Emerging & Re-emerging Infectiious Diseases
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Understanding Emerging and Re-emerging Infectious Diseases

The term "disease" refers to conditions that impair normal tissue function. For example, cystic fibrosis, atherosclerosis, and measles are all considered diseases. However, there are fundamentally different causes for each of these diseases. Cystic fibrosis (CF) is due to a specific genotype that results in impaired transport of chloride ions across cell membranes, leading to the production of abnormally thick mucus. Thus, CF is most accurately called a genetic or metabolic disease. Atherosclerosis, which can lead to heart attacks and strokes, may be considered a disease of aging, because it typically becomes a problem later in life after plaques of cholesterol have built up and partially blocked arteries. In contrast, measles is an infectious disease because it occurs when an individual contracts an outside agent, the measles virus. An infectious disease is a disease that is caused by the invasion of a host by agents whose activities harm the host's tissues (that is, they cause disease) and can be transmitted to other individuals (that is, they are infectious).

Nature of Infectious Diseases

Microorganisms that are capable of causing disease are called pathogens. Although microorganisms that cause disease often receive the most attention, it is important to note that most microorganisms do not cause disease. In fact, many probably provide some protection against harmful microorganisms because they effectively compete with the harmful organisms for resources, preventing them from growing.

A true pathogen is an infectious agent that causes disease in virtually any susceptible host. Opportunistic pathogens are potentially infectious agents that rarely cause disease in individuals with healthy immune systems. Diseases caused by opportunistic pathogens typically are found among groups such as the elderly (whose immune systems are failing), cancer patients receiving chemotherapy (which adversely affects the immune system), or people who have AIDS or are HIV-positive. An important clue to understanding the effect of HIV on the immune system was the observation of a rare type of pneumonia among young men caused by Pneumocystis carinii, an organism that causes disease only among the immunosuppressed.

The terms "infection" and "disease" are not synonymous. An infection results when a pathogen invades and begins growing within a host. Disease results only if and when, as a consequence of the invasion and growth of a pathogen, tissue function is impaired. Our bodies have defense mechanisms to prevent infection and, should those mechanisms fail, to prevent disease after infection occurs. Some infectious agents are easily transmitted (that is, they are very contagious), but they are not very likely to cause disease (that is, they are not very virulent). The polio virus is an example: It probably infects most people who contact it, but only about 5 to 10 percent of those infected actually develop clinical disease. Other infectious agents are very virulent, but not terribly contagious. The terror surrounding Ebola hemorrhagic fever is based on the virulence of the virus (50 to 90 percent fatality rate among those infected); however, the virus itself is not transmitted easily by casual contact. The most worrisome infectious agents are those that are both very contagious and very virulent.

an African village, the Nile River, and a building in Philadelphia
Figure 3 - Emerging and re-emerging infectious diseases threaten all countries. Ebola hemorrhagic fever emerged in African villages; schistosomiasis is re-emerging in Egypt, largely as a consequence of building the Aswan Dam; and legionellosis was identified after an outbreak of pneumonia among individuals attending a conference in Philadelphia.

In order to cause disease, pathogens must be able to enter the host body, adhere to specific host cells, invade and colonize host tissues, and inflict damage on those tissues. Entrance to the host typically occurs through natural orifices such as the mouth, eyes, or genital openings, or through wounds that breach the skin barrier to pathogens. Although some pathogens can grow at the initial entry site, most must invade areas of the body where they are not typically found. They do this by attaching to specific host cells. Some pathogens then multiply between host cells or within body fluids, while others such as viruses and some bacterial species enter the host cells and grow there. Although the growth of pathogens may be enough to cause tissue damage in some cases, damage is usually due to the production of toxins or destructive enzymes by the pathogen. For example, Corynebacterium diphtheriae, the bacterium that causes diphtheria, grows only on nasal and throat surfaces. However, the toxin it produces is distributed to other tissues by the circulatory system, damaging heart, liver, and nerve tissues. Streptococcus pyogenes, the infectious agent associated with several diseases including strep throat and "flesh-eating disease," produces several enzymes that break down barriers between epithelial cells and remove fibrin clots, helping the bacteria invade tissues.

Microbes That Cause Infectious Diseases

There are five major types of infectious agents: bacteria, viruses, fungi, protozoa, and helminths. In addition, a new class of infectious agents, the prions, has recently been recognized. A brief review of the general characteristics of each of these agents and examples of some diseases they cause follows.

Bacteria

Bacteria are unicellular prokaryotic organisms; that is, they have no organized internal membranous structures such as nuclei, mitochondria, or lysosomes. Their genomes are circular, double-stranded DNA that is associated with much less protein than eukaryotic genomes'. Most bacteria reproduce by growing and dividing into two cells in a process known as binary fission. Despite these commonalities that group them together in the Kingdom Monera, there is a wide range of diversity among the bacteria.

There is a variety of morphologies among bacteria, but three of the most common are bacillus (rodshaped), coccus (spherical), and spirillum (helical rods). The energy sources for bacteria also vary. Some bacteria are photosynthetic and obtain their energy directly from the sun. Others oxidize inorganic compounds to supply their energy needs. Still other bacteria generate energy by breaking down organic compounds such as amino acids and sugars in a respiratory process. Some bacteria require oxygen (aerobes), while others are unable to tolerate it (anaerobes). Some bacteria can grow either with or without oxygen (facultative anaerobes).

Bacteria are frequently divided into two broad classes based on their cell wall structures, which influences their Gram stain reaction. Gram-negative bacteria appear pink after the staining procedure. Familiar pathogenic gram-negative organisms are Salmonella typhi, which causes typhoid fever, and Yersinia pestis, which causes plague. Gram-positive bacteria appear purple after the Gram stain procedure. Examples of pathogenic gram-positive bacteria are Staphylococcus aureus, which causes skin, respiratory, and wound infections, and Clostridium tetani, which produces a toxin that can be lethal for humans.

Viruses

Microbiologists have found viruses that infect all organisms, from plants and animals to fungi and bacteria. Viruses, however, are not organisms themselves because, apart from a host cell, they have no metabolism and cannot reproduce. A virus particle is composed of a viral genome of nucleic acid that is surrounded by a protein coat called a capsid. In addition, many viruses that infect animals are surrounded by an outer lipid envelope, which they acquire from the host cell membrane as they leave the cell. Unlike organisms, in which the genetic material is always double-stranded DNA, viral genomes may be double- or single-stranded DNA (a DNA virus), or double- or single-stranded RNA (an RNA virus).

In the general process of infection and replication by a DNA virus, a viral particle first attaches to a specific host cell via protein receptors on its outer envelope, or capsid. The viral genome is then inserted into the host cell, where it uses host cell enzymes to replicate its DNA, transcribe the DNA to make messenger RNA, and translate the messenger RNA into viral proteins. The replicated DNA and viral proteins are then assembled into complete viral particles, and the new viruses are released from the host cell. In some cases, virus-derived enzymes destroy the host cell membranes, killing the cell and releasing the new virus particles. In other cases, new virus particles exit the cell by a budding process, weakening but not destroying the cell.

In the case of some RNA viruses, the genetic material can be used directly as messenger RNA to produce viral proteins, including a special viral RNA polymerase that copies the RNA template to produce the genetic material for new viral particles. Other RNA viruses, called retroviruses, use a unique enzyme called reverse transcriptase to copy the RNA genome into DNA. This DNA then integrates itself into the host cell genome. These viruses frequently exhibit long latent periods in which their genomes are faithfully copied and distributed to progeny cells each time the cell divides. The human immunodeficiency virus (HIV), which causes AIDS, is a familiar example of a retrovirus.

Just like other infectious agents, viruses cause disease by disrupting normal cell function. They do this in a variety of ways. Some viruses make repressor proteins that stop the synthesis of the host cell's proteins, RNA, and DNA. Viral activity may weaken cell membranes and lysosomal membranes, leading to cell autolysis. Some viral proteins are toxic to cells, and the body's immune defenses also may kill virus-infected cells.

Viruses are classified using a variety of criteria, including shape, size, and type of genome. Among the DNA viruses are the herpes viruses that cause chicken pox, cold sores, and painful genital lesions, and the poxvirus that causes smallpox. Significant RNA viruses that cause human disease include rhinoviruses that cause most common colds; myxoviruses and paramyxoviruses that cause influenza, measles, and mumps; rotaviruses that cause gastroenteritis; and the retroviruses that cause AIDS and several types of cancer.

Fungi

Fungi are eukaryotic, heterotrophic organisms that have rigid cellulose- or chitin-based cell walls and reproduce primarily by forming spores. Most fungi are multicellular, although some, such as yeasts, are unicellular. Together with bacteria, fungi fulfill the indispensable role of decomposers in the environment. Many fungi also infect plants and animals. Examples of diseases caused by fungi are ringworm and histoplasmosis (a mild to severe lung infection transmitted by bat or bird droppings). Yeasts of the Candida genus are opportunistic pathogens that may cause diseases such as vaginal yeast infections and thrush (a throat infection) among people who are immunocompromised or undergoing antibiotic therapy. Antibiotics reduce the bacterial population normally present in the throat and vagina, allowing the yeast to grow unchecked.

Protozoa

Protozoa are unicellular, heterotrophic eukaryotes that include the familiar amoeba and paramecium. Because protozoa do not have cell walls, they are capable of a variety of rapid and flexible movements. Protozoa can be acquired through contaminated food or water or by the bite of an infected arthropod such as a mosquito. Diarrheal disease in the United States can be caused by two common protozoan parasites, Giardia lamblia and Cryptosporidium parvum. Malaria, a tropical illness that causes 300 million to 500 million cases of disease annually, is caused by several species of the protozoan Plasmodium.

Helminths

Helminths are simple, invertebrate animals, some of which are infectious parasites. They are multicellular and have differentiated tissues. Because they are animals, their physiology is similar in some ways to ours. This makes parasitic helminth infections difficult to treat because drugs that kill helminths are frequently very toxic to human cells.

Many helminths have complex reproductive cycles that include multiple stages, many or all of which require a host. Schistosoma, a flatworm, causes the mild disease swimmer's itch in the United States; another species of Schistosoma causes the much more serious disease schistosomiasis, which is endemic in Africa and Latin America. Schistosome eggs hatch in freshwater, and the resulting larvae infect snails. When the snails shed these larvae, the larvae attach to and penetrate human skin. They feed, grow, and mate in the human bloodstream; the damage to human tissues caused by the accumulating schistosome eggs with their sharp spines results in disease symptoms including diarrhea and abdominal pain. Liver and spleen involvement are common. Another disease due to a helminth is trichinosis, caused by the roundworm Trichinella spiralis. This infectious agent is typically ingested in improperly cooked pork from infected pigs. Early disease symptoms include vomiting, diarrhea, and fever; later symptoms include intense muscle pain because the larvae grow and mature in those tissues. Fatal cases often show congestive heart failure and respiratory paralysis.

Prions

During the past two decades, evidence has linked some degenerative disorders of the central nervous system to infectious particles that consist only of protein. These "proteinaceous infectious particles" have been named prions (pree-ons). The known prion diseases include Creutzfeldt-Jakob disease (in humans), scrapie (in sheep), and bovine spongiform encephalopathy ("mad cow disease" in cattle); all known prion diseases frequently result in brain tissue that is riddled with holes. While some prion diseases are inherited, others are apparently due to infection by eating infected tissue or inadvertently through medical procedures such as tissue transplants.

Occurrence of Infectious Diseases

Epidemiology

Epidemiology is the study of the occurrence of disease in populations. Epidemiologists are concerned not only with infectious diseases, but also with noninfectious diseases such as cancer and atherosclerosis, and with environmental diseases such as lead poisoning. These professionals work to prevent or minimize the impact of diseases in the population. Their work may include such activities as identifying unusually high incidences of a particular disease, determining the effectiveness of a vaccine, and calculating the cost effectiveness of various means of controlling disease transmission. Occasionally, epidemiologists act as "detectives" who track down the cause of a "new" disease, determine its reservoir and mode of transmission, and help organize various health care workers to bring the disease under control.

Disease reservoirs

The reservoir for a disease is the site where the infectious agent survives. For example, humans are the reservoir for the measles virus because it does not infect other organisms.

Animals often serve as reservoirs for diseases that infect humans. The major reservoir for Yersinia pestis, the bacteria that causes plague, is wild rodents. There are also nonliving reservoirs. Soil is the reservoir for many pathogenic fungi as well as some pathogenic bacteria such as Clostridium tetani, which causes tetanus.

Modes of transmission

Infectious agents may be transmitted through either direct or indirect contact. Direct contact occurs when an individual is infected by contact with the reservoir, for example, by touching an infected person, ingesting infected meat, or being bitten by an infected animal or insect. Transmission by direct contact also includes inhaling the infectious agent in droplets emitted by sneezing or coughing and contracting the infectious agent through intimate sexual contact. Some diseases that are transmitted primarily by direct contact with the reservoir include ringworm, AIDS, trichinosis, influenza, rabies, and malaria.

Indirect contact occurs when a pathogen can withstand the environment outside its host for a long period of time before infecting another individual. Inanimate objects that are contaminated by direct contact with the reservoir (for example, a tissue used to wipe the nose of an individual who has a cold or a toy that has been handled by a sick child) may be the indirect contact for a susceptible individual. Ingesting food and beverages contaminated by contact with a disease reservoir is another example of disease transmission by indirect contact. The fecal-oral route of transmission, in which sewage-contaminated water is used for drinking, washing, or preparing foods, is a significant form of indirect transmission, especially for gastrointestinal diseases such as cholera, rotavirus infection, cryptosporidiosis, and giardiasis.

These modes of transmission are all examples of horizontal transmission because the infectious agent is passed from person to person in a group. Some diseases also are transmitted vertically; that is, they are transmitted from parent to child during the processes of reproduction (through sperm or egg cells), fetal development, or birth. Diseases in which vertical transmission occurs include AIDS and herpes encephalitis (which occurs when an infant contracts the herpes simplex type II virus during vaginal birth).

Role of Research in Prevention

Figure 4 - the infectious cycle
Figure 4 - The black arrows illustrate a generalized infectious cycle; the shaded arrows indicate points where infectious diseases can be prevented. (1) A host is infected by the reservoir or a vector for the pathogen. This individual may infect (2) other hosts in a population or (3) new vectors. (4) The pathogen also may cycle between the vector and a reservoir. D

Infectious diseases can be prevented at a variety of points, depending on the infectious cycle for the particular disease (Figure 4). Basic research, such as that sponsored by NIH, reveals the specific infectious cycle and details regarding the activities of the pathogen that cause disease (for example, the particular cells, if any, that are attacked, and the toxins produced by th e pathogen that damage host tissues).

Understanding the infectious cycle is critical in order to identify accessible targets for control strategies (Figure 4). For example, direct person-to-person transmission may be inhibited by proper hygiene and sanitary conditions as well as education. Vector-borne diseases may be prevented by control measures that either kill the vector or prevent its contact with humans. Infection by a pathogen or development of a pathogen within a host may be prevented by vaccination. Finally, drugs may be used to prevent infection or suppress the disease process.

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