BY NKECHI ISAAC,
As the globe tries to battle the novel coronavirus disease 2019 (COVID-19), Artemesia has been highlighted as one of the compounds with great potential in tackling the disease (though not clinically proven yet). In this interview with NKECHI ISAAC, the director-general of the Raw Material Research and Development Council, Prof. Hussaini Doko Ibrahim, underscores Nigeria’s prospects in developing and benefiting from this active pharmaceutical ingredient. The excerpts.
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 (APIs) 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 highly effective antimalarial plant extract it is often combined with other components to compound malaria drugs due to resistance. The World Health Organization recommended 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. As a result, the source of artemisinin globally at present 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 assiduously at global level.
Can you 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.
Why do you think this plant should be introduced to Nigeria when there are a number of those identified locally that have not been developed to any reasonable extent?
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 allied with 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 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 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. Due to this endorsement, RMRDC believe that Nigeria should intensify efforts to be part of global value chain development for A. annua.
What is your organization and other stakeholders doing to ensure the programme is successful this time around?
Like I said before, plans 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 derivatives 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 because the Chinese partner withdrew from the project for God knows why. 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 Raw Materials Research and Development Council 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 the officials of the Federal Ministry of Health. The objectives of the project remains the same but the decision 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.
In your estimation, how soon do you think Nigeria can start producing artemisinin crystals for local use and export purposes?
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.