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  • Open access
  • 13 Reads
Clinical review of a polyvalent F(ab’)2 antivenom (InoserpTM PAN-AFRICA) in the management of snakebite envenomation in sub-Saharan Africa: Clinical studies and actual use since its introduction in 2012

InoserpTM PAN-AFRICA is a polyvalent F(ab’)2 antivenom that has been specifically developed for the management of snakebite envenomation in sub-Saharan Africa. The antivenom provides a very large coverage of medically important species in sub-Saharan Africa with at least 24 species covered (1). This review presents all clinical data available on the use of InoserpTM PAN-AFRICA in sub-Saharan Africa since it has been introduced in 2012. The antivenom has been used in more than 20 countries from west to east Africa with approximately 200 000 vials distributed through marketing approvals, special import permits and through organizations such as armies or NGOs. Four clinical studies (2) (3) (4) (5) have been performed in 5 countries of West and Central Africa, encompassing 22 clinical sites and involving 676 patients exposed to InoserpTM PAN-AFRICA. Patients were rather young with a median age ranging from 18 to 38 years and in great majority males with a sex ratio (M/F) ranging from 2.7 to 4.5 according to the study. Snakebite envenomation was representative of the sub-Saharan African region with mostly hemorrhagic and cytotoxic but also neurotoxic syndromes. Overall, patients received an average dose of 2 to 3 vials which was enough to obtain a rapid control of symptoms in the great majority of cases. The observed lethality rate was 0% to 4.4% depending on the study. Adverse events were mostly of mild or moderate intensity and have been reported in 5 to 11% of patients. Other available data such as published reports of patient cases, as well as the most updated pharmacovigilance surveillance report in 2022 have been used to complete this review. Overall, InoserpTMPAN-AFRICA benefits from a large experience in sub-Saharan Africa. Clinical data available consistently show a very good efficacy and safety profile of the antivenom.

  1. Martinez et Al, Preclinical evaluation of the polyspecific antivenom InoserpTM PAN-AFRICA against the venoms of elapids and viperids of Sub-Saharan Africa region: Neutralization of toxic activities, IST congress Buenos Aires (Argentina), 2019.
  2. Chippaux J-P., Balde MC., Sessinou E. et Al. Evaluation d’un nouvel antivenin polyvalent contre les envenimations ophidiennes (Inoserp Panafricain) dans deux contextes épidémiologiques : le Nord Bénin et la Guinée Maritime. Médecine et Santé Tropicale, 2015. Vol. 25 (1): 56–64.
  3. Coulibaly SK, Diallo T, Diara A, Soulaymani A, Maiga AI. Sérothérapie antivenimeuse au Mali : expérience du centre de santé de référence de Kati région de Koulikoro. Congrès de la Société Française de Toxicologie Clinique Angers (France), 2018. 30(3):165.
  4. Lam A., Cabral M., Touré A., Ba F., Camara B., Kane O., Fall M., Diouf A., Chippaux J-P. Évaluation de l’efficacité et la tolérance d’Inoserp Panafricain au Sénégal. Toxicologie Analytique et Clinique, 2019. Vol. 31: 18–29.
  5. ESAA France and Cameroon Group. Snakebites in cameroon: evaluation of snake antivenom in Africa (ESAA) and real-life conditions. Venom Week Conference Scottsdale (US), 2022.
  • Open access
  • 11 Reads
Rapid Identification of the Mycotoxin Patulin by Gas Chromatography-Mass Spectrometry

Patulin (PAT) is one of the most common mycotoxins produced by Penicillium and Aspergillus species and are often associated with fruits and fruit by-products, mostly apple derivatives, although it has been detected in infant food and cereals. This toxin has shown a mutagenic and carcinogenic effect. Thus, the development of rapid and accurate methods for PAT detection is of utmost importance. Currently, the most widely used methods for the analysis and detection of mycotoxins are based on chromatography, including liquid chromatography (HPLC) and gas chromatography coupled to a mass detector (GC-MS) since these techniques provide high precision, selectivity, and sensitivity.

In this work we show the preliminary results about the development of a GC-MS method for the detection of PAT without derivatization. Usually, the detection of mycotoxins by GC-MS need a derivatization all non-volatile and polar compounds. This is one drawback of gas chromatography against liquid chromatographic technique for the determination of mycotoxins. In this sense, the PAT monitoring method by GC-MS here proposed is an alternative and useful technique to maintain high quality foodstuffs and to ensure food safety.

  • Open access
  • 15 Reads
Algal extracts as preventive mechanism for mycotoxins development

Macroalgae and microalgae are two sources of natural ingredients that are of interest for industrial sectors because of their multiple potential applications. Algal extracts are known to be rich in valuable compounds such as fatty acids, minerals, and secondary metabolites, among others. Bioactivities disclosed for these biocompounds include their antifungal capacity through the growth inhibition of foodborne pathogens and spoilage microorganisms such as Aspergillus sp., Fusarium sp. or Penicillium sp. Apart from their antifungal activity, algal extracts can minimize the toxicity of mycotoxins through two molecular mechanisms: their antioxidant and their chelating properties . Antioxidants may reduce the toxic effect of mycotoxins whereas algae bioadsorption due to their rich composition in macromolecules (polysaccharides or proteins) may have the capacity to bind mycotoxins, prevent their metabolism, and facilitate their systemic release. These three mechanisms involved in the antifungal activity of micro- and macroalgal extracts will be critically assessed along this review in order to disclose their potential application as key tools in food industry and public health. The use of algae extracts as antifungals and detoxifiers may underline their use of natural additives with no side effects associated that may represent an alternative to extend foodstuffs shelf-life and prevent the occurrence of mycotoxins, especially aflatoxin B1, aflatoxin M1 and ochratoxin A. Therefore, this review is aimed to evaluate the multiple benefits that algal extracts may provide to reinforce food safety, reduce food disposal and prompt the utilization of underused biomass such as algae.

  • Open access
  • 4 Reads
Insecticidal activity of microencapsulated Vip3Ag4 protein in Bacillus megaterium.

Bacillus thuringiensis (Bt) produces during its vegetative growth some insecticidal proteins that are secreted and diluted into the culture medium. These proteins are commonly known as vegetative insecticidal proteins (Vips) including binary Vpb/Vpa proteins (formerly known as Vip1/Vip2) with coleopteran activity, Vip with activity against lepidopterans and Vpb4 proteins (formerly Vip4) also with coleopteran activity. The Vip proteins are highly toxic to different species of lepidopteran pests; however, their difficulty to be produced in a concentrated form has not allowed their development as formulated biopesticides, being relegated only to be produced in transgenic crops. In this work, we demonstrated that the gene encoding Vip3Ag4 protein could be successfully expressed in an asporogenic strain of Bacillus megaterium using (D)-xylose as a low-cost inductor of protein expression. Under certain conditions (37 °C and induction with 0.5% w/v xylose), active Vip3Ag4 protein is primarily produced in soluble form remaining encapsulated within the cell wall of B. megaterium. After treatment with lugol (1% for 4 hours), induced cells were completely killed (fixed) but maintaining functional Vip3Ag4 protein, which produced above 95% mortality against first instar larvae of Chrysodeixis chalcites, Helicoverpa armigera, Spodoptera frugiperda, S. exigua, S. littoralis and Trichoplusia ni. The fact that the recombinant Vip3Ag4 protein was successfully produced in a soluble and an active form in this bacterium (with a low-cost inductor), suggest that B. megaterium is one of the hosts of choice for the production of sprayable formulations in “killed-microbial pesticides”, based on vegetative insecticidal proteins from Bt.

  • Open access
  • 0 Reads
Lipid membrane composition determines binding, disruption and cytotoxicity of Gomesin peptides
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Background. Gomesin is a cationic peptide originally isolated from the haemocytes of the Brazilian tarantula Acanthoscurria gomesiana that shows in-vitro and in-vivo efficacy against cancer. Several mechanisms have been proposed to explain the antitumoral activity of Gomesin. These include binding and disruption of the plasma membrane, and modulation of signalling cascades that control cell death and proliferation. Gomesin shows affinity for membranes containing negatively-charged phospholipids with a weak affinity for membranes rich in neutral lipids. However, the influence of cholesterol content has not been fully explored. The present study aims to further investigate the importance of cholesterol in the ability of Gomesin to interact with artificial membranes and cellular models to exert its cytotoxicity.

Methods. Electrochemical impedance spectroscopy and tethered bilayer lipid membranes assays were used to analyze protein binding to the membrane or membrane disruption induced by Gomesin, respectively. These assays were coupled to cellular models of BRAF-mutated melanoma and healthy fibroblast cells by studying changes in viability induced by Gomesin under the influence of modulators of the cholesterol content.

Results. Our investigations revealed that fibroblasts are less affected by Gomesin cytotoxicity and presented a higher content of cholesterol. Interestingly, we identified that two natural Gomesin variants, AgGom and HiGom, contain several consensus sequences for the binding of cholesterol. Studies in artificial membranes revealed that AgGom and HiGom bind preferentially to membranes containing phosphatidylserine and cholesterol in a manner that is dependent on both the cholesterol content and the peptide concentration. Additionally, cholesterol impaired membrane disruption induced by HiGom while differently regulating binding of AgGom and HiGom to artificial membranes. Moreover, the cytotoxicity of Gomesin was blunted by increasing concentrations of cholesterol in melanoma cells but potentiated by cholesterol depletion in healthy fibroblasts.


Our results support a specific role for cholesterol in the selective cytotoxicity of Gomesin peptides in a manner that can modulate membrane fluidity, peptide binding and membrane disruption.

  • Open access
  • 0 Reads
Analysis of European Union Rapid Alert System (RASFF) Notifications for emerging marine and freshwater toxins in the last decade: appearance trends and links with occurrence data and risk assessment advancements

The EU Rapid Alert System for Food and Feed (RASFF) is a tool for the rapid exchange of information on food and feed safety issues between EU member states and the European Commission. It is used to notify food safety authorities about products that pose a risk to human health, including those containing marine and freshwater toxins. Emerging marine and freshwater toxins and their impact on human health and aquatic ecosystems have become a growing concern in the recent years. This is also reflected in the RASFF notifications shared by European countries during the last decade, with the occasional appearance of records relevant to emerging toxins. In this work, RASFF notifications related to emerging marine and freshwater toxins from 2012 to date were retrospectively analyzed, to discover patterns of appearance, as well as explore their relationship with concurrent occurrence data and/or risk assessment advancements in the field. A total of 15 notifications involving emerging marine and freshwater toxins were found, of which ten on ciguatoxins’ presence in fisheries, three on tetrodotoxins in bivalve molluscs (oysters), one on cyanotoxins (microcystins) presence in algae powder and one on pinnatoxins presence in bivalve molluscs (mussels). More than half (6/10) of ciguatera-related notifications were triggered by food poisoning incidents from fishes of the genera Luthanus and Acanthocybium sp. originating from India or Vietnam, whereas the remaining four were connected to border controls on Caranx and Sphyraena sp. fishes imported from India, Sri Lanka and Senegal. All notifications on tetrodotoxins resulted from official market controls conducted in the Netherlands, based on the national measures adopted for tetrodotoxins in 2016. Records on cyanotoxins and pinnatoxins pertained also to official market controls, with the latter based on the risk evaluation of the French Agency for Food, Environmental and Occupational Health & Safety (ANSES) regarding pinnatoxins-associated health risks. The study contributes to better understanding of the main reasons behind RASFF notifications on emerging toxins in E.U. countries and also emphasizes the importance of new occurrence data and relevant risk assessment advancements in the interpretation of the trends observed in RASFF notifications.

  • Open access
  • 0 Reads
Genetic approach to target putative PKS genes in Aspergillus section Nigri species producing ochratoxin A
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A 700 pb PCR derived DNA fragment was isolated from Aspergillus carbonarius, Aspergillus niger and Aspergillus tubingensis using degenerated primers (LC1-LC2c) and two new designed primer pairs (KSLB-LC6) for Aspergillus niger and (AFl1F-LC2) for Apergillus tubingensis developed for the acyl transferase (AT) and the KS domains of fungal PKSs. DNA from the most of black Aspergillus species currently recognized was tested. Herein, we report on the identification and characterization of a part of novel putative OTA-polyketide synthase gene in A. carbonarius “ACpks”, A. niger “ANpks” and A. tubingenis “ATpks”. The sequences were aligned and analyzed using phylogenetic methods. Primers used in this study showed general applicability and other Aspergillus species belonging to section Nigri were successfully amplified specially in A. niger and A. tubingenis. The predicted amino acid sequences “ACpks” displayed 66 to 81% similarities to different polyketide synthase genes while “ANpks” similarities varied from 68 to 71% and “ATpks” were from 81 to 97%. The AT and the KS domains appeared to be specific for a particular type of fungal PKSs and were related to PKSs involved in different mycotoxin biosynthesis pathways, including ochratoxin A. The sequences presented in this work have a high utility for the discovery of novel fungal PKS gene clusters.