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      Genetic diversity and phylogenetic analysis of Crimean-Congo Hemorrhagic Fever viruses circulating in Pakistan during 2019

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          Abstract

          Being an endemic country for Crimean Congo hemorrhagic fever (CCHF), this study aimed to explore the genetic diversity of CCHF virus (CCHFV) detected in Pakistan during 2019. Serum samples from patients with clinical signs of hemorrhagic fever attending tertiary care hospitals in Pakistan were tested for CCHFV RNA using real-time PCR at Department of Virology, National Institute of Health. The partial S-gene fragments were directly sequenced to determine the prevailing CCHFV genotypes and their molecular epidemiology in Pakistan. During January-December 2019, 280 samples from suspected CCHF patients were tested and 28 (10%) were found positive on real-time PCR. Positive cases were detected from 14 districts and across all four provinces of Pakistan with majority reported during August-September. The mean age of CCHFV positive patients was 37.25 years (range 5–65 years) with a high frequency in males (92.8%; n = 26) and a case fatality rate of 40.7% was observed. Phylogenetic analysis showed that S- segment of 2019 PAK CCHFV strains (n = 13) belonged to Asia-1 genotype and clustered with regional strains from Iran, Oman, and Afghanistan. We conclude that Asia-1 genotype of CCHF virus remains endemic in Pakistan. Our findings emphasize to establish a laboratory based surveillance program to monitor the disease burden and identify outbreak hotspots for effective control.

          Author summary

          Crimean-Congo hemorrhagic fever, a tick-borne viral disease is a zoonotic priority disease in Pakistan. During the current study, we found a mortality rate of 40.7% due CCHF which is high in comparison to studies from regional countries Iran, Afghanistan and Oman. The disease was commonly associated with people involved in animal husbandry and farming however other occupations were also affected. High proportion of cases was observed in the summer months, around the Eid-Al-Ahda festival. Genetic analysis revealed Pakistani CCHF viruses to be closely related with strains from bordering countries Iran and Afghanistan as well as with Oman indicating that animal trade and movement of people serve as a common source for the disease transmission.

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          Most cited references 34

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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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            Crimean-Congo hemorrhagic fever virus genomics and global diversity.

            Crimean-Congo hemorrhagic fever (CCHF) is a severe illness with high case fatality that occurs in Africa, Europe, the Middle East, and Asia. The complete genomes of 13 geographically and temporally diverse virus strains were determined, and CCHF viruses were found to be highly variable with 20 and 8%, 31 and 27%, and 22 and 10% nucleotide and deduced amino acid differences detected among virus S (nucleocapsid), M (glycoprotein), and L (polymerase) genome segments, respectively. Distinct geographic lineages exist, but with multiple exceptions indicative of long-distance virus movement. Discrepancies among the virus S, M, and L phylogenetic tree topologies document multiple RNA segment reassortment events. An analysis of individual segment datasets suggests genetic recombination also occurs. For an arthropod-borne virus, the genomic plasticity of CCHF virus is surprisingly high.
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              The global distribution of Crimean-Congo hemorrhagic fever

              Background Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne infection caused by a virus (CCHFV) from the Bunyaviridae family. Domestic and wild vertebrates are asymptomatic reservoirs for the virus, putting animal handlers, slaughter-house workers and agricultural labourers at highest risk in endemic areas, with secondary transmission possible through contact with infected blood and other bodily fluids. Human infection is characterized by severe symptoms that often result in death. While it is known that CCHFV transmission is limited to Africa, Asia and Europe, definitive global extents and risk patterns within these limits have not been well described. Methods We used an exhaustive database of human CCHF occurrence records and a niche modeling framework to map the global distribution of risk for human CCHF occurrence. Results A greater proportion of shrub or grass land cover was the most important contributor to our model, which predicts highest levels of risk around the Black Sea, Turkey, and some parts of central Asia. Sub-Saharan Africa shows more focalized areas of risk throughout the Sahel and the Cape region. Conclusions These new risk maps provide a valuable starting point for understanding the zoonotic niche of CCHF, its extent and the risk it poses to humans.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: InvestigationRole: MethodologyRole: Writing – original draft
                Role: Formal analysisRole: Investigation
                Role: Data curationRole: Formal analysis
                Role: Investigation
                Role: Writing – review & editing
                Role: Supervision
                Role: Editor
                Journal
                PLoS Negl Trop Dis
                PLoS Negl Trop Dis
                plos
                plosntds
                PLoS Neglected Tropical Diseases
                Public Library of Science (San Francisco, CA USA )
                1935-2727
                1935-2735
                29 June 2020
                June 2020
                : 14
                : 6
                Affiliations
                [001]Department of Virology, National Institute of Health, Islamabad, Pakistan
                University of Texas Medical Branch, UNITED STATES
                Author notes

                The authors have declared that no competing interests exist.

                Article
                PNTD-D-20-00001
                10.1371/journal.pntd.0008238
                7351229
                32598383
                022d4d88-2f96-40c9-b45e-b1c5a8408f04
                © 2020 Umair et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                Page count
                Figures: 3, Tables: 1, Pages: 11
                Product
                Funding
                The authors received no specific funding for this work.
                Categories
                Research Article
                Medicine and health sciences
                Tropical diseases
                Neglected tropical diseases
                Viral hemorrhagic fevers
                Crimean-Congo hemorrhagic fever
                Medicine and health sciences
                Infectious diseases
                Viral diseases
                Viral hemorrhagic fevers
                Crimean-Congo hemorrhagic fever
                People and Places
                Geographical Locations
                Asia
                Pakistan
                Medicine and Health Sciences
                Diagnostic Medicine
                Signs and Symptoms
                Fevers
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Signs and Symptoms
                Fevers
                Medicine and Health Sciences
                Diagnostic Medicine
                Signs and Symptoms
                Pain
                Myalgia
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Signs and Symptoms
                Pain
                Myalgia
                Research and Analysis Methods
                Research Facilities
                Research Laboratories
                Government Laboratories
                Medicine and Health Sciences
                Diagnostic Medicine
                Signs and Symptoms
                Hemorrhage
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Signs and Symptoms
                Hemorrhage
                Medicine and Health Sciences
                Vascular Medicine
                Hemorrhage
                Biology and Life Sciences
                Evolutionary Biology
                Evolutionary Systematics
                Phylogenetics
                Phylogenetic Analysis
                Biology and Life Sciences
                Taxonomy
                Evolutionary Systematics
                Phylogenetics
                Phylogenetic Analysis
                Computer and Information Sciences
                Data Management
                Taxonomy
                Evolutionary Systematics
                Phylogenetics
                Phylogenetic Analysis
                Medicine and Health Sciences
                Public and Occupational Health
                Custom metadata
                vor-update-to-uncorrected-proof
                2020-07-10
                All relevant data are within the manuscript.

                Infectious disease & Microbiology

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