Re-Emergence of DENV-3 in French Guiana: Retrospective Analysis of Cases That Circulated in the French Territories of the Americas from the 2000s to the 2023-2024 Outbreak.

French Guiana experienced an unprecedented dengue epidemic during 2023-2024. Prior to the 2023-2024 outbreak in French Guiana, DENV-3 had not circulated in an epidemic manner since 2005. We therefore studied retrospectively the strains circulating in the French Territories of the Americas (FTA)-French Guiana, Guadeloupe, and Martinique-from the 2000s to the current epidemic. To this end, DENV-3 samples from the collection of the National Reference Center for Arboviruses in French Guiana (NRCA-FG) were selected and sequenced using next-generation sequencing (NGS) based on Oxford Nanopore Technologies, ONT. Phylogenetic analysis showed that (i) the 97 FTA sequences obtained all belonged to genotype III (GIII); (ii) between the 2000s and 2013, the regional circulation of the GIII American-I lineage was the source of the FTA cases through local extinctions and re-introductions; (iii) multiple introductions of lineages of Asian origin appear to be the source of the 2019-2021 epidemic in Martinique and the 2023-2024 epidemic in French Guiana. Genomic surveillance is a key factor in identifying circulating DENV genotypes, monitoring strain evolution, and identifying import events.

Molecular epidemiology identifies the expansion of the DENV2 epidemic lineage from the French Caribbean Islands to French Guiana and mainland France, 2023 to 2024.

In 2023, dengue virus serotype 2 (DENV2) affected most French overseas territories. In the French Caribbean Islands, viral circulation continues with > 30,000 suspected infections by March 2024. Genome sequence analysis reveals that the epidemic lineage in the French Caribbean islands has also become established in French Guiana but not Réunion. It has moreover seeded autochthonous circulation events in mainland France. To guide prevention of further inter-territorial spread and DENV introduction in non-endemic settings, continued molecular surveillance and mosquito control are essential.

Etiology of Acute Febrile Illnesses in Adults in the Defense Community in French Guiana.

In tropical countries, acute febrile illnesses represent a complex clinical problem for general practitioners. We describe the prevalence of different etiologies of acute febrile illnesses occurring among French service members and their families, excluding children, in general practice in French Guiana. From June 2017 to March 2020, patients with a fever ≥37.8°C with a duration of less than 15 days who sought medical care at the army medical centers in Cayenne and Kourou were prospectively enrolled. Based on clinical presentation, blood, urine, nasopharyngeal, and stool samples were collected for diagnostic testing for viruses, bacteria, and parasites (by direct examination, microscopic examination of blood smears, culture, serology, or polymerase chain reaction), and standardized biological tests were systematically performed. Among 175 patients retained for analysis, fever with nonspecific symptoms was predominant (46.9%), with 10 Plasmodium vivax malaria cases, 8 dengue infections, and 6 cases of Q fever. The second most frequent cause of acute febrile illness was upper respiratory tract infections (32.0%) due to influenza virus (n = 18) or human rhinovirus (n = 10). Among the causes of acute febrile illness in French Guiana, clinicians should first consider arboviruses and malaria, as well as Q fever in cases of elevated C-reactive protein with nonspecific symptoms and influenza in cases of signs and symptoms associated with upper respiratory tract infections. Despite an expanded microbiological search, the etiology of 51.4% of acute febrile illnesses remain unknown. Further investigations will be necessary to identify the etiology of acute febrile illnesses, including new pathogens, in French Guiana.

[Overview of infectious and non-infectious diseases in French Guiana in 2022]. / Panorama des pathologies infectieuses et non infectieuses de Guyane en 2022.

Source of many myths, French Guiana represents an exceptional territory due to the richness of its biodiversity and the variety of its communities. The only European territory in Amazonia, surrounded by the Brazilian giant and the little-known Suriname, Ariane 6 rockets are launched from Kourou while 50% of the population lives below the poverty line. This paradoxical situation is a source of health problems specific to this territory, whether they be infectious diseases with unknown germs, intoxications or chronic pathologies.Some infectious diseases such as Q fever, toxoplasmosis, cryptococcosis or HIV infection are in common with temperate countries, but present specificities leading to sometimes different management and medical reasoning. In addition to these pathologies, many tropical diseases are present in an endemic and / or epidemic mode such as malaria, leishmaniasis, Chagas disease, histoplasmosis or dengue. Besides, Amazonian dermatology is extremely varied, ranging from rare but serious pathologies (Buruli ulcer, leprosy) to others which are frequent and benign such as agouti lice (mites of the family Trombiculidae) or papillonitis. Envenomations by wild fauna are not rare, and deserve an appropriate management of the incriminated taxon. Obstetrical, cardiovascular and metabolic cosmopolitan pathologies sometimes take on a particular dimension in French Guiana that must be taken into account in the management of patients. Finally, different types of intoxication are to be known by practitioners, especially due to heavy metals.European-level resources offer diagnostic and therapeutic possibilities that do not exist in the surrounding countries and regions, thus allowing the management of diseases that are not well known elsewhere.Thanks to these same European-level resources, research in Guyana occupies a key place within the Amazon region, despite a smaller population than in the surrounding countries. Thus, certain pathologies such as histoplasmosis of the immunocompromised patient, Amazonian toxoplasmosis or Q fever are hardly described in neighboring countries, probably due to under-diagnosis linked to more limited resources. French Guiana plays a leading role in the study of these diseases.The objective of this overview is to guide health care providers coming to or practicing in French Guiana in their daily practice, but also practitioners taking care of people returning from French Guiana.

Review on Main Arboviruses Circulating on French Guiana, An Ultra-Peripheric European Region in South America.

French Guiana (FG), a French overseas territory in South America, is susceptible to tropical diseases, including arboviruses. The tropical climate supports the proliferation and establishment of vectors, making it difficult to control transmission. In the last ten years, FG has experienced large outbreaks of imported arboviruses such as Chikungunya and Zika, as well as endemic arboviruses such as dengue, Yellow fever, and Oropouche virus. Epidemiological surveillance is challenging due to the differing distributions and behaviors of vectors. This article aims to summarize the current knowledge of these arboviruses in FG and discuss the challenges of arbovirus emergence and reemergence. Effective control measures are hampered by the nonspecific clinical presentation of these diseases, as well as the Aedes aegypti mosquito's resistance to insecticides. Despite the high seroprevalence of certain viruses, the possibility of new epidemics cannot be ruled out. Therefore, active epidemiological surveillance is needed to identify potential outbreaks, and an adequate sentinel surveillance system and broad virological diagnostic panel are being developed in FG to improve disease management.

Dynamics of SARS-CoV-2 lineages in French Guiana in 2020-2021: 4 epidemic waves with cross-influences from Europe and South America.

Since the first cases of SARS-CoV-2 infection in Wuhan in December 2019, this RNA virus gave rise to different viral lineages with different virological, epidemiological and immunological properties. Here we describe the dynamics of circulation of SARS-CoV-2 lineages in an Amazonian South American French overseas territory, French Guiana (FG). The data analyzed are based on the general epidemic course, and genomic surveillance data come from whole genome sequencing (WGS) as well as typing PCRs. From March 2020 to October 2021, four COVID-19 epidemic waves were observed in FG with an evolution of viral lineages influenced by virus introductions from continental France and above all by land-based introductions from neighbouring countries. The third epidemic wave from March to June 2021 was driven by a predominant Gamma introduced from Brazil and a less frequent Alpha introduced from France. This coexistence was completely substituted by Delta that initiated the fourth epidemic wave.

Tonate Virus and Fetal Abnormalities, French Guiana, 2019.

We report a case of vertical transmission of Tonate virus in a pregnant woman from French Guiana. The fetus showed severe necrotic and hemorrhagic lesions of the brain and spinal cord. Clinicians should be made aware of possible adverse fetal outcomes in pregnant women infected with Tonate virus.

Seroprevalence of anti-SARS-CoV-2 IgG at the first epidemic peak in French Guiana, July 2020.

BACKGROUND: While Latin America has been heavily affected by the pandemic, only a few seroprevalence studies have been conducted there during the first epidemic wave in the first half of 2020. METHODOLOGY/PRINCIPAL FINDINGS: A cross-sectional survey was performed between 15 July 2020 and 23 July 2020 among individuals who visited 4 medical laboratories or 5 health centers for routine screening or clinical management, with the exception of symptomatic suggestive cases of covid-19. Samples were screened for the presence of anti-SARS-CoV-2 IgG directed against domain S1 of the SARS-CoV-2 spike protein using the anti-SARS-CoV-2 enzyme-linked immunosorbent assay (ELISA) from Euroimmun. CONCLUSIONS/SIGNIFICANCE: The overall seroprevalence was 15.4% [9.3%-24.4%] among 480 participants, ranging from 4.0% to 25.5% across the different municipalities. The seroprevalence did not differ according to gender (p = 0.19) or age (p = 0.51). Among SARS-CoV-2 positive individuals, we found that 24.6% [11.5%-45.2%] reported symptoms consistent with COVID-19. Our findings revealed high levels of infection across the territory but a low number of resulting deaths, which can be explained by French Guiana's young population structure.

Outbreak of Oropouche Virus in French Guiana.

Oropouche fever is a zoonotic dengue-like syndrome caused by Oropouche virus. In August-September 2020, dengue-like syndrome developed in 41 patients in a remote rainforest village in French Guiana. By PCR or microneutralization, 23 (82.1%) of 28 tested patients were positive for Oropouche virus, documenting its emergence in French Guiana.

Spatial Distribution and Burden of Emerging Arboviruses in French Guiana.

Despite the health, social and economic impact of arboviruses in French Guiana, very little is known about the extent to which infection burden is shared between individuals. We conducted a large multiplexed serological survey among 2697 individuals from June to October 2017. All serum samples were tested for IgG antibodies against DENV, CHIKV, ZIKV and MAYV using a recombinant antigen-based microsphere immunoassay with a subset further evaluated through anti-ZIKV microneutralization tests. The overall DENV seroprevalence was estimated at 73.1% (70.6-75.4) in the whole territory with estimations by serotype at 68.9% for DENV-1, 38.8% for DENV-2, 42.3% for DENV-3, and 56.1% for DENV-4. The overall seroprevalence of CHIKV, ZIKV and MAYV antibodies was 20.3% (17.7-23.1), 23.3% (20.9-25.9) and 3.3% (2.7-4.1), respectively. We provide a consistent overview of the burden of emerging arboviruses in French Guiana, with useful findings for risk mapping, future prevention and control programs. The majority of the population remains susceptible to CHIKV and ZIKV, which could potentially facilitate the risk of further re-emergences. Our results underscore the need to strengthen MAYV surveillance in order to rapidly detect any substantial changes in MAYV circulation patterns.

Reconstructing Mayaro virus circulation in French Guiana shows frequent spillovers.

Characterizing the circulation of Mayaro virus (MAYV), an emerging arbovirus threat, is essential for risk assessment but challenging due to cross-reactivity with other alphaviruses such as chikungunya virus (CHIKV). Here, we develop an analytical framework to jointly assess MAYV epidemiology and the extent of cross-reactivity with CHIKV from serological data collected throughout French Guiana (N = 2697). We find strong evidence of an important sylvatic cycle for MAYV with most infections occurring near the natural reservoir in rural areas and in individuals more likely to go to the forest (i.e., adult males) and with seroprevalences of up to 18% in some areas. These findings highlight the need to strengthen MAYV surveillance in the region and showcase how modeling can improve interpretation of cross-reacting assays.

Impact of Zika Virus Emergence in French Guiana: A Large General Population Seroprevalence Survey.

BACKGROUND: Since the identification of Zika virus (ZIKV) in Brazil in May 2015, the virus has spread throughout the Americas. However, ZIKV burden in the general population in affected countries remains unknown. METHODS: We conducted a general population survey in the different communities of French Guiana through individual interviews and serologic survey during June-October 2017. All serum samples were tested for anti-ZIKV immunoglobulin G antibodies using a recombinant antigen-based SGERPAxMap microsphere immunoassay, and some of them were further evaluated through anti-ZIKV microneutralization tests. RESULTS: The overall seroprevalence was estimated at 23.3% (95% confidence interval [CI], 20.9%-25.9%) among 2697 participants, varying from 0% to 45.6% according to municipalities. ZIKV circulated in a large majority of French Guiana but not in the most isolated forest areas. The proportion of reported symptomatic Zika infection was estimated at 25.5% (95% CI, 20.3%-31.4%) in individuals who tested positive for ZIKV. CONCLUSIONS: This study described a large-scale representative ZIKV seroprevalence study in South America from the recent 2015-2016 Zika epidemic. Our findings reveal that the majority of the population remains susceptible to ZIKV, which could potentially allow future reintroductions of the virus.

Yellow fever cases in French Guiana, evidence of an active circulation in the Guiana Shield, 2017 and 2018.

French Guiana (FG) is a French overseas region bordering Brazil and Suriname that is considered endemic for yellow fever (YF); vaccination is compulsory for residents and travellers. In August 2017 and 2018, two sporadic YF cases were notified 1 year apart, confirming that sylvatic YF virus circulation is active in the region. YF vaccination coverage should be closely monitored and improved in FG and neighbouring territories and clinicians should be aware of the risk.

The proportion of asymptomatic infections and spectrum of disease among pregnant women infected by Zika virus: systematic monitoring in French Guiana, 2016.

Zika virus (ZIKV) infection has been associated with complications during pregnancy. Although the presence of symptoms might be a risk factor for complication, the proportion of ZIKV-infected pregnant women with symptoms remains unknown. Following the emergence of ZIKV in French Guiana, all pregnancies in the territory were monitored by RT-PCR and/or detection of ZIKV antibodies. Follow-up data collected during pregnancy monitoring interviews were analysed from 1 February to 1 June 2016. We enrolled 3,050 pregnant women aged 14-48 years and 573 (19%) had laboratory-confirmed ZIKV infection. Rash, arthralgia, myalgia and conjunctival hyperaemia were more frequently observed in ZIKV-positive women; 23% of them (95% confidence interval (CI): 20-27) had at least one symptom compatible with ZIKV infection. Women 30 years and older were significantly more likely to have symptoms than younger women (28% vs 20%). The proportion of symptomatic infections varied from 17% in the remote interior to 35% in the urbanised population near the coast (adjusted risk ratio: 1.6; 95% CI: 1.4-1.9.). These estimates put findings on cohorts of symptomatic ZIKV-positive pregnant women into the wider context of an epidemic with mainly asymptomatic infections. The proportion of symptomatic ZIKV infections appears to vary substantially between populations.

Diagnostic Validation of the RealStar® Zika Virus Reverse Transcription Polymerase Chain Reaction Kit for Detection of Zika Virus RNA in Urine and Serum Specimens.

With the Zika virus outbreak in South America starting in 2015 and its potential to cause malformation of the fetus in infected women, the need for diagnostic methods became obvious. Until now, only limited data are available on the diagnostic performance of commercial kits. Here, we present data comparing the RealStar® Zika Virus RT-PCR Kit 1.0 for detection of Zika virus from 208 serum and urine samples collected in French Guiana with a reference method. Of these, 114 samples tested positive with the RealStar® Kit and 111 with the reference method.

Coxsackievirus A24 Variant Associated with Acute Haemorrhagic Conjunctivitis Cases, French Guiana, 2017.

In 2017, numerous cases of acute haemorrhagic conjunctivitis (AHC) were reported in the Caribbean and in South America. Preliminary reports identified adenoviruses and enteroviruses in some patient samples but, until now, none of the etiologic agents have been fully characterized. We report the full-length genomic sequences of 4 coxsackievirus A24 (CV-A24) isolates collected from AHC patients in French Guiana during this outbreak (May and June 2017). These isolates are very closely related and belong to the genotype IV of CV-A24 variant, which consists of strains sampled worldwide during AHC outbreaks in the 2000s and 2010s. No recombination events were detected within the genomic sequences, indicating that members of this genotype have continuously circulated worldwide for more than 10 years without undergoing recombination with other enteroviruses. This unusual trait could be due to their ocular tropism that could impede genetic exchanges between these viruses and other enteroviruses, which replicate mainly in the gut.

Whole-Genome Sequencing Analysis from the Chikungunya Virus Caribbean Outbreak Reveals Novel Evolutionary Genomic Elements.

BACKGROUND: Chikungunya virus (CHIKV), an alphavirus and member of the Togaviridae family, is capable of causing severe febrile disease in humans. In December of 2013 the Asian Lineage of CHIKV spread from the Old World to the Americas, spreading rapidly throughout the New World. Given this new emergence in naïve populations we studied the viral genetic diversity present in infected individuals to understand how CHIKV may have evolved during this continuing outbreak. METHODOLOGY/PRINCIPLE FINDINGS: We used deep-sequencing technologies coupled with well-established bioinformatics pipelines to characterize the minority variants and diversity present in CHIKV infected individuals from Guadeloupe and Martinique, two islands in the center of the epidemic. We observed changes in the consensus sequence as well as a diverse range of minority variants present at various levels in the population. Furthermore, we found that overall diversity was dramatically reduced after single passages in cell lines. Finally, we constructed an infectious clone from this outbreak and identified a novel 3' untranslated region (UTR) structure, not previously found in nature, that led to increased replication in insect cells. CONCLUSIONS/SIGNIFICANCE: Here we preformed an intrahost quasispecies analysis of the new CHIKV outbreak in the Caribbean. We identified novel variants present in infected individuals, as well as a new 3'UTR structure, suggesting that CHIKV has rapidly evolved in a short period of time once it entered this naïve population. These studies highlight the need to continue viral diversity surveillance over time as this epidemic evolves in order to understand the evolutionary potential of CHIKV.