Studies have shown that over 300,000 people die from malaria annually with children being the most infected. This is why the Raw Materials Research and Development Council (RMRDC) have been working to find a homegrown solution to bring an end to bring an end to the surge; BINTA SHAMA reports.
What is Artemisia annua and why is it so important in malaria control?
Artemisia annua is a medicinal plant whose use has long been reported in China where it is locally known as qinghao. A. annua yields artemisinin and its derivatives which are used as Active Pharmaceutical Ingredients (API’s) for the production of potent antimalarial drugs.
Artemisinin is effective against multidrug-resistant malaria and is also known to act on P. falciparum, the Plasmodium species that causes cerebral malaria.
Although, artemisinin is a highly effective antimalarial plant extract, it is often combined with other components to formulate malaria drugs due to its resistance. The World Health Organization (WHO), recommends the use of artemisinin-based combination therapy for malaria in 2004.
The chemical synthesis of Artemisinin for the production of Artemisinin – based Combination Therapies (ACTs) is complex, uneconomical and produces low yields. Presently, the source of artemisinin globally is Artemisia annua.
The malaria parasite Plasmodium falciparum is one of the world’s most lethal pests, accounting for over a million deaths per year of which 90 per cent of the cases are in Sub-Saharan Africa and 85 per cent of these are in children under five years old.
As we are all aware, for over 50 years, the main tool for controlling malaria parasite was chloroquine, a synthetic derivative of the plant-based extract quinine.
Chloroquine acts as both prophylactic and curative. It also has the advantage of very low cost of about $0.10 per treatment. Unfortunately, in most parts of Africa as well as South-East Asia, it is no longer effective due to the emergence of resistant strains of the malaria parasite.
As a result, various governments are looking for ways of combating the incidence of malaria in view of its high economic costs, which has been reported to be about 40 per cent of public health costs in Africa.
It costs African countries about $12 billion of their GDP annually. This is why the development of A. annua is being pursued vigorously at global level.
Throw more light on the active ingredient, Artemisinin?
Artemisinin was first isolated in 1972 and has served as prototype for many semisynthetic versions such as arteether and artemether. These compounds have increased solubility in vaccines and have improved antimalarial activities.
Artemisinin proved to be an excellent antimalarial agent, and artemisinin-based combination therapies (ACTs) are currently the preferred first-line antimalarial treatment for Plasmodium falciparum.
Artemisinin and its derivatives are highly effective against multidrug-resistant parasites and result in rapid clearance of parasitemia and clinical improvement, usually within 24 to 36 hours. They are well tolerated and safe in adults, children, and pregnant women.
They also have a broad spectrum of antimalarial efficacy and, in particular, show good activity against the young ring forms of the parasites and halts their development into the more mature pathogenic stages. These properties are especially important for the management of severe malaria.
Is there a possibility of plasmodium developing resistance against the ACT’s?
Well, one or two cases have been reported. They are characterized by delayed parasite clearance in treated patients, although the in vitro sensitivity of the parasites remains unaltered. An extended parasite clearance half-life in treated patients was reported in Cambodia, and Thailand.
Whether these initial signs of decreased parasite responsiveness will result in high-grade resistance and a loss of clinical effectiveness are being determined. However, after more than 20 years of clinical use, ACTs remain fully efficacious in most of the endemic countries such as in Nigeria.
Will the plant be introduced in Nigeria especially with the delay in the development of local components?
That is a very good question. We have identified more than twenty medicinal plants in Nigeria. Some of these exist in all communities, while some are indigenous to certain communities.
Let me point out the fact that while different communities have developed recipes or cocktails from various medicinal plants for the treatment of malaria; the increasing global attention paid to A. annua and the World Health Organization’s support for global development of the plant has made it of global importance.
Also, while the cocktails developed for malaria in different African communities may have been effective, the incidence of malaria is still increasing in rural communities. Closely related to this is the fact that the active ingredients in some of the medicinal plants have not been adequately characterized for standardization.
Also the recipes vary from one community to another. The impetus for global development of A. annua is premised on the urgency dictated by the decreasing effectiveness of chloroquine, the main tool for controlling malaria parasite for over 50 years.
As a result, countries in Africa are now rooting for treatment with drug based artemisinin.
Most countries in East Africa, have tapped into A. annua development. Today, it thrives well in East Africa where the farmers are cashing in on its value chain development, most especially, its production, crude processing into artemisinin and export of both the leaves and the product.
The leaves and crude artemisinin are exported to Europe and India for conversion to the industrial form and ACTs.
Current agro -economic analysis indicates that worldwide, 17,000 to 27,000 hectares of land are required to plant A. annua required to satisfy global demand. Present total area cultivated stands at 5000ha. Thus a number of opportunities exist globally in A. annua development. The opportunities cover the gamut of A. annua production, processing and marketing.
Until 2004 the price paid by pharmaceutical companies was below $300/kg and only six significant factories worldwide bought Artemisia leaf for extraction. In the following year, $200m became available to the Global Fund for AIDS, TB and Malaria principally from the Bill and Melinda Gates Foundation.
This rose to $600m in 2006/07 and reached $2 billion in 2008/09. Much of the money was earmarked for purchase and distribution of ACTs Some 81 countries, 44 of them in Africa, adopted ACT’s as the frontline drug against malaria and there was sudden acute global shortage of artemisinin. The price shot up to over $1000/kg.
A number of factories sprang up in China and Vietnam to manufacture artemisinin based drugs and a large number of farmers were encouraged to plant Artemisia annua. Due to this endorsement, RMRDC believe that Nigeria should intensify efforts to be part of global value chain development for A. annua.
Can its performance be ascertained in Nigeria?
The commercial cultivation A. annua has been embraced in some East African countries like Kenya, Tanzania, Uganda and Madagascar. Trial runs were also done in Nigeria from 2005 to 2011.
The result was good but the overall objectives were not achieved. Let me also say WHO has developed guidelines on good agricultural and collection practices (GACP) for Artemisia annua which if strictly complied with will ensure success of the initiative.
What is RMRDC and other stakeholders doing to ensure the programme is successful?
Like I said before, the plan to develop Artemisia annua in Nigeria is not new. Around 2005, there was a presidential initiative to develop the plant’s entire value chain in the Country.
The Federal Executive Council in 2005 approved the constitution of a Presidential Committee on Artemisinin-Based Combination Therapies. This led to establishment of Artemisinin Development Company (ADC), which was incorporated in 2007 under a PPP arrangement between the federal government and a Chinese technical partner.
The Company was mandated to domesticate and cultivate A. annua in Nigeria and to extract Artemisinin from the leaves and process it into derivates for use as pharmaceutical raw material in producing ACT’s anti-malaria drugs locally.
The Company conducted two trials in the six-geopolitical zones to study the adaptability of the plant in the Nigerian soil and assess the commercial viability of its cultivation.
The programme was a success as the plant was reported to be adaptable and to have a high artemisinin content of between 0.64 – 1.29%. The trial cultivation took place in Enugu, Katsina, Taraba, Gombe, Kano, Plateau, Karu in Abuja and Ogun State and was very successful.
The project was however stopped as we were made to understand the Chinese partner withdrew from the project. Thus in order not to waste the leaves, they were converted into Artemisia tea that became popular and sold nationwide.
However, there is now a standing collaboration between the RMRDC and the Federal Ministry of Health to kick-start the project again. Several meetings have been held between members of staff of the Council and officials of the health ministry.
The objectives of the project remains the same but the actors in terms of which country to collaborate with has changed. Instead of China, the country is now planning to source its technology for artemisinin and ACT’s production from elsewhere. Already negotiations with the country’s scientists on acquisition of Artemisinin extractors have reached an advanced stage.
Our initial focus is to import a 10 tonne capacity extraction plant which will be used for investment promotion, capacity building and if possible, development of necessary plants. Most of the seeds that were obtained from the earlier trials were converted to insecticides and sold out.
As a result, we have to source for hybrid seeds from parts of Africa and Asia. Already an Artemisia annua producers, processors and marketers association has been formed under the auspices of the Federal Ministry of Industry, Trade and Investment.
Our plan is to ensure that trials are conducted under small scale farmers’ condition to ensure the success, proliferation and sustainability of this rebirth. Also we are sending some people to the African Sustainable Agribusiness School in Nairobi, Kenya for training on Artemisia value chain development.
How soon can Nigeria start the production of artemisinin crystals for local use and export?
All things being equal, the process is on. We believe that by the next planting season, our farmers should commence commercial production. Also our discussion with collaborating countries has reached an advanced stage. By the end of next year ‘God willing’ we hope to commission the plant even if it is to begin production of a fraction of the domestic requirement.
Originally published at Blue print