{in-fek'-shuhs} All species of animals are afflicted with infections caused by a wide variety of organisms, from submicroscopic viruses to wormlike parasites. Infectious diseases range from the benign common cold to such fearsome conditions as \Tbubonic plague\t and \Trabies\t. Infections are usually characterized by several stages. First, the organism gains access to the patient, survives within the body, and multiplies. Next, the patient manifests symptoms of illness and, in some instances, sheds organisms that have the potential to infect other individuals. The patient may die or recover spontaneously, or the infection may respond to specific therapy. Often, there is a postinfection \Timmunity\t, which results in resistance to infection by the same organism in the future. Some infections have a quiescent, latent period that can be measured in years. Included in this group are those infections which cause chronic destruction of the brain. Certain viral infections in animals cause cancers. A viral etiology for human cancers has not been proved but seems likely for some tumors. Evidence has been found suggesting that patients may develop diabetes following viral invasion of the pancreas with resultant destruction of the insulin-producing islet cells. Infectious diseases have strongly influenced the course of history on Earth. The Black Plague changed the entire social structure of medieval Europe. The decrease in number of the working class, which led to the final downfall of the feudal system, was partially caused by decimation of the population from the plague. The outcome of major military campaigns has been profoundly influenced by outbreaks of diseases such as \Tdysentery\t and \Ttyphus\t. Infectious diseases have interfered with habitation and settlement of large areas of the world. \Tmalaria\t, \Tyellow fever\t, and \Tcholera\t have played an important role in influencing the development of society in certain regions of the Earth. AGENTS OF INFECTION The organisms responsible for human infections are extremely variable. \Lvirus\les are simple life forms consisting of nucleic acid, encoding genetic information, and surface components of protein that enable them to enter cells. Unable to multiply outside of living host cells, they are completely dependent on these cells for their continued maintenance. Viruses utilize the metabolic machinery of the cell and have the ability to interfere with, or direct in an adverse fashion, the activities of the cell. \Tmumps\t, \Tmeasles\t, \TGerman measles\t, and \Tchicken pox\t are common childhood illnesses caused by viruses. The common cold is usually due to the rhinovirus. The "flu" or the "grippe" is caused by \Tinfluenza\t viruses. \Thepatitis\t, an inflammation of the liver, may be the result of one of several viruses. Rabies, yellow fever, and Lassa fever are highly lethal viral diseases. Rickettsiae, small microbes that usually grow inside host cells, have a more complicated structure and metabolic makeup than the viruses. Unlike viruses, they are susceptible to antibiotics. Rickettsial diseases are frequently transmitted by arthropods, and stages in the development of the pathogen often take place in ticks or lice. Examples of rickettsial diseases include \TRocky Mountain spotted fever\t, Q FEVER, and typhus. Mycoplasma and Chlamydia are bacterialike organisms that frequently grow inside cells. Their outer cell walls are less complex than those of bacteria. Chlamydia cause \Ttrachoma\t (a scarring eye disease), certain types of urethritis (inflammation of the external urinary passage), and \Tpsittacosis\t (a pneumonia transmitted from birds to man). Mycoplasma are commonly associated with a relatively mild type of \Tpneumonia\t. Nearly all objects in the environment, including plants and animals, are associated with large numbers of bacteria. These organisms can grow and multiply in water and on foods. Certain species can thrive on inorganic nutrients. Garden soil contains countless bacteria per gram, and these organisms are largely responsible for the fertility of the soil. Bacterial diseases are common and include such conditions as streptococcal pharyngitis ("strep throat"), pneumococcal pneumonia, and staphylococcal boils. \Tdiphtheria\t, \Tgonorrhea\t, \Ttuberculosis\t, and \Tsyphilis\t are also caused by bacteria. Bacterial diseases respond to treatment with antibiotics. Fungi, commonly called yeasts or molds, are organisms that frequently grow as single cells (yeasts) and as long, branched filamentous structures (mycelia). Infections caused by these organisms are frequently chronic and slowly destructive. Cryptococcosis, histoplasmosis, and blastomycosis may involve the lung and brain tissue. \Tfungus diseases\t may be superficial, as illustrated by ringworm and thrush. Parasites that commonly cause infections include protozoa and helminths, or worms. Malaria and amebiasis are protozoal diseases common in the tropics. \Tschistosomiasis\t, which results in inflammation of the liver, and \Ttrichinosis\t, involving invasion of muscle and brain tissue, are examples of helminthic diseases. Ectoparasites, organisms that live on the surface of the body, may transmit infectious diseases. For example, lice may carry epidemic typhus, and ticks may be vectors for Rocky Mountain spotted fever (see \Tparasitic diseases\t). MICROBIAL VIRULENCE FACTORS Infectious agents cause disease in the host by several mechanisms. Most typically, microbial virulence, or the potential to cause disease, involves the ability of the pathogen to gain access to the host by surviving on mucous membranes or by being ingested or inhaled. Pili, submicroscopic hairlike structures on the surface of some bacteria, allow them to attach themselves firmly. Next, there is multiplication of the organism on or in the host. The invading microbe must have the capability of avoiding or counteracting the normal protective mechanisms of the host. Capsules surround some bacteria, and these structures serve to prevent the microbes from being ingested and killed by defending phagocytic cells. Other bacteria produce toxins that can destroy phagocytes. Certain highly virulent organisms produce disease in a large percentage of people whom they contact, while other microorganisms produce illness in only a small percentage. When a nonimmune person encounters the influenza virus, the organisms are inhaled, multiply in respiratory cells, damage these cells, and cause disease. In contrast, certain organisms produce toxins, making the patient ill without actually being invaded by the microbes. Clostridium botulinum, a bacterium that grows in improperly preserved foods, produces a potent toxin that when ingested may cause \Tbotulism\t, often leading to paralysis and death. Patients may die by ingesting products of this bacterium without actually being infected by the organism. Other organisms may produce a toxin only after infecting the patient. For example, certain strains of Escherichia coli, a common intestinal bacterium, produce a toxin when colonizing the intestine. This toxin, known as an enterotoxin, causes diarrhea. Infection with this organism has been shown to be the most common cause of diarrhea of travelers. In some instances the host's own defenses against infection may be responsible for the damage. For example, infections caused by Mycoplasma pneumoniae may result in inflammation of the airways and lungs. When the microbes grow in the respiratory cells, they do not damage the cells. However, during the host's attempt to kill foreign invaders, the infected cells are attacked and destroyed by immune mechanisms. HOST DEFENSE AGAINST INFECTION Since human beings exist in a veritable sea of microbes, defense against microbial attack is important for survival of the species. The skin, mucous membranes (interior of the nose, mouth, vagina, rectum), and intestines are colonized by large numbers of bacteria. These organisms are called the normal flora. They are protective and form a barrier against invasion by foreign microbes due, in part, to the metabolic products of these organisms, which may be harmful to potential invaders. In addition, utilization of essential metabolites by the normal flora may "starve" pathogenic invaders. If the normal flora are destroyed by agents such as \Tantibiotics\t, infection may become more likely. The skin and skin secretions are an effective barrier to invasion by most microorganisms. Tears and saliva have intrinsic antibacterial activity. The respiratory tract is kept clean by coughing and sneezing and by the continuous upward movement of particle-trapping mucus, which is transported by the continuous beating of tiny fibrils, or cilia, of the respiratory lining cells. Once microorganisms invade body tissues, mechanisms come into play that strive to neutralize and destroy them. These defenses may be divided into two major groups: humoral and cellular (for example, phagocytic cells). The humoral (or fluid) mechanisms include the \Tantibody\t and complement systems. Antibodies Antibodies are proteins produced by specialized white blood cells called lymphocytes. Antibodies have a strong chemical affinity for specific types of foreign biologic matter. \Lantigen\ls are components of foreign material (that is, microbes) that interact with antibodies. Thus, specific anti-influenza virus antibodies or specific antistaphylococcal antibodies may be present. The interaction of antibodies and components of microbes may serve to destroy, inactivate, or prevent the multiplication of microorganisms. In addition, when an antibody attaches to the surfaces of microorganisms, it makes these microbes more ingestible by phagocytic cells, which have the special role of engulfing and destroying invading microbes. Complement In addition to antibodies, another group of proteins circulates in the blood and body fluids, constituting the complement system. These proteins have the ability to destroy certain pathogens by interacting with them. This interaction may be promoted by antibodies or may take place in the absence of antibodies. Thus, blood serum from healthy individuals, lacking antibodies, will destroy many species of bacteria, and this additional means of protection may partially explain why most bacterial species are unable to cause disease in humans. Lymphocytes Lymphocytes have the ability to produce antibodies directed against specific foreign antigens to which they are exposed. This is the basis for prevention of disease by immunization. For example, patients may be infected with an attenuated, or weakened, strain of polio virus (see \Tpoliomyelitis\t). The lymphocytes will then make antibodies against the polio virus, which will also be active against wild type, fully virulent organisms. Thus, when patients come in contact with these organisms, they do not become ill because they are now immune. Inflammation \Tinflammation\t is the phenomenon by which the body responds to an irritant or to an infection. Small blood vessels dilate and leak fluid, producing swelling, redness, and warmth. In addition, phagocytic white blood cells enter the area, adhere to the lining of the blood vessels, and migrate out of the blood vessels into the tissue to attack microbial invaders. Fever, or elevation of the normal body temperature (37 deg C/98.6 deg F), is a common response to many infections. It is not clear whether fever aids the host in fighting infection. Fever results when a product of phagocytic cells known as endogenous pyrogens acts on a thermostatlike area (hypothalamus) of the brain to raise the body's "set point." Phagocytic Cells Three major types of phagocytic cells are involved in protecting human beings against infection. The polymorphonuclear neutrophil is a motile phagocytic cell that can engulf and destroy pathogens. Ingestion is more efficient when the pathogens have been coated with antibodies or complement or both. Neutrophils are the cells that constitute pus; they migrate to the site of trauma or infection in an attempt to destroy microbes. Macrophages are larger, slower-moving phagocytic cells that have the special capability of killing organisms that can survive ingestion by polymorphonuclear neutrophils. Thus, such organisms as Mycobacterium tuberculosis (the agent that causes tuberculosis) are not destroyed by polymorphonuclear neutrophils but are destroyed by macrophages. Macrophages are found in the liver, spleen, lungs, and bone marrow. The eosinophil is a cell that has special potential for killing multicellular microbes such as helminths. Patients with infections such as trichinosis caused by a helminth will frequently have high eosinophil count in the blood, and this is a clue to physicians as to the nature of the infection. Phagocytic cells kill organisms by engulfing them and enclosing them in a pouch called a phagosome. This pouch then becomes bathed with active metabolites of oxygen, including hydrogen peroxide and superoxide, and various enzymes found in the phagocytic cell. Most microbes are rapidly killed by these cells. Immunity Humans have a natural or inherent immunity to many infections. Intact barriers such as skin and mucous membrane secretions and normal function of the humoral and cellular systems help prevent infection. Recovery from infection most often results in acquired immunity. In addition to production of specific antibodies, the body may induce a state of cellular immunity whereby macrophages and certain types of lymphocytes that enhance macrophage function become able to destroy invaders more efficiently. Immunity may be passed from mother to fetus via the placenta, which serves as a bridge between maternal and fetal circulatory systems. Thus, newborn infants are protected against many infectious diseases for the first few months of life. Some evidence indicates that breast milk also contains antibodies that may be protective during this early period. Many childhood illnesses seem to be most common and most serious between the ages of 6 months and 6 years, when maternal immunity wanes and acquired immunity has not yet become effective. ROUTES AND MODES OF INFECTION Respiratory Route Pathogenic organisms may be inhaled. This mechanism by which infection is spread is especially significant in many respiratory diseases and is responsible for large epidemic outbreaks. Viral influenza is spread by tiny, airborne particles that can reach the lower airways of the lungs. Tuberculosis, smallpox, and measles are spread by contamination of the air by infected patients. In contrast, fungal diseases such as histoplasmosis and coccidioidomycosis are acquired by inhaling infectious particles derived from soil harboring the organisms, and \TLegionnaire\t'S DISEASE is spread by contaminated water droplets. Gastrointestinal Route Infections may be acquired by ingestion of the causative organism. Infectious hepatitis, poliomyelitis, and typhoid fever are transmitted by this means. The infecting dose varies from disease to disease. In some conditions as few as one or two organisms can initiate infection, whereas in others as many as 1 million organisms may be required. Certain features of the person encountering the organisms may potentiate their effects. For example, in patients ingesting Salmonella typhi, the causative organism of typhoid fever, who have a lack of acid production in their stomachs, many fewer organisms may be required to infect these persons than those who have normal acid production. Stomach acid is an important host defense because it can kill these microbes. Direct Contact Mucous membranes may be a portal of entry for many infections. The venereal diseases gonorrhea and syphilis are transmitted by direct contact of mucous membrane to mucous membrane. This may involve penis, vagina, urethra, mouth, or anus. The causative organisms lack the ability to penetrate and attack intact skin, but can infect via mucous membranes. Although the skin is an impenetrable barrier for most infections, certain organisms may break through. For example, staphylococci may cause boils on skin that is normal or has only a trivial irritation. The streptococcus may cause cellulitis (a spreading inflammation) or \Timpetigo\t (a crusting lesion) on skin that is intact. Mother to Child It is possible for a fetus to become infected while in the uterus. Therefore, infections that the mother acquires during pregnancy may damage the fetus. Some of the most dangerous of these include rubella (German measles), cytomegalovirus disease, and toxoplasmosis. All these conditions produce mild disease in the pregnant woman but may result in devastating damage to the developing fetus. In addition, infants may be infected at birth during passage through an infected birth canal. This can result in congenital (present since the time of birth) gonorrhea, syphilis, herpes viral infections, or streptococcal infections. RELATIONSHIP OF ENVIRONMENT TO INFECTION The ecology of infection is complex and involves interactions with climate, food and water supply, arthropod vectors, animal contacts, and other human beings. Many of the great scourges of humankind, such as tuberculosis, cholera, malaria, and typhoid fever, were markedly decreased in incidence by changes in the environment. These changes anteceded development of effective vaccines and therapeutic agents. The greatest danger to Homo sapiens, regarding the spread of infection, are other Homo sapiens. Organisms may spread from one person to another by direct contact, by the airborne route, or by oral ingestion of contaminated food or water. Food and water supplies may become contaminated with microbes derived from humans or animals or from the environment. For example, unpasteurized milk may serve to transmit disease if it is contaminated with organisms from an infected cow (for example, brucellosis) or from an infected dairy person (for example, streptococci emanating from a skin lesion). In some instances the microbe may actually grow and multiply on the food, increasing the efficiency of transmission. Density of population directly affects the spread of certain communicable diseases. Major epidemics have occurred in boarding schools and military barrack populations where contact is close. When people are confined to enclosed places, airborne pathogens tend to spread more readily. Thus, the peaks of respiratory diseases such as influenza and pneumonia are the fall, winter, and early spring months in temperate climates. Patients interacting with domestic or wild animals may have special problems with infections related to pathogens that are harbored by animal species. For example, butchers and meat packers have the highest incidence of brucellosis, a bacterial infection of liver, spleen, and bones. Hunters may contract \Ttularemia\t, a bacterial infection of rabbits that can be transmitted to humans through handling of pelts. Insects are significant in the transmission of many infections. The malaria parasite is transmitted from one human to another, or from an animal to a human being, by the bite of the anopheles mosquito. Because this mosquito cannot survive in cold climates, malaria is not a problem in temperate countries. The tick vector of Rocky Mountain spotted fever requires bushy underbrush and a small mammal population to feed on for survival. Areas that do not have these conditions will not support the tick and are thus free of Rocky Mountain spotted fever. Schistosomiasis is a parasitic disease caused by an organism that spends part of its life cycle in a snail. If the snail does not have the proper water conditions to survive, the disease will not be found in that area. THE IMPAIRED HOST It is clear that some people are more susceptible to infections than others. Sometimes the cause of the increased susceptibility is obvious. A severely burned person, for example, lacks the normal protective features of intact skin and suffers from infections as a result. Patients with \Timmunodeficiency\t \Tdiseases\t that impair the function of the immune system frequently have severe and fatal infections. One such disease, for example, is acquired immune deficiency syndrome (see \TAIDS\t), which is characterized by severe defects in the ability of lymphocytes and macrophages to function normally. Persons with \Tleukemia\t (cancer of the white blood cells) also frequently die of infections. In addition, drugs that interfere with normal host defenses may make the patient especially prone to infection. Patients receiving drugs that kill cancer cells frequently have suppressed phagocytic cell function because the drugs are known to also kill healthy cells. Severe malnutrition increases susceptibility to certain forms of infection. Recent evidence suggests that this vulnerability is due to impaired functioning of lymphocytes and macrophages. RESPIRATORY INFECTIONS The respiratory tract includes the nose, throat, bronchial tubes leading to the lungs, and the lungs. Closely associated with the system are the paranasal sinuses and the middle ear. The most common infections are viral infections of the upper respiratory tract, for example, the nose and the throat. The common cold, viral \Tpharyngitis\t, and \Tbronchitis\t are annoying, but rarely serious, illnesses. Occasionally, however, bacterial infections may supervene, and the illness may become more severe. Bacterial infections of the middle ear may, if untreated, result in loss of hearing. Infections of the sinuses occasionally lead to infection of the brain and surrounding structures. Streptococcal pharyngitis is of importance mainly because of the sequelae that may follow. Patients who suffer from untreated streptococcal disease may develop complications such as rheumatic fever (an inflammation of various organs, most prominently the heart valves) or inflammation of the kidneys (see \Tcold, common\t). More serious \Trespiratory system disorders\t involve the lungs. Bacterial pneumonias, especially those caused by the pneumococcus and the staphylococcus, are common and serious diseases. Tuberculosis and the fungal diseases such as histoplasmosis and coccidioidomycosis may also involve the lungs. Infections of the lungs may damage tissue and cause chronic scarring and impairment of respiratory activity. In acute infections, death resulting from interference with normal gas exchange may occur. Patients with underlying lung diseases such as chronic bronchitis, an irritative condition associated with smoking and air pollution, are more susceptible to pulmonary infections. GASTROINTESTINAL TRACT INFECTIONS The processes of digestion and absorption of nutrients take place in the gastrointestinal tract. Major components of this system include the esophagus, stomach, intestines (small intestine and large bowel, or colon), and the organs of digestion, including the liver and pancreas. The symptoms of the most common \Tgastrointestinal tract\t \Tdiseases\t include nausea, vomiting, and diarrhea. Disease may be caused by ingestion of a preformed toxin such as in some kinds of \Tfood poisoning\t, or illness may be due to a true infection as in viral or bacterial gastroenteritis. The most severe forms of gastroenteritis are those caused by bacteria. Shigella bacterial organisms cause bacillary dysentery, a fulminating form of diarrhea, which causes destruction of the lining of the bowel. Salmonella bacteria may cause gastroenteritis and at times invade the bloodstream, leading to infections in widespread areas of the body such as bone, liver, and blood vessels. Viral gastroenteritis is usually benign and self-limited, requiring no specific therapy. Various parasites that infect the gastrointestinal tract include protozoa such as Entamoeba histolytica, the cause of amebiasis, and Giardia lamblia, the cause of giardiasis. These two infections may be chronic and indolent and may mimic the signs and symptoms of noninfectious gastrointestinal diseases such as ulcerative colitis and regional enteritis. The majority of patients who develop acute symptoms of diarrhea with or without nausea and vomiting have a self-limited disease that requires no therapy. The most common identifiable causes of this syndrome include viral gastroenteritis and toxin-producing strains of the common colon baccilus Escherichia coli. Helminth, or worm, infections of the gastrointestinal tract range in severity from asymptomatic to those that may result in severe illness. Hookworms attach to the wall of the intestines and destroy red blood cells. A heavy infection may thus produce anemia. Large tapeworms in the gastrointestinal tract may induce illness by absorbing foodstuffs and vital nutrients. Hepatitis, an inflammation of the liver, is most commonly caused by viruses. Hepatitis A, or infectious hepatitis, is a disease that is transmitted by direct fecal-oral contact. It is a common illness in young children and is usually benign. Hepatitis B, or serum hepatitis, is transmitted by exposure to contaminated blood or blood products and by direct intimate (often sexual) contact. It may be a more serious disease, especially in older patients. Blood donors are carefully screened for evidence of hepatitis B. Those who have evidence of prior viral infection are excluded from donating blood. SKIN AND MUCOUS MEMBRANE INFECTIONS Infection may primarily involve the skin and mucous membranes, or skin lesions may indicate infection elsewhere. The most common bacterial \Tskin diseases\t include those caused by staphylococci, which tend to form boils (or pus-filled areas of inflammation), and streptococci, which result in a spreading area of skin inflammation. Measles, a systemic infection, is characterized by a generalized skin rash. Herpes simplex virus causes cold sores, and in impaired hosts, more widely spread lesions. Shingles, or herpes zoster, is an infection of the nerves supplying a specific area. The virus, identical to that which causes chicken pox, is thought to represent a reactivation of an old chicken pox infection. Diagnosis is usually easily made, because lesions characteristically cluster in a pattern representing the distribution of nerves on the surface of the skin. Parasites may invade the skin. For example, scabies is due to a small mite that burrows in the skin, causing intense itching and inflammation. The louse, which lays its eggs (nits) on hair, and ticks, which suck blood from the host, may transmit serious diseases. Fungal skin diseases, which are common and usually benign, include ringworm, athlete's foot, and thrush. VENEREAL DISEASES \Lvenereal disease\ls are transmitted by sexual contact. Syphilis is caused by a spiral-shaped bacterium, a spirochete. This disease is especially dangerous because after initial infection of the genitals or mucous membranes it may become quiescent for years and then activate and cause damage to the nervous system or cardiovascular system. The chancre, a painless ulcer, is the most common initial lesion. Syphilis may be diagnosed by blood tests. Treatment with antibiotics is very effective. Gonorrhea is a common bacterial disease characterized by inflammation of the urethra. In females, inflammation of the fallopian tubes may result in abdominal pain, fever, and sterility. Gonorrhea is diagnosed by bacterial cultures. Antibiotic therapy is extremely effective. Sexually transmitted urethritis may also be caused by other microorganisms including Chlamydia and Mycoplasma. These diseases are relatively benign in adults. When transmitted to infants, however, these agents may cause eye infection and pneumonia. Herpes simplex type 2 is a virus that causes painful involvement of the genital area. This disease tends to wax and wane. There is at present no established effective therapy, but new drugs are being evaluated. OTHER INFECTIONS The brain and spinal cord may be directly involved in infection. Viral encephalitis damages the brain, and poliomyelitis is an infection of the spinal cord. The lining of the nervous system may be affected by meningitis due to bacteria, viruses, or fungi. Bacterial infection of the urinary tract is common, especially in adult women. Antimicrobial therapy is effective unless there is a structural abnormality present. Infections of bone (osteomyelitis) and of joints (septic arthritis) may result in deformity and disability. Infective endocarditis is a serious infection of the valves inside the heart. In addition to antibiotic therapy, the involved heart valves may require surgical excision and replacement with artificial valves. PREVENTION Prevention is much more efficient than treating infectious diseases. Prevention may involve general improvements in sanitation and the nutritional state of the population or more specific maneuvers such as immunization. Toxoids, or altered toxins, are used to immunize against tetanus and diphtheria, two diseases where the major damage is done by the toxin rather than invasion by the microbe. Attenuated, or weakened, live viruses are used to immunize against poliomyelitis and rubella (German measles). Killed organisms or fractions of organisms are the immunizing agents for influenza and typhoid fever. The live virus vaccines usually give longer-lasting protection than killed vaccines. Immunization with a related virus (vaccinia, or cowpox virus) has been effective in eliminating smallpox as a threat to humans. Patients who may spread highly contagious diseases to other patients may have to be isolated while they are undergoing treatment. Thus, before chemotherapy for tuberculosis was available, patients with this disease were separated from the rest of society in sanitoriums. Now, since therapy is so effective, these patients may be treated in general hospitals, or even in their own homes. Infections that may be acquired in a hospital can be eliminated or reduced by strict attention to cleanliness and avoidance of cross-contamination from one patient to another; from patients to hospital personnel; and from personnel to susceptible patients. THERAPY OF INFECTIOUS DISEASES Most infections are self-limited and require no therapy. However, appropriate therapy is effective in shortening the cause of illness, reducing the risk of transmission to other patients, and in the case of severe infections, reducing mortality. No truly effective agents for the therapy of infection were available until the 1930s, when sulfonamides were developed. These agents interfere with steps in the metabolism of bacteria and are effective therapy for certain bacterial diseases. Penicillin, the first of the antibiotics, became available in the 1940s. Antibiotics are substances produced by microbes that act against other microbes. The useful antibiotics are relatively nontoxic to mammalian systems. Antibiotics have a specific spectrum of action, and thus some agents are more effective for certain infections. Commonly used antibiotics include the penicillins, tetracyclines, cephalosporins, and the aminoglycosides. In addition, several nonantibiotic drugs are effective against bacterial infections. Fungal infections will respond to chemotherapy, and recently drugs effective against a few viral infections have been developed. The vast majority of viral infections, however, remain unaffected by any known therapeutic agents. New antimicrobials are constantly being developed and tested. This research is important because microbes can develop resistance to established agents. CURRENT RESEARCH Although the major infectious scourges of society have been eliminated or reduced, the search for discoveries in infectious diseases is still of major importance. Infections continue to afflict millions of people each year and are still a significant cause of discomfort, severe illness, and death. Advances in medical technology help many patients overcome serious disease, but these new treatments also impair the defenses of these patients, leaving them susceptible to other severe infections. Therefore, if advances in cancer therapy and organ transplants are to continue, better methods of preventing and treating accompanying infections in these patients are vital. Some of the chronic debilitating diseases that have been previously thought to be noninfectious may in fact be related to infectious organisms. Thus, such diverse conditions as diabetes mellitus and multiple sclerosis may be caused by infectious agents. The new science of genetic engineering may enable us to alter the properties of microbes so that they can serve as effective immunizing strains without causing disease. In addition, alterations in microbes may result in production of antibiotics that may be more active and less toxic than those previously available. A more complete understanding of normal host defenses allows us to manipulate these mechanisms in an effort to prevent, control, and treat infections. Gerald Lee Mandell, M.D. Bibliography: Dodd, Roger Y., and Lewellys, F. Barker, eds., Infections, Immunity, and Blood Transfusion (1985); Illingworth, Ronald S., Infections and Immunization of Your Child (1990); Kennedy, Peter G., and Johnson, Richard T., eds., Infection of the Nervous System (1987); Krier, Julius P., and Mortensen, Richard F., Infection, Resistance, and Immunity (1990); Lord, John, Infections, the Immune System, and \TAIDS\t (1989); Remington, Jack S., and Klein, Jerome O., Infectious Diseases of the Fetus and Newborn Infant, 3d ed. (1990); Sweet, Richard, Infectious Disease (1990).