Advances in Treatment

An area of development that deserves more attention is research and testing of new drug treatments.  A major contributor to the extensive malaria problem is resistance to previously effective drugs. In sub-Saharan Africa, chloroquine is still a standard treatment despite its ineffectiveness.  Currently, researchers are examining every stage of the parasite life cycle to determine the best point of intervention.  Table 2 below shows some of the drugs being developed with their mode of action in the stages of Plasmodium development.  The most promising strategy is use of Artemisin combination treatments (ACTs) to prevent rapid development of resistance. [1] Artemisin combination drug treatments are now the standard that is supported by the Global Fund.

Vaccines

[Guerin et al., 2002]

Much of new funding and global efforts are concentrating on research for a vaccine to prevent malaria.  There are currently over 35 vaccines in development and these need to be extensively tested and reviewed before a successful one is widely available to populations in need.  The table above gives an overview of the stages of Plasmodium that vaccine candidates target.   Although there have been many efforts and projects devoted to finding a malaria vaccine, this parasite presents a greater challenge than most microbes due to its complex life cycle. 

David Schneider, a microbiologist from Stanford University is pessimistic about the development of a possible malaria vaccine.  He feels, “If people were mice we would have a vaccine for malaria already because we can vaccinate mice in several different ways. The reason I don’t think vaccines will work is people don’t get long-lasting sterile immunity to malaria when they get malaria.” [2]

Efforts focused on an asexual blood stage vaccine are looking to provide antibody mediated resistance to patients. This approach seems especially challenging since individuals do not commonly develop immunity to subsequent malaria infections. [3] Another innovative idea is to design a vaccine for the gamete stage of the parasite to prevent a mosquito from acquiring and passing on malaria from an infected host.  This vaccine may be difficult to market, however, since it focuses on community health and will not help the individual who receives it.  Now, since researchers are realizing that the many stages of the life cycle present challenges in an effective response, they are now recommend multi-stage vaccines as the best approach. 

Although numerous vaccine ideas are being tested, the only promising method to date has been using irradiated mosquitoes.  For this method, a patient receives hundreds of bites from irradiated mosquitoes to produce protective immunity.  Potential challenges to this approach include the risk of cells that mutate into infective forms and the difficulty in achieving a protective effect through vaccine proteins rather than live mosquitoes. [4]

Transgenic Mosquitoes

[http://www.genomenewsnetwork.org/articles/05_02/transgenic_mosquitoes.shtml]

Scientist are also examining the use of Genetically Modified Mosquitoes in suppressing or replacing populations that transmit malaria.  One strategy is to transpose or induce substances that inhibit the development of P. falciparum.  Two promising candidates are a bee venom phospholipase PLA1 and the SM1 peptide.  In addition, researchers have also looked into the RIDL method, or release of insects with a dominant lethal to control the mosquito population. [5]  To be successful, however, this gene must be spread throughout a vast population.  The replacement of mosquito populations with a transgenic strain presents logistical issues and ecological questions on the long term impact of changing the ecosystem of an area.  According to microbiologist David Schneider, transgenic mosquitoes are an impractical option because they are not likely to successfully replace the current mosquito populations of a large area such as the African continent. [6]

The Genome Project

The mapping of the P. falciparum genome has helped researchers identify enzymes and fatty acids involved in biosynthetic processes that have the potential to serve as drug targets. [6]   One way to accelerate this process is to search for proteins that are known targets and already have drugs developed against them.  Another method is to observe what genes and expressed proteins are critical at each stage of the life cycle to understand targets for inhibiting parasite growth.  This understanding of protein expression at specific stages of the life cycle will also provide valuable information for vaccine development.

References

[1] WHO (2005) Malaria Control Today

[2], [6] David Schneider Interview

[3], [4] Guerin et al., 2002

[5] Christophides, 2005

[6] Hoffman et al, 2002

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