Mpox
Mpox (formerly monkeypox)
To address the limited clinical evidence around mpox and therapeutic options available to patients, we have initiated a multi-pronged approach to support the generation of clinically meaningful and reliable data through methodological projects, data collection tools, and observational and interventional studies.
Characterising Disease
Clinical characterisation and outcomes of human mpox virus disease – an observational cohort study of patients with clade IIb mpox
Following the multi-country outbreak of clade IIb mpox in 2022 and a request from the European Medicines Agency’s Emergency Task Force (ETF), we initiated a multi-country observational cohort study (MOSAIC) with ANRS and Hôpitaux Universitaires de Genève in May 2022, with the primary objective to describe clinical and virological outcomes of patients treated with systemic antiviral medications and untreated patients. 602 participants with laboratory confirmed MPXV were enrolled in 6 European countries between June 2022 and July 2023.
Full details of the study design of the MOSAIC study can be found in the protocol. The results of the study are expected to be available mid-2024.
ISARIC-WHO Clinical Characterisation Protocol and Case Report Form
The Clinical Characterisation Protocol (CCP) is designed to accelerate a research response to any severe or potentially severe acute infection of public health interest. The protocol and case report form enable data and biological samples to be collected rapidly, in a globally-harmonised manner. All institutions planning to collect detailed clinical data and/or samples to characterise mpox cases are invited to adapt and/or implement these resources at their sites.
This CRF has been implemented in the UK in 2022, Nigeria in 2023 and Rwanda in 2024.
Uncertainties about clinical outcomes
Mpox highlights the difficulties in designing primary endpoints for under-researched emerging diseases. The clade IIb outbreak is characterised by clinical features that are different from the classical clade IIa and clade I. We critically reviewed current clinical and virologic outcomes and discuss their merits and limitation in this paper.
Read more: Monkeypox: how will we know if the treatments work?
Variability in assessment of mpox lesions
The assessment and classification of mpox lesions has two primary purposes. First, lesion assessment is used for the diagnosis of mpox in some settings with limited laboratory capacity and for making treatment decisions. Second, lesion presentation is also used to assess patient outcomes in research settings, including using lesion status in clinical trial endpoints.
However, there has been no formal investigation into whether clinicians can differentiate between different mpox lesion stages. It is also important to understand where mpox commonly arises with other poxviruses if clinicians can provide a differential diagnosis based on visual presentation of the lesions.
We therefore conducted two studies to evaluate the variability in the clinical assessment of clade I and clade IIb mpox lesions.
Challenges in Clinical Diagnosis of Clade I Mpox: Highlighting the Need for Enhanced Diagnostic Approaches
The objective of this study was to evaluate inter-rater reliability and agreement between clinicians assessing lesions in patients with Clade I mpox. We presented 16 experienced clinicians with 17 images of Clade I mpox or varicella and asked them the following questions for each image:
- What is the most likely diagnosis between mpox and varicella?
- What stage are the lesions in the photo – active, scabbed, resolved or unable to classify?
Our study found that there are limitations to using visual assessment of lesions to diagnose Clade I mpox and to evaluate lesion stage. There was better agreement if one lesion type was present in the photo, but worse agreement when there were multiple different types of lesions in the photo. This is particularly concerning for clinical practice, public health and clinical trials and demonstrates the need for improved tools to inform clinical, public-health, and research priorities that can be implemented in clade I-endemic countries.
The full results will be available upon publication.
Variability in clinical assessment of clade IIb mpox lesions
We presented 53 clinicians experienced in clade IIb mpox disease with 20 lesion images on an online questionnaire and asked them to categorize the lesion stage as either active, crusted, resolved, or unclassifiable.
Our study found moderate inter-rater reliability and agreement among participants. The findings emphasize the importance of standardizing lesion classification systems to facilitate clinical care (e.g., decision to start treatment) and public health (e.g., isolation) decisions and a need to explore alternative endpoints for clinical trials.
Improving treatment
Expanded access protocol for the use of tecovirimat for the treatment of mpox infection in Central African Republic (ISRCTN43307947)
In partnership with the Ministry of Health of the Central African Republic and Institut Pasteur de Bangui, ISARIC is conducting an Expanded Access Programme in which patients with laboratory-confirmed mpox are being offered treatment with tecovirimat – an antiviral manufactured and provided by SIGA Technologies Inc. The aim of the study is to describe the outcomes of patients treated with tecovirimat. This is the first protocolised use of tecovirimat in a mpox-endemic country.
Since December 2021, 26 confirmed Clade I MPXV patients have been enrolled.
The data collected from the first 13 participants were analysed and enriched our knowledge on the use of tecovirimat in the Central African Republic. Read more here.
Removing barriers
Stigma and Mpox
Stigma is a recognised barrier to outbreak control due to its impact on healthcare seeking. It is also known to have negative effects on the psychological, social, and physical well-being of affected people. The importance of addressing stigma during outbreak response is outlined in this publication.
Stigma scales measure the amount of stigma in a community. They are used routinely for diseases such as HIV and, if applied to other outbreak diseases such as mpox, they can help to identify and address stigma. We are in the process of developing a global cross-outbreak stigma survey.
Members of the gay and bi men who have sex with men (GBMSM) community are working with us to develop this survey in collaboration with those affected by mpox in the UK, among other communities affected by other outbreaks worldwide.
Community engagement in mpox clinical trials
PLATINUM is a UK-wide clinical trial testing an antiviral drug called tecovirimat, which may help people with mpox get better more quickly and could shorten the time that they are infectious. Together with Oxford Population Health at the University of Oxford, the PLATINUM trial was the first trial globally evaluating an mpox therapeutic, tecovirimat. PLATINUM opened in 2022 shortly after the May 2022 mpox outbreak in the UK. The trial is currently closed for enrolment and results will be published soon.
The PLATINUM team have been working with community representatives and groups, particularly those identifying as GBMSM, to design and implement the trial itself since early 2022. Community involvement activities include community advisory panel discussions, protocol reviews, recruitment support, discussions around results dissemination and further impact, and also working with relevant charities and organisations across the UK. Explore the full list of activities and their impact on the trial in our publication below which was co-authored by community members.
Removing barriers to clinical research
Outbreak clinical research presents special challenges, the most pressing one being speed; starting studies as early as possible is crucial to enrol meaningful numbers of patients and return answers to the research community and patients with minimal delay. However, we often only manage to catch the tail of an outbreak, when cases are dwindling, leaving critical questions hanging – and the mpox clade IIb PHEIC has been no exception. We have exposed the limitations of ill-adapted bureaucracy and regulations, and proposed concrete solutions for improved efficiencies in various papers:
Experiences and challenges with the new European Clinical Trials Regulation
MOSAIC: a European cohort study of human Mpox – the challenges of clinical research in outbreaks
Publications
News
A multi-country study of monkeypox being launched – first cases enrolled in Geneva
A multi-country study of monkeypox being launched – first cases enrolled in Geneva
Activities
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