemic re- gions.

WOS: 000364108900003, PubMed ID: 25243496, Aim. In children with Crimean-Congo hemorrhagic fever (CCHF), the aim of present study was to determine the cerebral hemodynamic changes assessed with Doppler ultrasonography with measurements of lumen diameter (LD), peak systolic velocity (PSV), end-diastolic velocity (EDV), resistive index (RI), pulsatility index (PI), and total cerebral blood flow volume (tCBFV) of common carotid artery (CCA), internal carotid artery (ICA, and vertebral artery (VA). Methods. This case-control study examined children with clinically defined CCHF as cases (N.=24) and healthy children as controls (N.=17). The CCHF and healthy children underwent ultrasonography of the CCA, ICA and VA for the measurements of flow velocity and cerebral blood flow volume. Doppler ultrasonography were performed in the CCHF children if vital signs were stable and fever lower than 37.5 degrees C. Results. There was no significant difference between the CCHF and healthy children in the lumen diameter of study arteries (P>0.05). PSV and EDV values were significantly higher in the CCHF children compared to the controls (P0.05). tCBFV values of CCHF children was found higher compared to healthy controls (P

WOS: 000330924900005, PubMed ID: 23448606, The purpose of this study is to determine erythrocyte sedimentation rate (ESR), C - reactive protein (CRP), serum amyloid-A (SAA) and cholesterol levels in patients with Crimean-Congo Hemorrhagic Fever (CCHF) and determine the relationship of these parameters with the severity of disease. By polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA) method 40 patients were diagnosed as CCHF and 39 volunteer without any systemic disease whose blood were taken and their serum separated. SAA, CRP and ESR were measured with ELISA, nephelometry and Mix-Rate x100 vital diagnostic device, respectively, in serum samples. High density lipoprotein (HDL), low density lipoprotein (LDL) and total cholesterol levels were determined by using autoanalyzer HDL, LDL and total cholesterol kit (Syncron LX20). Statistically significant difference was determined between patients and controls in terms of the levels of SAA, CRP, HDL, LDL and total cholesterol (p0.05). Using of CRP and SAA together might increase the sensitivity of diagnosis of CCHF infection. However, none of the parameters investigated in this study were found to be a proper marker of the prognosis in CCHF. Cholesterol levels were significantly decreased in patients with CCHF, which was suggested to be associated with the increased serum levels of SAA in the patient group. (C) 2013 Association of Basic Medical Sciences of FBIH. All rights reserved

We report a tick-borne case of severe Crimean-Congo haemorrhagic fever (CCHF) imported into Greece from Bulgaria. The patient presented severe thrombocytopenia, hemophagocytosis, haemodynamic instability, large haematomas and altered mental status. Supportive treatment and ribavirin were administered. Symptoms started one day after the tick was removed; the patient was discharged from the hospital 26 days after symptom onset. No secondary cases were observed. Phylogenetically the CCHF virus strain belongs to clade Europe 1.

Background & objectives: Zoonotic diseases are well recognised threat to public health globally. The information of regional prevalence and associated risk factors allow the national programmes to determine and frame better strategies for their control, as they also provide the actual status of zoonosis in the region. The aim of this study was to determine the seroprevalence of West Nile virus (WNV), Crimean-Congo hemorrhagic fever virus (CCHFV), Francisella tularensis and Borrelia burgdorferi among the rural residents of Manisa region, Turkey and to identify the associated risk factors. Methods: Cross sectional study was conducted in rural parts of Manisa, Aegean region of western Turkey in 2012. Blood samples from 324 randomly selected subjects were screened for the presence of IgG antibodies to WNV, CCHFV, F. tularensis and B. burgdorferi with commercially available kits. The demographic structure of the rural residents and risk factors related to lifestyle such as outdoor agriculture activities, animal husbandry, hunting and history of tick bite were questioned and their relationships with positive results were analyzed statistically. Results: It was observed that 49 subjects (15%) had IgG antibodies to at least one of the zoonotic agents studied. The seroprevalence of F. tularensis was highest with a percentage of 7.1% (n = 23). Distribution of the positive results for WNV, CCHFV and B. burgdorferi were 4.3% (n = 14), 3.7% (n = 12) and 0.9% (n = 3), respectively. Older age and uncompleted secondary education were the statistically significant risk factors for seropositivity to at least one zoonotic agent investigated. Logistic regression analyses confirmed that older age (over 50) increased the risk of WNV and CCHFV seropositivity. Interpretation & conclusion: Seropositivity rates were not found to be higher than the expected rates. Further, studies are needed to evaluate the threat of vector borne zoonoses and associated risk factors in the study area.

The paper gives information on the first case of Crimean-Congo hemorrhagic fever detected in a female resident of the Anapa District, Krasnodar Territory, in 2005 in the past 57 years.

Crimean-Congo hemorrhagic fever virus (CCHFV) is transmitted to humans by bite of infected ticks or by direct contact with blood or tissues of viremic patients or animals. It causes to humans a severe disease with fatality up to 30%. The current knowledge about the vector-host-CCHFV interactions is very limited due to the high-level containment required for CCHFV studies. Among ticks, Hyalomma spp. are considered the most competent virus vectors. CCHFV evades the tick immune response, and following its replication in the lining of the tick's midgut, it is disseminated by the hemolymph in the salivary glands and reproductive organs. The introduction of salivary gland secretions into the host cells is the major route via which CCHFV enters the host. Following an initial amplification at the site of inoculation, the virus is spread to the target organs. Apoptosis is induced via both intrinsic and extrinsic pathways. Genetic factors and immune status of the host may affect the release of cytokines which play a major role in disease progression and outcome. It is expected that the use of new technology of metabolomics, transcriptomics and proteomics will lead to improved understanding of CCHFV-host interactions and identify potential targets for blocking the CCHFV transmission.

Lassa, Ebola, Marburg and Crimean-Congo haemorrhagic fever viruses are the most important causes of viral haemorrhagic fever which is transmitted from person to person through contact with blood or excreta. A non-specific fever may be the initial symptom of viral haemorrhagic fever. By means of carefully noting where the patient has travelled, possible exposure to ill persons, vectors or an animal reservoir, and the incubation period (or = 21 days versus longer), it is possible to estimate the risk of infection with one of these viruses. Using this approach it is possible to diagnose high-risk patients in good time and to take appropriate measures.

Background Crimean-Congo hemorrhagic fever epidemics often occur in areas where health services are limited, and result in high case fatality rates. Besides intensive care, ribavirin is often recommended. A solid evidence base for the use of this drug will help justify assuring access to the drug in areas where epidemics are common. Methods We carried out a systematic review of observational and experimental studies of people with suspected or confirmed Crimean-Congo hemorrhagic fever that included comparisons between patients given ribavirin and those not. We extracted data on mortality, hospital stay, and adverse events. Risk of bias was assessed using a standard checklist, and data were presented in meta-analytical graphs, stratified by study design, and GRADE tables presented. The risk of bias was summarised using the GRADE method. Results 21 unique studies, including one randomised controlled trial of ribavirin, were included. Quality of the evidence was very low, with a Down and Black median score of 4 (maximum possible 33). Ribavirin treatment was not shown to be superior to no ribavirin treatment for mortality rate in a single RCT (RR: 1.13, 95%CI: 0.29 to 4.32, 136 participants, GRADE=low quality evidence); but ribavirin was associated with reduced mortality by 44% when compared to no ribavirin treatment in the pooled observational studies (RR: 0.56, 95%CI: 0.35 to 0.90, 955 participants; GRADE=very low quality evidence). Adverse events were more common with the ribavirin patients, but no severe adverse events were reported. No difference in length of hospital stay was reported. Conclusions No clear message of benefit is available from the current data on ribavirin as observational data are heavily confounded, and the one trial carried out has limited power. However, ribavirin could potentially have benefits in this condition and these results clearly indicate a pragmatic, randomised controlled trial in the context of good quality supportive care, is urgently needed and ethically justified.

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

Crimean–Congo haemorrhagic fever virus (CCHFV) is the medically most important member of the rapidly expanding bunyaviral family Nairoviridae. Traditionally, CCHFV isolates have been assigned to six distinct genotypes. Here, the International Committee on Taxonomy of Viruses (ICTV) Nairoviridae Study Group outlines the reasons for the recent decision to re-classify genogroup VI (aka Europe-2 or AP-92-like) as a distinct virus, Aigai virus (AIGV).

To determine the infectivity of Crimean-Congo hemorrhagic fever (CCHF) virus via routine contacts between serologically confirmed cases and their close relatives from May 2005 up to March 2006, 79 serum samples of 57 close relatives of 12 newly diagnosed serologically confirmed CCHF cases in the Sistan-va-Baluchestan province of Iran were tested for IgG and IgM antibodies against CCHF virus using the enzyme-linked immunosorbent assay technique. Nine levels of contacts were considered: percutaneous contact with the patient's blood, cutaneous contact with the patient's blood, cutaneous contact with non-sanguineous body fluids, cutaneous contact with the patient's skin, sexual contact, eating at the same table, being a roommate of the patient, being a housemate of the patient, and living with the patient in the same building. Only one out of 57 relatives was positive for anti-CCHF IgG (1.8%, 95% confidence interval 0.0 to 9.8%). Thus, the infectivity of the virus via usual routine contacts with patients appears to be low.

We have conducted experiments to assess the ability of Rhipicephalus evertsi evertsi tick to transmit the Crimean-Congo haemorrhagic fever (CCHF) and determine their reproductive cycle. The Rh. e. evertsi was infected by intracoelomic (transparietal and intra-anal) inoculation during the imaginal stases and by oral feeding on an infected viremic goat during imaginal and nymphal stases. The infection rate, transovarial and trans-stasial CCHF virus transmission were monitored for virus reisolation after suckling mice inoculation and the virus identified by ELISA and IFA for antigen detection. After intracoelomic inoculation, unfed adults had viral titers ranging from 0.67 to 2.9 log DL50/0.02 ml and had transmitted the virus to their vertebrate hosts by blood feeding. After 8 to 10 days of blood feeding duration, infection rates were respectively 36% and 100% for male and female ticks. In two instances out of seven transovarial transmission was observed and the virus reisolated from larvae of first generation. However, the virus was not detected after nymphal metamorphosis. After blood feeding on viremic goats, 71% of the nymphae were infected. After metamorphoses 22% of the males and 42% of the females had a low virus titer. Rh. e. evertsi appears to have a limited efficacy in transmitting and replicating the CCHF virus but must be not neglected as a potential vector during an epizootic manifestation.

In the last few years, Crimean-Congo haemorrhagic fever (CCHF) has been reported as an emerging tickborne disease in Turkey. This paper deals with the preparation of an early warning system, aimed to predict the beginning of the CCHF season in Turkey based on a clear, simple and repeatable remotely-sensed signal. Decadal (mean of 10 days) values of the normalized difference vegetation index (NDVI) at 1 km resolution were used on a set of 952 confirmed, accurately geo-referenced, clinical cases between 2003 and 2006. A prerequisite is that the signal should be observable between 2 and 3 decadals before a given moment of the season to be of value as early warning. Decadals marking the 10th percentile or the 25th quartile in the frequency distribution of case reporting were selected as markers for the beginning of season of risk. Neither raw nor accumulated decadal NDVI signals were able to predict the onset of this season. However, when we defined the NDVI anomaly (NDVIa) as the positive difference between decadal NDVI values and the average for the previous year, this standardized measure gave a homogeneous overview of the changes in the NDVI signal producing a NDVIa slope for the decadals 10 to 13 that was always greater than 0. We conclude that observing this slope over time can be used as an early-warning system as it would predict the build-up of the number of cases 20 days in advance with an accuracy of 82% (10th percentile) or 98% (25th quartile).

Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne disease described in more than 30 countries in Europe, Asia and Africa. The causative agent is the Crimean-Congo hemorrhagic fever virus (CCHFV) that is a member of the genus Nairovirus of the family Bunyaviridae. CCHFV that is characterized by a high genetic variability is transmitted to humans by tick bites or contact with fluids from an infected individual or animal. The initial symptoms of CCHF are nonspecific and gradually progress to a hemorrhagic phase that can be lethal (case-fatality rate: 10 to 50%). Characteristic laboratory findings of CCHF are thrombocytopenia, elevated liver and muscle enzymes, and coagulation defects. The pathogenesis of CCHF remains unclear but might involve excessive pro-inflammatory cytokine production and dysfunction of the innate immune response. Diagnosis of CCHF is based mainly on isolation of the virus, identification of the viral genome by molecular techniques (RT-PCR), and serological detection of anti-CCHFV antibodies. There is currently no specific treatment for CCHFV infection and the efficacy of ribavirin is controversial. In absence of an effective vaccine, prevention is based mainly on vector control, protection measures, and information to increase the awareness of the population and of healthcare workers.

Observation chez un homme de 48 ans admis a l'hopital avec de la fievre, des maux de tete et des myalgies. Durant la periode hemorragique le patient presente une leucopenie et une thrombocytopenie

Background Crimean Congo hemorrhagic fever (CCHF), caused by CCHF virus (CCFV), may cause a fatal hemorrhagic illness in humans with mortality rate of approximately 30%. However, in animals the disease is typically asymptomatic and no clinical hemorrhagic infections appears to be associated with CCHFV. Recently, CCHF activity has been detected in western and southern Kordufan region, Sudan. Currently, no information is available in regard to previous exposure of livestock to CCHFV infection in the region. Aims In the present study, a seroepidemiological survey was conducted to determine the prevalence of CCHF and to identify the potential risk factors associated with the disease among cattle in North Kordufan State, Sudan. Methods In this survey, 299 blood samples were collected randomly from six localities in North Kordufan State and were tested by enzyme-linked immunosorbent assay (ELISA) for detection of CCHFV-specific immunoglobulin G (IgG) antibodies. Results The result of the study indicated that the prevalence rate of CCHF was relatively high among cattle, where serological evidence of the infection was observed in 21 (7.0%) of 299 animals. Older cattle were eight times more likely to be infected with the virus (OR=8.0824, CI=1.174-66.317, p-value=0.034). Cross breeds were at 37 time higher at risk compared to endogenous breed (OR=37.06, CI=1.455-944, p-value=0.029). Highly tick-infested cattle are 6 times higher at risk for CCHF when compared to tick-free animals (OR=6.532, CI=1.042-10.852, p-value=0.030). Conclusion It is recommended that surveillance of CCHF should be extended to include other ruminant animals and to study the distribution of ticks in the region to better predict and respond to CCHF outbreak in the State of North Kordufan, Sudan.

Crimean-Congo Hemorrhagic Fever virus (CCHFV; family Nairoviridae) is an extremely pathogenic member of the Bunyavirales order. Previous studies have shown that the N-terminal domain of the CCHFV polymerase (L) contains an ovarian tumor-type protease (OTU) domain with the capability to remove both ubiquitin and ISG15 molecules from proteins. The approximately 200 amino acids-long OTU domain, if ectopically expressed, can interfere with both the induction of antiviral type I interferons (IFN) as well as the IFN-stimulated signaling. A OTU protease mutant (C40A), by contrast, was inactive in that respect. However, the effect of the OTU protease activity in the context of the full-length L protein (approximately 4000 amino acids) is only poorly characterized, and recombinant CCHFV with the C40A mutation could not be rescued. Here, we employed transcriptionally active virus-like particles (tc-VLPs) to investigate the interaction between the L-embedded OTU protease and the IFN system. Our data show a cis requirement of the OTU protease for optimal CCHFV polymerase activity in human HuH-7 cells. The L-embedded OTU did not influence IFN signaling, the sensitivity to IFN, or IFN induction. Moreover, the attenuation of OTU C40A-mutated L could not be relieved by inactivating the IFN response, but after overexpression of conjugation-competent ISG15 the polymerase activity recovered to wild-type levels. Consequently, ISG15 was used to produce OTU-deficient tc-VLPs, a potential vaccine candidate. Our data thus indicate that in the context of full-length L the OTU domain is important for the regulation of CCHFV polymerase by ISG15., Author summary Tick-transmitted Crimean-Congo Hemorrhagic Fever virus (CCHFV) causes a serious and potentially fatal disease in humans. The CCHFV polymerase possesses an N-terminal ovarian tumor-type protease (OTU) domain that cleaves ubiquitin and ISG15 modifiers from target proteins. Previous studies demonstrated that the ectopically expressed OTU domain can inhibit antiviral type I interferon responses. Hence, cleavage-negative OTU mutants of virus or transcriptionally active virus-like particles (tc-VLPs) are expected to exhibit elevated immunogenicity and would be candidates for a live vaccine. For unknown reasons, however, recombinant virus with just the OTU minus mutation cannot be generated. Using tc-VLPs, we show that in human HuH-7 cells the activity of the OTU minus polymerase is reduced by more than 80%. Curiously, the attenuation could not be compensated by inactivating the interferon system or by adding the OTU domain in trans. However, a complete reversion of the OTU minus phenotype was achieved by transcomplementation with ISG15, whereas the other OTU substrate, ubiquitin, had no such positive influence. Our data thus indicate a role of cis OTU in CCHFV polymerase regulation that is independent of an anti-interferon activity but connected to ISG15. Transcomplementation with ISG15 may be a means to rescue the OTU minus CCHV vaccine candidate.

Dugbe orthonairovirus (DUGV) is a tick-borne arbovirus within the order Bunyavirales. DUGV was first isolated in Nigeria, but virus isolations in ten further African countries indicate that DUGV is widespread throughout Africa. Humans can suffer from a mild febrile illness, hence, DUGV is classified as a biosafety level (BSL) 3 agent. In contrast, no disease has been described in animals, albeit serological evidence exists that ruminants are common hosts and may play an important role in the transmission cycle of this neglected arbovirus. In this study, young sheep and calves were experimentally inoculated with DUGV in order to determine their susceptibility and to study the course of infection. Moreover, potential antibody cross-reactivities in currently available diagnostic assays for Crimean-Congo hemorrhagic fever orthonairovirus (CCHFV) were assessed as DUGV is distantly related to CCHFV. Following subcutaneous inoculation, none of the animals developed clinical signs or viremia. However, all ruminants seroconverted, as demonstrated by two DUGV neutralization test formats (micro-virus neutralization test (mVNT), plaque reduction (PRNT)), by indirect immunofluorescence assays and in bovines by a newly developed DUGV recombinant N protein ELISA. Sera did not react in commercial CCHFV ELISAs, whereas cross-reactivities were observed by immunofluorescence and immunoblot assays.