Viral Haemorrhagic Fever (VHF) and Other Serious Viral Infections : First contact - how to act and protect
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ABSTRACT:
SUBMITTER: Andersen B
PROVIDER: S-EPMC7120164 | biostudies-literature | 2018 Sep
REPOSITORIES: biostudies-literature
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Project description:BackgroundCrimean-Congo haemorrhagic fever virus (CCHFV) is considered an emerging infectious disease threat in the European Union. Since 2000, the incidence and geographic range of confirmed CCHF cases have markedly increased, following changes in the distribution of its main vector, Hyalomma ticks.AimsTo review scientific literature and collect experts' opinion to analyse relevant aspects of the laboratory management of human CCHF cases and any exposed contacts, as well as identify areas for advancement of international collaborative preparedness and laboratory response plans.MethodsWe conducted a literature review on CCHF molecular diagnostics through an online search. Further, we obtained expert opinions on the key laboratory aspects of CCHF diagnosis. Consulted experts were members of two European projects, EMERGE (Efficient response to highly dangerous and emerging pathogens at EU level) and EVD-LabNet (Emerging Viral Diseases-Expert Laboratory Network).ResultsConsensus was reached on relevant and controversial aspects of CCHF disease with implications for laboratory management of human CCHF cases, including biosafety, diagnostic algorithm and advice to improve lab capabilities. Knowledge on the diffusion of CCHF can be obtained by promoting syndromic approach to infectious diseases diagnosis and by including CCHFV infection in the diagnostic algorithm of severe fevers of unknown origin.ConclusionNo effective vaccine and/or therapeutics are available at present so outbreak response relies on rapid identification and appropriate infection control measures. Frontline hospitals and reference laboratories have a crucial role in the response to a CCHF outbreak, which should integrate laboratory, clinical and public health responses.
| S-EPMC6386216 | biostudies-literature
Project description:BackgroundCrimean-Congo Haemorrhagic Fever Virus is a tick-borne bunyavirus prevalent across Asia, Africa, the Middle East, and Europe. The virus causes a non-specific febrile illness which may develop into severe haemorrhagic disease. To date, there are no widely approved therapeutics. Recently, we reported an alphavirus-based replicon RNA vaccine which expresses the CCHFV nucleoprotein (repNP) or glycoprotein precursor (repGPC) and is protective against lethal disease in mice.MethodsHere, we evaluated engineered GPC constructs to find the minimal enhancing epitope of repGPC and test two RNA vaccine approaches to express multiple antigens in vivo to optimize protective efficacy of our repRNA.FindingsVaccination with repNP and a construct expressing just the Gc antigen (repGc-FL) resulted in equivalent immunogenicity and protective efficacy compared to original repNP + repGPC vaccination. This vaccine was protective when prepared in either of two vaccine approaches, a mixed synthesis reaction producing two RNAs in a single tube and a single RNA expressing two antigens.InterpretationOverall, our data illustrate two vaccine approaches to deliver two antigens in a single immunization. Both approaches induced protective immune responses against CCHFV in this model. These approaches support their continued development for this and future vaccine candidates for CCHFV and other vaccines where inclusion of multiple antigens would be optimal.FundingThis work was supported by the Intramural Research Program, NIAID/NIH, HDT Bio and MCDC Grant #MCDC2204-011.
| S-EPMC10885550 | biostudies-literature
Project description:BackgroundPredicting when and where pathogens will emerge is difficult, yet, as shown by the recent Ebola and Zika epidemics, effective and timely responses are key. It is therefore crucial to transition from reactive to proactive responses for these pathogens. To better identify priorities for outbreak mitigation and prevention, we developed a cohesive framework combining disparate methods and data sources, and assessed subnational pandemic potential for four viral haemorrhagic fevers in Africa, Crimean-Congo haemorrhagic fever, Ebola virus disease, Lassa fever, and Marburg virus disease.MethodsIn this multistage analysis, we quantified three stages underlying the potential of widespread viral haemorrhagic fever epidemics. Environmental suitability maps were used to define stage 1, index-case potential, which assesses populations at risk of infection due to spillover from zoonotic hosts or vectors, identifying where index cases could present. Stage 2, outbreak potential, iterates upon an existing framework, the Index for Risk Management, to measure potential for secondary spread in people within specific communities. For stage 3, epidemic potential, we combined local and international scale connectivity assessments with stage 2 to evaluate possible spread of local outbreaks nationally, regionally, and internationally.FindingsWe found epidemic potential to vary within Africa, with regions where viral haemorrhagic fever outbreaks have previously occurred (eg, western Africa) and areas currently considered non-endemic (eg, Cameroon and Ethiopia) both ranking highly. Tracking transitions between stages showed how an index case can escalate into a widespread epidemic in the absence of intervention (eg, Nigeria and Guinea). Our analysis showed Chad, Somalia, and South Sudan to be highly susceptible to any outbreak at subnational levels.InterpretationOur analysis provides a unified assessment of potential epidemic trajectories, with the aim of allowing national and international agencies to pre-emptively evaluate needs and target resources. Within each country, our framework identifies at-risk subnational locations in which to improve surveillance, diagnostic capabilities, and health systems in parallel with the design of policies for optimal responses at each stage. In conjunction with pandemic preparedness activities, assessments such as ours can identify regions where needs and provisions do not align, and thus should be targeted for future strengthening and support.FundingPaul G Allen Family Foundation, Bill & Melinda Gates Foundation, Wellcome Trust, UK Department for International Development.
| S-EPMC5735217 | biostudies-literature
Project description:BackgroundParents of febrile children frequently contact primary care. Longer duration of fever has been related to increased risk for serious bacterial infections (SBI). However, the evidence for this association remains controversial. We assessed the predictive value of duration of fever for SBI.MethodsStudies from MEDLINE, Embase and Cochrane databases (from January 1991 to December 2009) were retrieved. We included studies describing children aged 2 months to 6 years in countries with high Haemophilus influenzae type b vaccination coverage. Duration of fever had to be studied as a predictor for serious bacterial infections.ResultsSeven studies assessed the association between duration of fever and serious bacterial infections; three of these found a relationship.ConclusionThe predictive value of duration of fever for identifying serious bacterial infections in children remains inconclusive. None of these seven studies was performed in primary care. Studies evaluating the duration of fever and its predictive value in children in primary care are required.
| S-EPMC3111584 | biostudies-literature
Project description:Background and objectivesTo determine the rate of serious-bacterial-infections (SBI) in young ex-premature infants with fever, and to develop a risk-stratification algorithm for these patients.MethodsA retrospective cohort study including all infants who presented to the pediatric emergency department (ED) of a tertiary-care university-hospital between 2010 and 2020 with fever (≥38°C), were born prematurely (<37-weeks), had post-conception age of <52-weeks, and had available blood, urine, or CSF cultures. The rates of SBI by age-of-birth and age-at-visit were calculated and compared to a cohort of matched full-term controls.ResultsThe study included a total of 290 ex-premature cases and 290 full-term controls. There were 11 cases (3.8%) with an invasive bacterial infection (IBI) of either bacteremia, meningitis or both and only six controls (2.1%) with IBI (p = 0.32). Over 28-days chronologic-age, there were 10 (3.6%) IBIs among cases and no IBIs among the controls (p = 0.02). There were eight (3%) cases and three (1%) controls with IBI who were well-appearing on physical examination (p = 0.19). All eight well-appearing ex-premature infants were under 60-days adjusted-age, seven of whom (88%) were also under 28-days adjusted-age. There were 28 (10.6%) cases and 34 (12%) controls with urinary tract infection (UTI) (p = 0.5). Among cases under 60-days adjusted-age, urinalysis was not reliable to exclude UTI (50% negative).ConclusionsWell-appearing ex-preterm infants have a significant risk for IBI until the adjusted age of 28-days and for UTI until the adjusted age of 60-days. Further studies are needed to evaluate the approach to fever in this unique population.
| S-EPMC9597199 | biostudies-literature
Project description:Type 1 diabetes (T1D) is an autoimmune disease that is caused by the destruction of insulin-producing beta cells. Viral infections induce immune responses that can damage beta cells and promote T1D or on the other hand prevent the development of the disease. However, the opposing roles of viral infections in T1D are not understood mechanistically. We report here that viruses that do not inflict damage on beta cells provided protection from T1D by triggering immunoregulatory mechanisms. Infection of prediabetic NOD mice with Coxsackie virus B3 or lymphocytic choriomeningitis virus (LCMV) delayed diabetes onset and reduced disease incidence. Delayed T1D onset was due to transient upregulation of programmed cell death-1 ligand 1 (PD-L1) on lymphoid cells, which prevented the expansion of diabetogenic CD8+ T cells expressing programmed cell death-1 (PD-1). Reduced T1D incidence was caused by increased numbers of invigorated CD4+CD25+ Tregs, which produced TGF-beta and maintained long-term tolerance. Full protection from T1D resulted from synergy between PD-L1 and CD4+CD25+ Tregs. Our results provide what we believe to be novel mechanistic insight into the role of viruses in T1D and should be valuable for prospective studies in humans.
| S-EPMC2689128 | biostudies-literature
Project description:Crimean-Congo haemorrhagic fever (CCHF) is the most medically significant tick-borne disease, being widespread in the Middle East, Asia, Africa and parts of Europe 1 . Increasing case numbers, westerly movement and broadly ranging case fatality rates substantiate the concern of CCHF as a public health threat. Ixodid ticks of the genus Hyalomma are the vector for CCHF virus (CCHFV), an arbovirus in the genus Orthonairovirus of the family Nairoviridae. CCHFV naturally infects numerous wild and domestic animals via tick bite without causing obvious disease2,3. Severe disease occurs only in humans and transmission usually happens through tick bite or contact with infected animals or humans. The only CCHF disease model is a subset of immunocompromised mice4-6. Here, we show that following CCHFV infection, cynomolgus macaques exhibited hallmark signs of human CCHF with remarkably similar viral dissemination, organ pathology and disease progression. Histopathology showed infection of hepatocytes, endothelial cells and monocytes and fatal outcome seemed associated with endothelial dysfunction manifesting in a clinical shock syndrome with coagulopathy. This non-human primate model will be an invaluable asset for CCHFV countermeasures development.
| S-EPMC6717652 | biostudies-literature
Project description:BackgroundDespite rhabdoviral infections being one of the best known fish diseases, the gene expression changes induced at the surface tissues after the natural route of infection (infection-by-immersion) have not been described yet. This work describes the differential infected versus non-infected expression of proteins and immune-related transcripts in fins and organs of zebrafish Danio rerio shortly after infection-by-immersion with viral haemorrhagic septicemia virus (VHSV).ResultsTwo-dimensional differential gel electrophoresis detected variations on the protein levels of the enzymes of the glycolytic pathway and cytoskeleton components but it detected very few immune-related proteins. Differential expression of immune-related gene transcripts estimated by quantitative polymerase chain reaction arrays and hybridization to oligo microarrays showed that while more transcripts increased in fins than in organs (spleen, head kidney and liver), more transcripts decreased in organs than in fins. Increased differential transcript levels in fins detected by both arrays corresponded to previously described infection-related genes such as complement components (c3b, c8 and c9) or class I histocompatibility antigens (mhc1) and to newly described genes such as secreted immunoglobulin domain (sid4), macrophage stimulating factor (mst1) and a cluster differentiation antigen (cd36).ConclusionsThe genes described would contribute to the knowledge of the earliest molecular events occurring in the fish surfaces at the beginning of natural rhabdoviral infections and/or might be new candidates to be tested as adjuvants for fish vaccines.
| S-EPMC2997011 | biostudies-literature
Project description:BACKGROUND:Fever is a cause for concern for both parents and the treating pediatrician and a common reason for antibiotic overuse. However, the proportion of children hospitalized for fever with serious bacterial infection (SBI) is uncertain. We aimed to evaluate the epidemiological, clinical, hematological, and biochemical risks for SBI among the children admitted with fever. METHOD:This prospective study was conducted in a rural teaching hospital in India on consecutive children, aged 3?months-12?years, presenting with fever 100?°F (37.7?°C) or higher. The presence of SBI was confirmed with one of the following criteria: (a) a positive blood culture; (b) roentgenographically confirmed pneumonia with high titres of C-reactive protein; (c) a culture-confirmed urinary tract infection; (d) enteric fever diagnosed clinically in addition to either a positive blood culture or high Widal titers; and (e) meningitis diagnosed clinically in addition to either a positive blood culture or cerebrospinal fluid culture. A predefined questionnaire was filled. RESULTS:A total of 302 children were included in the study, out of which 47% (95% CI 41.4-52.7%) presented with SBI. The factors associated with confirmed SBI in bivariate analysis were history of previous hospitalization, history of chronic illness, history of medication in the previous 1 week, a partially immunized child, history of common cold, moderate-grade fever, toxic look, significant lymphadenopathy, absence of BCG scar, delayed development, irritability, breathlessness, respiratory distress, poor feeding, significant weight loss, suspected urinary tract infection, hyponatremia, hypokalemia, and abnormal leucocyte count. The final generalized logistic regression model revealed partially immunized child (RR 4.26), breathlessness (RR 1.80), weight loss (RR 2.28), and suspected urinary tract infection (RR 1.95) as risk factors for the increased risk of SBI. CONCLUSION:The study identified multiple risk factors for SBI. Pediatricians can be made aware of these risk factors. Further studies are warranted to identify age-specific risk factors for SBI because most clinicians depend on clinical signs and symptoms to identify SBI.
| S-EPMC7035762 | biostudies-literature
Project description:Crimean-Congo haemorrhagic fever (CCHF) is an often fatal viral infection described in about 30 countries around the world. The authors report a fatal case of Crimean-Congo hemorrhagic fever (CCHF) observed in a patient from Kosova. The diagnosis of CCHF was confirmed by reverse transcription-PCR. Late diagnosis decreased the efficacy of treatment and patient died due to severe complications of infection.
| S-EPMC1624825 | biostudies-literature