Download PDF
Planta Med 2011; 77(6): 662-671
DOI: 10.1055/s-0030-1250548
Tropical Diseases
Reviews
© Georg Thieme Verlag KG Stuttgart · New York

Improved Traditional Phytomedicines in Current Use for the Clinical Treatment of Malaria

Merlin Willcox1 , 2
  • 1Department of Primary Health Care, University of Oxford, Oxford, UK
  • 2Research Initiative on Traditional Antimalarial Methods, Oxford, UK
Further Information

Publication History

received June 25, 2010 revised October 7, 2010

accepted October 23, 2010

Publication Date:
03 January 2011 (online)

Also available at
   Permissions and Reprints

Abstract

Phytomedicines and “green pharmacies” are promoted by some NGOs and governments as part of their efforts to control malaria. “Improved traditional medicines” (ITMs) are standardised as regards preparation and dose, although not always according to the concentration of active compounds. A systematic literature search revealed that six such phytomedicines are currently government-approved in at least one country and used on a relatively large scale nationally or internationally: Artemisia annua L. (Asteraceae), Cinchona bark (Rubiaceae), Cryptolepis sanguinolenta (Lindl.) Schltr. (Apocynaceae), “Ayush-64”, “Malarial-5” and Cochlospermum planchonii Hook. f. ex Planch. (Bixaceae). One further ITM has been developed and is in the process of being approved: Argemone mexicana decoction. Their development, phytochemistry, pharmacology, and clinical trials are reviewed, as well as priorities for future research.

Key words

malaria - herbal medicine - phytomedicine - government‐approved - clinical trials

References

  • 1 WHO .Guidelines for the treatment of malaria, 2nd edition. Geneva; World Health Organization 2010
    Google Scholar
  • 2 Breman J G. The ears of the hippopotamus: manifestations, determinants, and estimates of the malaria burden.  Am J Trop Med Hyg. 2001;  64 1-11
    CrossrefPubMedGoogle Scholar
  • 3 Willcox M, Burford G, Bodeker G. An overview of ethnobotanical studies on plants used for the treatment of malaria. Willcox M, Bodeker G, Rasoanaivo P Traditional medicinal plants and malaria. Boca Raton; CRC Press 2004: 187-197
    Google Scholar
  • 4 Willcox M L, Bodeker G. Traditional herbal medicines for malaria.  BMJ. 2004;  329 1156-1159
    CrossrefPubMedGoogle Scholar
  • 5 Willcox M, Bodeker G, Rasoanaivo P. Traditional medicinal plants and malaria. Boca Raton; CRC Press 2004
    Google Scholar
  • 6 Harper D. Early Chinese medical literature: the Mawangdui medical manuscripts. London; Routledge 1998
    Google Scholar
  • 7 Hsu E. The history of qing hao in the Chinese materia medica.  Trans R Soc Trop Med Hyg. 2006;  100 505-508
    CrossrefPubMedGoogle Scholar
  • 8 Delabays N. Biologie de la réproduction chez l’Artemisia annua L. et génétique de la production en artémisinine. Lausanne; Université de Lausanne 1997
    Google Scholar
  • 9 Hirt H, M'Pia B. Natural medicine in the tropics I. Winnenden; Foundation Text Anamed 2008
    Google Scholar
  • 10 Wan Y, Zhang Q, Wang J. Studies on the antimalarial action of gelatin capsule of Artemisia annua.  Chung Kuo Chi Sheng Chung Hsueh Yu Chi Sheng Chung Ping Tsa Chih. 1992;  10 290-294
    PubMedGoogle Scholar
  • 11 Bonati M, Severino F, Bagnati R, Carrà A, Fanelli R. Millet-porridge with Artemisia annua as first aid for African children with malaria?.  J Altern Complement Med. , in press
    PubMedGoogle Scholar
  • 12 Bhakuni R, Jain D, Sharma R. Phytochemistry of Artemisia annua and the development of artemisinin-derived antimalarial agents. Wright C Artemisia. London; Taylor & Francis 2002
    Google Scholar
  • 13 Tan R X, Zheng W F, Tang H Q. Biologically active substances from the genus Artemisia.  Planta Med. 1998;  64 295-302
    Article in Thieme ConnectPubMedGoogle Scholar
  • 14 Chang H, But P. Pharmacology and applications of Chinese Materia Medica. Singapore; World Scientific Publishing 1986
    Google Scholar
  • 15 Liu K-S, Yang S-L, Roberts M, Elford B, Phillipson J. Antimalarial activity of Artemisia annua flavonoids from whole plants and cell cultures.  Plant Cell Reports. 1992;  11 637-640
    PubMedGoogle Scholar
  • 16 Elford B C, Roberts M F, Phillipson J D, Wilson R J. Potentiation of the antimalarial activity of qinghaosu by methoxylated flavones.  Trans R Soc Trop Med Hyg. 1987;  81 434-436
    CrossrefPubMedGoogle Scholar
  • 17 Rath K, Taxis K, Walz G, Gleiter C H, Li S M, Heide L. Pharmacokinetic study of artemisinin after oral intake of a traditional preparation of Artemisia annua L. (annual wormwood).  Am J Trop Med Hyg. 2004;  70 128-132
    PubMedGoogle Scholar
  • 18 De Magalhães P, Debrunner N, Delabays N. Aqueous extracts of Artemisia annua L. International Conference on Malaria; Current status and future trends, Chulabhorn Research Institute, Bangkok, Thailand 2003
    Google Scholar
  • 19 Wright C W, Linley P A, Brun R, Wittlin S, Hsu E. Ancient Chinese methods are remarkably effective for the preparation of artemisinin-rich extracts of Qing Hao with potent antimalarial activity.  Molecules. 2010;  15 804-812
    CrossrefPubMedGoogle Scholar
  • 20 Atemnkeng M A, Chimanuka B, Dejaegher B, Heyden Y V, Plaizier-Vercammen J. Evaluation of Artemisia annua infusion efficacy for the treatment of malaria in Plasmodium chabaudi chabaudi infected mice.  Exp Parasitol. 2009;  122 344-348
    CrossrefPubMedGoogle Scholar
  • 21 Wilairatana P, Looaresuwan S. The clinical use of artemisinin and its derivatives in the treatment of malaria. Wright CW Artemisia. London; Taylor & Francis 2002
    Google Scholar
  • 22 WHO .The use of artemisinin & its derivatives as anti-malarial drugs. Geneva; Malaria Unit, Division of Control of Tropical diseases, WHO 1998
    Google Scholar
  • 23 WHO .The role of artemisinin and its derivatives in the current treatment of malaria (1994 – 1995). Geneva; WHO 1994
    Google Scholar
  • 24 Willcox M. Artemisia species: from traditional medicines to modern antimalarials-and back again.  J Altern Complement Med. 2009;  15 101-109
    CrossrefPubMedGoogle Scholar
  • 25 Willcox M, Burton S, Lindsey K. Evaluation and pharmacovigilance of projects promoting cultivation and local use of Artemisia annua for malaria. In preparation. 
    Google Scholar
  • 26 Honigsbaum M, Willcox M L. Cinchona. Willcox ML, Bodeker G, Rasoanaivo P Traditional medicinal plants and malaria. Boca Raton; CRC Press 2004: 21-41
    Google Scholar
  • 27 Jarcho S. Quinine's predecessor, Francesco Torti and the early history of cinchona. Baltimore; John Hopkins University Press 1993
    Google Scholar
  • 28 Duran-Reynals M L D A. The fever bark tree: the pageant of quinine. New York; Doubleday 1946
    Google Scholar
  • 29 Honigsbaum M. The fever trail: the hunt for the cure for malaria. London; Macmillan 2001
    Google Scholar
  • 30 OUA .Pharmacopée Africaine. Lagos; Organisation de l'Unité Africaine 1985
    Google Scholar
  • 31 Karle J M, Bhattacharjee A K. Stereoelectronic features of the Cinchona alkaloids determine their differential antimalarial activity.  Bioorg Med Chem. 1999;  7 1769-1774
    CrossrefPubMedGoogle Scholar
  • 32 Druilhe P, Brandicourt O, Chongsuphajaisiddhi T, Berthe J. Activity of a combination of three Cinchona bark alkaloids against Plasmodium falciparum in vitro.  Antimicrob Agents Chemother. 1988;  32 250-254
    CrossrefPubMedGoogle Scholar
  • 33 Solary E, Mannone L, Moreau D, Caillot D, Casasnovas R O, Guy H, Grandjean M, Wolf J E, Andre F, Fenaux P, Canal P, Chauffert B, Wotawa A, Bayssas M, Genne P. Phase I study of cinchonine, a multidrug resistance reversing agent, combined with the CHVP regimen in relapsed and refractory lymphoproliferative syndromes.  Leukemia. 2000;  14 2085-2094
    CrossrefPubMedGoogle Scholar
  • 34 Frappier F, Jossang A, Soudon J, Calvo F, Rasoanaivo P, Ratsimamanga-Urverg S, Saez J, Schrevel J, Grellier P. Bisbenzylisoquinolines as modulators of chloroquine resistance in Plasmodium falciparum and multidrug resistance in tumor cells.  Antimicrob Agents Chemother. 1996;  40 1476-1481
    PubMedGoogle Scholar
  • 35 Pampana E. Clinical tests carried out under the auspices of the malaria commission.  League of Nations: Quarterly Bulletin of the Health Organisation. 1934;  III 328-343
    PubMedGoogle Scholar
  • 36 Fletcher W. Critical analysis of the results achieved.  League of Nations: Quarterly Bulletin of the Health Organisation. 1934;  III 344-358
    PubMedGoogle Scholar
  • 37 Hicks E P, Diwan Chand S. The relative clinical efficacy of totaquina and quinine.  Records of the Malaria Survey of India. 1935;  5 39-50
    PubMedGoogle Scholar
  • 38 White N J, Looareesuwan S, Warrell D A, Chongsuphajaisiddhi T, Bunnag D, Harinasuta T. Quinidine in falciparum malaria.  Lancet. 1981;  2 1069-1071
    PubMedGoogle Scholar
  • 39 MacGilchrist A. The relative therapeutic value in malaria of the cinchona alkaloids quinine, cinchonine, quinidine, cinchonidine and quinoidine, and the two derivatives – hydroquinine and ethylhydrocupreine.  Indian J Med Res. 1915;  III 1-53
    PubMedGoogle Scholar
  • 40 Sinton J, Bird W. Studies in malaria, with special reference to treatment. Part XI: the Cinchona alkaloids in the treatment of benign tertian malaria.  Indian J Med Res. 1929;  16 725-746
    PubMedGoogle Scholar
  • 41 Bunnag D, Harinasuta T, Looareesuwan S, Chittamas S, Pannavut W, Berthe J, Mondesir J M. A combination of quinine, quinidine and cinchonine (LA 40221) in the treatment of chloroquine resistant falciparum malaria in Thailand: two double-blind trials.  Trans R Soc Trop Med Hyg. 1989;  83 66
    CrossrefPubMedGoogle Scholar
  • 42 Mshana N R, Abbiw D K, Addae-Mensah I, Adjanouhoun E, Ahyi M R A, Ekpere J A, Enow-Orock E G, Gbile Z O, Noamesi G K, Odei M A, Odunlami H, Oteng-Yeboah A A, Sarpong K, Sofowora A, Tackie A N. Traditional medicine and pharmacopoeia: Contribution to the revision of ethnobotanical and floristic studies in Ghana. Lagos; Organisation of African Unity/Scientific, Technical and Research Commission 2000
    Google Scholar
  • 43 Tona L, Ngimbi N P, Tsakala M, Mesia K, Cimanga K, Apers S, De Bruyne T, Pieters L, Totte J, Vlietinck A J. Antimalarial activity of 20 crude extracts from nine African medicinal plants used in Kinshasa, Congo.  J Ethnopharmacol. 1999;  68 193-203
    CrossrefPubMedGoogle Scholar
  • 44 Boye G L, Ampofo O. Clinical uses of C. sanguinolenta. Proceedings of the First International Seminar on Cryptolepine, Kumasi, Ghana 1983
    Google Scholar
  • 45 Addy M. Cryptolepis: an African traditional medicine that provides hope for malaria victims.  Herbalgram. 2003;  60 54-59
    PubMedGoogle Scholar
  • 46 Addae-Kyreme J. Cryptolepis sanguinolenta. Willcox ML, Bodeker G, Rasoanaivo P Traditional medicinal plants and malaria. Boca Raton; CRC Press 2004: 131-139
    Google Scholar
  • 47 Sarpong K. Morphology and alkaloid distribution in Cryptolepis sanguinolenta. First International Seminar on Cryptolepine, University of Science and Technology, Kumasi, Ghana 1983: 15-22
    Google Scholar
  • 48 Wright C W, Addae-Kyereme J, Breen A G, Brown J E, Cox M F, Croft S L, Gokcek Y, Kendrick H, Phillips R M, Pollet P L. Synthesis and evaluation of cryptolepine analogues for their potential as new antimalarial agents.  J Med Chem. 2001;  44 3187-3194
    CrossrefPubMedGoogle Scholar
  • 49 Kirby G C, Paine A, Warhurst D C, Noamese B K, Phillipson J D. In vitro and in vivo antimalarial activity of cryptolepine, a plant-derived indoloquinoline.  Phytother Res. 1995;  9 359-363
    CrossrefPubMedGoogle Scholar
  • 50 Bonjean K, De Pauw-Gillet M C, Defresne M P, Colson P, Houssier C, Dassonneville L, Bailly C, Greimers R, Wright C, Quetin-Leclercq J, Tits M, Angenot L. The DNA intercalating alkaloid cryptolepine interferes with topoisomerase II and inhibits primarily DNA synthesis in B16 melanoma cells.  Biochemistry. 1998;  37 5136-5146
    CrossrefPubMedGoogle Scholar
  • 51 Dassonneville L, Lansiaux A, Wattelet A, Wattez N, Mahieu C, Van Miert S, Pieters L, Bailly C. Cytotoxicity and cell cycle effects of the plant alkaloids cryptolepine and neocryptolepine: relation to drug-induced apoptosis.  Eur J Pharmacol. 2000;  409 9-18
    CrossrefPubMedGoogle Scholar
  • 52 Ansa-Asamoah R, Frempong-Asante J. Preliminary studies on the short term toxicity of cryptolepine in mice. Proceedings of the First International Seminar on Cryptolepine, Kumasi, Ghana 1983: 52-55
    Google Scholar
  • 53 Boye G L. Studies on the antimalarial action of Cryptolepis sanguinolenta extract. International Symposium on East-West Medicine, Seoul, Korea 1989: 242-251
    Google Scholar
  • 54 Sharma V. Ayush-64. Willcox M, Bodeker G, Rasoanaivo P Traditional medicinal plants and malaria. Boca Raton; CRC Press 2004: 83-89
    Google Scholar
  • 55 CCRAS .Ayush-64: A new Ayurvedic anti-malarial compound. New Delhi; Central Council for Research in Ayurveda and Siddha, Ministry of Health and Family Welfare, Government of India 1987: 128
    Google Scholar
  • 56 Valecha N, Devi C, Joshi H, Shahi V, Sharma V, Lal S. Comparative efficacy of Ayush-64 vs. chloroquine in vivax malaria.  Curr Sci. 2000;  78 1120-1122
    PubMedGoogle Scholar
  • 57 Sharma K D, Kapoor M L, Vaidya S P, Sharma L. A clinical trial of “Ayush-64” (a coded antimalarial medicine) in cases of malaria.  J Res Ayurveda Siddha. 1981;  II 309-326
    PubMedGoogle Scholar
  • 58 Anon. Formulaire National Thérapeutique. Bamako; Ministère de la Santé, des Personnnes Agées et de la Solidarité 1998
    Google Scholar
  • 59 Diallo D, Maiga A, Diakite C, Willcox M. Malarial-5: Development of an antimalarial phytomedicine in Mali. Willcox M, Bodeker G, Rasoanaivo P Traditional medicinal plants and malaria. Boca Raton; CRC Press 2004
    Google Scholar
  • 60 Iwalewa E O, Lege-Oguntoye L, Rai P P, Iyaniwura T T, Etkin N L. In vitro antimalarial activity of leaf extracts of Cassia occidentalis and Guiera senegalensis in Plasmodium yoelii nigeriensis.  West Afr J Pharmacol Drug Res. 1990;  9 19-21
    PubMedGoogle Scholar
  • 61 Kerharo J, Adam J G. La pharmacopée sénégalaise traditionnelle. Plantes médicinales et toxiques. Paris; Vigot Frères 1974
    Google Scholar
  • 62 Jellal A, Lemerre S, Michot P, Oger R, Rabiller P. Le Spilanthes. Dijon; Etablissement National d’Enseignement Supérieur Agronomique (ENESA) 1998
    Google Scholar
  • 63 Gasquet M, Delmas F, Timon-David P, Keita A, Guindo M, Koita N, Diallo D, Doumbo O. Evaluation in vitro and in vivo of traditional antimalarial, “Malarial 5”.  Fitoterapia. 1993;  64 423-426
    PubMedGoogle Scholar
  • 64 Koita N. A comparative study of the traditional remedy “Suma-Kala” and chloroquine as treatment for malaria in the rural areas. Mshigeni KE, Nkunya MHH, Fupi V, Mahunnah RLA, Mshiu E Proceedings of an International Conference of Experts from Developing Countries on Traditional Medicinal Plants. Arusha, Tanzania; Dar Es Salaam University Press 1990: 68-82
    Google Scholar
  • 65 Kéita A, Doumbo O, Koïta N, Diallo D, Guindo M, Traoré A K. Recherche expérimentale sur un anti-malarique traditionnel. “Etude préliminaire sur la faisabilité d'un protocole d'essai clinique”.  Bulletin de Médecine Traditionnelle et Pharmacopée. 1990;  4 139-146
    PubMedGoogle Scholar
  • 66 Doumbia S. Etude des plantes antipaludiques au Mali. Bamako; Universite de Bamako, Faculte de Medecine, Pharmacie et Odonto-Stomatologie 1997: 78
    Google Scholar
  • 67 Benoit-Vical F, Valentin A, Da B, Dakuyo Z, Descamps L, Mallie M. N'Dribala (Cochlospermum planchonii) versus chloroquine for treatment of uncomplicated Plasmodium falciparum malaria.  J Ethnopharmacol. 2003;  89 111-114
    CrossrefPubMedGoogle Scholar
  • 68 Vonthron-Senecheau C, Weniger B, Ouattara M, Bi F T, Kamenan A, Lobstein A, Brun R, Anton R. In vitro antiplasmodial activity and cytotoxicity of ethnobotanically selected Ivorian plants.  J Ethnopharmacol. 2003;  87 221-225
    CrossrefPubMedGoogle Scholar
  • 69 Adam J G, Echard N, Lescot M. Plantes médicinales Hausa de l'Ader (République du Niger).  J Agric Trop Bot Appl. 1972;  XIX 259-399
    PubMedGoogle Scholar
  • 70 Etkin N L, Ross P J. Recasting malaria, medicine and meals: A perspective on disease adaptation. Romanucci-Ross L, Moerman DE, Tancredi LR The anthropology of medicine: from culture to method. New York; Bergin & Garvey 1991: 230-258
    Google Scholar
  • 71 Benoit-Vical F. Evaluation de l'activité antimalarique in vitro de divers extraits végétaux bruts et purifiés sur Plasmodium falciparum. Montpellier; Université Montpellier I 1997
    Google Scholar
  • 72 Emmart E. The Badianus Manuscript: an Aztec herbal of 1552. Baltimore; John Hopkins Press 1940
    Google Scholar
  • 73 Guindo M. Contribution à l'étude du traitement traditionnel du “suma” (paludisme). Bamako; Universite de Bamako, École Nationale de Médecine et de Pharmacie du Mali 1988
    Google Scholar
  • 74 Adjobimey T, Edayé I, Lagnika L, Gbenou J, Moudachirou M, Sanni A. Activités antiplasmodiales in vitro de quelques plantes antipaludiques de la pharmacopée béninoise.  C R Chimie. 2004;  7 1023-1027
    CrossrefPubMedGoogle Scholar
  • 75 Diallo D, Diakite C, Mounkoro P P, Sangare D, Graz B, Falquet J, Giani S. [Knowledge of traditional healers on malaria in Kendi (Bandiagara) and Finkolo (Sikasso) in Mali].  Mali Med. 2007;  22 1-8
    PubMedGoogle Scholar
  • 76 Diallo D, Graz B, Falquet J, Traore A K, Giani S, Mounkoro P P, Berthe A, Sacko M, Diakite C. Malaria treatment in remote areas of Mali: use of modern and traditional medicines, patient outcome.  Trans R Soc Trop Med Hyg. 2006;  100 515-520
    CrossrefPubMedGoogle Scholar
  • 77 Graz B, Diallo D, Falquet J, Willcox M, Giani S. Screening of traditional herbal medicine: first, do a retrospective study, with correlation between diverse treatments used and reported patient outcome.  J Ethnopharmacol. 2005;  101 338-339
    CrossrefPubMedGoogle Scholar
  • 78 Willcox M L, Graz B, Falquet J, Sidibe O, Forster M, Diallo D. Argemone mexicana decoction for the treatment of uncomplicated falciparum malaria.  Trans Roy Soc Trop Med Hyg. 2007;  101 1190-1198
    CrossrefPubMedGoogle Scholar
  • 79 Graz B, Willcox M, Diakite C, Falquet J, Dakouo F, Sidibe O, Giani S, Diallo D. Argemone mexicana decoction versus Artesunate/Amodiaquine for the home-based management of malaria in Mali. Policy and public health implications.  Trans R Soc Trop Med Hyg. 2010;  104 33-41
    CrossrefPubMedGoogle Scholar
  • 80 Simoes-Pires C A. Investigation of antiplasmodial compounds from various plant extracts: Argemone mexicana L. (Papaveraceae), Licania octandra (Hoffmanns. ex. Roem & Schult) Kuntze (Chrysobalanaceae) and Syzygium cumini (L.) Skeels (Myrtaceae). Geneva; Universite de Geneve, Section des Sciences Pharmaceutiques, Laboratoire de Pharmacognosie et Phytochimie 2009
    Google Scholar
  • 81 WHO .Assessment and monitoring of antimalarial drug efficacy for the treatment of uncomplicated falciparum malaria. Geneva; World Health Organization 2003
    Google Scholar
  • 82 WHO .Assessment of therapeutic efficacy of antimalarial drugs for uncomplicated falciparum malaria in areas with intense transmission. WHO/MAL/96.1077. Geneva; World Health Organization 1996
    Google Scholar
  • 83 Willcox M, Olanrewaju I. Guidelines for clinical studies on herbal antimalarials. Willcox M, Bodeker G, Rasoanaivo P Traditional medicinal plants and malaria. Boca Raton; CRC Press 2004
    Google Scholar
  • 84 Willcox M, Graz B, Diakite C, Falquet J, Dackouo F, Sidibe O, Giani S, Diallo D. Is parasite clearance clinically important after malaria treatment in a high transmission area? A 3-month follow-up of home-based management with herbal medicine or ACT.  Trans R Soc Trop Med Hyg. 2011;  105 23-31
    CrossrefPubMedGoogle Scholar
  • 85 Willcox M L, Benoit-Vical F, Fowler D, Bourdy G, Burford G, Giani S, Graziose R, Houghton P, Randrianarivelojosia M, Rasoanaivo P. Do ethnobotanical and laboratory data predict clinical safety and efficacy of antimalarial plants?.  Mal J. , in press
    PubMedGoogle Scholar
  • 86 Benoit-Vical F, Soh P N, Salery M, Harguem L, Poupat C, Nongonierma R. Evaluation of Senegalese plants used in malaria treatment: focus on Chrozophora senegalensis.  J Ethnopharmacol. 2008;  116 43-48
    CrossrefPubMedGoogle Scholar
  • 87 do Ceu de Madureira M, Paula Martins A, Gomes M, Paiva J, Proenca da Cunha A, do Rosario V. Antimalarial activity of medicinal plants used in traditional medicine in S. Tome and Principe islands.  J Ethnopharmacol. 2002;  81 23-29
    CrossrefPubMedGoogle Scholar
  • 88 Kazim M, Puri S K, Dutta G P, Narasimham M V. Evaluation of Ayush-64 for blood schizontocidal activity against rodent and simian malaria parasites.  Indian J Malariol. 1991;  28 255-258
    PubMedGoogle Scholar
  • 89 Mueller M S, Runyambo N, Wagner I, Borrmann S, Dietz K, Heide L. Randomized controlled trial of a traditional preparation of Artemisia annua L. (Annual Wormwood) in the treatment of malaria.  Trans R Soc Trop Med Hyg. 2004;  98 318-321
    Google Scholar
  • 90 Mueller M S, Karhagomba I B, Hirt H M, Wemakor E. The potential of Artemisia annua L. as a locally produced remedy for malaria in the tropics: agricultural, chemical and clinical aspects.  J Ethnopharmacol. 2000;  73 487-493
    Google Scholar
  • 91 Hirt H-M, Lindsey K. Natural medicine in the tropics: Experiences. Winnenden; Anamed 2000
    Google Scholar

Dr. Merlin Willcox

Department of Primary Health Care

Old Road Campus, Roosevelt Drive

Oxford OX3 7LF

United Kingdom

Phone: +44 18 65 28 92 88

Fax: +44 18 65 28 92 87

Email: merlin.willcox@dphpc.ox.ac.uk