The Silent Spread of Toscana Virus: A Climate-Sensitive Threat
A growing health concern across the Mediterranean basin with potential for global expansion
Introduction
Imagine a summer headache so severe it lands you in the hospital with meningitis, all from an unseen bite of a tiny sand fly. This isn't a hypothetical scenario but the reality for a growing number of people across the Mediterranean basin infected with Toscana virus (TOSV). First identified in Italy in 1971, this neglected pathogen has become a leading cause of summer meningitis in regions where it circulates 1 7 .
2.6x
Increase in cases in Italy (2022-2023)
1971
Year of first identification
0.43%
Case fatality rate
What began as a localized health concern is now demonstrating an alarming pattern of geographic expansion, fueled by climate change and the adaptable nature of its insect vectors. With cases in Italy soaring 2.6 times higher in recent years, understanding this virus's ecology and global distribution is more critical than ever 4 . This article explores the hidden world of Toscana virus, from its biological mechanisms to its potential path toward becoming a broader global health threat.
What is Toscana Virus?
The Virus and Its Family
Toscana virus is a negative-sense RNA virus belonging to the Phlebovirus genus within the Phenuiviridae family 1 . Its genetic material is composed of three segments – small (S), medium (M), and large (L) – each encoding different viral components 1 . The virus particle is enveloped and approximately 100 nm in diameter, featuring surface glycoproteins that help it attach to and enter host cells 1 3 .
Transmission and Vectors
Unlike many familiar viruses that spread through respiratory droplets or direct contact, TOSV is an arbovirus – arthropod-borne – transmitted specifically through the bite of infected sand flies 1 . The primary vectors are Phlebotomus perniciosus and Phlebotomus perfiliewi, species whose distribution dictates where the virus can establish itself 5 .
Clinical Impact and Symptoms
From Mild Fever to Meningitis
TOSV infection presents a clinical spectrum ranging from no symptoms to severe neurological disease:
- Asymptomatic or Mild Illness: The majority of infections cause no symptoms or result in a mild, flu-like illness often called "sand fly fever" or "pappataci fever" 4 7 . This non-specific presentation includes fever, headache, muscle aches, and weakness, typically lasting 2-4 days 7 .
- Neuroinvasive Disease: In a significant minority of cases, the virus crosses into the central nervous system, causing aseptic meningitis, meningoencephalitis, or encephalitis 1 2 . Symptoms include intense headache, neck stiffness, fever, and occasionally more severe neurological manifestations 2 7 .
Epidemiology and Risk Groups
A comprehensive analysis of 1,381 cases revealed that the median patient age is 44.5 years, with males being twice as commonly affected as females 2 . The same study identified that while the case fatality rate is low at 0.43%, fatalities primarily affect patients over 65 years with comorbidities such as diabetes and hypertension 2 .
Clinical Profile of TOSV Infection
| Parameter | Finding | Notes |
|---|---|---|
| Median Age | 44.5 years | Affects all age groups |
| Gender Distribution | 2:1 Male to Female ratio | Possible behavioral or biological factors |
| Most Common Symptoms | Fever, Headache | Present in majority of symptomatic cases |
| Neuroinvasive Forms | Meningitis most common | Encephalitis less frequent |
| Case Fatality Rate | 0.43% | Primarily in elderly with comorbidities |
Global Distribution and Expanding Risk
Traditional Endemic Zones
TOSV was first identified in central Italy and has been well-established across the Mediterranean basin, including countries such as:
- Spain, Portugal, and France 5
- Greece and Cyprus 7
- Croatia and Turkey 1
- North African nations including Tunisia 7
In some of these regions, particularly central Italy, TOSV has surpassed enteroviruses as the leading cause of viral meningitis during summer months 1 .
Recent Expansion and Climate Linkage
Recent data indicates a concerning expansion in both the incidence and geographic range of TOSV:
Incidence Increase
In Italy, neuroinvasive TOSV infections increased nearly 2.6-fold in 2022-2023 compared to 2016-2021, with the annual incidence rising from 0.92 to 2.34 per million people 4 .
Geographic Spread
Cases are now being reported in previously unaffected Italian regions, including Sardinia, Molise, Umbria, and Trento 4 .
Climate Connection
Researchers attribute this expansion to climate anomalies, particularly record-high temperatures and prolonged dry periods, which create ideal conditions for sand fly proliferation 4 .
High-Risk Regions and Their Characteristics
| Region | Transmission Level | Primary Vectors | Notes |
|---|---|---|---|
| Central Italy (Tuscany) | High | P. perniciosus, P. perfiliewi | Original endemic focus |
| Emilia-Romagna (Italy) | High | P. perniciosus | Currently high incidence |
| Southern France | Moderate-High | P. perniciosus | Established endemic area |
| Spain & Portugal | Moderate | P. perniciosus, P. perfiliewi | Coastal areas most affected |
| Balkan Peninsula | Emerging | Multiple species | Recent reports of cases |
A Glimpse into the Laboratory: Tracing TOSV in Sand Flies
To understand and combat TOSV, scientists have designed intricate experiments to unravel the relationship between the virus and its sand fly vectors. One such experiment, published in 2024, examined how TOSV infects and spreads within Phlebotomus perniciosus sand flies and what impact this has on the insects' biology 5 6 .
Methodology: Step-by-Step
Sand Fly Colony Maintenance
Researchers maintained a laboratory colony of P. perniciosus under controlled conditions (26±1°C, 80% relative humidity) 5 6 .
Viral Preparation
TOSV (strain MRS2010, lineage B) was cultured in Vero E6 cells, with viral stocks titrated to determine concentration 6 .
Experimental Infection
Adult female sand flies (5-9 days old) were starved for 24 hours before being offered an artificial blood meal containing TOSV at different concentrations 6 . Control groups received virus-free blood.
Dissection and Monitoring
After infection, sand flies were dissected at regular intervals, with heads, bodies, wings, and legs separated and analyzed for viral presence using RT-qPCR 6 . Sugar pads from their enclosures were also tested to detect virus shed by the flies.
Life History Traits
To assess the virus's impact on sand fly biology, researchers tracked survival, egg-laying, and egg hatching in infected versus uninfected females 6 .
Key Findings and Implications
The virus spread systemically within infected sand flies approximately three days after infection, suggesting a short extrinsic incubation period 5 .
A significant finding was that eggs laid by TOSV-infected females took longer to hatch than those from uninfected females 5 . This developmental delay could potentially stagger the emergence of new infected sand fly generations.
Detection of TOSV RNA in sugar meals confirmed that infected sand flies shed the virus during feeding, supporting the possibility of non-venereal transmission between sand flies 6 .
These findings are vital for modeling transmission dynamics and understanding how TOSV persists in nature, especially through seasons when sand fly activity is low.
The Scientist's Toolkit: Essential Research Tools
| Tool/Reagent | Function/Application | Example in TOSV Research |
|---|---|---|
| Vero E6 Cells | Mammalian cell line for virus propagation | Culturing TOSV stocks 6 |
| RT-qPCR Assays | Detection and quantification of viral RNA | Measuring viral load in sand fly tissues 6 |
| Specific Primers/Probes | Target viral genetic material | STOS primers for TOSV detection 6 |
| Artificial Blood Feeding System | Experimental infection of sand flies | Membrane feeding with virus-spiked blood 6 |
| Serological Assays (ELISA, IFA) | Detect antibodies to TOSV | Human seroprevalence studies |
| Plaque Assay/TCID50 | Quantify infectious virus particles | Determining viral titers 6 |
Conclusion: A Call for Increased Awareness
Toscana virus represents a compelling example of how climate change, vector biology, and viral evolution converge to shape emerging infectious disease threats. From its initial identification in Tuscany to its current expansion across Italy and the Mediterranean, TOSV has demonstrated a remarkable ability to capitalize on environmental changes and establish itself in new territories.
Critical Gap in Treatment
The absence of a licensed vaccine or specific antiviral treatment underscores the importance of preventive strategies and early diagnosis 4 .As climate models predict continued warming and changing precipitation patterns, the geographic range of sand fly vectors will likely continue to expand, potentially carrying TOSV to naive populations.
For the Public
For residents of and travelers to endemic areas, awareness of TOSV risk during warm months, coupled with protective measures against sand fly bites (such as insect repellents and fine-mesh screens), remains the first line of defense.
For Researchers
For the scientific and public health communities, enhanced surveillance, improved diagnostic capacity, and continued research into the virus's ecology are essential to mitigate the impact of this neglected but increasingly relevant pathogen.