Andes hantavirus: characterization of a rare disease cluster by coordinated genomic sequencing
The Andes virus: a hantavirus capable of human-to-human transmission
The documented ability of the Andes virus to spread among individuals during close and prolonged contact or in confined environments sets it apart from most other hantaviruses that cause zoonoses, for which human-to-human transmission has not yet been observed. Although rare, human-to-human transmission has been documented for this pathogen, notably during the Epuyén outbreak in Argentina in 2018-2019, which remains an exceptional case. Indeed, an analysis of Andes virus disease clusters described in Argentina reveals that human-to-human transmission is not the norm for Andes. This characteristic is of major significance for public health surveillance, particularly since the geographical distribution of the virus correlates with the habitats of rodent reservoirs (mainly Oligoryzomys longicaudatus) in Patagonia.
Chronology and epidemiology of the MV Hondius cluster
The ship left Ushuaia (Tierra del Fuego, Argentina) on April 1, 2026. The index patient, a 70-year-old Dutch man, developed initial symptoms (fever, headache, diarrhea) on April 3, shortly after departure, and subsequently died aboard the ship on April 11. An epidemiological investigation pointed strongly to zoonotic exposure in Argentina or Chile, probably through contact with rodents.
After an interval of around two to three weeks, a secondary cluster emerged between April 21 and May 1, with five additional passengers, who had been in close contact with the index case, developing symptoms.
Four additional cases were detected on disembarkation of the ship in Tenerife on May 10, after passengers had been dispersed across several continents (South Africa, Switzerland, South Atlantic islands).
This progressive chronology is consistent with successive human-to-human transmission events within a confined environment. Andes virus' long incubation period (7 to 42 days) significantly complicated the process of contact-tracing and reconstructing transmission chains, since some cases emerged several weeks after last confirmed contact aboard the ship.
Limited respiratory transmission
The epidemiological data for this cluster provide no evidence of mass airborne transmission or of transmissibility comparable to modern respiratory viruses such as SARS-CoV-2. In contrast, all the documented cases of transmission were consistent with close and prolonged contact within a family setting (spouses, close friends) or in a confined medical environment. Transmission was not observed in instances of brief contact or distant proximity aboard the ship.
Coordinated genomic sequencing and multinational validation
The major contribution of this investigation lies in its approach of collaborative genomic sequencing conducted in real time by several laboratories (in the Netherlands, South Africa, Switzerland, France, Senegal, Spain and Canada). The Institut Pasteur National Reference Center for Hantaviruses in Paris was involved in analyzing the French case and coordinating the validation process.
Sharing of raw sequencing data among laboratories represented a crucial step in this process.
"This approach raised a major methodological challenge: initial analyses revealed 10 mutations with potential impact in several patients. However, a detailed comparison of the raw data and validation against standardized bioinformatic parameter sets revealed that 8 of these 10 mutations were in fact technical artifacts linked to the various sequencing platforms and bioinformatic pipelines used," explains Sarah Temmam, Head of the Center for the Genotyping of Pathogens within the Laboratory for Urgent Response to Biological Threats at the Institut Pasteur.
This is the institute's only entity authorized to sequence highly pathogenic agents subject to strict regulations due to their status as "MOTs" (microorganisms and toxins).
"This cross-validation of genomic data prevented the dissemination of misinterpretations that would have fueled uncertainty during a health crisis. This is a key finding: in cases of rare pathogen outbreaks, quality control must be just as rigorous for bioinformatics as for clinical diagnostics," explains Jean-Claude Manuguerra, Deputy Director of the National Reference Center for Hantaviruses at the Institut Pasteur.
Low genetic diversity indicative of a likely single introduction event
The validated genome sequences revealed a remarkable degree of uniformity:
- The viral S and M segments were completely identical in all patients for whom the viral strain had been sequenced. A mutation in glycoprotein (segment M) was observed in relation to the reference sequence characteristic of this cluster. The functional impact of this mutation is yet to be characterized.
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The L segment varied by just one mutation per patient, presenting minimal variation with no functional signature. This mutation had no impact on the protein sequence, and therefore did not affect viral polymerase function.
The very low genetic diversity observe – contrasting starkly with the genomic complexity seen in prolonged periods of outbreak transmission – supports the theory of a single viral introduction event followed by limited human-to-human transmission aboard the ship. A similar lack of diversity was also observed during the Epuyén outbreak in 2018.
The scientists specifically looked for genomic mutations that had previously been linked in the literature to increased human-to-human transmissibility or to "superspreading" events. None of these mutations were detected in the virus from the MV Hondius, confirming that the analyzed virus had retained its original virulence profile without acquiring any properties conferring increased transmissibility.
A phylogenetic analysis revealed that the virus involved in the cluster aboard the ship was very similar to human strains detected in Argentina in 2018 (98.7% similarity on the L segment), suggesting direct genetic lineage with documented Argentine clusters in humans. Improved knowledge of the virus' genetic diversity within the reservoir could provide a more accurate picture of genetic links between animal and human viral strains, enabling circumstances of exposure to be better defined in human cases.
Implications for the surveillance of rare emerging pathogens
"This disease cluster is the first documented episode of human-to-human Andes virus transmission in an international travel setting," states Virginie Sauvage, Director of the National Reference Center for Hantaviruses at the Institut Pasteur. "It reminds us that even rare and geographically limited pathogens can emerge far from their endemic areas, and that specialized expertise and rapid international coordination are essential for confirming diagnosis and guiding public health measures."
This investigation reveals the need to retain diagnostic and genomic capabilities for rare pathogens outside their endemic areas. Without the National Reference Center's expertise, diagnosis would have been delayed and the molecular epidemiology could have been misinterpreted. This situation also highlights the necessity for rapid and transparent sharing of raw genomic data and for collaborative quality control on an international scale.
Source
Hantavirus pulmonary syndrome outbreak linked to cruise ship travel, April–May 2026, Science, 12 novembre 2026
Bas B. Oude Munnink1†, Samuel Cordey2†, Moussa Moïse Diagne3†, Jonathan Featherstone4†, Anabel Negredo5,6†, Sarah Temmam7†, Jenniffer Angulo8†, Carla M. Bellomo9†, Ana Hoxha10†, Santiago Vidal-Freire11†, Lorenzo Subissi10†, Margreet te Wierik12†, David F. Nieuwenhuijse1, Jonathan Audet13, Ndeye Awa Ndiaye3, Laurent Dacheux7, Safiétou Sankhe3, Jens H. Kuhn14, Florian Laubscher2, Mouhamed Kane3, Jean-Claude Manuguerra7,15, Jessica Vanhomwegen7, International Consortium Investigating the M/V Hondius Outbreak16, David Safronetz12, Olivier Le Polain de Waroux10‡, Tjalling Leenstra12‡, Valeria P. Martínez9‡, Nicole D. Tischler17,18‡, Boris I. Pavlin10‡, Jacqueline Weyer4‡ , Isabella Eckerle19,20,21‡, Ibrahima Socé Fall3‡, Marion P. G. Koopmans1‡, María Paz Sánchez-Seco5,6‡, Virginie Sauvage14‡, Gustavo Palacios11‡*
1Virology Department and Pandemic and Disaster Preparedness Research Centre, Erasmus Medical Centre; Rotterdam, Netherlands.
2Laboratory of Virology, Laboratory Medicine Division, Diagnostic Department, Geneva University Hospitals; Geneva, Switzerland.
3Institut Pasteur de Dakar; Dakar, Senegal.
4National Institute for Communicable Diseases; Sandringham, Johannesburg, South Africa.
5Laboratory of Arboviruses and Imported Viral Diseases., National Center of Microbiology, National Institute of Health “Carlos III”; Madrid, Spain;
6Ciber of Infectious Diseases, National Institute of Health “Carlos III”; Madrid, Spain.
7Institut Pasteur, Université Paris Cité, Environment and Infectious Risk Research Unit - Laboratory for Urgent Response to Biological Threats (ERI-CIBU); Paris, France.
8Departamento de Enfermedades Infecciosas e Inmunología Pediátricas, Escuela de Medicina and Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile; Santiago, Chile.
9Laboratorio Nacional de Referencia de Hantavirus, Instituto Nacional de Enfermedades Infecciosas, Administración Nacional de Laboratórios e Institutos de Salud Dr. Carlos G. Malbrán; Buenos Aires, Argentina.
10Health Emergency Preparedness and Response Programme, World Health Organization; Geneva, Switzerland.
11 Department of Microbiology, Global Health Emergent Pathogens Institute, Icahn School of Medicine at Mount Sinai; New York, NY, USA.
12 National Institute for Public Health and the Environment; Bilthoven, Netherlands.
13Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada; Winnipeg, Manitoba, Canada.
14Frederick, MD, USA.
15Institut Pasteur, Université Paris Cité, Environment and Infectious Risk Research Unit - French National Reference Center for Hantaviruses; Paris, France.
16The full list of the authors and affiliations of this consortium can be found in the Supplementary Material.
17Laboratorio de Virología Molecular, Centro Ciencia & Vida, Fundación Ciencia & Vida, Santiago, Chile and Escuela de Bioquímica, Facultad de Ciencias, Universidad San Sebastián; Santiago, Chile.
18Escuela de Bioquímica, Facultad de Ciencias, Universidad San Sebastián; Santiago, Chile.
19Centre for Emerging Viral Diseases, Geneva University Hospitals and Faculty of Medicine, University of Geneva; Geneva Switzerland.
20Department of Medicine, Faculty of Medicine, University of Geneva; Geneva, Switzerland.
21Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva; Geneva, Switzerland.
*Corresponding author.
†These authors are the leads of the institutions that provided and shared initial data and contributed equally to this work.
‡These senior authors are the leads of the institutions that provided and shared initial data and contributed equally to this work.
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