Rapid risk assessment: Clades 1a and 1b mpox virus (MPXV) multi-country outbreaks – public health implications for Canada

Assessment completed: September 4, 2024 (with data as of August 30, 2024)

On this page

• Reason for assessment
• Risk question
• Risk statement
  • Future risk in Canada
• Proposed actions for public health authorities
• Technical annex
  • Event background
  • Definitions
  • Key assumptions
  • Detailed risk assessment results
• Appendix A: Methods
• Appendix B: Acknowledgements
• Footnotes
• References

Reason for assessment

Since the April 2024 clade I mpox virus (MPXV) rapid risk assessment (RRA), an unprecedented geographic expansion and increase in clade Ia and Ib mpox cases has occurred in Africa, with countries neighbouring the Democratic Republic of the Congo (DRC) reporting cases for the first time, including Burundi, Rwanda, Uganda, and Kenya. A Public Health Emergency of International Concern (PHEIC) was declared by the WHO on August 14, 2024, followed by two cases of the newer subclade, clade Ib MPXV, confirmed in Sweden and Thailand. In response to the evolving situation, the Public Health Agency conducted a new RRA of clade Ia and Ib MPXV.

Risk question

What is the likelihood of clade Ia or Ib MPXV importation into Canada and impact of onward spread in the next three months (September to November 2024)?

Risk statement

From September to November 2024, the likelihood of clade Ia MPXV importation into Canada is low (high uncertainty). Historically, clade Ia is associated with transmission from wildlife followed by limited chains of human-to-human transmission that die out. Although clade Ia is now showing more evidence of human-to-human transmission, it is still limited to endemic rural, forested areas, thus limiting the potential for a traveller to export clade Ia to Canada. For the same time period, the likelihood of clade Ib MPXV importation into Canada is high (moderate uncertainty). Clade Ib is characterized by sustained human-to-human transmission, particularly in urban areas, increasing the likelihood of export, particularly as more regions globally report cases of clade Ib MPXV.

If importation of clade Ia or Ib MPXV into Canada were to occur, transmission is primarily expected in the travellers’ households and non-household close contacts, including sexual contacts, with the potential for amplification within high-contact sexual networks, including among gay, bisexual and other men who have sex with men (gbMSM), as well as sex workers and their close contacts. There is strong evidence of sexual and non-sexual human-to-human transmission for clade Ib. This could result in longer chains of transmission in Canada, similar to the spread of clade IIb during the global mpox outbreak in 2022.

For individuals without known risk factors, the impact of a clade Ia MPXV infection is estimated to be moderate (moderate uncertainty), and the impact of a clade Ib MPXV infection is estimated as minor (high uncertainty). The impact is estimated to be higher for clade Ia compared to Ib based on historic and currently reported case fatality ratios (CFR). However, the reported morbidity and mortality of clade Ia may be higher due to the populations affected (i.e. predominantly children) and the local/regional context. For individuals with risk factors for adverse outcomes from mpox, including children, pregnant individuals, and the immunocompromised,^{Footnote a} the impact of either a clade Ia or Ib infection is estimated to be major (moderate uncertainty for clade Ia; high uncertainty for clade Ib).

The impact on affected populations (household and non-household close contacts, and individuals in high-contact sexual networks, such as among gbMSM and sex workers and their close contacts) for both clade Ia and Ib MPXV infection is estimated to be moderate, (moderate uncertainty). Evidence suggests a greater severity of health outcomes for clade Ia compared to clade Ib. However, there is growing evidence that clade Ib could result in human-to-human transmission via sexual and non-sexual close contact and thus spread in household and non-household contacts as well as individuals in high-contact sexual networks, with potentially less severe adverse health outcomes compared to what is reported for clade Ia.

The impact on the general population of Canada for infections caused by either clade Ia or Ib MPXV is estimated to be minor (low uncertainty). These estimates are based on substantial evidence from the ongoing clade IIb MPXV global outbreak, where there has been minimal impact on the general population. Additionally, in the DRC, there has been little reported spillover of either clade Ia or Ib outbreaks to the general population.

Table 1. Likelihood and impact estimates of importation and transmission of (clade Ia and Ib) mpox virus in Canada, September to November, 2024

Question	Clade Ia MPXVTable 1 Footnote a: Estimate [Uncertainty]	Clade Ib MPXV: Estimate [Uncertainty]
What is the likelihood of at least one traveller infected with clade Ia or Ib MPXV entering Canada in the next three months?	Low [High]	High [Moderate]
What is the most likely spread scenario should an infectious traveller enter Canada with clade Ia or Ib MPXV?	Transmission through households and non-household close contacts, including sexual contacts, with the potential for domestic amplification through high-contact sexual networks, including among gbMSMTable 1 Footnote b and sex workers and their close contacts.
What would be the impact on an individual infected with clade Ia or Ib MPXV (including impact on mental health, disease morbidity/mortality, and/or welfare)?	Children and infants, pregnant individuals, and immunocompromised individuals: Major [Moderate] Individual without known risk factors: Moderate [Moderate]	Children and infants, pregnant individuals, and immunocompromised individuals: Major [High] Individual without known risk factors: Minor [High]
What would be the population health impact on the affected and the general populations?	Households and non-household close contacts, including sexual contacts: Moderate [Moderate] Individuals in high-contact sexual networks, including gbMSM and sex workers and their close contacts: Moderate [Moderate] General population: Minor [Low]
Notes: See Technical Annex for definitions Table 1 Footnote a MPXV: mpox virus Table 1 Return to footnote a referrer Table 1 Footnote b gbMSM: gay, bisexual, and other men who have sex with men Table 1 Return to footnote b referrer

Future risk in Canada

The probability of importation of a clade Ia or Ib MPXV case into Canada is expected to increase if the current outbreaks continue to spread, especially to countries with higher travel volumes to and from Canada (e.g., United States, Mexico, United Kingdom), or if clade Ia or Ib MPXV enters high-contact sexual networks during an amplification event, similar to the start of the ongoing clade IIb global mpox outbreak. There are uncertainties and knowledge gaps (see Table 3) associated with the evolving clade Ia and Ib MPXV outbreaks, making it challenging to estimate the risk to the population of Canada in the next three months and beyond. It is unknown if clade Ia or Ib MPXV will behave like what we saw in Canada at the time of the global 2022 clade IIb MPXV outbreak.

The most plausible scenario in Canada beyond November 2024 is expected to be similar to the transmission scenario described in the technical annex and summarized in the risk statement above. This is expected to be transmission primarily in households and non-household close contacts, including sexual contacts, with the potential of domestic amplification through high-contact sexual networks, including among gbMSM and sex workers and their close contacts.

The worst-case scenario in Canada beyond November 2024 would be long-term transmission among the general population through sexual and direct contact. Drivers of such a scenario include lack of awareness about the disease among the general population, including disinformation and misinformation, mistrust/distrust of public health authorities, lack of risk communication, low mpox immunity in the general Canadian population, vaccine hesitancy, barriers to immunization, missed cases due to a low index of clinical suspicion, delayed access to diagnosis and care due to stigma and paucisymptomatic cases.^{Footnote 1Footnote 2} However, there remains uncertainty about the evidence for these potential drivers. The potential for further evolution of clade Ia or Ib MPXV could also pose challenges for mpox prevention and control in Canada.

Transmission in the general population could result in substantial health and socioeconomic burden. Even in the absence of widespread community transmission, small outbreaks could add strain on the medical and public health resources for diagnostics, treatment, outbreak management, and staff shortages through absenteeism if healthcare staff are affected.^{Footnote 2} In addition, there may be implications for health equity, and some populations could experience a disproportionate burden of the associated morbidity and mortality and exacerbate health inequities in vulnerable populations.

During the 2022 clade IIb outbreak in Canada, behavioural changes helped curb transmission among the gbMSM community. Rapid deployment of public awareness activities to encourage vaccination, as well as outreach and tailored communication in partnership with community-based organizations helped in preventing broader transmission. Interventions such as case and contact management, education and community outreach, implementation of biomedical prevention (condoms, vaccination) and behavioural change, have been effective in managing other infectious diseases such as syphilis, hepatitis B, human papilloma virus, and HIV.

From a natural environment and wildlife perspective, human-to-animal or animal-to-human transmission of MPXV in Canada could become a concern in the event of ongoing human-to-human transmission in the general population. Based on the 2022 Monkeypox in Canada: Human to Animal Exposure Pathway Analysis conducted by CFIA, infectious waste from infected humans was considered a potential route of exposure to MPXV for animals in Canada, particularly wildlife.^{Footnote 3} Although current research is limited on the transmissibility of MPXV clades Ia and Ib in Canadian wildlife, one study conducted in 2023 by the National Microbiology Laboratory indicated that although deer mice are permissive to experimental infection with clade I and II MPXV, the infection was short-lived, indicating limited capability for active transmission.^{Footnote 4} While limited previous evidence has indicated the potential for MPXV to spill back into animals from humans,^{Footnote 5Footnote 6} the ability for ongoing spread amongst animal species and enzootic establishment is less described.^{Footnote 7Footnote 8}

Proposed actions for public health authorities

The proposed actions from the previous rapid risk assessment continue to be relevant. Given the risk of importation of clade Ia or Ib MPXV into Canada, early detection, diagnosis, infection prevention and control measures, as well as increasing awareness of MPXV among the Canadian population, are key for the effective control of domestic clade Ia or Ib MPXV transmission. The access to and use of vaccines and antivirals, including associated guidance and protocols, is also important to Canada’s ability to control a likely spread scenario.

Recommendations provided below are based on findings of this risk assessment and informed by the WHO’s strategic preparedness and response plan (SPRP). These are for consideration by jurisdictions according to their local epidemiology, policies, resources, and priorities. Due to the current level of uncertainty associated with this event, it is important that the public health response be proportionate to the risk.

The Public Health Agency of Canada (PHAC) will continue to engage and collaborate with federal, provincial, territorial and non-governmental organizations to assess and manage public health risks associated with importation of clade Ia and Ib MPXV to Canada.

Public health interventions: Prevention and response

• Refer to Mpox (monkeypox): Public health management of human cases and associated human contacts in Canada for updated recommendations to help prevent human-to-human transmission of mpox in Canada.
• Refer to pre- and post-exposure prophylaxis vaccination guidance recommended by the National Advisory Committee on Immunization (NACI Rapid Response: Interim guidance on the use of Imvamune in the context of a routine immunization program).
• Access PHAC’s National Emergency Strategic Stockpile (NESS) for both vaccine (Imvamune^®) and therapeutics (TPOXX^®), when needed.

Risk communication

• Consider engaging early in infodemic management, including prebunking and debunking mis- and disinformation.
• Consider developing messages for the general population to raise awareness about mpox and preventive measures, as well as messages tailored for populations at increased risk of exposure and/or adverse outcomes. It is important to acknowledge uncertainty around the rapidly evolving evidence base.
• Consider developing messages tailored for health professionals to raise awareness about mpox with the goal of increasing early detection, diagnosis/testing and management of clade Ia and Ib MPXV infections and to discuss mpox with their patients intending to travel to endemic countries and the importance of mpox vaccination for those eligible.
• Consider developing messages for travellers and travel health stakeholders, encouraging travellers to consult a health care provider or visit a travel health clinic preferably at least 6 weeks before travel to get personalized health advice and recommendations. (Refer to PHAC’s travel health notice Mpox: Advice for travellers.)

Collaboration and coordination

• Consider engagement and communication with relevant community partners, populations at increased risk, federal, provincial/territorial, local and indigenous partners to support the public health response.
• Consider participating in research opportunities to address the key scientific uncertainties and knowledge gaps identified during this assessment and through other processes.

Surveillance and reporting

• Continue to remain vigilant and communicate new epidemiological signals with public health partners as soon as possible.
• Support readiness of existing surveillance tools and systems, including case definitions and reporting forms, to capture clade Ia and lb, in addition to clade II. Ensure detailed case data is collected in a timely and consistent manner.
• Support readiness of provincial and private labs to diagnose mpox.
• Continue to monitor vaccination coverage among affected populations to identify areas with higher susceptibility to outbreaks.
• Consider investigating the socioeconomic, cognitive, and motivational factors associated with uptake of the mpox vaccine among at-risk populations, including gbMSM for which data is currently limited.

Technical annex

Event background

Since July 2024, Africa has reported an unprecedented geographic expansion and increase in confirmed and suspected mpox cases. Countries neighbouring the DRC reported cases for the first time, including Burundi, Rwanda, Uganda, and Kenya. An Emergency Committee regarding the upsurge of mpox was convened by the WHO Director General on August 14, 2024, and subsequently communicated that the current mpox situation in Africa constitutes a Public Health Emergency of International Concern (PHEIC) under the provisions of the International Health Regulations (2005). As of August 22, 2024, two cases of the new subclade, clade Ib MPXV, were confirmed outside the Africa region, in Sweden and Thailand. In an updated rapid risk assessment, WHO assessed the risk of the multi-country mpox outbreaks (including clade Ia, Ib, and IIb) to countries outside the Africa region as moderate (WHO, unpublished report, 2024).

MPXV clades

To date, there are two known clades of MPXV: clade I (previously known as Congo Basin or central African clade) and clade II (the former west African clade).^{Footnote 9Footnote 10Footnote 11Footnote 12} Clade II is further divided into two subclades: IIa and IIb, with clade IIb MPXV responsible for the ongoing global clade IIb mpox outbreak. Clade I was recently divided into two subclades: Ia (previously clade I) and Ib, with clade Ib first detected in DRC’s eastern province of South Kivu around September 2023, and first reported in a pre-print study in April 2024.^{Footnote 13Footnote 14Footnote 15} Clade Ib is responsible for driving the geographic spread of mpox to DRC’s neighbouring countries and its emergence was an important factor which led to WHO’s August 14, 2024, PHEIC declaration for mpox.^{Footnote 16}

Prior to the divergence of clade I into Ia and Ib, the literature reported clade I (clade Ia) as more transmissible and causing more severe disease than clade II, as described in the previous April 2024 rapid risk assessment. Since clade Ib is a relatively newly emerged variant, less is known about its transmissibility, severity, and viral pathogenesis. The current evidence suggests that sustained human-to-human transmission, including via sexual contact, is driving the local transmission of clade Ib in parts of the DRC and Burundi. In DRC’s eastern province of South Kivu, cases have been primarily reported among youth and adults 15 years and older (86%). A study of the clade Ib-driven outbreak in South Kivu found that 29% of clade Ib cases reported involvement in sex work.^{Footnote 13} As the number of mpox cases in Burundi increases, the most affected populations have changed from mostly adults, to effecting both young adults and children, although the reason for this is unknown. As of August 19, 2024, 51.9% of confirmed cases in Burundi are over the age of 15.^{Footnote 17}

Evidence for severity of clade Ib MPXV is limited. Historically, clade I was considered to cause more severe disease and have poorer outcomes compared to clade IIb.^{Footnote 18} It is uncertain whether clade Ib has retained the severity historically associated with ‘clade I.’ A recent antiviral treatment study of clade Ia and Ib cases in DRC found that with supportive care, the CFR was 1.7%.^{Footnote 19} This is lower than recently published CFRs for mpox in the DRC, and at the lower range of the 0-10% CFR historically reported for clade I.^{Footnote 19Footnote 20Footnote 21} The outbreak in the province of Équateur, northwest DRC, appears to be driven by clade Ia and has reported a CFR of 5.7% to 5.9%.^{Footnote 19Footnote 20Footnote 21}The clade Ib-driven outbreaks in eastern provinces of DRC have reported a lower CFR of 0.7%. ^{Footnote 22Footnote 23} It is unclear at this time whether the higher proportion of children, who are high risk for severe disease, affected in the Équateur clade Ia outbreak accounts for the higher CFR, relative to the lower CFR in South Kivu where most cases are adults.^{Footnote 19Footnote 20Footnote 21Footnote 22} It is assumed that under diagnosis and under reporting is substantial in the affected countries in Africa. As a result, cases are likely an underestimation, and the case fatality is likely an overestimation.

Multi-country outbreaks of clade Ia and Ib MPXV

Since the DRC first reported a case of mpox roughly a decade ago, the number of cases reported each year has increased steadily, with ~3 times as many cases reported in 2023 compared to 2022.^{Footnote 24} Both clade Ia and Ib MPXV have been reported in the DRC. Between August 23 and 31, 2024, the DRC reported 2,933 new cases (1,838 confirmed; 1,095 suspected) and 35 deaths (CFR: 2.2%).^{Footnote 25}

On July 25, 2024, Burundi declared an outbreak of mpox following the confirmation of three cases.^{Footnote 26} This was the first time Burundi had reported mpox cases, and the outbreak appears to be driven by clade Ib. In August 2024, Burundi experienced a rapid increase in cases. As of August 31, 2024, 820 cases (231 confirmed, 589 suspected) and no deaths have been reported from 29 of Burundi’s 49 health districts.^{Footnote 25}

In the August 23, 2024, Africa CDC Epidemic Intelligence Report, Kenya reported one new confirmed case, bringing the cumulative cases to two and no deaths.^{Footnote 27} The clade of the recent case in Kenya is unknown at this time, but the previous case was identified as clade Ib.^{Footnote 28} As of August 23, 2024, four confirmed clade Ib mpox cases and zero deaths have cumulatively been reported by Rwanda, which declared an outbreak on July 27, 2024.^{Footnote 9Footnote 27} As of August 31, 2024, four confirmed cases of MPXV and no deaths have been reported in Uganda since July 24, at least two of the cases were clade Ib and had recent travel to the DRC.^{Footnote 25Footnote 29}

As of August 31, 2024, the Central Africa Republic (CAR) has reported 48 confirmed cases and one death, including spread within the capital of Bangui,^{Footnote 25Footnote 27} while the Republic of the Congo (ROC) has reported 21 confirmed and 154 suspected cases and no deaths.^{Footnote 25} These cases have been identified as clade Ia.^{Footnote 30}

On August 23, 2024, the Minister of Health and Social Affairs of Gabon announced the first confirmed case of MPXV in the nation.^{Footnote 31} The MPXV clade causing the case is not yet confirmed.^{Footnote 30}

Clade IIb MPXV outbreak and mpox susceptibility in Canada

Although no clade Ia or Ib MPXV cases have been detected in Canada, there has been an ongoing global clade IIb mpox outbreak since 2022, which includes Canada. In Canada, a total of 164 cases of clade IIb MPXV were reported to PHAC between January 1 and August 12, 2024, from Ontario (144), British Columbia (10), Quebec (8) and Alberta (2). This represents an increase in mpox cases in Canada compared to 2023. Most cases reported this year were from Ontario (88%), where there has been a sustained increase in cases since the start of 2024, mostly from the Greater Toronto Area. Cases of mpox in Canada have been reported primarily among gbMSM (92.3%); sexual contact is the predominantly reported mode of transmission. The majority of the Canadian population is fully susceptible to mpox; please see April 2024 rapid risk assessment for descriptions of mpox susceptibility in Canada.

Definitions

Amplification event:

Any event in which someone with mpox comes into contact and subsequently exposes and infects more people than average (i.e., mass exposure). Such events can include but are not limited to: cruise ships, parties, sex on premises venues.

Close contact:

The WHO definition for close contact in the context of mpox transmission includes skin-to-skin (such as touching or sex) and mouth-to-mouth or mouth-to-skin contact (such as kissing), and it can also include being face-to-face with someone who has mpox (such as talking or breathing close to one another, which can generate infectious respiratory particles).^{Footnote 32}

High-contact sexual network:

Refers to clustered sexual networks with a high number of sexual partners per individual (6-month average: ≥25 sexual partners). Based on a recent Canadian study,^{Footnote 33} the following sexual practices were associated with a higher number of sexual partners: attending group sex events, using dating applications, attending bathhouses and/or sex clubs, and engaging in transactional sex in the past 6 months. 

Immunocompromised:

Individuals with impaired immune response functions due to a variety of factors, including immunodeficiency disorders, treatment with immunosuppressives, cancer, unsuppressed HIV, and others.

Mpox exposure:

Refers to direct contact with an infected person’s skin lesions, blood, body fluids or mucosal surfaces (such as eyes, mouth, throat, genitalia, perianal area), or sharing clothing, bedding or common items that have been contaminated with the infected person's fluids or sores. Examples of behaviours with potential for exposure can include sexual contact, contact from providing care, or living in the same household as a case.

Key assumptions

This risk assessment is based on the evidence available at the time of writing. The risk might change as more information emerges or if the outbreaks continue to spread geographically.

• On August 14, 2024, the WHO declared the mpox outbreaks in Africa a PHEIC. The magnitude and potential impact of a coordinated mobilization of resources by the international community for prevention and response is unknown at this time and was not considered in the risk estimates.
• It is assumed that people living in Canada who received a smallpox routine immunization are susceptible to mpox based on insufficient evidence for residual, cross-protective immunity.
• This assessment assumes some similarities between clade Ib and clades Ia and IIb MPXV, though these assumptions are based on expert opinion and publications from the WHO, CDC and ECDC, and are captured in the uncertainty estimates.
• A standard level of treatment would be provided to any cases in Canada, except the first cases when the index of suspicion might be low particularly if the case has no history of travel to an outbreak area.
• Case and contact management guidance will be expected to be implemented as usual (i.e., as it was with the 2022-2023 clade IIb MPXV outbreak).

Detailed risk assessment results

Risk pathway

Figure 1 : Text Description

Importation to Canada

• Pathway connector from multi-country outbreaks of clade Ia or Ib MPXV to infectious traveller enters Canada
  • Risk sub-question: What is the likelihood of at least one traveller infected with clade Ia or Ib MPXV entering Canada in the next three months?

Spread

• Pathway connector from infectious traveller enters Canada leads to most likely spread scenario
  • Risk sub-question: What is the most likely spread scenario should an infectious traveller enter Canada with clade Ia or Ib MPXV?

Health impacts

• Pathway connector from most likely spread scenario to individual health impacts
  • Risk sub-question: What is the impact on an individual’s health with clade Ia or Ib MPXV?
• Pathway connector from most likely spread scenario to population health impacts
  • Risk sub-question: What are the population health level impacts in affected and general populations?

Likelihood and impact estimates

Sub-Question 1: What is the likelihood of at least one traveller with clade Ia or Ib MPXV entering Canada in the next three months (September to November 2024)?

The DRC remains the centre of the clade I outbreak and is currently reporting both clade Ia and Ib cases.^{Footnote 30} Given the central role of the DRC in the current situation and its implication as a source for other travel-related mpox clade I importations (e.g., Kenya, Uganda), mathematical modelling was completed by PHAC to estimate likelihood of importation to Canada specifically from the DRC (more detail in Appendix A: Methods). The model indicated a 19.4% chance of an infected traveller with clade Ia or clade Ib entering Canada via air travel from the DRC between September and November 2024. The model does not differentiate between clades, due to the limited proportion of cases in Africa that are confirmed as either clade Ia or Ib. Importation likelihood estimates and rationale specific to each of clade Ia and Ib are provided below.

Clade Ia – Low (high uncertainty)

The likelihood of a traveller entering Canada while infected with clade Ia MPXV is low. Clade Ia MPXV cases have been confirmed in the DRC, ROC, CAR, and Cameroon (Cameroon has reported both clade II and clade Ia MPXV).^{Footnote 21Footnote 30}Clade Ia MPXV continues to circulate in those provinces of the DRC where mpox was endemic prior to 2023 (e.g., Équateur).^{Footnote 34} Notably, a clade Ia MPXV case has not been reported outside the African continent.

Transmission of mpox within countries with only clade Ia MPXV (ROC and CAR) likely follows the epidemiology of mpox elucidated at the end of the 20th century, with zoonotic transmission from wildlife,^{Footnote 21} followed by limited chains of human-to-human transmission that die out due to inefficient human-to-human transmission.^{Footnote 35Footnote 36}While it is thought that rope squirrels are important reservoirs of clade Ia MPXV, there is little exploration and knowledge of animal reservoirs to assess risk to visitors to endemic countries.^{Footnote 37}

Where clade Ia MPXV is endemic in the DRC, the majority of mpox cases are amongst children under the age of 15 years and those in rural and forested areas. As children and those residing in rural/forested areas are anticipated to be less likely to travel internationally, they are less likely to contribute to an importation event into Canada.

Cumulatively between September and November 2023, an estimated 8,135 individuals travelled to Canada from Cameroon, the CAR, and the ROC (Table 2), with Cameroon ranking in the 64^th percentile of travel volume among nations and territories travelling to Canada in this period, ROC in the 28^th, and CAR in the 16^th percentile (IATA, unpublished data, 2023). Additionally, over this time, 50.8%, 47.0% and 19.5% of air passengers arriving in Canada from the CAR, ROC, and Cameroon, respectively, were Canadian passport holders who may spend less time in the affected countries compared to residents of those countries (CBSA, unpublished data, 2023). Should travel trends in 2024 be similar to those in 2023, importation of a clade Ia MPXV case may be unlikely given the comparatively moderate to low travel volume and moderate proportion of Canadians returning.

A high level of uncertainty exists regarding the likelihood of importation of clade Ia MPXV. While clade Ia has lead to an unprecedented number of mpox cases in the DRC in 2024 and spread to new, non-endemic areas of Africa much uncertainty remains regarding the transmission dynamics of clade Ia MPXV and how this may contribute to likelihood of importation, particularly the relative contributions of zoonotic, close contact, and sexual transmission in the ongoing outbreaks. Should evidence emerge of human-to-human transmission being the main driver of the outbreak, the likelihood of a traveller becoming infected and returning to Canada may increase. Infection control initiatives for mpox are planned for the DRC and surrounding region beginning September 2024, including enhanced surveillance and targeted vaccinations. As clade Ia MPXV has not yet been detected outside of Africa, the effect of these efforts may also prevent the inter-continental exportation of clade Ia MPXV from occurring.

Clade Ib – High (moderate uncertainty)

The likelihood of an individual infected with clade Ib MPXV entering Canada within the next three months is high. Case numbers and geographic spread of clade Ib MPXV within Africa has been increasing throughout 2024 and clade Ib cases have been detected in the DRC, Burundi, Uganda, Rwanda, and Kenya.^{Footnote 30} Human-to-human transmission has been strongly implicated in the clade Ib MPXV outbreaks in the North Kivu and South Kivu provinces, with patterns suggesting sexual contact. Samples of clade Ib MPXV recovered from South Kivu were reported to have hallmark genetic mutations associated with human-to-human transmission (please see Clade Ib – Most likely spread scenario for more detail).^{Footnote 12Footnote 30} Additionally, clade Ib cases are being reported within urban centres (e.g., Kampala, Uganda) suggesting ongoing human-to-human transmission.^{Footnote 8Footnote 23} Thus far, clade Ib MPXV has primarily impacted youth and adults in South Kivu, DRC, with 86% of confirmed cases being 15 years of age or older. In Burundi, the most affected populations have changed from mostly adults, to effecting both young adults and children, and as of August 19, 2024, 51.9% of confirmed cases in Burundi are over the age of 15.^{Footnote 17} Adults living in urban areas may represent a more internationally mobile population, and increase the likelihood of clade Ib MPXV being exported to new countries.

Cases of clade Ib have been reported outside the African continent. On August 15, 2024, the Public Health Agency of Sweden confirmed a case of clade Ib MPXV in an individual returning from an African country with circulating clade Ib MPXV.^{Footnote 11} One week later, the second case of clade Ib outside of Africa was reported in Thailand, also from an individual returning from travel in an affected African country.^{Footnote 10} Inter-continental spread may continue, increasing the likelihood of a case entering Canada and expanding the possible sources this travel may originate from.

Among the countries who have reported a confirmed case of clade Ib MPXV, those with the strongest air travel connections to Canada are Thailand, Kenya, and Sweden, with approximately 15,256, 14,835, and 11,437 passengers between September and November 2023 (Table 2), which ranges from the 70^th to 77^th percentile of travel volumes within this period (IATA, unpublished data, 2023). Notably, the cases reported in Thailand and Sweden and at least one of the two current cases reported in Kenya are travel-related, not locally-acquired.^{Footnote 9Footnote 10Footnote 11} Should evidence of local transmission of clade Ib MPXV emerge in each of these countries following importations, the likelihood of a clade Ib MPXV case entering Canada increases due to the relatively high travel volume to Canada.

Prior to an outbreak of clade IIb in Nigeria in 2017, which saw major human-to-human transmission in urban centres, cases of clade IIb in West African were almost exclusively due to zoonotic transmission with very rare secondary transmission.^{Footnote 38} The 2022 clade IIb global outbreak was almost exclusively driven through sexual transmission, and detection of APOBEC-type mutations in sequences from Nigeria support the idea of sustained human-to-human transmission before the epidemic became global.^{Footnote 13} The current epidemiology of clade Ib MPXV is currently exhibiting a similar shift in epidemiology towards youth and young adults reporting sexual contact and sustained human-to-human mpox transmission. The current epidemiological patterns described above are similar to what was observed in Nigeria with clade IIb MPXV leading up to the ongoing 2022 global mpox outbreak. It is speculated that clade IIb, which had previously been primarily caused from zoonotic spillover, became adapted to human sexual transmission in gbMSM networks within large urban centres, where it spread internationally via air travel networks.^{Footnote 38} It is possible that clade Ib may be in the beginning stages of a similar scenario.

The estimated high likelihood of clade Ib importation is associated with moderate uncertainty. While there is strong evidence that clade Ib MPXV will continue to appear internationally, it is uncertain whether an importation into Canada will occur within the next three months. Given the increased recognition of mpox as a public health concern, particularly clade Ib, and the mounting support to implement outbreak control measures, the spread of clade Ib within the African continent and to other regions may be slowed in the coming months.^{Footnote 24Footnote 39}

Table 2. Estimated travel volumes^{Table 2 Footnote a} from countries reporting clade Ia and Ib MPXV to Canada in 2023.

	September	October	November	Total
Countries only reporting clade Ia MPXV
CameroonTable 2 Footnote b	2,847	2,387	2,332	7,566
Republic of the Congo	191	174	112	477
Central African Republic	36	2	54	92
Countries reporting both clade Ia and Ib MPXV
Democratic Republic of the Congo	1,494	865	970	3,329
Countries only reporting clade Ib MPXV
Thailand	4,028	4,691	6,537	15,256
Kenya	5,407	4,914	4,514	14,835
Sweden	5,193	3,348	2,896	11,437
Uganda	2,385	1,835	1,791	6,011
Rwanda	1,528	1,051	967	3,546
Burundi	659	316	456	1,431
Notes: Table 2 Footnote a IATA data represents about 85% of commercial flights. Table 2 Return to footnote a referrer Table 2 Footnote b Cameroon has reported both clade Ia MPXV and clade II MPXV. The latter is not addressed in this assessment. Table 2 Return to footnote b referrer Source: IATA, unpublished data, 2023

Sub-Question 2: What is the most likely spread scenario given that an infectious traveller enters Canada with clade Ia or Ib MPXV?

The most likely spread scenarios for clade Ia and Ib are generally the same, with some differences anticipated based on evidence of sustained human-to-human transmission of clade Ib, suggesting likelihood of onward local spread (further evidence to support these differences is detailed below). While evidence suggests high susceptibility in the Canadian population (see April 2024 rapid risk assessment) to clade Ia or Ib MPXV, evidence from current outbreaks in the DRC and surrounding areas (some of which are reporting mpox cases for the first time, i.e., non-endemic settings) do not suggest widespread transmission in the general population. There is uncertainty with both likely spread scenarios due to the limited evidence for potential transmission dynamics (human-to-human or zoonotic) in high-income, non-endemic contexts such as Canada.

Clade Ia – Most likely spread scenario

The most likely spread scenario given that an infectious traveller enters Canada with clade Ia MPXV is estimated to be transmission through households and among their non-household close contacts, including sexual contacts, with the potential for domestic amplification through high-contact sexual networks, including among gay, bisexual, and other men who have sex with men (gbMSM) and sex workers and their contacts. Based on current clade Ia epidemiology in the Africa Region, it is expected that transmission would be predominantly limited to cases’ household and/or close contacts should it arrive in Canada. Historically, predominantly children have been impacted by clade Ia MPXV primarily via zoonotic transmission, and then limited human-to-human transmission by close contact; however, multiple modes of transmission have been implicated in the current clade Ia outbreaks.^{Footnote 40} As such, it is possible that close contact networks beyond households and patient caregivers are impacted, including high-contact sexual networks. However, clade Ia has not yet demonstrated sustained human-to-human transmission as is thought to have contributed to the recent geographic spread seen in clade Ib.

Some sources of uncertainty around this likely spread scenario include that evidence comes from the African context and it is unknown what adaptative advantages would allow clade Ia to transmit locally in Canada.

Clade Ib – Most likely spread scenario

The most likely spread scenario given that an infectious traveller enters Canada with clade Ib MPXV is estimated to be transmission through households and among non-household close contacts, including sexual contacts, with the potential for domestic amplification through high-contact sexual networks, including among gay, bisexual, and other men who have sex with men (gbMSM) and sex workers and their contacts.

The clade Ib spread scenario is estimated to be similar to clade Ia; however, there is evidence of more sustained human-to-human transmission for clade Ib MPXV, which could result in chains of transmission in Canada, similar to what happened with clade IIb MPXV in which cases have been predominantly among gbMSM. Emerging research suggests that some point-mutations (TC→TT), are characteristic of the action of APOBEC3 deaminase, which is found only in primates and is part of the innate immune system against viral infections. It is thought that relatively high numbers of these types of mutations likely signify changes to the viral genome that would be expected to occur when there are chains of human-to-human transmission, however there is much uncertainty around this assertion.^{Footnote 41Footnote 42} Analysis of clade Ia and Ib genetic sequences showed the presence of APOBEC-type mutations in clade Ib samples, and the absence of these mutations in the clade Ia samples.^{Footnote 13} Evidence from DRC and Burundi suggests both sexual and non-sexual human transmission of clade Ib.^{Footnote 43} It is not confirmed if sexual transmission may have played a role in the two clade Ib cases reported in Thailand and Sweden. To date clade Ib MPXV has predominantly impacted youth and adults in South Kivu and Burundi; individuals 15 years and older makeup 86% of cases in South Kivu, DRC and 51.9% of cases in Burundi.^{Footnote 17Footnote 26}

Similar to the experience when clade IIb MPXV entered Canada, sexual transmission via high contact sexual networks and community transmission among gbMSM could occur if clade Ib were to enter such networks. As was stated in the April 2024 rapid risk assessment, an analysis of the clade IIb epidemic in North America found that new travel-related cases played a limited role in the ongoing mpox spread and that community transmission among gbMSM sustained the outbreak.^{Footnote 44}

There are several sources of uncertainty associated with this likely spread scenario. While clade Ib demonstrates some similarities to clade IIb MPXV regarding modes of transmission and affected populations, the epidemiology of clade Ib continues to evolve as information is reported from the DRC and other affected countries. The global clade IIb outbreak disproportionately impacted gbMSM communities, whereas heterosexual sex work networks have been implicated in the current spread of clade Ib in the DRC and Burundi. Should this transmission dynamic continue in Canada, this change in groups at risk of exposure may allow some cases to go undetected for longer and it is uncertain what transmission will be like in the Canadian context.

Sub-Question 3: What would the impact be on an individual’s health if infected with clade Ia or Ib MPXV?

Clade Ia and Ib infections are generally anticipated to have moderate and minor individual impacts, respectively (further detailed below). Evidence from the DRC has found that with high quality supportive care, clade Ia or Ib MPXV patients’ mortality was lower (1.7%) compared to the national CFRs, and lesions resolved faster among clade Ia or Ib MPXV cases.^{Footnote 19} Additionally, as high-income countries contribute to disease response and prevention, fatality rates are anticipated to decrease. Canada’s surveillance, control, and medical countermeasures are anticipated to be effective should either clade Ia or Ib MPXV enter Canada.

For both clades Ia and Ib, pediatric, pregnant, and immunocompromised populations are generally considered to be at high risk of adverse impacts in the global literature, however the clinical course of mpox infections in these populations in the Canadian context is unknown. In addition, there is little evidence on the benefits and risks of the Imvamune® vaccine in individuals who are pregnant or breastfeeding, as well as in off-label use in pediatric (<18 years of age) populations. While some studies have reported clinical benefit of Imvamune® among individuals who are infected with HIV, evidence is also limited among other populations who are immunocompromised. This limited vaccine evidence introduces increased uncertainty regarding effective prevention measures available for these populations, though this is a research priority identified by NACI.

Clade Ia

The impact on an individual without known risk factors infected with clade Ia MPXV in Canada is estimated to be moderate with moderate uncertainty. Children, pregnant individuals, and the immunocompromised are estimated to have major individual level health impacts, with moderate uncertainty.

Evidence reported in the April 2024 rapid risk assessment regarding individual impacts and symptoms for clade I remain relevant to the current clade Ia estimate since much of the clade I literature was published prior to the emergence of clade Ib. Clade Ia MPXV is endemic in DRC and is associated with higher CFRs compared to clade IIb and clade Ib (<1%). DRC’s Équateur province, where clade Ia is believed to be the predominant or only strain (limited lab testing to confirm), reported 50% of the country’s suspected mpox cases between January 2023 to April 2024. In 2024, Équateur has also reported a higher CFR (5.7%) compared with CFRs reported elsewhere in the DRC (3-5%).^{Footnote 3}

The elevated CFR for clade Ia MPXV cases may reflect that young children, who are at higher risk of severe outcomes, have comprised a disproportionate number of cases. Delayed diagnoses, limited access to health care, and malnutrition in pediatric populations may also inflate reported morbidity and mortality among current and historic clade Ia MPXV cases.

Prior to detecting clade Ib MPXV, published research has described adverse fetal outcomes (e.g. miscarriages, still birth, and placental infections) among clade I (presumably Ia) infected pregnant individuals.^{Footnote 32} Perinatal mortality rates of up to 75% (n=4) have been reported before September 2023.^{Footnote 45} Overall, evidence on clade Ia MPXV infections among pregnant people is scarce, based on care reports or series.^{Footnote 46}

The clade Ia MPXV impact estimates are made with moderate uncertainty as they are based on suspected clade Ia mpox cases (i.e., Northwest DRC and before Fall 2023), clade Ia MPXV impacts documented in the African Region context, and the assumption that mpox cases detected in Canada would have access to sufficient high-quality care.

Clade Ib

The impact on an individual without known risk factors infected with clade Ib MPXV in Canada is estimated to be minor with high uncertainty. The impact on children, pregnant individuals, and immunocompromised individuals is estimated to be major with high uncertainty.

Clade Ib MPXV has predominantly affected youth and adults in South Kivu, DRC, where individuals; 15 years and older make up 86% of cases in South Kivu, DRC.^{Footnote 17Footnote 26} As of epidemiological week 31 in 2024 in the DRC, the clade Ib CFR is 0.7% (22 deaths among 3,039 cases). As of August 25, no deaths have been reported in Burundi, Rwanda, Uganda, or Kenya, which have clade Ib-driven outbreaks.

In addition to genetic differences between clade Ia and Ib MPXV,^{Footnote 13Footnote 14} lower clade Ib MPXV fatality may in part be explained by youth and adults being predominantly impacted by clade Ib infections in the DRC and improved surveillance resulting in detection of milder cases.

Key risk factors for severe disease from clade Ib MPXV infections are unknown at this time, but it is likely that similar risk factors exist for clade Ib MPXV as for clade Ia and clade IIb MPXV (i.e., potential for young children, pregnant people, and the immunocompromised to be at high of complex infections and death). In one study that enrolled patients admitted to the Kamituga Hospital, in the epicenter of the 2023-24 South Kivu outbreak where clade Ib mpox was first detected, four of eight pregnant patients had fetal losses (50% fetal mortality rate).^{Footnote 45} The four patients with fetal losses were in the first 20 weeks of gestation; it is possible fetuses early in gestation are more sensitive to mpox infections. Two of the four patients with fetal losses experienced severe mpox illness prior to having spontaneous fetal abortions; one patient was positive for HIV and the other had been hospitalized for 21 days. The study did not distinguish clade Ia or Ib, however, given the location and timing of cases, it is likely these data are indicative of clade Ib fetal outcomes.

Conversely, as of June 2024, no deaths or miscarriages were reported among pregnant people with documented clade IIb infections.^{Footnote 47} Severe clade IIb MPXV cases have mostly occurred among those with uncontrolled or advanced HIV infections.

There is high uncertainty for the clade Ib MPXV individual impact estimate as clade Ib MPXV is rapidly evolving as more information is reported among confirmed and suspected cases. Additionally, there is no evidence on clade Ib MPXV clinical impacts in the North American context and limited evidence of clade Ib MPXV morbidity and mortality in children and infants, pregnant individuals, and the immunocompromised.

Sub-Question 4: What would the population health impacts be on affected and general populations?

The population health impact on affected populations, including affected household members and non-household close contacts and individuals in high-contact sexual networks (e.g., gbMSM or sex workers and their close contacts), for either clade Ia or Ib MPXV is estimated to be moderate with moderate uncertainty. The impact on the general population is estimated to be minor with low uncertainty.

Improving awareness around mpox (clades Ia, Ib, and IIb) and available vaccines and treatments is important for both the general population and those most likely to be affected (either via exposure or infection). For example, data stemming from the 2024 Mpox Immunization Coverage Survey among 2SLGBTQI+ and MSM, found that among those part of the 2SLGBTQI+ community who had seen, read or heard about mpox at least a little, 46% were aware that a vaccine against mpox is currently available in Canada.^{Footnote 1} Addressing awareness of prevention and control measures could modify the projected impact on affected and general populations for both clade Ia and Ib.

Impact on affected populations – Moderate (moderate uncertainty)

For both clade Ia and Ib MPXV, affected household members and non-household close contacts and individuals in high-contact sexual networks (e.g., gbMSM and sex workers and their close contacts) may experience stigmatization and social isolation, which could impact mental health and increase existing barriers to healthcare seeking behaviour (see April 2024 rapid risk assessment for more detail).

If transmission of clade Ia or Ib MPXV occurs mainly amongst household and non-household close contacts, there is the potential for adverse outcomes if individuals in the household are children or infants, pregnant individuals, or immunocompromised individuals (see Individual Impact section above). However, the number of people impacted is expected to be less than if it were to enter a high-contact sexual network.

If clade Ia or Ib MPXV enters high-contact sexual networks in Canada, including among gbMSM and sex workers and their close contacts, it may disproportionately impact gbMSM, as was seen in the 2022-2023 clade IIb MPXV outbreak, as well as sex workers and their close contacts. Due to the higher rates of HIV in the gbMSM population, there are greater risks of severe and/or complicated symptoms and outcomes of mpox (see April 2024 rapid risk assessment for more detail). The main differences in anticipated population health impacts on affected populations between clade Ia and Ib are described below.

The uncertainty for this estimate is moderate due to the limited evidence on disease severity and transmissibility of clade Ia and clade Ib MPXV in non-endemic, high-income countries, namely differences in immunity to mpox, former natural exposure to orthopoxviruses, general health status, access to and standard of health services (e.g., vaccination and antivirals), and likelihood of exposure to zoonotic mpox vectors.

Clade Ia

In areas where clade Ia is circulating, most cases have occurred in children (66% of total cases and 82% of total deaths in DRC, 56% of cases in ROC).^{Footnote 40} It is unknown if clade Ia could lead to a high rate of pediatric cases in Canada or if Canadian children are at a high risk of severe outcomes. Canada’s population demographics are notably different compared to countries currently experiencing outbreaks, for example, in 2023, 15% of the Canadian population was less than 15 years of age compared to 47% in the DRC.^{Footnote 48Footnote 49} Overall, the uncertainty is driven by differences between children in the outbreak settings versus Canada, namely differences in immunity to mpox, general health status (including malnutrition), access to and standard of health services, and likelihood of exposure to zoonotic mpox vectors. There is stronger evidence regarding the severity of outcomes in individuals infected with clade Ia compared to clade Ib, a newer sub-lineage (see Individual Impact section above). However, there is more uncertainty about clade Ia compared to clade Ib MPXV in regards to spread. The current epidemiology of clade Ib shows greater evidence to support sustained human-to-human transmission; clade Ia cases are historically associated with zoonotic spillover followed by limited secondary human-to-human transmission.

Clade Ib

Overall, the possible human-to-human transmission advantage of clade Ib suggests more potential for wider spread (e.g., more cases within household and non-household close contacts) compared to clade Ia. However, early evidence suggests that individual health outcomes are less severe for clade Ib compared to clade Ia. Therefore, if clade Ib were to enter a high-contact sexual network in Canda (e.g., among some gbMSM populations), it could have substantial spread and therefore impact. The current outbreaks of clade Ib are characterized by sustained human-to-human transmission, including but not limited to sexual contact.^{Footnote 26} The pattern of transmission of clade Ib MPXV in the DRC is mainly via sexual transmission and high population movement.^{Footnote 43} Evidence from the clade Ib-driven outbreak in South Kivu specifically found 29% of clade Ib MPXV cases reported involvement in sex work.^{Footnote 13} However, there is uncertainty as transmission in Burundi involves a large contribution from non-sexual human-to-human transmission: children under the age of five years and adults between 20 and 30 each make up 21.9% of the cases, followed by those aged 5 to 9 years (17.5%), suggesting that there could be both sexual and non-sexual human to human transmission.^{Footnote 17}

Impact on general population – Minor (low uncertainty)

The impact on the health of the general population is estimated to be minor for both clade Ia and Ib MPXV. Evidence from the April 2024 rapid risk assessment remains valid and can be referred to for more detail. In short, evidence suggests little spillover of clade Ia and IIb MPXV outbreaks in the DRC to the general population. There is low uncertainty due to the substantial evidence from the 2022-2023 clade IIb global outbreak, where there was minimal impact to the general population. In addition, the DRC has not reported, either historically or recently, widespread impacts of clade I MPXV among the general population.^{Footnote 13}

Limitations and knowledge gaps

This assessment is based on facts and emerging evidence known to PHAC at the time of assessment and has several important limitations that affect the uncertainty in the estimates of likelihood and impact. The key scientific uncertainties and knowledge gaps in the present assessment include transmissibility of clade Ia and Ib MPXV and what the transmissibility would be in a non-endemic setting such as Canada, modes of transmission, severity of disease and risk factors for severe disease caused by clade Ib MPXV in a highly susceptible population such as Canada, and whether there is cross protection from infections with clade Ia, Ib, or IIb MPXV infection (see Table 3 below). There are also knowledge gaps in terms of public perceptions of the risk of mpox and risk behaviours in Canada. Current data on public perceptions of the risk of mpox and awareness of preventive behaviours is needed.

Some of the evidence from the DRC outbreaks between September 2023 to very recently was reported as clade I, which included clade Ia and/or Ib prior to the clade Ia and Ib distinction. Some evidence on clade I MPXV from before the current DRC outbreaks may exclude cases from sexual transmission (none reported until April 2023), which is a mode of transmission in the current outbreaks. The size of these outbreaks could be larger than reported due to under-ascertainment and under-reporting.

Many of the key scientific uncertainties and knowledge gaps from the April 2024 rapid risk assessment remain. Those specific to the present assessment are included below (see Table 3).

Table 3. Gaps in knowledge

Uncertainties identified	Unknown/More information needed
Introduction  e.g. routes of introduction	The degree of under-ascertainment and under-reporting of mpox in countries with outbreaks Population susceptibility to clade Ib MPXV Modes of transmission and their efficiency and proportion by clades Ia and Ib Unforeseen challenges to outbreak control in countries with clade Ia or Ib outbreaks e.g. civil unrest, environmental disasters, competing outbreaks Magnitude and effectiveness of the global support and interventions being mobilized to control clade Ia and Ib outbreaks in resource-limited, affected countries Potential for uptake of mpox vaccination in countries with clade Ia or Ib outbreaks receiving or about to receive vaccines Precise volume and origin of incoming travellers from countries with clade Ia and/or Ib MPXV outbreaks Likelihood of international travel by individuals residing in areas with clade Ia or Ib outbreaks, relative to the general population of the country Incubation period and infectious period of clade Ib MPXV
Exposure  e.g. incidence, prevalence	Degree of underdiagnoses in countries with outbreaks Drivers of geographic expansion of clade Ia in Africa What is driving the change observed in the epidemiology of clade Ib What is the significance of point mutations in clade Ia
Susceptibility	Duration of immunity from MPXV infection regardless of clade or subclade Cross protection across different clades or subclades of mpox infection Direct evidence on the effectiveness of Imvamune against mpox infection, or severe disease due to mpox, when given pre-exposure or post-exposure in the context of clade Ia or clade Ib. Vaccine coverage in Canada.
Spread within Canada	Transmissibility of clade Ib, e.g., R0, relative contribution of different modes of transmission, secondary attack rates Differences in clade Ib viral pathogenesis compared to clade Ia and clade IIb, e.g., viral load, tissue or body fluid tropism  Potential for clade Ia and Ib MPXV transmission to children as house-hold contacts Paucisymptomatic transmission and transmission prior to symptom onset Probability of clade Ia or Ib MPXV entering dense sexual networks in Canada Transmissibility of clades Ia and Ib amongst Canadian wildlife Likelihood that clade Ia or Ib MPXV becomes enzootic among animal species in Canada Public understanding of differences among mpox clade Ia, Ib, IIa and IIb. Perception of risk of mpox among the Canadian general population and populations at risk. Awareness of preventive behaviours among the Canadian general population and populations at risk. Drivers of and barriers to preventive behaviour among the Canadian general population and populations at risk.
Immediate/direct impacts e.g. mental health, morbidity/mortality, welfare	Clade Ib spectrum of clinical presentation and risk factors for severe disease Clade Ib severity and complications in pregnant individuals, neonates, and other groups at risk of poor outcomes from other strains of mpox
Longer-term/indirect impacts  e.g. social, economic, environmental, ethical, policy and political, regulatory	Potential healthcare utilization needs for clade Ia or Ib MPXV cases, with or without risk factors for severe disease, and impact on health systems
Interventions  e.g. availability of effective medical countermeasures, public health measures	A clade I/II differentiating molecular test has been developed by NMLB and is undergoing validation. This test does not distinguish between clade Ia and Ib, whole genome sequencing is currently performed to confirm which clade is present. A molecular test that can differentiate clade Ia and Ib is in development. Effectiveness of non-pharmaceutical public health measures (e.g. hand hygiene) to reduce transmission of clade Ia and Ib Early detection and diagnosis by health care professionals

Appendix A: Methods

This assessment was led by DSFB-SIIRA, within the Public Health Agency of Canada (PHAC) between August 22, 2024, and September 4, 2024, in collaboration with a multi-sectoral team (see Appendix B for a list of contributors). The rapid risk assessment (RRA) methodology used by DSFB-SIIRA has been adapted from the Joint Risk Assessment Operational Tool (JRA OT) to assess the risk posed by zoonotic disease hazards developed jointly by the World Health Organization (WHO), Food and Agriculture Organization of the United Nations (FAO), and the World Organization for Animal Health (WOAH).^{Footnote 50} A detailed description of the methodology is published in the journal Canada Communicable Disease Report.^{Footnote 51} Throughout the report, where appropriate, references have been included; where references are not included, the evidence was information by internal data, expert opinion, or personal communication. Definitions of likelihood, impact and uncertainty may be found below (Criteria to estimate likelihood, impact, and uncertainty).

Disease importation model

Evidence supporting the likelihood of importation was supplemented by mathematical modelling completed internally by PHAC. The disease importation model discussed in this rapid risk assessment is methodologically the same as detail in the April 2024 rapid risk assessment from PHAC. This model was parametrized with best data available as of August 16, 2024, data for all clade I MPXV cases (clade Ia and clade Ib) were aggregated, and only the DRC was included as a source country for importation. In some instances high-quality evidence regarding clade IIb MPXV was used when similar data was not available for clade Ia or Ib MPXV.

In brief, the model uses travel volume data from commercial airlines, border crossings by Canadian citizens, Canadians’ time in source country, cases in source country, correction factor, latent and infectious periods, and fractions of Canada and source country’s population either previously infected, previously vaccinated (and attendant vaccine efficacy). The probabilistic simulation-based model is run 200,000 times and the number of simulations where one or more traveller imports a case is used to construct probability distributions estimating the likelihood of at least one person entering Canada from the source country while infectious.

When considering the results provided by this model, readers are advised to consider the following assumptions and limitations:

• It is assumed that travel between the DRC and Canada in the model period (September through November 2024) will be equal that observed in 2023.
• It is assumed that the country population is representative of the traveller population (i.e., homogenous likelihood of travel for all residents in terms of socioeconomic status, age, gender and vaccine coverage).
• It is assumed that the incidence of suspected cases in the DRC in the model period will remain consistent with that reported in July 2024.
• Previous smallpox infections and historical vaccinations from the 20^th century were excluded in both Canada and the DRC.
• The infectious period and asymptomatic rate of infections with clade Ia or Ib MPXV is assumed to be equivalent to those reported for clade IIb MPXV infections.
• Reported seroprevalence of anti-orthopox antibodies in a sample from the DRC was used as proxy to estimate the population fraction in the DRC with immunity due to previous mpox infection.

Criteria to estimate likelihood, impact, and uncertainty

Table A.1. Criteria to estimate likelihood

Estimate	Criteria
High	The situation described in the risk assessment question is highly likely to occur (i.e. is expected to occur in most circumstances)
Moderate	The situation described in the risk assessment question is likely occur
Low	The situation described in the risk assessment question is unlikely to occur
Very low	The situation described in the risk assessment question is very unlikely to occur (i.e. is expected to occur only under exceptional circumstances)

Table A.2. Criteria for estimating magnitude of effect for directly affected individuals if the situation described in the risk assessment question occurs

Estimate	Criteria
Severe	Severe impact on mental health and/or disease morbidity/mortality, and/or welfare (e.g., loss of income)
Major	Major impact on mental health and/or disease morbidity/mortality, and/or welfare (e.g., loss of income)
Moderate	Moderate impact on mental health and/or disease morbidity/mortality, and/or welfare (e.g., loss of income)
Minor	Minor impact on mental health and/or disease morbidity/mortality, and/or welfare (e.g., loss of income)
Minimal	Negligible or no impact on mental health and/or disease morbidity/mortality, and/or welfare (e.g., loss of income)

Table A.3. Criteria for estimating population-level impact in Canada if the situation described in the risk assessment question occurs

Estimate	Criteria
Severe	Potential pandemic in the general population or large numbers of case reports, with significant impact on the well-being of the population. Severe impact on mental health and/or disease morbidity/mortality, and/or welfare (e.g., loss of income). Effect extremely serious and/or irreversible.
Major	Case reports with moderate to significant impact on the well-being of the population. Moderate to significant impact on mental health and/or disease morbidity/mortality, and/or welfare (e.g., loss of income) affecting a larger proportion of the population and/or several regions. Effect serious with substantive consequences, but usually reversible.
Moderate	Case reports with low to moderate impact on the well-being of the population. Low to moderate impact on mental health and/or disease morbidity/mortality, and/or welfare (e.g., loss of income) affecting a larger proportion of the population and/or several regions. Effect noticeable with important consequences, but usually reversible.
Minor	Rare case reports, mainly in small at-risk groups, with moderate to significant impact on the well-being of the population. Moderate to significant impact on mental health and/or disease morbidity/mortality, and/or welfare (e.g., loss of income) on a small proportion of the population and/or small areas (regional level or below). Effect marginal, but insignificant and/or reversible.
Minimal	No or very rare case reports with low to moderate impact on the well-being of the population. Negligible or no impact on mental health and/or disease morbidity/mortality, and/or welfare (e.g., loss of income).

Table A.4. Criteria for estimating level of uncertainty

Uncertainty	Criteria
Very High	Lack of data or reliable information; results based on crude speculation only
High	Limited data or reliable information available; results based on educated guess
Moderate	Some gaps in availability or reliability of data and information, or conflicting data; results based on limited consensus
Low	Reliable data and information available but may be limited in quantity, or be variable; results based on expert consensus
Very low	Reliable data and information are available in sufficient quantity; results strongly anchored in empiric data or concrete information

Appendix B: Acknowledgements

Completed by the Public Health Agency of Canada's Centre for Surveillance, Integrated Insights and Risk Assessment within the Data, Surveillance and Foresight Branch.

Clade I MPXV Rapid Risk Assessment Team

Public Health Agency of Canada: Rukshanda Ahmad, Melanie Cousins, Raquel Farias, Fiona Guerra, Jacqueline Middleton, Julia Paul, Sandra Radons Arneson, Sheenu Singla, Marianne Stefopulos, Dana Tschritter, Shelley Veilleux, Jeyasakthi Venugopal, Linda Vrbova

Mathematical modelling

Aamir Fazil, Vanessa Gabriele-Rivet, Valerie Hongoh, Lisa Kanary

Other individuals from various programs across PHAC

Lyne Bellemare, Anna Bellos, Philippe Berthiaume, Jillian Blackmore, Takoua Boukhris, Mable Chan, Andrea Chittle, Mette Cornelisse, Kristine Cruz, Emma Deeks, Catherine Elliott, Karen Ellis, Nicole Forbes, Stephan Gradient, Corey Green, Heather Hannah, Christina Jensen, Stefanie Kadykalo, Maryam Kamkar, Natalie Knox, Jacqueline Kosche, Fanie Lalonde, Julie A Laroche, Melissa Lavigne, Marc-Andre Leblanc, Michael WZ Li, Andrew MacKenzie, Chand Magnat, Caroline Marshall, Gila Metz, Joanna Merckx, Janice Merhej, Nicholas Ogden, Lisa Phan, Mireille Plamondon, Kusala Pussegoda, Marina Salvadori, Saadia Sarker, Jim Strong, Marsha Taylor, Matthew Tunis, Julie Vachon, Linlu Zhao

Other federal departments

Health Canada: Chris Hinds, Gabriela Capurro Estremadoyro, Lidia Guarna, Anne Brasset-Latulippe

Immigration, Refugees and Citizenship Canada: Elspeth Payne, Catherine Rutledge-Taylor, Jenney Wang, Janice Zhang

Footnotes

References