Skip directly to site content Skip directly to page options Skip directly to A-Z link Skip directly to A-Z link Skip directly to A-Z link
Volume 17, Number 5—May 2011

Seroprevalence of Toscana Virus in Blood Donors, France, 2007

On This Page
Article Metrics
citations of this article
EID Journal Metrics on Scopus

Cite This Article

To the Editor: Toscana virus (TOSV) is an arthropod-borne RNA virus (family Bunyaviridae and genus Phlebovirus) transmitted by sandflies in Mediterranean countries. TOSV causes acute meningitis and meningoencephalitis in patients. In France, cases of TOSV infections involving resident populations and cases imported by tourists traveling in TOSV-endemic countries have been reported (1,2); the virus has also been isolated from local wild-caught sandflies (1). The fact that TOSV has been isolated from human blood on several occasions (2) suggests a potential risk exists for transmitting the virus through blood transfusion or organ transplantation. We investigated the presence of TOSV antibodies in a sample of the healthy population, blood donors from southeastern France.

We tested plasma collected from 729 blood donors in 7 French territorial divisions during the summer of 2007. Plasma donors were analyzed according to their address of residence in each territorial division. Information related to these donors is reported in the Table.

Presence of immunoglobulin (Ig) G and IgM against TOSV was investigated by using a commercial enzyme immunoassay kit (EIA Enzywell Toscana virus IgG and IgM; DIESSE Diagnostica Senese S.p.A., Siena, Italy) developed by using the recombinant nucleocapsid (N) protein of TOSV. This serologic test was validated in a previous study that revealed high specificity and sensitivity (3).

Our results showed that 84 (11.5%) of 729 plasma samples were positive for IgG against TOSV N protein. Twenty-four (3.3%) plasma samples were positive for IgM, and 5 (0.7%) were positive for IgG and IgM (Table).

To confirm the ELISA results, IgG-positive samples were further subjected to Western blot (WB) analysis by using TOSV (isolate H/IMTSSA [2])–infected cell lysate (4). In 233 (32%) of samples, we detected a protein of molecular mass compatible with that of the N protein. A previously reported antibody-positive control was used to validate the WB assay (5). Our WB analysis showed a reduced sensitivity when compared with results of ELISA. After chemical/heat treatment of the protein samples, WB will only detect the linear epitopes on the N protein, while ELISA detects both linear and conformational epitopes. Furthermore, a less recent exposure of the blood donor population to the virus would have resulted in weaker N protein detection by WB as a consequence of a lower antibody titer. However, we cannot exclude some aspecific cross-reactivity as a consequence of well-conserved N protein sequence among the genus.

Finally, to detect TOSV RNA, we processed IgM-positive plasma samples by reverse transcription–PCR (6). The finding of IgM is an indication of a recent exposure to the virus and hence a possible presence in blood. Our PCR did not detect any viral RNA in the samples. Such negative results could indicate either cleared viremia or a low viral load, below the sensitivity limit of the test.

Serologic information obtained in our study confirms the circulation of TOSV in southeastern France. Factors such as commercial exchange and movement of humans, animals, and arthropods between France and Italy may explain the highest prevalence observed (18.8%) in the Alpes Maritimes territorial district, which borders Italy. Our results regarding this area appear of the same order of magnitude as those reported in the general Italian population (>20%) (1).

Geographic and climatic conditions (e.g., temperature, humidity), factors that affect vector distribution and abundance (7), could explain the lower prevalence found in the mountainous districts (collectively ≈400–2,000 meters in elevation). The lower temperatures in these districts may also affect the ability of vectors to efficiently transmit the virus in the field (8).

TOSV prevalence in Corsica, an island in the Mediterranean Sea, was unexpectedly high. In this region, ≈8.7% (10 donors of 115) of the population sampled showed an IgG- or IgM-positive response. In the other districts, the IgM seroprevalence did not exceed 4.4%. The vector that transmits TOSV is known to be present in this area (7), and TOSV infections have been reported on nearby Sardinia (9). The elevated IgM titer in the population in Corsica could indicate 1) recent virus contacts; 2) recent infections with a new TOSV strain circulating in Corsica; or 3) presence of related phleboviruses that are inducing cross-reactivity in the N protein–based IgM ELISA.

Our results demonstrate that 14.1% (IgG and IgM) of the healthy population (blood donors) in France living on the Mediterranean border have been in contact with TOSV and show asymptomatic or mild, unidentified symptoms, as it is the case for many other arbovirus infections (10). Such findings raise concerns about the risks of virus transmission to virus-naive persons by blood transfusions and organ transplants.

Further investigation is needed to better assess how widespread TOSV is in populations. For example, a donor–recipient investigation might confirm virus transmission by blood transfusion, and studies related to the behavior of sandfly vectors, virus biology, and mammalian reservoir hosts could help define populations at higher risk for exposure.



We thank Isabelle Leparc-Goffart, Marc Grandadam, and Hugues Tolou for providing an aliquot of Toscana virus isolate H/IMTSSA (FJ153286).


Nadège BrisbarreComments to Author , Houssam Attoui, Pierre Gallian, Paola Di Bonito, Colomba Giorgi, Jean-Francois Cantaloube, Philippe Biagini, Mhammed Touinssi, Francois Jordier, and Philippe de Micco
Author affiliations: Author affiliations: Université de la Méditerranée, Marseille, France (N. Brisbarre, P. Gallian, J.-F. Cantaloube, P. Biagini, M. Touinssi, F. Jordier, P. de Micco); Institute for Animal Health, Woking, UK (H. Attoui); Instituto Superiore di Sanità, Rome, Italy (P. Di Bonito, C. Giorgi)



  1. Cusi  MG, Savellini  GG, Zanelli  G. Toscana virus epidemiology: from Italy to beyond. Open Virol J. 2010;4:228.PubMedGoogle Scholar
  2. Peyrefitte  CN, Devetakov  I, Pastorino  B, Villeneuve  L, Bessaud  M, Stolidi  P, Toscana virus and acute meningitis, France. Emerg Infect Dis. 2005;11:77880.PubMedGoogle Scholar
  3. Soldateschi  D, dal Maso  GM, Valassina  M, Santini  L, Bianchi  S, Cusi  MG. Laboratory diagnosis of Toscana virus infection by enzyme immunoassay with recombinant viral nucleoprotein. J Clin Microbiol. 1999;37:64952.PubMedGoogle Scholar
  4. Attoui  H, Billoir  F, Bruey  JM, de Micco  P, de Lamballerie  X. Serologic and molecular diagnosis of Colorado tick fever viral infections. Am J Trop Med Hyg. 1998;59:7638.PubMedGoogle Scholar
  5. Di Bonito  P, Nicoletti  L, Mochi  S, Accardi  L, Marchi  A, Giorgi  C. Immunological characterization of Toscana virus proteins. Arch Virol. 1999;144:194760. DOIPubMedGoogle Scholar
  6. Sánchez-Seco  MP, Echevarria  JM, Hernandez  L, Estevez  D, Navarro-Mari  JM, Tenorio  A. Detection and identification of Toscana and other phleboviruses by RT-nested-PCR assays with degenerated primers. J Med Virol. 2003;71:1409. DOIPubMedGoogle Scholar
  7. Chamaillé  L, Tran  A, Meunier  A, Bourdoiseau  G, Ready  P, Dedet  JP. Environmental risk mapping of canine leishmaniasis in France. Parasit Vectors. 2010;3:31. DOIPubMedGoogle Scholar
  8. Barbazan  P, Guiserix  M, Boonyuan  W, Tuntaprasart  W, Pontier  D, Gonzalez  JP. Modelling the effect of temperature on transmission of dengue. Med Vet Entomol. 2010;24:6673. DOIPubMedGoogle Scholar
  9. Venturi  G, Madeddu  G, Rezza  G, Ciccozzi  M, Pettinato  ML, Cilliano  M, Detection of Toscana virus central nervous system infections in Sardinia Island, Italy. J Clin Virol. 2007;40:901. DOIPubMedGoogle Scholar
  10. Schmaljohn  CS, Nichol  ST. Bunyaviridae. In Fields BN, Knipe DM, Howley PM, DE, editors. Fields virology, 5th ed. Philadelphia: Lippincott Williams & Wilkins; 2007. p. 1741–78.




Cite This Article

DOI: 10.3201/eid1705.101052

Related Links


Table of Contents – Volume 17, Number 5—May 2011

EID Search Options
presentation_01 Advanced Article Search – Search articles by author and/or keyword.
presentation_01 Articles by Country Search – Search articles by the topic country.
presentation_01 Article Type Search – Search articles by article type and issue.



Please use the form below to submit correspondence to the authors or contact them at the following address:

Nadège Brisbarre, EFS-AM–Unité de Virologie Moléculaire, Faculté de Médecine, la Timone, 5ème Étage Aile Bleue 27, Blvd Jean Moulin, Marseille 13005, France

Send To

10000 character(s) remaining.


Page created: August 08, 2011
Page updated: August 08, 2011
Page reviewed: August 08, 2011
The conclusions, findings, and opinions expressed by authors contributing to this journal do not necessarily reflect the official position of the U.S. Department of Health and Human Services, the Public Health Service, the Centers for Disease Control and Prevention, or the authors' affiliated institutions. Use of trade names is for identification only and does not imply endorsement by any of the groups named above.