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Purpose The present study was undertaken with the objective to study the common etiology of Viral Haemorrhagic Fever (VHF) among patients attending tertiary health care centre in NE India and also to study the clinico-demographic profile of such patients. The agents of VHF included in the study were dengue, chikungunya and Crimean Congo haemorrhagic fever (CCHF) virus. The inclusion of CCHF was based on evidence of seroprevalence in livestock (bovine, sheep and goat) in various North Eastern states. Materials and methods Serum samples were collected from 51 suspected VHF patients. MAC-ELISA was done to detect dengue and chikungunya specific IgM antibody. The samples were also tested by real-time RT-PCR for detection of dengue, chikungunya and CCHF specific nucleic acid. The laboratory and clinico-demographic profile of these patients were noted in detail. Results Serum samples of 16 of 51 suspected cases were confirmed to be suffering from VHF. Among these confirmed cases, 12 were diagnosed with dengue haemorrhagic fever, one was diagnosed with chikungunya and three were diagnosed with dengue-chikungunya co-infection. Based on severity, DHF was further classified into- DHF I- (4,26.6%), DHF II (6,40%), DHF III (3,20%) and DHF IV (2,13.3%). There was no CCHFV infection detected in our study. Retro-orbital pain (P ​= ​0.02) and haematocrit level (P ​= ​0.03) were found to be statistically significant. Conclusions This study reiterates the fact that CCHF virus infection is still probably absent in human population of NE India and haemorrhagic symptoms, though rare maybe one of the atypical manifestations of chikungunya infection.

Viral haemorrhagic fever can be caused by one of a diverse group of viruses that come from four different families of RNA viruses. Disease severity can vary from mild self-limiting febrile illness to severe disease characterized by high fever, high-level viraemia, increased vascular permeability that can progress to shock, multi-organ failure and death. Despite the urgent need, effective treatments and preventative vaccines are currently lacking for the majority of these viruses. A number of factors preclude the effective study of these diseases in humans including the high virulence of the agents involved, the sporadic nature of outbreaks of these viruses, which are typically in geographically isolated areas with underserviced diagnostic capabilities, and the requirements for high level bio-containment. As a result, animal models that accurately mimic human disease are essential for advancing our understanding of the pathogenesis of viral haemorrhagic fevers. Moreover, animal models for viral haemorrhagic fevers are necessary to test vaccines and therapeutic intervention strategies. Here, we present an overview of the animal models that have been established for each of the haemorrhagic fever viruses and identify which aspects of human disease are modelled. Furthermore, we discuss how experimental design considerations, such as choice of species and virus strain as well as route and dose of inoculation, have an influence on animal model development. We also bring attention to some of the pitfalls that need to be avoided when extrapolating results from animal models.

Pathogens associated with haemorrhagic fever commonly have zoonotic origins. The first documented imported case of likely viral severe haemorrhagic fever in Sweden occurred in 1990. Despite extensive study, no aetiological agent was identified. Following retrospective investigation with total RNA-sequencing of samples collected between 7 and 36 days from onset of symptoms we identified dengue virus 3 (DENV-3) and a human pegivirus (HPgV). We conclude that the patient likely suffered from haemorrhagic symptoms due to an atypical severe and undiagnosed dengue infection. Funding Agencies|Swedish research council FORMASSwedish Research CouncilSwedish Research Council Formas [2015-710]; Swedish research council VRSwedish Research Council [2020-02593]; ARC Australian Laureate FellowshipAustralian Research Council [FL170100022]; Taishan Scholars program of Shandong Province [ts201511056]; Academic promotion programme of Shandong First Medical University [2019QL006]

Summary Background A case of Crimean-Congo haemorrhagic fever (CCHF) was imported into Scotland in 2012. Aim To discuss the public health response to the case, and the control measures taken to prevent secondary transmission. Methods Following confirmation of the case, an incident management team (IMT) was convened to ensure that: (i) all individuals exposed to the case and/or their blood/body fluids were identified, assessed and followed-up appropriately; and (ii) the appropriate disinfection or disposal of equipment was used to manage the patient, laboratory specimens obtained from the case, and their environment. Findings Contact tracing identified 19 individuals who required follow-up and monitoring. No secondary cases occurred. Identification of laboratory specimens obtained prior to diagnosis proved challenging. The majority were traced, temporarily stored in sharps boxes and subsequently incinerated. A small number could not be recovered and consequently would have been disposed of through the routine hospital waste system. Biochemical and haematology analysers were decontaminated according to the manufacturers' instructions and liquid waste was discharged to drains. The patient's mattress, sphygmomanometer and pulse oximeter probe were incinerated. Decontamination of the clinical environment was undertaken following guidance from national experts. Conclusions While national guidance for the management of cases of viral haemorrhagic fever (VHF) available at the time in the UK informed the approach taken to manage the risk of secondary transmission, a number of practical issues relating to infection control aspects of managing a patient with VHF in a non-high-level isolation unit environment were encountered. Close liaison between national experts and the IMT was key to the expedient response to the emerging issues.

Summary Background The recent Ebola epidemic has increased public awareness of the risk of travel associated viral haemorrhagic fever (VHF). International preparedness to manage imported cases Ebola virus infection was inadequate, highlighted by cases of nosocomial transmission. Crimean-Congo haemorrhagic fever (CCHF) is a re-emerging tick-borne VHF centred in the Eurasian region, affecting a large geographical area and with human-to-human transmission reported, especially in the healthcare setting. Objectives To systematically review the characteristics of travel associated Crimean-Congo haemorrhagic fever. Methods A systematic review of travel-associated cases of CCHF was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement protocol. PubMed, SCOPUS, Science Citation Index (SCI) and ProMED databases were searched for reports published between January 1960 and January 2016. Three independent reviewers selected and reviewed studies and extracted data. Results 21 cases of travel associated CCHF were identified, of which 12 died (3 outcome unknown) and 4 secondary (nosocomial) infections were reported. Risk occupations or activities for CCHF infection were reported in 8/12 cases when data were available. Travel from Asia to Asia occurred in 9 cases, Africa to Africa occurred in 5 cases, Africa to Europe in 3 cases, Asia to Europe in 2 cases and Europe to Europe in 2 cases. Conclusion CCHF related to travel is rare, is generally associated with at risk activities/occupation and is frequently fatal. Key to early diagnosis and prevention of nosocomial transmission is an understanding of CCHF risk factors and the geographical distribution of CCHF. International travel to CCHF endemic areas is increasing and clinicians and laboratory personnel managing returning travellers should maintain a high index of suspicion.

Objectives The aim of this study was to evaluate the possibility of using a PCR-based panel to identify bacterial and fungal bloodstream infections in the setting of suspected or confirmed viral haemorrhagic fever. Methods The accuracy of the FilmArray® Blood Culture Identification Panel (BCID) assay was assessed to identify the common bacterial and fungal pathogens associated with bloodstream infections after positive blood culture inactivation using a guanidinium thiocyanate containing buffer lysis that is commonly used for viral haemorrhagic fever molecular diagnostics. Results The FilmArray® BCID panel assay detected 95% (19/20) of the pathogens analysed in this study by using both protocols with and without inactivation. Absolute consistency (100%) was observed in all isolates with phenotypes compatible with the presence of the antibiotic resistance genes mecA, vanA, vanB and blaKPC. Conclusions The FilmArray® BCID panel assay coupled to inactivation using a guanidinium thiocyanate containing buffer lysis represents a convenient, sensitive and specific diagnostic tool to detect some of the most pathogens associated with bloodstream infections in the context of a suspected or confirmed viral haemorrhagic fever.

The viral haemorrhagic fevers are a group of potentially lethal infections, for which limited therapy is available and for which early diagnosis is desirable in order that meticulous isolation, contact tracing and public control measures can be instituted. It is important in these days of widespread foreign travel and integration that all clinicians especially intensivists be aware of this rare potential diagnosis in patients with organ failure, haemorrhage and a pyrexia of unknown origin. In addition these organisms have been considered to have a potential use as biological weapons. It is intended that this article will provide aid in the diagnosis, management and public health/ infectious control procedures required in the event of a patient presenting with a possible diagnosis of viral haemorrhagic fever.

A middle aged man had recently returned from the Republic of Congo where he had been working for several years. His vaccinations were up to date and he was taking doxycycline prophylaxis for malaria. He had complained of fever and headaches before being found deceased in a motel. Initial examination showed early decomposition with dark fluid exuding from his mouth. Due to the small possibility of a viral haemorrhagic fever (VHF), his body was transferred to Forensic and Scientific Services in Brisbane and polymerase chain reaction (PCR) testing was undertaken for VHF on a blood sample. This was negative, but PCR testing for malaria showed Plasmodium falciparum . A subsequent autopsy confirmed disseminated malaria infection, including cerebral malaria.