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      Risk factors for Crimean-Congo Haemorrhagic Fever (CCHF) virus exposure in farming communities in Uganda

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      a , b , c , b , d , c , a , e , b , b , e , c , e , f , g , a , c , c , e , f , e , h , d , b , i , a , *
      The Journal of Infection
      W.B. Saunders
      Crimean-Congo Hemorrhagic fever virus, CCHF antibodies, tick-borne viral infections, emerging and re-emerging infections, zoonotic disease, CCHF seroprevalence, CCHF risk factors, tick-borne arbovirus, CCHF, Viral Haemorrhagic Fever, Uganda

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          Highlights

          • Risk factors for zoonotic transmission of Crimean-Congo Haemorrhagic fever Virus (CCHFV) among livestock farming communities in Uganda.

          • Extremely high CCHFV seroprevalence was detected in humans and domestic animals in Uganda

          • The burden of CCHFV infection and risk factors has to date been underestimated in Uganda.

          • Detection of CCHV in multiple pools of Rhipicephalus appendiculatus suggest these ticks to be the likely vectors for CCHFV in Uganda

          • CCHFV risk in humans were associated with livestock rearing, age and collecting/ eating ticks

          • Further work is indicated to estimate the incidence of CCHFV infection as a cause of non-malarial fever

          Abstract

          Background

          Crimean-Congo Haemorrhagic Fever (CCHF) is an emerging human-health threat causing sporadic outbreaks in livestock farming communities. However, the full extent and the risks associated with exposure of such communities has not previously been well-described.

          Methods

          We collected blood samples from 800 humans, 666 cattle, 549 goats and 32 dogs in districts within and outside Ugandan cattle corridor in a cross-sectional survey, and tested for CCHFV-specific IgG antibodies using Enzyme-Linked Immunosorbent Assays. Sociodemographic and epidemiological data were recorded using structured questionnaire. Ticks were collected to identify circulating nairoviruses by metagenomic sequencing.

          Results

          CCHFV seropositivity was in 221/800 (27·6%) in humans, 612/666 (91·8%) in cattle, 413/549 (75·2%) in goats and 18/32 (56·2%) in dogs. Human seropositivity was associated with livestock farming (AOR=5·68, p<0·0001), age (AOR=2·99, p=0·002) and collecting/eating engorged ticks (AOR=2·13, p=0·004). In animals, seropositivity was higher in cattle versus goats (AOR=2·58, p<0·0001), female sex (AOR=2·13, p=0·002) and heavy tick infestation (>50 ticks: AOR=3·52, p=0·004). CCHFV was identified in multiple tick pools of Rhipicephalus appendiculatus.

          Interpretation

          The very high CCHF seropositivity especially among livestock farmers and multiple regional risk factors associated exposures, including collecting/eating engorged ticks previously unrecognised, highlights need for further surveillance and sensitisation and control policies against the disease.

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          Most cited references27

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          Crimean-Congo hemorrhagic fever: history, epidemiology, pathogenesis, clinical syndrome and genetic diversity.

          Crimean-Congo hemorrhagic fever (CCHF) is the most important tick-borne viral disease of humans, causing sporadic cases or outbreaks of severe illness across a huge geographic area, from western China to the Middle East and southeastern Europe and throughout most of Africa. CCHFV is maintained in vertical and horizontal transmission cycles involving ixodid ticks and a variety of wild and domestic vertebrates, which do not show signs of illness. The virus circulates in a number of tick genera, but Hyalomma ticks are the principal source of human infection, probably because both immature and adult forms actively seek hosts for the blood meals required at each stage of maturation. CCHF occurs most frequently among agricultural workers following the bite of an infected tick, and to a lesser extent among slaughterhouse workers exposed to the blood and tissues of infected livestock and medical personnel through contact with the body fluids of infected patients. CCHFV is the most genetically diverse of the arboviruses, with nucleotide sequence differences among isolates ranging from 20% for the viral S segment to 31% for the M segment. Viruses with diverse sequences can be found within the same geographic area, while closely related viruses have been isolated in far distant regions, suggesting that widespread dispersion of CCHFV has occurred at times in the past, possibly by ticks carried on migratory birds or through the international livestock trade. Reassortment among genome segments during co-infection of ticks or vertebrates appears to have played an important role in generating diversity, and represents a potential future source of novel viruses. In this article, we first review current knowledge of CCHFV, summarizing its molecular biology, maintenance and transmission, epidemiology and geographic range. We also include an extensive discussion of CCHFV genetic diversity, including maps of the range of the virus with superimposed phylogenetic trees. We then review the features of CCHF, including the clinical syndrome, diagnosis, treatment, pathogenesis, vaccine development and laboratory animal models of CCHF. The paper ends with a discussion of the possible future geographic range of the virus. For the benefit of researchers, we include a Supplementary Table listing all published reports of CCHF cases and outbreaks in the English-language literature, plus some principal articles in other languages, with total case numbers, case fatality rates and all CCHFV strains on GenBank. Copyright © 2013 Elsevier B.V. All rights reserved.
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            The WHO R&D Blueprint: 2018 review of emerging infectious diseases requiring urgent research and development efforts

            The Research and Development (R&D) Blueprint is a World Health Organization initiative to reduce the time between the declaration of a public health emergency and the availability of effective diagnostic tests, vaccines, and treatments that can save lives and avert a public health crisis. The scope of the Blueprint extends to severe emerging diseases for which there are insufficient or no presently existing medical countermeasures or pipelines to produce them. In February 2018, WHO held an informal expert consultation to review and update the list of priority diseases, employing a prioritization methodology which uses the Delphi technique, questionnaires, multi-criteria decision analysis, and expert review to identify relevant diseases. The committee determined that, given their potential to cause a public health emergency and the absence of efficacious drugs and/or vaccines, there is an urgent need for accelerated R&D for (in no order of priority) Crimean-Congo haemorrhagic fever, Ebola virus and Marburg virus disease, Lassa fever, Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS), Nipah and henipaviral diseases, Rift Valley fever and Zika virus disease. The experts also included “Disease X,” representing the awareness that a previously unknown pathogen could cause a major public health emergency. This report describes the methods and results of the 2018 prioritization review.
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              The role of ticks in the maintenance and transmission of Crimean-Congo hemorrhagic fever virus: A review of published field and laboratory studies

              This manuscript is part of a series of reviews that aim to cover published research on Crimean-Congo hemorrhagic fever (CCHF) and its etiological agent, CCHF virus (CCHFV). The virus is maintained and transmitted in a vertical and horizontal transmission cycle involving a variety of wild and domestic vertebrate species that act as amplification hosts, without showing signs of illness. These vertebrates have traditionally been considered reservoirs of CCHFV, but in fact they develop only a transient viremia, while the virus can persist in ticks for their entire lifespan, and can also be transmitted vertically to the next generation. As a result, ticks are now considered to be both the vector and the reservoir for the virus. CCHFV has been detected in a wide range of tick species, but only a few have been proven to be vectors and reservoirs, mainly because most published studies have been performed under a broad variety of conditions, precluding definitive characterization. This article reviews the published literature, summarizes current knowledge of the role of ticks in CCHFV maintenance and transmission and provides guidance for how to fill the knowledge gaps. Special focus is given to existing data on tick species in which vertical passage has been demonstrated under natural or experimental conditions. At the same time, we identify earlier reports that used unreliable methods and perceptions to ascribe a vector role to some species of ticks, and have contributed to confusion regarding viral transmission. We also examine epidemiological pathways of CCHFV circulation and discuss priority areas for future research.
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                Author and article information

                Contributors
                Journal
                J Infect
                J Infect
                The Journal of Infection
                W.B. Saunders
                0163-4453
                1532-2742
                1 December 2022
                December 2022
                : 85
                : 6
                : 693-701
                Affiliations
                [a ]College of Veterinary Medicine, Animal Resources and Biosecurity (CoVAB), Makerere University, Kampala, Uganda
                [b ]MRC-University of Glasgow Centre for Virus Research (CVR), Glasgow, United Kingdom
                [c ]Ministry of Agriculture, Animal Industry and Fisheries, Entebbe, Uganda
                [d ]The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
                [e ]Department of Arbovirology, Emerging and Re-emerging Infections, Uganda Virus Research Institute, Entebbe, Uganda
                [f ]MRC/UVRI and LSHTM Uganda Research Unit, Entebbe Uganda
                [g ]Institute of Biodiversity Animal Health and Comparative Medicine, University of Glasgow, Glasgow, United Kingdom
                [h ]College of Natural Resources (CoNAS), Makerere University, Kampala, Uganda
                [i ]London School of Hygiene and Tropical Medicine, London, UK
                Author notes
                Article
                S0163-4453(22)00537-0
                10.1016/j.jinf.2022.09.007
                9731351
                36108783
                0f48c0de-cb3b-455c-bdda-48e00bd6c465
                © 2022 The Authors. Published by Elsevier Ltd on behalf of The British Infection Association.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 6 September 2022
                Categories
                Article

                Infectious disease & Microbiology
                crimean-congo hemorrhagic fever virus,cchf antibodies,tick-borne viral infections,emerging and re-emerging infections,zoonotic disease,cchf seroprevalence,cchf risk factors,tick-borne arbovirus,cchf,viral haemorrhagic fever,uganda

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