Roger Hewson - Academia.edu (original) (raw)
Papers by Roger Hewson
Journal of Virological Methods, 2014
Lujo virus is an emerging arenavirus circulating in Southern Africa. Although to date there has o... more Lujo virus is an emerging arenavirus circulating in Southern Africa. Although to date there has only been a single outbreak of the novel haemorrhagic disease resulting from human infection with this virus, the case-fatality rate of exposed individuals, including nosocomial transmission, was 80%. The ability to identify viral haemorrhagic fevers accurately, especially those capable of nosocomial transmission, is of critical importance. Timely identification of these diseases allow medical professionals to isolate patients and implement barrier nursing techniques in order to prevent onward transmission of the virus. While rapid diagnostic methods are published for most viral haemorrhagic fevers, at present there are no such virus specific protocols for Lujo haemorrhagic fever. This report details the first set of diagnostic molecular assays designed to identify Lujo viral RNA rapidly, and demonstrates the potential functionality of these assays for use in the clinical setting. Although these assays have been designed and validated against a solitary isolate of Lujo virus, this represents the entirety of strains detected to date, and offer quick, cheap and easy methods for use in diagnostic laboratories.
Emerging Infectious Diseases, 2016
For nearly 8 decades, N. gonorrhoeae has been controllable. Continued investment in research and ... more For nearly 8 decades, N. gonorrhoeae has been controllable. Continued investment in research and the development of new laboratory technology are critical in supporting an effective response to mitigate the threat of untreatable gonorrhea.
Frontiers in Public Health
The current COVID-19 pandemic demonstrates the need for urgent and on-demand solutions to provide... more The current COVID-19 pandemic demonstrates the need for urgent and on-demand solutions to provide diagnostics, treatment and preventative measures for infectious disease outbreaks. Once solutions are developed, meeting capacities depends on the ability to mitigate technical, logistical and production issues. While it is difficult to predict the next outbreak, augmenting investments in preparedness, such as infectious disease surveillance, is far more effective than mustering last-minute response funds. Bringing research outputs into practice sooner rather than later is part of an agile approach to pivot and deliver solutions. Cooperative multi- country research programs, especially those funded by global biosecurity programs, develop capacity that can be applied to infectious disease surveillance and research that enhances detection, identification, and response to emerging and re-emerging pathogens with epidemic or pandemic potential. Moreover, these programs enhance trust building...
Vaccines
The flavivirus envelope protein domain III (EDIII) was an effective immunogen against dengue viru... more The flavivirus envelope protein domain III (EDIII) was an effective immunogen against dengue virus (DENV) and other related flaviviruses. Whether this can be applied to the Zika virus (ZIKV) vaccinology remains an open question. Here, we tested the efficacy of ZIKV-EDIII against ZIKV infection, using several vaccine platforms that present the antigen in various ways. We provide data demonstrating that mice vaccinated with a ZIKV-EDIII as DNA or protein-based vaccines failed to raise fully neutralizing antibodies and did not control viremia, following a ZIKV challenge, despite eliciting robust antibody responses. Furthermore, we showed that ZIKV-EDIII encoded in replication-deficient Chimpanzee adenovirus (ChAdOx1-EDIII) elicited anti-ZIKV envelope antibodies in vaccinated mice but also provided limited protection against ZIKV in two physiologically different mouse challenge models. Taken together, our data indicate that contrary to what was shown for other flaviviruses like the deng...
PLOS Neglected Tropical Diseases
Microorganisms
Crimean-Congo hemorrhagic fever virus (CCHFV) is the most geographically widespread of the tick-b... more Crimean-Congo hemorrhagic fever virus (CCHFV) is the most geographically widespread of the tick-borne viruses. However, African strains of CCHFV are poorly represented in sequence databases. In addition, almost all sequence data collected to date have been obtained from cases of human disease, while information regarding the circulation of the virus in tick and animal reservoirs is severely lacking. Here, we characterize the complete coding region of a novel CCHFV strain, detected in African blue ticks (Rhipicephalus (Boophilus) decoloratus) feeding on cattle in an abattoir in Kampala, Uganda. These cattle originated from a farm in Mbarara, a major cattle-trading hub for much of Uganda. Phylogenetic analysis indicates that the newly sequenced strain belongs to the African genotype II clade, which predominantly contains the sequences of strains isolated from West Africa in the 1950s, and South Africa in the 1980s. Whilst the viral S (nucleoprotein) and L (RNA polymerase) genome segme...
npj Vaccines
Zika virus (ZIKV) causes neurological complications in susceptible individuals, highlighted in th... more Zika virus (ZIKV) causes neurological complications in susceptible individuals, highlighted in the recent South American epidemic. Natural ZIKV infection elicits host responses capable of preventing subsequent re-infection, raising expectations for effective vaccination. Defining protective immune correlates will inform viral intervention strategies, particularly vaccine development. Non-human primate (NHP) species are susceptible to ZIKV and represent models for vaccine development. The protective efficacy of a human anti-ZIKV convalescent plasma pool (16/320-14) developed as a candidate reference material for a WHO International Standard was evaluated in macaques. Convalescent plasma administered to four cynomolgus macaques (Macaca fascicularis) intra-peritoneally 24 hrs prior to sub-cutaneous challenge with 103 pfu ZIKVPRVABC59 protected against detectable infection, with absence of detectable ZIKV RNA in blood and lymphoid tissues. Passively immunised anti-ZIKV immunoglobulin ad...
The Journal of Infectious Diseases
Background The largest West African monkeypox outbreak began September 2017, in Nigeria. Four ind... more Background The largest West African monkeypox outbreak began September 2017, in Nigeria. Four individuals traveling from Nigeria to the United Kingdom (n = 2), Israel (n = 1), and Singapore (n = 1) became the first human monkeypox cases exported from Africa, and a related nosocomial transmission event in the United Kingdom became the first confirmed human-to-human monkeypox transmission event outside of Africa. Methods Epidemiological and molecular data for exported and Nigerian cases were analyzed jointly to better understand the exportations in the temporal and geographic context of the outbreak. Results Isolates from all travelers and a Bayelsa case shared a most recent common ancestor and traveled to Bayelsa, Delta, or Rivers states. Genetic variation for this cluster was lower than would be expected from a random sampling of genomes from this outbreak, but data did not support direct links between travelers. Conclusions Monophyly of exportation cases and the Bayelsa sample, alo...
Archives of Virology
In March 2020, following the annual International Committee on Taxonomy of Viruses (ICTV) ratific... more In March 2020, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was amended and emended. At the genus rank, 20 new genera were added, two were deleted, one was moved, and three were renamed. At the species rank, 160 species were added, four were deleted, ten were moved and renamed, and 30 species were renamed. This article presents the updated taxonomy of Negarnaviricota as now accepted by the ICTV.
Cells
The family Hantaviridae within the Bunyavirales order comprises tri-segmented negative sense RNA ... more The family Hantaviridae within the Bunyavirales order comprises tri-segmented negative sense RNA viruses, many of which are rodent-borne emerging pathogens associated with fatal human disease. In contrast, hantavirus infection of corresponding rodent hosts results in inapparent or latent infections, which can be recapitulated in cultured cells that become persistently infected. In this study, we used Tula virus (TULV) to investigate the location of hantavirus replication during early, peak and persistent phases of infection, over a 30-day time course. Using immunofluorescent (IF) microscopy, we showed that the TULV nucleocapsid protein (NP) is distributed within both punctate and filamentous structures, with the latter increasing in size as the infection progresses. Transmission electron microscopy of TULV-infected cell sections revealed these filamentous structures comprised aligned clusters of filament bundles. The filamentous NP-associated structures increasingly co-localized wit...
PLOS Neglected Tropical Diseases
Vaccines
In the infectious diseases field, protective immunity against individual virus species or strains... more In the infectious diseases field, protective immunity against individual virus species or strains does not always confer cross-reactive immunity to closely related viruses, leaving individuals susceptible to disease after exposure to related virus species. This is a significant hurdle in the field of vaccine development, in which broadly protective vaccines represent an unmet need. This is particularly evident for filoviruses, as there are multiple family members that can cause lethal haemorrhagic fever, including Zaire ebolavirus, Sudan ebolavirus, and Marburg virus. In an attempt to address this need, both pre-clinical and clinical studies previously used mixed or co-administered monovalent vaccines to prevent filovirus mediated disease. However, these multi-vaccine and multi-dose vaccination regimens do not represent a practical immunisation scheme when considering the target endemic areas. We describe here the development of a single multi-pathogen filovirus vaccine candidate ba...
Ticks and Tick-borne Diseases
Viruses
Recent studies have shown that transcriptomic analysis of blood samples taken from patients with ... more Recent studies have shown that transcriptomic analysis of blood samples taken from patients with acute Ebola virus disease (EVD) during the 2013–2016 West African outbreak was suggestive that a severe inflammatory response took place in acutely ill patients. The significant knowledge gained from studying the Makona variant, a cause of the largest known EVD outbreak, may be applicable to other species of ebolavirus, and other variants of the Ebola virus (EBOV) species. To investigate the ability of Makona to initiate an inflammatory response in human macrophages and characterise the host response in a similar manner to previously characterised EBOV variants, the human monocytic cell line THP-1 was differentiated into macrophage-like cells and infected with Makona. RNA-Seq and quantitative proteomics were used to identify and quantify host mRNA and protein abundance during infection. Data from infection with Reston virus (RESTV) were used as comparators to investigate changes that may...
The Lancet Infectious Diseases
Background Data describing the coagulopathy of Crimean-Congo haemorrhagic fever are scarce. We di... more Background Data describing the coagulopathy of Crimean-Congo haemorrhagic fever are scarce. We did rotational thromboelastometry (ROTEM) and conventional coagulation testing in patients with Crimean-Congo haemorrhagic fever to increase our understanding of the coagulopathy of this infectious disease. Methods We did a prospective observational cohort study of adults aged 18 years and older and admitted to hospitals with PCR-confirmed Crimean-Congo haemorrhagic fever in Samsun and Tokat, Turkey. Demographic, clinical, and laboratory data were collected and blood samples for ROTEM analysis and coagulation testing were drawn at admission and during hospital admission and convalescence (up to 30 days after onset of illness). For the ROTEM analysis we recorded the following extrinsically activated ROTEM (EXTEM S) variables, with normal ranges indicated: clotting time (38-79 s), clot formation time (34-159 s), amplitude at 10 min after clotting time (43-65 mm), maximum clot firmness (50-72 mm), and maximum lysis (>15% at 1 h). The following fibrin-specific ROTEM (FIBTEM S) variables were also recorded: amplitude at 10 min after clotting time (normal range 7-23 mm) and maximum clot firmness (9-25 mm). Disease severity was assessed by Swanepoel criteria, severity grading score (SGS), and the severity scoring index (SSI), with mild disease defined as meeting no Swanepoel criteria, graded mild by SSI, and graded low risk by SGS. Findings Between May 27, 2015, and Aug 2, 2015, 65 patients with confirmed Crimean-Congo haemorrhagic fever were recruited and had blood taken at 110 time points. Most were male (40 [62%] of 65) with mild disease (49 [75%] of 65). Haemorrhage occurred in 13 (20%; 95% CI 11•1-31•8) of 65 patients and 23 (35%) of 65 received blood products (15 received fresh frozen plasma and eight received red blood cell concentrates), and 21 patients received platelet transfusions. At admission, the following EXTEM S variables differed significantly between mild cases and moderate to severe cases: median clotting time 56 s (range 42-81; IQR 48-64) versus 69 s (range 48-164; IQR 54-75; p=0•01); mean amplitude at 10 min after clotting time 45•1 mm (SD 7•0) versus 33•9 mm (SD 8•6; p<0•0001); median clot formation time 147 s (range 72-255; IQR 101-171) versus 197 s (range 98-418; IQR 156-296; p=0•006); and maximum clot firmness 54•4 mm (SD 7•2) versus 45•1 mm (SD 12•5; p=0•003). The EXTEM S variables were compared at different time points; maximum clot firmness (p=0•024) and amplitude at 10 min after clotting time (p=0•090) were lowest on days 4-6 of illness. We found no significant differences in FIBTEM variables between mild and moderate to severe cases (median amplitude at 10 min, 13 mm [range 8-20; IQR 11-15] vs 12 mm [range 6-25; IQR 10-15; p=0•68]; and median maximum clot firmness, 15 mm [range 9-60; IQR 13-21] vs 17 mm [range 7-39; IQR 13-23; p=0•21]); and no hyperfibrinolysis (maximum lysis >15%). Interpretation Coagulopathy of Crimean-Congo haemorrhagic fever is related to defects in clot development and stabilisation that are more marked in severe disease than in mild disease. The combination of normal and slightly deranged coagulation screens and FIBTEM results with the absence of hyperfibrinolysis suggests that the coagulopathy of Crimean-Congo haemorrhagic fever relates to platelet dysfunction.
Parasite
Free-ranging spur-thighed tortoises Testudo graeca, captured in different habitat types of Northe... more Free-ranging spur-thighed tortoises Testudo graeca, captured in different habitat types of Northern Tunisia from March to April 2017, were examined for tick infestation: 134/147 (91%) were infested. The overall infestation intensity and abundance was 8.5 and 7.8, respectively. From these tortoises, 1174 ticks were collected, of which 10% (n = 120) taken from 18 randomly-selected tortoises were identified at the species level; the remaining ticks were examined for the presence of Crimean-Congo haemorrhagic fever virus (CCHFv) by real time RT-PCR. Only adult Hyalomma aegyptium were found, suggesting a high degree of host specificity to tortoises. No CCHFv was detected in ticks. Considering the absence of CCHFv in Hyalomma aegyptium infesting its main host, the spur-thighed tortoise, this tick species is unlikely to play a major role in the epidemiology of CCHF. Therefore, more studies are needed to investigate the circulation of this arbovirus between livestock and other tick species ...
Memórias do Instituto Oswaldo Cruz
Here, we report the complete genome sequence of the Aporé virus (Bunyavirales: Arenaviridae), obt... more Here, we report the complete genome sequence of the Aporé virus (Bunyavirales: Arenaviridae), obtained from a wild rodent Oligoryzomys mattogrossae captured in Mato Grosso do Sul state, Brazil. The genome of this virus showed strong similarity to highly pathogenic mammarenavirus from South America.
Access Microbiology
This is a repository copy of Cellular cholesterol abundance regulates potassium accumulation with... more This is a repository copy of Cellular cholesterol abundance regulates potassium accumulation within endosomes and is an important determinant in bunyavirus entry.
Clinical & Experimental Immunology
During the past decade several notable viruses have suddenly emerged from obscurity or anonymity ... more During the past decade several notable viruses have suddenly emerged from obscurity or anonymity to become serious global health threats, provoking concern regarding their sustained epidemic transmission in immunologically naive human populations. With each new threat comes the call for rapid vaccine development. Indeed, vaccines are considered a critical component of disease prevention for emerging viral infections because, in many cases, other medical options are limited or non-existent, or that infections result in such a rapid clinical deterioration that the effectiveness of therapeutics is limited. While classic approaches to vaccine development are still amenable to emerging viruses, the application of molecular techniques in virology has profoundly influenced our understanding of virus biology, and vaccination methods based on replicating, attenuated and non-replicating virus vector approaches have become useful vaccine platforms. Together with a growing understanding of viral disease emergence, a range of vaccine strategies and international commitment to underpin development, vaccine intervention for new and emerging viruses may become a possibility.
Journal of Virological Methods, 2014
Lujo virus is an emerging arenavirus circulating in Southern Africa. Although to date there has o... more Lujo virus is an emerging arenavirus circulating in Southern Africa. Although to date there has only been a single outbreak of the novel haemorrhagic disease resulting from human infection with this virus, the case-fatality rate of exposed individuals, including nosocomial transmission, was 80%. The ability to identify viral haemorrhagic fevers accurately, especially those capable of nosocomial transmission, is of critical importance. Timely identification of these diseases allow medical professionals to isolate patients and implement barrier nursing techniques in order to prevent onward transmission of the virus. While rapid diagnostic methods are published for most viral haemorrhagic fevers, at present there are no such virus specific protocols for Lujo haemorrhagic fever. This report details the first set of diagnostic molecular assays designed to identify Lujo viral RNA rapidly, and demonstrates the potential functionality of these assays for use in the clinical setting. Although these assays have been designed and validated against a solitary isolate of Lujo virus, this represents the entirety of strains detected to date, and offer quick, cheap and easy methods for use in diagnostic laboratories.
Emerging Infectious Diseases, 2016
For nearly 8 decades, N. gonorrhoeae has been controllable. Continued investment in research and ... more For nearly 8 decades, N. gonorrhoeae has been controllable. Continued investment in research and the development of new laboratory technology are critical in supporting an effective response to mitigate the threat of untreatable gonorrhea.
Frontiers in Public Health
The current COVID-19 pandemic demonstrates the need for urgent and on-demand solutions to provide... more The current COVID-19 pandemic demonstrates the need for urgent and on-demand solutions to provide diagnostics, treatment and preventative measures for infectious disease outbreaks. Once solutions are developed, meeting capacities depends on the ability to mitigate technical, logistical and production issues. While it is difficult to predict the next outbreak, augmenting investments in preparedness, such as infectious disease surveillance, is far more effective than mustering last-minute response funds. Bringing research outputs into practice sooner rather than later is part of an agile approach to pivot and deliver solutions. Cooperative multi- country research programs, especially those funded by global biosecurity programs, develop capacity that can be applied to infectious disease surveillance and research that enhances detection, identification, and response to emerging and re-emerging pathogens with epidemic or pandemic potential. Moreover, these programs enhance trust building...
Vaccines
The flavivirus envelope protein domain III (EDIII) was an effective immunogen against dengue viru... more The flavivirus envelope protein domain III (EDIII) was an effective immunogen against dengue virus (DENV) and other related flaviviruses. Whether this can be applied to the Zika virus (ZIKV) vaccinology remains an open question. Here, we tested the efficacy of ZIKV-EDIII against ZIKV infection, using several vaccine platforms that present the antigen in various ways. We provide data demonstrating that mice vaccinated with a ZIKV-EDIII as DNA or protein-based vaccines failed to raise fully neutralizing antibodies and did not control viremia, following a ZIKV challenge, despite eliciting robust antibody responses. Furthermore, we showed that ZIKV-EDIII encoded in replication-deficient Chimpanzee adenovirus (ChAdOx1-EDIII) elicited anti-ZIKV envelope antibodies in vaccinated mice but also provided limited protection against ZIKV in two physiologically different mouse challenge models. Taken together, our data indicate that contrary to what was shown for other flaviviruses like the deng...
PLOS Neglected Tropical Diseases
Microorganisms
Crimean-Congo hemorrhagic fever virus (CCHFV) is the most geographically widespread of the tick-b... more Crimean-Congo hemorrhagic fever virus (CCHFV) is the most geographically widespread of the tick-borne viruses. However, African strains of CCHFV are poorly represented in sequence databases. In addition, almost all sequence data collected to date have been obtained from cases of human disease, while information regarding the circulation of the virus in tick and animal reservoirs is severely lacking. Here, we characterize the complete coding region of a novel CCHFV strain, detected in African blue ticks (Rhipicephalus (Boophilus) decoloratus) feeding on cattle in an abattoir in Kampala, Uganda. These cattle originated from a farm in Mbarara, a major cattle-trading hub for much of Uganda. Phylogenetic analysis indicates that the newly sequenced strain belongs to the African genotype II clade, which predominantly contains the sequences of strains isolated from West Africa in the 1950s, and South Africa in the 1980s. Whilst the viral S (nucleoprotein) and L (RNA polymerase) genome segme...
npj Vaccines
Zika virus (ZIKV) causes neurological complications in susceptible individuals, highlighted in th... more Zika virus (ZIKV) causes neurological complications in susceptible individuals, highlighted in the recent South American epidemic. Natural ZIKV infection elicits host responses capable of preventing subsequent re-infection, raising expectations for effective vaccination. Defining protective immune correlates will inform viral intervention strategies, particularly vaccine development. Non-human primate (NHP) species are susceptible to ZIKV and represent models for vaccine development. The protective efficacy of a human anti-ZIKV convalescent plasma pool (16/320-14) developed as a candidate reference material for a WHO International Standard was evaluated in macaques. Convalescent plasma administered to four cynomolgus macaques (Macaca fascicularis) intra-peritoneally 24 hrs prior to sub-cutaneous challenge with 103 pfu ZIKVPRVABC59 protected against detectable infection, with absence of detectable ZIKV RNA in blood and lymphoid tissues. Passively immunised anti-ZIKV immunoglobulin ad...
The Journal of Infectious Diseases
Background The largest West African monkeypox outbreak began September 2017, in Nigeria. Four ind... more Background The largest West African monkeypox outbreak began September 2017, in Nigeria. Four individuals traveling from Nigeria to the United Kingdom (n = 2), Israel (n = 1), and Singapore (n = 1) became the first human monkeypox cases exported from Africa, and a related nosocomial transmission event in the United Kingdom became the first confirmed human-to-human monkeypox transmission event outside of Africa. Methods Epidemiological and molecular data for exported and Nigerian cases were analyzed jointly to better understand the exportations in the temporal and geographic context of the outbreak. Results Isolates from all travelers and a Bayelsa case shared a most recent common ancestor and traveled to Bayelsa, Delta, or Rivers states. Genetic variation for this cluster was lower than would be expected from a random sampling of genomes from this outbreak, but data did not support direct links between travelers. Conclusions Monophyly of exportation cases and the Bayelsa sample, alo...
Archives of Virology
In March 2020, following the annual International Committee on Taxonomy of Viruses (ICTV) ratific... more In March 2020, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was amended and emended. At the genus rank, 20 new genera were added, two were deleted, one was moved, and three were renamed. At the species rank, 160 species were added, four were deleted, ten were moved and renamed, and 30 species were renamed. This article presents the updated taxonomy of Negarnaviricota as now accepted by the ICTV.
Cells
The family Hantaviridae within the Bunyavirales order comprises tri-segmented negative sense RNA ... more The family Hantaviridae within the Bunyavirales order comprises tri-segmented negative sense RNA viruses, many of which are rodent-borne emerging pathogens associated with fatal human disease. In contrast, hantavirus infection of corresponding rodent hosts results in inapparent or latent infections, which can be recapitulated in cultured cells that become persistently infected. In this study, we used Tula virus (TULV) to investigate the location of hantavirus replication during early, peak and persistent phases of infection, over a 30-day time course. Using immunofluorescent (IF) microscopy, we showed that the TULV nucleocapsid protein (NP) is distributed within both punctate and filamentous structures, with the latter increasing in size as the infection progresses. Transmission electron microscopy of TULV-infected cell sections revealed these filamentous structures comprised aligned clusters of filament bundles. The filamentous NP-associated structures increasingly co-localized wit...
PLOS Neglected Tropical Diseases
Vaccines
In the infectious diseases field, protective immunity against individual virus species or strains... more In the infectious diseases field, protective immunity against individual virus species or strains does not always confer cross-reactive immunity to closely related viruses, leaving individuals susceptible to disease after exposure to related virus species. This is a significant hurdle in the field of vaccine development, in which broadly protective vaccines represent an unmet need. This is particularly evident for filoviruses, as there are multiple family members that can cause lethal haemorrhagic fever, including Zaire ebolavirus, Sudan ebolavirus, and Marburg virus. In an attempt to address this need, both pre-clinical and clinical studies previously used mixed or co-administered monovalent vaccines to prevent filovirus mediated disease. However, these multi-vaccine and multi-dose vaccination regimens do not represent a practical immunisation scheme when considering the target endemic areas. We describe here the development of a single multi-pathogen filovirus vaccine candidate ba...
Ticks and Tick-borne Diseases
Viruses
Recent studies have shown that transcriptomic analysis of blood samples taken from patients with ... more Recent studies have shown that transcriptomic analysis of blood samples taken from patients with acute Ebola virus disease (EVD) during the 2013–2016 West African outbreak was suggestive that a severe inflammatory response took place in acutely ill patients. The significant knowledge gained from studying the Makona variant, a cause of the largest known EVD outbreak, may be applicable to other species of ebolavirus, and other variants of the Ebola virus (EBOV) species. To investigate the ability of Makona to initiate an inflammatory response in human macrophages and characterise the host response in a similar manner to previously characterised EBOV variants, the human monocytic cell line THP-1 was differentiated into macrophage-like cells and infected with Makona. RNA-Seq and quantitative proteomics were used to identify and quantify host mRNA and protein abundance during infection. Data from infection with Reston virus (RESTV) were used as comparators to investigate changes that may...
The Lancet Infectious Diseases
Background Data describing the coagulopathy of Crimean-Congo haemorrhagic fever are scarce. We di... more Background Data describing the coagulopathy of Crimean-Congo haemorrhagic fever are scarce. We did rotational thromboelastometry (ROTEM) and conventional coagulation testing in patients with Crimean-Congo haemorrhagic fever to increase our understanding of the coagulopathy of this infectious disease. Methods We did a prospective observational cohort study of adults aged 18 years and older and admitted to hospitals with PCR-confirmed Crimean-Congo haemorrhagic fever in Samsun and Tokat, Turkey. Demographic, clinical, and laboratory data were collected and blood samples for ROTEM analysis and coagulation testing were drawn at admission and during hospital admission and convalescence (up to 30 days after onset of illness). For the ROTEM analysis we recorded the following extrinsically activated ROTEM (EXTEM S) variables, with normal ranges indicated: clotting time (38-79 s), clot formation time (34-159 s), amplitude at 10 min after clotting time (43-65 mm), maximum clot firmness (50-72 mm), and maximum lysis (>15% at 1 h). The following fibrin-specific ROTEM (FIBTEM S) variables were also recorded: amplitude at 10 min after clotting time (normal range 7-23 mm) and maximum clot firmness (9-25 mm). Disease severity was assessed by Swanepoel criteria, severity grading score (SGS), and the severity scoring index (SSI), with mild disease defined as meeting no Swanepoel criteria, graded mild by SSI, and graded low risk by SGS. Findings Between May 27, 2015, and Aug 2, 2015, 65 patients with confirmed Crimean-Congo haemorrhagic fever were recruited and had blood taken at 110 time points. Most were male (40 [62%] of 65) with mild disease (49 [75%] of 65). Haemorrhage occurred in 13 (20%; 95% CI 11•1-31•8) of 65 patients and 23 (35%) of 65 received blood products (15 received fresh frozen plasma and eight received red blood cell concentrates), and 21 patients received platelet transfusions. At admission, the following EXTEM S variables differed significantly between mild cases and moderate to severe cases: median clotting time 56 s (range 42-81; IQR 48-64) versus 69 s (range 48-164; IQR 54-75; p=0•01); mean amplitude at 10 min after clotting time 45•1 mm (SD 7•0) versus 33•9 mm (SD 8•6; p<0•0001); median clot formation time 147 s (range 72-255; IQR 101-171) versus 197 s (range 98-418; IQR 156-296; p=0•006); and maximum clot firmness 54•4 mm (SD 7•2) versus 45•1 mm (SD 12•5; p=0•003). The EXTEM S variables were compared at different time points; maximum clot firmness (p=0•024) and amplitude at 10 min after clotting time (p=0•090) were lowest on days 4-6 of illness. We found no significant differences in FIBTEM variables between mild and moderate to severe cases (median amplitude at 10 min, 13 mm [range 8-20; IQR 11-15] vs 12 mm [range 6-25; IQR 10-15; p=0•68]; and median maximum clot firmness, 15 mm [range 9-60; IQR 13-21] vs 17 mm [range 7-39; IQR 13-23; p=0•21]); and no hyperfibrinolysis (maximum lysis >15%). Interpretation Coagulopathy of Crimean-Congo haemorrhagic fever is related to defects in clot development and stabilisation that are more marked in severe disease than in mild disease. The combination of normal and slightly deranged coagulation screens and FIBTEM results with the absence of hyperfibrinolysis suggests that the coagulopathy of Crimean-Congo haemorrhagic fever relates to platelet dysfunction.
Parasite
Free-ranging spur-thighed tortoises Testudo graeca, captured in different habitat types of Northe... more Free-ranging spur-thighed tortoises Testudo graeca, captured in different habitat types of Northern Tunisia from March to April 2017, were examined for tick infestation: 134/147 (91%) were infested. The overall infestation intensity and abundance was 8.5 and 7.8, respectively. From these tortoises, 1174 ticks were collected, of which 10% (n = 120) taken from 18 randomly-selected tortoises were identified at the species level; the remaining ticks were examined for the presence of Crimean-Congo haemorrhagic fever virus (CCHFv) by real time RT-PCR. Only adult Hyalomma aegyptium were found, suggesting a high degree of host specificity to tortoises. No CCHFv was detected in ticks. Considering the absence of CCHFv in Hyalomma aegyptium infesting its main host, the spur-thighed tortoise, this tick species is unlikely to play a major role in the epidemiology of CCHF. Therefore, more studies are needed to investigate the circulation of this arbovirus between livestock and other tick species ...
Memórias do Instituto Oswaldo Cruz
Here, we report the complete genome sequence of the Aporé virus (Bunyavirales: Arenaviridae), obt... more Here, we report the complete genome sequence of the Aporé virus (Bunyavirales: Arenaviridae), obtained from a wild rodent Oligoryzomys mattogrossae captured in Mato Grosso do Sul state, Brazil. The genome of this virus showed strong similarity to highly pathogenic mammarenavirus from South America.
Access Microbiology
This is a repository copy of Cellular cholesterol abundance regulates potassium accumulation with... more This is a repository copy of Cellular cholesterol abundance regulates potassium accumulation within endosomes and is an important determinant in bunyavirus entry.
Clinical & Experimental Immunology
During the past decade several notable viruses have suddenly emerged from obscurity or anonymity ... more During the past decade several notable viruses have suddenly emerged from obscurity or anonymity to become serious global health threats, provoking concern regarding their sustained epidemic transmission in immunologically naive human populations. With each new threat comes the call for rapid vaccine development. Indeed, vaccines are considered a critical component of disease prevention for emerging viral infections because, in many cases, other medical options are limited or non-existent, or that infections result in such a rapid clinical deterioration that the effectiveness of therapeutics is limited. While classic approaches to vaccine development are still amenable to emerging viruses, the application of molecular techniques in virology has profoundly influenced our understanding of virus biology, and vaccination methods based on replicating, attenuated and non-replicating virus vector approaches have become useful vaccine platforms. Together with a growing understanding of viral disease emergence, a range of vaccine strategies and international commitment to underpin development, vaccine intervention for new and emerging viruses may become a possibility.