Dynamics of emergence and genetic diversity of dengue virus in Reunion Island from 2012 to 2022.

BACKGROUND: Dengue is a major public health concern in Reunion Island, marked by recurrent epidemics, including successive outbreaks of dengue virus serotypes 1 and 2 (DENV1 and DENV2) with over 70,000 cases confirmed since 2017. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we used Oxford Nanopore NGS technology for sequencing virologically-confirmed samples and clinical isolates collected between 2012 and 2022 to investigate the molecular epidemiology and evolution of DENV in Reunion Island. Here, we generated and analyzed a total of 499 DENV1, 360 DENV2, and 18 DENV3 sequences. By phylogenetic analysis, we show that different genotypes and variants of DENV have circulated in the past decade that likely originated from Seychelles, Mayotte and Southeast Asia and highly affected areas in Asia and Africa. CONCLUSIONS/SIGNIFICANCE: DENV sequences from Reunion Island exhibit a high genetic diversity which suggests regular introductions of new viral lineages from various Indian Ocean islands. The insights from our phylogenetic analysis may inform local health authorities about the endemicity of DENV variants circulating in Reunion Island and may improve dengue management and surveillance. This work emphasizes the importance of strong local coordination and collaboration to inform public health stakeholders in Reunion Island, neighboring areas, and mainland France.

Severe leptospirosis in tropical and non-tropical areas: A comparison of two french, multicentre, retrospective cohorts.

BACKGROUND: Leptospirosis is an anthropozoonosis that occurs worldwide but is more common in tropical regions. Severe forms may require intensive care unit (ICU) admission. Whether the clinical patterns and outcomes differ between tropical and non-tropical regions with similar healthcare systems is unclear. Our objective here was to address this issue by comparing two cohorts of ICU patients with leptospirosis managed in mainland France and in the overseas French department of Réunion, respectively. METHODOLOGY/PRINCIPAL FINDINGS: We compared two retrospective cohorts of patients admitted to intensive care for severe leptospirosis, one from Reunion Island in the Indian Ocean (tropical climate) and the other from metropolitan France (temperate climate). Chi-square and Student's t tests were used for comparisons. After grouping the two cohorts, we also performed multiple correspondence analysis and hierarchical clustering to search for distinct clinical phenotypes. The Réunion and Metropolitan France cohorts comprised 128 and 160 patients respectively. Compared with the Réunion cohort, the metropolitan cohort had a higher mean age (42.5±14.1 vs. 51.4±16.5 years, p<0.001). Severity scores, length of stay and mortality did not differ between the two cohorts. Three phenotypes were identified: hepato-renal leptospirosis (54.5%) characterized by significant hepatic, renal and coagulation failure, with a mortality of 8.3%; moderately severe leptospirosis (38.5%) with less severe organ failure and the lowest mortality rate (1.8%); and very severe leptospirosis (7%) manifested by neurological, respiratory and cardiovascular failure, with a mortality of 30%. CONCLUSIONS/SIGNIFICANCE: The outcomes of severe leptospirosis requiring ICU admission did not differ between tropical and temperate regions with similar healthcare access, practices, and resources, despite some differences in patient characteristics. The identification of three different clinical phenotypes may assist in the early diagnosis and management of severe leptospirosis.

Diagnostic performance of the WHO definition of probable dengue within the first 5 days of symptoms on Reunion Island.

The relevance of the World Health Organization (WHO) criteria for defining probable dengue had not yet been evaluated in the context of dengue endemicity on Reunion Island. The objective of this retrospective diagnostic study was to evaluate the diagnostic performance of the 2009 WHO definition of probable dengue and to propose an improvement thereof. From the medical database, we retrieved the data of subjects admitted to the emergency department of the University Hospital of Reunion Island in 2019 with suspected dengue fever (DF) within a maximum of 5 days post symptom onset, and whose diagnosis was confirmed by a Reverse Transcriptase Polymerase Chain Reaction (RT-PCR). The intrinsic characteristics of probable dengue definitions were reported in terms of sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR-), using RT-PCR as the gold standard. Of the 1,181 subjects who exhibited a positive RT-PCR, 652 (55%) were classified as probable dengue. The WHO definition of probable dengue yielded a sensitivity of 64% (95%CI 60-67%), a specificity of 57% (95%CI 52-61%), a LR+ of 1.49 (95%CI 1.33-1.67), and a LR- of 0.63 (95%CI 0.56-0.72). The sensitivity and LR- for diagnosing and ruling out probable dengue could be improved by the addition of lymphopenia on admission (74% [95%CI: 71-78%] and 0.54 [95%CI: 0.46-0.63] respectively), at the cost of slight reductions of specificity and LR+ (48% [95%CI: 44-53%] and 1.42 [95%CI: 1.29-1.57], respectively). In the absence of, or when rapid diagnostic testing is unreliable, the use of the improved 2009 WHO definition of probable dengue could facilitate the identification of subjects who require further RT-PCR testing, which should encourage the development of patient management, while also optimizing the count and quarantine of cases, and guiding disease control.

Chlorophyllum molybdites poisoning on Reunion Island.

In France, mushroom picking is part of the culture. The practice is not without risk, as around 1300 people are poisoned each year by eating wild mushrooms on the French mainland. However, this practice is not part of local culture on Reunion Island, a French territory located in the Indian Ocean. Indeed, there are practically no reports of mushroom poisoning on Reunion Island. Here we describe, through a retrospective study, cases of mushroom poisoning recorded in the Indian Ocean toxicosurveillance system database from 2020 to 2021. Overall, 19 people were poisoned following wild mushroom ingestion on Reunion Island: 15 in 2020 and 4 in 2021. Six events were recorded: the majority of poisonings involved clusters (n = 5) during a shared meal (pan-fried), only one case was single mushroom poisoning by ingesting a raw mushroom. Of all patients, 15 cases presented a gastrointestinal irritant syndrome (latency between 30 min and 3 h). Chlorophyllum molybdites was positively identified by mycologists in 4 cases, suspected by emergency doctor in 1 case and in one self-declared case, Volvariella volvacea was consumed. Poisoning following ingestion of wild mushrooms does occur on Reunion Island, and Chlorophyllum molybdites is the main culprit.

Comparing the Performance of Three Models Incorporating Weather Data to Forecast Dengue Epidemics in Reunion Island, 2018-2019.

We developed mathematical models to analyze a large dengue virus (DENV) epidemic in Reunion Island in 2018-2019. Our models captured major drivers of uncertainty including the complex relationship between climate and DENV transmission, temperature trends, and underreporting. Early assessment correctly concluded that persistence of DENV transmission during the austral winter 2018 was likely and that the second epidemic wave would be larger than the first one. From November 2018, the detection probability was estimated at 10%-20% and, for this range of values, our projections were found to be remarkably accurate. Overall, we estimated that 8% and 18% of the population were infected during the first and second wave, respectively. Out of the 3 models considered, the best-fitting one was calibrated to laboratory entomological data, and accounted for temperature but not precipitation. This study showcases the contribution of modeling to strengthen risk assessments and planning of national and local authorities.

Ophthalmic complications during the dengue epidemic in Reunion Island in 2020: a case series and review of the literature.

INTRODUCTION: Dengue is an arboviral disease transmitted by the dengue virus, whose vectors are Aedes aegypti and Aedes albopictus. The acute phase with its cohort of well-known symptoms is usually spontaneously favorable. Since 2020 in Reunion Island, a new symptom has appeared: the ocular damage of dengue fever, which has already been described in South Asia and South-East Asia. We therefore decided to describe the clinical, biological, ophthalmological, therapeutic, and outcomes of patients with ocular manifestations during dengue fever in Reunion Island in 2020. PATIENTS AND METHODS: This was a retrospective observational study. Patients were included from January 2020 to August 2020 and then reassessed by teleconsultation 1 year later. The patients were identified from the French public health surveillance network by all ophthalmologists on the island. Medical data were collected directly from medical records. RESULTS: Twenty-eight patients were included. The mean age was 41.9 years. Ocular involvement occurred approximately 9.2 days after the onset of dengue symptoms. The main symptoms were scotoma (71.4%) and sudden decrease of visual acuity (39.2%). Eighteen patients (64.2%) had macular involvement. Fourteen patients were treated with oral or intravenous corticosteroids. Twenty-two (78.5%) patients were evaluated by telephone one year later. Scotoma and decreased visual acuity persisted in 15 patients. Thirteen patients (59%) were bothered by night driving, 32% of patients had reading difficulties and 27% of patients became sensitive to prolonged exposure to screens. CONCLUSION: Ocular complications of dengue require early and collegial management to limit the risk of long-term sequelae. Further studies on the characteristics and complications of dengue fever are needed to better understand this disease.

Impact of the COVID-19 pandemic on severe non-SARS-CoV-2 community-acquired pneumonia in Reunion Island: a multicenter retrospective observational study, 2016-2021.

The Coronavirus 2019 (COVID-19) pandemic has had a considerable impact on the incidence of severe community-acquired pneumonia (CAP) worldwide. The aim of this study was to assess the early impact of the COVID-19 pandemic in the Reunion Island. This multicenter retrospective observational study was conducted from 2016 to 2021 in the hospitals of Reunion Island. The incidence of severe non-SARS-CoV-2 CAP, microorganisms, characteristics and outcomes of patients hospitalized in intensive care unit were compared between the pre-COVID-19 period (January 1, 2016 to February 29, 2020) and the early COVID-19 period (March 1, 2020 to October 31, 2021). Over the study period, 389 patients developed severe non-SARS-CoV-2 CAP. The incidence of severe non-SARS-CoV-2 CAP significantly decreased between the two periods (9.16 vs. 4.13 cases per 100,000 person-years). The influenza virus was isolated in 43.5% patients with severe non-SARS-CoV-2 CAP in the pre-COVID-19 period and in none of the 60 patients in the early COVID-19 period (P < 0.0001). The only virus that did not decrease was rhinovirus. Streptococcus pneumoniae was the most frequently isolated bacterial microorganism, with no significant difference between the two periods. In Reunion Island, the COVID-19 pandemic led to a significant decrease in the incidence of influenza, which likely explains the observed decrease in the incidence of severe non-SARS-CoV-2 CAP. The pandemic had no impact on the incidence of other viral and bacterial severe non-SARS-CoV-2 CAP. Monitoring influenza incidence is crucial now that COVID-19 control measures have been removed.

Severe forms of influenza infections admitted in intensive care units: Analysis of mortality factors.

Background: The severe forms of influenza infection requiring intensive care unit (ICU) admission remain a medical challenge due to its high mortality. New H1N1 strains were hypothesized to increase mortality. The studies below represent a large series focusing on ICU-admitted influenza patients over the last decade with an emphasis on factors related to death. Methods: A retrospective study of patients admitted in ICU for influenza infection over the 2010-2019 period in Réunion Island (a French overseas territory) was conducted. Demographic data, underlying conditions, and therapeutic management were recorded. A univariate analysis was performed to assess factors related to ICU mortality. Results: Three hundred and fifty adult patients were analyzed. Overall mortality was 25.1%. Factors related to higher mortality were found to be patient age >65, cancer history, need for intubation, early intubation within 48 h after admission, invasive mechanical ventilation (MV), acute respiratory distress syndrome (ARDS), vaso-support drugs, extracorporal oxygenation by membrane (ECMO), dialysis, bacterial coinfection, leucopenia, anemia, and thrombopenia. History of asthma and oseltamivir therapy were correlated with a lower mortality. H1N1 did not impact mortality. Conclusion: Patient's underlying conditions influence hospital admission and secondary ICU admission but were not found to impact ICU mortality except in patients age >65, history of cancer, and bacterial coinfections. Pulmonary involvement was often present, required MV, and often evolved toward ARDS. ICU mortality was strongly related to ARDS severity. We recommend rapid ICU admission of patients with influenza-related pneumonia, management of bacterial coinfection, and early administration of oseltamivir.

Emerging Corynebacterium diphtheriae Species Complex Infections, Réunion Island, France, 2015-2020.

Clinical, epidemiologic, and microbiologic analyses revealed emergence of 26 cases of Corynebacterium diphtheriae species complex infections on Réunion Island, France, during 2015-2020. Isolates were genetically diverse, indicating circulation and local transmission of several diphtheria sublineages. Clinicians should remain aware of the risk for diphtheria and improve diagnostic methods and patient management.

From dengue outbreaks to endemicity: Reunion Island, France, 2018 to 2021.

BackgroundAfter 40 years of limited viral circulation, Reunion Island has since 2018 experienced recurrent dengue outbreaks of increasing intensity and severity.AimWe aimed to report on the epidemiology and characteristics of dengue in Reunion Island between 2018 and 2021.MethodsBetween 2018 and August 2021, we systematically collected data on dengue cases via an automated transmission system between the health authorities and the medical laboratories. We set up additional surveillance systems for dengue-related activity in primary care, in emergency departments and in inpatient departments.ResultsUntil 2020, despite numerous cases, outbreaks had a limited public health impact because of few severe cases, low lethality and no heavy burden for the health care system. In 2021, however, the number of severe cases increased (from 0.4% of all cases in 2018 to 0.8% in 2021), as did the number of paediatric cases (from 8% in 2018 to 15% in 2021) and atypical clinical forms of dengue (108 cases of post-dengue maculopathy). Of note, haemorrhagic forms were rare and multi-organ failure was the most frequent severity throughout the study period. In parallel, the dominant serotype switched from DENV2 to DENV1 in 2020 and DENV1 became the only serotype detected in 2021.ConclusionThese findings indicate that dengue is becoming endemic in Reunion Island. Since comorbidities associated with severity of dengue are common in the population, health authorities should carefully consider the impact of dengue when addressing public health policies.

Genetic characterization of dengue virus serotype 1 circulating in Reunion Island, 2019-2021, and the Seychelles, 2015-2016.

BACKGROUND: An unprecedent increase in the number of cases and deaths reported from dengue virus (DENV) infection has occurred in the southwestern Indian ocean in recent years. From 2017 to mid-2021 more than 70,000 confirmed dengue cases were reported in Reunion Island, and 1967 cases were recorded in the Seychelles from 2015 to 2016. Both these outbreaks displayed similar trends, with the initial circulation of DENV-2 which was replaced by DENV-1. Here, we aim to determine the origin of the DENV-1 epidemic strains and to explore their genetic characteristics along the uninterrupted circulation, particularly in Reunion. METHODS: Nucleic acids were extracted from blood samples collected from dengue positive patients; DENV-1 was identified by RT-qPCR. Positive samples were used to infect VERO cells. Genome sequences were obtained from either blood samples or infected-cell supernatants through a combination of both Illumina or MinION technologies. RESULTS: Phylogenetic analyses of partial or whole genome sequences revealed that all DENV-1 sequences from Reunion formed a monophyletic cluster that belonged to genotype I and were closely related to one isolate from Sri Lanka (OL752439.1, 2020). Sequences from the Seychelles belonged to the same major phylogenetic branch of genotype V, but fell into two paraphyletic clusters, with greatest similarity for one cluster to 2016-2017 isolate from Bangladesh, Singapore and China, and for the other cluster to ancestral isolates from Singapore, dating back to 2012. Compared to publicly available DENV-1 genotype I sequences, fifteen non-synonymous mutations were identified in the Reunion strains, including one in the capsid and the others in nonstructural proteins (NS) (three in NS1, two in NS2B, one in NS3, one in NS4B, and seven in NS5). CONCLUSION: In contrast to what was seen in previous outbreaks, recent DENV-1 outbreaks in Reunion and the Seychelles were caused by distinct genotypes, all likely originating from Asia where dengue is (hyper)endemic in many countries. Epidemic DENV-1 strains from Reunion harbored specific non-synonymous mutations whose biological significance needs to be further investigated.

[Oncogenetics in the French overseas departments and regions: Situation in Reunion Island]. / Oncogénétique dans les départements et régions d'Outre-mer français : situation à La Réunion.

In view of the use of oncogenetics as a lever for proposing new-targeted therapies whose indications are expanding, this article provides an overview of this discipline in the French overseas departments and regions (DROM). Contrary to the metropolitan departments, where the number of consultations exceeds 100 consultations per 100,000 inhabitants for most centres in 2019, the number of consultations in the DROMs remains insufficient to meet the national average of 117 per 100,000 inhabitants. The financial and structural support offered by the INCa and the DGOS since 2003 has contributed favourably to the deployment of this activity in metropolitan France. This activity, which seems to be suffering in the DROMs, probably requires particular attention in order to understand the difficulties encountered and thus to meet the INCa's objective as well as possible: to identify and support patients with mutations by providing them with appropriate care.

Associated risk factors of severe dengue in Reunion Island: A prospective cohort study.

BACKGROUND: Since 2018, a dengue epidemic has been raging annually in Reunion Island, which poses the major problem of its morbidity and mortality. However, there is no consensus in the literature on factors associated with severity of illness. The objective of this study was to identify the factors associated with the occurrence of severe dengue (SD) according to the criteria adopted in 2009 by the World Health Organization (WHO), during the 2019 epidemic. METHODOLOGY/PRINCIPAL FINDINGS: A total of 163 patients with RT-PCR-confirmed dengue were included in a multicenter prospective cohort study in Reunion Island between January and June 2019. Of these, 37 (23%) were classified as SD, which involves presentation dominated by at least one organ failure, and 126 (77%) classified as non-SD (of which 90 (71%) had warning signs). Confusion, dehydration, and relative hypovolemia were significantly associated with SD in bivariate analysis (p < 0.05). The factors associated with SD in multivariate analysis were a time from first symptom to hospital consultation over 2 days (OR: 2.46, CI: 1.42-4.27), a history of cardiovascular disease (OR: 2.75, 95%CI: 1.57-4.80) and being of Western European origin (OR: 17.60, CI: 4.15-74). CONCLUSIONS/SIGNIFICANCE: This study confirms that SD is a frequent cause of hospitalization during dengue epidemics in Reunion Island. It suggests that cardiovascular disease, Western European origin, and delay in diagnosis and management are risk factors associated with SD fever, and that restoration of blood volume and correction of dehydration must be performed early to be effective. TRIAL REGISTRATION: NCT01099852; clinicaltrials.gov.

Robotic surgery implementation in an isolated overseas territory - The case of Reunion Island.

INTRODUCTION: In February 2020, robotic surgery was introduced in University Hospital of St Pierre in Reunion Island. The aim of this study was to evaluate the implementation of robotic assisted surgery in the hospital and its impact on operating times and patient outcomes. METHODS: Data was prospectively collected on patients undergoing laparoscopic robotic assisted surgery between February 2020 and February 2022. Information included patient demographics, type of surgery, operating times and length of stay. RESULTS: Over the two-year study period, 137 patients underwent laparoscopic robotic assisted surgery performed by 6 different surgeons. 89 of the surgeries were in gynecology, including 58 hysterectomies, 37 were in digestive surgery, and 11 in urology. The installation and docking times decreased across all specialties and were found to be significantly reduced when comparing the first and last 15 hysterectomies: mean installation time decreased from 18.7 to 14.5 minutes (p=0.048), mean docking time decreased from 11.3 to 7.1 minutes (p = 0.009). CONCLUSIONS: The implementation of robotic assisted surgery in an isolated territory such as Reunion Island was slow due to a lack of trained surgeons, supply difficulties and Covid crisis. Despite these challenges, the use of robotic surgery allowed for technically more challenging surgeries and demonstrated similar learning curves to other centers.

Investigation of Dengue Infection in Asymptomatic Individuals during a Recent Outbreak in La Réunion.

The number of dengue cases has increased dramatically over the past 20 years and is an important concern, particularly as the trends toward urbanization continue. While the majority of dengue cases are thought to be asymptomatic, it is unknown to what extent these contribute to transmission. A better understanding of their importance would help to guide control efforts. In 2019, a dengue outbreak in La Reunion resulted in more than 18,000 confirmed cases. Between October 2019 and August 2020, 19 clusters were investigated in the south, west, and east of the island, enabling the recruitment of 605 participants from 368 households within a 200 m radius of the home of the index cases (ICs). No active asymptomatic infections confirmed by RT-PCR were detected. Only 15% were possible asymptomatic dengue infections detected by the presence of anti-dengue IgM antibodies. Only 5.3% of the participants had a recent dengue infection confirmed by RT-PCR. Although the resurgence of dengue in La Réunion is very recent (2016), the rate of anti-dengue IgG positivity, a marker of past infections, was already high at 43% in this study. Dengue transmission was focal in time and space, as most cases were detected within a 100-m radius of the ICs, and within a time interval of less than 7 days between infections detected in a same cluster. No particular demographic or socio-cultural characteristics were associated with dengue infections. On the other hand, environmental risk factors such as type of housing or presence of rubbish in the streets were associated with dengue infections.

Impact of regional climate change on the mosquito vector Aedes albopictus in a tropical island environment: La Réunion.

The recent expansion of Aedes albopictus across continents in both tropical and temperate regions and the exponential growth of dengue cases over the past 50 years represent a significant risk to human health. Although climate change is not the only factor responsible for the increase and spread of dengue cases worldwide, it might increase the risk of disease transmission at global and regional scale. Here we show that regional and local variations in climate can induce differential impacts on the abundance of Ae. albopictus. We use the instructive example of Réunion Island with its varied climatic and environmental conditions and benefiting from the availability of meteorological, climatic, entomological and epidemiological data. Temperature and precipitation data based on regional climate model simulations (3 km × 3 km) are used as inputs to a mosquito population model for three different climate emission scenarios. Our objective is to study the impact of climate change on the life cycle dynamics of Ae. albopictus in the 2070-2100 time horizon. Our results show the joint influence of temperature and precipitation on Ae. albopictus abundance as a function of elevation and geographical subregion. At low-elevations areas, decreasing precipitation is expected to have a negative impact on environmental carrying capacity and, consequently, on Ae. albopictus abundance. At mid- and high-elevations, decreasing precipitation is expected to be counterbalanced by a significant warming, leading to faster development rates at all life stages, and consequently increasing the abundance of this important dengue vector in 2070-2100.

Epidemiology of tuberculosis and susceptibility to antituberculosis drugs in Reunion Island.

BACKGROUND: Tuberculosis is the first fatal infectious agent in the world with 1.2 million annual deaths for 10 million cases. Little is known about the epidemiology of tuberculosis and its resistance in Reunion Island, which is at the heart of migratory flows from highly endemic Indian Ocean territories. METHODS: We carried out a retrospective observational study of cases of tuberculosis disease in Reunion Island between 2014 and 2018. The epidemiological, demographic, microbiological, clinical and social characteristics were analyzed from mandatory declarations, microbiology database and medical files. RESULTS: 265 cases of tuberculosis disease were recorded over the period, ie an incidence of 6.2 / 100,000 inhabitants. 114 patients (43%) were born or resided > 6 months in the rest of the Indian Ocean area. The risk of infection was increased if birth in Madagascar (OR 23.5), Comoros (OR 8.9) or Mayotte (OR 6.8). The prevalence of HIV co-infection was low (2.5%). There were 31 cases (14.4%) of resistance to antituberculosis including 3 (1.4%) of multidrug-resistant tuberculosis and 0 case of extensively drug-resistant tuberculosis. The female gender (61.3% of resistant) was associated with resistance. The resistance rate was not significantly different depending on the geographic origin. CONCLUSION: This is the first exhaustive epidemiological study of tuberculosis in Reunion Island. The incidence there is relatively low but increased for people with links to neighboring islands, particularly Madagascar. The prevalence of multidrug resistance is low, with no associated increased risk for patients from the Indian Ocean area.