Place of bacterial diversity and its dynamics in epidemiological surveillance

La surveillance épidémiologique joue un rôle de premier plan dans la prévention et le contrôle des épidémies, compléter ses indicateurs s’impose pour une meilleure détection précoce des épidémies. Les objectifs de cette thèse s’inscrivent dans ce cadre pour (i) faire un état des lieux de l’étude de la diversité bactérienne, (ii) évaluer l’impact du confinement sur la population bactérienne, (iii) comprendre la diversité des espèces bactériennes et (iv) identifier des associations entre des bactéries avec des facteurs météorologiques. Nous avons évalué la diversité bactérienne identifiée par le système de surveillance épidémiologique de la région Provence-Alpes-Côte d’Azur de l’Institut Hospitalo-Universitaire de Marseille. La richesse spécifique, l’abondance relative, l’indice de Shannon et la dissimilarité de Bray-Curtis ont été les paramètres évalués. Le test d’ANOVA a été appliqué pour comparer les moyennes de la richesse et de l’abondance observées. La statistique ANOSIM a été utilisée pour comparer la moyenne des dissemblances des groupes. Une analyse de corrélation des agents bactériens avec certains facteurs météorologiques a été effectuée. Nos résultats ont montré une répartition très variée de la diversité bactérienne dans les laboratoires, en plus le mix bactérien augmentait au fil du temps. Le confinement a conduit à la diminution de la fréquence de certaines espèces, en même temps, d’autres espèces n’ont subi aucun effet. Certaines espèces ont été corrélées à un ou plusieurs facteurs météorologiques. Vue les résultats obtenus, les indices de diversité évalués pourront être utiliser comme complément des indicateurs dans la surveillance épidémiologique.Epidemiological surveillance plays a key role in the prevention and control of epidemics, and completing its indicators is necessary for a better early detection of epidemics. The objectives of this thesis fall within this framework to (i) make an inventory of the study of bacterial diversity, (ii) assess the impact of lockdown on the bacterial population, (iii) understand the diversity of bacterial species, and (iv) identify associations between bacteria with meteorological factors. We have evaluated the bacterial diversity identified by the epidemiological surveillance system of the Provence-Alpes-Côte d'Azur region of the Institut Hospitalo-Universitaire de Marseille. The specific richness, the relative abundance, the Shannon index, and the Bray-Curtis dissimilarity were the parameters evaluated. ANOVA test was applied to compare the averages of observed richness and abundance. The ANOSIM statistic was used to compare the mean dissimilarity of the groups. A correlation analysis of bacterial agents with some meteorological factors was performed. Our results showed a very different distribution of bacterial diversity in the laboratory, in addition the bacterial mix increased over time. The lockdown led to the decrease in the frequency of certain species, at the same time, other species suffered no effect. Some species have been correlated with one or more meteorological factors. Given the results obtained, the diversity indices evaluated can be used as a complement to indicators in epidemiological surveillance

Epidémiologie de la PPR en Moyenne-Guinée

La peste des petits ruminants (PPR) est une maladie virale extrêmement contagieuse affectant les ovins et les caprins. Elle est caractérisée par une atteinte digestive, une stomatite érosive et nécrosante et une pneumonie.Décrite pour la première fois en Guinée en 1989, depuis lors aucune enquête spécifique n’a été consacrée à l’épidémiologie de cette maladie qui, pourtant continue à causer des perteséconomiques pour les éleveurs, en raison de son impactsur la productivité des troupeaux de petits ruminants.Une étude sérologique a été réalisée à partir de1170 échantillons de sérums.Les analysesont révélé un taux moyen de séroprévalence de 54%.La comparaison de ces résultats sérologiques et d’études participatives a montré que les éleveurs n’étaient pas en mesure de différencier les troupeaux infectés des troupeaux non infectés; en effet, il existe une circulation silencieuse du virus dans tous les troupeaux. La RT-PCR a confirmé la présence du PPRV et permis de mettre en évidence l’appartenance de la souche virale isolée àla lignée IIplus proche des souches isolées au Sénégal, en Mauritanie et au Mali,alors quecelle isolée en Guinéedans lesannées 80appartenait à la lignée I. Malgré l’absence de zone témoin due à la circulation silencieuse du virus ne nous permettant pas de caractériser avec précision l’effet de la PPR sur les troupeaux, nous avons été en mesure de mettre en évidence une forte association entre certains paramètres démographiques comme la mortalité et des caractéristiques propres aux individus du troupeau, telles que l’espèce, l’âge ou le sexe. Cette association se trouve fortement diminuée dans certains troupeaux probablement sous l’influence de facteurs extérieurs, comme l’occurrence d’un foyer de PPR. Pour la lutte et le contrôle de la PPR en Moyenne Guinée, il faudrait passer par la vaccination de masse, puis procéder à une surveillance événementielle périodiquement suivie d’analyses sérologiques en vue de détecter les foyers et de mettre en place un diagnostic rapide et simple, comme les pen-side tests

Consequences of the COVID-19 Outbreak Lockdown on Non-Viral Infectious Agents as Reported by a Laboratory-Based Surveillance System at the IHU Méditerranée Infection, Marseille, France

International audienceThe objective of this paper is to describe the surveillance system MIDaS and to show how this system has been used for evaluating the consequences of the French COVID-19 lockdown on the bacterial mix of AP-HM and the antibiotic resistance. MIDas is a kind of surveillance activity hub, allowing the automatic construction of surveillance control boards. We investigated the diversity and resistance of bacterial agents from respiratory, blood, and urine samples during the lockdown period (from week 12 to 35 of 2020), using the same period of years from 2017 to 2019 as control. Taking into account the drop in patient recruitment, several species have exhibited significant changes in their relative abundance (either increasing or decreasing) with changes up to 9%. The changes were more important for respiratory and urine samples than for blood samples. The relative abundance in respiratory samples for the whole studied period was higher during the lockdown. A significant increase in the percentage of wild phenotypes during the lockdown was observed for several species. The use of the MIDaS syndromic collection and surveillance system made it possible to efficiently detect, analyze, and follow changes of the microbiological population as during the lockdown period

A Non-Invasive Neonatal Signature Predicts Later Development of Atopic Diseases

International audienceBackground: Preterm birth is a major cause of morbidity and mortality in infants and children. Non-invasive methods for screening the neonatal immune status are lacking. Archaea, a prokaryotic life domain, comprise methanogenic species that are part of the neonatal human microbiota and contribute to early immune imprinting. However, they have not yet been characterized in preterm neonates. Objective: To characterize the gut immunological and methanogenic Archaeal (MA) signature in preterm neonates, using the presence or absence of atopic conditions at the age of one year as a clinical endpoint. Methods: Meconium and stool were collected from preterm neonates and used to develop a standardized stool preparation method for the assessment of mediators and cytokines and characterize the qPCR kinetics of gut MA. Analysis addressed the relationship between immunological biomarkers, Archaea abundance, and atopic disease at age one. Results: Immunoglobulin E, tryptase, calprotectin, EDN, cytokines, and MA were detectable in the meconium and later samples. Atopic conditions at age of one year were positively associated with neonatal EDN, IL-1β, IL-10, IL-6, and MA abundance. The latter was negatively associated with neonatal EDN, IL-1β, and IL-6. Conclusions: We report a non-invasive method for establishing a gut immunological and Archaeal signature in preterm neonates, predictive of atopic diseases at the age of one year

Dynamics of Variants of Concern (VOC) of SARS-CoV-2 during the Different Waves of COVID-19 in Senegal

Background: In Senegal, the incidence of SARS-CoV-2 evolved with four successive epidemic waves. The first wave started in March 2020 with low virus variability, whilst the second outbreak, which started in December 2020, was dominated by the Alpha variant. The third wave took place in June 2021, and the fourth at the end of November 2021. Our interest was to investigate the involvement of variants of concern during these four waves and to track the viral diversity of SARS-CoV-2. Methodology: During the four waves of the pandemic, 276,876 nasopharyngeal swabs were analyzed at the Institut de Recherche en Santé, de Surveillance Epidémiologique et de Formation (IRESSEF). Of these, 22,558 samples tested positive for SARS-CoV-2 by RT-PCR. Then, the virus genomes were sequenced in 817 positive samples using the ARTIC Network of Oxford Nanopore Technologies (ONT). In addition, 10% of the negative samples in RT-PCR new variants were also targeted for the detection of new and previously undescribed variants. Results: Our data have overall shown that the Senegalese strains are very similar to each other or closely related to other strains, such as Gambia, France etc. During the first wave, the most common clade found was 19A (67.5%) and a majority of the samples were of the B.1 (50%) lineage. We noted more diversity during the second wave where clade 20A (38.4%) was more frequent, followed by clade 20B (31.52%) and 20I (9.74%). At the level of lineages, we identified variants of concern as B.1.1.7 (9.74%) and B.1.617.2 (0.86%). In the third wave, we observed at the clade level with mainly 21A (32.63%) and 21J (16.84%). During the fourth wave at the end of November 2021, we mainly identified clade 21K Omicron variant 21K (B.1.1.529 and BA.1) (80.47%) and Delta variant (21A, 21J, and 21I) (AY.103, AY.122, AY.122.1, AY.26, AY.34, AY.36, AY.4, AY.48, AY.57, AY.61, and AY.87) (14.06%). Impact: SARS-CoV-2 diversity may affect the virus’s properties, such as how it spreads, disease severity, or the performance of vaccines, tools, or other public health and social measures. Therefore, such tracking of SARS-CoV-2 variants is not only of public interest, but also highlights the role some African institutes such as IRESSEF with surveillance capabilities through the real-time sequencing of SARS-CoV-2 genomes in the local context. Conclusion: In Senegal, the SARS-CoV-2 pandemic has disrupted the organization of the health system. IRESSEF contributed to put in place strategies to respond effectively to the expectations of medical authorities by providing them with data on the strains circulating in Senegal at each moment of the epidemic

Combining viral genetic and animal mobility network data to unravel peste des petits ruminants transmission dynamics in West Africa

International audiencePeste des petits ruminants (PPR) is a deadly viral disease that mainly affects small domestic ruminants. This disease threaten global food security and rural economy but its control is complicated notably because of extensive, poorly monitored animal movements in infected regions. Here we combined the largest PPR virus genetic and animal mobility network data ever collected in a single region to improve our understanding of PPR endemic transmission dynamics in West African countries. Phylogenetic analyses identified the presence of multiple PPRV genetic clades that may be considered as part of different transmission networks evolving in parallel in West Africa. A strong correlation was found between virus genetic distance and network-related distances. Viruses sampled within the same mobility communities are significantly more likely to belong to the same genetic clade. These results provide evidence for the importance of animal mobility in PPR transmission in the region. Some nodes of the network were associated with PPRV sequences belonging to different clades, representing potential "hotspots" for PPR circulation. Our results suggest that combining genetic and mobility network data could help identifying sites that are key for virus entrance and spread in specific areas. Such information could enhance our capacity to develop locally adapted control and surveillance strategies, using among other risk factors, information on animal mobility. As animals move so do viruses. The viral disease peste des petits ruminants (PPR) has a major impact on the livelihood of sheep and goat farmers across Africa, Middle-East and Asia. A global PPR eradication campaign is underway, but extensive movements of infected animals impede control efforts in many regions, such as West Africa. Here we show for the first time that PPR virus genetic data can be combined with information on animal mobility to identify routes of PPR circulation in Senegal and neighbouring countries. Such information can be used to design more efficient disease surveillance and control strategies adapted to local livestock farming practices

Comparative evolutionary analyses of peste des petits ruminants virus genetic lineages

International audiencePeste des petits ruminants virus (PPRV) causes a highly infectious disease affecting mainly goats and sheep in large parts of Africa, Asia, and the Middle East and has an important impact on the global economy and food security. Full genome sequencing of PPRV strains has proved to be critical to increasing our understanding of PPR epidemiology and to inform the ongoing global efforts for its eradication. However, the number of full PPRV genomes published is still limited and with a heavy bias towards recent samples and genetic Lineage IV (LIV), which is only one of the four existing PPRV lineages. Here, we generated genome sequences for twenty-five recent (2010–6) and seven historical (1972–99) PPRV samples, focusing mainly on Lineage II (LII) in West Africa. This provided the first opportunity to compare the evolutionary pressures and history between the globally dominant PPRV genetic LIV and LII, which is endemic in West Africa. Phylogenomic analysis showed that the relationship between PPRV LII strains was complex and supported the extensive transboundary circulation of the virus within West Africa. In contrast, LIV sequences were clearly separated per region, with strains from West and Central Africa branched as a sister clade to all other LIV sequences, suggesting that this lineage also has an African origin. Estimates of the time to the most recent common ancestor place the divergence of modern LII and LIV strains in the 1960s–80s, suggesting that this period was particularly important for the diversification and spread of PPRV globally. Phylogenetic relationships among historical samples from LI, LII, and LIII and with more recent samples point towards a high genetic diversity for all these lineages in Africa until the 1970s–80s and possible bottleneck events shaping PPRV’s evolution during this period. Molecular evolution analyses show that strains belonging to LII and LIV have evolved under different selection pressures. Differences in codon usage and adaptative selection pressures were observed in all viral genes between the two lineages. Our results confirm that comparative genomic analyses can provide new insights into PPRV’s evolutionary history and molecular epidemiology. However, PPRV genome sequencing efforts must be ramped up to increase the resolution of such studies for their use in the development of efficient PPR control and surveillance strategies