Mpox virus (MPXV) circulates endemically in incompletely characterized rodent reservoirs within Central and West Africa, with frequent spillover events into humans, in whom it causes mpox disease1. In some cases, these zoonotic infections can lead to onward human-to-human (H2H) transmission through close contact, including sexual contact, with MPXV-infected individuals2. Historically, chains of H2H transmission were short lived, self-limiting and geographically localized, with few onward infections per outbreak2. Within short-lived localized outbreaks, up to seven generations of H2H transmission have been inferred. However, in recent years, there has been sustained H2H transmission of multiple variants of MPXV from different clades in different sexual networks3, leading to the designation of mpox as a public health emergency of international concern in 2022 and again in 2024.

With sustained H2H transmission, there is a need for a nomenclature that integrates genetic and epidemiological evidence into a standardized outbreak-labeling system. The first evidence of sustained H2H transmission of MPXV was seen with clade IIb4. Although numerous mpox cases associated with this clade have been recorded in Nigeria since 2017 (ref. 5), retrospective analysis of mutational signatures suggested that sustained H2H transmission of this variant has occurred since at least 2016 (ref. 4). The early diversity within clade IIb is designated lineage A; in addition to causing mpox cases in Nigeria, lineage A and its descendants have occasionally been exported internationally starting in 2018 (ref. 6), and are causing outbreaks in various countries of West Africa in 2025. Lineage B.1 descends from lineage A and has been driving the ongoing global mpox outbreak since 2022 (Fig. 1).

Fig. 1: Application of MPXV nomenclature schemes in relation to sustained H2H transmission outbreaks.
figure 1

MPXV clades, clade Ia phylogenetic groups, clade IIb lineages and lineages associated with sustained H2H outbreaks (as proposed in this article) are labeled. Red phylogenetic branches are within sustained H2H outbreaks; sustained H2H transmission lineages are designated to coincide with the start of these outbreaks. We assembled a dataset containing clade Ia, clade Ib, clade IIa and clade IIb non-lineage B.1 genome sequences included in ref. 14, representative sequences from clade IIb lineage B.1 and descendant lineages (https://github.com/mpxv-lineages/lineage-designation/) and sequences that cluster within clade Ia/sh2024 (ref. 9). Sequences were aligned using squirrel (https://github.com/aineniamh/squirrel) and a phylogenetic tree reconstructed with IQ-TREE v2.1.3 (ref. 15) using the Jukes–Cantor (JC) model of nucleotide substitution. The scale bar shows the expected number of nucleotide substitutions per site. The inferred clustering of clade Ib sequences collected from Nord- and Sud-Kivu, DRC, in 2011 and 2012 (ref. 12) that do not belong to the sustained H2H outbreak is noted at far right7.

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Two additional mpox outbreaks associated with sustained H2H transmission have subsequently been detected; both were initially identified in the Democratic Republic of the Congo (DRC) and are ongoing. The first was caused by a variant of clade Ib detected initially in the human population in September 2023 in the Sud-Kivu province7,8; this variant has since spread to other provinces within the DRC and internationally3. Although clade Ia infections have been driven mainly by zoonotic transmissions in rural forested regions, with little evidence for sustained H2H transmission1, an outbreak of clade Ia associated with sustained H2H transmission was detected in Kinshasa and neighboring provinces within the DRC in the second half of 2024 (ref. 9). Evidence of sustained H2H transmission in each of these cases includes the presence of an APOBEC3-like mutational signature among mutations accumulated within the outbreak4.

As more MPXV outbreaks with sustained H2H transmission emerge, there is a need to identify their role in driving mpox incidence and severity across regions and through time. Investigation of the epidemiological, clinical and functional characteristics of individual outbreak variants requires a simple, precise and standardized label for each outbreak that can be used to facilitate consistent communication. These labels would also enable rapid inference of whether exported cases belong to specific lineages within clades.

Over time, different types of naming systems have been used to describe the diversity of clade Ia, Ib, IIa and IIb viruses. These have not been consistently applied across the clades. For clade Ia, the term ‘group’ has been used to describe the divisions of broad genetic diversity within the reservoir1. Although these groups can be useful for communicating findings, they do not provide explicit reference to the source. For the sustained human outbreak within clade IIb, a Pango lineage nomenclature10 is used to describe fine-scale phylogenetic clusters and therefore link cases11. Although the clade Ia, clade Ib and clade IIb labels have recently been used as a proxy for the sustained human outbreaks associated with these clades, related viruses that cluster phylogenetically outside the main human outbreaks and have not led to sustained transmission have been identified in each case12,13. The clade labels therefore do not refer exclusively to viruses isolated from sustained H2H outbreaks.

We propose here an addition to the existing nomenclatures that explicitly names mpox outbreaks driven by sustained H2H transmission and enables the identification of viruses associated with these outbreaks. This proposal is compatible with existing MPXV nomenclatures and adheres to World Health Organization best practices for the naming of infectious diseases and their agents.

A proposed nomenclature for MPXV lineages showing sustained H2H transmission

We propose a nomenclature for MPXV lineages showing sustained H2H transmission of the form ‘Clade/shYear suffix/lineage’: for example, Clade IIb/sh2017/lineage A’. Under this nomenclature:

  • ‘Clade’ indicates the clade within which the viruses driving the sustained H2H outbreak cluster.

  • ‘sh’ denotes sustained human-to-human transmission.

  • ‘Year’ indicates the year of first detection; this is the year of the earliest genetic sequence at the point of first detection, not the year inferred to be the ancestor date of the outbreak. This year will not be updated if earlier cases associated with the outbreak are subsequently detected after designation.

  • ‘suffix’ included when there are multiple named outbreaks first detected within the same year, is a single letter indicating the order of designation among named outbreaks within that year. The first named outbreak does not receive a suffix. Subsequent named outbreaks receive a letter suffix, starting with ‘b’ for the second named outbreak; this is incremented to the next available letter with each subsequent outbreak in the same year, regardless of the clade of the outbreak. In these cases, the suffix ‘a’ is synonymous to the absence of a suffix: for example, sh2023 and sh2023a are synonymous ways to describe the first named outbreak detected in 2023.

  • ‘lineage’ indicates the lineage of the virus, if a Pango-type lineage scheme has been designated. If a lineage scheme has not been established within an outbreak, the outbreak should be referred to by the first two fields — for example, ‘Clade Ib/sh2023’.

As the second field of this nomenclature (for example, sh2023) is unique, it may be used alone to refer to the outbreak.

This proposed nomenclature incorporates and bridges the existing clade and lineage nomenclatures. We do not include the existing clade Ia group labels within this nomenclature because of challenges in keeping these current and consistent as new virus diversity emerges and is discovered.

We propose to designate labels for outbreaks involving sustained H2H transmission that are likely to require communication and targeted interventions to control transmission. We do not propose to name self-limiting chains of H2H transmission. Furthermore, we do not aim to classify all MPXV genetic sequences under this nomenclature; only sequences that belong to a sustained H2H outbreak are to be named.

Criteria for designation of a new outbreak lineage

We propose that lineages associated with sustained H2H outbreak be identified on the basis of both genetic criteria and epidemiological criteria. A non-exhaustive set of criteria is outlined below. Importantly, not all criteria must be met for a lineage to be considered as causing a sustained H2H outbreak. We recognize that genetic and/or epidemiological data may at times be incomplete or difficult to obtain. Thus, the designation of a lineage as a sustained H2H outbreak lineage will rely on the synthesis of all available data, potentially including data sources not explicitly listed here, and will require multidisciplinary expert input. It is likely that evidence will accumulate over time, and we anticipate that available evidence will be reviewed regularly to determine whether a new sustained H2H outbreak lineage will be designated. Notably, the designation of a new lineage does not suggest the acquisition of any phenotypic differences.

For a lineage to be designated as a sustained H2H outbreak lineage, it is essential that there be genetic evidence of a linked outbreak. Specifically, the lineage will exhibit a monophyletic cluster of closely related high-quality genome sequences, supported by one or more reliable mutations. Sequencing data from the affected region(s) needs to have sufficient coverage for an outbreak to be identified.

In addition to this genetic evidence, it is essential that the lineage exhibit further support for sustained H2H transmission such that it is reasonable to rule out a point source outbreak or repeated zoonotic spillover of closely related viruses from animals. This evidence may include the following:

  • Mutational signatures: Sustained H2H transmission may be evidenced by the presence of an APOBEC3-like mutational signature among mutations acquired on internal phylogenetic branches between sequences in the lineage. Such a signature on tip phylogenetic branches alone may not be sufficient, as these mutations may have arisen in sampled human patients and not represent onward transmission. There is not currently a defined threshold for the proportion of APOBEC3-like mutations that is needed to define sustained H2H transmission; this will therefore be based on expert consensus.

  • Epidemiological data: These are data that include one or more of the following: (i) demographic characteristics of confirmed and/or suspected cases showing a shift away from the demographics expected from zoonotic spillovers (with most cases historically detected in children); (ii) demographic data highlighting the clustering of cases in a specific connected subpopulation (for example, men who have sex with men) or profession (for example, sex workers); (iii) an increase in confirmed and/or suspected mpox cases within a non-endemic or urban region where the phylogenetic cluster is detected; and (iv) documentation of H2H transmission chains above that expected from transient human outbreaks.

  • Geographical movement patterns: Support for sustained H2H transmission may also come from virus movements more plausibly explained by human rather than animal movements. This may include (i) multiple international exports of the same virus lineage, which are more likely the result of H2H transmission than independent zoonotic spillovers; (ii) detection of the lineage within multiple urban centers connected by high levels of human movements; and (iii) evidence of transmission in regions with no known animal reservoir.

  • Persistence over time: Detection of a lineage in human cases over several months may strengthen the evidence for sustained H2H transmission.

  • Serological evidence: Increases in seroprevalence indicating MPXV exposure and/or transmission in affected populations may increase support for sustained H2H transmission.

Application of the nomenclature to existing sustained H2H outbreaks

We applied the proposed nomenclature to the three known sustained H2H outbreaks (Fig. 1). Each of these outbreaks shows a phylogenetic cluster of high-quality genome sequences supported by one or more reliable mutations, an APOBEC3-like mutational signature, epidemiological data supporting sustained transmission and continued detection over at least 3 months. Each of these outbreaks therefore meets the criteria for designation of a sustained H2H outbreak lineage.

Applying the nomenclature outlined above results in the following labels for these lineages:

  • the clade IIb sustained H2H global outbreak would be named ‘Clade IIb/sh2017/lineage X’ (where X corresponds to the lineage name from the existing Pango nomenclature)10,11 — for example, a lineage A virus would be named ‘Clade IIb/sh2017/lineage A’, whereas a lineage B.1 virus would be named ‘Clade IIb/sh2017/lineage B.1’;

  • the clade Ib sustained H2H outbreak7,8 that emerged in the Sud-Kivu province of the DRC and has spread internationally would be named ‘Clade Ib/sh2023’;

  • the clade Ia sustained H2H outbreak that emerged in Kinshasa and neighboring provinces and is currently ongoing in the DRC9 would be named ‘Clade Ia/sh2024’ (Fig. 1).

Conclusion

We propose a nomenclature system and set of criteria to identify and name MPXV outbreaks associated with sustained H2H transmission. We envision that the proposed nomenclature will enable investigation of the factors driving mpox cases in different regions through time, for example, showing whether an increase in cases is driven by sustained H2H transmission or increased zoonotic spillover. Furthermore, this nomenclature will support efficient communication, facilitate the investigation and comparison of key virus characteristics (including, for example, transmissibility, immune escape potential and severity) and assist with implementation of timely and targeted public health responses.