Canada’s first Clade I mpox case a wake-up call for public health

Canada’s first confirmed case of the Clade I mpox variant raises urgent concerns about our ability to prevent and contain its spread.

Although Canada has managed previous outbreaks of pox, a patient who sought medical treatment in Manitoba in November 2024 shortly after returning from travel marks the first introduction of this strain – which is more severe disease and has a higher mortality rate than the Clade II strain that caused the global outbreak in 2022 in this country.

Mpox, previously known as monkeypox, is a viral illness caused by the monkeypox virus (MPXV), a double-stranded DNA virus from the Orthopoxvirus genus, which also includes variola virus (smallpox) and vaccinia virus. Mpox is zoonotic, with animal reservoirs primarily in rodents and non-human primates. The virus is divided into two genetically distinct clades:

• Clade I, previously known as the Congo Basin clade, is historically endemic to Central Africa, particularly in the Democratic Republic of the Congo (DRC) and its neighbouring regions. This clade has been linked to higher transmissibility, increased severity of illness and mortality rates that can reach up to 10 per cent. These rates are particularly concerning for immunocompromised individuals and young children.
• Clade II (formerly West African clade) is responsible for the 2022 global outbreak, with a fatality rate of 0.16 per cent. Human-to-human transmission was spread mostly in sexual networks.

The introduction of Clade I mpox into Canada represents an epidemiological shift. The virus had previously been limited to endemic regions, with no sustained transmission outside Africa – until recently.

Mpox is primarily transmitted through:

1. Close contact with infected individuals – via skin-to-skin contact, bodily fluids, respiratory droplets or contaminated objects (fomites).
2. Animal-to-human spillover – through contact with infected animals, mainly rodents in endemic areas.
3. Respiratory secretions – while less efficient than for COVID-19, sustained prolonged exposure in enclosed settings may facilitate transmission, though the likelihood of human-to-human respiratory transmission appears to be low.

Clade I has been shown to replicate more efficiently in human cells compared to Clade II, potentially leading to higher viral loads and prolonged shedding. Animal models suggest Clade I may also have enhanced immune evasion properties, allowing for increased transmissibility and severe disease.

While both pox clades cause similar symptoms – fever, lymphadenopathy and rash evolving into painful pustular lesions – Clade I is associated with:

• More extensive lesions, often necrotic, leading to secondary infections.
• Higher rates of severe complications, including encephalitis, pneumonitis, and septicemia.
• Increased risk of mortality in young children, pregnant individuals, and the immunocompromised.

Notably, neurological complications such as acute encephalitis and Guillain-Barré syndrome have been reported more frequently in Clade I infections, potentially due to direct viral neurotropism or an excessive immune response.

The introduction of Clade I mpox into Canada requires a more aggressive containment strategy compared to Clade II outbreaks. The following measures are critical:

1. Strengthen Surveillance and Rapid Genetic Sequencing

• Expansion of diagnostic capabilities, including PCR and next-generation sequencing, to distinguish between Clade I and Clade II infections .
• Enhanced airport screening for travelers from endemic regions.

2. Improve Access to Vaccination

• The JYNNEOS (Imvamune) vaccine has shown cross-protection against Clade I mpox. A targeted vaccination campaign for high-risk groups (e.g., immunocompromised patients, frontline healthcare workers) must be immediately implemented.

3. Strengthen Hospital Readiness

• Isolation protocols for suspected Clade I cases should be reinforced, including isolation rooms in hospitals.
• Expand access to antiviral treatment (e.g., tecovirimat (TPOXX)) that has been effective against both mpox clades.

4. Global Collaboration to Prevent Further Spread

• International cooperation is critical to contain Clade I mpox at its source. Canada must collaborate with WHO and African health authorities to limit cross-border transmission.
• Increased funding for mpox research, particularly regarding Clade I pathogenicity, vaccine effectiveness and long-term immunity, is urgently needed.

Canada has an opportunity to prevent sustained Clade I mpox transmission, but only if decisive action is taken now. The failure to contain this higher-risk strain could lead to regional outbreaks, increased hospitalization rates and a strain on the health-care system.

The arrival of Clade I mpox is a warning that we cannot afford to ignore.