Mpox, a member of the Orthopoxvirus genus like chickenpox and smallpox, exists in two distinct clades. Clade I, historically endemic to central Africa, is the focus of the ongoing 2024 outbreak. This variant is characterized by increased virulence and more diverse transmission pathways, including non-sexual skin-to-skin contact and contact with contaminated surfaces.

The 2024 outbreak differs significantly from the 2022 global outbreak, which was primarily attributed to clade II mpox, endemic to West Africa and typically spread through sexual networks. The reemergence of clade I necessitates a reevaluation of public health strategies due to its divergent epidemiological characteristics and clinical outcomes.

“The 2022 response was focused on rich countries who could afford the vaccines, public health education, and intervention at the time,” said Freedman, who specializes in tropical medicine and global health security. “Even though the clade II outbreak had its origins in Africa due to already stretched resources from the COVID-19 pandemic, no political will was present to intervene in the countries who caused that outbreak and where mpox continued to fester waiting for another mutation and spread.” 

In 2024, the Democratic Republic of the Congo (DRC) has reported over 21,000 cases and over 600 deaths related to clade I mpox, with the outbreak expanding to neighboring countries. While the epicenter remains in Africa, cases have been detected in countries like Sweden and Thailand, emphasizing that, like other infectious diseases, mpox knows no borders. 

The current mpox outbreak has exposed persistent disparities in global health resource allocation, echoing issues seen during the COVID-19 pandemic.

“We need vaccine coverage, diagnostics, and public education everywhere,” Freedman said. “We don’t need highly restrictive travel and trade blockades. Rich countries are still reluctant to share resources especially if there is no large direct threat.”

Low-to-middle income countries (LMICs) face struggle with limited access to essential tools and technologies, hampering their ability to conduct effective disease surveillance, diagnostic testing, and contact tracing. This likely results in underreported case counts, obscuring the true extent of the outbreak and impeding targeted interventions.

Efforts to improve regional response capabilities are underway, such as the African Union’s initiative to establish the African Medicines Agency (AMA), however the project has faced delays due to leadership and governance challenges. The response launched by the WHO emphasizes advancing research and ensuring equitable access to medical countermeasures by working with various international, regional, and local partners to enhance coordination and improve diagnostic capabilities, particularly in affected regions such as the DRC and neighboring countries. 

The recurring nature of epidemics across the African continent underscores the need for improved regional and global cooperation. As Freedman emphasized, “The public health lesson remains the same, no one is safe until we are all safe all over the world,” Freedman said.

Accurate diagnosis of mpox presents significant challenges due to its nonspecific clinical presentation and genetic similarity to other Orthopoxviruses. Moreover, the evolving epidemiology and transmission patterns of mpox further complicate the establishment of consistent case definitions and testing criteria.

To address the challenge of mpox diagnostics accessibility, the Africa CDC Diagnostic Advisory Committee (DAC) has established a  shortlist to provide guidance to Africa CDC, countries, and other partners on appropriate high-quality molecular tests to procure and use as part of the outbreak response.

In this context, highly specific diagnostic methods are crucial for accurate case identification and effective isolation of infected individuals. While several diagnostic assays are available in the market, their distribution and implementation face significant hurdles, particularly in severely affected areas.

According to Freedman, to enhance diagnostic capabilities several strategies warrant consideration: 

1.      Increased Availability of multiplex PCR assays.

“WHO recommends confirmation of MPXV infection based on nucleic acid amplification testing (NAAT), using a real-time or conventional polymerase chain reaction (PCR) on lesion material for detection of unique sequences of viral DNA,” said Freedman.

2.      Utilization of multiple genomic targets.

“Clade I from this outbreak has less known about its sequence and its variability, so much work needs to be done to perfect a PCR to detect the outbreak strain as opposed to other related viruses in the region,” said Freedman.  

3.      Validation of point-of-care diagnostic tools.

“PCR and subsequent sequencing are high tech and laborious, so clearly a rapid test at the point of care is ideal.  We are still far from this, although prototypes are being proposed,” Freedman said.

The development and distribution of reliable, cost-effective, and easy-to-use diagnostic tools could significantly enhance outbreak response efforts. Such advancements would not only improve case detection and management but also contribute to a more comprehensive understanding of the outbreak's true extent and evolution.