African medicinal plants against malaria

Dr Merlin Willcox, RITAM (Research Initiative on Traditional Antimalarial Methods)

Meeting Objectives

To share informationTo 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 malaria500 million cases of malaria1.1 million deaths90% of deaths are in African children58% of deaths in poorest 20% of population

Economics of malaria (2)

Up to 75% use traditional herbal medicine as first line treatmentAdult course of ACT = $2.4, may reduce to $1Diagnostic test = $1Big 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 developmentPhytomedicines: standardised herbal extracts.Traditional medicine: prepared according to traditional formulations

The competitive advantage of herbal antimalarials

AffordableAvailableSustainableReach the parts that modern drugs don’t reach…

Ways of using plants against malaria

Insect repellentsVector ControlProphylaxisTreatment

The limitations of traditional medicine

There is little clinical data on safety and efficacyContent of active compounds in plants is variableThere is no consensus on what plants, preparations and dosages to useThese are all remediable, through research…

RITAM

Research Initiative on Traditional Anti-Malarial MethodsFounded in 1999 by GIFTS of Health, with support from TDR, Rockerfellerwww.gifts-ritam.org

Specialist GroupsPolicy, Advocacy and Funding

Networking, publications, funding, ethics, intellectual property rights

PreclinicalDatabase, guidelines

Clinical DevelopmentDatabase, systematic reviews, guidelines

Insect repellence and vector controlDatabase, systematic reviews, guidelines

Artemisia annua Task ForceOverview of literatureClinical trials planned

The bottom line

Herbal insect repellents: some evidenceHerbal insecticides: some evidenceHerbal treatments: controversial, some clinical evidenceHerbal 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 clearanceSeveral herbal treatments could potentially be more cost-effective than ACTs in certain contexts

Where could herbal antimalarials be more cost-effective?

Home managementPresumptive malariaSemi-immune patients (Adults, children > 5 years old)

When is it unethical to recommend herbal antimalarials?

[on current evidence]Non-immune patientsChildren aged <5Pregnant 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 ACTsGrow the plant for local distribution as tea bagsGrow the plant in village “green pharmacies” where no other healthcare is available.

Problems with A. annua tea

High level of recrudescence at doses testedOptimal method of preparation and dosage not yet definedVariability in artemisinin content

Potential of A. annua tea

Cheaper than ACTsCould 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 usedAlmost 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 repellentNeem oil on cardboard mats is as effective as synthetic repellentsCosts $0.50 per room per year (cf. $25 for synthetic repellents)Also effective topically (2% in coconut oil) for 12 hoursNeem oil is larvicidal (LC50 = 3-8ppm)

Phytolacca dodecandraWidespread tropical plantCrushed, powdered berries used as soap and as pesticideEffective at killing schistosomiasis transmitting snailsEffective at killing mosquito larvae

24HR MORTALITY RATES OF Aedes aegypti LARVAE

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Control25ppm50ppmVectron

Possible roles for medicinal plants

Vector control and repellenceProphylaxisTreatment, especially:

Presumptive malariaHome managementAdults and children >5

Conclusions

Herbal antimalarials have huge potentialMore 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