Malaria after the genomes

Abstract

In 1880, Charles-Louis-Alphonse Laveran saw a malaria parasite under the microscope and, by 1898, transmission by the mosquito species Anopheles was established. A little more than 100 years later, we now know that Plasmodium falciparum, the parasite responsible for the most severe cases of malaria, has 14 chromosomes and about 5300 protein-encoding genes, that almost two-thirds of its proteins seem to be unique to this organism, and that about 208 genes are known to be involved in the evasion of the host immune system. We also know the genome of one of its vectors Anopheles gambiae or “man's deadliest foe” as Andrew Spielman describes it in his book Mosquito. Together with the expected completion of the human genome next year, this is the first time that all three elements leading to an infectious disease—organism, vector, and host—have been fully sequenced. Scientists around the world show optimism, hailing a new era of malaria research, and are rekindling the hope of conquering a disease that has proven extremely difficult to control and treat. Every year, more than 5% of the world's population are infected at any given time (most in sub-Saharan Africa), more than 1 million die from malaria (most are children younger than 5 years), and some economists believe that in countries with high transmission, economic growth is decreased by up to 1·3% every year. Efforts to combat malaria were once more given momentum in October, 1998, when Roll Back Malaria was initiated by WHO, UNDP, UNICEF, and the World Bank. The initiative's aim is to halve the burden of malaria by 2010 by enabling everyone at risk to sleep in a mosquito-free environment, providing prompt diagnosis and treatment, giving antimalarial treatment to all pregnant women at risk, and establishing early identification and effective response to epidemics. The plan, as agreed at the African Summit in Abuja, Nigeria, in 2000, was to achieve 60% coverage for the first three actions by 2005. These aims would go a long way towards alleviating burden of disease, and therefore poverty, in sub-Saharan Africa. But increasing resistance by the parasite to affordable drugs and by the vectors to insecticides, the phasing out of DDT as agreed at the Stockholm Convention on persistent organic pollutants in 2001, and the lack of funds to provide an adequate infrastructure and simple and affordable preventive measures, such as insecticide-treated bednets, make these goals increasingly unrealistic. New drug compounds are few and too expensive. Vaccines are at best more than 10 years away from being safe enough to be broadly applied to populations at risk. Will the knowledge about the genomes turn the tide? Perhaps it will open up new avenues for drug and vaccine development. Perhaps it will make a genetically modified mosquito that cannot act as vector a reality once processes are in place to deal with ethical, legal, and social issues. But any new developments are unlikely to happen before the 2010 deadline set for Roll Back Malaria. New drugs based on knowledge about the genome will probably not be affordable to those countries that need them most. Scientists are right to be excited from a scientific point of view and most are appropriately cautious. In a press conference, Neil Hall from the Wellcome Trust Sanger Institute likened the discovery to “a haystack … and now scientists have to find the needle”. Further research needs to be carefully planned and ideally should be a concerted effort between researchers in the developed world and those at the frontline in African countries. In the short-term, however, the danger is that even more funds will be poured into basic research and established and relatively cheap preventive measures will be further neglected. Of the more than 300 received proposals, the Global Fund to fight AIDS, Tuberculosis and Malaria awarded money for 40 in its first round, but only about 10% of resources went to the least “prestigious” disease malaria (see Lancet 2002; 360: 888–89). Hopefully this imbalance can be redressed in the second round of grants to be awarded in January, 2003. What is urgently needed is an increased effort by wealthy nations and the international community to pledge sufficient funds to malaria prevention. If the genome publications will indirectly contribute to this effort by shifting malaria into the limelight, there is hope for a new era of public health.