Download 21 Miscellaneous Bacterial Agents of Disease

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CHAPTER
21
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Miscellaneous Bacterial
Agents of Disease
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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
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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).
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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
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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
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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).
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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.
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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.
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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
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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.
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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
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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
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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.
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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.
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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
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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?
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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.
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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
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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
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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
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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
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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
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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.