Differential infectivity of gametocytes after artemisinin-based combination therapy of uncomplicated falciparum malaria

Background: Most malaria-endemic countries use artemisinin-based combination therapy (ACT) as their first-line treatment. ACTs are known to be highly effective on asexual stages of the malaria parasite. Malaria transmission and the spread of resistant parasites depend on the infectivity of gametocytes. The effect of the current ACT regimens on gametocyte infectivity is unclear. Objectives: This study aimed to determine the infectivity of gametocytes to Anopheles gambiae following ACT treatment in the field. Methods: During a randomised controlled trial in Bougoula-Hameau, Mali, conducted from July 2005 to July 2007, volunteers with uncomplicated malaria were randomised to receive artemether-lumefantrine, artesunate-amodiaquine, or artesunate-sulfadoxine/pyrimethamine. Volunteers were followed for 28 days, and gametocyte carriage was assessed. Direct skin feeding assays were performed on gametocyte carriers before and after ACT administration. Results: Following artemether-lumefantrine treatment, gametocyte carriage decreased steadily from Day 0 to Day 21 post-treatment initiation. In contrast, for the artesunate-amodiaquine and artesunate-sulfadoxine/pyrimethamine arms, gametocyte carriage increased on Day 3 and remained constant until Day 7 before decreasing afterward. Mosquito feeding assays showed that artemether-lumefantrine and artesunate-amodiaquine significantly increased gametocyte infectivity to Anopheles gambiae sensu lato (s.l.) (p < 10−4), whereas artesunate-sulfadoxine/pyrimethamine decreased gametocyte infectivity in this setting (p = 0.03). Conclusion: Different ACT regimens could lead to gametocyte populations with different capacity to infect the Anopheles vector. Frequent assessment of the effect of antimalarials on gametocytogenesis and gametocyte infectivity may be required for the full assessment of treatment efficacy, the potential for spread of drug resistance and malaria transmission in the field

Persistent Submicroscopic Plasmodium falciparum Parasitemia 72 Hours after Treatment with Artemether-Lumefantrine Predicts 42-Day Treatment Failure in Mali and Burkina Faso.

A recent randomized controlled trial, the WANECAM (West African Network for Clinical Trials of Antimalarial Drugs) trial, conducted at seven centers in West Africa, found that artemether-lumefantrine, artesunate-amodiaquine, pyronaridine-artesunate, and dihydroartemisinin-piperaquine all displayed good efficacy. However, artemether-lumefantrine was associated with a shorter interval between clinical episodes than the other regimens. In a further comparison of these therapies, we identified cases of persisting submicroscopic parasitemia by quantitative PCR (qPCR) at 72 h posttreatment among WANECAM participants from 5 sites in Mali and Burkina Faso, and we compared treatment outcomes for this group to those with complete parasite clearance by 72 h. Among 552 evaluable patients, 17.7% had qPCR-detectable parasitemia at 72 h during their first treatment episode. This proportion varied among sites, reflecting differences in malaria transmission intensity, but did not differ among pooled drug treatment groups. However, patients who received artemether-lumefantrine and were qPCR positive at 72 h were significantly more likely to have microscopically detectable recurrent Plasmodium falciparum parasitemia by day 42 than those receiving other regimens and experienced, on average, a shorter interval before the next clinical episode. Haplotypes of pfcrt and pfmdr1 were also evaluated in persisting parasites. These data identify a possible threat to the parasitological efficacy of artemether-lumefantrine in West Africa, over a decade since it was first introduced on a large scale

Assessment of breast milk microbiota

Malgré les progrès technologiques dans l'exploration du microbiote humain et les nombreuses études menées sur le microbiote du tube digestif, le microbiote du colostrum et du lait maternel demeure un microbiote négligé. Cependant, les résultats de quelques études ont montré une grande diversité de bactéries commensales qui constituent le microbiote du lait maternel qui pourrait coloniser l'intestin du nourrisson. Selon les auteurs de ces études, le colostrum et le lait maternel pourraient être impliqués dans la transmission verticale des phénotypes associés au microbiote intestinal maternel. Dans cette thèse, nous avons d'abord évalué la diversité bactérienne de 154 échantillons de colostrum et de lait maternel de 144 mères par culture à travers la «microbial culturomics» et par métagénomique ciblée à travers le séquençage du gène de L'ARN ribosomal 16S. Avec l'approche de la «culturomics microbienne», nous avons analysé 20 échantillons de colostrum et de lait et tous les échantillons ont été analysés par l’approche de métagénomique ciblée. Nous avons cultivé 20 échantillons de colostrum et de lait pour l'isolement des archées méthanogènes qui jouent un rôle important dans la digestion de certains aliments. Dans la deuxième partie, nous avons procédé à la description taxonogénomique des nouvelles bactéries isolées à partir du colostrum, du lait maternel et des selles des patients obèses. Nous avons observé une grande diversité bactérienne du colostrum et du lait maternel grâce aux approches de la «microbial culturomics» et de métagénomique ciblé. Nous avons pu cultiver deux espèces d'archée méthanogènes, Methanobrevibacter smithii et Methanobrevibacter oralis.Despite technological advances in human microbiota exploration and numerous studies on digestive tract microbiota, colostrum and breast milk microbiota remain neglected microbiotes. However, the results of few studies have shown a significant diversity of commensal bacteria that constitute the microbiota of colostrum and breast milk that could colonise infant gut. According to the authors of these studies, colostrum and breast milk could be involved in the vertical transmission of phenotypes associated to mother gut microbiota. In this thesis, we first evaluated the bacterial diversity of 154 colostrum and breast milk samples from 144 mothers using culture (culturomics) and targeted metagenomics (16S rRNA gene) approaches. With culturomics approach, we analysed 20 samples of colostrum and milk and all samples with targeted metagenomics. We also cultured 20 samples, including 9 colostrum and 11 mature milk, for the isolation of methanogenic archaea that play a key role in the digestion of certain foods. In the second part we proceeded to the taxonogenomic description of new bacteria isolated from colostrum, breast milk and stools of obese patients. We observed a high bacterial diversity of colostrum and breast milk through culturomics and metagenomics approaches. We have been able to cultivate two species of methanogenic archaea; Methanobrevibacter smithii is present in most people gut and Methanobrevibacter oralis colonizes the human oral cavity. We have thus increased the microbial repertoire associated with colostrum and human breast milk by discovering and describing several new bacterial species

Culturomics provide critical prokaryotes strains for anti-Listeria and anti-cancer probiotics

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“Bariatricus massiliensis” as a new bacterial species from human gut microbiota

International audienceWe report here the main phenotypic characteristics of "Bariatricus massiliensis" strain AT12 (CSUR P2179), isolated from the stool of a 58-year-old woman who underwent bariatric surgery

‘Negativicoccus massiliensis’, a new species identified from human stool from an obese patient after bariatric surgery

International audienceWe report here the main characteristics of 'Negativicoccus massiliensis' strain AT7 (CSURP=P2082, DSM=100853) isolated from a stool sample collected from a 47-year-old obese French man before bariatric surgery

Repertoire of human breast and milk microbiota: a systematic review

International audienceBreastfeeding is a major determinant of human health. Breast milk is not sterile and ecological large-scale sequencing methods have revealed an unsuspected microbial diversity that plays an important role. However, microbiological analysis at the species level has been neglected while it is a prerequisite before understanding which microbe is associated with symbiosis or dysbiosis, and health or disease. We review the currently known bacterial repertoire from the human breast and milk microbiota using a semiauto-mated strategy. Total 242 articles from 38 countries, 11,124 women and 15,489 samples were included. Total 820 species were identified mainly composed of Proteobacteria and Firmicutes. We report variations according to the analytical method (culture or molecular method), the anatomical site (breast, colostrum or milk) and the infectious status (healthy control, mastitis, breast abscess, neonatal infection). In addition , we compared it with the other human repertoires. Finally, we discuss its putative origin and role in health and disease. Breastfeeding has been associated with the health of the child and the mother, regardless of geography and socioeconomic level [1], child's growth and cognitive development [1,2]. Human studies suggest a protective effect against diarrhea, necrotizing enterocolitis, otitis media and respiratory infections in the short term and against leukemia, malocclusion, inflammatory bowel disease, malnutrition including kwashiorkor, obesity and diabetes in the long term [1,3,4]. Up to half of deaths caused by infections in children aged 6-23 months may be associated with the absence of adequate breastfeeding [1]. Breastfeeding has also been associated with a protective effect for mothers against breast cancer and possibly against ovarian cancer and diabetes [1]. In addition to nutrients, bioactive molecules such as human milk oligosaccharides, human maternal cells but also extracellular vesicles [5-8], milk contains many microbes and is therefore not sterile. The importance of the microbial diversity of human milk for the health of the offspring has been largely neglected to date. More recently, an increasing number of studies have reported an unsuspected diversity, including many health-promoting bacteria (probiotics) in the breast, colostrum or milk [9-11] but also bacteria usually considered pathogenic and frequently found in healthy controls [12]. The milk microbiota likely plays a critical role in the colonization of the child's digestive tract and in the development of its immunity [13-16]. Prolonged exclusive breastfeeding is associated with reduced diarrhea-related gut microbiota dysbiosis and microbiota differences that persist for life [8]. The disruption of this ecosystem has also been associated with maternal diseases, such as lactational mastitis and breast cancer [17-20]. Breast bacteria could also play a role in maintaining healthy breast tissue, including stimulating host immunity [17]. Many questions remain unanswered regarding the microbiome, such as the fact that microbes considered pathogenic are frequently found in controls, the mechanism by which the microbiota impacts immune development and how dysbiosis leads to gut inflammation [8]. Researchers suggested that future studies should employ metagenomics, metatranscriptomics and metabolomics approaches to understand the complete taxonomical, fun