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Combatting Malaria in Madagascar

Report for London School of Hygiene and Tropical Medicine by Richard Cowper in Antsirabe, Madagascar

A brave French-Malagasy joint venture called Bionexx, headquartered in Antananarivo, the capital of Madagascar, has begun to record its first successes in providing employment to small-scale farmers in the highlands of central Madagascar as well as providing the main ingredient for the latest artemisia-based drugs for treating malaria.

The venture, though as yet on a comparatively small-scale, is an important one because malaria is the leading cause of morbidity and mortality in Madagascar, with more than 1.4 million malaria cases per annum and nearly 30,000 deaths reported in 2000. It is also important because it is providing employment in an appropriate sector in one of the world’s poorest countries, though to date the drug itself has yet to be manufactured locally.

The mosquito-born disease has an overwhelming impact on children under the age of five in Madagascar, who are estimated to account for up to 90 percent of malaria deaths.   Malaria is responsible for about 16% of all outpatient visits and 20% of all children under five years of age admitted to a hospital are diagnosed with severe malaria. It is ranked as a leading cause of under-five mortality, and according to UNICEF, kills approximately 20,000 Malagasy children every year.

We visited the project earlier this week at the invitation of Francois Petit, (telephone number 00261 (0) 331502006) an agronomist and the leading driver of the project on the ground, which is based in and around the town of Antsirabe, three hours due south of the Madagascan capital and the country’s second largest city.

The French-owned Malagasy project was started in 2005 by Mr Charles Giblain, a Frenchman and his Malagasy wife, Lamia Giblain. It is a commercial venture which to date has invested around Euros 5m. It is unsupported by any aid agencies and is yet to make a profit. By this year (2008) Bionexx had 5,000 smallholder farmers growing Artemisia plants on 1,000 hectares of their own land. The plant is then dried by the farmers and sold to Bionexx, which has been undertaking the artemisinine extraction process, but not as yet its purification.

According to Mr Petit, a personable 25-year old Frenchman who has already been in Madagascar for almost three years, one artemisia plant produces 0.15g of artemisinine, enough medicine for two full treatments. In Madagascar farmers can grow up to three crops a year, though two is more normal and this requires use of a rotation system.

Bionexx provides the seeds and the farmers grow the medicinal plant - used for 2,000 years by the Chinese to treat fevers, and now a key ingredient in modern western treatments for malaria – as a cash crop next to their rice fields. The venture hopes its farmers will produce 1,000kg of the dried product in 2009, with the hope of doubling output to 2,000kg by 2010.

The Malagasy-French venture agrees a new contract with its farmers every six months and visits each one six times during the growing season to ensure quality of production.

Bionexx, which employs an estimated 400 people in the venture, this year (Feb 2008) bought a factory in Fianarantsoa, 5hrs south of Antsirabe, where it is already extracting artemisinine from the dried product. It is then sold to Sanofi, the French pharmaceutical company, though Bionexx is yet to have a formal contract with the French company. Sanofi then purifies the artemisinine to make artesunate and mixes it with anodioquinine to make the drug Arsucam.

Bionexx hopes to start purification in its own factory next year. Chinese investors are considering joining the project by providing purification technology and know-how for the Fianarantsoa factory.

Some 24 tablets of Arsucam provide one course of treatment for those with malaria. The artemisianine must be mixed with another product to ensure that the malaria parasite does not become resistant to the treatment. However it is extremely expensive, currently Euros 10 for a course of treatment, and far beyond the means of almost all Malagasy inhabitants, of whom there are around 20m.

The epidemiology of malaria varies considerably in different regions of Madagascar. On the East and West Coasts transmission is stable and perennial, while in the Central Highlands it is seasonal and moderately unstable with occasional epidemics. In the most recent large-scale epidemic in the late 1980s, an estimated 30,000 people died. In the semi-desert region of the South, malaria transmission is seasonal, very unstable and in many years almost completely absent. The last Demographic Health Survey (DHS) was conducted in 2003-2004, well before the recent, rapid scale up of Insecticide Treated Nets (ITNs) distribution and the introduction of Artemisinine-based combination therapy (ACTs) as a first-line treatment for severe malaria.  

All four species of human plasmodia are endemic in Madagascar. While Plasmodium falciparum predominates in all areas, P. vivax and other species may make up as much as 10-15% of all cases, especially in the highlands. The two primary vectors are Anopheles gambiae (East and West Coasts) and A. funestus (Central Highlands and South). Anopheles arabiensis is also present in all four epidemiological zones. Anopheles funestus increases in density during the rice-growing season and was the primary vector responsible for the outbreaks which occurred in the Central Highlands in the late 1980s. Since this vector is highly endophilic, it is quite sensitive to IRS. Anopheles arabiensis is also present in the highlands, but is more exophilic.

The Gates Foundation is understood to have very recently agreed to subsidise the treatmentof malaria using artemisinine and is continuing to put pressure on western drugs companies in a double effort to bring the treatment cost down to around Euro 1 per course of 24 tablets.

Despite the obvious benefits and successes of the project to date, several clouds may make the success of the venture less smooth than originally hoped.

First, in 2005 when the Artemisia venture was launched the price of artemisianine on the world market was around US dollars 1,000 per kilo. Today the price is around $200 per kilo. According to Mr Petit average production costs per kilo are currently $350.

Second, Chinese entrepreneurs are seeking to enter the market, sometimes without full product traceability and quality, may be creating price pressures which are tricky to deal with.

Third, the Gates Foundation is working with the French drugs company Sanofi to make artificial artemisinine.

Fourth, Western subsidies to reduce the price of the drugs to the end-user tend to go to western drugs companies. The peasant farmers growing the vital Artemisia plant - in Madagascar at least - do not see any of this money. Nor does Bionexx.

Conclusion: this is an excellent and innovative project , highly appropriate to Madagascar, which should be encouraged and helped by western agencies committed to ensuring long-term solutions to Madagscar’s employment and malaria-health problems.