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Multi-disciplinary University Traditional Health Initiative (MUTHI):
Building Sustainable Research Capacity on Plants for Better Public Health in Africa

Final Report Summary - MUTHI (Multi-disciplinary University Traditional Health Initiative (MUTHI):<br/>Building Sustainable Research Capacity on Plants for Better Public Health in Africa)

Executive Summary:
It is recognised that research must be a basis for better health throughout Africa (e.g. Global Ministerial Forum on Research for Health, Bamako 2008, Beijing declaration 2008). As a consequence it is a priority to build research capacities in the African continent that will set good standards for the development of improved health security and systems in the future. In several African countries western medicine is not widely available, and WHO has recognised the role of traditional medicine and its practitioners in primary health care. MUTHI is a Coordination and Support Action project under the EC’s 7th Framework Programme (Health). The overall objective of the project is to create sustainable research capacity and research networks between the participants in Africa (Mali, South Africa and Uganda), collaborating neighbouring institutions, and the European project participants to obtain improved health in Africa. We have identified needs and started to develop and deliver research training programmes. The research institutions from Africa taking part in the project have implemented research methodologies so that they are able to improve traditional medicines, identify bio-active compounds, and clinically evaluate and register medicinal products that are used for the treatment of illnesses that are frequent in African countries.
In most African countries the availability of so-called western medicine is scarce, and there is still a living tradition for the use of herbal remedies for treating the ailments the local population suffer from. Several of the remedies used have never undergone any quality control, neither on the chemical or biological side, nor on the possible toxicological problems some of these plant products may give rise to. When the MUTHI Project started there exist limited laboratory facilities, including personal skills, for analysing natural compounds, and clinical trials on herbal remedies were non-existent for most products. It was also important for the practitioners to improve their knowledge of intellectual property rights (IPR).
The overall objective of MUTHI was to create sustainable research capacity and research networks between the participants in Africa, collaborating neighbouring institutions, and the European project participants to obtain improved health in Africa. The primary object of research was thus traditional medicine and the project did especially focus on the products present in water extracts. Training in all the mentioned methodologies was finalised in period 3 of the MUTHI Project and now, all the African partners are able to perform both the chemical, biological and toxicological methods important for determining what products in the plants that are responsible for the bioactivities. They have all been trained in how to perform RTO (Retrospective treatment outcome) studies, as well as in preparing MOUs with traditional healers, they know how to deal with IPR (Intellectual property rights) as well as how to apply to ethics committees in the relevant countries for performing the RTO studies.
All the four African partners have also been trained in research methodologies that they can utilise in the future in collaboration with the European partners, they have been trained in conference presentations and also in writing research publications for peer reviewed international journals.

Project Context and Objectives:
The MUTHI project´s context and objectives

Background for the proposed project
In November 2008 the Global Ministerial Forum on Research for Health held a meeting in Bamako, Mali, where the focus was strengthening research for health, development and equity. In the call for action following this meeting, it was recognised that research must be a basis for better health throughout Africa, and that a lot of the diseases on the continent are caused by poverty.

Due to this, it was recommended that it should be a priority to build research capacities in the continent that could set good standards for development of better health security and better health systems in the future (The Bamako Call to Action on Research for Health The Lancet, Volume 372, Issue 9653, Page 1855, 29 November 2008; WHO’s role and responsibilities in health research EXECUTIVE BOARD EB124/12 Add.2 124th Session 6 January 2009 Provisional agenda item 4.9 ). The strengthening of scientific and technological collaboration between African research institutions and capacity building were put forward as important for better health on the continent. The lack of cost-effectiveness in the major health programs and more impact research was emphasized in the document following the Bamako meeting.

In October 2008 ANDI (African Network for Drugs and Diagnostic Innovation) had a meeting in Nigeria, and as part of the Executive summary from the meeting it is said that “In summary, initial data from mapping exercise suggest ..... 2) in the area of traditional medicines, there remains a need for more systematic research evaluation and validation of the biological activities of traditional medicines “.

It was for this reason as well, recommended that building research capacities in the continent that could set good standards for development of better health security and better health systems in the future should be a priority.

In several African countries western medicine was, and is still not widely available. This may be due to cost, distribution to rural areas being too difficult and an escalation in the production of counterfeit medicines. Due to these challenges, WHO has recommended the use of traditional medicine and has also discussed this in several meetings since the first in Alma Ata in 1978; being the first formal recognition of the role of traditional medicine and its practitioners in primary health care (Herbal and Traditional Medicines, WHO Congress on Traditional Medicine and the Beijing declaration, WHO Drug Information, Vol. 23, No.1 2009). In November 2008 the Beijing declaration was adopted by the WHO Congress on Traditional Medicine where it is also stated that the participants agreed on the following:
Recognizing traditional medicine as one of the resources of primary health care services to increase availability and affordability and to contribute to improve health outcomes including those mentioned in the Millennium Development Goals.
Governments have a responsibility for the health of their people and should formulate national policies, regulations and standards, as part of comprehensive national health systems to ensureappropriate, safe and effective use of traditional medicine.
Traditional medicine should be further developed based on research and innovation in line with the “Global strategy and plan of action on public health, innovation and intellectual property” adopted at the Sixty-first World Health Assembly in resolution WHA61.21 in 2008. Governments, international organizations and other stakeholders should collaborate in implementing the global strategy and plan of action.

The Concept of the four European and four African research teams in this Co-ordination and Support project, MUTHI, was to develop an Ethnopharmacology research training action. The project was addressing health research in Africa focusing in particular on the future potential of traditional medicine, and especially the use of African plants in a health context, and was designed to:
• Obtain sustainable research in this context through identifying optimal networks between the participants in Africa and collaborating neighbouring institutions in particular, as well as the European participants.
• Strengthen research capacity to identify bio-active compounds in traditional plant-derived medicines used in Mali, Uganda, and South Africa, with potential efficacy for improving health.
• Increase the research capability to the use of traditional medicines as alternative or complementary products to western medicine in the treatment of infectious diseases caused by microorganisms, fungi, parasites and other ailments.
• Assess specific training needs in the African partners in relation to their abilities to develop plant / compound identification and product development. This was to enable scaled up production and testing of the local compounds, applications for treatment, and assessments of the efficacy of those treatments.
• Develop a set of integrated science based, skills advancing, and applied innovation enhancing academic research training programs in the four African partners.
• Identify needs, develop and deliver research training programs to improve traditional medicines, identify bio-active compounds, clinically evaluate and register medicinal products.

In order to achieve this, we would:
• Use already recorded knowledge on the use of medicinal plants against the ailments in focus from the African countries for preparation of Improved Traditional Medicines (ITMs).
• Partner with African traditional health practitioners to share, integrate and evaluate new information using participatory medical anthropological and ethnopharmacological methods.
• Train all African participants in the domains of medical anthropology, local knowledge systems and local perceptions of the healers and the local population.
• Develop a systematic methodology for the screening and testing of plants that could be candidates for ITMs.
• Develop a methodology for the quality assurance (chemical) of the products from the identification of the plant material used all the way through to the final products with batch to batch standardisation.
• Develop bioassays for securing the desired bioactivity in the products produced.
• Develop methodologies and protocols for observational and clinical trials of ITMs.
• Assess training needs of participating African institutions, in order to enable them to conduct all the necessary steps to develop quality control, clinically evaluate and register standardised ITMs.
• Design appropriate forms of training to address these needs, including online courses on theoretical aspects, workshops and participation in research projects for training in practical aspects which may be used as modules in an existing MSc degree.
• Integrate all of these steps in training programs that are capable of being continued after the Co-ordination Action has ended in such a way as to ensure that the Action will result in the sustainable development of capacity for health research in three different African states from the North West, North East and South of Africa
• Make these training courses more widely available to other African institutions who are not partners in this project, but who have similar training needs.

The need for the African institutions was based on the strengthening of their research capacities within the areas of:

1. Medical Anthropology, Ethnobotany and Ethnopharmacology including rules and regulations related to Intellectual Property Rights.
2. Methodologies for determining which plants are the most relevant for the production of improved traditional medicines and nutraceuticals.
3. Methods for isolation and identification of natural products from the water extracts with important biological effects.
4. Methods for biological assays for efficacy and safety determination of important products from the relevant plants.
5. Development of methodologies and protocols for observational and clinical trials of plants with medicinal and nutraceutical value.
6. Method for producing monographs for medicinal and nutraceutical plants for the African Pharmacopoeia based on the standards from the European Pharmacopoeia.

The Overall Objective was to create sustainable research capacity and research networks between the participants in Africa and collaborating neighbouring institutions in particular, as well as with the European participants, in order to obtain improved health in Africa.

The Specific Objectives of the proposal included:
• To identify and respond to the training needs of researchers focused on medicinal plants as candidates for Improved Traditional Medicines (ITMs).
• To develop capacity of researchers to conduct high quality medical anthropology, ethnobotanical and ethnopharmacological research (WP1).
• To develop capacity of researchers to use quality analyses and bioassays to find and evaluate bioactivities of phytomedicines/nutraceuticals derived from plants (WP2 and WP3).
• To develop reference guidelines for quality analyses, biological testing, and safety evaluation of phytomedicines and nutraceuticals (WP2 and WP3).
• To assess and respond to needs in preclinical test-training of the participating African institutes (WP3 and WP4).
• To develop the capacity of researchers on ITMs and nutraceuticals to develop, conduct, assess, and analyse the outputs of observational and clinical trials using ITMs and plant derived compounds (WP4 and WP5).
• To train researchers in related fields, including ethics, legislative requirements, IPR protection and benefit-sharing (WP5) around ITM and plant-derived drugs.

Project Results:
RESULTS OF MUTHI
The MUTHI project is a coordination and support action, thus the focus has been on the training of the personnel in the four African partner institutions. The description of the results obtained in the MUTHI project is based on the deliverables related to each work package. The deliverables have all been uploaded and if further information than what can be found in the report below is desirable, this can be found in the relevant deliverables. The layout of the report follows the work packages and the deliverables belonging to these.
MUTHI WP1 Medical anthropology and ethnopharmacology.

MUTHI Deliverable D1.1 Ethnobotany, Traditional Medicine and Medical
Anthropology
Executive summary of D1.1
The aim of this work package (WP1) was to develop the capacity of researchers from a variety of disciplines to gain insights into the worldview and health paradigms of traditional healers and conduct high quality ethnobotanical and ethnopharmacological research. To develop the capacities of the researchers participating in this work package, trainings were provided based on individual and local needs. For the first deliverable of this work package (D1.1) 8 researchers were trained in a workshop in the fields of Medical anthropology and Ethnobotany to conduct an ethnographic study supervised by partner 7 (UvA) and by the different MUTHI partners situated in Uganda, Mali and South Africa. The participants finished the training trajectory by delivering 5 (collaborative) reports reflecting their study methods, process and outcome. Participants had given the highest level of importance – in rank order – to develop a solid research protocol within the field of medical anthropology and ethnobotany including interview techniques; collecting plants; preparing a botanical collection; recording use of plant parts and their condition in addition to developing more general aspects such as writing and speaking in English and publishing their results.
In this deliverable the outcome of our training need assessments and the ethnopharmacological studies are presented.

RESULTS AND DISCUSSION
Eight participants wrote six reports based on their cooperative anthropological fieldwork in several countries in Africa (Mali, Uganda, S Africa, Zimbabwe). The participants improved various skills as they started with limited knowledge of the medical anthropological approach to ethnobotany; they learned to formulate proper research questions, to develop a solid and clear research design, and to conduct proper ethnographic fieldwork. In the following sections we present the summaries of the research; summaries written by the participants themselves (full reports are attached to Deliverable D1.1).
These summaries represent the outcome of intensive training and supervision of different MUTHI partners and much effort done by participants themselves: a fruitful collaboration and synergy of various types of expertise and interests.

a.Exploration of antimalarial medicinal plants in headman Muzite area and Chriga village in Chipinge district, Zimbabe By Talkmore Ngarivhume.
Zimbabwe has a relatively high malaria prevalence rates and research on traditional herbs as a potential source of low-cost and effective antimalarial drugs could provide an alternative to existing therapeutic agents. This survey was aimed at establishing how malaria is conceptualized and diagnosed by traditional healers, and documenting medicinal plants and their administration in the management of malaria in Headman Muzite area and Chiriga village, in southeastern district of Chipinge in Manicaland province, Zimbabwe. Individual interviews were held with twelve traditional healers chosen with the help of the headman and leaders of the Zimbabwe National Traditional Healers Association (ZINATHA). The interview guide which was translated into the local language was divided in three sections: a) personal details of participants; b) diseases the participants consider their expert
areas and c) the malaria section. The objectives, benefits, risks and general procedures of the survey were explained to participants before asking them to sign informed consent forms. Twenty-six plants belonging to sixteen plant families were used to manage malaria in Headman Muzite area and Chiriga village. Specimen were collected and identified at the Harare Botanical Garden, Zimbabwe. All the interviewed healers are familiar with the malaria symptoms. Mostly tree roots are used for malaria prophylaxis and treatment in this area. Healers consider their knowledge of plant remedy as spiritual family heritages. They believe that plants lose their potential to heal when the identities of the plants are not strictly safeguarded. There is great need for sustainable collection techniques for the remedies because the predominant use of tree roots easily depletes the species. The results from this survey underscored the need to acquire and preserve the traditional system for managing malaria by proper documentation, identification of the species used and more scientific information concerning their efficacy and safety. This could lead to improved practices in the traditional health system and alternative cheaper medications.

b.Ethnobotanical survey of plants used by traditional healers and herbalists to treat HIV and related symptoms in Strand, Western Cape, South Africa by Tarryn Blouws and Denver Davids.
This study fell within the framework of the larger multidisciplinary university health initiative (MUTHI) objectives to investigate and document the use of local medicinal plants for the treatment of HIV and symptoms of related opportunistic infections such as tuberculosis, thrush and shingles. In this study we ethnographically document when, under which circumstances and where plants are collected for use.
The research results were from six months fieldwork in Strand, Western Cape and the collection of plants from Mpoza, Eastern Cape for analytical reasons. This was the first ethnobotanical study which ‘follows’ traditional healers in the Western Cape to a site in the Eastern Cape where they collect plants. It was collected seventeen plants from different plant families, which traditional healers reported to use as treatment for suspected HIV and related symptoms. For each plant it was described the medicinal uses, preparatory techniques and plant parts used as suggested by traditional healers. The seventeen collected plants were reported as “strong” for the treatment of HIV and TB as individual diseases, but
were almost always utilized in a mixture. These remedies work in a variety of ways to affect the entire body. The observations revealed that HIV and TB are conceptualized as “poisons” which stemmed from the external environment in the form of pollution as well as a result of social and economic conditions. Although the plants collected in this study revealed the most commonly used plants for treating HIV, TB, HIV-TB co-infection, and related opportunistic infections, the remedies utilized consisted of a diversity of plants to treat a variety of illness conditions. It would be beneficial to understanding the disease aetiologies of traditional healers, the plants utilized and the conservation of traditional plant knowledge.

c.Ethnobotanical Study of Plants Used Against Malaria in the Health Area of Selingue, Mali Nouhoum Diarra and Adiaratou Togola.
In Mali, malaria is the leading cause of medical consultation and death. This particularly affects the elderly mothers and children under 5 years.
The dam of Selingue in the District of Yanfolila allows the production of electricity, irrigation, development of fisheries market gardening etc. This has allowed a significant increase in villages around this area. However, the water storage at the dam of Selingue supported the proliferation of mosquitos, transforming the area of Selingue as a malaria area. The dam is a
significant factor of socio-economic development, by supporting activities like fishing, farming and gardening. Additionally it supports significant population growth, which without good hygiene leads to environmental pollution and the development of diseases such as malaria and diarrhea.
This survey was done in six villages and 50 traditional healers were interviewed. Two concepts of malaria (Simple and complicated malaria) were cited and 98 plants used to treat malaria were identified. These plants were mainly used as decoction or body bath.
The investigation showed a great diversity in Selingue local flora and its use in the treatment of malaria in this area. Malaria or Soumaya was a well-known disease in the zone of Sélingue. Food attitudes and mosquitos are perceived to be the most important causes of the disease. Trichilia emetica, Mitragyna inermis, Nauclea latifolia, Cassia sieberiana,
Cochlospermum tinctorium, Anogeissus leiocarpus, Guiera senegalensis, Entada africana were quoted as the most used in the treatment of malaria. Plant leaves were most often used in the treatment of malaria in Sélingué. Decoction was the general mode of preparation of plant materials. Oral and body bath represent the most used modes of administration. The plants were very useful in local people life style. They made their best to preserve them.

d.Medicinal Plants Used to Treat Malaria in Cegere Sub-County, Apac district, Northern Uganda Godwin Anywar.
This study was undertaken to document the medicinal plants used for treating malaria and how the people of the Apac district used these plants. The study was also geared towards understanding the traditional concept of malaria in Apac district. Apac is located in Northern Uganda and is one of the areas with the highest malaria infection rates in the world. This study focused on documenting the medicinal plants used for treating malaria, as well as the traditional practices involved. This information can form a useful basis for gaining deeper insights into how the malaria problem in Apac is locally managed. The required information was gathered using interviews, semi-structured questionnaires, focus group discussions, field observations and field walks. A total of 15 plant species belonging to 9 plant families were documented as being used for treating malaria in Apac. The most frequently cited plant for treating malaria was Schkuhria pinnata mentioned by 76.7% of the respondents. The family Asteraceae had most of the medicinal plant species used for treating malaria with 5 plant species. The commonest method of preparation was through making decoctions and the commonest method of administration was oral. Much as the malaria rates were reported to be among the highest in Apac, relatively fewer medicinal plants were used for treating malaria, compared to other regions in Uganda. Generally, there was wide spread knowledge on the use of medicinal plants to treat malaria. The people interviewed also demonstrated a clear understanding of what malaria is and how it can be prevented and treated traditionally.

e.Ethnopharmacological Survey of Plants Used in the Management of Tuberculosis in the Free State, South Africa. Khanya Phungulaa, Malefu Khamaneb.
Tuberculosis (TB) is a global health problem and one of the leading infectious diseases causing high mortality in developing countries. South Africa has one of the highest tuberculosis rates in the world. The area of study, the Free State, has the second smallest population but the fourth highest incidence of tuberculosis in South Africa. There have been claims that traditional healers are able to treat the symptoms of TB by plants but their work is not well documented. This stimulated a search for plant species used by the local traditional healers, in order to provide candidate plants for new drugs. The diagnosis of the illness, the mode of treatment and the preparation of remedies were all investigated.
From this study, it can be concluded that a large number of different plants are used for the treatment of TB in the 3 Free State communities investigated. There was little overlapping of the species of plants among the different THPs, probably because of the secrecy surrounding each DHP’s own personal recipe. The two most used plants were Dicoma anomala (Asteraceae) and Leonotis lanceolata (Fabaceae).

f.Ethnobotanical survey of plants used by traditional healers for the treatment of schizophrenia in Bandiagara district, Mali, West Africa, Pakuy Pierre Mounkoro.
Schizophrenia is the most serious mental illness in the world. According to studies conducted in the district of Bandiagara, its prevalence varied from 1 to 3%. The main goal of this study was to document medicinal plants and medicinal plant related knowledge used in management of schizophrenia in the district of Bandiagara. This explorative study was based on qualitative research methods (interviews using face to face questionnaire, discussion, field notes) to investigate the views of healers on schizophrenia and the plants used for healing schizophrenia in the district of Bandiagara. A total of 20 healers were interviewed. The main concepts of schizophrenia were: igne (wind), Guire (witchcraft), ogouloubelem (spirits of the bush), yebin (dwarf spirits), yapilin (spirits of dead pregnant women), Amba Wede (the madness of god), Wede welewele (hot madness), Wede Kalal (cold madness) and Wede pirou (true madness). Causes mentioned were the attack by the spirits of various kinds, bad luck, witchcraft and natural causes (God). The traditional treatment of schizophrenia reported by traditional medicine practitioners included 44 species belonging to 21 plant families. We notice that the most commonly used plants have already or are almost extinct from the Dogon country biodiversity. The traditional treatment of schizophrenia includes many resources among which endangered plants or plants that are in the process of being so in the Dogon Plateau of Bandiagara. It would also be necessary to carry out extensive studies of these plants used by traditional healers on the chemical, toxicological and pharmacological aspects in order to determine the acute toxicity of the three most commonly used plants and chemical groups of the ten most commonly used plants. The ultimate goal being the production of an improved traditional medicine against mental health by the Department of Traditional Medicine.

Conclusion
Participants started the project with limited or little understanding of medical anthropology as an academic field and specific methodology to study the use of traditional medicine. The full process demonstrated important improvements in their skills of research and knowledge of TM. Participants learned how to formulate good research questions, to design a solid research plan, to employ anthropological fieldwork and to report their findings in a proper and academically challenging way. Importantly, most participants are eager to continue pursuing studying traditional medicine and will benefit greatly from the last year of intensive training and research. Next to personal ambitions, their work reflects good and important insights in topics still understudied. This should be considered the beginning of fruitful alliances between ways of conducting research in the field of medicine, healthcare and between researchers from different parts of the world. As such, the aims to develop and
improve individual skills of researching TM as well as producing important, missing knowledge on the actual use and effect of plants and TM are being met.

MUTHI Deliverable No. 1.2 Treatment seeking strategies
Executive summary
For the second deliverable of this work package 8 researchers needed to be trained to conduct a Retrospective Treatment Outcome (RTO) study in order to identify treatment and help seeking strategies and the modification of explanatory models during the subsequent help seeking steps. The participating researchers were trained in a 2-day workshop that took place in Uganda on how to conduct an RTO study to be able to complete one in their own country supervised by partner 7 (UvA), partner 8 (UOXF) and by the different MUTHI partners situated in Mali, South Africa and Uganda. The participants finished the training trajectory for D 1.2 by delivering (collaborative) reports reflecting their study methods, process and outcome. In this report the training program is presented, their work and assessment of the outcome of the full training trajectory for this deliverable.

Retrospective treatment-outcome study of the traditional treatment of presumed malaria in a malaria endemic area in Mali (UdB)
Development of the protocol
A protocol was written by Dr Nouhoum Diarra and Dr Adama Denou, both researchers at the University of Bamako. The protocol was submitted to the Oxford Tropical Research Ethics Committee and received approval. The protocol was then submitted to the Ethics Committee of the Institut National de Recherche en Santé Publique (INRSP) in Bamako, Mali, and was approved.
Fieldwork
The fieldwork was conducted by Dr Nouhoum Diarra and Dr Adama Denou. 400 households were interviewed who all had a recent case of malaria. Voucher specimens were taken of all the plants and most have been identified.
Data entry and analysis
A database was created using the Epi-info software in September 2014 by Nouhoum Diarra, with hands-on training and supervision by partner 8, on site in Bamako. When data entry was completed, partner 8 trained him to do the analysis using Epi-info, and supported him in writing an article to be submitted for publication in an international scientific journal.

Retrospective Study of Treatment- Seeking for Presumed Malaria in Uganda (MAK)
Development of the protocol
The protocol was developed by particpants from Mak (partner4) and was submitted to the Institutional Ethical Review Board of Mbarara University of Science and Technology and formal approval for the study was given by the MUST. The protocol was then submitted for ethical approval to the Oxford Tropical Research Ethics Committee (OXTREC) and was approved prior to the field studies.
Fieldwork
This study was conducted using the same protocol in two different districts of Uganda: Apac district (central Uganda) and Mbarara district (south-west Uganda). In Apac district, the RTO was carried in the parishes of Chegere, Ongica, Atigolwok and Ilee. These parishes were randomly selected from a total of 64 parishes in the whole district using the lottery method. A total of 34 villages were used for conducting the study. A total of 400 respondents who met the inclusion criteria were interviewed by three research assistants under the
supervision of Godwin Anywar. In Mbarara district, the RTO study also started in mid-October. Thirty-five villages were selected at random within Nyakayojo and Mwiizi subcounties. Members of village health teams were also asked to help identify any patients who had recently had malaria.
Data entry and analysis
A database was designed in Epi-info by the investigators with hands-on training and support from partner 8. He trained the research assistants in data entry. The database
was piloted and modified following feedback from the investigators and fieldworkers.
Lessons learned
The investigators all agreed that writing the protocol, submitting it for ethical approval, responding to comments from the ethics committees, and conducting the research had been a very enriching and useful learning experience.
Reporting, dissemination and notification of results
Final reports will be submitted to the Uganda National Council of Science and Technology, Ministry of Health, OXTREC, Makerere University and Mbarara University libraries. Results will be reported in a scientific article and submitted to a peer-reviewed journal, and will be presented in scientific meetings. The results will be used to prioritise public health interventions and to prioritise medicinal plants for further research.

Retrospective treatment outcome study of medicinal plants used to
manage chronic cough in Genadendal, Western Cape (UWC)
Development of the protocol
The protocol was written by Denver Davids (a PhD student) and Prof Diana Gibson, with comments and feedback from partners 7 and 8. Both of these participated in the training workshop in Kampala (Feb 2013). Ethical approval for the RTO project was obtained from the Senate Ethics Committee UWC.
Fieldwork
The survey was carried out in the town of Genadendal, Western Cape, South Africa and two outstations Voorstekraal and Bereaville. Genadendal proper (oukraal, sewensfontein, kersiesdorp, berg and main) was surveyed using a convenience sampling method. A house-to-house approach was employed to screen potential participants for chronic cough.
Written prior informed consent was obtained from each participant prior to completion of the questionnaire. The semi-structured questionnaires were completed by three researchers in the preferred language of the respondents, which was most often Afrikaans. A treatment and outcomes table were used to enter data on duration of treatment, medicinal and allopathic medication usage Researchers screened 513 houses and 344 respondents were selected. The proportion of participants with chronic cough who sought treatment was 64.9%. The remaining 35.1% did not seek treatment (allopathic or herbal); or did not wish to continue with the questionnaire.
Data entry and analysis
Data was captured on paper forms, response papers, and field notes. The data was then coded and entered by category using Microsoft Excel. Data was analysed using SPSS 20 software with the aid of a statistician. Descriptive statistics such as frequency, tables, percentage and graphs were used for data description. Participants reported the names of 54 plants belonging to 47 families used to treat chronic cough. The plants were used in remedies containing up to nine plants. These plants are all indigenous to South Africa. It was found that 67.1% of participants prescribed their own herbal remedies and 5.2% sought herbal remedies from family and friends. The plants used are collected from the surrounding Genadendal and Greyton mountain ranges. Another 24.8% bought plants from herbalists (Bossiesdokors / kruiedoktors: bush doctors) and Rastafarians. Further analysis will continue beyond the end of the MUTHI project, with support from partner 7 and 8 to determine which remedies were associated with the best outcomes. It is hoped that a publication in a scientific journal will result from this.

Retrospective treatment outcome analysis on the use of medicinal plants to alleviate diarrhoea in the Thaba ‘Nchu area of the Free State Province, South Africa (UFS)
Development of the protocol
The protocol was developed by Susan Bonnet, Anke Wilhelm-Mouton, Khanya Phungula and Malefu Khamane, who are all associated with the University of the Free State, with support from partner 7 and 8. All the participants participated in training workshops, either as part of the Kampala Wp1 workshop in February 2013, or as part of the Durban WP4 workshop in October 2013. The protocol was accepted by the Ethics committee at the University of Frre State.
Fieldwork
The fieldwork was carried out in the Thaba ‘Nchu area of the Free State Province, South Africa. The questionnaires were completed by the research assistants during the interviews. A total of 32 participants were interviewed. Plants were identified via correlation of the Sesotho name with the scientific name in published plant lists.
Data entry and analysis
Overall 13 plants were cited, only 4 of them by more than 2 respondents. The most commonly used plants are Xysmalobium undulatum (pohotsela), 50%, Punica granatum L. (kgarinati), 35% and Dicoma anomala (hlwenya), 20%. These plants are often used together, with P. granatum (pomegranate peel) being used for abdominal pain.
Although this was only a pilot study on a small sample size, preliminary indications are that the traditional remedies are effective for treating diarrhea, with X. undulatum (pohotsela) used as the main medicine (or ingredient of a mixture of plants) to treat diarrhea in the Thaba ‘Nchu area. The sample size is too small to enable publication of these results, but by participating in the writing of the protocol, the conduct of interviews, and analysis of the results, the researchers at UFS have learned the principles of conducting an RTO study and will be able to apply this study design in future when the opportunity arises.

Discussion for D1.2
For deliverable 1.2 it was our goal for 8 researchers to have conducted a study on treatment seeking strategies and explanatory models related to major diseases and health problems (retrospective treatment-outcome study). We have exceeded this goal. All of the African MUTHI partners conducted a RTO study, involving at least 2 members from
each institution (2 from Mali, 3 from Uganda, 2 from UWC and 4 from UFS). In addition a RTO study was conducted by an Ethiopian participant who had attended the workshop in Kampala in Feb 2013 (using another source of funds), with support from partner 8. Prof Tabuti, of the Department of Botany in Makerere, who participated in the same workshop, has also obtained funds from another source and is planning to start another RTO study in the Jinja area of Uganda, with support from partners 7 and 8.

Conclusion for WP1
The MUTHI partners involved in WP1 have exceeded the goal set in the project, with in total 13 researchers having conducted a retrospective treatment-outcome study. Most of these are members of staff in their respective universities so will be able to cascade this learning to their students and other staff, and will be able to apply this method in future studies. In the course of the project the RTO methodology was tried in many different contexts and settings, and new challenges were discovered, which will also help to refine the methodology for future use. The partnerships and collaborations established will outlast the period of the MUTHI project and it is our intention that several scientific articles will be published as a result of this research. Additionally, all the 4 African partner laboratories have gained sufficient knowledge for performing ethnopharmacological and ethnobotanical studies.

WP2 Quality control of phytomedicines and nutraceuticals.
MUTHI Deliverable D2.1 Sustainable chemical methods
Executive summary:
The aim of D2.1 of the MUTHI project was to achieve sustainable chemical methods for quality control of ITMs and nutraceuticals at Partners 4 (Mak), 3 (UdB), 6 (UFS), and 5 (UWC) based on training of African scientists, and by implementation of relevant methods at the Africans partners institutions. The work performed was based upon an initial assessment where Partners 3 and 4 in particular, had identified their needs and required expertise. A total of 25 and 18 staff/students attending two workshops (in Bamako and Kampala, respectively), have got training in fingerprint methods as well as in extraction, isolation, purification, structure elucidation and quantitation of various plants products addressed through lectures, group work, and experimental exercises. Staff/students from the African partners have during the project period travelled to Partners 1, 2 and 4 to be trained in techniques needed for analysis and quality control of plants, plant preparations and products. This training has been focused on isolation and purification methods, in methods used for measurements of quantitative data, in production of pure reference compounds, and in structure determination of in particular anthocyanins and polysaccharides. Partners 3 and 6 have additionally focused on local training of staff/students in the field. Staff of Partners 4 and 3 have also been trained in maintenance of adequate instrumentation by Partners 2 and 1. Partners 1, 2 and 6 have provided advanced instrumentation and knowledge transfer necessary for adequate training in modern isolation and analytical techniques. In addition selected methods have been implemented at the Africans partners. Twelve African monographs described under D2.2 are also related to training and implementation of sustainable chemical methods in the laboratories of the African partners 3-6.
Workshops on sustainable chemical methods
Partners 2 (UiB), 1 (UiO), 3(UdB), 4 (Mak), and 6 (UFS), have organised two Chemical workshops at Department of Traditional Medicine in Bamako and at at Makerere University, Kampala. A total of 25 and 18 students attended, respectively.
The Chemical workshops covered training in isolation and purification methods, structure determination of pure compounds and fingerprint survey methods, and writing plant monographs. Practical aspects were also explored on analytical high-performance liquid chromatography (HPLC) and thin-layer chromatography (TLC) in the analysis of polyphenols, and in interpretation of various one-dimensional and two-dimensional nuclear magnetic resonance (NMR) data. The content of these training courses were methodologies related to the requirements for producing Monographs for Pharmacopoeias as well as for performing research on the content of compounds present in the plants. How to analyse polysaccharides were also included in the workshops. The laboratory courses started with a series of lectures covering important aspects related to chromatography, spectroscopy, mass spectrometry as well as methods related to different types of instrumentation. Methods relevant for each laboratory and especially the methods necessary for describing chemical qualities of plants were implemented in all 4 laboratories. These methods were used for the preparation of new monographs for the pharmacopoeias of the plants chosen by each partner.
Training of African students/researchers/technicians in sustainable chemical methods
All partners related to D2.1 had some basic infrastructure for carrying out purification, isolation and structural elucidation of natural compounds. Partners 1, 2 and 6 have provided advanced instrumentation required for adequate training in isolation and analytical techniques – mainly focussed on chromatographic and spectroscopic methods. African students/research personnel have visited Partners 1–6 for training in various techniques. Staff from Partners 3 and 4 has visited Partners 1 and 2 for training in use and maintenance of chromatographic and spectroscopic instrumentation. Partners 3 and 6 have additionally focused on local training of staff/students in the fields.
Training of African students/researchers/technicians in sustainable chemical methods have included botanical identification and preparation of samples, proper description of samples including microscopy, purification and isolation methods including various chromatographic techniques, and identification methods including chromatographic and spectroscopic techniques, and chemical tests. The African partners (Partners 3–6, UdB, Mak, UWC and UFS) have in particular learned how to treat and analyse plant and plant products based on advanced expertise existing in the consortium, focused on polysaccharides and polyphenols/anthocyanins as case studies of high and low molecular compounds, respectively:
Training of Partner 3 (UdB)
In Bamako, Mali, UdB (partner 3) led the theoretical and practical training of 5 researchers from the Faculty of Science and Technique and the Faculty of Pharmacy, Bamako, in the use of HPLC isolation techniques of plants compounds. The lectures were followed by practical session on HPLC. Partner 3 has collected several plants traditionally used against malaria, and the possible immunomodulating polysaccharides were isolated and their monosaccharide composition determined. This was done both in Oslo (Partner 1) and in Bamako. The monosaccharides of mango and banana peel were also investigated.
Partners 1 and 3 have also had collaborations involving master and PhD students, and post. docs. where the focus has been the analysis of traditionally used Malian medicinal plants, from a chemical and a biological point of view. Chemical characterization of medicinal plants and nutraceuticals traditionally used in treatment and management of Diabetes was performed; these plants were Solanum melongena, Eucalyptus globulus; Daucus carota, Allium sativum, Allium cepa and Psidium guajava. Analysis and chemical profiling of the content of several other plants used against hypertension, tuberculosis and wound healing was also performed. The monosaccharide composition and the complement fixing activities of plants used against wound healing, the total content of polyphenols and HPLC profiles of five samples of a traditional medicine used against hypertension was performed in Oslo by researchers Drissa Diallo and Adiaratou Togola from Mali, visiting Oslo. The methods for the measurement of total polyphenolic content in plant material and HPLC profiling of plant extracts were implemented at UdB. As part of the goal for WP2 was to train personnel in the maintenance of important research instrumentation, UdB (partner 3) visited Oslo (partner 1) in May 2013 for the training in various types of instrumentation maintenance, i.e. Atom Absorption Spectroscopy, High Performance Liquid Chromatography and Gas Chromatography. He also visited partner 2 in Bergen. Partner 3, UdB (Adama Denou) was hosted for five weeks by Partner 2 and Partner 1 for 4 weeks. At Partner 2 the training included isolation and purification methods needed for obtaining anthocyanin reference compounds for analytical work, training in structure determination of pure anthocyanin compounds based on chromatographic and spectrophotometric techniques, and some work on extracts of plants, which Mr. Denou did bring from Mali. He continued his training on the polysaccharides from malaria plants at partner 1 for 3 months.

Training of Partner 4 (Mak)
Mr. Christopher Adaku (PhD student and staff member, Partner 4) has been hosted by Partner 2, UiB, three times. He brought with him various samples of preselected plant species from Uganda. Based on these samples he was trained in the purification and structure elucidation of flavonoid compounds, in particular anthocyanins, using preparative high-performance liquid chromatography (HPLC) and various spectroscopic methods, especially Nuclear Magnetic Resonance (NMR) and Mass spectrometry. Mr. Adaku has also concentrated on plant characteristics of fruits and vegetables including recording of quantitative data. PhD student Adia Madina (Partner 4, Mak) has been hosted by Partner 6 (UFS) for three months. She was trained in several chromatographic methods for isolation of natural products from medicinal plants. Ms. Adia’s work is focusing on medicinal plants used in malaria treatment; Clerodendrum capitatum (Verbenaceae), Conyza pyrrhopappa (Asteraceae) and Zanthoxylum gilleti (Rutaceae). One technician from Partner 4 (Moses Nkolongo) was in 2012 trained by Partner 2 in the use and maintenance equipment, especially analytical and preparative HPLC instrumentation.

Training of Partners 5 (UWC) and 6 (UWC)
Professor Wilfred Mabusela (Partner 5) visited Partner 2 (UiB) and brought with him the following samples: Vegetables: Salicornia sp, Aponogeton distachyos, Tulbaghia violaceae. Fruits: Optunia ficus–indica, Carissa macrocarpa, Ficus sur, Citrullis lanatus, Carpobrotus edulis. The various samples have been investigated by various chromatographic and spectroscopic measurements. Professor Wilfred Mabusela (Partner 5) visited Partner 1 (UiO) two times. Partner 5 prepared and freeze-dried the following samples Ficus sp. (wild fig), Chrysanthemoides, Carpobrotus edulis, Carissa macrocarpa and Carob.
Professor Wilfred Mabusela represented UWC (Partner 5) during WP 2 MUTHI laboratory training at the workshop in Kampala. Two Postdoctoral fellows (Drs. Gustav Styger and Oluwaseyi Aboyade) represented UWC (Partner 5) at the MUTHI WP 2 training held at the Department of Chemistry, University of the Free State, Bloemfontein, (Partner 6. WP 2 training content covered included: Exploring the phytochemistry of medicinal plants based on their previous W2 training in Mali . Content covered was plant chemical extraction, phytochemical analysis, thin-layer chromatography (TLC) and an introduction to high-performance liquid chromatography (HPLC).
At Partner 6 (UFS) the following students has been trained in WP2 & WP3: Kun Du (PhD student), Talkmore Ngarivhume (part time PhD student and lecturer at the Walter Sisulu University in Mmtata, Eastern Cape), Khanya Phungula (MSc student) and Elmarie Nel ( MSc student). Their task in the MUTHI project is to study components of bioactivity in a variety of South African plants in order to obtaining sustainable systems for studying important medicinal plants for future. The plants under study are Colophospermum mopane, Boophane disticha, Combretum apiculatum and Galenia Africana.

The training involved in WP2 on chemical methods were all used for the preparation of the Twelve African monographs that was part of the deliverables for this WP, 8 was planned for.
Conclusion
Through the training related to sustainable chemical methods included in D2.1 (two workshops, training in laboratories of Partners 1–6, and through recording of data and preparation of publications) students/staff of the African partners have acquired knowledge and skills in:
• the isolation, characterisation and evaluation of different types of bioactive compounds in plants with medicinal and nutraceutical values,
• finger print survey methods,
• skills in quality control methods for improved traditional medicines other plants with nutraceutical potential,
• quality assurance and control methods for herbal medicine and nutraceuticals

MUTHI Deliverable D2.2 Monographs and plant characteristics
Executive summary of D2.2
Deliverable D2.2 of the MUTHI project contains a) development of monographs on plants for African Pharmacopoeia chosen by the four African partners, and b) reports on plant characteristics of African plants.
According to this monographs have been written for the following 12 plants: Terminalia macroptera, Ximenia americana and Biophytum petersianum at Partner 3 (UdB), Clerodendrum capitatum, Conyza pyrrhopappa and Zanthoxylum gilleti at Partner 4 (MAK), Sutherlandia frutescens, Artemisia afra and Tulbaghia alliaceae at Partner 5 (UWC), and Combretum apiculatum, Galenia africana and Microglossa pyrifolia at Partner 6 (UFS).
Through D2.2 the four African institutions participating in this project have increased their sustainable research capacities with respect to analyses and development of ITMs or nutraceuticals based on African plants. Partners 2 (UiB), 1 (UiO), and 6 (UFS) have together with Partners 4 (Mak), 3 (Udb) and 5 (UWC) performed case studies on selected African plants, with emphasis on flavonoids and polysaccharides.
Development of monographs on plants for African Pharmacopoeia
In order to produce products based on medicinal plants and their traditional uses, it was important to have methodologies that are standardized for the determination of the content, both qualitatively and quantitatively. For this reason it was important to train the African partners in the preparations of Pharmacopoeia monographs for plants that may be of relevance for the different African countries. The 4 different African partners in the MUTHI project have thus proposed a number of relevant plants for producing monographs. The scientific information has been obtained from the international scientific databases, or provided by the partner writing the monograph. All details on methods used for laboratory results have been incorporated in the monographs. A template for the preparation of plant monographs were prepared by Partners 1 (UiO) and 3 (UdB) and distributed to the 4 African partners as basis for preparation of monographs suitable for African pharmacopoeia.
12 monographs have been finalized in a format so that they can be presented for inclusion in relevant African pharmacopeia, which might be either Pan-African, regional or for one for the relevant country. The microscopic pictures were taken by Partner 1.These were prepared partially in collaboration with prof. Drissa Diallo (Partner 3, UdB) when he was in Oslo. The NMR spectra were also recorded by partner 1. All references are given at the end of each monograph (see D2.2).
Quality characteristics of fruits and vegetables used as food
Partners 2 (UiB), 1 (UiO), and 6 (UFS) have together with Partners 4 (Mak), 3 (Udb) and 5 (UWC) performed case studies on selected African plants, with emphasis on fruits and vegetables used as food. Here follows examples of case studies performed:
Professor Wifred Mabusela (Partner 5) visited Partner 2 (UiB) and brought with him the following samples: Vegetables: Salicornia sp, Aponogeton distachyos, Tulbaghia violaceae. Fruits: Optunia ficus–indica, Carissa macrocarpa, Ficus sur, Citrullis lanatus, Carpobrotus edulis. The various samples have been investigated by various chromatographic and spectroscopic measurements.
Christopher Adaku (Partner 4, Mak) has concentrated on plant characteristics of fruits, flowers, seeds, vegetables and other plant storage organs with a focus on the nutraceutical value of selected compounds (anthocyanins and other polyphenols) in collaboration with Partner 2 (UiB). High-performance liquid chromatography profiles of extracts of nine Ugandan plant species from Partner 4 (Mak)were recorded at partner 2 (UiB): Erlangea tomentosa, Strobilanthes dyerianus, Mimosa pudica, Gloriosa superba, Begonia glabra, Combretum comosum, Black ground nuts, Abrus precatorius, Echinochiloa pyramidalis .
Conclusion
In deliverable D.2.2 of the MUTHI project monographs for 8 plants for the African Pharmacopoeia was expected, while the final result of the MUTHI project was the production of 12 monographs for the African Pharmacopoeia. With respect to reports on plant characteristic one book chapter and 17 papers have been published, 7 manuscripts are in preparation.

WP3 Bioactivity and safety of phytomedicines and nutraceuticals.

MUTHI Deliverable D3.1: Development of Standard Operation Procedures (SOPs)
Executive summary of D3.1
In the Multi-Disciplinary University Traditional Health Initiative (MUTHI) project, aimed at building research capacity on plants for better health in Africa, UdB (partner 3) was responsible of developing SOPs on bioassay techniques and training other African partner in these techniques. In this framework standard operation procedures have been written for seven bioassays techniques of natural compounds. A Standard Operating Procedure (SOP) is a set of written instructions that document a routine or repetitive activity followed by an organization where these methods should be performed regularly.
Overview of the tests implemented in the MUTHI African laboratories.
ACETYL CHOLINESTERASE INHIBITORY ASSAY: THE TLC METHOD
Alzheimer’s disease (AD) patients present a progressive loss of cholinergic synapses in the brain regions associated with higher mental functions, mainly the hippocampus and neocortex. In the AD patients, a decrease in the acetylcholine (Ach) appears. Hence, AD and other form of dementia could be treated by the use of agents that restore the level of acetylcholine through the inhibition of both major forms of cholinesterase: acetylcholinesterase (AchE) and butyrylcholinesterase (BchE). Moreover, the inhibition of AchE plays a key role not only enhancing cholinergic transmission in the brain, but also reducing the aggregation of amyloid beta peptide (Aβ) and the formation of the neurotoxic fibrils in AD.
ΑLPHA- AND BETA- D-GLUCOSIDASE INHIBITION ACTIVITY
Bioautographic assays using TLC plates play an important role in the search for active compounds from plants, giving quick access to information concerning both the activity and the localization of the activity in complex plant matrices. This method is suitable for the detection of both α- and β-glucosidase inhibitors and applied to plant extract analysis. It is used for antidiabetic plants research.
HYALURONIDASE INHIBITION ASSAY
Hyaluronidase hydrolyzes glycosaminoglycans, including hyaluronan, an important component of the extracellular matrix, during tissue remodeling. The mammalian hyaluronidases are considered to be involved in many (patho) physiological processes like fertilization, tumor growth, and metastasis. Hyaluronidase activity increases in chronic inflammatory conditions, e.g. inflammatory joint disease. Bacterial hyaluronidases, also termed hyaluronate lyases, contribute to the spreading of microorganisms in tissues. Such roles for hyaluronidases suggest that inhibitors could be useful pharmacological tools.
DPPH RADICAL SCAVENGING QUALITATIVE (1) AND QUANTITAVIVE (2) MEASUREMENTs
Despite their beneficial activities, reactive oxygen species clearly can be toxic to cells. By definition, radicals possess an unpaired electron, which makes them highly reactive and thereby able to damage all macromolecules, including lipids, proteins and nucleic acids. Radical scavengers are important because they prevent lipid oxidation in food, and decrease the adverse effects of reactive species on normal physiological functions in humans. A wide variety of in vitro chemical models have been developed to assess the ability to prevent oxidative damages; amongst the chemical tests that measure radical scavenging capacity, the DPPH assay is one of the most widely employed method. An initial qualitative test is performed on a Thin Layer Chromatography plate (DPPH qualitative test) for screening of a large number of plant extracts, the radical scavenging property of the most active extracts are then measured in a spectrophotometry test (DPPH quantitative measurement).
BRINE SHRIMP TOXICITY TEST
This method is used for over 30 years in toxicological studies. Many researchers are now using brine shrimp (Artemia salina) as a pre-screen for plant extracts because they provide a quick, inexpensive and desirable alternative to testing on larger animals.
Partner 3(UdB) in collaboration with partner 1(UiO) were responsible for the training and implementation of these methods in the 4 African laboratories. The training of all partners was performed in 2 workshops (at UdB and Mak). The theoretical part was also performed by the former leader of partner 6(UFS) who unfortunately passed away soon after the last workshop. All partners were trained in how to write the SOP under the guidance of partner 3
The SOPs were all part of the Deliverable 3.1.
Conclusion
All the four African laboratories prepared SOPs for all the 7 tests and have them available in their laboratories. The SOPs were all part of the Deliverable 3.1.
Delivery D3.2: Implementation of bioassays in all relevant laboratories
Executive summary of D3.3
The Work Package 3 of the project was directed towards building sustainable research capacity in Bioactivity testing and safety evaluation of phytomedicines and nutraceuticals. Practical training of the MUTHI African partners´ laboratory personnel in conducting bioassays in on site lab courses and workshops has been performed.
The University of Bamako (UdB), partner 3, was responsible of the training of other African partner in Bioassay techniques. For this purpose, seven natural compounds testing bioassays have been developed, see D3.1 above. The Complement assay for immunomodulatory testing was also shown to the participants by partner 1.
Prof. Drissa Diallo (partner 3) has trained student at the University of Cape Town and Free State in South Africa in the techniques..
Three days training workshop on these bioassays was held at the chemistry Department of Makerere University which was facilitated by Dr Adiaratou Togola from UdB. In addition to the tests already described, personnel from partners 3, 4 and 5 have been trained at the laboratory of partner 1 for the testing of immunomodulatory activities of plant components. This is a method that can indicate whether the plant material have an influence on the immune system.
After the bioassays were implemented in the different African partner laboratories the tests can now be performed in the plants chosen by each partner. Partner 3 (UdB) made sure that both scientific and technical personnel at all the four laboratories were trained in performing the analyses after the SOPs as they were prepared. The personnel learned how to prepare all reagent and the calculations obtained in order to get quantitative results where this was relevant.
Conclusion
The training sessions have been beneficial for the laboratory personnel at all the partner institution. It will allow an indoor screening of their extracts and isolated compounds for their biological activities. These methods were used for the preparation of the Monographs that were deliverables for WP2.

WP4 Traditional medicine efficacy: The role of observational and clinical trials.
Deliverable No. 4.1 A needs assessment of and training manual on observational and clinical research approaches to traditional medicine for medical and public health personnel.

There is much research on traditional herbal medicines in Africa, but very little of it is clinical. For example, of over 1200 plant species reportedly used for the treatment of malaria, only 13 have undergone clinical trials, although hundreds have been tested in the laboratory. Of the few clinical trials which have been conducted, few are of adequate quality. In an effort to address this situation, the Multidisciplinary University Traditional Health Initiative (MUTHI), in collaboration with the Research Initiative on Traditional Antimalarial Methods (RITAM), conducted a training needs assessment for clinical and public health researchers in African universities who have conducted, or are planning to conduct, clinical research on herbal medicines.
The aim of this initial survey was to assess the training needs of clinical and public health researchers who have been involved, and/or plan to become involved, in clinical trials of herbal medicines in Africa. It was contacted over 90 researchers through pre-existing networks, of whom 57 (63%) responded, from 35 institutions in 14 African countries. Thirty percent were women, 34% were clinicians and 31% already held a PhD. Over half (57%) had already been involved in a clinical trial of a herbal medicine, and informed us about a total of 24 trials which have already been completed. Of these only four had been published, and only one had resulted in a licensed product. Fifty-four of the researchers were planning to conduct a clinical trial of a herbal medicine in the future, and gave information about 54 possible trials.
Respondents outlined the following most commonly encountered difficulties when conducting clinical trials:
• Resource constraints (including lack of funding, equipment, staff and infrastructure);
• Social acceptance of the clinical trial (including difficulty recruiting enough patients, poor rapport with traditional healers, and willingness of biomedical staff to be involved);
• Herbal medicine supply (including insufficient cultivation, production, and quality control);
• Lack of trained staff
• Logistical issues in conducting trials.

Respondents rated the following aspects of clinical trials as most important:
• Ethical issues
• Statistical analysis
• Protocol design
• Monitoring
• Reporting and publishing trial results
The items in which researchers were least confident were Intellectual Property Rights (IPR) issues, statistical issues, and issues related to Good Clinical Practice guidelines (GCP).
From our survey we conclude that that we should concentrate training efforts on those respondents who already have good plans and who are most likely to be able to bring these to fruition. In this way we hope to address many of the outlined difficulties in focused training workshops and online activities.
Conclusion
The areas for training prioritised by respondents are ethical issues, statistical analysis, protocol design, Good Clinical Practice guidelines (GCP), reporting and publishing trial results, and IPR issues. The lowest priority aspects for training (which were viewed as the least important, and in which people were most confident), were literature reviews and oral presentation of results. Most respondents would be able to participate in online training in English, although a significant minority would not, and alternatives should be considered for francophone respondents and those without easy access to the internet. It was also clear from the responses that some proposed trials had already been planned very carefully and was close to fruition; whereas others were no more than very preliminary ideas (which in some cases had not yet been carefully considered or developed). It would make sense to concentrate training efforts on those respondents who already have good plans and who are most likely to be able to bring these to fruition. In this way we hope to address many of the outlined difficulties in focused training workshops and online activities.
Deliverable No. 4.2 Training sessions: Training of 25 researchers from 5 African countries through online and workshop modules relevant to the needs annually.
Executive summary
Work Package 4 (WP4) is led by partner 5(UWC) with the South African Herbal Science and Medicine Institute (SAHSMI) of the University of Western Cape (UWC) in collaboration with the Department of Primary Health Care of the University of Oxford (OU), WP4 aims to develop and deliver training modules to improve investigator capacity in conducting clinical trials to demonstrate the efficacy of Improved Traditional Medicines (ITM).

Five official training workshops have been held since 2011:
1. University of the Western Cape, October 31st to November 4th 2011
2. Kampala Workshop, February 7th-12th 2013
3. Durban Workshop, October 2nd-6th 2013
4. Bamako Workshop, February 24th-28th 2014
5. Ile-Ife Workshop, August 8th-12th 2014
In 2012, UWC conducted an internal Seminar Series of six workshops using the “train-the-trainer” model based on WP4 training materials, which targeted postgraduate students from across departments in the university. In 2014, UWC held a week long accredited course on Clinical Trials and Indigenous Herbal Medicine training during the Public Health Winter School 7-11 July and a short course 21-23 October 2014.
Within these five workshops, UWC internal Seminar Series (6), UWC SOPH course and UWC short course, train-the-trainer model was utilized. Participants received preliminary training both during self-paced e-learning modules and in workshop course training.
The value and market demand for traditional and herbal medicines is larger than it has ever been, largely due to urbanization, increased population growth and rural unemployment. Along with a steady population and economic growth in Sub-Saharan Africa, there has been increasing commitment to pursue the development of African Traditional Medicine as an inclusive part of healthcare and with this, the standardization of African herbal medicines. In this context, improving research capacity, especially for the conduct of clinical trials is a crucial component of the drive towards integrative and safe healthcare. The Multi-University Traditional Health Initiative has been working on capacity building for clinical trials research by conducting workshops through various institutions in sub-Saharan Africa.
E-learning
In September 2013, UWC WP4 launched the online learning environment (http://muthi.uwc.ac.za). SAHSMI worked closely with the UWC Centre for Innovative Educational and Communication Technologies in 2013 to produce six interactive online training modules focused on key competencies required for clinical trial investigators. Over 1785 have accessed the e-learning platform site and over 641 users have registered for the module training from over 16 African countries. The free online platform can identify user geographic location, academic institution and frequently used resources. These e-learning modules are:
• Systematic Reviews and Meta-analysis
• Trial Registration
• Reporting of Trials / Critical Appraisal
• PICOs
• Estimates of effect
• The online platform also provides an introduction to Ethics for trials and GCP in a clinical trial environment.
UWC through MUTHI has created internal sustainability for user continued access and training far beyond the closure of the MUTHI project. The online platform offers general users access to clinical trials training. Through face-to-face workshops and e-learning, these training opportunities have allowed for extending the reach of MUTHI, increasing the numbers of African investigators trained, and importantly, building local capacity for teaching and delivery of clinical trials modules.
E-learning training can be viewed at http://muthi.uwc.ac.za. UWC e-learning content can be viewed in D4.2 Appendix 1.
RESULTS AND DISCUSSION
1. UWC workshop
Selection of participants for the workshop was based on online applications. This workshop was led by Dr Nandi Siegfried of UWC, who invited a six other facilitators to teach including Dr Merlin Willcox from Oxford, partner 8. Twenty-nine applicants completed an online application form. Applicants were required to motivate for their attendance and outline their research question, in addition to providing baseline demographic information. The selection process was co-ordinated by UWC. And selected 15 participants. The workshop comprised five days of eight teaching hours and included assessment of pre-workshop activities, formal lectures, interactive sessions and real-time knowledge testing using classroom performance software (‘clickers’).
The course curriculum included a two-hour tour of an active trial site. At the Tiervlei Trials Centre in Cape Town, the workshop participants observed the standard operating procedures and monitoring and clinical trial training activities.
The workshop programme can be viewed in D4.2 Appendix 2.
Dr Nandi Siegfried from UWC mentored Randa AlMahdi from the University of Science & Technology at the School of Pharmacy who later conducted a clinical trial of Grewia tenax for anaemia in Sudan. Ms. AlMahdi had been mentored through developing and conducting clinical trials for herbal medicine, including testing Moringa oleifera for diabetes, SAYE and Artemisia annua for malaria, and Hibiscus sabdariffa and Grewia tenax for anaemia in Sudan. Dr Patrick Ogwang from Uganda was mentored by Dr Merlin Willcox in the preparation of a clinical trial protocol, and conducted a clinical trial of Artemisia annua for the prevention of malaria.
Kampala Workshop
This workshop was held at the University of Makerere, and was facilitated by Dr Merlin Willcox (Oxford) and Dr Bertrand Graz (University of Lausanne). Dr Patrick Ogwang also made a presentation. It was held as part of a series of MUTHI workshops that included chemistry, IPR and ethnobotanical training. The organizers received 64 applications for the clinical trials training program, of whom 27 were offered a place and 18 attended all four compulsory days, although on some days there were up to 26 participants. Of these, only 13 people responded to the feedback questionnaire and the majority rated the sessions as ‘very good’.
Two of the participants, Dr Richard Ayebare and Ms Rehema Namyalo, have collaborated to develop a protocol for a clinical trial of Hibiscus sabdariffa for the treatment of anaemia. Dr Merlin Willcox, partner 8, was mentoring the development of this protocol.
Durban Workshop
This workshop was held at the MRC in Durban, South Africa, and facilitated by Dr Merlin Willcox, partner 8. There were 35 applicants for this training and 23 of these were offered a place. The majority of respondents to the post-workshop survey rated the training workshop as “very good”.
Adepiti Awodayo was mentored to develop a protocol for a clinical trial of “Mama decoction” for the treatment of malaria in Nigeria. Another participant, Dr Oluseye Bolaji, helped to plan and facilitate the workshop in Ile-Ife, Nigeria, in August 2014.
Bamako Workshop
This French workshop received 21 applications and 20 were offered a place. Over 90% of the respondents rated the sessions as “good” or “excellent”.
Three participants at this workshop were mentored in the development of their protocols. Mr Benjamin Koama and Dr Maminata Traore from Burkina Faso were mentored in the development of a GCP protocol for a clinical trial of a Burkina herbal medicine, SAYE, for the treatment of uncomplicated malaria in adults.. Dr Merlin Willcox, partner 8, was closely involved in mentoring this team in the preparation of their protocol.
Mr Lassana Sissoko from Mali prepared a protocol for a clinical trial of Moringa oleifera for the treatment of diabetes. Dr Merlin Willcox, partner 8, has been mentoring the development of this protocol and a pilot study was conducted.
Nigeria Workshop
This Nigerian workshop received 42 applications and 33 were offered a place. 26 participants attended from Nigeria and Ghana. The workshop report has been compiled with respondents rating sessions as very positive.
Dr Willcox has been closely involved in mentoring three participants at this workshop. Richard Ayebare and Rehema Namyalo from Uganda were mentored in the protocol development for a clinical trial of Hibiscus sabdariffa for anaemiaare. Adepiti Awodayo from Nigeria is being mentored in the protocol development for a clinical trial of “Mama decoction” for treatment of malaria.
Conclusion
The UWC and UO workshops were successful in providing clinical trials training for 136 researchers over the course of the project. Of the workshop participants, at least six were mentored through developing and conducting clinical trials for herbal medicine, including testing Moringa oleifera for diabetes, SAYE and Artemisia annua for malaria, and Hibiscus sabdariffa and Grewia tenax for anaemia.
WP 5 Ethics and Intellectual property Rights.
Deliverable No. 5.1. Memorandum of Understanding: 8 researchers and 4 traditional healers have written a memorandum of understanding (MOU)
Executive summary
The aim of this deliverable, MUTHI 5.1 was to train researchers from the University of the Western Cape (UWC, partner 5), University of the Free State (UFS, partner 6), Makerere University (MAK, partner 4), and University of Bamako (UdB, partner 3) in research ethics and the broad issues of IPR & TK.
Online modules, training workshops and individual mentoring were important means for achieving this training goal. There has been a particular focus on each university partner developing a Memorandum of Understanding (MOU) with a traditional healer or traditional healers’ association. In addition, observation of regulatory meetings, including with the Ministry of Health, University and Traditional Health Practitioners Associations, was facilitated.
ASSESSMENT OF TRAINING NEED: In March 2011 participants had been selected by the African partners (2 per institute) together with the WP5 team to develop the MOUs. To assess the training needs of these participants a training needs assessment (TNA) was designed asking researchers about their level of knowledge of different aspects of Intellectual Property Rights (IPRs) (in relation to ethnopharmacological research), their past experiences in ethnopharmacological research and their future plans to conduct such research. Examining their level of knowledge of IPR showed that the participants had no to little knowledge of IPR matters.
TRAINING WORKSHOPS: Based on the TNA results a one day workshop was organized on IPR and ethics which was held in Bamako, Mali on the 25th of November 2011 to prepare them for writing an MOU. A total number of 16 persons participated in the workshop (six from UdB, four from MAK, two from UFS and UWC and two persons from the satellite countries Burkino Faso and Niger). Another workshop was organized in the beginning of Feb 2013 in Kampala, Uganda which was attended by 42 participants.

TRAINING OUTCOMES: All African partners have been trained in how to produce an MOU. The MOU is an important agreement between the partners prior to fieldwork in the area of traditional medicine and the use of plants. They have also been trained in all legal aspects of IPR and ABS (Access and Benefit Sharing). To facilitate on-going learning, a database has been built so that all partners will have access to all legal documents relevant for the participant countries after the project has finished. These can be found attached to D5.1.
CHANGE IN RESPONSIBILITY FOR WP5: After the unfortunate death of Andrew Marston (Partner 6) in March 2013, who was previously leading WP5, partner 8 offered to take over the leadership of WP5. This offer was unanimously accepted and welcomed by all the MUTHI partners.

Results
Workshops
The main goal of the one day workshop in Bamako (Mali) was to introduce the participants to the field of IPR of TK and to help them start writing a MOU between a researcher (team) and a traditional healer (association). A number of lectures and case studies were presented by different MUTHI partners (3, 5, 6, 7, 8) to train the participants in legal aspects related to ethnopharmacological research on TK. All participants were asked to prepare a presentation before the workshop on an IPR issue related to TK of plants in their own country. They presented these to the other participants and facilitators explaining the background and highlighting the most important issues between the different stakeholders.
On the 4th of February 2013 a second one day workshop was organized in Kampala, Uganda developed by the Oxford team and UvA team in collaboration with partner 4 (MAK) that planned and coordinated this one-day workshop, which was attended by 42 participants from 9 countries: Mali (2), Uganda (24), Kenya (3), Ethiopia (1), Norway (3), Netherlands (2), Switzerland (1), South Africa (4) and UK (2). The aim of the workshop was to help participants further in formulating their MOUs between a traditional healer (association) and a research team.
Mentoring
Since the beginning of the MUTHI project each of the selected participants has been supervised by the Oxford and Amsterdam teams in developing their MOUs, by giving feedback on draft versions, including advice on free prior informed consent (FPIC) and access and benefit sharing which are essential aspects of the MOUs. We provided them with essential literature on ABS, International, regional and national legislation and organizations dealing with TK and IPR. However, the writing of a MOU is a long process which involves not only the research departments of the African partner institutes but also their legal departments and the traditional healers (or their associations) that are partners in this collaborative writing process. During the mentoring period a number of draft versions were prepared on which the Oxford and Amsterdam team gave continuous constructive feedback. Therefore the research teams needed all the months available in the MUTHI project to finalize their final MOUs (See APPENDIX 5a-e). The process will be discussed in short in the following sections.
Memoranda of Understanding (Del. 5.1)
Makerere University
The research team of Makerere successfully developed an agreement on research collaboration with the traditional healers’ association PROMETRA-Uganda, signed on the 25th November 2013. The development of the MOU was an ongoing process which started in 2011 and included intensive contact with PROMETRA to discuss the content of the articles in full detail. The research team succeeded in delivering a finalized MOU which satisfied both signing partners’ needs for a fruitful cooperation in the future.
University of Bamako
The research team of the DMT (University of Bamako) has a long tradition of working with traditional healers and successfully completed an agreement with a traditional health practitioner Mr. Djotigui Diarra on the transfer of plant materials for collaborative research and development of a phytomedicine based on traditional knowledge, signed on 14th of March 2014.
These first two partnerships mentioned above (between the researchers and the traditional healers) have met the basic requirements for MUTHI. However, continuous contact and discussions between the signing partners is essential in this ongoing process of research on TK which might lead to successful product development based on TK. When the research teams have positive results and show that commercialisation is possible, new agreements have to be developed to provide for the fair and equitable benefit sharing of the commercialised product.
University of the Free State
The research team of UFS finalized their MOU with Ms. Malefu Khamane, a private individual dealing with traditional healers and practicing as a traditional indigenous knowledge holder on the 27th of November 2013. However, the MUTHI requirement for the MOU was to sign a MOU with a traditional healer. Although Malefu Khamane has been officially recognized as a traditional indigenous knowledge holder one of the pre-requisites of the MUTHI project was to develop a MOU together with a traditional healer or traditional healers’ association. After receiving feedback on their signed MOU the research team decided to incorporate our feedback into a new MOU and contacted a traditional healers’ association to discuss the MOU to develop a fair and equitable MOU which is an important aspect of this capacity building exercise. Traditional Healer Anthony Williams (South African ID 720118520908) agreed to continue collaboration (including divulging traditional knowledge) based on this new MOU.
University of the Western Cape
The research team of UWC finalized their MOU on the 1st of April 2014. Due to changes in key personnel at UWC the development of the MOU was delayed resulting in a delayed opportunity to discuss and develop the MOU with a traditional healers’ association. This requisite component of IPR training, leading to the development of a fair and equitable MOU to be signed with a traditional healer, will still be an ongoing process for UWC. Despite these challenges, UWC did produce not just one but two MOU’s thereby exceeding the partner requirements for WP5.
The South African partners (UFS and UWC) are obliged to work with the Benefit Sharing Agreement provided by the Department of Environmental Affairs of the South African government which needs to be signed as well following national South African law and are presented here for UWC as well together with their Material Transfer Agreement next to the MOUs.
Additional MOUs
During the project two additional MOUs have been developed which were not part of the intensive mentoring process. The University of the Free State developed an MOU for the ethnopharmacological research conducted for WP1 which was conducted in Zimbabwe in 2012 by Talkmore Ngarivhume and signed with traditional healers in the research area.
The WP5 team is gratified that this extra effort from the University of the Free State and the University of Bamako has occurred beyond the basic requirements of the MUTHI terms of reference.

Discussion & Conclusions
At the beginning of the project the TNA results showed a relatively low level of knowledge of IPR. Related to ethnopharmacological research, this included knowledge of existing international, regional and national laws and legal instruments essential for conducting ethnopharmacological research on TK such as an MOU. During the MUTHI project participants have gained knowledge of various aspects of IPR through lectures and case studies but most of all by developing their own MOUs with a traditional healer (or THP Association) which was an essential part of the capacity building on medicinal plant research for WP5.
There was a range of levels of benefit sharing agreed to by the university partners with the THPs with whom they were working. This extended from as high as a 50% - 50% ratio, to the other end of the scale with just a 2-3% benefit being proposed for the THPs. Influencing this variation was the acceptable levels determined by university IPR policies and well as by the terms of national legislation.

D5.2 Ethics and Intellectual property rights. A generic model for benefit sharing, ethics and intellectual property rights is developed, and adapted to three country-specific submodels.
Executive summary
CONTEXT: Globally, traditional medical knowledge is now being used as the basis for the development of drugs, nutraceuticals, herbal products, pharmacological products and general medical products. Under international legal covenants such as the Convention on Biological Diversity (CBD) and regional frameworks such as the African Union Model Law on Traditional Knowledge, this knowledge is legally owned by its traditional knowledge (TK) holders. The MUTHI WP.5 team has been working to (a) inform all MUTHI members of this context and of their associated legal and ethical responsibilities, and (b) develop related teaching materials which will be available electronically for future educational use. Two manuscripts (e.g. Bodeker et al., 2014a (in press) and Bodeker et al, 2014b (in press) will be available online.
AIM: The aim of this deliverable 5.2 was to develop a generic model for benefit sharing, ethics and intellectual property, adapted to three country specific sub-models. Information gathered over the last four years by means of literature research, developing online modules, training workshops and individual mentoring were important means to achieve this goal.
Training in Ethics and IPR
During the MUTHI project researchers from the University of the Western Cape (UWC, partner 5), University of the Free State (UFS, partner 6), Makerere University (MAK, partner 4), and University of Bamako (UdB, partner 3) and other stakeholders have been trained in Ethics and IP regulations related to ethnopharmacological research in Africa. This has been achieved via workshops and mentoring in order to develop a Memorandum of Understanding (MOU) between the university research group and a traditional healers association. The outcome of this training program in these three countries formed the basis for the development of the generic model for benefit sharing, ethics and intellectual property which is presented in the results section of D5.2.

Throughout research on herbal and traditional medicine, it is important to ensure the ethical and fair treatment of traditional knowledge holders, be they individuals or communities. In fulfillment of MUTHI’s work package 5 required deliverables, the team was tasked with developing a model framework for researchers to ethically structure their projects.

The International Society of Ethnobiology’s Code of Ethics
Were developed for researchers involved in research among indigenous or traditional living communities to conduct their research in a proper ethical way. This Code of Ethics provides a framework for decision-making and how to conduct ethnobiological research and related activities. As these principles are considered to be the Gold Standard for ethics, we built the model framework based on these 17 points.

Discussion
Within MUTHI it was our goal to adhere to the 17 Principles of the International Society of Ethnobiology’s Code of Ethics as a Gold Standard to develop a new generic model framework based on our experiences during the MUTHI project or other relevant experiences.
During the final stage of the project it became evident that the ISE Code of Ethics remains as a Gold Standard of ethical principles in ABS. What is needed is the addition of case examples, which was prepared by way of reference to the published work from MUTHI and also drawing on other case examples in this field. Awareness of the ethical principles in ABS is a pre-requisite of any type of research being conducted based on traditional knowledge. Now that the Nagoya Protocol on ABS has been in force since the 12th of October 2014, countries will need to develop national laws on this matter (if not done already) and researchers will need to take full account of their ethical responsibilities. It is the hope of the MUTHI WP5 team that this generic model will help researchers further in incorporation the requisite ethical foundations into their future research.

Totally, in the MUTHI project is has been developed various documents, standard operation procedures and training courses that were goals of the MUTHI project. Training in Ethnopharmacology, ethnobotany and how to perform RTO studies was the content of WP1, WP 2 trained personnel at the four African laboratories in the chemical methods necessary for analyses of plants used in traditional medicine as well as training the personnel in advanced research methods for structural elucidation of bioactive compounds. WP3 trained the personnel in performing bioassays of relevance for several of the prevalent illnesses on the African continent as well as training them in toxicological assays. Training in how to perform clinical trials of herbal products, how to write the protocols was covered in WP4, while W5 took care of ethical principles, how to write memorandum of understanding and also how to abide the international rules within IPR and ABS. Various publications were also written as well as oral presentations at national and international conferences based on the training of the personnel in the African laboratories. This was an integral part of all work packages.
In addition to the publications loaded up in the portal that already are published, the following bookchapters and publications in preparation will also appear as a product of MUTHI:

Bodeker, Gerard, Weisbord, Emma, Diallo, Drissa, Byamukama, Robert, Sekagya, Yahaya and van ’t Klooster, Charlotte. “African Medicinal Plants & Traditional Medical Knowledge: Access & Benefit Sharing in the context of R&D. In Wambebe & Rasaoanaivo Traditional Medicine Research in Africa. HSRC Press (In Press 2014).
Merlin Willcox, Drissa Diallo, Rokia Sanogo, Sergio Giani, Bertrand Graz, Jacques Falquet, Gerry Bodeker (submitted). Intellectual property rights and “Reverse pharmacology”: The development of Argemone mexicana as a traditional antimalarial. Journal of Ethnopharmacology.
Partners 1 and 8 contributed to the consultative process of CP12 of the CBD in the form of an article on Traditional Medicine, Medicinal Plants & IPR. Drawing on MUTHI experience, this was a direct input into framing IPR protection guidelines for traditional knowledge within the CBD framework.
Diarra, N. C.I.E.A. van ’t Klooster, A. Togola, D. Diallo, J.T.V.M. de Jong. Ethnobotanical study of plants used against malaria in the health area of Selingue, Mali (under review in Journal of Ethnopharmacology, Feb 2015)
Hughes, G. T. Blouws, O. Aboyade, D. Davids, O. Mbamalu, C. Van’t Klooster, J. De Jong , D. Gibson. An ethnobotanical survey of medicinal plants used by traditional health practitioners to manage HIV and its related opportunistic infections in Mpoza, Eastern Cape Province, South Africa (submitted to Journal of Ethnobiology and Ethnomedicine)
Unnikrishnan, P. M., Suneetha, M.S. Anastasiya Timoshyna, Bertrand Graz, Danna Leaman, Rainer W. Bussman, Hariramamurthi.G. Darshan Shankar, Charlotte i. E. A. van’t Klooster, Gerard Bodeker, Yahaya Sekagya, Wim Hemstra, Felipe Gomez, Bas Verschuuren. Traditional Medicine. (In Press 2015). COP 12, CBD http://www.cbd.int/getattachment/health/stateofknowledge/Traditional-Medicine_advanced-draft-updated.pdf
Willcox, Merlin, Diallo, Drissa, Sanogo, Rokia, Giani, Sergio, Graz, Bertand, Falquet, Jacques, Bodeker, Gerry. “Intellectual Property Rights and “Reverse Pharmacology”: The development of Argemone mexicana as a traditional antimalarial.” Submitted to the Journal of Ethnopharmacology (2014).
Christopher Adaku, Irene Skaar, David F. Okot, Robert Byamukama, Monica Jordheim, Bernard T. Kiremire and Oyvind M. Andersen. New anthocyanin with potential beneficial nutraceutical and colorant properties isolated from Cyphostemma adenocaule fruits. (Food journal)
Christopher Adaku, Irene Skaar, Robert Byamukama, Monica Jordheim, Bernard T. Kiremire and Oyvind M. Andersen. New anthocyanidins from Erlangea tomentosa flowers. (Phytochemistry journal)
Christopher Adaku, Irene Skaar, Robert Byamukama, Monica Jordheim, Bernard T. Kiremire and Oyvind M. Andersen. Anthocyanins from Abrus precatorius seed coat. (Nature)
Christopher Adaku, Irene Skaar, Robert Byamukama, Monica Jordheim, Bernard T. Kiremire and Oyvind M. Andersen. Anthocyanins from pink-white flowers of Dracaena terminalis. (Horticultural journal)
Christopher Adaku, Irene Skaar, Robert Byamukama, Monica Jordheim, Bernard T. Kiremire and Oyvind M. Andersen. Phytochemicals responsible for the color of Gloriosa superba flowers. (Scientia Horticulturae).
Andersen, Ø. M.; Skaar, I.; Jordheim, M.; Bjorøy, Ø.; Adaku, C.; Byamukama, R. Chameleonic behavior and stability of anthocyanidin secondary structures. Manuscript in preparation.
Adaku, Christopher; Skaar, Irene; Okot, David; Byamukama, Robert; Jordheim, Monica; Kiremire, Bernard T.; Andersen, Øyvind M. The main anthocyanin from fruits of Cyphostemma adenocaule with aromatic acylation. Manuscript in preparation.
Skaar, Irene; Mabusela, Wilfred; Eldholm, Helen; Andersen, Øyvind M. Anthocyanins from the edible fruits of Natal plum (Carissa macrocarpa). Manuscript in preparation.
Adaku, Christopher; Skaar, Irene; Berland, Helge; Byamukama, Robert; Jordheim, Monica; Andersen, Øyvind M. Anthocyanins from seeds of Erlangea based on a novel anthocyanidin. Manuscript in preparation.
Togola A, Karabinta K, Dénou A, Haidara M, Sanogo R, Diallo D. Polysaccharides cicatrisants isolés des feuilles de Opilia celtidifolia (Guill. et Perr.) Endl. ex Walp. (Opiliacées) (Submitted to Mali Medical)

Adiaratou Togola, Korotimi Karabinta, Mahamane Haidara, Adama Dénou, Rokia Sanogo, Drissa Diallo. Effet Protecteur des extraits aqueux des feuilles de Opilia celtidifolia contre l’ulcère induit par l’éthanol chez le rat (Submitted to the International Journal of biological and Chemical Sciences)

Adiaratou Togola, Amadingué Guindo, Nana Mariama Chétima, Drissa Diallo. α-D-Glucosidase Inhibition Property of Malian Antidiabetic plants (Draft in progress)

Adiaratou Togola Nouhoumn Sadou Cissé, Amadou Doumbia, Berit Smestad Paulsen, Drissa Diallo. Healing of Donkeys´ wounds and complement fixing properties of Cassia nigricans Vahl and Leptadenia hastata (Pers.) Decne (Draft in Progress)

Potential Impact:
Potential Impact
The expectation of the project was that the African laboratories should become important key institutions for the innovative discovery and development of phytomedicines and nutraceuticals that are affordable and will act for better wellness and health in the African countries participating in the project and their surrounding countries. This should be achieved as specified in the following points:
1. develop capacity of researchers to conduct high quality ethnobotanical and ethnopharmacological research.

2. develop capacity of researchers to use quality analyses and bioassays to find and evaluate
bioactivities of phytomedicines and nutraceuticals derived from plants.
3. develop referential guidelines for quality analyses, biological testing, and safety evaluation of
phytomedicines/nutraceuticals.
4. assess and respond to needs in preclinical test training of the participating African institutes and develop the capacity of researchers on ITMs and nutraceuticals so that they are capable to develop, conduct, assess, and analyse the outputs of clinical trials using compounds derived from the plants.

The work program as a cooperation action with focus on health in Africa was a program for collaborative health research with Africa entitled “Better Health for Africa”. The MUTHI program was based on the results from the meeting in Bamako, Mali, in November 2008 organized by the Global Ministerial Forum on Research for Health where the focus was strengthening research for health, development and equity. In the call for action following this meeting, it was recognised that research must be a basis for better health throughout Africa, and that a lot of the diseases on the continent are caused by poverty.
The strengthening of science and technology collaboration between the African research institutions and capacity building were put forward as important for better health on the continent. The document following the Bamako meeting emphasized the lack of cost-effectiveness in the major health programs and the need for more impact research.
Due to this, it was recommended that building research capacities in the continent that could set good standards for development of better health security and better health systems in the future should be a priority.
It is well recognized that the population of Africa has health problems of a different level and type than do the so called Western world, with poverty-related illnesses and a lack of affordable and available medicines for the majority of the population. Due to this, the majority of the African people, in some countries up to 90 % rely on traditional medicines for primary health care. Anecdotal evidence suggests that many are effective, but in order to make sure that the treatment is optimal, knowledge on doses, preparations, efficacy, safety as well as clinical studies on the traditional remedies are needed in Africa.
Based on these facts, it was important for all partners involved in MUTHI to create sustainable research facilities within the whole area of traditional medicine in the four African partner laboratories in order to provide the population with safe and affordable medicines based on their traditional knowledge. In this context it was also of importance to gain more knowledge on several of the plants used more as health food or nutraceuticals in order to provide information to the population on what plant food is more healthy than other types of plants. The scientific knowledge that is of importance for these aspects covers areas like medical anthropology, ethnopharmacology, chemistry and biology for the quality assurance of the products that are developed for use. Knowledge on clinical trials on herbal remedies as well as aspects related to ethics and intellectual property rights must also be the knowledge of scientists involved in the development of what could be called Improved Traditional Medicines and nutraceuticals that will be available for the population for a price they can afford, and thus being more available for them.
Based on what is said above, and also on the focus of the Work program, MUITHI was developed as a project within the Coordination Action that should develop and implement a concept for sustainable development of capacity for research to gain better health in Africa in close cooperation with the African institutions, and the project should also contain a substantial element of South-South collaboration. When the project started training needs were assessed between the southern and northern stakeholders of the project and these needs were adjusted to the needs of the African partners in the four participating centres and the surrounding countries. It was also a prerequisite that emphasis should be given to achieve excellent teaching and research networks through the project which should be sustainable after the period of the project. Our goal was to build up the skills of the African partners taking part in the MUTHI project so that they should be in a position to perform teaching at master levels within all the areas of the project as well as performing science of excellence when the project period is over. The institutions participating in the project were geographically well situated, with centres in west (Mali), east (Uganda) and southern (South Africa) Africa, providing the possibility of maximum impact in surrounding areas. It was also or goal to make sure the networks formed during the project period should continue in the future and that the strengthening of the south-south network should be a solid basis for the future. In order to achieve this, the following aspects were important for the project:
• To provide Africa with highly skilled human capital in the field of Herbal Science to help ensure that the collaborating laboratories become centres of excellence in Africa for the innovative discovery and development of phytomedicines and nutraceuticals that are affordable and will act for better wellness and health in the African countries participating in the project and in neighbouring countries.
• To create extensive regional and international networks through which researchers can collaborate to investigate the utility of the most important herbal medicines and nutraceuticals used to prevent and treat human disease.
• To build important bridges of learning between the different participating laboratories in Africa and Europe within the use of traditional medical and nutraceutical knowledge, to the benefit of people in the African participating countries.

It was expected that the the Co-ordination and Support Action should build important bridges of learning between the different participating laboratories in Africa and Europe within the use of traditional medical and nutraceutical knowledge, to the benefit of people in the African participating countries, and identify new and potentially more effective products relevant for the management of infectious diseases and other ailments in Europe.
The aim of our program was to provide sustainable methodologies for the development of new standardised and approved phytomedicines, both for local use and for export. This did include studies of components like polysaccharides and polyhydroxyphenols so that the laboratories involved will have methodologies and instrumentation available for the chemical quality control of products to be developed based on the local traditional uses both as medicines and as nutraceutical products. It had been proven that polysaccharides from Malian medicinal plants as well as from medicinal plants in China and Japan have effects on the immune system as well as being wound-healing agents. It had also been shown that people suffering from HIV/AIDS had a better wellbeing situation after having consumed plants with high content of polysaccharides with immuno stimulating properties. Proanthocyanins, being water-soluble polyphenols, have also been shown to reduce symptoms of bacterial infections, i.e. urinary tract infections due to the fact that the pili of the bacteria have lost their ability to bind to cell surfaces. These are just some examples of why it was of importance to study the water extracts of medicinal plants to a greater extent than what has been done up to now.
The two Norwegian groups were specialists in the studies of these two types of molecules and the transfer of this knowledge to the African laboratories have made the African laboratories able to perform state of the art research within these areas for the benefit of a good quality control of the products to be prepared as remedies for gaining better health for the African population. Personnel from the African labs have been in Norway for training; they have transferred the knowledge to their own research laboratories and will thus be able to perform most these studies themselves and also train their master students in these techniques. For the most advanced methodologies, they know that they can contact the European partners also in the future, so the South-north network within these areas have been established for future and has become sustainable.
Through WP 2 and 3 workshops were held, one with focus on chemical methods, and the other on bioassays that were necessary for sustainable quality control of the products. For especially the bioassays and toxicological tests, training were performed in all African laboratories as well, they were trained in making SOPs (Standard Operating procedures). This has led to sustainability for future, and as the scientific personnel have been trained, the so-called train the trainer´s model was important for creating this sustainability. This model was used throughout the MUTHI project to make all learning sustainable.
In order to determine what plants should be the focus for the products of the African laboratories, medical anthropology and ethnopharmacology were areas of importance. Both areas were needed in the African collaborating laboratories, and both WP 1, 4 and 5 included important training aspects that were needed both for the identification of the plants to be used for further studies as well as involving all legal aspects related to IPR, clinical trials and other studies necessary for the knowledge needed for production of products that are efficient and affordable. The focus of the ethnopharmacological studies was on poverty-related illnesses like those caused by micro-organisms and HIV/AIDS that all will have an influence on the immune system. Plants identified as effective by the healers did undergo both chemical and biological tests in order to identify what compounds were active in the water extracts. Methodologies for the quality control of the plants and their related products were developed. These aspects are found in WP 2 and 3, and were important for the production of the plant monographs for Pharmacopoeias that were produced.
To conclude, the MUTHI project lead to sustainable methods at the African institutions to address the objectives within the different work packages described. Networks have been formed both between the partner universities, as well as with institutions in the nearby regions that were invited to participate in the relevant workshops that were held by the consortium throughout the project period. Permanent networks have also been formed with the European partners. Sustainability has been achieved and it is clear that collaboration between the partners also will take place in future.

Additionally, it is the hope of all project participants, that the knowledge now being sustainable at the African institutions can be part and integral process for the discovery and production of herbal remedies, so-called quality controlled Improved Traditional Medicines for several of the severe illnesses that the African population suffer from. It is also hoped that these will be affordable for the population to a greater extent than the so-called Western medicine is. This will of socioeconomic importance for the African continent.

Dissemination of project results
The MUTHI project recognizes the importance of the appropriate dissemination of results, and did succeed in (a) sharing of information within the consortium, (b) sharing information with the stakeholders (e.g. those familiar with the use of traditional medicines, the people with the aliments/diseases, the doctors and hospitals, students and researchers, possible companies etc.), and (c) sharing of information in the public domain.
Although MUTHI was not a research project, but a coordination action, research was performed as part of the training during the project period and led to totally 57 publications. These were written by personnel from all the partners collaborating in the project. Some publications are under process and will be published after the MUTHI project has been terminated.
One important issue of the project was also to train the people from the African partners to prepare oral communications for international meeting, as well as presenting posters. As can be seen from the list of presentations, this was a very successful part of the project.
Additionally, several of the consortium members have been interviewed by both national and international press or television where the MUTHI project was in focus.
Awards
Participation of Adama DENOU to the International Congress of phytotherapy in Ouagadougou 9 to 12 October 2012. He made an oral communication. Title of Presentation: Contribution à l’étude de la conservation des sirops d’extraits de Guiera senegalensis J.F.Gmel (Combretacées) Price of the best young researcher communication.
Partners 1 and 3, UiO and UdB. Austarheim, Ingvild; Diallo, Drissa; Paulsen, Berit Smestad: “Anti-ulcer and immunomodulating properties of pectins form Cola cordifolia leaves”. Nordic Natural Products Conference; 2013-06-03 - 2013-06. Best Poster Award.
Partners 1 and 3, UiO and UdB. Paulsen, BS, Inngjerdingen, KT, Fjellestad, AM, Cheung, MG, Zhang, B, Denou, A, Diallo, D. “Plants used in Mali against malaria and their contents of polysaccharides with immunomodulating properties.” 2013 GA conference from September 1st to 6th 2013 in Münster (Germany); Poster. Poster award

Mr. Adaku Christopher was awarded a certificate as the 3rd best presenter at the Pan African Chemistry network Congress, Addis Abba, Ethiopia from 30th November – 2nd December 2014.
Title Of the paper: Christopher Adaku, Irene Skaar, David F. Okot, Robert Byamukama, Monica Jordheim, Øyvind M. Andersen, Bernard T. Kiremire. New anthocyanin with potential beneficial nutraceutical and colorant properties isolated from Cyphostemma adenocaule. The Pan Africa Chemistry Network Congress, Addis-Ababa, Ethiopia, 30th November-2nd December 2014.

Online presentations
MUTHI online learning (http://muthi.uwc.ac.za)
Active website presence and online networking through http://globalhealthtrials.tghn.org
Management of website and online discussions: http://globaltraditionalmedicine.tghn.org/key-areas/
In addition to the MUTHI website hosted at UiO, the project is featured at the Global Traditional Medicine website: http://globaltraditionalmedicine.tghn.org/key-areas/
Interviews with partners 1 and 3 presented on the website of the Science Faculty of University of Oslo http://www.mn.uio.no/farmasi/forskning/aktuelt/aktuelle-saker/2014/pa-lag-med-healerne.html
WP5 have built a literature resource database including information on ABS, International, regional and national legislation and organizations dealing with TK and IPR (WIPO, CBD, WTO etc). This has been continuously updated, including links to over two hundred online resources and will be presented through the Oslo MUTHI website and hosted on the Global Health website.

Online presence
In addition to the MUTHI website hosted at UiO, the project is featured at the Global Health Trials website: http://globalhealthtrials.tghn.org
Interviews with partners 1 and 3 presented on the website of the Science Faculty of University of Oslo http://www.mn.uio.no/farmasi/forskning/aktuelt/aktuelle-saker/2014/pa-lag-med-healerne.html