Update on Mpox: Sierra Leone’s Fast, Adaptable, Community-Led Approach
Q&A with Pardis Sabeti, MD and Colby Wilkason, MPH (Part 2)
Pardis Sabeti, MD (left) is a professor at Harvard University and a core institute member of the Broad Institute. Her lab has pioneered technologies for detecting, tracking, and countering deadly pathogens, including Ebola, Zika, and SARS-CoV-2. They have also created some of the most powerful algorithms and molecular tools to characterize the human genome and transformative methods for gene delivery of new biomedicines. Sabeti co-founded the African Center of Excellence for Genomics of Infectious Diseases (now the Institute of Genomics and Global Health) and Sentinel, which trains frontline scientists from 53 of 54 African countries. Sabeti’s many honors include TIME magazine’s “Person of the Year” as one of the Ebola fighters, 100 Most Influential People, and Impact award. She is a National Academy of Medicine member and Howard Hughes Medical Institute investigator, and holds a B.S. from MIT, D.Phil. from the University of Oxford as a Rhodes Scholar, and M.D. from Harvard Medical School summa cum laude.
Colby Wilkason, MPH (right) is the Program Manager for Sentinel at the Broad Institute, where she leads the implementation of an infectious disease surveillance system in West Africa. A global health strategist with over a decade of experience in pandemic prevention and disaster response efforts across Africa, Asia, and the United States, her expertise lies in leveraging data to guide decision-making during emergencies. She has previously held roles at the American Red Cross and Resolve to Save Lives, building and applying data-driven systems for epidemic intelligence. Wilkason earned a Master of Public Health in infectious disease epidemiology at Johns Hopkins Bloomberg School of Public Health and her BA at Harvard University.
On November 18, 2025, the Sentinel project was awarded $100M from the MacArthur Foundation to advance its surveillance and training efforts in Nigeria, Sierra Leone, the Democratic Republic of Congo, Rwanda and Senegal.
Sierra Leone’s Public Health Response
Tom Mahoney: My thanks to both of you, Dr. Sabeti and Ms. Wilkason, for sharing your insights on the current outbreaks of mpox in Africa, the epidemiological surveillance and analysis tools you have devised and deployed to help cope with the disease, and why it is a syndrome of global rather than merely regional concern. Sierra Leone was reporting about half of Africa’s new mpox cases. From your vantage point, what specific measures taken by the National Public Health Agency and local communities have helped reverse that trajectory?
Dr. Pardis Sabeti: Sierra Leone turned the tide through a powerful combination of community action and advanced science. First, the National Public Health Agency, the NPHA, mobilized extensive social campaigns, from posters in restaurants and public spaces to door-to-door outreach, so that families knew how to reduce person-to-person transmission through practices like handwashing and limiting close contact. At the same time, public health facilities rapidly scaled up molecular testing across the country, ensuring suspected cases could be confirmed quickly. Partnerships with groups like Cepheid helped expand access to diagnostic assays, extending capacity to even remote districts.
Colby Wilkason: In addition to the work Pardis mentions, NPHA’s ability to get data into the hands of decision-makers in real-time was equally impactful. Sierra Leone first built simple epidemiological dashboards and later adopted Lookout, a more advanced platform that integrates testing, sequencing, and geolocation data. This provided officials with a live map of the outbreak, showing where cases were rising, how the virus was spreading, and where to focus interventions such as contact tracing. Finally, the rapid deployment of genomic sequencing allowed scientists to track the evolution of the virus and confirm when transmission was driven by local spread versus imported cases. Together, these efforts created a comprehensive, locally led response that dramatically slowed the outbreak.
Mahoney: Which elements of Sierra Leone’s outbreak response – such as community engagement, contact tracing, or use of genomic surveillance – do you think can be adapted as a broader model for outbreak preparedness globally?
Sabeti: The lessons from Sierra Leone are not confined to one country or one pathogen. This reflects the broader framework we have developed with Sentinel, a surveillance and response system that brings together rapid diagnostics, real-time data platforms, and local capacity building. The core principle is that preparedness depends on systems that are fast, adaptable, and rooted in local capacity.
Sierra Leone’s response highlights that those three elements, and many others, can be applied anywhere. Community engagement is the starting point and a constant throughout, ensuring people know how outbreaks spread and how they can protect themselves and their families. Contact tracing provides a structured way to follow cases, identify exposures, and interrupt chains of transmission. Genomic surveillance adds another critical dimension by showing how viruses move and evolve, and by guiding public health decisions with real-time evidence. Together, these elements illustrate how a comprehensive, flexible framework can be adapted across countries to stop outbreaks before they become crises.
Mahoney: What role did trust-building within communities play in containing the outbreak, and how can other countries replicate that success?
Sabeti: Trust is the foundation of every outbreak response. No matter how advanced the tools or how detailed the data, if communities do not believe in the system or the people delivering the message, recommendations will not be adopted, and outbreaks will continue to spread.
In Sierra Leone, the Ministry of Health and the NPHA led with transparency. They showed communities what the data revealed, for example, that cases were rising because of certain patterns of interaction, and explained why specific actions like reducing close contact or seeking early testing could make a difference. By grounding their guidance in evidence and treating people as partners rather than passive recipients, they built confidence and encouraged adoption.
Wilkason: We were there to support testing and data, but it was the country team that led the trust-building. Their work shows how openness and clear communication turns public health advice into community action. For other countries, the lesson is simple: transparency and locally led communication are not side strategies, they are the core of effective outbreak response.
Pandemic Potential of Mpox
Mahoney: You’ve written about the potential for zoonotic diseases to erupt into global crises. What characteristics of mpox today make it a credible pandemic threat compared with its first global spread in 2022?
Sabeti: Mpox today has several characteristics that make it a credible pandemic threat. Since 2024, we have seen the emergence of a more severe clade that spreads more easily and causes higher rates of hospitalization and death, particularly in children and pregnant people. Unlike in 2022, when transmission of clade IIb was largely confined to sexual networks, recent outbreaks show the virus moving through households and day-to-day contact in schools, markets, and workplaces. This diversification of transmission routes means the virus can spread more widely and reach more vulnerable populations.
Wilkason: As we look more closely at the analysis coming out of Sierra Leone and surrounding countries, we are also seeing sustained community transmission across Africa and repeated travel-associated introductions to other continents. Cases have been detected in the United States and Europe, confirming that mpox is no longer geographically contained. At the same time, most of the world’s population has no immunity because smallpox vaccination campaigns ended decades ago. That gap in protection, combined with the ability of mpox to evolve, increases the risk of further spread.
Sabeti: Taken together, these factors – greater severity, expanded transmission pathways, global mobility, and limited population immunity – show why mpox is not just a regional concern but a real pandemic threat if left unchecked.
Mahoney: What signs should global health agencies and governments be watching for to identify an inflection point where localized mpox outbreaks might escalate toward a broader pandemic?
Wilkason: One of the earliest warning signs is sustained community transmission that cannot be linked to known cases. This indicates the virus is spreading beyond identifiable chains of contact. Closely tracking the reproductive number and the doubling time of cases also gives a clear sense of how quickly an outbreak is accelerating.
The populations being affected matter as well. Rising caseloads in children, pregnant women, or healthcare workers are red flags because these groups are especially vulnerable and can amplify spread. Sustained transmission in households or healthcare settings, especially when linked to secondary and tertiary cases, signals a higher risk of wider community outbreaks.
Sabeti: Genomic surveillance provides a critical set of signals. Scientists look for increasing genetic diversity and the establishment of lineages that persist over time and across geographies. In mpox, one important marker is a pattern of mutations known as APOBEC. It serves as a kind of molecular fingerprint that shows the virus is being passed repeatedly from person to person rather than spilling over repeatedly from animals. Detecting these changes confirms when human-to-human transmission is firmly established.
Finally, systemic weaknesses – i.e., latent deficiencies or vulnerabilities within the structure, processes, or regulatory framework of the healthcare system that can enable local problems to cascade into wider emergencies when put under pressure – can serve as an early alarm. Limited access to tests, vaccines, or antivirals not only hampers response but also creates conditions where localized outbreaks can expand unchecked. Taken together, these epidemiological, genomic, and systemic signals can give governments a clear picture of when decisive action is needed to prevent a local crisis from tipping into a global one. These gaps in access reveal the underlying vulnerabilities that make it difficult to sound an early alarm and mount a timely response. Addressing such systemic weaknesses requires more than incremental improvements – it calls for innovative tools that can help bridge these divides. Advances in surveillance systems and real-time data platforms are now helping public health agencies move beyond the constraints of limited resources, opening new avenues for rapid detection and targeted intervention
Surveillance Tools and Technology
Mahoney: Can you describe how Sentinel tools like Lookout have been deployed in Sierra Leone and other African contexts, and in what ways they have changed the timeline or accuracy of outbreak detection?
Wilkason: Sentinel is a comprehensive system for outbreak preparedness that brings together diagnostics, data, and training so that countries can detect and respond to emerging threats more quickly. It is organized around three pillars:
detect, which develops and deploys rapid diagnostics and sequencing;
connect, which integrates laboratory, clinical, and epidemiological data into real-time platforms; and
empower, which builds local capacity through training, mentorship, and infrastructure.
Sabeti: In Sierra Leone, these elements worked together during the mpox outbreak. A cornerstone of the connect pillar is Lookout, a national data platform that brings test results, genomic sequences, and case reports into a single live dashboard. This allowed health officials to see in real time where cases were increasing, how the virus was spreading, and where to focus interventions such as contact tracing or targeted testing. Instead of waiting for delayed reports, they had a clear, near real-time view of the outbreak.
Wilkason: Lookout is supported by analytic tools that add further depth. Delphy accelerates the reconstruction of evolutionary trees, helping scientists track how the virus is changing. Juniper reconstructs transmission networks, showing how cases are connected across households and communities. Together, these tools have reduced the time it takes to move from suspected cases to actionable insights, giving public health agencies a better chance to stay ahead of the virus. By combining these technologies with strong local leadership and training, Sentinel is helping countries shift from reactive response to proactive prevention.
Mahoney: How has genomic sequencing capacity in Africa advanced since the early days of mpox, and what breakthroughs are still needed for surveillance to scale effectively?
Wilkason: Sequencing capacity in Africa has grown tremendously in just a few years. At the start of COVID-19, only a handful of labs could perform genomic sequencing, and results often took weeks to return. Today, countries like Nigeria and Sierra Leone can generate sequences locally within days and upload data to national or international databases to guide response. Training programs have also expanded, and thousands of African scientists and health workers now have experience in laboratory and bioinformatics methods for pathogen surveillance. This has created a strong foundation for continent-wide capacity.
Sabeti: Even with this progress, there are still significant barriers. The cost of sequencing remains high, and most reagents and equipment still need to be shipped from Europe or the United States. This creates delays and makes it difficult to sustain large-scale sequencing during outbreaks. There are also workforce gaps, since advanced sequencing and data analysis require specialized training that is not yet widely distributed.
To truly scale surveillance, we need breakthroughs that make sequencing cheaper, faster, and more locally sustainable. This includes technologies that can handle large batches of samples at lower cost, regionally manufactured reagents and equipment to reduce dependence on imports, and continued investment in training so expertise is spread across countries rather than concentrated in a few centers. With these advances, genomic sequencing can become a routine part of public health, rather than a tool reserved for crises.
Mahoney: Could these systems realistically serve as platforms for other emerging infectious diseases beyond mpox?
Wilkason: Yes. Sentinel was designed to be pathogen-agnostic, meaning it can be applied to any emerging disease. In Nigeria, it already supports surveillance of multiple pathogens including Lassa fever, malaria, HIV, and dengue. In Sierra Leone, it is being adopted as the backbone of the entire outbreak response system. By integrating diagnostics, data platforms, and training, Sentinel provides a flexible framework that strengthens health systems before, during, and after crises.
But Sentinel is more than a set of tools. It represents a shift in how surveillance is built and sustained. Rather than being developed abroad and exported into African settings, it was co-created with African institutions, frontline health workers, and public health leaders. It has been tested and refined during real-world emergencies and is deployed directly by national public health agencies.
Because it was built with and for those on the frontlines, Sentinel is now being integrated into national budgets and embedded within local systems. This ensures expertise remains in-country and that surveillance capacity is sustainable, scalable, and resilient. In this way, Sentinel is not only responding to outbreaks but also helping transform how preparedness and response are conceived across Africa.
Global Funding and Institutional Challenges
Mahoney: With US agencies like the Centers for Disease Control and Prevention (CDC) facing funding and staffing cutbacks, and global organizations like Gavi, the Vaccine Alliance contracting in their efforts (in important part due to suspension of US support), what have you observed as the most acute downstream effects for African health systems battling mpox?
Sabeti: The effects have been immediate and stark. Mpox has re-emerged in West Africa with a fast-spreading new variant, while other threats such as Ebola in the DRC and measles across the region are rising. Yet just as these outbreaks are accelerating, major funders are pulling back. The US canceled a $120 million CDC initiative in Sierra Leone, USAID programs that supported surveillance and spillover prevention have been cut, and Gavi is scaling back. Similar reductions are happening across the global health and preparedness landscape.
For health systems already operating with limited resources, the impact is profound. Surveillance networks are disrupted, procurement of reagents and diagnostics is delayed, and already thin workforces are stretched even further. Ministries of Health that had relied on international support to help fund testing and sequencing capacity are now scrambling to keep these critical functions running. Vaccine access remains far below what is needed, with supply constrained and distribution deeply inequitable.
Wilkason: We have seen philanthropy and industry partners step in admirably to help fill some of these gaps. However, the loss of steady, large-scale support undermines the stability of systems that are essential to protecting both local and global health. The result is slower detection, weaker response, and an increased risk that localized outbreaks will expand unchecked.
Mahoney: How do we reconcile rising outbreak frequency with diminishing international support, and what models of financing or collaboration do you think might fill that gap?
Sabeti: The model for outbreak preparedness is shifting from reliance on international aid to local sustainment. That means developing tools and systems that are affordable, accessible, and practical for countries to operate themselves. It is no longer enough to deliver technology that works only in well-resourced labs or depends on constant external support. For preparedness to be sustainable, diagnostics, data systems, and sequencing platforms must be designed to run at lower cost, and with lower maintenance burden, with supply chains that are reliable and increasingly regional.
Governments are beginning to take up this responsibility. Nigeria is directly funding genomics through its national strategy, and Sierra Leone is embedding Sentinel’s tools into its public health system. Philanthropy still plays a catalytic role by supporting innovation and bridging gaps when budgets fall short, but long-term success requires that governments plan for and invest in these systems as part of their core health infrastructure.
Private companies also have a critical role to play. Industry partners can help lower costs by manufacturing reagents and equipment closer to where they are used, adapting tools to local contexts, and ensuring that innovations reach the health systems that need them most. Partnerships between public health agencies, philanthropy, and the private sector can align incentives so that sustainable, affordable outbreak preparedness is in everyone’s interest.
The shift is already underway. If we continue to design for affordability and local ownership, and bring governments, philanthropy, and private companies together, we can build systems that are not only resilient to funding cycles but durable enough to prevent the next pandemic.
Mahoney: What role can regional organizations and African-led initiatives play in ensuring sustained capacity independent of traditional Western funding sources?
Sabeti: Regional organizations are central to building resilience that lasts. The Africa CDC and its Institute of Pathogen Genomics are already coordinating training, harmonizing data sharing, and supporting continent-wide genomic capacity. Their leadership helps countries align on standards and collaborate across borders, which is critical since pathogens do not respect national boundaries.
African-led initiatives like Sentinel complement this work by creating systems that are designed to be faster, more affordable, and easier for governments to operate. During the current mpox outbreak, NPHA took the lead in using these tools to guide the national response, showing how locally led action can drive both effectiveness and sustainability.
Building sustained capacity requires governments, regional organizations, and the private sector working together. National agencies provide leadership and embed surveillance in public health systems. Regional bodies like Africa CDC set standards and coordinate across borders. And private companies contribute by localizing manufacturing and supply chains, lowering costs and ensuring that essential tools are available where they are needed most, not only during crises but in routine surveillance. When these efforts are aligned, they create systems that are less dependent on Western donor cycles and better tailored to African realities.
Ultimately, regional organizations and African-led initiatives are shifting the center of gravity for pandemic preparedness. They are ensuring that solutions are developed, owned, and sustained on the continent, while still connected to global networks of data and expertise.
Continental Perspective Beyond Sierra Leone
Mahoney: While Sierra Leone has brought numbers down, we’re now seeing a surge in Burundi, Kenya, Uganda, Liberia, and Guinea. How should African nations and external stakeholders interpret this regional spread?
Wilkason: The rise in cases across neighboring countries shows how quickly mpox can move and why preparedness cannot stop at national borders. Travel is playing a key role in spread, which means borders need to be equipped with testing and surveillance capacity. Right now, in Sierra Leone, some Guineans and Liberians are crossing into nearby districts for testing, but not at the point of entry, which delays both detection and onward containment.
Strengthening surveillance at points of entry, coupled with near real-time data sharing and visualization tools, can give countries earlier warning of potential outbreaks. Equally important is the rapid release of data. Publishing genomic sequences and epidemiological findings quickly, rather than holding them for manuscripts, allows neighboring countries to prepare and act on the latest information.
Sabeti: Sierra Leone’s recent experience really demonstrates why early interventions, robust pathogen detection, cohesive data systems, and coordinated response efforts are essential. As other countries face rising cases, adopting similar approaches will be critical to containing outbreaks before they escalate.
Mahoney: Does this pattern suggest the virus is adapting to circulate more broadly, or are these surges more reflective of under-resourced surveillance catching up with existing transmission?
Wilkason: A recent study by Sierra Leone’s NPHA, in which we participated, suggests that the surges are at least in part explained by delayed detection. The new G.1 lineage appears to have circulated silently for several months before it was identified, spreading through households and communities and moving between districts through travel and mobility. This helps explain why cases seemed to rise so sharply once the outbreak was recognized.
At the same time, genomic sequencing analysis indicated an increase in the reproductive number and a shorter doubling time. The data showed the APOBEC signature of sustained human-to-human transmission, but initial analyses did not identify mutations that would clearly increase transmissibility. That said, mpox has a large and complex genome, and there may be mutations whose effects are not yet understood. It is possible that both gaps in surveillance and viral evolution are contributing.
So, while multiple factors may have contributed to the surge, what is clear is that once the outbreak was detected, Sierra Leone mounted a rapid and coordinated response that slowed transmission significantly. That experience underscores the importance of early detection, real-time data, and swift action in bringing outbreaks under control.
Mahoney: Are there risks that complacency from localized declines in caseload could undermine the broader continental or global response?
Sabeti: Yes. Local declines can create a false sense of security, and when attention shifts elsewhere the systems needed to control outbreaks can quickly erode. Surveillance may weaken, testing and sequencing capacity may decline, and vaccine access can become even more limited. These gaps allow the virus to continue circulating quietly, particularly in vulnerable or hard-to-reach populations, and when transmission resurfaces it may be harder to contain.
Sierra Leone has shown how robust action and consistent community engagement can bring numbers down but sustaining that progress requires continued vigilance. Complacency at this stage risks undoing the hard-won gains, both within individual countries and across the region. The lesson is that momentum must be maintained even when case counts appear to fall, because pathogens like mpox can exploit any lapse in preparedness.
Broader Lessons and Looking Forward
Mahoney: Looking five years ahead, what would have to change today for you to feel confident that Africa – and the world – can manage, rather than merely react to, emerging pathogens of high global consequence like mpox?
Sabeti: Five years from now, I would want to see the foundations of a truly global, locally led surveillance system in place. That means every country having trained frontline workers who can detect pathogens in their own communities, analyze the data, and share results quickly and transparently. It also means giving those workers the ability not only to run tests but to design new ones as needed, so they are never waiting on outside solutions to act. The technological capabilities to achieve this are already within reach, even if the exact tools will continue to evolve. The key is to apply, implement, and scale these capabilities everywhere.
At the same time, we cannot focus only on tools. Education and outreach are just as important. This is why the empower pillar of Sentinel is central to our work. Scientific literacy, community engagement, and trust-building are what make systems work in practice. If communities understand how outbreaks spread, if they see their own data reflected in decisions, and if they trust their public health leaders, then response becomes faster, more collaborative, and more effective.
So the changes needed today are both technical and cultural: advancing and scaling capabilities that are already within reach and embedding them in a culture of local leadership, education, and trust. If we can achieve that, I believe we will be in a position to consistently manage pathogens like mpox before they become crises, rather than scrambling to react after the fact.
Mahoney: Thank you both for sharing your invaluable insights and for the extraordinary commitment you have shown in responding to the mpox crisis across West Africa. This interview has highlighted not only the daunting scope and continuing severity of recent outbreaks, especially in Sierra Leone, but also the profound impact that advances in epidemiological surveillance and genomic sequencing have had on containment efforts. Your work is a testament to the critical role of scientific innovation and cross-border collaboration in strengthening epidemic preparedness and protecting vulnerable communities. As the situation continues to evolve, the lessons learned from these interventions offer hope - not just for stemming current outbreaks, but for building a more resilient future in public health, in Africa and throughout the world.
About the Author:
Tom Mahoney, a 2024 Senior Fellow at the Harvard Advanced Leadership Initiative, is focused on global venture philanthropy initiatives to catalyze investment in development of breakthrough vaccines, therapeutics and diagnostics for infectious diseases. A career investment banker, technology entrepreneur and asset management senior executive, Tom is a member of the Advisory Board of EdJen BioTech, LLC, a developer of novel viral vaccines, and Virufy, a respiratory disease diagnostics platform; a Founding Sponsor of the Harvard Alumni Entrepreneurs Accelerator; and a member of the Venture Board of the Harvard HealthLab Accelerators, the Massachusetts Consortium on Pathogen Readiness, and the Council on Foreign Relations.
This Q&A has been edited for length and clarity.