PerspectivesAre you interested in submitting a Perspective Article? Be sure to read The Science Advisory Board's Editorial Guides for Perspective Articles. Click here. Parasitic Diseases: Opportunities and Challenges in the 21st Century by Daniel G Colley, Ph.D. The opportunities and challenges for the study and control of parasitic diseases in the 21st century are both exciting and daunting. Based on the contributions from this field over the last part of the 20th century, we should expect new biologic concepts will continue to come from this discipline to enrich the general area of biomedical research. The general nature of such a broad category of infections is difficult to distill, but they often depend on well-orchestrated, complex life cycles and they often involve chronic, relatively well-balanced host/parasite relationships. Such characteristics force biological systems to their limits, and this may be why studies of these diseases have made fundamental contributions to molecular biology, cell biology and immunology. However, if these findings are to continue apace, parasitologists must capitalize on the new findings being generated though genomics, bioinformatics, proteomics, and genetic manipulations of both host and parasite. Furthermore, they must do so based on sound biological insights and the use of hypothesis-driven studies of these complex systems. A major challenge over the next century will be to capitalize on these new findings and translate them into successful, sustainable strategies for control, elimination and eradication of the parasitic diseases that pose major public health threats to the physical and cognitive development and health of so many people worldwide. Basic Science Needs in Parasitology The genome sequencing programs under way with various protozoans and helminths are a clear indication of the intent of investigators in this field to move forward. Because of its obvious public health importance, work on the P. falciparum genome is leading the way, but following closely are T. gondii, L. major and the trypanosomes. The initial push will certainly be to use these tools for drug target and vaccine target discovery, but the yield will also be in areas of basic understanding of the genetics, biochemistry, cell biology, and even epidemiology of the organisms. Helminth genomics has struggled to develop apace, and now, with the completion of the Caenorhabditis elegans genome sequencing, an emphasis in parasitic nematode genomics is greatly needed. Trematode genomics is beginning to take shape with recent renewed interest in Schistosoma mansoni, but work in cestode genetics is still at the analysis stage. The incipient development of DNA microarrays to detect gene expression of P. falciparum is a welcome arrival on the current scene. These technologies will clearly contribute greatly to the ability to detect expression under multiple conditions of interest. Initially these are likely to yield profiling (or "fishing") expeditions, but hypothesis-driven studies will soon follow as the techniques are further developed and made more readily available to a larger number of investigators. The vast development of immune cell markers; transgenic and knockout hosts; recombinant immune components, such as cytokines, chemokines and their receptors; and monoclonal reagents have made experimental and human immune studies much more wondrous and amazing. Much of this work is still in the dissecting phase, where the amount of information generated is far ahead of our true understanding. Yet even so, important insights have been made. The future will rest on the effective use of genomics, reverse genetic analysis, proteomics and bioinformatics. Using these exciting tools in the proper host/parasite/vector context should yield new and useful understandings, leading to such tools as vaccines, drugs, and genetic manipulations that will substantially increase our ability to treat, control, and prevent many of these diseases. Parasitic Diseases that Pose Public Health Threats: Where Are We? What Is to Be Done? The list of parasitic diseases that are known to pose serious public health problems often depends on where one is on the globe. However, whichever candidates make one's final list, the picture is long and sobering. Yet major advances against these scourges have been made, are currently being made, and will continue to be made to an even greater degree in the 21st century. How has this occurred thus far, and how will it progress in the future? The path is not a simple one. It is a long and winding road that begins with scientific discovery and understanding, leads to tool development and comprehension of how best to use these tools, and progresses on to policy and decision making, implementation and management. Throughout this entire process the need for scientific research continues, but the nature of that research effort changes and refocuses as the process moves ahead. So where are we now in the world of curtailing morbidity and mortality caused by parasitic diseases? First, I should define what I mean by the various levels of limiting parasitic diseases or their consequences. The entry level of such programs is control. The term control implies that through deliberate efforts we can decrease transmission or severity of a given infection, and that the implementation of this ability will need to be an ongoing activity for the foreseeable future. Examples of diseases that are currently thought to be—with sufficient effort—controllable are malaria and the soil-transmitted helminths. Elimination of a disease is the next step past control. This means that appropriate implementation of the available tools can reduce the incidence of the disease in people (not necessarily other host species) to zero. Some have also inserted in this definition the phrase "as a public health problem". This then might apply to a zoonosis that no longer threatens people, but continues to be transmitted among other potential reservoir hosts. Elimination of an infection (either complete or as a public health problem) is defined as removing the threat of infection to a level at which it is no longer transmitted, but from which it could return. In the case of elimination, surveillance for a re-emergence of the disease is still needed, but further efforts at elimination are not warranted unless surveillance detects the occurrence of cases. The next level of such activities is eradication. Full eradication is the permanent reduction to zero of the global incidence of a disease. Once accomplished, neither further prevention nor surveillance is needed. In theory, an infection could be eradicated and yet the organism that causes the disease could be housed in a secure condition. To carry eradication to its full and logical conclusion, the total expungement of the organism responsible would require a further step, that is the extinction of that species. In addition to these strict definitions of control, elimination and eradication, it is possible to think of them as being applied to a given geographic area. Thus, elimination of polio has been achieved in the Americas, yet imported cases do still occur, so continued immunization must continue. When polio is eradicated from the world, as smallpox has been, there will no longer be any need to be immunized against polio, or to maintain surveillance for cases of polio. Similarly, India, once the country with a high number of cases of dracunculiasis (Guinea worm disease), has now been certified by the International Commission for the Certification of the Eradication of Dracunculiasis as having eradicated this debilitating infection. How does the decision get made to launch a control, elimination, or eradication program? The combination of appropriate tools, and the ability to use them in an effective and cost-effective manner must be coupled solidly to both the availability of sustained funds for the job, and the will to do the job. It bears remembering that the cost of a bad decision, that is, one based on an inappropriate strategy or misreading of public support, is very high, and can result in major adverse consequences for other fledgling or future efforts. The Future Now I enter into the wild world of forecasting, prediction, and gambling. What will the future look like for those who investigate parasitic diseases and those who seek to deliver us from their devastation? I predict that the future will be very busy. Based on the ongoing successes in both the basic science and field implementation areas of parasitic diseases during the last 15-25 years, I fully believe that the next century will see major advances in our understanding of both the biologic and behavioral science aspects of these diseases, and that this will be translated into successes in greatly decreasing their impact on human health around the globe. With these advances will come progress in human and societal development. The potential in vaccine development and delivery (i.e., progress in adjuvants based on better basic immunologic understandings), coupled with further recognition of the role of host genetics, will greatly change what is in the tool box for preventing parasitic infections. The promise of genetic manipulations of vectors, always an appropriate target for attacking transmission, is outstanding. Genomic information, translated into functional understandings of pathways and targets, will surely assist in the war against drug resistance and provide us with the means to design multi-focal drugs to delay such resistance. Regarding host genetics, some of the pioneering works indicating that infectious diseases have "helped" shape human evolution have been based on malaria and the genes for sickle cell anemia and HLA antigens. It is not yet clear how to turn these fascinating findings into interventions, but the scientific avenues that will open up during the 21st century will certainly hold many new opportunities, and genetic manipulations of hosts may be among them. The societal challenges are a bit more daunting to some of us, but here again research into the behavioral and societal aspects of these diseases will greatly assist in the implementation of effective measures against them. Also, another major shift in perspective in the last few years has been the recognition by agencies and governments that these infections not only result from poverty and poor standards of living, but also, in fact, are major contributors to poverty. This fundamental shift in perspective leads to the promotion of economic and social development by attacking these major public health problems. This promises to be a major, driving theme of much of the work on parasitic diseases in the future. So, sitting on the doorstep of the 21st century, we see that much has changed in the last 25 years. The first is the greatly increased understanding of the basic science of these organisms. The second is the translation of that understanding into tools appropriate to the task (e.g., new drugs, new diagnostics, the continued promise of new vaccines and vector manipulations). The third is the ability to analyze the public health impact of these diseases. The fourth is a recent influx of major new sources of funding (e.g., The Bill and Melinda Gates Foundation, The Turner Foundation, Rotary International, private industry, The Wellcome Trust, and many others). The fifth is the perception of health as a cornerstone of development, and the political will that is generated by that understanding. Human parasitic diseases caused by protozoans and helminths include a wide variety of infectious organisms, a broad spectrum of disease processes, and some of the most fascinating scientific and important public health challenges that we will face in the 21st century. Many of these diseases represent very well adapted host/parasite/vector relationships that imply a degree of co-evolution of these "partners in disease" that stretches the imagination. This is often exemplified by chronic infections that, in a high percentage of hosts, cause little morbidity, and life cycles that are exquisitely timed and organized for optimal, but regulated, transmission of the pathogen. A few of these diseases are more fulminant, and some clearly lead to more disease in recently infected populations of hosts than in long-standing situations of medium-to-high prevalence. Work with these parasites and their hosts and vectors span the gamut from very basic scientific research, to extremely practical implementation of eradication programs. It is, however, critical to remember that a sound scientific understanding of the organism, the vector and the host, and how they interact biologically, spatially, and temporally, is always the foundation upon which effective control, elimination, or eradication programs are based. Until the proper understanding of the situation is in hand, and the appropriate tools are assembled, sheer determination is simply usually not enough to effectively dominate these well established and spreading diseases. However, when science and public health progress together and join forces, creating a critical mass, true progress can definitely be made. We have good reasons to be highly optimistic regarding future efforts to make strong progress against some of the oldest and most widespread scourges of mankind. Such progress will undoubtedly need to be based on the aggressive pursuit of a better understanding of the organisms, vectors, and hosts. But that alone will not be enough. It is the responsibility of all involved to forge active links between those making these new findings and those seeking to implement the appropriate resultant principles and methodologies in the public health arena. We need to continue to press forward to create the atmosphere that will allow this critical bridge between research and control to flourish, so that all parties—the investigators, the clinicians, the public health officials, patients, and the public—benefit to the greatest extent possible. Daniel G Colley, Ph.D. Division of Parasitic Diseases National Center for Infectious Diseases Centers for Disease Control and Prevention Public Health Service U.S. Department of Health and Human Services Atlanta, Georgia ### Excerpted with kind permission from the journal, Memórias do Instituto Oswaldo Cruz, Vol. 95, Suppl. I: 79-87, 2000 The Memórias do Instituto Oswaldo Cruz website is http://www.dbbm.fiocruz.br/www-mem/index.html ### << Previous Next >> [ View All Perspectives ] |
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