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Crimean-Congo hemorrhagic fever (CCHF) is a tickborne infection that can range from asymptomatic to fatal and has been described in >30 countries. Early identification and isolation of patients with suspected or confirmed CCHF and the use of appropriate prevention and control measures are essential for preventing human-to-human transmission. Here, we provide an overview of the epidemiology, clinical features, and prevention and control of CCHF. CCHF poses a continued public health threat given its wide geographic distribution, potential to spread to new regions, propensity for genetic variability, and potential for severe and fatal illness, in addition to the limited medical countermeasures for prophylaxis and treatment. A high index of suspicion, comprehensive travel and epidemiologic history, and clinical evaluation are essential for prompt diagnosis. Infection control measures can be effective in reducing the risk for transmission but require correct and consistent application.

Crimean–Congo haemorrhagic fever (CCHF) is a severe tick-borne illness with a wide geographical distribution and case fatality rates of 30% or higher. Caused by infection with the CCHF virus (CCHFV), cases are reported throughout Africa, the Middle East, Asia and southern and eastern Europe. The expanding range of the Hyalomma tick vector is placing new populations at risk for CCHF, and no licensed vaccines or specific antivirals exist to treat CCHF. Furthermore, despite cases of CCHF being reported annually, the host and viral determinants of CCHFV pathogenesis are poorly understood. CCHFV can productively infect a multitude of animal species, yet only humans develop a severe illness. Within human populations, subclinical infections are underappreciated and may represent a substantial proportion of clinical outcomes. Compared with other members of the Bunyavirales order, CCHFV has a more complex genomic organization, with many viral proteins having unclear functions in viral pathogenesis. In recent years, improved animal models have led to increased insights into CCHFV pathogenesis, and several antivirals and vaccines for CCHFV have shown robust efficacy in preclinical models. Translation of these insights and candidate therapeutics to the clinic will hopefully reduce the morbidity and mortality caused by CCHFV.Crimean–Congo haemorrhagic fever (CCHF) is a severe and often lethal tick-borne illness that is caused by infection with the CCHF virus (CCHFV). In this Review, Hawman and Feldmann explore recent insights into the function of viral proteins in CCHFV pathogenesis, our current understanding of CCHF and the state of treatments and vaccines for CCHFV.

Crimean-Congo hemorrhagic fever (CCHF) is an emerging tickborne disease and a World Health Organization priority. Although humans are accidental hosts, infection can lead to hemorrhagic fever with a high fatality rate. Domestic animals play a critical role in disease transmission, but infected animals do not show clinical signs and viremia is short; thus, CCHF virus (CCHFV) infections can remain unobserved. During 2017-2019, we conducted 2 sequential observational studies followed by a multisite randomized controlled trial to determine spatial-temporal patterns and quantify drivers for CCHFV exposure in a natural host (sheep) in a CCHF-endemic area of Bulgaria. We found high-risk areas embedded in endemic regions. Animal characteristics were not correlated with seropositivity; however, a seasonality effect was observed, suggesting sampling time was a potential confounder. Force of infection varied across farms and over time. CCHFV transmission heterogeneity among farms is driven by preventive measures used to reduce exposure to ticks.

Crimean–Congo haemorrhagic fever (CCHF) is a widely distributed and potentially fatal tick-borne viral disease with no licensed specific treatments or vaccines. In 2019, WHO published an advanced draft of a research and development roadmap for CCHF that prioritised the development and deployment of the medical countermeasures most needed by CCHF-affected countries. This Personal View presents updated CCHF research and development priorities and is the product of broad consultation with a working group of 20 leading experts in 2023–24. The strategic goals, milestones, and timelines have been revised and expanded to reflect scientific advances since 2019, including the identification of antibodies with therapeutic potential and the progression of four vaccine candidates through phase 1 clinical trials. This update emphasises the need for a One Health approach to manage CCHF, from integrated cross-sectoral surveillance to novel interventions that target ticks and their vertebrate hosts to reduce CCHF virus transmission to humans. The overarching vision for rapid diagnostics and specific therapeutics by 2028, followed by options to limit CCHF virus transmission and control disease by 2030, is deliberately ambitious and will only be achieved through coordinated international action from affected countries, funders, scientists, product developers, manufacturers, regulators, national authorities, and policy makers.

Crimean-Congo Haemorrhagic Fever (CCHF) is a severe tick-borne disease, endemic in many countries in Africa, the Middle East, Eastern Europe and Asia. Between 15-70% of reported cases are fatal. There is no approved vaccine available, and preclinical protection in vivo by an experimental vaccine has not been demonstrated previously. In the present study, the attenuated poxvirus vector, Modified Vaccinia virus Ankara, was used to develop a recombinant candidate vaccine expressing the CCHF virus glycoproteins. Cellular and humoral immunogenicity was confirmed in two mouse strains, including type I interferon receptor knockout mice, which are susceptible to CCHF disease. This vaccine protected all recipient animals from lethal disease in a challenge model adapted to represent infection via a tick bite. Histopathology and viral load analysis of protected animals confirmed that they had been exposed to challenge virus, even though they did not exhibit clinical signs. This is the first demonstration of efficacy of a CCHF vaccine.

Crimean-Congo haemorrhagic fever virus (CCHFV) is a deadly human pathogen of the utmost seriousness being highly lethal causing devastating disease symptoms that result in intense and prolonged suffering to those infected. During the past 40years, this virus has repeatedly caused sporadic outbreaks responsible for relatively low numbers of human casualties, but with an alarming fatality rate of up to 80% in clinically infected patients. CCHFV is transmitted to humans by Hyalomma ticks and contact with the blood of viremic livestock, additionally cases of human-to-human transmission are not uncommon in nosocomial settings. The incidence of CCHF closely matches the geographical range of permissive ticks, which are widespread throughout Africa, Asia, the Middle East and Europe. As such, CCHFV is the most widespread tick-borne virus on earth. It is a concern that recent data shows the geographic distribution of Hyalomma ticks is expanding. Migratory birds are also disseminating Hyalomma ticks into more northerly parts of Europe thus potentially exposing naïve human populations to CCHFV. The virus has been imported into the UK on two occasions in the last five years with the first fatal case being confirmed in 2012. A licensed vaccine to CCHF is not available. In this review, we discuss the background and complications surrounding this limitation and examine the current status and recent advances in the development of vaccines against CCHFV.

Objectives Arboviruses pose a significant global health challenge. This study investigated the seroprevalence of major human arboviral infections, including yellow fever (YFV), dengue (DENV), Crimean-Congo hemorrhagic fever (CCHF), Rift Valley fever (RVF), West Nile virus (WNV), and chikungunya (CHIK), in Darfur region from September to December 2018. ELISA-IgM was used to detect antibodies. RT‒PCR was used to differentiate YFV infection from vaccine-immuno-response in IgM samples. Results A total of 152 blood samples were collected, with 123 (80.9%) from males and 29 (19.1%) from females. The participants were grouped by age: 50 (32.9%) were under 20 years, 96 (63.2%) were aged 20–45 years, and 6 (3.9%) were over 45 years. The seroprevalence rates for YFV, DENV, and CHIKV were 68 (44.7%), 23 (15.1%), and 5 (3.3%), respectively. There were 11 molecularly-confirmed YFV cases (7.2%). Among these, 3/11 were positive for DENV-IgM, and 1/11 was positive for CHIKV-IgM. Among the 68 YFV-positive individuals, 15 (22.1%) had been exposed to DENV, and 2 (2.9%) had been exposed to CHIKV. Co-exposure to DENV and CHIKV was detected in 3 (1.9%) patients, while 2 (1.3%) patients had triple exposure to YFV, CHIKV, or DENV. No exposure to CCHF, RVFV, or WNV was detected.

Crimean-Congo hemorrhagic fever (CCHF) is a highly severe and virulent viral disease of zoonotic origin, caused by a tick-born CCHF virus (CCHFV). The virus is endemic in many countries and has a mortality rate between 10% and 40%. As there is no licensed vaccine or therapeutic options available to treat CCHF, the present study was designed to focus on application of modern computational approaches to propose a multi-epitope vaccine (MEV) expressing antigenic determinants prioritized from the CCHFV genome. Integrated computational analyses revealed the presence of 9 immunodominant epitopes from Nucleoprotein (N), RNA dependent RNA polymerase (RdRp), Glycoprotein N (Gn/G2), and Glycoprotein C (Gc/G1). Together these epitopes were observed to cover 99.74% of the world populations. The epitopes demonstrated excellent binding affinity for the B- and T-cell reference set of alleles, the high antigenic potential, non-allergenic nature, excellent solubility, zero percent toxicity and interferon-gamma induction potential. The epitopes were engineered into an MEV through suitable linkers and adjuvating with an appropriate adjuvant molecule. The recombinant vaccine sequence revealed all favorable physicochemical properties allowing the ease of experimental analysis in vivo and in vitro . The vaccine 3D structure was established ab initio . Furthermore, the vaccine displayed excellent binding affinity for critical innate immune receptors: TLR2 (−14.33 kcal/mol) and TLR3 (−6.95 kcal/mol). Vaccine binding with these receptors was dynamically analyzed in terms of complex stability and interaction energetics. Finally, we speculate the vaccine sequence reported here has excellent potential to evoke protective and specific immune responses subject to evaluation of downstream experimental analysis.

Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne virus capable of causing a severe hemorrhagic fever disease in humans. There are currently no licensed vaccines to prevent CCHFV-associated disease. We developed a DNA vaccine expressing the M-segment glycoprotein precursor gene of CCHFV and assessed its immunogenicity and protective efficacy in two lethal mouse models of disease: type I interferon receptor knockout (IFNAR-/-) mice; and a novel transiently immune suppressed (IS) mouse model. Vaccination of mice by muscle electroporation of the M-segment DNA vaccine elicited strong antigen-specific humoral immune responses with neutralizing titers after three vaccinations in both IFNAR-/- and IS mouse models. To compare the protective efficacy of the vaccine in the two models, groups of vaccinated mice (7-10 per group) were intraperitoneally (IP) challenged with a lethal dose of CCHFV strain IbAr 10200. Weight loss was markedly reduced in CCHFV DNA-vaccinated mice as compared to controls. Furthermore, whereas all vector-control vaccinated mice succumbed to disease by day 5, the DNA vaccine protected >60% of the animals from lethal disease. Mice from both models developed comparable levels of antibodies, but the IS mice had a more balanced Th1/Th2 response to vaccination. There were no statistical differences in the protective efficacies of the vaccine in the two models. Our results provide the first comparison of these two mouse models for assessing a vaccine against CCHFV and offer supportive data indicating that a DNA vaccine expressing the glycoprotein genes of CCHFV elicits protective immunity against CCHFV.

Background On December 8 th , 2015, World Health Organization published a priority list of eight pathogens expected to cause severe outbreaks in the near future. To better understand global research trends and characteristics of publications on these emerging pathogens, we carried out this bibliometric study hoping to contribute to global awareness and preparedness toward this topic. Method Scopus database was searched for the following pathogens/infectious diseases: Ebola, Marburg, Lassa, Rift valley, Crimean-Congo, Nipah, Middle Eastern Respiratory Syndrome (MERS), and Severe Respiratory Acute Syndrome (SARS). Retrieved articles were analyzed to obtain standard bibliometric indicators. Results A total of 8619 journal articles were retrieved. Authors from 154 different countries contributed to publishing these articles. Two peaks of publications, an early one for SARS and a late one for Ebola, were observed. Retrieved articles received a total of 221,606 citations with a mean ± standard deviation of 25.7 ± 65.4 citations per article and an h -index of 173. International collaboration was as high as 86.9%. The Centers for Disease Control and Prevention had the highest share (344; 5.0%) followed by the University of Hong Kong with 305 (4.5%). The top leading journal was Journal of Virology with 572 (6.6%) articles while Feldmann, Heinz R . was the most productive researcher with 197 (2.3%) articles. China ranked first on SARS, Turkey ranked first on Crimean-Congo fever, while the United States of America ranked first on the remaining six diseases. Of retrieved articles, 472 (5.5%) were on vaccine – related research with Ebola vaccine being most studied. Conclusion Number of publications on studied pathogens showed sudden dramatic rise in the past two decades representing severe global outbreaks. Contribution of a large number of different countries and the relatively high h -index are indicative of how international collaboration can create common health agenda among distant different countries.