2022-06-06-世界卫生组织-A_WHO-Strategic_Research_Agenda_for_Filovirus_Research_and_Monitoring_WHO-AFIRM_24页_571kb

Summary of WHO-AFIRM Strategy Roadmap 2021-2031

Core Content

The WHO-AFIRM Strategy Roadmap 2021-2031 outlines a long-term global research strategy for filovirus diseases, specifically Ebola virus disease (EVD) and Marburg virus disease (MVD). It is based on the WHO R&D Blueprint and emphasizes three strategic principles: Anticipation, Reinforcement, and Cure. These principles aim to improve the global capacity to detect, prevent, and treat filovirus outbreaks through coordinated research, surveillance, and development of medical countermeasures (MCMs).

Main Points

Vision

The vision is to improve the availability and accessibility of robust methods to detect, control, and cure EVD and MVD. This includes:

• Establishing prediction methods for future outbreaks and rapid, accurate diagnostics.
• Accelerating the development of safe and effective vaccines.
• Developing treatments and post-exposure prophylaxis (PEP) to reduce morbidity and mortality.

Aim

The aim is to establish a set of research priorities for filovirus diseases over the next decade, addressing critical knowledge gaps and enhancing preparedness through scientific and regulatory capacity building.

Primary Challenges

• Weak commercial markets for diagnostics, therapeutics, and vaccines in low-income countries.
• High financial and legal risks in developing and deploying MCMs during public health emergencies.
• Limited resources such as funding, biological samples, and BSL-4 facilities.
• Challenges in conducting clinical trials due to unpredictable outbreak locations and small outbreak sizes.
• Inadequate data management and sharing mechanisms in under-resourced areas.
• Insufficient pharmacovigilance systems to monitor the safety and effectiveness of MCMs.
• Sociocultural and political barriers that may hinder public acceptance of vaccines and treatments.

Key Needs

• Funding sources including public-private partnerships, government agencies, and philanthropy.
• Strengthened scientific and regulatory capacity in at-risk regions.
• Clear prioritization and coordination mechanisms for preclinical and clinical studies.
• Interoperable data collection and sharing systems across study sites.
• Standardized assays, reagents, and challenge strains for R&D.
• Detailed planning and preparation for clinical trials during future outbreaks.
• Adequate supplies of MCMs for rapid deployment.
• Material transfer agreements (MTAs) to enable efficient sample sharing.
• Operational planning to establish and maintain global stockpiles of licensed and experimental MCMs.

Key Knowledge Gaps

• Refinement and standardization of animal models for filovirus infection and disease.
• Improved understanding of immunology and pathogenesis of filoviruses, including mechanisms of viral persistence and immune correlates of survival.
• Research on sociocultural and behavioral factors to support the development of socially acceptable MCMs.
• Prediction models and diagnostic tools to detect and respond to future outbreaks.

Strategic Goals

Anticipation

Rationale: Enhanced surveillance and detection have led to increased reporting of EVD outbreaks, suggesting that many previous cases were undetected. Future outbreaks can be initiated by human-to-human transmission from survivors, making early detection and prediction critical.

Strategic Goals:

1. Enhance multi-country coordination to improve outbreak detection and response.
2. Strengthen diagnostic tools and expand genomic sequencing research.
3. Improve laboratory capacity for diagnostics, serosurveillance, and clinical investigation.
4. Develop a survivor follow-up network to study virus persistence and immune responses.
5. Engage social sciences to promote community engagement and address misperceptions.

Reinforcement

Rationale: The development of vaccines is essential to protect populations at risk from filovirus diseases. Current vaccines are available for EBOV but not for MARV.

Strategic Goals:

• Accelerate preclinical and clinical testing of vaccines against Sudan virus, Marburg virus, and other filoviruses.
• Determine the epidemic potential of poorly characterized filoviruses.
• Establish research strategies to evaluate vaccine-induced immune responses, using the DIVA principle (Differentiating Infected from Vaccinated Animals).

Cure

Rationale: Post-exposure therapies and improved standard of care are needed to reduce mortality and transmission.

Strategic Goals:

• Foster research to improve post-exposure treatments and therapeutic agents.
• Develop safe and effective therapies and PEP.
• Support clinical trials and pharmacovigilance to monitor the safety and effectiveness of MCMs.

Milestones

1. By 2025, develop a WHO-coordinated multi-country network to facilitate the sharing of biological samples, ecological, and genomic data.
2. By 2025, develop novel multiplex diagnostic assays to enable the detection of different filoviruses.
3. By 2030, establish global stockpiles of licensed and experimental MCMs and ensure alignment with anticipated needs.
4. By 2030, develop standardized assays and reagents for filovirus R&D.
5. By 2030, implement comprehensive clinical trial planning and ensure ethical and regulatory approvals are in place.

Conclusion

The WHO-AFIRM Roadmap emphasizes the need for global collaboration and scientific innovation to address the challenges of filovirus outbreaks. It calls for the development of robust surveillance systems, advanced diagnostics, vaccines, and therapies, supported by international coordination, data sharing, and capacity building in at-risk regions. The success of this strategy will depend on the collective efforts of scientists, policymakers, and industry partners to ensure timely and effective responses to future filovirus epidemics.