Thrombocytopaenia Syndrome Research Articles

Background rate estimations for thrombosis with thrombocytopaenia: challenges in evaluating rare safety signals following vaccination in real time during a pandemic

ObjectivesDuring COVID-19 vaccination programmes, new safety signals have emerged for vaccines, including extremely rare cases of thrombosis with thrombocytopaenia syndrome (TTS). Background event rates before and during the pandemic are...

Vaccine safety in Australia during the COVID-19 pandemic: Lessons learned on the frontline.

Surveillance of Adverse Events Following Vaccination in the Community (SAEFVIC), Victoria's vaccine safety service for reporting adverse events following immunisation (AEFI), has provided integrated spontaneous surveillance and clinical services for individuals affected by AEFI since 2007. We describe SAEFVIC's response to the COVID-19 vaccine program, and reflect on lessons learned for vaccine safety. The massive scale of the Australian COVID-19 vaccine program required rapid adaptations across all aspects of SAEFVIC's vaccine safety services. Collection of AEFI reports was streamlined and expanded, incorporating both spontaneous and active surveillance data. Dramatically increased report volumes were managed with additional staffing, and innovations to automate, filter, and triage reports for priority follow up. There were two major adverse events of special interest (AESI): thrombosis with thrombocytopaenia syndrome and myocarditis, with multiple other AESI also investigated. Rapid escalation mechanisms to respond to AESI were established, along with AESI-specific databases for enhanced monitoring. Vaccine education and training resources were developed and public-facing vaccine safety reports updated weekly. Frequent communication with local and national government and regulatory bodies, and consultation with specialist groups was essential. The COVID-19 vaccine program has highlighted the importance of vaccine safety in supporting public confidence in vaccines and informing evidence-based immunisation policy. Supporting the COVID-19 vaccine program has required flexibility in adapting to policy changes and evolving vaccine safety signals, careful triage and prioritisation, informatics innovation, and enhanced engagement with the public regarding vaccine safety. Long-term investment to continue strengthening vaccine safety systems, building on lessons learned, will be essential for the ongoing success of Australian vaccination programs.

Impact of COVID vaccination rollout on the use of computed tomography venography for the assessment of cerebral venous sinus thrombosis.

IntroductionCerebral venous sinus thrombosis (CVST) is rare; however, it has been observed in patients with vaccine‐induced immune thrombotic thrombocytopaenia syndrome (VITT) following the use of adenovirus vector vaccines against COVID‐19. Adverse vaccine effects have been heavily addressed in mainstream media, likely contributing to vaccination anxiety. This study aimed to assess how the vaccine rollout and media coverage has influenced the use of computed tomography venography (CTV) in an acute care setting of a tertiary hospital.MethodSingle‐centre retrospective cohort study from 30 March 2021 to 13 June 2021. Direct comparison to same calendar dates in the preceding 3 years.ResultsIn 2021, 57 patients received CTV with headache being the reason in 48 (84%) and 40 (70%) had received ChAdOx1 nCov‐19 (AstraZeneca COVID‐19 vaccination). Only 20 of these patients received CTV after platelets and D‐Dimer had returned, and only three patients met existing guidelines for imaging. Zero cases were positive. The number of CTV studies was 5.2 times than in 2020 and 2.7 times the mean number for the 3 preceding years.ConclusionThe use of CTV in patients with headache has markedly increased at our centre since negatively biased vaccination influence of mainstream media. Headache is a common vaccine‐related side effect and VITT is exceptionably rare. With the rates of vaccination increasing in the community, these results highlight the importance of strict adherence to established evidence‐based guidelines. Otherwise, critical care capacity, and in particular imaging resources already under pressure will be strained further.

Development research that contributes to saving lives of patients with severe fever with thrombocytopenia syndrome (SFTS)

Severe fever with thrombocytopaenia syndrome (SFTS) is a tick-borne viral haemorrhagic fever with a high case fatality rate. Clinicians, veterinarians and scientists are working together to elucidate its pathophysiology and develop effective vaccines and treatments. The work is led by Dr Masayuki Saijo from the National Institute of Infectious Diseases (NIID) and also involves researchers from Yamaguchi University, Ehime University and Yamaguchi Grand Medical Center. The team is investigating the maintenance of the SFTS virus in nature by exploring the relationship of the virus between animals and ticks and the researchers are also working to clarify the pathophysiology of the disease, which will lead to the development of diagnostics, specific treatments and additional treatments and contribute to the further development of a vaccine. The researchers believe that a 'one health' approach to tackling SFTS is crucial, which is why they are tackling human and animal treatment and prevention in parallel. Favipiravir is an antiviral agent developed by Dr Yosuke Furuta from Toyama Chemicals and is the primary candidate for treatment. The team believes that if favipiravir can be administered to patients in the early stages of SFTS, this will reduce the case fatality rate of the disease. So far, the team has developed two recombinant vaccine candidates for SFTS that have so far demonstrated no major adverse effects. The researchers plan to develop other types of vaccines that will be safe for humans and animals.

One in a million: COVID-19 vaccine-induced thrombosis with thrombocytopaenia syndrome

One in a million: COVID-19 vaccine-induced thrombosis with thrombocytopaenia syndrome

Structure of severe fever with thrombocytopenia syndrome virus L protein elucidates the mechanisms of viral transcription initiation.

Segmented negative-sense RNA viruses (sNSRVs) encode a single-polypeptide polymerase (L protein) or a heterotrimeric polymerase complex to cannibalize host messenger RNA cap structures serving as primers of transcription, and catalyse RNA synthesis. Here, we report the full-length structure of the severe fever with thrombocytopaenia syndrome virus (SFTSV) L protein, as determined by cryogenic electron microscopy at 3.4 Å, leading to an atomic model harbouring three functional parts (an endonuclease, an RNA-dependent RNA polymerase and a cap-binding domain) and two structural domains (an arm domain with a blocker motif and a carboxy-terminal lariat domain). The SFTSV L protein has a compact architecture in which its cap-binding pocket is surprisingly occupied by an Arg finger of the blocker motif, and the endonuclease active centre faces back towards the cap-binding pocket, suggesting that domain rearrangements are necessary to acquire the pre-initiation state of the active site. Our results provide insight into the complete architecture of sNSRV-encoded L protein and further the understanding of sNSRV transcription initiation.

Persistence and gender differences in protection against severe fever with thrombocytopaenia syndrome virus with natural infection: a 4-year follow-up and mathematical prediction study.

Severe fever with thrombocytopaenia syndrome (SFTS) is an emerging infectious disease discovered in 2010 and has a case fatality as high as 30%. We intended to study the immune protection conferred by SFTS with natural infection. We collected and analysed 4-year follow-up data to study the characteristics of neutralising antibodies against SFTS virus (SFTSV). The 50% plaque reduction neutralisation test was used for the detection of neutralising antibodies against SFTSV. Geometric mean titres (GMTs) and proportions of patients with a protective titre were analysed, and the persistence of protection was predicted. The titre of antibodies declined yearly in the 4-year study period. Approximately 3 months after infection, the GMT was 143 (95% confidence interval (CI): 89-231), and 100% of patients had a protective titre. In the fourth year, the GMT declined to 53 (95% CI: 37-76), and 95% of patients had a protective titre. The titre was higher in females than in males. On average, the protection offered by neutralising antibodies against SFTSV could last as long as 9 years. The durations of protection were different for different initial titres. The characteristics of neutralising antibodies can be used as a reference for the vaccination doses and schedules of forthcoming vaccines.