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      Multiple Crimean-Congo Hemorrhagic Fever Virus Strains Are Associated with Disease Outbreaks in Sudan, 2008–2009

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          Abstract

          Background

          Crimean-Congo hemorrhagic fever (CCHF) activity has recently been detected in the Kordufan region of Sudan. Since 2008, several sporadic cases and nosocomial outbreaks associated with high case-fatality have been reported in villages and rural hospitals in the region.

          Principal Findings

          In the present study, we describe a cluster of cases occurring in June 2009 in Dunkop village, Abyei District, South Kordufan, Sudan. Seven CCHF cases were involved in the outbreak; however, clinical specimens could be collected from only two patients, both of whom were confirmed as acute CCHF cases using CCHF-specific reverse transcriptase polymerase chain reaction (RT-PCR). Phylogenetic analysis of the complete S, M, and L segment sequences places the Abyei strain of CCHF virus in Group III, a virus group containing strains from various countries across Africa, including Sudan, South Africa, Mauritania, and Nigeria. The Abyei strain detected in 2009 is genetically distinct from the recently described 2008 Sudanese CCHF virus strains (Al-fulah 3 and 4), and the Abyei strain S and L segments closely match those of CCHF virus strain ArD39554 from Mauritania.

          Conclusions

          The present investigation illustrates that multiple CCHF virus lineages are circulating in the Kordufan region of Sudan and are associated with recent outbreaks of the disease occurring during 2008–2009.

          Author Summary

          The tick-borne virus which causes the disease Crimean-Congo hemorrhagic fever (CCHF) is known to be widely distributed throughout much of Africa, Southern Europe, the Middle East, Central Asia, and Southern Russia. Humans contract the virus from contact with infected people, infected animals (which do not show symptoms), and from the bite of infected ticks. CCHF was recently recognized in the Sudan when several hospital staff and patients died from the disease in a rural hospital. The genetic analysis of viruses associated with the 2008 and 2009 outbreaks shows that several CCHF viral strains currently circulate and cause human outbreaks in the Sudan, highlighting CCHF virus as an emerging pathogen. The Sudanese strains are similar to others circulating in Africa, indicating movement of virus over large distances with introduction and disease outbreaks in rural areas possible. Understanding the epidemiology of zoonotic diseases such as CCHF is especially important in the Sudan given the large numbers of livestock in the country, and their importance to the economy and rural communities. It is imperative that hospital staff consider CCHF as a possible disease agent, since they are at a high risk of contracting the disease, especially in hospitals with limited medical supplies.

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          Most cited references30

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          Crimean-Congo haemorrhagic fever

          Summary Crimean-Congo haemorrhagic fever (CCHF) is an often fatal viral infection described in about 30 countries, and it has the most extensive geographic distribution of the medically important tickborne viral diseases, closely approximating the known global distribution of Hyalomma spp ticks. Human beings become infected through tick bites, by crushing infected ticks, after contact with a patient with CCHF during the acute phase of infection, or by contact with blood or tissues from viraemic livestock. Clinical features commonly show a dramatic progression characterised by haemorrhage, myalgia, and fever. The levels of liver enzymes, creatinine phosphokinase, and lactate dehydrogenase are raised, and bleeding markers are prolonged. Infection of the endothelium has a major pathogenic role. Besides direct infection of the endothelium, indirect damage by viral factors or virus-mediated host-derived soluble factors that cause endothelial activations and dysfunction are thought to occur. In diagnosis, enzyme-linked immunoassay and real-time reverse transcriptase PCR are used. Early diagnosis is critical for patient therapy and prevention of potential nosocomial infections. Supportive therapy is the most essential part of case management. Recent studies suggest that ribavirin is effective against CCHF, although definitive studies are not available. Health-care workers have a serious risk of infection, particularly during care of patients with haemorrhages from the nose, mouth, gums, vagina, and injection sites. Simple barrier precautions have been reported to be effective.
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            Rapid detection and quantification of RNA of Ebola and Marburg viruses, Lassa virus, Crimean-Congo hemorrhagic fever virus, Rift Valley fever virus, dengue virus, and yellow fever virus by real-time reverse transcription-PCR.

            Viral hemorrhagic fevers (VHFs) are acute infections with high case fatality rates. Important VHF agents are Ebola and Marburg viruses (MBGV/EBOV), Lassa virus (LASV), Crimean-Congo hemorrhagic fever virus (CCHFV), Rift Valley fever virus (RVFV), dengue virus (DENV), and yellow fever virus (YFV). VHFs are clinically difficult to diagnose and to distinguish; a rapid and reliable laboratory diagnosis is required in suspected cases. We have established six one-step, real-time reverse transcription-PCR assays for these pathogens based on the Superscript reverse transcriptase-Platinum Taq polymerase enzyme mixture. Novel primers and/or 5'-nuclease detection probes were designed for RVFV, DENV, YFV, and CCHFV by using the latest DNA database entries. PCR products were detected in real time on a LightCycler instrument by using 5'-nuclease technology (RVFV, DENV, and YFV) or SybrGreen dye intercalation (MBGV/EBOV, LASV, and CCHFV). The inhibitory effect of SybrGreen on reverse transcription was overcome by initial immobilization of the dye in the reaction capillaries. Universal cycling conditions for SybrGreen and 5'-nuclease probe detection were established. Thus, up to three assays could be performed in parallel, facilitating rapid testing for several pathogens. All assays were thoroughly optimized and validated in terms of analytical sensitivity by using in vitro-transcribed RNA. The >or=95% detection limits as determined by probit regression analysis ranged from 1,545 to 2,835 viral genome equivalents/ml of serum (8.6 to 16 RNA copies per assay). The suitability of the assays was exemplified by detection and quantification of viral RNA in serum samples of VHF patients.
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              Crimean-Congo hemorrhagic fever.

              Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne disease caused by the arbovirus Crimean-Congo hemorrhagic fever virus (CCHFV), which is a member of the Nairovirus genus (family Bunyaviridae). CCHF was first recognized during a large outbreak among agricultural workers in the mid-1940s in the Crimean peninsula. The disease now occurs sporadically throughout much of Africa, Asia, and Europe and results in an approximately 30% fatality rate. After a short incubation period, CCHF is characterized by a sudden onset of high fever, chills, severe headache, dizziness, back, and abdominal pains. Additional symptoms can include nausea, vomiting, diarrhea, neuropsychiatric, and cardiovascular changes. In severe cases, hemorrhagic manifestations, ranging from petechiae to large areas of ecchymosis, develop. Numerous genera of ixodid ticks serve both as vector and reservoir for CCHFV; however, ticks in the genus Hyalomma are particularly important to the ecology of this virus. In fact, occurrence of CCHF closely approximates the known world distribution of Hyalomma spp. ticks. Therefore, exposure to these ticks represents a major risk factor for contracting disease; however, other important risk factors are known and are discussed in this review. In recent years, major advances in the molecular detection of CCHFV, particularly the use of real-time reverse transcription-polymerase chain reaction (RT-PCR), in clinical and tick samples have allowed for both rapid diagnosis of disease and molecular epidemiology studies. Treatment options for CCHF are limited. Immunotherapy and ribavirin have been tried with varying degrees of success during sporadic outbreaks of disease, but no case-controlled trials have been conducted. Consequently, there is currently no antiviral treatment for CCHF approved by the U.S. Food and Drug Administration (FDA). However, renewed interested in CCHFV, as well as increased knowledge of its basic biology, may lead to improved therapies in the future. This article reviews the history, epidemiology, ecology, clinical features, pathogenesis, diagnosis, and treatment of CCHF. In addition, recent advances in the molecular biology of CCHFV are presented, and issues related to its possible use as a bioterrorism agent are discussed.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS Negl Trop Dis
                plos
                plosntds
                PLoS Neglected Tropical Diseases
                Public Library of Science (San Francisco, USA )
                1935-2727
                1935-2735
                May 2011
                31 May 2011
                : 5
                : 5
                : e1159
                Affiliations
                [1 ]Molecular Biology Laboratory, Department of Clinical Medicine, Faculty of Veterinary Medicine, University of Khartoum, Khartoum North, Sudan
                [2 ]Molecular Biology Laboratory, Viral Special Pathogens Branch, Division of High Consequence Pathogens and Pathology, United States Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America
                [3 ]Division of Virology, National Medical Health Laboratory, Federal Ministry of Health, Khartoum, Republic of Sudan
                [4 ]Biotechnology Core Facility Branch, Division of Scientific Resources, United States Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America
                Tulane School of Public Health and Tropical Medicine, United States of America
                Author notes

                Conceived and designed the experiments: IEA BRE STN. Performed the experiments: BRE IEA RME. Analyzed the data: BRE MLK STN IEA MSK RME MEHM. Contributed reagents/materials/analysis tools: BRE STN. Wrote the paper: IEA BRE STN.

                Article
                PNTD-D-10-00288
                10.1371/journal.pntd.0001159
                3104971
                21655310
                41a08ac2-c555-46b8-9018-966ba8d6a18e
                This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
                History
                : 21 December 2010
                : 16 March 2011
                Page count
                Pages: 9
                Categories
                Research Article
                Biology
                Genomics
                Medicine
                Infectious Diseases
                Neglected Tropical Diseases
                Viral Hemorrhagic Fevers
                Viral Diseases
                Crimean-Congo hemorrhagic fever

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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