New nomenclature for mpox (monkeypox) and monkeypox virus clades

In May, 2015, WHO recommended best practices for naming new infectious diseases to avoid offense or economic effect for any ethnic, regional, or other groups.¹ Although mpox (formerly known as monkeypox) is not new, WHO has endorsed mpox as the new name for this re-emerging disease and backed the scientific community to agree on neutral nomenclature for variants of viruses.

The first report of mpox that led to the discovery of the global outbreak was made to WHO on May 13, 2022. The outbreak spread to 110 countries² and was declared a public health emergency of international concern. The Director-General of WHO called on member states to ensure respect for human rights and to address stigma and discrimination.³ As of Jan 31, 2023, there were 85 549 confirmed cases of mpox reported by 110 countries, including 89 deaths.²

Mpox is caused by the species monkeypox virus (MPXV), genus Orthopoxvirus, discovered in 1958 in a primate research facility in Denmark, with the first human case reported in 1970.⁴ Two virus clades were identified: the Congo Basin (or central African) clade and the west African clade.⁵ Although stigma became a concern during outbreaks in Africa,⁶ the 2022 global outbreak reignited discussion with proposals to rename virus clades.⁷

Although the nomenclature of virus variants is the remit of scientists, reaching consensus quickly was important. On Aug 8, 2022, WHO convened an ad-hoc expert meeting to discuss characteristics of MPXV clades and propose names for them. Participants included orthopoxvirologists, evolutionary biologists, and other scientists from (1) WHO collaborating centres on orthopoxviruses at the US Centers for Disease Control and Prevention and the Russian State Research Centre of Virology and Biotechnology; (2) the WHO Technical Advisory Group on SARS-CoV-2 Virus Evolution; (3) the WHO Advisory Committee on Variola Virus Research; (4) the Poxviridae study group of the International Committee on the Taxonomy of Viruses; (5) research and public health institutes in Africa and around the world; and (6) public virus-sequence databases.

The meeting reviewed the phylogeny and characteristics of MPXVs and proposed a neutral naming convention.⁷ MPXV phylogeny shows two distinct clusters corresponding to the previously recognised clades. Consensus was reached for nomenclature of a Roman numeral for each clade with lowercase Latin characters for subclades; the Congo Basin clade became Clade I and the west African clade became Clade II, encompassing two phylogenetically distinct subclades, IIa and IIb.⁸

There are appreciable genetic differences between Clades I and II, showing nearly twice the divergence as that between subclades IIa and IIb. Nonetheless, both subclades include genomes from the 1960s and 1970s and appear to have evolved separately from a most recent common ancestor dating back hundreds of years. Neither subclade is descended from the other.⁵ Although the current global outbreak is related primarily to Clade IIb, new cases related to Clade IIa continue to be reported, requiring the tracking of numerous clades and lineages.

To distinguish emerging lineages, nomenclature that encodes genealogical relationships between variants was proposed. Lineage labels would follow the convention used for SARS-CoV-2, with an uppercase Latin character followed by a period, and a number representing the nth descendant of the Latin character (eg, Clade IIb.A.1).⁹ The assignment of virus lineage will help to identify epidemiological links within and across geographic regions and support the understanding of evolutionary dynamics.

Parallel discussions considered changing the disease name in the WHO International Classification of Diseases (ICD). WHO issued a public call for new name suggestions for monkeypox in August, 2022. Over 200 proposals received on the ICD platform were reviewed with criteria such as rationale, appropriateness, current usage, scientific accuracy, pronounceability, translatability, potential for confusion, and the guidance for the naming of new diseases. Consultations involved the ICD Medical and Scientific Advisory Committee, the Classification and Statistics Advisory Committee with representation from WHO member states, and the WHO Family of International Classifications. The review recommended the use of mpox as a synonym or inclusion name for monkeypox. The new name was proposed by a men's health community organisation, endorsed by WHO after all suggestions were considered,¹⁰ and is being phased in as a synonym to become the preferred term of the ICD after December, 2023. Discussions on terminology in other languages will continue throughout 2023, providing member states with a choice of preferred term in their language for national usage and statistics. Mpox is now included in ICD-10 and ICD-11, effective as of January, 2023.¹⁰ WHO encourages all member states and stakeholders to follow these recommendations on mpox and its virus clades.

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EJL was supported by the US National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award number U24AI162625. All other authors declare no competing interests. The working group thanks African scientists who advocated for new clade names for MPXV, and front-line health workers and advocates at Rézo, a Montreal community based organisation for gay, bisexual, queer, cis, and trans men who have sex with men, who led a grassroots movement to rename mpox. DU chaired the ad-hoc experts meeting on MPXV clades and variants, which involved authors AA, JB, KK, EJL, MRM, TdO, JO, AR, and RFL, and experts Ifedayo Adetifa, Oluwatoni Akinola, Olajumoke Babatunde, Sylvie Briand, Clarissa Damaso, Inger Damon, Drew Endy, Delia Enria, Mariano Esteban, Bradley Hersh, Christina Hutson, Yu Li, Abdi Mahamud, Sandy Mak, Peter Mala, Colin McInnes, Jean-Vivien Mombouli, Richard Neher, Nnaemeka Ndodo, Mark Perkins, Mike Ryan, Jilian Sacks, Soumya Swaminathan, Henda Triki. We thank Meng Zhang, Co-Chair of the ICD Classification and Statistics Advisory Committee, all participants in these discussions, and Maria Van Kerkhove for ongoing support. The findings and conclusions in this Comment are those of the authors and do not necessarily represent the views of their respective institutions.