Research and product development for Crimean-Congo haemorrhagic fever: priorities for 2024-30.

Crimean-Congo haemorrhagic fever (CCHF) is a widely distributed and potentially fatal tick-borne viral disease with no licensed specific treatments or vaccines. In 2019, WHO published an advanced draft of a research and development roadmap for CCHF that prioritised the development and deployment of the medical countermeasures most needed by CCHF-affected countries. This Personal View presents updated CCHF research and development priorities and is the product of broad consultation with a working group of 20 leading experts in 2023-24.

Imported rickettsial infections to the United Kingdom, 2015-2020.

Objective: The burden of imported rickettsial infection in the UK is not previously described. This retrospective review identifies rickettsial cases diagnosed at the national reference laboratory between 2015 and 2022.

Methods: Samples testing positive for spotted fever group, typhus group, and scrub typhus IgG/IgM on acute and convalescent blood samples, and/or PCR on tissue/blood were categorized as suspected, confirmed or past infection.

Infections in travellers returning to the UK: a retrospective analysis (2015-2020).

Background: Every year, many thousands of travellers return to the United Kingdom (UK) from visits to other countries and some will become unwell due to infections acquired abroad. Many imported infections have similar clinical presentations, such as fever and myalgia, so diagnostic testing is an important tool to improve patient management and outcomes. The aim of this study was to examine the demographics, travel history, presenting symptoms and diagnostic outcomes of referrals to the UK's specialist diagnostic Rare & Imported Pathogens Laboratory (RIPL) for the period 2015-2020.

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

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.

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

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.

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

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.

Melioidosis diagnostic workshop, 2013.

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.

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

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.

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

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.

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

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.

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

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.

A strategic vaccine facility for the 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.