Kelch 13 propeller gene polymorphism among Plasmodium falciparum isolates in Lagos, Nigeria: Molecular Epidemiologic Study.

OBJECTIVE: To assess polymorphism in Kelch 13 gene of Plasmodium falciparum isolates in Lagos, Nigeria. METHODS: 195 Plasmodium falciparum-positive dried blood spots collected from individuals that accessed diagnostic care at some health facilities and during community surveys across several Local Government Areas of Lagos State, Nigeria, were investigated for the presence of mutations in the K13 gene by nested polymerase chain reaction (PCR) using haplotype-specific probes and sequencing. RESULTS: Three mutant genotypes of K13 gene were observed: A578S in 0.5%, D464N in 0.5% and Q613H in 1.5%. The frequency of K13 polymorphism was 3.1%, while the remaining parasite population had the wild K13 propeller genes. CONCLUSION: No validated Kelch 13 polymorphism associated with artemisinin resistance was seen among P. falciparum isolates from Lagos, Nigeria. As no clinical study was done, this could not be correlated with artemisinin sensitivity.

OBJECTIF: Evaluer le polymorphisme du gène Kelch 13 dans les isolats de Plasmodium falciparum à Lagos, au Nigéria. MÉTHODES: 195 gouttes de sang séchées positives pour Plasmodium falciparum recueillies auprès d'individus ayant accédé à des soins de diagnostic dans certains centres de santé et lors d'enquêtes communautaires menées dans plusieurs zones du gouvernement local de l'Etat de Lagos, au Nigéria, ont été examinées pour rechercher la présence de mutations du gène K13 par la réaction en chaîne imbriquée de la polymérase (PCR) en utilisant des sondes spécifiques à l'haplotype et par le séquençage. RÉSULTATS: Trois génotypes mutants du gène K13 ont été observés: A578S dans 0,5%, D464N dans 0,5% et Q613H dans 1,5%. La fréquence du polymorphisme K13 était de 3,1%, alors que la population parasitaire restante avait les gènes sauvages de l'hélice K13. CONCLUSION: Aucun polymorphisme validé de Kelch 13 associé à une résistance à l'artémisinine n'a été observé parmi les isolats de P. falciparum de Lagos, au Nigéria. Aucune étude clinique n'ayant été réalisée, il n'a pas été possible d'établir une corrélation entre cette observation et la sensibilité à l'artémisinine.

Access to artemisinin-based combination therapies and other anti-malarial drugs in Kinshasa.

OBJECTIVE: Artemisinin-based combination therapies have been available since 2005 in the Democratic Republic of the Congo to treat malaria and to overcome the challenge of anti-malarial drug resistance as well as to improve access to effective treatments. The private sector is the primary distribution source for anti-malarial drugs and thus, has a key position among the supply chain actors for a rational and proper use of anti-malarial drugs. We aimed to assess access to nationally recommended anti-malarial drugs in private sector pharmacies of the capital-city of Kinshasa. METHOD: We performed a cross-sectional survey of 404 pharmacies. RESULTS: Anti-malarial drugs were stocked in all surveyed pharmacies. Non-artemisinin-based anti-malarial therapies such as quinine or sulfadoxine-pyrimethamine, were the most frequently stocked drugs (93.8% of pharmacies). Artemisinin-based combination therapies were stocked in 88% of pharmacies. Artemether-lumefantrine combinations were the most frequently dispensed drugs (93% of pharmacies), but less than 3% were quality-assured products. Other non-officially recommended artemisinin-based therapies including oral monotherapies were widely available. CONCLUSION: Artemisinin-based combination therapies were widely available in the private pharmacies of Kinshasa. However, the private sector does not guarantee the use of nationally recommended anti-malarial drugs nor does it give priority to quality-assured anti-malarial drugs. These practices contribute to the risk of emergence and spread of resistance to anti-malarial drugs and to increasing treatment costs.

[Threats to the Effectiveness of Malaria Treatment]. / Menaces sur l'efficacité du traitement contre le paludisme.

Une résistance de très haut niveau de P. falciparum vient d'être induite expérimentalement in-vivo dans un modèle souris NOD/SCID IL-Ry - / - par des doses infrathérapeutiques d'artésunate [2]. En réaction à la facilité et à la rapidité avec lesquelles cela s'est fait, ce texte amorce un plaidoyer pour la prise de mesures concrètes afin de limiter le risque de voir à terme apparaitre le même phénomène sur le terrain. Ces mesures comprennent notamment un renforcement de la lutte contre l'utilisation de l'artésunate en monothérapie par voie orale, en comprimés souvent sousdosés ou de l'artémisinine en tisane, et l'adoption de moyens plus fiables et plus performants que ceux utilisés actuellement pour détecter plus précocement l'apparition des résistances ainsi qu'une relance de la recherche de nouveaux antipaludiques.

[Adverse effects of antimalarial drugs spontaneously reported to pharmacovigilance national center in Burkina Faso: descriptive study and factors associated]. / Effets indesirables des antipaludiques notifies spontanement au centre national de vigilance des produits de sante au Burkina Faso: etude descriptive et facteurs associes.

AIM: To study spontaneous reporting of adverse effects of antimalarial drugs sent to pharmacovigilance national center. METHOD: A cross-sectional study was conducted to explore spontaneous reporting of adverse effects of antimalarial drugs sent to pharmacovigilance center from January 1, 2009 to December 31, 2013. RESULTS: In total 104 spontaneous reporting forms regarding antimalarial drugs were analysed. The sex ratiowas (male/female) 0,8. The majority of patients were aged over 13 years (66,3%). Self-medication and use of concomitant drug (>2) were observed in 22,1% and 46,2% of cases respectively. The artemisinin-based combination therapies (ACTs) were used in 77,8%. Several categories of adverse effects were observed among which skin and annexes disorders(34,6%), disorders of general health conditions, (29,8%), central nervous system disorders(29,8%), gastro-enterological disorders (23,0%). The most part of adverse effects was mild (67,3%).The adverse effects regarding central nervous (p=0,009)and gastro-enterological (p=0,0009) systems were significantly associated to the ACT use compared with use of other antimalarial drugs. CONCLUSION: These results show the importance to implement active surveillance of ACTs to have a safety profile in our real conditions of use.

BUT: Analyser les notifications spontanées des effets indésirables des antipaludiques transmises au centre national de pharmacovigilance. MÉTHODE: Il s'est agid'une étude transversale à visée exploratoire des notifications spontanées comportant un antipaludique, reçues au centre national de vigilance des produits de santé, du 1er janvier 2009 au 31 décembre 2013. RÉSULTATS: Au total, 104 fiches de notification ont été étudiées. Le sexe ratio hommes/femmes était égal à 0,8 et les patients de plus de 13 ans représentaient 66,3%. Les effets indésirables survenaient dans des circonstances d'automédication, de traitement concomitant de plus de deux médicaments dans 22,1% et 46,2% des cas respectivement. Les combinaisons thérapeutiques à base d'artémisinine (CTA) représentaient 77,8% des cas. Plusieurs types d'effets indésirables ont été observés, parmi lesquels les atteintes de la peau et ses annexes (34,6%), les troubles de l'état (29,8%),les troubles du système nerveux (29,8%), les troubles gastroentérologiques (23,0%). Les effets indésirables étaient le plus souvent modérés (67,3%). Ceux se rapportant au système nerveux (p=0,009) et à l'appareil gastroentérologique(p=0,0009) étaient associés significativement à l'utilisation d'une CTA. CONCLUSION: Ces résultats montrent la nécessité d'une surveillance plus intense des CTA pour mieux décrire leur profil de tolérance dans nos conditions réelles d'utilisation.

Botanical drugs in Ayurveda and Traditional Chinese Medicine.

ETHNOPHARMACOLOGICAL RELEVANCE: China and India have a long history in the therapeutic application of botanical drugs in traditional medicine. Traditional Chinese Medicine (TCM) and Ayurveda are considered as two of the most ancient systems of medicine, with history of more than two millennia. Medicinal plants are the principal medicinal materials used in both these systems. AIM OF THE REVIEW: This review discusses about the histories of Ayurveda and TCM, the common medicinal plants species, the drug processing strategies used, and the current statuses of these traditional systems of medicine (TSM). Through the views presented in this article, we aim to provide a new perspective to herbal drug researchers for expanding and improving the utilization of botanical drugs and their therapeutic applications. METHODS: A bibliographic investigation of Chinese and Indian pharmacopoeias, monographs and official websites was performed. Furthermore, information was obtained from scientific databases on ethnobotany and ethno medicines. RESULTS: The review of Ayurveda and TCM ethno medicine indicates that both these systems have many medicinal materials in common. The studies carried out by the authors for comparison of plants from same genus from both these TSM's have been discussed to further bring focus to the utilization of "qualitatively" similar species which can be utilized and substituted for endangered or economically valued species. The overview of ancient literature and scientific findings for drugs in both these systems suggests that, the botanical drugs used in common and their processing methods can be explored further for extensive utilization in traditional medicine. CONCLUSION: This review describes the histories, common medicinal plant species, their processing methods and therapeutic applications in Ayurveda and TCM. The insights provided through this article may be used by herbal drug researchers and pharmacologists for further exploration of botanical drugs from these two traditional systems of medicine.

Appropriate targeting of artemisinin-based combination therapy by community health workers using malaria rapid diagnostic tests: findings from randomized trials in two contrasting areas of high and low malaria transmission in south-western Uganda.

OBJECTIVE: To compare the impact of malaria rapid diagnostic tests (mRDTs), used by community health workers (CHWs), on the proportion of children <5 years of age receiving appropriately targeted treatment with artemisinin-based combination therapy (ACT), vs. presumptive treatment. METHODS: Cluster-randomized trials were conducted in two contrasting areas of moderate-to-high and low malaria transmission in rural Uganda. Each trial examined the effectiveness of mRDTs in the management of malaria and targeting of ACTs by CHWs comparing two diagnostic approaches: (i) presumptive clinical diagnosis of malaria [control arm] and (ii) confirmatory diagnosis with mRDTs followed by ACT treatment for positive patients [intervention arm], with village as the unit of randomisation. Treatment decisions by CHWs were validated by microscopy on a reference blood slide collected at the time of consultation, to compare the proportion of children <5 years receiving appropriately targeted ACT treatment, defined as patients with microscopically-confirmed presence of parasites in a peripheral blood smear receiving artemether-lumefantrine or rectal artesunate, and patients with no malaria parasites not given ACT. RESULTS: In the moderate-to-high transmission area, ACT treatment was appropriately targeted in 79.3% (520/656) of children seen by CHWs using mRDTs to diagnose malaria, vs. 30.8% (215/699) of children seen by CHWs using presumptive diagnosis (P < 0.001). In the low transmission area, 90.1% (363/403) children seen by CHWs using mRDTs received appropriately targeted ACT treatment vs. 7.8% (64/817) seen by CHWs using presumptive diagnosis (P < 0.001). Low mRDT sensitivity in children with low-density parasitaemia (<200 parasites/µl) was identified as a potential concern. CONCLUSION: When equipped with mRDTs, ACT treatments delivered by CHWs are more accurately targeted to children with malaria parasites. mRDT use could play an important role in reducing overdiagnosis of malaria and improving fever case management within iCCM, in both moderate-to-high and low transmission areas. Nonetheless, missed treatments due to the low sensitivity of current mRDTs in patients with low parasite density are a concern. For community-based treatment in areas of low transmission and/or non-immune populations, presumptive treatment of all fevers as malaria may be advisable, until more sensitive diagnostic assays, suitable for routine use by CHWs in remote settings, become available.

Seasonal malaria chemoprevention in an area of extended seasonal transmission in Ashanti, Ghana: an individually randomised clinical trial.

OBJECTIVE: To investigate the effectiveness of seasonal malaria chemoprevention (SMC) and community case management with long-acting artemisinin-based combination therapies (ACTs) for the control of malaria in areas of extended seasonal malaria transmission. METHOD: Individually randomised, placebo-controlled trial in the Ashanti Region of Ghana. A total of 2400 children aged 3-59 months received either: (i) a short-acting ACT for case management of malaria (artemether-lumefantrine, AL) plus placebo SMC, or (ii) a long-acting ACT (dihydroartemisinin-piperaquine, DP) for case management plus placebo SMC or (iii) AL for case management plus active SMC with sulphadoxine-pyrimethamine and amodiaquine. SMC or placebo was delivered on five occasions during the rainy season. Malaria cases were managed by community health workers, who used rapid diagnostic tests to confirm infection prior to treatment. RESULTS: The incidence of malaria was lower in children given SMC during the rainy season. Compared to those given placebo SMC and AL for case management, the adjusted hazard ratio (aHR) was 0.62 (95% CI: 0.41, 0.93), P = 0.020 by intention to treat and 0.53 (95% CI: 0.29, 0.95), P = 0.033 among children given five SMC courses. There were no major differences between groups given different ACTs for case management (aHR DP vs. AL 1.18 (95% CI 0.83, 1.67), P = 0.356). CONCLUSION: SMC may have an important public health impact in areas with a longer transmission season, but further optimisation of SMC schedules is needed to maximise its impact in such settings.

Treatment of uncomplicated malaria with artesunate plus sulfadoxine-pyrimethamine is failing in Somalia: evidence from therapeutic efficacy studies and Pfdhfr and Pfdhps mutant alleles.

OBJECTIVE: Artesunate plus sulfadoxine-pyrimethamine (AS + SP) has been Somalia's national treatment policy since 2006. Routine monitoring of first-line malaria treatment is needed to ensure appropriate national malaria treatment policy and early detection of drug resistance. For this purpose, we conducted therapeutic efficacy studies of AS + SP for the treatment of uncomplicated malaria in Somalia in 2011. METHODS: Studies were conducted in three sentinel sites. Eligible patients were evaluated for clinical and parasitological outcomes according to the WHO standard protocol. Molecular surveillance was conducted on resistance conferring mutations in the P.falciparum dihydrofolate reductase (dfhr) and dihydropteroate synthase (dhps) genes. RESULTS: The proportion of PCR-corrected treatment failures was high in Jamame (22%, 95% CI: 13.7-32.8%) and low (<5%) in Janale and Jowhar. All patients cleared parasites by day 3. Molecular markers associated with SP resistance were detected in all three sites. Treatment failure was associated with the presence of the double mutant dhps A437G/K540E (OR = 22.4, 95% CI: 5.1-98.1), quadruple mutant dhfr N51I/S108N+dhps A437G/K540E (OR = 5.5, 95% CI: 2.3-13.6), quintuple mutant dhfr N51I/C59R/S108N+dhps A437G/K540E (OR = 3.5, 95% CI: 1.4-8.8) and younger age (OR=0.86, 95% CI: 0.76-0.96). CONCLUSIONS: The high treatment failure rate observed in Jamame, together with the presence of molecular mutations associated with SP resistance, indicates P. falciparum resistance to SP. In Jowhar, high treatment failure rates were absent despite the presence of molecular mutations; signs of resistance in vivo may have been masked by the stronger immunity of the older study population. The study underscores the need to update Somalia's national malaria treatment policy.

Botánica, biología, composición química y propiedades farmacológicas de Artemisia annua L / Botanic, biology, chemical composition and pharmacological properties of Artemisia annua L

INTRODUCCIÓN: se presenta una revisión bibliográfica sobre Artemisia annua L., una hierba perteneciente al género Artemisia, la cual incluye alrededor de 400 especies. A. annua ha sido utilizada tradicionalmente como tratamiento herbario contra la malaria en China y en otras partes del mundo.OBJETIVOS: recopilar y actualizar la información publicada sobre A. annua.MÉTODOS: se realizó una amplia búsqueda bibliográfica que permitió identificar y consultar varias decenas de artículos científicos referentes a A. annua, sobre todo de los últimos 20 años, así como varios libros y monografías sobre la planta. En el presente trabajo se analizan los aspectos históricos más importantes relacionados con la planta, descripción botánica, origen y distribución geográfica, requerimientos ambientales, composición química, producción de aceites y sus propiedades farmacológicas...

INTRODUCTION: this is a bibliographic review on Artemisia annua L., a medicinal herb from Artemisia gender, which includes approximately 400 species. A. annua, traditionally is used as an herbal treatment against malaria in China and in other world zones.OBJETIVE: to collect and update the information published on Artemisia annua L. METHODS: authors conducted a wide bibliographic review allowed them to identify and to look for some ten scientific articles on A. annua, mainly of the past 20 years, as well as some books and monographs on this plant. Aim of present paper is to analyze the most important historical features related to this plant, a botanical description, origin and geographical distribution, environmental requirements, chemical composition, oil production and its pharmacological properties...

Improvement in the synthetic process of some derivatives of artemisinine containing fluor

The improvement of synthesis of 10-(trifluoroethoxy)-dihydroartemisinin was described. The improved procedure has some advantages like mild reaction conditions, good yields of products, operational simplicity and the ease of isolation and purification of the products

A new catalyst in the synthesis of fluroalkylether derivatives of artemisinine

Synthetic process fluoroalkylether from artemisinine carried out with 2 TF-DHA and DHA derivatives by etherification reaction with fluoroalkylalcohol in appropriate solvent and catalysis. In research process, author found a catalysis for synthetic reaction of 2 non-flo ethyls of DHA that is sulfuric acid. This catalysis is popular and inexpensive, can replace expensive catalysis in previous experimentations

Study on the solid dispersion system of artemisinine

Enteric solid dispersions of artemisinine were prepared by spray drying using methacrylic acid copolymer (Eudragit L100) as carrier and hydroxypropylmethylcellulose (HPMC), Tween 20, PEG 6000, colloidal silica (aerosil) as additives. Spherical solid dispersion particles were obtained. Both solubility and dissolution rate of artemisinine studied in the medium pH 7.2 from all solid dispersions were markedly improved compared with that from the original or spray dried drug powder. The drug release rate of tablets that were made from the solid dispersion with drug-carrier ratio of 1:2 was nearly unchanged in medium pH 7.2 and was retarded in medium pH 1.5 in comparison with the solid dispersion powder.

Exploration of the effects an artemisinine suspension by subcutaneous injection in white mice infected with Plasmodium berghei

Artemisinine was prepared into a suspension suitable for subcutaneous administration in Plasmodium berghei- infected mice. This formulation (20mg/kg b.i.d, total dosage of 200mg/kg) was compared to oral artemisinine (at the same dose) in 50 Plasmodium berghei infected mice. The study also included a non treated control group and a placebo suspension group. The drug was applied for 5 days, beginning at 4 hours after infection. All mice treated by subcutaneous application were alive and did not show any toxicity or side effects due artemisinine. There was no recrudescence during 60 days of follow-up. All mice in the control, placebo and oral artemisinin group died with hyperparasitemia. The result showed that subcutaneous formulation of artemisinin is more effective than oral ones at the same dose.

Study on the oral bio-availability of artemisinin solid dispersion system using Eudragit 100 as a carrier

The oral Bio-availability of two different capsule formulations of artmisinin was carried out in six rabbits divided in two groups and seven healthy male volunteers in a single-dose crossover design with randomization for dosing sequence. The experimental results showed that the relative bioavailability of the formulation, that was made of artemisinin solid dispersion system using Eudragit L100 as a carrier on ratio 1:1, was more two times higher than the modification of artemisinin capsules without any modifications. There was a good correlation between in vitro dissolution data obtained by dissolution test with the mean AUG values of each studied group after oral administration.

Therapeutic Efficacy of Naphthoquine Phosphate Combined with Artemisinine against Plasmodium knowlesi / 中国寄生虫学与寄生虫病杂志

Objective To study the antimalarial activity of naphthoquine phosphate combined with artemisinine against Plasmodium knowlesi in rhesus monkey.Methods Monkeys were randomly divided into 9 groups(3/group).The monkeys in groups A and B were treated i.g.once daily for 3 days with 6 or 10 mg/kg of naphthoquine phosphate respectively.Those in groups C and D were treated i.g.twice for the 1st day and once for the 2nd and 3rd day with 31.6 or 100 mg/kg of artemisinine respectively.In groups E, F and G, they were treated i.g.only once with the combination of naphthoquine phosphate 10 mg/kg and artemisinine 10, 20 or 25 mg/kg respectively.Groups H and I served as controls which were treated i.g.only once with 10 mg/kg of naphthoquine phosphate and 30 mg/kg of artemisinine respectively.Parasitemia was examined beginning 24 h after drug administration.The observation lasted 105 days when no more parasite was found.Results At 24 h after drug administration, the parasite reduction rate in all groups was higher than 90%.The parasite clearance time for groups E, F and G was(56.0?16.0),(53.3?4.6), and(56.0?8.0) h respectively, more rapid than that of Group H(69.3?4.6) h.There were 1, 3, 3, 2, 2, and 3 monkeys in groups A, B, D, E, F, and G respectively which were cured.No monkeys were cured in groups C, H and I.Conclusion The combination of naphthoquine phosphate and artemisinine is superior to the single component and the optimum proportion in the combination is 1:2.5 in treating P.knowlesi infection in monkeys.

Efficacy of Naphthoquine, Artemisinine and a Combination of the Two Drugs in the Treatment of Falciparum Malaria / 中国寄生虫学与寄生虫病杂志

Objective To compare the efficacy and safety of naphthoquine, artemisinine and a combination of the two drugs in the treatment of faciparum malaria. Methods Of 230 patients, 100 patients were treated with combined regime (Co-NQ), 100 patients were treated with naphthoquine (NQ) and 30 patients were treated with artemisinine (QHS). All patients were hospitalized for 7 days and followed up for 28 days. Results The mean fever clearance time for Co-NQ, NQ, and QHS was (17.5 ?12.3)h, (32.7?17.7)h and (18.1?9.7)h respectively; the mean parasite clearance time was (30.0?8. 8)h,(45.5?10.0)h and (29.1?6.0)h respectively; and the 28 days cure rate was 97.0% ,100.0% and 66.7% respectively. Conclusion The Co-NQ possesses benefits of both naphthoquine and artemisinine, acting rapidly, with a short course of only one dose and a high cure rate. The regime is well tolerated by patients.