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Publications

The Pirbright Institute publication directory contains details of selected publications written by our researchers.

There were a total of 2456 results for your search.

Abstract

Crimean-Congo hemorrhagic fever (CCHF) is a zoonotic arboviral disease that poses a great threat to global health in the Old World, and it is endemic in Europe, Asia, and Africa, including Sudan. In this retrospective study, we reviewed previous epidemiological reports about the major epidemics of CCHF throughout Sudan between 2010 and 2020. During these epidemics, the infection of humans with Crimean-Congo hemorrhagic fever virus (CCHFV), the causative agent of CCHF, was diagnosed using qRT-PCR. We have identified 88 cases of CCHF, including 13 fatalities reported during five epidemics that occurred in 2010, 2011, 2015, 2019, and 2020. The two epidemics in 2010 and 2011 were by far the largest, with 51 and 27 cases reported, respectively. The majority of cases (78%) were reported in the endemic region of Kordofan. Here, we document that the first emergence of CCHFV in the Darfur region, West Sudan, occurred in 2010. We were not able to investigate outbreak dynamics through phylogenetic analysis due to the limited diagnostic capacity and the lack of sequencing services in the country. These findings call for establishing a genomic-based integrated One Health surveillance and response system for the early preparedness, prevention, and control of CCHF in the country.

Abstract

Predicting the likelihood of wildlife presence at potential wildlife-livestock interfaces is challenging. These interfaces are usually relatively small geographical areas where landscapes show large variation over small distances. Models of wildlife distribution based on coarse data over wide geographical ranges may not be representative of these interfaces. High-resolution data can help identify fine-scale predictors of wildlife habitat use at a local scale and provide more accurate predictions of species habitat use. These data may be used to inform knowledge of interface risks, such as disease transmission between wildlife and livestock, or human-wildlife conflict.This study uses fine-scale habitat use data from wild boar (Sus scrofa) based on activity signs and direct field observations in and around the Forest of Dean in Gloucestershire, England. Spatial logistic regression models fitted using a variant of penalized quasi-likelihood were used to identify habitat-based and anthropogenic predictors of wild boar signs.Our models showed that within the Forest of Dean, wild boar signs were more likely to be seen in spring, in forest-type habitats, closer to the center of the forest and near litter bins. In the area surrounding the Forest of Dean, wild boar signs were more likely to be seen in forest-type habitats and near recreational parks and less likely to be seen near livestock.This approach shows that wild boar habitat use can be predicted using fine-scale data over comparatively small areas and in human-dominated landscapes, while taking account of the spatial correlation from other nearby fine-scale data-points. The methods we use could be applied to map habitat use of other wildlife species in similar landscapes, or of movement-restricted, isolated, or fragmented wildlife populations.

Abstract

The primary transmission route for foot-and-mouth disease (FMD), a contagious viral disease of cloven-hoofed animals, is by direct contact with infected animals. Yet indirect methods of transmission, such as via the airborne route, have been shown to play an important role in the spread of the disease. Airborne transmission of FMD is referred to as a low probability- high consequence event as a specific set of factors need to coincide to facilitate airborne spread. When conditions are favourable, airborne virus may spread rapidly and cause disease beyond the imposed quarantine zones, thus complicating control measures. Therefore, it is important to understand the nature of foot-and-mouth disease virus (FMDV) within aerosols; how aerosols are generated, viral load, how far aerosols could travel and survive under different conditions. Various studies have investigated emissions from infected animals under laboratory conditions, while others have incorporated experimental data in mathematical models to predict and trace outbreaks of FMD. However, much of the existing literature focussing on FMDV in aerosols describe work which was undertaken over 40 years ago. The aim of this review is to revisit existing knowledge and investigate how modern instrumentation and modelling approaches can improve our understanding of airborne transmission of FMD.

Abstract

Culicoides biting midges (Diptera: Ceratopogonidae) are biting nuisances and arbovirus vectors of both public health and veterinary significance in Trinidad. We compared sampling methods to define the behaviour and bionomics of adult Culicoides populations at a commercial dairy goat farm. Three static trap designs were compared: (a) Centre for Disease Control (CDC) downdraft UV trap; (b) CDC trap with an incandescent bulb and (c) CDC trap with semiochemical lure consisting of R-(-)-1-octen-3-ol and CO2 (no bulb). Sweep netting was used to define diel periodicity. A total of 30,701 biting midges were collected using static traps, dominated by female Culicoides furens (>70% of trap collections across all three designs). There was no significant difference in the Margalef's index between the three traps; however, trap designs A and C collected a significantly greater number of individuals than trap B, and trap C gained highest species richness. The greatest species richness and abundance of Culicoides collected by sweep net was observed between 6:00 and 6:15 pm and notable differences in the crepuscular activity pattern of several species were identified. Comparative data on Culicoides species richness, abundance, sex and reproductive status is discussed and can be used to improve surveillance strategies, research designs and risk management.

Cantoni D, Mayora-Neto M, Thakur N, Elrefaey A M E, Newman J, Vishwanath S, Nadesalingam A, Chan A, Smith P, Castillo-Olivares J, Baxendale H, Charleston B, Heeney J, Bailey D, Temperton N (2022)

Pseudotyped bat coronavirus RaTG13 is efficiently neutralised by convalescent sera from SARS-CoV-2 infected patients

Communications Biology 5 (1), 409

Abstract

RaTG13 is a close relative of SARS-CoV-2, the virus responsible for the COVID-19 pandemic, sharing 96% sequence similarity at the genome-wide level. The spike receptor binding domain (RBD) of RaTG13 contains a number of amino acid substitutions when compared to SARS-CoV-2, likely impacting affinity for the ACE2 receptor. Antigenic differences between the viruses are less well understood, especially whether RaTG13 spike can be efficiently neutralised by antibodies generated from infection with, or vaccination against, SARS-CoV-2. Using RaTG13 and SARS-CoV-2 pseudotypes we compared neutralisation using convalescent sera from previously infected patients or vaccinated healthcare workers. Surprisingly, our results revealed that RaTG13 was more efficiently neutralised than SARS-CoV-2. In addition, neutralisation assays using spike mutants harbouring single and combinatorial amino acid substitutions within the RBD demonstrated that both spike proteins can tolerate multiple changes without dramatically reducing neutralisation. Moreover, introducing the 484 K mutation into RaTG13 resulted in increased neutralisation, in contrast to the same mutation in SARS-CoV-2 (E484K). This is despite E484K having a well-documented role in immune evasion in variants of concern (VOC) such as B.1.351 (Beta). These results indicate that the future spill-over of RaTG13 and/or related sarbecoviruses could be mitigated using current SARS-CoV-2-based vaccination strategies.

Abstract

Alphaviruses are positive-strand RNA viruses, mostly being mosquito-transmitted. Cells infected by an alphavirus become resistant to superinfection due to a block that occurs at the level of RNA replication. Alphavirus replication proteins, called nsP1-4, are produced from nonstructural polyprotein precursors, processed by the protease activity of nsP2. Trans-replicase systems and replicon vectors were used to study effects of nsP2 of chikungunya virus and Sindbis virus on alphavirus RNA replication in mosquito cells. Co-expressed wild-type nsP2 reduced RNA replicase activity of homologous virus; this effect was reduced but typically not abolished by mutation in the protease active site of nsP2. Mutations in the replicase polyprotein that blocked its cleavage by nsP2 reduced the negative effect of nsP2 co-expression, confirming that nsP2-mediated inhibition of RNA replicase activity is largely due to nsP2-mediated processing of the nonstructural polyprotein. Co-expression of nsP2 also suppressed the activity of replicases of heterologous alphaviruses. Thus, the presence of nsP2 inhibits formation and activity of alphavirus RNA replicase in protease activity-dependent and -independent manners. This knowledge improves our understanding about mechanisms of superinfection exclusion for alphaviruses and may aid the development of anti-alphavirus approaches.

Abstract

The antiviral role of innate immune responses mediated by the NF-κB family of transcription factors is well established in vertebrates but was for a long time less clear in insects. Insects encode two canonical NF-κB pathways, the Toll and Imd ('immunodeficiency') pathways, which are best characterised for their role in antibacterial and antifungal defence. An increasing body of evidence has also implicated NF-κB-mediated innate immunity in antiviral responses against some, but not all, viruses. Specific pattern recognition receptors (PRRs) and molecular events leading to NF-κB activation by viral pathogen-associated molecular patterns (PAMPs) have been elucidated for a number of viruses and insect species. Particularly interesting are recent findings indicating that the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway detects viral RNA to activate NF-κB-regulated gene expression. We summarise the literature on virus-NF-κB pathway interactions across the class Insecta, with a focus on the dipterans Drosophila melanogaster and Aedes aegypti. We discuss potential reasons for differences observed between different virus-host combinations, and highlight similarities and differences between cGAS-STING signalling in insects versus vertebrates. Finally, we summarise the increasing number of known molecular mechanisms by which viruses antagonise NF-κB responses, which suggest that NF-κB-mediated immunity exerts strong evolutionary pressures on viruses. These developments in our understanding of insect antiviral immunity have relevance to the large number of insect species that impact on humans through their transmission of human, livestock and plant diseases, exploitation as biotechnology platforms, and role as parasites, pollinators, livestock and pests.

Abstract

Foot-and-mouth disease is an economically devastating disease of livestock caused by foot-and-mouth disease virus (FMDV). Vaccination is the most effective control measure in place to limit the spread of the disease; however, the success of vaccination campaigns is hampered by the antigenic diversity of FMDV and the rapid rate at which new strains emerge that escape pre-existing immunity. FMDV has seven distinct serotypes, and within each serotype are multiple strains that often induce little cross-protective immunity. The diversity of FMDV is a consequence of the high error rate of the RNA-dependent RNA polymerase, accompanied by extensive recombination between genomes during co-infection. Since multiple serotypes and strains co-circulate in regions where FMDV is endemic, co-infection is common, providing the conditions for recombination, and also for other events such as trans-encapsidation in which the genome of one virus is packaged into the capsid of the co-infecting virus. Here, we demonstrate that the co-infection of cells with two FMDVs of different serotypes results in trans-encapsidation of both viral genomes. Crucially, this facilitates the infection of new cells in the presence of neutralizing antibodies that recognize the capsid that is encoded by the packaged genome.

Abstract

BACKGROUND: Non-targeted whole genome sequencing is a powerful tool to comprehensively identify constituents of microbial communities in a sample. There is no need to direct the analysis to any identification before sequencing which can decrease the introduction of bias and false negatives results. It also allows the assessment of genetic aberrations in the genome (e.g., single nucleotide variants, deletions, insertions and copy number variants) including in noncoding protein regions.

METHODS: The performance of four different random priming amplification methods to recover RNA viral genetic material of SARS-CoV-2 were compared in this study. In method 1 (H-P) the reverse transcriptase (RT) step was performed with random hexamers whereas in methods 2-4 RT incorporating an octamer primer with a known tag. In methods 1 and 2 (K-P) sequencing was applied on material derived from the RT-PCR step, whereas in methods 3 (SISPA) and 4 (S-P) an additional amplification was incorporated before sequencing.

RESULTS: The SISPA method was the most effective and efficient method for non-targeted/random priming whole genome sequencing of SARS-CoV-2 that we tested. The SISPA method described in this study allowed for whole genome assembly of SARS-CoV-2 and influenza A(H1N1)pdm09 in mixed samples. We determined the limit of detection and characterization of SARS-CoV-2 virus which was 103 pfu/ml (Ct, 22.4) for whole genome assembly and 101 pfu/ml (Ct, 30) for metagenomics detection.

CONCLUSIONS: The SISPA method is predominantly useful for obtaining genome sequences from RNA viruses or investigating complex clinical samples as no prior sequence information is needed. It might be applied to monitor genomic virus changes, virus evolution and can be used for fast metagenomics detection or to assess the general picture of different pathogens within the sample.

Judson S D, Torimiro J, Pigott D M, Maima A, Mostafa A, Samy A, Rabinowitz P, Njabo K (2022)

COVID-19 data reporting systems in Africa reveal insights for future pandemics

Epidemiology and infection 150, e119

Abstract

Globally, countries have used diverse methods to report data during the COVID-19 pandemic. Using international guidelines and principles of emergency management, we compare national data reporting systems in African countries in order to determine lessons for future pandemics. We analyse COVID-19 reporting practices across 54 African countries through 2020. Reporting systems were diverse and included summaries, press releases, situation reports and online dashboards. These systems were communicated via social media accounts and websites belonging to ministries of health and public health. Data variables from the reports included event detection (cases/deaths/recoveries), risk assessment (demographics/co-morbidities) and response (total tests/hospitalisations). Of countries with reporting systems, 36/53 (67.9%) had recurrent situation reports and/or online dashboards which provided more extensive data. All of these systems reported cases, deaths and recoveries. However, few systems contained risk assessment and response data, with only 5/36 (13.9%) reporting patient co-morbidities and 9/36 (25%) including total hospitalisations. Further evaluation of reporting practices in Cameroon, Egypt, Kenya, Senegal and South Africa as examples from different sub-regions revealed differences in reporting healthcare capacity and preparedness data. Improving the standardisation and accessibility of national data reporting systems could augment research and decision-making, as well as increase public awareness and transparency for national governments.

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