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Crimean-Congo haemorrhagic fever (CCHF) is a severe tick-borne viral zoonosis endemic to parts of Africa, Europe, the Middle East and Central Asia. Human cases are reported annually in South Africa, with a 25% case fatality rate since the first case was recognized in 1981. We investigated CCHF virus (CCHFV) seroprevalence and risk factors associated with infection in cattle and humans, and the presence of CCHFV in Hyalomma spp. ticks in central South Africa in 2017–18. CCHFV IgG seroprevalence was 74.2% (95%CI: 64.2–82.1%) in 700 cattle and 3.9% (95%CI: 2.6–5.8%) in 541 farm and wildlife workers. No veterinary personnel (117) or abattoir workers (382) were seropositive. The prevalence of CCHFV RNA was significantly higher in Hyalomma truncatum (1.6%) than in H. rufipes (0.2%) (P = 0.002). Seroprevalence in cattle increased with age and was greater in animals on which ticks were found. Seroprevalence in cattle also showed significant geographic variation. Seroprevalence in humans increased with age and was greater in workers who handled livestock for injection and collection of samples. Our findings support previous evidence of widespread high CCHFV seroprevalence in cattle and show significant occupational exposure amongst farm and wildlife workers. Our seroprevalence estimate suggests that CCHFV infections are five times more frequent than the 215 confirmed CCHF cases diagnosed in South Africa in the last four decades (1981–2019). With many cases undiagnosed, the potential seriousness of CCHF in people, and the lack of an effective vaccine or treatment, there is a need to improve public health awareness, prevention and disease control. Author summary: Crimean-Congo haemorrhagic fever (CCHF) is an infection caused by a tick-borne virus endemic to a large geographic area, that is asymptomatic in animals but presents a significant health risk to humans with no effective vaccine. Serological surveys were carried out in rural populations and animals shortly after the first reported case in South Africa in 1981, but little is known about the current seroprevalence of CCHFV in humans and animals, and tick infection rates. We conducted a survey in 2017–18 to obtain recent estimates and examined exposure factors in an area of South Africa where cases are known to occur. We observed a high seroprevalence in cattle of 74.2%. Farm and wildlife workers at risk of occupational exposure to CCHFV had a seroprevalence of 3.9%, which was higher than previously reported. No evidence of CCHFV infection was found in abattoir workers or veterinary professionals in that area. CCHFV RNA was detected in both species of Hyalomma ticks but with a higher prevalence (1.6%) in H. truncatum. This study suggests that CCHFV is widespread in South Africa, that exposure to CCHFV is more common than generally believed in animal-related occupations and that increased public health awareness of risk factors associated with CCHFV infection are required to reduce morbidity and mortality from CCHF. [ABSTRACT FROM AUTHOR]

Crimean-Congo haemorrhagic fever virus (CCHFV) is a member of the Orthonairovirus genus of the Nairoviridae family and is associated with haemorrhagic fever in humans. Although T lymphocyte responses are known to play a role in protection from and clearance of viral infections, specific T cell epitopes have yet to be identified for CCHFV following infection. A panel of overlapping peptides covering the CCHFV nucleoprotein and the structural glycoproteins, GN and GC, were screened by ELISpot assay to detect interferon gamma (IFN-γ) production in vitro by peripheral blood mononuclear cells from eleven survivors with previous laboratory confirmed CCHFV infection. Reactive peptides were located predominantly on the nucleoprotein, with only one survivor reacting to two peptides from the glycoprotein GC. No single epitope was immunodominant, however all but one survivor showed reactivity to at least one T cell epitope. The responses were present at high frequency and detectable several years after the acute infection despite the absence of continued antigenic stimulation. T cell depletion studies confirmed that IFN-γ production as detected using the ELISpot assay was mediated chiefly by CD8+ T cells. This is the first description of CD8+ T cell epitopic regions for CCHFV and provides confirmation of long-lived T cell responses in survivors of CCHFV infection. [ABSTRACT FROM AUTHOR]

In contrast to animals, Crimean-Congo hemorrhagic fever (CCHF) causes a severe disease in humans with a high mortality rate. The etiological agent, CCHF virus (CCHFV), can be transmitted by argasid and ixodid ticks, but arachnids of the genus Hyalomma, followed by Rhipicephalus and Dermacentor serve as the major vectors of this virus. The goal of the study was to assess the epidemiological situation of CCHFV infection in cattle in south-east Poland, and survey for potential tick vector species. A total of 592 bovine blood samples from animals located in the southernmost region in Poland were tested by IgG sandwich enzyme-linked immunosorbent assay. Ticks ( n = 993) from south-east Poland were collected from dogs, cats, cattle, and horses and tested by RT-PCR. All 592 serum samples were negative for IgG antibodies to CCHFV. Of the ticks collected, 125 were Dermacentor reticulatus and 868 represented Ixodes ricinus, both species are regarded as potential vectors of CCHFV. All tick samples were negative for the presence of CCHFV. Considering the zoonotic nature, public health importance, and the virus increasing spread, it was prudent to assess the seroprevalence of CCHFV in the south-east area of Poland, bordering with CCHFV endemic areas. It seems unlikely that CCHFV infection will suddenly spread in Poland, but considering the multiple possibilities of the virus introduction, serosurveys and vector biosurveillance should be conducted at regular intervals. [ABSTRACT FROM AUTHOR]

A patient with Crimean-Congo haemorrhagic fever (CCHF) presented with a high white cell count and splenomegaly. Underlying chronic myeloid leukaemia was diagnosed. The management of this complex case was difficult, and the patient demised. This case illustrates that in patients with an acute febrile illness with haemorrhage, a thorough history and examination, as well as a high index of suspicion for concurrent conditions, is important. [ABSTRACT FROM PUBLISHER]

Background: In 2008 a nosocomial outbreak of five cases of viral hemorrhagic fever due to a novel arenavirus, Lujo virus, occurred in Johannesburg, South Africa. Lujo virus is only the second pathogenic arenavirus, after Lassa virus, to be recognized in Africa and the first in over 40 years. Because of the remote, resource-poor, and often politically unstable regions where Lassa fever and other viral hemorrhagic fevers typically occur, there have been few opportunities to undertake in-depth study of their clinical manifestations, transmission dynamics, pathogenesis, or response to treatment options typically available in industrialized countries. Methods and Findings: We describe the clinical features of five cases of Lujo hemorrhagic fever and summarize their clinical management, as well as providing additional epidemiologic detail regarding the 2008 outbreak. Illness typically began with the abrupt onset of fever, malaise, headache, and myalgias followed successively by sore throat, chest pain, gastrointestinal symptoms, rash, minor hemorrhage, subconjunctival injection, and neck and facial swelling over the first week of illness. No major hemorrhage was noted. Neurological signs were sometimes seen in the late stages. Shock and multi-organ system failure, often with evidence of disseminated intravascular coagulopathy, ensued in the second week, with death in four of the five cases. Distinctive treatment components of the one surviving patient included rapid commencement of the antiviral drug ribavirin and administration of HMG-CoA reductase inhibitors (statins), N-acetylcysteine, and recombinant factor VIIa. Conclusions: Lujo virus causes a clinical syndrome remarkably similar to Lassa fever. Considering the high case-fatality and significant logistical impediments to controlled treatment efficacy trials for viral hemorrhagic fever, it is both logical and ethical to explore the use of the various compounds used in the treatment of the surviving case reported here in future outbreaks. Clinical observations should be systematically recorded to facilitate objective evaluation of treatment efficacy. Due to the risk of secondary transmission, viral hemorrhagic fever precautions should be implemented for all cases of Lujo virus infection, with specialized precautions to protect against aerosols when performing enhanced-risk procedures such as endotracheal intubation. Author Summary: Viral hemorrhagic fever is a syndrome often associated with high fatality and risk of secondary transmission. In 2008, an outbreak of a novel hemorrhagic fever virus called Lujo occurred in Johannesburg, South Africa, with secondary transmission from the index patient to four healthcare workers. Four of the five patients died. Lujo belongs to the arenavirus family and is only the second pathogenic arenavirus, after Lassa virus, to be recognized in Africa and the first in over 40 years. Because most viral hemorrhagic fevers occur in remote, resource-poor settings, few in-depth controlled studies of their clinical manifestations, transmission dynamics, pathogenesis, or response to treatment options are possible. We describe the clinical features of the five cases in this outbreak and summarize the clinical management, as well as providing additional epidemiologic detail. Lujo virus causes a clinical syndrome remarkably similar to Lassa fever. The treatment options used in these five cases are discussed as well as the recommended precautions to prevent secondary transmission. [ABSTRACT FROM AUTHOR]

Crimean-Congo hemorrhagic fever virus (CCHFV) is a bunyavirus causing severe hemorrhagic fever disease in humans, with high mortality rates. The requirement of a high-containment laboratory and the lack of an animal model hampered the study of the immune response and protection of vaccine candidates. Using the recently developed interferon alpha receptor knockout (IFNAR-/-) mouse model, which replicates human disease, we investigated the immunogenicity and protection of two novel CCHFV vaccine candidates: a DNA vaccine encoding a ubiquitin-linked version of CCHFV Gc, Gn, and N and one using transcriptionally competent virus-like particles (tc-VLPs). In contrast to most studies that focus on neutralizing antibodies, we measured both humoral and cellular immune responses. We demonstrated a clear and 100% efficient preventive immunity against lethal CCHFV challenge with the DNA vaccine. Interestingly, there was no correlation with the neutralizing antibody titers alone, which were higher in the tc-VLP-vaccinated mice. However, the animals with a lower neutralizing titer, but a dominant cell-mediated Th1 response and a balanced Th2 response, resisted the CCHFV challenge. Moreover, we found that in challenged mice with a Th1 response (immunized by DNA/DNA and boosted by tc-VLPs), the immune response changed to Th2 at day 9 postchallenge. In addition, we were able to identify new linear B-cell epitope regions that are highly conserved between CCHFV strains. Altogether, our results suggest that a predominantly Th1-type immune response provides the most efficient protective immunity against CCHFV challenge. However, we cannot exclude the importance of the neutralizing antibodies as the surviving immunized mice exhibited substantial amounts of them. [ABSTRACT FROM AUTHOR]