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Published: 01 December 2022

Invasive fungal infections are a growing global threat to human health, accounting for more than 1 million deaths per year.

However, this burden is under-appreciated and medical mycology (the study of fungal diseases) is chronically underfunded receiving less than 1.5% of global infectious diseases research funds.

Research into improvements in diagnosis and treatment of fungal infections and implementation of this research are essential to reduce death and disability.

An estimated 500,000 to 1 million AIDS-related deaths occur annually in low- and middle-income countries, the majority in sub-Saharan Africa and South East Asia.

Four HIV-associated fungal infections - cryptococcal meningitis, histoplasmosis, Pneumocystis pneumonia (PCP) and talaromycosis - are responsible for up to 20% of these AIDS-related deaths.

The World Health Organization (WHO) has recognised that AIDS deaths cannot be further reduced until the major fungal complications of AIDS/ advanced HIV disease are effectively addressed. And in its 2022 Fungal Pathogens Priority List, WHO has flagged Cryptococcus (critical priority), Histoplasma (high priority), Pneumocystis (medium priority) and Talaromyces (medium priority) for global/ regional surveillance, public health interventions, R&D and innovation.

St George's will partner in a new NIHR-funded Global Health Group named IMPRINT (an acronym for International Mycoses Prevention, Research, Implementation, Networks and Training) aims to capitalise on the opportunities presented by recent clinical research advances in cryptococcal meningitis to improve the diagnosis and treatment not just of cryptococcal meningitis, but also the three other major HIV-associated mycoses of public health importance.

The group brings together leading academic researchers, clinical and public health leaders, non-governmental organisations including Médecins Sans Frontières and the Drugs for Neglected Diseases initiative, and community and patient representatives.

The aim is to improve the diagnosis and treatment of HIV fungal infections and ensure that these improvements are made widely available to populations most commonly affected in Africa (Democratic Republic of Congo, Mozambique, Guinea, Malawi, Botswana, South Africa), and South East Asia (Vietnam). The partnership will be equitable, with leadership shared across six work packages delivered from 2022 through to 2026, insights from qualitative research and guidance from a steering committee and community advisory board.

In addition to the direct impact of the work, the group will liaise with national, regional, and international bodies (ministries of health, major NGOs, UNITAID, WHO, Africa CDC) in order to effectively scale the results and impact of its work.

Focused on people living with advanced HIV disease (or AIDS), the group’s objectives are:

  1. TREATMENT: To implement novel, short-course treatment for cryptococcal meningitis in routine care in African and South East Asian countries, building on the results of two landmark trials, ACTA and AMBITION-cm, completed by partners in the consortium, both of which demonstrated improved survival with regimens that are practical and affordable in resource-limited settings. And to support preliminary work using a single high-dose liposomal amphotericin B treatment approach in talaromycosis and to lay the foundations for future studies in histoplasmosis.
  2. PREVENTION: To optimize the screen-and-treat strategy, to identify and treat early cryptococcal disease, before it becomes clinically apparent, in Africa and South East Asia. Semi-quantitative tests will be evaluated for cryptococcal antigen screening, and the pharmacokinetics of pre-emptive treatment with sustained-release flucytosine will be determined, within the ongoing EFFECT trial. Screening will be evaluated to prevent talaromycosis, cryptococcosis and histoplasmosis in South East Asia and histoplasmosis and emergomycosis in Africa.
  3. HEALTH ECONOMICS: To generate essential economic data to support the different screening and treatment approaches being investigated for cryptococcosis, histoplasmosis and talaromycosis. These individual and, if appropriate, combined analyses will be crucial evidence in the group’s efforts to effect the policy changes needed to reduce mortality from HIV fungal infections.
  4. DIAGNOSTICS: To initiate a programme of earlier-stage, laboratory-based work on PCP, and to develop a clinical cohort and sample bio-bank as a resource to develop and test novel diagnostic tests for PCP, which constitutes the major barrier to reducing PCP deaths.
  5. TRAINING: As integral to the work proposed, to support a comprehensive training and capacity strengthening programme in clinical (epidemiology, health economics and/or public health), and laboratory research. Training will be enabled by a recent strategic UK-African partnership and will build on extensive experience of training and capacity strengthening within existing multinational projects. The group’s goal is to train and mentor clinicians and researchers who will help drive and develop this partnership beyond the initial 4-year period.
  6. COMMUNITY ENGAGEMENT: To ensure that the voices of people living with advanced HIV disease and community representatives are meaningfully included and heard across the entire scope of work, the group will develop strategies and tools to increase patient health literacy around HIV-associated fungal infections, collect qualitative data to learn from the experience of patients with HIV-associated fungal infections and facilitate meaningful engagement through community advisory boards.

About The National Institute for Health and Care Research (NIHR)

The mission of the National Institute for Health and Care Research (NIHR) is to improve the health and wealth of the nation through research. We do this by:

  • Funding high quality, timely research that benefits the NHS, public health and social care;
  • Investing in world-class expertise, facilities and a skilled delivery workforce to translate discoveries into improved treatments and services;
  • Partnering with patients, service users, carers and communities, improving the relevance, quality and impact of our research;
  • Attracting, training and supporting the best researchers to tackle complex health and social care challenges;
  • Collaborating with other public funders, charities and industry to help shape a cohesive and globally competitive research system;
  • Funding applied global health research and training to meet the needs of the poorest people in low and middle income countries.
  • NIHR is funded by the Department of Health and Social Care. Its work in low and middle income countries (LMICs) is principally funded through UK Aid from the UK government.
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