Towards elimination of chronic viral hepatitis in French Polynesia: results from a national population-based survey.

Background: In French Polynesia, hepatitis B virus (HBV) infection appears as a major risk factor for hepatocellular carcinoma (HCC), which detection rate in the Austral archipelago is among the highest in the world. Through a nationally representative cross-sectional survey of the adult population, this study aimed at assessing the prevalence of HBV, but also hepatitis C virus (HCV), and hepatitis delta virus (HDV). Methods: A total of 1942 blood samples from participants aged 18-69 years were tested for anti-HBc, anti-HBs, HBsAg, anti-HCV IgG, and HDV RNA. Complete genome sequencing of detected HBV strains was performed. Findings: Among participants, 315/1834, 582/1834, 33/1834, 0/1857, and 0/33 tested positive for anti-HBc, anti-HBs, HBsAg, anti-HCV IgG, and HDV RNA, respectively. The population prevalence of HBsAg was estimated at 1.0% (95% CI: 0.6-1.7). All HBsAg carriers were born in French Polynesia before vaccination at birth became mandatory. In multivariate analyses, identified factors associated with HBsAg carriage included: the archipelago of residence (p < 0.0001), age (p < 0.0001), and education level (p = 0.0077). HBV genotypes B, C, and F were detected. Interpretation: French Polynesia has a low endemicity level of HBV and its population may be considered at low risk for HCV and HDV infection. However, prevalence of HBsAg was found concerning in Austral (3.8%; 95% CI: 1.9-7.5) and Marquesas (6.5%; 95% CI: 3.8-11) archipelagoes. In the Austral archipelago, the presence of genotype C may account for the elevated rate of HCC. Our findings warrant more efforts to improve access to detection, prevention and care to people born before the systematic vaccination policy application, and residing in higher-risk areas, to achieve HBV elimination in French Polynesia. Funding: Research Delegation of French Polynesia.

SARS-CoV-2 seroprevalence and associated factors of infection before and after the Delta wave in French Polynesia: a cross-sectional study.

BACKGROUND: French Polynesia (FP) comprises 75 inhabited islands scattered across five archipelagos. Between July and October 2021, the SARS-CoV-2 Delta variant triggered a much stronger second epidemic wave in FP than the original Wuhan strain, which was dominant from August 2020 to March 2021. Although previous seroprevalence surveys made it possible to determine the proportion of the population infected by SARS-CoV-2 on the two most populated islands (Tahiti and Moorea) after the first (20.6% in Tahiti and 9.4% in Moorea) and second (57.7% in Tahiti) epidemic waves, no data are available for more remote islands. We used blood samples and personal data collected before, during, and after the second wave from inhabitants of several islands within the five archipelagos to assess the prevalence of SARS-CoV-2 infections and identify associated factors. METHODS: Blood samples and personal data were collected between April and December 2021 as part of the MATAEA study, a cross-sectional survey conducted on a random sample of the adult population representative of the five FP archipelagos and stratified by age and gender. IgG antibodies targeting the SARS-CoV-2 nucleocapsid (N) protein were detected using a recombinant antigen-based microsphere immunoassay. Factors associated with anti-SARS-CoV-2-N seropositivity were identified using logistic regression models. RESULTS: Of 1,120 participants, 503 (44.9%) tested positive for anti-SARS-CoV-2-N antibodies, corresponding to a weighted prevalence of 56.8% for the FP population aged 18-69 years. The seroprevalence increased from 21.9% to 62.1% before and during/after the Delta wave. Of these infections, only 28.4% had been diagnosed by health professionals. The odds of being seropositive were lower in males, participants recruited before the Delta wave, those who had never been married, those with a diagnosed respiratory allergy, smokers, and those vaccinated against COVID-19. CONCLUSIONS: Our results confirm the high impact of the Delta wave in FP. By the end of 2021, 56.8% of the FP population aged 18-69 years had been infected by SARS-CoV-2; the majority of these infections went undetected. Individuals with respiratory allergies were found to be less susceptible to SARS-CoV-2 infection.

Impact of vaccinations, boosters and lockdowns on COVID-19 waves in French Polynesia.

Estimating the impact of vaccination and non-pharmaceutical interventions on COVID-19 incidence is complicated by several factors, including successive emergence of SARS-CoV-2 variants of concern and changing population immunity from vaccination and infection. We develop an age-structured multi-strain COVID-19 transmission model and inference framework to estimate vaccination and non-pharmaceutical intervention impact accounting for these factors. We apply this framework to COVID-19 waves in French Polynesia and estimate that the vaccination programme averted 34.8% (95% credible interval: 34.5-35.2%) of 223,000 symptomatic cases, 49.6% (48.7-50.5%) of 5830 hospitalisations and 64.2% (63.1-65.3%) of 1540 hospital deaths that would have occurred in a scenario without vaccination up to May 2022. We estimate the booster campaign contributed 4.5%, 1.9%, and 0.4% to overall reductions in cases, hospitalisations, and deaths. Our results suggest that removing lockdowns during the first two waves would have had non-linear effects on incidence by altering accumulation of population immunity. Our estimates of vaccination and booster impact differ from those for other countries due to differences in age structure, previous exposure levels and timing of variant introduction relative to vaccination, emphasising the importance of detailed analysis that accounts for these factors.

Real-time surveillance of international SARS-CoV-2 prevalence using systematic traveller arrival screening: An observational study.

BACKGROUND: Effective Coronavirus Disease 2019 (COVID-19) response relies on good knowledge of population infection dynamics, but owing to under-ascertainment and delays in symptom-based reporting, obtaining reliable infection data has typically required large dedicated local population studies. Although many countries implemented Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) testing among travellers, it remains unclear how accurately arrival testing data can capture international patterns of infection, because those arrival testing data were rarely reported systematically, and predeparture testing was often in place as well, leading to nonrepresentative infection status among arrivals. METHODS AND FINDINGS: In French Polynesia, testing data were reported systematically with enforced predeparture testing type and timing, making it possible to adjust for nonrepresentative infection status among arrivals. Combining statistical models of polymerase chain reaction (PCR) positivity with data on international travel protocols, we reconstructed estimates of prevalence at departure using only testing data from arrivals. We then applied this estimation approach to the United States of America and France, using data from over 220,000 tests from travellers arriving into French Polynesia between July 2020 and March 2022. We estimated a peak infection prevalence at departure of 2.1% (95% credible interval: 1.7, 2.6%) in France and 1% (95% CrI: 0.63, 1.4%) in the USA in late 2020/early 2021, with prevalence of 4.6% (95% CrI: 3.9, 5.2%) and 4.3% (95% CrI: 3.6, 5%), respectively, estimated for the Omicron BA.1 waves in early 2022. We found that our infection estimates were a leading indicator of later reported case dynamics, as well as being consistent with subsequent observed changes in seroprevalence over time. We did not have linked data on traveller demography or unbiased domestic infection estimates (e.g., from random community infection surveys) in the USA and France. However, our methodology would allow for the incorporation of prior data from additional sources if available in future. CONCLUSIONS: As well as elucidating previously unmeasured infection dynamics in these countries, our analysis provides a proof-of-concept for scalable and accurate leading indicator of global infections during future pandemics.

Unravelling the determinants of human health in French Polynesia: the MATAEA project.

Background: French Polynesia is a French overseas collectivity in the Southeast Pacific, comprising 75 inhabited islands across five archipelagoes. The human settlement of the region corresponds to the last massive migration of humans to empty territories, but its timeline is still debated. Despite their recent population history and geographical isolation, inhabitants of French Polynesia experience health issues similar to those of continental countries. Modern lifestyles and increased longevity have led to a rise in non-communicable diseases (NCDs) such as obesity, diabetes, hypertension, and cardiovascular diseases. Likewise, international trade and people mobility have caused the emergence of communicable diseases (CDs) including mosquito-borne and respiratory diseases. Additionally, chronic pathologies including acute rheumatic fever, liver diseases, and ciguatera, are highly prevalent in French Polynesia. However, data on such diseases are scarce and not representative of the geographic fragmentation of the population. Objectives: The present project aims to estimate the prevalence of several NCDs and CDs in the population of the five archipelagoes, and identify associated risk factors. Moreover, genetic analyses will contribute to determine the sequence and timings of the peopling history of French Polynesia, and identify causal links between past genetic adaptation to island environments, and present-day susceptibility to certain diseases. Methods: This cross-sectional survey is based on the random selection of 2,100 adults aged 18-69 years and residing on 18 islands from the five archipelagoes. Each participant answered a questionnaire on a wide range of topics (including demographic characteristics, lifestyle habits and medical history), underwent physical measurements (height, weight, waist circumference, arterial pressure, and skin pigmentation), and provided biological samples (blood, saliva, and stool) for biological, genetic and microbiological analyses. Conclusion: For the first time in French Polynesia, the present project allows to collect a wide range of data to explore the existence of indicators and/or risk factors for multiple pathologies of public health concern. The results will help health authorities to adapt actions and preventive measures aimed at reducing the incidence of NCDs and CDs. Moreover, the new genomic data generated in this study, combined with anthropological data, will increase our understanding of the peopling history of French Polynesia. Clinical trial registration: https://clinicaltrials.gov/, identifier: NCT06133400.

Reconstructing long-term dengue virus immunity in French Polynesia.

BACKGROUND: Understanding the underlying risk of infection by dengue virus from surveillance systems is complicated due to the complex nature of the disease. In particular, the probability of becoming severely sick is driven by serotype-specific infection histories as well as age; however, this has rarely been quantified. Island communities that have periodic outbreaks dominated by single serotypes provide an opportunity to disentangle the competing role of serotype, age and changes in surveillance systems in characterising disease risk. METHODOLOGY: We develop mathematical models to analyse 35 years of dengue surveillance (1979-2014) and seroprevalence studies from French Polynesia. We estimate the annual force of infection, serotype-specific reporting probabilities and changes in surveillance capabilities using the annual age and serotype-specific distribution of dengue. PRINCIPAL FINDINGS: Eight dengue epidemics occurred between 1979 and 2014, with reporting probabilities for DENV-1 primary infections increasing from 3% to 5%. The reporting probability for DENV-1 secondary infections was 3.6 times that for primary infections. We also observed heterogeneity in reporting probabilities by serotype, with DENV-3 having the highest probability of being detected. Reporting probabilities declined with age after 14 y.o. Between 1979 and 2014, the proportion never infected declined from 70% to 23% while the proportion infected at least twice increased from 4.5% to 45%. By 2014, almost half of the population had acquired heterotypic immunity. The probability of an epidemic increased sharply with the estimated fraction of susceptibles among children. CONCLUSION/SIGNIFICANCE: By analysing 35 years of dengue data in French Polynesia, we characterised key factors affecting the dissemination profile and reporting of dengue cases in an epidemiological context simplified by mono-serotypic circulation. Our analysis provides key estimates that can inform the study of dengue in more complex settings where the co-circulation of multiple serotypes can greatly complicate inference.

Considering waning immunity to better explain dengue dynamics.

Life-long serotype-specific immunity following dengue virus infection may not always occur, but the true extent of this effect is unknown. Analysis of more than 20 years of monotypic epidemics in the isolated French Polynesian islands revealed that whilst the risk of symptomatic dengue infection did conform to the classical paradigms of homotypic immunity and increased disease risk in heterotypic secondary infections, incorporation of waning immunity improved the ability of epidemiological models to capture the observed epidemic dynamics. Not only does this show how inclusion of waning immunity into classical models can reveal important facets of the immune response to natural dengue virus infection, it also has significant ramifications for vaccine development and implementation in dengue endemic areas.

Perspective on the Use of Innovative Surveillance Strategies Implemented for COVID-19 to Prevent Mosquito-Borne Disease Emergence in French Polynesia.

In French Polynesia, following the emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in March 2020, several control measures were implemented to prevent virus spread, including a population lockdown and the interruption of international air traffic. SARS-CoV-2 local transmission rapidly stopped, and circulation of dengue virus serotypes 1 and 2, the only arboviruses being detected at that time, decreased. After the borders re-opened, a surveillance strategy consisting of the testing by SARS-CoV-2 RT-PCR of travelers entering French Polynesia, and isolating those with ongoing infection, was implemented. This strategy proved efficient to limit the introduction of SARS-CoV-2, and should be considered to prevent the importation of other pathogens, including mosquito-borne viruses, in geographically isolated areas such as French Polynesia.

Self-collection and pooling of samples as resources-saving strategies for RT-PCR-based SARS-CoV-2 surveillance, the example of travelers in French Polynesia.

In French Polynesia, the first case of SARS-CoV-2 infection was detected on March 10th, 2020, in a resident returning from France. Between March 28th and July 14th, international air traffic was interrupted and local transmission of SARS-CoV-2 was brought under control, with only 62 cases recorded. The main challenge for reopening the air border without requiring travelers to quarantine on arrival was to limit the risk of re-introducing SARS-CoV-2. Specific measures were implemented, including the obligation for all travelers to have a negative RT-PCR test for SARS-CoV-2 carried out within 3 days before departure, and to perform another RT-PCR testing 4 days after arrival. Because of limitation in available medical staff, travelers were provided a kit allowing self-collection of oral and nasal swabs. In addition to increase our testing capacity, self-collected samples from up to 10 travelers were pooled before RNA extraction and RT-PCR testing. When a pool tested positive, RNA extraction and RT-PCR were performed on each individual sample. We report here the results of COVID-19 surveillance (COV-CHECK PORINETIA) conducted between July 15th, 2020, and February 15th, 2021, in travelers using self-collection and pooling approaches. We tested 5,982 pools comprising 59,490 individual samples, and detected 273 (0.46%) travelers positive for SARS-CoV-2. A mean difference of 1.17 Ct (CI 95% 0.93-1.41) was found between positive individual samples and pools (N = 50), probably related to the volume of samples used for RNA extraction (200 µL versus 50 µL, respectively). Retrospective testing of positive samples self-collected from October 20th, 2020, using variants-specific amplification kit and spike gene sequencing, found at least 6 residents infected by the Alpha variant. Self-collection and pooling approaches allowed large-scale screening for SARS-CoV-2 using less human, material and financial resources. Moreover, this strategy allowed detecting the introduction of SARS-CoV-2 variants of concern in French Polynesia.

Interactions between timing and transmissibility explain diverse flavivirus dynamics in Fiji.

Zika virus (ZIKV) has caused large, brief outbreaks in isolated populations, however ZIKV can also persist at low levels over multiple years. The reasons for these diverse transmission dynamics remain poorly understood. In Fiji, which has experienced multiple large single-season dengue epidemics, there was evidence of multi-year transmission of ZIKV between 2013 and 2017. To identify factors that could explain these differences in dynamics between closely related mosquito-borne flaviviruses, we jointly fit a transmission dynamic model to surveillance, serological and molecular data. We estimate that the observed dynamics of ZIKV were the result of two key factors: strong seasonal effects, which created an ecologically optimal time of year for outbreaks; and introduction of ZIKV after this optimal time, which allowed ZIKV transmission to persist over multiple seasons. The ability to jointly fit to multiple data sources could help identify a similar range of possible outbreak dynamics in other settings.

Recent African strains of Zika virus display higher transmissibility and fetal pathogenicity than Asian strains.

The global emergence of Zika virus (ZIKV) revealed the unprecedented ability for a mosquito-borne virus to cause congenital birth defects. A puzzling aspect of ZIKV emergence is that all human outbreaks and birth defects to date have been exclusively associated with the Asian ZIKV lineage, despite a growing body of laboratory evidence pointing towards higher transmissibility and pathogenicity of the African ZIKV lineage. Whether this apparent paradox reflects the use of relatively old African ZIKV strains in most laboratory studies is unclear. Here, we experimentally compare seven low-passage ZIKV strains representing the recently circulating viral genetic diversity. We find that recent African ZIKV strains display higher transmissibility in mosquitoes and higher lethality in both adult and fetal mice than their Asian counterparts. We emphasize the high epidemic potential of African ZIKV strains and suggest that they could more easily go unnoticed by public health surveillance systems than Asian strains due to their propensity to cause fetal loss rather than birth defects.

Enhanced Zika virus susceptibility of globally invasive Aedes aegypti populations.

The drivers and patterns of zoonotic virus emergence in the human population are poorly understood. The mosquito Aedes aegypti is a major arbovirus vector native to Africa that invaded most of the world's tropical belt over the past four centuries, after the evolution of a "domestic" form that specialized in biting humans and breeding in water storage containers. Here, we show that human specialization and subsequent spread of A. aegypti out of Africa were accompanied by an increase in its intrinsic ability to acquire and transmit the emerging human pathogen Zika virus. Thus, the recent evolution and global expansion of A. aegypti promoted arbovirus emergence not solely through increased vector-host contact but also as a result of enhanced vector susceptibility.

Long-term persistence of monotypic dengue transmission in small size isolated populations, French Polynesia, 1978-2014.

Understanding the transition of epidemic to endemic dengue transmission remains a challenge in regions where serotypes co-circulate and there is extensive human mobility. French Polynesia, an isolated group of 117 islands of which 72 are inhabited, distributed among five geographically separated subdivisions, has recorded mono-serotype epidemics since 1944, with long inter-epidemic periods of circulation. Laboratory confirmed cases have been recorded since 1978, enabling exploration of dengue epidemiology under monotypic conditions in an isolated, spatially structured geographical location. A database was constructed of confirmed dengue cases, geolocated to island for a 35-year period. Statistical analyses of viral establishment, persistence and fade-out as well as synchrony among subdivisions were performed. Seven monotypic and one heterotypic dengue epidemic occurred, followed by low-level viral circulation with a recrudescent epidemic occurring on one occasion. Incidence was asynchronous among the subdivisions. Complete viral die-out occurred on several occasions with invasion of a new serotype. Competitive serotype replacement has been observed previously and seems to be characteristic of the South Pacific. Island population size had a strong impact on the establishment, persistence and fade-out of dengue cases and endemicity was estimated achievable only at a population size in excess of 175 000. Despite island remoteness and low population size, dengue cases were observed somewhere in French Polynesia almost constantly, in part due to the spatial structuration generating asynchrony among subdivisions. Long-term persistence of dengue virus in this group of island populations may be enabled by island hopping, although could equally be explained by a reservoir of sub-clinical infections on the most populated island, Tahiti.

First evidence of concurrent enzootic and endemic transmission of Ross River virus in the absence of marsupial reservoirs in Fiji.

BACKGROUND: Ross River virus (RRV) is a zoonotic alphavirus transmitted by several mosquito species. Until recently, endemic transmission was only considered possible in the presence of marsupial reservoirs. METHODS: RRV seroprevalence was investigated in placental mammals (including horses, cows, goats, pigs, dogs, rats, and mice) in Fiji, where there are no marsupials. A total of 302 vertebrate serum samples were collected from 86 households from 10 communities in Western Fiji. RESULTS: Neutralizing antibodies against RRV were detected in 28% to 100% of sera depending on the species, and neutralization was strong even at high dilutions. CONCLUSIONS: These results are unlikely to be due to cross-reactions. Chikungunya is the only other alphavirus known to be present in the Pacific Islands, but it rarely spills over into non-humans, even during epidemics. The study findings, together with a recent report of high RRV seroprevalence in humans, strongly suggest that RRV is circulating in Fiji in the absence of marsupial reservoirs. Considering that all non-human vertebrates present in Fiji are pan-global in distribution, RRV has the potential to further expand its geographic range. Further surveillance of RRV and access to RRV diagnostics will be critical for the early detection of emergence and outbreaks.

Zika seroprevalence declines and neutralizing antibodies wane in adults following outbreaks in French Polynesia and Fiji.

It has been commonly assumed that Zika virus (ZIKV) infection confers long-term protection against reinfection, preventing ZIKV from re-emerging in previously affected areas for several years. However, the long-term immune response to ZIKV following an outbreak remains poorly documented. We compared results from eight serological surveys before and after known ZIKV outbreaks in French Polynesia and Fiji, including cross-sectional and longitudinal studies. We found evidence of a decline in seroprevalence in both countries over a two-year period following first reported ZIKV transmission. This decline was concentrated in adults, while high seroprevalence persisted in children. In the Fiji cohort, there was also a significant decline in neutralizing antibody titres against ZIKV, but not against dengue viruses that circulated during the same period.

Low chikungunya virus seroprevalence two years after emergence in Fiji.

OBJECTIVES: In Fiji, autochthonous chikungunya virus (CHIKV) infection was first detected in March 2015. In a previous serosurvey conducted during October-November 2015, we reported a prevalence of anti-CHIKV IgG antibodies of 0.9%. In the present study, we investigated the seroprevalence of CHIKV two years after its emergence in Fiji. METHODS: Sera from 320 residents of Fiji recruited in June 2017, from the same cohort of individuals that participated in the serosurvey in 2015, were tested for the presence of IgG antibodies against CHIKV using a recombinant antigen-based microsphere immunoassay. RESULTS: Between 2015 and 2017, CHIKV seroprevalence among residents increased from 0.9% (3/333) to 12.8% (41/320). Of the participants with available serum samples collected in both 2015 and 2017 (n=200), 31 (15.5%) who were seronegative in 2015 had seroconverted to CHIKV in 2017. CONCLUSIONS: Our findings suggest that low-level transmission of CHIKV occurred during the two years following the emergence of the virus in Fiji. No CHIKV infection has been reported in Fiji since 2017, but due to the presumed low herd immunity of the population, the risk of CHIKV re-emergence is high. Consequently, chikungunya should be considered in the differential diagnosis of acute febrile diseases in Fiji.

Dengue virus serotype 2 (DENV-2) outbreak, French Polynesia, 2019.

In 1996-97, the last dengue virus serotype 2 (DENV-2) outbreak occurred in French Polynesia. In February 2019, DENV-2 infection was detected in a traveller from New Caledonia. In March, autochthonous DENV-2 infection was diagnosed in two residents. A DENV-2 outbreak was declared on 10 April with 106 cases as at 24 June. Most of the population is not immune to DENV-2; a large epidemic could occur with risk of imported cases in mainland France.

Sustained Low-Level Transmission of Zika and Chikungunya Viruses after Emergence in the Fiji Islands.

Zika and chikungunya viruses were first detected in Fiji in 2015. Examining surveillance and phylogenetic and serologic data, we found evidence of low-level transmission of Zika and chikungunya viruses during 2013-2017, in contrast to the major outbreaks caused by closely related virus strains in other Pacific Island countries.