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Chapter 8 - Infectious Diseases

Alexander J. McAdam MD, PhD

Arlene H. Sharpe MD, PhD *

*The contributions of Dr. John Samuelson and Dr. Franz von Lichtenberg to the previous editions are gratefully acknowledged.

General Principles of Microbial Pathogenesis

Despite the availability and use of effective vaccines and antibiotics, infectious diseases remain an important cause of death in the United States and worldwide. In the United States, two of

the top 10 leading causes of death are infectious diseases (pneumonia and influenza, and septicemia).[1] Infectious diseases are particularly important causes of death among the elderly and

people with acquired immunodeficiency syndrome (AIDS), those with chronic diseases, and those receiving immunosuppressive drugs. In developing countries, unsanitary living

conditions and malnutrition contribute to a massive burden of infectious diseases that kills more than 10 million people each year. Most of these deaths are among children, especially from

respiratory and diarrheal infections.[2]


The history of infectious disease pathology is intertwined with that of microbiology. Some of the major historical events in these fields are briefly described here to provide a perspective

for the concepts of pathogenesis to be discussed later. Some important experiments that were performed in the past would not be ethically acceptable today.

Louis Pasteur and Robert Koch were pioneers in establishing the microbiologic etiology of infectious diseases. Pasteur is credited with proving that microorganisms can cause disease (the

germ theory of disease). Pasteur also created the first attenuated vaccines, including a rabies vaccine for humans in 1885. In 1882, Koch championed criteria for linking a specific

microorganism to a disease. Koch's postulates require that (1) the organism is found in the lesions of the disease, (2) the organism can be isolated as single colonies on solid media, (3)

inoculation of the organism causes lesions in experimental animals, and (4) the organism can be recovered from the experimental animal. Koch also isolated the bacteria that cause

tuberculosis (Mycobacterium tuberculosis) and anthrax (Bacillus anthracis).

Ronald Ross, an English military physician posted in India, demonstrated in 1897 that mosquitoes carry malaria. At the time, it was believed that malaria was caused by breathing the air

near swamps ("malaria" comes from the Italian for "bad air"). Ross's demonstration that Anopheles mosquitoes transmit malaria led to public health efforts to reduce malaria through

control of mosquitoes. This was successful in the United States, but malaria continues to be a major health problem in many parts of the world.

Walter Reed, an American military physician, led a team of investigators in Cuba in 1900 who demonstrated that yellow fever, like malaria, is transmitted by the bite of mosquitoes.

Military volunteers allowed themselves to be bitten by mosquitoes that had previously bitten people sick with yellow fever. Following Reed's result, Dr. James Carroll showed in 1901 that

yellow fever was caused by a virus. This was the first demonstration that a virus causes disease in humans.

F. Peyton Rous found the first evidence for an infectious cause of cancer in 1909. In 1911, Rous demonstrated that a virus causes sarcoma in chickens. Although a viral cause has not been

found for most human cancers, we now know that viruses can contribute to the development of some; such associations include human papillomaviruses and cervical cancer.

The dawn of modern microbiology, which is based on molecular genetics, came in 1944, when Oswald Avery demonstrated that transfer of DNA from virulent to avirulent Streptococcus

pneumoniae transformed the latter into a virulent phenotype. This showed that DNA is the genetic material, leading to an explosion of research in molecular genetics. Today, the entire

genomic sequences of many species, including microbes and humans, are known, and this holds great promise for future research into the pathogenesis, diagnosis, and treatment of

infectious diseases. Knowledge of the genomes of the host and pathogens promise to produce a much richer description of the host response to infectious

agents than the morphologic descriptions of antimicrobial responses in this chapter.


Although infectious diseases such as leprosy have been known since biblical times and parasitic schistosomes and mycobacteria have been demonstrated in Egyptian mummies, a

surprising number of new infectious agents continue to be discovered ( Table 8-1 ). The infectious causes of some diseases with significant morbidity and mortality (e.g., Helicobacter

pylori gastritis, hepatitis B and hepatitis C, human metapneumovirus respiratory disease, and Legionnaire's pneumonia) were previously unrecognized because the infectious agents are

difficult to culture. Some infectious agents are genuinely new to humans, e.g., human immunodeficiency virus (HIV), which causes the acquired immunodeficiency syndrome (AIDS);

Borrelia burgdorferi, which causes Lyme disease; and the coronavirus that may cause severe acute respiratory syndrome (SARS) ( Chapter 15 ). Other infections are much more

TABLE 8-1-- Some Recently Recognized Infectious Agents and Manifestations

1977 Ebola virus Epidemic hemorrhagic fever

Hantaan virus Hemorrhagic fever with renal disease

Legionella pneumophila Legionnaire's disease

Campylobacter jejuni Enteritis

1980 HTLV-I T-cell lymphoma or leukemia

1981 Staphylococcus aureus Toxic shock syndrome

1982 HTLV-II Hairy cell leukemia

Escherichia coli O 157:H7 Hemolytic-uremic syndrome

Borrelia burgdorferi Lyme disease


Helicobacter pylori Gastric ulcers

1985 Enterocytozoon bieneusi Chronic diarrhea

1988 HHV-6 Roseola subitum

Hepatitis E Enterically transmitted hepatitis

1989 Hepatitis C Hepatitis C

Ehrlichia chaffeensis Human monocytic ehrlichiosis

1992 Vibrio cholerae O 139 New epidemic cholera strain

Bartonella henselae Cat-scratch disease

1993 Encephalitozoon cuniculi Opportunistic infections

1994 Anaplasma phagocytophilium Human granulocytic ehrlichiosis (anaplasmosis)

1995 KSHV (HHV-8) Kaposi sarcoma in AIDS

2001 Human metapneumovirus Respiratory infections

2002 West Nile virus Acute flaccid paralysis

2003 SARS coronavirus Severe acute respiratory syndrome

Adapted from Lederberg J: Infectious disease as an evolutionary paradigm. Emerg Infect Dis 3:417, 1997.

commonly seen because of immunosuppression caused by AIDS (e.g., cytomegalovirus [CMV], Kaposi sarcoma herpesvirus, Mycobacterium avium-intracellulare, Pneumocystis jiroveci

(carinii), and Cryptosporidium parvum).[3] [4] Finally, infectious diseases that are common in one area may be introduced into a new area. West Nile virus was common in Europe, Asia,

and Africa when it was first described in the United States in 1999.

Human demographics and behavior are among the many factors that contribute to the emergence of infectious diseases. AIDS has been predominantly (but not exclusively) a disease of

homosexuals and drug abusers in the United States and Western countries, while in Africa, AIDS is predominantly a heterosexual disease that is much more frequent in areas where men

remain uncircumcised.[5] Changes in the environment occasionally drive rates of infectious diseases. Reforestation of the eastern United States has led to massive increases in the

populations of deer and mice, which carry the ticks that transmit Lyme disease, babesiosis, and ehrlichiosis. [6] Failure of DDT to control the mosquitoes that transmit malaria and the

development of drug-resistant parasites have dramatically increased the morbidity and mortality of Plasmodium falciparum in Asia, Africa, and Latin America. Microbial adaptation to

widespread antibiotic use contributed to the development of new drug-resistant strains of Mycobacterium tuberculosis, Neisseria gonorrhoeae, Staphylococcus aureus, and Enterococcus


Date: 2016-04-22; view: 1163

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