In 1971, I appeared before my state medical licensing board for a required routine interview before being able to practice medicine in Rhode Island. I was asked what my specialty was, and when I replied "Infectious Diseases," the group of wizened physicians on the Board looked at me rather incredulously and asked, "Are you going to have enough to do?" They were not being sarcastic or even naive. In fact, these experienced physicians were convinced that infectious diseases were solved, cured by antibiotics or eliminated by vaccines.

Over the past four decades enormous changes in clinical infectious diseases have been recognized. We have seen a myriad of infecting agents "emerge," and with them new clinical syndromes and diseases. It is not that the microbes themselves are necessarily new, as the microbial world has existed for millions and millions of years, but rather that new clinical illnesses have been described and ultimately discovered to be caused by micro-organisms hitherto either unrecognized or clearly known to cause disease. Human behavior and social ecology surely have had major influences on these phenomena. In addition, we have recently encountered growing problems with antimicrobial resistance among bacteria that for the past 50 years had been treatable with available antibiotics, but which now threaten our ability to cure common infections.

Social changes have had enormous impact on infectious diseases. For example, the death rate from tuberculosis in the United States declined considerably as housing conditions improved, well in advance of any active treatments for the tubercle bacillus. Similarly, the incidence of rheumatic fever and acute glomerulonephritis, sequellae of infections with Streptococcus pyogenes, also known as "Group A beta-hemolytic streptococci," declined with decreased crowding in households. It is clear that penicillin was and is indeed a wonder drug in terms of eradicating streptococcal skin and pharyngeal infections, but social changes impacted these diseases greatly as well.

Over the past half century, several "new" infections have been identified or have increased in number as a direct or indirect result of social changes. For example, it is highly likely that Lyme disease "existed" for centuries before it was identified in the last half of the twentieth century, and its specific pathogenic bacteria were identified and characterized so beautifully by modern epidemiology and molecular biology. It is highly likely that suburbanization and exurbanization was responsible for bringing more and more people in direct contact with the Ixodes tick that transmits the causative organism of Lyme disease, Borrelia burgdorferi.

Legionnaire's disease was first recognized in the 1970s after veterans attending a Legionnaires' convention in Philadelphia became ill with a respiratory illness. The causative organism, Legionella pneumophila, surely existed for eons before these first cases came to light. Modern epidemiology and bacteriology relatively quickly associated the dissemination of these water-borne bacteria with air-conditioning cooling systems - an example of modern technology making possible the convening of large groups of people in relative comfort. It has also been shown that this organism lives comfortably in the scaly sediment on the inner surface of water pipes in many areas. Outbreaks of Legionnaire's disease have been associated with building construction, as the "jackhammering" of ground near water pipes helps these organisms to leave their comfortable environment in the pipe scale and enter the water supply itself.

As illustrated in this book, there is no more obvious association of changing human behavior and infectious diseases than that linking social change and sexually transmitted infections (STI). Fifty years ago, any textbook on sexually transmitted diseases would have included chapters on diseases caused by two or three microbes known to be transmitted sexually. The enormous changes in sexual mores, possibly initiated by the introduction of oral contraceptives, have led to a dramatic expansion in the number of pathogenic microbes that can be spread sexually. Well over 35 micro-organisms are known to cause human infection in association with sexual behavior. For example, a formerly rarely seen infection of the uterus with Actinomyces has been well described in association with the use of certain indwelling contraceptive devices or coils. Oral contraceptives were introduced in the 1960s, and this was followed by dramatic increases in syphilis and gonorrhea as well as the description of "new" genital infections caused by Chlamydia trachomatis, Herpes simplex virus, and, of course, Human Immunodeficiency Virus (HIV) and AIDS.

The introduction of the Internet has led to new outlets for "instantaneous" sexual mating, and recent outbreaks of syphilis and other STIs are well described. The gay liberation movement in the past century made it possible for more and more homosexuals to live openly, and in the years prior to the HIV/AIDS epidemic sexual contacts were facilitated and transmission of many organisms occurred. The introduction of the Human Immunodeficiency Virus in the population of men who have sex with men is well described in this book. HIV existed long before its first recognized clinical manifestations 25 years ago, but the importance of social changes in sexual mores of gay men in the developed world as well as heterosexual Africans and Asians, where this infection has spread rampantly, are clear examples of the interaction of social behavior, social ecology, and the microbial world. Women's movements have also impacted STIs, first liberating them to have more sexual encounters (the so-called "swingers" of the early 1970s) but now empowering women to take more proactive roles in the prevention of STI transmission.

Over the past five or six decades, intravenous drug use was well known to be a risk factor for staphylococcal, pseudomonas, and fungal infections, and physicians became familiar with the occurrence of serious bloodstream, cardiac, and bone infections caused by these organisms in IV drug users. HIV, hepatitis B and C, and other blood-borne pathogens are increasingly being recognized in patients who use intravenous drugs. It is also not uncommon for physicians to overlook the possibility of drug use in their patients. The frequency of drug use across all strata of society is not well understood, but an important chapter in this book on this topic brings this clearly into focus.

As the world has been "shrunk" by thousands of daily flights from everywhere to anywhere, the influence of travel on infectious diseases has been magnified. Years ago international travel was available only to the very rich, who rarely came in contact with sick people during their trips. The recent epidemics of SARS and West Nile Virus (WNV) in North America call attention to the ease with which infectious agents can be transported around the world by people incubating infectious diseases. While most people do not travel when they are very ill, many people can and do travel while they are in the "incubation phase" of an infection. Neither the West Nile Virus nor the coronavirus associated with SARS evolved overnight, but the ability to fly quickly from continent to continent clearly allowed these agents to enter new areas of the world and spread rapidly to close contacts. The spread of WNV from the eastern to the western part of the United States over a few summers indicates how susceptible the population is to infection with a newly introduced virus. (Infection with WNV itself is not necessarily associated with symptomatic illness.) Outbreaks of tuberculosis and food-and water-borne infections are well described aboard airplanes and cruise liners. Travel-associated infections are also being increasingly recognized as an outcome of "adventure travel" and other trips that bring tourists and business people into areas not previously frequented by these groups. The new discipline of Travel Medicine, championed by Dr Mary Wilson and others, has arisen in response to imported infections in returning travelers.

The association of pestilence and war is well established in medical history. In early wars, death from infected wounds was the major fate of those who survived the initial trauma of battle. Today, soldiers billeted in parts of the world where vector-borne parasitic diseases are common are obviously exposed to agents they had never encountered in basic training. War wrenchingly disrupts society, and often leads to the displacement of large numbers of people from their homes. Prisons and refugee camps are well known to allow the rampant spread of infections, and these are all too common in these socially displaced people. Prisons have a special ecology, and have been associated with the transmission of drug resistant tuberculosis, hepatitis, HIV and other STIs and, more recently, staphylococcal skin infections caused by antibiotic-resistant bacteria. Society is now being challenged by the specter of bioterrorism-related spread of infectious agents. The still unsolved distribution of anthrax via the mail a few years ago reminds us how fragile this ecology is, and how aberrant behavior armed with biological weapons could affect populations around the globe. The tragic juxtaposition of terror and pathogens is a warning for all concerned people of the world, and this arena is brought into clear if dangerous focus in this book.

Since their introduction in the middle of the twentieth century, antibiotics have been seen as wonder drugs. The early drugs, penicillins and cephalosporins, were incredibly effective in the treatment of bacterial diseases caused by streptococci, staphylococci, and common gram-negative bacteria such as E. coli - the principal cause of urinary tract infections. Morbidity and mortality associated with common bacterial illnesses such as pneumonia, bacteremia and endocarditis, urosepsis, osteomyelitis, peritonitis, syphilis, gonorrhea, and many, many others dramatically decreased as a direct result of these life-saving wonder drugs. The early antibiotics were extraordinarily safe and not associated with serious toxicity (other than anaphylaxis in patients with severe antibiotic allergies). Their wide availability, safety, and relative affordability led to rampant social demand, subsequent use and surely eventual misuse. In the mid-1970s, enough antibiotic was marketed to treat every man, woman, and child in the United States for two bacterial infections per year -far more than the actual number of bacterial infections that occurred. It has been estimated that about 50 percent of antibiotic use now is for the treatment of respiratory infections in children, the vast majority of which are due to viruses that do not respond in any way to antibiotics.

As bacteria are able to rapidly "evolve" systems to overcome the actions of antibiotics, it is no wonder that many antibiotics in common use only 10 years ago are losing their punch. Bacteria have "learned" how to destroy the penicillins and cephalosporins, as well as aminoglycosides, with enzymes that they manufacture, and they can modify their structures with slight genetic changes that result in alterations in the targets of the heavily-used and successful fluoroquinolone and macrolide classes of antibiotics. They have evolved "efflux pumps" that can eliminate the antibiotic from the bacterial cell and make it difficult or impossible for the drug to reach its target. The clinical result of these manipulations is increasing failure of antibiotics to cure more and more infections, the causative organisms of which have been called "killer bacteria," such as methicillin-resistant Staphylococcus aureus (MRSA), currently causing large numbers of skin infections in many otherwise healthy people around the world. These infections are still susceptible to some old and new antibiotics, but how long this will continue is arguable. Another "social" change is the recent decline in the number of pharmaceutical companies willing to invest in the discovery and development of new antibiotics in the face of increasing antibiotic resistance -surely an ominous situation. It could be argued that antibiotics have made possible so many advances in modern medicine - including bone-marrow and solid organ transplantation, and the treatment of cancer with drugs that temporarily ablate the immune system, rendering people very susceptible to bacterial (and other) infections - that it is hard to imagine continued success in these important advances without antibiotics to treat life-threatening bacterial infections in these seriously ill patients.

It seems obvious to me after almost four decades of work in the field of infectious diseases that there is still much to be done. The brilliant text that follows gives testimony to the critical interaction of germs and people, of societal upheavals and infectious diseases. The world can learn much from the past, and hopefully our leaders can apply these lessons to achieving a healthier future for us all.

Stephen H. Zinner MD

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