Assessment of ex vivo antimalarial drug efficacy in African Plasmodium falciparum parasite isolates, 2016-2023: a genotype-phenotype association study.

Background: Given the altered responses to both artemisinins and lumefantrine in Eastern Africa, monitoring antimalarial drug resistance in all African countries is paramount.

Methods: We measured the susceptibility to six antimalarials using ex vivo growth inhibition assays (IC) for a total of 805 Plasmodium falciparum isolates obtained from travellers returning to France (2016-2023), mainly from West and Central Africa. Isolates were sequenced using molecular inversion probes (MIPs) targeting forty-three genes across the parasite genome, of which nineteen are drug resistance genes.

SARS-CoV-2 lineage-dependent temporal phylogenetic distribution and viral load in immunocompromised and immunocompetent individuals.

Objectives: Mutational dynamics of SARS-CoV-2 in immunocompromised hosts, although well documented, remain a relatively unexplored mechanism. This study aims to compare the viral replication load and genetic diversity of SARS-CoV-2 in immunocompromised patients and non-immunocompromised individuals (NICs) from two major hospitals in Paris from January 2021 to May 2023.

Methods: Cycle threshold (CT) values were measured by TaqPath COVID-19 RT-PCR (Thermo Fisher Scientific).

CONSTRUCT: an algorithmic tool for identifying functional or structurally important regions in protein tertiary structure.

Motivation: Evolutionary rates in protein-coding genes vary widely, reflecting functional and/or structural constraints. Essential or highly expressed proteins tend to evolve more slowly, and within a protein, different amino acid sites experience distinct selective pressures. Accurately modeling this variation is critical for identifying functional and/or structurally important amino acid sites.

Genomic investigation of an antifungal-resistant Aspergillus fumigatus outbreak in a French hospital.

Aspergillus fumigatus is associated with various invasive, chronic, and allergic fungal diseases. The emergence of environmental azole-resistant strains complicates the treatment of these infections. The use of whole-genome sequencing (WGS), which is widely used to study bacterial and viral outbreaks, could be beneficial for characterizing azole-resistant A.

Artemisinin pressure in field isolates can select highly resistant parasites with unconventional phenotype and no K13 mutation.

Artemisinin resistance, which poses a serious threat to malaria control efforts, is monitored in the field by delayed parasite clearance in patients, elevated parasite survival rate in the ring-stage survival assay, and mutations in the gene. However, sporadic cases of artemisinin-resistant malaria do not meet all of these criteria, highlighting that our understanding of artemisinin resistance is still incomplete. Here, we selected for artemisinin resistance in nine field isolates from Africa, Asia, and South America.

Ex vivo susceptibility to antimalarial drugs and polymorphisms in drug resistance genes of African Plasmodium falciparum, 2016-2023: a genotype-phenotype association study.

Given the altered responses to both artemisinins and lumefantrine in Eastern Africa, monitoring antimalarial drug resistance in all African countries is paramount. We measured the susceptibility to six antimalarials using growth inhibition assays (IC ) for a total of 805 isolates obtained from travelers returning to France (2016-2023), mainly from West and Central Africa. Isolates were sequenced using molecular inversion probes (MIPs) targeting fourteen drug resistance genes across the parasite genome.

Plasmodium ovale spp dhfr mutations associated with reduced susceptibility to pyrimethamine in sub-Saharan Africa: a retrospective genetic epidemiology and functional study.

Background: Mutations in the Plasmodium falciparum dhfr gene confer resistance to pyrimethamine, which is widely used for malaria chemoprevention in Africa. We aimed to evaluate the frequency and evolution of dhfr mutations in Plasmodium ovale spp in Africa and their functional consequences, which are incompletely characterised.

Methods: We analysed dhfr mutations and their frequencies in P ovale spp isolates collected between Feb 1, 2004, and Aug 31, 2023, from the French National Malaria Reference Centre collection and from field studies in Benin, Gabon, and Kenya.

Pharmaco-virological Outcomes and Genotypic Resistance Profiles Among Children and Adolescents Receiving a Dolutegravir-Based Regimen in Togo.

Background: Few data are available on the real-world efficacy of receiving tenofovir-lamivudine-dolutegravir (-DTG) as human immunodeficiencyvirus (HIV) treatment, particularly among young people in West Africa. Here, we evaluated pharmaco-virological outcomes and resistance profiles among Togolese children and adolescents.

Methods: A cross-sectional study was conducted in Lomé, Togo, enrolling antiretroviral-treated people with HIV aged from 18 months to 24 years.

RSV-GenoScan: An automated pipeline for whole-genome human respiratory syncytial virus (RSV) sequence analysis.

Background: Advances in high-throughput sequencing (HTS) technologies and reductions in sequencing costs have revolutionised the study of genomics and molecular biology by making whole-genome sequencing (WGS) accessible to many laboratories. However, the analysis of WGS data requires significant computational effort, which is the major drawback in implementing WGS as a routine laboratory technique.

Objective: Automated pipelines have been developed to overcome this issue, but they do not exist for all organisms.

Evolution and spread of Plasmodium falciparum mutations associated with resistance to sulfadoxine-pyrimethamine in central Africa: a cross-sectional study.

Background: Efficacy of sulfadoxine-pyrimethamine, the malaria chemoprophylaxis used in pregnant women, and in children when combined with amodiaquine, is threatened by the accumulation of mutations in the Plasmodium falciparum dihydropteroate synthase (pfdhps) and dihydrofolate reductase (pfdhfr) genes. Data on the prevalence of resistant alleles in central Africa and the new pfdhps I431V mutation, particularly associated with other mutations to form the pfdhps vagKgs allele, are scarce. We explored the frequency and geographical distribution of pfdhps and pfdhfr mutations in central Africa in 2014-18, and assessed the evolutionary origin of the vagKgs allele.

Genomic diversity of mpox virus in Paris area (France) during the 2022 outbreak.

In May 2022, several countries reported mpox cases from patients without history of traveling to endemic areas. France was one of the most affected European countries by this outbreak. In this study, the clinical characteristics of mpox cases in France were described, and the genetic diversity of the virus was studied.

Ex vivo RSA and pfkelch13 targeted-amplicon deep sequencing reveal parasites susceptibility to artemisinin in Senegal, 2017.

Background: Malaria control is highly dependent on the effectiveness of artemisinin-based combination therapy (ACT), the current frontline malaria curative treatment. Unfortunately, the emergence and spread of parasites resistant to artemisinin (ART) derivatives in Southeast Asia and South America, and more recently in Rwanda and Uganda (East Africa), compromise their long-term use in sub-Saharan Africa, where most malaria deaths occur.

Methods: Here, ex vivo susceptibility to dihydroartemisinin (DHA) was evaluated from 38 Plasmodium falciparum isolates collected in 2017 in Thiès (Senegal) expressed in the Ring-stage Survival Assay (RSA).

Phylodynamics of SARS-CoV-2 in France, Europe, and the world in 2020.

Although France was one of the most affected European countries by the COVID-19 pandemic in 2020, the dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) movement within France, but also involving France in Europe and in the world, remain only partially characterized in this timeframe. Here, we analyzed GISAID deposited sequences from January 1 to December 31, 2020 ( = 638,706 sequences at the time of writing). To tackle the challenging number of sequences without the bias of analyzing a single subsample of sequences, we produced 100 subsamples of sequences and related phylogenetic trees from the whole dataset for different geographic scales (worldwide, European countries, and French administrative regions) and time periods (from January 1 to July 25, 2020, and from July 26 to December 31, 2020).

Ex vivo RSA and Pfkelch13 targeted-amplicon deep sequencing reveal parasites susceptibility to artemisinin in Senegal, 2017.

Introduction: Malaria control is highly dependent on the effectiveness of artemisinin-based combination therapies (ACTs), the current frontline malaria curative treatments. Unfortunately, the emergence and spread of parasites resistant to artemisinin (ART) derivatives in Southeast Asia and South America, and more recently in Rwanda and Uganda (East Africa), compromise their long-term use in Sub-Saharan Africa where most malaria deaths occur.

Methods: Here, we evaluated susceptibility to dihydroartemisinin (DHA) from 38 isolates collected in 2017 in Thiès (Senegal) expressed with the Ring-stage Survival Assay (RSA).

sporozoites require the protein B9 to invade hepatocytes.

sporozoites are transmitted to a mammalian host during blood feeding by an infected mosquito and invade hepatocytes for initial replication of the parasite into thousands of erythrocyte-invasive merozoites. Here we report that the B9 protein, a member of the 6-cysteine domain protein family, is secreted from sporozoite micronemes and is required for productive invasion of hepatocytes. The N-terminus of B9 forms a beta-propeller domain structurally related to CyRPA, a cysteine-rich protein forming an essential invasion complex in merozoites.

Pharmaco-virological algorithm to target risk of drug resistance among a population of HIV-infected key populations in Togo.

No data about antiretroviral (ARV) treatment coverage and virological response are available among key populations (female sex workers [FSW] and Men having Sex with Men [MSM]) in Togo. This study aimed to both describe Human Immunodeficiency Virus (HIV) immunovirological status and evaluate the pertinence of an original algorithm combining pharmacology (PK) and viral load (VL) to identify subjects at risk of ARV drug resistance. A cross-sectional multicentric study was conducted in 2017 in Togo.

Nosocomial Malaria Transmissions Resolved by Genomic Analyses-A Retrospective Case Report Study in France: 2007-2021.

Background: Exposure of blood to malaria parasites can lead to infection even in the absence of the mosquito vector. During a stay in a healthcare facility, accidental inoculation of the skin with blood from a malaria patient might occur, referred to as nosocomial malaria.

Methods: Between 2007 and 2021, we identified 6 autochthonous malaria cases that occurred in different French hospitals, originating from nosocomial transmission and imported malaria cases being the infection source.

Temporal dynamics of RSV shedding and genetic diversity in adults during the COVID-19 pandemic in a French hospital, early 2021.

Human respiratory syncytial virus (RSV) is responsible of lower respiratory tract infections which may be severe in infants, elderly and immunocompromised adults. Europe and North-American countries have observed a massive reduction of RSV incidence during the 2020-2021 winter season. Using a systematic RSV detection coupled to SARS-CoV-2 for all adult patients admitted at the Foch hospital (Suresnes, France) between January and March 2021 (n = 11,324), only eight RSV infections in patients with prolonged RNA shedding were diagnosed.