Asymptomatic <i>Plasmodium falciparum</i> carriage at the end of the dry season is associated with subsequent infection and clinical malaria in Eastern Gambia

BACKGROUND: Chronic carriage of asymptomatic low-density Plasmodium falciparum parasitaemia in the dry season may support maintenance of acquired immunity that protects against clinical malaria. However, the relationship between chronic low-density infections and subsequent risk of clinical malaria episodes remains unclear.METHODS: In a 2-years study (December 2014 to December 2016) in eastern Gambia, nine cross-sectional surveys using molecular parasite detection were performed in the dry and wet season. During the 2016 malaria transmission season, passive case detection identified episodes of clinical malaria.RESULTS: Among the 5256 samples collected, 444 (8.4%) were positive for P. falciparum. A multivariate model identified village of residence, male sex, age ≥ 5 years old, anaemia, and fever as independent factors associated with P. falciparum parasite carriage. Infections did not cluster over time within the same households or recurred among neighbouring households. Asymptomatic parasite carriage at the end of dry season was associated with a higher risk of infection (Hazard Ratio, HR = 3.0, p &lt; 0.0001) and clinical malaria (HR = 1.561, p = 0.057) during the following transmission season. Age and village of residence were additional predictors of infection and clinical malaria during the transmission season.CONCLUSION: Chronic parasite carriage during the dry season is associated with an increased risk of malaria infection and clinical malaria. It is unclear whether this is due to environmental exposure or to other factors.</p

Asymptomatic <i>Plasmodium falciparum</i> carriage at the end of the dry season is associated with subsequent infection and clinical malaria in Eastern Gambia

Background: Chronic carriage of asymptomatic low-density Plasmodium falciparum parasitaemia in the dry season may support maintenance of acquired immunity that protects against clinical malaria. However, the relationship between chronic low-density infections and subsequent risk of clinical malaria episodes remains unclear. Methods: In a 2-years study (December 2014 to December 2016) in eastern Gambia, nine cross-sectional surveys using molecular parasite detection were performed in the dry and wet season. During the 2016 malaria transmission season, passive case detection identified episodes of clinical malaria. Results: Among the 5256 samples collected, 444 (8.4%) were positive for P. falciparum. A multivariate model identified village of residence, male sex, age ≥ 5 years old, anaemia, and fever as independent factors associated with P. falciparum parasite carriage. Infections did not cluster over time within the same households or recurred among neighbouring households. Asymptomatic parasite carriage at the end of dry season was associated with a higher risk of infection (Hazard Ratio, HR = 3.0, p &lt; 0.0001) and clinical malaria (HR = 1.561, p = 0.057) during the following transmission season. Age and village of residence were additional predictors of infection and clinical malaria during the transmission season. Conclusion: Chronic parasite carriage during the dry season is associated with an increased risk of malaria infection and clinical malaria. It is unclear whether this is due to environmental exposure or to other factors.</p

A Cohort Study on the Duration of Plasmodium falciparum Infections During the Dry Season in The Gambia.

BACKGROUND: In areas where Plasmodium falciparum malaria is seasonal, a dry season reservoir of blood-stage infection is essential for initiating transmission during the following wet season. METHODS: In The Gambia, a cohort of 42 individuals with quantitative polymerase chain reaction-positive P falciparum infections at the end of the transmission season (December) were followed monthly until the end of the dry season (May) to evaluate infection persistence. The influence of human host and parasitological factors was investigated. RESULTS: A large proportion of individuals infected at the end of the wet season had detectable infections until the end of the dry season (40.0%; 16 of 40). At the start of the dry season, the majority of these persistent infections (82%) had parasite densities >10 p/µL compared to only 5.9% of short-lived infections. Persistent infections (59%) were also more likely to be multiclonal than short-lived infections (5.9%) and were associated with individuals having higher levels of P falciparum-specific antibodies (P = .02). CONCLUSIONS: Asymptomatic persistent infections were multiclonal with higher parasite densities at the beginning of the dry season. Screening and treating asymptomatic infections during the dry season may reduce the human reservoir of malaria responsible for initiating transmission in the wet season

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P &lt; 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Approches génomiques pour aborder la malaria chronique asymptomatique

In The Gambia, malaria is seasonal with a succession of high and low transmission seasons resulting in roughly seven continuous months of almost no malaria transmission every year. Despite this apparent absence of malaria parasites for most of the time, The Gambia and neighbouring countries are hit by endless malaria waves recurring every year. First, little is known about the impact of constantly switching from high to low transmission seasons on the Plasmodium falciparum genetic diversity. As it is unlikely that imported cases are responsible for the totality of new reinfections at each high transmission season, human host are seemingly used by the parasite as a reservoir for the whole duration of the low transmission season. These long infections could be sustained by the parasites enhancing their antigenic repertoire through the generation of chimeric var genes during the course of an infection. To address these questions, we conducted a longitudinal study in four nearby villages in the Upper River Region of The Gambia from 2014 to 2017. Blood samples from 1505 participants over 16 time points were collected during both wet and dry seasons. In total, 436 Plasmodium falciparum positive samples from asymptomatic infections were successfully genotyped by 89 single nucleotide polymorphisms and 334 were whole genome sequenced. During the dry season in 2016/2017, 11 individuals had their chronic asymptomatic infection precisely followed monthly with some the blood samples single-cell sequenced just 36 hours after thawing or long-read sequenced after one month of culture adaptation. We used identity by descent (IBD), a pairwise comparison method to estimate the relationships between genotyped and sequenced isolates. Parasite samples collected within the same household were significantly more genetically related especially when distant by three months at most. Also, parasites isolated during the low transmission seasons were more related to the previous high transmission season than to the following one. We could estimate that most of the parasite diversity renewed after approximately one year. An interesting exception is a 9-year old individual who had been infected with the same parasite strain for at least one year and a half. Long-read assemblies of parasite clones yielded few chromosomal-long contigs that were annotated with the almost complete set of genes expected in Plasmodium falciparum, including the hypervariable family of var genes. Also, the single-cell sequencing performed well, as indicated by the IBD clusters of single-cell genomes effectively segregating parasite strains. According to our findings, low transmission seasons are a reservoir of parasites from asymptomatic infections that are waiting for the high transmission season to spread and recombine, hence renewing the genetic diversity at every high transmission season. Additionally, we provide a dense quantity of genomic data on individual infections, including brand new high quality var gene sequences that can be added to the existing databases. We argue that the active case detection is key to understand asymptomatic chronic infections, the invisible reservoir of malaria.En Gambie, le paludisme est saisonnier avec une succession de saisons à forte et faible transmission résultant en à peu près sept mois sans transmission chaque année. Malgré cette apparente absence de parasites pendant la majorité du temps, la Gambie et les pays voisins sont touchés par des vagues de paludisme sans fin revenant chaque année. Premièrement, l'impact de l'alternance constante entre saisons à forte et faible transmission sur la diversité génétique de Plasmodium falciparum est mal connue. Puisqu'il est peu probable que les cas importés sont responsables de la totalité des nouvelles infections à chaque saison de forte transmission, les hôtes humains sont vraisemblablement utilisés par le parasite comme réservoir pendant la saison à faible transmission. Ces infections longues pourraient être maintenues par des parasites augmentant la taille de leur répertoire antigénique par la génération de gènes var chimères au cours dune infection. Pour répondre à ces questions, nous avons mené une étude longitudinale dans quatre villages de la Gambie entre 2014 et 2017. Les échantillons sanguins de 1505 participants ont été collectés pendant les saisons sèches et humides sur 16 échantillonnages. Au total, 436 échantillons positifs pour Plasmodium falciparum issus d'infections asymptomatiques ont été génotypés par 89 single nucléotide polymorphisms, et 334 ont été séquencés en génome entier avec succès. Pendant la saison sèche 2016/2017, 11 individus ont eu leur infection asymptomatique chronique précisément suivie mensuellement avec certains des échantillons sanguins séquencés en cellule unique 36 heures après décongélation ou séquencés en lectures longues un mois après adaptation à la culture. Nous avons utilisé l'identité par descendance (IBD), une méthode de comparaison pour estimer les liens de parenté entre les échantillons génotypés ou séquencés. Les parasites échantillonnés dans le même foyer étaient significativement plus liés génétiquement, plus particulièrement si obtenus à trois mois d'intervalle au plus. Aussi, les parasites isolés pendant les saisons à faible transmission étaient plus liés à la saison de forte transmission précédente que la suivante. Nous avons déterminé que la plupart de la diversité génétique du parasite était renouvelée après un an. Une exception concerne un individu de 9 ans qui a été infecté par la même souche de parasite pendant au moins un an et demi. Les assemblages en lecture longue des parasites clonés ont donné des larges contigs qui ont pu être annotés avec la quasi totalité des gènes attendus chez Plasmodium falciparum, dont la famille hyper variable des gènes var. De plus, le séquençage en cellule unique a été performant, comme indiqué par les clusters d'IBD des génomes des cellules uniques ségréguant efficacement entre les différentes souches parasitaires. D'après nos résultats, les saisons à faible transmission sont un réservoir de parasites d'infections asymptomatiques en attente de la saison à forte transmission pour se répandre et recombiner, renouvelant ainsi la diversité génétique à chaque saison de paludisme. Aussi, nous fournissons une quantité importante de données génomiques sur des infections, incluant de nouvelles séquences de gènes var de grande qualité. Nous défendons que la détection active de cas est capitale pour comprendre les infections chroniques asymptomatiques, le réservoir invisible du paludisme

Co-expression network analysis identifies gonad- and embryo- associated protein modules in the sentinel species Gammarus fossarum

Next generation sequencing and mass spectrometry technologies have recently expanded the availability of whole transcriptomes and proteomes beyond classical model organisms in molecular biology, even in absence of an annotated genome. However, the fragmented nature of transcriptomic and proteomic data reduces the ability to interpret the data, notably in non-model organisms. Network-based approaches may help extracting important biological information from -omics datasets. The reproductive cycle of the freshwater crustacean Gammarus fossarum. provides an excellent case study to test the relevance of a network analysis in non-model organisms. Here, we illustrated how the use of a co-expression network analysis (based on Weighted Gene Co-expression Network Analysis algorithm, WGCNA) allowed identifying protein modules whose expression profiles described germ cell maturation and embryonic development in the freshwater crustacean Gammarus fossarum. Proteome datasets included testes, ovaries or embryos samples at different maturation or developmental stages, respectively. We identified an embryonic module correlated with mid-developmental stages corresponding to the organogenesis and it was characterized by enrichment in proteins involved in RNA editing and splicing. An ovarian module was enriched in vitellogenin-like proteins and clottable proteins, confirming the diversity of proteins belonging to the large lipid transfer family involved in oocytes maturations in this freshwater amphipod. Moreover, our results found evidence of a fine-tuned regulation between energy production by glycolysis and actin-myosin-dependent events in G. fossarum spermatogenesis. This study illustrates the importance of applying systems biology approaches to emergent animal models to improve the understanding of the molecular mechanisms regulating important physiological events with ecological relevance

Impact on disease mortality of clinical, biological, and virological characteristics at hospital admission and overtime in COVID‐19 patients

International audienc

Long-term neurological symptoms after acute COVID-19 illness requiring hospitalization in adult patients: insights from the ISARIC-COVID-19 follow-up study

in this study we aimed to characterize the type and prevalence of neurological symptoms related to neurological long-COVID-19 from a large international multicenter cohort of adults after discharge from hospital for acute COVID-19