Medical Microbiology

Lecture 9
 Actinomyces
Actinomyces are typically elongated Gram-positive rods that branch at acute
angles.
• grow slowly (4-10 days)
• microaerophilic or strictly anaerobic.
• Most human actinomycosis is caused by Actinomyces israelii, but other species
have been isolated from typical actinomycotic lesions.
• Other species of Actinomyces have been associated with dental and periodontal
infections
• Actinomyces are normal inhabitants of some areas of the gastrointestinal
tract of humans and animals from the oropharynx to the lower bowel.
• These species are highly adapted to mucosal surfaces and do not produce disease unless
they transgress the epithelial barrier under conditions that produce a sufficiently low
oxygen tension for their multiplication.
• Such conditions usually involve mechanical disruption of the mucosa with necrosis of
deeper, normally sterile tissues (e.g, following tooth extraction).
• The lesion is composed of inflammatory sinuses, which ultimately discharge to the surface.
• As the lesion enlarges, it becomes firm.
• As with other anaerobic infections, most cases are polymicrobial involving other flora from
the mucosal site of origin.
• Human cases of actinomycosis provide little evidence of immunity to Actinomyces.
• Once established, infections typically become chronic and resolve only with the aid of
antimicrobial therapy.
• Infections with Actinomyces are endogenous, and case-to-case transmission does not
appear to occur.
 MANIFESTATIONS
Actinomycosis exists in several forms that differ according to the original site and
circumstances of tissue invasion.
• Infection of the cervicofacial area, the most common site of actinomycosis, is usually
related to poor dental hygiene, tooth extraction, or some other trauma to the mouth
or jaw.
• Lesions in the submandibular region and the angle of the jaw give the face a
swollen, indurated appearance.

 Diagnosis is usually delayed, because only nonspecific symptoms are

produced until a vital organ is eroded or obstructed.
• The firm, fibrous masses are often initially mistaken for a malignancy.
• It is particularly difficult to distinguish from other inflammatory conditions or
malignancies.
• A more localized chronic endometritis, due to Actinomyces, is associated with the
use of intrauterine contraceptive devices.
A clinical diagnosis of actinomycosis is based on the nature of the lesion,
• Although the lesions may be extensive, the organisms in pus may be few and
concentrated in sulfur granule microcolonies deep in the indurated tissue. .
• Material for direct smear and culture should include as much pus as possible to
increase the chance of collecting the diagnostic sulfur granules.
 TREATMENT
Penicillin G is the treatment of choice for actinomycosis
• High doses of penicillin must be used and therapy prolonged for up to 6 weeks or longer
before any response is seen.
 Nocardia
Nocardia species are Gram-positive, rod-shaped bacteria related to
mycobacteria that show true branching both in culture and in stains from
clinical lesions.
• The microscopic morphology is similar to that of Actinomyces, although
Nocardia tend to fragment more readily and are found as shorter
branched units throughout the lesion rather than concentrated in a few
colonies or granules.
• In contrast to Actinomyces, Nocardia species are strict aerobes.
• Growth typically appears on ordinary laboratory medium (blood agar)
after 2 to 3 days incubation in air.
EPIDEMIOLOGY
Nocardia species are in the environment, particularly in soil.
• In fact, fully developed colonies of Nocardia give off the aroma of wet
dirt.
• The organisms have been isolated in small numbers from the respiratory
tract of healthy persons, but are not considered members of the normal
flora.
• Most pulmonary cases occur in patients with compromised immune
systems due to underlying disease or the use of immunosuppressive
therapy.
• There is no case-to-case transmission.
PATHOGENESIS
 Factors leading to disease after inhalation of Nocardia are poorly understood.
 The bacteria have the ability to resist the microbicidal actions of phagocytes
and may be related to the disruption of phagosome acidification or resistance
to the oxidative burst.
• The primary lesions in the lung show acute inflammation, with suppuration
and destruction of parenchyma. Multiple, confluent abscesses may occur.
• Unlike Actinomyces infections, there is little tendency toward fibrosis and
localization.
DIAGNOSIS
• The diagnosis of Nocardia infection is much easier than that of actinomycosis,
because the organisms are present in greater numbers and distributed more
evenly throughout the lesions.
• Demonstration of acid-fastness, when combined with other observations, is
diagnostic of Nocardia .
• Culture of Nocardia is not difficult because the organisms grow on blood agar.
 TREATMENT
• For decades Nocardia infection has been one of the few indications for
systemic use of sulfonamides alone or combined with trimethoprim.
 Recent surveys indicate an increase in resistance to sulfonamides
including the Trimethoprim–sulfamethoxazole combination.
 Spirochetes
spirochetes are bacteria with a spiral morphology ranging from loose coils to a rigid
corkscrew shape.
 MORPHOLOGY AND STRUCTURE
• The cell wall and axial fibrils are completely covered by an outer bilayered membrane
similar to the outer membrane of other Gram-negative bacteria.
• Although they are Gram negative, many either take stains poorly or are too thin to fall
within the resolving power of the light microscope. Only darkfield microscopy ,
immunofluorescence, or special staining techniques can demonstrate these spirochetes.
• Other spirochetes such as Borrelia are wider and readily visible in stained preparations,
even routine blood smears.
 SPIROCHETA L DISEASES
• Some spirochetes are free living; some are members of the resident flora of
humans and animals.
• The oral cavity, particularly the dental crevice, harbors a number of nonpathogenic
species of Treponema and Borrelia as part of its flora.
• Most Borrelia and Leptospira infections are zoonoses transmitted from wild
and domestic animals.
• Treponema pallidum is a strict human pathogen transmitted by sexual
contact.
 Leptospira interrogans
It is the member of the genus Leptospira
that is pathogenic to humans and
animals.
• Leptospira interrogans has over 200
serotypes.
• Leptospira interrogans can survive days
or weeks in some waters in the
environment at a pH above 7.0.
• Acidic conditions, such as those that
may be found in urine, rapidly kill the
organism.
• It is highly sensitive to drying and to a
wide range of disinfectants.
 EPIDEMIOLOGY
• It is usually transmitted to humans through water contaminated with animal urine.
• Secondary human-to-human transmission occurs rarely.
 PATHOGENESIS AND IMMUNITY
• The organism gains entrance to the tissues through small skin breaks, the
conjunctiva, or, most commonly, ingestion through the upper tract mucosa.
• The active motility of the hooked ends driven by periplasmic flagella may allow the
organism to burrow into tissues.
• The organisms spread widely through the bloodstream to all parts of the body
including the CSF.
• The kidney is also a target organ in human disease, causing tubular infection
and nephritis.
 MANIFESTATIONS
Most infections are subclinical and detectable only serologically.
• After an incubation period of 7 to 13 days, an influenza-like febrile illness with
fever, chills, headache, conjunctival suffusion, and muscle pain develops in
persons who become ill. This disease phase is associated with bacteremia.
• This second phase of the disease usually lasts 3 or more weeks and may
manifest as an aseptic meningitis resembling viral meningitis or as a more
generalized illness with muscle aches, headache, rash, pretibial
erythematous lesions, biochemical evidence of hepatic and renal
involvement, or all of these.
• In its most severe form (Weil disease), there is extensive vasculitis,
jaundice, renal damage, and sometimes a hemorrhagic rash.
• The mortality rate in such cases may be as high as 10%.
DIAGNOSIS
The diagnosis of leptospirosis is primarily serologic.
• Although the spirochetes can theoretically be detected, dark field
examination of body fluids is not recommended.
TREATMENT AND PREVENTION
Penicillin is the primary treatment for all forms of leptospirosis. Doxycycline and
ceftriaxone are alternatives. BORRELIA
 Borrelia
EPIDEMIOLOGY
• Relapsing fever occurs in two forms linked to the mode of transmission and the Borrelia
species involved.
• the two forms are sometimes called epidemic (louse-borne) and endemic (tick-borne)
relapsing fever. Here they are identified simply by the insect involved.
• Ticks may remain infectious for several years even without feeding and transovarial
passage.
• infected lice live no more than 2 months, and there is no transovarial passage to progeny.
• Infected lice must be passed human to human for the disease to persist. These conditions
are met by circumstances that combine overcrowding with extremely low levels of general
hygiene.
 PATHOGENESIS
• The febrile illness has endotoxin-like features, but the exact mechanisms of disease are
unknown.
• Between episodes, the organisms disappear from the blood and are sequestered in internal
organs only to reappear during relapses.
 MANIFESTATIONS
After a mean incubation period of 7 days, massive spirochetemia develops, with high fever,
rigors, severe headache, muscle pains, and weakness.
• The febrile period lasts about 1 week and terminates abruptly with the development of an
adequate immune response.
• The disease relapses 2 to 4 days later, usually with less severity, but following the same
general course.
• Tick-borne relapsing fever is usually limited to one or two relapses, but with louse borne
disease three or four may occur.
• Louse-borne relapsing fever is more severe than tick-borne disease
• Fatalities are rare in tick-borne disease but may be as high as 40% in untreated louse-borne
• Fatal outcomes are due to myocarditis, cerebral hemorrhage, and hepatic failure.
 TREATMENT
Patients with relapsing fever respond well to doxycycline or tetracycline (louse-
borne) therapy, with erythromycin and ceftriaxone as alternatives.
 PREVENTION
Prevention of tick-borne relapsing fever involves attention to deticking, insecticide
treatment, and rodent control.
 Treponema pallidum
 is the causative agent of syphilis.
• Treponema pallidum is a slim spirochete resemble a corkscrew.
• It multiplies for only a few generations in cell cultures and is
difficult to subculture.
• growing very slowly.
• Treponema pallidum shares the Gram-negative structural style of
other spirochetes,
EPIDEMIOLOGY
In most cases, infection is acquired from direct sexual contact with a
person who has an active primary or secondary syphilitic lesion.
 PATHOGENESIS
The spirochete reaches the subepithelial tissues through unapparent breaks
in the skin or possibly by passage between the epithelial cells of mucous
membranes
• In the submucosa, it multiplies slowly stimulating little initial tissue reaction.
• the organisms spread from the primary site to the bloodstream within minutes
and
• are established in distant tissues within hours.
• The small arterioles show swelling and proliferation of their endothelial
cells.
• This reduces or obstructs local blood supply, probably accounting for the
necrotic ulceration of the primary lesion and subsequent destruction at other
sites.
• The disease is clinically silent until the disseminated secondary stage
develops and then is silent again with entry into latency.
 MANIFESTATIONS
Primary Syphilis
The primary syphilitic lesion is a papule that evolves to an ulcer at the site of
infection. This is usually the external genitalia or cervix.
• The lesion becomes indurated and ulcerates but remains painless, though slightly
sensitive to touch.
• The fully developed ulcer with a firm base and raised margins is called the chancre.
• Firm, non suppurative, painless enlargement of the regional lymph nodes usually
develops within 1 week of the primary lesion and may persist for months.
• It heals spontaneously after 4 to 6 weeks.
Secondary Syphilis
Secondary or disseminated syphilis develops 2 to 8 weeks after the
appearance of the chancre.
• The primary lesion has usually healed but may still be present.
• rash and generalized non tender lymph node enlargement with fever, malaise, and
other manifestations of systemic infection.
• Skin lesions are distributed on the trunk and extremities, often including the palms,
soles, and face.
• About one-third of patients develop painless mucosal warty erosions called
condylomata lata. They resolve spontaneously after a few days to many weeks, but
the infection itself has resolved in only one-third of patients. In the remaining two-
thirds, the illness enters the latent state.
Latent Syphilis
Latent syphilis is by definition a stage in which no clinical manifestations are present,
but continuing infection is evidenced by serologic tests.
• In the first few years, latency may be interrupted by progressively less severe relapses
of secondary syphilis. Transmission to others is possible from relapsing secondary
lesions and by transfusion or other contact with blood products.
Tertiary Syphilis
Another one-third of patients with untreated syphilis develop tertiary syphilis.
• The manifestations may appear as early as 5 years after infection but
characteristically occur after 15 to 20 years.
• The manifestations depend on the body sites involved, the most important of which
are the nervous and cardiovascular systems.
• The most advanced central nervous system (CNS) findings include a combination of
neurologic deficits and behavioral disturbances called paresis, which is also a
mnemonic (personality, affect, reflexes, eyes, sensorium, intellect, speech) for the
myriad of changes seen.
• Cardiovascular syphilis is due to arteritis involving the vasa vasorum of the aorta and
causing a medial necrosis and loss of elastic fibers.
 TREATMENT AND PREVENTION
Treponema pallidum remains exquisitely sensitive to penicillin, which is the
preferred treatment in all stages. In primary, secondary, or latent syphilis,
persons hypersensitive to penicillin may be treated with doxycycline.
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