French Polynesia is located in the Southeast Pacific and within the Polynesian triangle, which is bounded by the islands of Hawaii to the North, Aotearoa (New Zealand) to the West and Rapa Nui (Easter Island) to the East. This French overseas collectivity extends over a maritime area as large as Europe and includes 121 islands, of which 75 are inhabited, distributed within five archipelagoes: Society, Marquesas, Tuamotu, Gambier and Austral (Figure 1). According to the previous national population census conducted in 2017, there are about 276,000 inhabitants distributed in the various archipelagoes, of which nearly 75% are concentrated in the islands of Tahiti and Moorea (Windward Islands, Society archipelago) (1).

In the course of the history of human migrations around the world, Pacific islands, and East Polynesia in particular, were the last empty lands to be settled. This settlement process began approximately 1,200 to 1,000 years ago and ended around 750 years ago (2). Although archaeological and linguistic data have provided evidence for the geographical and temporal origin of the populations of the Eastern Pacific islands, the sequence and timings of settlement of the Polynesian islands are still debated (3). To help elucidate these gaps, a few genetic studies including samples from Pacific populations have been conducted over the past five years (2– 6). However, for the studies involving the use of samples from the population of French Polynesia, only a limited number of samples collected in a few islands were available. Some studies also aimed to identify genomic variations related to adaptation of the populations to island environments. In a study including genomes from 20 populations from the Pacific region, candidate variants for positive selection were found in genes related to immunity and metabolism, suggesting genetic adaptation to pathogens and food sources specific to Pacific islands (4). However, further investigations are needed to identify causal links between past genetic adaptation and present-day disease risk in Pacific settings. Indeed, most studies investigating genetic links with vulnerabilities to non-communicable (NCDs) and communicable (CDs) diseases have focused on populations in Africa, Europe, Asia, and the USA (7–10). The same observation is made for the research investigating the link between human gut microbiome composition and susceptibility to diseases (7). Despite the high burden of various NCDs and CDs, Pacific islands remain highly underrepresented in genomic studies.

In addition to genetic and microbial factors, social and environmental factors such as poverty, education, and access to healthcare are thought to be major drivers of disease burden in the Pacific islands (7). In French Polynesia, prevention measures against NCDs and CDs have been enhanced, and access to healthcare has been improved in all archipelagoes over the past 3 decades (11). This has certainly contributed to the extension of life expectancy at birth, which has increased from 67.1 years to 74.7 for men and 72.8 years to 79.1 for women between 1990 and 2020 (12). However, transition from traditional to modern lifestyles in the Pacific islands (including overconsumption of processed food along with reduced uptake of fruit and vegetables, as well as physical inactivity) and increased longevity have led to a rise in the incidence of NCDs (13). The most recent data collected in French Polynesia in 2010 indicated that the prevalence of obesity and hypertension in adults was 40.4% and 26.7%, respectively. It was estimated that only 1.7% of the population of French Polynesia presented a low risk of developing a NCD whereas 45% were at high risk (14). According to the latest reports from the health authorities of French Polynesia, the leading causes of death are cardiovascular diseases (26.1%) mainly associated with lifestyle, and cancers (25.1%) (15, 16). Among the Pacific island countries and territories (PICTs), French Polynesia displayed one of the highest age-standardized cancer incidence (267.9 for males and 214.0 for females per 100,000) and age-standardized cancer mortality (157.2 for males and 106.8 for females per 100,000) in 2020 (17–19). The most frequently reported cancers are prostate (73.3 per 100,000), breast (66.5 per 100,000), lung (40.4 per 100,000), thyroid (16.1 per 100,000), and colorectal (12.3 per 100,000) cancers (19). Moreover, the incidence of hepatocellular carcinoma recorded in the Austral archipelago between 2013 and 2017 is among the highest in the world (43.1/100,000 inhabitants), this pathology being associated with a high prevalence of infection with hepatitis B virus (HBV) and obesity (20).

Dietary habits, especially high fish consumption, also expose the population of French Polynesia to seafood-related NCDs. Among them, ciguatera poisoning, a disease caused by the consumption of reef fishes or marine invertebrates contaminated by neurotoxins (ciguatoxins) produced by a microalgae that belongs to the Gambierdiscus genus, is highly prevalent in French Polynesia where it constitutes an important public health issue (21). In 2021, the overall incidence rate of ciguatera, based on the number of symptomatic cases reported by healthcare workers or by the patients themselves, was 6.9/10,000 inhabitants (22). However, as (i) ciguatera is not on the list of notifiable diseases, (ii) a large proportion of ciguatera-affected people do not consult a healthcare worker, and (iii) cases requiring emergency care or hospitalization in the main hospital of French Polynesia (Centre Hospitalier de la Polynésie française, Tahiti) are not systematically recorded, the true incidence rate of this disease is underestimated. Another source of seafood-related contaminants are heavy metals including mercury and lead. Indeed, high levels of mercury were detected in adolescents and adults from two atolls of the Tuamotu archipelago (Hao and Makemo) (23), in adults from the Leeward islands (Tahiti and Moorea) (24), and in cord blood samples of delivering women from all archipelagoes, suggesting that Polynesian newborns may be prenatally exposed to high doses of mercury (25). Moreover, concentrations of lead exceeding toxicological reference values were found in a significant proportion of the residents of Hao and Makemo islands tested to assess their exposure to toxic metals and polychlorinated biphenyls (PCBs) (23). Although levels of PCBs found in both atolls were low compared to international standards, there was a higher body burden of PCBs in residents of Hao which was suggested to be potentially linked to some contamination of the environment by military support activities in this island. Another source of environmental contamination that may have an impact on the population's health are pesticides. To our knowledge, there are no data concerning the level of exposure to pesticides of the population of French Polynesia. However, surveys on the pollution of French Polynesia coral reefs by pesticides found the presence of herbicides and insecticides in fishes which are commonly consumed by the local inhabitants (26–28).

In addition to NCDs, CDs represent major health problems in French Polynesia. As a result of the prevention, screening, treatment and vaccination programs implemented by the health authorities, the incidence of several CDs has decreased (29). Despite these efforts, some CDs caused by bacterial infections persist, including leprosy (mean incidence of 1.6 cases per 100,000 inhabitants reported from 2000 to 2017) and tuberculosis (incidence of 19.4 cases per 100,000 inhabitants in 2018) (30, 31). As a comparison, the last epidemiological survey of leprosy conducted in metropolitan France in 2010 showed a prevalence of 0.011 per 10,000 inhabitants, with most cases imported from French overseas territories (32), and the incidence of tuberculosis reported in metropolitan France in 2021 was 6.4 cases per 100,000 inhabitants (33). Moreover, in 2013, the prevalence of Bancroftian lymphatic filariasis, an infection caused by the nematode worm Wuchereria bancrofti transmitted by mosquitoes, had still not reached the elimination threshold (i.e., filarial antigenemia <1%) defined by the World Health Organization (WHO) in Tahiti, Huahine (Leeward Islands, Society archipelago) and three islands in the Marquesas archipelago (Tahuata, Hiva Oa and Fatu Hiva), despite several years of community treatment (34–37). Furthermore, HBV remains a public health problem, despite the availability of an effective vaccine. Following the finding of hepatitis B surface antigens (HBsAg) among 10.48% inhabitants of the Austral archipelago randomly selected in 1987 (38), vaccination of children at birth started to be implemented in 1992 to decrease the burden of chronic HBV infection in French Polynesia (39), and became mandatory in 1995 (40). A nationwide serosurvey conducted in 2014 in 6-year-old schoolchildren from the five archipelagoes showed a three-dose vaccination coverage of 98% and a prevalence of HBsAg of 0% (41). However, a screening in 2019 of all adult residents of Rapa, the most isolated island of the Austral archipelago, revealed a prevalence of HBsAg of 11% in people born before 1992 (20).

Among the CDs considered as important public health issues in French Polynesia, those caused by arthropod-borne viruses (arboviruses) represent the highest risk for the population. Indeed, the four serotypes of dengue virus (DENV-1 to −4) have caused multiple outbreaks over the last decades, with deaths frequently reported in children (42, 43). Moreover, Zika virus (ZIKV) and chikungunya virus (CHIKV) caused explosive outbreaks in 2013–2014 (44) and 2014–2015 (45), respectively. During the ZIKV outbreak, severe neurologic complications in adults (46) and central nervous system malformations in newborns and fetuses (47) were recorded. In addition to arboviral diseases, CDs caused by respiratory viruses have become major health concerns over the past decades. Several epidemics of variable severity caused by influenza A and/or B viruses have been reported in French Polynesia (29). While influenza was not considered a public health priority until the early 2000s, an epidemic caused by the influenza A virus subtype H1N1 highly affected the population of French Polynesia in 2009, with 13 severe cases requiring hospitalization in a critical care service and 7 recorded deaths (48). More recently, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reached French Polynesia in March 2020 and caused several epidemic waves, with a total of 78,864 confirmed cases, 3,315 hospitalizations and 783 deaths reported as of August 31, 2022. A serosurvey conducted at the end of 2021, from a representative sample of the adult population of Tahiti, found that 57.7% of the study participants had been infected by SARS-CoV-2 during the first two epidemic waves (49).

Bacterial infections also represent a significant risk for the population of French Polynesia. The incidence of leptospirosis, a rodent-borne disease caused by bacteria belonging to the order Spirochaetales, exploded in 2017 with a rate of 72/100,000 inhabitants (50). Moreover, the incidence of Staphylococcus aureus (S. aureus) infections was estimated at 38/100,000 inhabitants in 2008, and this bacterium was shown to be responsible for one third of the community bacterial infections documented in French Polynesia. The proportion of S. aureus strains resistant to methicillin increased from less than 10% in 1995 to more than 35% in 2001 (51). French Polynesia is also characterized by the unusual high prevalence of acute rheumatic fever associated with infection by Group A streptococcus, with an incidence of 0.06% and a prevalence of 1.29% reported in 2015 (29, 52).

Although data exist on the levels of exposure of the population and the risk factors associated with NCDs and CDs in French Polynesia, these data are often old, fragmentary and concern a few islands. Moreover, genomic data, based on whole genomes, from the Polynesian populations are lacking, precluding a comprehensive assessment of the settlement history of the various islands and archipelagoes, and of the history of genetic adaptation of these populations to island environments—an information that should be of great benefit for the study of the genetic basis of certain diseases that present high incidence in the region. Here we describe the MATAEA project, a wide cross-sectional population-based survey designed to investigate the determinants of health in the adult population of French Polynesia, using a combination of data obtained from a questionnaire, physical measurements, and biological analyses in 2,100 inhabitants of 18 different islands distributed among the five archipelagoes.

MATAEA is a Tahitian compound word (“MATA” means “eye” and “EA” means “health”) which can be translated as “take a look at health”. The first objective of the MATAEA project was to collect a wide range of data from a large number of inhabitants to assess the health status of the adult population of the five French Polynesian archipelagoes, and identify risk factors for NCDs and CDs related to the specific living context (including the lifestyle, place of residence, history of infections) and intrinsic characteristics of individuals (such as genetics, age, sex, oral and gut microbiome). Results will be made available to health authorities for them to adapt actions and preventive measures to better reduce disease incidence. The second objective of the project was to use genomic data obtained from the residents to increase our understanding of the history of the settlement of the French Polynesian islands, and to identify the major demographic and adaptive events that may explain the current incidence of some NCDs, and the higher susceptibility to certain NCDs and CDs. Although designed as a general-purpose survey with a broad scope, topics identified as major public health issues will be given priority treatment by specialized laboratories involved in the project, as described below.

First, prevalence data for metabolic diseases (including obesity and diabetes) dating from 2010 will be updated (14), and their associated risk factors (such as dietary habits, physical activity, blood pressure, high blood sugar, excess body fat around the waist, abnormal cholesterol or triglyceride level, genetic susceptibility factors, microbiome composition) will be investigated.

Second, the seroprevalence of mosquito-borne diseases known to have previously circulated in French Polynesia (including the four serotypes of dengue, Zika and chikungunya) will be measured as previously published (53, 54), to assess the risk for new outbreaks to occur. In addition, the prevalence of filarial antigenemia will be evaluated to check whether the elimination threshold recommended by the WHO has been reached in all archipelagoes, subsequent to the strengthening of community treatment in islands most affected by Bancroftian lymphatic filariasis (37). Risk factors for those mosquito-borne diseases will also be sought. Among them, the level of exposure of the population to mosquito bites will be measured by analyzing the presence of IgG antibodies targeting mosquito salivary proteins in the blood of participants, as previously described (55).

Third, screening for HBsAg and anti-HBV total antibodies will be performed to assess the prevalence of current and past HBV infections among the inhabitants of the five archipelagoes, especially those with increased risk factors, such as being born before 1995 and living in the Austral archipelago. As there is no available data regarding the prevalence of hepatitis C virus (HCV) infections in French Polynesia, the presence of anti-HCV IgG antibodies will also be tested.

Fourth, concentrations of several heavy metals (including mercury and lead) and pesticides will be measured in the blood of inhabitants of the five archipelagoes to assess the degree of environmental contamination and the risk for human health. Data collected in the questionnaire, such as the island of residence and dietary habits, will be used to identify risk factors associated with contamination with toxic metals and pesticides, as well as ciguatera poisoning. As there is no confirmatory test available to detect current or past ciguatera poisoning, the estimate of the prevalence of this disease in the population of the five archipelagoes will be based on the information self-reported by the participants in the questionnaire.

Fifth, as SARS-CoV-2 was introduced into French Polynesia during the participants' inclusion period and a large number of cases with mild or no symptoms might have not been reported, the presence of specific IgG antibodies will be analyzed in the blood samples of participants to evaluate the real proportion of the population infected in the different archipelagoes after the emergence of the virus.

Sixth, serological analysis will be conducted for a panel of viruses known to regularly cause infections in French Polynesia (such as influenza viruses, human immunodeficiency virus, rotaviruses and enteroviruses), but for which there is little data on the immune status of the population.

Finally, the seroprevalence of rodent-borne pathogens including Hantaviruses will be determined, as the high incidence of leptospirosis suggests that other diseases transmitted by rodents may circulate in French Polynesia. The only serosurvey of hantavirus infections in French Polynesia was conducted in 1989 and found specific antibodies in a few samples from rats and humans (56). Consequently, data collected in the present study will allow detection of possible silent circulation of Hantaviruses.

The MATAEA project is the first cross-sectional survey designed to investigate a broad range of health issues in the five archipelagoes of French Polynesia. The high number of participants and their wide geographical distribution guarantee a good representativeness of the population of French Polynesia. The large amount of data obtained for each participant from the CRF, physical measurements and biological analyses will make it possible to update the information on the prevalence of numerous NCDs and CDs known as major public health concerns in French Polynesia, and possibly identify specific indicators and/or risk factors for these diseases. The study will also provide new epidemiological information on poorly studied or unknown pathologies. Finally, the MATAEA project will generate a high amount of genetic data for a population that, so far, has been poorly represented in human genetic studies.

Nevertheless, the MATAEA project has some limitations that should be acknowledged. First, the population aged under 18 years was not included in the survey, which might have an impact on the estimate of the prevalence of certain pathologies, such as arboviral diseases and viral hepatitis. Second, participants were recruited in only 18 of the 75 inhabited islands while differences may exist between the inhabitants of distinct islands within the same archipelago. Third, there might be an underrepresentation of hard-to-reach subjects, such as heavy drinkers or socially excluded persons, which might be more prone to some pathologies. Fourth, the number of participants recruited for the study may not be sufficient to investigate rare pathologies. Fifth, the cross-sectional nature of the survey does not allow to examine the temporal relationship between exposures and diseases under study. Finally, the sampling period has been interrupted three times because of the COVID-19 pandemic and more than two years elapsed between the first and last inclusion (Figure 2). Restrictive measures implemented to prevent the spread of COVID-19 may have affected the transmission of other CDs, and also changed the study population's lifestyle habits, including diet and physical activity which are risk factors for metabolic diseases. Consequently, the time of inclusion should be considered in the analyses.

The main objectives of the MATAEA project have already been presented to the Health and Research authorities of French Polynesia as well as, in several occasions, to the general French Polynesian populations, in particular in the form of conferences principally conducted by Van-Mai Cao-Lormeau and Lluis Quintana-Murci. Furthermore, a video presenting the MATAEA project is already accessible online (https://youtube.com/playlist?list=PLVLsoPZrkK4ipioiTOhGh0z05XZSHPC6H). All the results generated in the framework of the MATAEA project will also be made available to the population of French Polynesia through various communication channels. The results will be presented in an accessible way for the public, through conferences, seminars, and roundtables, and will be sent to the mayors of the islands that participated in the study to be relayed to the community. Finally, the public will be informed of the results published in scientific journals through popularized summaries translated into both French and Tahitian.

The studies involving human participants were reviewed and approved by French Comité de protection des personnes (CPP—OUEST III no. 19.08.60/SI CNRIPH 19.07.02.38421) and Comité d'Ethique de la Polynésie française (Avis no. 80 CEPF-03/09/2019). The patients/participants provided their written informed consent to participate in this study.