Cryptococcal meningitis: a review of cryptococcal antigen screening programs in Africa

ABSTRACT

Introduction

Cryptococcal meningitis remains a significant contributor to AIDS-related mortality despite widened access to antiretroviral therapy. Cryptococcal antigen (CrAg) can be detected in the blood prior to development of meningitis. Development of highly sensitive and specific rapid diagnostic CrAg tests has helped facilitate the adoption of CrAg screening programs in 19 African countries.

Areas covered

The biological rationale for CrAg screening and the programmatic strategies for its implementation are reviewed. We describe the approach to the investigation of patients with cryptococcal antigenemia and the importance of lumbar puncture to identify individuals who may have cryptococcal meningitis in the absence of symptoms. The limitations of current treatment recommendations and the potential role of newly defined combination antifungal therapies are discussed. A literature review was conducted using a broad database search for cryptococcal antigen screening and related terms in published journal articles dating up to December 2019. Conference abstracts, publicly available guidelines, and project descriptions were also incorporated.

Expert opinion

As we learn more about the risks of cryptococcal antigenemia, it has become clear that the current management paradigm is inadequate. More intensive investigation and management are required to prevent the development of cryptococcal meningitis and reduce mortality associated with cryptococcal antigenemia.

KEYWORDS:

• AIDS
• Africa
• antifungal therapy
• amphotericin
• cryptococcal antigen
• cryptococcal meningitis
• fluconazole
• flucytosine
• advanced HIV disease
• opportunistic infection

Article highlights

• Cryptococcal disease continues to cause significant mortality in sub-Saharan Africa.

• CrAg screening has been widely adopted into policy across African countries, and the prevalence of cryptococcal antigenemia is now known in many key regions.

• Different approaches to CrAg screening have been developed and each can provide context-specific options for implementation. The operational benefits and challenges of these approaches are described.

• The presence of cryptococcal antigenemia warrants investigation for cryptococcal meningitis with diagnostic lumbar puncture, where feasible.

• Treatment outcomes among those with cryptococcal antigenemia treated only with oral fluconazole are suboptimal.

• New optimized oral or short-course treatment options for cryptococcal meningitis may be transferrable to patients with cryptococcal antigenemia.

Disclaimer

The content is solely the responsibility of the authors and does not necessarily represent the official views of the Centers for Disease Control and Prevention.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

JNJ is co-Chief Investigator and DSL is Lead Clinician on the AMBIsome Therapy Induction OptimisatioN (AMBITION) trial which is jointly funded through the European Developing Countries Clinical Trials Partnership (EDCTP), the Swedish International Development Cooperation Agency (SIDA), and the Wellcome Trust / Medical Research Council (UK) / UKAID Joint Global Health Trials. This work was funded by the National Institute for Health Research (NIHR) through a Global Health Research Professorship to JNJ (RP-2017-08-ST2-012) using UK aid from the UK Government to support global health research. The views expressed in this publication are those of the author(s) and not necessarily those of the NIHR or the UK Department of Health and Social Care.