Artemisia annua and Development of Africa by Iday-International

Raising Voices for Education in Africa

Argumentation ARTEMISIA ANNUA & DEVELOPMENT OF AFRICA

By IDAY-‐International

« To remain neutral in situations of injustice, you have chosen the side of the oppressor » Desmond Tutu (Nobel Prize 84’)

IDAY International Day of the African Child and Youth aisbl – www.iday.org Rue des Jambes 19, BE-‐1420 Braine-‐l’Alleud | Tel. : +32 (0)2 385 44 13 | Email : info@iday.org | Entreprise n° 0895.443.325

INTRODUCTION 12

Jared Diamond , Professor of Geography at the University of California, noted that most developing countries were located around the Equator where the most debilitating tropical diseases are endemic. He predicated that lifelong exposure to such diseases was at least as much a causal factor for their poor economic development as bad governance, perhaps even more so. No country or continent has achieved economic “take-‐off” without having earlier at minimum eradicated malaria. 3

At a conference in 2011 , several experts stated that no improvement in the quality of educational systems in Africa could be achieved without simultaneously improving public health standards. There has been massive investment in providing preventive anti-‐malarial responses such as bed-‐nets, medication, and early detection, on the one hand, and on medical research on the other. The measures have proven only partly effective and there are doubts regarding their sustainability. Use of medicinal plants, either for disease vector control in malaria or as therapy, is widespread in Africa [1]. A study by Dr P Ogwang [2] and his team indicated that clinic attendance due to fevers or symptoms associated with malaria was reduced by 80% in a study sample of farm workers who consumed Artemisia annua ‘tea’ once a week to prevent malaria and related fevers. Recent research on rodents has confirmed the greater efficiency 4 of Artemisia annua natural extracts compared to chemical compounds . Use of this plant against malaria and other infectious endemic diseases are widespread in Africa (Gambia, Cameroun, and DR Congo...). These instances occur randomly and spontaneously. Because education contributes to personal development, maximises task performance and enables citizen participation, IDAY feels that the rate of African development can be substantially enhanced through supporting the introduction of Artemisia annua into school gardens as an efficacious anti-‐malarial substance (details of the IDAY network are given in Annexe 1). In addition, Artemisia annua has proven its effectiveness in treating the two most common 5 infections in Africa: malaria and intestinal parasites .

Jared Diamond is an American scientist conducting research in a variety of fields, including anthropology, ecology, geography, and evolutionary biology. He is the author of “Guns, Germs and Steel: The Fates of Human Societies” which was awarded the Pulitzer Prize in 1998. 2 References to publications in the text are given at the bottom of each page. A full bibliography on research regarding Artemisia annua is given at annex 1. 3 IDAY International Conference /IFBV, Santé et éducation en Africa, Santé et éducation en Afrique, 16 juin 2011, Parlement européen. Voir www.iday.org> 4 Pamela Weathers, RICH Stephen W., et al., “Dried whole plant Artemisia annua as an antimalarial Therapy”, Plos One, December 2012. 5 According to the World Health Organisation, the main causes of mortality in Africa are : HIV-‐AIDS, malaria, respiratory diseases and digestive diseases. Different studies (Robledo et al. 2008 ; Sharma et al. 2013 ; Cheah et al. 2013) suggest that Artemisia annua could also be effective against neglected tropical diseases (NTD) like leichmaniosis, dengue or schistosomiasis that also plague these less favoured areas . IDAY International Day of the African Child and Youth aisbl – www.iday.org Rue des Jambes 19, BE-‐1420 Braine-‐l’Alleud | Tel. : +32 (0)2 385 44 13 | Email : info@iday.org | Entreprise n° 0895.443.325

I. THE IMPACT OF ENDEMIC MALARIA AND INTESTINAL PARASITES ON DEVELOPMENT IN AFRICA The impact of endemic malaria ! It is estimated that in Africa, malaria is the cause of about 20% of all infant mortality: this is equivalent to one infant death per minute [3]. ! The economic cost of endemic malaria is estimated at 10 billion US dollars per year or the loss of 1.5 % of African annual GDP [4]. ! The cognitive ability of children aged 6 to 14 years that have undergone 5 or more instances of malaria may be definitively impaired by as much as 15% [5][6]. The Impact of endemic intestinal parasite infections ! ! !

One person in 4 is infected by intestinal parasites [7]. In sub-‐Sahara Africa, 90% of children aged 6 -‐ 18 suffer from intestinal parasites [7]. The pathogenic impact of intestinal parasites varies between subjects and ranges between asymptomatic carrier status and acute infestation which at times result in death [8]. In the longer term, the rate of absenteeism among school-‐age children and of teachers as well as cognitive impairment negatively impacts both on school-‐going children and the school system. Other diseases, such as HIV-‐AIDS and bilharzia or pains from menorrhea also take their toll on school attendance and any relieve from them will be welcome.

II. CONVENTIONAL MALARIA CONTROL METHODS The conventional methods of malaria control most commonly used include bed-‐nets, impregnated with mosquito repellent or not, insecticides, early detection, quinine derivatives and ACT. These control methods have proven successful within the control areas. WHO statistics indicate a 38 to 50% drop in the incidence of malaria in these areas. (Source WHO). Nonetheless, the costs, emergence of resistances, negative side effects and counterfeit pharmaceuticals all limit the impact of current conventional control methods. Moreover, the medication and materials required in successful convention treatments and mosquito control may not be accessible to the entire population without widespread subsidies or targeted aid donor funding. In addition, there is still no authorized anti-‐malarial 6 vaccine. In his article, “Stopping Malaria: the wrong road” , Richard Horton is critical of current strategies : “For a disease that exacts such and enormous toll of human deaths and misery, it remains shocking that so little has been done by affected countries and large international donors to control malaria”. The WHO, in its 2012 Annual Report, estimates the annual cost of world-‐wide malaria control as 5 billion US dollars. However, the international donor community has difficulty in raising 2 billion US dollars. This figure doesn’t take into account the additional costs of controlling the development of new, resistant forms. 6

Stopping Malaria: The Wrong Road from Richard Horton (Chief Editor of “Lancet”) University of California Press as quoted in the New York review of Books, February 2011.

III. ARTEMISIA ANNUA BACKGROUND Artemisia annua (soft wormwood) has attracted growing medical interest. Used in ancient Chinese medicine as a means to alleviate fever it was found -‐ more than 30 years ago – to contain a molecule with anti-‐malarial properties. With various chemical modifications and in combination with other compounds this molecule is one of the few remaining, dependable treatments of malaria, particularly the variety due to the Plasmodium falciparum, by far the most pathogenic and deadly of the four malaria parasites of importance in human medicine. Cultivation of Artemisia annua spread rapidly across the world once it’s effectiveness as an anti-‐malarial 7 remedy was demonstrated in 1975 among Viet Cong troops . The wide-‐spread diffusion of Artemisia annua production initially resulted from its cultivation by large pharmaceutical firms to extract the artemisinine molecule which is still officially considered the effective compound against malaria.

ARTEMISIA CULTIVATION Geographic Spread

Artemisinin Conference, Madagascar, 12–14 October 2010

Lutgen P., (2012), Artemisia annua, Artemisin, ACTs open questions, Malaria World, http://www.malariaworld.org/search/site/Artemisia%20annual%20artemisia%20ACT%20open%20questions

THE ACTIVE SUBSTANCES The name of what is generally considered the anti-‐malarial compound found in Artemisia annua is artemisinin. Today, it lies at the core of the global campaign for malaria eradication. Artemisinin belongs to a diverse group of organic, often aromatic compounds, called terpenes. Artemisia annua contains 29 terpenes. As many other plants, and notably fruits and vegetables, as well as e.g. red wine, coffee and tea, Artemisia annua also contains flavonoids, a 4000-‐member strong class of chemical compounds known for their antioxidant effects. Antioxidants are beneficial in that they inhibit or impede oxidizing chain reactions, thus protecting cells against oxidative stress -‐ a biological equivalent of rusting, a phenomenon linked to cancer, ageing, inflammation, ischemic circulatory problems and various degenerative diseases. Some people claim that artemisinin is not the only active compound in the infusion and that synergism plays an important role in the overall efficacy [9]. ARTEMISIA ANNUA AND MALARIA The value of artemisinin and several other pharmaceutical compounds derived by modification of this molecule (artesunate, artemether, and others) as anti-‐malarials is undisputed, particularly as the parasite has developed resistance all other older drugs such as Chloroquine, Méfloquine, Primaquine. A resistance to artemisinin has also been detected in South-‐East Asia [10], presumably due to poor medical practices, inadequate patient compliance, and the marketing of substandard forms of the drug. Understandably, the World Health Organisation (WHO) is vigilant in its efforts to prevent -‐ or at least delay -‐ the development of parasite resistance to artemisinin. In this context, the WHO strongly advises against the proliferation of non-‐ pharmaceutical forms, e.g. infusions of Artemisia annua [11]. Opposition to the WHO’s position is mounting, though. Firstly, parasite resistance linked to the ingestion of Artemisia annua infusion has not been reported [12]. Secondly, it has even been suggested that an aqueous preparation from Artemisia annua, i.e. infusion, with a low content of artemisinin may reduce the risk of resistance of the parasite and be relatively more effective in the treatment of the disease [13]. Further, many public health experts and health economists argue that a ‘home-‐grown’ remedy, such as Artemisia annua infusion, is likely to be the only treatment available to the majority of those – mostly poor -‐ experiencing the global annual estimate of five billion malaria-‐like illnesses, as proper pharmaceuticals and modern health services for financial or geographic reasons will remain unavailable. Lastly, a recent paper [14] found a single dose of dried Artemisia annua leaves to reduce the blood parasite load more effectively than a comparable dose of purified drug. The authors speculate that a higher efficacy may derive from better absorption of the active compounds in the plant than in the synthetic drug, or the presence of other anti-‐malarial compounds in the plant, or both. The findings are not directly applicable to the practice of drinking Artemisia annua infusion, as the study was conducted in an animal model and it used dried leaves rather than infusion. Nonetheless, the study merits great interest in this context because if Artemisia annua can be shown to be clinically efficacious, well-‐tolerated, and compatible with the imperative of evading the evolution of drug resistance, it will be an inexpensive addition to the global effort to reduce malaria morbidity and mortality. 8

ARTEMESIA ANNUA AND INTESTINAL PARASITES (BY DR. RENE CHRISTENSEN) Although the WHO’s reservations about its use for any illness other than malaria place certain limits on demonstrating the drug’s anthelmintic effects, Artemisinin’s therapeutic range, in particular with regard to parasitic infestations, brings the account ‘full circle’: “wormwood”, as Artemisia species were called in older times, was indeed an effective remedy against intestinal worms and perhaps other abdominal complaints brought on by unhygienic food. A systematic review [15] concludes that relative to intestinal worm infections artemisinin derivatives [...] are promising products, but their therapeutic place needs to be further defined’. An

Bibliography on this subject grouped in Annex 1.

extensive literature from veterinary medicine generally supports the notion of members of the Artemisia genus, e.g. as feeds, having anthelmintic activity in animals [16]. Although further research to establish the effectiveness of Artemisia annua and its derivatives in prophylaxis and curative treatment of intestinal parasites in humans must still be undertaken, it is cautiously submitted that Artemisia annua compounds may have a useful role in control of helminths. Parasitic infection of the digestive tract is a major public health problem in itself. It can also aggravate the effects of acute nutritional deficiencies and impede the cognitive development of children. Research findings published by the J-‐PAL organisation with respect to the programme of deworming distribution and use for helminth parasite control in Kenyan schools support this premise. Historically, intestinal parasite eradication programmes have been health centre-‐based. This approach has only encountered partial success in view of the high costs of medication and also because of the loss of time and income for patients undergoing treatment. On the other hand, the J-‐PAL study has shown that eradication of intestinal parasites among school-‐children is the second most cost-‐effective means to reduce absenteeism 9 from school and abandoning education .

If intestinal parasite control programmes were to be offered even at lower cost in schools and regularly repeated for prophylaxis, such programmes may become even more effective. The spectacular improvement in 10 school results in schools which implemented programmes of Artemisia annua prophylaxis might not be attributed to the drop in malarial infection alone. It is justifiable to speculate that the efficacy of Artemisia annua in treatment and prophylaxis of other conditions, such as intestinal worms, also played a part.

As the Cost-‐Effectiveness graph below indicates, the first most effective school attendance programmes is increasing parent’s awareness of the benefits to their children of school attendance. Awareness -‐ raising at both the government and community level -‐ is the driving principal of IDAY’s work. 10 Report by Dr. T. Arudo, / IDAY-‐Kenya, 2011. IDAY International Day of the African Child and Youth aisbl – www.iday.org Rue des Jambes 19, BE-‐1420 Braine-‐l’Alleud | Tel. : +32 (0)2 385 44 13 | Email : info@iday.org | Entreprise n° 0895.443.325

ARTEMISIA ANNUA AND HIV/AIDS (BY PROFESSOR PAMELA WEATHERS) Malaria and HIV co-‐infection represent a major health burden in Africa mainly because it is now “well established that HIV infection results in higher incidence and more severe manifestations of malaria” (Marconi 2011). With their weakened immune system AIDS patients are more susceptible to malaria and also respond slower to malaria therapy (Kamya et al 2006; Marconi 2011; Ezeamama et al. 2012). Furthermore, in a recent meta-‐analysis by Tusting et al. (2013), socioeconomic development strongly correlated with better malaria therapeutic outcomes. The A. annua herb also has demonstrated anti HIV activity (Lubbe et al. 2012; Efferth et al. 2009) and thus oral consumption of the dried leaves of this herb will not only treat malaria, but should also enhance the well-‐being of HIV/AIDS patients by allowing their compromised immune systems to rebound more quickly against Plasmodium infections.” This finding has been confirmed by anecdotical evidence in the Kenya project initiated by IDAY. IV. SOCIO-‐ECONOMIC FACTORS # The current trend in the area of public health is to emphasise community health services involving the active participation of patients. The approach outlined here enables anti-‐malarial therapy not only to become universally affordable, in particular for the poorest, but also encourages greater participation by patients. This is made possible due to the very low cost of preparing Artemisia annua infusions and by the relative ease of expanding coverage through growing of the plant locally. # This approach is also sustainable in that, once local production and use of Artemisia annua is commonly adopted in rural areas; extending coverage is simplified, particularly in that no major, ongoing external financing is required. This approach must necessarily have the support of the national public health authorities and be included in their planning. IDAY seeks close involvement in support to such programmes.

# Artemisia annua may also be effective against other parasitic infections and thereby enable the local

population to prevent other public health conditions such as dysentery. Encouraging the widespread production and use of Artemisia annua would assist effective control of several endemic tropical diseases & malaria eradication in certain regions in which malaria still presents a significant health problem. V. PROPOSED IDAY -‐ FUNDED PROGRAMMES A. RESEARCH PROGRAMME WITH KENYATTA UNIVERSITY Various institutions have expressed a need for a strategy to enable more broad-‐based access, at lower cost, to malaria control methods; one of the most active of these institutions is the WHO Regional Committee for Africa. (Malaria Journal 2011, 10, Supp. 1:S6). Member organization of the IDAY -‐ Kenya network achieved very 12 encouraging results in the course of field trials with Artemisia annua both during a piloting phase (March 2010 to October 2010,) and an intervention phase (November 2010 to December 2011). These trials demonstrated positive therapeutic effects (reduction in malaria and typhus cases compare to pre-‐intervention years as well as in menorrhea among teenage girls) and associated reduction in absenteeism of students and teachers. These observations, however, have raised a series of questions from different sources (specifically, WHO and Malaria Control Committee of Ministry of Public Health of Kenya), including: 1. The effectiveness of Artemisia annua treatments in disease control in comparison with other methods introduced into Kenya such as bed-‐nets, insecticides and “conventional” medication, and validated on the basis of results from clinical trials. 2. Possibility of rapid development of resistance against Artemisia annua tea with its restricted composition relative to the full phytochemical blend of the plant, and comparative evaluation of alternatives that provide the full blend of Artemisia annua. 11

Bibliography is grouped in Annex 1. IDAY Conference Report of 24 June 2010, downloadable at www.iday.org. IDAY International Day of the African Child and Youth aisbl – www.iday.org Rue des Jambes 19, BE-‐1420 Braine-‐l’Alleud | Tel. : +32 (0)2 385 44 13 | Email : info@iday.org | Entreprise n° 0895.443.325 12

3. Quality control and monitoring procedures necessary to ensure the efficacy and replicability of therapeutic effects induced by Artemisia annua use in therapy (and that of other Artemisia varieties) in different agro-‐climatic zones, both as a repellent, in vivo, and its prophylactic or curative use. 4. The possibility of use of Artemisia annua -‐ based products -‐ such as Artemisia annua infusions or as the whole leaf presented as tablets or capsules -‐ by pregnant women, to establish its efficacy and bio-‐safety as a therapy for pregnant women infected with malaria In view of the significant number of positive results from field-‐trials with Artemisia annua, IDAY and Kenyatta University have agreed to jointly undertake multidisciplinary research to answer the above mentioned questions; the study will be conducted in accordance with the norms set by WHO. To this effect, the parties signed a Memorandum of Understanding to conduct a programme of research by Dr Ahmed Hassanali (Chemistry Department-‐ Kenyatta University) who has specialised in this field. The research has been certified ISO 9001 -‐ 2000. IDAY has also established collaborations with the University of Liege (Belgium), and with the Worcester Polytechnic Institute (USA), to validate internationally the research findings. The programme will be conducted over a period of 3 years including the publication of final results. IDAY -‐ International is looking for funding for the initial phase of the project. The overall cost of the research programme is estimated at 1,269,790 US dollars or €UR 941,000. These costs do not include the provision of foreign participating universities. ITEM USD Sub-‐project 1 699 000 Sub project2 70 000 Sub-‐project 3 126 800 Communication, Administration, Overheads 330 450 Contingencies 43 540 Total 1 269 790 This cost estimate does not take into account the expenditures incurred by European or US partners. Kenyatta University has pledged to cover the recurrent costs of staff and laboratory trials, amounting to 220,000 US dollars. IDAY-‐International and Kenyatta University seek donors to cover a total of 1,049,690 US dollars over 3 years. Based on the positive outcome of the first Phase of the research programme, Kenyatta University will initiate further multidisciplinary research on agronomic and social aspects relating to optimal production and use of Artemisia annua. B. SCHOOL GARDENS PROGRAMME Whilst malaria remains one of the main cause of absenteeism in schools, it is not the only one. Intestinal parasites, together with inadequate diet lacking nutritious elements, also seriously affect children’s’ school 13 performance in Africa. IDAY has therefore initiated a programme of school gardens in which Artemisia annua will be grown, together with fruit, vegetables and other nutritious plants. Fruits and vegetables grown in the school gardens will provide children with a rich source of flavonoids which have preventive and curative qualities against disease. IDAY -‐ Uganda began a school gardens programme in 2010. Today, the programme successfully covers 12 schools. In Kenya, an Artemisia annua production and use project directly resulted in improved school results and enabled major savings of between 80% to 90% of health spending. The programme commenced in 2010 in 2 pilot schools in Nyanza Province and rapidly expanded to cover adjoining areas, and today fifty schools and three prisons in 6 provinces. 13

Details of these programmes can be found in the Project Bank on the IDAY website : www.iday.org IDAY International Day of the African Child and Youth aisbl – www.iday.org Rue des Jambes 19, BE-‐1420 Braine-‐l’Alleud | Tel. : +32 (0)2 385 44 13 | Email : info@iday.org | Entreprise n° 0895.443.325

Presently, 11 IDAY-‐country networks are geared up to launch a school gardens programme. In three years, a sufficient number of schools will take part in this programme bringing governments to include a school gardens component in the national curriculum. The overall cost of a school garden project is estimated at 60,000 US dollars (EUR 45,000) per country. Proposals are in the course of preparation in four countries (Tanzania, Burundi, Senegal, Mauritania,) for a total amount estimated at 300 000 $. The impact of national school gardens programmes on the overall health status of school children may be significant on condition that these results are endorsed by WHO. Low cost Artemisia annua production in school gardens may attract public and private donor funding for its replication throughout Africa. Other donors, UN specialised organisations such as the FAO, World Food Programs and other agencies may opt to promote Artemisia annua production within their own national schools programmes once WHO lifts its opposition to the use of the plant against malaria. C. COLLOQUIUM. WHO’s opposition to the use of Artemisia annua against malaria is being questioned by researchers, practitioners and several governments. Cameroon and Uganda, for instance, have officially integrated the use of the plant in their strategy against malaria. Several countries – Mauritania, the Gambia, Benin, Gabon, DRC, Burundi, Kenya, South Africa – have accepted planting Artemisia annua in schoolgardens and the use and sale of natural extracts of the plant against malaria. In order to reconcile these positions, IDAY is seeking support from a key African Minister of Health and financing to organise on African soil a colloquium similar to the ones that are being held in other continents. The meeting would assemble researchers, practitioners, political leaders (Ministers of Health), a representative of the African Union and WHO representatives to seek a way forward taking into account both WHO’s arguments against the use of and in vivo research on Artemisia annua and the protagonists of the plant whose numbers are expanding fast. Costs for about 50 participants including travel arrangements of African private participants and foreign researchers are estimated at 60 000 € (81 000 $). VI. CONCLUSIONS Artemisinin and perhaps other bioactive principles in Artemisia annua [17] and other members of the genus demonstrate potential as future agents vis-‐à-‐vis a host of health problems. However, in most instances more research will be needed to confirm, respectively refute, this, let alone turn it into practical clinical application. Executing its global health curator mandate evidently imposes a balancing act on the WHO, in which a host of considerations -‐ often difficult to reconcile -‐ must be taken into account. As far as the use of Artemisia annua infusion against malaria is concerned, the Organisation’s stance looks increasingly untenable. Indeed, it amounts to turning a blind eye to reality, given that Artemisia annua infusions’ already extensive use, particularly by people for whom modern pharmaceutical therapy is and will remain unavailable. Would not a more accommodating position, inviting collaboration with the research community and development organisations, be more becoming? Pilot projects supported through IDAY offer the possibility of reducing the incidence and effects of malaria among school age children through local production and use of Artemisia annua. Its availability at local level may also enable limiting the incidence and the negative consequences of intestinal parasite infection in the overall population. Additionally, enabling local production and use of Artemisia annua would enable awareness-‐raising among patients, particularly among young people and women, and offer them the opportunity of affordable and participative therapy.

VII. ACKNOWLEDGEMENT IDAY wishes to thank Dr Tobias Arudo for his commitment to promoting use of Artemesia annua in schools and prisons in Kenya. Without his dedication and perseverance this project would not have been developed. IDAY is also indebted to Geert Flamang, long a promoter and grower of Artemesia annua who has actively supported IDAY in its work. Our thanks too to Dr Christine Niyonsayve for her invaluable advice regarding the organisation of this campaign. It would not have been possible to prepare this document without the technical and medical advice of Dr Pierre Lutgen of the Luxemburg NGO IWERLIEWEN who pioneered a significant part of the Artemesia annua-‐ based campaign against malaria in Africa. IDAY is also indebted to Dr René Christiansen and the J-‐Poverty Laboratory (J-‐PAL), of the Massachussetts Institute of Technology (MIT) regarding the part on deworming. IDAY received valuable input from Agricultural Engineers Camille Heylen and Félicien Meunier, who benevolently prepared a video on cultural aspects of Artemesia annua on the basis of their experience gathered over three months in Benin, Togo and Burkina-‐Faso. IDAY-‐International is pleased to announce that a Memorandum of Understanding was signed in 2012 with Kenyatta University to conduct further research on the repellent, prophylactic and curative properties of Artemesia annua in the treatment of malaria. With the valuable assistance of Dr Jöelle Quentin-‐Leclerc and Dr Guy Mergeai, research will be conducted on the basis of a collaborative understanding with the University of Liège and the Catholic University of Louvain regarding cultivation of Artemesia annua and possibly on the pharmacological and repellent effects of the plant. For other information, please contact. IDAY‐International aisbl Email : jjschul@iday.orgoufmbelalusendi@iday.org Tel : +32 2 385 44 13 Mobile : +32 476 75 06 01

ANNEX 1 BIBLIOGRAPHY

References for research concerning the efficacy of Artemisia annua as a means to fight malaria, intestinal worms and HIV/AIDS, and purify water 1. Malaria studies and publications # ARUDO T. s– June 16th conference presentation at the European Parliament on the results obtained from preventive use of Artemisia annua tea in two schools in Kisumu and Kenya. June 2011 # BOURDY G., “Malaria: searching for forgotten plants”, Development Research Institut, June 2011 # CALA Aida Cristina, « Avaliaçao Da Atividade De Artemisia annua L., Melia Azedaeach L. E Trichilia Claussenii C. Sobre Nematodeos Gastrintestinais De Ovinos », Universidade Estudual Paulista, 2010, Dissertacao Faculdade de Ciencias # CARBONARA Teresa, PASCALE Rossana, ARGENTIERI Maria Pia, PAPADIA Paride, FANIZZI Francesco Paolo, VILLANOVA Luciano, AVATO Pinarosa, “Phytochemical analysis of a herbal tea from Artemisia annua L.” Journal of Pharmaceutical and Biomedical Analysis, January 2012. # Chougouo Kengne Rosine Désirée, Natural Plants chemical laboratory, Cameroun : Psycho-‐chemical analysis of Artemisia annua # Eliningaya J. Kweka, Humphrey D. Mazigo, Stephen Munga, Stephen M. Magesa, Leonard E. G. Mboera, Challenges to malaria control and success stories in Africa, Maralte, GPH October 2013. # FAUDA Emilien– Clinical study on the therapeutic efficacy of Artemisia annua on uncomplicated malaria. Pilot project made by the Cite Verte health district – Yaounde. # GRAZ Bertrand, KITUA Andrew Y. and MALEBO Hamisi, “To what extent can traditional medicine contribute a complementary or alternative solution to malaria control programmes? Malaria Journal 2011, 10(Suppl 1):S6 doi:10.1186/1475-‐2875-‐10-‐S1-‐S6 # GUEYE Papa, EL HADJI Omar & al. “Artemisia annua tea inhibits Plasmodium falciparum isolates”, Pikine, Senegal, 2012 # TIRUNEH Gebeyaw, KEBEDE Yigzaw, YIGZAW Tekbar, “Use of Plant Artemisia annua as a natural anti-‐malarial herb in Arbaminch Town (Ethiopia)”, J. Health Biomed Science, 2010. Vol.2, No.2 # HIRT Hans M. & al. “Natural medicine. Practical recipes in Kinshasa, Kongo”, 2003. Considers that Artemisia annua is efficient against several diseases (malaria, bilharzioze, HIV/AIDS, hay-‐fever, skin rash) (confirmed in Kenya). HORTON Richard, “Stopping Malaria: the Wrong Road”, New York Review of Books, February 24, 2011 # KEIPES Georges (President of Kraaidergaart Wanseler), letter to the Development Cooperation Ministry of the Grand Duchy of Luxembourg, 2007, with reference to the OMS’ medicinal herbs programme # KEISER J., GRUYER M-‐S, PERROTTET N., ZANOLARI B., MERCIER T., DECOSTERD L., “Pharmacokinetic parameters of artesunate and dihydroartemisinin in rats infected with Fasciola hepatica”, Journal of Antimicrobial Chemotherapy 63, January 2009, pp.543 – 549 # LUTGEN Pierre, “Polysacharids”, October 2011 # LUTGEN Pierre, « Artemisia annua et prophylaxie du paludisme », February 2012 # LUTGEN Pierre, “Open Questions concerning artemisinin & its derivatives”, Malaria World, October 2012. Article submitted by Bart Knols. # LUTGEN Pierre, “Artemisia annua prevents the transmission of malaria from man to mosquito”, blog MalariaWorld. # LUTGEN Pierre, HASSANALI Ahmed, Is PCR genotyping of Plasmodium falciparum a reliable tool to monitor drug resistance?, blog MalariaWorld, 8 February 2013.

# LUTGEN Pierre, “Immunosuppression, ACT and malaria resistance, blog MalariaWorld, July 16, 2013. # LUTGEN Pierre, Artemisia ketone, phytosterols, lipid metabolism, Malaria World, September 2013. # MEIER ZU BIESEN Caroline, “The rise to prominence of Artemisia annua L.-‐the transformation of a Chinese plant to a global pharmaceutical”, African Sociological Review, 14 February 2010, p. 24-‐44 # MELILLO DE MAGALHAES Pedro, Campinas University, Brasil, “Working actions for clinical trials on Artemisia annua infusion to malaria treatment”, paper presented in Rome, 23/04/2010. # MESHNICK, S.R., “Artemisinin: Mechanism of action, resistance and toxicity”, International Journal for Parasitology, Vol. 32, issue 13, Dec. 2002, pp 1655-‐1660 # MUZEMIL A., PhD Thesis I, Addis Ababa University, 2009 # OGWANG Patrick & al. -‐, “Preventive use of Artemisia tea in a flower plantation in Uganda”, British Journal of Pharmaceutical Research, 2011 # ONIMUS M. 14, VOUILLOT J.-‐V. 15, Clerk. G., “Artemisia annua tea: a local production project for malaria treatment in the poor countries”, February 2009, November 2012. # REHWAGEN Christiane, “WHO ultimatum on artemisinin monotherapy is showing”, British Medical Journal, 2006 May 20 # RIBEIRO Ir, OLLIARO P., “Safety of artemisinin and its derivatives. A review of published and unpublished clinical trials”, Médecine Tropicale, Vol. 58, Issue:3 Suppl., 1998, pp.50-‐3 # SCHWARTZ E., “Tropical Diseases in Travelers”, Ed E. Schwartz, 2010, Wiley-‐Blackwell, Oxford, 504 pp. # TOUFIGH Gordi, LEPIST Eve-‐Irene, “Artemisinin derivatives: toxic for laboratory animals, safe for humans?”, Toxicology letters, Vol.147, Issue 2, 2004, pp. 99-‐107 # VAN DER KOOY, Frank, SULLIVAN S.E., The complexity of medicinal plants: The traditional Artemisia annua formulation, current status and future perspectives. Journal of Ethnopharmacology (2013), http://dx.doi.org/10.1016/j.jep.2013.08.021i # WEATHERS Pamela, RICH Stephen W., et al., “Dried whole plant Artemisia annua as an antimalarial Therapy”, Plos One, December 2012. # WHO Tropical Disease Research, “Pre-‐referral rectal artesunate to prevent death and disability in severe malaria: a placebo-‐controlled trial”, British Medical Journal, February 2009. [Note: confirms the efficacy of Artesunate suppository against malaria, yet as an artemisinin derivate used in monotherapy]. # Willcox M., Bodeker G., Bourdy G., Dhingra, V., Falquet J., Ferreira J.F.S., Graz B., Hirt H.-‐M., Hsu E., de Magalhães P.M., Provendier D., Wright C.W. “Artemisia annua as a traditional herbal antimalarial”. p. 43-‐59. In: Willcox, M.L., Bodeker, G., Rasoanaivo, P. (Eds), 2004. Traditional Medicinal Plants and Malaria. CRC Press, Boca Raton, FL. # Zatra R. et al, In Vitro antimalarial scusceptibility and molecular markers of drug resistance in Franceville, Gabon, BMC Infectious Diseases 2012, 12:307. 2. Intestinal Worms (taken from Dr. René Christensen’s note of October 2013 #

Ferreira JFS, Luthria DL, Sasaki, Arne Heyerick A. Flavonoids from Artemisia annua L. as Antioxidants and Their Potential Synergism with Artemisinin against Malaria and Cancer Molecules 2010, 15, 3135-‐3170; doi:10.3390/molecules1505313. Lai HC, Singh NP, Sasaki T. Development of artemisinin compounds for cancer treatment. Invest New Drugs. 2013 Feb; 31(1):230-‐46. doi: 10.1007/s10637-‐012-‐9873-‐z.

Honorary professor of children orthopaedic surgery, University of Franche Compte. F-‐25000 Besancon. www.acmc-‐org.net Agricultural engineer, ISARA Lyon. Artemisia Against Malaria. Grande Rue Street no. 7, F-‐ 25330 Longeville. www.acp-‐ paludisme. org 15

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Wang Y, Huang Z, Wang L, Meng S, et al. The anti-‐malarial artemisinin inhibits pro-‐inflammatory cytokines via the NF-‐κB canonical signaling pathway in PMA-‐induced THP-‐ 1 monocytes. Int J Mol Med. 2011 Feb; 27(2):233-‐41. doi: 10.3892/ijmm.2010.580. Lubbe A, Seibert I, Klimkait T, van der Kooy F. Ethnopharmacology in overdrive: the remarkable anti-‐HIV activity of Artemisia annua. J Ethnopharmacol. 2012 Jun 14;141(3):854-‐9. doi: 10.1016/j.jep.2012.03.024. Craciunescu O, Constantin D, Gaspar A, Toma L, Utoiu E, Moldovan L.Evaluation of antioxidant and cytoprotective activities of Arnica montana L. and Artemisia absinthium L. ethanolic extracts. Chem Cent J. 2012 Sep 9;6(1):97. doi: 10.1186/1752-‐153X-‐6-‐97. Brodin K, Alahyar H, Hedner T, Sterner O, Faergemann J. In vitro activity of artemisia abrotanum extracts against Malassezia Spp., Candida albicans and Staphylococcusaureus. Acta Derm Venereol. 2007;87(6):540-‐2. Rasal V P, Ajay Kshirsagar, Raj Bagali, Santosh K. Rai. Influence of Artemisia pallens wall plant on experimental wounds in albino rats. In: Recent Advances in Medicinal Plant Research. 2005; 393-‐401. Foglio MA, Dias PC, Antônio MA, Possenti A, Rodrigues RA, da Silva EF, Rehder VL, de Carvalho JE. Antiulcerogenic activity of some sesquiterpene lactones isolated from Artemisia annua. Planta Med. 2002 Jun;68(6):515-‐8. WHO Position Statement: Effectiveness of Non-‐Pharmaceutical Forms of Artemisia annua L. against malaria, June 2012, at: http://www.who.int/malaria/position_statement_herbal_remedy_artemisia_annua_l.pdf Willcox ML, Burton S, Oyweka R, Namyalo R, Challand S, Lindsey K. Evaluation and pharmacovigilance of projects promoting cultivation and local use of Artemisia annua for malaria. Malaria Journal 2011, 10:84.doi:10.1186/1475-‐2875-‐10-‐84 Carbonara T, Pascale R, Argentieri MP, Papadia P, Fanizzi FP, Villanova L, Avato P. Phytochemical analysis of a herbal tea from Artemisia annua L. J Pharm Biomed Anal. 2012 Mar 25;62:79-‐86. doi: 10.1016/j.jpba.2012.01.015. Elfawal MA, Towler MJ, Reich NG, Golenbock D, Weathers PJ, et al. (2012) Dried Whole Plant Artemisia annua as an Antimalarial Therapy. PLoS ONE 7(12): e52746. doi:10.1371/journal.pone.0052746 van den Enden E. Pharmacotherapy of helminth infection. Expert Opin Pharmacother. 2009 Feb;10(3):435-‐51. doi: 10.1517/14656560902722463. Ferreira, JFS. Artemisia species in small ruminant production: their potential antioxidant and anthelmintic effects. In Appalachian Workshop and Research Update: Improving small ruminant grazing practices; Morales, M., Ed.; Mountain State University/USDA: Beaver, WV, USA, 2009; pp. 53–70. Guarrera PM. Traditional antihelmintic, antiparasitic and repellent uses of plants in Central Italy. J. Ethnopharmacol. 1999 Dec 15;68(1-‐3):183-‐92. 3. Impact on HIV/AIDS (According to Professor Pamela Weathers’ note of January 2014)

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Efferth T (2009) Artemisinin: a versatile weapon from traditional Chinese medicine. Herbal drugs: ethnomedicine to modern medicine. K. G. Ramawat. Heidelberg, Springer Verlag: 179-‐194. Ezeamama AE, Spieelman D, Hertzmark e, Bosch RJ, Manji KP, Duggan C, Kupka R, Lo MW, Okuma JO, Kisenge R, Aboud S, Fawzi WW (2012) J Infect dis 205:1486-‐1494. Lubbe A, Seibert I, Klimkait T, van der Kooy F (2012) Ethnopharmacology in overdrive: the remarkable anti-‐HIV activity of Artemisia annua. J Ethnopharmacol 141:854-‐859. Marconi VC (2011) Commentary: Malaria and HIV transmission: old meets new in a deadly partnership or an opportunity for healthcare synergism? International J Epidemiol. 40:940–944

Kamya M, Gsasira AF, Yeka A, Bakyaita N, Nsobya SL, Francis D, Rosenthal PJ, Dorsey g, HavlirD (2006) Effect of HIV-‐1 infection on antimalarial treatment outcomes in Uganda: a population-‐based study. J Infect Dis 193:9-‐15. Tusting LS, Willey B, Lucas H, Thompson J, Kafy HT, Smith R, Lindsay SW (2013) Socioeconomic development as an intervention against malaria: a systematic review and meta-‐analysis. Lancet 382: 963–72. 4. Water purification

# GUEYE Elhadji Omar, Artistide Le Dantec Hospital, Bacteriology Virology Laboratory, Malaria Section, Dakar (financed by Foundation ARCELORMITAL), non dated. # Research team of Lavoisier Hydro sciences Laboratory, Bangui, March 2008. PhD Human Biology and Pathology. (ED-‐SEV) 5. Studies on the School Performance of Children # FERNANDO S. DD. M. GUNAWARDENA, M. R. S. S. BANDARA, D. DE SILVA, R. CARTER, K. N. MENDIS, AND A. R. WICKREMASINGHE, The Impact of Repeated Malaria Attacks on the School Performance of Children. Department of Parasitology, Faculty of Medicine, University of Colombo, PO Box 271, Kynsey Road, Colombo 8, Sri Lanka. August 2003. # THULLIEZ J. Malaria and Primary Education!: A Cross-‐Country Analysis on Primary Repetition and Completion Rates, Document de travail du Centre d’Economie de la Sorbone. Centre National de la Recherche Scientifique. 2007.13. Mai 2007. 6. Other studies # Clinical study managed by a research team from Montagnes University in Cameroun, 2009 # COUPER Mary R., “Quality Problems with Antimalarials. Quality Assurance And Safety: Medicines”, World Health Organization presentation # MESHNICK S.R., in FERREIRA Jorge & JANICK Jules, “New Crop Factsheet, Annual Wormwood (Artemisia annua L.)”, 2009, see # www.hort.purdue.edu/newcrop/cropfactsheets/artemisia.pdf # National Institute of Health of the Ministry of Health of Mozambique, through the Department of Medicinal Plants and Traditional Medicine (studies initiated in 2004) # Radiology an Oncology Research Institut research team, “In vitro study of antitumor effect of Artemisia annua tea”, Belgrade, Serbia. # Research conducted by the National Health Ministry, Mozambique, March 2009 # WHO Website: www.who.int

ANNEX 2 BACKGROUND INFORMATION ON IDAYINTERNATIONAL I.1. LEGAL AND CONTACT INFORMATION Name: IDAY-International (IDAY) Year of creation: 2005 Date of registration : 28/01/2008 as non-profit seeking international association (aisbl) and status:under Belgium law.Registration n°0895.443.325 Address: Rue des Jambes 191420 Braine-l’Alleud, Belgium Email: info@iday.org Tel: +32 (0)2 385 44 13 Website:

www.iday.org

Legal representative : Jean-Jacques SCHUL - Chairman of the Board Email :jjschul@iday.org The IDAY network is committed to promoting quality basic education for all children and youth in Africa, with a particular focus on vulnerable and marginalized children. A majority of IDAY members are African civil society organisations that form national coalitions that advocate for the right to basic education in their country. The IDAY network comprises 18 national coalitions in Africa and members in 4 European countries. IDAY-International is the apex organisation of the network: it coordinates and supports the local coalitions under a bottom-up decision-making and communication system. Each national coalition elects its advocacy themes based on local priorities and opportunities. They also participate in IDAY regional programmes coordinated by IDAY-International: legal recognition and vocational literacy training of domestic workers in East African and in the DRC; education of minors deprived of liberty; improvement of the learning environment through improved health in African schools.

I.2. GOVERNANCE IDAY-International is governed by 3 bodies: -‐

the General Assembly, which comprises all national coalitions (Africa and Europe)

-‐

The Board of Directors (7 members)

-‐

The Management Committee (11 members operating from Belgium)

Organigram of IDAY

AFRICAN EFFECTIVE MEMBERS

EUROPEAN EFFECTIVE MEMBERS

(NATIONAL COALITIONS)

GENERAL ASSEMBLY

nominates

nominates HONORARY COMMITTEE

BOARD OF DIRECTORS

IMPLEMENTATION PARTNERS

appoints MANAGEMENT COMMITTEE

I.3. FINANCES IDAY-International’s annual Activity and Financial Reports are published on its website (www.iday.org). Accounts are audited yearly by an external auditor.

I.4. PARTNER NETWORKS AND ORGANISATIONS •

the Nigerians in Diaspora Organisations in Europe (NIDOE),

•

the Forum of African Women Educationalists (FAWE),

•

the African Network for the Prevention and Protection against Children Abuse and Neglect (ANPPCAN),

•

The Kenyatta University (conduct of clinical tests on the use of natural extracts of Artemisia annua against malaria),

•

Iwerliewen (Luxembourg NGO),

•

Defence for Children International (DCI)-‐Belgium,

•

Global Campaign for Education (IDAY-‐International is a regional member)