Bunyavirus Infection: Symptoms, Types, Causes and Treatment

Bunyaviruses represent a diverse family of viruses with global distribution, notable for their capacity to cause a wide array of diseases in humans and animals. While many infections are mild or even asymptomatic, some bunyaviruses can provoke severe, life-threatening illnesses, including hemorrhagic fevers, encephalitis, and multiorgan dysfunction. Recent years have seen the emergence of novel bunyaviruses, like Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV), raising public health concerns and highlighting the need for greater awareness and research. In this comprehensive guide, we break down the symptoms, types, causes, and current treatment options for bunyavirus infections.

Symptoms of Bunyavirus Infection

Bunyavirus infections can present a broad spectrum of symptoms, ranging from mild, flu-like illness to severe, life-threatening conditions. Recognizing these symptoms early is crucial for prompt diagnosis and management.

Symptom	Severity	Commonly Associated Virus	Source(s)
Fever	Mild to Severe	SFTSV, BUNV	1245
Thrombocytopenia	Moderate-Severe	SFTSV	1245
Leukocytopenia	Moderate-Severe	SFTSV, others	125
Multiorgan Dysfunction	Severe	SFTSV	125
Hemorrhagic Signs	Severe	Rift Valley, Ngari	610
Encephalitis	Moderate-Severe	La Crosse, BUNV	610
Neurological Symptoms	Moderate-Severe	SFTSV, La Crosse	210
Pulmonary Disease	Moderate-Severe	Rift Valley, NRIV	610
Gastrointestinal	Mild-Moderate	SFTSV, others	24
Asymptomatic/Mild	Mild	Various	10

Table 1: Key Symptoms

Overview of Clinical Presentation

Symptoms depend on the specific bunyavirus, the patient’s age, and underlying health. While some infections cause only mild, non-specific symptoms, others can swiftly progress to severe disease.

Common Initial Symptoms

Most bunyavirus infections begin with non-specific symptoms such as:

• Sudden onset of fever
• Headache
• Malaise and muscle aches
• Gastrointestinal disturbances (nausea, vomiting, diarrhea) 24

Hallmark Features: SFTSV and Others

Severe Fever with Thrombocytopenia Syndrome (SFTS) is a prominent example of a severe bunyavirus infection. Its key features include:

• High fever
• Significant drop in platelet count (thrombocytopenia)
• Leukocytopenia (low white blood cell count)
• Elevated liver enzymes
• Multiorgan dysfunction, which can progress to failure 1245

Severe Manifestations

Some bunyaviruses, including SFTSV, Rift Valley Fever Virus, and Ngari Virus, can lead to:

• Hemorrhagic signs (bleeding, bruising)
• Neurological symptoms (confusion, seizures, encephalitis)
• Acute respiratory distress or pulmonary involvement 2610

Risk Factors for Severe Disease

Certain laboratory findings and clinical indicators can predict more severe outcomes in bunyavirus infections:

• Low albumin, low sodium
• Prolonged clotting times (APTT)
• Presence of neurological symptoms
• Acute lung injury and disseminated intravascular coagulation 2

Asymptomatic or Mild Infections

Many bunyavirus infections, particularly those caused by less virulent strains or in healthy individuals, may present with only mild, flu-like illness or remain completely asymptomatic 10.

Types of Bunyavirus Infection

The Bunyaviridae family encompasses numerous genera and species, each with unique epidemiological and clinical traits. Understanding the diversity of bunyaviruses is key to grasping the range of diseases they cause.

Virus/Group	Transmission	Geographical Range	Notable Disease(s)	Source(s)
SFTSV	Tick-borne	East Asia	SFTS, multiorgan failure	1248
Rift Valley Fever Virus	Mosquito-borne	Africa, Arabia	Hemorrhagic fever, encephalitis	610
La Crosse Virus	Mosquito-borne	North America	Encephalitis	1012
Bunyamwera Virus (BUNV)	Mosquito-borne	Africa	Mild flu-like, encephalitis	610
Ngari Virus	Mosquito-borne	Africa	Hemorrhagic fever	6
Heartland Virus	Tick-borne	USA	Fever, leukopenia, thrombocytopenia	710
Cache Valley Virus	Mosquito-borne	North America	CNS disease, birth defects	710
Others (Main Drain, Bhanja, Ingwavuma)	Various	Localized	Mild-moderate disease	710

Table 2: Main Types of Bunyaviruses and Associated Diseases

Major Genera and Key Viruses

The bunyaviruses are categorized into several genera relevant to human and animal health:

Phlebovirus

• SFTSV: Emerged in China, now reported in other Asian countries. Causes severe multiorgan disease with high mortality 1248.
• Rift Valley Fever Virus: Causes hemorrhagic fever and encephalitis, mainly in Africa and the Middle East 10.

Orthobunyavirus

• Bunyamwera Virus (BUNV): Found in Africa; can cause mild illness or neurological disease 610.
• Ngari Virus (NRIV): A reassortant that can cause severe hemorrhagic disease in Africa 6.
• La Crosse Virus: North American virus, notable for causing encephalitis in children 1012.
• Cache Valley Virus: North America; causes rare CNS disease and congenital defects 710.

Other Notable Viruses

• Heartland Virus: Discovered in the United States; causes SFTS-like illness 710.
• Bhanja, Main Drain, Ingwavuma Viruses: Less common, but still of veterinary and human health interest 7.

Geographic and Host Diversity

Bunyaviruses are globally distributed due to their use of various vectors (ticks, mosquitoes, sandflies) and broad host ranges, including humans, livestock, and wildlife 6710. Some, like SFTSV, have rapidly expanding endemic areas 8.

Animal and Human Disease

Many bunyaviruses are zoonotic, infecting both animals and humans. Outbreaks in livestock can precede or accompany human cases, as seen with Rift Valley fever 6. Some viruses, like Cache Valley virus, are also linked to reproductive losses in animals 7.

Causes of Bunyavirus Infection

Bunyavirus infections arise from a combination of viral, environmental, and host factors. Understanding how these viruses are transmitted and what increases risk is vital for prevention and control.

Cause/Factor	Description	At-Risk Group(s)	Source(s)
Arthropod Vectors	Ticks, mosquitoes, sandflies	Rural, outdoor workers	467810
Animal Reservoirs	Livestock, wildlife, birds	Farmers, animal handlers	468
Person-to-Person	Contact with blood/body fluids	Family, caregivers	38
Environmental Factors	Seasonality, geography	Residents in endemic areas	4810
Viral Reassortment	Genetic mixing of viruses	All populations	610

Table 3: Main Causes and Risk Factors for Bunyavirus Infection

Arthropod Transmission

Most bunyaviruses are transmitted by arthropod vectors:

• Ticks: Notably Haemaphysalis longicornis (SFTSV), and others for Heartland, Bhanja viruses 478.
• Mosquitoes: Primary vectors for Rift Valley fever, Bunyamwera, Ngari, La Crosse, Cache Valley viruses 610.
• Sandflies: Some phleboviruses use sandflies as vectors 10.

Animal Reservoirs

Many bunyaviruses persist in nature through cycles involving animal hosts:

• Domestic animals (sheep, goats, cattle, pigs, dogs, chickens) are important reservoirs for SFTSV, with high seroprevalence 48.
• Wildlife and birds can also harbor and amplify these viruses 610.

Person-to-Person Transmission

Although rare, direct human-to-human transmission has been documented:

• SFTSV can be transmitted via close contact with infected patients, particularly through blood or body fluids, highlighting risks for family members and healthcare workers 38.

Environmental and Demographic Risk Factors

• Seasonality: Many bunyavirus outbreaks occur in warmer months, coinciding with peak vector activity 48.
• Geography: Rural and forested regions are higher risk due to greater vector and animal reservoir presence 410.
• Age and Occupation: Older adults and those with outdoor jobs (farmers, herders) are more frequently affected 4.

Viral Evolution and Reassortment

Bunyaviruses have segmented genomes, allowing them to reassort and generate new variants with altered virulence or host range. This can lead to the emergence of novel, potentially more pathogenic viruses 610.

Treatment of Bunyavirus Infection

Managing bunyavirus infections poses significant challenges due to the lack of widely approved, specific antiviral therapies or vaccines. However, advances in experimental treatments offer hope.

Treatment Approach	Status/Effectiveness	Notes	Source(s)
Supportive Care	Mainstay	Fluids, organ support	2410
Ribavirin	Limited, variable efficacy	Some benefit in early use	1213
Favipiravir (T-705)	Promising, experimental	Shown to reduce mortality	121314
Diketo Acids	Experimental	Inhibits viral replication	15
Potassium Channel Modulators	Investigational	May inhibit infection	11
Polyamine Depletion	Research stage	Limits viral replication	9
Vaccines	Not available for humans	Some in animal research	4810

Table 4: Current and Emerging Treatments for Bunyavirus Infection

Supportive Care

• Key Approach: Supportive management remains the cornerstone for most bunyavirus infections.
• Measures include:
  • Intravenous fluids and electrolyte management
  • Monitoring and support of organ systems (renal, hepatic, respiratory)
  • Treatment of secondary infections and complications (e.g., DIC, acute lung injury) 2410

Antiviral Therapies

Ribavirin

• Usage: Has been used off-label with some benefit, especially in early infection stages. Its efficacy varies between viruses and is not universally established 1213.

Favipiravir (T-705)

• Recent Evidence: Favipiravir has demonstrated strong antiviral activity against a range of bunyaviruses. In clinical studies, it has reduced mortality in SFTS patients, with good tolerability except for some hepatic side effects 14. Animal and cell studies also show superiority to ribavirin 1213.
• Dosing: Administered orally, typically with a loading dose followed by maintenance doses for 7–14 days 14.

Diketo Acids

• Mode of Action: Inhibit the cap-snatching endonuclease vital for viral replication. Still in the experimental phase, but show promise for developing pan-bunyavirus antivirals 15.

Novel and Investigational Therapies

• Potassium Channel Modulators: Certain cellular potassium channels are essential for bunyavirus infection, and their modulation can block viral replication in cell studies 11.
• Polyamine Depletion: Targeting host cell polyamines disrupts bunyavirus replication and may stimulate antiviral immunity. This approach could offer new therapeutic strategies in the future 9.

Vaccine Development

• Status: No licensed vaccines exist for human use against bunyavirus infections. Some animal vaccines, particularly for Rift Valley fever, are in use. Development of human vaccines is ongoing but faces technical hurdles 4810.

Prognosis and Outcomes

• Mortality: Ranges by virus and patient. SFTS, for example, has reported case fatality rates from 10–15%, higher in severe cases with multiorgan failure 24814.
• Recovery: Early diagnosis and supportive care can improve outcomes. Emerging antiviral therapies like favipiravir may further reduce mortality 14.

Conclusion

Bunyavirus infections are complex, with a spectrum ranging from mild illness to severe, life-threatening disease. Awareness of their symptoms, transmission routes, and the latest treatment options is vital, especially as new and more pathogenic strains emerge. Ongoing research is crucial to develop effective antiviral therapies and vaccines.

Key Takeaways:

• Bunyaviruses cause a wide range of symptoms, from mild fever to severe multiorgan failure.
• SFTSV, Rift Valley fever, La Crosse, and Bunyamwera viruses are among the most clinically significant.
• Transmission occurs mainly via arthropod vectors (ticks, mosquitoes), animal reservoirs, and occasionally person-to-person.
• Supportive care is the mainstay of treatment; promising antivirals like favipiravir and innovative approaches are under investigation.
• No human vaccines are available yet; prevention relies on vector control and avoidance of exposure.

Staying informed on bunyavirus infection risks and advances in treatment is essential for clinicians, public health workers, and at-risk populations alike.