Emerging & Re-emerging Infectiious Diseases
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Understanding Emerging and Re-emerging Infectious Diseases (continued)

In some cases, the tools, including drugs, vaccines, and vector-control methods, are already available to deal with these diseases. For other diseases, the methods for control are inadequate, undeveloped, or nonexistent. Scientists are trying to develop the new tools needed to banish these scourges of mankind. This requires basic research into the life processes of the pathogen and its interaction with the host in order to identify points within the life cycle where the pathogen is vulnerable to intervention, translational research to develop new tools (such as vaccines or antimicrobial drugs), and clinical research to test the safety and efficacy of these new tools.

Host Defenses Against Infectious Diseases

The human body has several general mechanisms for preventing infectious diseases. Some of these mechanisms are referred to as nonspecific defenses because they operate against a wide range of pathogens. Other mechanisms are referred to as specific defenses because they target particular pathogens and pathogen-infected cells.

Nonspecific mechanisms

Nonspecific mechanisms are the body's primary defense against disease. These mechanisms include anatomical barriers to invading pathogens, physiological deterrents to pathogens, and the presence of normal flora. An example of an anatomical barrier is the nasal opening to the respiratory system. This natural opening is a long, convoluted passage covered by mucous membranes that trap airborne particles and prevent most of them from reaching the lungs. Other anatomical barriers are the skull and vertebral column, which protect the central nervous system — few pathogens are able to penetrate bone. The skin also is a major anatomical barrier to microorganisms. The surface layer of dead, hardened cells is relatively dry, and skin secretions make the surface somewhat acidic. When sweat evaporates, salt is left behind on the skin. All of these conditions (low moisture, low pH, and high salinity) prevent most microorganisms from growing and multiplying on the skin. The major medical challenge in treating burn patients is preventing and treating infections that result because of the absence of skin that ordinarily would prevent invasion of microorganisms.

Natural openings also are protected by a variety of physiological deterrents. For example, tears continually flush debris from the eyes. Vaginal secretions are acidic, a hostile environment that discourages the growth of many pathogens. The eye, mouth, and nasal openings are protected by tears, saliva, or nasal secretions that contain lysozyme, an enzyme that breaks down bacterial cell walls. Blood, sweat, and some tissue fluids contain lysozyme as well.

In addition to lysozyme, the blood has many elements that defend the body from disease-causing organisms. The white blood cells include several types of phagocytic cells that detect, track, engulf, and kill invading bacteria and viruses, as well as infected host cells and other debris. These phagocytic cells are part of the nonspecific immune system. Blood plasma also includes clotting factors that initiate a clot at the injury site, preventing pathogens from invading the body further. Finally, the complement proteins in the blood participate in a cascade of molecular events that result in inflammation, the release of molecules that stimulate phagocytic cells, and the formation of a complex of proteins that binds to the surface of bacterial or infected host cells and lyses those cells.

The inflammatory response is another nonspecific defense mechanism that helps prevent infectious agents from spreading in the body. Inflammation involves swelling, reddening, elevated temperature, and pain. Unfortunately, inflammation itself frequently causes tissue damage and, in severe cases, even death.

Finally, the protective role of the "normal flora" of microorganisms present on and in the body should not be overlooked. These organisms survive and grow on the skin and in the mouth, gastrointestinal tract, and other areas of the body, but do not cause disease because their growth is kept under control by the host's defense mechanisms and by the presence of other microorganisms. These organisms protect the host by successfully competing with disease-causing organisms, preventing the latter from invading host tissues. When the growth of the normal flora is suppressed (for example, due to antibiotic treatment), other "opportunistic" agents that normally do not grow in or on the body may be able to infect and cause disease.

Specific mechanisms of host resistance

When these nonspecific mechanisms fail, the body initiates a second, specific line of defense. This specific immune response enables the body to target particular pathogens and pathogen-infected cells for destruction. It depends on specialized white blood cells called lymphocytes and includes T-cells (produced from lymphocytes that matured in the thymus gland) and B-cells (produced from lymphocytes that matured in the bone marrow).

The two complementary components of the specific immune response are the cell-mediated response and the antibody-mediated response (Figure 5). The cell-mediated response involves T-cells and is responsible for directly destroying body cells that are infected with a virus or have become cancerous, or for activating other immune cells to be more efficient microbe killers. The antibody-mediated response involves both T-cells and B-cells and is critical for the destruction of invading pathogens as well as the elimination of toxins.

Both the cell-mediated and antibody-mediated responses are initiated after a particular type of phagocytic cell, a macrophage, engulfs a pathogen. Macrophages digest the pathogen and then display antigens from the pathogen on their surface. Antigens are specific molecules, such as the proteins on the surface of pathogens, that elicit an immune response. This display helps the macrophages stimulate specific helper T-cells to release signal molecules called lymphokines. The lymphokines, in turn, stimulate the cell-mediated and antibody-mediated responses.

The cell-mediated response occurs when the lymphokines released from the helper T-cells stimulate other cell types to participate in the immune response. Lymphokine-stimulated killer T-cells attach to the pathogen-infected cells and destroy them, whereas lymphokine-activated phagocytic cells produce more toxic molecules that can kill the pathogen directly.

The antibody-mediated response occurs when the lymphokines activate specific B-cells to produce antibodies (proteins that specifically recognize and bind to antigens). These antibodies attach to antigens on the surface of the pathogens and signal attack by phagocytic cells and complement system. Other B-cells go on to become memory B-cells, which respond quickly by producing more antibodies upon subsequent infection.

Immunity

When a host encounters an antigen that triggers a specific immune response for the second or later time, the memory lymphocytes recognize it and quickly begin growing and dividing, as well as producing high levels of lymphokines and antibodies. Because memory cells are present, this response happens much more quickly than in the initial encounter with the antigen. This rapid response explains why hosts are immune to developing many diseases a second time: The immune response occurs so quickly in a second encounter with the pathogen that the pathogen does not have enough time to reproduce to levels that result in disease before the host's body has destroyed it. The memory response also explains the effectiveness of vaccination for preventing even the first occurrence of many diseases.

Figure 5
Figure 5 - This diagram provides an overview of specific immunity. D

Vaccination

A vaccine is either a killed or weakened (attenuated) strain of a particular pathogen, or a solution containing critical antigens from the pathogen. The body's immune system will respond to these vaccines as if they contain the actual pathogen, even though the vaccine is not capable of causing the disease. As a result of the specific immune response, memory lymphocytes will be present that respond rapidly when the actual pathogen is encountered. The resulting rapid activation of immune cells prevents disease.

Currently new types of vaccines, the DNA vaccines, are in early stage trials. These vaccines contain genes that encode proteins from pathogens. When these genes are inserted into host cells and are expressed in the form of pathogen proteins, an immune reaction may result.

The ultimate effectiveness of vaccination—eradication of the infectious agent—has been achieved only for smallpox. The World Health Organization has identified the polio and measles viruses among the next targets for global eradication.

For a variety of reasons, many diseases are not easily prevented by vaccination. Antibody response is generally the simplest to induce by vaccination, but some pathogens have ways to evade the immune response. Intracellular pathogens (such as viruses and some bacterial and protozoan pathogens) are not directly affected by antibodies because antibodies cannot pass inside cells. Moreover, during the disease process, some pathogens acquire an external coat composed of host-derived material while others disguise themselves by making molecules that resemble host molecules. Thus, the host's immune system does not identify them as foreign invaders. Still other pathogens mutate quickly, producing variants of their antigens that are not recognized by the host's immune system, even though the host survived a previous encounter with that pathogen. Cold and influenza viruses are examples of rapidly mutating pathogens. Scientists are working to improve vaccines against these pathogens.

Public Health Measures to Prevent Infectious Diseases

Developed countries have regulations that help protect the general public from infectious diseases. Public health measures typically involve eliminating the pathogen from its reservoir or from its route of transmission. Those measures include ensuring a safe water supply, effectively managing sewage treatment and disposal, and initiating food safety, animal control, and vaccination programs.

Safewater

Many pathogens that cause gastrointestinal diseases (for example, those that cause cholera and typhoid fever) are transmitted via water. Travelers to developing countries are frequently advised to be immunized against these diseases. This is generally unnecessary in the United States and other developed countries because the water used for washing, drinking, and preparing food is purified before it goes into homes. Purification methods include settling, filtration, and chlorination. The water for homes that use well water or springs is usually safe if guidelines about distance from sewage disposal facilities are followed; however, this water should be checked periodically. When breakdowns in a purification system occur, or when a system is overwhelmed (for example, due to unusual flooding), drinking water may not be safe and should be boiled or treated with chlorine before it is ingested.

Because gastrointestinal pathogens typically leave the body in the feces, public water must be guarded against contamination from sewage. Municipal water is usually tested for the presence of coliform organisms (nonpathogenic microorganisms that are part of the normal flora of the gastrointestinal tract) as indicators of sewage contamination. This procedure is necessary because when the water contains pathogens and is potentially dangerous, the pathogenic organisms are usually present in such small numbers that they are hard to detect.

Sewage treatment and disposal

Sewage includes wash water, water from toilets, and storm run-off. These fluids may carry the pathogens for many waterborne diseases, including giardiasis and hepatitis A; therefore, to ensure public safety the U.S. government (and the governments of other developed countries) requires that sewage be treated to eliminate pathogens. The minimal acceptable level of treatment involves collection and sedimentation of sewage waters, separating solid matter (sludge) from the liquid (effluent) portion of sewage. The effluent is chlorinated to kill pathogens before it is released to rivers or lakes. The sludge is burned or dumped.

More advanced methods of treatment use a secondary treatment following this primary treatment. The effluent is transferred to tanks containing a population of microorganisms that decompose more than 90 percent of the organic wastes and eliminate pathogens by competition (this is another example of the important role of microorganisms in preventing disease). The resulting effluent is chlorinated before it is released to the environment. Some sewage treatment plants include a tertiary treatment that involves additional chemicals that also eliminate pathogens.

Food safety programs

The United States has many standards, inspection plans, and regulations about food preparation, handling, and distribution. Meat-packing facilities are inspected regularly to detect and eliminate diseased animals, ensure that standards for processes such as meat cutting and refrigeration are observed, and detect residues from pesticides and antibiotics as well as contamination by bacteria and other parasites. Restaurants and supermarkets are similarly inspected. Milk is pasteurized and dated for sale and is analyzed periodically for contamination. Industry standards for canning and preserving foods are maintained through periodic quality control checks and, if contamination is found in representatives of any batches, public health officials recall the entire batch and alert the public through the media.

Animal-control programs

Animals are carriers of many diseases that also affect humans. Inspecting domestic herd animals for tuberculosis (due to the bacterium Mycobacterium bovis) and brucellosis (a disease that causes spontaneous abortion in domestic herd animals and abscesses of the liver, spleen, bone marrow, and lymph nodes in humans) has helped eliminate the threat of passing the pathogens for those diseases to humans in contaminated milk and meat. Before their pets can be licensed, dog owners must show proof of rabies vaccination. Because most cases of rabies among people in the United States are due to bites from wild and stray animals, health officials are mandated to impound and destroy these animals. Many diseases, including bubonic plague, are spread by rodents, and rat control, especially in urban areas, is a major component of public health efforts. Insects also transmit many diseases (a notable example is malaria). The spread of insect-borne diseases can be controlled by eliminating breeding areas for insects (for example, draining areas where stagnant water collects) and using pesticides. Many imported animals must be tested for specific diseases to prevent the introduction of those diseases into the country.

Figure 6
Figure 6 - Vaccination programs are important components of public health systems.

Vaccination programs

Most states now require that parents or guardians show proof of vaccination before their children can be enrolled in day-care facilities or public schools, although some states allow certain exemptions, including exemptions based on religious beliefs. The value of immunization for an individual's health is obvious; however, it is also important for public health. If a certain proportion of a population (called the threshold proportion) is immune to a disease, the pathogen that causes that disease will be unable to reproduce itself at a high enough level to maintain itself in the population. This is because once the infected host recovers or dies, there will not be enough new, susceptible hosts for the pathogen to infect. Eventually, the pathogen cannot spread any further and could be eliminated from the population. Even if elimination of the pathogen does not occur, there will be relatively few cases of the related disease and epidemics of the disease in the population will be avoided. This phenomenon is called herd immunity.

The threshold proportion varies depending on the disease and other conditions in the relevant population. Vaccination programs led by public health officials aim to achieve the immunization of at least the threshold number of individuals for the population.

Public health organizations

Cities and other local areas have public health agencies that enforce regulations, provide public health services such as vaccination programs, and monitor and report the incidence of particular diseases to state and federal agencies. State public health agencies are affiliated with laboratories and staff epidemiologists for investigating disease cases.

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