Recovery from cholera results in an effective immunity, but only to bacterial strains of the same antigenic characteristics. The serogroup O:1 (see the footnote in Chapter 11, page 299), which caused a pandemic in the 1880s, is known as the classical strain. A later pandemic was caused by a biotype of O:1 named El Tor (for the El Tor quarantine camp for pilgrims to Mecca, where it was first isolated). They occasionally cause wound infections or sepsis, especially in people with liver disease or who are immunosuppressed. In the United States there have been occasional cases of cholera caused by the O:1 serogroup. These have all occurred in the Gulf Coast area, and the pathogen may be endemic in these coastal waters. This represents the primary means of control and is important because stools may contain 100 million V. An example of how this can change quickly was illustrated in 2010, when the Caribbean nation of Haiti experienced an earthquake that seriously damaged much of the water supply and other systems. Available oral vaccines provide immunity of relatively short duration and only moderate effectiveness. Treatment often includes the use of antibiotics such as doxycycline, but the most effective therapy is intravenous replacement of the lost fluids and electrolytes. Rehydration therapy is so effective that in Bangladesh, for example, where cholera is common, deaths are considered "unusual. The bacterium is present in coastal waters of the continental United States and Hawaii. Raw oysters and crustaceans, such as shrimp and crabs, have been associated with several outbreaks of gastroenteritis in the United States in recent years. Escherichia coli gastroenteritis One of the most prolific microorganisms in the human intestinal tract is Escherichia coli. Some toxin-secreting pathogenic strains are well adapted to invasion of intestinal epithelial cells, causing E. Other locations, such as the urinary tract, bloodstream, and central nervous system, can also be affected. They are named for their growth habit, in which the bacteria cause a "stacked-brick" configuration on tissue culture cells. Cattle, which are not affected by the pathogen, are the main reservoir; infections are spread by contaminated food or water. There are requirements for testing ground meats for the presence of this strain of E. The infective dose is estimated to be very small, probably fewer than 100 bacteria. In humans, the Shiga toxins often cause only self-limiting diarrhea, but in about 6% of infected people, it produces an inflammation of the colon (the last part of the large intestine, ending just above the rectum) involving profuse bleeding, called hemorrhagic colitis. Some 5­10% of young children who have been infected progress to this stage, which has a mortality rate of about 5%. Management of these patients primarily involves intravenous rehydration and careful monitoring of serum electrolytes. Because of the attention this pathogen has attracted, researchers have been working, with some success, to develop rapid methods of detecting its presence in food without the need for time-consuming culturing methods. Accurate tracking of the true causes of these epidemics can lead to better treatment and prevention. Many people assume that the greatest source of disease that breaks out after natural disasters is dead bodies. However, studies show that displacement of the survivors and disruption of access to safe water are the biggest contributors. Cholera is a diarrheal disease that can increase when sanitation and modern sewage disposal systems are compromised. In 2004, 17,000 cases of diarrheal disease, including cholera, struck Bangladesh after severe floods. And in 2010, a cholera epidemic affected over 600,000 people in earthquakeravaged Haiti, resulting in over 7000 deaths. The epidemic also occurred nearly 10 months after the earthquake, well into relief and rebuilding efforts. It is hypothesized that infected Nepalese soldiers who were part of a United Nations (U. The initial outbreak developed among people who drank water downstream from the base. News of the possible source of the epidemic sparked widespread anger and accusations in Haiti. Teaching global citizens how to prepare this life-saving solution can prevent many deaths from diarrheal diseases after disasters. At health care facilities, cholera cots, specially designed beds, are also used to collect and measure feces lost during infection so the same amount of fluid can be replaced in the patient. Stockpiling Vaccines Disaster preparedness experts have learned from the Haiti earthquake and subsequent cholera outbreak that stockpiling vaccines, when possible, can help to prevent future outbreaks like this one. Oral vaccine stockpiles, when quickly dispensed, can help curb outbreaks before they become widespread. According to the World Health Organization, about 3­5 million cholera cases occur annually, with 100,000­120,000 deaths due to fluid loss. The World Health Organization estimates that over 760 million people lack access to safe water and 2. Many public and private agencies are developing programs to tackle this large goal. Their efforts have resulted in a 25% decrease in childhood diarrheal infections within four Central American countries, and 50% fewer diarrheal infections in children receiving weekly handwashing lessons. The data are entered into a national PulseNet database so that epidemiological information can be compared. Vaccines that greatly lower the numbers of O157: H7 bacteria in cattle have been licensed, but it is uncertain whether they will find widespread use. In fact, in most cases the causative agent is never identified, and chemotherapy is not attempted. Once contracted, the best treatment is the usual oral rehydration recommended for all diarrhea. Prescribed antibiotics may provide some protection; another option is to take bismuth-containing preparations, such as Pepto-Bismol, but the best advice in risky areas is to prevent infection. Helicobacter Peptic ulcer Disease In 1982, a physician in Australia cultured a spiral-shaped, microaerophilic bacterium observed in the biopsied tissue of stomach ulcer patients. Now named Helicobacter pylori, it is accepted that this microbe is responsible for most cases of peptic ulcer disease. Only about 15% of those infected develop ulcers, so certain host factors are probably involved. For example, people with type O blood are more susceptible, which is also true of cholera. The stomach mucosa contains cells that secrete gastric juice containing proteolytic enzymes and hydrochloric acid that activates these enzymes. Other specialized cells produce a layer of mucus that protects the stomach itself from digestion. Bismuth subsalicylate (Pepto-Bismol) is also effective and is often part of the drug regimen. When the bacteria are successfully eliminated, the recurrence rate of the ulcer is only about 2­4% a year. Reinfection can result from many environmental sources but is less likely in areas with high standards of sanitation; in fact, there is some evidence that infection by H. The most reliable diagnostic test requires a biopsy of tissue and culture of the organism. This test is most useful for determining the effectiveness of chemotherapy because a positive test is an indication of live H. Serological tests to detect antibodies are inexpensive but not useful in determining eradication. Campylobacter gastroenteritis Campylobacter are gram-negative, microaerophilic, spirally curved bacteria that have emerged as the leading cause of foodborne illness in the United States. They adapt well to the intestinal environment of animal hosts, especially poultry. Culturing Campylobacter requires conditions of low oxygen and high carbon dioxide developed in special apparatus. Nearly 60% of cattle excrete the organism in feces and milk, but retail red meats are less likely to be contaminated. There are more than an estimated 2 million cases of Campylobacter gastroenteritis in the United States annually, usually caused by C. Clinically, it is characterized by fever, cramping abdominal pain, and diarrhea or dysentery. An unusual complication of campylobacterial infection is that it is linked, in about 1 in 1000 cases, to the neurological disease Guillain-Barré syndrome, a temporary paralysis. Helicobacter pylori Mucus layer Urease, a bacterial enzyme, produces highly alkaline ammonia by activity on urea. These gramnegative bacteria are intestinal inhabitants of many domestic animals and are often transmitted in meat and milk. Both microbes are distinctive in their ability to grow at refrigerator temperatures of 4°C. This ability increases their numbers in stored refrigerated blood, to the extent that their endotoxins can result in shock to the blood recipient. Yersinia has occasionally been the cause of severe reactions when it contaminates transfused blood. Diagnosis requires culturing the organism, which can then be evaluated by serological tests. Adults suffering from yersiniosis usually recover in 1 or 2 weeks; children may take longer. Clostridium perfringens gastroenteritis One of the more common, if underrecognized, forms of food poisoning in the United States is caused by Clostridium perfringens, a large, gram-positive, endospore-forming, obligately anaerobic rod. This bacterium is also responsible for human gas gangrene (see Chapter 23, page 646). Most outbreaks of Clostridium perfringens gastroenteritis are associated with meats or meat stews contaminated with intestinal contents of the animal during slaughter. The endospores survive most routine heatings, and the generation time of the vegetative bacterium is less than 20 minutes under ideal conditions. Large populations can therefore build up rapidly when foods are being held for serving or when inadequate refrigeration leads to slow cooling. The microbe grows in the intestinal tract and produces an exotoxin that causes the typical symptoms of abdominal pain and diarrhea. Most cases are mild and self-limiting and probably are never clinically diagnosed. Diagnosis is usually based on isolating and identifying the pathogen in stool samples. Clostridium difficile­associated Diarrhea Clostridium difficile­associated diarrhea is a disease condition that has appeared in recent decades and has been described as being responsible for more deaths than all other intestinal infections combined. The exotoxins it produces cause a disease that manifests itself in symptoms ranging from a mild case of diarrhea to life-threatening colitis (inflammation of the colon). The colitis can result in ulceration, and possible perforation, of the intestinal wall. The disease is usually precipitated by the extended use of antibiotics, especially fluoroquinolones. The elimination of most competing intestinal bacteria permits rapid proliferation of the toxinproducing C. Occurring mostly as a healthcare-associated disease in hospitals and nursing homes, C. Outbreaks have occurred in day-care centers, and caregivers have been known to acquire it from patients. Heating the food does not always kill the spores, which germinate as the food cools. Other episodes involve nausea and vomiting (usually 2 to 5 hours after ingestion). Because the parotids are one of the three pairs of salivary glands of the digestive system, it is appropriate to include a discussion of mumps in this chapter. The virus is transmitted in saliva and respiratory secretions, and its portal of entry is the respiratory tract. An infected person is most infective to others during the first 48 hours before clinical symptoms appear. Once the viruses have begun to multiply in the respiratory tract and local lymph nodes in the neck, they reach the salivary glands via the blood. Viremia (the presence of virus in the blood) begins several days before the onset of mumps symptoms and before the virus appears in saliva. The virus is present in the blood and saliva for 3 to 5 days after the onset of the disease and in the urine after about 10 days. Mumps is characterized by inflammation and swelling of the parotid glands, fever, and pain during swallowing. About 4 to 7 days after the onset of symptoms, the testes can become inflamed, a condition called orchitis. This happens in about 20­40% of men past puberty; sterility is a possible but rare consequence.

Additional information:

• Amiloride-hydrochlorothiazide
• Ethambutol

At the left side of each plate, the tests show that hexachlorophene was effective against gram-positive bacteria only. At the right sides, O-phenylphenol was ineffective against pseudomonads but was almost equally effective against the grampositive bacteria and the gram-negative bacteria. All four chemicals worked against the grampositive test bacteria, but only one of the four chemicals affected pseudomonads. Q Why are the pseudomonads less affected by the four chemicals shown in the figure Q Some lozenges intended to alleviate the symptoms of a sore throat contain phenol. Types of Disinfectants Phenol and Phenolics Lister was the first to use phenol (carbolic acid) to control surgical infections in the operating room. It is now rarely used as an antiseptic or disinfectant because it irritates the skin and has a disagreeable odor. It is often used in throat lozenges for its local anesthetic effect but has little antimicrobial effect at the low concentrations used. At concentrations above 1% (such as in some throat sprays), however, phenol has a significant antibacterial effect. Derivatives of phenol, called phenolics, contain a molecule of phenol that has been chemically altered to reduce its irritating qualities or increase its antibacterial activity in combination with a soap or detergent. Phenolics exert antimicrobial activity by injuring lipid-containing plasma membranes, which results in leakage of cellular contents. The cell wall of mycobacteria, the causes of tuberculosis and leprosy, are rich in lipids, which make them susceptible to phenol derivatives. A useful property of phenolics as disinfectants is that they remain active in the presence of organic compounds, are stable, and persist for long periods after application. For these reasons, phenolics are suitable agents for disinfecting pus, saliva, and feces. One of the most frequently used phenolics is derived from coal tar, a group of chemicals called cresols. Gram-positive staphylococci and streptococci, which can cause skin infections in newborns, are particularly susceptible to hexachlorophene, so it is often used to control such infections in nurseries. Triclosan has even been incorporated into kitchen cutting boards and the handles of knives and other plastic kitchenware. Triclosan inhibits an enzyme needed for the biosynthesis of fatty acids (lipids), which mainly affects the integrity of the plasma membrane. It is especially effective against gram-positive bacteria but also works well against yeasts and gram-negative bacteria. There are certain exceptions, such as Pseudomonas aeruginosa, a gram-negative bacterium that is very resistant to triclosan, as well as to many other antibiotics and disinfectants (see the discussions on pages 296, 403, and 586). Biguanides are also effective against gram-negative bacteria, with the significant exception of most pseudomonads. The best known biguanide is chlorhexidine, which is frequently used for microbial control on skin and mucous membranes. Combined with a detergent or alcohol, chlorhexidine is very often used for surgical hand scrubs and preoperative skin preparation in patients. Alexidine is a similar biguanide and is more rapid in its action than chlorhexidine. Eventually, alexidine is expected to replace Betadine in many applications (see below). Halogens the halogens, particularly iodine and chlorine, are effective antimicrobial agents, both alone and as constituents of inorganic or organic compounds. It is active against all kinds of bacteria, many endospores, various fungi, and some viruses. Iodine impairs protein synthesis and alters cell membranes, apparently by forming complexes with amino acids and unsaturated fatty acids. Iodine is available as a tincture-that is, in solution in aqueous alcohol-and as an iodophor. An iodophor is a combination of iodine and an organic molecule, from which the iodine is released slowly. Iodophors have the antimicrobial activity of iodine, but they do not stain and are less irritating. Povidone is a surface-active iodophor that improves the wetting action and serves as a reservoir of free iodine. Chlorine (Cl2), as a gas or in combination with other chemicals, is another widely used disinfectant. Alcohol usually denatures protein, but it can also disrupt membranes and dissolve many lipids, including the lipid component of enveloped viruses. Alcohols have the advantage of acting and then evaporating rapidly and leaving no residue. When the skin is swabbed (degermed) before an injection, most of the microbial control activity comes from simply wiping away dirt and microorganisms, along with skin oils. They cause coagulation of a layer of protein under which bacteria continue to grow. The recommended optimum concentration of ethanol is 70%, but concentrations between 60% and 95% seem to kill as well (Table 7. Pure ethanol is less effective than aqueous solutions (ethanol mixed with water) because denaturation requires water. Isopropanol, often sold as rubbing alcohol, is slightly superior to ethanol as an antiseptic and disinfectant. Moreover, it is less volatile, less expensive, and more easily obtained than ethanol. Alcohol-based (about 62% alcohol) hand sanitizers such as Purell and Germ-X are very popular for use when hands are not visibly soiled. Hypochlorous acid is the most effective form of chlorine because it is neutral in electrical charge and diffuses as rapidly as water through the cell wall. A liquid form of compressed chlorine gas is used extensively for disinfecting municipal drinking water, water in swimming pools, and sewage. This compound, once called chloride of lime, was used as early as 1825, long before the concept of a germ theory for disease, to soak hospital dressings in Paris hospitals. It was also the disinfectant used in the 1840s by Semmelweis to control hospital infections during childbirth, as mentioned in Chapter 1, page 9. When the quality of drinking water is in question, household bleach can provide a rough equivalent of municipal chlorination. After two drops of bleach are added to a liter of water (four drops if the water is cloudy) and the mixture has sat for 30 minutes, the water is considered safe for drinking under emergency conditions. The food-processing industry makes wide use of chlorine dioxide solution as a surface disinfectant because it does not leave residual tastes or odors. As a disinfectant, it has a broad spectrum of activity against bacteria and viruses and at high concentrations is even effective against cysts and endospores. Most municipal water-treatment systems mix ammonia with chlorine to form chloramines. Chloramines are also used to sanitize glassware and eating utensils and to treat dairy and food-manufacturing equipment. Clear zones where bacterial growth has been inhibited are seen around the sombrero charm (pushed aside), the dime, and the penny. Q the coins used in this demonstration were minted many years ago; why were more contemporary coins not used Ethanol and isopropanol are often used to enhance the effectiveness of other chemical agents. For example, an aqueous solution of Zephiran (described on page 191) kills about 40% of the population of a test organism in 2 minutes, whereas a tincture of Zephiran kills about 85% in the same period. Heavy Metals and Their Compounds Several heavy metals can be biocidal or antiseptic, including silver, mercury, and copper. The ability of very small amounts of heavy metals, especially silver and copper, to exert antimicrobial activity is referred to as oligodynamic action (oligo means few). Centuries ago, Egyptians found that putting silver coins in water barrels served to keep the water clean of unwanted organic growths. This action can be seen when we place a coin or other clean piece of metal containing silver or copper on a culture on an inoculated Petri plate. When the metal ions combine with the sulfhydryl groups on cellular proteins, denaturation results. At one time, many states required that the eyes of newborns be treated with a few drops of silver nitrate to guard against an infection of the eyes called ophthalmia neonatorum, which the infants might have contracted as they passed through the birth canal. Recently, there has been renewed interest in the use of silver as an antimicrobial agent. Silver-impregnated dressings that slowly release silver ions have proven especially useful against antibiotic-resistant bacteria. The enthusiasm for incorporating silver in all manner of consumer products is increasing. Among the newer products being sold are plastic food containers infused with silver nanoparticles, which are intended to keep food fresher, and silver-infused athletic shirts and socks, which are claimed to minimize odors. A combination of silver and the drug sulfadiazine, silversulfadiazine, is the most common formulation. Silver can also be incorporated into indwelling catheters, which are a common source of hospital infections, and in wound dressings. Surfacine is a relatively new antimicrobial for application to surfaces, either animate or inanimate. It contains water-insoluble silver iodide in a polymer carrier and is very persistent, lasting at least 13 days. Inorganic mercury compounds, such as mercuric chloride, have a long history of use as disinfectants. They have a very broad spectrum of activity; their effect is primarily bacteriostatic. However, their use is now limited because of their toxicity, corrosiveness, and ineffectiveness in organic matter. Copper in the form of copper sulfate or other coppercontaining additives is used chiefly to destroy green algae (algicide) that grow in reservoirs, stock ponds, swimming pools, and fish tanks. If the water does not contain excessive organic matter, copper compounds are effective in concentrations of one part per million of water. To prevent mildew, copper compounds such as copper 8-hydroxyquinoline are sometimes included in paint. In the nineteenth century, the wine regions of Europe were plagued by fungal diseases that affected the grapevines. It was observed that vines near the road were less affected than those further afield. The reason was that these roadside vines had been sprayed with a mixture of copper sulfate and lime (both visible and bitter to the taste) to deter passers-by on the road from eating the grapes. Because of this chance observation, mixtures based on copper ions (known as Bordeaux mixture) have long been used to control fungal diseases of plants. Long term use of alcohol-based hand sanitizers often causes problems with skin dryness. A relatively new hand sanitizer, Xgel, does not contain alcohol but uses copper contained in a skin lotion formulation. X-gel may be more effective as an antimicrobial than alcohol-based hand sanitizers. The effect of trace amounts of zinc can be seen on weathered roofs of buildings down-slope from galvanized (zinc-coated) fittings. Zinc chloride is a common ingredient in mouthwashes, and zinc pyrithione is an ingredient in antidandruff shampoos. Soaps and Detergents Soap has little value as an antiseptic, but it does have an important function in the mechanical removal of microbes through scrubbing. The skin normally contains dead cells, dust, dried sweat, microbes, and oily secretions from oil glands. Soap breaks the oily film into tiny droplets, a process called emulsification, and the water and soap together lift up the emulsified oil and debris and float them away as the lather is washed off. Use soap and warm water (if possible), and rub hands together for 20 seconds (imagine singing "Happy Birthday" twice through). Then rinse, dry with a paper towel or air dryer, and try to use a paper towel to turn off the faucet. They are strongly antimicrobial, colorless, odorless, tasteless, stable, easily diluted, and nontoxic, except at high concentrations. If your mouthwash bottle fills with foam when shaken, the mouthwash probably contains a quat. However, organic matter interferes with their activity, and they are rapidly neutralized by soaps and anionic detergents. Anyone involved in medical applications of quats should remember that certain bacteria, such as some species of Pseudomonas, not only survive in quaternary ammonium compounds but actively grow in them. These microbes are resistant not only to the disinfectant solution but also to gauze and bandages moistened with it, because the fibers tend to neutralize the quats. Chemical Food Preservatives Chemical preservatives are frequently added to foods to retard spoilage. Among the more common additives are sodium benzoate, sorbic acid, and calcium propionate. These chemicals are simple organic acids, or salts 100 80 Percentage of bacteria surviving 60 Soap and water tant in cleaning food-processing facilities, especially dairy utensils and equipment. Their sanitizing ability is related to the negatively charged portion (anion) of the molecule, which reacts with the plasma membrane. These sanitizers, which act on a wide spectrum of microbes, including troublesome thermoduric bacteria, are odorless, nontoxic, noncorrosive, and fast acting. Aqueo u 1% io di ne Tin c tur eo s Zeph iran 1:1 000 40 in % 70 et l(no ha tin ct fZ ep hir an used surface-active agents are the cationic detergents, especially the quaternary ammonium compounds (quats). Their cleansing ability is related to the positively charged portion- the cation-of the molecule.

Jalap (Pokeweed). Geodon.

• Arthritis-like pain, tonsillitis, laryngitis, mumps, swelling of the lymph glands, scabies, acne, skin cancers, painful menstruation, tonsillitis, and other conditions.
• How does Pokeweed work?
• What is Pokeweed?
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• Dosing considerations for Pokeweed.

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Extended respiratory assistance may be needed, and some neurological impairment may persist for months. To determine whether botulinal toxin is present, mice are injected with the liquid portion of food extracts or cell-free cultures. To determine the specific type of toxin, groups of mice are passively immunized with antisera specific for C. If one group of mice receiving a specific antitoxin lives and the other mice die, the type of toxin in the food or culture has been identified. This severely deformed hand shows the progressive tissue damage to the cooler parts of the body typical of this later stage. Antitoxins aimed at neutralizing A, B, and E toxins are available and are usually administered together. This trivalent antitoxin will not affect the toxin already attached to the nerve endings and is probably more effective on type E than on types A and B. The antitoxin used in adults is derived from horses and has serious side effects, including serum sickness (immune complexes formed by reaction with antigens in the antitoxin) and potential anaphylaxis. The deadly toxin of botulism (Botox) has therapeutic uses for a number of medical conditions, such as chronic headaches. Injections in the area of facial wounds prevent muscle movement during healing and result in more presentable scar formation. It has been approved to control involuntary eyelid twitching (blepharospasm), crossed eyes (strabismus), and even excessive sweating (hyperhidrosis). This latter use, even though it requires expensive twice-yearly injections, prevents armpit sweating and is favored by professional models to help protect expensive designer clothing. However, the most publicized application has been purely cosmetic: periodic local injections of Botox to eliminate forehead wrinkles (worry lines). This distinction, however, is likely also shared with the recently discovered (in 2008) leprosy-causing bacterium M. Hansen of Norway; his discovery was one of the first links ever made between a specific bacterium and a disease. These bacteria have an optimum growth temperature of 30°C and show a preference for the outer, cooler portions of the human body. They survive ingestion by macrophages and eventually invade cells of the myelin sheath of the peripheral nervous system, where their presence causes nerve damage from a cell-mediated immune response. Armadillos have been found to be a useful way to culture the leprosy bacillus; they have a body temperature of 30­35°C and are often infected in the wild. Several people have actually contracted leprosy from contact with armadillos in Texas. The ability to grow the bacteria in an animal is invaluable for evaluating chemotherapeutic drugs. Patients with this type of leprosy have had the least effective cell-mediated immune response, and the disease has progressed from the tuberculoid stage. Mucous membranes of the nose tend to become affected, and a lion-faced appearance is associated with this type of leprosy. The progression of the disease is unpredictable, and remissions may alternate with rapid deterioration. The exact means of transfer of the leprosy bacillus is uncertain, but patients with lepromatous leprosy shed large numbers in their nasal secretions and in exudates (oozing matter) of their lesions. Most people probably acquire the infection when secretions containing the pathogen contact their nasal mucosa. However, leprosy is not very contagious and usually is transmitted only between people in fairly intimate and prolonged contact. The time from infection to the appearance of symptoms is usually measured in years, although children can have a much shorter incubation period. Death usually results not from the leprosy itself, but from complications, such as tuberculosis. In the Middle Ages, people with leprosy were rigidly excluded from normal European society and sometimes even wore bells so that people could avoid them. This isolation might have contributed to the near disappearance of the disease in Europe. But patients with leprosy are no longer kept in isolation, because they can be made noncontagious within a few days by the administration of sulfone drugs. The National Leprosy Hospital in Carville, Louisiana, once housed several hundred patients but was closed in 1999. Most are imported by infected immigrants from endemic countries; the disease is usually found in tropical climates. Millions of people, most of them in Asia, Africa, and Brazil, suffer from leprosy today, and over half a million new cases are reported each year. The standard diagnostic test for leprosy is a skin biopsy sample taken from the margin of an active lesion. To read this sample reliably, looking for characteristic tissue damage and identifying acid-fast bacilli within nerves, requires an experienced pathologist. Associated procedures, such as the slit-skin smear, can be used to enumerate acid-fast bacteria in infected skin. A recent development has been an inexpensive blood test for leprosy that can detect the infection as early as 9 to 12 months, which is in advance of the most damaging clinical symptoms. Dapsone (a sulfone drug), rifampin, and clofazimine, a fatsoluble dye, are the principal drugs used for treatment, usually in combination. Most viruses affecting the nervous system enter it by circulating in the blood or the lymphatic system. However, the paralytic form of poliomyelitis probably affects fewer than 1% of those infected with the poliovirus. The great majority of cases are asymptomatic or exhibit only mild symptoms, such as headache, sore throat, fever, and nausea. Polio made its first appearance in the United States in an outbreak in Vermont in the summer of 1894. These annual outbreaks increasingly affected adolescents and young adults, and the number of paralytic cases steadily increased. Many victims died as their respiratory muscles were paralyzed, and thousands of infants and youths were left with their extremities permanently crippled. The primary mode of transmission is ingestion of water ChaPtEr 22 Microbial Diseases of the Nervous System 619 contaminated with feces containing the virus. Improved sanitation delayed exposure to polioviruses in feces until after the protection provided by maternal antibodies had waned. At one time, exposure to the poliovirus was frequent (and is still so today in parts of the world with poor sanitation). Infants were usually exposed to poliovirus while still protected by maternal antibodies. The result was usually an asymptomatic case of the disease and a lifelong immunity. When infection is delayed until adolescence or early adulthood, the paralytic form of the disease appears more frequently. During the 1980s, many middle-aged adults who had had polio as children began showing a muscle weakness now called postpolio syndrome. Because the infection begins when the virus is ingested, its primary areas of multiplication are the throat and small intestine. Next, the virus invades the tonsils and the lymph nodes of the neck and ileum (the terminal portion of the small intestine). In most cases the viremia is only transient, the infection does not progress past the lymphatic system, and clinical disease does not result. As the virus multiplies within the cytoplasm of the motor nerve cells, the cells die, and paralysis results. Diagnosis Polio is usually diagnosed by isolating the virus from feces and throat secretions. Cell cultures can be inoculated, and cytopathic effects on the cells can be observed (see Table 15. It consists of viruses of all three types that have been inactivated (killed) by treatment with formalin. The other vaccine type, introduced in 1963, contains living, attenuated (weakened) strains of the virus in a suspension that is ingested. Some 6­8 survivors from these polio epidemics still use these machines, at least part of the time. This vaccine mimics an actual infection and induces excellent, and probably life-long, immunity, although its use is precluded in immunodeficient individuals. The live virus is also shed by the recipient and has the effect of immunizing others within the community. However, this shedding can represent a serious disadvantage-the attenuated strains of the disease occasionally revert to virulence and cause the disease. The incidence of this varies by region but is usually about 1 case per 750,000 recipients. Research into polio vaccines continues, especially for use in less-developed areas. This dose is administered into the skin rather than the muscle by means of an investigational needle-free device. Worldwide, humans usually are infected with the rabies virus in saliva from the bite of an infected animal-especially dogs. On rare occasions, the virus can be transmitted through fresh skin abrasions and may cross the mucous membranes of the nose, mouth, and even eyes. In the United States, the most common cause of rabies is a variant of the virus found in silverhaired bats. Rabies is unique in that the incubation period is usually long enough to allow immunity to develop from postexposure vaccination. The natural immune response is ineffective because the viruses are introduced into the wound in numbers too low to provoke it; also, they do not travel through the bloodstream or lymphatic system, where the immune system could best respond. Whether it can ever be eradicated completely in less-developed parts of the world is becoming questionable. Although the goal of eradication was not met, great gains were made, and by 2000 the number of case reports had fallen by 99%. In some extreme cases, incubation periods of as long as 6 years have been reported, but the average is 30 to 50 days. Bites in areas rich in nerve fibers, such as the hands and face, are especially dangerous, and the resulting incubation period tends to be short. At this time, a frequent symptom is spasms of the muscles of the mouth and pharynx that occur when the patient feels air drafts or swallows liquids. In fact, even the mere sight or thought of water can set off the spasms-thus the common name hydrophobia (fear of water). The final stages of the disease result from extensive damage to the nerve cells of the brain and the spinal cord. Animals with furious (classical) rabies are at first restless, then become highly excitable and snap at anything within reach. The biting behavior is essential to maintaining the virus in the animal population. When paralysis sets in, the flow of saliva increases as swallowing becomes difficult, and nervous control is progressively lost. Some animals suffer from paralytic (dumb or numb) rabies, in which there is only minimal excitability. The animal remains relatively quiet and even unaware of its surroundings, but it might snap irritably if handled. A similar manifestation of rabies occurs in humans and is often misdiagnosed as Guillain-Barré syndrome, a form of paralysis that is usually transient but sometimes fatal, or other neurological conditions. There is some speculation that the two forms of the disease may be caused by slightly different forms of the virus. Prevention of rabies Only high-risk individuals, such as laboratory workers, animal control professionals, and veterinarians, are routinely vaccinated against rabies before known exposure. Another indication for antirabies treatment is any unprovoked bite by a skunk, bat, fox, coyote, bobcat, or raccoon not available for examination. Treatment after a dog or cat bite, if the animal cannot be found, is determined by the prevalence of rabies in the area. The bite of a bat may not be perceptible and may be impossible to rule out in cases where the bat had access to sleeping persons or small children. These vaccines are administered in a series of four injections at intervals during a 14-day period. The primary treatment, which succeeds in a minority of cases, is to induce an extended coma to minimize excitability while administering antiviral drugs. This procedure was first used in the case of a Wisconsin girl bitten by a rabid cat and has come to be called the Milwaukee protocol. Distribution of rabies Rabies occurs all over the world, mostly a result of dog bites. Vaccination of pets is prohibitively expensive in most of Africa, Latin America, and Asia. As many as 40,000 people are administered postexposure rabies vaccine each year, often as a precaution when the rabies status of the biting animal cannot be determined. In Europe and North America, there are ongoing experiments to immunize wild animals with live rabies vaccine produced in genetically modified vaccinia viruses that are added to food left for the animals to find. An unfortunate consequence of this approach is that certain serious infections with lower incidence rates never meet the criteria for major health campaigns. They disproportionately infect the poorest people living in the least developed areas. Main approaches include new and intensified disease management; zoonotic disease management; preventive chemotherapy; vector control and pesticide management; and improvement of sanitation and drinking water safety.

Usage: q._h.

The specific route by which a particular pathogen gains access to the body is called its portal of entry. Many microorganisms can penetrate mucous membranes of the conjunctiva and the respiratory, gastrointestinal, and genitourinary tracts. Most microorganisms cannot penetrate intact skin; they enter hair follicles and sweat ducts. Some microorganisms can gain access to tissues by inoculation through the skin and mucous membranes in bites, injections, and other wounds. Many microorganisms can cause infections only when they gain access through their specific portal of entry. Surface projections on a pathogen called adhesins (ligands) adhere to complementary receptors on the host cells. Host cells can be destroyed when pathogens metabolize and multiply inside the host cells. Poisonous substances produced by microorganisms are called toxins; toxemia refers to the presence of toxins in the blood. A-B toxins consist of an active component that inhibits a cellular process and a binding component that attaches the two portions to the target cell. Superantigens cause release of cytokines, which cause fever, nausea, and other symptoms;. Bacterial cell death, antibiotics, and antibodies may cause the release of endotoxins. Plasmids may carry genes for antibiotic resistance, toxins, capsules, and fimbriae. Lysogenic conversion can result in bacteria with virulence factors, such as toxins or capsules. Viruses gain access to host cells because they have attachment sites for receptors on the host cell. Some viruses cause cytocidal effects (cell death), and others cause noncytocidal effects (damage but not death). Cytopathic effects include stopping mitosis, lysis, formation of inclusion bodies, cell fusion, antigenic changes, chromosomal changes, and transformation. Symptoms of fungal infections can be caused by capsules, toxins, and allergic responses. Symptoms of protozoan and helminthic diseases can be caused by damage to host tissue or by the metabolic waste products of the parasite. Three common portals of exit are the respiratory tract via coughing or sneezing, the gastrointestinal tract via saliva or feces, and the genitourinary tract via secretions from the vagina or penis. Compare and contrast the following aspects of endotoxins and exotoxins: bacterial source, chemistry, toxicity, and pharmacology. Describe how hemolysins, leukocidins, coagulase, kinases, hyaluronidase, siderophores, and IgA proteases might contribute to pathogenicity. Streptococcus pyogenes M protein ChaPter 15 Microbial Mechanisms of Pathogenicity 437 7. Describe the factors contributing to the pathogenicity of fungi, protozoa, and helminths. Campylobacter and Cryptosporidium are equally virulent; they cause infections in the same number of test animals. Cryptosporidium infections are acquired more easily than Campylobacter infections. The earliest smallpox vaccines were infected tissue rubbed into the skin of a healthy person. The recipient of such a vaccine usually developed a mild case of smallpox, recovered, and was immune thereafter. Which of the following does not represent the same mechanism for avoiding host defenses as the others The cyanobacterium Microcystis aeruginosa produces a peptide that is toxic to humans. However, her condition worsened, and she was unable to eat for 4 days because of severe pain and tightness of the jaw. She reported that on July 5 she had incurred a puncture wound at the base of her big toe; she cleaned the wound but did not seek medical attention. Explain whether each of the following examples is a food infection or intoxication. Eighty-two people in Louisiana developed diarrhea, nausea, headache, and fever from 4 hours to 2 days after eating shrimp. Two people in Vermont developed malaise, nausea, blurred vision, breathing difficulty, and numbness 3 to 6 hours after eating barracuda caught in Florida. Cancer patients undergoing chemotherapy are normally more susceptible to infections. However, a patient receiving an antitumor drug that affects eukaryotic cytoskeletons was resistant to Salmonella. How do each of the following strategies contribute to the virulence of the pathogen She is currently receiving treatment for septic shock-her third episode of this infection in her lifetime. Madge says that since childhood she has always been very susceptible to recurring infections. For this reason, she is especially thankful that so far, her transplanted kidney is functioning well and shows no signs of rejection or damage. You run tests that show leukocytosis, normal levels of antibodies, and a C6 deficiency. Hint: Read about leukocyte response to infections on page 448, the complement system on pages 456­460, and testing for complement in the Applications of Microbiology box on page 462. If microorganisms never encountered resistance from the host, we would constantly be ill and would die of various diseases after a short life. Some of these defenses are designed to keep out microorganisms altogether, other defenses remove the microorganisms if they do get in, and still others combat them if they remain inside. In this chapter we discuss the first two lines of defense against pathogens, which we call the innate immunity defenses. The second line of defense consists of phagocytes, inflammation, fever, and antimicrobial substances produced by the body. Many leukocytes (white blood cells) coordinate efforts in controlling infections in the second and third lines of immune defense. First-Line Defenses First-line defenses keep pathogens on the outside or neutralize them before infection begins. The skin, mucous membranes, and certain antimicrobial substances are part of these defenses. Skin, mucous membranes, antimicrobial substances Second-Line Defenses Second-line defenses slow or contain infections when first-line defenses fail. It includes a memory component that allows the body to more effectively respond to that same pathogen in the future. Some macrophages are fixed in certain organs while others wander tissues, causing inflammation. In skin and respiratory and intestinal mucosa, phagocytizes bacteria and presents antigens to T cells. A related test, called differential white blood cell count, breaks down the white blood cell count further, identifying the percentage of eosinophils, basophils, neutrophils, monocytes, and lymphocytes. Abnormal blood cell counts give health care providers important clues for diagnosing infections and other conditions. Low White Blood Cell Counts A low white blood cell count shows the patient has fewer leukocytes than expected. They may also be caused from autoimmune diseases such as lupus; certain cancers, such as lymphoma; and radiation and other cancer treatments. White blood cell counts may also be low when a patient has an extremely severe bacterial infection, such as septicemia. Finally, numerous drugs may also cause low white blood cell counts, including a variety of antibiotics, diuretics, and anticancer medications. Neutrophils: 60% to 70% Lymphocytes: 20% to 25% Monocytes: 3% to 8% Eosinophils: 2% to 4% Basophils: 0. High white blood cell counts may also stem from autoimmune disorders that result in too much inflammatory response, such as rheumatoid arthritis, and from leukemia, a cancer of the blood. Some drugs can cause high white blood cell counts as a side effect; these include certain asthma medications such as albuterol, epinephrine, corticosteroids, and the anticoagulant heparin. Rapidly rising high white blood cell counts have been shown to be associated with higher mortality among infants. Adaptive immune actions are slower but specific to pathogens and have a memory component. When microbes attack our bodies, we defend ourselves by utilizing our various mechanisms of immunity. Immunity, also called resistance, is the ability to ward off disease caused by microbes or their products and to protect against environmental agents such as pollen, chemicals, and animal dander. They are always available to provide rapid responses to protect us against disease. Further, innate immunity has no memory response, that is, a more rapid and stronger immune reaction to the same microbe at a later date. Innate immunity first-line defenses include skin and mucous membranes, and the second-line defenses include natural killer cells, phagocytes, inflammation, fever, and antimicrobial substances. Adaptive immunity is based on a specific response to a specific microbe once a microbe has breached the innate immunity defenses. Unlike innate immunity, adaptive immunity is slower to respond, but it does have a memory component that allows the body to more effectively target the same pathogens in the future. Adaptive immunity involves lymphocytes (a type of white blood cell) called T cells (T lymphocytes) and B cells (B lymphocytes) and will be discussed in detail in Chapter 17. Responses of the innate system are activated by protein receptors in the plasma membranes of defensive cells. You will learn later in this chapter that two of the defensive cells involved in innate immunity are called macrophages and dendritic cells and provide a link between innate immunity and adaptive immunity. Cytokines (cyto- 5 cell; -kinesis 5 motion) are proteins that regulate the intensity and duration of immune responses. One role of cytokines is to recruit other macrophages and dendritic cells, as well as other defensive cells, to isolate and destroy the microbes as part of the inflammatory response. Cytokines can also activate the T cells and B cells involved in adaptive immunity. You will learn more about the different cytokines and their functions in Chapter 17. Jacob has a history of recurrent skin infections, fever, and chronically enlarged lymph nodes. The epidermis consists of many layers of continuous sheets of tightly packed epithelial cells with little or no material between the cells. The top layer of epidermal cells is dead and contains a protective protein called keratin. In addition, the dryness of the skin is a major factor in inhibiting microbial growth on the skin. Although normal microbiota and other microbes are present on the entire skin, they are most numerous on moist areas. If we consider the closely packed cells, continuous layering, the presence of keratin, and the dryness and shedding of the skin, we can see why the intact skin provides such a formidable barrier to the entrance of microorganisms. Microorganisms rarely, if ever, penetrate the intact surface of healthy epidermis. However, when the epithelial surface is broken as a result of burns, cuts, puncture wounds, or other conditions, a subcutaneous (below-the-skin) infection often develops. The bacteria most likely to cause infection are the staphylococci that normally inhabit the epidermis, hair follicles, and sweat and oil glands of the skin. Epithelial cells called endothelial cells that line blood and lymphatic vessels are not closely packed like those of the epidermis. This arrangement permits defensive cells to move from blood into tissues during inflammation, but it also permits microbes to move into and out of blood and lymph. Mucous membranes also consist of an epithelial layer and an underlying connective tissue layer. Mucous membranes line the entire gastrointestinal, respiratory, and genitourinary tracts. The epithelial layer of a mucous membrane secretes a fluid called mucus, a slightly viscous (thick) glycoprotein produced by goblet cells of a mucous membrane. Some pathogens that can thrive on the moist secretions are able to penetrate the membrane if the microorganism is present in sufficient numbers. This penetration may be facilitated by toxic substances produced by the microorganism, prior injury by viral infection, or mucosal irritation. Besides the physical barrier presented by the skin and mucous membranes, several other physical factors help protect certain epithelial surfaces. The lacrimal glands, located toward the upper, outermost portion of each eye socket, produce the tears and pass them under the upper eyelid. From here, tears pass toward the corner of the eye near the nose and into two small holes that lead through tubes (lacrimal canals) to the nose. This continual washing action helps keep microorganisms from settling on the surface of the eye. If an irritating substance or large numbers of microorganisms come in contact with the eye, the lacrimal glands start to secrete heavily, and the tears accumulate more rapidly than they can be carried away. The washing action of tears over the surface of the eyeball is shown by the red arrow. Tears produced by the lacrimal glands pass across the surface of the eyeball into two small holes that convey the tears into the lacrimal canals and the nasolacrimal duct.