Pharmacological screening of some traditionally-used antimalarial plants from the Democratic Republic of Congo compared to their ecological taxonomic equivalence in Madagascar

Hydro-alcoholic extracts of some plant species growing in two different geographical regions (Democratic Republic of Congo and Madagascar) were evaluated for their inhibitory effects on two malaria parasites strains (P. falciparum FcM29 & P. yoelii subsp nigeriensis) and cytotoxicity towards leukaemia P- 388 cell lines. Results indicate that, the antiplasmodial activity of tested plants varied geographically. Plants growing in continent ecosystem are more active in vitro while their ecological equivalence inhabiting island ecosystems are more active in vivo. It would be conclude that, the development of phytomedicines from plants of different geographical regions selected by bioguided fractionation would allow the populations to reduce the health care cost. The chemotaxonomic approach has also permitted us to detect moderate antiplasmodial activities in Neobegua mahafaliensis, a plant species not previously reported as antimalarial in the traditional medicine knowlegde of Madagascar. The use of a pharmacological property such as the antimalarial activity, in this study, in order to establish genetic filiations between the plants species is an original approach. Keywords: Malaria, medicinal plants, cytotoxicity, Dem. Rep. of Congo, Madagascar, phenotypic marker, genetic filiatio

Evaluation in vitro de l’activité antifalcémiante et effet antioxydant des extraits d’Uapaca heudelotii Baill. (Euphorbiaceae)

En République Démocratique du Congo, comme dans de nombreux pays Africains, la drépanocytose ou anémie SS est l’une des causes majeures de morbidité et de mortalité et constitue un grave problème de Santé Publique. Dans cette partie du continent, la prévalence estimée varie entre 15 et 20% et est parmi les plus élevée en Afrique. En Afrique subsaharienne, plus de 80% d’enfants atteints de l’Anémie SS meurent avant l’âge de cinq ans. A ce jour, bien que quelques moyens thérapeutiques permettent d’améliorer le pronostic de la drépanocytose notamment l’allogreffe, il s’avère que ces moyens sont coûteux et hors de portée des pays pauvres. Les moyens les plus utilisés, notamment les transfusions sanguines répétées, prédisposent les malades à un risque d’infections au VIH/SIDA. Cependant, en RD Congo, plusieurs travaux relatifs à l’utilisation des plantes médicinales contre la drépanocytose ont été rapportés dans la littérature. C’est dans ce cadre que cette étude a été réalisée en vue d’évaluer l’activité antifacémiante des écorces de tige d’Uapaca heudelotii Baill. , une plante médicinale dont la convergence d’utilisation ethnomédicale par l’homme et le bonobo (Pan paniscus) est bien établie, en recourant au test d’Emmel. Les résultats expérimentaux obtenus indiquent un taux de normalisation supérieur à 97% et une nette réduction du taux de méthémoglobine en solution aqueuse. Ceci montre que les extraits totaux méthanoliques d’écorces de tige d’Uapaca heudelotii Baill. possèdent une activité antidrépanocytaire. Ainsi, la pharmacopée des grands singes (Zoopharmacognosie) peut constituer une source des nutraceutiques anti-drépanocytaires.Mots clés: Drépanocytose, Nutraceutiques, Zoopharmacognosie, Uapaca  heudelotii Baill., République Démocratique du Congo

Michellamines A6 and A7, and further mono- and dimeric naphthylisoquinoline alkaloids from a Congolese Ancistrocladus liana and their antiausterity activities against pancreatic cancer cells

Michellamines A6 (1) and A7 (2) are the first dimers of 5,8′-coupled naphthylisoquinoline alkaloids with cis-configured stereocenters in both tetrahydroisoquinoline subunits. They were isolated from the leaves of a recently discovered, yet unidentified Congolese Ancistrocladus liana that shares some morphological characteristics with Ancistrocladus likoko. Two further new dimeric analogs, michellamines B4 (3) and B5 (4), were obtained, along with two previously likewise unknown monomers, ancistrobonsolines A1 (5) and A2 (6), which, besides one single known other example, are the only naphthyldihydroisoquinolines with an M-configured biaryl axis and R-configuration at C-3. Moreover, five compounds earlier reported from other Ancistrocladus species were identified, ancistroealaine C (7), korupensamines A (8a) and B (8b), and michellamines A2 (9) and E (10). Their complete structural elucidation succeeded due to the fruitful interplay of spectroscopic, chemical, and chiroptical methods. Chemotaxonomically, the stereostructures of the metabolites clearly delineate this Congolese Ancistrocladus liana from all known related species, showing that it might be a new taxon. Ancistrobonsolines A1 (5) and A2 (6) exhibited strong preferential cytotoxicities against human PANC-1 pancreatic cancer cells under nutrient-deprived conditions, without displaying toxicity in normal, nutrient-rich medium. Against cervical HeLa cancer cells, the dimeric alkaloids michellamines A6 (1) and E (10) displayed the highest cytotoxic activities, comparable to that of the standard agent, 5-fluorouracil. Furthermore, ancistrobonsolines A1 (5) and A2 (6) showed weak-to-moderate antiprotozoal activities

The cost‐effectiveness of prophylaxis strategies for individuals with advanced HIV starting treatment in Africa

Introduction Many HIV‐positive individuals in Africa have advanced disease when initiating antiretroviral therapy (ART) so have high risks of opportunistic infections and death. The REALITY trial found that an enhanced‐prophylaxis package including fluconazole reduced mortality by 27% in individuals starting ART with CD4 <100 cells/mm3. We investigated the cost‐effectiveness of this enhanced‐prophylaxis package versus other strategies, including using cryptococcal antigen (CrAg) testing, in individuals with CD4 <200 cells/mm3 or <100 cells/mm3 at ART initiation and all individuals regardless of CD4 count. Methods The REALITY trial enrolled from June 2013 to April 2015. A decision‐analytic model was developed to estimate the cost‐effectiveness of six management strategies in individuals initiating ART in the REALITY trial countries. Strategies included standard‐prophylaxis, enhanced‐prophylaxis, standard‐prophylaxis with fluconazole; and three CrAg testing strategies, the first stratifying individuals to enhanced‐prophylaxis (CrAg‐positive) or standard‐prophylaxis (CrAg‐negative), the second to enhanced‐prophylaxis (CrAg‐positive) or enhanced‐prophylaxis without fluconazole (CrAg‐negative) and the third to standard‐prophylaxis with fluconazole (CrAg‐positive) or without fluconazole (CrAg‐negative). The model estimated costs, life‐years and quality‐adjusted life‐years (QALY) over 48 weeks using three competing mortality risks: cryptococcal meningitis; tuberculosis, serious bacterial infection or other known cause; and unknown cause. Results Enhanced‐prophylaxis was cost‐effective at cost‐effectiveness thresholds of US$300 and US$500 per QALY with an incremental cost‐effectiveness ratio (ICER) of US$157 per QALY in the CD4 <200 cells/mm3 population providing enhanced‐prophylaxis components are sourced at lowest available prices. The ICER reduced in more severely immunosuppressed individuals (US$113 per QALY in the CD4 <100 cells/mm3 population) and increased in all individuals regardless of CD4 count (US$722 per QALY). Results were sensitive to prices of the enhanced‐prophylaxis components. Enhanced‐prophylaxis was more effective and less costly than all CrAg testing strategies as enhanced‐prophylaxis still conveyed health gains in CrAg‐negative patients and savings from targeting prophylaxis based on CrAg status did not compensate for costs of CrAg testing. CrAg testing strategies did not become cost‐effective unless the price of CrAg testing fell below US$2.30. Conclusions The REALITY enhanced‐prophylaxis package in individuals with advanced HIV starting ART reduces morbidity and mortality, is practical to administer and is cost‐effective. Efforts should continue to ensure that components are accessed at lowest available prices

Late Presentation With HIV in Africa: Phenotypes, Risk, and Risk Stratification in the REALITY Trial.

This article has been accepted for publication in Clinical Infectious Diseases Published by Oxford University PressBackground: Severely immunocompromised human immunodeficiency virus (HIV)-infected individuals have high mortality shortly after starting antiretroviral therapy (ART). We investigated predictors of early mortality and "late presenter" phenotypes. Methods: The Reduction of EArly MortaLITY (REALITY) trial enrolled ART-naive adults and children ≥5 years of age with CD4 counts .1). Results: Among 1711 included participants, 203 (12%) died. Mortality was independently higher with older age; lower CD4 count, albumin, hemoglobin, and grip strength; presence of World Health Organization stage 3/4 weight loss, fever, or vomiting; and problems with mobility or self-care at baseline (all P < .04). Receiving enhanced antimicrobial prophylaxis independently reduced mortality (P = .02). Of five late-presenter phenotypes, Group 1 (n = 355) had highest mortality (25%; median CD4 count, 28 cells/µL), with high symptom burden, weight loss, poor mobility, and low albumin and hemoglobin. Group 2 (n = 394; 11% mortality; 43 cells/µL) also had weight loss, with high white cell, platelet, and neutrophil counts suggesting underlying inflammation/infection. Group 3 (n = 218; 10% mortality) had low CD4 counts (27 cells/µL), but low symptom burden and maintained fat mass. The remaining groups had 4%-6% mortality. Conclusions: Clinical and laboratory features identified groups with highest mortality following ART initiation. A screening tool could identify patients with low CD4 counts for prioritizing same-day ART initiation, enhanced prophylaxis, and intensive follow-up. Clinical Trials Registration: ISRCTN43622374.REALITY was funded by the Joint Global Health Trials Scheme (JGHTS) of the UK Department for International Development, the Wellcome Trust, and Medical Research Council (MRC) (grant number G1100693). Additional funding support was provided by the PENTA Foundation and core support to the MRC Clinical Trials Unit at University College London (grant numbers MC_UU_12023/23 and MC_UU_12023/26). Cipla Ltd, Gilead Sciences, ViiV Healthcare/GlaxoSmithKline, and Merck Sharp & Dohme donated drugs for REALITY, and ready-to-use supplementary food was purchased from Valid International. A. J. P. is funded by the Wellcome Trust (grant number 108065/Z/15/Z). J. A. B. is funded by the JGHTS (grant number MR/M007367/1). The Malawi-Liverpool–Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine (grant number 101113/Z/13/Z) and the Kenya Medical Research Institute (KEMRI)/Wellcome Trust Research Programme, Kilifi (grant number 203077/Z/16/Z) are supported by strategic awards from the Wellcome Trust, United Kingdom. Permission to publish was granted by the Director of KEMRI. This supplement was supported by funds from the Bill & Melinda Gates Foundation

Mapping the medical outcomes study HIV health survey (MOS-HIV) to the EuroQoL 5 Dimension (EQ-5D-3L) utility index

10.1186/s12955-019-1135-8Health and Quality of Life Outcomes1718

Spirombandakamine A3 and cyclombandakamines A8 and A9, polycyclic naphthylisoquinoline dimers, with antiprotozoal activity, from a Congolese Ancistrocladus plant

Spirombandakamine A3 (7) is only the third known naphthylisoquinoline dimer with a spiro-fused novel molecular framework and the first such representative to possess a relative trans-configuration at the two chiral centers in both tetrahydroisoquinoline subunits. It was found in the leaves of a botanically as yet unidentified Congolese Ancistrocladus plant, which is morphologically closely related to the Central African taxon Ancistrocladus ealaensis. Likewise isolated were the new cyclombandakamines A8 (8) and A9 (9), which belong to another most recently discovered type of unusual oxygen-bridged naphthylisoquinoline dimers and two previously described "open-chain" analogues, mbandakamines C (10) and D (11). The full absolute stereostructures of these compounds were assigned by combining spectroscopic, chemical, and chiroptical methods. Preliminary biomimetic investigations indicated that both spirombandakamine- and cyclombandakamine-type dimers result from the oxidation of their open-chain mbandakamine-type congeners. The new dimeric alkaloids 7-9 displayed potent growth-inhibitory activity against Plasmodium falciparum, the protozoal pathogen causing malaria, and moderate effects on Trypanosoma brucei rhodesiense, the parasite responsible for African sleeping sickness

Comparative antimalarial and cytotoxic activities of two Vernonia species: V. amygdalina from the Democratic Republic of Congo and V. cinerea subsp vialis endemic to Madagascar

Vernonia amygdalina Del. is a conventional herbal drug in Congolese traditional medicine and is widely used for the treatment of malaria.The aim of this work is to evaluate its efficacy and safety and the potential antimalarial activity of another species originating from Madagascar. Standard bioassay models based on in vitro and in vivo systems that enable bioactivity screening of traditionally used medicinal plants wereused. In particular, hydro-alcoholic extracts of two Vernonia species growing in two different geographical regions(Congo DR and Madagascar) were evaluated for the inhibitory effects on two malaria parasites strainsand cytotoxicity towards leukaemia P-388 cell lines. Results indicate that, V. amygdalina possess a very good in vitro and in vivo activities and a good therapeutic index than V. cinerea subsp vialis endemic to Madagascar, thus validate scientifically the efficacy and safety of Vernonia amygdalina in the traditional treatment of malaria in Congo DR. Using chemotaxonomic approach, we also detected moderate antiplasmodial activities in V. cinerea subsp vialis a plant species not previously reported as antimalarial in the traditional medicine knowlegde of Madagascar. It would be concluded that despite the long spatial isolation of Madagascar and allopatric speciation, Vernonia ecotype as V. cinerea subsp vialis has preserved the antiplasmodial properties. This approach gives the possibility to select plant species of the same genus from different geographical regions in order to increase the chance of discovering new biologically active plants

Fluorescence energy transfer on erythrocyte membranes

Supported by the Swedish Agency for Research Cooperation with Developing Countries (SAREC)Consiglio Nazionale delle Ricerche (CNR). Biblioteca Centrale / CNR - Consiglio Nazionale delle RichercheSIGLEITItal

Six naphthylisoquinoline alkaloids and a related benzopyranone from a Congolese Ancistrocladus species related to Ancistrocladus congolensis

From the roots of a recently discovered Ancistrocladus taxon, with close affinities to Ancistrocladus congolensis regarding molecular ITS sequence data, six naphthylisoquinoline alkaloids, 5′-O-demethylhamatine (2), 5′-O-demethylhamatinine (3), 6-O-demethylancistroealaine A (4), 6,5′-O,O-didemethylancistroealaine A (5), 5-epi-6-O-methylancistrobertsonine A (6), and 5-epi-4′-O-demethylancistrobertsonine C (7), have been isolated, along with a likewise benzopyranone carboxylic acid, 8. The structural elucidation succeeded by chemical, spectroscopic, and chiroptical methods. Their bioactivities were tested against protozoan parasites causing severe tropical diseases. Furthermore, eight known related alkaloids were identified