Mpox virus lineage A.2.2 identified in the Republic of the Congo amid concurrent circulation of Ia, Ib, and IIb
Background
A case of infection with A.2.2, a lineage within mpox virus (MPXV) clade IIb, was confirmed in the Republic of the Congo. Researchers also reported the concurrent circulation of Ia, Ib, and IIb during surveillance in 2025. This was not the discovery of a new lineage; it documents A.2.2, already known from other regions, in the Republic of the Congo.
Historically, mpox outbreaks in the Republic of the Congo have mainly been attributed to Ia, and the subsequent introduction of Ib was also confirmed. Detection of IIb shows that the pattern of circulating viruses is becoming more complex. The country studied is the Republic of the Congo, distinct from the Democratic Republic of the Congo.
Key findings
Researchers confirmed mpox in a 43-year-old man who visited an outpatient clinic in Pointe-Noire in March 2025. He had fever, weakness, and skin lesions, and had recently traveled to France and Côte d’Ivoire. Molecular testing of skin-lesion and blood samples was positive for clade II.
The team then obtained the virus’s complete 197,200-base-pair genome and conducted phylogenetic analysis, classifying it as A.2.2 within IIb. The patient recovered after 19 days following home isolation and symptomatic treatment. No transmission to family members or healthcare workers was observed, but this single case cannot establish the transmissibility or severity of the lineage as a whole.
Passive surveillance from January to August 2025 identified 16 cases of Ia, 32 of Ib, and two imported cases of IIb. Passive surveillance involves testing suspected cases reported by healthcare facilities. Here, concurrent circulation means that multiple lineages were detected in the regional population during the same period; it does not mean that one person was coinfected with multiple lineages.
Implications and outlook
The study documents the concurrent circulation of diverse MPXV lineages and supports the need for diagnostics that distinguish lineages and for genomic surveillance. The researchers discussed how circulation of multiple lineages in a limited area could increase the risk of genetic recombination between viruses. However, the study did not observe actual recombination or the emergence of a new phenotype, nor did it validate performance in predicting the emergence of variants.
The route of introduction also remains uncertain. Only one A.2.2 genome from the Republic of the Congo was analyzed, and regional genomic data and contact-tracing information for the patient were limited. Travel history or genetic similarity to viruses from other countries alone cannot establish the country where infection occurred or the direction of transmission. Continued sample collection and contact tracing will be needed to characterize local transmission more accurately.
The diagnostic and phylogenetic analysis results, along with the limitations of their interpretation, are presented in the full Nature Medicine paper.
Nature Medicine, Published online: 03 April 2026; doi:10.1038/s41591-026-04256-2 Whole-genome phylogenetic analyses have identified a case of monkeypox virus clade IIb lineage in the Republic of the Congo and co-circulation of three clade lineages, emphasizing the importance of improved surveillance given the risk of possible recombination events in the future.
The practical significance of this study lies in distinguishing circulating mpox lineages and using that information to inform the local response, beyond simply confirming infection. The researchers reported that, after sharing the A.2.2 detection results with health authorities, they strengthened GeneXpert-based local diagnostics, next-generation sequencing surveillance, healthcare worker training, and measures to prevent transmission in hospitals in Pointe-Noire. For example, when a suspected case is identified at a local healthcare facility, molecular testing can check for infection, while genomic analysis and contact tracing can be combined to investigate imported cases and possible local transmission. The study did not assess whether these measures reduced transmission or were cost-effective. Using surveillance findings to guide a response should be distinguished from demonstrating that the response was effective.