The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance.

Investment in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing in Africa over the past year has led to a major increase in the number of sequences that have been generated and used to track the pandemic on the continent, a number that now exceeds 100,000 genomes. Our results show an increase in the number of African countries that are able to sequence domestically and highlight that local sequencing enables faster turnaround times and more-regular routine surveillance. Despite limitations of low testing proportions, findings from this genomic surveillance study underscore the heterogeneous nature of the pandemic and illuminate the distinct dispersal dynamics of variants of concern-particularly Alpha, Beta, Delta, and Omicron-on the continent. Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve while the continent faces many emerging and reemerging infectious disease threats. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

La leptospirose aux Seychelles : investigation d'une maladie zoonotique en environnement insulaire tropical par des approches géographique, moléculaire et épidémiologique

Leptospirosis is an emerging neglected disease representing a heavy burden in the tropics, especially in tropical islands such as Seychelles, which record among the highest human incidence worldwide. This thesis aims at exploring the eco-epidemiology of leptospirosis in Seychelles by (i) using rats as markers of environmental exposure to Leptospira infection, (ii) describing the molecular epidemiology of the disease in humans and animals in a One Health framework, and (iii) identifying occupational and behavioural risk factors while comparing the current situation to that described 25 years ago. The combination of fine spatial distribution, molecular and clinical epidemiology complement each other in providing a comprehensive picture of the continuum involving reservoirs and human hosts within a shared environment.Habitat fragmentation and proximity to nutritional sources are found good predictors of Leptospira-laden Rattus spp. Geospatial analyses determined a selection of other important variable factors that are strongly correlated with Leptospira infection in Rattus spp., including altitude or distance to surface water (negative correlation), urbanization and heavy rainfall (positive correlation). Results of these analyses can guide policy makers and especially urban planners to best implement landscape structures for conservation or pest control goals leading to reduced exposure of humans to rat-borne diseases.Rattus norvegicus is found significantly more infected than Rattus rattus. Therefore, increased infection in urbanized/fragmented habitats may result at least in part from Rattus spp distribution, as R. norvegicus is mostly found in urban areas. Most importantly, genotyping of Leptospira in human acute cases and rats suggests that these rodents are involved in only a third of human acute infections, while most human cases originate from yet to be identified reservoir(s).An annual incidence of 54.6 (95% CI 40.7-71.8) per 100,000 confirms the major medical and public health importance of the disease in the country. The disease affects mainly men (96%) and displays a case fatality rate of 11.2%, mostly associated with severe forms (acute renal failure, hepatic failure and pulmonary haemorrhage). Farming and gardening related activities, proximity to cattle and cats, thrombocytopaenia, leukocytosis, elevated bilirubin and high values for renal function tests are predictors of leptospirosis. The geographical distribution of human cases poorly overlaps districts of high prevalence in rats in keeping with a restricted role of rats in human disease.The comparison of figures reported herein and in previous studies published 25 years ago reveals changes in behaviour and exposure, and shows that the development of health care has lowered the case fatality despite still high disease incidence in the country. A low level of knowledge on leptospirosis is reported, urging the need for implementing health education campaigns. Altogether, the data presented in this thesis strongly supports the implementation of a research program aiming at discovering alternative reservoir(s) to provide a full understanding of the epidemiological situation, which will allow fine tuning preventive measures for an efficient control of a disease that is still recognised as the infectious disease causing the highest mortality in the country.La leptospirose est une maladie négligée émergente touchant plus particulièrement les régions tropicales, et plus encore les îles tropicales telles que les Seychelles, qui enregistrent des incidences humaines parmi les plus élevées au monde. Cette thèse a pour objectifs d’explorer l’éco épidémiologie de la leptospirose aux Seychelles (i) en utilisant les rats comme marqueurs d’exposition environnementale, (ii) en décrivant l’épidémiologie moléculaire de la maladie chez l’homme et l’animal à travers une approche “One Health”, et enfin (iii) en identifiant les comportements et professions à risque tout en en comparant la situation actuelle à celle décrite il y a 25 ans. La combinaison d’approches géographique, moléculaire et clinique vise à dresser un tableau complet de la situation épidémiologique de cette maladie aux Seychelles en intégrant les réservoirs animaux, l’homme et l’environnement qu’ils occupent.La fragmentation de l’habitat et la proximité de ressources alimentaires apparaissent comme de bons prédicteurs d’infection chez les rats. Les analyses géo-spatiales permettent de mettre en évidence d’autres variables corrélées négativement (altitude ou distance à un point d’eau douce) ou positivement (niveau d’urbanisation, pluviométrie) au statut d’infection chez les rats. Ces résultats pourraient être pris en compte dans les politiques d’aménagement du territoire mises en place dans des buts de conservation des habitats ou de contrôle des rongeurs, afin de réduire l’exposition de l’homme à des pathogènes maintenus dans l’environnement par les rats. Si le niveau d’urbanisation est positivement corrélé avec le statut d’infection, ce patron pourrait au moins en partie résulter de la distribution des deux espèces Rattus norvegicus et Rattus rattus. En effet la première espèce, retrouvée essentiellement en milieu urbain, est nettement plus infectée que la deuxième que l’on retrouve partout sur l’île. Néanmoins, la comparaison des leptospires retrouvés chez les rats et chez les cas humains graves indique que les rats ne sont impliqués que dans un tiers des transmissions à l’homme, la majorité des cas humains étant causée par des leptospires dont le(s) réservoir(s) reste(nt) à identifier. Une incidence annuelle de 54,6 (95% IC 40,7-71,8) pour 100 000 habitants confirme l’importance médicale majeure de cette maladie dans le pays. La maladie touche très majoritairement les hommes (96%) et présente un taux de mortalité élevé (11,2%), essentiellement associé à des formes sévères (dysfonctions rénales et hépatiques, hémorragie pulmonaire). Les activités agricoles et le jardinage, la proximité d’élevages et de chats, une thrombocytopénie, une leucocytose, un taux de bilirubine élevé et des valeurs élevées aux tests de fonction rénale sont de bons prédicteurs de leptospirose. La distribution géographique des cas humains ne correspond pas à celle des districts hébergeant des populations de rats aux prévalences d’infection élevées, en cohérence avec un rôle restreint des rats dans la leptospirose humaine.La comparaison des données présentées ici avec celles publiées il y a 25 ans révèle un changement dans les comportements et les expositions, et montre qu’une meilleure prise en charge hospitalière a vraisemblablement contribué à faire diminuer la mortalité liée à la leptospirose, même si celle-ci reste élevée. Un faible niveau de connaissance de la maladie en population générale souligne l’importance de mettre en place des campagnes de sensibilisation. Les données produites dans le cadre de cette thèse stimulent la mise en place d’études complémentaires visant à mettre en évidence le(s) réservoir(s) complémentaire(s) et adapter les mesures de prévention pour limiter le fardeau que représente cette maladie aux Seychelles, aujourd’hui encore reconnue comme la maladie infectieuse causant le plus de décès dans le pays

An Observational Study of Human Leptospirosis in Seychelles

International audienceA 1-year population-based prospective study was launched in Seychelles, a country with one of the highest human incidence of leptospirosis worldwide, to describe the characteristic features of the epidemiology of the disease and highlight the most prominent risk factors. Diagnosis was based on the IgM enzyme-linked immunosorbent assay, microscopic agglutination test, and real-time PCR. A standardized questionnaire was administered to 219 patients aged ³ 13 years consulting for acute febrile illness. The high incidence of leptospirosis in Seychelles was confirmed. The disease was particularly severe, as the case fatality rate was 11.8%. Leptospirosis was positively associated in univariate analysis with socio-professional and clinical variables including gardening/farming, oliguria, jaundice, conjunctivitis, history of hepatitis C virus infection, anemia, thrombocytopenia, and/or biological renal failure. Epidemiological analyses of the questionnaires highlighted a link of the disease with living in houses (versus apartment), the presence of animals around and in houses, gardening, and misuse of personal protective equipment. Multivariate analyses indicated that being a farmer/landscaper and having cattle and cats around the home are the most significant drivers of leptospirosis. Biological features most associated with leptospirosis were thrombocytopenia, leukocytosis, high values for renal function tests, and elevated total bilirubin. We report changes in behavior and exposure compared with data collected on leptospirosis 25 years ago, with indication that healthcare development has lowered case fatality. Continuous health education campaigns are recommended as well as further studies to clarify the epidemiology of human leptospirosis, especially the role of domestic animals

Complete Genome Sequences of Dengue Virus Type 2 Epidemic Strains from Reunion Island and the Seychelles

International audienceDengue virus has recently reemerged in the southern Indian Ocean islands, causing outbreaks in Reunion Island and the Seychelles. In the present study, we determined the complete genome sequences of closely related clinical isolates of dengue virus type 2 circulating in the Seychelles in 2016 and Reunion Island in 2018

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

Abstract 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

Predicting the Presence of Leptospires in Rodents from Environmental Indicators Opens Up Opportunities for Environmental Monitoring of Human Leptospirosis

International audienceLeptospirosis, an environmental infectious disease of bacterial origin, is the infectious disease with the highest associated mortality in Seychelles. In small island territories, the occurrence of the disease is spatially heterogeneous and a better understanding of the environmental factors that contribute to the presence of the bacteria would help implement targeted control. The present study aimed at identifying the main environmental parameters correlated with animal reservoirs distribution and Leptospira infection in order to delineate habitats with highest prevalence. We used a previously published dataset produced from a large collection of rodents trapped during the dry and wet seasons in most habitats of Mahé, the main island of Seychelles. A land use/land cover analysis was realized in order to describe the various environments using SPOT-5 images by remote sensing (object-based image analysis). At each sampling site, landscape indices were calculated and combined with other geographical parameters together with rainfall records to be used in a multivariate statistical analysis. Several environmental factors were found to be associated with the carriage of leptospires in Rattus rattus and Rattus norvegicus, namely low elevations, fragmented landscapes, the proximity of urbanized areas, an increased distance from forests and, above all, increased precipitation in the three months preceding trapping. The analysis indicated that Leptospira renal carriage could be predicted using the species identification and a description of landscape fragmentation and rainfall, with infection prevalence being positively correlated with these two environmental variables. This model may help decision makers in implementing policies affecting urban landscapes and/or in balancing conservation efforts when designing pest control strategies that should also aim at reducing human contact with Leptospira-laden rats while limiting their impact on the autochthonous fauna

Human leptospirosis in Seychelles: A prospective study confirms the heavy burden of the disease but suggests that rats are not the main reservoir

International audienceBackground: Leptospirosis is a bacterial zoonosis caused by pathogenic Leptospira for which rats are considered as the main reservoir. Disease incidence is higher in tropical countries, especially in insular ecosystems. Our objectives were to determine the current burden of leptospirosis in Seychelles, a country ranking first worldwide according to historical data, to establish epidemiological links between animal reservoirs and human disease, and to identify drivers of transmission.Methods: A total of 223 patients with acute febrile symptoms of unknown origin were enrolled in a 12-months prospective study and tested for leptospirosis through real-time PCR, IgM ELISA and MAT. In addition, 739 rats trapped throughout the main island were investigated for Leptospira renal carriage. All molecularly confirmed positive samples were further genotyped.Results: A total of 51 patients fulfilled the biological criteria of acute leptospirosis, corresponding to an annual incidence of 54.6 (95% CI 40.7–71.8) per 100,000 inhabitants. Leptospira carriage in Rattus spp. was overall low (7.7%) but dramatically higher in Rattus norvegicus (52.9%) than in Rattus rattus (4.4%). Leptospira interrogans was the only detected species in both humans and rats, and was represented by three distinct Sequence Types (STs). Two were novel STs identified in two thirds of acute human cases while noteworthily absent from rats.Conclusions: This study shows that human leptospirosis still represents a heavy disease burden in Seychelles. Genotype data suggests that rats are actually not the main reservoir for human disease. We highlight a rather limited efficacy of preventive measures so far implemented in Seychelles. This could result from ineffective control measures of excreting animal populations, possibly due to a misidentification of the main contaminating reservoir(s). Altogether, presented data stimulate the exploration of alternative reservoir animal hosts

Spatiotemporal circulation of influenza viruses in 5 African countries during 2008-2009: a collaborative study of the Institut Pasteur International Network.

International audienceBACKGROUND: Although recent work has described the spatiotemporal diffusion of influenza viruses worldwide, comprehensive data on spatiotemporal patterns of influenza from the African continent and Madagascar are still lacking. METHODS: National Influenza Centers from 5 countries-Cameroon, Côte d'Ivoire, Madagascar, Niger, and Senegal--collected specimens from patients presenting with influenza-like illness who visited sentinel surveillance clinics during a 2-year period (2008-2009). Isolates were genetically and antigenically characterized. RESULTS: Overall, 8312 specimens were tested. Seasonal influenza A virus subtypes H1N1 and H3N2 and influenza B viruses were detected in 329, 689, and 148 specimens, respectively. In 2009, pandemic influenza A virus subtype H1N1 was detected in Madagascar most commonly (98.5% of cases). Influenza activity was either significant year-round or occurred during a specific period of the year in the African countries we evaluated. CONCLUSIONS: Our results demonstrate that, from Madagascar to Senegal, the epidemiologic and virologic characteristics of influenza viruses are diverse in terms of spatiotemporal circulation of the different virus types, subtypes, and strains. Our data highlight the importance of country-specific surveillance and of data and virus sharing, and they provide a rational basis to aid policy makers to develop strategies, such as vaccination at the right moment and with the right formulation, aimed at reducing the disease burden in Africa and Madagascar