The Real Millennium Bugs

Emerging Infections 3 By Scheld W. Michael, Craig William A., Hughes James M. Washington DC: ASM Press (1999). 258 pp. $79.95Emerging Infections: Biomedical Research Reports By Krause Richard M. San Diego CA: Academic Press (1998). 513 pp. $84.95Infectious diseases have been powerful forces in both evolution and human history, as emphasized recently by Jared Diamond in his book Guns, Germs and Steel: The Fates of Human Societies. When the conquistadors arrived in Central and South America, they brought with them their infectious diseases, which had never before been seen in the New World. The resulting epidemics of smallpox and other infections in an immunologically naive population devastated the native civilizations and ensured the success of the invasion. These are among the best-documented historical examples of “emerging infections” and illustrate the spread of disease along ocean trade routes. Now, disease can travel even faster, as airplanes can move people and their infections around the world in a day. Whether any given introduction of a pathogen results in an epidemic depends on many factors, including the availability of competent vectors, the density of susceptible populations, and the transmissibility of the agent.Given the history of infectious diseases, it was perhaps naive to believe that we could eliminate them as a significant problem. Nevertheless, anyone looking at public health statistics for industrialized countries in the twentieth century would have to agree that the control of infectious diseases was one of our great successes. The fearsome killers of the past—diphtheria, tuberculosis, typhoid fever, typhus, measles, etc.—are now largely diseases of historic interest or foreign climes. In the decades after WW II it was widely believed that vaccines and antibiotics had solved the problems of infectious diseases, and the NIH turned its attentions toward chronic diseases that had become the leading causes of death, such as atherosclerosis and cancer. We also began to spend less on public health infrastructure at every level of government, and some medical schools even stopped teaching microbiology.Imagine our surprise then when we were confronted with a series of outbreaks due to previously unknown pathogens. Legionaires disease burst on the scene during the bicentennial convention of the American Legion, and after months of speculation about everything from bioterrorism to heavy metal poisoning, investigators at CDC discovered Legionella pneumophila and showed that it had been the cause of several prior unsolved epidemics. Shortly thereafter, menstrual toxic shock syndrome was recognized and came to involve 1/1,000 menstruating women in the U.S., with many deaths before investigators at CDC established the relationship of this illness to a new catamenial product that was then taken off the market. In this case, the disease was due to the spread of a transposable element among strains of an old pathogen, coinciding with the introduction of a new tampon that somehow promoted the secretion or absorption of the exotoxin. Thus, the epidemiology of infectious diseases is not only a consequence of the spread of organisms, but of genetic elements that spread within organisms and contribute to their virulence.The list of infectious diseases that have been discovered since 1976 is quite long and diverse. The factors that contributed to their appearance are also quite diverse, ranging from ecological shifts both in this country (Lyme disease) and in Africa (HIV and ebola), to changes in weather patterns (pulmonary hantavirus), to geological catastrophes (coccidioidomycosis in California). Finally, to everyone's amazement we are now learning that several chronic diseases are in fact infectious diseases. This includes all the major diseases of the stomach, and several malignancies that are clearly due to chronic viral infections such as cervical cancer caused by HPV and hepatomas caused by HCV and HBV. There is even suggestive evidence that atherosclerosis may be caused by chronic chlamydial infections.Faced with the apparent resurgence of infectious diseases, the IOM/National Academy of Science formed a committee headed by Joshua Lederberg, which issued a report in 1992 on Emerging Infections. They defined the concern as “clinically distinct conditions whose incidence in humans has increased regionally or worldwide.” The lengthy report recognized that all manner of pathogens had been involved, and that the problem should be defined broadly enough to include the rising prevalence of antibiotic-resistant pathogens. The report made several recommendations, including a call for more research and for increased spending on public health. Partly in response to this imperative, for the last three years the annual ICAAC meeting of the American Society of Microbiology has had a symposium on emerging infections and the ASM Press has published three volumes based on these symposia. Volume 3 has 14 chapters, of which the first 9 are devoted to specific agents. The chapter on hepatitis E is the only one devoted to a viral agent. (The two earlier volumes include several chapters on viral infections including hemorrhagic fevers and hantavirus.) The majority of the chapters are written by authors from CDC, so it is not surprising that the emphasis is on epidemiology. The clinical descriptions of some of the infections are brief, and there is often little about pathogenesis of infection.The various diseases covered in this volume illustrate the varied circumstances that lead to the emergence of an infectious disease. For instance, typhus is again rampant in Africa, as civil wars have displace thousands of people into refugee camps, forcing them to live under conditions that favor the spread of body lice, the vector of this ancient plague. In contrast, we have the unexpected health effects of the rise of new industry, aquaculture, which supplies finfish for consumption in much of the world. Not surprisingly, just as commercial livestock farms are a breeding ground for animal pathogens, fish farms are a breeding ground for aquatic pathogens, some of which cross over to humans. An example of such a pathogen is Streptococcus iniae, first reported to infect people by a group in Toronto. Asians who like to buy live fish and prepare them for eating are most often infected from handling infected fish. The aquatic environment is also represented by a chilling chapter on Pfiisteria piscidia, a microalgae with a remarkably complex life cycle that can fill fish and release a neurotoxin that affects humans who work in close and prolonged contact with contaminated water. The chapters on Rickettsioses and Microsporidia largely catalog the newly discovered members of the species and briefly describe the illnesses they cause. There is an interesting chapter on emerging infections in animals, a reminder to us not to be so homocentric in our thinking about infectious diseases. The chapter on bioterrorism might seem out of place in this book, but it emphasizes how difficult it may be to distinguish between a natural epidemic and one that is perpetrated intentionally. The recent episode of West Nile virus infections being introduced into New York City and environs illustrated that connection. Good epidemiology showed that the virus was spreading by classical and expected means from mosquitoes to birds, even though it had never before been seen on this side of the Atlantic Ocean. This apparently was enough to reassure the FBI. All three volumes in this series include chapters on parasitic infections such as Chagas disease that are of interest to infectious diseases specialists, but these are not necessarily emerging infections. Given the difficulty of obtaining reliable incidence figures for endemic diseases in many countries, this may be only a technicality.Another book with the same title was published in 1998, edited by William M. Krause, the Director of the National Institute of Allergy and Infectious Diseases for many years. It includes a chapter on mathematical models of epidemics by Roy Anderson from Oxford, 14 chapters on specific diseases, and one on antibiotic resistance. The chapters range in length from a comprehensive 80-page treatise on tuberculosis, to brief chapters that discuss cholera and E. coli O157 almost exclusively from the perspective of the new discovery of mobile genetic elements that contain almost all the genetic information that make them pathogens (see the following review by Finlay). The chapter on influenza by Robert Webster is a model of clarity. All the chapters in both books are well referenced.Neither book is a comprehensive textbook of infectious diseases, nor even a comprehensive treatise on “emerging infections.” Both are well-written and authoritative texts that should provide readers with a starting place to learn about these problems. Both are reminders of Louis Pasteur's famous maxim, “Messieurs, c'est les microbes qui auront le denier mot.”