Publications by authors named "Daniel P Carter"

10 Publications

  • Page 1 of 1

Metagenomic identification of a new sarbecovirus from horseshoe bats in Europe.

Sci Rep 2021 07 19;11(1):14723. Epub 2021 Jul 19.

Centre for Ecology, Evolution and Conservation, School of Biological Sciences, University of East Anglia, Norwich, NR4 7TJ, UK.

The source of the COVID-19 pandemic is unknown, but the natural host of the progenitor sarbecovirus is thought to be Asian horseshoe (rhinolophid) bats. We identified and sequenced a novel sarbecovirus (RhGB01) from a British horseshoe bat, at the western extreme of the rhinolophid range. Our results extend both the geographic and species ranges of sarbecoviruses and suggest their presence throughout the horseshoe bat distribution. Within the spike protein receptor binding domain, but excluding the receptor binding motif, RhGB01 has a 77% (SARS-CoV-2) and 81% (SARS-CoV) amino acid homology. While apparently lacking hACE2 binding ability, and hence unlikely to be zoonotic without mutation, RhGB01 presents opportunity for SARS-CoV-2 and other sarbecovirus homologous recombination. Our findings highlight that the natural distribution of sarbecoviruses and opportunities for recombination through intermediate host co-infection are underestimated. Preventing transmission of SARS-CoV-2 to bats is critical with the current global mass vaccination campaign against this virus.
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http://dx.doi.org/10.1038/s41598-021-94011-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8289822PMC
July 2021

Ixodes ricinus and Borrelia burgdorferi sensu lato in the Royal Parks of London, UK.

Exp Appl Acarol 2021 Jul 14;84(3):593-606. Epub 2021 Jun 14.

Medical Entomology & Zoonoses Ecology, Emergency Response Department Science & Technology, Public Health England, Porton Down, UK.

Assessing the risk of tick-borne disease in areas with high visitor numbers is important from a public health perspective. Evidence suggests that tick presence, density, infection prevalence and the density of infected ticks can vary between habitats within urban green space, suggesting that the risk of Lyme borreliosis transmission can also vary. This study assessed nymph density, Borrelia prevalence and the density of infected nymphs across a range of habitat types in nine parks in London which receive millions of visitors each year. Ixodes ricinus were found in only two of the nine locations sampled, and here they were found in all types of habitat surveyed. Established I. ricinus populations were identified in the two largest parks, both of which had resident free-roaming deer populations. Highest densities of nymphs (15.68 per 100 m) and infected nymphs (1.22 per 100 m) were associated with woodland and under canopy habitats in Richmond Park, but ticks infected with Borrelia were found across all habitat types surveyed. Nymphs infected with Borrelia (7.9%) were only reported from Richmond Park, where Borrelia burgdorferi sensu stricto and Borrelia afzelii were identified as the dominant genospecies. Areas with short grass appeared to be less suitable for ticks and maintaining short grass in high footfall areas could be a good strategy for reducing the risk of Lyme borreliosis transmission to humans in such settings. In areas where this would create conflict with existing practices which aim to improve and/or meet historic landscape, biodiversity and public access goals, promoting public health awareness of tick-borne disease risks could also be utilised.
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http://dx.doi.org/10.1007/s10493-021-00633-3DOI Listing
July 2021

"Kankasha" in Kassala: A prospective observational cohort study of the clinical characteristics, epidemiology, genetic origin, and chronic impact of the 2018 epidemic of Chikungunya virus infection in Kassala, Sudan.

PLoS Negl Trop Dis 2021 04 30;15(4):e0009387. Epub 2021 Apr 30.

Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.

Background: The public health impact of Chikungunya virus (CHIKV) is often underestimated. Usually considered a mild condition of short duration, recent outbreaks have reported greater incidence of severe illness, fatality, and longer-term disability. In 2018/19, Eastern Sudan experienced the largest epidemic of CHIKV in Africa to date, affecting an estimated 487,600 people. Known locally as Kankasha, this study examines clinical characteristics, risk factors, and phylogenetics of the epidemic in Kassala City.

Methodology/principal Findings: A prospective cohort of 102 adults and 40 children presenting with chikungunya-like illness were enrolled at Kassala Teaching Hospital in October 2018. Clinical information, socio-demographic data, and sera samples were analysed to confirm diagnosis, characterise illness, and identify viral strain. CHIKV infection was confirmed by real-time reverse transcription-PCR in 84.5% (120/142) of participants. Nine (7.5%) CHIKV-positive participants had concurrent Dengue virus (DENV) infection; 34/118 participants (28.8%) had a positive Rapid Diagnostic Test for Plasmodium falciparum; six (5.0%) had haemorrhagic symptoms including two children with life-threatening bleeding. One CHIKV-positive participant died with acute renal injury. Age was not associated with severity of illness although CHIKV-infected participants were younger (p = 0.003). Two to four months post-illness, 63% of adults available for follow-up (30) were still experiencing arthralgia in one or more joints, and 11% remained moderately disabled on Rapid3 assessment. Phylogenetic analysis showed all CHIKV sequences from this study belonged to a single clade within the Indian Ocean Lineage (IOL) of the East/Central/South African (ECSA) genotype. History of contact with an infected person was the only factor associated with infection (p = 0.01), and likely related to being in the same vector environment.

Conclusions/significance: Vulnerability to CHIKV remains in Kassala and elsewhere in Sudan due to widespread Aedes aegypti presence and mosquito-fostering household water storage methods. This study highlights the importance of increasing awareness of the severity and impact of CHIKV outbreaks, and the need for urgent actions to reduce transmission risk in households.
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http://dx.doi.org/10.1371/journal.pntd.0009387DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8115788PMC
April 2021

Diagnosis of SARS-CoV-2 Infection with LamPORE, a High-Throughput Platform Combining Loop-Mediated Isothermal Amplification and Nanopore Sequencing.

J Clin Microbiol 2021 05 19;59(6). Epub 2021 May 19.

Public Health England, National Infection Service, Salisbury, United Kingdom.

LamPORE is a novel diagnostic platform for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA combining loop-mediated isothermal amplification with nanopore sequencing, which could potentially be used to analyze thousands of samples per day on a single instrument. We evaluated the performance of LamPORE against reverse transcriptase PCR (RT-PCR) using RNA extracted from spiked respiratory samples and stored nose and throat swabs collected at two UK hospitals. The limit of detection of LamPORE was 10 genome copies/μl of extracted RNA, which is above the limit achievable by RT-PCR, but was not associated with a significant reduction of sensitivity in clinical samples. Positive clinical specimens came mostly from patients with acute symptomatic infection, and among them, LamPORE had a diagnostic sensitivity of 99.1% (226/228; 95% confidence interval [CI], 96.9% to 99.9%). Among negative clinical specimens, including 153 with other respiratory pathogens detected, LamPORE had a diagnostic specificity of 99.6% (278/279; 98.0% to 100.0%). Overall, 1.4% (7/514; 0.5% to 2.9%) of samples produced an indeterminate result on first testing, and repeat LamPORE testing on the same RNA extract had a reproducibility of 96.8% (478/494; 94.8% to 98.1%). LamPORE has a similar performance as RT-PCR for the diagnosis of SARS-CoV-2 infection in symptomatic patients and offers a promising approach to high-throughput testing.
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http://dx.doi.org/10.1128/JCM.03271-20DOI Listing
May 2021

Dose-dependent response to infection with SARS-CoV-2 in the ferret model and evidence of protective immunity.

Nat Commun 2021 01 4;12(1):81. Epub 2021 Jan 4.

National Infection Service, Public Health England (PHE), Porton Down, Salisbury, Wiltshire, SP4 0JG, UK.

There is a vital need for authentic COVID-19 animal models to enable the pre-clinical evaluation of candidate vaccines and therapeutics. Here we report a dose titration study of SARS-CoV-2 in the ferret model. After a high (5 × 10 pfu) and medium (5 × 10 pfu) dose of virus is delivered, intranasally, viral RNA shedding in the upper respiratory tract (URT) is observed in 6/6 animals, however, only 1/6 ferrets show similar signs after low dose (5 × 10 pfu) challenge. Following sequential culls pathological signs of mild multifocal bronchopneumonia in approximately 5-15% of the lung is seen on day 3, in high and medium dosed groups. Ferrets re-challenged, after virus shedding ceased, are fully protected from acute lung pathology. The endpoints of URT viral RNA replication & distinct lung pathology are observed most consistently in the high dose group. This ferret model of SARS-CoV-2 infection presents a mild clinical disease.
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http://dx.doi.org/10.1038/s41467-020-20439-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7782478PMC
January 2021

X-ray inactivation of RNA viruses without loss of biological characteristics.

Sci Rep 2020 12 8;10(1):21431. Epub 2020 Dec 8.

National Infection Service, Public Health England, Porton Down, SP4 0JG, UK.

In the event of an unpredictable viral outbreak requiring high/maximum biosafety containment facilities (i.e. BSL3 and BSL4), X-ray irradiation has the potential to relieve pressures on conventional diagnostic bottlenecks and expediate work at lower containment. Guided by Monte Carlo modelling and in vitro 1-log decimal-reduction value (D-value) predictions, the X-ray photon energies required for the effective inactivation of zoonotic viruses belonging to the medically important families of Flaviviridae, Nairoviridae, Phenuiviridae and Togaviridae are demonstrated. Specifically, it is shown that an optimized irradiation approach is attractive for use in a multitude of downstream detection and functional assays, as it preserves key biochemical and immunological properties. This study provides evidence that X-ray irradiation can support emergency preparedness, outbreak response and front-line diagnostics in a safe, reproducible and scalable manner pertinent to operations that are otherwise restricted to higher containment BSL3 or BSL4 laboratories.
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http://dx.doi.org/10.1038/s41598-020-77972-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7722841PMC
December 2020

Amplicon-Based Detection and Sequencing of SARS-CoV-2 in Nasopharyngeal Swabs from Patients With COVID-19 and Identification of Deletions in the Viral Genome That Encode Proteins Involved in Interferon Antagonism.

Viruses 2020 10 14;12(10). Epub 2020 Oct 14.

Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19). Sequencing the viral genome as the outbreak progresses is important, particularly in the identification of emerging isolates with different pathogenic potential and to identify whether nucleotide changes in the genome will impair clinical diagnostic tools such as real-time PCR assays. Although single nucleotide polymorphisms and point mutations occur during the replication of coronaviruses, one of the biggest drivers in genetic change is recombination. This can manifest itself in insertions and/or deletions in the viral genome. Therefore, sequencing strategies that underpin molecular epidemiology and inform virus biology in patients should take these factors into account. A long amplicon/read length-based RT-PCR sequencing approach focused on the Oxford Nanopore MinION/GridION platforms was developed to identify and sequence the SARS-CoV-2 genome in samples from patients with or suspected of COVID-19. The protocol, termed Rapid Sequencing Long Amplicons (RSLAs) used random primers to generate cDNA from RNA purified from a sample from a patient, followed by single or multiplex PCRs to generate longer amplicons of the viral genome. The base protocol was used to identify SARS-CoV-2 in a variety of clinical samples and proved sensitive in identifying viral RNA in samples from patients that had been declared negative using other nucleic acid-based assays (false negative). Sequencing the amplicons revealed that a number of patients had a proportion of viral genomes with deletions.
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http://dx.doi.org/10.3390/v12101164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7602519PMC
October 2020

Detection of new endemic focus of tick-borne encephalitis virus (TBEV), Hampshire/Dorset border, England, September 2019.

Euro Surveill 2019 Nov;24(47)

Virology and Pathogenesis Group, National Infection Service, Public Health England, Porton Down, United Kingdom.

The presence of tick-borne encephalitis virus (TBEV) was detected in a questing tick pool in southern England in September 2019. Hitherto, TBEV had only been detected in a limited area in eastern England. This southern English viral genome sequence is distinct from TBEV-UK, being most similar to TBEV-NL. The new location of TBEV presence highlights that the diagnosis of tick-borne encephalitis should be considered in encephalitic patients in areas of the United Kingdom outside eastern England.
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http://dx.doi.org/10.2807/1560-7917.ES.2019.24.47.1900658DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6885748PMC
November 2019

Rhombencephalitis and Myeloradiculitis Caused by a European Subtype of Tick-Borne Encephalitis Virus.

Emerg Infect Dis 2019 12;25(12):2317-2319

We report a case of a previously healthy man returning to the United Kingdom from Lithuania who developed rhombencephalitis and myeloradiculitis due to tick-borne encephalitis. These findings add to sparse data on tick-borne encephalitis virus phylogeny and associated neurologic syndromes and underscore the importance of vaccinating people traveling to endemic regions.
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http://dx.doi.org/10.3201/eid2512.191017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6874248PMC
December 2019

Tick-Borne Encephalitis Virus, United Kingdom.

Emerg Infect Dis 2020 01 17;26(1):90-96. Epub 2020 Jan 17.

During February 2018-January 2019, we conducted large-scale surveillance for the presence and prevalence of tick-borne encephalitis virus (TBEV) and louping ill virus (LIV) in sentinel animals and ticks in the United Kingdom. Serum was collected from 1,309 deer culled across England and Scotland. Overall, 4% of samples were ELISA-positive for the TBEV serocomplex. A focus in the Thetford Forest area had the highest proportion (47.7%) of seropositive samples. Ticks collected from culled deer within seropositive regions were tested for viral RNA; 5 of 2,041 ticks tested positive by LIV/TBEV real-time reverse transcription PCR, all from within the Thetford Forest area. From 1 tick, we identified a full-length genomic sequence of TBEV. Thus, using deer as sentinels revealed a potential TBEV focus in the United Kingdom. This detection of TBEV genomic sequence in UK ticks has important public health implications, especially for undiagnosed encephalitis.
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http://dx.doi.org/10.3201/eid2601.191085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6924911PMC
January 2020
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