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Many African countries have reported declines in malaria incidence, attributed to the implementation of control strategies. In Mali, artemisinin-based combination therapy (ACT) was introduced in 2004, and long-lasting insecticide-treated nets (LLINs) have been partially distributed free of charge since 2007. In the Malian town of Bandiagara, a study conducted from 2009 to 2013 showed a stable incidence of malaria compared with 1999, despite the implementation of ACTs and LLINs. Since 2016, seasonal malaria chemoprevention has been scaled up across the country. In addition to these strategies, the population of Bandiagara benefited from indoor residual spray implementation in 2017 and 2018 and continued universal bed net coverage. This study aimed to measure the incidence of malaria in Bandiagara, given this recent scaling up of control strategies. A cohort of 300 children aged 6 months to 15 years was followed up from October 2017 to December 2018. We performed monthly cross-sectional surveys to measure anemia and the prevalence of malaria infection by microscopy. The overall incidence of symptomatic malaria was 0.5 episodes/person-year. Malaria incidence in children up to 5 years old significantly declined since 2012 and since 1999 (incidence rate ratio estimates: 6.7 [95% CI: 4.2–11.4] and 13.5 [95% CI: 8.4–22.7]), respectively. The average prevalence of malaria parasitemia was 6.7%. Malaria incidence was higher in children older than 5 years than in those younger than 5 years, highlighting the need to extend malaria control efforts to these older children.

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.

International audience; The nature of the relationship between the communities of microorganisms making up the microbiota in and on a host body has been increasingly explored in recent years. Microorganisms, including bacteria, archaea, viruses, parasites and fungi, have often long co-evolved with their hosts. In human, the structure and diversity of microbiota vary according to the host's immunity, diet, environment, age, physiological and metabolic status, medical practices (e.g., antibiotic treatment), climate, season and host genetics. The recent advent of next generation sequencing (NGS) technologies enhanced observational capacities and allowed for a better understanding of the relationship between distinct microorganisms within microbiota. The interaction between the host and their microbiota has become a field of research into microorganisms with therapeutic and preventive interest for public health applications. This review aims at assessing the current knowledge on interactions between prokaryotic and eukaryotic communities. After a brief description of the metagenomic methods used in the studies were analysed, we summarise the findings of available publications describing the interaction between the bacterial communities and protozoa, helminths and fungi, either in vitro, in experimental models, or in humans. Overall, we observed the existence of a beneficial effect in situations where some microorganisms can improve the health status of the host, while the presence of other microorganisms has been associated with pathologies, resulting in an adverse effect on human health.

Eukaryotic enteric pathogens (EEP) are a public health issue in tropical areas. Yet, their interactions with the gut mycobiota remain poorly understood. We conducted a cross-sectional study in Malian children to analyze the impact of EEP on the gut fungal community. EEP were assessed by qPCR and the gut mycobiota was characterized by ITS1-2 metabarcoding in stool samples collected from 296 children. The 100 controls, in whom no EEP was detected, were compared to: a) 196 children with ≥1 EEP; b) 91 with only Blastocystis; c) 35 with only Giardia intestinalis; and d) 12 with another (

BackgroundDeclines in malaria incidence attributed to the implementation of control strategies have been reported in many African countries. The declines are often accompanied by a shift in clinical burden to older children. In Mali, artemisinin-based combination therapy (ACT) was introduced in 2004, and Long-lasting insecticide-treated nets (LLINs) have been partially distributed free of charge since 2007. In Bandiagara, a study conducted from 2009 to 2013 showed a stable incidence of malaria compared to 1999 despite the use of ACTs and LLINs. Since 2016, seasonal malaria chemoprevention (SMC) has been scaled up across the country. In addition to these strategies, the population of Bandiagara benefited the universal bed net coverage and indoor residual spray (IRS) implementation in 2017 and 2018.This study aimed to measure the incidence of malaria in the context of recent scaling-up of control strategies.MethodsA cohort of 300 children aged 6 months to 15 years was followed from October 2017 to December 2018 in Mali. Monthly cross-sectional surveys were done to measure the prevalence of malaria infection by microscopy and anaemia. The study outcomes included the monthly prevalence of malaria infection and the incidence of symptomatic malaria.ResultsThe incidence of symptomatic malaria was 0.5 episodes/person-year. The average prevalence of malaria parasitaemia was 6.7%. The incidence was higher in the oldest age group than the youngest one (0.6 episodes/person-year in children above 10 years vs 0.29 in 6 months to 5 years age group).ConclusionsThis study showed a reduction of malaria incidence compared to 1999 and 2009-2013. An age shift in the susceptibility to malaria was also observed; older children experienced more clinical malaria than younger ones. These findings suggest to extend malaria control efforts to older children.

Blastocystis is the most common protozoan colonizing the gut of vertebrates. It modulates the human digestive microbiota in the absence of inflammation and gastrointestinal disease. Although it has been associated with human diseases, including inflammatory bowel disease, its pathogenicity remains controversial. This study aimed to assess the influence of Blastocystis on the gut bacterial communities in healthy children. We conducted a cross-sectional study on 147 Blastocystis-colonized and 149 Blastocystis-noncolonized Malian children, with Blastocystis colonization assessed by real-time PCR and gut microbial communities characterized via 16S rRNA gene (Illumina MiSeq) sequencing and bioinformatics analysis. The gut microbiota diversity was higher in Blastocystis-colonized compared to Blastocystis-noncolonized children. The phyla Firmicutes, Elusimicrobia, Lentisphaerae, and Euryarchaeota were higher in Blastocystis-colonized children, whereas Actinobacteria, Proteobacteria, unassigned bacteria, and Deinococcus&ndash, Thermus were higher in Blastocystis-noncolonized children. Moreover, Faecalibacterium prausnitzii (family Ruminococcaceae) and Roseburia sp. (family Lachnospiraceae) abundance was higher in Blastocystis-colonized children. We conclude that Blastocystis colonization is significantly associated with a higher diversity of the gut bacterial communities in healthy children, while it is not associated with the presence of potentially pathogenic bacteria in the human gut.

Control of uncomplicated cases of malaria has been greatly impaired by development of resistance against mainstay antimalarial agents [1, 2]. The first–line antimalarial strategy is presently artemisinin combination therapy. Quinine (QN) is used in many malaria-endemic countries for the management of severe life–threatening malaria and as rescue therapy for parasites resistant to other antimalarial drugs. As a monotherapy, QN is associated with significant recrudescence rates [3]. This may be because QN is a rapidly acting drug with a relatively short elimination half–life [4, 5]. Failure of QN in malaria treatment has been long documented, particularly in South America [6, 7] and Southeast Asia [8]. Although high–level resistance of Plasmodium falciparum to QN is rare, in vivo and in vitro decreases in parasite susceptibility have led to the use of this drug in combination, particularly with the antibiotics tetracycline or doxycycline [9–13]. The mechanisms of decreased P. falciparum susceptibility to QN are not clearly understood. Modulation of in vitro QN sensitivity has been associated with single nucleotide polymorphisms in the pfcrt (chloroquine–resistance transporter) and pfmdr1 (multidrug resistance 1) genes [14, 15]. Involvement of additional genes also seems to be important, because the association of pfcrt and pfmdr1 is not always observed [16]. This reality of a complex phenotype is also supported by the frequent efficacy of QN against chloroquine-resistant parasites [17, 18]. The availability of a laboratory-derived genetic cross between 2 parasites of markedly different in vitro QN responses [19] permitted a quantitative trait loci–based approach that identified genomic regions contributing to the phenotypes [18]. Analysis showed a possible association between reduced P. falciparum susceptibility to QN and a locus on chromosome 13. A pairwise effect was also detected between that chromosome 13 locus and an additional locus on chromosome 9. The set of predicted genes on the chromosome 13 locus included a homologue to the family of Na+/H+ exchanger (NHE) proteins [18]. The P. falciparum–encoded PfNHE–1 is 1920 amino acids long and harbors an open reading frame with a microsatellite polymorphism consisting of variable DNNND repeat units, designated ms4760. The predicted pfnhe–1 sequence was analyzed in the Dd2 × HB3 progeny, as well as in a range of field isolates and laboratory strains with variable susceptibilities to QN. Eight variants of ms4760 were originally discovered. The variant ms4760–1 with 2 copies of DNNND repeat units was significantly associated with reduced in vitro QN sensitivity [18]. These results were later supported by transfection experiments [20]. The aforementioned studies were performed with in vitro cultured laboratory strains. However, these polymorphisms were also present in natural P. falciparum populations [21] and found to be associated with QN sensitivity among field isolates in in vitro assays [22–24]. Here we extend these studies to clinical settings by exploring the in vivo impact of QN therapy on the prevalence of the pfnhe–1 ms4760 and pfcrt polymorphisms in 2 Malian villages.

Plasmodium falciparum resistance to the former first-line antimalarials chloroquine and sulfadoxine/pyrimethamine has reached critically high levels in many malaria-endemic regions. This has spurred the introduction of several new artemisinin-based combination therapies (ACTs) that display excellent potency in treating drug-resistant malaria. Monitoring for the emergence of drug resistant P. falciparum is important for maximizing the clinically effective lifespan of ACTs. Here, we provide a commentary on the article by Kaddouri et al., published in this issue of the International Journal of Parasitology, which documents the levels of susceptibility to ACT drugs and chloroquine in P. falciparum isolates from Mali. These authors report that some isolates approached a proposed in vitro threshold of resistance to monodesethyl-amodiaquine (the principal effective metabolite of amodiaquine, an important ACT partner drug), and establish baseline levels of susceptibility to the ACT drugs dihydroartemisinin and lumefantrine. In contrast, the majority of clinical isolates manifested in vitro resistance to chloroquine. The authors also show good concordance between field-based assays employing a non-radioactive lactate dehydrogenase-based method of determining in vitro drug IC50 values and the optimal [3H]-hypoxanthine-based radioactive method. This work illustrates a good example of drug resistance surveillance, whose global coordination is being championed by the World Antimalarial Resistance Network. Our commentary also more generally discusses the complexities inherent to conducting in vitro investigations with P. falciparum patient isolates and correlating these findings with treatment outcome data.