Current Diagnosis & Treatment in Infectious Diseases

1. Introduction

Merle A. Sande MD

As a leading cause of death worldwide, infectious diseases have hardly been conquered or controlled. In fact, one might consider the 1990s as an era of reawakening, when new and reemerging infectious diseases were recognized as a major worldwide health problem. The continued explosion of cases of infections caused by the human immunodeficiency virus has now produced negative population growth and major disruption in the societies of many African countries, where more than 35% of young adults are infected and more than 25% of children are orphans. By the end of the millennium, the virus had infected more than 50 million people; it now ranks with childhood diarrheal diseases, pneumonia, malaria, and tuberculosis as a leading cause of death. While highly active antiretroviral therapy (HAART) has been astonishingly effective in treating the disease, the necessary drugs are available to only a small percentage of infected populations, and transmission of the virus continues unabated in many regions of the world.

The ability of modern technology to control infectious diseases has been found lacking. Antibiotics, which were developed within the last 60 years, resulted in the cure of many previously lethal infections, rightfully earning the name “wonder drugs.” However, only several years into the “antibiotic age,” pathogenic staphylococci were found to have the ability to produce enzymes (penicillinases) that destroyed penicillin, thus rendering the drug useless against these strains. The future quickly became clear to microbiologists and infectious disease clinicians studying bacterial genetics; the methods used to impede the organism's ambition to multiply and grow will eventually be defeated by the power of natural selection through the rapid emergence of resistant mutations. The more antibiotic pressure that has been applied, the more rapidly these subpopulations of drug-resistant pathogenic organisms have emerged. Public health-minded clinicians and scientists have issued warnings that overuse and misuse of these “wonder drugs” will eventually render them useless. These warnings have gone largely unheeded.

As we enter the next century, the possibility is quite real that these organisms have won and that we will return, in a sense, to the preantibiotic era. It will remain for our children or grandchildren to try to answer the question: Why did this generation of health providers not take better care of the future? It will be incomprehensible to them that we allowed antibiotics to be used in animal feed, to be used to treat colds and bronchitis due to viruses, and to be given to inpatients and outpatients without careful diagnostic evaluation. Will future generations eventually blame societal need to be “cost-effective” and the emergence of so-called managed care? Will they blame the pharmaceutical industry, whose need to make a profit led to misleading advertising, often directed at patients themselves? Will they blame physicians who did not learn microbiology and never bothered to consider the public health implications of their prescribing practices? Or will they blame our governmental agencies (the FDA, CDC, EPA, or NIH), whose job was to protect the public's health and make available scientific information that would dictate public policy but who did not do this? Will they blame patients themselves, who, because of misperceptions of the value and effectiveness of antibiotics, insisted on having their physicians prescribe them? Whatever future generations conclude about us, the facts are obvious: we continue to misuse and abuse antibiotics, one of the most important advances in human history, with little attempt to change.

The impact of antibiotic resistance is especially felt in hospitals, where infections caused by resistant organisms are increasing dramatically and have the potential to destroy gains enjoyed in other medical disciplines, such as organ transplantation, prosthetic devices, artificial organs, indwelling pacemakers, and neonatal and adult intensive care. Future medical advances will be determined to a large extent by the ability to prevent and successfully treat the nosocomial infections caused by antibiotic-resistant pathogens. The great irony is that the same areas of medicine where these latest dramatic advances are happening are also those where the most dramatic changes in microbes have taken place. Physicians involved in caring for transplant recipients, cancer patients, and patients requiring intensive care are entirely free to prescribe any and all antibiotics they want without consulting infectious disease specialists. There seems to be a puritanical obsession at work in medicine whereby narcotics, which relieve a patient's pain, are considered controlled substances that require a prescribing physician to fill out duplicate and triplicate forms, whereas any physician is free to prescribe any antibiotic, whether indicated or not.

Another great human accomplishment during the last century was the worldwide elimination of smallpox though vaccination. It was an example of warring nations actually cooperating for the common good. In the early 1970s, the majority of the world stopped vaccinating against smallpox. Only two vials of the virus were thought to be preserved and the two “superpowers” had agreed to destroy those vials in 1999, to rid the world forever of this deadly virus. It therefore came as a horrible shock, in 1998, to find out from Russian scientists that they had “weaponized” the smallpox virus and readied it for use against the West, along with anthrax spores, Yersinia pestis, and other organisms. The human potential for destructive acts seems limitless.

Other infectious diseases have also slipped back into our society. Our attempts to control mosquitoes were initially successful, and federally funded programs reduced the Aedes aegypti and Anopheles species to the point where the arthropod-borne encephalitis viruses almost disappeared.

Malaria, once the scourge of the southern United States and Central America, was nearly eliminated. However, while these mosquitoes became resistant to DDT, apathy dominated the governments' response, and funding was cut. The mosquitoes have returned en masse, as have dengue, yellow fever, diseases induced by the various encephalitis viruses, and malaria. Finally, cholera, which had disappeared from the Western Hemisphere for decades, reappeared in Peru in the early 1990s and spread throughout Central and South America, wherever poor sanitation and poverty dominate the domestic scene. Within several years, over a million cases and thousands of deaths were reported, another reminder of the fragile control we have on infectious diseases.

When the public health infrastructure of our cities is allowed to deteriorate, microbial pathogens are ready and willing to take advantage of our citizens. In New York City in the late 1980s, funding for the tuberculosis program, among many others, was reduced and case follow-up was discontinued; the follow-up rate for patients discharged from hospitals with a diagnosis of active tuberculosis was approximately 10%. Partly because of poor patient compliance with therapy, multiple-drug-resistant tuberculosis emerged and began to spread to other parts of the country. Many people, especially AIDS patients, died before the epidemic was finally controlled, when directly observed therapy was widely embraced and implemented. Similarly, when immunization slackened in Eastern Europe after the fall of communism, diphtheria reappeared, and more than 50,000 cases per year were reported in the early 1990s.

Our record of dealing with infectious diseases has been a checkered one, with some fantastic successes followed by dramatic mistakes and failures. It now seems clear that the virtual sea of microorganisms with which we must share this planet must be treated with care and understanding. We must learn to live in harmony with our normal flora and protect it from factors that breed resistance. We need to understand better the public health implications of unwise interventions such as mass use of antibiotics for the purpose of stimulating animal growth, or prophylaxis to prevent otitis media, or routine antibiotic treatment of respiratory tract infections caused by viruses.

One might be justified in greeting these challenges with an air of optimism. The requisite tools and insight necessary to predict, blunt, or suppress microbial virulence are at hand. The molecular language spoken between microbe and host cell is increasingly well described. So far, we know that the host-pathogen relationship is a two-way, intricate affair with features of codependence.

This textbook of infectious diseases is aimed at the student, house officer, or other trainee and at the practicing healthcare provider, with the hope of teaching these principles while providing a source of information that will help in the recognition, diagnosis, treatment, and prevention of these many emerging and reemerging infections. The book's format is one we hope allows easy access to the pertinent information that will facilitate the decision-making process and become a useful reference as we fight these current and future battles.