Malaria - Research

Research

Immunity (or, more accurately, tolerance) to P. falciparum malaria does occur naturally, but only in response to years of repeated infection. An individual can be protected from a P. falciparum infection if they receive about a thousand bites from mosquitoes that carry a version of the parasite rendered non-infective by a dose of X-ray irradiation. An effective vaccine is not yet available for malaria, although several are under development. The highly polymorphic nature of many P. falciparum proteins results in significant challenges to vaccine design. Vaccine candidates that target antigens on gametes, zygotes, or ookinetes in the mosquito midgut aim to block the transmission of malaria. These transmission-blocking vaccines induce antibodies in the human blood; when a mosquito takes a blood meal from a protected individual, these antibodies prevent the parasite from completing its development in the mosquito. Other vaccine candidates, targeting the blood-stage of the parasite's life cycle, have been inadequate on their own. For example, SPf66 was tested extensively in endemic areas in the 1990s, but clinical trials showed it to be insufficiently effective. Several potential vaccines targeting the pre-erythrocytic stage of the parasite's life cycle are being developed, with RTS,S showing the most promising results so far. A US biotech company, Sanaria, is developing a pre-erythrocytic attenuated vaccine called PfSPZ that uses whole sporozoites to induce an immune response. In 2006, the Malaria Vaccine Advisory Committee to the WHO outlined a "Malaria Vaccine Technology Roadmap" that has as one of its landmark objectives to "develop and license a first-generation malaria vaccine that has a protective efficacy of more than 50% against severe disease and death and lasts longer than one year" by 2015.

Malaria parasites contain apicoplasts, an organelle usually found in plants, complete with their own functioning genomes. These apicoplasts are thought to have originated through the endosymbiosis of algae and play a crucial role in various aspects of parasite metabolism, for example in fatty acid biosynthesis. Over 400 proteins have been found to be produced by apicoplasts and these are now being investigated as possible targets for novel anti-malarial drugs.

With the onset of drug-resistant Plasmodium parasites, new strategies are being developed to combat the widespread disease. One such approach lies in the introduction of synthetic pyridoxal-amino acid adducts, which are taken up by the parasite and ultimately interfere with its ability to create several essential B-vitamins. Antimalarial drugs utilising synthetic metal-based complexes are attracting research interest.

A non-chemical vector control strategy involves genetic manipulation of malaria mosquitoes. Advances in genetic engineering technologies make it possible to introduce foreign DNA into the mosquito genome and either decrease the lifespan of the mosquito, or make it more resistant to the malaria parasite. Sterile insect technique is a genetic control method whereby large numbers of sterile males mosquitoes are reared and released. Mating with wild females reduces the wild population in the subsequent generation; repeated releases eventually eliminate the target population.