Unsure about the mpox outbreaks? Here's a guide to what's spreading, where it's occurring, and why.

The decision by the Africa Centers for Disease Control and Prevention (Africa CDC) and the World Health Organization (WHO) to declare back-to-back public health emergencies over the spread of mpox last week have rekindled global interest in the disease.

The situation surrounding mpox has been confusing. Are the new outbreaks in the Democratic Republic of the Congo (DRC) and neighboring areas—sparked by recent alarms—more deadly or transmissible than the global variant that surged two years ago? How do we reconcile reports of the virus spreading sexually in the DRC with the fact that most cases there involve children?

The complexity arises from three concurrent epidemics, each with distinct virus variants, occurring in different regions and populations, and involving varied modes of transmission. ScienceInsider consulted with mpox researchers to clarify these issues.

Where and how is mpox currently spreading?

Recent media coverage has highlighted the mpox outbreak in the Democratic Republic of the Congo (DRC)—where the first known case was identified in 1970—and its spread to neighboring countries. In the DRC, a strain known as clade I has historically transmitted from animal reservoirs, likely small rodents, to humans, occasionally resulting in limited human-to-human transmission. This strain primarily affects the western and central regions of the country, with many cases occurring in children, who are particularly vulnerable to severe disease. According to Anne Rimoin, an epidemiologist at the University of California, Los Angeles, who has extensively studied mpox in the DRC, clade I cases have been increasing for several years.

In 2023, however, mpox also started spreading in the eastern DRC, in a region that used to have very few cases. “There is little forest there and contact with bush meat is limited,” says Placide Mbala, an epidemiologist at the DRC’s National Institute of Biomedical Research (INRB). Most of these cases are in adolescents and adults, and transmission is primarily through sexual contact. A paper describing the first known outbreak, in a mining town named Kamituga in South Kivu province, reported that about a third of 108 cases occurred in women sex workers.

The same virus has also appeared in a refugee camp near Goma, where it seems to spread mainly through general contact rather than sexual transmission, according to Jason Kindrachuk, a virologist at the University of Manitoba and co-leader of the International Mpox Research Consortium. "In environments with poor sanitation, limited healthcare access, and high-density living conditions, the virus has the potential to spread through everyday interactions," he explains.

The virus now circulating in eastern DRC has shown enough genetic differences from previously identified strains to be classified as clade Ib, with other strains in the region designated as clade Ia. According to Andrew Rambaut from the University of Edinburgh, who analyzes genomic data from these outbreaks, clade Ib has likely diverged from clade Ia centuries ago but was only recently identified.

Clade Ib has also spread to Uganda, Kenya, Rwanda, and Burundi, raising concerns about further transmission. Additionally, travelers have brought the virus to Sweden and Thailand. “It’s likely we’ll see clade Ib appear in several countries worldwide,” predicts Salim Abdool Karim, an epidemiologist at the Centre for the AIDS Programme of Research in South Africa. “It seems inevitable.”

That’s two epidemics. Where is the third one?

The third outbreak originated in Nigeria, where clade II of the virus has occasionally spilled over from animal reservoirs to humans. In 2014, one such spillover likely led to sustained human-to-human transmission, some of which was through sexual contact, but this was not recognized until 2017, as uncovered by a Science investigation into the early outbreak years. The current variant, clade IIb, remains active in Nigeria and was responsible for the global mpox epidemic that began in May 2022, predominantly affecting gay men and their sexual networks. To date, around 100,000 cases have been reported in over 100 countries.

Although the number of cases in the global outbreak decreased sharply after a few months—thanks to targeted vaccination, natural immunity from infections, and changes in sexual behavior—the epidemic is not over. For example, in June, Europe reported 100 cases, while the Americas had 175. South Africa has recorded 24 cases this year, including three deaths, all among men who have sex with men, according to Abdool Karim.

Are clade I viruses more dangerous than clade II?

“The data to support this claim simply isn’t robust,” says Laurens Liesenborghs, an infectious disease researcher at the Institute of Tropical Medicine in Antwerp, Belgium. While reports often cite a 10% mortality rate for clade I in the DRC and up to 3.6% for clade II, Liesenborghs notes that the actual mortality rate for clade I over the past decade in the DRC is closer to 3%.

He explains that comparing mortality data from Nigeria and the DRC is like “comparing apples and oranges.” Differences in how cases are reported, variations in healthcare access, and factors such as pre-existing health conditions—like HIV—can all influence mortality rates. Additionally, age plays a significant role; the DRC is experiencing a higher incidence of mpox among children, who are particularly vulnerable to severe outcomes, especially if they are very young or malnourished.

One intriguing data point comes from an unpublished study of the antiviral drug tecovirimat to treat mpox patients in the DRC, carried out by the National Institute of Allergy and Infectious Diseases and INRB. The drug did not work, but a 15 August press release summarizing the outcomes notes that the mortality rate was 1.7% in both the treatment and placebo groups, likely because study participants received better care than people in the DRC usually do.

Only in animal studies has clade I been conclusively shown to be more lethal than clade II, but that does not necessarily translate to humans, Liesenborghs cautions.

What are the reported differences between clades Ia and Ib, both present in the DRC?

That too is unclear. The mortality from Ib—around 0.6% so far in South Kivu province—has been far lower than from Ia, but the fact that Ib spreads primarily through sexual contacts means it affects mostly adults, who are at lower risk of severe disease to begin with.

The transmission route could also play a role, according to Liesenborghs. Consuming the virus through bushmeat or inhaling it from close contact with household members might result in a more severe systemic infection. In contrast, transmission via genital mucosa may primarily cause local skin lesions that are less likely to be fatal. "However, these are just hypotheses," Liesenborghs notes. "We need more research to understand this fully."

There’s also nothing to suggest Ib has evolved to spread more readily through sex, Rambaut says. Although Ia and Ib may have split hundreds of years ago, there is no evidence that Ib spent any of that time spreading in humans. (If it did, scientists would expect to see more specific mutations introduced by a human protein called APOBEC3 intended to cripple the virus.) Indeed, viral fragments from mpox patients sampled in 2011 and 2012 suggest Ib has spilled over in the eastern DRC before, but disappeared again, just like Ia has often done in the west of the country.

Mpox has been known for decades, so why is it becoming a significant issue now?

A major factor in the rise of both zoonotic cases and human-to-human transmission is the decline in population immunity following the eradication of smallpox in 1980. With the cessation of smallpox vaccination— which also provided protection against mpox— immunity levels have dropped. An unpublished study by Liesenborghs and colleagues indicates that the upper age limit for mpox infections in the DRC has increased over time as the vaccinated population ages.

Additionally, the frequency of animal-to-human spillovers may have increased as large forest animals have been nearly driven to extinction. This has led people to hunt and consume smaller rodents that are likely carriers of the mpox virus. "The expansion of farming into previously forested areas is also bringing people into closer contact with infected rodents," says Rimoin. Meanwhile, factors such as population growth, urbanization, and increased mobility are likely enhancing the virus's opportunities for human transmission.

While these factors likely contribute to the accelerated spread of mpox, understanding their exact impact remains challenging. “We’re still trying to understand the full picture,” Kindrachuk says. “The situation is complex and continues to evolve.”

Video Source: Washingtonpost.com

Mpox declared a public health emergency:

Global Vaccination Race Intensifies Amidst Clade 1b Mpox Surge

According to Lancet, As mpox returns to global headlines, with the World Health Organization (WHO) and the Africa Centres for Disease Control and Prevention (Africa CDC) declaring it a public health emergency, the situation has escalated dramatically. The Democratic Republic of the Congo (DRC), the epicenter of the outbreak, is now facing an urgent crisis as the virus spreads beyond Africa, particularly with the emergence of the new clade 1b. Health officials are grappling with limited vaccine supplies, insufficient testing, and the challenge of managing multiple public health threats simultaneously.

On August 14, WHO Director-General Tedros Adhanom Ghebreyesus declared mpox a Public Health Emergency of International Concern (PHEIC), while Africa CDC Director-General Jean Kaseya declared it a Public Health Emergency of Continental Security (PHECS) on August 13. Ghebreyesus cited the significant rise in mpox cases and the rapid spread of clade 1b as key reasons for the declaration. Clade 1b, noted for its higher transmissibility and potential for severe outcomes, has heightened global concern. Kaseya emphasized that this declaration, Africa CDC's first of its kind, highlights the urgent need for immediate and coordinated action. According to an Africa CDC report from August 16, there have been 18,737 mpox cases (3,101 confirmed and 15,636 suspected) across 12 African countries this year, resulting in 541 deaths. This compares to 14,838 cases (1,665 confirmed and 13,173 suspected) and 738 deaths reported across seven countries in 2023.

The DRC alone accounts for 95% (17,794) of the cases and 99% (535) of the deaths reported in 2024, making it the focal point of the response efforts. The declarations of PHEIC and PHECS, coupled with the confirmation of clade 1b cases outside Africa in Sweden and Pakistan, have raised global alert levels. The WHO’s expert advisory committee has called for a coordinated international response to curb the virus’s spread and save lives.

This marks the second time mpox has been declared a PHEIC. Following the 2022 global outbreak, Ghebreyesus made a similar declaration despite the International Health Regulations (IHR) Emergency Committee's divided vote. Ghebreyesus noted the effectiveness of the declaration in raising awareness and mobilizing resources to address the current outbreak.

Unlike the 2022 outbreak, which primarily affected men who have sex with men, the 2024 outbreak is impacting a broader demographic, including men, women, and children. In the DRC, where cases have been reported in all 26 provinces, children under 15 account for 66% of reported cases and more than 82% of deaths.

“Mpox is endemic in our region, making exposure inevitable. Children are especially vulnerable due to contact, malnutrition, and compromised immunity. The lack of smallpox vaccination, which could have provided some protection, also contributes to the high impact,” said Merawi Aragaw Tegegne, Acting Head of the Division of Emergency Preparedness & Response at Africa CDC.

Compounding the crisis is a severe lack of testing and surveillance, which obscures the true scale of the outbreak. Dimie Ogoina, WHO’s IHR Committee Chair, highlighted the significant testing challenges in the DRC, where fewer than 30% of cases might be tested. “Without comprehensive testing, we are essentially operating in the dark,” Ogoina stated. He attributed this shortfall to logistical issues in transporting samples from collection sites to laboratories.

Need for Enhanced Surveillance and Vaccine Distribution Amid Mpox Surge

Maria Van Kerkhove, WHO's Acting Director for Epidemic and Pandemic Preparedness, highlighted the urgent need for improved surveillance and accurate diagnostics in response to the mpox outbreak. She emphasized ongoing efforts to refine PCR tests and other diagnostic tools to differentiate between mpox virus clades while ensuring broad accessibility. “We've witnessed issues with access during the COVID-19 pandemic, particularly in low- and middle-income countries, and we're seeing similar challenges with mpox,” Kerkhove told The Lancet. She also underscored the importance of effective contact tracing to curb further spread.

The WHO's Strategic Advisory Group of Experts on Immunization has identified two vaccines for mpox, and the process for their emergency use listing is underway. Both the Democratic Republic of the Congo (DRC) and Nigeria have approved these vaccines. WHO, Africa CDC, and Gavi, the Vaccine Alliance, are in discussions with manufacturers to meet Africa's mpox vaccine needs, estimated at 10 million doses, although only 200,000 doses are currently available.

Gavi has declared the mpox outbreak a regional emergency, allowing for the reallocation of funds for operational costs and bypassing the formal independent review process for new vaccine introductions. “From a vaccine perspective, the main challenge is supply. We are still weeks away from any vaccine being approved for emergency use by WHO, and even then, it will take time for manufacturers to produce doses in large quantities,” said Gavi Chief Executive Officer Sania Nishtar.

Nishtar noted that due to supply constraints, donations are a crucial short-term solution. “Once a formal request is received from the DRC, Gavi is prepared to send 65,000 doses into the country,” Nishtar added, which will support the initial phase of the country's vaccination plan.

The Africa CDC has secured over 200,000 doses for 2024, with additional doses expected in 2025. The European Commission’s Health Emergency Preparedness and Response Authority (HERA) is procuring and donating 175,420 doses of the MVA-BN mpox vaccine to address the outbreak in Africa, with Bavarian Nordic donating an additional 40,000 doses to HERA. The Africa CDC will manage the distribution based on regional needs.

Recently, the US Government announced the donation of 50,000 doses of the JYNNEOS mpox vaccine to the DRC and allocated nearly US$157 million to the manufacturer for increased production. Nigeria will also receive 10,000 doses of the JYNNEOS vaccine from the USA. Nishtar emphasized that while the current vaccine supply is insufficient to cover everyone at risk, it is critical to prioritize distributing available doses to those in greatest need. “It's essential that other effective countermeasures are also utilized. The lessons from COVID-19 are still relevant, and I urge all partners to work together and act swiftly to alleviate this crisis,” Nishtar told The Lancet.

Jide Idris, Director-General of the Nigeria Centre for Disease Control and Prevention, stressed the importance of not letting the mpox outbreak overshadow other significant health issues such as cholera and Lassa fever. “Given the higher number of cholera and Lassa fever cases compared to mpox, our messaging should focus on a data-driven, integrated approach to public health, ensuring that resources are allocated based on the severity and prevalence of diseases. While mpox is a concern, it’s crucial to manage all health threats concurrently to maintain comprehensive health security. An integrated disease management approach is vital,” Idris told The Lancet. In Nigeria, 39 mpox cases have been confirmed in 2024 with no deaths, while nearly 6,000 suspected cholera cases and 176 deaths have been reported, predominantly affecting children under five years old.

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DOI: https://doi.org/10.1016/S0140-6736(24)01751-3

World Report| Volume 404, ISSUE 10454, e1-e2, August 24, 2024, Download the full Report

https://www.science.org/content/article/confused-about-mpox-outbreaks-here-s-what-s-spreading-where-and-wh