infectious disease

Introduction

      in medicine, a process caused by a microorganism that impairs a person's health. An infection, by contrast, is the invasion of and replication in the body by any of various microbial agents—including bacteria, viruses (virus), fungi (fungus), protozoans (protozoan), and worms (worm)—as well as the reaction of tissues to their presence or to the toxins that they produce. When health is not altered, the process is termed a subclinical infection. Thus, a person may be infected but not have an infectious disease. This principle is illustrated by the use of vaccines (vaccine) for the prevention of infectious diseases. For example, a virus such as that which causes measles may be attenuated (weakened) and used as an immunizing agent. The immunization is designed to produce a measles infection in the recipient but generally causes no discernible alteration in the state of health. It produces immunity to measles without producing a clinical illness (an infectious disease).

      The most important barriers to invasion of the human host by microorganisms are the skin and mucous membranes (the tissues that line the nose, mouth, and upespiratory tract). When these tissues have been broken or affected by earlier disease, invasion by microorganisms may occur. These microorganisms may produce a local infectious disease, such as boils (boil), or may invade the bloodstream and be carried throughout the body, producing generalized bloodstream infection ( septicemia) or localized infection at a distant site, such as meningitis (an infection of the coverings of the brain and spinal cord). Infectious agents swallowed in food and drink can attack the wall of the intestinal tract and cause local or general disease. The conjunctiva, which covers the front of the eye, may be penetrated by viruses that cause a local inflammation of the eye or that pass into the bloodstream and cause a severe general disease, such as or smallpox. Microorganisms can enter the body through the genital tract, causing the acute inflammatory reaction of gonorrhea in the genital and pelvic organs or spreading out to attack almost any organ of the body with the more chronic and destructive lesions of syphilis. Even before birth, viruses and other infectious agents can pass through the placenta and attack developing cells, so that an infant may be diseased or deformed at birth.

      From conception to death, humans are targets for attack by multitudes of other living organisms, all of them competing for a place in the common environment. The air people breathe, the soil they walk on, the waters and vegetation around them, the buildings they inhabit and work in, all can be populated with forms of life that are potentially dangerous. Domestic animals may harbour organisms that are a threat, and wildlife teems with agents of infection that can afflict humans with serious disease. However, the human body is not without defenses against these threats, for it is equipped with a comprehensive immune system that reacts quickly and specifically against disease organisms when they attack. Survival throughout the ages has depended largely on these reactions, which today are supplemented and strengthened through the use of medical drugs (drug).

Infectious agents

Categories of organisms

      The agents of infection can be divided into different groups on the basis of their size, biochemical characteristics, or manner in which they interact with the human host. The groups of organisms that cause infectious diseases are categorized as bacteria, viruses, Chlamydia, rickettsias, mycoplasmas and ureaplasmas, fungi, and parasites.

bacteria

       bacteria can survive within the body but outside individual cells. Some bacteria, classified as aerobes (aerobe), require oxygen for growth, while others, such as those normally found in the small intestine of healthy persons, grow only in the absence of oxygen and, therefore, are called anaerobes. Most bacteria are surrounded by a capsule that appears to play an important role in their ability to produce disease. Also, a number of bacterial species give off toxins that, in turn, may damage tissues. Bacteria are generally large enough to be seen under a light microscope. Streptococci, the bacteria that cause scarlet fever, are about 0.75 micrometre (0.00003 inch) in diameter. The spirochetes (spirochete), which cause syphilis, leptospirosis, and rat-bite fever, are 5 to 15 micrometres long. Bacterial infections can be treated with antibiotics (antibiotic).

      Bacterial infections are commonly caused by pneumococci (pneumococcus), staphylococci (staphylococcus), and streptococci (Streptococcus), all of which are often commensals (that is, organisms living harmlessly on their hosts) in the upper respiratory tract but that can become virulent and cause serious conditions, such as pneumonia, septicemia (blood poisoning), and meningitis. The pneumococcus is the most common cause of lobar pneumonia, the disease in which one or more lobes, or segments, of the lung become solid and airless as a result of inflammation. Staphylococci (staphylococcus) affect the lungs either in the course of staphylococcal septicemia—when bacteria in the circulating blood cause scattered abscesses in the lungs—or as a complication of a viral infection, commonly influenza—when these organisms invade the damaged lung cells and cause a life-threatening form of pneumonia. Streptococcal pneumonia is the least common of the three and occurs usually as a complication of influenza or other lung disease.

      Pneumococci often enter the bloodstream from inflamed lungs and cause septicemia, with continued fever but no other special symptoms. Staphylococci produce a type of septicemia with high, swinging fever; the bacteria reach almost any organ of the body, the brain, the bones, and especially the lungs, and destructive abscesses form in the infected areas. Streptococci (Streptococcus) also cause septicemia with fever, but the organisms tend to cause inflammation of surface lining cells rather than abscesses—for example, pleurisy (inflammation of the chest lining) rather than lung abscess, and peritonitis (inflammation of the membrane lining the abdomen) rather than liver abscess. In the course of either of the last two forms of septicemia, organisms may enter the nervous system and cause streptococcal or staphylococcal meningitis, but these are rare conditions. Pneumococci, on the other hand, often spread directly into the central nervous system, causing one of the common forms of meningitis.

      Staphylococci and streptococci are common causes of skin diseases. Boils and impetigo (in which the skin is covered with blisters, pustules, and yellow crusts) may be caused by either. The staphylococcus also can cause a severe skin infection that strips the outer skin layers off the body and leaves the underlayers exposed, as in severe burns, a condition known as toxic epidermal necrolysis. In the 1980s causes of severe streptococcal necrotizing fasciitis, causing disease and death, began to be noticed. Streptococci can be the cause of the red cellulitis of the skin known as erysipelas.

      Some staphylococci produce an intestinal toxin and cause food poisoning. Streptococci settling in the throat produce a reddening toxin that speeds through the bloodstream and produces the symptoms of scarlet fever. Streptococci and staphylococci also can cause toxic shock syndrome, a potentially fatal disease.

      Meningococci (meningococcus) are fairly common inhabitants of the throat, in most cases causing no illness at all. As the number of healthy carriers increases in any population, however, there is a tendency for the meningococcus to become more invasive. When an opportunity is presented, it can gain access to the bloodstream, invade the central nervous system, and cause meningococcal meningitis (formerly called cerebrospinal meningitis or spotted fever). Meningococcal meningitis, at one time a dreaded and still a very serious disease, usually responds to treatment with penicillin if diagnosed early enough. When meningococci invade the bloodstream, some gain access to the skin and cause bloodstained spots, or purpura. If the condition is diagnosed early enough, antibiotics can clear the bloodstream of the bacterium and prevent any from getting far enough to cause meningitis. Sometimes the septicemia takes a mild, chronic, relapsing form with no tendency toward meningitis; this is curable once it is diagnosed. The meningococcus also can cause one of the most fulminating of all forms of septicemia, meningococcemia, in which the body is rapidly covered with a purple rash, purpura fulminans; in this form the blood pressure becomes dangerously low, the heart and blood vessels are affected by shock, and the infected person dies within a matter of hours. Few are saved, despite treatment with appropriate drugs.

      Haemophilus influenzae is a microorganism named for its occurrence in the sputum of patients with influenza—an occurrence so common that it was at one time thought to be the cause of the disease. It is now known to be a common inhabitant of the nose and throat that may invade the bloodstream, producing meningitis, pneumonia, and various other diseases. In children it is the most common cause of acute epiglottitis, an infection in which tissue at the back of the tongue becomes rapidly swollen and obstructs the airway, creating a potentially fatal condition. H. influenzae also is the most common cause of meningitis and pneumonia in children under five years of age, and it is known to cause bronchitis in adults. The diagnosis is established by cultures of blood, cerebrospinal fluid, or other tissue from sites of infection. Antibiotic therapy is generally effective, although death from sepsis or meningitis is still common. In developed countries where H. influenza vaccine is used, there has been a great decrease in serious infections and deaths.

Viruses (virus)

      Viruses (virus) are not, strictly speaking, living organisms. Instead, they are nucleic acid fragments packaged within protein coats that require the machinery of living cells to replicate. Viruses are visible by electron microscopy (electron microscope); they vary in size from about 25 nanometres for poliovirus to 250 nanometres for smallpox virus. Vaccination (vaccine) has been the most successful weapon against viral infection; some infections may be treated with antiviral drugs (antibiotic) or interferon.

      Viruses of the Herpesviridae family cause a multiplicity of diseases. Those causing infections in humans are the varicella-zoster virus (VZV), which causes chickenpox and herpes zoster (shingles); the Epstein-Barr virus, which causes infectious mononucleosis; the cytomegalovirus, which is most often associated with infections of newborn infants and immunocompromised people; and herpes simplex virus, which causes cold sores and herpetic venereal (sexually transmitted) diseases.

      There are two serotypes of herpes simplex virus, HSV-1 and HSV-2. HSV-1 is the common cause of cold sores. The primary infection usually occurs in childhood and is without symptoms in 50 to 80 percent of cases. Between 10 and 20 percent of infected individuals have recurrences precipitated by emotional stress or by other illness. HSV-1 can also cause infections of the eye, central nervous system, and skin. Serious infections leading to death may occur in immunocompromised persons. HSV-2 is associated most often with herpetic lesions of the genital area. The involved area includes the vagina, cervix, vulva, and, occasionally, the urethra in females and the head of the penis in males; it may also cause an infection at the site of an abrasion. The disease is usually transmitted by sexual contact. In herpetic venereal diseases (sexually transmitted disease), the lesions are small, red, painful spots that quickly vesiculate, become filled with fluid, and quickly rupture, leaving eroded areas that eventually become scabbed. These primary lesions occur from two to eight days after exposure and may be present for up to three weeks. Viral shedding and pain usually resolve in two weeks. When infections recur, the duration of the pain, lesions, and viral shedding is approximately 10 days.

Chlamydia

       Chlamydia are intracellular organisms found in many vertebrates, including birds and humans and other mammals. Clinical illnesses are caused by two species, C. trachomatis and C. psittaci. The former is a frequent cause of genital infections in women, and, if an infant passes through an infected birth canal, it can produce disease of the eye ( conjunctivitis) and pneumonia in the newborn. Young children sometimes develop ear infections, laryngitis, and upper respiratory tract disease from Chlamydia. Such infections can be treated with erythromycin.

      C. psittaci produces psittacosis, a disease that results from exposure to the discharges of infected birds. The illness is characterized by high fever with chills, a slow heart rate, pneumonia, headache, weakness, fatigue, muscle pains, anorexia, nausea, and vomiting. The diagnosis is usually suspected if the patient has a history of exposure to birds and is confirmed by blood tests. Mortality is rare, and specific antibiotic treatment is available.

Rickettsias (rickettsia)

      The rickettsias (rickettsia) are a family of microorganisms named for American pathologist Howard T. Ricketts, who died of typhus in 1910 while investigating the spread of the disease. The rickettsias, which range in size from 250 nanometres to more than 1 micrometre and have no cell wall but are surrounded by a cell membrane, cause a group of diseases characterized by fever and a rash. Except for Coxiella burnetii, the cause of Q fever, they are intracellular parasites, most of which are transmitted to humans by an arthropod carrier such as a louse or tick. C. burnetii, however, can survive in milk, sewage, and aerosols and can be transmitted to humans by a tick or by inhalation, causing pneumonia in the latter case. Rickettsial diseases can be treated with antibiotics.

      Humans contract most rickettsial diseases only when they break into a cycle in nature in which the rickettsias live. In murine typhus, for example, Rickettsia mooseri is a parasite of rats conveyed from rat to rat by the rat flea, Xenopsylla cheopis; it bites humans if they intrude into its environment. scrub typhus is caused by R. tsutsugamushi, but it normally parasitizes only rats and mice and other rodents, being carried from one to the other by a small mite, Leptotrombidium (previously known as Trombicula). This mite is fastidious in matters of temperature, humidity, and food and finds everything suitable in restricted areas, or “mite islands,” in South Asia and the western Pacific. It rarely bites humans in their normal environment, but if people invade its territory en masse it will attack, and outbreaks of scrub typhus will follow.

      The spotted fevers are caused by rickettsias that spend their normal life cycles in a variety of small animals, spreading from one to the other inside ticks; these bite human intruders and cause African, North Asian, and Queensland tick typhus, as well as Rocky Mountain spotted fever. One other spotted fever, rickettsialpox, is caused by R. akari, which lives in the body of the ordinary house mouse, Mus musculus, and spreads from one to another inside the house mite Allodermanyssus sanguineus. This rickettsia is probably a parasite of wild field mice, and it is perhaps only when cities push out into the countryside that house mice catch the infection.

Mycoplasmas (mycoplasma) and ureaplasmas

      Mycoplasmas (mycoplasma) and ureaplasmas, which range in size from 150 to 850 nanometres, are the smallest free-living microorganisms. They are ubiquitous in nature and capable of causing widespread disease, but the illnesses they produce in humans are generally milder than those caused by bacteria. Diseases due to mycoplasmas and ureaplasmas can be treated with antibiotics (antibiotic).

      Mycoplasma pneumoniae is the most important member of its genus. M. pneumoniae is associated with 20 percent of all cases of pneumonia in adults and children over five years of age. Patients have fever, cough, headache, and malaise and, upon physical examination, may be found to have pharyngitis (inflamed throat), enlarged lymph nodes, ear or sinus infection, bronchitis, or croup. Diagnosis is established by chest X-rays and blood tests. Although treatment with erythromycin or tetracycline may shorten the illness, it can last for weeks.

      Mycoplasmas may also cause a red, bumpy rash—usually on the trunk or back—that is occasionally vesicular (with blisters). Inflammation of the heart muscle and the covering of the heart (pericardium) is rare but can be caused by mycoplasmas. About one-fourth of the people infected with these organisms experience nausea, vomiting, diarrhea, and cramping abdominal pain. Inflammation of the pancreas ( pancreatitis) or the liver ( hepatitis) may occur, and infection of the brain and spinal cord is a serious complication.

      Ureaplasmas can be recovered frequently from the genital areas of healthy persons. The organism can cause inflammation of the urethra and has been associated with infertility, low birth weight of infants, and repeated stillbirths. In general, however, ureaplasma infections are mild. Tetracycline is the preferred treatment once the organism has been established as the cause of infection by microscopic examination of urethral secretions.

Fungi (fungus)

      Fungi (fungus) are large organisms that usually live on dead and rotting animal and plant matter. They are found mostly in soil, on objects contaminated with soil, on plants and animals, and on skin, and they may also be airborne. Fungi may exist as yeasts (yeast) or molds (mold) and may alternate between the two forms, depending on environmental conditions. Yeasts are simple cells, 3 to 5 micrometres (0.0001 to 0.0002 inch) in diameter. Molds consist of filamentous branching structures (called hyphae), 2 to 10 micrometres in diameter, that are formed of several cells lying end to end. Fungal diseases in humans are called mycoses (mycosis); they include such disorders as histoplasmosis, coccidioidomycosis, and blastomycosis. These diseases can be mild, characterized by an upper respiratory infection, or severe, involving the bloodstream and every organ system. Fungi may cause devastating disease in persons whose defenses against infection have been weakened by malnutrition, cancer, or the use of immunosuppressive drugs. Specific types of antibiotics known as antifungals are effective in their treatment.

Parasites (parasitism)

      Among the infectious parasites are the protozoans (protozoan), unicellular organisms that have no cell wall, that cause such diseases as malaria. The various species of malarial parasites are about 4 micrometres (0.0002 inch) in diameter. At the other extreme, the tapeworm can grow to several metres in length; treatment is designed either to kill the worm or to dislodge it from its host.

      The worm Ascaris lumbricoides causes ascariasis, one of the most prevalent infections in the world. Ascaris lives in the soil, and its eggs are ingested with contaminated food. The eggs hatch in the human intestine, and the worms then travel through the bloodstream to the liver, heart, and lungs. They can cause pneumonia, perforations of the intestine, or blockage of the bile ducts, but infected people usually have no symptoms beyond the passage of worms in the stool. Specific treatment is available and prognosis is excellent.

      Infections are also caused by whipworms (whipworm), genus Trichuris, and pinworms (pinworm), Enterobius vermicularis, each popularly named for its shape. The former is parasitic in the human large intestine and may cause chronic diarrhea. The latter can be found throughout the gastrointestinal tract, especially in children, and can cause poor appetite, loss of weight, anemia, and itching in the anal area (where it lays its eggs). Both conditions are easily diagnosed and treated with drugs.

Modes of survival

      Infectious agents have various methods of survival. Some depend on rapid multiplication and rapid spread from one host to another. For example, when the measles virus enters the body, it multiplies for a week or two and then enters the bloodstream and spreads to every organ. For several days before a rash appears, the surface cells of the respiratory tract are bursting with measles virus, and vast quantities are shed every time the infected person coughs or sneezes. A day or two after the rash appears, the amount of antibody (protein produced in response to a pathogen) rises in the bloodstream, neutralizing the virus and stopping further shedding. The patient rapidly becomes noninfectious but already may have spread the virus to others. In this way an epidemic can rapidly occur. Many other infectious agents—for example, influenza virus—survive in this manner. How such viruses exist between epidemics is, in some cases, less clear.

      The picture is different in more-chronic infections. In tuberculosis there is neither overwhelming multiplication nor rapid shedding of the tubercle bacillus. Rather, the bacilli remain in the infected person's body for a long period, slowly forming areas of chronic inflammation that may from time to time break down and allow them to escape.

      Some organisms form spores, a resting or dormant stage that is resistant to heat, cold, drying, and chemical action. Spore-forming organisms can survive for months or years under the most adverse conditions and may not, in fact, be highly infectious. The bacterium that causes tetanus, Clostridium tetani, is present everywhere in the environment—in soil, in dust, on window ledges and floors—and yet tetanus is an uncommon disease, especially in developed countries. The same is true of the anthrax bacterium, Bacillus anthracis. Although usually present in abundance in factories in which rawhides and animal wool and hair are handled, it rarely causes anthrax in employees. Clostridium botulinum, the cause of botulism, produces one of the most lethal toxins that can afflict humans, and yet the disease is one of the rarest because the microorganism depends for its survival on its resistant spore.

      In contrast to these relatively independent organisms, there are others that cannot exist at all outside the human body. The germs of syphilis and gonorrhea, for example, depend for survival on their ability to infect and their adaptation to the human environment.

      Some organisms have complicated life cycles and depend on more than one host. The malarial parasite must spend a portion of its life cycle inside a mosquito, while the liver fluke Fasciola hepatica, an occasional human parasite, spends part of its life in the body of a land animal such as a sheep, part in a water snail, and part in the open air as a cyst attached to grass.

Commensal (commensalism) organisms

      All of the outer surfaces of the human body are covered with microorganisms that normally do no harm and may, in fact, be beneficial. Those commensal organisms on the skin help to break down dying skin cells or to destroy debris secreted by the many minute glands and pores that open on the skin. Many of the organisms in the intestinal (colon) tract (small intestine) break down complex waste products into simple substances, and others help in the manufacture of chemical compounds that are essential to human life.

      The gastrointestinal tract is considered in this regard to be one of these “outer” surfaces since it is formed by the intucking, or invagination, of the ectoderm, or outer surface, of the body. The mouth, nose, and sinuses (spaces inside the bones of the face) are also considered to be external structures because of their direct contact with the outside environment. Both the gastrointestinal tract and the mouth, nose, and sinuses are heavily populated with microorganisms, some of which are true commensals—living in humans and deriving their sustenance from the surface cells of the body without doing any harm—and others of which are indistinguishable from disease germs. The latter may live like true commensals in a particular tract in a human and never cause disease, despite their potential to do so. When the environment is altered, however, they are capable of causing severe illness in their host, or, without harming their host, they may infect another person with a serious disease.

      It is not known why, for example, the hemolytic Streptococcus bacterium can live for months in the throat without causing harm and then suddenly cause an acute attack of tonsillitis or how an apparently harmless pneumococcus gives rise to pneumonia. Similarly, it is not understood how a person can harmlessly carry Haemophilus influenzae type B in the throat but then become ill when the organism invades the body and causes one of the most severe forms of meningitis. It may be that external influences, such as changes in temperature or humidity, are enough to upset the balance between host and parasite or that a new microbial invader enters and, by competing for some element in the environment, forces the original parasite to react more violently with its host. The term lowered resistance, often used to describe conditions at the onset of infectious disease, is not specific and simply implies any change in the immune system of the host.

      A microorganism's environment can be changed radically, of course. If antibiotics (antibiotic) are administered, the body's commensal organisms can be killed, and other, less-innocuous organisms may take their place. In the mouth and throat, penicillin may eradicate pneumococci, streptococci, and other bacteria that are sensitive to the drug, while microorganisms that are insensitive, such as Candida albicans, may then proliferate and cause thrush (an inflammatory condition of the mouth and throat). In the intestinal tract, an antibiotic may kill most of the microorganisms that are normally present and allow dangerous organisms, such as Pseudomonas aeruginosa, to multiply and perhaps to invade the bloodstream and the tissues of the body. If an infectious agent—for example, Salmonella—reaches the intestinal tract, treatment with an antibiotic may have an effect that differs from what was intended. Instead of attacking and destroying the salmonella, it may kill the normal inhabitants of the bowel and allow the salmonella to flourish and persist in the absence of competition from other microorganisms.

Effects of environment on human disease

Human activity

Family patterns

      Humans are social (sociology) animals. As a result, human social habits and circumstances influence the spread of infectious agents. Poorer families tend to live in more-crowded conditions, which facilitate the passage of disease-causing organisms from one person to another. This is true whether the germs pass through the air from one respiratory tract to another or whether they are bowel organisms that depend for their passage on close personal hand-to-mouth contact or on lapses of sanitation and hygiene.

      The composition of the family unit is also important. In families with infants and preschool children, infection spreads more readily, for children of this age are both more susceptible to infection and, because of their undeveloped hygiene habits, more likely to share their microbes with other family members. Because of this close and confined contact, infectious agents are spread more rapidly.

 Distinction must be made between disease and infection. The virus of poliomyelitis, for example, spreads easily in conditions of close contact (infection), but it usually causes no active disease. When it does cause active disease, it attacks older people much more severely than the young. Children in more-crowded homes, for example, are likely to be infected at an early age and, if illness results, it is usually mild. In less-crowded conditions, young children are exposed less often to infection; when they first encounter the virus at an older age, they tend to suffer more severely. The difference between infection and disease is seen even more rapidly in early childhood, when infection leads more often to immunity than to illness. Under high standards of hygiene, young children are exposed less frequently, and fewer develop immunity in early life, with the result that paralytic illness, a rarity under the former conditions, is seen frequently in older children and adults. The pattern of infection and disease, however, can be changed. In the case of the poliomyelitis virus, only immunization can abolish both infection and disease.

Population density

      Density of population does not of itself determine the ease with which infection spreads through a population. In New York City, with its many high-rise dwellings, the density of the population per square mile is much greater than in some of the world's older cities, but the hepatitis virus, for example, spreads much faster in the latter. A family in a New York City apartment may never see the inhabitants of most of the other apartments in the block, while neighbours in an ancient Asian city are in daily contact. In New York state, the incidence of infectious hepatitis has been shown to vary inversely with population density—to be lowest in New York City, higher in other urban areas of the state, and highest in rural areas. This pattern reflects the population's chances of contact and social habits, as well as its density.

Social habits

      The vampire bats (vampire bat) of Brazil, which transmit paralytic rabies, bite cattle but not ranchers, presumably because ranchers are few but cattle are plentiful on the plains of Brazil. Bat-transmitted rabies, however, does occur in humans in Trinidad, where herdsmen sleep in shacks near their animals. The mechanism of infection is the same in Brazil and Trinidad, but the difference in social habits affects the incidence of the disease.

      During the early 20th century in Malta, goats were milked at the customers' doors, and a Brucella species in the milk caused a disease that was common enough to be called Malta fever (brucellosis). When the pasteurization of milk became compulsory, Malta fever almost disappeared from the island. (It continued to occur in rural areas where people still drank their milk raw and were in daily contact with their infected animals.)

      Important alterations in environment also occur when children in a modern community first go to school. Colds, coughs, sore throats, and swollen neck glands can occur one after the other. In a nursery school, with young children whose hygiene habits are undeveloped, outbreaks of dysentery and other bowel infections may occur, and among children who take their midday meal at school, foodborne infection caused by a breakdown in hygiene can sweep through entire classes of students. These are dangers against which the children are protected to some extent at home but against which they have no defense when they move to the school environment.

      Changing food habits among the general population also affect the environment for humans and microbes. Meals served in restaurants, for example, offer a greater danger of food poisoning if the standard of hygiene for food preparation is flawed. The purchase and preparation of poultry—which is often heavily infected with Salmonella—present a particular danger. If chickens are bought fresh from a farm or shop and cooked in an oven at home, food poisoning from eating them is rare. If poultry is purchased while it is deep-frozen and then not fully thawed before it is cooked, there is a good chance that insufficient heat penetration will allow the Salmonella—which thrive in the cold—to survive in the meat's centre and infect the people who eat it.

temperature and humidity

      At a social gathering, the human density per square yard may be much greater than in any home, and humidity and temperature may rise to levels uncomfortable for humans but ideal for microbes. Virus-containing droplets pass easily from one person to another, and an outbreak of the common cold may result.

      In contrast, members of scientific expeditions have spent whole winters in the Arctic or Antarctic without any respiratory illness, only to catch severe colds upon the arrival of a supply ship in the early summer. This is because viruses, not cold temperatures, cause colds. During polar expeditions, the members rapidly develop immunity to the viruses they bring with them, and, throughout the long winter, they encounter no new ones. Their colds in the summer are caused by viruses imported by the crew of the supply ship. When the members of the expedition return on the ship to temperate zones, they again come down with colds, this time caught from friends and relatives who have spent the winter at home.

Movement

 Movement into a new environment often is followed by an outbreak of infectious disease. On pilgrimages and in wars, improvised feeding and sanitation lead to outbreaks of such intestinal infections as dysentery, cholera, and typhoid fever, and sometimes more have died in war from these diseases than have been killed in the fighting.

      People entering isolated communities may carry a disease such as measles with them, and the disease may then spread with astonishing rapidity and often with enhanced virulence. A traveler from Copenhagen carried measles virus with him to the Faroe Islands in 1846, and 6,000 of the 8,000 inhabitants caught the disease. Most of those who escaped were old enough to have acquired immunity during a measles outbreak 65 years earlier. In Fiji a disastrous epidemic of measles in 1875 killed one-fourth of the population. In these cases, the change of environment favoured the virus. Nearly every person in such “virgin” populations is susceptible to infection, so that a virus can multiply and spread unhindered. In a modern city population, by contrast, measles virus mainly affects susceptible young children. When it has run through them, the epidemic must die down because of a lack of susceptible people, and the virus does not spread again until a new generation of children is on hand. With the use of measles vaccine, the supply of susceptible young children is reduced, and the virus cannot spread and multiply and must die out.

      An innocent change in environment such as that experienced during camping can lead to infection if it brings a person into contact with sources of infection that are absent at home. Picnicking in a wood, a person may be bitten by a tick carrying the virus of one of several forms of encephalitis; as he swims in a canal or river, his skin may be penetrated by the organisms that cause leptospirosis. He may come upon some watercress growing wild in the damp corner of a field and may swallow with the cress almost invisible specks of life that will grow into liver flukes (liver fluke) in his body, giving him fascioliasis, an illness that is common in cattle and sheep but that can spread to humans when circumstances are in its favour.

Occupation (occupational disease) and commerce

      In occupational and commercial undertakings, people often manipulate their environment and, in so doing, expose themselves to infection. A farmer in his fields is exposed to damp conditions in which disease microorganisms flourish. While clearing out a ditch, he may be infected with leptospires passed into the water in rats' urine. In his barns he may be exposed to brucellosis if his herd of cattle is infected or to salmonellosis or Q fever. Slaughterhouse workers run similar risks, as do veterinarians. A worker in a dock or tannery may get anthrax from imported hides; an upholsterer may get the disease from wool and hair; and a worker mending sacks that have contained bone meal may contract the disease from germs still clinging to the sack.

      Workers in packing plants and shops often are infected from the raw meat that they handle; they are sometimes regarded as carriers and causes of outbreaks of Salmonella food poisoning, but as often as not they are victims rather than causes. Workers in poultry plants can contract salmonellosis, more rarely psittacosis or a viral infection of the eye, from the birds that they handle. Forestry workers who enter a reserve may upset the balance of nature of the area and expose themselves to attack from the undergrowth or the trees by insect vectors of disease that, if undisturbed, would never come into contact with humans. Whenever people manipulate the environment—by herding animals, by importing goods from abroad, by draining a lake, or by laying a pipe through swampy land, and in many other seemingly innocent ways—they run the chance of interfering with microbial life and attracting into their own environment agents of disease that they might not otherwise ever encounter.

The inanimate environment

      Dust cannot cause infectious disease unless it contains the living agents of the infection. Yet the term inanimate is a convenient one to use when infectious disease arises from contact with an environment in which there is no obvious direct living contact between the source and the victim of an infection. A pencil is an inanimate object, but if it is sucked by a child with scarlet fever and then by a second child, the organisms causing the disease can be conveyed to the second child. Many such objects—a handkerchief or a towel, for example—may convey infection under favourable conditions, and, when they do so, they are known as fomites.

      Dust is perhaps one of the most common inanimate elements capable of conveying disease. Organisms present in dust may get on food and be swallowed, settle on the skin and infect it, or be breathed into the respiratory passages. Some germs—the causative agents of anthrax and tetanus, of Q fever, brucellosis, and psittacosis, for example—can live for long periods dried in dust. Under certain conditions all may be dangerous, but under different conditions there may be no danger. The germ that causes tetanus, Clostridium tetani, is one of the most common germs in dust, but the incidence of tetanus varies greatly in different parts of the world. In many countries it is rare, in others common, and the difference may be related to slight differences in human behaviour or custom. The wearing of shoes in temperate climates protects the wearer against many wounds, while the barefoot child in the tropics sustains many puncture wounds of the feet that, although minor, may yet carry tetanus spores into the tissues of the foot, where conditions may be ideal for germination and the production of toxin. Obstetrical practices in some parts of the world can lead to infection of the newborn child. Other, more subtle influences, such as changes of temperature or humidity, may affect the spread of diseases by dust. A long wet winter followed by a dry summer may encourage the growth of molds in hay, and the dust, when the hay is disturbed, may lead to infection of the farmer's lungs.

       water is not a favourable medium for the growth and multiplication of microorganisms, and yet many can survive in it long enough to carry infection to humans. Cholera and typhoid fever are both waterborne diseases, and the virus of hepatitis A also can survive in water. But the mere presence of a microorganism in water does not necessarily lead to the spread of disease. People have swum in water polluted with Salmonella typhi without getting typhoid fever, while others eating shellfish from the same water have developed the disease. The same may be true of hepatitis; the eating of clams from infected water has often caused the disease, whereas swimming has not proved to be a hazard. Shellfish concentrate germs in their tissues, which is probably why they can transmit diseases.

      Water is carried to humans in pipes for drinking, but it is also carried away in pipes as sewage. Defects in these systems may permit water to pass from one to the other, and microorganisms from sewage may get into drinking water. Wells and other water sources can be contaminated by badly sited septic tanks, manure heaps, or garbage dumps. Properly treated, such water is safe to drink; if drunk untreated, disease may follow.

      The soil of gardens and farmlands can harbour disease organisms, as can food. Smoke, fog, and tobacco can affect the human respiratory tract and render it more vulnerable to disease. Air is probably the most common source of infectious agents. The whole of the environment is, in fact, filled with organisms and objects that can transmit infectious agents to humans.

Immune response to infection

      When a pathogenic (disease-causing) microorganism invades the body for the first time, the clinical (observable) response may range from nothing at all, through various degrees of nonspecific reactions, to specific infectious disease. Immunologically, however, there is always a response, the purpose of which is defense. If the defense is completely successful, there is no obvious bodily reaction; if it is partially successful, the affected person exhibits symptoms but recovers from an infectious disease; if unsuccessful, the person may be overwhelmed by the infectious process and die.

      The two responses—the clinical and the immunologic—can be illustrated by the natural history of the disease poliomyelitis (polio). When the virus of this disease enters the body for the first time, it multiplies in the throat and in the intestinal tract. In some people, it gets no farther; virus is shed to the outside from the throat and the bowel for a few weeks, and then the shedding ceases and the infection is over. The host, however, has responded and has developed circulating antibodies (antibody) to a type of poliovirus. These antibodies are specific antipoliovirus proteins in the blood and body fluids that subsequently prevent disease should the poliovirus again be encountered. In addition, the infected individual develops an antipoliovirus response in a subset of white blood cells (blood disease) known as T cells. Antipoliovirus T cells persist throughout the individual's lifetime.

      In other people, the same process occurs but some virus also gets into the bloodstream, where it circulates for a short time before being eliminated. In a few individuals, the virus passes from the bloodstream into the central nervous system, where it circulates for a short time before being eliminated. Finally, in some individuals, the virus passes from the bloodstream into the central nervous system, where it may enter and destroy some of the nerve cells that control movement in the body and so cause paralysis. Such paralysis is the least-common result of infection with poliomyelitis virus; most infected persons have no symptoms at all. Those whose bloodstream contains virus often have a mild illness, consisting of no more than malaise, slight headache, and possibly a sore throat. This so-called minor illness of poliomyelitis is unlikely to be recognized except by those in close contact with someone later paralyzed by the disease.

      If the nervous system becomes invaded by the virus, the infected person has a severe headache and other symptoms suggesting meningitis. Such persons are acutely ill, but most recover their normal health after about one week. Only a few of those with this type of infection have paralysis. Of all the people infected with poliomyelitis virus, not more than 1 in 100, possibly as few as 1 in 1,000, has paralysis, though paralysis is the dominant feature of the fully developed clinical picture of poliomyelitis. This poliomyelitis is actually an uncommon complication of poliovirus infection.

      This wide range of response to the poliomyelitis virus is characteristic of most infections, though the proportions may vary. influenza virus, for example, may cause symptoms ranging from a mild cold to a feverish illness, severe laryngitis (inflammation of the larynx, or voice box) or bronchitis, or an overwhelming and fatal pneumonia. The proportions of a population with these differing outcomes may vary from one epidemic to another. There is perhaps more uniformity of pattern in the operation of the defense mechanisms of the body, called the immune response.

Natural and acquired immunity

      Every animal species possesses some natural resistance to disease. Humans have a high degree of resistance to foot-and-mouth disease, for example, while the cattle and sheep with which they may be in close contact suffer in the thousands from it. Rats are highly resistant to diphtheria, whereas unimmunized children readily contract the disease.

      What such resistance depends on is not always well understood. In the case of many viruses, resistance is related to the presence on the cell surface of protein receptors that bind to the virus, allowing it to gain entry into the cell and thus cause infection. Presumably, most causes of absolute resistance are genetically determined; it is possible, for example, to produce by selective breeding two strains of rabbits, one highly susceptible to tuberculosis, the other highly resistant. In humans there may be apparent racial differences, but it is always important to disentangle such factors as climate, nutrition, and economics from those that might be genetically determined. In some tropical and subtropical countries, for example, poliomyelitis is a rare clinical disease, though a common infection, but unimmunized visitors to such countries often contract serious clinical forms of the disease. The absence of serious disease in the residents is due not to natural resistance, however, but to resistance acquired after repeated exposure to poliovirus from infancy onward. Unimmunized visitors from other countries, with perhaps stricter standards of hygiene, are protected from such immunizing exposures and have no acquired resistance to the virus when they encounter it as adults.

      Natural resistance, in contrast to acquired immunity, does not depend upon such exposures. The human skin obviously has great inherent powers of resistance to infection, for most cuts and abrasions heal quickly, though often they are smothered with potentially pathogenic microorganisms. If an equal number of typhoid (typhoid fever) bacteria are spread on a person's skin and on a glass plate, those on the skin die much more quickly than do those on the plate, suggesting that the skin has some bactericidal property against typhoid germs. The skin also varies in its resistance to infectious organisms at different ages: impetigo is a common bacterial infection of children's skin but is rarer in adults, and acne is a common infection of the skin of adolescents but is uncommon in childhood or in older adults. The phenomenon of natural immunity can be illustrated equally well with examples from the respiratory, intestinal, or genital tracts, where large surface areas are exposed to potentially infective agents and yet infection does not occur.

      If an organism causes local infection or gains entry into the bloodstream, a complicated series of events ensues. These events are described in detail in the article immune system, but they can be summarized as follows: special types of white blood cells called polymorphonuclear leukocytes (leukocyte) or granulocytes, which are normally manufactured in the bone marrow and which circulate in the blood, move to the site of the infection. Some of these cells reach the site by chance, in a process called random migration, since almost every body site is supplied constantly with the blood in which these cells circulate. Additional granulocytes are attracted and directed to the sites of infection in a process called directed migration, or chemotaxis.

      When a granulocyte reaches the invading organism, it attempts to ingest the invader. Ingestion of bacteria may require the help of still other components of the blood, called opsonins, which act to coat the bacterial cell wall and prepare it for ingestion. An opsonin generally is a protein substance, such as one of the circulating immunoglobulins or complement components.

      Once a prepared bacterium has been taken inside the white blood cell, a complex series of biochemical events occurs. A bacterium-containing vacuole (phagosome) may combine with another vacuole that contains bacterial-degrading proteins (lysozymes (lysozyme)). The bacterium may be killed, but its products pass into the bloodstream, where they come in contact with other circulating white blood cells called lymphocytes (lymphocyte). Two general types of lymphocytes—T cells and B cells—are of great importance in protecting the human host. When a T cell encounters bacterial products, either directly or via presentation by a special antigen-presenting cell, it is sensitized to recognize the material as foreign, and, once sensitized, it possesses an immunologic memory. If the T cell encounters the same bacterial product again, it immediately recognizes it and sets up an appropriate defense more rapidly than it did on the first encounter. The ability of a T cell to function normally, providing what is generally referred to as cellular immunity, is dependent on the thymus gland (thymus). The lack of a thymus, therefore, impairs the body's ability to defend itself against various types of infections.

      After a T cell has encountered and responded to a foreign bacterium, it interacts with B cells (B cell), which are responsible for producing circulating proteins called immunoglobulins or antibodies (antibody). There are various types of B cells, each of which can produce only one of the five known forms of immunoglobulin (Ig). The first immunoglobulin to be produced is IgM. Later, during recovery from infection, the immunoglobulin IgG, which can specifically kill the invading microorganism, is produced. If the same microorganism invades the host again, the B cell immediately responds with a dramatic production of IgG specific for that organism, rapidly killing it and preventing disease.

      In many cases, acquired immunity is lifelong, as with measles or rubella. In other instances, it can be short-lived, lasting not more than a few months. The persistence of acquired immunity is related not only to the level of circulating antibody but also to sensitized T cells (cell-mediated immunity). Although both cell-mediated immunity and humoral (B-cell) immunity are important, their relative significance in protecting a person against disease varies with particular microorganisms. For example, antibody is of great importance in protection against common bacterial infections such as pneumococcal pneumonia or streptococcal disease and against bacterial toxins, whereas cell-mediated immunity is of greater importance in protection against viruses such as measles or against the bacteria that cause tuberculosis.

immunization

      Antibodies (antibody) are produced in the body in response to either infection with an organism or, through vaccination (vaccine), the administration of a live or inactivated organism or its toxin by mouth or by injection. When given alive, the organisms are weakened, or attenuated, by some laboratory means so that they still stimulate antibodies but do not produce their characteristic disease. However stimulated, the antibody-producing cells of the body remain sensitized to the infectious agent and can respond to it again, pouring out more antibody. One attack of a disease, therefore, often renders a person immune to a second attack, providing the theoretical basis for active immunization by vaccines.

      Antibody can be passed from one person to another, conferring protection on the antibody recipient. In such a case, however, the antibody has not been produced in the body of the second person, nor have his antibody-producing cells been stimulated. The antibody is then a foreign substance and is eventually eliminated from the body, and protection is short-lived. The most common form of this type of passive immunity is the transference of antibodies from a mother through the placenta to her unborn child. This is why a disease such as measles is uncommon in babies younger than one year. After that age, the infant has lost all of its maternal antibody and becomes susceptible to the disease unless protective measures, such as measles vaccination, are taken. Sometimes antibody is extracted in the form of immunoglobulin from blood taken from immune persons and is injected into susceptible persons to give them temporary protection against a disease, such as measles or hepatitis A.

      Generally, active immunization is offered before the anticipated time of exposure to an infectious disease. When unvaccinated people are exposed to an infectious disease, two alternatives are available: active immunization may be initiated immediately in the expectation that immunity can be developed during the incubation period of the disease, or passive immunity can be provided for the interim period and then active immunization given at an appropriate time. The antigens (antigen) (foreign substances in the body that stimulate the immune defense system) introduced in the process of active immunization can be live attenuated viruses or bacteria, killed microorganisms or inactivated toxins (toxoids), or purified cell wall products (polysaccharide capsules, protein antigens).

      There are five basic requirements for an ideal vaccine. The agents used for immunization should not in themselves produce disease. The immunizing agent should induce long-lasting, ideally permanent, immunity. The agent used for immunization should not be transmissible to susceptible contacts of the person being vaccinated. The vaccine should be easy to produce, its potency easy to assess, and the antibody response to it measurable with common and inexpensive techniques. Finally, the agent in the vaccine should be free of contaminating substances. It is also recognized, however, that vaccine transmissibility can be helpful—e.g., in the case of live polio vaccine, which can be spread from vaccinated children to others who have not been vaccinated.

      The route by which an antigen is administered frequently determines the type and duration of antibody response. For example, intramuscular injection of inactivated poliomyelitis virus (Salk vaccine) generates less production of serum antibody and induces only a temporary systemic immunity; it may not produce substantial local gastrointestinal immunity and, therefore, may not prevent the carrying of the virus in the gastrointestinal tract. Live, attenuated, oral poliomyelitis virus (Sabin vaccine) induces both local gastrointestinal and systemic antibody production; thus, immunization by mouth is preferred.

      The schedule by which a vaccine is given depends upon the epidemiology of the naturally occurring disease, the duration of immunity that can be induced, the immunologic status of the host, and, in some cases, the availability of the patient. Measles, for example, is present in many communities and poses a potential threat to many children over 5 months of age. A substantial number of infants, however, are born with measles antibody from their mothers, and this maternal antibody interferes with an adequate antibody response until they are between 12 and 15 months of age. Generally, the immunization of infants after the age of 15 months benefits the community at large. In measles outbreaks, however, it may be advisable to alter this schedule and immunize all infants between 6 and 15 months of age.

Diphtheria toxoid

      The introduction of diphtheria toxoid in the early 20th century led to a dramatic reduction in the incidence of the disease in many parts of the world. Primary prevention programs consisting of communitywide routine immunization of infants and children have largely eliminated the morbidity and mortality previously associated with diphtheria. Although the reported annual incidence of diphtheria has been relatively constant since the 1960s, local epidemics continue to occur. A complacent attitude toward immunization in some nations largely reflects a lack of awareness of the public health hazard that can arise if the proportion of susceptible individuals is significant enough to allow renewed outbreaks. Also, adequate immunization does not completely eliminate the potential for transmission of the bacterium Corynebacterium diphtheriae. Carriage of C. diphtheriae in the nose or throat has been well documented in fully immunized persons who clearly may transmit the disease to susceptible individuals.

      The vaccine—prepared by the treatment of C. diphtheriae toxin with formaldehyde—is available in both fluid and adsorbed forms, the latter being recommended. Diphtheria toxoid is also available combined with tetanus toxoid and pertussis vaccine (DPT), combined with tetanus toxoid alone (DT), and combined with tetanus toxoid for adults (Td). The Td preparation contains only 15 to 20 percent of the diphtheria toxoid present in the DPT vaccine and is more suitable for use in older children and adults.

Pertussis vaccine

      The number of cases of pertussis ( whooping cough), a serious disease that is frequently fatal in infancy, can be dramatically reduced by the use of the pertussis vaccine. The pertussis immunizing agent is included in the DPT vaccine. Active immunity can be induced by three injections given eight weeks apart.

Tetanus toxoid

      The efficacy of active immunization against tetanus was illustrated most dramatically during World War II, when the introduction of tetanus toxoid among military personnel virtually eliminated the occurrence of the disease as a result of war-related injuries. Since then, the routine immunization of civilian populations with tetanus toxoid has resulted in the decreased incidence of tetanus. In the United States, for example, 50 or fewer cases of tetanus are reported each year, the majority of deaths occurring in persons more than 60 years of age. In virtually all cases, the disease has been reported in unimmunized or inadequately immunized individuals.

      Because it provides long-lasting protection and relative safety in humans, tetanus toxoid has proved to be an ideal vaccine. Tetanus toxoid is available in both vaccine fluid and alum-precipitated preparations. Commercially, tetanus toxoid is available in DPT, Td, and T (tetanus toxoid, adsorbed) preparations. DPT is recommended for infants, while the Td form is recommended at 12 and again at 18 years of age and only once every 10 years thereafter. If a person sustains a wound prone to tetanus (such as a puncture wound or a wound contaminated with animal excreta), Td is given along with tetanus immune globulin (TIG) to prevent occurrence of the disease.

polio vaccine

 The value of primary prevention of disease through active immunization programs has been most convincingly demonstrated in the case of poliomyelitis. Before the vaccine was known, more than 20,000 cases of paralytic disease occurred in the United States alone every year. With use of the vaccine after 1961, the last case of transmission of wild-type poliomyelitis was in 1979. However, such achievement toward eliminating the clinical disease does not justify a casual attitude toward compliance with the recommended polio (polio vaccine) vaccine schedules. Low immunization rates are still evident in children in certain disadvantaged urban and rural groups, among which most of the cases of paralytic disease continue to occur. This is all the more important as international attempts to eradicate poliomyelitis are achieving remarkable success, with most nations of the world now polio-free.

      Live trivalent oral poliovirus vaccine (OPV) is used for routine mass immunization but is not recommended for patients with altered states of immunity (for example, those with cancer or an immune deficiency disease or those receiving immunosuppressive therapy) or for children whose siblings are known to have an immune deficiency disease. Inactivated poliovirus vaccine (IPV) is used for immunodeficient or immunosuppressed patients and for the primary immunization of adults because of their greater susceptibility to paralytic disease. In 2000, as poliomyelitis eradication appeared imminent, the United States switched from OPV to IPV as a routine recommended infant vaccine.

Rubella (German measles) vaccine

      A major epidemic in the United States in 1964 resulted in more than 20,000 cases of congenital rubella. In consequence, active immunization programs with attenuated rubella vaccine were initiated in 1969 in an attempt to prevent an expected epidemic in the early 1970s. The immunization of all children from 1 to 12 years of age was aimed at reducing the reservoir and transmission of wild rubella virus and, secondarily, at diminishing the risk of rubella infection in susceptible pregnant women. This national policy contrasts with that of the United Kingdom, where only girls from 10 to 14 years of age who do not have detectable antibody levels to rubella virus are immunized. Proponents of the British policy have argued that natural rubella infection, which confers lifelong immunity, is more effective than vaccine-induced protection of uncertain duration and that continued outbreaks of rubella in the United States (largely in older children and young adults) since the introduction of rubella vaccines attest to the difficulty of achieving herd (group) immunity for this disease.

      Live attenuated rubella vaccine is available in combination with measles vaccine (MR) and in combination with measles and mumps vaccines (MMR). For routine infant immunization, MMR is given one time at about 15 months of age. Rubella vaccination can be accompanied by mild joint pain and fever in 5 percent of those who receive it. Vaccination is recommended for all children between the ages of 12 months and puberty. Vaccination is not recommended for pregnant women. A number of women, however, have inadvertently received rubella vaccine during pregnancy with no harm to their fetuses being noted.

Measles (rubeola) vaccine

      The licensing and distribution of killed measles vaccine in 1963, followed by the development and widespread use of live attenuated vaccine, have sharply reduced the prevalence of measles and its related morbidity and mortality in many parts of the world. Additional attenuated vaccine preparations have been developed; though not fully evaluated, they appear to be safe and highly effective and to confer prolonged, if not lifelong, protection.

      Despite the introduction of effective immunizing agents, measles continues to be a major public health concern. The continued occurrence of outbreaks of measles, especially among young adults, emphasizes the probable failure of herd immunity to eliminate measles transmission, despite high local immunization rates in young children. The outbreaks also indicate the possibility that a small number of appropriately immunized individuals may not develop solid immunity. It is estimated that about 700,000 to 800,000 people, mostly children, die of measles each year.

      Measles vaccine is commercially available in live attenuated form and is used routinely in the MMR preparation for infant immunization at about 15 months of age. Susceptible older children or adults who have not had measles or have not previously received measles vaccine also should receive a single dose.

mumps vaccine

       mumps is generally a self-limited disease in children but occasionally is moderately debilitating. A live attenuated mumps vaccine is available alone or in combination with measles and rubella vaccines. No serious adverse reactions have been reported following mumps immunization.

Pneumococcal vaccine

      Streptococcus pneumoniae ( pneumococcus) is the most frequent cause of bloodstream infection, pneumonia, and ear infection and is the third most common cause of bacterial meningitis in children. Pneumococcal infection is particularly serious among the elderly and among children with sickle-cell anemia, with congenital or acquired defects in immunity, without spleens, or with abnormally functioning spleens.

      Immunity after pneumococcal disease is type-specific and lifelong. The pneumococcal vaccine now available consists of polysaccharide antigens from many of the most common types of pathogenic pneumococci. It can be given to children two years of age or older or to adults in a single intramuscular injection. The duration of protection is unknown.

Meningococcal vaccine

      Neisseria meningitidis (meningococcus) can cause meningitis (infection of the coverings of the brain and spinal cord) or severe bloodstream infection known as meningococcemia. In the general population, less than 1 per 400,000 persons is attacked by the bacterium, while among those younger than one year, the ratio rises to 1 per 100,000. In a day-care centre in which a primary case of meningococcal disease has occurred, the ratio has been reported at 2 to 100 per 100,000, and the danger from household contact from an infected person is believed to be 200 to 1,000 times greater than that of the general population. Because of these statistics, anyone who has had contact with the disease in a home, day-care centre, or nursery school should receive prophylactic antibiotic treatment as soon as possible, preferably within 24 hours of the diagnosis of the primary case of the disease.

      Group-specific meningococcal polysaccharide vaccines can be used to control outbreaks of disease and may benefit travelers to countries where these diseases are endemic. Certain of the vaccines are administered routinely to military recruits in the United States.

Hepatitis B vaccine

      Hepatitis B virus (HBV) produces an illness characterized by jaundice, poor appetite, malaise, and nausea. Chronic liver disease may follow the infection. hepatitis B vaccine is recommended for infants and for persons who are at a greater risk of contracting the disease because of their lifestyles or jobs. These include health care personnel who are exposed to blood products, hemodialysis patients, institutionalized patients and their staffs, patients receiving multiple transfusions, prostitutes and the sexual partners of individuals with the disease, users of illicit intravenous drugs, and homosexual males.

      Hepatitis B vaccine consists of recombinant viral surface antigen particles and is given in a three-dose series.

influenza vaccine

      The manufacture of influenza vaccine is complicated by the many influenza viruses and by the major changes in antigenic composition that these viruses continually undergo. Routine immunization against influenza viruses is recommended for all healthy individuals before the respiratory disease season commences (in the fall) and may be recommended throughout the year for travelers to a different hemisphere (e.g., from North to South America, because their winter seasons are reversed).

Haemophilus influenzae type B vaccine

      The bacterium Haemophilus influenzae is a major cause of morbidity and mortality in children, particularly in those under six years of age. Because it is highly contagious among people in close contact with one another, antibiotics were traditionally used to prevent infection. In 1990 a powerful vaccine called a conjugate vaccine was licensed, and it has caused a dramatic decrease in H. influenzae disease in many countries.

chickenpox (varicella) vaccine

      The low morbidity of chickenpox in healthy children does not arguably support the universal use of vaccine. In certain persons, especially those with immunodeficiency disease or cancer, however, chickenpox can be devastating. A live attenuated vaccine has been found to be safe and immunogenic in healthy children and has recently been licensed, although its use has been questioned.

Passive immunity

      Passive immunity is the administration of antibodies (antibody) to an unimmunized person from an immune subject to provide temporary protection against a microbial agent or toxin. This type of immunity can be conferred on persons who are exposed to measles, mumps, whooping cough, poliomyelitis, rabies, rubella (German measles), tetanus, chickenpox, and herpes zoster (shingles). The process is also used in the treatment of certain disorders associated with bites (snake and spider) and as a specific (Rho-GAM) or nonspecific (antilymphocyte serum) immunosuppressant. Other antibody preparations are available under specific conditions for specific disorders. Passive immunization is not always effective; the duration of immunity provided is brief and variable, and undesirable reactions may occur, especially if the antiserum is of nonhuman origin. Several preparations are available for use as passive immunizing agents.

HISG

      Human immune serum globulin (HISG) is prepared from human serum. Special treatment of the serum removes various undesirable proteins and infectious viruses, thus providing a safe product for intramuscular injection. HISG is used for the treatment of antibody deficiency conditions and for the prevention of hepatitis A and hepatitis B viral infections, measles, chickenpox, rubella, and poliomyelitis.

      The most widespread use of HISG is in the prevention of hepatitis A infection, a disease for which active immunization has only recently become available, in individuals known to have had intimate exposure to the disease. Hepatitis B immunoglobulin should be given immediately to susceptible persons who are exposed to contaminated blood or who have had intimate physical contact with a person who has hepatitis B infection. Because of the scarcity of the product, hepatitis B immune globulin is not recommended routinely for those who are continuously at high risk of exposure to hepatitis B. It should be given, however, in conjunction with vaccination, to infants born to mothers who have serological evidence of hepatitis B viral infection.

      Several investigators have claimed a beneficial effect of HISG in persons with HIV infection and AIDS, as well as in persons with asthma and other allergic disorders; evidence confirming its efficacy in these conditions is lacking, however. Monthly HISG is not beneficial in the prevention of upper respiratory infections, otitis, skin infections, gastrointestinal disorders, or fever of undetermined cause. HISG has been used inconclusively in the treatment of infants with significantly low levels of immunoglobulins and patients with severe burns who are at an increased risk of infection. Antivenoms derived from horses are used effectively to treat snake or spider bites, but not without significant risk of reaction to the equine antibody preparation.

Rho-GAM

      Rho-GAM is a human anti-RhD immune serum globulin used in the prevention of Rh hemolytic disease of the newborn. Rho-GAM is given to Rh-negative mothers after the delivery of Rh-positive infants or after miscarriage or abortion to prevent the development of anti-Rh antibodies, which could cause hemolysis (red blood cell destruction) in the infant of a subsequent pregnancy.

Antitoxins (antitoxin)

       botulism, a severe paralytic poisoning, results from the ingestion or absorption of the toxin of the bacterium Clostridium botulinum. As a preventive measure, antitoxin can be given to individuals known to have ingested contaminated food and to patients with symptoms as soon as possible after exposure.

      Most of the damaging effect of diphtheria results from the toxin produced by the bacterium Corynebacterium diphtheriae. This toxin not only has local effects but also is distributed through the blood to the heart, nervous system, kidneys, and other organs. Diphtheria antitoxin of animal origin remains the principal treatment, along with antibiotics.

      Gas gangrene is caused by infection with clostridial (Clostridium) organisms, usually following a traumatic injury that has caused extensive local tissue damage. An antitoxin derived from horses is available as an adjunct to surgical and other treatment of these infections.

Ralph D. Feigin Renu Garg Andrew Barnett Christie

Additional Reading

General information

Gerald L. Mandell, John E. Bennett, and Raphael Dolin (eds.), Principles and Practice of Infectious Diseases, 5th ed. (2000), is a modern textbook that the general reader may find informative and useful. H.A.K. Rowland and Philip D. Welsby, A Color Atlas of Infectious Diseases, 3rd ed. (1995), reveals through the use of colour photographs the actual clinical features associated with various infectious diseases. Laurie Garrett, The Coming Plague: Newly Emerging Diseases in a World out of Balance (1994), is a Pulitzer Prize-winning account that focuses on emerging infectious diseases. Richard M. Krause (ed.), Emerging Infections: Biomedical Research Reports (1998, reissued 2000), is an excellent collection of articles edited by the former director of the U.S. National Institute of Allergy and Infectious Diseases. King K. Holmes (ed.), Sexually Transmitted Diseases, 3rd ed. (1999), is a well-written text on a facet of infectious disease that is assuming increasing importance in society. Paul W. Ewald, Evolution of Infectious Disease (1993, reissued 1996), an accessible work, was the first to present a Darwinian perspective on infectious disease.

History of infectious disease

André Siegfried, Routes of Contagion (also published as Germs and Ideas: Routes of Epidemics and Ideologies, 1965; originally published in French, 1960); and Henry E. Sigerist, Civilization and Disease (1943, reissued 1970), deal with the effect of disease on human life and history; both are nontechnical. William H. McNeill, Plagues and Peoples (1976, reissued 1998), is a modern classic that looks at the role of epidemics in human history from an interdisciplinary perspective. Two other excellent books on the history of infectious disease are Charles-Edward Amory Winslow, The Conquest of Epidemic Disease: A Chapter in the History of Ideas (1943, reprinted 1980); and H. Zinsser, Rats, Lice, and History (1935, reissued 2000).Ralph D. Feigin Renu Garg Andrew Barnett Christie

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