Diversification of Rice Yellow Mottle Virus and Related Viruses Spans the History of Agriculture from the Neolithic to the Present

The mechanisms of evolution of plant viruses are being unraveled, yet the timescale of their evolution remains an enigma. To address this critical issue, the divergence time of plant viruses at the intra- and inter-specific levels was assessed. The time of the most recent common ancestor (TMRCA) of Rice yellow mottle virus (RYMV; genus Sobemovirus) was calculated by a Bayesian coalescent analysis of the coat protein sequences of 253 isolates collected between 1966 and 2006 from all over Africa. It is inferred that RYMV diversified approximately 200 years ago in Africa, i.e., centuries after rice was domesticated or introduced, and decades before epidemics were reported. The divergence time of sobemoviruses and viruses of related genera was subsequently assessed using the age of RYMV under a relaxed molecular clock for calibration. The divergence time between sobemoviruses and related viruses was estimated to be approximately 9,000 years, that between sobemoviruses and poleroviruses approximately 5,000 years, and that among sobemoviruses approximately 3,000 years. The TMRCA of closely related pairs of sobemoviruses, poleroviruses, and luteoviruses was approximately 500 years, which is a measure of the time associated with plant virus speciation. It is concluded that the diversification of RYMV and related viruses has spanned the history of agriculture, from the Neolithic age to the present

Theme and Variations in the Evolutionary Pathways to Virulence of an RNA Plant Virus Species

The diversity of a highly variable RNA plant virus was considered to determine the range of virulence substitutions, the evolutionary pathways to virulence, and whether intraspecific diversity modulates virulence pathways and propensity. In all, 114 isolates representative of the genetic and geographic diversity of Rice yellow mottle virus (RYMV) in Africa were inoculated to several cultivars with eIF(iso)4G-mediated Rymv1-2 resistance. Altogether, 41 virulent variants generated from ten wild isolates were analyzed. Nonconservative amino acid replacements at five positions located within a stretch of 15 codons in the central region of the 79-aa-long protein VPg were associated with virulence. Virulence substitutions were fixed predominantly at codon 48 in most strains, whatever the host genetic background or the experimental conditions. There were one major and two isolate-specific mutational pathways conferring virulence at codon 48. In the prevalent mutational pathway I, arginine (AGA) was successively displaced by glycine (GGA) and glutamic acid (GAA). Substitutions in the other virulence codons were displaced when E48 was fixed. In the isolate-specific mutational pathway II, isoleucine (ATA) emerged and often later coexisted with valine (GTA). In mutational pathway III, arginine, with the specific S2/S3 strain codon usage AGG, was displaced by tryptophane (TGG). Mutational pathway I never arose in the widely spread West African S2/S3 strain because G48 was not infectious in the S2/S3 genetic context. Strain S2/S3 least frequently overcame resistance, whereas two geographically localized variants of the strain S4 had a high propensity to virulence. Codons 49 and 26 of the VPg, under diversifying selection, are candidate positions in modulating the genetic barriers to virulence. The theme and variations in the evolutionary pathways to virulence of RYMV illustrates the extent of parallel evolution within a highly variable RNA plant virus species

Efficacy of Artesunate + Sulfamethoxypyrazine/Pyrimethamine versus Praziquantel in the Treatment of Schistosoma haematobium in Children

BACKGROUND:This study was conducted to determine the efficacy of the antimalarial artemisinin-based combination therapy (ACT) artesunate +sulfamethoxypyrazine/pyrimethamine (As+SMP), administered in doses used for malaria, to treat Schistosoma haematobium in school aged children. METHODOLOGY/PRINCIPAL FINDINGS:The study was conducted in Djalakorodji, a peri-urban area of Bamako, Mali, using a double blind setup in which As+SMP was compared with praziquantel (PZQ). Urine samples were examined for Schistosoma haematobium on days -1, 0, 28 and 29. Detection of haematuria, and haematological and biochemical exams were conducted on day 0 and day 28. Clinical exams were performed on days 0, 1, 2, and 28. A total of 800 children were included in the trial. The cure rate obtained without viability testing was 43.9% in the As+SMP group versus 53% in the PZQ group (Chi(2) = 6.44, p = 0.011). Egg reduction rates were 95.6% with PZQ in comparison with 92.8% with As+SMP, p = 0.096. The proportion of participants who experienced adverse events related to the medication was 0.5% (2/400) in As+SMP treated children compared to 2.3% (9/399) in the PZQ group (p = 0.033). Abdominal pain and vomiting were the most frequent adverse events in both treatment arms. All adverse events were categorized as mild. CONCLUSIONS/SIGNIFICANCE:The study demonstrates that PZQ was more effective than As+SMP for treating Schistosoma haematobium. However, the safety and tolerability profile of As+SMP was similar to that seen with PZQ. Our findings suggest that further investigations seem justifiable to determine the dose/efficacy/safety pattern of As+SMP in the treatment of Schistosoma infections. TRIAL REGISTRATION:ClinicalTrials.gov NCT00510159

A comprehensive analysis of drug resistance molecular markers and Plasmodium falciparum genetic diversity in two malaria endemic sites in Mali.

BACKGROUND: Drug resistance is one of the greatest challenges of malaria control programme in Mali. Recent advances in next-generation sequencing (NGS) technologies provide new and effective ways of tracking drug-resistant malaria parasites in Africa. The diversity and the prevalence of Plasmodium falciparum drug-resistance molecular markers were assessed in Dangassa and Nioro-du-Sahel in Mali, two sites with distinct malaria transmission patterns. Dangassa has an intense seasonal malaria transmission, whereas Nioro-du-Sahel has an unstable and short seasonal malaria transmission. METHODS: Up to 270 dried blood spot samples (214 in Dangassa and 56 in Nioro-du-Sahel) were collected from P. falciparum positive patients in 2016. Samples were analysed on the Agena MassARRAY® iPLEX platform. Specific codons were targeted in Pfcrt, Pfmdr1, Pfdhfr, and Pfdhps, Pfarps10, Pfferredoxin, Pfexonuclease and Pfmdr2 genes. The Sanger's 101-SNPs-barcode method was used to assess the genetic diversity of P. falciparum and to determine the parasite species. RESULTS: The Pfcrt_76T chloroquine-resistance genotype was found at a rate of 64.4% in Dangassa and 45.2% in Nioro-du-Sahel (p = 0.025). The Pfdhfr_51I-59R-108N pyrimethamine-resistance genotype was 14.1% and 19.6%, respectively in Dangassa and Nioro-du-Sahel. Mutations in the Pfdhps_S436-A437-K540-A581-613A sulfadoxine-resistance gene was significantly more prevalent in Dangassa as compared to Nioro-du-Sahel (p = 0.035). Up to 17.8% of the isolates from Dangassa vs 7% from Nioro-du-Sahel harboured at least two codon substitutions in this haplotype. The amodiaquine-resistance Pfmdr1_N86Y mutation was identified in only three samples (two in Dangassa and one in Nioro-du-Sahel). The lumefantrine-reduced susceptibility Pfmdr1_Y184F mutation was found in 39.9% and 48.2% of samples in Dangassa and Nioro-du-Sahel, respectively. One piperaquine-resistance Exo_E415G mutation was found in Dangassa, while no artemisinin resistance genetic-background were identified. A high P. falciparum diversity was observed, but no clear genetic aggregation was found at either study sites. Higher multiplicity of infection was observed in Dangassa with both COIL (p = 0.04) and Real McCOIL (p = 0.02) methods relative to Nioro-du-Sahel. CONCLUSIONS: This study reveals high prevalence of chloroquine and pyrimethamine-resistance markers as well as high codon substitution rate in the sulfadoxine-resistance gene. High genetic diversity of P. falciparum was observed. These observations suggest that the use of artemisinins is relevant in both Dangassa and Nioro-du-Sahel

Effect of red blood cell variants on childhood malaria in Mali: a prospective cohort study

Red blood cell (RBC) variants protect African children from severe Plasmodium falciparum malaria. Their individual and interactive impacts on mild disease and parasite density, and their modification by age-dependent immunity, are poorly understood

Peritoneal Sclerosis in a Patient on Long-term Continuous Ambulatory Peritoneal Dialysis (CAPD). : An Autopsy Case.

若年性ネフロン癆による慢性腎不全でCAPD (continuous ambulatory peritoneal dialysis)導入し, 6年6ヵ月後に死亡した20歳男性の1剖検例を報告した。CAPD導入数カ月後, 腹膜炎による除水能低下を起こしたが, 約5ヵ月後に回復した。CAPD導入1年5ヵ月以降重症な腹膜炎罹患により除水能低下状態が遷延したが, 次第に回復した。しかし, 体液貯留傾向のため, 3年2ヵ月後より高張透析液を使用し除水量の増加を得たが, 3年9ヵ月後に不可逆的な除水能低下状態となった。一方, クレアチニンの透析排液/血漿濃度比(D/P)から見た溶質除去能は, その約半年後まで保たれており, 血清クレアチニン値の上昇は軽度であった。剖検にて腹膜の線維性肥厚と高度の内腔狭窄を伴う動静脈硬化を認め, 腹膜硬化症と診断した。本例の腹膜硬化症は, 頻回の腹膜炎と高張透析液の使用が主な原因と考えられた。腹膜機能を長期に維持するためには, 腹膜炎の予防と高張透析液の使用を最小限にすることが重要と考えられた。A 20-year-old man, treated with continuous ambulatory peritoneal dialysis (CAPD) for 6.5 years because of-end-stage renal disease due to juvenile nephronophthysis, died of ultrafiltration failure, and the morphological examination of peritoneum was carried out at autopsy. Nine episodes of peritonitis developed, and ultrafiltration transiently decreased after each episodes. At 2 years after the start of CAPD, severe peritonitis occurred, and then his body weight and blood pressure gradually increased. At 4 years after the beginning of CAPD, when hyperosmotic dialysate was frequently used, ultrafiltration was irreversively deteriorated. On the other hand, creatinine dialysate/plasma ratio remained within normal limits for about several months, and the increase in the level of serum creatinine was very little. The peritoneum obtained at autopsy revealed marked fibrous thickening as well as the conspicuous luminal narrowing of arteries and veins due to intimal thickening. The development of peritoneal sclerosis seemed to be related with the frequency and severity of peritonitis and the use of hyperosmotic dialysate

Pf7: an open dataset of Plasmodium falciparum genome variation in 20,000 worldwide samples

We describe the MalariaGEN Pf7 data resource, the seventh release of Plasmodium falciparum genome variation data from the MalariaGEN network.  It comprises over 20,000 samples from 82 partner studies in 33 countries, including several malaria endemic regions that were previously underrepresented.  For the first time we include dried blood spot samples that were sequenced after selective whole genome amplification, necessitating new methods to genotype copy number variations.  We identify a large number of newly emerging crt mutations in parts of Southeast Asia, and show examples of heterogeneities in patterns of drug resistance within Africa and within the Indian subcontinent.  We describe the profile of variations in the C-terminal of the csp gene and relate this to the sequence used in the RTS,S and R21 malaria vaccines.  Pf7 provides high-quality data on genotype calls for 6 million SNPs and short indels, analysis of large deletions that cause failure of rapid diagnostic tests, and systematic characterisation of six major drug resistance loci, all of which can be freely downloaded from the MalariaGEN website

Bee pollination increases yield quantity and quality of cash crops in Burkina Faso, West Africa

Mutualistic biotic interactions as among flowering plants and their animal pollinators are a key component of biodiversity. Pollination, especially by insects, is a key element in ecosystem functioning, and hence constitutes an ecosystem service of global importance. Not only sexual reproduction of plants is ensured, but also yields are stabilized and genetic variability of crops is maintained, counteracting inbreeding depression and facilitating system resilience. While experiencing rapid environmental change, there is an increased demand for food and income security, especially in sub-Saharan communities, which are highly dependent on small scale agriculture. By combining exclusion experiments, pollinator surveys and field manipulations, this study for the first time quantifies the contribution of bee pollinators to smallholders’ production of the major cash crops, cotton and sesame, in Burkina Faso. Pollination by honeybees and wild bees significantly increased yield quantity and quality on average up to 62%, while exclusion of pollinators caused an average yield gap of 37% in cotton and 59% in sesame. Self-pollination revealed inbreeding depression effects on fruit set and low germination rates in the F1-generation. Our results highlight potential negative consequences of any pollinator decline, provoking risks to agriculture and compromising crop yields in sub-Saharan West Africa

Resurgence of Malaria Transmission and Incidence after Withdrawal of Indoor Residual Spraying in the District of Koulikoro, Mali

In Mali, malaria vector control relies mostly on long-lasting insecticidal nets and indoor residual spraying (IRS). From 2008 to 2016, an IRS program was implemented in the district of Koulikoro. After a significant reduction in malaria indicators, IRS was stopped in 2016. This study evaluated the effect of IRS withdrawal on entomological parameters of malaria transmission and incidence in children aged 6 months to 10 years in the district of Koulikoro. Entomological parameters of malaria transmission during the last year of IRS implementation in 2016 were compared with those obtained 2 years after IRS withdrawal in 2018 in two villages of Koulikoro. Mosquito vectors were collected by mouth aspiration and pyrethrum spray catches in the villages to monitor these transmission parameters. A sharp increase (10.8 times higher) in vector abundance after IRS withdrawal was observed. The infection rate of Anopheles gambiae sensu lato to Plasmodium falciparum increased from zero during IRS implementation to 14.8% after IRS withdrawal. The average entomological inoculation rate, which was undetectable before, was 1.22 infected bites per person per month 2 years after IRS was withdrawn, and the cumulative malaria incidence rate observed after IRS was 4.12 times (15.2% versus 3.7%) higher than that observed in 2016 in the villages before IRS withdrawal. This study showed a resurgence of malaria transmission and incidence in the Koulikoro health district after IRS was withdrawn. Thus, to manage the potential consequences of malaria transmission resurgence, alternative approaches are needed when stopping successful malaria control interventions

Preventive and Curative treatment of malaria during pregnancy in Mali: Evaluation of the Healthcare Professionals based on the Malian National Malaria Control Program (NMCP) Guidelines

Malaria infections in pregnancy should be treated promptly with safe and efficacious antimalarial drugs to prevent harmful effects on the mother and fetus. To succeed, the Malian has developed NMCP guidelines for the management of malaria cases in pregnant women. The study aimed at the analysis of the prescription of antimalarial drugs based on the Mali's NMCP guidelines. We conducted a cross-sectional study during malaria transmission season from June to August 2020. The sampling concerned all prescriptions for pregnant women containing at least one antimalarial drug. The frequency of prescription of antimalarial drugs was 85%. 132 (74.16%) were preventive treatments and 46 (25.84%) curative treatments. 30 (90.91%) of pregnant women in the first trimester received one dose of Sulfadoxine-Pyrimethamine. 6 (12.5%) received three doses in the third trimester. Of the 46 antimalarial drugs prescribed for the treatment of uncomplicated malaria, 30 (65.22%) were Artemether-lumefantrine (tablet), 10 (21.74%) were Quinine (tablet). 29 (63.04%) were compliant with NMCP guidelines and 17 (36.96%) were not. The non-compliances concerned 3 prescriptions of Artemether-lumefantrine in the first trimester, 3 and 5 prescriptions of Quinine (tablet) in the second and third trimester respectively and at the end 2 and 4 non-compliances respectively for the prescription of injectable dosage forms of Quinine and Artesunate. This study showed a great noncompliance with the Mali's NMCP guidelines in the prescription of antimalarial in pregnant women. Chemoprophylaxis should be prohibited in the first trimester.   Keywords: Curative and Preventive Treatment, Malaria in Pregnancy, Malaria Transmission, Mal