Head: Mireille CHINAIN (ILM)
Scientific context and objectives
The changes occurring in island ecosystems under the impact of anthropic forcing (global change, chemical contamination, eutrophication, transfer of biological material related to uses, etc.) justify an increase in the research effort devoted to current and emerging human health and animal health issues related to biotoxins, the resurgence of infectious disease in aquaculture stocks (in particular due to changes in modes of production), or diseases attributable to the way of life of human populations and the transfer of contaminants in the food chain.
The increasing severity of the health and economic risk related to marine biotoxins and its spread to other geographical regions - including Europe - highlights the urgency of the need for enhanced health and economic security measures in the Polynesian aquaculture sectors. This is the case in particular with regard to ciguatera, a food-based infection that is widespread in French Polynesia, the management of which is problematic because of the lack of effective treatment or early diagnostic tools, and the occurrence of highly debilitating forms of the disease. Furthermore, this ichtyosarcotoxism constitutes a major obstacle to the emergence of large-scale aquaculture projects and to the development of local or export-focused lagoon fisheries. The corpus of knowledge and the monitoring tools developed in recent years have enabled the introduction of a more exhaustive system of surveillance of infection by marine biotoxins, but the recent increase and diversification of atypical forms of ciguatera in various Polynesian islands, in particular those associated with the consumption of marine invertebrates (giant clams, sea snails, sea urchins), confirms the need for in-depth research, targeting: 1) the ad hoc clinical description and improved treatment of these infection syndromes, and 2) the most exhaustive screening possible of the various toxic micro-organisms and marine toxins likely to have a deleterious impact on the lagoon ecosystems of French Polynesia. More broadly, the toxico-kinetic of the ciguatera toxins in emblematic host-vectors such as the fishes and the giant clam remains largely unknown, as do the mechanisms controlling the bio-magnification and the bio-transformation of these toxins in the food webs. Finally, given the currently poor availability in pure standards of cigatoxins internationally, the production of ciguatoxins to supply medical analysis laboratories is a sector that is currently commercially exploited, although this is more a semi-industrial valorisation project rather than scientific research stricto sensu.
From the economic point of view, worldwide aquaculture production of molluscs, crustaceans and fishes has increased strongly over the past ten years. Changes in the systems of exploitation and the increasing numbers of new species of commercial interest, in relation with this extremely rapid increase, have had an impact on the structure of ecosystems and on the state of health of both farmed and wild organisms. There has in particular been a resurgence of infectious diseases due to a range of pathogenic agents: bacteria, viruses, fungal infections, protozoan and metazoan parasites, the development and spread of which are favoured by the practice of aquaculture. At present, the 4 main aquaculture sectors in French Polynesia, the pearl oyster P. margaritifera, the shrimp Litopeaneus stylirostri, the giant clam Tridacna maxima and the batfish Platax orbicularis, ranked in order of socio-economic importance, enjoy a very favourable animal health status mainly because of their geographical isolation from the production zones and the epidemiological surveillance and monitoring measures adopted in French Polynesia. Nevertheless, over recent years, several pathogenic infectious agents have been identified, such as the bacteria of the genera Vibrio and Tenacibaculum (in P. margaritifera and P. orbicularis), the nodavirus (in P. orbicularis), and a parasite, Perkinsus olseni (in T. maxima), one of the seven infectious agents in molluscs that is subject to compulsory declaration to the World Organisation for Animal Health (OIE). It is of primordial importance to strengthen the existing surveillance system targeting these newly identified infectious agents. Better identification and characterisation of their mode of action should enable the optimisation of the zootechnical protocols and surveillance systems required.
Finally, according to a recent report from the World Health Organisation, the countries of the Asia-Pacific zone face a new threat, that of diseases related to the way of life and the ageing of the population, which constitutes a major health challenge for the populations concerned. This alarming development may be explained mainly by alterations in diet and the decline of physical activity among these populations. French Polynesia is no exception to this trend. Nevertheless, because of the distribution of the populations among 5 distinct archipelagos over a surface area as vast as Europe, and of life styles that are often radically different, it is likely that factors such as the distance from the main island of Tahiti, the availability of food produced in the island itself, the level of toxic risk related to infection by marine toxins (e.g. ciguatera), or the mode of waste disposal (open air incineration or 'lagooning', exposing populations to impregnation by polychlorobiphenyl (PCB) and heavy metals in airborne form and / or in food), may result in a health picture that differs from one archipelago to another. Thus, it is of primordial importance with regard to public health management and the anticipation of future needs to know the health status of a population in its environmental context. Similarly, it is of crucial importance to better document the entry pathways and fate of chemical contaminants in marine ecosystems, and in particular the role of the primary producers in the transfer of contaminants in the food webs of the OIEs. This theme devoted to health and animal health issues in the island ecosystems of French Polynesia is thus organised on the basis of three research axes.
Axis 1 : Health issues related to infection by marine biotoxins
On one hand, we are working to consolidate and improve the existing epidemiological surveillance system with regard to the main types of infection identified in the 5 archipelagos of French Polynesia. Particular attention is focused on the emerging infections of the Ciguatera Shellfish Poisoning type, involving invertebrates. In parallel, exhaustive taxonomic and chemical characterisation is undertaken of the microorganisms (dinoflagellates, diatoms, cyanobacteria) and toxic compounds that are the cause of these infections. Programmes dedicated to the establishment of cultures in vitro of species of interest is an essential part of our work. Given the diversity of the marine products and toxin families to monitor, a particular effort is dedicated to the technological improvement of existing detection tests, to adapt them to the particular eco-toxicological context of the Polynesian OIEs, if possible, in such a way as to make possible their use with minimum cost.
On the other hand, we study the toxic and toxico-kinetic effects of ciguatoxins (CTXs) in two host-vector models: fishes for the vertebrates and giant clams for the invertebrates. For this purpose, experimental contamination trials (experimental feeding) are carried out among lagoon fishes of different trophic levels. A bio-bank of different tissues (blood, liver, muscle, etc.) is thus constituted. These are analysed for their CTX content and the chemical characterisation of the different CTX analogs present. These data will serve for subsequent in vitro and in silico experiments (enzymatic and electrochemical transformations) aimed at decrypting and mimicking in silico the bio-transformation pathways of CTXs found in fishes. The aim is to produce from the panel of CTXs derived from the micro-alga Gambierdiscus, more oxidized metabolic forms which might be used as potential sources of standards). In addition, the transcriptomic analysis of levels of genic expression by RNAseq of the different tissues of fishes from the toxic experimental feeding trials will be undertaken with a two-fold aim: 1) to better understand the effects of the CTXs on the fishes through a systems biology approach; 2) to perform a discriminatory analysis of the genic signatures of infected fishes vs. controls at different durations of exposure in order to attempt to identify potential specific biomarkers of toxic fishes. It should be noted that if the genic signatures discriminating between the toxic fishes and the healthy fishes are sufficiently powerful, this approach which places the emphasis on the effects of the CTXs in the fish rather than on the detection of the CTXs themselves, might in due course lead to a change in the paradigm of the existing methods of detection and the development of a reliable and inexpensive detection test for toxic fishes. Similar contamination tests will be undertaken on the giant clam (T. maxima) model, paying particular attention to the pathways and purification time of the CTXs in this marine invertebrate that is highly prized by the local populations.
With regard to the management of ciguatera-type infections, our aim is to contribute to the more effective treatment of infected patients, both by means of early diagnosis of the disease and by the treatment of the clinical symptoms of the infection, whether in acute or chronic form. For the treatment of ciguatera, no specific antidote has been clearly identified to date, whence the essentially palliative approach which is favoured in western medecine. Currently, however, a plant used in the traditional pharmacopoeia, Heliotropium foertherianum , or octopus bush, has aroused considerable hope, its major active principle, rosmarinic acid, having clearly shown neuro-protective properties against the action of the CTXs. The elucidation of the mode of action of this molecule thus constitutes today a research priority, and if there is significant progress, might add matter to the discussions in progress regarding possible clinical trials. In addition, we also target the residual sporadic and / or chronic forms of ciguatera that remain, even today, a real enigma, with the aim of attempting to identify the therapeutic pathways for providing relief. To that end, we focus our efforts on the precise and objective definition of the notion of 'chronicity', the exhaustive characterisation of the symptoms observed during this phase (essentially of a neurological order) and of factors likely to aggravate them, as well as the identification of potential immunogenetic markers of predisposition to the development of chronic forms of the disease.
Axis 2: Animal health issues related to pathogenic agents of aquatic organisms
Our aims are to identify and characterise the infectious agents responsible for transmissible diseases in the aquaculture stocks in French Polynesia, to develop and validate under laboratory conditions several molecular diagnostic techniques, specifying their interest (rapidity, sensitivity and specificity), to study the factors of virulence in bacteria in particular, to provide information on the epidemiology of diseases (incidence, pathogenesis, transmissibility, effects of biotic and abiotic factors), to assess the health status of animals by the use of molecular biomarkers and finally to play a role in the development and improvement of animal health surveillance systems. To achieve these objectives, analytical techniques are applied in bacteriology, virology, parasitology, histology, epidemiology and molecular biology. The use of experimental infection protocols in apparently health animals, free from disease, also provides a means to study the development of the disease and to identify biotic and abiotic factors influencing the physiology of the animals. These challenging tasks are undertaken under controlled conditions within dedicated facilities. The expected results relate to i) the improvement of our knowledge of the taxonomy of the infectious agents responsible for emergent serious diseases, or already occurring among the main aquaculture stocks in French Polynesia, and their degree of genetic variability, ii) the development and validation of diagnostic techniques, iii) the use of molecular biomarkers associated with the fitness of commercially exploited organisms, iv) the contribution to studies of epidemiological interest aiming to limit the impact of diseases in aquaculture.
Axis 3 : Chemical contaminants in the marine food webs and the eco-health of populations
Because of the processes of bioaccumulation and bioamplification of certain chemical elements, the contamination of marine resources may reach very high levels with potentially serious socio-economic consequences (e.g. health risks, degradation of the environmental quality). In the framework of this research axis, it is a matter of drawing up health status maps of the populations exposed to chemical contamination in the various Polynesian archipelagos, and in addition acquiring the knowledge necessary to better understand the pathways of entry and the fate of organic and inorganic chemical contaminants (e.g. trace-metals, polycyclical aromatic hydrocarbons, pesticides, emergent contaminants), from the first links in the food chain to the higher predators. The mode and degree of impregnation of the populations by various chemical pollutants are recorded by means of biological analyses (urine, blood) and analyses of the environmental quality (analyses of food products, drinking and bathing water). The entry of contaminants in the first food chain links is determined by means of studies of speciation and the bioavailability of chemical elements. The determination of the trophic fate of contaminants is developed through an approach combining ecological studies of the food web and biogeochemical studies of contaminants; biological tracers (carbon and nitrogen isotopes) and chemical tracers (inorganic and organic contaminants) are thus analysed in parallel.
The role of the primary producers, the cornerstone of the food webs in the transfer of chemical contaminants to the higher trophic levels, could thus be better understood. We attempt to specify the buffer or amplification role of this first food chain link with regard to contaminants in the OIEs where, to date, we only dispose of very sparse knowledge.
This work targets the food chains or marine resources of economic interest in the South Pacific, such as the giant clam and the fishes (lagoon or open sea), which constitute the major or even sole food resource for the populations of the OIEs.