By Paul Benkimoun
    Le Monde

    Tuesday 26 April 2005

    Monday, April 25, was chosen as African Malaria Day 2005, an opportunity to highlight the ravages caused by this infectious illness caused by a parasite - of which four forms exist, the main one of which is Plasmodium falciparum - transmitted to humans by the bite of certain mosquitoes. There are ways to prevent the illness and effective treatments; however, about 40% of the world's population is exposed to malaria. Between now and 2010, half the planet's inhabitants, or close to 3.5 billion human beings, will be in that situation. Dr. Wenceslaus Kilama, President of the International Malaria Foundation, provided a measure of the number of victims of this epidemic: "Seven Boeing 747s full of passengers that crash into Mount Kilimanjaro every day."

    Africa is on the front line. About 90% of the million deaths attributed to malaria and counted by the WHO take place in this part of the globe, mostly among young children. The WHO also counts 300 million cases in the world every year. And it is most likely that these estimates are lower than reality. In the March 10 issue of Nature, the renowned epidemiologist Robert Snow and his co-workers just published new estimates of the geographic distribution of malaria episodes and crises in the world. They arrive at an average of 515 million malaria outbreaks with a range of between 300 million and 660 million. "These global estimates are as much as 50% higher than those reported by the WHO and 200% higher for the areas outside of Africa, which reflects the WHO's dependence on passive national notification for these countries," concludes Robert Snow's team. Similarly, Jean-François Trape, who directs the UR 77 on tropical parasitology at the Dakar Institute for Development Research (IDR), gives a range of "2.7 to 3 million deaths a year," instead of the official figure of one million deaths from malaria. "The strong increase in mortality from the illness observed starting in 1989-1990 is directly linked to increased resistance to chloroquine," explains Jean-François Trape. The fight against this plague had, in fact, experienced a leap ahead with the development of chloroquine, a cheap, well-tolerated medicine, effective in the prevention and treatment of malaria.

    Unfortunately, the appearance of forms of the parasite, the plasmodium, resistant to chloroquine has progressively posed a major public health problem. "Today," explains Jean-Marie Kindermans of Doctors Without Borders (DWB), "we count four times as many cases and three times as many deaths from malaria as during the 1970s." The levels of resistance to chloroquine are as high as 70% to 80% of cases, in some regions of Africa. Several other molecules have been used during the last few decades, but to these also, resistances have appeared. The real breakthrough is represented by "Artemisinine-based combination treatments" or ACT, a derivative of a variety of ginkgo used in traditional Chinese medicine. These combinations are very effective when one oral dose is taken daily. Starting in 2001, the WHO recommended that countries strongly affected by resistance to the traditional anti-malarials start using ACTs. There are several kinds, depending on the associated molecule (lumefantrine - the only one combined in a single tablet - amodiaquine or sulfadoxine-pyrimethamine, both in the form of separate pills).

    A new set combination of amodiaquine and artemisinine in a single tablet should come out in 2006, thanks to the joint efforts of the DNDi Foundation, created by DWB and the Pasteur Institute and the Sanofi-Aventis laboratory (April 11 edition of Le Monde). Several clinical trials published in the April 23 issue of Lancet, as well as in the April edition of the online magazine Public Library of Science (www.plosmedicine.org) attest to the effectiveness of the ACT. The only hitch is that if "about fifty African countries have decided to change their treatment protocol to include the ACT drugs, today only nine of them have taken any concrete steps towards this change," rails Jean-Marie Kindermans.

    The supply of artemisinine is a problem that has not been resolved, and in spite of the warnings coming from DWB for the last year and a half about the interruption in raw material supplies, nothing has happened, and the available supply remains well below the demand. Along with the use of mosquito netting soaked in insecticides, new paths to prevention appear promising. In The Lancet, David Schellenberg's team demonstrates that a "preemptive intermittent treatment," which consists of administering a dose of sulfadoxine-pyrimethamine to a child three times during vaccination sessions (at 2, 3, and 9 months) allows a reduction in the incidence of malaria by 59% during the first year of life and by 36 % in the course of the first two years.

    "That could constitute one of the most effective methods in the fight against malaria," comments Jean-François Trape - on the condition that a mobilization commensurate to the stakes involved occurs. Both a health and a development problem, malaria represents a loss of 12 billion dollars a year to Africa's Gross Domestic Product (GDP), while three billion dollars a year would suffice to control this disease world wide.

    No Vaccination for At Least Ten Years

    "Research into an anti-malarial vaccine has progressed rapidly the last few years. (...) However, it will most likely take a decade before an effective vaccination is available for wide usage in the countries where malaria is endemic," deem the Lancet columns of Professor Bernard Greenwood of the prestigious London School of Hygiene and Tropical Medicine. The realization of such a vaccine slams up against the complexity of the parasite involved. The latter takes successive forms inside the human organism, each of which differs at the immunological level: immunity to one of these forms confers no immunity to other forms, and it has not been possible to experimentally provoke immunity against the plasmodium before its passage into the blood stream. Moreover, the parasite provokes disorders in the human immune system. Nonetheless, the completion of the complete genetic sequencing of the Plasmodium falciparum genome, as well as that of the mosquito which is the vector between it and humans, could offer an opportunity for research based on biotechnologies.