Objective. Ostreopsis ovata and Ostreopsis siamensis are tropical unicellular algae that have been found recently in the Mediterranean. Both of these dinoflagellates produce palytoxin (PTX)-like toxins that are powerful vasoconstrictors in mammals. Since 2003, Ostreopsis blooms in Italy and Spain have been accompanied by reports of respiratory problems and skin/mucosa irritation in persons in contact with toxic microalgal cells (epiphytes, plankton, or sea spray) or associated toxins. Methods. In France, a surveillance network has been set up to monitor water conditions and to protect swimmers from contamination due to Ostreopsis. Results. Between 2006 and 2009, a total of nine blooms were observed on the French Mediterranean coast including five that led to manifestations in divers, swimmers, and shoreline inhabitants. A total of 47 patients presented symptoms of involving benign or mild skin, mucosal, and/or respiratory irritation that regressed spontaneously without treatment within 12–72 h (4–12 h with nonsteroidal anti-inflammatory drugs). During the study period, five beaches were temporarily closed. Discussion. In the Mediterranean, Ostreopsis blooms induce skin and respiratory disorders when human beings are exposed to saltwater with a high concentration of algal cells. However, palytoxin dosages carried out on the food chain (urchins, mussels) indicate that this risk of toxins accumulation in seafood must be taken into account and that the surveillance network should be upgraded accordingly.

Neurotransmitter release involves the assembly of a heterotrimeric SNARE complex composed of the vesicle protein synaptobrevin (VAMP 2) and two plasma membrane partners, syntaxin 1 and SNAP‐25. Calcium influx is thought to control this process via Ca2+‐binding proteins that associate with components of the SNARE complex. Ca2+/calmodulin or phospholipids bind in a mutually exclusive fashion to a C‐terminal domain of VAMP (VAMP77–90), and residues involved were identified by plasmon resonance spectroscopy. Microinjection of wild‐type VAMP77–90, but not mutant peptides, inhibited catecholamine release from chromaffin cells monitored by carbon fibre amperometry. Pre‐incubation of PC12 pheochromocytoma cells with the irreversible calmodulin antagonist ophiobolin A inhibited Ca2+‐dependent human growth hormone release in a permeabilized cell assay. Treatment of permeabilized cells with tetanus toxin light chain (TeNT) also suppressed secretion. In the presence of TeNT, exocytosis was restored by transfection of TeNT‐resistant (Q76V, F77W) VAMP, but additional targeted mutations in VAMP77–90 abolished its ability to rescue release. The calmodulin‐ and phospholipid‐binding domain of VAMP 2 is thus required for Ca2+‐dependent exocytosis, possibly to regulate SNARE complex assembly.

The variation of venom composition with geography is an important aspect of intraspecific variability in the Vipera genus, although causes of this variability remain unclear. The diversity of snake venom is important both for our understanding of venomous snake evolution and for the preparation of relevant antivenoms to treat envenomations. A geographic intraspecific variation in snake venom composition was recently reported for Vipera aspis aspis venom in France. Since 1992, cases of human envenomation after Vipera aspis aspis bites in south-east France involving unexpected neurological signs were regularly reported. The presence of genes encoding PLA₂ neurotoxins in the Vaa snake genome led us to investigate any neurological symptom associated with snake bites in other regions of France and in neighboring countries. In parallel, we used several approaches to characterize the venom PLA₂ composition of the snakes captured in the same areas. We conducted an epidemiological survey of snake bites in various regions of France. In parallel, we carried out the analysis of the genes and the transcripts encoding venom PLA₂s. We used SELDI technology to study the diversity of PLA₂ in various venom samples. Neurological signs (mainly cranial nerve disturbances) were reported after snake bites in three regions of France: Languedoc-Roussillon, Midi-Pyrénées and Provence-Alpes-Côte d'Azur. Genomes of Vipera aspis snakes from south-east France were shown to contain ammodytoxin isoforms never described in the genome of Vipera aspis from other French regions. Surprisingly, transcripts encoding venom neurotoxic PLA₂s were found in snakes of Massif Central region. Accordingly, SELDI analysis of PLA₂ venom composition confirmed the existence of population of neurotoxic Vipera aspis snakes in the west part of the Massif Central mountains. The association of epidemiological studies to genetic, biochemical and immunochemical analyses of snake venoms allowed a good evaluation of the potential neurotoxicity of snake bites. A correlation was found between the expression of neurological symptoms in humans and the intensity of the cross-reaction of venoms with anti-ammodytoxin antibodies, which is correlated with the level of neurotoxin (vaspin and/or ammodytoxin) expression in the venom. The origin of the two recently identified neurotoxic snake populations is discussed according to venom PLA₂ genome and transcriptome data.

European viper bite is relatively uncommon but can cause serious envenoming, particularly swelling and hemorrhage spreading from limb to trunk that can cause long term disability. Systemic features are relatively mild compared to many other venomous species. Moderate-to-severe envenoming requires antivenom, which is given many hundreds of times each year across the continent. Several Vipera spp antivenoms are produced in Europe, but there is little comparative information available for the antivenoms and none is licensed with the European Medicines Agency. We aimed to collect descriptive data on European viper antivenoms and assess their relative effectiveness. A systematic review of articles relating to antivenom in Europe was performed using the Medline medical database. The following keywords "Europ*" or the individual names of each European country and "antiven*" or "immun*" or "envenom*" and "snake" or "viper*" or "adder" were used. Articles published between 1 January 1996 and 11 March 2016 pertaining to clinical outcome, including case reports, were selected. Referenced articles in the indexed articles were explored for suitability and included if they met any of the criteria: specific antivenom used, route of antivenom administration, adverse reactions to antivenom therapy and length of hospital admission. All accepted abstracts from EAPCCT conferences since 2000 were searched and abstracts relating to Vipera spp envenoming were assessed for suitability. We extracted data on study type, safety and effectiveness. We sought information on antivenoms from manufacturers and individual patient data from authors of publications. Since individual patient data were only rarely available, we compared median length of stay between case series reporting each antivenom. We identified 40 papers and six published abstracts, and one unpublished paper that reported clinical cases and case series of envenomed patients treated with antivenom. No publication reported randomized controlled trials comparing any European Vipera antivenom with either placebo or another antivenom. 25 reports were of retrospective hospital- (n = 13) or poison center-based (n = 12) case series including five or more patients; a further 12 reports were either case reports or case series with less than five patients and one paper was a limited literature review. An additional nine papers reported prospective data; seven collected data remotely through poison service telephone communication with the attending physicians. Antivenoms available in Europe: Eight antivenoms are available for European Vipera spp envenoming; a material safety data sheet providing information on manufacture was available for seven. Six are raised against V. berus or V. ammodytes venom; the seventh is raised against a mixture of V. ammodytes, V. aspis and V. berus venom and the eighth is raised against V. ammodytes, Macrovipera lebetina and Montivipera xanthina venom. Six manufacturers recommended intramuscular administration while two recommended intravenous administration. No randomized control trials comparing the effectiveness of antivenoms were identified. Pre-clinical data: We found two papers presenting comparative preclinical data. Clinical data: Clinical studies were predominantly retrospective and contained clinical data on antivenom used in 2602 patients; where the antivenom was identified (n = 2174), 2061 (94.8%) received Zagreb, ViperFAV or ViperaTAb antivenoms. There were few published data on the other antivenoms. Repeated use of antivenom: Repeat doses were reported in 230/1491 of cases (15.4%) where this information was recorded. Outcome and length of hospital stay: Intravenous administration of antivenom was associated with shorter length of hospital stay (median length of hospital stay in studies of intravenous ViperFAV or ViperaTAb ranged from 1 to 4.8 days versus 2 to 18 days for intramuscular Bulbio or Zagreb antivenoms). Antivenom versus no antivenom: Some small studies demonstrated no difference in the length of hospital stay in patients with equivalent envenomation grading who either did or did not receive antivenom. Adverse events: Adverse reactions were reported in 37 of 2408 cases (1.5%) including seven cases of anaphylaxis. There are very limited pre-clinical comparative data and no randomised controlled trials assessing effectiveness of the antivenoms against different Vipera species. Most descriptive data suggest the efficacy of Zagreb, ViperFAV and ViperaTAb antivenoms by the intravenous route but not intramuscular route, although this is level D evidence. Reported adverse reactions were rare, suggesting that the modern intravenous antivenoms are of good quality. Better and more systematic data, including perhaps randomized controlled trials comparing different antivenoms, are required for the many hundreds of antivenom administrations that occur annually across Europe.