African medicinal plants against malaria Dr Merlin Willcox, RITAM (Research Initiative on Traditional Antimalarial Methods)

Meeting Objectives To share information To develop a collaborative action programme for Africa-wide production and distribution of appropriate herbal antimalarials

The economics of malaria 2-5 billion febrile episodes a year resembling malaria 500 million cases of malaria 1.1 million deaths 90% of deaths are in African children 58% of deaths in poorest 20% of population

Economics of malaria (2) Up to 75% use traditional herbal medicine as first line treatment Adult course of ACT = $2.4, may reduce to $1 Diagnostic test = $1 Big pharma is not investing in malaria

What is your main objective? To reduce malaria mortality and morbidity? To create jobs and businesses?

What is your market? Poor people in remote areas with no access to modern health care? People who already have access to modern pharmaceuticals? Public health programmes? Herbal prophylactics for ex-pats?

What is an “appropriate” herbal antimalarial? Standardised phytomedicine or home-grown plants? Cheaper than ACTs? Parasite clearance or adequate clinical response? Efficacy or cost-effectiveness? Depends on context….

Types of R&D: Different products, endpoints & methodologies Bioprospecting for active molecules: new leads for conventional drug development Phytomedicines: standardised herbal extracts. Traditional medicine: prepared according to traditional formulations

The competitive advantage of herbal antimalarials Affordable Available Sustainable Reach the parts that modern drugs don’t reach…

Ways of using plants against malaria Insect repellents Vector Control Prophylaxis Treatment

The limitations of traditional medicine There is little clinical data on safety and efficacy Content of active compounds in plants is variable There is no consensus on what plants, preparations and dosages to use These are all remediable, through research…

RITAM Research Initiative on Traditional Anti-Malarial Methods Founded in 1999 by GIFTS of Health, with support from TDR, Rockerfeller www.gifts-ritam.org

Specialist Groups Policy, Advocacy and Funding Preclinical Networking, publications, funding, ethics, intellectual property rights Preclinical Database, guidelines Clinical Development Database, systematic reviews, guidelines Insect repellence and vector control Artemisia annua Task Force Overview of literature Clinical trials planned

The bottom line Herbal insect repellents: some evidence Herbal insecticides: some evidence Herbal treatments: controversial, some clinical evidence Herbal prophylactics: NO clinical evidence

Chicken or egg? “Show us the evidence that it works” Who will pay to generate the evidence?

Herbal treatments No herbal treatments have yet been described to be as efficacious as ACTs for parasite clearance Several herbal treatments could potentially be more cost-effective than ACTs in certain contexts

Where could herbal antimalarials be more cost-effective? Home management Presumptive malaria Semi-immune patients (Adults, children > 5 years old)

When is it unethical to recommend herbal antimalarials? [on current evidence] Non-immune patients Children aged <5 Pregnant women ? If a proven treatment is locally available and affordable to the patient?

The Artemisia annua debate Jansen, 2006: “I believe that the herbal tea approach to artemisinin as a therapy for malaria is totally misleading and should be forgotten as quickly as possible”. Anamed: promoting A. annua cultivation and use as a tea. RITAM response: Need more research

Approaches to A. annua Grow the plant as a cash crop, to sell to pharmaceutical companies, which will make ACTs Grow the plant for local distribution as tea bags Grow the plant in village “green pharmacies” where no other healthcare is available.

Problems with A. annua tea High level of recrudescence at doses tested Optimal method of preparation and dosage not yet defined Variability in artemisinin content

Potential of A. annua tea Cheaper than ACTs Could it be more cost-effective in certain situations, e.g. for home treatment of malaria? Could it be more effective if combined with other herbal antimalarials?

Prophylaxis Many herbal prophylactic preparations are used Almost none have been investigated Some Hausa tribes have lower than expected incidence of malaria (Etkin & Ross, 1991) In the malaria season, they eat plants with antimalarial properties

Neem as a repellent Neem oil on cardboard mats is as effective as synthetic repellents Costs $0.50 per room per year (cf. $25 for synthetic repellents) Also effective topically (2% in coconut oil) for 12 hours Neem oil is larvicidal (LC50 = 3-8ppm)

Phytolacca dodecandra Widespread tropical plant Crushed, powdered berries used as soap and as pesticide Effective at killing schistosomiasis transmitting snails Effective at killing mosquito larvae

Possible roles for medicinal plants Vector control and repellence Prophylaxis Treatment, especially: Presumptive malaria Home management Adults and children >5

Conclusions Herbal antimalarials have huge potential More research IS needed (esp clinical and public health) But who will pay for it? Need to go beyond laboratory studies in order to deliver a health impact.

www.gifts-ritam.org