ACT ON MALARIA: making it a reality

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Without successful implementation of ACT now, significant progress in controlling malaria will be impossible. This is because there is no miracle non-act combination waiting in the wings and because malaria control that consists of prevention without effective treatment is doomed to failure. Despite this reality - and despite the rising mortality rates, despite the desire of many African governments to use drug combinations that work,1 despite endorsement by the World Health Organization,2 ACT is still not available to the vast majority of Africans who need it. We know which treatment works - so why do so few people have access to it? ACT treatment is currently much more expensive than other standard treatments; in addition, supplies of the drug are still limited. Yet both of these obstacles can be overcome. In fact, funding ACT treatment for all of Africa is economically feasible and scaling up production is technically possible. What is missing is political will. Unless this changes, people will continue to die needlessly from taking drugs that no longer work. The money problem The cost of ACT is currently much higher than the previous "gold standard" treatments (eg, chloroquine monotherapy). The cost of treating an adult with chloroquine or SP monotherapy is around US$0.10.3
The lowest quotes to humanitarian and government organizations for combination therapy artesunate-amodiaquine have been about $1.50.4 Yet, based on current price trends and historical experience, MSF estimates that the price of the artesunate-amodiaquine combination should be $0.50-$0.80 by 2004-2005.5 As orders for the drug increase, the price of ACT will go down over time, becoming more and more affordable. The poor people who represent most of the continent's malaria disease burden cannot afford to pay much more than what they currently pay for the old treatments, so costs must be subsidised by national governments with the help of international donors. MSF estimates that provision of ACT for all African countries that need it today would cost about $US 100-200 million a year at current drug prices.6 International donors must step in and assist governments in meeting these funding gaps. MSF estimates that for five countries - Kenya, Rwanda, Burundi, Uganda and Tanzania - only $19 million in total would be needed to switch to ACT instead of a sub-optimal interim protocol.7 Nineteen million dollars may be a lot for the five countries, but with US and UK aid budgets of US$8.5 billion8 and $5.25 billion,9 respectively, these key international donors should easily be able to foot this bill. The US Agency for International Development spends $586 million on operating expenses alone.10 The Global Fund for AIDS, Tuberculosis and Malaria, established in 2001, has awarded money to Zambia, Tanzania (Zanzibar) and Burundi for projects involving ACT treatment during the first and second rounds of grants; while a promising initiative, the several millions of dollars that have so far been made available are a fraction of what is needed for effective implementation of ACT in all the African regions that need it today. The solution could come from an increase in bilateral and Global Fund money. The US$100-200 million necessary to provide ACT represents only a fraction of the billions needed to fight the Global Fund-targeted diseases. To date, the Global Fund has received US$2.15 billion in pledges. Yet, despite direct pleas from African governments, major international donors have so far been reticent to help pay for ACT implementation.11 Are international donors denying Africa's children the malaria treatment they would give to their own sons and daughters? Availability - Current challenges and future possibilities Initial efforts to supply the first countries that have switched to ACT have been thwarted by a lack of supplies of needed drugs. However, scaling up has begun and is feasible. The technology needed for extracting the raw material and processing and formulating it is not that sophisticated. Even putting the combination drugs into blister packs or into a single pill does not present a serious challenge to drug developers and producers. Once markets are established by pooling orders and securing financing, producers will respond to the challenge. The WHO recommendation to use ACT in April 2001 was not followed up by securing the funds necessary to entice European, Indian, African, Vietnamese and Chinese producers to scale up production. The World Health Organization, donors and involved governments must work together to encourage ACT production and to work with new producers to assist them in meeting WHO quality standards. In Vietnam, where much of the Artemisia plants are grown and raw material extracted, farmers are willing to plant additional acreage of this cash crop if they can be assured of demand.12 (See box page 20 for more on challenges for ACT producers.) The WHO pre-qualification process, which certifies qualified producers, has made a call for "expression of interest" to producers of ACT and is currently undergoing examinations of products and facilities, but the future of the pre-qualification process is being put at risk by a lack of long-term funding. It will take political will and expressed commitment to generate a demand-driven cycle for quality ACT raw material and finished products. The future of artemisinins How to protect artemisinins Large scale use of chloroquine and SP throughout much of Africa has led to rising levels of resistance. Isn't it reasonable to believe that artemisinin drugs will travel the same path? If they are used alone, there is a high risk of this. That's why the World Health Organization is clearly recommending the use of combinations containing artemisinin drugs, rather than artemisinins alone. Using artemisinins in combination with another effective antimalarial will help protect them against resistance. Conversely, since there are so few other drugs that still work, it makes sense to use them along with artemisinins to increase their longevity. When resistance to the companion drug is still very low, it is the ideal time to introduce ACT, as treatment outcomes will be better and the life of the companion drug will be prolonged. For example, in Tanzania and southern Sudan where resistance to SP is still quite low, it makes sense to begin combining SP with artesunate as soon as possible. Artemisinin derivatives are already widely available as single drugs (not as part of combinations) in private pharmacies in many parts of Africa for people who can afford them. This availability in monotherapy invites the development of resistance. The availability of ACT in public facilities would both set a treatment standard and reduce the inappropriate use of artemisinin derivative monotherapy by individuals who are not currently being served by the public system. What next in R&D Blister packs of artesunate plus SP and artesunate plus amodiaquine to facilitate artemisinin-based combination treatment are expected in the short term (2003). The future availability of ACT in fixed-dose combinations (FDCs) will further increase their ease of use. MSF is supporting the Drugs for Neglected Diseases Initiative (DNDi) in developing FDCs of artesunate/amodiaquine and artesunate/mefloquine, which should become available in 2005. Several companies are also working on the development of artemisinin-based FDCs. Chinese company Holleykin is developing a dihydro-artemisinin/piperaquine fixed dose combination (also known as ArtekinÃ?®), which should be available by 2005. Medicines for Malaria Venture, a non-profit foundation developing malaria drugs, and GlaxoSmithKline have been collaborating on the development of artesunate/LapDap&##8482;, which should be available in 2006, and the Korean company Shin Poong and TDR are also expected to make available a fixed-dose combination of artesunate/pyronaridine in 2006. Synthetic versions of artemisinin derivatives are also an important element of ACT development, as they will eliminate the labour-intensive process of plant cultivation and extraction. They are likely to make up a major part of the next phase of antimalarial drug development. For example, the Medicines for Malaria Venture is planning to develop synthetic peroxides with a group of university researchers and artemisone with the pharmaceutical company Bayer. These products could become available by the end of the decade. From past lessons learnt in the malaria field, we know that no drugs last forever, and increased levels of research are urgently needed to develop brand new drugs for malaria treatment. Unfortunately, few major multinational pharmaceutical companies have ongoing malaria drug development projects, and the non-profit sector has so far been handicapped by insufficient financing. For instance, the Medicines for Malaria Venture claims that the biggest limiting factor for its work is lack of funds. As a result, no new chemical entities against malaria are likely to become available in the next ten years. Political and financial support for research and development of antimalarial drugs is therefore critical.