Lassa fever (LF) is a life-threatening viral hemorrhagic disease endemic to West Africa; early clinical symptoms are indistinguishable from other febrile illnesses, complicating diagnosis and surveillance (1). The causative agent, Lassa virus (LASV), is a Mammarenavirus (Arenaviridae family) with a bisegmented (small [S] and large [L] segments) ambisense RNA genome that exhibits distinct phylogenetic structure across its endemic regions. Lineages I–III and VI circulate in Nigeria, lineage IV predominates in the Mano River Union countries (Guinea, Sierra Leone, and Liberia), and additional distinct lineages circulate in Mali/Côte d’Ivoire (lineage V) and Togo (lineage VII). Although LF cases are only sporadically reported in Guinea, serologic evidence from the southeastern (forested) and central regions indicates broad population exposure (2,3). Sequencing efforts thus far have generated partial LASV genomes from rodent reservoirs in Upper Guinea (4), whereas genomes from human infections remain limited (5,6). Sparse genomic data limit our understanding of geogenomic variation, outbreak dynamics, and clinical correlations, highlighting the need for enhanced genomic surveillance to inform diagnostics, epidemiology, and patient management.

To expand viral surveillance and diagnostic capabilities locally in Guinea, genomic capacity strengthening was initiated in 2021 at the Centre de recherche en Virologie–Laboratoire des Fièvres Hémorragiques Virales de Guinée (CRV-LFHVG; Conakry, Guinea). Sequencing infrastructure was initially established in response to the COVID-19 pandemic using targeted Nanopore sequencing (Oxford Nanopore Technologies, https://nanoporetech.com) (7). In 2022–2023, laboratory capacity was expanded to include metagenomic sequencing (8,9), integrated within the diagnostic network of 3 surveillance laboratories for viral hemorrhagic fevers across Guinea: CRV-LFHVG, the national reference laboratory in Conakry, and 2 satellite laboratories in the forest region, in Guéckédou (Laboratoire des Fièvres Hémorragiques Virales de Guéckédou; LFHV-GKD) and N’Zérékoré (Laboratoire des Fièvres Hémorragiques Virales de Hôpital Régional de N’Zérékoré; LFHV-HRNZE). During 2020–2024, this laboratory network confirmed a total of 36 LF cases (F.R. Koundouno et al., unpub. data, https://www.medrxiv.org/content/10.64898/2026.02.24.26346968v1), including a nosocomial outbreak in Conakry in 2022. In-country metagenomic nanopore sequencing was performed at CRV-LFHVG to investigate the viral diversity of the confirmed LF cases. A total of 28 LF cases were successfully sequenced, all of which yielded sufficient genomic coverage for downstream phylogenetic analysis (Appendix Table). Most sequencing yielded near-complete genomes for both segments (Appendix Table), and all sequences were phylogenetically classified as lineage IV.

Figure 1

Figure 1. Phylogeographic reconstruction of the dispersal history of Lassa virus lineage IV from study of genomic surveillance of Lassa virus through in-country sequencing, Guinea. A, B) Results of the continuous phylogeographic...

Figure 2

Figure 2. Temporal evolution of the large and small segments of Lassa virus from study of genomic surveillance of Lassa virus through in-country sequencing, Guinea. Time-scaled maximum clade credibility trees are shown...

Phylogenetic analysis revealed that many of the newly sequenced genomes from Guinea are substantially divergent from previously characterized cases; branch lengths suggest years to decades of virus circulation in the natural reservoir before sampling in human cases (Figures 1, 2). Bayesian phylogeographic reconstruction estimated substitution mean rates of 8.5 × 10⁻⁴ (S segment) and 8.2 × 10⁻⁴ (L segment) substitutions/site/year, placing the root of lineage IV in the 17th–18th Centuries, likely originating in southeastern (forested) Guinea (Figures 1, 2).

Spatial viral diversity in Guinea is organized into 3 predominant geographic clusters, mainly associated with the areas of Guéckédou, N’Zérékoré, and Faranah. That factor should be interpreted cautiously, because Guéckédou and N’Zérékoré both have surveillance laboratories, and sequences from the Faranah region originate from rodent reservoirs sampled during previous studies. Consequently, the inferred geographic clustering might be driven, at least in part, by uneven sampling. Two cocirculating sublineages of LASV were identified in the N’Zérékoré region: an older IVb lineage, which has been long-established locally (M00539, M00541, G0405, G0870, G0934); and the IVa lineage, which traces back to multiple independent introductions (M00363, M00542, M00364, G0274) from Ganta, northeastern Liberia, with common ancestors dating to the 1950s–1980s (Figure 1, panel D; Figure 2). In Guéckédou, we detected an imported LASV case originating from the Kenema area of Sierra Leone (G0959) (Figure 1, panel C; Figure 2), illustrating that sporadic introductions from neighboring LASV-endemic regions to Guinea can occur and contribute to Guinean LASV diversity.

We included 4 LF cases from Conakry, in the western part of Guinea, all of which were associated to a previously reported nosocomial transmission chain linked to a travel case from a LASV-endemic area (10) (Appendix). The LASV sequences (G0780, G0795, G0796, G0797) show minimal between-sequence variation (L segment, 0–4 mutations; S segment, 0–1 mutations), consistent with a single transmission event. We identified all 4 genomes as a reassortant LASV variant with their 2 segments clustering significantly differently (Appendix). Their L segments clustered with sequences previously identified in Faranah (lineage IVb in Figure 2, panel A), and their S segments clustered with sequences previously identified in Guéckédou (lineage IVb in Figure 2, panel B).

This study increases the available LASV sequences derived from human clinical cases and provides new genomic insights into LASV circulation in Guinea. Our findings were made possible through strengthened laboratory diagnostics in LF-endemic areas (Guéckédou and N’Zérékoré) and the establishment of new sequencing capacity for viral hemorrhagic fevers at CRV-LFHVG, Conakry. Ongoing genomic surveillance remains crucial for guiding public health interventions, as well as for the development of appropriate medical countermeasures.

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Suggested citation for this article: Camara J, Annibaldis G, Klaps J, Ifono K, Koundouno FR, Sidibé Y, et al. Genomic surveillance of Lassa virus through in-country sequencing, Guinea. Emerg Infect Dis. 2026 May [date cited]. https://doi.org/10.3201/eid3205.260386