-Choose ONE of these re-emerging diseases…Measles, Mumps or Cholera
-Locate an article in a newspaper, in a lay magazine, or on an organizational website that discusses an emerging or re-emerging infectious disease that is currently affecting your community. Reflect on the article you selected and think about how the emerging or re-emerging disease might affect nursing practice
-Briefly summarize the article you selected and provide the reference. Then, address the following:
Support your response with references from the professional nursing literature. 3-paragraph (at least 350 words)
Be sure to use evidence from the readings and include in-text citations. A reference list is required. Use the most current evidence (usually ≤ 5 years old)
National Institutes of Health (US); Biological Sciences Curriculum Study. NIH Curriculum Supplement Series [Internet]. Bethesda (MD): National Institutes of Health (US); 2007. Understanding Emerging and Re-emerging Infectious Diseases. Available from: https://www.ncbi.nlm.nih.gov/books/NBK20370/
NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.
National Institutes of Health (US); Biological Sciences Curriculum Study. NIH Curriculum Supplement Series [Internet]. Bethesda (MD): National Institutes of Health (US); 2007.
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.
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 bacteria 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 strepthroat 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 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 are a variety of morphologies among bacteria, but three of the most common are bacillus (rod-shaped), coccus (spherical), or 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 Yersiniapestis, 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.
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 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 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 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.
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 (preeons). 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 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 cal collating 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.
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
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 the 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.
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 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 sys tem. 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.
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.
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.
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 sys tem 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.
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.
All of these agencies report data to the U.S. Public Health Service. NIH, the funding agency of this module, began in 1887 as the Laboratory of Hygiene; NIH is one of eight health agencies of the U.S. Public Health Service. It supports health-related research aimed at understanding, preventing, treating, and controlling infectious and other diseases of humankind. The Public Health Service also operates the Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia, and the Food and Drug Administration (FDA). CDC staff investigate disease outbreaks, publish a summary of current epidemiological reports, and sponsor a variety of education programs, research projects, and reference laboratories. FDA monitors the safety of our food, medicines, and many other products that we use daily. Finally, the World Health Organization (WHO) provides international surveillance and control of disease. Among other efforts, WHO coordinates multinational vaccination campaigns.
Treatment of Infectious Diseases
While literally meaning “destroyer of life,” the term “antibiotic” has become the most commonly used word to refer to a chemical substance used to treat bacterial infections. The term “antimicrobial” has a somewhat broader connotation, generally referring to anything that inhibits the growth of microbes. Technically, the term antimicrobial does not encompass the “antihelminthic” drugs because worms are not microscopically small. Antimicrobials can be either microbistatic (inhibiting the replication of the microbe) or microbicidal (actually killing the target microorganism). In the former case, a combination of therapy and immunity may be required to finally terminate the infection.
Treatment of bacterial diseases
Because bacteria are prokaryotes, it has been relatively easy to find and develop antibacterial drugs that have minimal side effects. These drugs target structural features and metabolic characteristics of prokaryotes that are significantly different from those in eukaryotic cells. Drugs used to treat bacterial diseases can be grouped into categories based on their modes of action. In general, these drugs inhibit cell wall synthesis, protein synthesis, nucleic acid synthesis, or other enzyme-catalyzed reactions.
The penicillins and cephalosporins all interfere with the synthesis of the peptidoglycan layer in prokaryotic cell walls. Because eukaryotes have neither the peptidoglycan components nor the enzymes that synthesize them, these drugs do not affect the host cells. A second class of drugs, including chloramphenicol, the tetracyclines, and erythromycin, bind to prokaryotic ribosomes and inhibit protein synthesis. Prokaryotic ribosomes are structurally different from eukaryotic ribosomes, so these drugs have minimal effect on eukaryotic cells. Nevertheless, some of them may be toxic to some human tissues when they are used in high doses or for prolonged periods of time.
Rifampicin is one of the antibiotics frequently used for treating tuberculosis. This drug inhibits prokaryotic RNA synthesis. DNA synthesis in prokaryotes may be inhibited by the fluoroquinolones. In contrast, the sulfonamides stop bacterial infections by inhibiting other enzymes. Sulfonamides interfere with the synthesis of folic acid, a vitamin necessary for nucleic acid synthesis. Most bacteria must synthesize their own folic acid because their membranes are impermeable to external folic acid. Mammalian cells are not affected by sulfonamides because they are unable to make their own folic acid and have evolved mechanisms for transporting external folic acid across their membranes.
Treatment of viral diseases
In general, drugs that effectively inhibit viral infections are highly toxic to host cells because viruses use the host’s metabolic enzymes in their reproduction. For this reason, most illnesses due to viruses are treated symptomatically until the host’s immune system controls and eliminates the pathogen (or the host dies). Antiviral drugs that are used typically target virus-specific enzymes involved in viral nucleic acid synthesis. One of the most familiar of these drugs is acyclovir, which is used to treat outbreaks of genital herpes. Amantadine is an antiviral drug sometimes used to prevent or moderate influenza among those at high risk of severe illness from the disease. In addition to antiviral drugs that inhibit the replication of the HIV genome (such as AZT), AIDS patients today are also prescribed proteases that interfere with the packaging of the HIV genome into virus particles.
Treatment of fungal and parasitic diseases
The development of drugs to treat fungal, protozoan, and helminthic diseases is challenging because agents that kill or inhibit the growth of these eukaryotic organisms are also highly toxic to mammalian cells. Because fungi and protozoa are rapidly proliferating cells, drugs against these organisms tend to target key components of their replicative or biosynthetic pathways. Common antifungals inhibit sterol syntheses (the azole derivatives) or disrupt the cell membrane (polyenes like amphotericin B). Most antihelminthic drugs target adult worms, which are no longer growing and do not replicate. These drugs are often aimed at inhibiting fundamental processes, such as energy production and muscle function (for example, the benzimidazoles and avermectins), or at targets involved in egg production or larval development.
Malaria, a protozoan disease, was successfully treated for many years with chloroquine. In recent decades, Plasmodium species that are resistant to this drug have appeared and spread to areas where malaria is a common threat. In those areas, a combination of the drugs sulfonamide and pyrimethamine is frequently used to treat the disease.
Resistance to antimicrobial agents
One of the ongoing problems scientists and medical workers face in the fight against infectious diseases is the development of resistance to the agents used to control them. The phenomenon of resistance has been known since almost the beginning of antibiotic use. For example, penicillin was introduced for clinical use in treating bacterial infections in the 1940s. As early as 1943, Alexander Fleming, the discoverer of penicillin, observed that some bacteria were resistant to the drug and warned that indiscriminate use of penicillin would lead to the proliferation of resistant pathogenic bacteria. By 1946, medical staff at a London hospital estimated that 14 percent of the staphylococcal strains isolated from their patients were resistant to penicillin. Today, more than 90 percent of these bacteria are resistant. In an environment of widespread penicillin use, selection for resistant bacteria occurred; that is, the pathogenic organisms evolved.
The same process has occurred for many other antimicrobial drugs. Alarmingly, many pathogens are simultaneously acquiring resistance to multiple drugs. For example, some strains of Mycobacterium tuberculosis are resistant to all of the currently available drugs used for treatment.
Mechanisms of antimicrobial resistance
Antibiotic resistance appears as a result of changes in genes or the acquisition of genes that allow the pathogen to evade the action of antimicrobial drugs. Resistance mechanisms include structural changes in or around the target molecule that inhibit the drugs’ ability to bind to it; reduced permeability of the cell membrane to the drug, actively pumping the drug out of the cell after it has entered; and production of enzymes that inactivate the antibiotic after it has been taken up by the cell. Microbes that produce larger than normal amounts of the target molecule may be “less susceptible” (as opposed to resistant) to a drug, meaning it takes a higher drug level to adversely affect that microbe.
Transfer of antimicrobial-resistance genes
Bacteria have many methods for developing resistance. Antibiotic resistance initially arises as mutations to existing genes; however, many (probably most) bacteria acquire these genes rather than experience the mutation themselves. Resistance genes are transferred to other members of the same species and across species by a variety of bacterial genetic exchange mechanisms. Many gram-negative bacteria, including Escherichia coli and Salmonella species, can transfer extra-chromosomal genetic material called plasmids via the process of conjugation. Bacteria endowed with the plasmids have numerous pili along their surfaces; one of these extends to a plasmid-lacking bacterium as a conjugation tube. The plasmid then replicates, and one copy travels through the conjugation tube into the recipient bacterium. One large class of plasmids is called resistance plasmids because they carry genes that confer antibiotic resistance. Many resistance plasmids carry genes for resistance to multiple antibiotics; thus, one conjugation event can simultaneously transfer resistance to several antibiotics.
Some species of bacteria are capable of taking up free-floating bits of DNA from their environments in a process known as bacterial transformation. If they take up a DNA fragment containing an antibiotic resistance gene, they may become resistant to that antibiotic. Another mechanism of genetic exchange in bacteria is transduction. Bacteria are subject to viral infection. When a bacteria cell is infected, the virus takes over the cell’s metabolism, directing synthesis of its genetic material and production of the components of the viral particle. Simultaneously, the host bacterial DNA is degraded. In the last stage of virus production, its genetic material is encapsulated in a protein coat. Occasionally, a piece of the host bacterial DNA may be packaged in a viral particle. The resulting “transducing particle,” like a normal viral particle, has the ability to attach to a recipient bacterium and transfer its genetic material into the cell. However, in this case, the transferred genetic material may be a bacterial gene that pro vides resistance to an antibiotic.
Finally, many transposons carry antibioticresistance genes. Transposons are sequences of DNA that are capable of inserting themselves randomly into genomes. Because they do not appear to rely on specific genetic sequences of the target insertion site, they can readily move across species.
Although mutations that result in antibiotic resistance and, less so, bacterial genetic exchange, are rare events, they need occur only once. In an environment of heavy antibiotic use, the forces of natural selection will favor the propagation of resistant variants of a pathogen. The human body is a rich environment for the growth of large numbers of bacteria and for the interaction of a variety of pathogenic and nonpathogenic bacteria. Thus, there is optimal opportunity for rare mutational and genetic exchange events.
Other pathogens have more limited options for drug resistance. Strains of pathogens develop that are naturally less susceptible to a particular drug due to a normally occurring mutation. In the face of continuing drug use, this strain rapidly grows out of the population being spread through the usual transmission process. Malaria, a protozoan disease, was successfully treated for many years with chloroquine, a drug that was widely available over the counter in regions where malaria was a problem. In recent decades, Plasmodium strains that are resistant to this drug have appeared and spread throughout Africa, South America, and Southeast Asia.
Emerging and Re-emerging Infectious Diseases
Fifty years ago many people believed the age-old battle of humans against infectious disease was virtually over, with humankind the winners. The events of the past two decades have shown the foolhardiness of that position. At least a dozen “new” diseases have been identified (such as AIDS, Legionnaire disease, and hantavirus pulmonary syndrome), and traditional diseases that appeared to be “on their way out” (such as malaria and tuberculosis) are resurging. Globally, infectious diseases remain the leading cause of death, and they are the third leading cause of death in the United States. Clearly, the battle has not been won.
Emerging infectious diseases are diseases that (1) have not occurred in humans before (this type of emergence is difficult to establish and is probably rare); (2) have occurred previously but affected only small numbers of people in isolated places (AIDS and Ebola hemorrhagic fever are examples); or (3) have occurred throughout human history but have only recently been recognized as distinct diseases due to an infectious agent (Lyme disease and gastric ulcers are examples). Figure 7 lists several examples of infectious diseases that have emerged in the last three decades.
A review of Figure 7 reveals that environmental changes are related to the emergence of many infectious diseases. For example, Lyme disease, hantavirus pulmonary syndrome (HPS), and Lassa fever all emerged when humans began encountering the insect vector (for Lyme disease) or rodent host (for HPS and Lassa fever) of the causative agents in greater numbers than ever before. Factors related to the emergence of infectious diseases such as Legionnaire disease and hemolytic uremic syndrome include changing technologies: air conditioning systems for the former disease and mass food production for the latter.
Re-emerging infectious diseases are diseases that once were major health problems globally or in a particular country, and then declined dramatically, but are again becoming health problems for a significant proportion of the population (malaria and tuberculosis are examples). Many specialists in infectious diseases include re-emerging diseases as a subcategory of emerging diseases. Figure 8 lists examples of re-emerging infectious diseases.
A review of Figure 8 reveals some explanations for the re-emergence of infectious diseases. Tuberculosis has re-emerged due to evolution of the causative bacteria. The pathogen has acquired resistance to the antibiotics used to treat tuberculosis (either through mutation or genetic exchange) and the long-term use of antibiotics (both within one individual and across the population) has selected for the pathogen’s proliferation. Malaria has also become drug resistant, and the vector mosquito has acquired resistance to pesticides as well. The re-emergence of diseases such as diphtheria and whooping cough (pertussis) is related to inadequate vaccination of the population. When the proportion of immune individuals in a population drops below a particular threshold, introduction of the pathogen into the population leads to an outbreak of the disease.
Despite the challenges of emerging and re-emerging infectious diseases, the results of basic research, such as that sponsored by NIH, show that there is reason for hope. AIDS was first described in 1981, and it took two years to identify the retrovirus that causes AIDS, which was named the human immunodeficiency virus. In contrast, less than four months elapsed between the description of hantavirus pulmonary syndrome (HPS) in 1993 and the identification of the previously unknown viral agent, now called Sin Nombre virus. One difference between these two cases is that the years that intervened between the advent of AIDS and the advent of HPS saw the development of polymerase chain reaction, a powerful new research technique that allows rapid identification of causative agents. Recommendations for avoiding and/or treating of new infectious diseases become possible when new techniques, developed through basic research, are applied to the problem of disease emergence.
Other examples of the benefits of basic research include the development of HIV protease inhibitors by researchers funded by NIH and others. These drugs, when used in combination with other anti-HIV drugs, are responsible for the dramatic decrease in deaths from AIDS in the United States. One active area of research at NIH is the development of new types of vaccines based on our new understanding of the immune system. In addition, basic research on the immune system and host pathogen interactions has revealed new points at which vaccines could work to prevent diseases.
Finally, basic research on the ecology of disease organisms—their reservoirs, modes of transmission, and vectors, if any—reveals points at which preventive measures can be used to interrupt this cycle and prevent the spread of disease. For example, research supported by NIAID delineated the mechanism of Lyme disease transmission and how disease results: The tick vector was identified and the life cycle of the causative bacterium was traced through deer and rodent hosts. Understanding this ecology has led to predictions about the regions where and years when the threat of Lyme disease is greatest, as well as recommendations to the public for avoiding infection. These examples and others demonstrate that investment in basic research has great long-term payoffs in the battle against infectious diseases.
Infectious Diseases and Society
What are the implications of using science to improve personal and public health in a pluralist society? As noted earlier, one of the objectives of this module is to convey to students the relationship between basic biomedical research and the improvement of personal and public health. One way to address this question is by attending to the ethical and public policy issues raised by our understanding and treatment of infectious diseases.
Ethics is the study of good and bad, right and wrong. It has to do with the actions and character of individuals, families, communities, institutions, and societies. During the last two and one-half millennia, Western philosophy has developed a variety of powerful methods and a reliable set of concepts and technical terms for studying and talking about the ethical life. Generally speaking, we apply the terms “right” and “good” to those actions and qualities that foster the interests of individuals, families, communities, institutions, and society. Here, an “interest” refers to a participant’s share or participation in a situation. The terms “wrong” or “bad” apply to those actions and qualities that impair interests.
Ethical considerations are complex, multifaceted, and raise many questions. Often, there are competing, well-reasoned answers to questions about what is right and wrong, and good and bad about an individual’s or group’s conduct or actions. Thus, although science has developed vaccines against many diseases, and public health laws encourage their widespread use, individuals are permitted (in most, but not all, states) to choose not to be vaccinated.
Typically, answers to these questions all involve an appeal to values. A value is something that has significance or worth in a given situation. One of the exciting events to witness in any discussion in ethics in a pluralist society is the varying ways in which the individuals involved assign value to things, persons, and states of affairs. Examples of values that students may appeal to in discussions of ethical issues include autonomy, freedom, privacy, protecting another from harm, promoting another’s good, justice, fairness, economic stability, relationships, scientific knowledge, and technological progress.
Acknowledging the complex, multifaceted nature of ethical discussions is not to suggest that “anything goes.” Experts generally agree on the following features of ethics. First, ethics is a process of rational inquiry. It involves posing clearly formulated questions and seeking well-reasoned answers to those questions. For example, developing countries suffer particularly severely from many infectious diseases because conditions of crowding and poor sanitation are ideal for the growth and spread of pathogens. The same is true for many inner city environments. These places provide a constant reservoir of disease-causing agents. We can ask questions about what constitutes an appropriate ethical standard for allocating health care funds for curtailing the spread of infectious diseases. Should we expend public research dollars to develop drugs whose cost will be out of reach for developing countries or those in the inner cities? Is there any legal and ethical way for the United States to prevent over-the-counter sales of antibiotics in other countries, a practice that may enhance the evolution of antibiotic resistant pathogens? Well-reasoned answers to ethical questions constitute arguments. Ethical analysis and argument, then, result from successful ethical inquiry.
Second, ethics requires a solid foundation of information and rigorous interpretation of that information. For example, one must have a solid understanding of infectious disease to discuss the ethics of requiring immunizations and reporting of infectious diseases. Ethics is not strictly a theoretical discipline but is concerned in vital ways with practical matters. This is especially true in a pluralist society.
Third, because tradeoffs among interests are complex, constantly changing, and sometimes uncertain, discussions of ethical questions often lead to very different answers to questions about what is right and wrong and good and bad. For example, we acknowledge that individuals have a right to privacy regarding their infectious disease status. Yet, some argue that AIDS patients who knowingly infect others may have their right to privacy overridden so that partners may be notified of the risk of contracting AIDS.
It is our hope that completing the activities in this module will help students see how understanding science can help individuals and society make reasoned decisions about issues relating to infectious diseases and health. Science provides evidence that can be used to support ways of understanding and treating human disease, illness, deformity, and dysfunction. But the relationships between scientific information and human choices, and between choices and behaviors, are not linear. Human choice allows individuals to choose against sound knowledge, and choice does not necessarily lead to particular actions.
Nevertheless, it is increasingly difficult for most of us to deny the claims of science. We are continually presented with great amounts of relevant scientific and medical knowledge that is publicly accessible. As a consequence, we can think about the relationships among knowledge, choice, behavior, and human welfare in the following ways:
One of the goals of this module is to encourage students to think in terms of these relationships, now and as they grow older.