Tim Brooks - Academia.edu (original) (raw)

Papers by Tim Brooks

Eurosurveillance, 2014

Crimean-Congo haemorrhagic fever (CCHF) was diagnosed in a United Kingdom traveller who returned ... more Crimean-Congo haemorrhagic fever (CCHF) was diagnosed in a United Kingdom traveller who returned from Bulgaria in June 2014. The patient developed a moderately severe disease including fever, headaches and petechial rash. CCHF was diagnosed following identification of CCHF virus (CCHFV) RNA in a serum sample taken five days after symptom onset. Sequence analysis of the CCHFV genome showed that the virus clusters within the Europe 1 clade, which includes viruses from eastern Europe.

The Lancet Infectious Diseases, 2016

Background Limited data are available on the prevalence and predictors of clinical sequelae in su... more Background Limited data are available on the prevalence and predictors of clinical sequelae in survivors of Ebola virus disease (EVD). The EVD Survivor Clinic in Port Loko, Sierra Leone, has provided clinical care for 603 of 661 survivors living in the district. We did a cross-sectional study to describe the prevalence, nature, and predictors of three key EVD sequelae (ocular, auditory, and articular) in this cohort of EVD survivors. Methods We reviewed available clinical and laboratory records of consecutive patients assessed in the clinic between March 7 and April 24, 2015. We used univariate and multiple logistic regression to examine clinical and laboratory features of acute EVD with the following outcomes in convalescence: new ocular symptoms, uveitis, auditory symptoms and arthralgias. Findings Among 277 survivors (59% female), median age was 29 years (IQR 20-36) and median time from discharge from an EVD treatment facility to first survivor clinic visit was 121 days (82-151). Clinical sequelae were common, including arthralgias (n=210, 76%), new ocular symptoms (n=167, 60%), uveitis (n=50, 18%), and auditory symptoms (n=67, 24%). Higher Ebola viral load at acute EVD presentation (as shown by lower cycle thresholds on real-time RT-PCR testing) was independently associated with uveitis (adjusted odds ratio [aOR] 3•33, 95% CI 1•87-5•91, for every five-point decrease in cycle threshold) and with new ocular symptoms or ocular diagnoses (aOR 3•04, 95% CI 1•87-4•94). Interpretation Clinical sequelae during early EVD convalescence are common and sometimes sight threatening. These findings underscore the need for early clinical follow-up of EVD survivors and urgent provision of ocular care as part of health systems strengthening in EVDaffected West African countries.

PLOS ONE, 2019

Background Without an effective vaccine, as was the case early in the 2014-2016 Ebola Outbreak in... more Background Without an effective vaccine, as was the case early in the 2014-2016 Ebola Outbreak in West Africa, disease control depends entirely on interrupting transmission through early disease detection and prompt patient isolation. Lateral Flow Immunoassays (LFI) are a potential supplement to centralized reference laboratory testing for the early diagnosis of Ebola Virus Disease (EVD). The goal of this study was to assess the performance of commercially available simple and rapid antigen detection LFIs, submitted for review to the WHO via the Emergency Use Assessment and Listing procedure. The study was performed in an Ebola Treatment Centre laboratory involved in EVD testing in Sierra Leone. In light of the current Ebola outbreak in May 2018 in the Democratic Republic of Congo, which highlights the lack of clarity in the global health community about appropriate Ebola diagnostics, our findings are increasingly critical. Methods A cross-sectional study was conducted to assess comparative performance of four LFIs for detecting EVD. LFIs were assessed against the same 328 plasma samples and 100 whole EDTA blood samples, using the altona RealStar Filovirus Screen real-time RT-PCR as the bench mark assay. The performance of the Public Health England (PHE) in-house Zaire ebolavirus-specific real time RT-PCR Trombley assay was concurrently assessed. Statistical analysis using generalized estimating equations was conducted to compare LFI performance.

Protocol for the evaluation of four commercial immunoassays (Abbott's SARS-CoV-2 Immunoassay,... more Protocol for the evaluation of four commercial immunoassays (Abbott's SARS-CoV-2 Immunoassay, DiaSorin's LIAISON® SARS-CoV-2 S1/S2 IgG, Roche's Elecsys® Anti-SARS-CoV-2, Siemens' SARS-CoV-2 Total [COV2T]) and a novel 384-well format ELISA (the Oxford immunoassay [OIA]) for the detection of SARS-CoV-2 antibodies (author list is alphabetical).

Antiviral Research, 1999

In common with other flaviviruses, there is no specific therapy for St Louis encephalitis (SLE) v... more In common with other flaviviruses, there is no specific therapy for St Louis encephalitis (SLE) virus infections. A number of cases have occurred where infection may have been acquired by the aerosol route in laboratory accidents. The recombinant human interferon hybrids IFN-α A/D (Roche Laboratories) and IFN-α B/D (Ciba-Geigy) have activity in murine models. Given for several days around the

Journal of Clinical Virology, 2015

PloS one, 2015

Evidence to inform decontamination practices at Ebola holding units (EHUs) and treatment centres ... more Evidence to inform decontamination practices at Ebola holding units (EHUs) and treatment centres is lacking. We conducted an audit of decontamination procedures inside Connaught Hospital EHU in Freetown, Sierra Leone, by assessing environmental swab specimens for evidence of contamination with Ebola virus by RT-PCR. Swabs were collected following discharge of Ebola Virus Disease (EVD) patients before and after routine decontamination. Prior to decontamination, Ebola virus RNA was detected within a limited area at all bedside sites tested, but not at any sites distant to the bedside. Following decontamination, few areas contained detectable Ebola virus RNA. In areas beneath the bed there was evidence of transfer of Ebola virus material during cleaning. Retraining of cleaning staff reduced evidence of environmental contamination after decontamination. Current decontamination procedures appear to be effective in eradicating persistence of viral RNA. This study supports the use of viral...

Emerging Infectious Diseases, 2016

Journal of Clinical Microbiology, 2015

Rapid Ebola virus (EBOV) detection is crucial for appropriate patient management and care. The pe... more Rapid Ebola virus (EBOV) detection is crucial for appropriate patient management and care. The performance of the FilmArray Biothreat E-test (v2.5), against whole blood samples, was evaluated in Sierra Leone and the United Kingdom (UK), and compared with results generated by a real-time Ebola Zaire PCR reference method. In diagnostic laboratories samples were tested on availability, included successive samples from individual patients, and were heat treated to facilitate EBOV inactivation prior to PCR. In Sierra Leone (n=60; 44 patients), the Biothreat E-test had a sensitivity of 84% (confidence interval, CI: 64-95%) and specificity of 89% (CI: 73-97%); and in the UK (n=108; 70 patients), a sensitivity of 75%, (CI: 19-99%) and specificity of 100% (CI: 97-100%), when compared to the reference real-time PCR. Statistical analysis (Fisher's Exact test) indicated there was no significant difference between methods at the 99% confidence level in either country. In 9 discrepant results (5 real-time PCR positives and E-test negatives; 4 real-time PCR negatives and E-test positives), the majority (8) were obtained from samples with an observed, or probable, low viral load. The FilmArray E-test (v2.5) therefore provides an attractive option for laboratories (either in austere field settings or in countries with an advanced technological infrastructure), which do not routinely offer an EBOV diagnostic capability.

Frontiers in Microbiology, 2015

A commercial Bacillus anthracis (Anthrax) whole genome protein microarray has been used to identi... more A commercial Bacillus anthracis (Anthrax) whole genome protein microarray has been used to identify immunogenic Anthrax proteins (IAP) using sera from groups of donors with (a) confirmed B. anthracis naturally acquired cutaneous infection, (b) confirmed B. anthracis intravenous drug use-acquired infection, (c) occupational exposure in a wool-sorters factory, (d) humans and rabbits vaccinated with the UK Anthrax protein vaccine and compared to naïve unexposed controls. Anti-IAP responses were observed for both IgG and IgA in the challenged groups; however the anti-IAP IgG response was more evident in the vaccinated group and the anti-IAP IgA response more evident in the B. anthracis-infected groups. Infected individuals appeared somewhat suppressed for their general IgG response, compared with other challenged groups. Immunogenic protein antigens were identified in all groups, some of which were shared between groups whilst others were specific for individual groups. The toxin proteins were immunodominant in all vaccinated, infected or other challenged groups. However, a number of other chromosomally-located and plasmid encoded open reading frame proteins were also recognized by infected or exposed groups in comparison to controls. Some of these antigens e.g., BA4182 are not recognized by vaccinated individuals, suggesting that there are proteins more specifically expressed by live Anthrax spores in vivo that are not currently found in the UK licensed Anthrax Vaccine (AVP). These may perhaps be preferentially expressed during infection and represent expression of alternative pathways in the B. anthracis "infectome." These may make highly attractive candidates for diagnostic and vaccine biomarker development as they may be more specifically associated with the infectious phase of the pathogen. A number of B. anthracis small hypothetical protein targets have been synthesized, tested in mouse immunogenicity studies and validated in parallel using human sera from the same study.

The Lancet Infectious Diseases, 2015

Clinical management of Ebola virus disease remains challenging. Routine laboratory analytics are ... more Clinical management of Ebola virus disease remains challenging. Routine laboratory analytics are often unavailable in the outbreak setting, and few data exist for the associated haematological and biochemical abnormalities. We aimed to assess laboratory and clinical data from patients with Ebola virus disease to better inform clinical management algorithms, improve understanding of key variables associated with outcome, and provide insight into the pathophysiology of Ebola virus disease. We recruited all patients, alive on arrival, with confirmed Ebola virus disease who were admitted to the Kerry Town Ebola treatment centre in Sierra Leone. At admission, all patients had clinical presentation recorded and blood taken for Ebola confirmation using reverse-transcriptase-PCR (RT-PCR) and for haematological and biochemical analysis. We studied the association between these and clinical outcome. The primary outcome was discharge from the Ebola treatment centre. 150 patients were admitted to the treatment centre between Dec 8, 2014, and Jan 9, 2015. The mean age of patients was 26 years (SD 14·7). Case fatality rate was 37% (55/150). Most patients presented with stage 2 (gastrointestinal involvement, 72/118 [61%]) and stage 3 (severe or complicated, 12/118 [10%]) disease. Acute kidney injury was common (52/104 [50%]), as were abnormal serum potassium (32/97 [33%]), severe hepatitis (54/92 [59%]), and raised C-reactive protein (21/100 [21%]). Haematological abnormalities were common, including raised haematocrit (15/100 [15%]), thrombocytopenia (47/104 [45%]), and granulocytosis (44/104 [42%]). Severe acute kidney injury, low RT-PCR cycle threshold (<20 cycles), and severe hepatitis were independently associated with mortality. Ebola virus disease is associated with a high prevalence of haematological and biochemical abnormalities, even in mild disease and in the absence of gastrointestinal symptoms. Clinical care that targets hypovolaemia, electrolyte disturbance, and acute kidney injury is likely to reduce historically high case fatality rates. None.

Lancet (London, England), Jan 25, 2015

At present, diagnosis of Ebola virus disease requires transport of venepuncture blood to field bi... more At present, diagnosis of Ebola virus disease requires transport of venepuncture blood to field biocontainment laboratories for testing by real-time RT-PCR, resulting in delays that complicate patient care and infection control efforts. Therefore, an urgent need exists for a point-of-care rapid diagnostic test for this disease. In this Article, we report the results of a field validation of the Corgenix ReEBOV Antigen Rapid Test kit. We performed the rapid diagnostic test on fingerstick blood samples from 106 individuals with suspected Ebola virus disease presenting at two clinical centres in Sierra Leone. Adults and children who were able to provide verbal consent or assent were included; we excluded patients with haemodynamic instability and those who were unable to cooperate with fingerstick or venous blood draw. Two independent readers scored each rapid diagnostic test, with any disagreements resolved by a third. We compared point-of-care rapid diagnostic test results with clinic...

Lecture Notes in Computer Science, 2004

Today's crucial information networks are vulnerable to fastmoving attacks by Internet worms and c... more Today's crucial information networks are vulnerable to fastmoving attacks by Internet worms and computer viruses. These attacks have the potential to cripple the Internet and compromise the integrity of the data on the end-user machines. Without new types of protection, the Internet remains susceptible to the assault of increasingly aggressive attacks. A platform has been implemented that actively detects and blocks worms and viruses at multi-Gigabit/second rates. It uses the Field-programmable Port Extender (FPX) to scan for signatures of malicious software (malware) carried in packet payloads. Dynamically reconfigurable Field Programmable Gate Array (FPGA) logic tracks the state of Internet flows and searches for regular expressions and fixedstrings that appear in the content of packets. Protection is achieved by the incremental deployment of systems throughout the Internet.

XXIst International Carbohydrate Symposium 2002, 2002

Emerging infectious diseases, 2014

Outbreaks of serious infections associated with heroin use in persons who inject drugs (PWIDs) oc... more Outbreaks of serious infections associated with heroin use in persons who inject drugs (PWIDs) occur intermittently and require vigilance and rapid reporting of individual cases. Here, we give a firsthand account of the cases in London during an outbreak of heroin-associated anthrax during 2009-2010 in the United Kingdom. This new manifestation of anthrax has resulted in a clinical manifestation distinct from already recognized forms. During 2012-13, additional cases of heroin-associated anthrax among PWIDs in England and other European countries were reported, suggesting that anthrax-contaminated heroin remains in circulation. Antibacterial drugs used for serious soft tissue infection are effective against anthrax, which may lead to substantial underrecognition of this novel illness. The outbreak in London provides a strong case for ongoing vigilance and the use of serologic testing in diagnosis and serologic surveillance schemes to determine and monitor the prevalence of anthrax e...

Emerging infectious diseases, 2014

Military personnel are at high risk of contracting vector-borne and zoonotic infections, particul... more Military personnel are at high risk of contracting vector-borne and zoonotic infections, particularly during overseas deployments, when they may be exposed to endemic or emerging infections not prevalent in their native countries. We conducted seroprevalence testing of 467 UK military personnel deployed to Helmand Province, Afghanistan, during 2008-2011 and found that up to 3.1% showed seroconversion for infection with Rickettsia spp., Coxiella burnetii, sandfly fever virus, or hantavirus; none showed seroconversion for infection with Crimean-Congo hemorrhagic fever virus. Most seroconversions occurred in personnel who did not report illness, except for those with hantavirus (70% symptomatic). These results indicate that many exposures to infectious pathogens, and potentially infections resulting from those exposures, may go unreported. Our findings reinforce the need for continued surveillance of military personnel and for education of health care providers to help recognize and pr...

Vector-Borne and Zoonotic Diseases, 2012

Crimean-Congo hemorrhagic fever (CCHF) is a virus transmitted predominantly by ticks. However, co... more Crimean-Congo hemorrhagic fever (CCHF) is a virus transmitted predominantly by ticks. However, contact with infected body fluids or tissues can result in animal-to-human or humanto-human transmission. Numbers of CCHF cases appear to be increasing, especially in Europe. We reviewed cases admitted to a tertiary referral unit in Kosova with suspected CCHF in 2008 and 2009, and looked at a smaller number of specimens which were sent to the Health Protection Agency, Porton Down, U.K., in further detail. The clinical features of cases admitted with suspected CCHF infection were assessed in more detail, and these are the focus of this article. Between 2008 and 2009, the numbers of patients admitted for suspected CCHF infection increased. Of the samples received in Porton Down, CCHF virus was detected in urine samples, and these patients were found to have prolonged viremia. The detection of CCHF in urine, as well as the prolonged viremias seen, are important for clinicians to know, as they may have public health implications with regard to the risk of infection, as well as provide insights into the biology and pathophysiology of infection. Further studies are required regarding the pathogenesis of this virus.

Reviews in Medical Microbiology, 2001

Botulinum toxin is the most toxic substance known to mankind. It is involved in infant botulism, ... more Botulinum toxin is the most toxic substance known to mankind. It is involved in infant botulism, classical food-borne botulism, wound botulism, and is a threat in biological warfare or bioterrorism. The only successful drug currently available to treat botulinum intoxication ...

Eurosurveillance, 2014

Crimean-Congo haemorrhagic fever (CCHF) was diagnosed in a United Kingdom traveller who returned ... more Crimean-Congo haemorrhagic fever (CCHF) was diagnosed in a United Kingdom traveller who returned from Bulgaria in June 2014. The patient developed a moderately severe disease including fever, headaches and petechial rash. CCHF was diagnosed following identification of CCHF virus (CCHFV) RNA in a serum sample taken five days after symptom onset. Sequence analysis of the CCHFV genome showed that the virus clusters within the Europe 1 clade, which includes viruses from eastern Europe.

The Lancet Infectious Diseases, 2016

Background Limited data are available on the prevalence and predictors of clinical sequelae in su... more Background Limited data are available on the prevalence and predictors of clinical sequelae in survivors of Ebola virus disease (EVD). The EVD Survivor Clinic in Port Loko, Sierra Leone, has provided clinical care for 603 of 661 survivors living in the district. We did a cross-sectional study to describe the prevalence, nature, and predictors of three key EVD sequelae (ocular, auditory, and articular) in this cohort of EVD survivors. Methods We reviewed available clinical and laboratory records of consecutive patients assessed in the clinic between March 7 and April 24, 2015. We used univariate and multiple logistic regression to examine clinical and laboratory features of acute EVD with the following outcomes in convalescence: new ocular symptoms, uveitis, auditory symptoms and arthralgias. Findings Among 277 survivors (59% female), median age was 29 years (IQR 20-36) and median time from discharge from an EVD treatment facility to first survivor clinic visit was 121 days (82-151). Clinical sequelae were common, including arthralgias (n=210, 76%), new ocular symptoms (n=167, 60%), uveitis (n=50, 18%), and auditory symptoms (n=67, 24%). Higher Ebola viral load at acute EVD presentation (as shown by lower cycle thresholds on real-time RT-PCR testing) was independently associated with uveitis (adjusted odds ratio [aOR] 3•33, 95% CI 1•87-5•91, for every five-point decrease in cycle threshold) and with new ocular symptoms or ocular diagnoses (aOR 3•04, 95% CI 1•87-4•94). Interpretation Clinical sequelae during early EVD convalescence are common and sometimes sight threatening. These findings underscore the need for early clinical follow-up of EVD survivors and urgent provision of ocular care as part of health systems strengthening in EVDaffected West African countries.

PLOS ONE, 2019

Background Without an effective vaccine, as was the case early in the 2014-2016 Ebola Outbreak in... more Background Without an effective vaccine, as was the case early in the 2014-2016 Ebola Outbreak in West Africa, disease control depends entirely on interrupting transmission through early disease detection and prompt patient isolation. Lateral Flow Immunoassays (LFI) are a potential supplement to centralized reference laboratory testing for the early diagnosis of Ebola Virus Disease (EVD). The goal of this study was to assess the performance of commercially available simple and rapid antigen detection LFIs, submitted for review to the WHO via the Emergency Use Assessment and Listing procedure. The study was performed in an Ebola Treatment Centre laboratory involved in EVD testing in Sierra Leone. In light of the current Ebola outbreak in May 2018 in the Democratic Republic of Congo, which highlights the lack of clarity in the global health community about appropriate Ebola diagnostics, our findings are increasingly critical. Methods A cross-sectional study was conducted to assess comparative performance of four LFIs for detecting EVD. LFIs were assessed against the same 328 plasma samples and 100 whole EDTA blood samples, using the altona RealStar Filovirus Screen real-time RT-PCR as the bench mark assay. The performance of the Public Health England (PHE) in-house Zaire ebolavirus-specific real time RT-PCR Trombley assay was concurrently assessed. Statistical analysis using generalized estimating equations was conducted to compare LFI performance.

Protocol for the evaluation of four commercial immunoassays (Abbott's SARS-CoV-2 Immunoassay,... more Protocol for the evaluation of four commercial immunoassays (Abbott's SARS-CoV-2 Immunoassay, DiaSorin's LIAISON® SARS-CoV-2 S1/S2 IgG, Roche's Elecsys® Anti-SARS-CoV-2, Siemens' SARS-CoV-2 Total [COV2T]) and a novel 384-well format ELISA (the Oxford immunoassay [OIA]) for the detection of SARS-CoV-2 antibodies (author list is alphabetical).

Antiviral Research, 1999

In common with other flaviviruses, there is no specific therapy for St Louis encephalitis (SLE) v... more In common with other flaviviruses, there is no specific therapy for St Louis encephalitis (SLE) virus infections. A number of cases have occurred where infection may have been acquired by the aerosol route in laboratory accidents. The recombinant human interferon hybrids IFN-α A/D (Roche Laboratories) and IFN-α B/D (Ciba-Geigy) have activity in murine models. Given for several days around the

Journal of Clinical Virology, 2015

PloS one, 2015

Evidence to inform decontamination practices at Ebola holding units (EHUs) and treatment centres ... more Evidence to inform decontamination practices at Ebola holding units (EHUs) and treatment centres is lacking. We conducted an audit of decontamination procedures inside Connaught Hospital EHU in Freetown, Sierra Leone, by assessing environmental swab specimens for evidence of contamination with Ebola virus by RT-PCR. Swabs were collected following discharge of Ebola Virus Disease (EVD) patients before and after routine decontamination. Prior to decontamination, Ebola virus RNA was detected within a limited area at all bedside sites tested, but not at any sites distant to the bedside. Following decontamination, few areas contained detectable Ebola virus RNA. In areas beneath the bed there was evidence of transfer of Ebola virus material during cleaning. Retraining of cleaning staff reduced evidence of environmental contamination after decontamination. Current decontamination procedures appear to be effective in eradicating persistence of viral RNA. This study supports the use of viral...

Emerging Infectious Diseases, 2016

Journal of Clinical Microbiology, 2015

Rapid Ebola virus (EBOV) detection is crucial for appropriate patient management and care. The pe... more Rapid Ebola virus (EBOV) detection is crucial for appropriate patient management and care. The performance of the FilmArray Biothreat E-test (v2.5), against whole blood samples, was evaluated in Sierra Leone and the United Kingdom (UK), and compared with results generated by a real-time Ebola Zaire PCR reference method. In diagnostic laboratories samples were tested on availability, included successive samples from individual patients, and were heat treated to facilitate EBOV inactivation prior to PCR. In Sierra Leone (n=60; 44 patients), the Biothreat E-test had a sensitivity of 84% (confidence interval, CI: 64-95%) and specificity of 89% (CI: 73-97%); and in the UK (n=108; 70 patients), a sensitivity of 75%, (CI: 19-99%) and specificity of 100% (CI: 97-100%), when compared to the reference real-time PCR. Statistical analysis (Fisher's Exact test) indicated there was no significant difference between methods at the 99% confidence level in either country. In 9 discrepant results (5 real-time PCR positives and E-test negatives; 4 real-time PCR negatives and E-test positives), the majority (8) were obtained from samples with an observed, or probable, low viral load. The FilmArray E-test (v2.5) therefore provides an attractive option for laboratories (either in austere field settings or in countries with an advanced technological infrastructure), which do not routinely offer an EBOV diagnostic capability.

Frontiers in Microbiology, 2015

A commercial Bacillus anthracis (Anthrax) whole genome protein microarray has been used to identi... more A commercial Bacillus anthracis (Anthrax) whole genome protein microarray has been used to identify immunogenic Anthrax proteins (IAP) using sera from groups of donors with (a) confirmed B. anthracis naturally acquired cutaneous infection, (b) confirmed B. anthracis intravenous drug use-acquired infection, (c) occupational exposure in a wool-sorters factory, (d) humans and rabbits vaccinated with the UK Anthrax protein vaccine and compared to naïve unexposed controls. Anti-IAP responses were observed for both IgG and IgA in the challenged groups; however the anti-IAP IgG response was more evident in the vaccinated group and the anti-IAP IgA response more evident in the B. anthracis-infected groups. Infected individuals appeared somewhat suppressed for their general IgG response, compared with other challenged groups. Immunogenic protein antigens were identified in all groups, some of which were shared between groups whilst others were specific for individual groups. The toxin proteins were immunodominant in all vaccinated, infected or other challenged groups. However, a number of other chromosomally-located and plasmid encoded open reading frame proteins were also recognized by infected or exposed groups in comparison to controls. Some of these antigens e.g., BA4182 are not recognized by vaccinated individuals, suggesting that there are proteins more specifically expressed by live Anthrax spores in vivo that are not currently found in the UK licensed Anthrax Vaccine (AVP). These may perhaps be preferentially expressed during infection and represent expression of alternative pathways in the B. anthracis "infectome." These may make highly attractive candidates for diagnostic and vaccine biomarker development as they may be more specifically associated with the infectious phase of the pathogen. A number of B. anthracis small hypothetical protein targets have been synthesized, tested in mouse immunogenicity studies and validated in parallel using human sera from the same study.

The Lancet Infectious Diseases, 2015

Clinical management of Ebola virus disease remains challenging. Routine laboratory analytics are ... more Clinical management of Ebola virus disease remains challenging. Routine laboratory analytics are often unavailable in the outbreak setting, and few data exist for the associated haematological and biochemical abnormalities. We aimed to assess laboratory and clinical data from patients with Ebola virus disease to better inform clinical management algorithms, improve understanding of key variables associated with outcome, and provide insight into the pathophysiology of Ebola virus disease. We recruited all patients, alive on arrival, with confirmed Ebola virus disease who were admitted to the Kerry Town Ebola treatment centre in Sierra Leone. At admission, all patients had clinical presentation recorded and blood taken for Ebola confirmation using reverse-transcriptase-PCR (RT-PCR) and for haematological and biochemical analysis. We studied the association between these and clinical outcome. The primary outcome was discharge from the Ebola treatment centre. 150 patients were admitted to the treatment centre between Dec 8, 2014, and Jan 9, 2015. The mean age of patients was 26 years (SD 14·7). Case fatality rate was 37% (55/150). Most patients presented with stage 2 (gastrointestinal involvement, 72/118 [61%]) and stage 3 (severe or complicated, 12/118 [10%]) disease. Acute kidney injury was common (52/104 [50%]), as were abnormal serum potassium (32/97 [33%]), severe hepatitis (54/92 [59%]), and raised C-reactive protein (21/100 [21%]). Haematological abnormalities were common, including raised haematocrit (15/100 [15%]), thrombocytopenia (47/104 [45%]), and granulocytosis (44/104 [42%]). Severe acute kidney injury, low RT-PCR cycle threshold (<20 cycles), and severe hepatitis were independently associated with mortality. Ebola virus disease is associated with a high prevalence of haematological and biochemical abnormalities, even in mild disease and in the absence of gastrointestinal symptoms. Clinical care that targets hypovolaemia, electrolyte disturbance, and acute kidney injury is likely to reduce historically high case fatality rates. None.

Lancet (London, England), Jan 25, 2015

At present, diagnosis of Ebola virus disease requires transport of venepuncture blood to field bi... more At present, diagnosis of Ebola virus disease requires transport of venepuncture blood to field biocontainment laboratories for testing by real-time RT-PCR, resulting in delays that complicate patient care and infection control efforts. Therefore, an urgent need exists for a point-of-care rapid diagnostic test for this disease. In this Article, we report the results of a field validation of the Corgenix ReEBOV Antigen Rapid Test kit. We performed the rapid diagnostic test on fingerstick blood samples from 106 individuals with suspected Ebola virus disease presenting at two clinical centres in Sierra Leone. Adults and children who were able to provide verbal consent or assent were included; we excluded patients with haemodynamic instability and those who were unable to cooperate with fingerstick or venous blood draw. Two independent readers scored each rapid diagnostic test, with any disagreements resolved by a third. We compared point-of-care rapid diagnostic test results with clinic...

Lecture Notes in Computer Science, 2004

Today's crucial information networks are vulnerable to fastmoving attacks by Internet worms and c... more Today's crucial information networks are vulnerable to fastmoving attacks by Internet worms and computer viruses. These attacks have the potential to cripple the Internet and compromise the integrity of the data on the end-user machines. Without new types of protection, the Internet remains susceptible to the assault of increasingly aggressive attacks. A platform has been implemented that actively detects and blocks worms and viruses at multi-Gigabit/second rates. It uses the Field-programmable Port Extender (FPX) to scan for signatures of malicious software (malware) carried in packet payloads. Dynamically reconfigurable Field Programmable Gate Array (FPGA) logic tracks the state of Internet flows and searches for regular expressions and fixedstrings that appear in the content of packets. Protection is achieved by the incremental deployment of systems throughout the Internet.

XXIst International Carbohydrate Symposium 2002, 2002

Emerging infectious diseases, 2014

Outbreaks of serious infections associated with heroin use in persons who inject drugs (PWIDs) oc... more Outbreaks of serious infections associated with heroin use in persons who inject drugs (PWIDs) occur intermittently and require vigilance and rapid reporting of individual cases. Here, we give a firsthand account of the cases in London during an outbreak of heroin-associated anthrax during 2009-2010 in the United Kingdom. This new manifestation of anthrax has resulted in a clinical manifestation distinct from already recognized forms. During 2012-13, additional cases of heroin-associated anthrax among PWIDs in England and other European countries were reported, suggesting that anthrax-contaminated heroin remains in circulation. Antibacterial drugs used for serious soft tissue infection are effective against anthrax, which may lead to substantial underrecognition of this novel illness. The outbreak in London provides a strong case for ongoing vigilance and the use of serologic testing in diagnosis and serologic surveillance schemes to determine and monitor the prevalence of anthrax e...

Emerging infectious diseases, 2014

Military personnel are at high risk of contracting vector-borne and zoonotic infections, particul... more Military personnel are at high risk of contracting vector-borne and zoonotic infections, particularly during overseas deployments, when they may be exposed to endemic or emerging infections not prevalent in their native countries. We conducted seroprevalence testing of 467 UK military personnel deployed to Helmand Province, Afghanistan, during 2008-2011 and found that up to 3.1% showed seroconversion for infection with Rickettsia spp., Coxiella burnetii, sandfly fever virus, or hantavirus; none showed seroconversion for infection with Crimean-Congo hemorrhagic fever virus. Most seroconversions occurred in personnel who did not report illness, except for those with hantavirus (70% symptomatic). These results indicate that many exposures to infectious pathogens, and potentially infections resulting from those exposures, may go unreported. Our findings reinforce the need for continued surveillance of military personnel and for education of health care providers to help recognize and pr...

Vector-Borne and Zoonotic Diseases, 2012

Crimean-Congo hemorrhagic fever (CCHF) is a virus transmitted predominantly by ticks. However, co... more Crimean-Congo hemorrhagic fever (CCHF) is a virus transmitted predominantly by ticks. However, contact with infected body fluids or tissues can result in animal-to-human or humanto-human transmission. Numbers of CCHF cases appear to be increasing, especially in Europe. We reviewed cases admitted to a tertiary referral unit in Kosova with suspected CCHF in 2008 and 2009, and looked at a smaller number of specimens which were sent to the Health Protection Agency, Porton Down, U.K., in further detail. The clinical features of cases admitted with suspected CCHF infection were assessed in more detail, and these are the focus of this article. Between 2008 and 2009, the numbers of patients admitted for suspected CCHF infection increased. Of the samples received in Porton Down, CCHF virus was detected in urine samples, and these patients were found to have prolonged viremia. The detection of CCHF in urine, as well as the prolonged viremias seen, are important for clinicians to know, as they may have public health implications with regard to the risk of infection, as well as provide insights into the biology and pathophysiology of infection. Further studies are required regarding the pathogenesis of this virus.

Reviews in Medical Microbiology, 2001

Botulinum toxin is the most toxic substance known to mankind. It is involved in infant botulism, ... more Botulinum toxin is the most toxic substance known to mankind. It is involved in infant botulism, classical food-borne botulism, wound botulism, and is a threat in biological warfare or bioterrorism. The only successful drug currently available to treat botulinum intoxication ...