Publications by authors named "Timothy J G Brooks"

13 Publications

  • Page 1 of 1

Serological surveillance of SARS-CoV-2: Six-month trends and antibody response in a cohort of public health workers.

J Infect 2021 05 22;82(5):162-169. Epub 2021 Mar 22.

Immunisation and Countermeasures Division, PHE Colindale, National Infection Service, 61 Colindale Avenue, London NW9 5EQ, UK; Paediatric Infectious Diseases Research Group (PIDRG), St. Georges University of London (SGUL), London, UK. Electronic address:

Background: Antibody waning after SARS-CoV-2 infection may result in reduction in long-term immunity following natural infection and vaccination, and is therefore a major public health issue. We undertook prospective serosurveillance in a large cohort of healthy adults from the start of the epidemic in England.

Methods: Clinical and non-clinical healthcare workers were recruited across three English regions and tested monthly from March to November 2020 for SARS-CoV-2 spike (S) protein and nucleoprotein (N) antibodies using five different immunoassays. In positive individuals, antibody responses and long-term trends were modelled using mixed effects regression.

Findings: In total, 2246 individuals attended 12,247 visits and 264 were seropositive in ≥ 2 assays. Most seroconversions occurred between March and April 2020. The assays showed > 85% agreement for ever-positivity, although this changed markedly over time. Antibodies were detected earlier with Abbott (N) but declined rapidly thereafter. With the EuroImmun (S) and receptor-binding domain (RBD) assays, responses increased for 4 weeks then fell until week 12-16 before stabilising. For Roche (N), responses increased until 8 weeks, stabilised, then declined, but most remained above the positive threshold. For Roche (S), responses continued to climb over the full 24 weeks, with no sero-reversions. Predicted proportions sero-reverting after 52 weeks were 100% for Abbott, 59% (95% credible interval 50-68%) Euroimmun, 41% (30-52%) RBD, 10% (8-14%) Roche (N) < 2% Roche (S).

Interpretation: Trends in SARS-CoV-2 antibodies following infection are highly dependent on the assay used. Ongoing serosurveillance using multiple assays is critical for monitoring the course and long-term progression of SARS-CoV-2 antibodies.
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http://dx.doi.org/10.1016/j.jinf.2021.03.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982645PMC
May 2021

Presence and Persistence of Zika Virus RNA in Semen, United Kingdom, 2016.

Emerg Infect Dis 2017 04 15;23(4):611-615. Epub 2017 Apr 15.

Zika virus RNA has been detected in semen collected several months after onset of symptoms of infection. Given the potential for sexual transmission of Zika virus and for serious fetal abnormalities resulting from infection during pregnancy, information regarding the persistence of Zika virus in semen is critical for advancing our understanding of potential risks. We tested serial semen samples from symptomatic male patients in the United Kingdom who had a diagnosis of imported Zika virus infection. Among the initial semen samples from 23 patients, Zika virus RNA was detected at high levels in 13 (56.5%) and was not detected in 9 (39.1%); detection was indeterminate in 1 sample (4.4%). After symptomatic infection, a substantial proportion of men have detectable Zika virus RNA at high copy numbers in semen during early convalescence, suggesting high risk for sexual transmission. Viral RNA clearance times are not consistent and can be prolonged.
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http://dx.doi.org/10.3201/eid2304.161692DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5367426PMC
April 2017

Experimental Treatment of Ebola Virus Disease with TKM-130803: A Single-Arm Phase 2 Clinical Trial.

PLoS Med 2016 Apr 19;13(4):e1001997. Epub 2016 Apr 19.

Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, United Kingdom.

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.
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http://dx.doi.org/10.1371/journal.pmed.1001997DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4836798PMC
April 2016

Melioidosis diagnostic workshop, 2013.

Emerg Infect Dis 2015 Feb;21(2)

Melioidosis is a severe disease that can be difficult to diagnose because of its diverse clinical manifestations and a lack of adequate diagnostic capabilities for suspected cases. There is broad interest in improving detection and diagnosis of this disease not only in melioidosis-endemic regions but also outside these regions because melioidosis may be underreported and poses a potential bioterrorism challenge for public health authorities. Therefore, a workshop of academic, government, and private sector personnel from around the world was convened to discuss the current state of melioidosis diagnostics, diagnostic needs, and future directions.
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http://dx.doi.org/10.3201/eid2102.141045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4313648PMC
February 2015

Ebola and other viral haemorrhagic fevers.

BMJ 2014 Aug 11;349:g5079. Epub 2014 Aug 11.

Liverpool School of Tropical Medicine, Liverpool L3 5QA, UK

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http://dx.doi.org/10.1136/bmj.g5079DOI Listing
August 2014

UK hantavirus, renal failure, and pet rats.

Lancet 2013 Mar 22;381(9871):1070. Epub 2013 Mar 22.

Rare and Imported Pathogens Department, Porton Down, UK.

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http://dx.doi.org/10.1016/S0140-6736(13)60599-1DOI Listing
March 2013

Evaluation of azithromycin, trovafloxacin and grepafloxacin as prophylaxis for experimental murine melioidosis.

Int J Antimicrob Agents 2010 Jul 11;36(1):87-9. Epub 2010 May 11.

Department of Biomedical Sciences, Defence Science and Technology Laboratory, Porton Down, Salisbury SP4 0JQ, UK.

The efficacies of the azalide azithromycin and the fluoroquinolones trovafloxacin and grepafloxacin for pre- and post-exposure prophylaxis of infection with high or low challenge doses of Burkholderia pseudomallei strain 576 were assessed in an experimental mouse model. Trovafloxacin and grepafloxacin afforded significant levels of protection, whereas azithromycin was ineffective and potentially detrimental. Overall, the data suggest that some fluoroquinolones may have potential utility in prophylaxis of melioidosis and suggest that azithromycin would not be effective in prophylaxis of B. pseudomallei infection.
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http://dx.doi.org/10.1016/j.ijantimicag.2010.03.019DOI Listing
July 2010

Evaluation of azithromycin, trovafloxacin and grepafloxacin as prophylaxis against experimental murine Brucella melitensis infection.

Int J Antimicrob Agents 2010 Jul 21;36(1):66-8. Epub 2009 Dec 21.

Department of Biomedical Sciences, Defence Science and Technology Laboratory, Porton Down, Salisbury SP4 0JQ, UK.

The prophylactic potential of the azalide azithromycin as well as the fluoroquinolones trovafloxacin and grepafloxacin was assessed for the control of infection with Brucella melitensis in an experimental mouse model, determined by reduction in splenic bacterial burden. Trovafloxacin showed limited protective efficacy when administered 2h following a low-dose B. melitensis challenge, whereas grepafloxacin was ineffective. In comparison, azithromycin provided significant control of infection both following low- and high-dose challenges. Overall, the data confirm the potential utility of azithromycin in the prophylaxis of brucellosis and suggest that neither trovafloxacin nor grepafloxacin would likely be valuable for post-exposure prophylaxis of Brucella infection.
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http://dx.doi.org/10.1016/j.ijantimicag.2009.10.003DOI Listing
July 2010

Efficacy of moxifloxacin or gatifloxacin as prophylaxis against experimental murine Brucella melitensis infection.

Int J Antimicrob Agents 2009 Nov 13;34(5):471-3. Epub 2009 Aug 13.

Department of Biomedical Sciences, Defence Science and Technology Laboratory, Porton Down, Salisbury SP4 0JQ, UK.

The prophylactic potential of moxifloxacin and gatifloxacin was assessed in comparison with doxycycline, an established therapeutic antibiotic, to limit or control infection by Brucella melitensis in an experimental mouse model, determined by reduced bacterial burden in the spleen. Although moxifloxacin was found to have a small protective effect when administered 6 h following infection, neither moxifloxacin nor gatifloxacin showed significant efficacy in vivo. In comparison, doxycycline provided significant protection when prophylaxis was started at 6 h, 7 days or 14 days following infection. Overall, these results confirm the utility of doxycycline in the prophylaxis of brucellosis and suggest that neither moxifloxacin nor gatifloxacin are likely to be valuable for post-exposure prophylaxis of Brucella infection.
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http://dx.doi.org/10.1016/j.ijantimicag.2009.06.018DOI Listing
November 2009

Structural modification of a base disaccharide alters antiadhesion properties towards Yersinia pestis.

FEMS Immunol Med Microbiol 2007 Apr 22;49(3):410-4. Epub 2007 Feb 22.

Defence, Science & Technology Laboratories (Dstl), Wiltshire, UK.

Incubation in the presence of structurally modified disaccharides altered the in vitro attachment of Yersinia pestis GB to three human respiratory epithelial cell lines. Each disaccharide resulted in decreased attachment to the alveolar epithelial (A549) cell line. The best inhibitor of attachment for each cell line was the benzylated derivative of Galbeta1-4GalNAc. Highly negatively charged saccharides were efficient inhibitors, particularly for the bronchial epithelial (BEAS2-B) cell line. The data indicate that targeted modification of receptor ligands could offer a novel therapeutic preventing Y. pestis attachment to host cells.
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http://dx.doi.org/10.1111/j.1574-695X.2007.00220.xDOI Listing
April 2007

A strategic vaccine facility for the UK.

Vaccine 2005 Mar;23(17-18):2090-4

Public Health Affairs, Health Protection Agency, Porton Down, Wiltshire SP40JG, UK.

This paper describes a proposed Strategic Vaccine Facility (SVF) to provide a capability to the UK to deal with new and emerging disease threats. It would underpin the vaccine manufacturing industry by developing expertise and technology to enable rapid manufacture of small batches of vaccines for emergency use against agents, such as bioterrorist agents and emerging diseases. It would have a rare ability to work with dangerous pathogens under containment, allowing the production of inactivated and live vaccines, which would be difficult in a conventional plant. The facility's output will include vaccine candidates and manufacturing protocols for transfer to industry, small vaccine batches for emergency use or clinical trials, and vaccine reference standards. It would also be available for manufacturing small batches of experimental and public health vaccines for the UK and the developing world, allowing clinical trials to be undertaken against key diseases.
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http://dx.doi.org/10.1016/j.vaccine.2005.01.066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7131621PMC
March 2005
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