Hemorrhagic Fever Research Articles

Evaluation of comparative effect between aluminum hydroxide gel and montanide (ISA 70) in potency and protection of locally prepared rabbit hemorrhagic disease virus 2 (RHDV2) vaccines in rabbits

BackgroundRabbit hemorrhagic disease (RHD) is an acute infectious disease that damages the rabbit industry by producing significant mortality rates in young and adult rabbits. RHD is better controlled by vaccination.ObjectiveThe current study's goal was to prepare and evaluate the immuno-enhancing effect of montanide ISA70 and aluminum hydroxide (Al(OH)3) gel incorporated within the inactivated RHDV2 vaccine and assess the vaccine's protective efficacy against the homologous and heterologous local RHDV2 strains in rabbits.MethodsInactivated RHDV vaccines were prepared using Montanide ISA70 oil or Al(OH)3 gel adjuvants and submitted to sterility, safety, and potency tests. 200 rabbits were equally divided into 4 groups: G1 (control), G2 (vaccinated with gel-incorporated vaccine), G3 (vaccinated with montanide-incorporated vaccine), and G4 (vaccinated with gel- and montanide-incorporated vaccines). Individual blood samples were collected from one week to six months from all groups. The vaccine's potency was measured by the HI test and protection percentage post challenge.ResultsData revealed slightly increasing HI titer means reaching the 1st peak at 4 weeks post-vaccination (7.33, 7.67, and 7.33 log2 in the 2nd, 3rd, and 4th groups, respectively), then slightly decreasing and peaked again, giving 9.33 log2 for the2nd group at 3 months post-vaccination (MPV), 10.67 log2 for 3rd the group, and 10.33 log2 for the 4th group at 5 months post-vaccination. Titer gradually decreased but remained protective. The protection rate ranged from 80–100% and 80–90% for homologous and heterologous local RHDV2 vaccines, respectively, within 3 weeks and 6 months post-challenge. The montanide oil RHDV2 vaccine induced better protection than the aluminum gel RHDV2 vaccine.ConclusionThe results demonstrated evidence of cross-protection between RHDV2 strains. The oil emulsion vaccine induced higher and longer-lasting antibody titers than those obtained with the RHDV2 aluminum gel vaccine.

Discovery and biological confirmation of a highly divergent Tacaribe virus in metatranscriptomic data from neotropical bats.

Clade B New World arenaviruses (NWA) include rodent-borne lethal hemorrhagic fever viruses, whereas Tacaribe virus (TCRV) stands out because of its detection in bats and its presumably low zoonotic potential. However, the bat association of TCRV was put into question by lethal experimental neotropical fruit bat infections and rare TCRV detection in bats. Scarce genomic data include near-identical viruses from Caribbean bats and ticks from the US sampled 50 years later. The prototype TCRV isolate used for experimental risk assessments has an extensive passage history in suckling mouse brains. Exploring the true genetic diversity, geographic distribution, and host range of bat-borne NWA is pivotal to assess their zoonotic potential and transmission cycles. We analyzed metatranscriptomic data for evidence of NWA identifying a highly divergent TCRV in bats and confirmed virus detection in original biological materials, supporting the association of TCRV with neotropical bats and warranting investigation of strain-associated TCRV pathogenicity.

Transcriptomic analysis reveals key molecular signatures across recovery phases of hemorrhagic fever with renal syndrome

BackgroundHemorrhagic fever with renal syndrome (HFRS), a life-threatening zoonosis caused by hantavirus, poses significant mortality risks and lacks specific treatments. This study aimed to delineate the transcriptomic alterations during the recovery phases of HFRS.MethodsRNA sequencing was employed to analyze the transcriptomic alterations in peripheral blood mononuclear cells from HFRS patients across the oliguric phase (OP), diuretic phase (DP), and convalescent phase (CP). Twelve differentially expressed genes (DEGs) were validated using quantitative real-time PCR in larger sample sets.ResultsOur analysis revealed pronounced transcriptomic differences between DP and OP, with 38 DEGs showing consistent expression changes across all three phases. Notably, immune checkpoint genes like CD83 and NR4A1 demonstrated a monotonic increase, in contrast to a monotonic decrease observed in antiviral and immunomodulatory genes, including IFI27 and RNASE2. Furthermore, this research elucidates a sustained attenuation of immune responses across three phases, alongside an upregulation of pathways related to tissue repair and regeneration.ConclusionOur research reveals the transcriptomic shifts during the recovery phases of HFRS, illuminating key genes and pathways that may serve as biomarkers for disease progression and recovery.

Overview of Dengue Hemorrhagic Fever (DHF) Prevention in The Community Health Center

Overview of Dengue Hemorrhagic Fever (DHF) Prevention in The Community Health Center

A Longitudinal Analysis of Memory Immune Responses in Convalescent Crimean-Congo Hemorrhagic Fever Survivors in Uganda.

Evaluating the adaptive immune responses to natural infection with Crimean-Congo hemorrhagic fever (CCHF) virus (CCHFV) in human survivors is critical to the development of medical countermeasures. However, the correlates of protection are unknown. As the most prevalent tick-borne human hemorrhagic fever virus with case fatality rates of 5%-30% and worldwide distribution, there is an urgent need to fill these knowledge gaps. Here, we describe adaptive immune responses in a cohort of Ugandan CCHF survivors via serial sampling over 6 years. We demonstrate persistent antibodies after infection and cross-neutralization against various clades of authentic CCHFV, as well as potent effector function. Moreover, we show for the first time persistent, polyfunctional antigen-specific memory T-cell responses to multiple CCHFV proteins up to 9 years after infection. Together, this data provides immunological benchmarks for evaluating CCHFV medical countermeasures and information that can be leveraged toward vaccine immunogen design and viral target identification for monoclonal antibody therapies.

Mathematical Model for the Dynamics of Lassa Fever Incorporating Treatment and Isolation

Lassa Fever (Hemorrhagic Fever) is a widespread disease cause by Mastomys rodent and cause serious health problem leading to loss of lives. This research aims to analyze some existing with the intention of modifying or developing new one Mathematical Model for the Dynamics of Lassa Fever Incorporating Treatment and Isolation. We establish the positivity, boundedness, diseases free and endemic equilibria, basic reproduction number, local and global stability and carried out numerical simulation of the modified model. We formulate and analyze deterministic mathematical model of nine compartments for the transmission dynamics of Lassa Fever infection using a non-linear ordinary differential equation. We investigated a dynamic behavior of the modified model and performed the qualitative analysis of the model. The system has two equilibrium points, namely the disease-free equilibrium and the endemic equilibrium points. The basic reproduction number was calculated using the next-generation matrix and the stability of the model equations were carried out using MATLAB R2021a. the finding of this study shows that Lassa Fever can be significantly curtailed having the basic reproduction number less than unity and that if the implementation of Lassa Fever treatment, isolation is very effective this can reduced or eliminate the number of infected individuals.

Identification and evaluation of multi-antigenic epitopes of immunodominant protein from the selected Crimean–Congo hemorrhagic fever virus genome towards the development of diagnostic and vaccine candidates by reverse vaccinology approach

Identification and evaluation of multi-antigenic epitopes of immunodominant protein from the selected Crimean–Congo hemorrhagic fever virus genome towards the development of diagnostic and vaccine candidates by reverse vaccinology approach

Physical and Chemical Inactivators Evaluation for the Puumala Virus Vaccine Technology Development

Relevance. Hemorrhagic fever with renal syndrome (HFRS) is leading among natural focal human diseases in Russia, the causative agents of which - orthohantaviruses - belong to the order Bunyavirales, family Hantaviridae. More than 98% of HFRS cases in Russia are caused by the Puumala virus. It is a serious zoonosis for which there is still no specific treatment. The WHO has not approved a vaccine. The aim of this study was to investigate the effect of formaldehyde, β-propiolactone, hydrogen peroxide, ultraviolet rays, gamma irradiation and thermal inactivation on the immunogenic activity of inactivated vaccine preparations against HFRS Materials and methods. To achieve this aim, experimental vaccine preparations based on the PUU-TKD/VERO strain of Puumala virus were prepared and inactivated using the methods described above. The time intervals required for complete inactivation of the virus were determined, and the effects of the inactivators on viral RNA and immunogenic activity of the vaccine preparations were evaluated in BALB/c mouse and Syrian hamster models. Results. According to our results, vaccine preparations inactivated by different chemical and physical methods, which differ significantly in the mechanism of the mechanism of interaction with the virus, show no significant differences in immunogenic activity, except for thermal inactivation. Conclusion. A certain advantage of β-propiolactone is the short virus inactivation time, its complete degradation into non-toxic compounds within a few hours, and the reduction of total protein content after sterilization filtration, which is probably due to less aggregation of virus particles and cellular proteins

Crimean-Congo Hemorrhagic Fever Virus: An Emerging Threat in Europe with a Focus on Epidemiology in Spain.

Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne disease transmitted by ticks of the genus Hyalomma and caused by a virus of the Nairoviridae family. In humans, the virus can generate different clinical presentations that can range from asymptomatic to mild illness or produce an hemorrhagic fever with a mortality rate of approximately 30%. The virus pathogenicity and the lack of effective treatment or vaccine for its prevention make it an agent of concern from a public health point of view. The main transmission route is tick bites, so people most exposed to this risk are more likely to become infected. Another risk group are veterinarians and livestock farmers who are in contact with the blood and other fluids of animals that are mostly asymptomatic. Finally, due to its first phase with a non-characteristic symptomatology, there exists a risk of nosocomial infection. It is endemic in Africa, the Balkans, the Middle East, and those Asian countries south of the 50th parallel north, the geographical limit of the main vector. Recently, autochthonous cases have been observed in areas of Europe where the virus was not previously present. Human cases have been detected in Greece, Bulgaria, and Spain. Spain is one of the most affected countries, with a total of 17 autochthonous cases detected since 2013. In other countries, such as France, the virus is present in ticks and animals but has not spread to humans. A high-quality epidemiological surveillance system in these countries is essential to avoid the expansion of this virus to new areas and to limit the impact of current cases.

Applied and Theoretical Aspects of the Ecology of Pathogens of Hemorrhagic Fever with Renal Syndrome and Tick-Borne Encephalitis

Relevance. Hemorrhagic fever with renal syndrome (HFRS) and tick-borne encephalitis (TBE) are the most common natural focal diseases of viral etiology In Russia. The medical and social significance of these two infections is determined by the extensive fociof their spread, high annual morbidity rates in the population, and the possibility of developing severe forms of the disease leading to permanent disability and death. The causative agents of HFRS In Russia are 6 types of hantaviruses Hantaan, Amur, Seoul, Puumala, Kurkino and Sochi, which, immunologically and genetically significantly different from each other, support their existence in nature through six different species of small mammals, which are sources of infection in humans. TBE virus strains that cause disease in humans belong to five phylogenetically distinct subtypes, including: Far Eastern, European, Siberian, “178-79” and Baikal. Aim. Analysis of the role of small mammals and ticks in the ecology of HFRS and TBE pathogens. Conclusions. Small mammals retain and transmit hantaviruses to uninfected animals and ticks. At the same time, ticks retain and transmit to ticks and mammals not only the TBE virus, but also hantaviruses. Despite the taxonomic difference between the viruses that cause HFRS and TBE, some of their ecological properties are similar.

PREVENTIVE BEHAVIORS FOR DENGUE HEMORRHAGIC FEVER

Dengue fever is a viral infection caused by the dengue virus which is transmitted to humans through the bite of an infected mosquito. About half of the world's population is now at risk of dengue fever with an estimated 100–400 million infections occurring annually. This study aims to determine factors related to dengue prevention behavior in the East Ogan Komering Ulu District Health Service in 2024. The design of this research is quantitative with a cross-sectional approach. The population of this study was visits to the Gumawang Health Center in 2024. The sample in this study consisted of 93 respondents. The sampling method used purposive sampling. This research was carried out on 15-26 February 2024. Data was collected using a questionnaire. Bivariate data analysis used the Chi-Square test and multivariate logistic regression. Data collection using questionnaires. Results of statistical test analysis using the Chi-Square statistical test. The results of the study knowledge (p value 0.022), draining the landfill (p value 0.047), preventive measures (p value 0.005) and ventilation (p value (0.017). Age (p value 0.35), mosquito wire installation (p value 0.47) with dengue hemorrhagic fever (DHF) prevention behaviour at the East Ogan Komering Ulu District Health Office in 2024. The most dominant factor with dengue hemorrhagic fever (DHF) prevention behaviour is DHF prevention measures (p Value = 0.003) (OR 0.252). Conclusion There is a relationship between knowledge, landfill draining, preventive measures and ventilation. For the Health Office to carry out dengue prevention activities, carried out routinely and scheduled integrated in basic health services.

Dengue NS1 interaction with lipids alters its pathogenic effects on monocyte derived macrophages

BackgroundWhile dengue NS1 antigen has been shown to be associated with disease pathogenesis in some studies, it has not been linked in other studies, with the reasons remaining unclear. NS1 antigen levels in acute dengue are often associated with increased disease severity, but there has been a wide variation in results based on past dengue infection and infecting dengue virus (DENV) serotype. As NS1 engages with many host lipids, we hypothesize that the type of NS1-lipid interactions alters its pathogenicity.MethodsPrimary human monocyte derived macrophages (MDMs) were co-cultured with NS1 alone or with HDL, LDL, LPS and/or platelet activating factor (PAF) from individuals with a history of past dengue fever (DF = 8) or dengue haemorrhagic fever (DHF = 8). IL-1β levels were measured in culture supernatants, and gene expression analysis carried out in MDMs. Monocyte subpopulations were assessed by flow cytometry. Hierarchical cluster analysis with Euclidean distance calculations were used to differentiate clusters. Differentially expressed variables were extracted and a classifier model was developed to differentiate between past DF and DHF.ResultsSignificantly higher levels of IL-1β were seen in culture supernatants when NS1 was co-cultured with LDL (p = 0.01, median = 45.69 pg/ml), but lower levels when NS1 was co-cultured with HDL (p = 0.05, median = 4.617 pg/ml). MDMs of those with past DHF produced higher levels of IL-1β when NS1 was co-cultured with PAF (p = 0.02). MDMs of individuals with past DHF, were significantly more likely to down-regulate RPLP2 gene expression when macrophages were co-cultured with either PAF alone, or NS1 combined with PAF, or NS1 combined with LDL. When NS1 was co-cultured with PAF, HDL or LDL two clusters were detected based on IL10 expression, but these did not differentiate those with past DF or DHF.ConclusionsAs RPLP2 is important in DENV replication, regulating cellular stress responses and immune responses and IL-10 is associated with severe disease, it would be important to further explore how differential expression of RPLP2 and IL-10 could lead to disease pathogenesis based on NS1 and lipid interactions.

Space-time scanning statistics in the prediction and evaluation of dengue epidemic clusters

ObjectivesTo detect clusters of dengue hemorrhagic fever in an urbanized district of Hai Phong City, Vietnam using Poisson space-time retrospective and prospective analysis. MethodsA cross-sectional and retrospective study analyzed dengue surveillance data in the period from January 01, 2018, to December 31, 2022. Spatial-temporal scanning statistics were performed using the free software SatScan v10.1.2. ResultsA total of 519 cases were recorded. The cumulative incidence per 100,000 inhabitants was 3.37, 127.36, 10.96, 0, and 296.04 in 2018, 2019, 2020, 2021, and 2022, respectively. By retrospective Poisson model-based analysis, seven clusters were detected. Six of these seven detected outbreaks occurred in November and December 2022. The largest cluster had a relative risk (RR) of 1539.5 (P <0.00001). The smallest cluster has a RR of 316.1 (P = 0.006). Prospective analysis using the Poisson model significantly detected four active case clusters at the time of the study. The largest cluster of cases with RR was 47.7 (P <0.00001) and the smallest cluster with RR was 18.2 (P <0.00001). ConclusionsThis study provides a basis for improving the effectiveness of interventions and conducting further investigations into risk factors in the study area, as well as in other urban and suburban areas nationwide.

Lysosome-Associated Membrane Protein Targeting Strategy Improved Immunogenicity of Glycoprotein-Based DNA Vaccine for Marburg Virus.

Marburg hemorrhagic fever (MHF) is a fatal infectious disease caused by Marburg virus (MARV) infection, and MARV has been identified as a priority pathogen for vaccine development by the WHO. The glycoprotein (GP) of MARV mediates viral adhesion and invasion of host cells and therefore can be used as an effective target for vaccine development. Moreover, DNA vaccines have unique advantages, such as simple construction processes, low production costs, and few adverse reactions, but their immunogenicity may decrease due to the poor absorption rate of plasmids. Lysosome-associated membrane protein 1 (LAMP1) can direct antigens to lysosomes and endosomes and has great potential for improving the immunogenicity of nucleic acid vaccines. Therefore, we constructed a DNA vaccine based on a codon-optimized MARV GP (ID MF939097.1) fused with LAMP1 and explored the effect of a LAMP targeting strategy on improving the immunogenicity of the MARV DNA vaccine. ELISA, ELISpot, and flow cytometry revealed that the introduction of LAMP1 into the MARV DNA candidate vaccine improved the humoral and cellular immune response, enhanced the secretion of cytokines, and established long-term immune protection. Transcriptome analysis revealed that the LAMP targeting strategy significantly enriched antigen processing and presentation-related pathways, especially the MHC class II-related pathway, in the candidate vaccine. Our study broadens the strategic vision for enhanced DNA vaccine design and provides a promising candidate vaccine for MHF prevention.

MicroRNAs Regulate the Expression of Genes Related to the Innate Immune and Inflammatory Response in Rabbits Infected with Lagovirus europaeus GI.1 and GI.2 Genotypes.

MicroRNAs (miR) are a group of small, non-coding RNAs of 17-25 nucleotides that regulate gene expression at the post-transcriptional level. Dysregulation of miRNA expression or function may contribute to abnormal gene expression and signaling pathways, leading to disease pathology. Lagovirus europaeus (L. europaeus) causes severe disease in rabbits called rabbit hemorrhagic disease (RHD). The symptoms of liver, lung, kidney, and spleen degeneration observed during RHD are similar to those of acute liver failure (ALF) and multi-organ failure (MOF) in humans. In this study, we assessed the expression of miRs and their target genes involved in the innate immune and inflammatory response. Also, we assessed their potential impact on pathways in L. europaeus infection-two genotypes (GI.1 and GI.2)-in the liver, lungs, kidneys, and spleen. The expression of miRs and target genes was determined using quantitative real-time PCR (qPCR). We assessed the expression of miR-155 (MyD88, TAB2, p65, NLRP3), miR-146a (IRAK1, TRAF6), miR-223 (TLR4, IKKα, NLRP3), and miR-125b (MyD88). We also examined biomarkers of inflammation: IL-1β, IL-6, TNF-α, and IL-18 in four tissues at the mRNA level. Our study shows that the main regulators of the innate immune and inflammatory response in L. europaeus/GI.1 and GI.2 infection, as well as RHD, are miR-155, miR-223, and miR-146a. During infection with L. europaeus/RHD, miR-155 has both pro- and anti-inflammatory effects in the liver and anti-inflammatory effects in the kidneys and spleen; miR-146a has anti-inflammatory effects in the liver, lungs and kidneys; miR-223 has anti-inflammatory effects in all tissues; however, miR-125b has anti-inflammatory effects only in the liver. In each case, such an effect may be a determinant of the pathogenesis of RHD. Our research shows that miRs may regulate three innate immune and inflammatory response pathways in L. europaeus infection. However, the result of this regulation may be influenced by the tissue microenvironment. Our research shows that infection of rabbits with L. europaeus/GI.1 and GI.2 genotypes causes an overexpression of two critical acute phase cytokines: IL-6 in all examined tissues and TNF-α (in the liver, lungs, and spleen). IL-1β was highly expressed only in the lungs after L. europaeus infection. These facts indicate a strong and rapid involvement of the local innate immune and inflammatory response in L. europaeus infection-two genotypes (GI.1 and GI.2)-and in the pathogenesis of RHD. Profile of biomarkers of inflammation in rabbits infected with L. europaeus/GI.1 and GI.2 genotypes are similar regarding the nature of changes but are different for individual tissues. Therefore, we propose three inflammation profiles for L. europaeus infection for both GI.1 and GI.2 genotypes (pulmonary, renal, liver, and spleen).

A Virtual Assessment Model for At-Home Evaluation of Suspected Viral Hemorrhagic Fever Cases.

The Sudan virus disease outbreak in 2022 prompted the Denver Health High-Risk Infection Team (HITeam) to evaluate and implement novel strategies to respond to viral hemorrhagic fever (VHF) events. To improve the VHF response, HITeam members developed a virtual assessment model (VAM) for at-home evaluation of individuals who are suspected of having a VHF. The VAM incorporates aspects of care that would normally be rendered in a high-level isolation unit-including assessment and monitoring, specimen collection, provider consultation, patient and family teaching, and pharmaceutical intervention-into a mobile framework in which team members respond to a suspected case at the individual's home. Building this capability allows for more thorough assessment of a suspect case in the field, as well as the postponement of a decision about activation of the high-level isolation unit until more information is available. Development, testing, and implementation of the VAM required input from an interdisciplinary group of partners that demonstrated the ability of nurses, physicians, laboratorians, paramedics, emergency medical technicians, and public health personnel to integrate into 1 cohesive care team. The resulting model recenters VHF care on the patient by allowing the care team to gather critical information in an environment that is more comfortable for the suspect case while keeping communities safe and lowering exposure risks. The VAM has long-term sustainability implications for global VHF programs and provides solutions for broader challenges in healthcare by modeling cost-effective, patient-centered care within the highly nuanced subspecialty of special pathogen care.

Clinical and etiological characteristics of severe hemorrhagic fever caused by coinfection of hantaan orthohantavirus and severe fever with thrombocytopenia syndrome virus.

Severe fever with thrombocytopenia syndrome (SFTS) and hemorrhagic fever with renal syndrome (HFRS) usually have different infection routes, and coinfection is relatively rare. This study examines the clinical and etiological characteristics of coinfection by these two pathogens to provide important references for clinical diagnosis and treatment. Blood samples from 22 clinically diagnosed patients with HFRS were collected for molecular detection of HFRS and common tick and mouse borne diseases. Inoculate the blood of six severe and critically patients into cells to isolate and proliferate potential viruses, and retest the cell culture to determine the pathogen. In addition, complete data were collected from these 22 HFRS and concurrent SFTS patients, and white blood cells (WBCs), platelet (PLT), blood urea nitrogen (BUN), creatinine (Cr) and other data were compared and analyzed. A total of 31 febrile patients, including 22 HFRS patients and 9 SFTS patients, were collected from September 2021 to October 2022. Among these HFRS patients, 11 were severe or critical. Severe and critical HFRS patients were characterized by rodent exposure history, pharyngeal and conjunctival hyperemia, abnormal WBC and PLT counts, and elevated BUN and Cr values. Virus isolation and molecular detection on blood samples from 6 patients showed that three of the six severe patients were positive for hantaan virus (HTNV), and two of the three HTNV positives were also positive for SFTS bunyavirus (SFTSV). The two coinfected patients exhibited different clinical and laboratory characteristics compared to those infected by either virus alone. Coinfection of HTNV and SFTSV leads to severe and complex hemorrhagic fever. Laboratory characteristics, such as the indicators of WBC, PLT, BUN, and Cr, may differ between HFRS and SFTS. These findings have implications and provide references for the diagnosis and treatment of coinfected cases.

RHDV2 outbreak reduces survival and juvenile recruitment, causing European rabbit population collapse

AbstractInfectious diseases can cause considerable mortality in vertebrate populations, especially when a new pathogen emerges. Quantifying the impact of diseases on wild populations and dissecting the underlying mechanisms requires longitudinal individual monitoring combining demographic and epidemiologic data. Such longitudinal population studies are rare. Rabbit hemorrhagic disease (RHD) is one of the main causes of the decline in European wild rabbit (Oryctolagus cuniculus) populations. A new genotype of RHD virus (RHDV), called RHDV2 or GI.2, emerged in 2010, posing a new threat to previously weakened populations, particularly as this virus can infect individuals already immune to classical RHDV strains. Taking advantage of intensive monitoring from 2009 to 2014 by physical captures and microchip detections of a semi‐captive population of rabbits, we finely assessed the demographic impact of an initial RHDV2 outbreak that occurred in the population and identified the most affected demographic parameters. A multi‐event modeling analysis revealed decreased survival in both juveniles and adults in 2011 and 2012, suggesting an RHDV2 outbreak for two consecutive years. The short‐term survival benefit of vaccination against classical RHDV strains only during these years, and the recovery of carcasses with RHDV2 detection, supported this hypothesis. Variations in population vaccination coverage also explain the difference in adult survival between the two years of the outbreak. And the transient protective effect of vaccination could explain the prolonged duration of the outbreak. A brief episode of myxomatosis in 2011 seems to have had only a limited impact on the population. During outbreak years, in individuals not recently vaccinated, monthly juvenile survival crashed (0.55), and annual adult survival was three times lower than in normal years (0.21 vs. 0.69). The combination of successive juvenile and adult survival estimates for unvaccinated rabbits during the outbreak years resulted in a very low recruitment rate in the breeding population. Finally, RHDV2 outbreaks appear to have caused mortalities comparable to those caused by older classical RHDV strains and may have a strong demographic impact on wild populations of European rabbit. This work highlights the importance of long‐term observational and experimental studies to better understand the impact of epidemics on animal populations.

Clinical Management of Hospitalized Patients With High-Consequence Infectious Diseases in England.

Infectious disease physicians in England have been diagnosing and managing occasional cases of viral hemorrhagic fever since 1971, including the United Kingdom's first case of Ebola virus disease in 1976. Specialist isolation facilities to provide safe and effective care have been present since that time. Following the emergence of Middle East respiratory syndrome (MERS) in 2012, and the avian influenza A (H7N9) outbreak in 2013, and the 2014-2016 Ebola virus disease outbreak in West Africa, clinical and public health preparedness and response pathways in England have been strengthened for these types of diseases, now called high-consequence infectious diseases (HCIDs). The HCID program, led by NHS England and Public Health England between 2016 and 2018, helped to deliver these enhancements, which have since been used on multiple occasions for new UK cases and outbreaks of MERS, mpox, avian influenza, and Lassa fever. Additionally, HCID pathways were activated for COVID-19 during the first 3 months of 2020, before the pandemic had been declared and little was known about COVID-19 but HCID status had been assigned temporarily to COVID-19 as a precaution. The HCID program also led to the commissioning of a network of new airborne HCID treatment centers in England, to supplement the existing network of contact HCID treatment centers, which includes the United Kingdom's only 2 high-level isolation units. In this case study, the authors describe the airborne and contact HCID treatment center networks in England, including their formation and structures, their approach to safe and effective clinical management of patients with HCIDs in the United Kingdom, and challenges they may face going forward.

Ticks and tick-borne pathogens in selected abattoirs and a slaughter slab in Kumasi, Ghana.

Ticks are vectors of pathogens that affect the health of animals and humans. With the constant trade of livestock across borders, there is the risk of new tick species invasion accompanied by the spread of infectious tick-borne pathogens. This study sought to determine the diversity of tick species within abattoirs and a slaughter slab as well as identify the pathogens carried by these ticks. The ticks were collected from slaughtered cattle, identified and screened for pathogens using PCR and sequencing. A total of 371 ticks were collected from slaughtered cattle across the three sampling sites: Kumasi abattoir (288, 77.63%), Akwatia Line slaughter slab (52, 14.02%) and Suame abattoir (31, 8.35%). The predominant species was Amblyomma variegatum (85.44%) with Rhipicephalus sanguineus (s.l.) (0.27%) as the least occurring species. Total nucleic acid from the tick pools was screened for pathogens based on the nucleoprotein gene region in the S segment of the Crimean-Congo haemorrhagic fever virus (CCHFV) genome, the 295-bp fragment of the transposase gene of the Coxiella burnetii IS1111a element, the 560bp segment of the ssrRNA gene of Babesia and Theileria, the 345bp fragment of the Ehrlichia genus 16SrRNA gene and the rOmpA gene (OmpA) of Rickettsia. From the 52 tick pools screened, 40 (76.92%) were found positive for pathogen DNA. The pathogens identified were Rickettsia africae (69.23%), Rickettsia aeschlimannii (7.69%), C. burnetii (5.77%), uncultured Ehrlichia sp. (5.77%), Candidatus Midichloria mitochondrii (3.85%) and CCHFV (3.85%). A significant association was observed among A. variegatum, Hyalomma rufipes, Hyalomma truncatum and occurring tick-borne pathogens R. africae, R. aeschlimannii and uncultured Ehrlichia sp. (p<0.001). The findings show the occurrence of zoonotic pathogens, suggesting an increased risk of infections among the abattoir workers. There is a need to adopt control measures within the abattoirs to prevent pathogen spread.