Etudes in vivo de la tisane d’Artemisia annua sur le Plasmodium falciparum

Artemisia annua L.

Cet article recense et donne accès aux études relatives aux études in vivo propriétés antipaludiques d’extraits d’Artemisia annua. Les publications sont ordonnés thématiquement : 1. Action in vivo de la poudre de parties aériennes de la plante sur modèle animal. 2. Action in vivo de la tisane de parties aériennes chez l’humain. 3. Action in vivo de la poudre de parties aériennes chez l’humain.

Action in vivo de la tisane de parties aériennes sur la Malaria chez l’humain

2000

M.S. Mueller, I.B. Karhagomba, H.M. Hirt, E. Wemakor
The potential of Artemisia annua L. as a locally produced remedy for malaria in the tropics : agricultural, chemical and clinical aspects
Journal of Ethnopharmacology 73 (2000) 487–493
Short communication Received 11 November 1999 ; received in revised form 4 June 2000 ; accepted 6 June 2000

The potential of Artemisia annua L. as a locally produced remedy for malaria in the tropics : agricultural, chemical and clinical aspects

Abstract : The plant Artemisia annua L. (Asteraceae) is listed in the Chinese pharmacopoeia as a remedy for various fevers including malaria, and contains the well-established antimalarial compound artemisinin. In this study, a hybrid form of A. annua was successfully cultivated in Central Africa. The aerial parts of the plant contained 0.63–0.70% artemisinin per dry weight, and approximately 40% of this artemisinin could be extracted by simple tea preparation methods. Five malaria patients who were treated with A. annua tea showed a rapid disappearance of parasitaemia within 2–4 days. An additional trial with 48 malaria patients showed a disappearance of parasitaemia in 44 patients (92%) within 4 days. Both trials showed a marked improvement of symptoms. In our opinion, these results justify further examinations of the antimalarial effect of A. annua preparations. © 2000 Elsevier Science Ireland Ltd.
Keywords : Antimalarials ; Artemisia annua ; Medicinal plant

2004

Markus S. Mueller, Nyabuhanga Runyambo, Irmela Wagner, Steffen Borrmann, Klaus Dietz, Lutz Heide
Randomized controlled trial of a traditional preparation of Artemisia annua L. (Annual Wormwood) in the treatment of malaria
Transactions of the Royal Society of Tropical Medicine and Hygiene (2004) 98, 318—321

Full text submitted to request

Summary : The Chinese medicinal plant Artemisia annua L. (Annual Wormwood) contains the antimalarial compound artemisinin. The locally grown herbmay offer an additional tool for the control of malaria, especially in poor countries where modern antimalarial drugs are often unavailable. In an open, randomized, controlled pilot trial, we investigated the efficacy and safety of traditional tea preparations of Artemisia annua in the treatment of uncomplicated malaria. Treatment resulted in a quick resolution of parasitaemia and of clinical symptoms. After 7 d of medication, cure rates were on average 74% for the Artemisia preparations compared with 91% for quinine. However, recrudescence rates were high in the Artemisia groups. Therefore, monotherapy with Artemisia annua L. cannot be recommended as alternative to modern antimalarials, but may deserve further investigation.
Keywords : Malaria, Plasmodium falciparum, Artemisia annua, Artemisinin, Traditional antimalarials, Congo

***

Merlin Willcox, Philippe Rasoanaivo, V.P. Sharma, Gerard Bodeker
Comment on : Randomized controlled trial of a traditional preparation of Artemisia annua L. (Annual Wormwood) in the treatment of malaria
Transactions of the Royal Society of Tropical Medicine and Hygiene (2004) 98, 755—756

Randomized controlled trial of a traditional preparation of Artemisia annua L. (Annual Wormwood) in the treatment of malaria

Excerpt :

Mueller et al. (2004) showed that Artemisia annua tea was better tolerated than oral quinine, with much less tinnitus and nausea. Outside of the trial situation, compliance with Artemisia annua may be better than with quinine, especially if the herb is cheap and readily available. Furthermore, as the dose of Artemisia annua given was safe, it may be possible to increase the dose in the tea in an attempt to reduce recrudescence rates.

The authors raise concerns about the possible development of resistance to artemisinin. However, artemisinin levels in the plasma remain at an antiplasmodial level for about four hours after administration of the tea, and thereafter the artemisinin is eliminated rapidly (Räth et al., 2004). Therefore, parasites will be exposed to subtherapeutic concentrations for only a very short time (in comparison, for example, to sulfadoxine-pyrimethamine, which remains at subtherapeutic levels in the plasma for up to 37 days). Furthermore, Artemisia annua contains many compounds other than artemisinin, some of which also have antimalarial activity, and act synergistically with it (Willcox et al., 2004). There is no evidence of resistance to artemisinin in China, although Artemisia annua teas have been used there for over 2000 years.

We consider the findings of Mueller et al. (2004) to be very encouraging, and believe that research on the traditional preparations of Artemisia annua should continue. We agree that future trials should consider combinations of Artemisia annua, either with other drugs or with other antimalarial plants, with the aim of reducing recrudescence rates. Future trials in endemic areas should measure clinical as well as parasitological outcomes.

2005

ICIPE, KEMRI AND N.U.S.AG
Whole -Leaf Artemisia annua-Based Antimalarial Drug : Report on Proof-of-concept Studies, A Collaborative Project Between ICIPE, KEMRI AND N.U.S.AG
International Centre of Insect Physiology and Ecology (ICIPE)

Whole -Leaf {Artemisia annua}-Based Antimalarial Drug : Report on Proof-of-concept Studies, A Collaborative Project Between ICIPE, KEMRI AND N.U.S.AG

Summary of results :

This ‘proof-of-concept’ studies has demonstrated that :
(i) It is possible to manufacture whole-leaf A. annua antimalarial tables with more or less comparable levels of artemisinin and other constituents if the key steps in the manufacturing process is guided by phytochemical analyses.
(ii) The results of the clinical study show impressive efficacy of these tablets in treating malaria with no significant side effects. Interestingly, there were no discernable differences between the
results obtained from different dose regimes (Table 1). The performance of the lowest dose (with 14.8mg of artemisinin on day 1, followed by 7.4mg daily until day 6) is remarkable, suggesting the operation of synergistic effects of artemisinin and other constituents in the whole-leaf tablets.
(iii) Cases of recrudescence/re-infection represent about 10% and suggests that a different drug administration regime comprising an initial intake for a period of say 5 days followed by another intake for the same period 5-6 days later (to counter slower maturing parasites that may emerge later into the blood stream) may reduce recrudescence further or eliminate it all together.

Recommendations :
The following follow-up activities are recommended :
(i) Characterization of key constituents that contribute to the antimalaria activity of A. annua, which would allow refinement of the quality control process.
(ii) Pharmacokinetic studies of the key constituents of the antimalarial blend to help us optimize the most effective drug administration regime.
(iii) Follow-up large-scale clinical trials involving different drug administration regimes and other categories of malaria patients.
(iv) Select appropriate varieties/hybrids of A. annua on the basis of the optimum ‘constituents profile’.
(v) Develop a detailed business plan for large-scale planting and commercial production of the A. annua drug for different age categories of malaria patients.

2007

Dr Merlin Willcox, Dr. Jacques Falquet, Dr. Jorge F.S. Ferreira, Dr Ben Gilbert, Dr. Elisabeth Hsu, Dr Pedro Melillo de Magalhães, Prof. J. Plaizier-Vercammen, Prof V.P. Sharma, Dr Colin W., Prof Wan Yaode
.Artemisia annua as a Herbal Tea for Malaria
African Journal of Traditional & Complementary and Alternative Medicines (2007) 4 (1) : 121 - 12

Artemisia annua as a Herbal Tea for Malaria

Lettre de l’équipe scientifique de RITAM Artemisia annua Task Force (www.gifts-ritam.org) à l’éditeur de la revue en réponse l’article de Jansen (2006) condamnant l’usage d’Artemisia annua

2008

Christoph H Blanke, B Naisabha, Mussa B Balema, Godfrey M Mbaruku, Lutz Heide, Markus, S Muller
Herba Artemisiae annuae tea preparation compared to sulfadoxinepyrimethamine in the treatment of uncomplicated falciparum malaria in adults : a randomized double-blind clinical trial
Tropical Doctor, May 2008

Herba Artemisiae annuae tea preparation compared to sulfadoxinepyrimethamine in the treatment of uncomplicated falciparum malaria in adults : a randomized double-blind clinical trial

Summary : Tea preparations from the herb Artemisia annua L. (Aa) which is used in traditional Chinese medicine might offer an inexpensive way of producing artemisinin drugs locally. We compared Artemisia annua with sulfadoxine-pyrimethamine in the treatment of uncomplicated falciparum malaria in semi-immune adults. After seven days, the cure rate was 7/10 for the Artemisia annua compared to 7/9 for sulfadoxine-pyrimethamine ; this dropped to 4/10 for Artemisia annua and 4/9 for sulfadoxine-pyrimethamine at day14 and to1/9 for Artemisia annua and 3/8 for sulfadoxine-pyrimethamine at day 28.
Discussion : Despite the small number of patients recruited, our primary cure rates in the Aa groups at day 7 were similar to the 74% reported my Müller et al. in their open pilot trial. Follow-up of patients was almost complete and showed high rates of recrudescence. Artemisinin-based combination therapy is being introduced in the treatment guidelines of several countries in sub-Saharan Africa. The expensive part is the artemisinin derivative. Local cultivation of Aa and the preparation of medicinal tea would reduce costs and might therefore be a consideration for financially restricted health systems. However, the artemisinin content of the traditional Aa preparations contained, at best, 94 mg artemisinin/ L,4 i.e. 19% of the usual clinical dose of pure artemisinin (500 mg/day). Insufficient doses and incomplete treatments without complete cure are major reasons for the induction of resistance to many antimalarials. Inappropriate drug use in artemisinin-based combination therapies in French Guiana exerted selection pressures that favoured led to the emergence of parasites with an artemether-resistant in-vitro profile. Therefore, it is important to introduce a risk assessment of the use of Aa tea preparations in treatment schedules in order to avoid under-dosing and to ensure patient compliance.

2009

Émilien Fouda
Étude clinique sur l’efficacité thérapeutique de l’Artemisia annua sur l’accès palustre simple. Projet pilote réalisé au district de santé de la Cité Verte
Document Maison de l’Artemisia non accessible sur Internet

Étude clinique sur l’efficacité thérapeutique de l’{Artemisia annua} sur l’accès palustre simple. Projet pilote réalisé au district de santé de la Cité Verte

Extrait : Nous constatons dans le temps que le taux de parasitémie dimunie progressivement après la prise de tisane d’Artemisia annua d’une façon exponentielle. Ce pourcentage des parasites éradiqués après la prise de tisane d’artémisinine en fonction du temps va dépendre de plusieurs facteurs à savoir la prise correcte du médicament pendant 07 jours, sans associer un autre antipaludique, le respect des doses, le suivi périodique chez le clinicien. Compte tenue de la réponse clinique et parasitologique active que l’Artemisia annua le thé est en train de faire ses preuves d’efficacité car la couverture est de 93,70% avec un taux d’échec qui est de 8,30%

***

Chougouo-Kengne Rosine D, Kouamo J, Moyou Somo R, Penge On’Okoko
Comparative study on quality and efficiency of medicines based on artemisinin and Artemisia annua cultivated in Cameroon
Document powerpoint Presented at the MLM Pan-African Malaria Conference, 2 to 6 November 2009, Nairobi, Kenya (no 312)

Comparative study on quality and efficiency of medicines based on artemisinin and {Artemisia annua} cultivated in Cameroon

Excerpt :

Conclusion I

The three different experimental protocols gave satisfactory results. BCEA exceeds 80% in all 3 protocols.
There are no signs of danger according to WHO criteria.
The combination of artesunate and amodtagblme has a beneficiai effect on clinical response. Fever reduced more quickly than with monotherapy

Conclusion II

- Artemisia annua teas have the best efficacy if they taken at least for 7 days.
- Analysed dried leaves of Artemisia annua had a good content of artemisinin (1 ,3%).
° They have the quality of the best leaves of A. annua
° lt can be concluded that Artemisia annua tea is a good treatment for Malaria.
° Due to its many constituents (coumarin, sesquiterpenes, flavonoid, essential oils etc…) it must be taken for at least 7 days for optimal efficacy

Conclusion III

° In order to prevent the development of resistance to these medicines,their quality must be vigorously controlled.
° Although demand for these medicines in the informal market is still weak, there are already signs of alarm.
Perspectives
° Our future work concerning malaria intends to include monitoring the chemosensitivity and
quality of medicines based on artemisinin.
° We will also share our experience in the cultivation of Artemisia annua and the analysis of the dried leaves with businessmen who want to cultivate A. annua.
° Finally we will give a lot of attention to finding new antimalarial medicines based on our own local herbs here in Cameroon.

2010

Gebeyaw Tiruneh, Yigzaw Kebede, Tegbar Yigzaw
Use of the plant Artemisia annua as a natural anti-malarial herb in Arbaminch town
Ethiopian Journal of. Health Biomedicine Science., 2010. Vol.2, No.2

Use of the plant {Artemisia annua} as a natural anti-malarial herb in Arbaminch town Ethiopian

Abstract :

Background : The estimated malaria cases per annum in Ethiopia are about 4-5 million. Chemotherapy is a major element of malaria control. Because the WHO recommended anti-malarial, Artemisinin combination therapy, is expensive and the health service coverage in the country is low, the practical use of this drug for the treatment of malaria will be restricted to the small segment of the population. Therefore, it is high time to look for other cheap and effective alternatives to treat malaria, traditional medicine being one of the areas to be explored.

Objective : To assess the extent of use and perceived effectiveness as well as the adverse effects of the plant Artemisia annua as a natural ant-malarial herb in Arbaminch town.

Methods : A qualitative study involving health workers, users of the herb, natural medicine practitioners, university professors, and a researcher on traditional medicine meant, to explore the use of the plant Artemisia annua as an anti-malarial herb was carried out. Sampling was purposive. In addition, a cross-sectional household survey was conducted to assess malaria-related health seeking behavior. Systematic sampling technique was employed. The study was done in Arbaminch town in 2006.

Results : The qualitative study revealed a high level of acceptance and utilization of the herb. Similarly, the quantitative study showed that 22.4% of malaria cases in the previous year used the herb as a treatment. The outcome of the treatment was effective with a cure rate of 91.8% with no major adverse effect. The treatment modality was clear and well-understood at all levels of the study subjects.

Conclusion : The effectiveness of the herb in treating malaria and the absence of major adverse effects created a high level of utilization. Therefore policy, regulatory mechanisms, and guidelines should be formulated for the use of the herb. Safety, efficacy and quality assessment on the herb should continue. Mechanisms for integrating the herb with modern health care system, should be studied.

2012

Chougouo-Kengne Rosine D, Kouamouo Jonas, Moyou Somo Roger, Penfe On’ Okoko
Etude comparative de l’efficacité thérapeutique de l’Artesunate seul ou en association avec l’amodiaquine et de la tisane d’Artemisia annua cultivée à l’ouest de Cameroun
Annales de Pharmacie, Université de Kinshasa Vol 4, N1, Avril 2012 pp127-148

Etude comparative de l’efficacité thérapeutique de l’Artesunate seul ou en association avec l’amodiaquine et de la tisane d’Artemisia annua cultivée à l’ouest de Cameroun

Résumé : Ce travail a été effectué de la période de Juin en octobre 2006 dans le district de santé de Bangangté dans le département du NDE au Cameroun. Il avait pour objectif de comparer : l’efficacité de l’Artésunate en monothérapie, en association avec l’Amodiaquine sur P. falciparum, en même temps que l’étude de l’efficacité thérapeutique de Artémisia annua comme plante antipaludique dans le département du NDE. L’Artésunate prit en 5 jours et l’association Artésunate/Amodiaquine prit en 3 jours ont donné respectivement 81,25% et 85,70%. L’association Artésunate/Amodiaquine augmente de façon significative le taux de succès thérapeutique. Les tisanes de Artemisia annua pris en 5 jours ou en 7 jours donnent respectivement 71,3% et 100% de réponses thérapeutiques. On constate que la réponse thérapeutique d’un traitement par les tisanes est améliorée en prolongeant la durée. Les effets indésirables liés à l’Artésunate sont la sensation d’hyperthermie tandis que ceux liés à l’association Artésunate/Amodiaquine sont surtout les myalgies, l’anorexie, douleurs abdominales et la flatulence pour le cas des tisanes.

Abstract :

This work was carried out period of June in October 2006 at the hospital of district of Bangangté in the department of the NDE. It aimed to compare the effectiveness of Artésunate alone, in partnership with Amodiaquine on P. falciparum and the same time study of therapeutic effectiveness of Artémisia annua like plants antimalaria in the department of the NDE. The Artesunate took in 5 days and Artesunate/Amodiaquine association took in 3 days gave 81,25% and 85,70% respectively. The therapeutic response increased with association form.The herb tea of Artemisia annua taken in 5 days or 7 days gives the following therapeutic response respectively : 71, 3% and 100%. It is noted that the therapeutic response of herb teas is improved by prolonging the time. Adverse events associated with Artesunate is the sensation of hyperthermia while those related to the association Artesunate / Amodiaquine is mainly myalgia, anorexia,abdominal pain and flatulence in the case of herbal.

Mots clés  : Artemisia annua, efficacité, Plasmodium falciparum, Amodiaquine, Artésunate, ETT, ETP, RCA

2012

Patrick E Ogwang, Jasper O Ogwal, Simon Kasasa, Deogratius Olila,
Francis Ejobi, David Kabasa and Celestino Obua
Artemisia Annua L. Infusion Consumed Once a Week Reduces Risk of Multiple Episodes of Malaria : A Randomised Trial in a Ugandan Community
Tropical Journal of Pharmaceutical Research, June 2012 ; 11 (3) : 445-453

Artemisia Annua L. Infusion Consumed Once a Week Reduces Risk of Multiple Episodes of Malaria : A Randomised Trial in a Ugandan Community

Abstract

Purpose : To evaluate the protective effect of Artemisia annua infusion against malaria in a community that uses it as herbal ‘tea’ for malaria prevention.
Methods : 132 flower farm workers who met the study inclusion criteria and were not yet using A. annua infusion were randomized either to A. annua or placebo groups in the ratio of 1:1. Treatments were administered once a week under direct observation to participants. Malaria episodes were documented over a 9-month period while adverse effects were documented over 12 months.

Results : A. annua herbal ‘tea’ significantly reduced the risk of suffering more than one episode of malaria in nine months by 55 % (12/67 vs 26/65, p = 0.005 No participant experienced any serious adverse effect although bitter taste was the most common side effect of the infusion.

Conclusion : Artemisia annua infusion consumed once a week was effective in preventing multiple episodes of malaria in humans living in malaria endemic areas. However, its bitter taste and the risk of development of malaria parasite resistance to the artemisinin contained in it remain major challenges for its use in the mass control of malaria.

Keywords : Artemisia annua, Herbal tea, Community, Malaria prevention

2013

Chougouo-Kengne Rosine D, Ketchiozo L Wilfried, Lutgen Pierre, Tane P, Moyous Roge
Efficacity and tolerancy of Artemisia annua lemonade in treatment of Plasmodium Falciparum Malaria of children between 6 months to 10 years at Bahouoc and Bangang Fokam (Cameroon).
6 th MIM PanAfrican Malaria Conference. Durban, South Africa ; 2013

Efficacity and tolerancy of {Artemisia annua} lemonade in treatment of Plasmodium Falciparum Malaria of children between 6 months to 10 years at Bahouoc and Bangang Fokam (Cameroon

Introduction :

Artemisia annua has been reported to be effective against uncomplicated Plasmodium falciparum malaria in adults but no clinical trial has been done on children because of the bitter taste of tea, so we use a lemonade form to evaluate the efficacy, tolerability, and acceptability of in children aged between 6 months to 10 years in the Bangangté health district in Cameroon. Method The WHO protocol for undertaking clinical trial for antimalarial drugs was followed. Bahouoc and Bangang-Fokam health centers were used for the study. Amongst other criteria, parasite density > 1000/μl of blood was enrolled. The inform consent document was administered. The drugs were prepared by infusion of 5g of dried leaves of A.annua in 1L of water sweetened with 200 mg of Stevia rebaudiana and given from day 0 to day 6 at the dose of 16.66ml/BW/24h 4 times every 30 minutes . Each patient was followed up to day 28, with the assessment of the parasitological and hematological parameters.

Results : A total of 153 patients were screened, 62 met enrolment criteria 53 were followed up to day 14 but 49 patients completed the trial. Results showed that the geometric mean parasite density (GMPD) of enrolled children was reduced from 1.860 to 35 per μl of blood on day 2 and completely cleared by day 3. There were no ETF (early treatment failure). Analysis on day 14 revealed 3 cases of LPF (late parasitological failure) (6%) and 46 cases clinical and parasitological acceptable response (CPAR) of 94%. On day 28, the analysis revealed 4 cases (8%) of LCF (late clinical failure), 9 cases of LPF (18%) and 36 cases (73.48%) of CPAR. Patients had a mean increase in hematocrit levels (34.8%) on day 0 vs 37.4% on day 28.. The mean temperature decreased. The drug was well tolerated but difficultly accepted by the children under 2 years. Gametocytemia was not detected during follow up in any of the patients.

Conclusion : We conclude that annual wormwood lemonade is efficacious, and well tolerated.

2015

Hermine Zime-Diawara, Yolande Sissinto-Savi De Tove, Oscar Eric Akogbeto, Aurore Ogouyemi-Hounto, Fernand A. Gbaguidi, Dorothée Kinde-Gazard, Achille Massougbodji, André Bigot, Brice Sinsin, Joëlle Quetin-Leclercq, Brigitte Evrard et Mansourou Moudachirou
Étude de l’efficacité et de la tolérance d’une tisane à base de Artemisia annua L. (Asteraceae) cultivée au Bénin pour la prise en charge du paludisme simple
International Journal of Biological and Chemical Sciences. 9(2) : 692-702, April 2015

Étude de l’efficacité et de la tolérance d’une tisane à base de Artemisia annua L. (Asteraceae) cultivée au Bénin pour la prise en charge du paludisme simple

Résumé :

Artemisia annua L. est une plante annuelle, glabre, de la famille des Asteraceae et originaire de la Chine. Cette plante contient plusieurs sesquiterpènes dont l’artémisinine (0,01% à 1,4% du poids des feuilles sèches) et d’autres composés comme les flavonoïdes, les coumarines, les triterpènes, les stéroïdes, les composés phénoliques, les purines, les lipides et les composés aliphatiques. Cette plante a été acclimatée et cultivée au Bénin. Elle a ensuite été testée pour la prise en charge du paludisme simple par un essai clinique.

La concentration en artémisinine de cette plante était d’environ 0,30%.Il ressort de notre étude que la tisane de Artemisia annua L. (Asteraceae) obtenue au Bénin a une capacité d’action sur Plasmodium falciparum avec un taux d’efficacité supérieur à 95%, taux retenu par l’OMS pour valider un traitement.

Mots clés : Malaria, Artemisia annua, clairance thermique, parasitémie, essais cliniques.

***

Hermine Zime-Diawara, Habib Ganfon, Fernand Gbaguidi, Achille Yemoa, Joanne Bero, Olivia Jansen, Brigitte Evrard, Mansourou Moudachirou, Michel Frederich and Joëlle Quetin-Leclercq
The antimalarial action of aqueous and hydro alcoholic extracts of Artemisia annua L. cultivated in Benin : In vitro and in vivo studies
Journal of Chemical and Pharmaceutical Research" - Vol. 7, no.8, p. 817-823 (2015)

The antimalarial action of aqueous and hydro alcoholic extracts of Artemisia annua L. cultivated in Benin : In vitro and in vivo studies

Abstract :

The aqueous and hydro alcoholic extracts of Artemisia annua plants acclimatized and set in culture in Benin, were investigated for their in vitro and in vivo antimalarial value. These extracts were prepared by decoction and maceration using water and ethanol, and were tested for in vitro activity against the strains of Plasmodium falciparum. Those extracts were also investigated in vivo against Plasmodium berghei NK 173 infected mice by the 4-day suppressive test. The action of these extracts was similar in vitro to the action of pure artemisinin at the same dosage. But, the in vivo studies on mice show that we have the same efficacy with aqueous extract of A. annua (artemisinin content of 20 mg/kg) than with pure artemisinin at a dosage of 140 mg/kg. The hydro alcoholic extract of A. annua (artemisinin content of 20 mg/kg) was better than the both other conditions. The others components of the plant Artemisia annua potentiate artemisinin activity on Plasmodium. The aqueous and hydro alcoholic extracts of Artemisia annua L. are very effective on malaria and they can be used by populations to cure this disease, especially in endemic areas where modern medicines are expensive.

Keywords : Artemisia annua extracts, in vitro studies, in vivo studies, artemisinin potentiation.

2016

Pedro Melillo de Magalhãe1, Glyn Mara Figueira, José Maria de Souza, Ana Maria Revorêdo Ventura, Maria Deise de Oliveira Ohnishi, Darci Rodrigues da Silva, Luiz Alberto Gonçalves Lobo, Fabrício Bezerra Eleres, Rosana Libonati, Merlin Willcox, Eloisa Cavassani Pimentel
.Artemisia annua : A New Version of a Traditional Tea under Randomized, Controlled Clinical Trial for the Treatment of Malaria
Advances in Bioscience and Biotechnology, 2016, 7, 545-563

Artemisia annua. A New Version of a Traditional Tea under Randomized, Controlled Clinical Trial for the Treatment of Malaria

Abstract :

Introduction : The traditional antimalarial tea Artemisia annua, indicated for centuries in China to treat fevers, is again arousing interest for the treatment of malaria due to improvements attained in the plant composition by a few Institutions throughout the world, including the State University of Campinas (UNICAMP), Brazil, increasing its principal component by more than 100 times as from standard varieties, giving 1% in artemisinin and an expressive biomass yield such as 2 tons of dried leaves/hectare. Clinical trials carried out with this material in African countries have proven its therapeutic potential for a new generation of Artemisia tea in the treatment of falciparum malaria. In addition to artemisinin, recent studies have identified and quantified other compounds present in the crude extract and characterized their contributions to the anti-malarial efficacy, including their action against chloroquineresistant strains. The majority of the clinical trials carried out with Artemisia tea in African countries have shown that the control of the parasitaemia is efficient in the initial treatment period, but few trials have followed the patients up to the 28th day.

This first clinical trial carried out in Brazil with the A. annua infusion, after toxicological trials that defined the safety of this form of medication. Methods : The therapeutic efficacy of the tea was measured in patients with falciparum malaria over 28 days, comparing it with the current first-line treatment namely artemether-lumefantrine (Coartem®). The trial was carried out in controlled groups according to official protocol approved by the National Ethics in Research Committee (CONEP : 77/ 2011) and a rigorous control of the 17 patients with non-serious cases of falciparum malaria, recruited in the following three municipalities of the State of Para, Brazil : Tucurui, Goianesia do Para and Anajas. The tea group received the infusion prepared in the proportion of 1.25 g of dry leaves of the variety CPQBA with 1% artemisinin for 250 mL of just boiled water, taken every 6 hours for 7 days, giving a total of approximately 175 mg of artemisinin, whilst the artemether-lumefantrine (Coartem®) group received a total of 525 mg of artemisinin equivalent to artemether.

Results : The parasitaemia by the tea treatment became negative in the first days, even though it was administered with a dose that was one third of the recommended dose of artemisinin. However, as in the case artemisinin or artesunate monotherapies, 57.1% of the patients treated with the A. annua tea presented type I resistance, with a return of the parasitaemia around the 14th or 21st day. The other patients in the tea group showed type II/III resistance without manifestation of any serious signs or symptoms. In these cases, according to the protocol, the patients were redirected for treatment with artemether-lumefantrin (Coartem®) with subsequent negativity of the parisitaemia.

Discussion : The fact that the efficacy of the tea with 1/3 of the dose of artemisinin was similar to that of the full dose of this medication infers that other compounds present in the crude extract, probably flavonoids, had contributed to the negativity of the parasitaemia at the start of the treatment. Considering that the positive control group, where the compound derived from artemisinin (artemether) was associated with another antimalarial agent (lumefantrine), presented excellent efficacy throughout the entire control of the cure, future trials with the A. annua tea should use the same strategy of association with another antimalarial agent, preferably from A. annua itself, in order to extend its therapeutic action during the whole control period. The Artemisia annua tea in the form standardized and used in this research, should not substitute the most efficient treatment, but could be considered as an emergency therapeutic resource in the first hours of symptoms as a function of its availability, anti-inflammatory action and lack of side effects. Other regimes and standardizations deserve investigation, mainly those with a high content of arteannuin B, as occurs in the initial cultivation phase.

2018

Nyamsi Nguenda Guy Martial
Etude comparative de l’efficacité antipaludique de la tisane à base d’Artemisia annua et de l’association Artéméther – Luméfantrine vis-à-vis de P. falciparum dans le C.S.I de Lokoti
Thèse présentée et soutenue publiquement en vue de l’obtention du grade de Docteur en Pharmacie, année 2017-2018, Institut Supérieur Des Sciences de La Santé, Université des montagnes, Cameroun

Full text submitted to request

Conclusion :

La lutte anti paludisme a été confrontée au fil du temps, à de sérieux problèmes dont le majeur est la résistance aux antipaludéens. Face à cela, l’OMS recommande l’utilisation des combinaisons thérapeutiques à base de dérivés d’artémisinine.
Nous avions pour objectif de comparer l’efficacité antipaludique et la tolérance de la tisane à base d’Artemisia annua et de la combinaison Artéméther-Luméfantrine :
- Le temps de clairance parasitaire était de 5 ± 0,50 jours pour la tisane à base d’Artemisia annua et de 2± 0,50 jours pour l’Artéméther-Luméfantrine. Tandis que le temps de clairance de la fièvre était de 1±0.5 jours pour les deux traitements.
- A J3 de traitement, la proportion de patients parasités était de 72.73% pour le traitement à base d’Artemisia annua contre 25% pour l’Artéméther-Luméfantrine, mais avec une parasitémie moyenne abaissée. Par contre, à J7 on a respectivement 18,18% et 24,32%. A J.28 ces proportions sont de 20,49% pour la tisane et 66,67% pour la combinaison.
- Nous avons obtenu 88,34% de réponse clinique et parasitologique adequate chez les patients traitrés à base de la tisane d’Artemisia annua contre 71,53% chez les patients traités a base d’Artéméther-Luméfantrine.
- Après le traitement, les transaminases baissent chez les patients ayant reçu la tisane, tandis qu’elles s’élèvent chez les patients traités par la combinaison Artéméther-Lumefantrine.

La RCPA de la tisane est meilleure que celle de la combinaison, la tisane a un effet bénéfique sur le foie.

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Témoignage d’une infirmière Burundaise

Ce document présente l’expérience de terrain d’une infirmière burundaise et témoigne de l’efficacité curative et préventive de la tisane et de la poudre de la plante avec différentes catégories de patients y compris des nourrissons.
Document transmis par Pierre Lutgen et mis en ligne après accord par lavie rebelle.org

2019

Jérome Munyangi, Lucile Cornet-Vernet, Michel Idumbo, Chen Lu, Pierre Lutgen, Christian Perronne, Nadege Ngombe, Jacques Bianga, Bavon Mupenda, Paul Lalukala, Guy Mergeai, Dieudonne Mumba, Melissa Towler, Pamela Weathers
.Artemisia annua and Artemisia afra tea infusions vs. Artesunate-amodiaquine (ASAQ) in treating Plasmodium falciparum malaria in a large scale, double blind, randomized clinical trial
Phytomedicine 57 (2019) 49–56

Artemisia annua and Artemisia afra tea infusions vs. Artesunate-amodiaquine (ASAQ) in treating Plasmodium falciparum malaria in a large scale, double blind, randomized clinical trial

Abstract : Background and Objective : Prior small-scale clinical trials showed that Artemisia annua and Artemisia afra infusions, decoctions, capsules, or tablets were low cost, easy to use, and efficient in curing malaria infections. In a larger-scale trial in Kalima district, Democratic Republic of Congo, we aimed to show A. annua and/or A. afra infusions were superior or at least equivalent to artesunate-amodiaquine (ASAQ) against malaria.
Methods : A double blind, randomized clinical trial with 957 malaria-infected patients had two treatment arms : 472 patients for ASAQ and 471 for Artemisia (248 A. annua, 223 A. afra) remained at end of the trial. ASAQtreated patients were treated per manufacturer posology, and Artemisia-treated patients received 1 l/d of dry leaf/twig infusions for 7 d ; both arms had 28 d follow-up. Parasitemia and gametocytes were measured microscopically with results statistically compared among arms for age and gender.
Results : Artemisinin content of A. afra was negligible, but therapeutic responses of patients were similar to A. annua-treated patients ; trophozoites cleared after 24 h, but took up to 14 d to clear in ASAQ-treated patients. D28 cure rates defined as absence of parasitemia were for pediatrics 82, 91, and 50% for A. afra, A. annua and ASAQ ; while for adults cure rates were 91, 100, and 30%, respectively. Fever clearance took 48 h for ASAQ, but 24 h for Artemisia. From D14-28 no Artemisia-treated patients had microscopically detectable gametocytes, while 10 ASAQ-treated patients remained gametocyte carriers at D28. More females than males were gametocyte carriers in the ASAQ arm but were unaffected in the Artemisia arms. Hemoglobin remained constant at 11 g/dl for A. afra after D1, while for A. annua and ASAQ it decreased to 9–9.5 g/dl. Only 5.0% of Artemisia-treated patients reported adverse effects, vs. 42.8% for ASAQ.
Conclusion : A. annua and A. afra infusions are polytherapies with better outcomes than ASAQ against malaria. In contrast to ASAQ, both Artemisias appeared to break the cycle of malaria by eliminating gametocytes. This study merits further investigation for possible inclusion of Artemisia tea infusions as an alternative for fighting and eradicating malaria.
Keywords : ACT, ASAQ, Artemisinin, Malaria, Clinical trial, Tea infusion
Abstract : Artemisia annua and Artemisia afra tea infusions vs. Artesunate-amodiaquine (ASAQ) in treating Plasmodium falciparum malaria in a large scale, double blind, randomized clinical trial, Comparaison d’efficacité par un essai clinique aléatoire d’envergure en double aveugle entre des tisanes d’Artemisia annua ou d’Artemisia afra et l’artesunate-amodiaquine (ASAQ) dans le traitement du paludisme à Plasmodium falciparum.

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André Gillibert, Yves Hansmann, Xavier Argemi
Correspondence : Comment on “A. annua and A. afra infusions vs. Artesunate-amodiaquine (ASAQ) in treating Plasmodium falciparum malaria in a large scale, double blind, randomized clinical trial”
Phytomedicine, June 2019

The potential of Artemisia annua L. as a locally produced remedy for malaria in the tropics : agricultural, chemical and clinical aspects

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Lucile Cornet-Vernet, Jérôme Munyangi, Lu Chen, Melissa Towler, Pamela Weathers
Response to Gillibert et al. 2019
Phytomedicine · June 2019

Response to Gillibert
Mis en ligne par La vie re-belle
 29/03/2020
 https://lavierebelle.org/artemisia-annua-l-etudes-in-vivo

 Documents

 Dried Whole Plant Artemisia annua as an Antimalarial Therapy
PDF 
 In Vivo Trials on The Therapeutic Effects of Encapsulated Artemisia annua and Artemisia afra
PDF 
 Global Journal For Research Analysis
 Artemisia annua dried leaf tablets treated malaria resistant to ACT and i.v. artesunate : case reports
PDF 
 Phytomedicine
 The potential of Artemisia annua L. as a locally produced remedy for malaria in the tropics : agricultural, chemical and clinical aspects
PDF 
 Journal of Ethnopharmacology

Etudes in vivo

Ce dossier regroupe des articles publiés concernant l’activité in vivo d’Artemisia annua L.

Les articles 2

Ce document rassemble les études relatives aux activités anti-infectieuses d’Artemisia annua autres qu’antipaludique, et à l’utilité potentielle des extraits de (...)
Action in vivo de la poudre de parties aériennes d’Artemisia annua sur la Malaria (Modèle animal)2012Mostafa A. Elfawal, Melissa J. Towler, Nicholas G. (...)
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