Non-Targeted Dried Blood Spot-Based Metabolomics Analysis Showed Rice Bran Supplementation Effects Multiple Metabolic Pathways during Infant Weaning and Growth in Mali.

Rice bran contains essential nutrients, antioxidants, and bioactives with anti-inflammatory and diarrheal protective properties important for infants. This 6-month randomized controlled trial investigated the effects of heat-stabilized rice bran supplementation during Malian infant weaning. Fifty healthy 6-month-old infants were randomized to a rice bran intervention (N = 25) or non-intervention control group (N = 25). Intervention infants received dose-escalating rice bran supplementation for 6 months (1-5 g/day). Monthly infant dried blood spot and anthropometric measurements were collected. Dried blood spot metabolite abundances were compared monthly according to diet for six months. Supplementation resulted in favorable weight-for-age and weight-for-length z-score changes. Non-targeted dried blood spot-based metabolomics identified 796 metabolites, of which 33% had significant fold differences between groups (7-12 months). Lipids and amino acids represented 70.6% of the metabolites identified. Rice bran supplementation during infant weaning significantly modulated the metabolites involved in antioxidant defenses and with neuroactive properties including reduced glutathione, glycine, glutamate, cysteinylglycine, tryptophan betaine, and choline. These findings support rice bran as a weaning ingredient to meet infant nutritional requirements and with the potential to reduce oxidative stress and improve cognitive outcomes. This study provides evidence for dried blood spots as a cost-effective tool to detect infant biomarkers of nutritional and metabolic status.

Therapeutic efficacy of artemether-lumefantrine and artesunate-amodiaquine for the treatment of uncomplicated Plasmodium falciparum malaria in Mali, 2015-2016.

BACKGROUND: The current first-line treatments for uncomplicated malaria recommended by the National Malaria Control Programme in Mali are artemether-lumefantrine (AL) and artesunate-amodiaquine (ASAQ). From 2015 to 2016, an in vivo study was carried out to assess the clinical and parasitological responses to AL and ASAQ in Sélingué, Mali. METHODS: Children between 6 and 59 months of age with uncomplicated Plasmodium falciparum infection and 2000-200,000 asexual parasites/µL of blood were enrolled, randomly assigned to either AL or ASAQ, and followed up for 42 days. Uncorrected and PCR-corrected efficacy results at days 28 and 42. were calculated. Known markers of resistance in the Pfk13, Pfmdr1, and Pfcrt genes were assessed using Sanger sequencing. RESULTS: A total of 449 patients were enrolled: 225 in the AL group and 224 in the ASAQ group. Uncorrected efficacy at day 28 was 83.4% (95% CI 78.5-88.4%) in the AL arm and 93.1% (95% CI 89.7-96.5%) in the ASAQ arm. The per protocol PCR-corrected efficacy at day 28 was 91.0% (86.0-95.9%) in the AL arm and 97.1% (93.6-100%) in the ASAQ arm. ASAQ was significantly (p < 0.05) better than AL for each of the aforementioned efficacy outcomes. No mutations associated with artemisinin resistance were identified in the Pfk13 gene. Overall, for Pfmdr1, the N86 allele and the NFD haplotype were the most common. The NFD haplotype was significantly more prevalent in the post-treatment than in the pre-treatment isolates in the AL arm (p < 0.01) but not in the ASAQ arm. For Pfcrt, the CVIET haplotype was the most common. CONCLUSIONS: The findings indicate that both AL and ASAQ remain effective for the treatment of uncomplicated malaria in Sélingué, Mali.

[Management of addictions at the University Hospital Center Point G, Bamako-Mali]. / Prise en charge des addictions au Centre Hospitalier Universitaire du Point G, Bamako-Mali.

OBJECTIVE: To evaluate the health impact of drug use among patients in care in the psychiatric unit of the University Hospital Center Point G. METHOD: This was a prospect in description study of drug users admitted to the G-UHC for care. From January to July 2018. It was performed in the Psychiatry Department of the University Hospital Center Point G in Bamako, which is the only structure in Mali that deals with addiction. RESULTS: Our results show that young people in the 20-30 year group were the most affected. Cannabis was the most consumed, followed by Alcohol, and Tramadol Hydrochloride. There were cases of poly-drug abuse as well as new forms of consumption. Drug use has multiple negative consequences on health and social life: addiction, psychopathological disorders. CONCLUSION: Substance abuse of drugs is a reality that is gaining momentum in Mali. Our study have demonstrated its sanitary impact among patients with adduction. The fight against the use of drugs requires the combined efforts of all the actors involved.

OBJECTIF: Evaluer l'impact sanitaire de la consommation des drogues chez les patients pris en charge au service de psychiatrie du Centre Hospitalier universitaire du Point G. MÉTHODE: Il s'agissait d'une étude prospective descriptive chez les patients consommateurs de drogues admis au CHU du Point G pour des soins. Elle a été réalisée de janvier à juillet 2018. Elle a été réalisée dans le service de Psychiatrie du Centre Hospitalier Universitaire du Point G à Bamako, Mali, l'unique structure au Mali qui fait la prise en charge de l'addiction. RÉSULTATS: Nos résultats ont montré que les jeunes de la tranche 20-30 ans étaient les plus touchés. Le Cannabis était le plus consommé, suivi la de l'Alcool, et du Chlorhydrate de Tramadol. La polytoxicomanie ainsi que des nouvelles formes de consommation avait été notée. La consommation de drogues avait généré de multiples conséquences néfastes sur la santé et la vie sociale : la dépendance, les troubles psychopathologiques. CONCLUSION: L'abus de substances psychoactives, est une réalité qui prend de l'ampleur au Mali. Notre étude a démontré son impact sur la santé des consommateurs. La lutte contre l'usage des drogues nécessite la conjugaison des efforts de tous les acteurs impliqués.

Rice bran supplementation modulates growth, microbiota and metabolome in weaning infants: a clinical trial in Nicaragua and Mali.

Rice bran supplementation provides nutrients, prebiotics and phytochemicals that enhance gut immunity, reduce enteric pathogens and diarrhea, and warrants attention for improvement of environmental enteric dysfunction (EED) in children. EED is a subclinical condition associated with stunting due to impaired nutrient absorption. This study investigated the effects of rice bran supplementation on weight for age and length for age z-scores (WAZ, LAZ), EED stool biomarkers, as well as microbiota and metabolome signatures in weaning infants from 6 to 12 months old that reside in Nicaragua and Mali. Healthy infants were randomized to a control (no intervention) or a rice bran group that received daily supplementation with increasing doses at each month (1-5 g/day). Stool microbiota were characterized using 16S rDNA amplicon sequencing. Stool metabolomes were analyzed using ultra-high-performance liquid-chromatography tandem mass-spectrometry. Statistical comparisons were completed at 6, 8, and 12 months of age. Daily consumption of rice bran was safe and feasible to support changes in LAZ from 6-8 and 8-12 months of age in Nicaragua and Mali infants when compared to control. WAZ was significantly improved only for Mali infants at 8 and 12 months. Mali and Nicaraguan infants showed major differences in the overall gut microbiota and metabolome composition and structure at baseline, and thus each country cohort demonstrated distinct microbial and metabolite profile responses to rice bran supplementation when compared to control. Rice bran is a practical dietary intervention strategy that merits development in rice-growing regions that have a high prevalence of growth stunting due to malnutrition and diarrheal diseases. Rice is grown as a staple food, and the bran is used as animal feed or wasted in many low- and middle-income countries where EED and stunting is prevalent.

AQ-13, an investigational antimalarial, versus artemether plus lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria: a randomised, phase 2, non-inferiority clinical trial.

BACKGROUND: Chloroquine was used for malaria treatment until resistant Plasmodium falciparum was identified. Because 4-aminoquinolines with modified side chains, such as AQ-13, are active against resistant parasites, we compared AQ-13 against artemether plus lumefantrine for treatment of uncomplicated P falciparum malaria. METHODS: We did a randomised, non-inferiority trial. We screened men (≥18 years) with uncomplicated malaria in Missira (northeast Mali) and Bamako (capital of Mali) for eligibility (≥2000 asexual P falciparum parasites per µL of blood). Eligible participants were randomly assigned to either the artemether plus lumefantrine group or AQ-13 group by permuting blocks of four with a random number generator. Physicians and others caring for the participants were masked, except for participants who received treatment and the research pharmacist who implemented the randomisation and provided treatment. Participants received either 80 mg of oral artemether and 480 mg of oral lumefantrine twice daily for 3 days or 638·50 mg of AQ-13 base (two oral capsules) on days 1 and 2, and 319·25 mg base (one oral capsule) on day 3. Participants were monitored for parasite clearance (50 µL blood samples twice daily at 12 h intervals until two consecutive negative samples were obtained) and interviewed for adverse events (once every day) as inpatients during week 1. During the 5-week outpatient follow-up, participants were examined for adverse events and recurrent infection twice per week. All participants were included in the intention-to-treat analysis and per-protocol analysis, except for those who dropped out in the per-protocol analysis. The composite primary outcome was clearance of asexual parasites and fever by day 7, and absence of recrudescent infection by parasites with the same molecular markers from days 8 to 42 (defined as cure). Non-inferiority was considered established if the proportion of patients who were cured was higher for artemether plus lumefantrine than for AQ-13 and the upper limit of the 95% CI was less than the non-inferiority margin of 15%. This trial is registered at ClinicalTrials.gov, number NCT01614964. FINDINGS: Between Aug 6 and Nov 18, 2013, and between Sept 18 and Nov 20, 2015, 66 Malian men with uncomplicated malaria were enrolled. 33 participants were randomly assigned to each group. There were no serious adverse events (grade 2-4) and asexual parasites were cleared by day 7 in both groups. 453 less-severe adverse events (≤grade 1) were reported: 214 in the combination group and 239 in the AQ-13 group. Two participants withdrew from the AQ-13 group after parasite clearance and three were lost to follow-up. In the artemether plus lumefantrine group, two participants had late treatment failures (same markers as original isolates). On the basis of the per-protocol analysis, the AQ-13 and artemether plus lumefantrine groups had similar proportions cured (28 [100%] of 28 vs 31 [93·9%] of 33; p=0·50) and AQ-13 was not inferior to artemether plus lumefantrine (difference -6·1%, 95% CI -14·7 to 2·4). Proportions cured were also similar between the groups in the intention-to-treat analysis (28 of 33, 84·8% for AQ-13 vs 31 of 33, 93·9% for artemether and lumefantrine; p=0·43) but the upper bound of the 95% CI exceeded the 15% non-inferiority margin (difference 9·1%, 95% CI -5·6 to 23·8). INTERPRETATION: The per-protocol analysis suggested non-inferiority of AQ-13 to artemether plus lumefantrine. By contrast, the intention-to-treat analysis, which included two participants who withdrew and three who were lost to follow-up from the AQ-13 group, did not meet the criterion for non-inferiority of AQ-13, although there were no AQ-13 treatment failures. Studies with more participants (and non-immune participants) are needed to decide whether widespread use of modified 4-aminoquinolones should be recommended. FUNDING: US Food and Drug Administration Orphan Product Development, National Institutes of Health, US Centers for Disease Control and Prevention, Burroughs-Wellcome Fund, US State Department, and WHO.

Assessing Community Readiness to Reduce Childhood Diarrheal Disease and Improve Food Security in Dioro, Mali.

Diarrhea and malnutrition represent leading causes of death for children in Mali. Understanding a community's needs and ideas are critical to ensure the success of prevention and treatment interventions for diarrheal disease, as well as to improve food security to help reduce malnutrition. The objective of this study was to incorporate the Community Readiness Model (CRM) for the issues of childhood diarrheal disease and food security in Mali to measure baseline community readiness prior to any program implementation. Thirteen key respondents residing in Dioro, Mali were selected based on varied social roles and demographics and completed two questionnaires on these public health issues. The overall readiness score to reduce childhood diarrheal disease was 5.75 ± 1.0 standard deviation (preparation stage). The overall readiness score to improve food security was 5.5 ± 0.5 standard deviation (preparation stage). The preparation stage indicates that at least some of the community have basic knowledge regarding these issues, and want to act locally to reduce childhood diarrhea and improve food security and nutrition. Proposed activities to increase community readiness on these issues are provided and are broad enough to allow opportunities to implement community- and culturally-specific activities by the Dioro community.

[Epidemiology and risk factors for voluntary intoxication in Mali]. / Épidémiologie et facteurs de risque des intoxications volontaires au Mali.

INTRODUCTION: Voluntary intoxication is a major medical and social problem in developing countries and the most common method of suicide attempt. The purpose of this paper is to describe the main characteristics of voluntary intoxication in Mali and the risk factors associated with the outcome of poisoning. More generally, the aim is to contribute to the reduction of morbidity and mortality associated with self-poisoning. METHODS: We conducted a retrospective descriptive study of the cases of deliberate self-poisoning recorded between 2000 and 2010 in 15 Malian hospitals. RESULTS: 884 cases of self-poisoning (233 men and 651 women) were identified during the period of study, representing 28% of all cases of poisoning reported during this period. The mean age of the victims was 23 ± 8.9 years. The available data indicate that the most common cases were suicide attempts and self-induced abortion using toxic substances (respectively 62.8% and 29% of all cases). The most common methods were drugs (74.5%), especially chloroquine (65%), followed by industrial products (9.1%). The most commonly used industrial products were hydrochloric acid (26.7%), sodium hypochlorite (bleach) (22.2%) and sulphuric acid (15.6%). The findings suggest that poisoning symptoms vary depending on the type of substance, the amount ingested and the delay before treatment. 86 of the 877 cases with known outcome resulted in death. CONCLUSION: The number of cases of poisoning is probably underestimated since many cases remain undiagnosed and unreported.

Antioxidant and 15-lipoxygenase inhibitory activities of the Malian medicinal plants Diospyros abyssinica (Hiern) F. White (Ebenaceae), Lannea velutina A. Rich (Anacardiaceae) and Crossopteryx febrifuga (Afzel) Benth. (Rubiaceae).

The African flora contains numerous medicinal plants whose biological and chemical properties are incompletely known. Antioxidant and radical scavenging properties of plants are subject to intensive research. In the work described here, we have investigated the antioxidant activity of the plants Diospyros abyssinica (root bark), Lannea velutina (root bark and stem bark) and Crossopteryx febrifuga (seeds). Extracts of different polarity were assayed for radical scavenging activity, using the stable free radical diphenylpicrylhydrazyl, and for inhibition of enzymatic lipid peroxidation mediated by soybean 15-lipoxygenase. All plants investigated showed activity, but there were large differences between plants and between extracts. In general, Diospyros abyssinica and Lannea velutina were richer in antioxidants than Crossopteryx febrifuga. Lipophilic extracts were not active as radical scavengers, but did inhibit 15-lipoxygenase. Semipolar extracts (80% aqueous ethanol and methanol) of Diospyros abyssinica and Lannea velutina showed the highest activity both as radical scavengers and lipoxygenase inhibitors, and also gave the highest extract yields. These plants therefore appear to be excellent sources of antioxidants.

Determination of some toxic and essential metal ions in medicinal and edible plants from Mali.

Plants are used in different ways in Mali, among those as medicine and as food. The monitoring of metals in the plants is of great importance for protecting the public from the hazards of possible toxic effects and also for informing the population about the nutritional value of the plants. The concentrations of some toxic and essential metal ions were surveyed in seven medicinal and edible plants from Mali. Dry ashing of the plant material and subsequent use of atomic absorption spectrophotometry were the analytical methodologies used. Iron, manganese, and zinc were found in high concentrations in some of the plants, i.e., 1.4 and 1.5 mg/g iron in Cuminum cyminum and Bombax costatum, respectively, 243 microg/g manganese in Hibiscus sabdariffa, and 62.8 and 67.1 microg/g zinc in Spilanthes oleracaea and B. costatum, respectively, whereas cobalt and cadmium were not detected in any of the plant material studied. The other ions detected, Cr, Ni, Pb, and Cu, were present in minor amounts, in the ranges of 2.2-17.2 microg/g for Cr, 1.6-8.1 microg/g for Ni, 0.7-5.2 microg/g for Pb, and 2.4-17.1 microg/g for Cu. From a toxicological point of view, none of these plants would be harmful for the user by taking in the plant material in the traditional manner, which is preparing an infusion of the plant using amounts not adding up to those necessary to reach a harmful level of the metal ions detected. The plants B. costatum and C. cyminum could be of interest as sources for iron for humans in the case of too low of a level of hemoglobin.

A survey of toxic plants on the market in the district of Bamako, Mali: traditional knowledge compared with a literature search of modern pharmacology and toxicology.

In Mali, the empirical knowledge on plant medicine is held by traditional practioners. Scientific studies have been carried on some plants and they have confirmed their local uses, but few data are available on the toxicity of Malian medicinal plants. In the present work, we record the toxic plants used as medicines in the Bamako district, Mali, with the aim to evaluate the knowledge of traditional healers and herbalists on the toxicity of the plant used. A survey was carried out on the market places in the Bamako district and 106 healers and herbalists were interviewed. A survey of the scientific literature was conducted to verify or sustain the claimed toxicological data. Nineteen plants are arranged according to their frequency of quotation based on the questionnaire. The information includes the botanical name, literature survey on the pharmacology of the plants, the healers' knowledge on plant toxicity and its prevention by some of the healers.