Abstract
On August 14, 2024, the World Health Organization (WHO) declared an outbreak of Mpox (formerly Monkeypox) originating in the Democratic Republic of the Congo (DRC) as a Public Health Emergency of International Concern (PHEIC). 1 One day prior, the African Centres for Disease Control and Prevention (Africa CDC) declared this a Public Health Emergency of Continental Security. This is the second time Mpox has been declared as a PHEIC, leading to public confusion, given that the WHO organization declared the end of the first Mpox emergency in May 2023. It was thought that such an ending of the previous Mpox PHEIC was premature. 2 However, the most recent announcement is not connected to the outbreak of 2022–2023, and the responses cannot be identical.
Mpox is a disease caused by the monkeypox virus, a zoonotic virus of the Orthopoxvirus genus. Two major subspecies of the monkeypox virus exist—clade I, endemic to the Central African Republic and the DRC, and clade II, endemic to West African nations including Benin, Cameroon, and Cote d’Ivoire. The 2022–2023 outbreak was caused by a mutated subspecies of the clade II variant, termed clade IIb, first detected on May 6, 2022, in a patient in London, UK, who had traveled from Nigeria; subsequently, it spread among humans and was reported in several countries and regions.3,4 Following an increase in cases in Africa, the clade IIb virus spread internationally, causing a total of 99,388 cases and 208 deaths in 116 countries (https://www.who.int/publications/m/item/multi-country-outbreak-of-mpox–external-situation-report-35–12-august-2024) (Figure 1). While the clade IIb strain continues to circulate at low levels, and indeed has recently surged in South Africa and the Cote d’Ivoire; the new outbreak in central Africa, which triggered the Africa CDC/WHO declarations, is unrelated to this clade.
Two outbreaks of different Mpox variants: Urgent need for vaccinations. The 2022–2023 clade IIb outbreak, originating in Nigeria, resulted in 99,388 cases and 208 deaths across 116 countries, with a recent re-emergence in South Africa and Côte d’Ivoire. Clade I, prevalent in the Central African Republic and the Democratic Republic of the Congo (DRC), experienced a surge due to the clade Ib subvariant with APOBEC3 mutations, affecting both sexual and non-sexual transmission, including increased cases among children under 15 years old. As of September 24, 2024, clade Ib has caused over 18,500 cases (4,089 lab confirmed) and 629 deaths (22 confirned all in the DRC), showing higher mortality (3.5%) compared to the earlier clade II outbreak (0.2%), leading to the Africa CDC (Public Health Emergency of Continental Security) and WHO (Public Health Emergency of International Concern) declarations. Three cases of clade Ib outside of Africa were recently confirmed, one in Sweden, one in Thailand and one in India, all three were returned travelers. Figure made using Biorender.com
In January 2024, cases of clade I Mpox began to rise in the DRC. While clade I Mpox is endemic to the region and is primarily spread through sexual contact, the recent surge has been linked to a variant termed clade Ib, 5 which is more easily transmissible between humans. Clade Ib is spreading rapidly in the DRC and being reported for the first time in nearby countries of Burundi, Kenya, Rwanda, and Uganda (Figure 1). The clade Ib variant has a large proportion of APOBEC3 mutations, a protein thought to drive viral evolution and transmissibility.6,7 Notably, the clade Ib variant is spreading through non-sexual routes and infecting children younger than 15 years of age, who account for 85% of fatalities. Transmission occurs in crowded spaces, such as health facilities, though a specific transmission route has not yet been identified. However, a large number of individuals infected initially were sex workers, suggesting that sexual transmission still plays an essential role in the spread. 8 The clade I subspecies is more dangerous than clade II, with mortality rates as high as 10%. 6 This makes an outbreak of clade Ib Mpox far more concerning than the previous outbreaks, with a much higher potential for loss of life and health impact globally, should it escape containment. As of September 15, 2024, the clade Ib outbreak has caused more than 18,500 cases (4,089 lab confirmed), with 629 deaths (22 confirmed, all in the DRC) since the beginning of 2024, a marked increase in mortality over the original clade II surge globally (https://cdn.who.int/media/docs/default-source/documents/emergencies/20240922_mpox_external-sitrep_-37.pdf?sfvrsn=1c5db9d1_1&download=true). On August 15, 2024, the first case of Mpox clade Ib outside of Africa was reported in Sweden by a returned traveler who had visited DRC (https://amp-dw-com.cdn.ampproject.org/c/s/amp.dw.com/en/sweden-reports-first-mpox-clade-1-case-outside-africa/a-69955272); a second case was reported on August 22, 2024, in Thailand of a 66-year-old European male who returned to Thailand having visited an unspecified country in Africa where clade Ib was active (https://www.reuters.com/business/healthcare-pharmaceuticals/thailand-confirms-its-mpox-case-is-clade-1b-strain-first-country-2024-08-22/); and a third case was reported on September 23, 2024 in India of a returned traveler from the United Arab Emirates (https://cdn.who.int/media/docs/default-source/documents/emergencies/20241006_mpox_external-sitrep_-39.pdf?sfvrsn=a07716dc_1&download=true) (Figure 1). These cases outside Africa raise significant concerns in light of the increased mortality associated with the new clade I variant and the human-to-human transmission especially given that children under 15-years account for over 70% of cases.
The implications of the emergence of this new variant are significant. Firstly, given the spread of the virus in 2022–2023, it should be expected that it will reach far beyond Africa without aggressive containment. The two new variant cases reported from Sweden and Thailand underpin WHO’s decision to declare a PHEIC to trigger a more rapid intervention and cooperation. Governments must rapidly engage with global public health organizations to coordinate responses to mitigate the spread as much as possible, with heightened vigilance in travelers from locations with active disease. Rapid education campaigns to halt the spread should be developed and disseminated so that individuals are aware of essential transmission routes, including sexual health practices, as well as overcrowding in health and public settings. Rapid upscaling of vaccination programs in heavily affected areas, targeting vulnerable populations, is critical to limit mortality, especially with the well-known disparities in the distribution of vaccine supplies to affected African areas 9 https://www.nytimes.com/2024/08/23/health/mpox-vaccines-who-africa.html?unlocked_article_code=1.FE4.g0JG.rMonWAoluJE6&smid=url-share. Africa remains underserved in terms of vaccine supply. The international community would be well advised to recognize the severity of this PHEIC and act swiftly to deliver vaccines for compassionate use to study their highly probable life-saving efficacy in the DRC. Ensuring vaccine availability is crucial to preventing further spread and protecting vulnerable populations, especially children, the elderly and the immue compromised. The third-generation Orthopoxvirus vaccine Jynneos by Bavarian Nordic, used during the 2022–2023 clade IIb surge, has been shown to be safe but is only approved for adults. With the recent clade Ib, where Mpox mainly affects children, vaccinating adults might be less effective but should be studied for this indication in naturalistic studies as experimental infections in humans would not be ethical. Nevertheless, Bavarian Nordic can produce up to 2 million doses by late 2024, with more by 2025; there is an urgent need for the development of new safe vaccines, and academic institutions may choose to help as well https://www.scientificamerican.com/article/a-covid-vaccine-for-all/. There is an urgent need for rapid global cooperation against the rising threat of Mpox, not only to counter the current outbreak but to prevent future outbreaks and potential future pandemics through effective virus control in regions where it is endemic.
