Ciguatera, a growing challenge

The Canary Islands marine environment, a source of resources for so many sectors of our society, is beginning to show symptoms that could be associated with the phenomenon of tropicalization; among them, the increase in average temperatures and average levels of CO2 in dissolution, according to data from the EPA (United States Environmental Protection Agency) and Jose Luis Martín et al (2012). In spite of not knowing with certainty the triggers of such symptoms, studies carried out by Jesús Manuel Falcón in 2005, affirm that of the 30 new records of coastal bony fish carried out in the period 1991-2005, 80% correspond to species of tropical origin.

The presence of these new species in our ecosystems could correspond to various factors such as maritime traffic (vector of marine life throughout the planet), overfishing, water pollution with the consequent modification of physical-chemical conditions of the environment, etc..

The invasion of these species can be as detectable as predators on native fauna, or as invisible to the naked eye as the appearance of microscopic beings; however, increasingly common are outcrops of phytoplankton or microalgae, known in the scientific community as "Blooms" or HABs (Harmful Algae Blooms). Some of these blooms can reach such dimensions that they can be clearly seen from the shore as a stain on the water.

Despite the lack of knowledge of the specific causes of its appearance, the Canary Islands are already affected by the timid but alarming appearance of a disease called ciguatera, an endemic affection of tropical areas caused by the ingestion of fish contaminated by ciguatoxin. The main effect of this substance is the modification of neuronal activity and its synthesis by microalgae of the genus Gambierdiscus.

"Toxicity becomes manifest as the toxin concentrates through the food chain, ultimately reaching the human being. Bigger, older fish are more toxic" ( Web by the Canary Islands Government about  the presence of ciguatera in the islands).

Data have been recorded on the consumption of fish affected by ciguatoxin in the Canary Islands, mainly medregal, grouper and greater silver smelt. These have been ingested both privately and in the hotel industry, according to documentation available to date from the Epidemiological Surveillance System for Ciguatera Poisoning in the Canary Islands (SVEICC). The symptoms of the infection begin to appear in the first 24 hours after ingestion, in the form of nausea, diarrhoea, vomiting or abdominal pain, as far as the digestive system is concerned. As for the effects on the circulatory system, the disease results in lower blood pressure and bradycardias, among others.

A pesar de ser una enfermedad con baja mortalidad (desde 1% a 12% de los casos según estudios realizados por Álvarez et al en 1990), los síntomas pueden llegar a ser crónicos, según datos de la investigadora Melissa A. Friedman (2017). Sin embargo, la colección de datos epidemiológicos a nivel mundial es ineficiente; se estima que se reportan menos del 20% de los casos según Lewis y Sellin. Además, en zonas no endémicas como Canarias se registran muy pocos datos de la enfermedad por desconocimiento, tanto de los ciudadanos como de los facultativos sanitarios. A pesar de estas consideraciones, el servicio de Vigilancia Epidemiológica de la Intoxicación por Ciguatera en Canarias ha reportado 15 brotes, con un total de 109 personas afectadas desde el 2004.

Studies by Francisco Rodríguez et al, 2017, report that the Canary Islands are already considered a "hot spot" of genus diversity, with the presence of at least 5 species cited to date on the islands (G. australes, G. caribaeus, G.carolinianus, G. ecentricus and G. silvae). On the basis of the climatological and epidemiological evidence currently existing, it is possible to affirm that the Canary Islands are facing a potentially dangerous disease: no cure is known to date, as the related pharmacology revolves around treatments that help to bear the symptoms, but that do not make them disappear altogether.

In this sense, the IPNA-CSIC Sustainable Metallic Catalysis research group, led by researcher Juan Ignacio Padrón, is working on the development of a conjugated vaccine against ciguatoxin. The synthesis of a vaccine in this scenario would be a great advantage, as it would involve a controlled simulation that trains our defences to respond adequately to the natural pathogen.

Currently, there are a number of strategies available to address vaccine synthesis. Inactivated or attenuated vaccines are based on the use of the vaccine synthesizing organism: the former "inactivate" their toxicity by modifying it, while in the latter these living beings are cultivated under conditions in which they do not show harmful properties. On the other hand, the substances that are capable of manufacturing these pathogens are also used as a first step for synthesis. Along the same lines, we have toxoids: substances which, whether chemically modified or not, immunise against the harmful effects of infection. And finally, conjugate vaccines, in which the union of polysaccharides (commonly called sugars) and polypeptides (proteins) allows us to simulate the original structure of the natural toxin and thus create an immune response sufficient to protect the body in cases of real infection.

Given the group's experience in synthesizing molecules that form part of the structure of these toxins, work is being done on the development of haptenes that can give rise to antibodies against ciguatera. Haptenes are small molecules that by themselves do not induce the formation of antibodies, which is the desired reaction when the vaccine is injected, but when they bind to a carrier protein they stimulate an immune response. Achieving an immune response on the part of the organism would be a significant advance in this field, since, except for the contribution of certain research groups (mainly in Japan), there are currently no conclusive advances in the fight against ciguatera.

The project is part of the Knowledge Transfer Plan of the Institute of Natural Products and Agrobiology, which is developed thanks to the support of the Cabildo de Tenerife and is financed by the Canary Islands Development Fund (FDCAN), within the Strategic Framework for Island Development (MEDI). Thanks to this programme, the researcher Pedro Miranda Chinea, who will lead this new line of research, has recently joined the programme.

By Vaitiare Estupiñán Díaz.