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Humanity has but three great enemies: fever, famine, and war; of these by far the greatest, by far the most terrible, is fever.

—Sir William Osler, 1896*

When Sir William Osler, the great physician/humanist, wrote these words, fever (infection) was indeed the scourge of the world. Tuberculosis and other forms of pulmonary infection were the leading causes of premature death among the well-to-do and the less fortunate. The terror was due to the fact that, although some of the causes of infection were being discovered, little could be done to prevent or alter the course of disease. In the 20th century, advances in public sanitation and the development of vaccines and antimicrobial agents changed this (Figure 1–1), but only for the nations that can afford these interventions. As we move through the second decade of the 21st century, the world is divided into countries in which heart attacks, cancer, and stroke have surpassed infection as causes of premature death and those in which infection is still the leader. That is, unless there is a pandemic causing infection to again become the leading killer everywhere.


Death rates for infectious disease in the United States in the 20th century. Note the steady decline in death rates related to the introduction of public health, immunization, and antimicrobial interventions.

A new uneasiness that is part evolutionary, part discovery, and part diabolic has taken hold. Infectious agents once conquered have shown resistance to established therapy, such as multiresistant Mycobacterium tuberculosis, and diseases, such as acquired immunodeficiency syndrome (AIDS), have emerged. The spectrum of infection has widened, with discoveries that organisms earlier thought to be harmless can cause disease under certain circumstances. Who could have guessed that Helicobacter pylori, not even mentioned in the first edition of this book (1984), would be the major cause of gastric and duodenal ulcers and an officially declared carcinogen? Bioterrorist forces have unearthed two previously controlled infectious diseases—anthrax and smallpox—and threatened their distribution as agents of biological warfare. Finally, our current COVID-19 pandemic caused by the emergence of a new member of the well-known Coronavirus genus threatens to become the leading killer, not just in a century but ever. For students of medicine, understanding the fundamental basis of infectious diseases has more relevance than ever.

*Osler W. JAMA. 1896;26:999.


The science of medical microbiology dates back to the pioneering studies of Pasteur and Koch, who isolated specific agents and proved that they could cause disease by introducing the experimental method. The methods they developed lead to the first golden age of microbiology (1875-1910), when many bacterial diseases and the organisms responsible for them were defined. These efforts, combined with epidemiologic work begun by Semmelweis and Lister, which showed how these diseases spread, ...

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