WHO Sets Global Standards to Boost Speed and Accuracy of Yellow Fever Diagnostics

The World Health Organization’s detailed technical blueprint aimed at accelerating, standardizing, and improving yellow fever (YF) testing, with contributions from renowned institutions such as the Centre Pasteur du Cameroun, Robert Koch Institute in Germany, Institut Pasteur de Dakar in Senegal, Uganda Virus Research Institute, Brazilian Health Regulatory Agency (Anvisa), Congo National Yellow Fever Reference Laboratory, South Africa’s National Institute for Communicable Diseases, Rwanda Food & Drugs Authority, Institut Pasteur de Bangui, and the Kenya Medical Research Institute. Yellow fever, a mosquito-borne viral disease found in tropical and subtropical areas of South America and Africa, continues to cause severe illness and death despite the availability of a safe and lifelong protective vaccine. The global burden in 2018 was estimated at 109,000 severe infections and 51,000 deaths, with major outbreaks between 2016 and 2018 in Angola, Democratic Republic of Congo, Uganda, Nigeria, Brazil, Bolivia, Ecuador, Colombia, French Guiana, Peru, and Suriname, as well as imported cases in China and Europe. Rapid case confirmation is critical for triggering timely vaccination campaigns, especially in densely populated or under-immunized regions. In Africa, confirmation can take over a month due to multi-stage serological testing, while the Americas, though quicker thanks to molecular testing, still face high costs and limited procurement support. WHO’s Eliminate Yellow Fever Epidemics (EYE) strategy has expanded laboratory capacity, adding regional reference laboratories (RRLs) in Uganda and Cameroon alongside the Institut Pasteur de Dakar to improve speed and resilience in confirmatory testing.

Expanding the Scope of Diagnostics

This updated WHO-led target product profile builds on a 2019 version developed with the Foundation for Innovative New Diagnostics (FIND), expanding the scope to include four categories of diagnostic tools: standardized molecular assays, standardized IgM ELISA kits, rapid IgM tests, and rapid antigen tests. The intention is to close gaps in rapid outbreak detection, reduce dependence on limited manufacturing sources, and guide developers toward technologies that meet both minimal and optimal performance criteria. The profiles cover a wide range of parameters, including intended use, target populations, use settings, end users, analytes, kit formats, specimen requirements, operational features, environmental tolerances, quality controls, time-to-result targets, analytical and clinical performance, and affordability. For molecular assays, expectations include detecting YF RNA within three hours, tolerating temperature fluctuations during transport, achieving at least 95% sensitivity and specificity (optimally 99%), and costing under US$5 per test. ELISA kits should provide same-day results, function without cold-chain requirements at optimal design, support partial-plate testing, and differentiate YF from other flaviviruses such as dengue, Zika, and West Nile.

Raising the Bar for Rapid Testing

Rapid IgM tests, designed for primary care or field deployment, must be simple to operate, ideally in one step, deliver results in under 20 minutes, and maintain high accuracy while costing no more than US$1 per test at optimal scale. Rapid antigen tests, a newer focus in this TPP, are intended to detect viral proteins directly, potentially offering a longer detection window after symptom onset than molecular methods and enabling point-of-care testing without the need for specimen shipment. By specifying both minimal and optimal characteristics, the WHO aims to encourage innovation while ensuring that even the most basic acceptable products meet essential standards for reliability, usability, and durability in challenging environments.

Designing for Real-World Conditions

A key emphasis throughout the document is aligning diagnostic design with the operational realities of endemic regions. For molecular assays, this includes reagent stability without refrigeration, compatibility with widely used thermocyclers, and tolerance to environmental extremes such as high humidity and altitude. For serological and rapid tests, ease of use by minimally trained personnel, minimal preparation steps, and the inclusion of clear pictogram-based instructions are critical. All assays should incorporate internal quality controls, and packaging should minimize environmental impact, ideally using recyclable or compostable materials. Pricing targets are deliberately low to ensure scalability in resource-limited settings, as affordability is seen as central to adoption and sustained use.

Building Consensus Through Expert Collaboration

The development of these profiles followed WHO’s structured TPP process. Since the need and scope for YF assay profiles had already been established in 2019, the new effort began with convening a steering group and a TPP Development Group made up of experts in arboviruses, diagnostics, regulation, manufacturing quality systems, and end users. A Delphi-like consultation process engaged 16 members, who reviewed and scored each proposed characteristic on a Likert scale, with consensus defined as more than 75% agreement. Feedback, collated with FIND’s support, led to revisions addressing areas with lower agreement. Version 0.1 was posted for a 28-day public consultation, after which refinements were discussed with the group and finalized through a consensus vote. In the end, a unanimous agreement was reached on all characteristics for the four TPPs. Independent peer reviewers assessed the final draft before publication, ensuring technical rigor and field relevance.

Driving a Unified Global Response

These target product profiles are intended as a strategic reference for manufacturers, regulators, procurement agencies, and funders. By setting clear and consensus-driven priorities, WHO seeks to direct research and development investments toward diagnostic tools that are not only scientifically robust but also practical, affordable, and resilient under the challenging field conditions of endemic countries. The overarching aim is to shorten the time from symptom onset to laboratory confirmation, allowing for faster outbreak detection, more targeted vaccination campaigns, and a stronger global capacity to prevent yellow fever epidemics from escalating into large-scale health crises. In doing so, the profiles serve as both a technical specification and a public health mandate, ensuring that diagnostic innovation is guided by real-world needs, operational feasibility, and the imperative to save lives.