This survey conducted among a large random sample of the general population living in Mayotte enabled us to provide original and robust estimates of hepatitis B, C, and delta prevalence and the distribution of HBV infection status, to identify the determinants of HBV infection and to describe the epidemiological and virological characteristics of people infected with HBV.
Current HBV infection prevalence was estimated to be 3.0% (95% CI: 2.3–3.9) in 15–69 year-olds, corresponding to a prevalence 10 times higher than that estimated in the general population in mainland France in 2016 (0.3%) . This is consistent with previous estimates that focussed on specific populations such as pregnant women (2.3–4.8%) [11–14], hospitalised patients (4.3%) , and people tested at the CHM laboratory (3.8%)  or in anonymous free testing consultations (4.5%) . Our findings confirm that Mayotte is an area of intermediate endemicity for HBV. The results also highlight that men were more affected by HBV with an estimated prevalence of 4.3%, which is more than twice as high as that estimated in women (1.9%), while they also had a significantly higher risk of being infected regardless of their other characteristics. Men should therefore constitute a target population for HBV testing. Indeed, with a high fertility rate (5.0 children per woman)  and a high rate of prenatal screening for hepatitis B (96.4%)  (mandatory since 1992), HBV testing may not be a pressing issue in women. Furthermore, testing is even more important, as nearly three quarters of people testing positive for HBsAg declared that they were living with a partner, with a risk of transmission to their spouse and children. The estimated proportion of HBsAg positive people indicating that a doctor had told them that they had hepatitis B (32%) should be interpreted with caution due to the small numbers of respondents and the fact that the question may have been misunderstood during the interview. In terms of age, the highest prevalence was observed among 30–49 year-olds (4.1%), although it exceeded 2% in the other age groups except for 15–19 year-olds (0.7%). Indeed, more than 80% of 15–19 year-olds were born in Mayotte and were therefore eligible for HBV vaccination at birth, a policy that was implemented at CHM in 1999 and officially recommended in Mayotte in 2012 [14, 20]. This was not the case with 20–29 year-olds given that they were born before 1999 and mostly in the Comoros (almost 60%) . In multivariate analysis, people of this age group were at a higher risk of having a current HBV infection compared to the youngest age group and the 30–49 age group. It should nevertheless be noted that multivariate analysis could not take into account the place of birth as it would have resulted in the loss of statistical power, since this information was only provided by people who answered the long questionnaire.
Our results suggest that the transmission modes of HBV are varied and that contamination occurs at all ages, as classically described in areas of intermediate HBV endemicity. Indeed, 1.3% of people who declared no sexual intercourse were positive for HBsAg, thus suggesting perinatal or childhood transmission. Conversely, the five times higher prevalence among people who declared not using a condom during their first sexual intercourse points toward sexual transmission. The heterogeneity of the population living in Mayotte, with more than half of adults born abroad , mainly in the Comoros where the health and social context is particularly unfavourable , also probably contributes to this variability regarding HBV transmission. Even if the economic situation is more privileged in Mayotte compared to the Comoros, it is important to note that more than a third of the population is estimated to lack health insurance coverage according our results (this proportion was 32.4% in 2019 according to the Mayotte Social Security Fund ). This proportion was estimated at 23% among people positive for HBsAg, with a possible impact on screening and management. It should be noted that state medical aid, a specific French health insurance coverage for irregular migrants, does not exist in Mayotte, where only legal residents can be insured. This is an issue for health care access, since half of residents of foreign nationality were in an irregular situation in 2015 .
In terms of comorbidities, no cases of co-infection with HIV or HCV were identified, reflecting the limited circulation of these viruses in Mayotte and more widely in the Comoros archipelago , probably linked to the low frequency of injecting drug use and sex between men . The proportion of diabetes (14%) and obesity (30%) was high in HBsAg positive people (also in those who were negative), thus constituting additional risk factors for progression to cirrhosis or liver cancer . Regarding virological characteristics, the proportion of people with HBV DNA level > 20,000 IU / mL (11.8%), positive HBeAg (6.5%) or positive HDV antibodies (0.65%) was lower than observed in patients treated in expert hepatology wards in France between 2008 and 2012 (22.2%, 12.2%, and 3.7%, respectively), as these services generally care for severe patients with more advanced liver disease . The HBV genotypes identified (A and D) correspond to those circulating in Africa, especially in East Africa .
The proportion of people with a resolved HBV infection was estimated at 27.8% (95% CI: 25.8–29.9), increasing sharply with age to reach 51% among 50–69 year-olds. Consequently, more than three in ten people aged 15–69 years living in Mayotte have a lifetime HBV infection (resolved or current). As expected, the risk of lifetime HBV infection in multivariate analysis was significantly higher in men and in people over 30 years (compared to those under 20). More surprisingly, compared to those born in Mayotte, people born in the Comoros were more likely to have been infected during their lifetime in univariate analysis, but this association was not statistically significant after adjustment to other variables, especially gender and age group, in multivariate analysis. This could be explained by significant differences between the age and sex distributions of people born in Mayotte and the Comoros, whereas the proportion of infected people varied greatly according to gender and age group . The risk of lifetime HBV infection was higher in the areas of Dembeni-Mamoudzou and Petite-Terre (though not significant for the latter) compared to the West-Centre of Mayotte in multivariate analysis. These areas are characterised by the highest proportions of people born in the Comoros (respectively 58% and 54% vs 42% in the rest of the island). After adjusting to other variables, this association, especially place of birth, suggests a higher past or current circulation of HBV in these areas, regardless of the place of birth. Finally, a significant association between condom non-use and risk of lifetime HBV infection was observed, as previously shown in pregnant women by Saindou et al. .
In this context of significant HBV circulation, the implementation of preventive measures, in particular vaccination, is essential. While the implementation of anti-HBV vaccination at birth [14, 20] since 1999 has made it possible to achieve high levels of vaccination coverage in children (95% in children aged 24–59 months) and adolescents (75% in 14–15 year-olds) , which are greater than for other vaccinations , HBV vaccination coverage still needs to be enhanced. Thus, only 37% of young people aged 15 to 19 years at the beginning of their sexual life presented a serological profile indicating immunisation by vaccination. This proportion remains insufficient even considering the possible loss of HBs antibodies, estimated to concern about 40–45% of adolescents vaccinated at birth . Indeed, it has been shown that protection persists for at least 30 years or even throughout life, even in the case of disappearing HBs antibodies . The determinants of immunisation by HBV vaccination, which would be useful to guide the implementation of a potential new vaccination catch-up campaign as previously performed in 2018 , will be the subject of a specific article.
Besides the insufficient immunisation rate, the vaccine status against HBV was poorly known by participants, since more than half of the population in Mayotte was estimated to be unaware of their HBV vaccine status. In mainland France, this estimated proportion was 7% in 2016 . Among people declaring to be vaccinated, 2.4% were estimated to be HBsAg positive and therefore at risk of transmitting the infection in a context of probably insufficient preventive sexual behaviours. Thus, only 19.5% of people indicated using a condom at their first sexual intercourse. This proportion was estimated to be 35.2% among 18–29 year-olds living in Mayotte (data not shown) versus 85% in the same population in mainland France in 2016 .
For hepatitis C virus, only six of the 2,917 people tested for HCV antibodies were positive (0.21%), including three positive for HCV RNA. This result confirms that Mayotte is a low endemic area for HCV, similarly to mainland France where the prevalence of HCV RNA was estimated at 0.3% among the general population in 2016 .
As the objective of the Unono Wa Maore survey was to describe the state of health and health care use for the population living in Mayotte, choices were made to limit the length of time for completing the questionnaires. Thus, the epidemiological data collected on hepatitis were limited and only appeared in the long questionnaire (e.g., questions on country of birth or sexuality). Therefore, this limited the power of the statistical analyses. Further, comparisons with the results of other health surveys performed in mainland France [19, 32] must be interpreted with caution given the methodological differences and the cultural specificities of the population living in Mayotte. Finally, due to difficulties relating to the context of the survey, not all respondents could have a blood sample and thus be screened for HBV and HCV. However, thanks to a very high participation rate in the survey (89%), nearly 3,000 people, or almost 2% of all residents aged 15–69 years, were tested for HBV and HCV. Their characteristics were close to those of all participants after weighting and adjustment. The implementation of the survey, directly in the homes of participants, also made it possible to take venous blood samples to search for numerous serological and molecular markers of hepatitis B, C, and delta.