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Author(s): Adam J. Kucharski 1,2,*, Kiyojiken Chung 2, Maite Aubry 2, Iotefa Teiti 2, Anita Teissier 2, Vaea Richard 2, Timothy W. Russell 1, Raphaëlle Bos 3, Sophie Olivier 3, [...], 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.

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. Author summary: Characterising the true extent of dengue circulation and the level of population immunity is essential to assess the burden of disease, evaluate epidemic risk and organise prevention strategies against future epidemics. However, this is difficult in a context where most people who are infected by dengue virus (DENV) only have mild symptoms which may not be reported to surveillance systems. In this article, we develop a mathematical model to evaluate the fraction of unreported dengue infections from case data. The key idea is to introduce reporting probabilities that depend on the infecting serotype and the infection history of patients. These factors are known to contribute to variations in the severity of symptoms and hence the reporting probabilities, but have rarely been taken into account in model frameworks to study population immunity from the case data. Using the developed model, we study long-term dengue virus immunity in French Polynesia. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. Author summary: Dengue virus is the most significant arthropod-borne virus infecting man. Understanding how long dengue virus can persist in populations of varying size is key to understanding its epidemiology. This is, however, impossible to achieve in settings where dengue is endemic, because of continued human movement and is further complexified by the occurrence of several co-circulating serotypes. By contrast, French Polynesia, an isolated group of 72 inhabited islands in the South Pacific, has had intermittent majoritarily monotypic dengue epidemics since the 1940s and offers a unique opportunity to address questions of viral persistence, turnover and the importance of spatial sub-structure in determining dengue epidemiology. Collating and analyzing a database of laboratory-confirmed dengue cases from across French Polynesia over a 35 year period we were able to show that dengue virus die-out can occur with or without replacement by a new serotype, monotypic transmission of dengue viruses fails to be maintained within small island populations but can persist for years among isolated islands connected via air and sea links. This remarkable long-term persistence of dengue virus in French Polynesia could be maintained by asynchronous viral transmission among connected islands and/or by repeated seeding from a reservoir of sub-clinical infections in the most populated island, Tahiti. [ABSTRACT FROM AUTHOR]

Background: In 2013, Zika virus (ZIKV) emerged in French Polynesia and spread through the Pacific region between 2013 and 2017. Several potential Aedes mosquitoes may have contributed to the ZIKV transmission including Aedes aegypti, the main arbovirus vector in the region, and Aedes polynesiensis, vector of lymphatic filariasis and secondary vector of dengue virus. The aim of this study was to analyze the ability of these two Pacific vectors to transmit ZIKV at a regional scale, through the evaluation and comparison of the vector competence of wild Ae. aegypti and Ae. polynesiensis populations from different Pacific islands for a ZIKV strain which circulated in this region during the 2013–2017 outbreak. Methodology/principal findings: Field Ae. aegypti (three populations) and Ae. polynesiensis (two populations) from the Pacific region were collected for this study. Female mosquitoes were orally exposed to ZIKV (107 TCID50/mL) isolated in the region in 2014. At 6, 9, 14 and 21 days post-infection, mosquito bodies (thorax and abdomen), heads and saliva were analyzed to measure infection, dissemination, transmission rates and transmission efficiency, respectively. According to our results, ZIKV infection rates were heterogeneous between the Ae. aegypti populations, but the dissemination rates were moderate and more homogenous between these populations. For Ae. polynesiensis, infection rates were less heterogeneous between the two populations tested. The transmission rate and efficiency results revealed a low vector competence for ZIKV of the different Aedes vector populations under study. Conclusion/significance: Our results indicated a low ZIKV transmission by Ae. aegypti and Ae. polynesiensis tested from the Pacific region. These results were unexpected and suggest the importance of other factors especially the vector density, the mosquito lifespan or the large immunologically naive fraction of the population that may have contributed to the rapid spread of the ZIKV in the Pacific region during the 2013–2017 outbreak. [ABSTRACT FROM AUTHOR]

Background: In 2013–2014, French Polynesia experienced for the first time a Zika outbreak. Two Aedes mosquitoes may have contributed to Zika virus (ZIKV) transmission in French Polynesia: the worldwide distributed Ae. aegypti and the Polynesian islands-endemic Ae. polynesiensis mosquito. Methodology/Principal Findings: To evaluate their vector competence for ZIKV, mosquitoes were infected per os at viral titers of 7 logs tissue culture infectious dose 50%. At several days post-infection (dpi), saliva was collected from each mosquito and inoculated onto C6/36 mosquito cells to check for the presence of ZIKV infectious particles. Legs and body of each mosquito were also collected and submitted separately to RNA extraction and ZIKV RT-PCR. In Ae. aegypti the infection rate was high as early as 6 dpi and the dissemination efficiency get substantial from 9 dpi while the both rates remained quite low in Ae. polynesiensis. The transmission efficiency was poor in Ae. aegypti until 14 dpi and no infectious saliva was found in Ae. polynesiensis at the time points studied. Conclusions/Significance: In our experimental conditions, the late ability of the French Polynesian Ae. aegypti to transmit ZIKV added by the poor competence of Ae. polynesiensis for this virus suggest the possible contribution of another vector for the propagation of ZIKV during the outbreak, in particular in remote islands where Ae. polynesiensis is predominating. [ABSTRACT FROM AUTHOR]

Background: From October 2014 to March 2015, French Polynesia experienced for the first time a chikungunya outbreak. Two Aedes mosquitoes may have contributed to chikungunya virus (CHIKV) transmission in French Polynesia: the worldwide distributed Ae. aegypti and the Polynesian islands-endemic Ae. polynesiensis mosquito. Methods: To investigate the vector competence of French Polynesian populations of Ae. aegypti and Ae. polynesiensis for CHIKV, mosquitoes were exposed per os at viral titers of 7 logs tissue culture infectious dose 50%. At 2, 6, 9, 14 and 21 days post-infection (dpi), saliva was collected from each mosquito and inoculated onto C6/36 mosquito cells to check for the presence of CHIKV infectious particles. Legs and body (thorax and abdomen) of each mosquito were also collected at the different dpi and submitted separately to viral RNA extraction and CHIKV real-time RT-PCR. Results: CHIKV infection rate, dissemination and transmission efficiencies ranged from 7–90%, 18–78% and 5–53% respectively for Ae. aegypti and from 39–41%, 3–17% and 0–14% respectively for Ae. polynesiensis, depending on the dpi. Infectious saliva was found as early as 2 dpi for Ae. aegypti and from 6 dpi for Ae. polynesiensis. Our laboratory results confirm that the French Polynesian population of Ae. aegypti is highly competent for CHIKV and they provide clear evidence for Ae. polynesiensis to act as an efficient CHIKV vector. Conclusion: As supported by our findings, the presence of two CHIKV competent vectors in French Polynesia certainly contributed to enabling this virus to quickly disseminate from the urban/peri-urban areas colonized by Ae. aegypti to the most remote atolls where Ae. polynesiensis is predominating. Ae. polynesiensis was probably involved in the recent chikungunya outbreaks in Samoa and the Cook Islands. Moreover, this vector may contribute to the risk for CHIKV to emerge in other Polynesian islands like Fiji, and more particularly Wallis where there is no Ae. aegypti. [ABSTRACT FROM AUTHOR]

Dengue virus (DENV) is an arbovirus transmitted to humans by the bite of infected Aedes mosquitoes. Experimental per os infection of mosquitoes with DENV is usually a preliminary step in virus/vector studies but it requires being able to prepare artificial blood-meals with high virus titers. We report here the convenient use of centrifugal filter devices to quickly concentrate DENV particles in cell-culture supernatants. The median viral titer in concentrated-supernatants was 8.50 log10 TCID50/mL. By using these DENV concentrated-supernatants to prepare infectious blood-meals in Aedes aegypti per os infection experiments, we obtained a mean mosquito-infection rate of 94%. We also evaluated the use of centrifugal filter devices to recover DENV particles from non-infectious blood-meals presented to infected mosquitoes through a feeding membrane to collect their saliva. [ABSTRACT FROM AUTHOR]

Background: Dengue fever (DF) is an emerging infectious disease in the tropics and subtropics. Determinants of DF epidemiology and factors involved in severe cases—dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS)—remain imperfectly characterized. Since 2000, serotype 1 (DENV-1) has predominated in the South Pacific. The aim of this study was (i) to determine the origin and (ii) to study the evolutionary relationships of DENV-1 viruses that have circulated in French Polynesia (FP) from the severe 2001 outbreak to the recent 2006 epidemic, and (iii) to analyse the viral intra-host genetic diversity according to clinical presentation. Methodology/Principal Findings: Sequences of 181 envelope gene and 12 complete polyproteins of DENV-1 viruses obtained from human sera in FP during the 2001–2006 period were generated. Phylogenetic analysis showed that all DENV-1 FP strains belonged to genotype IV–"South Pacific" and derived from a single introduction event from South-East Asia followed by a 6-year in situ evolution. Although the ratio of nonsynonymous/synonymous substitutions per site indicated strong negative selection, a mutation in the envelope glycoprotein (S222T) appeared in 2002 and was subsequently fixed. It was noted that genetic diversification was very significant during the 2002–2005 period of endemic DENV-1 circulation. For nine DF sera and eight DHF/DSS sera, approximately 40 clones/serum of partial envelope gene were sequenced. Importantly, analysis revealed that the intra-host genetic diversity was significantly lower in severe cases than in classical DF. Conclusions/Significance: First, this study showed that DENV-1 epidemiology in FP was different from that described in other South-Pacific islands, characterized by a long sustained viral circulation and the absence of new viral introduction over a 6-year period. Second, a significant part of DENV-1 evolution was observed during the endemic period characterized by the rapid fixation of S222T in the envelope protein that may reflect genetic drift or adaptation to the mosquito vector. Third, for the first time, it is suggested that clinical outcome may be correlated with intra-host genetic diversity. Author Summary: The molecular characterization of 181 serotype 1 Dengue fever (DENV-1) viruses collected regularly during the 2001–2006 period in French Polynesia (FP) from patients experiencing various clinical presentations revealed that the virus responsible for the severe 2001 outbreak was introduced from South-East Asia, and evolved under an endemic mode until a new epidemic five years later. The dynamics of DENV-1 epidemics in FP did not follow the model of repeated virus introductions described in other South Pacific islands. They were characterized by a long sustained viral circulation and the absence of new viral introduction over a six-year period. Viral genetic variability was not observed only during outbreaks. In contrast with conventional thinking, a significant part of DENV-1 evolution may occur during endemic periods, and may reflect adaptation to the mosquito vector. However, DENV-1 evolution was globally characterized by strong purifying selection pressures leading to genome conservation, like other DENV serotypes and other arboviruses subject to constraints imposed by the host-vector alternating replication of viruses. Severe cases—dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS)—may be linked to both viral and host factors. For the first time, we report a significant correlation between intra-host viral genetic variability and clinical outcome. Severe cases were characterized by more homogeneous viral populations with lower intra-host genetic variability. [ABSTRACT FROM AUTHOR]