PerspectivesAre you interested in submitting a Perspective Article? Be sure to read The Science Advisory Board's Editorial Guides for Perspective Articles. Click here. Malaria: “Here I come!” by Wim D’Haeze, Ph.D. Malaria is one of the most devastating vector-born diseases and is responsible for the highest global morbidity and mortality. The statistics are stunning in that over 40% of the world’s population is at risk, and that 0.7 to 2.7 million individuals die of malaria each year; 75% of them are African children younger than five years old. In other words, over 3,000 children die from malaria every day. In the United States, 1,337 cases of malaria, including eight deaths, were reported in 2002. Generally, the major at-risk groups include those persons whose immunity has not yet developed (e.g., travelers, young children in endemic areas), and those whose immunity is compromised (e.g., pregnant women, routinely exposed people). Obviously, because of the global burden caused by malaria, its control is a priority. Four species of malaria parasites can infect humans under natural conditions. These are Plasmodium falciparum, P. vivax, P. ovale, and P. malariae. P. falciparum causes severe, potentially fatal malaria, P. vivax and P. ovale have dormant liver stage parasites that may reactivate and cause malaria several months or years after the respective mosquito bite, while P. malariae produces long-lasting infections. Development of the Plasmodium sp. within the mosquito mainly depends on the temperature and humidity. Malaria is transmitted to humans by female Anopheles mosquitoes that live and breed in areas with stagnant water (e.g., swamps) and during the rainy seasons in Africa while taking a blood meal to carry out egg production. Upon the mosquito bite, malaria sporozoites are injected into the human skin. Once entered in the blood of a human, the parasites grow and multiply initially in liver cells followed by a colonization of red blood cells which ultimately leads to a spread over the entire body. Broods of parasites grow in the red blood cells and destroy them, releasing more parasites into the blood ready to infect more blood cells. The symptoms associated with malaria infection may vary and include asymptomatic infections with no apparent illness, to the classic symptoms of malaria (i.e., fever, chills, sweating, headaches, muscle pain) to severe complications (i.e., cerebral malaria, anemia, kidney failure) that can result in death. Of note is that a malaria infection often starts off with symptoms similar to those of a flu which may mislead to misdiagnosis and relatively short but important delays in the treatment of the disease. Although no powerful medicine that would protect us and/or would be able to cure the disease is yet available on the pharmacy shelves, immense progress has been made during the last decade in our understanding of the infection process. Using fluorescently labeled parasites and real-time confocal microscopy, researchers have thoroughly characterized the sporozoites infection process in the skin of mammals, and their subsequent passage through blood and lymph vessels which led to the discovery of new stages of the life cycle. In addition, a tremendous amount of energy and funds have been invested in the discovery of a suitable vaccine against malaria. Recently, a vaccine construct has been designed using unique and conserved regions of the P. falciparum surface protein 3. The antibodies induced upon injection of this vaccine construct inhibited parasite growth in a manner which was greater than that induced by natural antibodies retrieved from immune African adults. Although this putative malaria vaccine still needs to be thoroughly tested in future clinical trials, the first results strongly suggest that anti-parasitic activity can be achieved using a parasite protein-derived vaccine. In general, it is thought that a suitable malaria vaccine should be cleared and ready for use by 2010, but whether there will be enough produced by then to protect all people at risk, and whether it will be affordable and accessible for all African nations remains uncertain. Despite all the efforts to restrict the spread of malaria, it is unfortunate to learn that malaria is considered a re-emerging disease. This is caused in part by the appearance and spread of drug-resistant parasite strains which hinders the efficacy of commonly used antimalaria drugs, and necessitates the use of other more expensive drugs, the application of which may be less safe because of the severe side effects. Resistance has been reported to all drugs available to date which is most probably due to inadequate drug usage. In addition, the complexity of the Plasmodium sp. genomes and the quick adaptability to various microenvironments within the host render the exact mode of action of antimalarial drugs difficult to investigate and understand. Furthermore, insecticide resistance of the Anopheles vectors decreases the efficiency of interventions that relay on insecticides including insecticide-treated nets to cover beds. The health infrastructures in developing countries that cope with hunger and often wars are cumbersome and do not necessarily allow recommended interventions. It is also problematic that the majority of the at-risk population is poor and uneducated. In addition to these factors, one should also consider the influence that global warming and accompanying changes will have on the global spread of malaria. Although opposed by some voices, the measurements and long-lasting data collections convincingly illustrate that the global climate is rapidly changing. The average temperature of the earth's surface has risen by about 1 ° Fahrenheit in the past century as a result of accelerated warming. This accelerated global warming is most likely due to human activities which have in fact altered the chemical composition of the atmosphere via the century-long build up of greenhouse gasses such as CO2, CH4, and NO which are generated during the combustion of fossil fuels and by other human activities. Those greenhouse gasses accumulate in the lower atmosphere forming a layer that insulates the earth. Warming of the atmosphere heats the oceans, melts the ice, and increases the atmospheric water vapor which has a considerable influence on the weather. Ample examples exist: Greenland is losing its ice mass at 3% per decade and the melting rates have accelerated; major glaciers in Switzerland are shrinking; South and Central Europe have experienced long-lasting unprecedented heat waves and droughts; the United States has faced extremely destructive hurricanes; lower parts of Europe are more frequently flooded than before. Obviously this global warming and the accompanying climate changes will have severe effects on the world’s population, economy, agriculture, and, maybe most importantly, on the spread of infectious diseases such as malaria. Extended periods of droughts and flooding will facilitate outbreaks and the higher temperatures will stimulate the spread. Of note is that rising temperatures not only increase the parasite and vector survival rates, but also boost biting and reproduction rates; and prolonged breeding seasons shortens the maturation period of the parasite in the mosquito vector. For example, at 68° F, P. falciparum requires 26 days to mature whereas at 77° F, the parasite develops in half of the time. In other words, higher temperatures will not only increase the spread of malaria, but will also exponentially enhance the infection rate and progression. Obviously, the general trend suggests that the climate is warming, and the effects that we are able to observe now are most likely due to human activities performed about a decade ago. I am convinced that hurricanes may appear in regions were they are not common and that the known hurricane regions may have to tackle much more severe ones. In addition, generally wet regions in Central and Northern Europe may become considerably drier. Those and other factors will induce the spread of malaria and allow it to re-emerge in regions where this disease is new to its inhabitants. Are we all ready for this, and by all means, can we stop it? The answer is probably “no.” Obviously, governments should not ignore those upcoming issues, and should continue to support the study of affordable cures to protect us against malaria and other (re)-emerging infectious diseases. The big efforts that are being undertaken to harmonize economies in such a way that the global production of greenhouse gasses diminishes are promising, but as long as not all countries worldwide combat the problem together and uniformly, its success will only be mediocre. Moreover, malaria is probably not the only disease that will spread and re-emerge as a consequence of human life on earth during the industrial evolution. Maybe it might be smart to start small and think of environment -friendly ways to travel between cities that are located close to each other (e.g., by train), or to ask ourselves twice before taking the car to visit the local supermarket. ### Wim D’Haeze is a Bio-Engineer in Chemistry and received his Ph.D. in Biotechnology at Ghent University (Belgium) in June 2001. His doctoral thesis work was focused on the understanding of several early steps of the symbiotic interaction between the Gram-negative soil bacterium Azorhizobium caulinodans and the tropical legume Sesbania rostrata. The initial steps require the production of bacterial compounds including signal molecules and complex surface polysaccharides that are pivotal for invasion of the plant tissue and the formation of new organ tissues. In the three subsequent years, he performed post-doctoral research at the Complex Carbohydrate Research Center at the University of Georgia (Athens, GA) dealing in part with the structural and functional characterization of azorhizobial extracellular polysaccharides. Currently, Wim D’Haeze is employed at The Scripps Research Institute (La Jolla, CA) as Science Writer and focuses on a new horizon regarding the molecular basis of devastative neurodegenerative diseases, such as Alzheimer’s and Parkinson’s diseases, in order to screen for and develop new therapeutics. E-mail: wim.dhaeze@sbcglobal.net ### << Previous Next >> [ View All Perspectives ] |
|
