register interest

Gail Carson

Research Area: Global Health
Scientific Themes: Tropical Medicine & Global Health and Immunology & Infectious Disease

The International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) is a network of networks that was established in 2011 to ensure a rapid research response to outbreaks of pandemic potential. Having experienced the 2009 pandemic, SARS, and other outbreaks, many of ISARIC’s founding investigators acknowledged the need for a multidisciplinary and global approach that would encourage preparedness and collaboration in the interpandemic period.

ISARIC has, to date, gathered 50 networks and 35 individual members globally – all of whom are directly involved with outbreak response and preparedness locally, regionally, and internationally. Our membership includes clinicians, clinical researchers, clinical trials professionals, virologists, microbiologists, geneticists, epidemiologists and public health professionals, statisticians, and ethicists among others – active within 110 countries across resource settings.

In order to ensure preparedness and an efficient response, ISARIC activities have aimed to fulfil its main objectives, which are to: 

  • develop standardised and globally accessible research tools
  • set up platforms for data collection and data sharing
  • establish a primed infrastructure to epidemic responses
  • enable research in resource poor settings

Since setting up, ISARIC has had the opportunity to implement these objectives in preparedness for and during outbreaks, such as for MERS-CoV, the West African Ebola outbreak, and currently in response to ZIKV.

Name Department Institution Country
Brian Angus FRCP Tropical Medicine Oxford University, John Radcliffe Hospital United Kingdom
Buddha Basnyat Tropical Medicine Oxford University, Kathmandu Nepal
David Dance Tropical Medicine Oxford University, Vientiane Laos
Nicholas Day MA BM BCh DM FRCP FMedSci Tropical Medicine Oxford University, Bangkok Thailand
Adrianus Dondorp Tropical Medicine Oxford University, Bangkok Thailand
Mike English Tropical Medicine Oxford University, Nairobi Kenya
Philippe Guérin Tropical Medicine Oxford University, NDM Research Building United Kingdom
Adrian Hill Jenner Institute Oxford University, Old Road Campus Research Building United Kingdom
Peter Horby Tropical Medicine Oxford University, Old Road Campus Research Building United Kingdom
Trudie Lang Tropical Medicine Oxford University, NDM Research Building United Kingdom
Kevin Marsh Tropical Medicine Oxford University, NDM Research Building United Kingdom
François Nosten Tropical Medicine Oxford University, Mae Sot Thailand
Daniel Paris Tropical Medicine Oxford University, Bangkok Thailand
Arturo Reyes-Sandoval Jenner Institute Oxford University, Henry Wellcome Building for Molecular Physiology United Kingdom
Guy Thwaites Tropical Medicine Oxford University, Ho Chi Minh City Vietnam
Paul Turner MB BS, PhD, FRCPCH, FRCPath Tropical Medicine Oxford University, Siem Reap Cambodia
H Rogier van Doorn Tropical Medicine Oxford University, Hanoi Vietnam
Heiman Wertheim Tropical Medicine Oxford University, Hanoi Vietnam
Nicholas White FRS Tropical Medicine Oxford University, Bangkok Thailand
Gobat N, Amuasi J, Yazdanpanah Y, Sigfid L, Davies H, Byrne J-P, Carson G, Butler C, Nichol A, Goossens H. 2019. Advancing preparedness for clinical research during infectious disease epidemics. ERJ Open Res, 5 (2), | Show Abstract | Read more

Clinical research is vital for an effective response to infectious disease epidemics. To be viable, preparations must be made in anticipation of infectious disease epidemics and must address barriers to rapid deployment and implementation. bit.ly/2IzUlyv.

Murthy S, Carson G, Horby P, Merson L, Webb S. 2019. Clinical research networks and assessing pandemic severity. Lancet Glob Health, 7 (1), pp. e33. | Read more

Fusco FM, Brouqui P, Ippolito G, Vetter N, Kojouharova M, Parmakova K, Skinhoej P, Siikamaki H, Perronne C, Schilling S et al. 2018. Highly infectious diseases in the Mediterranean Sea area: Inventory of isolation capabilities and recommendations for appropriate isolation New Microbes and New Infections, 26 pp. S65-S73. | Show Abstract | Read more

© 2018 Epidemics such as viral haemorrhagic fevers, severe acute respiratory syndrome, Middle East respiratory syndrome coronavirus or yet unknown ones have few chances of disappearing. Globalization, worldwide travel, climate change, social conflicts and wars, among others, are likely to favor the emergence of epidemics. Preparedness of hospitals to prevent the spread of these outbreaks is among the prioritized political programmes of many countries. The EuroNHID network has in the past drawn a map of features and equipment of hospitals across Europe to take care of highly contagious patients. We update the data regarding isolation capabilities and recommendations, with an emphasis on Mediterranean countries.

Tyrrell CSB, Allen JLY, Carson G. 2017. Influenza and other emerging respiratory viruses Medicine, 45 (12), pp. 781-787. | Show Abstract | Read more

© 2017 Acute respiratory infections are one of the top five causes of mortality worldwide and contribute to >4 million deaths per year. Consequently, emerging respiratory viruses are a continuing threat to global health security and have the potential to affect our economies. Since the millennium, there have been around a dozen different outbreaks, several capturing international interest. The outbreak of severe acute respiratory syndrome coronavirus saw the beginning of an extensive global collaboration and has influenced many outbreak preparedness protocols now in place. Avian influenza is a particular threat, with cases of A(H5N1) and A(H7N9) reported most recently. Middle East respiratory syndrome coronavirus is causing continuing concerns with outbreaks in the Arabian Peninsula. Healthcare facilities worldwide play a crucial role in identifying threats and must be vigilant. Particularly important is identifying and managing emerging respiratory viruses when they are infrequently encountered. Surveillance, continuing research, vaccine and treatment developments are key to guiding the efforts and actions of healthcare workers, international health organizations, governments and other stakeholders. Each individual has a part to play in protecting our global health.

Rojek AM, Dunning J, Leliogdowicz A, Castle L, Van Lieshout M, Carson G, Sahr F, Olliaro P, Horby PW. 2018. Regulatory and Operational Complexities of Conducting a Clinical Treatment Trial During an Ebola Virus Disease Epidemic. Clin Infect Dis, 66 (9), pp. 1454-1457. | Show Abstract | Read more

The first phase II and III clinical trials for Ebola virus disease treatments were conducted during the West Africa outbreak. We report the operational practicalities of conducting a phase II clinical trial of TKM-130803 to international standards during this outbreak.

Littler K, Boon W-M, Carson G, Depoortere E, Mathewson S, Mietchen D, Moorthy VS, O'Connor D, Roth C, Segovia C. 2017. Progress in promoting data sharing in public health emergencies. Bull World Health Organ, 95 (4), pp. 243. | Read more

Van Kerkhove MD, Reveiz L, Souza JP, Jaenisch T, Carson G, Broutet N, Working Group on ZIKV Harmonized Research. 2016. Harmonisation of Zika virus research protocols to address key public health concerns. Lancet Glob Health, 4 (12), pp. e911-e912. | Read more

Dunning J, Kennedy SB, Antierens A, Whitehead J, Ciglenecki I, Carson G, Kanapathipillai R, Castle L, Howell-Jones R, Pardinaz-Solis R et al. 2016. Experimental Treatment of Ebola Virus Disease with Brincidofovir. PLoS One, 11 (9), pp. e0162199. | Show Abstract | Read more

BACKGROUND: The nucleotide analogue brincidofovir was developed to prevent and treat infections caused by double-stranded DNA viruses. Based on in vitro data suggesting an antiviral effect against Ebola virus, brincidofovir was included in the World Health Organisation list of agents that should be prioritised for clinical evaluation in patients with Ebola virus disease (EVD) during the West African epidemic. METHODS AND FINDINGS: In this single-arm phase 2 trial conducted in Liberia, patients with laboratory-confirmed EVD (two months of age or older, enrolment bodyweight ≥50 kg) received oral brincidofovir 200 mg as a loading dose on day 0, followed by 100 mg brincidofovir on days 3, 7, 10, and 14. Bodyweight-adjusted dosing was used for patients weighing <50 kg at enrolment. The primary outcome was survival at Day 14 after the first dose of brincidofovir. Four patients were enrolled between 01 January 2015 and 31 January 2015. The trial was stopped following the decision by the manufacturer to terminate their program of development of brincidofovir for EVD. No Serious Adverse Reactions or Suspected Unexpected Serious Adverse Reactions were identified. All enrolled subjects died of an illness consistent with EVD. CONCLUSIONS: Due to the small sample size it was not possible to determine the efficacy of brincidofovir for the treatment of EVD. The premature termination of the trial highlights the need to establish better practices for preclinical in-vitro and animal screening of therapeutics for potentially emerging epidemic infectious diseases prior to their use in patients. TRIAL REGISTRATION: Pan African Clinical Trials Registry PACTR201411000939962.

Arabi YM, Hajeer AH, Luke T, Raviprakash K, Balkhy H, Johani S, Al-Dawood A, Al-Qahtani S, Al-Omari A, Al-Hameed F et al. 2016. Feasibility of Using Convalescent Plasma Immunotherapy for MERS-CoV Infection, Saudi Arabia. Emerg Infect Dis, 22 (9), pp. 1554-1561. | Show Abstract | Read more

We explored the feasibility of collecting convalescent plasma for passive immunotherapy of Middle East respiratory syndrome coronavirus (MERS-CoV) infection by using ELISA to screen serum samples from 443 potential plasma donors: 196 patients with suspected or laboratory-confirmed MERS-CoV infection, 230 healthcare workers, and 17 household contacts exposed to MERS-CoV. ELISA-reactive samples were further tested by indirect fluorescent antibody and microneutralization assays. Of the 443 tested samples, 12 (2.7%) had a reactive ELISA result, and 9 of the 12 had reactive indirect fluorescent antibody and microneutralization assay titers. Undertaking clinical trials of convalescent plasma for passive immunotherapy of MERS-CoV infection may be feasible, but such trials would be challenging because of the small pool of potential donors with sufficiently high antibody titers. Alternative strategies to identify convalescent plasma donors with adequate antibody titers should be explored, including the sampling of serum from patients with more severe disease and sampling at earlier points during illness.

Arabi YM, Al-Enezi F, Longuere K-S, Balkhy HH, Al-Sultan M, Al-Omari A, Al-Hameed FM, Carson G, Shindo N, Fowler R. 2016. Feasibility of a randomized controlled trial to assess treatment of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection in Saudi Arabia: a survey of physicians. BMC Anesthesiol, 16 (1), pp. 36. | Show Abstract | Read more

BACKGROUND: The Middle East Respiratory Syndrome coronavirus (MERS-CoV) is an emerging respiratory pathogen with a high mortality rate and no specific treatments available to date. The purpose of this study was to determine the feasibility of conducting a randomized controlled trial (RCT) of convalescent plasma therapy for MERS-CoV-infected patients by using MERS-CoV-specific convalescent plasma obtained from previously recovered patients. METHODS: A survey was adapted from validated questionnaire originally aimed to measure network capacities and capabilities within the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC). The questionnaire was modified for this study to include 26 items that were divided into three main domains of interest: (1) the ability to care for critically ill MERS-CoV patients; (2) laboratory capacity to diagnose MERS-CoV and blood bank ability to prepare convalescent plasma; and (3), research capacity to conduct randomized controlled trials. The questionnaire was emailed to physicians. RESULTS: Of 582 physicians who were invited to the survey, 327 responded (56.2 %). The professional focus of the majority of respondents was critical care (106/249 (43 %)), pediatrics (59/249, (24 %)) or internal medicine (52/249 (21 %)) but none was blood banking. Nearly all respondents (251/263 (95 %)) reported to have access to ICU facilities within their institutions. Most respondents (219/270 (81 %)) reported that intensivists were the most physician group responsible for treatment decisions about critically ill SARI patients. While 125/165 respondents (76 %) reported that they conduct research in ICUs, and 80/161 (49.7 %) had been involved in the conduct of RCTs, including using a placebo comparison (60/161 (37 %)), only 49/226 (21 %) of respondents regularly participated in research networks. CONCLUSIONS: Our survey indicated that in the Kingdom of Saudi Arabia (KSA), ICUs are the most likely clinical locations for conducting a clinical trial of convalescent plasma therapy for MERS-CoV, and that most ICUs have experience with such research designs.

Seddon O, Ashrafi R, Duggan J, Rees R, Tan C, Williams J, Carson G, Healy B. 2016. Seroprevalence of Q Fever in Patients Undergoing Heart Valve Replacement Surgery. J Heart Valve Dis, 25 (3), pp. 375-379. | Show Abstract

BACKGROUND AND AIM OF THE STUDY: Q fever, caused by the rickettsia Coxiella burnetii, is a worldwide zoonotic disease with both acute and chronic manifestations. Endocarditis is the principal chronic manifestation. Q fever can easily be mistaken for degenerative valve disease due to its indolent presentation, the fastidious nature of the organism (routine cultures are negative), and the absence of a typical echocardiographic and macroscopic appearance for endocarditis. Prosthetic valve failure, with associated morbidity and mortality, have been described following unrecognized infections. METHODS: Previous studies have documented the value of screening strategies in areas of high prevalence. Hence, a pilot study was conducted in a low-prevalence setting, in which 139 patients at two tertiary cardiac centers attending for elective valve replacement for degenerative valvular disease underwent testing for chronic Q fever infection by serological and molecular methods on blood and valve tissue. RESULTS: Five patients (3.7%) had serological evidence of past exposure to Q fever (consistent with rates in the literature). None had evidence of chronic Q fever endocarditis. The cost of adopting a universal screening strategy is around £40,000 per case (if serology is used to screen patients prior to surgery). CONCLUSIONS: Alternative and more cost-effective methods for identifying clinically quiet cases of chronic Q fever endocarditis are required.

Dunning J, Sahr F, Rojek A, Gannon F, Carson G, Idriss B, Massaquoi T, Gandi R, Joseph S, Osman HK et al. 2016. Experimental Treatment of Ebola Virus Disease with TKM-130803: A Single-Arm Phase 2 Clinical Trial. PLoS Med, 13 (4), pp. e1001997. | Show Abstract | Read more

BACKGROUND: TKM-130803, a small interfering RNA lipid nanoparticle product, has been developed for the treatment of Ebola virus disease (EVD), but its efficacy and safety in humans has not been evaluated. METHODS AND FINDINGS: In this single-arm phase 2 trial, adults with laboratory-confirmed EVD received 0.3 mg/kg of TKM-130803 by intravenous infusion once daily for up to 7 d. On days when trial enrolment capacity was reached, patients were enrolled into a concurrent observational cohort. The primary outcome was survival to day 14 after admission, excluding patients who died within 48 h of admission. After 14 adults with EVD had received TKM-130803, the pre-specified futility boundary was reached, indicating a probability of survival to day 14 of ≤0.55, and enrolment was stopped. Pre-treatment geometric mean Ebola virus load in the 14 TKM-130803 recipients was 2.24 × 109 RNA copies/ml plasma (95% CI 7.52 × 108, 6.66 × 109). Two of the TKM-130803 recipients died within 48 h of admission and were therefore excluded from the primary outcome analysis. Of the remaining 12 TKM-130803 recipients, nine died and three survived. The probability that a TKM-130803 recipient who survived for 48 h will subsequently survive to day 14 was estimated to be 0.27 (95% CI 0.06, 0.58). TKM-130803 infusions were well tolerated, with 56 doses administered and only one possible infusion-related reaction observed. Three patients were enrolled in the observational cohort, of whom two died. CONCLUSIONS: Administration of TKM-130803 at a dose of 0.3 mg/kg/d by intravenous infusion to adult patients with severe EVD was not shown to improve survival when compared to historic controls. TRIAL REGISTRATION: Pan African Clinical Trials Registry PACTR201501000997429.

Sigfrid L, Reusken C, Carson G, Koopmans M. 2016. Zika: structuring the European research response. ERJ Open Res, 2 (1), pp. 00025-2016. | Show Abstract | Read more

Studies are needed to assess #Zika virus risks and to develop diagnostic tests http://ow.ly/ZaOZw.

Schilling S, Maltezou HC, Fusco FM, De Iaco G, Brodt H-R, Bannister B, Brouqui P, Carson G, Puro V, Gottschalk R et al. 2019. Transportation capacity for patients with highly infectious diseases in Europe: a survey in 16 nations. Clin Microbiol Infect, 21S pp. e1-e5. | Show Abstract | Read more

Highly infectious diseases (HIDs) are defined as being transmissible from person to person, causing life-threatening illnesses and presenting a serious public health hazard. In most European Union member states specialized isolation facilities are responsible for the management of such cases. Ground ambulances are often affiliated with those facilities because rapid relocation of patients is most desirable. To date, no pooled data on the accessibility, technical specifications and operational procedures for such transport capacities are available. During 2009, the 'European Network for HIDs' conducted a cross-sectional analysis of hospitals responsible for HID patients in Europe including an assessment of (a) legal aspects; (b) technical and infrastructure aspects; and (c) operational procedures for ground ambulances used for HID transport. Overall, 48 isolation facilities in 16 European countries were evaluated and feedback rates ranged from 78% to 100% (n = 37 to n = 48 centres). Only 46.8% (22/47) of all centres have both national and local guidelines regulating HID patient transport. If recommended, specific equipment is found in 90% of centres (9/10), but standard ambulances in only 6/13 centres (46%). Exclusive entrances (32/45; 71%) and pathways (30/44; 68.2%) for patient admission, as well as protocols for disinfection of ambulances (34/47; 72.3%) and equipment (30/43; 69.8%) exist in most centres. In conclusion, the availability and technical specifications of ambulances broadly differ, reflecting different preparedness levels within the European Union. Hence, regulations for technical specifications and operational procedures should be harmonized to promote patient and healthcare worker safety.

Arabi Y, Balkhy H, Hajeer AH, Bouchama A, Hayden FG, Al-Omari A, Al-Hameed FM, Taha Y, Shindo N, Whitehead J et al. 2015. Feasibility, safety, clinical, and laboratory effects of convalescent plasma therapy for patients with Middle East respiratory syndrome coronavirus infection: a study protocol. Springerplus, 4 (1), pp. 709. | Show Abstract | Read more

As of September 30, 2015, a total of 1589 laboratory-confirmed cases of infection with the Middle East respiratory syndrome coronavirus (MERS-CoV) have been reported to the World Health Organization (WHO). At present there is no effective specific therapy against MERS-CoV. The use of convalescent plasma (CP) has been suggested as a potential therapy based on existing evidence from other viral infections. We aim to study the feasibility of CP therapy as well as its safety and clinical and laboratory effects in critically ill patients with MERS-CoV infection. We will also examine the pharmacokinetics of the MERS-CoV antibody response and viral load over the course of MERS-CoV infection. This study will inform a future randomized controlled trial that will examine the efficacy of CP therapy for MERS-CoV infection. In the CP collection phase, potential donors will be tested by the enzyme linked immunosorbent assay (ELISA) and the indirect fluorescent antibody (IFA) techniques for the presence of anti-MERS-CoV antibodies. Subjects with anti-MERS-CoV IFA titer of ≥1:160 and no clinical or laboratory evidence of MERS-CoV infection will be screened for eligibility for plasma donation according to standard donation criteria. In the CP therapy phase, 20 consecutive critically ill patients admitted to intensive care unit with laboratory-confirmed MERS-CoV infection will be enrolled and each will receive 2 units of CP. Post enrollment, patients will be followed for clinical and laboratory outcomes that include anti-MERS-CoV antibodies and viral load. This protocol was developed collaboratively by King Abdullah International Medical Research Center (KAIMRC), Gulf Cooperation Council (GCC) Infection Control Center Group and the World Health Organization-International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC-WHO) MERS-CoV Working Group. It was approved in June 2014 by the Ministry of the National Guard Health Affairs Institutional Review Board (IRB). A data safety monitoring board (DSMB) was formulated. The study is registered at http://www.clinicaltrials.gov (NCT02190799).

Horby PW, Endzt H, Muyembe-Tamfum J-J, van Griensven J, Gevao S, Goossens H, Malvy D, Haba NY, Yazdanpanah Y, Olliaro P et al. 2015. Ebola: Europe-Africa research collaborations. Lancet Infect Dis, 15 (11), pp. 1258-1259. | Read more

Inverarity DJ, Forrester VM, Cumming JGR, Paterson PJ, Campbell RJ, Brooks TJG, Carson GL, Ruddy JP. 2015. Injectional anthrax at a Scottish district general hospital. Epidemiol Infect, 143 (6), pp. 1311-1321. | Show Abstract | Read more

This retrospective, descriptive case-series reviews the clinical presentations and significant laboratory findings of patients diagnosed with and treated for injectional anthrax (IA) since December 2009 at Monklands Hospital in Central Scotland and represents the largest series of IA cases to be described from a single location. Twenty-one patients who fulfilled National Anthrax Control Team standardized case definitions of confirmed, probable or possible IA are reported. All cases survived and none required limb amputation in contrast to an overall mortality of 28% being experienced for this condition in Scotland. We document the spectrum of presentations of soft tissue infection ranging from mild cases which were managed predominantly with oral antibiotics to severe cases with significant oedema, organ failure and coagulopathy. We describe the surgical management, intensive care management and antibiotic management including the first description of daptomycin being used to treat human anthrax. It is noted that some people who had injected heroin infected with Bacillus anthracis did not develop evidence of IA. Also highlighted are biochemical and haematological parameters which proved useful in identifying deteriorating patients who required greater levels of support and surgical debridement.

Carson GL, Dunning J, Longuere KS, Brooks WA. 2014. Ebola: controlling the nightmare. Trans R Soc Trop Med Hyg, 108 (12), pp. 741-742. | Read more

Schilling S, Fusco FM, De Iaco G, Bannister B, Maltezou HC, Carson G, Gottschalk R, Brodt H-R, Brouqui P, Puro V et al. 2014. Isolation facilities for highly infectious diseases in Europe--a cross-sectional analysis in 16 countries. PLoS One, 9 (10), pp. e100401. | Show Abstract | Read more

BACKGROUND: Highly Infectious Diseases (HIDs) are (i) easily transmissible form person to person; (ii) cause a life-threatening illness with no or few treatment options; and (iii) pose a threat for both personnel and the public. Hence, even suspected HID cases should be managed in specialised facilities minimizing infection risks but allowing state-of-the-art critical care. Consensus statements on the operational management of isolation facilities have been published recently. The study presented was set up to compare the operational management, resources, and technical equipment among European isolation facilities. Due to differences in geography, population density, and national response plans it was hypothesized that adherence to recommendations will vary. METHODS AND FINDINGS: Until mid of 2010 the European Network for Highly Infectious Diseases conducted a cross-sectional analysis of isolation facilities in Europe, recruiting 48 isolation facilities in 16 countries. Three checklists were disseminated, assessing 44 items and 148 specific questions. The median feedback rate for specific questions was 97.9% (n = 47/48) (range: n = 7/48 (14.6%) to n = 48/48 (100%). Although all facilities enrolled were nominated specialised facilities' serving countries or regions, their design, equipment and personnel management varied. Eighteen facilities fulfilled the definition of a High Level Isolation Unit'. In contrast, 24 facilities could not operate independently from their co-located hospital, and five could not ensure access to equipment essential for infection control. Data presented are not representative for the EU in general, as only 16/27 (59.3%) of all Member States agreed to participate. Another limitation of this study is the time elapsed between data collection and publication; e.g. in Germany one additional facility opened in the meantime. CONCLUSION: There are disparities both within and between European countries regarding the design and equipment of isolation facilities. With regard to the International Health Regulations, terminology, capacities and equipment should be standardised.

Dunning JW, Merson L, Rohde GGU, Gao Z, Semple MG, Tran D, Gordon A, Olliaro PL, Khoo SH, Bruzzone R et al. 2014. Open source clinical science for emerging infections. Lancet Infect Dis, 14 (1), pp. 8-9. | Read more

Coia JE, Ritchie L, Adisesh A, Makison Booth C, Bradley C, Bunyan D, Carson G, Fry C, Hoffman P, Jenkins D et al. 2013. Guidance on the use of respiratory and facial protection equipment. J Hosp Infect, 85 (3), pp. 170-182. | Show Abstract | Read more

Infectious micro-organisms may be transmitted by a variety of routes, and some may be spread by more than one route. Respiratory and facial protection is required for those organisms that are usually transmitted via the droplet/airborne route, or when airborne particles have been artificially created, such as during 'aerosol-generating procedures'. A range of personal protective equipment that provides different degrees of facial and respiratory protection is available. It is apparent from the recent experiences with severe acute respiratory syndrome and pandemic (H1N1) 2009 influenza that healthcare workers may have difficulty in choosing the correct type of facial and respiratory protection in any given clinical situation. To address this issue, the Scientific Development Committee of the Healthcare Infection Society established a short-life working group to develop guidance. The guidance is based upon a review of the literature, which is published separately, and expert consensus.

Thompson K-A, Pappachan JV, Bennett AM, Mittal H, Macken S, Dove BK, Nguyen-Van-Tam JS, Copley VR, O'Brien S, Hoffman P et al. 2013. Influenza aerosols in UK hospitals during the H1N1 (2009) pandemic--the risk of aerosol generation during medical procedures. PLoS One, 8 (2), pp. e56278. | Show Abstract | Read more

BACKGROUND: Nosocomial infection of health-care workers (HCWs) during outbreaks of respiratory infections (e.g. Influenza A H1N1 (2009)) is a significant concern for public health policy makers. World Health Organization (WHO)-defined 'aerosol generating procedures' (AGPs) are thought to increase the risk of aerosol transmission to HCWs, but there are presently insufficient data to quantify risk accurately or establish a hierarchy of risk-prone procedures. METHODOLOGY/PRINCIPAL FINDINGS: This study measured the amount of H1N1 (2009) RNA in aerosols in the vicinity of H1N1 positive patients undergoing AGPs to help quantify the potential risk of transmission to HCWs. There were 99 sampling occasions (windows) producing a total of 198 May stages for analysis in the size ranges 0.86-7.3 µm. Considering stages 2 (4-7.3 µm) and 3 (0.86-4 µm) as comprising one sample, viral RNA was detected in 14 (14.1%) air samples from 10 (25.6%) patients. Twenty three air samples were collected while potential AGPs were being performed of which 6 (26.1%) contained viral RNA; in contrast, 76 May samples were collected when no WHO 2009 defined AGP was being performed of which 8 (10.5%) contained viral RNA (unadjusted OR = 2.84 (95% CI 1.11-7.24) adjusted OR = 4.31 (0.83-22.5)). CONCLUSIONS/SIGNIFICANCE: With our small sample size we found that AGPs do not significantly increase the probability of sampling an H1N1 (2009) positive aerosol (OR (95% CI) = 4.31 (0.83-22.5). Although the probability of detecting positive H1N1 (2009) positive aerosols when performing various AGPs on intensive care patients above the baseline rate (i.e. in the absence of AGPs) did not reach significance, there was a trend towards hierarchy of AGPs, placing bronchoscopy and respiratory and airway suctioning above baseline (background) values. Further, larger studies are required but these preliminary findings may be of benefit to infection control teams.

Atkinson B, Latham J, Chamberlain J, Logue C, O'Donoghue L, Osborne J, Carson G, Brooks T, Carroll M, Jacobs M et al. 2012. Sequencing and phylogenetic characterisation of a fatal Crimean - Congo haemorrhagic fever case imported into the United Kingdom, October 2012. Euro Surveill, 17 (48), pp. 235. | Show Abstract

A patient with fever, and haemorrhagic symptoms was admitted to a hospital in Glasgow on 2 October 2012. Since he had returned from Afghanistan, serum samples were sent for diagnosis at the Rare and Imported Pathogens Laboratory, where a real-time reverse transcriptase-PCR diagnosis of Crimean – Congo haemorrhagic fever was made within 3 hrs after receipt of the sample. Hereafter the patient was transferred to a high-security infectious diseases unit in London but died on 6 October.

Thomas S, Thomson G, Dowall S, Bruce C, Cook N, Easterbrook L, O'Donoghue L, Summers S, Ajazaj L, Hewson R et al. 2012. Review of Crimean Congo hemorrhagic fever infection in Kosova in 2008 and 2009: prolonged viremias and virus detected in urine by PCR. Vector Borne Zoonotic Dis, 12 (9), pp. 800-804. | Show Abstract | Read 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 human-to-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.

Thomson G, Glaser V. 2012. Gail Thomson, M.D. Health Protection Agency (HPA), Porton, United Kingdom. Vector Borne Zoonotic Dis, 12 (9), pp. 715-717. | Read more

Read RC, Carson G. 2012. Using the NIHR Comprehensive Clinical Research Network for infectious diseases and microbiology research. J Infect, 65 (2), pp. 99-101. | Read more

Maltezou HC, Fusco FM, Schilling S, De Iaco G, Gottschalk R, Brodt H-R, Bannister B, Brouqui P, Thomson G, Puro V et al. 2012. Infection control practices in facilities for highly infectious diseases across Europe. J Hosp Infect, 81 (3), pp. 184-191. | Show Abstract | Read more

BACKGROUND: The management of patients with highly infectious diseases (HIDs) is a challenge for healthcare provision requiring a high level of care without compromising the safety of other patients and healthcare workers. AIM: To study the infection control practice in isolation facilities participating in the European Network for Highly Infectious Diseases (EuroNHID) project. METHODS: A survey was conducted during 2009 of 48 isolation facilities caring for patients with HIDs in 16 European countries. Checklists and standard evaluation forms were used to collect and interpret data on hand hygiene, routine hygiene and disinfection, and waste management. FINDINGS: Forty percent of HIDs had no non-hand-operated sinks or alcohol-based antiseptic distributors, while 27% did not have procedures for routine hygiene, final disinfection, or safe discarding of non-disposable objects or equipment. There was considerable variation in the management of waste and in the training of housekeeping personnel. EuroNHID has developed recommendations for hand hygiene, disinfection, routine hygiene, and waste management. CONCLUSIONS: Most aspects of hand hygiene, routine hygiene and disinfection, and waste management were considered at least partially adequate in the majority of European isolation facilities dedicated for the care of patients with HIDs. But considerable variability was observed, with management of waste and training of housekeeping personnel being generally less satisfactory.

Puro V, Fusco FM, Schilling S, Thomson G, De Iaco G, Brouqui P, Maltezou HC, Bannister B, Gottschalk R, Brodt H-R et al. 2012. Biosecurity measures in 48 isolation facilities managing highly infectious diseases. Biosecur Bioterror, 10 (2), pp. 208-214. | Show Abstract | Read more

Biosecurity measures are traditionally applied to laboratories, but they may also be usefully applied in highly specialized clinical settings, such as the isolation facilities for the management of patients with highly infectious diseases (eg, viral hemorrhagic fevers, SARS, smallpox, potentially severe pandemic flu, and MDR- and XDR-tuberculosis). In 2009 the European Network for Highly Infectious Diseases conducted a survey in 48 isolation facilities in 16 European countries to determine biosecurity measures for access control to the facility. Security personnel are present in 39 facilities (81%). In 35 facilities (73%), entrance to the isolation area is restricted; control methods include electronic keys, a PIN system, closed-circuit TV, and guards at the doors. In 25 facilities (52%), identification and registration of all staff entering and exiting the isolation area are required. Access control is used in most surveyed centers, but specific lacks exist in some facilities. Further data are needed to assess other biosecurity aspects, such as the security measures during the transportation of potentially contaminated materials and measures to address the risk of an "insider attack."

Tyrrell CSB, Allen JLY, Carson G. 2017. Influenza and other emerging respiratory viruses Medicine, 45 (12), pp. 781-787. | Show Abstract | Read more

© 2017 Acute respiratory infections are one of the top five causes of mortality worldwide and contribute to >4 million deaths per year. Consequently, emerging respiratory viruses are a continuing threat to global health security and have the potential to affect our economies. Since the millennium, there have been around a dozen different outbreaks, several capturing international interest. The outbreak of severe acute respiratory syndrome coronavirus saw the beginning of an extensive global collaboration and has influenced many outbreak preparedness protocols now in place. Avian influenza is a particular threat, with cases of A(H5N1) and A(H7N9) reported most recently. Middle East respiratory syndrome coronavirus is causing continuing concerns with outbreaks in the Arabian Peninsula. Healthcare facilities worldwide play a crucial role in identifying threats and must be vigilant. Particularly important is identifying and managing emerging respiratory viruses when they are infrequently encountered. Surveillance, continuing research, vaccine and treatment developments are key to guiding the efforts and actions of healthcare workers, international health organizations, governments and other stakeholders. Each individual has a part to play in protecting our global health.

Rojek AM, Dunning J, Leliogdowicz A, Castle L, Van Lieshout M, Carson G, Sahr F, Olliaro P, Horby PW. 2018. Regulatory and Operational Complexities of Conducting a Clinical Treatment Trial During an Ebola Virus Disease Epidemic. Clin Infect Dis, 66 (9), pp. 1454-1457. | Show Abstract | Read more

The first phase II and III clinical trials for Ebola virus disease treatments were conducted during the West Africa outbreak. We report the operational practicalities of conducting a phase II clinical trial of TKM-130803 to international standards during this outbreak.

Littler K, Boon W-M, Carson G, Depoortere E, Mathewson S, Mietchen D, Moorthy VS, O'Connor D, Roth C, Segovia C. 2017. Progress in promoting data sharing in public health emergencies. Bull World Health Organ, 95 (4), pp. 243. | Read more

Van Kerkhove MD, Reveiz L, Souza JP, Jaenisch T, Carson G, Broutet N, Working Group on ZIKV Harmonized Research. 2016. Harmonisation of Zika virus research protocols to address key public health concerns. Lancet Glob Health, 4 (12), pp. e911-e912. | Read more

Dunning J, Kennedy SB, Antierens A, Whitehead J, Ciglenecki I, Carson G, Kanapathipillai R, Castle L, Howell-Jones R, Pardinaz-Solis R et al. 2016. Experimental Treatment of Ebola Virus Disease with Brincidofovir. PLoS One, 11 (9), pp. e0162199. | Show Abstract | Read more

BACKGROUND: The nucleotide analogue brincidofovir was developed to prevent and treat infections caused by double-stranded DNA viruses. Based on in vitro data suggesting an antiviral effect against Ebola virus, brincidofovir was included in the World Health Organisation list of agents that should be prioritised for clinical evaluation in patients with Ebola virus disease (EVD) during the West African epidemic. METHODS AND FINDINGS: In this single-arm phase 2 trial conducted in Liberia, patients with laboratory-confirmed EVD (two months of age or older, enrolment bodyweight ≥50 kg) received oral brincidofovir 200 mg as a loading dose on day 0, followed by 100 mg brincidofovir on days 3, 7, 10, and 14. Bodyweight-adjusted dosing was used for patients weighing <50 kg at enrolment. The primary outcome was survival at Day 14 after the first dose of brincidofovir. Four patients were enrolled between 01 January 2015 and 31 January 2015. The trial was stopped following the decision by the manufacturer to terminate their program of development of brincidofovir for EVD. No Serious Adverse Reactions or Suspected Unexpected Serious Adverse Reactions were identified. All enrolled subjects died of an illness consistent with EVD. CONCLUSIONS: Due to the small sample size it was not possible to determine the efficacy of brincidofovir for the treatment of EVD. The premature termination of the trial highlights the need to establish better practices for preclinical in-vitro and animal screening of therapeutics for potentially emerging epidemic infectious diseases prior to their use in patients. TRIAL REGISTRATION: Pan African Clinical Trials Registry PACTR201411000939962.

Arabi YM, Hajeer AH, Luke T, Raviprakash K, Balkhy H, Johani S, Al-Dawood A, Al-Qahtani S, Al-Omari A, Al-Hameed F et al. 2016. Feasibility of Using Convalescent Plasma Immunotherapy for MERS-CoV Infection, Saudi Arabia. Emerg Infect Dis, 22 (9), pp. 1554-1561. | Show Abstract | Read more

We explored the feasibility of collecting convalescent plasma for passive immunotherapy of Middle East respiratory syndrome coronavirus (MERS-CoV) infection by using ELISA to screen serum samples from 443 potential plasma donors: 196 patients with suspected or laboratory-confirmed MERS-CoV infection, 230 healthcare workers, and 17 household contacts exposed to MERS-CoV. ELISA-reactive samples were further tested by indirect fluorescent antibody and microneutralization assays. Of the 443 tested samples, 12 (2.7%) had a reactive ELISA result, and 9 of the 12 had reactive indirect fluorescent antibody and microneutralization assay titers. Undertaking clinical trials of convalescent plasma for passive immunotherapy of MERS-CoV infection may be feasible, but such trials would be challenging because of the small pool of potential donors with sufficiently high antibody titers. Alternative strategies to identify convalescent plasma donors with adequate antibody titers should be explored, including the sampling of serum from patients with more severe disease and sampling at earlier points during illness.

Arabi YM, Al-Enezi F, Longuere K-S, Balkhy HH, Al-Sultan M, Al-Omari A, Al-Hameed FM, Carson G, Shindo N, Fowler R. 2016. Feasibility of a randomized controlled trial to assess treatment of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection in Saudi Arabia: a survey of physicians. BMC Anesthesiol, 16 (1), pp. 36. | Show Abstract | Read more

BACKGROUND: The Middle East Respiratory Syndrome coronavirus (MERS-CoV) is an emerging respiratory pathogen with a high mortality rate and no specific treatments available to date. The purpose of this study was to determine the feasibility of conducting a randomized controlled trial (RCT) of convalescent plasma therapy for MERS-CoV-infected patients by using MERS-CoV-specific convalescent plasma obtained from previously recovered patients. METHODS: A survey was adapted from validated questionnaire originally aimed to measure network capacities and capabilities within the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC). The questionnaire was modified for this study to include 26 items that were divided into three main domains of interest: (1) the ability to care for critically ill MERS-CoV patients; (2) laboratory capacity to diagnose MERS-CoV and blood bank ability to prepare convalescent plasma; and (3), research capacity to conduct randomized controlled trials. The questionnaire was emailed to physicians. RESULTS: Of 582 physicians who were invited to the survey, 327 responded (56.2 %). The professional focus of the majority of respondents was critical care (106/249 (43 %)), pediatrics (59/249, (24 %)) or internal medicine (52/249 (21 %)) but none was blood banking. Nearly all respondents (251/263 (95 %)) reported to have access to ICU facilities within their institutions. Most respondents (219/270 (81 %)) reported that intensivists were the most physician group responsible for treatment decisions about critically ill SARI patients. While 125/165 respondents (76 %) reported that they conduct research in ICUs, and 80/161 (49.7 %) had been involved in the conduct of RCTs, including using a placebo comparison (60/161 (37 %)), only 49/226 (21 %) of respondents regularly participated in research networks. CONCLUSIONS: Our survey indicated that in the Kingdom of Saudi Arabia (KSA), ICUs are the most likely clinical locations for conducting a clinical trial of convalescent plasma therapy for MERS-CoV, and that most ICUs have experience with such research designs.

Dunning J, Sahr F, Rojek A, Gannon F, Carson G, Idriss B, Massaquoi T, Gandi R, Joseph S, Osman HK et al. 2016. Experimental Treatment of Ebola Virus Disease with TKM-130803: A Single-Arm Phase 2 Clinical Trial. PLoS Med, 13 (4), pp. e1001997. | Show Abstract | Read more

BACKGROUND: TKM-130803, a small interfering RNA lipid nanoparticle product, has been developed for the treatment of Ebola virus disease (EVD), but its efficacy and safety in humans has not been evaluated. METHODS AND FINDINGS: In this single-arm phase 2 trial, adults with laboratory-confirmed EVD received 0.3 mg/kg of TKM-130803 by intravenous infusion once daily for up to 7 d. On days when trial enrolment capacity was reached, patients were enrolled into a concurrent observational cohort. The primary outcome was survival to day 14 after admission, excluding patients who died within 48 h of admission. After 14 adults with EVD had received TKM-130803, the pre-specified futility boundary was reached, indicating a probability of survival to day 14 of ≤0.55, and enrolment was stopped. Pre-treatment geometric mean Ebola virus load in the 14 TKM-130803 recipients was 2.24 × 109 RNA copies/ml plasma (95% CI 7.52 × 108, 6.66 × 109). Two of the TKM-130803 recipients died within 48 h of admission and were therefore excluded from the primary outcome analysis. Of the remaining 12 TKM-130803 recipients, nine died and three survived. The probability that a TKM-130803 recipient who survived for 48 h will subsequently survive to day 14 was estimated to be 0.27 (95% CI 0.06, 0.58). TKM-130803 infusions were well tolerated, with 56 doses administered and only one possible infusion-related reaction observed. Three patients were enrolled in the observational cohort, of whom two died. CONCLUSIONS: Administration of TKM-130803 at a dose of 0.3 mg/kg/d by intravenous infusion to adult patients with severe EVD was not shown to improve survival when compared to historic controls. TRIAL REGISTRATION: Pan African Clinical Trials Registry PACTR201501000997429.

Sigfrid L, Reusken C, Carson G, Koopmans M. 2016. Zika: structuring the European research response. ERJ Open Res, 2 (1), pp. 00025-2016. | Show Abstract | Read more

Studies are needed to assess #Zika virus risks and to develop diagnostic tests http://ow.ly/ZaOZw.

Arabi Y, Balkhy H, Hajeer AH, Bouchama A, Hayden FG, Al-Omari A, Al-Hameed FM, Taha Y, Shindo N, Whitehead J et al. 2015. Feasibility, safety, clinical, and laboratory effects of convalescent plasma therapy for patients with Middle East respiratory syndrome coronavirus infection: a study protocol. Springerplus, 4 (1), pp. 709. | Show Abstract | Read more

As of September 30, 2015, a total of 1589 laboratory-confirmed cases of infection with the Middle East respiratory syndrome coronavirus (MERS-CoV) have been reported to the World Health Organization (WHO). At present there is no effective specific therapy against MERS-CoV. The use of convalescent plasma (CP) has been suggested as a potential therapy based on existing evidence from other viral infections. We aim to study the feasibility of CP therapy as well as its safety and clinical and laboratory effects in critically ill patients with MERS-CoV infection. We will also examine the pharmacokinetics of the MERS-CoV antibody response and viral load over the course of MERS-CoV infection. This study will inform a future randomized controlled trial that will examine the efficacy of CP therapy for MERS-CoV infection. In the CP collection phase, potential donors will be tested by the enzyme linked immunosorbent assay (ELISA) and the indirect fluorescent antibody (IFA) techniques for the presence of anti-MERS-CoV antibodies. Subjects with anti-MERS-CoV IFA titer of ≥1:160 and no clinical or laboratory evidence of MERS-CoV infection will be screened for eligibility for plasma donation according to standard donation criteria. In the CP therapy phase, 20 consecutive critically ill patients admitted to intensive care unit with laboratory-confirmed MERS-CoV infection will be enrolled and each will receive 2 units of CP. Post enrollment, patients will be followed for clinical and laboratory outcomes that include anti-MERS-CoV antibodies and viral load. This protocol was developed collaboratively by King Abdullah International Medical Research Center (KAIMRC), Gulf Cooperation Council (GCC) Infection Control Center Group and the World Health Organization-International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC-WHO) MERS-CoV Working Group. It was approved in June 2014 by the Ministry of the National Guard Health Affairs Institutional Review Board (IRB). A data safety monitoring board (DSMB) was formulated. The study is registered at http://www.clinicaltrials.gov (NCT02190799).

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