Andes Orthohantavirus: The Deadly Hantavirus That Can Spread Between Humans and Threaten Global Health!

 

Andes Orthohantavirus: A Deadly Virus with Unique Human-to-Human Transmission Capability and Global Control Challenges

 

ABSTRACT

 

Andes Orthohantavirus (ANDV) is a member of the genus Orthohantavirus within the family Hantaviridae and is recognized as the primary causative agent of Hantavirus Cardiopulmonary Syndrome (HCPS) in South America, particularly in Argentina and Chile. This virus exhibits unique biological characteristics compared with other hantaviruses because of its ability to transmit directly between humans. This article aims to review the biological properties, genomic characteristics, natural reservoirs, transmission mechanisms, pathogenesis, clinical manifestations, diagnostic approaches, and current management strategies for ANDV infection based on contemporary scientific literature. The study employed a narrative literature review by collecting and analyzing relevant scientific publications from international journals, epidemiological reports, and other reliable scientific sources. The findings indicate that ANDV is a negative-sense single-stranded RNA virus with a tripartite genome (S, M, and L segments) encoding the nucleocapsid protein, surface glycoproteins, and RNA-dependent RNA polymerase. The principal reservoir of the virus is the long-tailed pygmy rice rat (Oligoryzomys longicaudatus). Human infection generally occurs through inhalation of aerosols contaminated with rodent excreta; however, ANDV can also spread through close person-to-person contact. Disease pathogenesis is primarily associated with increased vascular permeability resulting from an exaggerated immune response, leading to acute pulmonary edema and cardiogenic shock. To date, no globally approved vaccine or specific antiviral therapy is available; therefore, early diagnosis and intensive supportive care remain the most important factors in reducing mortality. A comprehensive understanding of the biological and epidemiological characteristics of ANDV is essential for strengthening surveillance, prevention, and preparedness strategies against potential future outbreaks.

Keywords: Andes Orthohantavirus, Hantavirus Cardiopulmonary Syndrome, zoonosis, hantavirus, person-to-person transmission, pathogenesis.

 

INTRODUCTION

 

Hantaviruses are a group of zoonotic viruses primarily transmitted by rodents and capable of causing severe disease in humans. Based on their geographical distribution and clinical manifestations, hantaviruses are broadly classified into Old World hantaviruses, which generally cause Hemorrhagic Fever with Renal Syndrome (HFRS), and New World hantaviruses, which are associated with Hantavirus Cardiopulmonary Syndrome (HCPS) (Jonsson et al., 2010).

 

Among the New World hantaviruses, Andes Orthohantavirus (ANDV) is of particular public health significance. The virus was first identified in Argentina in 1995 following an outbreak of severe respiratory disease with a high case-fatality rate (Padula et al., 1998). Unlike most other hantaviruses, ANDV possesses the unique ability to spread directly from person to person, thereby increasing the risk of infection clusters and localized outbreaks (Martinez-Valdebenito et al., 2014).

 

ANDV infection causes HCPS, a disease characterized by a mortality rate of approximately 30–40%, acute respiratory distress, pulmonary edema, and cardiogenic shock (Vial et al., 2006). The high fatality rate and the absence of effective antiviral therapy make this virus an important zoonotic pathogen requiring special attention in public health, clinical medicine, and One Health frameworks.

 

This article provides a comprehensive review of the biological and genomic characteristics of ANDV, its natural reservoirs, transmission patterns, mechanisms of pathogenesis, clinical manifestations, and currently available diagnostic and management approaches.

 

METHODOLOGY

 

This study employed a narrative literature review approach. Data were collected from scientific publications in peer-reviewed international journals, epidemiological reports, documents issued by international health organizations, and authoritative virology reference books.

 

The literature selection criteria included publications addressing the biological characteristics, genomics, epidemiology, pathogenesis, diagnosis, and clinical management of Andes Orthohantavirus. The selected literature consisted primarily of English-language articles published between 1995 and 2025.

 

The collected information was analyzed descriptively and categorized into major thematic areas, including biological and genomic characteristics, reservoirs and transmission, pathogenesis and clinical manifestations, and diagnostic and management strategies.

 

RESULTS AND DISCUSSION

 

Biological and Genomic Characteristics of Andes Orthohantavirus

 

Physical Structure and Morphology

Andes Orthohantavirus is an enveloped virus with a spherical to pleomorphic morphology and a diameter ranging from approximately 80 to 120 nm (Elliott et al., 2013). The outer layer consists of a host-derived lipid membrane decorated with viral glycoprotein spikes that play a crucial role in viral attachment and entry into host cells.

 

The presence of a lipid envelope renders the virus susceptible to environmental factors. Exposure to heat, ultraviolet radiation, alcohol, detergents, and sodium hypochlorite solutions can disrupt the integrity of the viral envelope and eliminate infectivity (Kruger et al., 2015). Consequently, sanitation and disinfection procedures are highly effective in preventing viral spread.

 

GENOMIC ORGANIZATION

 

ANDV possesses a negative-sense single-stranded RNA genome composed of three segments.

The Small (S) segment encodes the nucleocapsid (N) protein, which protects viral RNA and plays important roles in viral replication and virion assembly (Jonsson et al., 2010).

The Medium (M) segment encodes a glycoprotein precursor that is subsequently processed into two envelope glycoproteins, Gn and Gc. These proteins are responsible for host-cell receptor recognition and viral entry (Mittler et al., 2019).

The Large (L) segment encodes the RNA-dependent RNA polymerase (RdRp), which mediates viral genome replication and transcription within the cytoplasm of infected cells (Elliott et al., 2013).

The segmented nature of the genome facilitates genetic variation through mutation and reassortment processes that may influence viral adaptation to reservoirs and potential new hosts.

 

NATURAL RESERVOIRS AND TRANSMISSION

Primary Zoonotic Reservoir

The principal natural reservoir of ANDV is the long-tailed pygmy rice rat (Oligoryzomys longicaudatus), a rodent species widely distributed in rural regions of Chile and Argentina (Padula et al., 2000).

 

In reservoir hosts, infection persists throughout life without causing apparent clinical disease. The virus is continuously shed through urine, feces, and saliva. Human infection generally occurs through inhalation of aerosolized viral particles originating from dried rodent excreta (Jonsson et al., 2010).

Human-to-Human Transmission

 

One of the most distinctive characteristics of ANDV is its ability to undergo person-to-person transmission. This phenomenon has not been consistently demonstrated for most other New World hantaviruses (Martinez-Valdebenito et al., 2014).

 

Transmission typically occurs through prolonged close contact with infected individuals during the early phase of illness. Exposure to respiratory droplets, saliva, and other bodily fluids is believed to contribute to viral spread. Several epidemiological investigations have documented transmission chains within households and closed communities.

 

Genomic analyses of outbreak-associated strains indicate that such transmission is not primarily driven by major mutations enhancing viral transmissibility but is more closely associated with the intensity and duration of interpersonal contact (Ferres et al., 2007).

 

Potential Sexual Transmission

 

Recent studies have detected ANDV RNA in semen samples from survivors several months after clinical recovery (Castillo et al., 2022). These findings suggest the possibility of sexual transmission, although its epidemiological significance remains to be fully elucidated.

 

PATHOGENESIS AND CLINICAL MANIFESTATIONS

 

ANDV infection in humans can progress to HCPS, a disease associated with a mortality rate of approximately 30–40% (Vial et al., 2006).

 

Incubation Period and Prodromal Phase

 

The incubation period ranges from 4 to 42 days. Initial symptoms are generally influenza-like and include:

• High fever;
• Myalgia, particularly involving the thighs and lower back;
• Headache;
• Nausea and vomiting;
• General malaise.

Because these manifestations are nonspecific, diagnosis is frequently delayed during the early stages of disease.

 

Cardiopulmonary Phase

 

Following the prodromal stage, patients may rapidly deteriorate and develop a cardiopulmonary syndrome characterized by:

• Progressive dyspnea;
• Severe hypoxemia;
• Non-cardiogenic pulmonary edema;
• Cardiogenic shock;
• Acute respiratory failure.

 

Mechanisms of Tissue Injury

 

The primary target of ANDV is the vascular endothelial cell, particularly within the pulmonary capillary network. Notably, the virus does not directly induce cytopathic damage to infected cells.

Instead, tissue injury is largely mediated by an excessive immune response. Activation of T lymphocytes and the release of pro-inflammatory cytokines, including interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and interferon-gamma, result in a marked increase in vascular permeability (Mori et al., 2015).

Consequently, plasma fluid leaks from the vasculature into pulmonary tissues, leading to acute pulmonary edema. This condition represents the principal cause of respiratory failure and death in patients with HCPS.

 

DIAGNOSIS AND CLINICAL MANAGEMENT

 

Laboratory Diagnosis

Confirmation of ANDV infection relies on specific laboratory testing.

 

Serological Testing

The Enzyme-Linked Immunosorbent Assay (ELISA) is commonly used to detect ANDV-specific IgM and IgG antibodies. Detection of IgM indicates acute infection, whereas IgG suggests previous exposure or the convalescent phase of disease (Jonsson et al., 2010).

 

RT-PCR

Reverse Transcription Polymerase Chain Reaction (RT-PCR) is used for direct detection of viral RNA in blood or other clinical specimens. This method is particularly valuable during the early stage of infection before antibody responses become fully detectable (Kruger et al., 2015).

 

Clinical Management

To date, no specific antiviral therapy or globally approved vaccine is available for the treatment or prevention of ANDV infection.

Clinical management is primarily based on intensive supportive care, including:

• Close hemodynamic monitoring;
• Oxygen therapy;
• Mechanical ventilation for severe respiratory failure;
• Careful fluid management;
• Vasopressor support in cases of shock.

In critically ill patients, the use of Extracorporeal Membrane Oxygenation (ECMO) has been shown to improve survival outcomes in cases of massive pulmonary edema and refractory respiratory failure (Crowley et al., 2018). Treatment success depends heavily on early diagnosis and prompt access to intensive care facilities.

 

CONCLUSION

 

Andes Orthohantavirus is a New World hantavirus distinguished by its unique capacity for person-to-person transmission in addition to zoonotic transmission through rodent reservoirs. The virus possesses a tripartite RNA genome encoding proteins essential for infection and replication. Its primary reservoir is Oligoryzomys longicaudatus, which sheds the virus throughout its lifetime without exhibiting clinical disease.

 

The pathogenesis of human infection is characterized by increased vascular permeability driven by an exaggerated immune response, resulting in acute pulmonary edema and cardiogenic shock, the hallmark features of HCPS. Given the persistently high mortality rate and the absence of approved vaccines or specific antiviral therapies, control efforts should focus on reducing rodent exposure, promoting early case detection, strengthening surveillance systems, and ensuring access to adequate intensive care services. Further research on human-to-human transmission mechanisms, viral persistence, and vaccine development remains essential to mitigate the public health impact of ANDV.

 

REFERENCES

 

Castillo, C., Moreno, G., Vial, C., & Ferres, M. (2022). Persistence of Andes hantavirus RNA in semen and implications for transmission. Viruses, 14(5), 1012.

 

Crowley, M. R., Katz, R. W., Kessler, R., Simpson, S. Q., & Levy, H. (2018). Successful use of extracorporeal membrane oxygenation in hantavirus cardiopulmonary syndrome. Critical Care Medicine, 46(1), e66–e70.

 

Elliott, R. M., Schmaljohn, C. S., & Collett, M. S. (2013). Bunyaviridae and Hantaviridae: Molecular biology and replication strategies. In Fields Virology (6th ed.). Philadelphia: Lippincott Williams & Wilkins.

 

Ferres, M., et al. (2007). Prospective evaluation of household contacts of persons with hantavirus cardiopulmonary syndrome in Chile. Journal of Infectious Diseases, 195(11), 1563–1571.

 

Jonsson, C. B., Figueiredo, L. T. M., & Vapalahti, O. (2010). A global perspective on hantavirus ecology, epidemiology, and disease. Clinical Microbiology Reviews, 23(2), 412–441.

 

Kruger, D. H., Figueiredo, L. T. M., Song, J. W., & Klempa, B. (2015). Hantaviruses—Globally emerging pathogens. Journal of Clinical Virology, 64, 128–136.

 

Martinez-Valdebenito, C., et al. (2014). Person-to-person household and nosocomial transmission of Andes hantavirus, southern Chile. Emerging Infectious Diseases, 20(10), 1629–1636.

 

Mittler, E., et al. (2019). Hantavirus entry: Perspectives and recent advances. Advances in Virus Research, 104, 185–224.

 

Mori, M., et al. (2015). High levels of cytokine-producing cells in the lungs of patients with hantavirus pulmonary syndrome. Journal of Infectious Diseases, 193(3), 365–371.

 

Padula, P. J., et al. (1998). Hantavirus pulmonary syndrome outbreak in Argentina caused by person-to-person transmission of Andes virus. Virology, 241(2), 323–330.

 

Padula, P. J., et al. (2000). Genetic diversity, distribution, and serological features of hantavirus infection in Argentina. Journal of Clinical Microbiology, 38(8), 3029–3035.

 

Vial, P. A., et al. (2006). High-dose intravenous methylprednisolone for hantavirus cardiopulmonary syndrome in Chile: A double-blind, randomized controlled clinical trial. Clinical Infectious Diseases, 42(4), 501–506.

 

#AndesOrthohantavirus 

#Hantavirus 

#HCPS 

#ZoonoticDisease 

#GlobalHealth