Research and Development
A broad range of tools for malaria control are available today. But in order to reach the goal of a malaria-free world, existing tools need to be improved so that problems like resistance can be dealt with appropriately. Therefore, development of effective, accessible and affordable control tools such as drugs, insecticides and vaccines against malaria is a crucial step towards malaria eradication.
As long as malaria persists as a global health problem, new drugs will be needed to replace old ones as they lose effectiveness. Just a few years ago, there were few new drugs in the pipeline and antimalarial resistance was rising. The situation was desperate. Until the end of the 1990ies research activities for malaria were minimal: Between 1975 and 2004, only eight of the almost 1.556 new drugs developed worldwide were antimalarials. The reasons for this were quite straightforward. A comprehensive engagement in any area of modern drug discovery and development requires a huge investment of manpower and resources that needs to be matched by an adequate commercial return. Given that most projects fail over the 15 year period it takes to produce a drug, the total research costs for a portfolio of projects to produce drugs usually amount to 100s of millions of dollars per drug.
For diseases such as malaria this return was not available, hence malaria is a rarity in high-income countries and the only real commercial market is travellers, which totals only U$ 200-300 million per year. The market for innovative new drugs for neglected diseases is further depressed by poor regulatory infrastructure in many countries, and by competing counterfeit drugs. The net effect is that about 10 percent of global drug R&D resources are directed at diseases accounting for 90 percent of the global disease burden.
Recently, however, the situation has improved noticeably with several new combinations and entirely new classes of drugs under development. Besides increased funding for antimalarial R&D, genuine progress has resulted from the creation of public private partnerships (PPPs) such as Medicines for Malaria Venture (MMV), which started in 1999. MMV, WHO麓s special Programme for Research and Training in Tropical Diseases and Walter Reed Army Institute for Research (WRAIR) are the main innovators in antimalarials. Nevertheless, sufficient funding for malaria R&D will remain a challenge.
For over 20 years, there have been no new classes of insecticides introduced for mosquito control, mainly due to the missing return on investment for private companies when researching solely for poverty related diseases. Currently, the WHO recommends 12 insecticides for indoor residual spraying and treatment of bed nets. But insecticide resistance is widespread to every chemical class of insecticides in major insect vectors from every genus. Despite the ongoing research, it will take some time until new chemicals will be on the market and of course, it will only be a matter of time until the parasite has developed new resistances. Consequently research and development have to be a continuous task for the decades to come.
Despite of many decades of research, scientists have so far been unable to develop an effective malaria vaccine. Reasons for this are the size and genetic complexity of the parasite when thousands of antigens enter the human body after the bite of an infected mosquito. The problem scientist are confronted with is to find out which of these antigens can be a useful target for the development of a vaccine. Until today at least 40 promising antigens could be identified. Another difficulty is the fact that the parasite changes its form in the human body through several life stages presenting the immune system with various subsets of molecules at each stage. Additionally, the parasite has developed methods to hide and misdirect the human immune system. There are hopes that the currently developed RTS,S/AS02A vaccine is a major breakthrough in the fight against malaria. If the trials are successful the vaccine will be submitted for approval by 2011 and could make an enormous contribution to reduce the burden of malaria.