Spatial mapping of Ethiopian cutaneous leishmaniasis lesions reveals distinct tissue level immune programs.

Rare diseases have increasingly been recognized as a significant public health challenge, profoundly affecting patients, their families and caregivers, healthcare systems, and society at large (). Although each rare disease affects fewer than 1 in 2,000 individuals, the cumulative global burden is substantial, with over 7,000 identified rare diseases and an estimated prevalence of 3.5 to 5.9% in the general population—equating to approximately 263–446 million people worldwide (, ). Healthcare services for individuals with rare diseases are often under-prioritized, particularly in low- and middle-income countries (). The economic burden on affected individuals and families is considerable, with costs per patient per year estimated to be 10 times higher than those for common diseases (, ). The costs are also overwhelmingly indirect/non-health in nature (). Due to high treatment costs and limited market demand, health insurance programs frequently struggle to negotiate affordable access to therapies, necessitating state intervention (, ). High-income countries have adopted various mechanisms to address these challenges (). In Australia, ultra-orphan drugs () are funded through the Pharmaceutical Benefits Scheme (PBS) under the Rule of Rescue (RoR) or via the Life Saving Drugs Program (LSDP), which applies more stringent and objective criteria (, ). In the United States, the Inflation Reduction Act (IRA) of 2022 empowered Medicare to negotiate drug prices, although orphan-only drugs were excluded to preserve innovation incentives (, ). In contrast, Canada lacks a national orphan drug strategy, resulting in lower approval and reimbursement rates for orphan medicines compared to the United States and EU ().