Major Viral, Fungal and Bacterial Diseases PDF

MAJOR VIRAL, FUNGAL AND BACTERIAL DISEASES  Learning Outcomes: At the end of this lecture, you should be able to: 2 GRAM POSITIVE AND GRAM NEGATIVE COCCI OF MEDICAL IMPORTANCE  STAPHYLOCOCCI. The genus Staphylococcus is a common inhabitant of the skin and mucou...

MAJOR VIRAL, FUNGAL AND BACTERIAL DISEASES  Learning Outcomes: At the end of this lecture, you should be able to: 2 GRAM POSITIVE AND GRAM NEGATIVE COCCI OF MEDICAL IMPORTANCE  STAPHYLOCOCCI. The genus Staphylococcus is a common inhabitant of the skin and mucous membranes, and it accounts for a considerable proportion of human infections (often called “staph” infections). Its spherical cells are arranged primarily in irregular clusters and occasionally in short chains and pairs 4  STAPHYLOCOCCI Currently, 47 species have been placed in the genus Staphylococcus, but the most important human pathogens are: 1. Staphylococcus aureus 2. Staphylococcus epidermidis, Staphylococcus capitis, Staphylococcus hominis; and 3. Staphylococcus saprophyticus 5  STAPHYLOCOCCI Of these, S. aureus is considered the most serious pathogen, although the other species have become increasingly associated with opportunistic infections and can no longer be regarded as harmless commensals. As a group, the staphylococci are implicated in nearly 80,000 deaths nationwide and account for a fair percentage of nosocomial infections annually. 6 7  Epidemiology and Pathogenesis of S. aureus ▪ It is surprising that a bacterium with such great potential for virulence as Staphylococcus aureus is a common, intimate human associate. The microbe is present in most environments frequented by humans and is readily isolated from fomites. ▪ The carriage rate for normal healthy adults varies anywhere from 20% to 60%, and the pathogen tends to be harbored intermittently rather than chronically 8  Epidemiology and Pathogenesis of S. aureus ▪ Staphylococcus aureus is the third most common cause of infections in the newborn nursery and surgical wards. The so-called “hospital strains” can readily spread in an epidemic pattern within and outside the hospital ▪ A serious concern has arisen from the increase in community infections by strains of S. aureus called MRSA (methicillin-resistant S. aureus). Several outbreaks have been reported in prison inmates, athletes, and schoolchildren. The infections are spread by contact with skin lesions and have proved to be very diffi cult to treat and control. 9  Epidemiology and Pathogenesis of S. aureus 10  Invasive Group A Streptococci and “Flesh- Eating” Syndrome ▪ Streptococcal infections are “occupational diseases of childhood” that usually follow a routine and uncomplicated course. The greatest cause for concern are those few occasions when such infections erupt into far more serious ailments. ▪ One dramatic example is necrotizing fasciitis,* a complication of S. pyogenes infection that has received heavy publicity as the “flesh-eating disease.” 11  Invasive Group A Streptococci and “Flesh- Eating” Syndrome It can begin with an innocuous cut in the skin and spread rapidly into nearby tissue, causing severe disfigurement and even death 12  Invasive Group A Streptococci and “Flesh- Eating” Syndrome 13  Beta-Hemolytic Streptococci: Streptococcus pyogenes ▪ By far the most serious streptococcal pathogen of humans is Streptococcus pyogenes. ▪ It is a relatively strict pathogen, inhabiting the throat, nasopharynx, and occasionally the skin of humans. ▪ The involvement of this species in severe disease is partly due to the substantial array of surface antigens, toxins, and enzymes it can generate.. 14  Epidemiology and Pathogenesis of Streptococcus pyogenes ▪ The bacteria gain a foothold at periods of lowered host resistance, primarily on the skin or in the pharynx. ▪ The incidence and types of infections are altered by climate, season, and living conditions. ▪ In addition to local cutaneous and throat infections, S. pyogenes can give rise to a variety of systemic infections and progressive sequelae if not properly treated. 15  Epidemiology and Pathogenesis of Streptococcus pyogenes ▪ Humans are the only signifi cant reservoir for S. pyogenes. ▪ About 5% to 15% of the population are subclinical carriers of virulent strains ▪ Infection is generally transmitted through direct contact, droplets, and, occasionally, fomites. 16  Epidemiology and Pathogenesis of Streptococcus pyogenes 17  Epidemiology and Pathogenesis of Streptococcus pyogenes ▪ Streptococcus pyogenes has traditionally been linked with a diverse spectrum of disease. ▪ Before the era of antibiotics, it accounted for a major portion of serious human infections and deaths from such diseases as rheumatic fever and puerperal sepsis. 18  Epidemiology and Pathogenesis of Streptococcus pyogenes ▪ Most people associate streptococci with the condition called strep throat or, more technically, streptococcal pharyngitis. ▪ Most humans will acquire this particular infection. ▪ At some time during their lifetime. The organism multiplies in the tonsils or pharyngeal mucous membranes, causing redness, edema, enlargement, and extreme tenderness, which make swallowing diffi cult and painful (figure 18.12). 19  Epidemiology and Pathogenesis of Streptococcus pyogenes ▪ These symptoms can be accompanied by fever, headache, nausea, and abdominal pain. Other signs include a purulent* exudate over the tonsils; swollen lymph nodes; and occasionally, white, pus- filled abscesses on the 20 tonsils.  Epidemiology and Pathogenesis of Streptococcus pyogenes ▪ The most severe and invasive infections is streptococcal toxic shock syndrome. It is the result of a profound bacteremia and deep tissue infection and rapidly progresses to multiple organ failure. Even with treatment, around 30% of patients die. 21 22  Group B: Streptococcus agalactiae ▪ Streptococcus agalactiae is primarily implicated in neonatal meningitis, wound and skin infections, and endocarditis. ▪ Elderly people suffering from diabetes and vascular disease are particularly susceptible to wound infections. ▪ Because of its location in the vagina, GBS can be transferred to the infant during delivery, sometimes with dire consequences. ▪ An early-onset infection develops a few days after birth and is accompanied by sepsis, pneumonia, and high mortality. 23  Group D Enterococci and Groups C and G Streptococci ▪ Enterococcus faecalis, E. faecium, and E. durans are collectively referred to as “enterococci” because they are normal colonists of the human large intestine. ▪ Two other members of group D, Streptococcus bovis and S. equinus, are nonenterococci that colonize other animals and occasionally humans. 24  Group D Enterococci and Groups C and G Streptococci Infections caused by E. faecalis arise most often in elderly patients undergoing surgery and affect the urinary tract, wounds, blood, the endocardium, the appendix, and other intestinal structures. Enterococci are emerging as serious nosocomial opportunists, primarily because of the rising incidence of multidrug- resistant strains, especially vancomycin-resistant enterococci (VRE). 25  Alpha-Hemolytic Streptococci: The Viridans Group ▪ The viridans* category includes streptococci of human origin not entirely groupable by Lancefi eld serology. ▪ They are the most numerous and widespread residents of the oral cavity (gingiva, cheeks, tongue, saliva) and are also found in the nasopharynx, genital tract, and skin. ▪ These species can cause serious systemic infections, although most of them are opportunists and lack a full set of toxins and enzymes common in more virulent streptococci. 26  Streptococcus pneumoniae: The Pneumococcus ▪ High on the list of signifi cant human pathogens is Streptococcus pneumoniae, a unique species that was formerly called Diplococcus until its genetic similarity to the streptococci was demonstrated. ▪ S. pneumoniae is also referred to as the pneumococcus. ▪ This bacterium is involved in the majority of bacterial pneumonias, which primarily affect immunocompromised patients. 27  Epidemiology and Pathology of the Pneumococcus ▪ From 5% to 50% of all people carry S. pneumoniae as part of the normal microbiota in the nasopharynx. Although infection is often acquired endogenously from one’s own microbiota, it occasionally occurs after direct contact with respiratory secretions or droplets from carriers. Streptococcus pneumoniae is very delicate and does not survive long out of its habitat. Factors that predispose patients to pneumonia are old age, the season (rate of infection is highest in the winter), other lung diseases or viral infections that weaken defenses, and living in close 28 proximity to infected people. 29  The Family Neisseriaceae: Gram-Negative Cocci ▪ Members of the Family Neisseriaceae are residents of the mucous membranes of warm-blooded animals. Most species are relatively innocuous commensals, but two are primary human pathogens with far- reaching medical impact. The genera contained in this group are Neisseria, Branhamella, and Moraxella. Of these, Neisseria has the greatest clinical significance. 30  Neisseria gonorrhoeae: The Gonococcus ▪ Gonorrhea* has been known as a sexually transmitted disease since ancient times. Its name originated with the Greek physician Claudius Galen, who thought that it was caused by an excess flow of semen. For a fairly long period in history, gonorrhea was confused with syphilis. Later, microbiologists went on to cultivate N. gonorrhoeae, also known as the gonococcus, and to prove conclusively that it alone was the etiologic agent of gonorrhea. 31 32  Neisseria gonorrhoeae: The Gonococcus Gonorrheal damage to the male reproductive tract. (a) Frontal view of the male reproductive tract. (Left side) The normal, uninfected state. The sperm- carrying ducts are continuous from the testis to the urethral opening. (Right side) The route of ascending gonorrhea complications. Infection begins at the tip of the urethra, ascends the urethra through the penis, and passes into the vas deferens. Occasionally, it can even enter the epididymides and testes. (Inset) Damage to the ducts carrying sperm can create scar tissue and blockage, which reduce sperm passage and can lead to sterility. 33  Neisseria gonorrhoeae: The Gonococcus ▪ 34 35  Neisseria meningitidis: The Meningococcus Another serious human pathogen is Neisseria meningitidis, a bacterium known commonly as the meningococcus and usually associated with epidemic cerebrospinal meningitis 36  Epidemiology and Pathogenesis of Meningococcal Disease ▪ The diseases of N. meningitidis generally have a sporadic or epidemic incidence in late winter or early spring. ▪ The continuing reservoir of infection is humans who harbor the pathogen in the nasopharynx ▪ It is the second most common cause of meningitis in adults, after Streptococcus pneumoniae. 37  Epidemiology and Pathogenesis of Meningococcal Disease 38 39  THE GRAM- POSITIVE BACILLI OF MEDICAL IMPORTANCE  Gram-Positive Spore- Forming Bacilli ▪ Most endospore-forming bacteria are gram-positive, motile, rodshaped forms in the genera Bacillus and Clostridium. An endospore is a dense survival unit that develops in a vegetative cell in response to nutrient deprivation. ▪ The extreme resistance to heat, drying, radiation, and chemicals accounts for the survival, longevity, and ecological niche of sporeformers, and it is also a signifi cant factor in their pathogenicity 41  HOW ENDOSPORES FORM AND GERMINATE? 42 43 44  General Characteristics of the Genus Bacillus ▪ The genus Bacillus includes a large assembly of mostly saprobic bacteria widely distributed in the earth’s habitats. ▪ Bacillus species are aerobic and catalase-positive, and, though they have varied nutritional requirements, none is fastidious. ▪ The group is noted for its versatility in degrading complex macromolecules, and it is also a common source of antibiotics 45  General Characteristics of the Genus Bacillus ▪ Because the primary habitat of many species is the soil, spores are continuously dispersed by means of dust into water and onto the bodies of plants and animals. ▪ Despite their ubiquity, the two species with primary medical importance are B. anthracis, the cause of anthrax, and B. cereus, the cause of one type of food poisoning. 46  Bacillus anthracis and Anthrax ▪ Bacillus anthracis is among the largest of all bacterial pathogens, composed of block-shaped, angular nonmotile rods 3 to 5 mm long and 1 to 1.2 mm wide and central spores that develop under all growth conditions except in the living body of the host. ▪ Its virulence factors include a polypeptide capsule and exotoxins that in varying combinations produce edema and cell death. 47  Bacillus anthracis and Anthrax ▪ For centuries, anthrax* has been known as a zoonotic disease of herbivorous livestock (sheep, cattle, goats). It has an important place in the history of medical microbiology because it was Robert Koch’s model for developing his postulates in 1877; ▪ later, Louis Pasteur used the disease to prove the usefulness of vaccination 48 49  Other Bacillus Species Involved in Human Disease ▪ Bacillus cereus is a common airborne and dust-borne contaminant that multiplies very readily in cooked foods such as rice, potato, and meat dishes. ▪ The spores survive short periods of cooking and reheating; when the food is stored at room temperature, the spores germinate and release enterotoxins. ▪ Ingestion of toxin-containing food causes nausea, vomiting, abdominal cramps, and diarrhea. There is no specific treatment, and the symptoms usually disappear within 24 hours. 50  The Genus Clostridium ▪ Another genus of gram-positive, spore-forming rods that is widely distributed in nature is Clostridium.* It is differentiated from Bacillus on the basis of being anaerobic and catalase-negative. ▪ Clostridia produce oval or spherical spores that often swell the vegetative cell. Spores are produced only under anaerobic conditions. ▪ Their nutrient requirements are complex, and they can decompose a variety of substrates. 51  The Role of Clostridia in Infection and Disease ▪ Clostridial disease can be divided into (1) wound and tissue infections, including myonecrosis, antibiotic- associated colitis, and tetanus; and (2) food intoxication of the perfringens and botulism varieties. Most of these diseases are caused by the release of potent exotoxins that act on specific cellular targets. In fact, the toxins responsible for these diseases are among the most poisonous substances on earth, being millions of times more toxic than strychnine or 52 arsenic  Gas Gangrene/Myonecrosis ▪ The majority of clostridial soft tissue and wound infections are caused by Clostridium perfringens, C. novyi, and C. septicum. ▪ The spores of these species can be found in soil, on human skin, and in the human intestine and vagina. ▪ The disease they cause has the common name gas gangrene* in reference to the gas produced by the bacteria growing in the tissue 53  Gas Gangrene/Myonecrosis ▪ The majority of clostridial soft tissue and wound infections are caused by Clostridium perfringens, C. novyi, and C. septicum. ▪ The spores of these species can be found in soil, on human skin, and in the human intestine and vagina. ▪ The disease they cause has the common name gas gangrene* in reference to the gas produced by the bacteria growing in the tissue 54  Tetanus, or Lockjaw ▪ Tetanus* is a neuromuscular disease whose alternate name, lockjaw, refers to an early effect of the disease on the jaw muscle. ▪ The etiologic agent, Clostridium tetani, is a common resident of cultivated soil and the gastrointestinal tracts of animals. ▪ Spores usually enter the body through accidental puncture wounds, burns, the umbilicus, frostbite, and crushed body parts. 55 56 57  Clostridium difficile– Associated Disease (CDAD) A clostridial disease called antibiotic-associated (or pseudomembranous) colitis is the second most common intestinal disease after salmonellosis in industrialized countries. It is caused by Clostridium difficile, a normal resident of the intestine that is usually present in low numbers. 58  Gas Gangrene/Myonecrosis ▪ Clostridium perfringens produces several physiologically active toxins; the most potent one, alpha-toxin (lecithinase), causes red blood cell rupture, edema, and tissue destruction. ▪ Additional virulence factors that enhance tissue destruction are collagenase, hyaluronidase, and DNase. ▪ The gas formed in tissues, due to fermentation of muscle carbohydrates, can also destroy muscle structure. 59  Clostridium difficile– Associated Disease (CDAD) ▪ Although C. difficile is relatively noninvasive, it can superinfect the colon when the normal microbiota have been disrupted. It produces enterotoxins that trigger necrosis in the wall of the intestine. ▪ The predominant symptom is diarrhea commencing late in therapy or even after therapy has stopped. More severe cases exhibit abdominal cramps, fever, and leukocytosis. The colon is inflamed and gradually sloughs off loose, membranelike patches called pseudomembranes consisting of fibrin and cells. ▪ If the condition is not arrested, cecal perforation and death can 60 result. 61  Clostridial Food Poisoning ▪ Two Clostridium species are involved in food poisoning. Clostridium botulinum produces a severe intoxication, usually from home bottled food. Clostridium perfringens, type A, accounts for a mild intestinal illness that is one of the most common forms of food poisoning worldwide. 62  Epidemiology of Botulinum Food Poisoning ▪ Clostridium botulinum is a spore-forming anaerobe that commonly inhabits soil and water and, occasionally, the intestinal tract of animals. ▪ Botulism* is an intoxication usually associated with eating canned or preserved foods, though it can occur as a result of infection. ▪ Until recent times, it was relatively prevalent and commonly fatal, but modern techniques of food preservation and medical treatment have reduced both its incidence and its fatality rate. ▪ However, botulism is a common cause of death in livestock that have grazed on contaminated food and in aquatic birds that have eaten decayed vegetation. 63  Pathogenesis of Botulism ▪ When contaminated food is bottled and steamed in a pressure cooker that does not reach reliable pressure and temperature, some spores survive (botulinum spores are highly heat-resistant). At the same time, the pressure is sufficient to evacuate the air and create anaerobic conditions ideal for spore germination and vegetative growth. One of the products of metabolism is botulinum toxin, the most potent microbial toxin known 64  Botox: No Wrinkles. No Headaches. No Worries? ▪ In 2012, people paid $1.8 billion to have one of the most potent toxins on earth injected into their face. ▪ The toxin, of course, is botulinum toxin type A, or Botox, a medical form of botulism toxin. ▪ The story of how these injections came to be the most common cosmetic procedure in the United States is a welcome respite from talk of flesh-eating bacteria and germ warfare 65  Botox: No Wrinkles. No Headaches. No Worries? ▪ In 1989, Botox was first approved to treat cross-eyes and uncontrollable blinking, two conditions resulting from the inappropriate contracting of muscles around the eye. Success soon led to Botox treatment for a variety of disorders that cause painful contraction of neck and shoulder muscles ▪ Botox injections were approved for treating chronic migraines and are now a routine part of therapy. 66  Botox: No Wrinkles. No Headaches. No Worries? 67  SIDE EFFECTS OF BOTOX ▪ The dominant side effect of Botox treatment is excessive ▪ paralysis of facial muscles resulting from poorly targeted injections. ▪ Other results include drooping eyelids, facial paralysis, slurred speech, and drooling. ▪ Even if the treatment works perfectly, patients are generally unable to move their eyebrows or in some cases frown or squint. 68  SIDE EFFECTS OF BOTOX ▪ Although most experts agree that Botox is relatively safe, some rare cases of severe reactions and deaths have been reported. ▪ Reacting to a spate of adverse events, the FDA in 2009 required all packages of Botox to display a so- called black box warning—one of the strongest safety actions the agency can take—informing doctors and consumers of dangers associated with the toxin 69  SIDE EFFECTS OF BOTOX ▪ Botox effects are not permanent. As the toxin wears off, the wrinkles (or headaches, as the case may be) return, and every 4 to 6 months, the treatment must be repeated. ▪ This last fact has been welcomed by plastic surgeons because a permanent solution to wrinkles would rule out any repeat clientele. ▪ Malpractice lawsuits are also reduced because, by the time a patient has consulted a lawyer, any consequences of a botched treatment have usually worn off. 70  THE GRAM- NEGATIVE BACILLI OF MEDICAL IMPORTANCE  AEROBIC GRAM- NEGATIVE NONENTERIC BACILLI The aerobic gram-negative bacteria of medical importance are a loose assortment of genera including the soil bacteria Pseudomonas and Burkholderia; the zoonotic pathogens Brucella and Francisella; and Bordetella and Legionella, which are mainly human pathogens. The gram-negative rods can be organized in several ways. To simplify coverage here, they are grouped into three major categories based on oxygen requirements and fermentation of lactose. 72  AEROBIC GRAM- NEGATIVE NONENTERIC BACILLI One notable component of all gram-negative rods is a lipopolysaccharide in the outer membrane of the cell wall that acts as an endotoxin. The release of endotoxin in the blood from gram-negative septicemia can have severe and far-reaching pathophysiological effects. 73  AEROBIC GRAM- NEGATIVE NONENTERIC BACILLI 74  PSEUDOMONAS: THE PSEUDOMONADS The pseudomonads are members of the Family Pseudomonadaceae, a large group of free-living bacteria that live primarily in soil, seawater, and fresh water. They also colonize plants and animals and are frequent contaminants in homes and clinical settings. These small, gram-negative rods have a single polar flagellum, produce oxidase and catalase, and do not ferment carbohydrates. 75  PSEUDOMONAS: THE PSEUDOMONADS Pseudomonas* species are highly versatile. They can adapt to a wide range of habitats and manage to extract needed energy from minuscule amounts of dissolved nutrients. Most members can grow in a medium containing minerals and a simple organic compound. This adaptability accounts for their constant presence in the environment and their capacity to thrive on hosts. numerous extracellular substances by means of protease, amylase, pectinase, cellulase, and numerous other enzymes. 76  Pseudomonas aeruginosa Pseudomonas aeruginosa is a common inhabitant of soil and water and an intestinal resident in about 10% of healthy people. On occasion it can be isolated from saliva or even the skin. Because the species is resistant to soaps, dyes, certain disinfectants, drugs, and drying, it is a frequent contaminant of ventilators, intravenous solutions, and anesthesia equipment. Even disinfected instruments, utensils, bathroom fixtures, and mops have been incriminated in hospital outbreaks. 77 78 79  Burkholderia cepacia Burkholderia cepacia is a common isolate from moist environments; it appears to play an important ecological role in controlling fungal disease on plants. It is also active in biodegradation of a wide variety of toxic substances, which would ordinarily make it a useful addition to bioremediation programs. Unfortunately it also has a potential for opportunistic infections in the respiratory tract, the urinary tract, and occasionally the skin. 80  Burkholderia pseudomallei Burkholderia pseudomallei is a relative of B. cepacia that resides in the soil and water of tropical climates. Chronic infection may progress to septicemia, endotoxic shock, and abscesses in organs such as the liver and brain. In persons with compromised immune systems, the infection can cause severe disseminated disease that is occasionally fatal. 81  Stenotrophomonas maltophilia It is a prominent clinical isolate most often found in respiratory, blood, spinal fluid, and ophthalmic specimens. Higher rates of infection occur in cancer patients and people with indwelling invasive devices. Although this species is one of the most drug- resistant of bacteria, therapy with a combination of trimethoprim and sulfamethoxazole is usually effective. 82  BRUCELLA AND BRUCELLOSIS In humans, Brucella enters through damaged skin or mucous membranes of the digestive tract, conjunctiva, and respiratory tract. One of Brucella’s most effective virulence factors lies in its capacity to survive and grow inside of macrophages. These infected macrophages transport the pathogen into the bloodstream, creating focal lesions in the liver, spleen, bone marrow, and kidney. The cardinal manifestation of human brucellosis is a fluctuating pattern of fever, which is the origin of the common name, undulant fever. It is also accompanied by chills, profuse sweating, headache, muscle pain and weakness, 83 and weight loss  BRUCELLA AND BRUCELLOSIS In humans, Brucella enters through damaged skin or mucous membranes of the digestive tract, conjunctiva, and respiratory tract. One of Brucella’s most effective virulence factors lies in its capacity to survive and grow inside of macrophages. These infected macrophages transport the pathogen into the bloodstream, creating focal lesions in the liver, spleen, bone marrow, and kidney. The cardinal manifestation of human brucellosis is a fluctuating pattern of fever, which is the origin of the common name, undulant fever. It is also accompanied by chills, profuse sweating, headache, muscle pain and weakness, 84 and weight loss 85 86  ALCALIGENES The genus Alcaligenes* is another group of nonfermentative, oxidase-positive, motile bacteria in the same family as Bordetella. Members of Alcaligenes live primarily in soil and water habitats, and they may also become established as normal microbiota. The most common clinical species, A. faecalis, is isolated from feces, sputum, and urine. It is occasionally associated with opportunistic infections such as pneumonia, septicemia, and meningitis. 87  Coliform Organisms and Diseases The Family Enterobacteriaceae is traditionally divided into two subcategories. The coliforms include Escherichia coli and other gram-negative normal enteric microbiota that ferment lactose rapidly (within 48 hours). Noncoliforms are generally non-lactosefermenting or slow lactose-fermenting bacteria that are either normal microbiota or regular pathogens. 88 89 Escherichia coli: The Most Prevalent Enteric Bacillus Escherichia* coli is the best-known coliform, largely because of its use as a subject for laboratory studies. Although it is called the colon bacillus and sometimes regarded as the predominant species in the intestine of humans, E. coli is actually outnumbered 9 to 1 by strictly anaerobic bacteria of the gut (Bacteroides and Bifidobacterium) that are not readily cultured. Its prevalence in clinical specimens and infections is due to its being the most common aerobic and nonfastidious bacterium in the gut. 90  THE SIX PATHOTYPES OF E. COLI Enterohemorrhagic E. coli (EHEC) causes hemorrhagic colitis and may lead to hemolytic uremic syndrome (HUS), which can cause severe damage to the kidney. Because much of its virulence is derived from the shiga toxin acquired from Shigella, it is also known Shiga toxin producing E. coli, or STEC. 91  THE SIX PATHOTYPES OF E. COLI Enterotoxigenic E. coli (ETEC) causes a severe diarrheal illness brought on by two exotoxins, termed heat-labile toxin (LT) and heat-stable toxin (ST), that stimulate heightened secretion and fluid loss. In this way, it mimics the pathogenesis of cholera (see figure 21.11). This serotype of E. coli also has fimbriae that provide adhesion to the small intestine. 92  THE SIX PATHOTYPES OF E. COLI Enteroinvasive E. coli (EIEC) causes an inflammatory disease similar to dysentery* from Shigella that involves invasion and ulceration of the mucosa of the large intestine. Enteropathogenic strains of E. coli (EPEC) are linked to a wasting form of infantile diarrhea whose pathogenesis is not well understood. 93  THE SIX PATHOTYPES OF E. COLI Enteroaggregative E. coli (EAEC) cells aggregate and colonize the intestinal mucosa; enterotoxins they release damage the host cells and induce inflammation, leading to diarrhea. Pediatric diarrhea is commonly caused by EAEC. Diffusely adherent E. coli (DAEC) is thought to be a 94 minor cause of pediatric diarrhea.  CLINICAL DISEASES OF E. COLI Most clinical diseases of E. coli are transmitted exclusively among humans. Pathogenic strains of E. coli are frequent agents of infantile diarrhea, the greatest single cause of mortality among babies. Worldwide, 15% of childhood deaths are due to diarrhea. The rate of infection is higher in crowded tropical regions where sanitary facilities are poor, water supplies are contaminated, and adults carry pathogenic strains to which they have developed immunity. 95  THE ROLE OF ESCHERICHIA COLI IN FOOD INFECTIONS The most highly publicized strain of Escherichia coli is an enterohemorrhagic strain famous for its involvement in infections traced to fastfood hamburgers that first appeared in 1982. Since that time, it has been commonly referred to by its antigen profile: O157:H7, which stands for somatic (O) type 157 and flagellar (H) type 7. This bacterial strain owes much of its virulence to a cell wall receptor that can fuse with the host cell membrane, creating a direct port into which the bacteria secrete toxins and other proteins into the host cell. 96  MISCELLANEOUS INFECTIONS Escherichia coli often invades sites other than the intestine. For instance, it causes 50% to 80% of urinary tract infections (UTI) in healthy people. Urinary tract infections usually result when the urethra is invaded by its own endogenous bacterial colonists. The infection is more common in women because their relatively short urethras promote ascending infection to the bladder (cystitis) and occasionally the kidneys. Patients with bladder catheters are also at risk for E. coli urethritis. 97  E. COLI AND THE COLIFORM COUNT Because of its prominence as a normal intestinal bacterium in most humans, E. coli is currently one of the indicator bacteria to monitor fecal contamination in water, food, and dairy products. According to this rationale, if E. coli is present in a water sample, fecal pathogens such as Salmonella, viruses, or even pathogenic protozoa may also be present. Coliforms such as E. coli are used because they are present in larger numbers, can survive in the environment, and are easier and faster to detect than true pathogens. If a certain number of coliforms are detected in 98 a sample, the water is judged unsafe to drink. 99  True Enteric Pathogens: Salmonella and Shigella The salmonellae and shigellae are distinguished from the coliforms and the Proteus group by having well- developed virulence factors, being primary pathogens, and not being normal residents of respectively—show some humans. The illnesses they gastrointestinal involvement cause—called salmonelloses and diarrhea but often affect and shigelloses, other systems as well. 100  Typhoid Fever and Other Salmonelloses Typhoid fever is so named because it bears a superficial resemblance to typhus, a rickettsial disease, even though the two diseases are otherwise very different. Typhoid fever is caused by Salmonella serotype Typhi. Salmonella serotype Paratyphi causes paratyphoid, a very similar disease; both bacteria are considered typhoidal Salmonella. 101  THE PHASES OF TYPHOID FEVER 102  SHIGELLA AND BACILLARY DYSENTERY Shigella* causes a common but often incapacitating dysentery called shigellosis, which is marked by fever, nausea, painful abdominal cramps, and frequent defecation of watery stool filled with mucus and blood. The etiologic agents (Shigella dysenteriae, S. sonnei, S. flexneri, and S. boydii) are primarily human pathogens, though they can infect apes. All produce a similar disease that can vary in intensity. They are nonmotile, nonencapsulated, and not fastidious. The shigellae resemble some types of pathogenic E. coli so closely that 103 they are placed in the same subgroup 104 105 106 107 MISCELLANEOUS BACTERIA AGENTS OF DISEASE 109 110 111  FUNGI OF MEDICAL IMPORTANCE  PRIMARY/TRUE FUNGAL PATHOGENS A true or primary fungal pathogen is a species that can invade and grow in a healthy, non-compromised animal host. This behavior is contrary to the metabolism and adaptation of fungi, most of which are inhibited by the relatively high temperature and low oxygen tensions of a warm-blooded animal’s body. But a small number of fungi have the morphological and physiological adaptations required to survive and grow in this habitat. 113  PRIMARY/TRUE FUNGAL PATHOGENS By far their most striking adaptation is a switch from hyphal cells typical of the mycelial or mold phase to yeast cells typical of the parasitic phase. This biphasic characteristic of the life cycle is termed thermal dimorphism* because it is initiated by changing temperature. 114 115  EMERGING FUNGAL PATHOGENS An opportunistic fungal pathogen is different from a true pathogen in several ways. An opportunist has weak to nonexistent invasiveness or virulence, and the host’s defenses must be impaired to some degree for the microbe to gain a foothold. Although some species have both mycelial and yeast stages in their life cycles, they usually do not show thermal dimorphism. Opportunistic mycoses vary in their manifestations from superficial and benign colonizations to spreading systemic disease 116 that is rapidly fatal.  EPIDEMIOLOGY OF THE MYCOSES Most fungal pathogens do not require a host to complete their life cycles, and the infections they cause are not communicable. Notable exceptions are some dermatophyte and Candida species that naturally inhabit the human body and are transmissible. For the remainder of the pathogens, exposure and infection occur when a human happens upon fungal spores in the environment (usually air, dust, or soil). True fungal pathogens, unlike opportunists, are distributed in a predictable pattern that coincides with the pathogen’s adaptation to the specific climate, soil, or other factors of a relatively restricted geographic region 117 118  PATHOGENESIS OF THE FUNGI Mycoses involve complex interactions among the portal of entry, the nature of the infectious dose, the virulence of the fungus, and host resistance. Fungi enter the body mainly via respiratory, mucous, and cutaneous routes. In general, the agents of primary mycoses have a respiratory portal (spores inhaled from the air); subcutaneous agents enter through inoculated skin (trauma); and cutaneous and superficial agents enter through contamination of the skin surface. Spores, hyphal elements, and yeasts can all be infectious, but spores are most often involved because of their durability and 119 abundance. 120  PATHOGENESIS OF THE FUNGI Thermal dimorphism greatly increases virulence by enabling fungi to tolerate the relatively high temperatures and low oxygen tensions of the body. Fungi in the yeast form can be more invasive than hyphal forms because they grow more rapidly and spread through tissues and blood, whereas those producing hyphae tend to localize along the course of blood vessels and lymphatics. 121  DIAGNOSIS OF MYCOTIC INFECTIONS Accurate and speedy diagnosis is especially critical to the immunocompromised patient, who must have prompt antifungal chemotherapy. For example, a patient with systemic Candida infection can die if the infection is not detected and treated within 5 to 7 days. Because therapy can vary among the pathogenic fungi, identification to the species 122 level is often necessary.  DIAGNOSIS OF MYCOTIC INFECTIONS A suitable specimen can be obtained from sputum, skin scrapings, skin biopsies, cerebrospinal fluid, blood, tissue exudates, urine, or vaginal samples, as determined by the patient’s symptoms. Routine laboratory procedures include isolation, microscopic and macroscopic examination, histological stains, serology, animal inoculation, and genetic 123 testing  Methods of processing specimens and identifying fungal isolates. References indicate figures showing these techniques. (left, middle): Source: CDC; (right) 124 125 126 127 128 129 130 131 132 133 134  OPPORTUNISTIC MYCOSES Candida is the dominant opportunistic pathogen, and it accounts for the majority of invasive infections. The mold Aspergillus is the second in incidence, accounting for the most lung infections. Other fungi that are appearing more often in clinical isolates are Cryptococcus, Alternaria, Paecilomyces, Fusarium, Rhizopus, and Torulopsis—all genera that were once considered “harmless” air contaminants. 135  INFECTIONS BY CANDIDA: CANDIDIASIS Candida albicans,* an extremely widespread yeast, is the major cause of candidiasis (also called candidosis or moniliasis). Manifestations of infection run the gamut from short-lived, superficial skin irritations to overwhelming, fatal systemic diseases. Microscopically, C. albicans has budding cells of varying size that may form both elongate pseudohyphae and true hyphae macroscopically, it forms an off-white, pasty colony with a yeasty odor 136 137 138 139  ASPERGILLOSIS: DISEASES OF THE GENUS ASPERGILLUS Molds of the genus Aspergillus* are possibly the most pervasive of all fungi. The estimated 600 species are widely dispersed in dust a nd air and can be isolated from vegetation, food, and compost matter. Of the eight species involved in human diseases, the thermophilic fungus A. fumigatus accounts for the most cases. Aspergillosis is almost always an opportunistic infection, lately posing a serious threat to AIDS, leukemia, and immunodeficient patients. It is also involved in allergies 140 and toxicoses.  ASPERGILLOSIS: DISEASES OF THE GENUS ASPERGILLUS Aspergillus infections usually occur in the lungs. People breathing clouds of conidia from the air of granaries, barns, and silos are at greatest risk. In healthy people with extensive exposure, the spores simply germinate in the lungs and form fungus balls. Similar benign, noninvasive infections occur in colonization of the sinuses, ear canals, eyelids, and conjunctiva. 141  MUCORMYCOSIS also known as zygomycosis, common airborne molds in the genera Rhizopus, Mucor, and Absidia are most often involved in these mycoses. 142 143 144 VIRUSES THAT INFECTS HUMANSːTHE DNA VIRUSES  VIRUSES IN HUMAN INFECTIONS AND DISEASES Viruses are the smallest parasites with the simplest biological structure. Essentially they are particles composed of DNA or RNA molecules surrounded by a protein coat. They are completely dependent on a host cell for their continued existence. Viruses have special adaptations for entering a cell and instructing the cell’s genetic and molecular machinery to produce and release new viruses. 146 147 148 149  Enveloped DNA Viruses: Poxviruses Poxviruses produce eruptive skin pustules called pocks or pox, which leave small, depressed scars (pockmarks) upon healing. The poxviruses are distinctive because they are the largest and most complex of the animal viruses, and they multiply in the cytoplasm in well- defined sites called factory areas, which appear as inclusion bodies in infected cells 150  CLASSIFICATION AND STRUCTURE OF POXVIRUSES Among the best-known poxviruses are variola, the cause of smallpox, and vaccinia, a closely related virus used in vaccinations. Other members are carried by domestic or wild animals and may occasionally be transmitted to humans. A common feature of all poxvirus infections is a specificity for the cytoplasm of epidermal cells and subcutaneous connective tissues. In these sites, they produce the typical pox lesions, and some may later stimulate cell growth and tumor formation. 151  SMALLPOX: A PERSPECTIVE 152 153  ENVELOPED DNA VIRUSES: THE HERPESVIRUSES The herpesviruses* were named for the tendency of some herpes infections to produce a rash that spreads (creeps). The term is used to designate a large family whose members include the following: ∙ herpes simplex 1 and 2 (HSV), the cause of fever blisters and genital infections; 154  ENVELOPED DNA VIRUSES: THE HERPESVIRUSES ∙ varicella-zoster virus (VZV), the cause of chickenpox and shingles; ∙ cytomegalovirus (CMV), which infects the salivary glands and other viscera; ∙ Epstein-Barr virus (EBV), associated with infection of the lymphoid tissue; ∙ human herpesviruses 6 and 7 (HHVs), which cause roseola; and ∙ herpesvirus 8 (KSHV), which is implicated in Kaposi 155 sarcoma. ENVELOPED DNA VIRUSES: THE HERPESVIRUSES 156 157 158  LIFE-THREATENING COMPLICATIONS OF HERPES Although herpes simplex encephalitis is a rare complication of type 1 infection, it is probably the most common sporadic form of viral encephalitis in the United States. The infection disseminates along nerve pathways to the brain or spinal cord. The effects on the CNS begin with headache and stiff neck and can progress to mental disturbances and coma. The fatality rate in untreated cases is 70%. 159 160 161 162 163 164 165 166 167  THE VIRAL AGENTS OF HEPATITIS When certain viruses infect the liver, they cause hepatitis, an inflammatory disease marked by necrosis of hepatocytes and a mononuclear response that swells and disrupts the liver architecture. This pathologic change interferes with the liver’s excretion of bile pigments such as bilirubin into the intestine. When bilirubin, a greenish- yellow pigment, accumulates in the blood and tissues, it causes jaundice,* a yellow tinge in the skin and eyes. 168  THE VIRAL AGENTS OF HEPATITIS The major group of DNA viruses involved in hepatitis are the hepadnaviruses.* These enveloped viruses have never been grown in tissue culture and have an unusual genome containing both double- and single-stranded DNA. Hepadnaviruses show a decided tropism for the liver, where they persist and usually trigger liver cell carcinoma. One member of the group, hepatitis B virus (HBV), causes a common form of hepatitis in humans, and related viruses cause hepatitis in other vertebrates. 169  THE VIRAL AGENTS OF HEPATITIS Hepatitis A virus (HAV) is a nonenveloped RNA enterovirus transmitted through contaminated food. In general, HAV disease is far milder, shorter term, and less virulent than the other forms. Another significant RNA virus is hepatitis C virus (HCV), a flavivirus that causes many cases of transfusion hepatitis. HCV is involved in a chronic liver infection that can go undiagnosed, later leading to severe liver damage and cancer. It is spread primarily by exposure to blood and blood products 170 171 172  NONENVELOPED DNA VIRUSES During a study seeking the cause of the common cold, a new virus was isolated from the adenoids* of young children. It turned out that this virus, termed adenovirus, was not the sole agent of colds but one of numerous others (described in chapter 25). It was also the first of about 80 strains of nonenveloped, double-stranded DNA viruses classified as adenoviruses, including 30 types associated with human infection 173 174  Papilloma- and Polyomaviruses Two families of small, nonenveloped double- stranded DNA viruses are papillomaviruses* and polyomaviruses.* They are similar in having circular DNA and causing persistent infections and tumors. They differ in their size and the makeup of their genomes. 175  EPIDEMIOLOGY AND PATHOLOGY OF THE HUMAN PAPILLOMAVIRUSES A papilloma is a squamous epithelial growth commonly referred to as a wart, or verruca, caused by over 100 different strains of human papillomavirus (HPV). Some warts are specific for the mucous membranes; others invade the skin. The appearance and seriousness of the infection vary somewhat from one anatomical region to another. Painless, elevated, rough growths on the fingers and occasionally on other body parts are called common, or seed, warts 176 177 178 179  NONENVELOPED SINGLE- STRANDED DNA VIRUSES: THE PARVOVIRUSES The parvoviruses* (PVs) are unique among the human viruses in having single-stranded DNA molecules. They are also notable for their extremely small diameter (18–26 nm) and genome size. Parvoviruses are indigenous to and can cause disease in several mammalian groups: for example, distemper in cats, an enteric disease in adult dogs, and a potentially fatal cardiac infection in puppies. 180  NONENVELOPED SINGLE- STRANDED DNA VIRUSES: THE PARVOVIRUSES The most important human parvovirus is B19, the cause of erythema infectiosum (figure 24.23). It is also known as fifth disease because it is the fifth rash of childhood (the four others being rubella, rubeola, scarlet fever, and scarletina). It is a common childhood infection spread primarily by droplets. 181 VIRUSES THAT INFECTS HUMANSːTHE RNA VIRUSES  ENVELOPED SEGMENTED SINGLE-STRANDED RNA VIRUSES The Biology of Orthomyxoviruses: Influenza Orthomyxoviruses are spherical particles with an average diameter of 80 nm to 120 nm. There are three distinct influenza virus types (A, B, C), but type A causes the most cases of infection and is the one we discuss in the greatest detail. The virus attaches to and multiplies in cells of the respiratory tract 183 184 185  EMERGING AVIAN INFLUENZA VIRUSES Starting in 2003, strains of influenza A viruses that usually infect birds underwent an antigenic shift and began to infect humans. The first of these emerging bird flu viruses, H5N1, originated from poultry in Southeast Asia and caused a highly virulent disease with about a 60% fatality rate in humans. All of these cases apparently arose through bird-to-human transmission, and there was no evidence of person-to-person transmission. 186  EMERGING AVIAN INFLUENZA VIRUSES In 2013 another bird flu virus, H7N9, appeared in Chinese patients. By the middle of 2016 at least 807 cases and 151 deaths had been attributed to the flu, almost all of then in China. The vast majority of the cases involved direct contact with birds, often at live poultry markets, indicating that while the strain moved quickly from bird to human, person to person transmission was far less efficient. 187 188 189 190  RHABDOVIRUSES The most conspicuous rhabdovirus* is the rabies* virus, genus Lyssavirus.* The particles of this virus have a distinctive bulletlike appearance, round on one end and flat on the other. Additional features are a helical nucleocapsid and spikes that protrude through the envelope 191 192  EPIDEMIOLOGY OF RABIES Rabies is a slow, progressive zoonotic disease characterized by a fatal meningoencephalitis. It is distributed nearly worldwide, except for 34 countries that have remained rabies-free by practicing rigorous animal control. The primary reservoirs of the virus are wild mammals such as canines, skunks, raccoons, cats, and bats. These can spread the infection to domestic cats and dogs. Cats are so important in spreading the virus that most states require vaccination of pet cats as well 193 as dogs.  SEVERE ACUTE RESPIRATORY SYNDROME– ASSOCIATED CORONAVIRUS The disease was given the name SARS for severe acute respiratory syndrome. By early 2003 the World Health Organization (WHO) issued a global health alert about the new illness. In a short time, scientists had sequenced the entire genome of the causative agent, revealing it to be a new type of coronavirus. 194  SEVERE ACUTE RESPIRATORY SYNDROME– ASSOCIATED CORONAVIRUS The epidemic was contained by mid-year, but in less than a year, it had sickened more than 8,000 people. About 9% of those died. Symptoms begin with a fever of above 38°C (100.4°F) and progress to body aches and an overall feeling of malaise. Early in the infection, there seems to be little virus in the patient and a low probability of transmission. Within a week, viral numbers surge and transmissibility is very high. After 3 weeks, viral levels decrease significantly and symptoms subside 195  SEVERE ACUTE RESPIRATORY SYNDROME– ASSOCIATED CORONAVIRUS In late 2012 a novel coronavirus caused 130 infections and 58 deaths in patients in the United Kingdom and Arabian peninsula. Christened Middle East respiratory syndrome coronavirus (MERSCoV), it was, like the virus that causes SARS, similar to coronaviruses found in bats in certain parts of the world. Since 2012, 27 countries have reported a total of 1,806 infections, and the virus has been responsible for 643 deaths. The largest outbreak of the virus outside of the Arabian Peninsula was in the Republic of Korea in 2015, where 185 196 confirmed cases and 36 deaths were reported. 197 198 199 20 0 201  References Tallaro, K. P., Chess, B. 2018. FOUNDATIONS IN MICROBIOLOGY, TENTH EDITION. McGraw-Hill Education Chapter 18 – 25. 20 2