Transmission and genomics of 2025-2026 Andes orthohantavirus clusters

Environmental Drivers and Terrestrial Ecology

The emergence and spillover of zoonotic pathogens are fundamentally tied to the ecological dynamics of their terrestrial reservoirs. In the case of the Andes orthohantavirus (ANDV), the primary recognized reservoir is the long-tailed pygmy rice rat (Oligoryzomys longicaudatus), a species deeply integrated into the temperate Valdivian rainforests and Andean-Patagonian forests of southern Chile and Argentina ¹²³. The epidemiological trajectory of the 2025-2026 ANDV clusters was heavily influenced by regional climatic extremes and the ecological cycles of local vegetation, which collectively drove increased rodent density and human-wildlife interface.

Bamboo Masting Cycles and Rodent Dynamics

The population density of O. longicaudatus is highly susceptible to "pulsed resources" in the environment. The most significant of these ecological pulses is the gregarious, synchronous flowering (masting) of native woody bamboo species, primarily Chusquea culeou and Chusquea quila ⁴⁵⁶. These bamboo species function as keystone elements in the forest understory and exhibit monocarpy, meaning they remain in a vegetative state for decades before a massive, synchronized blooming event occurs, followed by widespread plant death and seed drop ²⁷⁸.

The reproductive cycles of these bamboos vary significantly by species. C. quila typically exhibits a modal flowering cycle of 12 to 15 years, while C. culeou possesses a much longer cycle, historically recorded between 30 and 60 years ⁶⁷⁹. When these masting events occur, the sudden, overwhelming availability of highly nutritious seeds triggers an explosive reproductive response in granivorous rodents. This sudden population irruption is locally termed a ratada ⁴⁶¹⁰. Historical data confirms that numerous ratadas in southern South America over the past century have directly followed Chusquea blooms, leading to sharp increases in hantavirus spillover events as starving, hyper-abundant rodents subsequently invade human settlements and agricultural areas in search of alternative food sources during the winter die-off ⁴¹⁰¹¹.

While comprehensive botanical field confirmation of a pan-Patagonian Chusquea masting event specific to 2025 is not definitively established in the literature, environmental monitoring indicates that the ecological preconditions for severe rodent displacement were highly active ¹¹¹². Additionally, historical records note that the aftermath of bamboo flowering and death leaves vast quantities of dry, highly flammable biomass in the forest understory, drastically altering soil properties and compounding the risk of environmental disturbances ¹³.

Climate Anomalies in Patagonia

Compounding the biological cycles of the reservoir host, the late 2025 and early 2026 seasons featured severe climate anomalies that significantly disrupted the Patagonian ecosystem. Driven by a persistent La Niña phase and the Southern Annular Mode, the region experienced extreme anticyclonic anomalies that established warm and profoundly dry conditions ¹⁴¹⁶.

Meteorological data indicates that precipitation levels from November 2025 to January 2026 dropped by approximately 20% in Argentine Patagonia and 25% in central Chile compared to pre-industrial baselines ¹⁴¹⁶. This acute moisture deficit led to severe soil stress and vegetation die-off. Utilizing the heat-dryness-wind index (HDWI), climatologists determined that the likelihood of extreme fire conditions increased by a factor of 2.5 in Argentine Patagonia and 3.0 in central Chile due to anthropogenic global warming and these acute cyclical anomalies ¹⁴¹⁵.

The resulting environmental degradation - marked by over 3,800 focal forest fires recorded in Chile since July 2025 and severe outbreaks in Argentina's Los Alerces National Park - destroyed vast tracts of primary O. longicaudatus habitat ¹⁴¹⁶. This widespread habitat destruction is an established driver of zoonotic spillover, as displaced rodent populations are forced into peri-urban and rural human environments, thereby escalating the probability of human exposure to aerosolized rodent excreta ³¹⁶.

Regional Epidemiology in South America

The confluence of ecological disturbances and displaced rodent populations resulted in a highly active and lethal epidemiological season for hantavirus cardiopulmonary syndrome (HCPS) in both Argentina and Chile during 2025 and early 2026.

Incidence Trends in Argentina

The Argentine public health apparatus reported a historically severe outbreak period. According to the National Epidemiological Bulletin, Argentina recorded 101 to 102 confirmed cases of hantavirus between the beginning of the epidemiological season in early July 2025 and the end of April 2026 ^17181920. This figure maintained the national incidence rate at 0.21 cases per 100,000 inhabitants, keeping the country above the official outbreak threshold for nearly the entire analyzed period ¹⁷²⁰.

The 2025-2026 case count represents a 77% increase over the preceding 2024-2025 season (which saw 57 cases) and easily surpassed recent elevated seasons in 2023-2024 (75 cases) and 2019 ²⁰²¹. Within the calendar year of 2026 alone, 41 to 42 new infections were recorded by May ¹⁷¹⁸²⁰. The geographic distribution of the virus was widespread but concentrated in specific regions. The Central Region accounted for 54% of national cases, heavily driven by the province of Buenos Aires ¹⁷¹⁸. However, the Northwest Region exhibited the highest per capita incidence rate at 0.60 cases per 100,000 inhabitants, with the province of Salta accounting for 83% of the cases in that specific zone ¹⁷¹⁸.

Despite a lower absolute case count in the Southern Region (Patagonia), the epidemiological profile of the cases in provinces like Chubut, Río Negro, and Neuquén was critical due to the endemicity of the highly virulent Andes orthohantavirus ¹¹¹⁷²¹. During the 2025-2026 season, authorities closely monitored an intrafamilial cluster in the locality of Cerro Centinela (Chubut) involving three cohabitating individuals. Subsequent environmental focus studies in the area captured wild rodents that tested positive for ANDV, confirming active local zoonotic transmission ¹⁹. Nationally, the outbreak resulted in 32 confirmed deaths, pushing the case fatality rate (CFR) for the Argentine season to 31.7%, a figure matching the upper bounds of historical lethality for the Andes strain ¹⁸²⁰.

Epidemiological Situation in Chile

Parallel viral activity was documented in Chile, which shares the Patagonian ecosystem and the O. longicaudatus reservoir. The Chilean Ministry of Health (MINSAL) reported a sharp increase in lethality and widespread geographic distribution of the virus ¹⁶²²²³.

By the first week of May 2026, Chile had confirmed 39 to 44 cases of HCPS since the beginning of the year ^22232425. The infections were distributed across nine of the country's regions, spanning from the Metropolitan area down to Aysén, including O'Higgins, Maule, Ñuble, Biobío, La Araucanía, Los Ríos, and Los Lagos ²²²⁴. The outbreak claimed 13 lives, establishing a CFR of 33% ²²²³. This represents a significant escalation in virulence or a shift in diagnostic capture compared to the prior year; in 2025, Chile recorded 44 cases total with 8 deaths, yielding a CFR of 18% ¹⁶¹⁸²³.

Public health officials maintained a continuous epidemiological alert, noting that the Andes variant is the sole etiologic agent of human hantavirus confirmed in Chile ²²²⁴. To mitigate exposure in the context of the elevated case counts, authorities advised strict environmental controls, including ventilating enclosed rural spaces for at least 30 minutes prior to entry and disinfecting surfaces with a chlorine-water solution to neutralize viral particles ¹⁶²².

Table 1 summarizes the regional epidemiological statistics for the 2025-2026 season prior to and concurrent with the maritime cluster.

The MV Hondius Cruise Ship Outbreak

Against the backdrop of heightened regional endemicity in South America, an anomalous and severe cluster of ANDV emerged in April 2026 aboard the Dutch-flagged expedition cruise ship, the MV Hondius. The event represents one of the most operationally complex hantavirus outbreaks in history, demonstrating how long-incubation pathogens can intersect with maritime environments and global travel networks ²⁶²⁹²⁷.

Outbreak Timeline and Case Progression

The MV Hondius is an expedition vessel specialized in navigating remote polar and sub-polar environments. On April 1, 2026, the ship departed from Ushuaia, Argentina - the southernmost city in Tierra del Fuego - carrying between 147 and 149 passengers and crew members representing 23 different nationalities ^26282930. The vessel's transatlantic itinerary included stops across isolated environments in the South Atlantic, including mainland Antarctica, South Georgia, Nightingale Island, Tristan da Cunha, Saint Helena, and Ascension Island, with a scheduled route toward Cabo Verde ²⁶³⁰³¹.

The index case (Case 1), an adult male, began exhibiting symptoms on April 6, 2026, a mere five days after the vessel's departure from Argentina ²⁷²⁹. The initial clinical presentation included fever, headache, abdominal pain, and diarrhea - symptoms that align with the non-specific prodromal phase of hantavirus infection ²⁷²⁹. Driven by the rapid cardiopulmonary deterioration characteristic of ANDV, the index case died onboard on April 11 ²⁷²⁹. At the time, the specific etiology of the illness remained unknown to the ship's medical staff.

The outbreak remained epidemiologically opaque for several weeks. During a scheduled stop in Saint Helena on April 24, approximately 30 passengers disembarked, including the wife of the index case (Case 2), while the body of Case 1 was removed from the vessel ²⁷²⁹. Most of these disembarked passengers boarded commercial flights, transiting through Johannesburg, South Africa, to reach their home countries ²⁹³². Shortly after arriving and collapsing at the airport in Johannesburg, Case 2 died ²⁷²⁹. A third passenger (Case 3), who had fallen ill aboard the ship on April 22, was subsequently medically evacuated to South Africa on April 27, where he was admitted to an intensive care unit (ICU) ²⁹³¹³³.

Diagnostic clarity was finally achieved in early May. On May 2, polymerase chain reaction (PCR) testing of serum and blood samples from Case 3 confirmed hantavirus infection ²⁹³³. The following day, May 3, testing confirmed the presence of hantaviral RNA in the post-mortem samples of Case 2 ²⁹³¹.

Evacuation and Contact Tracing Operations

Genomic sequencing conducted by the National Institute for Communicable Diseases (NICD) in South Africa, alongside affiliated institutes in Switzerland and the Netherlands, rapidly identified the pathogen as the Andes orthohantavirus ²⁹³⁴. Because ANDV is the only hantavirus strain with documented human-to-human transmissibility, the confirmation prompted an immediate international health emergency response coordinated by the World Health Organization (WHO) and the European Centre for Disease Prevention and Control (ECDC) ^29283031.

By May 12, 2026, the cluster had grown to include between eight and eleven suspected or confirmed cases, including three fatalities ^17272835. Due to the severe nature of the illness, the MV Hondius was held stationary off the coast of Cabo Verde, as local facilities lacked the capacity for safe medical evacuation ²⁷²⁸. Once clearance was granted by the Spanish Ministry of Health, the vessel sailed to Tenerife in the Canary Islands, where final medical evacuations and repatriations were conducted under stringent biocontainment protocols on May 10 ²⁷²⁸.

Epidemiological consensus suggests that the index case was exposed to the virus via environmental zoonotic spillover in Argentina prior to embarkation ²³³⁰. The incubation period for ANDV ranges from 7 to 42 days, making the April 6 symptom onset perfectly aligned with exposure on the South American mainland in late March ²⁸³⁹³⁶. However, the subsequent secondary cases aboard the vessel - including the spouse of the index case, another passenger, and the ship's doctor - strongly indicated instances of onboard human-to-human transmission facilitated by the confined maritime environment ²⁶²⁷³². Consequently, an extensive international contact tracing operation was launched to monitor the 30 passengers who had disembarked early and utilized commercial flights (such as Airlink flight 4Z 132 from Saint Helena), highlighting the capacity of a virus with a long incubation period to infiltrate global transit networks ²⁷³².

Genomic Characteristics of the 2026 Strain

The successful identification of the MV Hondius cluster was the result of a coordinated multinational effort utilizing advanced genomic techniques. Participating laboratories in South Africa, Senegal, Switzerland, and the Netherlands employed sequence-independent single-primer amplification (SISPA), unbiased metagenomics, and TWIST capture-based enrichment using Illumina and Oxford Nanopore platforms to secure full viral genomes directly from clinical samples ³⁴.

Sequence Identity and Phylogenetic Relationships

Analysis of the viral RNA definitively confirmed the pathogen as Orthohantavirus andesense. The consensus sequences from the 2026 maritime cluster demonstrated an exceptionally high degree of sequence identity with historical ANDV strains known for severe lethality and interhuman transmissibility in Argentina.

Specifically, when compared to the well-documented human-isolated strains from the 1997 and 2018 Argentine outbreaks, the 2026 sequences shared over 98.7% identity across all three viral segments ²⁹³⁴. The virus's tripartite RNA genome consists of the L segment (encoding the RNA-dependent RNA polymerase), the M segment (encoding the Gn and Gc envelope glycoproteins), and the S segment (encoding the nucleocapsid protein and small nonstructural protein, NSs) ³⁷³⁸.

Table 2 illustrates the precise nucleotide sequence identity of the 2026 MV Hondius strain segments relative to the 1997 and 2018 benchmark sequences.

Nucleotide Polymorphisms and Viral Stability

A defining genomic hallmark of the MV Hondius cluster was the profound stability observed across the infected individuals. Genomic sequencing of the S and M segments revealed that they were entirely identical across all tested patients within the cluster, indicating a stark lack of viral diversity ²⁹³⁹. This genetic uniformity strongly supports the epidemiological hypothesis that the outbreak originated from a single zoonotic spillover event, or a very limited number of closely related events, which then propagated via an unbroken chain of human-to-human transmission ²⁹³⁹.

Detailed comparative alignment of the L segment (relative to the reference sequence MN258159) identified only two "true" single nucleotide polymorphisms (SNPs) distinguishing specific cases within the outbreak: a transition at position C2139T (detected in Case 5) and G576A (detected in Case 7) ²⁹³⁴. Both of these isolated SNPs were synonymous mutations, meaning they did not alter the amino acid sequence of the RNA-dependent RNA polymerase ²⁹³⁴.

This absence of coding mutations confirms that the virus did not require novel or rapid phenotypic adaptation to sustain human-to-human transmission aboard the ship ³⁹. This observation aligns with experimental in vivo research utilizing the Syrian hamster model, which faithfully recapitulates human HCPS. Studies tracking the human-isolated ANDV strain CHI-7913 demonstrated that even over 25 serial passages in mammals, the virus accumulated only a single coding mutation ⁴⁰⁴¹. The data suggests that wild-type ANDV circulating in the rodent reservoir is already fully competent for human infection and limited interhuman spread, requiring no intermediate evolutionary pressure ³⁹⁴¹.

Structural Biology and Glycoprotein Architecture

Recent advances in structural virology have provided deep insights into the mechanical functionality of the highly conserved ANDV genome. By leveraging virus-like particle (VLP) systems, researchers have successfully established cryo-electron microscopy workflows capable of determining the structure of the membrane-embedded ANDV glycoprotein tetramer (Gn-Gc) at a 2.35 Å resolution ³⁷⁴².

These high-resolution structures reveal previously uncharacterized features of glycoprotein organization, lattice formation, stability, and pH-sensing - critical components for viral assembly and cellular entry ³⁷⁴². While these structures define the baseline mechanics of hantavirus infection, comparative genomic studies point to specific amino acid configurations within these glycoproteins and the small nonstructural protein (NSs) that dictate virulence. Research has identified discrete amino acid substitutions in the NSs and glycoprotein open reading frames that correlate specifically with the clade of ANDV strains capable of efficient person-to-person spread, distinguishing them from purely zoonotic strains ³⁸. Immunological research utilizing self-amplifying replicon RNA (repRNA) encoding these ANDV-VLPs has shown promise in eliciting robust glycoprotein-binding antibodies, laying the groundwork for future structure-based vaccine designs, though currently no approved vaccines exist in the Americas ³⁹³⁷⁴².

Transmission Dynamics and Interhuman Spread

The global landscape of hantaviruses encompasses dozens of distinct species, the vast majority of which - including the Sin Nombre virus in North America and the Puumala and Hantaan viruses in Eurasia - are strictly zoonotic ³⁹⁴³⁴⁸. The Andes orthohantavirus is unique within the Bunyavirales order as the sole agent with a verified capacity for direct human-to-human transmission ²⁹³⁶⁴⁴.

Zoonotic Aerosolization and Viral Entry

The transmission architecture of ANDV relies on dual pathways: primary zoonotic spillover followed by secondary interhuman spread. Primary infection occurs predominantly via the inhalation of aerosolized excreta (urine, feces, and saliva) from the O. longicaudatus reservoir ²⁹³⁹⁴³. This typically occurs when humans encroach upon infested environments or disturb desiccated rodent droppings during activities such as sweeping enclosed cabins or agricultural sheds, which lofts infectious virions into the air ³⁹⁴³⁴⁵.

Following the primary zoonotic introduction, ANDV allows for secondary human-to-human transmission. Unlike highly contagious respiratory pathogens such as SARS-CoV-2 - which utilize ACE2 receptors in the upper respiratory tract for rapid replication and easy exhalation - hantaviruses bind to β3 integrins ³⁵. These integrin receptors are located deep within the pulmonary architecture and on the inner lining of vascular endothelial cells ³³⁵. Consequently, simple exhalation, sneezing, or casual social contact sheds very little virus. Instead, secondary transmission requires sustained close proximity to an infected individual, facilitating the transfer of deeper respiratory droplets or salivary aerosols ³⁵³⁹⁴⁶.

Secondary Attack Rates and Superspreading

The kinetics and efficiency of ANDV's interhuman spread differ fundamentally from viruses that cause mass pandemics. The most exhaustive baseline for ANDV transmission dynamics is derived from the 2018-2019 outbreak in Epuyén, Argentina. Triggered by a single rodent-to-human infection, the virus spread through 34 confirmed cases due to three symptomatic individuals attending crowded social gatherings (a birthday party and a funeral) ²⁸⁴⁷.

Prior to the implementation of aggressive public health interventions, including strict quarantine and isolation, the estimated basic reproduction number (R0) in Epuyén was 2.12 ²⁸⁴⁷. Subsequent contact tracing and reanalysis of the cluster revealed that household members exposed during the late prodromal phase exhibited a secondary attack rate (SAR) of approximately 8%, while sexual partners faced a significantly higher transmission risk of 17.6% ²⁸⁴⁶.

A critical limiting factor in ANDV's spread is the timing of patient infectivity. COVID-19 thrives on presymptomatic transmission, with estimates suggesting up to 44% of secondary infections occur before the index case feels ill ²⁸. ANDV, however, requires the patient to reach the late prodromal phase - the period marked by high fever and intense viremia just prior to cardiopulmonary collapse - to become infectious ^28464849. Because patients rapidly deteriorate into severe respiratory distress, their ability to circulate in the community and act as superspreaders over an extended period is severely curtailed ²⁸.

On the MV Hondius, the transmission efficiency proved lower than in severe terrestrial clusters but functionally lethal in the confined maritime setting. Generating roughly 8 to 11 infections from a pool of 147 passengers over five weeks, the attack rate aboard the ship hovered near 5% to 7% ²⁸.

Table 3 compares the transmission metrics of historical ANDV outbreaks against a benchmark respiratory virus.

Airborne Transmission and Ventilation in Confined Settings

The emergence of a cluster on a modern cruise ship prompted intense debate regarding the mechanics of airborne versus droplet transmission and the role of HVAC systems. The WHO traditionally frames hantavirus interhuman spread around droplet and contact precautions ⁴⁸⁵¹. However, the physical realities of the MV Hondius challenged this paradigm.

Epidemiological experts and the ECDC argued that in enclosed spaces - where individuals share cabins, dining rooms, and corridors for extended periods - the concentration of exhaled breath effectively acts as an aerosol hazard, blurring the operational distinction between large droplets and true airborne transmission ²⁶⁴⁸. Consequently, public health recommendations for managing the maritime cluster shifted toward treating ANDV as an airborne threat. Stringent interventions were mandated, prioritizing the optimization of ventilation, the absolute avoidance of unfiltered air recirculation, the deployment of portable High-Efficiency Particulate Air (HEPA) filters in quarantine zones, and the required use of N95 or FFP2 respirators for all healthcare workers and high-risk contacts during medical evacuations ³¹⁴⁸.

Clinical Profile and Pathogenesis

Once human infection is established, the pathogenesis of ANDV is exceptionally severe, governed by the virus's specific cellular tropism and the profound systemic immune response it provokes in the host.

Symptomatology and Prodromal Shedding

The clinical progression of ANDV makes early detection extraordinarily difficult. Following an incubation period averaging 2 to 4 weeks (but ranging anywhere from 7 to 42 days), patients enter a non-specific prodromal phase ²⁸³⁹³⁶. Initial symptoms mimic severe influenza or gastrointestinal infections: sudden onset high fever, severe myalgia (particularly in the large muscle groups of the thighs, hips, and back), intense headache, dizziness, nausea, vomiting, and abdominal pain ^26303648.

This lack of distinctive early symptoms often leads to misdiagnosis in non-endemic areas ³⁰⁴³. Crucially, it is during this late prodromal window - when viremia peaks and viable virus becomes detectable in saliva and respiratory secretions - that patients are most infectious to their close contacts ²⁸⁴⁶⁴⁸.

Cardiopulmonary Phase and Therapeutic Interventions

Within one to seven days of the prodromal onset, the disease rapidly transitions into the cardiopulmonary phase ²⁸³³. The ANDV glycoproteins target β3 integrins, facilitating viral entry into vascular endothelial cells ³³⁵. Rather than causing direct cytopathic cell death, the virus triggers a massive, dysregulated inflammatory cascade - often described as the immune system going into "overdrive" ⁵²⁵³.

This robust host immune response induces extreme vascular permeability, causing blood plasma to leak uncontrollably from the capillaries into the alveolar spaces. This non-cardiogenic pulmonary edema effectively fills the lungs with fluid, precipitating acute respiratory distress syndrome (ARDS), profound hypotension, hemodynamic instability, and shock ³⁵⁴⁸⁵³.

Currently, there are no approved targeted antiviral therapeutics for ANDV (while ribavirin has shown promise in HFRS, evidence for HCPS remains inconclusive), nor are there any licensed vaccines available in the Americas or Europe ²⁹³⁹⁴⁸. Patient survival hinges entirely on early admission to an intensive care unit for aggressive supportive care. Treatment protocols mandate fluid and electrolyte management, vasopressors, mechanical ventilation, and, in severe cases of cardiopulmonary failure, early referral for extracorporeal membrane oxygenation (ECMO) ³²⁹³⁹.

Public Health Implications

The 2025-2026 Andes orthohantavirus clusters vividly illustrate the fragile boundaries separating shifting ecological systems from modern global transit networks. In Patagonia, acute climate extremes exacerbated by La Niña and widespread environmental disturbances disrupted the equilibrium of terrestrial rodent reservoirs, precipitating a historically severe epidemiological season characterized by mortality rates exceeding 31%.

When this heightened regional endemicity intersected with the enclosed, high-density environment of an international cruise ship, it provided a highly visible testing ground for ANDV's unique biological capability: human-to-human transmission. Genomic analyses confirm that the outbreak was not the product of a novel viral mutation, but rather the exploitation of an enclosed environment by a wild-type virus inherently capable of interhuman spread during its prodromal phase.

The MV Hondius event serves as a critical warning regarding zoonotic spillover. It demonstrates that public health paradigms must proactively address pathogens possessing latent interhuman transmission capabilities. However, the successful containment of the cruise ship cluster via rapid international genomic sequencing, the cessation of air recirculation, and rigorous contact tracing confirms that while ANDV is highly lethal, its transmission chains can be broken through classical epidemiological interventions. Moving forward, integrating ecological surveillance of terrestrial reservoir populations with heightened awareness in the global travel and maritime sectors will be essential to anticipating and neutralizing future viral incursions before they escalate into uncontrolled regional emergencies.