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taL22600_ch21_633-665.indd Page 633 11/12/13 9:13 PM f-w-166 CHAPTER 21 /202/MH02004/taL22600_disk1of1/0073522600/taL22600_pagefiles Miscellaneous Bacterial Agents of Disease A spirochete of of Leptospira interrogans Natural waters often serve as a source of infection. s ro g in ic he pa l m t g of ua ted sin g ad ivid trac A u nnin x d e DN tu be in e hey he ir s um t t he d n ea t, as zed **. T an s oc y l a ers iety iou ut var rev M o icr CASE STUDY Part 1 Working Overtime S ometimes dedication to your job can get you in trouble. In another phase of illness that featured tremors, impaired balance, 2004, a 56-year-old genetics professor at the University of and illusions of color before his eyes. Hawaii in Oahu was determined to conc Do you know of any diseases that a person can tinue working in his lab even though a local “For 4 days, he slogged acquire simply by walking through standing stream had overflowed and the campus was through standing water water? flooded. For 4 days, he slogged through standin his lab to keep his ing water in his lab to keep his research going. c Does the geographic location of the case Two weeks afterward, the professor develprovide a clue as to what the infectious agent research going.” oped blisters on his feet. A few days later, he might be? started having flulike symptoms—fever and chills, followed by nausea and vomiting. He began to feel better but then developed To continue the Case Study, go to page 661. 633 taL22600_ch21_633-665.indd Page 634 11/27/13 5:09 PM f-w-166 634 /202/MH02004/taL22600_disk1of1/0073522600/taL22600_pagefiles Chapter 21 Miscellaneous Bacterial Agents of Disease A number of bacterial pathogens do not fit the usual categories of gram-positive or gram-negative rods or cocci. This group includes spirochetes and curviform bacteria, obligate intracellular parasites such as rickettsias and chlamydias, and mycoplasmas. This chapter covers not only those agents but also the mixed bacterial infections that are responsible for the diseases of the oral cavity. 21.1 The Spirochetes species Treponema pallidum pallidum* is responsible for venereal and congenital syphilis (see Pathogen Profile #1, page 639); the subspecies T. p. endemicum causes nonvenereal endemic syphilis, or bejel; and T. p. pertenue causes yaws. Treponema carateum is the cause of pinta. Infection begins in the skin, progresses to other tissues in gradual stages, and is often marked by periods of healing interspersed with relapses. The major portion of this discussion centers on syphilis, and any mention of T. pallidum refers to the subspecies T. p. pallidum. Other treponemes of importance are involved in infections of the gingiva. Expected Learning Outcomes Treponema pallidum: The Spirochete of Syphilis 1. Differentiate among the different stages of syphilis. 2. Explain the different ways in which syphilis infections may be diagnosed. 3. List the nonsyphilitic treponematoses. 4. Justify the strategies used to prevent leptospirosis. 5. Identify the vectors and behaviors associated with Borrelia infection. Spirochetes typically display a helical form and flagellar mode of locomotion that apQuick Search pear especially striking in live, unstained Point your browser preparations using the dark-field or phasetoward YouTube and search contrast microscope. Other traits include a “Spirochetes” to see typical gram-negative cell wall and a welltheir fascinating developed periplasmic space that encloses mode of motility. the flagella (called endoflagella or periplasmic flagella) (figure 21.1a). Although internal flagella are constrained somewhat like limbs in a sleeping bag, their flexing propels the cell by rotation and even crawling motions. The spirochetes are classified in the Phylum Spirochaetes, which contains three families and 13 genera. The majority of spirochetes are free-living saprobes or commensals of animals and are not primary pathogens. Major pathogens are found in three genera: Treponema, Leptospira, and Borrelia (figure 21.1b, figure 21.6, and Case Study inset). Treponemes: Members of the Genus Treponema The origin of syphilis* is an obscure yet intriguing topic of speculation. The disease was first recognized at the close of the fifteenth century in Europe, a period coinciding with the return of Columbus from the West Indies, which led some medical scholars to conclude that syphilis was introduced to Europe by early explorers. DNA analyses indicate that treponemal disease is ancient and widespread. Even wild primates carry strains of Treponema that are related to the human forms. Whatever its origins, once it became sexually transmitted, the pathogen was ultimately carried worldwide. Epidemiology and Virulence Factors of Syphilis Although infection can be induced in laboratory animals, the human is evidently the sole natural host and source of T. pallidum. It is an extremely fastidious and sensitive bacterium that cannot survive for long outside the host, being rapidly destroyed by heat, drying, disinfectants, and other adverse conditions. It survives a few minutes to hours when protected by body secretions and about 36 hours in stored blood. Research with human subjects has demonstrated that the risk of infection from an infected sexual partner is 12% to 30%. Less common modes of transmission are passage to the fetus in utero and laboratory or medical accidents. Syphilitic infection through blood transfusion or exposure to fomites is rare. Syphilis, like other sexually transmitted diseases (STDs), has experienced periodic increases during times of social disruption. After experiencing a decline during the 1990s, case reports are once again increasing (see figure 18.22). In fact, the case rate has more Treponemes are thin, somewhat regular, coiled bacteria that live in the oral cavity, intestinal tract, and perigenital regions of humans and animals. The pathogens are strict parasites with complex growth requirements that necessitate cultivating them in live cells. Diseases caused by Treponema are called treponematoses. The sub- Endoflagellum (a) Periplasmic space Outer membrane * Treponema pallidum (trep0-oh-nee9-mah pal9-ih-dum) Gr. trepo, turn, and nema, thread; L. pallidum, pale. The spirochete does not stain with the usual bacteriologic methods. * syphilis The term syphilis first appeared in a poem entitled “Syphilis sive Morbus Gallicus” by Fracastorius (1530) about a mythical shepherd whose name eventually became synonymous with the disease from which he suffered. Endoflagellum Cell body (b) Figure 21.1 Typical spirochete. (a) Representation of general spirochete morphology with endoflagella inserted in the opposite poles, lying beneath the outer membrane and within the periplasmic space. (b) Members vary in the number of coils. For example, Borrelias have 3 to 10 loose, irregular coils (1,5003). taL22600_ch21_633-665.indd Page 635 11/12/13 9:13 PM f-w-166 /202/MH02004/taL22600_disk1of1/0073522600/taL22600_pagefiles 21.1 Systems Profile 21.1 635 Miscellaneous Bacterial Pathogens Organism Skin/Skeletal Cardiovascular/ Lymphatic/ Nervous/Muscle Systemic Treponema pallidum pallidum Skin rash (secondary syphilis) Tertiary syphilis Leptospira interrogans Borrelia burgdorferi The Spirochetes Lyme disease Gastrointestinal Respiratory Urogenital Secondary syphilis Tertiary syphilis Chancre (primary syphilis) Leptospirosis Leptospirosis Leptospirosis Lyme disease Lyme disease Vibrio cholerae Secretory diarrhea Vibrio parahaemolyticus Gastroenteritis Campylobacter jejuni Gastroenteritis Helicobacter pylori Gastritis, peptic and duodenal ulcers Rickettsia prowazekii Epidemic typhus Epidemic typhus Rickettsia rickettsii Rocky Mountain spotted fever Rocky Mountain spotted fever Rocky Mountain spotted fever Ehrlichia spp. Ehrlichiosis Coxiella burnetii Q fever Bartonella henselae Local papules Chlamydia trachomatis 1. Neonatal conjunctivitis 2. Trachoma Mycoplasma pneumoniae than doubled since 2000. Major contributors to this trend are gay and bisexual men in large urban areas. Other increases are associated with prostitution and intravenous drug abuse. Because many cases go unreported, the actual incidence is likely to be several times higher than these reports show. Syphilis continues to be a serious problem worldwide, especially in Africa and Asia. Persons with syphilis often suffer concurrent infection with other STDs such as chlamydia, herpes simplex, gonorrhea, and AIDS. A Dark Event in Human Experimentation One of the most disturbing events in the study of syphilis occurred in the United States. Beginning in 1932, the U.S. government conducted a study called the “Tuskegee Study of Untreated Syphilis in the Negro Male,” which eventually involved 399 indigent African-American men living in the South. Infected men were recruited into the study, which sought to document the natural progression of the disease. These men were never told that they had syphilis and were never treated for it, even after penicillin was shown to be an effective cure. The study ended in 1972, after it became public. In 1997, the government issued a public apology for permitting the study to proceed for so long and began paying millions of dollars in compensation to the victims and their heirs. Cat scratch disease Chlamydiosis, lymphogranuloma venereum Atypical pneumonia Pathogenesis and Host Response Brought into direct contact with mucous membranes or abraded skin, T. pallidum binds avidly by its hooked tip to the epithelium. The number of cells required for infection using human volunteers was established at 57 organisms. At the binding site, the spirochete multiplies and penetrates the capillaries within a short time. Once in the general circulation, the pathogen grows in virtually any tissue. Specific factors that account for the virulence of the syphilis spirochete appear to be its outer membrane proteins. It produces no toxins and does not appear to kill cells directly. Studies have shown that phagocytes are active against it and several types of antitreponemal antibodies are formed, but cell-mediated immune responses are unable to contain it. The primary lesion occurs when the spirochetes invade the spaces around arteries and stimulate an inflammatory response. Organs are damaged when granulomas form at these sites and block circulation. Clinical Manifestations Untreated syphilis is marked by distinct clinical stages designated as primary, secondary, and tertiary syphilis. These phases exhibit multiple signs and symptoms, which cause it to “imitate” many other diseases (table 21.1). It also has latent periods of varying duration during which the disease is taL22600_ch21_633-665.indd Page 636 11/12/13 9:13 PM f-w-166 636 /202/MH02004/taL22600_disk1of1/0073522600/taL22600_pagefiles Chapter 21 Miscellaneous Bacterial Agents of Disease TABLE 21.1 Syphilis: Stages, Symptoms, Diagnosis, and Control Stage Average Duration Clinical Setting Diagnosis Treatment Incubation 3 weeks No lesion; treponemes adhere and penetrate the epithelium; after multiplying, they disseminate. Asymptomatic phase Not applicable Primary 2–6 weeks Initial appearance of chancre at inoculation site; intense treponemal activity in body; chancre later disappears. Dark-field microscopy; VDRL, FTA-ABS, MHA-TP testing Benzathine penicillin G, 2 3 106 units; doxycycline Primary latency 2–8 weeks Healed chancre; little scarring; treponemes in blood; few if any symptoms Serological tests (1) As above Secondary 2–6 weeks after chancre leaves Skin, mucous membrane lesions; hair loss; patient highly infectious; fever, lymphadenopathy; symptoms can persist for months. Dark-field testing of lesions; serological tests (1) As above Latency 6 months to 8 or more years Treponemes quiescent unless relapse occurs; lesions can reappear. Seropositive blood test As above Tertiary Variable, up to 20 years Neural, cardiovascular symptoms; gummas develop in organs; seropositivity Treponeme may be demonstrated by DNA analysis of tissue. As above but about 20% occur on the lips, nipples, or fingers or around the anus. Because genital lesions tend to be painless, they may escape notice in some cases. Lymph nodes draining the affected region become enlarged and firm, but systemic symptoms are usually absent. The chancre heals spontaneously without scarring in 3 to 6 weeks, but this healing is deceptive, because the spirochete is entering a period of tremendous systemic activity. Figure 21.2 Primary syphilis lesion: chancre. The chancre is a dense, off-colored patch that ulcerates. Common locations for chancres include the genitals and mouth. quiescent. The spirochete appears in the lesions and blood during the primary and secondary stages and, thus, is communicable at these times. Syphilis is largely noncommunicable during the tertiary stage, though it can be transmitted during early latency. Primary Syphilis The earliest indication of syphilis infection is the appearance of a hard chancre* at the site of inoculation, after an incubation period that varies from 9 days to 3 months (figure 21.2). The chancre begins as a small, red, hard bump that enlarges and breaks down, leaving a shallow crater with firm margins. The base of the chancre beneath the encrusted surface swarms with spirochetes. Most chancres appear on the internal and external genitalia, * chancre (shang9-ker) Fr. for canker; from L. cancer, crab. An injurious sore. Secondary Syphilis About 3 weeks to 6 months (average is 6 weeks) after the chancre heals, the secondary stage appears. By then, many systems of the body have been invaded, and the signs and symptoms are more profuse and intense. Initially, fever, headache, and sore throat occur, followed by lymphadenopathy and a peculiar red or brown rash that breaks out on all skin surfaces, including the palms and the soles (figure 21.3). Like the chancre, the lesions contain viable spirochetes and disappear spontaneously in a few weeks. The major complications, occurring in the bones, hair follicles, joints, liver, eyes, and brain, can linger for months and years. Latency and Tertiary Syphilis After resolution of secondary syphilis, about 30% of infections enter a highly varied latent period that can last for 20 years or longer. Latency is divisible into early and late phases, and though antitreponemal antibodies are readily detected, the spirochete itself is not. The final stage of disease— late, or tertiary, syphilis—is quite rare today because of widespread use of antibiotics to treat other infections. By the time a patient reaches this phase, numerous pathologic complications occur in susceptible tissues and organs. Cardiovascular syphilis is a late complication of the disease. Infection of the small blood vessels that supply blood to the heart and aorta causes constriction and taL22600_ch21_633-665.indd Page 637 11/12/13 9:13 PM f-w-166 /202/MH02004/taL22600_disk1of1/0073522600/taL22600_pagefiles 21.1 The Spirochetes 637 Clinical and Laboratory Diagnosis The pattern of syphilis imposes many complications on diagnosis. Not only do the stages mimic other diseases, but their appearance can be so separated in time as to seem unrelated. The chancre and secondary lesions must be differentiated from various bacterial, fungal, and parasitic infections, tumors, and even allergic reactions. Overlapping symptoms of concurrent, sexually transmitted infections such as gonorrhea or chlamydiosis can further complicate diagnosis. The clinician must Figure 21.3 Symptom of secondary syphilis. The skin rash in secondary syphilis can form on most areas of the body. The rash does not hurt or itch and can persist for months. blockage. In time, compromised circulation to these organs can give rise to heart failure and aortic aneurysms. In one form of tertiary syphilis, painful swollen syphilitic tumors called gummas* develop in tissues such as the liver, skin, bone, and cartilage (figure 21.4). Gummas are usually benign and only occasionally lead to death, but they can impair function. Neurosyphilis can involve any part of the nervous system, but it shows particular affinity for the blood vessels in the brain, cranial nerves, and dorsal roots of the spinal cord. Destruction of parts of the spinal cord can lead to muscle wasting and loss of activity and coordination. Other manifestations include severe headaches, convulsions, mental derangement, atrophy of the optic nerve, blindness, and the Argyll-Robertson pupil reaction. The latter condition typically displays small pupils that do not react to light (figure 21.4). This is perhaps the most common sign still seen today and is caused by adhesions along the inner edge of the iris that fix the pupil’s position into an irregular-shaped circle. Congenital Syphilis Treponema pallidum can pass from a pregnant woman’s circulation into the placenta and can be carried throughout the fetal tissues. An infection leading to congenital syphilis can occur in any of the three trimesters, though it is most common in the second and third. The pathogen inhibits fetal growth and disrupts critical periods of development with varied consequences, ranging from mild to the extremes of spontaneous miscarriage or stillbirth. Early congenital syphilis encompasses the period from birth to 2 years of age and is usually first detected 3 to 8 weeks after birth. Infants often demonstrate such signs as nasal discharge, skin eruptions and loss, bone deformation, and nervous system abnormalities. The late form gives rise to an unusual assortment of stigmata in the bones, eyes, inner ear, and joints, and causes the formation of Hutchinson’s teeth (figure 21.5). The number of congenital syphilis cases is closely tied to the incidence in adults; because it is sometimes not diagnosed, some children sustain lifelong disfiguring disease. * gumma (goo9-mah) L. gummi, gum. A soft tumorous mass containing granuloma tissue. (a) Pupil with an (b) irregular shape Figure 21.4 The pathology of late, or tertiary, syphilis. (a) An ulcerating syphilis tumor, or gumma, appears on the nose of this patient. Other gummas can be internal. (b) The Argyll-Robertson pupil constricts into an irregular-shaped opening, indicating damage to the nerves that control the iris. The iris itself may have prominent areas of discoloration. Figure 21.5 Congenital syphilis. A common characteristic of late congenital syphilis is notched, barrel-shaped teeth (Hutchinson’s teeth). taL22600_ch21_633-665.indd Page 638 11/19/13 4:55 PM f-w-166 638 /202/MH02004/taL22600_disk1of1/0073522600/taL22600_pagefiles Chapter 21 Miscellaneous Bacterial Agents of Disease called the FTA-ABS (fluorescent treponemal antibody absorbance) test. The test serum is first absorbed with treponemal cells and reacted with antihuman globulin antibody labeled with fluorescent dyes. If antibodies to the treponeme are present, the fluorescence on the outside of these cells is highly visible with a fluorescent microscope. Another variant, the T. pallidum immobilization (TPI) test, mixes live syphilis spirochetes with test serum to assay the spirochete’s loss of motility. These tests are highly sensitive and specific and can rule out false-positive results. Children with suspected cases of congenital syphilis may be verified by a Western blot test. Figure 21.6 A bright-field view of Treponema pallidum, highlighted by a special stain. Treponema spirochetes generally display 6-14 coils. weigh presenting symptoms, patient history, and microscopic and serological tests in rendering a definitive diagnosis. Although spirochetes like Treponema do not stain well with traditional dyes, certain special techniques using silver can make them more visible with a bright-field microscope (figure 21.6). A faster and less involved technique for diagnosing primary, early congenital, and, to a lesser extent, secondary syphilis is dark-field microscopy of a suspected lesion (See the Pathogen Profile, page 639). The lesions are gently squeezed or scraped to extract clear serous fluid. A wet mount prepared from the exudate is then observed for the characteristic size, shape, and motility of T. pallidum. A single negative test is insufficient to exclude syphilis, so follow-up tests are recommended. Another microscopic test for discerning the spirochete directly in samples is direct immunofluorescent staining with monoclonal antibodies (see figure 17.3, page 526). Patient samples can also be tested with a DNA probe specific to various spirochete gene sequences. Testing Blood for Syphilis Serological tests are based upon detection of antibody formed in response to T. pallidum infection (see table 21.1). Several of the tests (rapid plasma reagin [RPR], VDRL, Kolmer) are variations on the original test developed by Wasserman using cardiolipin, a natural constituent of many cells, as the antigen. Although anticardiolipin antibodies are not specific for syphilis, the test is an effective way to screen the population for people who may be infected. This includes high-risk groups such as homosexual men, male and female prostitutes, people with other STDs, and pregnant women. With positive results, it is important to detect an elevated antibody titer indicative of active infection and to rule out residual antibodies from a prior cured infection. Because the most common screening tests (RPR and VDRL) are based on reactions to a substance found normally in human tissue, biological false positives can occur, especially in patients with other infections or immunopathologies. A more specific test is needed for those who are suspected of having a false-positive result. Typical of these specific tests is the T. pallidum microhemagglutination assay (MHA-TP), which employs red blood cells that have been coated with treponemal antigen. Agglutination of the cells by serum indicates antitreponemal antibodies and infection. Another standard test is an indirect immunofluorescent method Treatment and Prevention Penicillin G retains its status as a wonder drug in the treatment of all stages and forms of syphilis. It is given parenterally in large doses with benzathine or procaine to maintain a blood level lethal to the treponeme for at least 7 days (see table 21.1). Alternative drugs (tetracycline and doxycycline) are less effective and indicated only if penicillin allergy has been documented. It is important that all patients be monitored for compliance or possible treatment failure. The core of an effective prevention program depends upon detection and treatment of the sexual contacts of syphilitic patients. Public health departments and physicians are charged with the task of questioning patients and tracing their contacts. All individuals identified as being at risk, even if they show no signs of infection, are given immediate prophylactic penicillin in a single, long-acting dose. Protective immunity does arise in humans and in experimentally infected rabbits, which raises the prospect of an effective immunization program in the future. The cloning of treponemal surface antigens using recombinant DNA technology will support development of vaccines and new diagnostic testing methods. Nonsyphilitic Treponematoses The other treponematoses are ancient diseases that closely resemble syphilis in their effects, though they are rarely transmitted sexually or congenitally. These infections, known as bejel, yaws, and pinta, are endemic to certain tropical and subtropical regions of the world. The treponemes that cause these infections are nearly indistinguishable from those of syphilis in morphology and behavior. The diseases are slow and progressive and involve primary, secondary, and tertiary stages. They begin with local invasion by the treponeme into the skin or mucous membranes and its subsequent spread to subcutaneous tissues, bones, and joints. Drug therapy with penicillin, erythromycin, or tetracycline remains the treatment of choice for these treponematoses. Bejel Bejel is also known as endemic syphilis and nonvenereal childhood syphilis. The pathogen, the subspecies T. pallidum endemicum, is harbored by a small reservoir of nomadic and seminomadic people in arid areas of the Middle East and North Africa. It is a chronic, inflammatory childhood disease transmitted by direct contact or shared household utensils and other fomites and is facilitated by minor abrasions or cracks in the skin or a mucous membrane. Often the infection begins as small, moist patches in the oral cavity (figure 21.7a) and spreads to the skin folds of the body and to the palms. taL22600_ch21_633-665.indd Page 639 11/12/13 9:13 PM f-w-166 /202/MH02004/taL22600_disk1of1/0073522600/taL22600_pagefiles 21.1 The Spirochetes 639 Pathogen Profile #1 Treponema pallidum (T. pallidum pallidum) Microscopic Morphology Thin, gram-negative spirochetes. Identified by The slender nature of T. pallidum often makes it invisible in a Gram stain. Wet mounts of fluid taken from suspected syphilitic lesions may be examined with dark-field Darkfield view of T. pallidum microscopy for motile spirochetes. Immunofluorescent staining and DNA probes may also be used to detect the pathogen. Infection may be determined using serological testing to detect antibodies to T. pallidum. Habitat Humans are the only host of T. pallidum. Virulence Factors The hooked tip of the spirochete is responsible for initial binding of the pathogen to epithelial cells. Proteins within the outer membrane of T. pallidum induce an inflammatory response in the host, eventually leading to tissue damage. Primary Infections/Disease Infection with T. pallidum causes syphilis, a sexually transmitted disease. The disease has three distinct stages, separated by periods of latency. Primary syphilis occurs within 3 months of infection and is marked by the formation of a chancre at the site of infection. Secondary syphilis appears a few weeks to several months later and is marked by fever, headache, sore throat, lymphadenopathy, and a red or brown rash that occurs on all skin surfaces. Like chancres, the lesions spontaneously heal after a few weeks. Complications of secondary syphilis may occur in the bones, hair follicles, joints, eyes, liver, and brain and may remain for years. Tertiary syphilis occurs in about 30% of untreated syphilis cases—often many years later—and is marked by the formation of swollen tumors called gummas, along with neural and cardiovascular complications. Congenital syphilis occurs when T. pallidum passes from the circulation of a pregnant woman to the placenta, infecting the fetus and causing a wide variety of symptoms. Control and Treatment Penicillin G is the treatment of choice for syphilis. Control of the disease relies on detection and treatment of sexual contacts of syphilitic patients. The use of condoms reduces but does not eliminate the chance of infection because T. pallidum may infect sites that are not normally protected by a condom. Pinta The names mal del pinto and carate are regional synonyms for pinta, a chronic skin infection caused by T. p. carateum.* Transmission evidently requires several years of close personal contact accompanied by poor hygiene and inadequate health facilities. Even though pinta is not currently widespread, the disease is still found in isolated populations inhabiting the tropical forest and valley regions of Latin America. Infection begins in the skin with a dry, scaly papule reminiscent of psoriasis or leprosy. In time, pigmented secondary macules and blanched tertiary lesions appear. Pinta is not life-threatening, but it often creates scars on the afflicted area. (a) (b) Figure 21.7 Endemic treponematoses. (a) Skin and membrane nodules in a young boy with endemic syphilis (bejel). (b) The clinical appearance of yaws. The bowing of the lower leg is seen in some children with congenital syphilis, and patients with yaws. Yaws Yaws is a West Indian name for a chronic disease known by the regional names bouba, frambesia tropica, and patek. It is endemic to warm, humid, tropical regions of Africa, Asia, and South America. The microbe, subspecies T. pallidum pertenue, is readily spread by direct contact with skin lesions or fomites. Crowded living conditions and poor community or personal hygiene are contributing factors. The earliest sign is a large, abscessed papule called the “mother yaw,” usually on the legs or lower trunk. After the initial lesion has healed, a secondary crop of moist nodular masses develop in the skin, periosteum, and bones but do not penetrate to the viscera (figure 21.7b). Yaws can be prevented by improved hygiene, shielding minor skin injuries from contamination, and surveillance for new cases. Leptospira and Leptospirosis Leptospires are typical spirochetes marked by 12-18 tight, regular, individual coils with a bend or hook at one or both ends (see Case Study figure, page 633). There are only two species in the genus: Leptospira interrogans,* which causes leptospirosis in humans and animals, and L. biflexa, a harmless, free-living saprobe. The two species are serologically, genetically, and physiologically distinct. Leptospira interrogans demonstrates nearly 200 serotypes distributed among various animal groups, which accounts for the extreme variations in leptospirosis among humans. Epidemiology and Transmission of Leptospirosis Leptospirosis is a zoonosis associated with wild animals such as rodents, skunks, raccoons, foxes, and some domesticated animals, * carateum (kar-uh9-tee-um) From carate, the South American name for pinta. * Leptospira interrogans (lep0-toh-spy9-rah in-terr9-oh-ganz) Gr. leptos, slender or delicate, and speira, a coil; interrogans because it has a single hook that makes it look like a question mark. taL22600_ch21_633-665.indd Page 640 11/12/13 9:13 PM f-w-166 640 /202/MH02004/taL22600_disk1of1/0073522600/taL22600_pagefiles Chapter 21 Miscellaneous Bacterial Agents of Disease particularly horses, dogs, cattle, and pigs. Although these reservoirs are distributed throughout the world, the disease is concentrated mainly in the tropics. Leptospires shed in the urine of an infected animal can survive for several months in neutral or alkaline soil or water. Infection occurs almost entirely through contact of skin abrasions or mucous membranes with animal urine or some environmental source containing urine. It is not associated with animal bites, inhalation, or human contact. In the United States, about 100 cases of leptospirosis are reported annually, with about half of the cases occurring in Hawaii. Those most commonly affected include older children and young adults exposed to water polluted with animal urine and soldiers involved in jungle training. Pathology of Leptospirosis and Host Response Leptospirosis proceeds in two phases, and its principal targets are the kidneys, liver, brain, and eyes. During the early, or leptospiremic, phase, the pathogen appears in the blood and cerebrospinal fluid. Symptoms are sudden high fever, chills, headache, muscle aches, conjunctivitis, and vomiting. During the second, or immune, phase, the blood infection is cleared by natural defenses. This period is marked by milder fever, headache due to leptospiral meningitis, and Weil’s syndrome, a cluster of symptoms characterized by kidney invasion, hepatic disease, jaundice, anemia, and neurological disturbances. Long-term disability and even death can result from injury to the kidneys and liver, but they occur primarily with virulent strains and in elderly patients. Diagnosis, Treatment, and Prevention A history of environmental exposure, along with presenting symptoms, can support initial diagnosis of leptospirosis, but definitive diagnosis relies on dark-field microscopy of specimens, Leptospira culture, and serological tests. Because leptospiral infection stimulates a strong humoral response, it is possible to test the patient’s serum for its antibody titer. A fast, specific, and effective test called the macroscopic slide agglutination test is most often employed for routine screening. Live or formalinized L. interrogans is mixed with the patient’s serum and observed for agglutination or lysis with a dark-field microscope. Early treatment with penicillin or doxycycline rapidly reduces symptoms and shortens the course of disease, but delayed therapy is less effective. Strain-specific vaccines made from killed cells are available for humans, dogs, and cattle, but these can confer protection only to a specific endemic strain. Vaccination is aimed at those with greatest risk such as combat troops training in jungle regions and animal care and livestock workers. The best controls are to wear protective footwear and clothing and to avoid swimming or wading in natural waters used by animals. Borrelia: Arthropod-Borne Spirochetes Members of the genus Borrelia* are morphologically distinct from other pathogenic spirochetes. They are comparatively larger, ranging from 0.2 to 0.5 mm in width and from 10 to 20 mm in length, and they contain 3 to 10 irregularly spaced and loose coils (see figure 21.1b) * Borrelia (boh-ree9-lee-ah) Named after Amédé Borrel, a French bacteriologist. with an abundance (30–40) of periplasmic flagella. The nutritional requirements of Borrelia are so complex that the bacterium can be grown artificially only on specially formulated media. Human infections with Borrelia, termed borrelioses, are all transmitted by some type of arthropod vector, usually ticks or lice. The two most important human diseases are relapsing fever and Lyme disease. Epidemiology of Relapsing Fever Borrelia hermsii, the cause of tick-borne relapsing fever, is carried by soft ticks of the genus Ornithodoros. The mammalian reservoirs of this zoonosis are squirrels, chipmunks, and other wild rodents, and the human is generally an accidental host. The spirochetes mature and persist in the salivary glands and intestines of the tick. As a result, both the bite itself and attempts to scratch it can initiate infection. Tick-borne relapsing fever occurs sporadically in the United States, usually in campers, backpackers, and forestry personnel who frequent the higher elevations of western states. The incidence of infection is higher in endemic areas of the tropics, especially where rodents have easy access to dwellings. Epidemics of louse-borne relapsing fever occur whenever famine, war, or natural disasters are coupled with poor hygiene, crowding, and inadequate medical attention. Such conditions favor the survival and spread of the louse vector Pediculus humanus, which harbors the spirochete B. recurrentis in its body cavity. A host is infected when lice are smashed and scratched into a wound or the skin. Louse-borne fever is most common in parts of China, Afghanistan, and Africa. Pathogenesis and the Nature of Relapses The pathologic manifestations are similar in tick- and louse-borne relapsing fever. After a 2- to 15-day incubation period, patients experience the abrupt onset of high fever, shaking chills, headache, and fatigue. Later features of the disease include nausea, vomiting, muscle aches, and abdominal pain. Extensive damage to the liver, spleen, heart, kidneys, and cranial nerves occurs in many cases. Half of the patients hemorrhage profusely into organs, and some develop a rash on the shoulders, trunk, and legs. Untreated cases are often lengthy and debilitating and may have a 40% mortality rate. As the name relapsing fever indicates, the fever follows a fluctuating course that is explained by changes in the spirochete and the attempts of the immune system to control it (figure 21.8). Borrelia have adopted a remarkable strategy for evading the immune system and avoiding destruction. They change surface antigens during growth, so that, in time, the antibodies formed against the earlier antigens lose effectiveness. Cells in the new antigen phase survive, multiply, and cause a second wave of symptoms. In time, the immune system forms new antibodies, but it is soon challenged with yet another antigenic phase. A single strain has been known to generate 24 distinct serological types. Eventually, cumulative immunity against the variety of antigens develops, and complete recovery can occur. Diagnosis, Treatment, and Prevention A patient’s history of exposure, clinical symptoms, and the presence of Borrelia in stained blood smears are very definitive evidence of borreliosis. Except for pregnant women and young children, doxycycline or tetracycline is the treatment of choice, with erythromycin serving taL22600_ch21_633-665.indd Page 641 11/12/13 9:13 PM f-w-166 /202/MH02004/taL22600_disk1of1/0073522600/taL22600_pagefiles 21.1 641 The Spirochetes 21.1 MAKING CONNECTIONS The Disease Named for a Town In the 1970s, an enigmatic cluster of arthritis cases appeared in the town and surrounding suburbs of Old Lyme, Connecticut. This phenomenon caught the attention of nonprofessionals and professionals alike, whose persistence and detective work ultimately disclosed the unusual nature and epidemiology of Lyme disease. The process of discovery began in the home of Polly Murray, who, along with her family, was beset for years by recurrent bouts of stiff neck, swollen joints, malaise, and fatigue that seemed vaguely to follow a rash from tick bites. When Mrs. Murray’s son was diagnosed as having juvenile rheumatoid arthritis, she became skeptical. Conducting her own literature research, she began to discover inconsistencies. Rheumatoid arthritis was described as a rare, noninfectious disease, yet over an 8-year period, she found that 30 of her neighbors had experienced similar illnesses. Eventually, this cluster of cases and several others were reported to state health authorities. (1) Primary infection induces high fever. The reports caught the attention of Dr. Allen Steere, a rheumatologist with a Centers for Disease Control and Prevention (CDC) background. He was able to forge the vital link between the case histories, the disease symptoms, and the presence of unique spirochetes in ticks preserved by some of the patients. These same spirochetes had been previously characterized in 1981 by Dr. Willy Burgdorfer, though he did not realize their importance at the time. In the years since Lyme disease was formally characterized, retrospective studies showed that this is not really a new disease and was first reported in Europe at the turn of the twentieth century. Recent PCR analysis of tick museum specimens from 50 years ago documents the presence of Borrelia burgdorferi. It is now thought that Lyme disease has been present in North America for centuries. Explain why an infection such as Lyme disease mimics other noninfectious diseases. Answer available at http://www.mhhe.com/talaro9 (2) Initial antibody response at first reduces fever. (3) Reinfection by mutant Borrelia causes a relapse of fever. (1) (4) The immune reaction to second antigen slows symptoms for a time. (5) New antigenic form causes another relapse. (3) (6) Antibody response again reduces symptoms of infection, followed by relapse. (5) 106 Figure 21.8 The pattern in relapsing fever, based on symptoms (fever) over time. The antigen phase changes can continue for several more days. 98 Third antibody response (2) Third antigenic challenge Second antibody response 100 Second antigenic challenge 102 First antibody response 104 First antigenic challenge Body Temperature °F Variable (4) (6) Normal temperature 1 2 4 6 as an alternative. Because vaccines are not available, prevention of relapsing fever is dependent upon controlling rodents and avoiding tick bites. Louse-borne relapsing fever can be controlled with improved hygiene. Borrelia burgdorferi and Lyme Disease Lyme disease, the most prominent borreliosis in the United States (21.1 Making Connections), is caused by Borrelia burgdorferi* * burgdorferi (berg-dor9-fer-eye) Named for its discoverer, Dr. Willy Burgdorfer. 8 10 12 Days 14 16 18 20 22 24 and is transmitted primarily by hard ticks of the genus Ixodes. In the northeastern part of the United States, Ixodes scapularis (the black-legged deer tick) passes through a complex 2-year cycle that involves two principal hosts (figure 21.9). The larva or nymph stage feeds on the white-footed mouse, where it picks up the infectious agent. The nymph is relatively nonspecific and will try to feed on nearly any type of vertebrate; thus, it is the form most likely to bite humans. The adult tick reproductive phase of the cycle is completed on deer. In California, the transmission cycle involves Ixodes pacificus and the dusky-footed woodrat reservoir. taL22600_ch21_633-665.indd Page 642 11/12/13 9:13 PM f-w-166 642 /202/MH02004/taL22600_disk1of1/0073522600/taL22600_pagefiles Chapter 21 Miscellaneous Bacterial Agents of Disease 2. In the second year the larvae molt into the nymph, an aggressive feeding stage. 2 lopment deve e t le mp Co Infected nymph (b) Actual size of tick stages 3 Infected larval tick Human (accidental host) Second year First year 3. The nymph takes blood from a number of hosts, including deer and humans. Borrelia spirochetes Mouse infected with Borrelia burgdorferi Deer 1 Larval tick 1. Newly hatched larvae become infected when they feed on small animals such as mice, which harbor the spirochete. The larvae continue development through this year. E ggs h atc h Adult ticks 4 (a) 4. On deer, the nymphs mature into adult male and female ticks, which mate. The female lays eggs in plant litter, where they hatch and once again begin the cycle. (c) Figure 21.9 The cycle of Lyme disease in the northeastern United States. (a) The disease is tied intimately into the life cycle of a tick vector, which generally is completed over a 2-year period. The exact hosts and species of tick vary from region to region but still display this basic pattern. (b) Black-legged ticks, lxodes scapularis, transmit Lyme disease to humans and animals during feeding. (c) About 80% of Lyme disease cases present with erythema migrans, a red, often bull’s-eye-shaped rash surrounding the initial infection site. The incidence of Lyme disease is showing a gradual upward trend from about 10,000 cases per year in 1991 to around 27,000 in 2012. This increase may be partly due to improved diagnosis, but it also reflects changes in the numbers of hosts and vectors. The greatest concentrations of Lyme disease are in areas having high mouse and deer populations. Most of the cases have occurred in New York, Pennsylvania, Connecticut, New Jersey, Rhode Island, and Maryland, though the number in the Midwest and West is growing. Highest-risk groups include hikers, backpackers, and people living in newly developed communities near woodlands and forests. Peak seasons are the summer and early fall. Lyme disease is nonfatal but often evolves into a slowly progressive syndrome that mimics neuromuscular and rheumatoid conditions. An early symptom in 50% to 70% of cases is a rash at the site of a larval tick bite. The lesion, called erythema migrans, can appear something like a bull’s-eye, with a raised erythematous ring that gradually spreads outward and a pale central region (see figure 21.9c). In other cases, it may be a series of red papules or a spotty rash. Other early symptoms are fever, headache, stiff neck, and dizziness. If not treated or if treated too late, the disease can advance to the second stage, during which cardiac and neurological symptoms (facial palsy) develop. After several weeks or months, a crippling polyarthritis can attack joints, especially in the European strain of the agent. Some people acquire chronic neurological complications that are severely disabling. Diagnosis of Lyme disease can be difficult because of the range of symptoms it presents. Most suggestive are the ring-shaped lesions, isolation of spirochetes from the patient, and early serological testing with an ELISA method that tracks a rising antibody titer (see Clinical Connections, page 533). Tests for spirochetal DNA in specimens is especially helpful for late-stage diagnosis. Early treatment with doxycycline or amoxicillin is effective, and other antibiotics such as ceftriaxone and azithromycin are used in late Lyme disease therapy. Because dogs can also acquire the disease, a vaccine has been marketed to protect them. A human vaccine for high-risk populations has been discontinued due to lack of sales over fear of side effects. Anyone involved in outdoor activities should wear protective clothing, boots, leggings, and insect repellent containing taL22600_ch21_633-665.indd Page 643 11/12/13 9:13 PM f-w-166 /202/MH02004/taL22600_disk1of1/0073522600/taL22600_pagefiles 21.2 Curviform Gram-Negative Bacteria and Enteric Diseases 643 DEET.* Individuals exposed to heavy infestation should routinely inspect their bodies for ticks and remove ticks gently without crushing, preferably with forceps or fingers protected with gloves, because it is possible to become infected by tick feces or body fluids. Check Your Progress SECTION 21.1 1. Construct a table comparing the symptoms of primary, secondary, and tertiary syphilis. 2. How is syphilis diagnosed? 3. Besides syphilis, what other diseases are caused by bacteria in the genus Treponema? 4. List several behaviors that would put one at risk for infection with Leptospira or Borrelia and explain why. 21.2 Curviform Gram-Negative Bacteria and Enteric Diseases Expected Learning Outcomes 6. Relate the physical characteristics seen in the three groups of curviform bacteria. 7. Understand the pathogenesis of cholera. 8. Name the usual source of infection for each genus of commonly acquired curviform bacteria. 9. Explain the adaptations present in Helicobacter that help the pathogen survive in the stomach. Three groups of curviform bacteria are represented by the following families, genera, and characteristics: Vibrionaceae Vibrio* Comma-shaped rods with one flagellum Campylobacteraceae Campylobacter* Short spirals or curved rods with one flagellum Helicobacteraceae Helicobacter* Tight spirals and curved rods with several polar flagella Many of the pathogens in these groups share adaptations to survival in the often inhospitable environment of the intestine. They readily move within the mucous coating and avoid being swept away by intestinal motility. Species of Helicobacter are uniquely adapted to survival in the stomach with its high acid content. The Biology of Vibrio cholerae The most prominent species of pathogenic vibrios is Vibrio cholerae,* the cause of cholera. A freshly isolated specimen reveals quick, darting cells slightly resembling a wiener or a comma (figure 21.10). Vibrio shares many cultural and physiological characteristics with * N-diethyl-m-toluamide The active ingredient in OFF! and Cutter repellents. * Vibrio (vib9-ree-oh) L. vibrare, to shake. * Campylobacter (kam0-pih-loh-bak9-ter) Gr. campylo, curved, and bacter, rod. * Helicobacter (hee0-lih-koh-bak9-ter) Gr. helicos, a coil. * cholerae (kol9-ur-ee) Gr. chole, bile. The bacterium was once named V. comma for its comma-shaped morphology. Figure 21.10 The agent of cholera. Vibrio cholerae, showing its characteristic curved shape and single polar flagellum (2,5003). members of the Enterobacteriaceae, a closely related family. They are fermentative and grow on ordinary or selective media containing bile at 378C. They possess unique O (somatic) antigens, H (flagella) antigens, and membrane receptor antigens that provide some basis for classifying members of the family. Epidemiology of Cholera Epidemic cholera, or Asiatic cholera, has been a devastating disease for centuries. Although the human intestinal tract was once thought to be the primary reservoir, it is now known that the pathogen is free-living in certain endemic regions. The pattern of cholera transmission and the onset of epidemics are greatly influenced by the season of the year and the climate. Cold, acidic, dry environments inhibit the migration and survival of Vibrio, whereas warm, monsoon, alkaline, and saline conditions favor them. The disease has persisted in a pandemic pattern since 1961, when the El Tor biotype began to prevail worldwide. This strain survives longer in the environment, infects a higher number of people, and is more likely to be chronically carried than any other strain. One of the worst epidemics in recent history started shortly after the 2010 earthquake in Haiti and continues to the present time. As of late 2013, the WHO has reported 670,000 cases and 8,300 deaths, most of which were probably preventable. The overwhelming disruption to vital services and santitation greatly complicated control measures. It ranks among the top seven causes of morbidity and mortality, affecting several million people in endemic regions of Asia and Africa. In nonendemic areas such as the United States, the microbe is spread by water and food contaminated by asymptomatic carriers, but it is relatively uncommon. Sporadic outbreaks occasionally occur along the Gulf of Mexico, and the cholera vibrio is sometimes isolated from shellfish in this region. Pathogenesis of Cholera: Toxigenic Diarrhea After being ingested with food or water, V. cholerae must pass through the acid environment of the stomach. To compensate, the size of the infectious dose is quite high (108 cells). The dose may be reduced by certain types of food that can more readily shelter the pathogen. At the mucosa of the duodenum and jejunum, the vibrios penetrate the mucous barrier and come to rest near the surface of the epithelial cells. The cholera vibrio is strictly an epipathogen that does not enter cells or deeper tissues. The virulence is due entirely to an enterotoxin called cholera toxin (CT) that disrupts the normal physiology of intestinal cells. When this toxin binds to specific intestinal receptors, a secondary signaling system is activated. Under taL22600_ch21_633-665.indd Page 644 11/12/13 9:13 PM f-w-166 644 /202/MH02004/taL22600_disk1of1/0073522600/taL22600_pagefiles Chapter 21 Miscellaneous Bacterial Agents of Disease Intestinal lumen Cl⫺ HCO3⫺ Na⫹ K⫹ H2O severe cases, and an untreated patient can lose up to 50% of body weight during the course of the disease. The diarrhea causes reduced blood volume, acidosis from bicarbonate loss, and potassium depletion. These conditions predispose the patient to muscle cramps, severe thirst, flaccid skin, and sunken eyes and, in young children, coma and convulsions. Secondary circulatory consequences can include hypotension, tachycardia, cyanosis, and collapse from shock within 18 to 24 hours. If cholera is left untreated, death can occur in less than 48 hours, and the mortality rate approaches 55%. Blood vessel Intestinal lumen the influence of this system, the cells shed large amounts of electrolytes into the intestine, an event that is accompanied by profuse water loss (figure 21.11). Most cases of cholera are mild or selflimited, but in children and weakened individuals, the disease can strike rapidly and violently. After an incubation period of a few hours to a few days, symptoms begin abruptly with vomiting, followed by copious watery feces called secretory diarrhea. This voided fluid contains flecks of tissue debris, hence the description “rice-water stool.” Fluid losses of nearly 1 liter per hour have been reported in Cl⫺ H2O HCO3⫺ H 2O Na⫹ K⫹ H2O Intestinal cell (a) Normal (b) Cholera 1 The Vibrio cholerae cell comes to rest in the protective mucous coating near the cell surface and secretes the cholera toxin. Vibrio cholerae 2 The toxin has an affinity for specialized receptors on the glycocalyx and binds there. Cell membrane 3 The active portion of the toxin is released, is transported through the membrane, and enters the cytoplasm. 4 It becomes a signal in a system that converts inactive adenyl cyclase into an active state. 5 This enzyme converts ATP into a molecule called cyclic AMP (cAMP). The cAMP is used by the cell to control a major membrane pump for negative ions. 6 The result is that the membrane begins to actively pump Cl⫺ and HCO3⫺ into the intestinal lumen. One additional effect of the toxin is that it overrides the usual controls for the adenyl cyclase/cAMP system so that the cell continues to pump out these ions for an extended time. 7 Positive ions (Na⫹ and K⫹) follow the anions and are also lost into the intestinal fluid, along with large amounts of water, causing secretory diarrhea and dehydration. Glycocalyx 1 Adenyl cyclase, inactive 4 2 3 Cholera toxin molecules Adenyl cyclase, active ⫹ Membrane pump ⫺ HCO3 Cl⫺ Na⫹, K⫹ HCO3⫺ Cl⫺ 6 ATP 5 Cyclic AMP Na⫹, K⫹ 7 H2O H2O (c) Process Figure 21.11 Alterations in intestinal function caused by cholera toxin. (a) Normal actions of intestinal absorption. (b) General actions of cholera toxin on electrolytes and water. (c) Magnified view of intestinal cell reacting to cholera toxin. taL22600_ch21_633-665.indd Page 645 11/12/13 9:13 PM f-w-166 /202/MH02004/taL22600_disk1of1/0073522600/taL22600_pagefiles 21.2 Curviform Gram-Negative Bacteria and Enteric Diseases 645 21.2 MAKING CONNECTIONS Oral Rehydration Therapy Drinking a simple sugar-salt mixture is often a miracle cure for cholera. This solution, developed by the World Health Organization and termed oral rehydration therapy (ORT), consists of a mixture of sodium chloride, sodium bicarbonate, potassium chloride, and glucose or sucrose dissolved in water (table 21.A). When administered early in amounts ranging from 100 to 400 ml/hour, the solution can restore patients in 4 hours, literally bringing them back from the brink of death. It works even if the individual has diarrhea, because the particular combination of ingredients is well tolerated and rapidly absorbed. Infants and small children who once would have died now survive so often that the mortality rate for treated cases of cholera is near zero. This therapy has several advantages, especially for countries with few resources. It does not require medical facilities, high-technology equipment, or complex medication protocols. It is also inexpensive, noninvasive, fast-acting, and useful for a number of diarrheal diseases besides cholera. How could one put this solution together from everyday kitchen supplies? Answer available at http://www.mhhe.com/talaro9 TABLE 21.A Recommendations for Oral Rehydration Therapy (ORT) Standard Composition of Oral Rehydration Solution (ORS) NaCl NaHCO3 KCl Glucose* Grams per Liter (g/l) 3.5 g/l 2.5 g/l 1.5 g/l 20 g/l Concentration in Millimoles 90 (Na) 80 (Cl) 30 (HCO3) 20 (K) 111 Guidelines for Preparation and Treatment • Components are dissolved in 1 liter of water that has been boiled to disinfect it. It is thoroughly mixed and tasted for saltiness. It should be only slightly salty. This product is similar to a commercial product called Pedialyte or Oralyte. • Moderately dehydrated children and adults should receive frequent small amounts of ORS at the rate of 4 to 8 ounces per hour over 6 hours. Plain water can be administered in between ORS administrations. • To check the patient for the return of normal hydration, test the skin turgor (pinch it to see if a fold remains), and observe whether the eyes are still sunken. *Sucrose or rice powder may be substituted if glucose is not available. Diagnosis and Remedial Measures During epidemics, clinical evidence is usually sufficient to diagnose cholera. But confirmation of the disease is often required for epidemiological studies and detection of sporadic cases. Vibrio cholerae can be readily isolated and identified in the laboratory from stool samples. Direct dark-field microscopic observation reveals characteristic curved cells with brisk, darting motility as confirmatory evidence. Immobilization or fluorescent staining of feces with group-specific antisera is supportive as well. Difficult or elusive cases can be traced by detecting a rising antitoxin titer in the serum. The key to cholera therapy is prompt replacement of water and electrolytes. This can be accomplished by various rehydration techniques that replace the lost fluid and electrolytes (oral rehydration therapy [ORT]; 21.2 Making Connections). Cases in which the patient is unconscious or has complications from severe dehydration require intravenous replenishment as well. Oral antibiotics such as doxycycline and drugs such as trimethoprim/ sulfamethoxazole can terminate the diarrhea in 48 hours, and they also promote recovery and diminish the period of vibrio excretion. Effective prevention is contingent upon proper sewage disposal and water purification. Detecting and treating carriers with mild or asymptomatic cholera are serious goals but ones that are frequently difficult to attain because of inadequate medical provisions in those countries where cholera is endemic. Vaccines are available for travelers and people living in endemic regions. Both are whole-cell killed vaccines that provide limited protection for about 2 years. The World Health Organization (WHO) recommends immunization in endemic areas, while long-term improvements to water quality and sanitation are undertaken. Vibrio parahaemolyticus and Vibrio vulnificus: Pathogens Carried by Seafood Two pathogenic relatives of V. cholerae share its morphology, physiology, and ecological adaptation. Vibrio parahaemolyticus and V. vulnificus are both salt-tolerant inhabitants of coastal waters and associate with marine invertebrates. In temperate zones, vibrios survive over the winter by settling into the ocean sediment; when resuspended by upwelling during the warmer seasons, they become incorporated into the food web, eventually growing on fish, shellfish, and other edible seafood. Features of V. parahaemolyticus Gastroenteritis Vibrio parahaemolyticus infection, an acute form of gastroenteritis, was first described in Japan more than 30 years ago. The great majority of cases appear in individuals who have eaten raw, partially cooked, or poorly stored seafood. The vehicles most often implicated are squid, mackerel, sardines, crabs, tuna, shrimp, oysters, and clams. Outbreaks tend to be concentrated along coastal regions during the summer and early fall. The incubation period of nearly 24 hours is followed by explosive, watery diarrhea accompanied by nausea, vomiting, abdominal cramps, and sometimes fever. Vibrio toxins cause symptoms that last about 72 hours but can persist for 10 days. taL22600_ch21_633-665.indd Page 646 11/12/13 9:13 PM f-w-166 646 /202/MH02004/taL22600_disk1of1/0073522600/taL22600_pagefiles Chapter 21 Miscellaneous Bacterial Agents of Disease Food infection caused by V. vulnificus is similar in symptoms to that caused by V. parahaemolyticus. It is most often associated with ingesting raw oysters and can have a much more severe outcome in critically ill patients with diabetes or liver disease. It is the leading cause of death from food-borne illness in some areas. Treatment of severe gastroenteritis can require fluid and electrolyte replacement and occasionally antibiotics. Control measures aim to keep the bacterial count in all seafood below the infective dose by continuous refrigeration during transport and storage, sufficient cooking temperatures, and prompt serving. Consumers of raw oysters (or other shellfish) should understand their possible risk. In some regions, the U.S. Department of Agriculture mandates that health warnings be posted about this danger in markets and restaurants. Review the Case Study on page 521 for information on the identification of Vibrio species. Diseases of the Campylobacter Vibrios Campylobacters are curved or spiral bacilli, often appearing in S-shaped or gull-winged pairs (figure 21.12). Their polar flagellum imparts active spinning motility. Their physiological profile includes being microaerophilic, oxidase-positive, and nonfermenting. These bacteria are common residents of the intestinal tract, genitourinary tract, and oral cavity of birds and mammals. Species of Campylobacter most significant in medical and veterinary practice are C. jejuni and C. fetus. Campylobacter jejuni Enteritis Campylobacter jejuni* has emerged as a pathogen of such imposing proportions that it is considered one of the most important causes of bacterial gastroenteritis worldwide (see Pathogen Profile #2). In the United States, approximately 1.3 million cases occur every year. Epidemiological and pathologic studies have shown that this * jejuni (jee-joo9-nye) L. jejunum. The small section of intestine between the duodenum and the ileum. S species is a primary pathogen transmitted through contaminated beverages and food, especially water, milk, meat, and chicken. Ingested C. jejuni cells travel to the mucosa at the last segment of the small intestine (ileum) near its junction with the colon. They adhere, burrow through the mucus, and are taken in by intestinal cells. The pathogen disrupts the cytoskeleton, damages the epithelium, and penetrates the intestinal wall. After an incubation period of 1 to 7 days, acute symptoms of headache, fever, abdominal pain, and bloody or watery diarrhea develop. The mechanisms of pathology involve a heat-labile enterotoxin called CJT that stimulates secretory diarrhea like cholera. An occasional sequela of this infection is the development of a neurological disease called Guillain-Barré syndrome. Diagnosis of C. jejuni enteritis is usually made with fecal samples and occasionally blood samples. This species is microaerophilic and thermophilic, and isolation requires special culturing media. It can be grown on CCD medium held in reduced oxygen chambers. More rapid presumptive diagnosis can be obtained from examination of feces with a dark-field microscope, which accentuates the characteristic curved rods and darting motility. Resolution of infection occurs in most instances with rehydration and electrolyte balance therapy. In more severely affected patients, it may be necessary to administer erythromycin or ciprofloxacin. Because vaccines are yet to be developed, prevention depends upon rigid sanitary control of water and milk supplies and care in food preparation. Traditionally of interest to the veterinarian, C. fetus (subspecies venerealis) causes a sexually transmitted disease of sheep, cattle, and goats. Its role as an agent of abortion in these animals has considerable economic impact on the livestock industry. About 40 years ago, the significance of C. fetus as a human pathogen was first uncovered, though its exact mode of transmission in humans is yet to be clarified. This bacterium appears to be an opportunistic pathogen that attacks debilitated persons or women late in pregnancy. Diseases to which C. fetus has been linked are meningitis, pneumonia, arthritis, septicemic infection in the newborn, and occasionally, sexually transmitted proctitis in adults. Helicobacter pylori: Gastric Pathogen Comma Spiral Figure 21.12 Scanning micrograph of Campylobacter jejuni, showing comma, S, and spiral forms (750X). Although the human stomach is too harsh for most bacteria, it serves as a primary habitat for an unusual spiral bacterium, Helicobacter pylori. Like Campylobacter, it is microaerophilic and oxidative, but it differs in having multiple sheathed polar flagella. Not only does it thrive in the acidic environment, but evidence has clearly linked it to a variety of gastrointestinal ailments. It is known to cause an inflammation of the stomach lining called gastritis and is implicated in 90% of stomach and duodenal ulcers. It is also an apparent cofactor in the development of a common type of stomach cancer called adenocarcinoma. This novel pathogen was first detected by J. Robin Warren in 1979 in stomach biopsies from ulcer patients. He and an assistant, Barry J. Marshall, isolated the microbe in culture and even tested its effects by swallowing a good-sized inoculum. Both developed a short-term case of gastritis. For their extraordinary discovery of this microbe and its connection to gastric diseases, the two scientists were awarded a Nobel Prize in 2005. Continued research has revealed that the bacterium is present in a large proportion of people. It occurs in the stomachs of 25% of taL22600_ch21_633-665.indd Page 647 11/12/13 9:13 PM f-w-166 /202/MH02004/taL22600_disk1of1/0073522600/taL22600_pagefiles 21.2 Curviform Gram-Negative Bacteria and Enteric Diseases 647 Pathogen Profile #2 Campylobacter jejuni Microscopic Morphology Small, curved, gram-negative rods. Identified by Dark-field examination of stool samples, revealing curved cells with a darting motility provides presumptive identification. Positive identification requires culturing the pathogen on specialized media under conditions of low oxygen concentration. Habitat C. jejuni is a common resident of the intestinal tract, genitourinary tract, and oral cavity of birds and mammals. Virulence Factors The primary virulence factor in C. jejuni is CJT, a heat-labile enterotoxin that stimulates secretory diarrhea. Primary Infections/Disease C. jejuni is one of the most important causes of gastroenteritis, with over 1.3 million cases of the disease healthy middle-aged adults and in more than 50% of adults over 60 years of age. Helicobacter pylori is probably transmitted from person to person by the oral-oral or oral-fecal route. It can also be spread by houseflies acting as mechanical vectors. It seems to be acquired early in life and carried asymptomatically until its activities begin to damage the digestive mucosa. Because other animals are also susceptible to H. pylori and even develop chronic gastritis, it has been proposed that the disease is a zoonosis transmitted from an animal reservoir. Several other species of this genus have been isolated from cats, dogs, and other mammals. Other studies have helped to explain how the pathogen takes up residence in the gastrointestinal tract. First, it bores through the outermost mucus that lines the epithelial tissue. Then it attaches to specific binding sites on the cells and entrenches itself (figure 21.13). It turns out that one receptor specific for Helicobacter is the same receptor as type O blood, which accounts for the higher rate of ulcers in people with this blood type (1.5–2 times). Another protective adaptation is the formation of urease, an enzyme that converts urea into ammonium and bicarbonate, both alkaline compounds that can neutralize stomach acid. As the immune system recognizes and attacks the pathogen, certain white blood cells damage the epithelium to some degree, leading to chronic active gastritis. In some people, these lesions lead to deeper erosions and ulcers and, eventually, can lay the groundwork for cancer to develop. Helicobacter pylori is isolated primarily from biopsy specimens. Serological detection of H. pylori antigens in the stool has become a favored diagnostic test as it is noninvasive and has a high degree of sensitivity. Understanding the underlying pathology has useful applications in treatment. Gastritis and ulcers have traditionally been treated with drugs (cimetidine [Tagamet], ranitidine [Zantac]) that suppress symptoms by slowing the secretion of acid in the stomach. They must be taken continuously for indefinite periods, and relapses are common. Current recommended therapy is 2 to 4 weeks of clarithromycin to eliminate the bacterial infection, along with stomach acid inhibitors. This regimen can actually cure the infection and eliminate symptoms. occurring every year in the United States. Common symptoms include fever, diarrhea, and abdominal pain within 2 to 5 days after exposure to the organism. Illness typically lasts about 1 week and is self-limiting, although it is estimated that C. jejuni is responsible for about 75 deaths annually in the United States, mostly among people with compromised immune systems. Control and Treatment Prevention depends on proper sanitary control of water and milk supplies, along with care in food harvesting and preparation. Rehydration therapy is usually adequate to resolve infection, whereas antibiotics—erythromycin or ciprofloxacin—may be necessary in more severe cases. Stomach mucosa Helicobacter cells Figure 21.13 The causative agent of stomach ulcers. Colorized scanning electron microscope view of Helicobacter pylori nestled into the stomach lining. Characteristics include loose, shallow coils and a rough surface (2,5003). Check Your Progress SECTION 21.2 5. How could one differentiate the genera Vibrio, Campylobacter, and Helicobacter? 6. Relate the successful use of oral rehydration therapy to the pathogenesis of cholera. 7. Which two species of curviform bacteria are associated with consumption of seafood? 8. Briefly describe the nature of food infection in species of Vibrio and the diseases of Campylobacter. 9. What diseases involve Helicobacter pylori infection? taL22600_ch21_633-665.indd Page 648 11/12/13 9:13 PM f-w-166 648 /202/MH02004/taL22600_disk1of1/0073522600/taL22600_pagefiles Chapter 21 Miscellaneous Bacterial Agents of Disease 21.3 Medically Important Bacteria of Unique Morphology and Biology Expected Learning Outcomes 10. Recall the characteristics seen in the Rickettsia that make them unique. 11. Understand the epidemiology and pathology of Rocky Mountain spotted fever. 12. Name the human pathogens within the genera Ehrlichia and Anaplasma and the diseases they cause. 13. Recognize behaviors or activities that would increase the risk of contracting Q fever. 14. Recall the body systems commonly affected by species in the genus Chlamydia. 15. Recall the names and characteristics of diseases attributable to infection with Chlamydophila species. Pathogenic bacteria that exhibit atypical morphology, physiology, and behavior include: (1) rickettsias and (2) chlamydias, obligately parasitic gram-negative coccobacilli, and (3) mycoplasmas, highly pleomorphic bacteria that lack cell walls (see figure 21.24). The three groups are not closely related but are included together because of similar morphology and pathogenicity. Order Rickettsiales The Order Rickettsiales contains about two dozen species of pathogens, mostly in the genus Rickettsia.* Other members include Ehrlichia,* Anaplasma, and the recently renamed Orientia (formerly Rickettsia). These organisms are known commonly as rickettsias, or rickettsiae, and the diseases they cause are called rickettsioses. The rickettsias are all obligate to their host cells and require live cells for cultivation; they also spend part of their life cycle in the bodies of arthropods, which serve as vectors. Rickettsioses are among the most important emerging diseases. Six of the 14 recognized diseases have been identified in the last 20 years. Morphological and Physiological Distinctions of Rickettsias Rickettsias possess a gram-negative cell wall, binary fission, metabolic pathways for synthesis and growth, and both DNA and RNA. They are among the smallest cells, ranging from 0.3 to 0.6 mm wide and from 0.8 to 2.0 mm long. They are nonmotile pleomorphic rods or coccobacilli (figure 21.14). The precise nutritional requirements of the rickettsias have been difficult to demonstrate because of a close association with host cell metabolism. Their obligate parasitism originates from an inability to metabolize AMP, an important precursor to ADP and ATP, which they must obtain from the host. Rickettsias are generally sensitive to environmental exposure, although R. typhi can survive several years in dried flea droppings. * Rickettsia (rik9-ett9-see-ah) After Howard Ricketts, an American bacteriologist who worked extensively with this group. * Ehrlichia (ur-lik9-ee-ah) After Paul Ehrlich, a German immunologist. (a) (b) Figure 21.14 The morphology of Rickettsia. (a) Several features, including the cell wall (CW), cell membrane (CM), chromatin granules (CG), and mesosome (IM), identify these as tiny, pleomorphic, gram-negative bacteria (185,0003). (b) View of rickettsias budding off the surface of a mouse tissue culture cell. Distribution and Ecology of Rickettsial Diseases The Role of Arthropod Vectors The rickettsial life cycle depends upon a complex exchange between blood-sucking arthropod1 hosts and vertebrate hosts (see section 23.8). Eight tick genera, two fleas, and one louse are involved in the spread of rickettsias to humans. Humans accidently enter the zoonotic life cycles through occupational contact with the animals except in the cases of louseborne typhus and trench fever. Most vectors apparently harbor rickettsias with no ill effect, but others, like the human body louse, die from typhus infection and do not continuously harbor the pathogen. In certain vectors (Rocky Mountain spotted fever ticks), rickettsias are transferred to offspring by the eggs of an infected female. Such continuous inheritance of the microbe through multiple generations of ticks creates a long-standing reservoir. These arthropods feed on the blood or tissue fluids of their mammalian hosts, but not all of them transmit the rickettsial pathogen through direct inoculation with saliva. Ticks directly inoculate the skin lesion from their mouths, but fleas and lice harbor the infectious agents in their intestinal tracts. During their stay on the host’s body, these latter insects defecate or are smashed, thereby releasing the rickettsias onto the skin or into a wound. Ironically, scratching the bite helps the pathogen invade deeper tissues. General Factors in Rickettsial Pathology and Isolation A common target in rickettsial infections is the endothelial lining of the small blood vessels. The bacteria recognize, enter, and multiply within endothelial cells, causing necrosis of the vascular lining. Among the immediate pathologic consequences are vasculitis, perivascular infiltration by inflammatory cells, vascular leakage, and thrombosis. These pathologic effects are manifested by skin rash, edema, hypotension, and gangrene. Intravascular clotting in the brain accounts for the stuporous mental changes and other neurological symptoms that sometimes occur. Isolation of most rickettsias from clinical specimens requires a suitable live medium and specialized laboratory facilities, including 1. Ticks are in the Class Arachnida, and lice and fleas are in the Class Insecta, both in the Phylum Arthropoda. taL22600_ch21_633-665.indd Page 649 11/12/13 9:13 PM f-w-166 /202/MH02004/taL22600_disk1of1/0073522600/taL22600_pagefiles 21.3 Medically Important Bacteria of Unique Morphology and Biology controlled access and safety cabinets. The usual choices for routine growth and maintenance are the yolk sacs of embryonated chicken eggs, chick embryo cell cultures, and, to a lesser extent, mice and guinea pigs. Specific Rickettsioses Rickettsioses can be differentiated on the basis of their clinical features and epidemiology as (table 21.2): 1. 2. 3. 4. the typhus group, the spotted fever group, scrub typhus, and ehrlichiosis and anaplasmosis. Rickettsia prowazekii and Epidemic Typhus Epidemic, or louse-borne, typhus* has been a constant accompaniment to war, poverty, and famine. The extensive investigations of Dr. Howard Ricketts and Stanislas von Prowazek in the early 1900s led to the discovery of the vector and the rickettsial agent but not without mortal peril; both men died of the very disease they investigated. Rickettsia prowazekii was named in honor of their pioneering efforts. Epidemiology of Epidemic Typhus Humans are the sole hosts of human body lice and the only reservoirs of R. prowazekii. The louse spreads infection by defecating into its bite wound or other breaks in the skin. Infection of the eye or respiratory tract can take place by direct contact or inhalation of dust containing dried louse feces, but this is a rarer mode of transmission. * typhus (ty9-fus) Gr. typhos, smoky or hazy, underlining the mental deterioration seen in this disease. The term typhus is commonly confused with typhoid fever, an unrelated enteric illness caused by Salmonella typhi. TABLE 21.2 The transfer of lice is increased by crowding, infrequently changing clothing, and sharing clothing. The overall incidence of epidemic typhus in the United States is very low, with no epidemics since 1922. Although no longer common in regions of the world with improved standards of living, epidemic typhus presently persists in regions of Africa, Central America, and South America. Disease Manifestations and Immune Response in Typhus After entering the circulation, rickettsias pass through an intracellular incubation period of 10 to 14 days. The first clinical manifestations are sustained high fever, chills, frontal headache, and muscular pain. Within 7 days, a generalized rash appears, initially on the trunk, and then spreads to the extremities. Personality changes, oliguria (low urine output), hypotension, and gangrene complicate the more severe cases. Mortality is lowest in children and as high as 40% to 60% in patients over 50 years of age. Recovery usually confers resistance to typhus, but in some cases, the rickettsias are not completely eradicated by the immune response and enter into latency. After several years, a milder recurring form of the disease, known as Brill-Zinsser disease, can appear. This disease is seen most often in people who have immigrated from endemic areas and is of concern mainly because these immigrants provide a continuous reservoir of the pathogen. Treatment and Prevention of Typhus Standard chemotherapy for typhus is doxycycline or chloramphenicol. Despite antibiotic therapy, however, the prognosis can be poor in patients with advanced circulatory or renal complications. Eradication of epidemic typhus is theoretically possible by exterminating the vector. Widespread dusting of human living quarters with insecticides has provided some environmental control, and individual treatment with an antilouse shampoo or ointment is also effective. Characteristics of Major Rickettsias Involved in Human Disease Disease Group Species Disease Vector Primary Reservoir Typhus Rickettsia prowazekii Epidemic typhus Body louse Humans R. typhi (mooseri) Murine typhus Flea Rodents R. rickettsii Rocky Mountain spotted fever Rickettsialpox Tick Spotted Fever 649 R. akari Mite Mode of Transmission to Humans Where Found Louse feces rubbed into bite; inhalation Flea feces rubbed into skin; inhalation Worldwide Small mammals Mice Tick bite; aerosols North and South America Worldwide Mite bite Worldwide Scrub Typhus Orientia tsutsugamushi — Immature mite Rodents Bite Asia, Australia, Pacific Islands Human Ehrlichiosis Ehrlichia chaffeensis Human monocytic ehrlichiosis Tick — Tick bite Human Anaplasmosis Anaplasma phagocytophilum Human granulocytic anaplasmosis Tick Deer, rodents Tick bite Similar to Rocky Mountain spotted fever Unknown taL22600_ch21_633-665.indd Page 650 11/12/13 9:13 PM f-w-166 650 /202/MH02004/taL22600_disk1of1/0073522600/taL22600_pagefiles Chapter 21 Miscellaneous Bacterial Agents of Disease Epidemiology and Clinical Features of Endemic Typhus The agent for endemic typhus is Rickettsia typhi (R. mooseri), which shares many characteristics with R. prowazekii except that R. typhi has pronounced virulence. Synonyms for this rickettsiosis are endemic typhus, murine (mouse) typhus, and flea-borne typhus. The disease is endemic to certain parts of Central and South America and the Southeast, Gulf Coast, and Southwest regions of the United States. The native rodents and opossums in these areas are a reservoir for R. typhi and transmit it to fleas feeding on blood. Humans become infected through flea bites and occasionally inhalation. In the United States, most reported cases arise sporadically among workers in rat-infested industrial sites. The clinical manifestations of endemic typhus include fever, headache, muscle aches, and malaise. After 5 days, a skin rash, transient in milder cases, begins on the trunk and radiates toward the extremities. Symptoms dissipate in about 2 weeks. Doxycycline and chloramphenicol are effective therapeutic agents, and various pesticides are available for vector and rodent control. DC Incidence rates (per 1,000,000 persons) 0 0.2–1.5 1.5–19 19–63 Not a notifiable disease Figure 21.15 Trends in infection for Rocky Mountain spotted Rocky Mountain Spotted Fever: Epidemiology and Pathology fever. A summary map showing the distribution of Rocky Mountain spotted fever cases. The disease is not reportable in Alaska or Hawaii. The rickettsial disease with greatest impact on people living in North America is Rocky CNS Mountain spotted fever (RMSF), named for tick damage, the place it was first seen—the Rocky Mouncoma with eggs tains of Montana and Idaho (see Pathogen Rash Profile #3, page 651). Ricketts identified the Egg (b) etiologic agent Rickettsia rickettsii in smears from infected animals and patients and later discovered that it was transmitted by ticks. Despite its geographic name, this disease occurs infrequently in the western United States. The majority of cases are concentrated in the Southeast and eastern seaboard regions (figure 21.15). It also occurs in Can(a) Vascular ada and Central and South America. InfecTick/Dog Infection damage tions occur most frequently in the spring and Human Infection summer, when the tick vector is most active. (c) The yearly rate of RMSF averages six to (d) seven cases per million population, with Figure 21.16 The transmission cycle in Rocky Mountain spotted fever. Dog ticks fluctuations coinciding with weather and and wood ticks (Dermacentor) are the principal vectors. (a) Ticks are infected from a tick infestations. The incidence has been mammalian reservoir during a blood meal. (b) Transovarial passage of Rickettsia rickettsii to tick eggs steadily increasing since 2010. serves as a continual source of infection within the tick population. Infected eggs produce infected The principal reservoirs and vectors of adults. (c) A tick attaches to a human, embeds its head in the skin, feeds, and sheds rickettsias into R. rickettsii are hard ticks such as the wood the bite. (d) Systemic involvement includes severe headache, fever, rash, coma, and vascular tick (Dermacentor andersoni), the American damage such as blood clots and hemorrhage. dog tick (D. variabilis, among others), and the Lone Star tick (Amblyomma americanum). The dog tick is probappears within 1 to 3 days after the prodromium (figure 21.17). ably most responsible for transmission to humans because it is the Early lesions are slightly mottled like measles, but later ones are major vector in the southeastern United States (figure 21.16). macular, maculopapular, and even petechial. In the severest untreated cases, the enlarged lesions merge and can become necrotic, Pathogenesis and Clinical Manifestations of Spotted Fever predisposing to gangrene of the toes or fingertips. After 2 to 4 days incubation, the first symptoms are sustained fever, Grave manifestations of disease are cardiovascular disruption, chills, headache, and muscular pain. The distinctive spotted rash including hypotension, thrombosis, and hemorrhage. Conditions of taL22600_ch21_633-665.indd Page 651 11/12/13 9:13 PM f-w-166 /202/MH02004/taL22600_disk1of1/0073522600/taL22600_pagefiles 21.3 Medically Important Bacteria of Unique Morphology and Biology 651 Pathogen Profile #3 Rickettsia rickettsii Microscopic Morphology Very small, gram-negative pleomorphic rods or coccobacilli. host. The bacterium is able to induce its own phagocytosis by cells of the body and multiply within the cytoplasm, eventually leading to disease. Identified by Cultivation of R. rickettsii is difficult, and detection of bacterial cells from tissue samples is often accomplished using fluorescent antibodies. Definitive identification may be achieved using PCR and a presumptive diagnosis can be achieved through an ELISA test that detects a rising antibody titer. Primary Infections/Disease Symptoms of Rocky Mountain spotted fever (RMSF) are first noticed 2 to 4 days after infection and include fever, chills, headache, and muscle pain. Shortly thereafter, a red spotted rash appears and worsens, occasionally becoming necrotic in some areas. Progression of the disease includes cardiovascular disruption and involvement of the central nervous system. Fatality results in 10% of untreated cases but less than 1% of treated cases. Habitat Within the United States, R. rickettsii is found in the Southeast and eastern seaboard regions, where it is transmitted by several species of hard tick, including the wood tick, American dog tick, and Lone Star tick. With the tick serving as a biological vector, the bacterium is spread between mammalian reservoirs and humans. Virulence Factors Proteins residing on the outer membrane of R. rickettsii are responsible for binding to the endothelial cells of the Control and Treatment Early doxycycline therapy is the treatment of choice for RMSF. Prevention of the disease is synonymous with prevention of tick bites when involved in outdoor activities, and the use of protective clothing, boots, and insect repellent containing DEET is recommended. from the rash lesions are suitable for PCR assay, which is very specific and sensitive and can circumvent the need for culture. Because antibodies appear relatively soon after infection, a change in serum titer detected through an ELISA test can confirm a presumptive diagnosis. The drug of choice for suspected and known cases is doxycycline administered for 1 week. Chloramphenicol is an alternate choice used for pregnant patients or if an allergic reaction to tetracycline-class antibiotics is noted. Preventive measures follow the pattern for Lyme disease and other tick-borne disease: wearing protective clothing, using insect sprays, and fastidiously removing ticks. Emerging Rickettsioses Figure 21.17 The spotted appearance of the rash in RMSF. This case occurred in a child several days after the onset of fever. It may occur on most areas of the body. restlessness, delirium, convulsions, tremor, and coma are alarming indications of central nervous system involvement. Fatalities occur in an average of 10% of untreated cases but less than 1% of treated cases. Diagnosis, Treatment, and Prevention of Spotted Fever Any case of Rocky Mountain spotted fever is a cause for great concern and requires immediate treatment, even before laboratory confirmation. Indications sufficiently suggestive to start antimicrobic therapy are the following: 1. a cluster of symptoms, including sudden fever, headache, and rash; 2. recent contact with ticks or dogs; and 3. possible occupational or recreational exposure in the spring or summer. Early diagnosis can be made by staining rickettsias directly in a tissue biopsy using fluorescent antibodies. Isolating rickettsias from the patient’s blood or tissues is desirable, but it is expensive and requires specially qualified personnel and laboratory facilities. Specimens taken Other genera that share similarities with Rickettsia are Ehrlichia and Anaplasma, two closely related obligate parasites spread by ticks. Although these rickettsial pathogens have been known as pathogens of dogs, horses, and other mammals for some time, infections caused by them have emerged more recently in humans. Ehrlichia chaffeensis is the cause of human monocytic ehrlichiosis (HME), and Anaplasma phagocytophilum is the cause of human granulocytic anaplasmosis (HGA). The diseases are reported in many regions of the United States and Europe and appear to be on the increase at the present time. Both human pathogens cause an acute flulike disease that ranges from mild to severe and can even be fatal. In both pathogens, white blood cells are the primary targets of infections. Human monocytic ehrlichiosis is associated with contact with the Lone Star tick. The rickettsia enters the tick bite and is phagocytosed by monocytes and macrophages, which can lead to cell death and leukopenia. It is carried to many organs, leaving widespread inflammation in its path. The main symptoms are fever, muscle pains, headache, and a rash. Approximately 850 cases per year are reported to the CDC. Anaplasma phagocytophilum is the cause of human granulocytic anaplasmosis (HGA). The primary reservoirs and vectors for taL22600_ch21_633-665.indd Page 652 11/12/13 9:13 PM f-w-166 652 /202/MH02004/taL22600_disk1of1/0073522600/taL22600_pagefiles Chapter 21 Miscellaneous Bacterial Agents of Disease Endospore Vegetative cell Figure 21.18 The agent of Q fever. The vegetative cells of Coxiella burnetii produce unique endospores that are released when the cell disintegrates. Free spores survive outside the host and are important in transmission (150,0003). Figure 21.19 Cat-scratch disease. Primary nodules appear at the site of the scratch or bite after about 21 days. Note the scab formation, swelling, and inflammation around the bite infection. the pathogen are very similar to those of Borrelia burgdorferi. It is carried by white-footed mice and deer, and its vectors are ticks in the genus Ixodes. The primary targets of infection are neutrophils and other granulocytes. The pathogen disrupts neutrophil function and causes diminished immunities. The symptoms are similar to ehrlichiosis but can also involve the respiratory and gastrointestinal tracts, kidney, and liver. Approximately 1,000 cases are reported each year in the United States, but epidemiologists suspect the true number of cases is much higher. Most patients recover rapidly with no lasting effects, but around 5% of older chronically ill patients die from disseminated infection. Rapid diagnosis is enabled by PCR tests and indirect fluorescent antibody tests. It can be critical to differentiate or detect coinfection with the Lyme disease Borrelia, which is carried by the same tick. Doxycycline will clear up most infections within 7 to 10 days. and consumers of raw milk. The clinical manifestations typical of Coxiella infection are abrupt onset of fever, chills, head and muscle ache, and, occasionally, a rash. Disease is sometimes complicated by pneumonitis, hepatitis, and endocarditis. Mild or subclinical cases resolve spontaneously, and more severe cases respond to doxycycline therapy. A vaccine is available in many parts of the world and is used on military personnel in the United States. People working with livestock should avoid contact with excrement and secretions and should observe decontamination precautions. The Family Bartonellaceae contains the genus Bartonella,* which now includes species formerly known as Rochalimaea. These small, gram-negative rods are fastidious but not obligate intracellular parasites, readily cultured on blood agar. Bartonella species are currently considered a group of emerging pathogens. One disease with a long history is trench fever, once a common condition of soldiers in battle. The causative agent, Bartonella quintana, is carried by lice. Most cases occur in endemic regions of Europe, Africa, and Asia. Highly variable symptoms can include a 5- to 6-day fever (hence, 5-day, or quintana, fever); leg pains, especially in the tibial region (shinbone fever); headache; chills; and muscle aches. A macular rash can also occur. The microbe can persist in the blood long after convalescence and is responsible for later relapses. Bartonella henselae is the most common agent of cat-scratch disease (CSD), an infection connected with being clawed or bitten by a cat. The pathogen can be isolated in over 40% of cats, especially kittens. There are approximately 25,000 cases per year in the United States, 80% of them in children 2 to 14 years old. Symptoms start after 1 to 2 weeks, with a cluster of small papules at the site of inoculation. In a few weeks, the lymph nodes along the lymphatic drainage swell and can become pus-filled (figure 21.19). Most infections remain localized and resolve in a few weeks, but drugs such as doxycycline, erythromycin, and rifampin can be effective therapies. The disease can be prevented by thorough degerming of a cat bite or scratch. Bartonella is recognized as an important emerging pathogen in AIDS patients. It is the cause of bacillary angiomatosis, a severe cutaneous and systemic infection. The cutaneous lesions arise as Coxiella and Bartonella: Other Vector-Borne Pathogens Q fever2 was first described in Queensland, Australia. Its origin was mysterious for a time, until Harold Cox working in Montana and Frank Burnet in Australia discovered the agent later named Coxiella burnetii.* This bacterium is similar to rickettsias in being an intracellular parasite, but it is much more resistant because it produces an unusual type of spore (figure 21.18). It is apparently harbored by a wide assortment of vertebrates and arthropods, especially ticks, which play an essential role in transmission between wild and domestic animals. Humans acquire infection largely by means of environmental contamination and airborne spread. Sources of infectious material include urine, feces, milk, and airborne particles from infected animals. The primary portals of entry are the lungs, skin, conjunctiva, and gastrointestinal tract. Coxiella burnetii has been isolated from most regions of the world. In the United States, it occurs sporadically, and it is believed that most cases probably go undetected. People at highest risk are farm workers, meat cutters, veterinarians, laboratory technicians, 2. For “query,” meaning to question, or of unknown origin. * Coxiella burnetii (kox9-ee-el9-uh bur9-net-ee9-eye) * Bartonella (barr0-tun-el9-ah) After A. L. Barton, a Peruvian physician who first described the genus. taL22600_ch21_633-665.indd Page 653 11/12/13 9:13 PM f-w-166 /202/MH02004/taL22600_disk1of1/0073522600/taL22600_pagefiles 21.3 Medically Important Bacteria of Unique Morphology and Biology 653 reddish nodules or crusts that can be mistaken for Kaposi’s sarcoma. Systems most affected are the liver and spleen, and symptoms are fever, weight loss, and night sweats. Treatment is similar to that for CSD. the trachoma strain, which attacks the squamous or columnar cells of mucous membranes in the eyes, genitourinary tract, and lungs; and the lymphogranuloma venereum (LGV) strain, which invades the lymphatic tissues of the genitalia. Other Obligate Parasitic Bacteria: The Chlamydiaceae Chlamydial Diseases of the Eye The two forms of chlamydial eye disease, ocular trachoma and inclusion conjunctivitis, differ in their patterns of transmission and ecology. Ocular trachoma, an infection of the epithelial cells of the eye, is an ancient disease and a major cause of blindness in certain parts of the world. Although a Even though they are not close relatives of rickettsias, members of Family Chlamydiaceae are also obligate intracellular parasites that depend on certain metabolic constituents of host cells for growth and maintenance. They show further resemblance to the rickettsias with their small size and pleomorphic morphology, but they are markedly different in several aspects of their life cycle. The species of greatest medical significance is Chlamydia trachomatis,* a very common pathogen involved in sexually transmitted, neonatal, and ocular disease (trachoma) (see Pathogen Profile #4, page 655). A related genus, Chlamydophila, includes C. pneumoniae, the cause of one type of atypical pneuNew host cell monia; and C. psittaci,* a zoonosis of birds and mammals that causes ornithosis in humans. The Biology of Chlamydia and Related Forms Chlamydias alternate between two distinct stages: (1) a metabolically inactive, infectious form called the elementary body that is released by the infected host cell; and (2) a noninfectious, actively dividing form called the reticulate body that grows within host cell vacuoles. The reticulate body completes the cycle by forming new elementary bodies (figure 21.20). Elementary bodies are shielded by a rigid, impervious envelope that ensures survival outside the eukaryotic host cell. Reticulate bodies are energy parasites, lacking enzyme systems for catabolizing glucose and synthesizing ATP. They do possess ribosomes and pathways for synthesizing proteins, DNA, and RNA. Diseases of Chlamydia trachomatis The reservoir of pathogenic strains of Chlamydia trachomatis is the human body. The microbe shows astoundingly broad distribution within the population, often being carried with no symptoms. Elementary bodies are transmitted through contact with secretions. Although infection occurs in all age groups, disease is most severe in infants and children. The two human strains are * Chlamydia trachomatis (klah-mid9-ee-ah trah-koh9mah-tis) Gr. chlamys, a cloak, and trachoma, roughness. * psittaci (sih-tah9-see) Gr. psittacus, a parrot. Nucleus RBs EBs Phagosome EB EB 2 m Host cell 6 Nucleus 1 4 RB 5 Phagosomes with EB EB 3 Binary fission EB RB 2 Enlarged view of cycle in phagosome Process Figure 21.20 The life cycle of Chlamydia. (1) The infectious stage, or elementary body (EB), is taken into phagocytic vesicles by the host cell. (2) In the phagosome, each elementary body develops into a reticulate body (RB). (3) Reticulate bodies multiply by regular binary fission. (4)–(5) Mature RBs become reorganized into EBs. (6) Completed EBs are released from the host cell. Inset is a micrograph of a phagosome with reticulate (RB) bodies and elementary bodies (EB) forming (2,0003). Bar is 2 mm. taL22600_ch21_633-665.indd Page 654 11/12/13 9:13 PM f-w-166 654 /202/MH02004/taL22600_disk1of1/0073522600/taL22600_pagefiles Chapter 21 Miscellaneous Bacterial Agents of Disease Figure 21.21 The pathology of primary ocular chlamydial infection. (a) Ocular (a) (b) few cases occur yearly in the United States, several million cases occur endemically in parts of Africa and Asia. Transmission is favored by contaminated fingers, fomites, flies, and a hot, dry climate. The first signs of infection are a mild conjunctival exudate and slight inflammation of the conjunctiva. These are followed by marked infiltration of lymphocytes and macrophages into the infected area. As these cells build up, they impart a pebbled (rough) appearance to the inner aspect of the upper eyelid (figure 21.21a). In time, a vascular pseudomembrane of exudate and inflammatory leukocytes forms over the cornea, a condition called pannus that lasts a few weeks. Chronic and secondary infections can lead to corneal damage and impaired vision. Early treatment of this disease with azithromycin is highly effective and prevents all of the complications. It is a tragedy that in this day of preventive medicine, millions of children worldwide will develop blindness for lack of a few dollars’ worth of antibiotics. Inclusion conjunctivitis is usually acquired through contact with secretions of an infected genitourinary tract. Infantile conjunctivitis develops 5 to 12 days after a baby has passed through the birth canal of its infected mother and is the most prevalent form of conjunctivitis in the United States (100,000 cases per year). The initial signs are conjunctival irritation, a profuse adherent exudate, redness, and swelling (figure 21.21b). Although the disease usually heals spontaneously, trachoma-like scarring occurs often enough to warrant routine eye prophylaxis of all newborns (as for gonococcal infection) with antibiotics such as erythromycin and doxycycline. Sexually Transmitted Chlamydial Diseases It has been estimated that C. trachomatis is carried in the reproductive tract of up to 10% of the population, with even higher rates among promiscuous individuals. About 70% of infected women harbor it asymptomatically on the cervix, while 10% of infected males show no signs or symptoms. The potential for this disease to cause longterm reproductive damage has initiated its listing as a reportable disease since 1995. Statistics now show that chlamydiosis is the most prevalent bacterial STD. The reported incidence for 2012 was over 1.2 million cases, but its true incidence probably exceeds that level by 10 times. The occurrence of this infection in young, sexually active teenagers is increasing by 8% to 10% per year. Medically and socioeconomically, its clinical significance now eclipses gonorrhea, herpes simplex 2, and syphilis. A syndrome among males with chlamydial infections is an inflammation of the urethra called nongonococcal urethritis (NGU). This diagnosis is derived from the symptoms that mimic gonorrhea trachoma, an early, pebblelike inflammation of the conjunctiva and inner lid. (Note: The eyelid has been retracted to make the lesion more visible.) (b) Inclusion conjunctivitis in a newborn. Within 5 to 6 days, an abundant, watery exudate collects around the conjunctival sac. This is currently the most common cause of ophthalmia neonatorum. yet do not involve gonococci. Women with symptomatic chlamydial infection have cervicitis accompanied by a white drainage, endometritis, and salpingitis (pelvic inflammatory disease—PID). As is often the rule with sexually transmitted diseases, chlamydia frequently appears in mixed infections with the gonococcus and other genitourinary pathogens, thereby greatly complicating treatment. When a particularly virulent strain of Chlamydia chronically infects the genitourinary tract, the result is a severe, often disfiguring disease called lymphogranuloma venereum.3 The disease is endemic to regions of South America, Africa, and Asia but occasionally occurs in other parts of the world. Its incidence in the United States is about 500 cases per year. Chlamydias enter through tiny nicks or breaks in the perigenital skin or mucous membranes and form a small, painless vesicular lesion that often escapes notice. Other acute symptoms are headache, fever, and muscle aches. As the lymph nodes near the lesion begin to fill with granuloma cells, they enlarge and become firm and tender (figure 21.22). These nodes, or buboes, can cause long-term lymphatic obstruction that leads to chronic, deforming edema of the genitalia and anus. Identification, Treatment, and Prevention of Chlamydiosis Because chlamydias reside intracellularly, specimen sampling requires enough force to dislodge some of the cells from the mucosal 3. Also called tropical bubo or lymphogranuloma inguinale. Figure 21.22 The clinical appearance of advanced lymphogranuloma venereum in a man. A chronic local inflammation blocks the lymph channels, causing swelling and distortion of the tissues near the scrotum. taL22600_ch21_633-665.indd Page 655 11/12/13 9:13 PM f-w-166 /202/MH02004/taL22600_disk1of1/0073522600/taL22600_pagefiles 21.3 Medically Important Bacteria of Unique Morphology and Biology 655 Pathogen Profile #4 Chlamydia trachomatis Microscopic Morphology Very small, gram-negative pleomorphic rods. Identified by Definitive identification involves cultivation in chicken, mice, or tissue cell lines but is rarely done due to time and cost constraints. Immunofluorescent staining of specimens and PCR are commonly employed. Habitat C. trachomatis resides within the human body, where it is often carried without symptoms. It invades primarily epithelial and lymphatic cells. Virulence Factors The cell wall of Chlamydia is able to inhibit phagolysosome fusion, allowing reticulate bodies to survive and multiply within phagosomes. Elementary bodies are encased in an impervious envelope that ensures survival outside of the host cell. surface. Genital samples are taken with a swab inserted a few centimeters into the urethra or cervix, rotated, and removed. Although the most reliable diagnosis comes from culture in chicken embryos, mice, or cell lines, this procedure is too costly and time-consuming to be used routinely in STD clinics; however, it is an essential part of diagnosing neonatal infections. The most sensitive and specific tests currently available are a direct assay of specimens using immunofluorescence and a PCR-based probe. Methods useful in diagnosing inclusion conjunctivitis are Giemsa or iodine stains (figure 21.23), but they are not recommended for urogenital specimens because of low sensitivity and the possibility of obtaining false-negative results in asymptomatic patients. Urogenital chlamydial infections are most effectively treated with drugs that act intracellularly, such as doxycycline and azithromycin. Penicillin and aminoglycosides are not effective and must not be used. Because of the high carrier rate and the difficulty in detection, prevention of chlamydial infections is a public health priority. As a general rule, sexual partners of infected people should Figure 21.23 Cells in tissue culture infected with Chlamydia trachomatis. The dark staining inclusion bodies (arrows) indicate a phagosome containing Chlamydia in various stages of development. These can be diagnostic of chlamydiosis. Primary Infections/Disease Chlamydia trachomatis is the causative agent of chlamydiosis, nongonococcal urethritis, pelvic inflammatory disease, and lymphogranuloma venereum. It also causes the eye infections ocular trachoma and inclusion conjunctivitis. Control and Treatment Condoms provide limited protection as the pathogen can invade multiple cell types. Newborns are treated prophylactically with erythromycin or doxycycline; the treatment of urogenital infections relies on doxycycline or azithromycin. be treated with drug therapy to prevent infection, and sexually active people can achieve some protection with a condom. Chlamydophila Chlamydophila is a genus of obligate pathogens; it contains members that used to be included with Chlamydia. One of these is Chlamydophila pneumoniae, a strict human pathogen with characteristics that distinguish it from other species in the genus. It has been linked to a type of respiratory illness that includes pharyngitis, bronchitis, and pneumonitis. It is usually a mild illness in young adults, though it can cause a severe reaction in asthmatic patients that is responsible for increased rates of death in this group. Some evidence exists to implicate it in heart disease. Chlamydophila psittaci and Ornithosis The term psittacosis was adopted to describe a pneumonia-like illness contracted by people working with imported parrots and other psittacine birds in the last century. As outbreaks of this disease appeared in areas of the world having no parrots, it became evident that other birds could carry and transmit the microbe to humans and other animals. The term ornithosis* has since been adopted as a replacement. Ornithosis is a worldwide zoonosis that is carried in a latent state in wild and domesticated birds but becomes active under stressful conditions such as overcrowding. In the United States, poultry have been subject to extensive epidemics that killed as many as 30% of flocks. Infection is communicated to other birds, mammals, and humans by contaminated feces and other discharges that become airborne and are inhaled. Sporadic cases in the United States occur mainly among poultry and pigeon handlers. The symptoms of human ornithosis mimic those of influenza and pneumococcal pneumonia. Early manifestations are fever, chills, frontal headache, and muscle aches, and later ones are coughing and * ornithosis (or0-nih-thoh9-sis) Gr. ornis, bird. More than 90 species of birds harbor C. psittaci. taL22600_ch21_633-665.indd Page 656 11/12/13 9:13 PM f-w-166 656 /202/MH02004/taL22600_disk1of1/0073522600/taL22600_pagefiles Chapter 21 Miscellaneous Bacterial Agents of Disease lung consolidation. Unchecked, infection can lead to systemic complications involving the meninges, brain, heart, or liver. Although most patients respond well to doxycycline or erythromycin therapy, recovery is often slow and fraught with relapses. Control of the disease is usually attempted by quarantining imported birds and by taking precautions in handling birds, feathers, and droppings. Check Your Progress SECTION 21.3 10. What do rickettsias and chlamydias derive from the host? 11. Provide an example of a species, vector, and disease for each of the four major groups of rickettsioses. 12. Where is Rocky Mountain spotted fever commonly found? What symptoms and activities would justify treatment for the disease prior to laboratory confirmation? 13. Why do ranchers have an increased risk of becoming infected with Coxiella burnetii? Who else would have a similar level of risk? 14. How are chlamydias transmitted? 15. Describe the major complications of eye infections and STDs. 16. Name three diseases caused by species within the genus Chlamydia. 17. How do the respiratory infections attributable to the two species of Chlamydophila differ? (a) 21.4 Mollicutes and Other Cell-Wall-Deficient Bacteria Expected Learning Outcomes 16. Describe the characteristics and diseases of mycoplasmas. 17. Describe how L forms may arise. Bacteria in the Class Mollicutes, also called the mycoplasmas, are among the smallest self-replicating microorganisms. All of them naturally lack a cell wall (figure 21.24a), and except for one genus, all species are parasites of animals and plants. The two most clinically important genera are Mycoplasma and Ureaplasma. Disease of the respiratory tract has been primarily associated with Mycoplasma pneumoniae; M. hominis and Ureaplasma urealyticum are implicated in urogenital tract infections. Biological Characteristics of the Mycoplasmas Without a rigid cell wall to delimit their shape, mycoplasmas are exceedingly pleomorphic. The small (0.3–0.8 mm), flexible cells assume a spectrum of shapes, ranging from cocci and filaments to doughnuts, clubs, and helices (see figure 4.16). Mycoplasmas are not strict parasites, and they can grow in cell-free media, generate metabolic energy, and synthesize proteins with their own enzymes. However, most are fastidious and require complex media containing sterols, fatty acids, and preformed purines and pyrimidines. Mycoplasmas are sometimes referred to as membrane parasites because they acquire certain necessary lipids from host cell membranes (figure 21.24b). Infections are chronic and difficult to eliminate, because mycoplasmas bind tenaciously to receptor sites (b) Figure 21.24 The morphology of mycoplasmas. (a) A colorenhanced scanning electron micrograph of Mycoplasma pneumoniae (10,0003). Note pleomorphic shapes and elongate attachment tips. The cells use these to anchor themselves to host cells. (b) Figure depicts how M. pneumoniae becomes a membrane parasite that adheres tightly and fuses with the host cell surface. This fusion makes destruction and removal of the pathogen very difficult. on cells of the respiratory and urogenital tracts and they are not easily removed by usual defense mechanisms. Mycoplasma pneumoniae and Atypical Pneumonia Mycoplasma pneumoniae is a human parasite that is the most common agent of primary atypical pneumonia (PAP).4 This syndrome is atypical in that its symptoms do not resemble those of pneumococcal pneumonia. Mycoplasmal pneumonia is transmitted by aerosol droplets among people confined in close living quarters, especially families, students, and the military. Community resistance to this pneumonia is high; only 3% to 10% of those exposed become infected, and fatalities are rare. Mycoplasma pneumoniae binds to specific receptors of the epithelial cells of the respiratory tract. Gradual spread of the bacteria over the next 2 to 3 weeks disrupts the cilia and damages the respiratory epithelium. The first symptoms—fever, malaise, sore 4. Primary atypical pneumonia can also be caused by rickettsias, chlamydias, respiratory syncytial viruses, and adenoviruses. taL22600_ch21_633-665.indd Page 657 11/12/13 9:14 PM f-w-166 /202/MH02004/taL22600_disk1of1/0073522600/taL22600_pagefiles 21.5 Bacteria in Dental Disease throat, and headache—are not suggestive of pneumonia. A cough is not a prominent early symptom, and when it does appear, it is mostly unproductive. As the disease progresses, nasal symptoms, chest pain, and earache can develop. The lack of acute illness in most patients has given rise to the nickname “walking pneumonia.” Diagnosis Because a culture can take 2 or 3 weeks, early diagnosis of mycoplasma pneumonia is difficult and relies chiefly on close clinical observation to rule out other bacterial or viral agents. Stains of sputum appear devoid of bacterial cells, leukocyte counts are within normal limits, and X-ray findings are nonspecific. Serological tests based on complement fixation, immunofluorescence, and indirect hemagglutination are useful later in the disease. Doxycycline and azithromycin inhibit mycoplasmal growth and help to rapidly diminish symptoms, but they do not stop the shedding of viable mycoplasmas. Patients frequently experience relapses if treatment is not continued for 14 to 21 days. Preventive measures include controlling contamination of fomites, avoiding contact with droplet nuclei, and reducing aerosol dispersion. Other Mycoplasmas Mycoplasma genitalium and Ureaplasma urealyticum are regarded as weak reproductive pathogens. They are frequently encountered in samples from the urethra, vagina, and cervix of newborns and adults. These species initially colonize an infant at birth and subsequently diminish through early and late childhood. A second period of colonization and persistence is initiated by the onset of sexual intercourse. Evidence linking genital mycoplasmas to human disease is substantial and growing every year. Ureaplasma urealyticum is implicated in some types of nonspecific or nongonococcal urethritis and prostatitis. There is increasing evidence that this mycoplasma plays a role in opportunistic infections of the fetus and fetal membranes. It appears to cause some cases of miscarriage, stillbirth, premature birth, and respiratory infections of newborns. Mycoplasma genitalium is an agent of STDs. It is very common in the genital tract of both women and men, and it often accompanies other STDs. In women, it is one cause of PID, cervicitis, urethritis, and vaginitis. Studies have also shown it can be carried into the uterus by spermatozoa. In males, M. genitalium can cause a form of NGU, prostatitis, and epididymitis. Bacteria That Have Lost Their Cell Walls Exposure of typical walled bacteria to certain drugs (penicillin) or enzymes (lysozyme) can result in wall-deficient bacteria called L forms or L-phase variants. L forms are induced or occur spontaneously in numerous species and can even become stable and reproduce themselves, but they are not naturally related to mycoplasmas. L Forms and Disease The role of certain L forms in human and animal disease is a distinct possibility, but proving etiology has been complicated because infection is difficult to verify. One theory proposes that antimicrobic therapy with cell-wall-active agents induces certain infectious agents to become L forms. In this wall-free state, they resist further treatment with these drugs and remain latent until the therapy ends, 657 at which time they reacquire walls and resume their pathogenic behavior. Infections involving L-phase variants of group A streptococci, Proteus, and Corynebacterium have occasionally been reported. In a number of chronic pyelonephritis and endocarditis cases, cell-wall-deficient bacteria have been the only isolates. Research on people with a chronic intestinal syndrome called Crohn’s disease has uncovered a strong association with a wall-deficient form of Mycobacterium avium paratuberculosis (MAP), a relative of the TB bacillus. When technicians used a PCR technique to analyze the DNA of colon specimens, it was found that 65% of Crohn’s patients tested positive for M. a. paratuberculosis. It is likely to be at least a cofactor for developing this disease. Check Your Progress 18. 19. 20. 21. SECTION 21.4 Explain the unique features of mycoplasmas. What are the pathologic effects of Mycoplasma pneumoniae? Which body systems are affected by mycoplasma infection? Explain why penicillin therapy may result in the formation of L forms but tetracycline therapy would not. 21.5 Bacteria in Dental Disease Expected Learning Outcomes 18. Discuss the formation of plaque on tooth surfaces. 19. Relate the formation of plaque to periodontitis. The relationship between humans and their oral microbiota is a complex, dynamic microecosystem. The mouth contains a diversity of surfaces for colonization, including the tongue, teeth, gingiva, palate, and cheeks; and it provides numerous aerobic, anaerobic, and microaerophilic microhabitats for the estimated 600 different oral species with which humans coexist. The habitat of the oral cavity is warm, moist, and greatly enriched by the periodic infusion of food. In most humans, this association remains in balance with little adverse effect, but in people with poor oral hygiene, it teeters constantly on the brink of disease. The Structure of Teeth and Associated Tissues Dental diseases can affect nearly any part of the oral cavity, but most of them involve the dentition (teeth) and the surrounding supportive structures, collectively known as the periodontium* (gingiva, ligaments, membrane, bone) (figure 21.25). A tooth is composed of a flared crown that protrudes above the gum and a root that is inserted into a bony socket. The outer surface of the crown is protected by a dense coating of enamel, an extremely hard, noncellular material composed of tightly packed rods of hydroxyapatite crystals [(Ca10(OH)2(PO4)6]. The root is surrounded by a layer of cementum, which is anchored by ligaments to the periodontal membrane that * periodontium (per0-ee-oh-don9-shee-um) Gr. peri, around, and odous, tooth. Gums, bones, and cementum. taL22600_ch21_633-665.indd Page 658 11/12/13 9:14 PM f-w-166 658 /202/MH02004/taL22600_disk1of1/0073522600/taL22600_pagefiles Chapter 21 Miscellaneous Bacterial Agents of Disease Tooth Surface (enamel, root) Pellicle Formation Plaque Formation Acidification and Cavitation Calculus (Tartar) Formation Dental Caries Damage to enamel Gingivitis/Periodontal Disease Tooth Destruction (exposure of dentin, pulp, root) Bone Resorption Tooth Loss Figure 21.26 Summary of the events leading to dental caries, periodontal disease, and bone and tooth loss. Figure 21.25 The anatomy of a tooth. lines the socket. The major portion of the tooth inside the crown and root is composed of a highly regular calcified material called dentin, and the core contains a pulp cavity that supplies the living tissues with blood vessels and nerves. The root canal is the portion of the pulp that extends into the roots. The space surrounding the teeth is protected by the gingiva (gum), a soft tissue composed of connective tissue covered by a mucous membrane. The primary sites for dental infections are grooves in the enamel, especially the cusps, and the crevice, or sulcus, formed where the gingiva meets the tooth. Dental pathology generally affects both hard and soft tissues (figure 21.26). Although both categories of disease are initiated when microbes adhere to the tooth surface and produce dental plaque, their outcomes vary. In the case of dental caries, the gradual breakdown of the enamel leads to invasive disease of the tooth itself. In soft-tissue disease, calcified plaque damages the delicate gingival tissues and predisposes them to bacterial invasion of the periodontium. These conditions are responsible for the loss of teeth, though dental caries are usually implicated in children and periodontal infections in adults. Hard-Tissue Disease: Dental Caries Dental caries* is the most common human disease. It is a complex biofilm infection of the dentition that gradually destroys the enamel * caries (kar9-eez) L. rottenness. and often lays the groundwork for the destruction of deeper tissues. It occurs most often on tooth surfaces that are less accessible and harder to clean and on those that provide pockets or crevices where bacteria can cling. Caries commonly develop on enamel pits and fissures, especially those of the occlusal (grinding) surfaces, though they can also occur on the smoother crown surfaces and subgingivally on the roots. Several views have been suggested to explain how dental caries originate. For some time experts knew that sugar, microbes, and acid were involved in tooth decay. It was studies with germ-free animals that finally showed that no single factor can account for caries—all three are necessary. Caries development occurs in many phases and requires multiple interactions involving the anatomy, physiology, diet, and microbiota of the host. Plaque and Dental Caries Formation A freshly cleaned tooth is a perfect landscape for colonization by microbes (figure 21.27). Within a few moments, it develops a thin, mucous coating called the acquired pellicle, which is made up of adhesive salivary proteins. This structure presents a potential substrate upon which certain bacteria first gain a foothold. The process of colonization of the tooth follows a classic pattern of biofilm formation. The most prominent pioneering colonists belong to the genus Streptococcus. These gram-positive cocci have adhesive receptors such as lectins and slime layers that allow them to cling to the tooth surfaces and to each other, forming a foundation for the mature biofilm aggregate known as plaque.* Fed by a diet high in * plaque (plak) Fr. a patch. taL22600_ch21_633-665.indd Page 659 11/18/13 4:42 PM f-w-166 /202/MH02004/taL22600_disk1of1/0073522600/taL22600_pagefiles 21.5 Bacteria in Dental Disease 6 1 A freshly cleaned tooth surface immediately develops a thin layer of salivary glycoproteins (the acquired pellicle). 2 Fibers of proteins, antibodies, salivary enzymes, bacterial debris, and other salivary molecules adhere to the pellicle (M). 3 The earliest tooth colonizers are the Streptococcus mutans group(s) (S. oralis and S. gordonii). These bacteria have specific receptors that adhere to the outer pellicle molecules. The streptococci likewise bind to each other, forming the initial base of plaque. 4 The next phase involves cell-cell signaling and coaggregation with additional colonists. The most common bacteria to add to the biofilm during this phase are filamentous rods in the genus Actinomyces (A). Other species of Streptococcus (the mutans group) use dietary carbohydrates to secrete glucans that add bulk to the matrix and serve as a source of sugars. 5 Once this initial framework has been laid down, it enters a second phase of aggregation which creates the final dense mat of plaque. Bacteria that colonize at this point are frequently anaerobes such as Fusobacterium (F), Porphyromonas (PO), Prevotella (PR), Veillonella (V), and Treponema (T). 6 See upper left. Initial damage to the enamel occurs when streptococci near the enamel surface ferment the sugars in plaque to lactic, acetic, and other acids. When these acids are trapped against the tooth surface and etch through it, a dental caries has developed. V A S M F PR V S Tooth enamel PO Acquired pellicle T 659 A Process Figure 21.27 Stages in the formation of plaque biofilm and dental caries. The process involves 1 2 3 4 5 sucrose, glucose, and certain complex carbohydrates, the Streptococcus mutans group secretes sticky polymers of glucose called fructans and glucans that form the matrix and bulk of the biofilm. As these primary invaders continue to build up on the tooth surface, they aggregate with thin, branching Actinomyces cells. As the plaque biofilm thickens, it creates an oxygen-free microenvironment that favors colonization by anaerobic bacteria. Among these secondary invaders are specific binding to enamel by a multilayered biofilm of oral microbes that interact, recognize, and aggregate. species of Fusobacterium, Porphyromonas, and Treponema. A microscopic view of plaque reveals a rich and varied network of bacteria and their products along with epithelial cells and fluids (figure 21.28). If mature plaque is not removed from sites that readily trap food, it can develop into a dental caries (see figure 21.27). The role of plaque in caries development is related directly to the fermentation of dietary carbohydrates by streptococci. In the denser regions Calculus Caries Areas of bone destruction (a) (b) Figure 21.28 The microscopic and macroscopic appearance of plaque. (a) Scanning electron micrograph of plaque displaying the development of a rich biofilm (1,8003). (b) Radiograph of a mandibular premolar and molar, showing calculus at the top and a caries lesion on the right. Bony defects caused by periodontitis affect both teeth. taL22600_ch21_633-665.indd Page 660 11/12/13 9:14 PM f-w-166 660 /202/MH02004/taL22600_disk1of1/0073522600/taL22600_pagefiles Chapter 21 Miscellaneous Bacterial Agents of Disease of plaque, the acid can accumulate in direct contact with the enamel surface and lower the pH to below 5, which is acidic enough to begin to dissolve (decalcify) the calcium phosphate of the enamel in that spot. This initial lesion can remain localized in the enamel (first-degree caries) and can be repaired with various inert materials (fillings). Once the deterioration has reached the level of the dentin (second-degree caries), tooth destruction speeds up, and the tooth can be rapidly destroyed. Exposure of the pulp (third-degree caries) is attended by severe tenderness and toothache, and the chance of saving the tooth is diminished. Soft-Tissue and Periodontal Disease Gingival and periodontal disease are so common that 97% to 100% of the population has some manifestation of it by age 45. The most common predisposing condition occurs when the plaque becomes mineralized (calcified) with calcium and phosphate crystals. This process produces a hard, porous substance called calculus above and below the gingiva that can induce varying degrees of periodontal damage (see figure 21.28b). Other factors that contribute to gingival and periodontal disease are diabetes, smoking, immune deficiency, and stress. Calculus accumulating in the gingival sulcus causes abrasions to the delicate gingival membrane, and the chronic trauma causes a pronounced inflammatory reaction. The damaged tissues become a portal of entry for a variety of bacterial residents. These include genera such as Actinobacillus, Porphyromonas, Bacteroides, Fusobacterium, Prevotella, and Treponema spirochetes. The anaerobic bacteria in these infections outnumber aerobes by 100 to 1. In response to the mixed infection, the damaged area becomes infiltrated by white blood cells, which cause further inflammation and tissue damage (figure 21.29a). The initial signs of gingivitis are swelling, loss of normal contour, patches of redness, and increased bleeding of the gingiva. Spaces or pockets of varying depth also develop between the tooth and the gingiva. Inflammation of gingiva Pocket (a) If this condition persists, a more serious disease called periodontitis results. This is the natural extension of the disease into the periodontal membrane and cementum. The deeper involvement results in chronic inflammation, loss of the ligament, and deeper pockets in the sulcus. It can cause bone resorption severe enough to loosen the tooth in its socket. If the condition is allowed to progress, the tooth can be lost (figure 21.29b). Chronic periodontal infections may lead to necrotizing ulcerative gingivitis (NUG), formerly called trench mouth or Vincent disease. This disease is a synergistic infection involving Treponema vincentii, Bacteroides forsythus, and fusobacteria (figure 21.30). These pathogens together produce several invasive factors that cause rapid advancement into the periodontal tissues. The condition is associated with severe pain, bleeding, pseudomembrane formation, and necrosis. NUG usually results from poor oral hygiene, altered host defenses, or prior gum disease, and is not considered communicable. It does respond well to broad-spectrum antibiotics. Factors in Dental Disease Nutrition and eating patterns are closely tied to oral diseases. People whose diet is high in refined sugar (sucrose, glucose, and fructose) tend to have more caries, especially if these foods are eaten constantly throughout the day without brushing the teeth. The practice of putting a baby down to nap with a bottle of fruit juice or formula can lead to rampant dental caries (“nursing bottle caries”). In addition to diet, numerous anatomical, physiological, and hereditary factors influence oral diseases. The structure of the tooth enamel can be influenced by genetics and by environmental factors such as fluoride, which strengthens the enamel bonds. Inhibitory factors in saliva such as antibodies and lysozyme can also help prevent dental disease by inhibiting bacterial attachment and growth. The best control of dental diseases comes from preventive dentistry, including regular brushing and flossing to remove plaque, because stopping plaque buildup automatically reduces caries and calculus production. Mouthwashes are relatively ineffective in Bleeding gingiva Calculus Bone resorption Streptobacilli Spirochetes Fusiform bacilli (b) Figure 21.29 Stages in soft-tissue infection, gingivitis, and periodontitis. (a) Calculus buildup and gingivitis. (b) Late-stage periodontitis, with tissue destruction, deep pocket formation, loosening of teeth, and bone loss. Figure 21.30 A sample of exudate from a gingival pocket (560X). Note the numerous spirochetes, fusiform bacilli, and streptobacilli. taL22600_ch21_633-665.indd Page 661 11/12/13 9:14 PM f-w-166 /202/MH02004/taL22600_disk1of1/0073522600/taL22600_pagefiles Chapter Summary with Key Terms controlling plaque formation because of the high bacterial content of saliva and the relatively short acting time of mouthwashes. Once calculus has formed on teeth, it cannot be removed by brushing but can be dislodged only by special mechanical procedures (scaling) in the dental office. One of the most exciting prospects is the possibility of a vaccine to protect against the primary colonization of the teeth. Some success in inhibiting plaque formation has been achieved in experimental animals with vaccines raised against the whole cells of cariogenic Streptococcus and the fimbriae of species of Actinomyces. Check Your Progress SECTION 21.5 22. What is the relationship between dietary carbohydrates, plaque, and dental caries? 23. Explain the stepwise progression of plaque deposition to periodontal disease. 24. Describe areas of the teeth and gums that support growth of microbes and infections. 25. Explain the colonization of teeth and the development of a biofilm. s ro g in ic he pa l m t g of ua ted sin g ad ivid trac A u nnin x e d e DN tu b in e hey he ir s um t t he d n ea t, as zed **. T an s oc y y l s t u r a e ie io ut var rev M o icr CASE STUDY 661 Part 2 The dedicated genetics professor was diagnosed with leptospirosis, a bacterial infection caused by Leptospira interrogans, which is usually transmitted by direct or indirect contact with animal urine. It is considered the most common zoonosis in the world, with about half of the cases in the United States occurring in Hawaii. Animals most commonly infected are cows, sheep, deer, and pigs. Floodwaters contaminated with animal waste are a common source of infection, with the Leptospira spirochete entering the body through minute breaks in the skin. ■ People in certain occupations are more likely than others to come in contact with Leptospira. What occupations might these be? To conclude this Case Study, go to Perspectives on the Connect website. See: CDC. 2006. Brief Report. Leptospirosis after flooding of a university campus—Hawaii, 2004. MMWR 55:125–27. Chapter Summary with Key Terms 21.1 The Spirochetes A. Spirochetes are helical, flexible bacteria that move by periplasmic flagella. Several Treponema species are obligate parasitic spirochetes with 8 to 12 regular spirals; best observed under dark-field microscope; cause treponematoses. 1. Direct observation of treponeme in tissues and blood tests is important in diagnosis. 2. Cannot be cultivated in artificial media; treatment by large doses of penicillin or doxycycline. B. Treponemes: Members of the Genus Treponema 1. Syphilis: Treponema pallidum causes complex progressive disease in adults and children. a. Sexually transmitted syphilis is acquired through close contact with a lesion; untreated sexual disease occurs in stages over long periods. (1) At site of entrance, multiplying treponemes produce a primary lesion, a hard ulcer or chancre, which disappears as the microbe becomes systemic. (2) Secondary syphilis is marked by skin rash, fever, damage to mucous membranes. Both primary and secondary syphilis are communicable. Latent period establishes pathogen in tissues. (3) Final, noncommunicable tertiary stage is marked by tumors called gummas and lifethreatening cardiovascular and neurological effects. b. Congenital syphilis is acquired transplacentally; disrupts embryonic and fetal development; survivors may have respiratory, skin, bone, teeth, eye, and joint abnormalities if not treated. 2. Nonsyphilitic treponematosis: Slow progressive cutaneous and bone diseases endemic to specific regions of tropics and subtropics; usually transmitted under unhygienic conditions. a. Bejel is a deforming childhood infection of the mouth, nasal cavity, body, and hands. b. Yaws occurs from invasion of skin cut, causing a primary ulcer that seeds a second crop of lesions. c. Pinta is superficial skin lesion that depigments and scars the skin. C. Leptospira interrogans causes leptospirosis, a worldwide zoonosis acquired through contact with urine of wild and domestic animal reservoirs. Spirochete enters cut, multiplies in blood and spinal fluid. Long-term infections may affect the kidneys and liver. D. Borrelia species are loose, irregular spirochetes that cause borreliosis; infections are vector-borne (mostly by ticks). Borrelias cause recurrent fever and other symptoms because the spirochetes repeatedly change antigenically and force the immune system to keep adapting. 1. Both B. hermsii and B. recurrentis cause relapsing fever. 2. Borrelia burgdorferi. a. Causes Lyme disease, a syndrome that occurs endemically in several regions of the United States. b. A zoonosis carried by mice and spread by a hard tick (Ixodes) that lives on deer and mice. c. Tick bite leads to fever and a prominent ring-shaped rash; if left untreated, may cause cardiac, neurological, and arthritic symptoms. d. Can be controlled by antibiotics and by avoiding tick contact. taL22600_ch21_633-665.indd Page 662 11/12/13 9:14 PM f-w-166 662 /202/MH02004/taL22600_disk1of1/0073522600/taL22600_pagefiles Chapter 21 Miscellaneous Bacterial Agents of Disease 21.2 Curviform Gram-Negative Bacteria and Enteric Diseases A. Vibrios are short spirals or sausage-shaped cells with polar flagella. 1. Vibrio cholerae causes epidemic cholera, a human disease that is distributed worldwide in natural waters. a. Organism is ingested in contaminated food and water and infects the surface of the small intestine, is not invasive. b. Severity of cholera due to potent cholera toxin that causes electrolyte and water loss through secretory diarrhea. c. Resulting dehydration leads to muscle, circulatory, and neurological symptoms. d. Treatment is with oral rehydration (electrolyte and fluid replacement); vaccine available. 2. Vibrio parahaemolyticus causes food infection associated with seawater and seafood; symptoms similar to mild cholera. B. Campylobacter species: C. jejuni is a common cause of severe gastroenteritis worldwide; acquired through water contaminated by animal feces and meats, eggs, and other food products; enteritis is due to enterotoxin; C. fetus causes diseases in pregnant women and fatal septicemia in neonates. C. Helicobacter pylori is a helical cell adapted to the stomach lining that may invade it and cause gastric diseases such as ulcers and gastritis. Treatment includes antibiotics and antacid drugs. 21.3 Medically Important Bacteria of Unique Morphology and Biology A. Rickettsias are tiny, gram-negative rods or cocci that are metabolic and intracellular parasites; diseases treatable with doxycycline and chloramphenicol. Rickettsia causes rickettsioses; most are zoonoses spread by arthropod vectors. 1. Epidemic typhus: Caused by Rickettsia prowazekii; carried by lice; disease starts with high fever, chills, headache; rash occurs; Brill-Zinsser disease is a chronic, recurrent form. 2. Endemic (murine) typhus: Zoonosis caused by R. typhi, harbored by mice and rats; occurs sporadically in areas of high flea infestation; symptoms like epidemic form but milder. 3. Rocky Mountain spotted fever: Etiologic agent is R. rickettsii; zoonosis carried by dog and wood ticks (Dermacentor); most cases on eastern seaboard; infection causes distinct spotted, migratory rash; effects may include heart damage, CNS damage; disease controlled by drug therapy and avoidance of ticks. 4. Ehrlichia and Anaplasma are two species of rickettsias that infect humans. These tick-borne bacteria cause human monocytic ehrlichiosis and human granulocytic anaplasmosis. Both cause acute febrile infections. B. Coxiella and Bartonella: Other Vector-Borne Pathogens 1. Q fever: Caused by Coxiella burnetii; agent has a resistant spore form that can survive out of host; a zoonosis of domestic animals; transmitted by air, dust, unpasteurized milk, ticks; usually inhaled, causing pneumonitis, fever, hepatitis. 2. Bartonella: A related genus is the cause of trench fever, spread by lice; and cat-scratch disease, a lymphatic infection associated with a clawing or biting injury by cats. C. Chlamydia is another genus of tiny, gram-negative coccobacilli that are obligate intracellular parasites of animals. 1. Organisms in the genus Chlamydia pass through a transmission phase involving a hardy elementary body and an intracellular reticulate body that has pathologic effects. a. Chlamydia trachomatis: A strict human pathogen that causes eye diseases and STDs. Ocular trachoma is a severe infection that deforms the eyelid and cornea and may cause blindness. Conjunctivitis occurs in babies following contact with birth canal; prevented by ocular prophylaxis after birth. b. C. trachomatis causes very common bacterial STDs: nongonococcal urethritis in males, and cervicitis, salpingitis (PID), infertility, and scarring in females; also lymphogranuloma venereum, a disfiguring disease of the external genitalia and pelvic lymphatics. c. Obligate pathogens in the related genus Chlamydophila are involved in pneumonia and ornithosis, a zoonosis associated with birds. 21.4 Mollicutes and Other Cell-Wall-Deficient Bacteria A. Mycoplasmas naturally lack cell walls and are thus highly pleomorphic; not obligate parasites but require special lipids from host membranes; diseases treated with doxycycline and azithromycin. 1. Mycoplasma pneumoniae: Causes primary atypical pneumonia; pathogen slowly spreads over interior respiratory surfaces, causing fever, chest pain, and sore throat. 2. L forms: Bacteria that normally have cell walls but have transiently lost them through drug therapy. They may be involved in certain chronic diseases. 21.5 Bacteria in Dental Disease A. The oral cavity contains hundreds of microbial species that participate in interactions between themselves, the human host, and the nutritional role of the teeth and mouth. 1. Hard-Tissue (Tooth) Disease Dental caries is a slow, progressive breakdown of irregular areas of tooth enamel; it begins with colonization of teeth by slime-forming species of Streptococcus, Actinomyces, and numerous other oral bacteria. This process forms a layer of thick, adherent material called plaque. Acid formed by agents in plaque dissolves the inorganic salts in enamel and may lead to caries and tooth damage. B. Disease of Tooth Support Structures Infection occurs in the periodontium (gingiva and surrounding tissues); it starts when plaque forms on root of tooth and is mineralized to a hard concretion called calculus; this irritates tender gingiva; inflammatory reaction and swelling create gingivitis and pockets between tooth and gingiva invaded by bacteria (spirochetes and anaerobic bacilli); tooth socket may be involved (periodontitis), and the tooth may be lost. taL22600_ch21_633-665.indd Page 663 11/12/13 9:14 PM f-w-166 /202/MH02004/taL22600_disk1of1/0073522600/taL22600_pagefiles 663 Multiple-Choice Questions Level I. Knowledge and Comprehension These questions require a working knowledge of the concepts in the chapter and the ability to recall and understand the information you have studied. Multiple-Choice Questions Select the correct answer from the answers provided. For questions with blanks, choose the combination of answers that most accurately completes the statement. 1. Treponema pallidum is cultured in/on a. blood agar c. serum broth b. animal tissues d. eggs 14. Ornithosis is a a. rickettsial, parrots b. chlamydial, mice 2. A gumma is a. the primary lesion of syphilis b. a syphilitic tumor c. the result of congenital syphilis d. a damaged aorta 15. Mycoplasmas attack the a. nucleus b. cell walls 3. The treatment of choice for syphilis is a. chloramphenicol c. penicillin b. antiserum d. sulfa drugs infection associated with c. chlamydial, birds d. rickettsial, flies of host cells. c. ribosomes d. cell membranes 16. The earliest process at the basis of most dental disease is a. acquired pellicle c. enamel destruction b. acid release d. plaque accumulation 4. Which of the treponematoses is/are not (an) STD(s)? a. yaws c. syphilis b. pinta d. both a and b 17. Dental caries are directly due to a. microbial acid etching away tooth structures b. buildup of calculus c. death of tooth by root infection d. the acquired pellicle 5. Lyme disease is caused by a. Borrelia recurrentis, lice b. Borrelia hermsii, ticks 18. Necrotizing ulcerative gingivitis is a infection. a. contagious c. spirochete b. mixed d. systemic and spread by . c. Borrelia burgdorferi, fleas d. Borrelia burgdorferi, ticks 6. Which of the following conditions may occur in untreated Lyme disease? a. arthritis d. a and b b. rash e. all of these c. heart disorder 7. Relapsing fever is spread by a. lice b. ticks c. animal urine d. a and b 8. The primary habitat of Vibrio cholerae is a. intestine of humans c. natural waters b. intestine of animals d. exoskeletons of crustaceans 9. The best therapy for cholera is a. oral doxycycline c. antiserum injection b. oral rehydration therapy d. oral vaccine 10. Rickettsias and chlamydias are similar in being a. free of a cell wall b. the cause of eye infections c. carried by arthropod vectors d. obligate intracellular bacteria 11. Which of the following is not an arthropod vector of rickettsioses? a. mosquito c. tick b. louse d. flea 12. Chlamydiosis caused by C. trachomatis attacks which structure(s)? a. eye c. fallopian tubes b. urethra d. all of these 13. What stage(s) of Chlamydia is/are infectious? a. reticulate body c. vegetative cell b. elementary body d. both a and b . 19. Single Matching. Match each disease in the left column with its vector or vectors in the right column. a. wild animals leptospirosis b. flea Lyme disease c. tick murine typhus d. birds ornithosis e. louse relapsing fever f. domestic animals lymphogranuloma venereum g. none of these cat-scratch disease epidemic typhus Rocky Mountain spotted fever Q fever cholera anaplasmosis 20. Single Matching. Match each disease in the left column with its portal of entry in the right column. a. skin Q fever b. mucous membrane ornithosis c. respiratory tract dental caries d. urogenital tract NUG e. eye mycoplasma f. oral cavity syphilis g. gastrointestinal tract leptospirosis lymphogranuloma venereum cholera Lyme disease trachoma Campylobacter infection gastric ulcers taL22600_ch21_633-665.indd Page 664 11/12/13 9:14 PM f-w-166 664 Chapter 21 /202/MH02004/taL22600_disk1of1/0073522600/taL22600_pagefiles Miscellaneous Bacterial Agents of Disease Case Study Review 1. The patient in this case was probably treated with a. fluoroquinolones c. vaccination b. specific immunoglobulin d. doxycycline 3. Relate the epidemiology of leptospirosis with the fact that Hawaii typically receives more rainfall than any other state. 2. What other risk factors could have alerted physicians to the possibility of leptospirosis in this case? a. contact with a person suffering from leptospirosis b. consumption of raw milk c. being an avid kayaker d. advanced age Writing Challenge For each question, compose a one- or two-paragraph answer that includes the factual information needed to completely address the question. Check Your Progress questions can also be used for writing-challenge exercises. 1. Describe the conditions leading to congenital syphilis and the longterm effects of the disease. 2. a. Trace the route of the infectious agent from a tick bite to infection in relapsing fever. b. Explain the events in infection that give rise to relapses. 3. a. In what ways are dental diseases mixed infections? b. Discuss the major factors in the development of dental caries and periodontal infections. 4. a. Which diseases in this chapter are zoonoses? b. Name them and the major vector involved. Concept Mapping An Introduction to Concept Mapping found at http://www.mhhe.com/talaro9 provides guidance for working with concept maps. 1. Construct your own concept map using the following words as the concepts. Supply the linking words between each pair of concepts. 2. Supply the linking words, phrases, lines (linkers), and concepts in the following concept map. ticks lice Syphilis Sexual fleas Rocky Mountain spotted fever epidemic typhus endemic typhus bites feces small mammals rodents humans Doxycycline Pinta taL22600_ch21_633-665.indd Page 665 11/12/13 9:14 PM f-w-166 /202/MH02004/taL22600_disk1of1/0073522600/taL22600_pagefiles Visual Challenge 665 Level II. Application, Analysis, Evaluation, and Synthesis These problems go beyond just restating facts and require higher levels of understanding and an ability to interpret, problem solve, transfer knowledge to new situations, create models, and predict outcomes. Critical Thinking Critical thinking is the ability to reason and solve problems using facts and concepts. These questions can be approached from a number of angles, and in most cases, they do not have a single correct answer. 1. a. Why does syphilis have such profound effects on the human body? b. Why is long-term immunity to syphilis so difficult to achieve? 2. a. In view of the fact that cholera causes the secretion of electrolytes into the intestine, explain what causes the loss of water. b. Explain why ORT is so effective in restoring victims of cholera. 3. What would be the best type of vaccine for cholera? 4. a. Explain the general relationships of the vector, the reservoir, and the agent of infection. b. Can you think of an explanation for Lyme disease having such a low incidence in the southern United States? (Hint: In this region, the larval stages of the tick feed on lizards, not on mice.) 5. Humans are accidental hosts in many vector-borne diseases. What does this indicate about the relationship between the vector and the microbial agent? 6. Name four bacterial diseases for which the dark-field microscope is an effective diagnostic tool. 7. Describe the conditions that lead to disease by L forms. 9. a. In what way is the oral cavity an ecological system? b. What causes an imbalance? c. Explain how it is possible for the gingiva and tooth surface to provide an anaerobic habitat. d. What are some logical ways to prevent dental disease besides removing plaque? 10. Have Koch’s postulates been carried out for Lyme disease? Explain. 11. Case Study 1. A journalist returning from a trip experienced severe fever, vomiting, chills, and muscle aches, followed by symptoms of meningitis and kidney failure. Early tests were negative for septicemia; throat cultures were negative; and penicillin was an effective treatment. Doctors believed the patient’s work in the jungles of South America was a possible clue to his disease. What do you think might have been the cause? 12. Case Study 2. A man went for a hike in the mountains of New York State and later developed fever and a rash. What two totally different diseases might he have contracted, and what could have been the circumstances of infection? 8. Which two infectious agents covered in this chapter would be the most resistant to the environment and why are they so resistant? Visual Challenge 1. Identification of a unique skin rash can often be the first step in diagnosing a disease. What infectious agents are indicated by the rashes below? www.mcgrawhillconnect.com Enhance your study of this chapter with study tools and practice tests. Also ask your instructor about the resources available through ConnectPlus, including the media-rich eBook, interactive learning tools, and animations.