Mpox – A Humanitarian Crisis Returns
Q&A with Marie Roseline Darnycka Belizaire, MD, MPH
Marie Roseline Darnycka Belizaire, MD, MPH, MSc, A-FETP, PhD, Harvard LEAD Fellow, Specialist in family and community medicine, a Senior Emergency Manager at the Headquarters of the World Health Organization (WHO), is a public health leader recognized for her work in infectious disease outbreaks and emergency response. Dr. Belizaire has been instrumental in managing major health crises in Africa, including Ebola and yellow fever outbreaks shaping strategies for outbreak detection, rapid response, and containment.
Dr. Belizaire’s work spans fragile and conflict-affected regions, including Angola, the Democratic Republic of Congo (DRC), Central African Republic (CAR), and Mauritania, where epidemics pose severe public health threats. During the Ebola outbreaks in the DRC, she served as Deputy Incident Manager for WHO, coordinating efforts between international organizations, national governments, and local health workers. Beyond outbreak response, she has strengthened health systems in fragile contexts, ensuring they are not only reactive but also prepared for future crises.
Dr. Belizaire is an advocate for community-based approaches to public health, emphasizing that effective outbreak response must consider local customs, beliefs, and social structures. This culturally competent approach has been critical in addressing challenges such as mistrust among healthcare workers and community resistance, particularly during Ebola outbreaks. As a prominent female leader in global health emergency response, Dr. Belizaire also serves as a mentor and role model, inspiring young professionals to pursue leadership roles in public health.
Tom Mahoney: Thank you, Dr. Belizaire, for joining me to discuss the current resurgence of mpox and the virulent clade Ib strain in the Democratic Republic of Congo (DRC) and neighboring regions. This strain has caused severe illness and a high fatality rate, especially among children under age five. Can you briefly review the history of mpox, including its origins in central and West Africa, past outbreaks, and the underlying causes of the current resurgence?
Dr. Marie Roseline Darnycka Belizaire: Mpox is a viral zoonotic disease first identified in 1958 in a research laboratory studying monkeys, with the first human case documented in the DRC in 1970. The disease is primarily found in Central and West Africa, with occasional outbreaks elsewhere. Mpox is caused by the monkeypox virus (MPXV), which is related to smallpox and can cause serious illness, particularly in vulnerable populations. Historically, three clades of monkeypox virus were recognized: clade Ia, clade IIa and clade IIb. The ongoing outbreaks involve clade Ia in the DRC and clade Ib in the DRC, Burundi, Kenya, and Uganda, with the latter raising concerns due to its severe clinical manifestations, including vertical transmission and complications in people living with HIV, especially those with limited access to antiretroviral therapy and other medical countermeasures.
Common symptoms of mpox are skin rash or mucosal lesions which can last 2-4 weeks with fever, headache, muscle aches, back pain, low energy and swollen lymph nodes. While most individuals fully recover, severe complications can occur, particularly in children, pregnant women, and immunocompromised (e.g. people with HIV not taking antiretroviral treatment or with advanced HIV) individuals. Children represent the most affected age group, with 39% of cases and 62% of deaths reported in children under 5 years as of May 2024.
Mahoney: What factors contributed to the global spread of mpox in 2022, accounting for almost 103,000 cases across 121 countries?
Belizaire: During the 2022 global outbreak of clade IIb, the virus mostly spread through sexual contact especially among men who have sex with men (MSM). Several factors then facilitated the global spread of mpox. First, the easing of travel restrictions following the COVID-19 pandemic played a major role. According to UNWTO, international tourism increased 182% year-on-year January to March 2022. This allowed mpox to spread worldwide, often undetected. Travelers often didn’t recognize early symptoms, causing delayed diagnosis and inadvertent transmission in non-endemic countries. Unlike COVID-19, for which most countries instituted stringent travel-related health checks, mpox was not well-recognized globally. Some theories suggest the virus originated in Nigeria, where it had been circulating for many years after crossing from animals to humans.
Second, large social gatherings created environments for close physical contact, enhancing transmission. In 2022, several large-scale gatherings, like music festivals and Pride events in Europe and North America, assembled large numbers of people from different countries in close contact, mpox’s primary transmission mode.
Third, changes in sexual behavior also played a significant role. Mpox is transmitted through close contact, including during sexual activity. Clinical and epidemiological findings suggest that human-to-human transmission of mpox can be sustained through sexual contact in some networks. Clusters of cases within specific sexual networks drove the initial rise in cases in 2022. Stigmatization fears delayed response in some regions, exacerbating viral spread. While vaccination campaigns using smallpox vaccine, and changes in behavior helped control the outbreak in Western countries, the situation persisted in Africa where vaccines were not available.
Mahoney: Can you explain the unique characteristics of clade Ib mpox virus, including its increased virulence and potential for more severe illness?
Belizaire: Clade Ib is a genetic variant of the mpox virus. Some studies suggest it might have greater capacity to cause severe illness than other clades and higher transmission potential, particularly in non-endemic areas, contributing to more widespread outbreaks. Its increased virulence could stem from mutations that enhance its ability to evade host immune responses, promoting more aggressive infections and disease progression. Besides common mpox symptoms, infections by clade Ib could lead to extensive skin lesions and in some cases, complications such as pneumonia, encephalitis (brain inflammation) and sepsis. Secondary bacterial infections and severe outcomes have also been observed, particularly in high-risk groups like immunocompromised individuals, pregnant women, and children. These characteristics impose a significant burden on healthcare systems, especially in regions with limited access to medical care and diagnostics. Research is still ongoing on the evolution of the virus, but data collection is challenging given mpox primarily affects populations in remote settings.
At WHO we are still searching for more evidence of the virulence. It is currently unclear if this difference in case fatality ratio is due to the viral clade or differences in factors such as population vulnerability, healthcare access, demographic characteristics, and case reporting, among others. The majority of deaths in endemic provinces are among unconfirmed but suspected (clinically compatible) cases due to still-limited access to diagnostic testing in some remote areas. It is difficult to compare clades Ia and Ib because cases of Ib include more children so far. The affected populations are different, and a 100% comparison is difficult.
Mahoney: How is clade Ib mpox transmitted, particularly in the DRC and other African countries, and what are the public health challenges?
Belizaire: Mpox primarily spreads from person to person through skin-to-skin, mouth-to-mouth, or mouth-to-skin contact with infected individuals. Transmission also occurs via close face-to-face proximity through respiratory particles or contact with contaminated objects. As of October 6, 2024, 9,939 laboratory confirmed cases, including 55 deaths, had been reported to WHO. Sixteen countries had reported 7,535 confirmed cases, including 32 deaths. The most cases have been in the DRC, Burundi, and Nigeria.
Human-to-human transmission of mpox occurs in several patterns, one of the most significant being intra-household spread. Close family members, often women caring for infected individuals in households where isolation is impractical, are frequently infected and may transmit the virus to children. Healthcare workers in the DRC are another vulnerable group due to inconsistent access to adequate training and infection prevention equipment. Contact during patient examinations, wound care, or respiratory procedures increases their exposure risk.
Another mode of transmission involves sexual contact within specific networks, which has been observed in some regions. Many regions affected by mpox in the DRC are remote and difficult to access, hindering timely diagnosis of cases and delivery of vaccines or other public health interventions. Endemic mpox coupled with limited vaccine availability and diagnostic capacity continue to strain local healthcare systems.
Mahoney: How concerned are you about Clade Ib mpox’s potential to spread globally, as evidenced by cases in countries like Sweden and Thailand?
Belizaire: The global spread of clade Ib mpox in non-endemic regions outside Africa is troubling due to increased virulence, changing transmission dynamics, and challenges from global interconnectedness. The world already faces multiple health emergencies and humanitarian crises post the COVID-19 pandemic.
The 2022 mpox outbreak demonstrated the virus’s potential to move rapidly across borders and continents. Western countries have been largely protected by availability of vaccines, both from historical smallpox immunization campaigns and newer products specifically targeting mpox. Access to vaccines and robust healthcare systems greatly limit viral transmission in these regions, whereas many African countries face vaccine shortages and limited healthcare infrastructure, allowing the virus to circulate unchecked.
Mahoney: What is the effectiveness of the Jynneos vaccine against Clade Ib mpox and any potential limitations? What is the current funding situation for vaccines against clade Ib?
Belizaire: The Jynneos vaccine, known as MVA-BN, is an attenuated, non-replicating vaccine initially developed for smallpox, largely homologous with the mpox virus. Studies indicate that Jynneos provides cross-protection due to this similarity, reducing symptomatic severity and potentially lowering transmission rates. Two doses are typically required for optimal immunity, with immunocompromised individuals and high-risk groups receiving priority during outbreaks. WHO has prequalified Jynneos to be used in the ongoing outbreak involving clade Ib. While smallpox vaccines are protective against mpox, access is limited in African countries. There is growing need for novel and more efficacious vaccines for clade Ib, given the severity and persistence of the outbreak in regions like the DRC. Despite a significant pledge of $1 billion to respond to the ongoing outbreak, including $500 million from the United States and over $300 million from African countries, more funding is needed – especially for research and development of novel prophylactics.
Mahoney: Beyond vaccines, are there other available treatment options for mpox, such as antiviral medications and supportive care?
Belizaire: Tecovirimat (TPOXX) is an antiviral that has received emergency use authorization in some countries and is being evaluated in multiple clinical trials. Despite recent clinical trial results indicating it did not significantly improve outcomes for mpox patients, it remains a treatment option, particularly for severe cases. The CAR was the first to use tecovirimat in mpox patients for compassionate treatment only. Supportive care including pain management, hydration, treatment of secondary infections, proper wound care and maintaining overall health can reduce symptom severity and aid recovery, as was shown in the DRC clinical trial, despite showing no efficacy of tecovirimat in this population. WHO, with partners, has set several research agendas to deploy various therapeutics through the MEURI (Monitored Emergency Use of Unregistered and Investigational Interventions) protocol. More information will be shared in due course.
Mahoney: How can NGOs, global health organizations like WHO, and ministries of health develop innovative strategies for strengthening surveillance systems, including perhaps novel diagnostics, to detect and track mpox cases?
Belizaire: The WHO Health Emergency Prevention, Preparedness, Response and Resilience (HEPR) framework forms the foundation of the Strategic Framework for Enhancing Prevention and Control of MPox 2024-2027 and guides the ongoing response to the mpox Public Health Emergency of International Concern (PHEIC). Aligned with this framework, the Global Strategic Preparedness and Response Plan (SPRP) outlines the importance of building stronger emergency coordination mechanism between member states and partners for public health response appropriate for local context and risk.
Collaborative surveillance is another critical element, involving monitoring and information – sharing to improve collective understanding of outbreak patterns, identifying specific risks, and refine response strategies. This requires a dual approach to case detection. Passive case detection leverages hospital-based surveillance to identify symptomatic patients seeking while engaging community organizations monitor and report early cases. Active case detection complements this by deploying health professionals and community workers to conduct door-to-door case searches in at-risk communities and raise awareness.
Animal surveillance also plays key a vital role in preventing outbreaks through a One Health approach, which monitors the virus in animal populations to reduce the risk of human transmission. Laboratory surveillance is vital, combining centralized PCR testing and sequencing to identify variants for targeted responses, and molecular diagnostic testing systems such as GeneXpert in mobile and peripheral labs for quick diagnosis and early intervention.
WHO has further strengthened diagnostic capabilities by granting Emergency Use Listing (EUL) to several diagnostic tests. Abbott’s Alinity m MPXV assay, a PCR-based test for detecting the virus in human skin lesions, was approved in October 2024, followed shortly by Roche’s cobas MPXV test. These efforts expand testing capacity in outbreak regions, with more diagnostic tools expected to follow.
Ensuring equitable access to diagnostics, vaccines, and therapeutics is a central priority. In coordination with member states, WHO and its partners have established an Access and Allocation Mechanism (AAM) for mpox medical countermeasures based on lessons learned from COVID-19 including vaccines, treatments and diagnostic tests. The AAM operates within the interim Medical Countermeasures Network (i-MCM-Net), a global initiative that brings together UN agencies, international agencies, health organizations, civil society, private-sector stakeholders. This collaboration builds an effective network to develop, manufacture, allocate and deliver medical countermeasures. WHO and Africa CDC have collaborated to establish the Continental Mpox Incident Management Support Team (IMST) in the Democratic Republic of Congo (DRC). This initiative involves NGOs and other stakeholders in creating a unified Continental Mpox Preparedness and Response Plan (CMPRP). The plan underscores the critical role of leadership and coordination in managing outbreaks, addressing gaps seen in previous health crises. This unified approach ensures more effective and comprehensive efforts to combat mpox across the continent.
Mahoney: What lessons, positive and negative, were learned from the COVID-19 pandemic that are applicable to the mpox crisis? What policy interventions could be upgraded?
Belizaire: I believe three sets of key lessons emanated from the COVID-19 pandemic.
The first lesson pertains to governance. High-level political commitment, effective partner coordination, and synchronized actions were crucial in managing the pandemic at national, subregional, and global levels.
The second set of lessons relates to systems. The pandemic exposed significant gaps in the public health infrastructure. Between March 2020 to October 2023, I was in the Central African Republic (CAR), where I witnessed the challenges of establishing temporary health treatment centers in remote areas with inadequate hygiene and infection control. This condition deepened access inequalities in healthcare services. Throughout Africa, the heavy reliance on global supply chains for medical supplies and vaccines exposed vulnerabilities. For example, the CAR received its first medical materials more than four months after the first case of COVID-19 was confirmed. Additionally, the development of healthcare workers is not proportional to needs. The CAR has six health professionals per 10,000 inhabitants versus the WHO recommended level of 23 per 10,000.
The last lesson concerns financing. The African healthcare sector has long struggled with chronic underfunding, limiting its response capacity. More domestic funding is required to respect the Abuja Declaration of 2001. We should empower the community to lead to safeguard Africa's health security.
The ongoing mpox outbreak highlights similar challenges. However, only the next pandemic will reveal if lessons from COVID-19 have been learned. Both COVID-19 and Ebola illustrated that much infrastructure developed during these emergencies did not endure in most affected nations. This reactive approach where systems are scaled up temporarily and then dismantled or neglected, weakens long-term resilience. Investment in long-term capacity will strengthen healthcare infrastructure, train healthcare workers, improve diagnostics and ensure access to vaccines and treatments. Community engagement is also critical. By integrating community leaders and members into health response, we create sustainable systems continuing to provide care even after external support ends.
Policy intervention that could be upgraded include decentralizing health services, which was critical factor during COVID-19 for timely response. Enhancing community-based surveillance and integrating digital health tools can improve data tracking and health management. Finally, we need policies that promote continuous investment in public health infrastructure, rather than emergency-driven to ensure robust health systems capable to manage future crises.
Mahoney: Thank you, Dr. Belizaire, for your tireless and skilled humanitarian work on the front lines of the current epidemic in one of the world’s poorest regions. Considering your distinguished career across several continents in infectious medicine and public health, do you have any closing observations for our global readers on the importance of international cooperation and collaboration to address the global mpox crisis?
Belizaire: Outbreak containment begins and ends with community members. Anything done for them without their involvement, ultimately risks working against them. A successful and sustainable response to mpox, and all epidemiological emergencies must be tailored to the specific realities of each country and community. The mpox outbreak in the DRC, for example, cannot be managed in the same way as in Uganda, Kenya or the CAR. Local realities, challenges, and needs differ significantly.
Community engagement is key, as local customs, primary healthcare, infrastructure and cultural practices vary across regions. Therefore, responses must be contextualized, involving community leaders and members in decision-making processes to ensure appropriate, effective, and sustainable interventions do not “fall from the sky” in every outbreak.
Primary healthcare should be empowered to respond adequately. By working closely with communities and strengthening health systems overall we can build lasting solutions that address immediate outbreaks and strengthen resilience for future health challenges. The response to mpox is an integrated one involving surveillance, community engagement, infection prevention, vaccination, and treatment of cases.
About the Author:
Tom Mahoney is a Senior Fellow at the Harvard Advanced Leadership Initiative focused on building a novel global venture philanthropy accelerator 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 Strategic Advisory Board of viral vaccine developer EdJen Biotech, LLC, an Associate in the Department of Immunology and Infectious Diseases at the Harvard T.H. Chan School of Public Health, 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.