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in Dental Research
The Origin of Periodontal Infections
R.J. Genco, J.J. Zambon and L.A. Christersson
ADR 1988 2: 245
DOI: 10.1177/08959374880020020901
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THE ORIGIN OF PERIODONTAL
INFECTIONS
RJ. GENCO, J. J. ZAMBON, AND L. A. CHRISTERSSON
Departments of Oral Biology and Periodontology and Periodontal Disease Clinical Research Center,
State University of New York at Buffalo, Poster Hall Buffalo, New York 14214
Adv Dent Res 2(2) :245-259, Month, 1988
ABSTRACT
P
eriodontal diseases are recognized as bacterial infections, and some forms are associated with specific
organisms, such as Actinobacillus actinomycetemcomitans in juvenile periodontitis, and Bacteroides gingi-
valis and others in adult periodontitis. The source of the periodontal organisms, whether they are part of the
indigenous or resident flora and overgrow to become opportunistic oral pathogens, or whether they are exogenous oral pathogens, is important to determine. The chain of periodontal infection, microbial agent(s) and
their transmission, and host response are reviewed with respect to the role of A. actinomycetemcomitans in
localized juvenile periodontitis and B. gingivalis in adult periodontitis. The present data lead us to hypothesize
that some periodontal organisms may be exogenous pathogens.
Prevention of periodontal diseases may be influenced by the knowledge of whether various forms are caused
by opportunistic organisms or exogenous pathogens. If exogenous pathogens are responsible, prevention can
be directed to intercepting transmission, thereby preventing colonization. On the other hand, if the organisms
are opportunistic pathogens, prevention might be directed at interfering with initial acquisition of the flora
earlier in life, as well as suppressing them to low levels consistent with health. For those exogenous periodontal
infections, attempts at eradication and prevention of re-infection are likely to be effective. If the organisms are
part of the indigenous flora, there is little hope of complete elimination of the organism.
Criteria for distinguishing exogenous periodontal pathogens from opportunistic periodontal pathogens include the prediction that exogenous pathogens would be transient members of the oral flora associated with
periodontal disease, likely to be comprised of one or a few clonal types, and intrinsically virulent. In contrast,
opportunistic periodontal pathogens would likely be members of the indigenous flora and would overgrow.
They would likely be comprised of many clonal types, and have an intrinsically low level of virulence.
I. INTRODUCTION
Most forms of periodontal disease are bacteria infections (Socransky, 1970,1977; Slots, 1979; Loesche,
1982; Slots and Genco, 1984). Understanding the relationships among the causative bacteria, their transmission, and important host reactions to infection is
critical in the control of periodontal diseases. In this
report, we will address the pathogenesis of the infectious process, with emphasis on the source of the
pathogenic periodontal microbiota. Do these microPresented at the Sunstar Portside Symposium, November 14-15,
1986, Kobe, Japan
This work was supported in part by USPHS Grants No. DE07034,
DE04898, and DE07497. Dr. Zambon is the recipient of a Research
Career Development Award from the National Institute of Dental
Research.
organisms exist as part of the resident oral microflora,
or are they transported to subgingival sites from an
external source? Furthermore, what are the microbial
agents, what is their mode of transmission, and what
is their interaction with the host?
A brief historical overview of periodontal research,
implicating specific bacteria as etiologic agents, will
provide a background. Evidence that bacteria play a
role in periodontal disease will be discussed under
studies of periodontal syndromes in animals, and
studies of human periodontal disease.
The following definitions will be used to help clarify the discussions. The indigenous or resident oral
flora consists of those organisms whose habitat is the
oral cavity, regardless of their pathogenic potential.
They need not be present in the oral cavity in all
patients at all times. In contrast, exogenous oral pathogens are transient members of the oral flora asso245
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246
GENCO et al.
ciated with pathologic states. Exogenous pathogens
exhibit various degrees of virulence and are transmitted from their natural habitat to non-infected oral
sites, which then become diseased. Opportunistic oral
pathogens are those organisms which overgrow because of changes in the oral environment, or because
of loss of host resistance factors, and cause disease.
They may be components of the indigenous oral flora,
but can also be free-living saprophytic organisms. In
general, opportunistic pathogens are normally nonpathogenic, but become important pathogens in immunocompromised patients or under conditions of
increased organ susceptibility, e.g., subacute endocarditis with mitral valve damage.
A. Studies of Periodontal Syndromes in Animals
Periodontal disease does not occur spontaneously
in many species of experimental animals, or occurs
when they are very old. However, Keyes and Likins
(1946) made the important observation that periodontal pathosis does occur spontaneously in young
Syrian hamsters. This observation led to a series of
experiments, with the Syrian hamster used as a model
for periodontal disease, which demonstrated the following: First, the periodontal syndrome in the hamster was both infectious and transmissible. The disease
could be transmitted from infected Golden hamsters
to the non-infected Albino hamsters (in which the
disease does not occur spontaneously) through dental plaque or feces (Keyes and Jordan, 1964). Second,
in this model the transmissible microbial agent was
Actinomyces viscosus, an aerobic Gram-positive filamentous bacterium (Jordan and Keyes, 1964; Ho well
et al., 1965). Other organisms isolated from the hamster — including Streptococci, Sarcina, Gram-negative
rods, and oval or spiral-shaped cells — failed to produce significant pathology when inoculated into uninfected Albino hamsters. Hence, the hamster
periodontitis model was one of the first to show microbiological specificity. Third, filamentous bacteria
isolated from human root-surface caries —including
Rothia dentocariosa, and strains of Actinomyces resembling A. naeslundii, A. viscosus, and A. odontolyticus —
induced the periodontal syndrome as well as cervical
caries in the hamster model system. Subsequent
studies, including those in the rice rat (Dick and Shaw,
1966) and the gnotobiotic rat (Socransky, 1977), have
also demonstrated the essential role of specific bacteria in rodent periodontal syndromes.
Longitudinal studies examining the progression from
naturally-occurring gingivitis to ligature-induced
periodontitis in monkeys show the presence of increased numbers of Gram-negative anaerobes, including black-pigmented Bacteroides (Slots and
Hausmann, 1979; Kornman et al., 1981), in sites with
periodontal loss. For example, B. macacae, a B. gingivalis-like monkey species (Slots and Genco, 1980),
increased to as high as 66% of the total cultivable
organisms, concomitant with a significant loss in alveolar bone mass (Slots and Hausmann, 1979). Sim-
Adv Dent Res November 1988
ilar results have also been obtained using beagle dogs
(Siegrist et al, 1980).
These animal studies are consistent with the hypothesis that periodontal diseases result from specific
and transmissible bacterial infections; they do not address the issue of whether they are exogenous or opportunistic infections.
B. Studies of Human Periodontal Disease
Epidemiologic studies of periodontal diseases carried out in the 1950's and 1960's were reviewed by
Russell (1967). He concluded that there is a direct
relationship between the amount of plaque, oral debris, and calculus, on the one hand, and the severity
of periodontal disease on the other. Furthermore, the
linear correlation between oral debris and the periodontal disease index values is so strong as to leave
little variation in disease severity to be accounted for
by factors other than age or oral hygiene. The strong
positive correlation between oral debris and periodontal disease established an association, but not
necessarily a cause-and-effect relationship, between
these factors.
A direct cause-and-effect relationship between dental
plaque and gingivitis has been demonstrated by Loe et
al. (1965) and Theilade et al. (1966). In these experiments, dental plaque was allowed to accumulate by
cessation of oral hygiene. Clinically measurable gingivitis resulted in most subjects after two to three weeks
of plaque accumulation. Furthermore, when oral hygiene was re-instituted, the crevicular plaque material
was reduced and gingivitis resolved. Hence, these
studies provide convincing evidence that local alterations in the environment, such as occur with cessation
of oral hygiene, allow for the growth of periodontal
micro-organisms and the development of gingivitis.
The gingival flora not only increases in mass, but
there is also a shift from predominantly Gram-positive
aerobic or facultative flora, consisting primarily of Streptococcus sanguis and Actinomyces species, to a much greater
proportion of anaerobic Gram-negative rods and motile
organisms. Bacteroides intermedius, for example, is isolated from the crevicular flora in gingivitis (van Palenstein Helderman, 1981; Moore et al., 1982a).
Since gingivitis can be induced in most if not all
oral sites in humans by dental plaque accumulation,
it is reasonable to postulate that gingivitis is an opportunistic infection caused by an overgrowth of organisms which are part of the indigenous flora.
However, the appearance of organisms such as Bacteroides intermedius raises the question of whether there
are exogenous organisms which can colonize oral sites
only when there are large amounts of pre-existing
plaque. Or put another way, "Are periodontal pathogens such as B. intermedius members of the indigenous oral flora?" Given the apparent heterogeneity
of B. intermedius, it may be that there are virulent and
relatively avirulent forms of this micro-organism. The
virulent forms may colonize as an exogenous infection, or they may be present at extremely low levels
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Vol. 2 No. 2
PER1ODONTAL INFECTIONS
247
in the indigenous flora and overgrow during the depate in active peridontal disease (Tanner et al, 1987).
velopment of gingivitis. Similar variability in strain
In a recent analysis of the predominant cultivable mipathogenicity may occur among strains of other gincrobiota in active destructive lesions of patients with
givitis-associated organisms, such as spirochetes, Fuperiodontitis, Dzink et al (1988) found that subginsobacterium species, and Adinomyces.
gival sites undergoing active loss were often inhabLongitudinal experiments, in humans, demonited by Bacteroides forsythus, B. gingivalis,
strating a cause-and-effect relationship between the
Peptostreptococcus micros, Adinobacillus actinomycetemperiodontal microbiota and the development of pericomitans, Wolinella recta, or B. intermedius, or combiodontitis have not been performed. However, crossnations of these organisms.
sectional studies of adults (Schei et al, 1959) show
Localized juvenile periodontitis (LJP) patients harthat alveolar bone loss is most severe in individuals
bor a subgingival flora different from that found in
judged to have poor oral hygiene, i.e., those who
gingivitis or adult periodontitis. In LJP, Adinobacillus
have the largest accumulation of bacterial plaque at
adinomycetemcomitans (A.a.) is often a predominant
the gingival margin. These and other studies carried
subgingival organism (Slots, 1976; Newman and Soout over the past three decades have established that
cransky, 1977; Slots et al, 1980; Slots and Rosling,
various forms of periodontal disease are initiated by
1983; Zambon, 1985; Asikainen et al, 1987). Capnomicro-organisms through the establishment of a
cytophaga (Newman and Socransky, 1977) and Eikesubgingival microbiota.
nella corrodens in combination with A.
adinomycetemcomitans have also been reported to be
Recently, the microbial specificity of human periprominent in LJP (Mandell and Socransky, 1981;
odontal infections has been appreciated. This conMandell, 1984). Others, however, did not find this
ceptual breakthrough was achieved by application of
association (Okuda et al, 1984; Moore et al, 1985).
technical advances in anaerobic microbiology as well
Capnocytophaga species and Actinobacillus have been
as the accumulation of advanced information on speassociated with advanced periodontitis in juvenile dicies identification and taxonomy to studies of the
abetics (Mashimo et al, 1983) and in granulocytosubgingival flora of man.
penic
and other immunocompromised hosts. In acute
The concept that specific bacteria are essential etinecrotizing ulcerative gingivitis, Baderoides intermeologic factors in different forms of human periodontal
dius and intermediate-sized spirochetes appear to be
disease has received convincing scientific support in
prominent (Loesche et al, 1982; Chung et al, 1983).
recent years (Socransky, 1977; Slots, 1979; van Palenstein Helderman, 1981; Loesche, 1982; Socransky
Hence, it appears — from microbiologic studies of
et al, 1982; Zambon et al, 1983a). Clear differences
periodontal syndromes in animals, and from microin the subgingival microbiota between health and disbiologic studies of human adult and juvenile periease have been well-documented. For example, healthy
odontitis — that these diseases exhibit significant
sites are associated with sparse plaque which consists
microbial specificity.
largely of Gram-positive cocci (Listgarten, 1976; SavFor gingivitis, indigenous organisms may likely play
ett and Socransky, 1984). These cocci are predomian important role, although the contribution, if any,
nantly Adinomyces and streptococci (Moore et al.,
of exogenous pathogens to gingivitis is not clear. For
1982b). Plaque associated with gingivitis appears to
some forms of periodontitis, we hypothesize that excontain increased numbers of Adinomyces species and
ogenous pathogens acquired from an external source
reduced numbers of Streptococci (Loesche and Syed,
are responsible for tissue destruction. Knowledge of
1978). Moore et al. (1982a) have implicated Adinothe source of the micro-organisms which cause perimyces odontolyticus, Adinomyces naeslundii, Fusobader- odontitis is important and has several clinically imiwn nucleatum, Ladobacillus strain type D-2, Streptococcusportant implications. If the causative agents are
angiosus, Veillonella parvnla, and Treponema species as members of the indigenous flora, they would likely
the most likely etiologic agents of experimental ginbe difficult to eradicate, since they have an ecologic
givitis in humans. Plaque associated with gingivitis
advantage in the oral cavity. If they are suppressed
has also been shown to contain Baderoides intermedius indigenous organisms might be expected to recolo(Kornman and Loesche, 1980; Jensen et al., 1981). In
nize oral sites easily. In contrast, exogenous pathosevere forms of adult periodontitis, the subgingival
gens are likely to be more easily eliminated from oral
microflora contains Baderoides gingivalis (Spiegel et al., sites, since they may not be adapted to thrive in the
1979; Tanner et al, 1979; Zambon et al, 1981; Slots,
healthy oral cavity, where many host and microbiol1982; Slots and Genco, 1984; White and Mayrand,
ogical factors act to suppress their colonization.
1981; Van Winkelhoff et al, 1986). Other organisms
found as prominent members of the subgingival flora
II. THE CHAIN OF PERIODONTAL
in periodontitis include Fusobaderium nucleatum, Eubaderium timidum (Moore et al, 1982c), and Bacteroides INFECTION: THE MICROBIAL AGENT,
ITS TRANSMISSION AND THE HOST
capillus (Kornman and Holt, 1981).
Organisms including Haemophilus species, Wolinella
species, Bacteroides forsythus, Selenomonas sputigena, Over the last two and one-half decades, there has
Eikenella corrodens, and spirochetes may also partici- been considerable progress in the understanding of
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248
Adv Dent Res November 1988
GENCO et al.
the infectious etiology of periodontal diseases. The
concepts of bacterial specificity which have emerged
allow us to hypothesize that some forms of periodontal diseases are the result of exogenous pathogens and are, therefore, amenable to effective control
and prevention as with other exogenous infectious
diseases, such as tuberculosis and polio. Knowledge
of the route of infection is a key factor in the prevention and treatment of such diseases. Understanding
the entire chain of infectious disease begins with
identification of the agent, followed by knowledge of
the route of transmission of the agent and, finally,
with characterization of the host response to the agent.
The infectious disease chain as it relates to periodontal infections is described in Table 1.
A. The Microbial Agent
The infectious agent is the first link in the chain of
infection. Identification of the micro-organism(s) associated with many forms of periodontal disease has
proceeded rapidly in the last decade. The next step
is to determine whether the infection is caused by
opportunistic organisms, i.e., does the agent already
reside in the indigenous oral flora and the disease
develop due to changes in the local environment or
host susceptibility which allow its emergence or overgrowth? Or does the agent infect the host from an
external source — is it an exogenous infection? Association of an exogenous bacterium with a disease
provides circumstantial evidence that this bacterium
is causative rather than merely a secondary invader
which has emerged from the resident flora. Full evidence of a causative role, however, requires a detailed understanding of the host bacterial interactions
leading to disease.
Understanding several important characteristics of
the infecting agent may help in disease control. For
example, pathogenicity, which is the ability of an agent
to cause disease, may be high or low. For an agent
with high pathogenicity, disease invariably follows
infection of the host. An example of this is the smallpox virus. Bacteria such as Actinomyces vicosus may
be considered of low pathogenicity, since they have
a high oral colonization rate in man, and only when
they increase to large numbers are they associated
with diseases such as gingivitis, likely as opportunistic pathogens. Pathogenicity may be further characterized by virulence, which describes the ability of
the organisms to cause disease of various degrees of
severity; strains of exogenous pathogens may vary in
virulence. Another feature of pathogenicity is invasiveness, or the ability of the agent to enter the host,
move through tissues, and replicate in situ. Pathogenicity is further defined by the ability of the organism either to evade important defense mechanisms
and/or to produce histiolytic enzymes and toxins that
destroy host tissues and cells.
Other characteristics of the infecting agent which
TABLE 1
INFECTIOUS DISEASE CHAIN IN PERIODONTAL DISEASES:
FACTORS OF IMPORTANCE IN CONTROL AND PREVENTION
I.
II.
III.
Identification of Infectious Agent(s) for Each Form of Periodontal Disease.
A)
Are they endogenous or exogenous agents?
B)
What are their characteristics?
1) pathogenicity; virulence and invasiveness
2) infective dose
3) host specificity
4) antigenic variation
5) physical characteristics (survival)
6) genetic factors (resistance transfer plasmids)
C)
What are their antimicrobial specificities?
Transmission (if exogenous
A)
What is their route or mode of transmission?
1) Contact; either direct (person-to-person), indirect, or droplet (< 1 meter)
2) Common vehicle such as food, water, or contaminated instruments
3) Airborne by droplet nuclei or dust (> 1 meter)
4) Vector
What is their reservoir, natural habitat, and source of immediate transmission to the host?
B)
Host
What is the site of entrance of the agent?
A)
What is the site of colonization of the agent?
B)
What are the important host defense mechanisms?
C)
1) non-specific such as saliva, and inflammation, or
2) specific such as antibodies or cellular immunity (either natural or artificial)
For description of these factors, see Mandell et al., 1985.
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Vol. 2 No. 2
PER1ODONTAL INFECTIONS
are important include the infective dose — that is,
the number of organisms necessary to cause an infection - and the host specificity, which is defined
by the species susceptible to infection. Further important characteristics include antigenic variation over
time, which may occur in a single species of microorganism and change its pathogenicity markedly; the
agent's physical characteristics, which affect its ability
to survive outside of the host; and genetic factors,
such as resistance transfer plasmids or chromosomally based antibiotic resistance.
A feature of prime clinical importance in the characterization of the organism is its spectrum of antimicrobial susceptibility, which allows for selection of
chemotherapeutic or chemoprophylactic measures.
B. Transmission of the Organism
Knowledge of transmission is important for control
of exogenous infections. The route of transmission
may occur through one or more of four modes: contact, common vehicle, airborne, or vector. Transmission by contact may occur through direct person-toperson contact, by indirect contact through an inanimate object such as a shared toothbrush, or by droplets of saliva or other fluid which harbor the agent.
Transmission by contact is functionally defined as direct, or if indirect, by transmission over distances of
less than 1 meter, as would be expected to occur via
droplets of body fluids in which the organism was
contained. A second route of transmission is through
a common vehicle such as food, water, or soil which
contains the agent. The third route of transmission is
airborne by droplet nuclei or dust particles which can
be carried over distances greater than 1 meter. These
airborne particles may carry the agent over distances
of several miles. The fourth route of transmission is
by vectors, which are often insects.
C. Reservoir and Source of Infection
Another major consideration in transmission of the
organism is its reservoir, defined as the natural habitat or the location in which the organism normally
becomes established and multiplies. The source of
transmission is the location from which the organism
is immediately transmitted to the host, either directly
or indirectly through a vehicle. In some instances, the
reservoir and the source may be the same. For example, it is conceivable that the oral cavity of a periodontally diseased individual is both the natural habitat
of certain pathogenic periodontal bacteria and the
source of transmission by direct contact or via droplets. The reservoir and source may also be different.
For example, the reservoir of many pathogens is the
soil, but the direct source of transmission may be
food contaminated by soil.
D. The Host - The Last Link
in the Chain of Infection
The last link in the cycle or chain of infection is the
host. The response of the host to the infection agent
249
determines one of three outcomes: (1) whether the
infected individual is a carrier — that is, the subject
harbors the agent and is able to transmit the agent
but has little or no immunologic or tissue-destructive
response to the agent; (2) the subject maybe subclinically infected, in which case there is often an immunologic response to the agent, but no overt signs
or symptoms of disease; or (3) the host is diseased,
when the infecting organisms cause signs and symptoms of disease and, most often, there is a host immune response to this infection.
The site of entrance of the agent is of critical importance for control. This may be through skin, or
through a mucous membrane in the gastro-intestinal,
genito-urinary, or respiratory tracts. The site of colonization is another important host consideration. An
organism may colonize one site, not cause a disease,
but result in a carrier state. However, when the same
agent colonizes a target organ, it may cause disease.
Hence, the site of colonization may be different for
carriers as compared with those subclinically infected
or diseased.
Knowledge of the key host-response mechanisms
against the infecting agents may allow for the control
or prevention of infectious diseases, not only by eliminating the agent, but also by enhancing potential
host defenses or by suppressing host-destructive effects with agents such as anti-inflammatory drugs.
The natural history of the disease is, to a large extent,
determined by the host response. For example, periods of exacerbation and remission are characteristic
of periodontitis and may be associated with changes
in the host's specific immune status — changes which
may affect the growth rate of the organisms.
Defense mechanisms are either non-specific, such
as many of those operative in saliva, or the mucous
secretions or serum, or specific, such as the antibody
response or cell-mediated immunity. This immunity
may be natural, i.e., present prior to the onset of
colonization, or it may occur as a result of infection.
Specific immunity may provide long-lasting protection, unless it declines rapidly or there are changes
in the antigens of the organism. Artificial immunity
induced by vaccination or immunoprophylaxis has
been among the most effective means of controlling
infections. Vaccinations also offer the possibility of
eradicating the agent from the population, as has been
accomplished for smallpox. This is the ultimate goal
in infection control.
The long-term control and prevention of periodontal
diseases are likely to result from measures directed
toward steps in the infectious chain which are most
susceptible to intervention. Therefore, it is important
that we understand the infectious disease chain as it
operates in the various forms of periodontal disease. It
is instructive to review the research on host-parasite
interactions in periodontal disease to identify those steps
in the infectious chain which are well-described and
those steps where gaps in our knowledge occur. Two
forms of periodontal disease — localized juvenile peri-
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250
Adv
GENCO et al.
odontitis and severe adult periodontitis — will be described, since we have some information about the
specific candidate pathogens for these infections.
III. THE INFECTIOUS DISEASE CHAIN FOR
LOCALIZED JUVENILE PERIODONTITIS
Actinobacillus (Haemophilus) actinomycetemcomitans is
strongly associated with localized juvenile periodontitis (LJP), and the evidence for its role as a pathogen
has been reviewed by Slots and Genco (1984), Zambon (1985), and Zambon et al. (1986a). This evidence
can be summarized as follows: A. actinomycetemcomitans levels in the subgingival flora are high in localized juvenile periodontitis patients and were not
detectable or were at low levels in normal humans.
For example, of a total of 60 LJP patients studied in
our laboratories (Genco et al., 1986a) suffering from
the classic molar-incisor pattern of bone and attachment loss, 57 harbored high levels of A. actinomycetemcomitans in approximately two-thirds of subgingival
sites adjacent to periodontal lesions. This prevalence
of 95% of LJP patients infected with A. actinomycetemcomitans can be compared with 4-5-times-lower prevalence in healthy subjects and adult periodontitis
patients. Of the 142 healthy subjects evaluated, 17%
harbored low levels of A. actinomycetemcomitans, and
in 134 adult periodontitis patients, 24% harbored A.
actinomycetemcomitans (Zambon et al., 1983a).
The second line of evidence is the pathogenicity of
A. actinomycetemcomitans, which is reviewed by Slots
and Genco (1984). Briefly, this organism produces a
leukotoxin active against neutrophils, an endotoxin,
collagenase, and other histiolytic enzymes which may
be of importance in tissue destruction. Furthermore,
A. actinomycetemcomitans is resistant to the bactericidal
activity of human serum. In the absence of serum
killing, phagocytes such as neutrophils become a very
important line of defense.
The third line of evidence is the specific antibody
response seen to this organism (see review by Genco
and Slots, 1984). A great majority of LJP patients (over
98%) have serum antibody to A. actinomycetemcomitans, whereas only 8-10% of normals have serum antibody reactive with this organism. The association
of A. actinomycetemcomitans with localized juvenile
periodontitis and the host immune response to A.
actinomycetemcomitans infection suggest a role for this
organism in the pathogenesis of LJP.
The question can then be asked, is A. actinomycetemcomitans an indigenous or exogenous organism?
In several studies comparing small numbers of nondiseased subjects to LJP patients, A. actinomycetemcomitans was found either in low levels or not at all
in the oral flora of periodontally healthy humans (for
review, see Slots and Genco, 1984). Van der Velden
et al. (1986) found that before or after induction of
experimental gingivitis in humans, no A. actinomycetemcomitans could be cultured on mucosal surfaces
Dent Res November 1988
of the oral cavity or from subgingival plaque. For further assessment of the natural habitat of A. actinomycetemcomitans, 283 patients presenting to the
Preventive Dentistry Clinic at the SUNY/AB School
of Dental Medicine were evaluated for the presence
of A. actinomycetemcomitans in subgingival dental plaque
samples (Zambon et al., 1986b). This group of patients included some seeking service for dental restorations, and others seeking preventive dental services
or routine tooth-cleaning. Most had healthy periodontal tissues or mild gingivitis, and others had mild
periodontitis. However, none suffered from moderate or severe periodontitis, or localized juvenile periodontitis. Sixty-four percent of these subjects did not
demonstrate detectable A. actinomycetemcomitans in
subgingival sites examined by indirect immunofluorescence, with a sensitivity of 0.1% (Fig. 1). None of
the remaining subjects who harbored the organism
had levels greater than 5% of the total subgingival
flora. The subjects in whom A. actinomycetemcomitans
was detected may be carriers, subclinically infected
or suffering from mild adult periodontitis.
In a study comparing the cultivable levels of A.
actinomycetemcomitans in LJP patients with carefully
matched controls, Asikainen and co-workers (1987)
found that 19 of 22 LJP patients harbored A. actinomycetemcomitans in subgingival sites, while none of
the 22 controls had detectable levels of A. actinomycetemcomitans.
An important aspect of these studies is that A. acti-
Distribution of
Actinobacillus actinomycetemcomitans
in Preventive Dentistry Sample
A. actinomycetemcomitans level
(% total cell count in pooled sample)
Fig. 1 —Distribution of Actinobacillus actinomycetcmcomitans in the
University of Buffalo Preventive Dentistry Sample. Two hundred
eighty-three patients presenting to a Preventive Dentistry Clinic
mainly corresponding to patients with little or no periodontal disease, but requiring preventive and restorative procedures and belonging to the American Dental Association Class I and II were
included. B. gingivalis and A. actinomycetemcomitans were assessed
by the indirect immunofluorescence procedure from four subgingival plaque samples taken from the mesial of the four first molars.
There were no patients with LJP or severe periodontitis in this
patient group, (adapted from Zambon et al., 1986b)
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Vol. 2 No. 2
PERIODONTAL INFECTIONS
nomycetemcomitans is present either not at all or only in
low numbers in the flora of most humans not suffering
from periodontal disease, suggesting that this organism
is not a member of the indigenous oral flora. It is reasonable to hypothesize that A. actinomycetemcomitans is
an exogenous pathogen associated with localized juvenile periodontitis and possibly some forms of adult
periodontitis, since it is found to be associated with
disease. If A. actinomycetemcomitans is established to be
an exogenous pathogen, the carrier rate and rate of
subclinical infection will be important to establish.
What are the characteristics of A. actinomycetemcomitans which influence its ability to cause disease? The
production of a leukotoxin for neutrophils and direct
histiolytic properties of A. actinomycetemcomitans point
to this organism as being highly pathogenic, capable
of subverting key host defenses and causing severe
periodontal destruction (Slots and Genco, 1984; Zambon et al., 1986a). Furthermore, A. actinomycetemcomitans appears to be tissue-invasive and can be regularly
found in the gingival connective tissue of LJP patients
(Saglie et al., 1982; Gillett and Johnson, 1982; Christersson et al, 1987a,b).
Additional evidence for its virulence comes from
reports of its participation in extra-oral infections. A.
actinomycetemcomitans has been isolated, together with
Actinomyces israelii, from the "sulfur granules'' of cervicofacial actinomycosis (Klinger, 1912), and it can cause
other severe extra-oral infections, including endocarditis (Page and King, 1966; Peters et al., 1983; Pierce
et al., 1984), abscesses of the brain (Garner, 1979),
abscesses of the face (Page and King, 1966), thyroid
gland (Burgher et al., 1973), urinary tract infections
(Townsend and Gillenwater, 1969), meningitis (Genco
et al., 1980), and vertebral osteomyelitis (Muhle et al.,
1979). Hence, A. actinomycetemcomitans is an exogenous pathogen in human extra-oral sites, capable of
causing severe and often fatal infections.
Knowledge of the A. actinomycetemcomitans infectious dose is lacking, as is information on host preference. It is clear that Actinobacillus species are widely
distributed among primates. For example, many individuals of several species of monkeys harbor A.
actinomycetemcomitans in the gingival flora. It is noteworthy that most of these monkeys do not suffer from
periodontal disease, hence either the monkey strains
of Actinobacillus are non-virulent, or the monkeys are
not susceptible to periodontal disease. This finding
in monkeys points to the pitfall of concluding that
Actinobacillus is part of the indigenous flora based upon
its presence in animals.
A. Antigenic Variations of
A. actinomycetemcomitans
Evidence from our laboratories (Umemoto et al.,
1986) suggests that A. actinomycetemcomitans can
undergo changes in colony morphology from rough
to smooth colonies after being subcultured on agar
media. A. actinomycetemcomitans isolates demonstrate
three types of colony morphology: rough, often seen
251
on primary culture; intermediate, seen during transformation; and mucoid or smooth, seen after transformation. The organism can also revert to the rough
type by repeated animal passage. Electron microscopic examination of the A. actinomycetemcomitans cells
revealed that the rough type are heavily piliated with
type A fimbriae, whereas the rough-to-smooth transition results in loss of fimbriae. Further studies
showed that the ultrastructural and surface protein
profiles of A. actinomycetemcomitans, cultured aerobically, differ from those cells grown anaerobically
(Scannapieco et al., 1987). The extent to which this
variation in surface antigens occurs during natural
infection is unknown, but points to the possibility of
antigenic or phase variation of Actinobacillus strains.
The physical characteristics of the organism affecting its survival outside the body are unknown, and
survival forms such as spores have not been described. However, A. actinomycetemcomitans is a capnophilic, facultative anaerobe, not particularly oxygensensitive, and would be expected to be reasonably
stable outside the host.
B. Transmission of Infection in Actinobacillus
The evidence pointing to A. actinomycetemcomitans
as an exogenous pathogen in man also points to the
importance of understanding its transmission. The
route of transmission for Actinobacillus is not clear;
however, there are several studies which shed some
light on human transmission. In a study of Zambon
et al. (1983b), intrafamilial transmission of A. actinomycetemcomitans is strongly suggested, based upon a
determination of the serotypes (three possible) and
biotypes (10 possible) of A. actinomycetemcomitans isolated from individual family members. Zambon and
co-workers found that each individual is infected with
only one of the three serotypes of Actinobacillus. In
any one family where more than one sibling suffers
from LJP, they are all infected with A. actinomycetemcomitans. Furthermore, in any one family, all infected
members harbor A. actinomycetemcomitans of the same
serotype and also of the same biotype. When the antibody response of these family members is assessed,
they all respond to antigens of the same infecting
serotype of A. actinomycetemcomitans (Genco et al.,
1980). The above studies suggest that the transmission of A. actinomycetemcomitans among family members possibly occurs by contact. Further studies
assessing clonal types among family members may
provide further insight into intrafamilial transmission
of A. actinomycetemcomitans. Whether the contact is
direct, indirect, or by droplet is not known. Preus
and Olsen (1988) found that the strains of A. actinomycetemcomitans infecting a child with periodontitis
and his pet dog were the same clonal type, again
suggesting transmission of A. act inonn/cetenicomi tans
by close household contact.
Investigation of the common vehicle mode of transmission of A. actinomycetemcomitans by use of contaminated instruments was carried out bv Christersson
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252
GENCO et al.
et al. (1985a). They showed that this species of Actinobacillus can be transmitted within an individual patient from an infected periodontal lesion to a noninfected periodontal site. However, A. actinomycetemcomitans only transiently colonizes these previously
uninfected gingival sites, since in 2-3 weeks A. actinomycetemcomitans is no longer demonstrable in the
recipient sites. Furthermore, A. actinomycetemcomitans
does not cause disease at the recipient site. This experiment argues against simple transmission by a single or a few inoculations with a common vehicle such
as a contaminated instrument in an already-infected
patient. These experiments suggest that repeated, direct contact with an A. cictinomycetemcomitcins-iniected
person (or pet?) is necessary for its transmission.
The reservoir of A. actinomycetemcomitans is not
known. It can be hypothesized that the reservoir or
the natural habitat of A. actinomycetemcomitans is the
subgingival flora of patients suffering from Actinobacillary-associated periodontal disease (Slots et al.,
1980; Preus et al., 1987). Other reservoirs, of course
— such as the soil, animals (including pets), or even
other sites in the human body — are possible. The
immediate source of the infecting organism is not
known; however, it may well be saliva from the oral
cavities of infected individuals.
C. Host Factors in Localized Juvenile Periodontitis
The site of entrance of the agent(s) is not known.
They most likely gain entrance through the mucous
membranes of the oral cavity, but other sites (such
as through the skin or the gastro-intestinal tract) are
also possible. The site of initial colonization is also
not known; however, it is clear that the site of colonization during infection is the subgingival area adjacent to the periodontal pocket and within the gingival
tissue. This is particularly important in therapy directed to removing or eradicating A. actinomycetemcomitans, since its presence within the gingival
connective tissue in over 80% of LJP patients makes
it difficult to remove by debridement of the periodontal pocket (Slots and Rosling, 1983; Christersson
et al., 1985b).
The host-bacterial interactions have been well studied in juvenile periodontitis and are summarized by
Genco and Slots (1984) and Genco et al. (1986b). Briefly,
it has been found that: (1) some strains of A. actinomycetemcomitans produce a leukotoxin which kills
neutrophils and, to some extent, macrophages; (2) A.
actinomycetemcomitans also produces a factor which inhibits neutrophil chemotaxis; (3) A. actinomycetemcomitans produces a host of histiolytic and tissuedestructive toxins, such as collagenase and endotoxin; (4) 70% of patients with LJP have defective
neutrophil chemotaxis; and (5) the defective neutrophil chemotaxis seen in LJP is familial and is related
to reduced levels of receptors for chemotactic agents
on the neutrophil surface. This reduced neutrophil
function may explain, in part, the increased susceptibility of certain individuals and families to infection
Adv Dent Res November 1988
by A. actinomycetemcomitans resulting in localized juvenile periodontitis.
A. actinomycetemcomitans also induces a very marked
antibody response characterized by specific antibodies to various Actinobacillus antigens, including the
serotype antigens (Genco and Slots, 1984). In addition, serum antibodies in LJP patients inhibit leukotoxin and are often opsonic. The serum antibody
response, therefore, may be protective. Further identification of the protective antibodies and design of
strategies for inducing these protective antibodies
(leading to vaccine) are certainly desirable goals for
immunoprophylaxis of periodontitis associated with
A. actinomycetemcomitans.
Briefly then, A. actinomycetemcomitans is a candidate
for an exogenous infectious agent in LJP (Table 2).
Control or treatment of LJP has been successfully carried out with methods that result in reduced levels
of A. actinomycetemcomitans from the subgingival microflora and the gingival tissues of periodontal patients (Christersson et al., 1985b). Further studies
directed to preventing the spread of the organism in
families and in other contacts of LJP patients can be
rationally designed once we have more information
about the route of A. actinomycetemcomitans transmission, its reservoir, and its source. Future directions
also include intercepting the cycle of infection by enhancing the host response — for example, by reconstitution of neutrophil abnormalities in LJP (Genco et
al., 1986b) and vaccination against relevant antigens.
IV. ASSESSMENT OF THE INFECTIOUS
DISEASE CYCLE IN ADULT PERIODONTITIS
Identification of the Infectious Agent(s)
In adult periodontitis there may be several infectious agents. At the present time, Bacteroides gingivalis, Bacteroides intermedius,
Actinobacillus
actinomycetemcomitans, Bacteroides, forsythus, Fusobacterium nucleatum, Eikenella corrodens, and Wolinella recta
are candidate pathogens, since they have been associated with active lesions in patients with severe
periodontitis (Slots and Genco, 1984; Tanner et al.,
1987; Dzink et al, 1988).
Adult periodontitis may represent a series of infections similar to the pattern seen in acute otitis media.
In a tabulation of 12 reports involving 4,675 cases of
acute otitis media from centers in the United States,
Finland, and Sweden between 1952 and 1981 (Bluestone and Klein, 1983), it was found that Streptococcus
pneumonia accounted for 33%, Haemophilus influenzae
accounted for 21%, and other Streptococcus species for
8% of the cases. Together, these three organisms account for 62% of the cases of acute otitis media. Another series of bacteria, including Streptococcus aureus,
Branhamella catarrhalis, Gram-negative enteric bacilli,
and several other miscellaneous bacteria, each accounted for anywhere from 1-2% of the remaining
infections. No pathogens could be demonstrated in
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Vol. 2 No. 2
PER1ODONTAL INFECTIONS
253
TABLE 2
INFECTIOUS DISEASE CHAIN IN LOCALIZED JUVENILE PERIODONTITIS
I.
Factor or Process
Findings
Agent
A. actinomycetemcomitans strongly associated with LJP.
95% of LJP patients harbor A. a. in lesions.
AM. strongly associated with disease and not health,
hence likely exogenous.
A) Indigenous or Exogenous
B) Characteristics of Organisms
1. Pathogenicity
Virulence
Invasiveness
Toxicity
2. Infective Dose
3. Host Specificity
4. Antigenic Variation
5. Physical Characteristics
6. Genetic Factors
C) Antimicrobial Susceptibility
Transmission
A) Route
B) Reservoir and Source
III. Host
A) Site of Entrance
B) Site of Colonization
C) Host Defense Mechanisms
A. a. can cause severe extra-oral infections.
A. a. found in LJP.
A. a. produces a leukotoxin, collagenase, LPS.
Not known
Found in normal flora of monkey and rice rat, pathogenic
in horses, swine, and man.
Fimbriation and other surface structures vary.
Unknown
Resistance transfer plasmids found.
Susceptible to tetracycline, some strains resistant to
penicillin, metronidazole, erythromycin.
II.
Not known, may be contact.
Unknown
Unknown
Periodontal lesion sites, oral mucous membranes.
Neutrophils and antibodies likely important.
the SUNY at Buffalo School of Dental Medicine Preventive Dentistry Clinic, we assessed whether B. gingivalis was a member of the gingival flora of normal
periodontally healthy humans (Zambon et al., 1986b).
The results are summarized in Figs. 2 a and b. In this
study, 283 subjects seen in the Preventive Dentistry
Clinic with little or no periodontal disease were compared with 70 subjects with moderate to severe periodontitis who were referred for periodontal treatment
(Johansson et al., 1987). Indirect fluorescence microscopy was used to detect subgingival B. gingivalis and
A. actinomycetemcomitans. From four to ten gingival or
Bacteroids forsythus ("fusiform" Bacteroides), B. gingisubgingival plaque samples were analyzed for each
valis, B. intermedius, Wolinella recta, or Peptostreptococsubject
or patient. Alveolar bone heights were also
cus micros was elevated either singly or in combination,
measured and correlated with the microbiologic findthe likelihood that the lesion was actively undergoing
ings. In the adult periodontitis group (Fig. 2.b), 65/
attachment loss was increased.
70, or 93%, harbored B. gingivalis, while in the PreIn the last decade, evidence has accumulated
ventive
Dentistry group (Fig. 2a.), 37% of the subjects
strongly implicating Bacteroides gingivalis as one of the
harbored
subgingival B. gingivalis. Statistically, this
prominent members of the pathogenic microbiota asdifference was highly significant (p< 0.001). The Presociated with severe adult periodontitis (Slots and
ventive Dentistry group included some patients with
Genco, 1984; Spiegel et al, 1979; Tanner et al., 1984;
mild periodontitis, and these were the patients in
White and Mayrand, 1981; Loesche et al., 1985; Van
whom B. gingivalis was most often detected. There
Winkelhoff et al., 1986; Dzink et al., 1988). Often, B.
was a direct correlation between the amount of bone
gingivalis is a prominent subgingival black-pigmented
loss in this group and the levels of B. gingivalis found.
Bacteroides. B. intermedius is also present in the
It is reasonable to hypothesize from these results,
subgingival flora of adult periodontitis patients, as is
and from previous studies showing that B. gingivalis
A. actinomycetemcomitans.
is not found at detectable levels in the subgingival
The question of whether B. gingivalis is indigenous
flora of most normal humans, that B. gingivalis is an
or exogenous has begun to be evaluated. In a study
specific pathogen found in the lesions of a large
of B. gingivalis in a population of patients coming to
30% of the cases. Hence, the pattern in otitis media,
which may be analogous to that in adult periodontitis, is that a few pathogens account for a large percentage of the cases, with a large number of other
organisms accounting for the remaining cases. Another possibility for explaining the role of specific
pathogens in adult periodontitis is that the pathogenic bacteria occur in combinations. For example,
Dzink and co-workers (1988), in a comparison of the
cultivable microbiota of active and inactive periodontal lesions, found that when A. actinomycetemcomitans,
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Adv Dent Res November 1988
GENCO et al.
254
TABLE 3
INFECTIOUS DISEASE CHAIN IN ADULT PERIODONTITIS
I.
Factor or Process
Findings
Agent
Bacteroides gingivalis strongly associated, likely others such
as B. intermedius, F. nucleatum, W. recta, E. corrodens.
A) Endogenous or Exogenous
B. gingivalis found in AP, but in few if any normal humans,
hence likely an exogenous pathogen.
Not known for other suspected pathogens for adult
periodontitis.
B) Characteristics of Organisms
1. Pathogenicity
Virulence
Invasiveness
Toxicity
2. Infective Dose
3. Host Specificity
4. Antigenic Variation
5. Physical Characteristics
6. Genetic Factors
C) Antimicrobial Susceptibility
Transmission
A) Route
B) Reservoir and Source
III. Host
A) Site of Entrance
B) Site of Colonization
B. gingivalis can cause severe extra-oral infections.
Unknown, except for oral-facial abscesses.
B. gingivalis produces collagenase, a host of
proteolytic enzymes, and LPS; resists phagocytosis.
Unknown.
B. gingivalis-like organisms found in beagle dogs, cats,
jaguars, and monkeys. May be part of indigenous flora in
monkeys.
Unknown.
B. gingivalis sensitive to oxygen.
Unknown.
B. gingivalis susceptible to tetracyclines, penicillins,
metronidazole, clindamycin and erythromycin.
No p-lactamase.
II.
C) Host Defense Mechanisms
proportion of periodontitis patients. Further experiments using more sensitive measures of detecting B.
gingivalis in the subgingival flora, at sites other than
in the oral pharynx, as well as at other sites in the
body, will be necessary for further determination of
B. gingivalis as a resident of the indigenous flora of
man, or if it is an exogenous pathogen. The carrier
rate and the subclinical infection rate for B. gingivalis
are as yet not described.
The pathogenicity of B. gingivalis has been studied
(see review by Slots and Genco, 1984). Many strains
of B. gingivalis are virulent and associated with destruction of both connective tissues and bone in periodontal disease. B. gingivalis can cause severe extraoral infections, including mediastinal, fascial plane,
brain, and lung abscesses (see Slots and Genco, 1984).
The invasiveness of B. gingivalis has been evaluated
in a study by Petrovic and Fillery (1984), and the organism was found to be attached to the epithelium
of the periodontal pocket.
B. gingivalis produces collagenase and a large battery of proteolytic enzymes (see review by Slots and
Genco, 1984). It also demonstrates resistance to
Unknown.
Unknown.
Unknown.
May be the oral cavity, subgingival flora, oral mucous
membranes, tonsils.
Humoral antibodies may be important in defense, otherwise unknown.
phagocytosis. B. gingivalis has also been shown to
resist serum bactericidal mechanisms (Sundqvist and
Johansson, 1980), and some strains are lethal when
injected subcutaneously into mice (Van Steenbergen
et al., 1982). The infective dose has not been established, and a good animal model is still needed for
B. gingivalis infection.
A. Important Host Preferences
A B. gingivalis-\ike organism is found in beagle dogs
(Kornman et al., 1981) as well as in monkeys (Slots et
al., 1980a). Of considerable interest is the finding from
both animal models of a B. gingivalis-like species in
the oral flora prior to the initiation of ligature-induced
periodontitis. Hence, a B. gingivalis-like organism may
be a member of the indigenous oral flora of beagles
and monkeys. The host preference of B. gingivalis may
be based upon specific adherence factors to epithelial
tissues or oral organisms via ligands on the bacterial
surface. These specific reactions may exhibit marked
species differences, accounting for the differences in
distribution of B. gingivalis among man, beagles, and
monkeys.
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Vol. 2 No. 2
PERIODONTAL INFECTIONS
Distribution of Bacteroides gingivalis
Levels in Preventive Dentistry Sample
gingivalis', however, plasmids have been found in B.
intermedius (Dickinson et al., 1987).
(a)
I
0.1-0.9
1.0-1.9
2.0-2.9
3.0-3.9
ft gingivalis level
(% total cell count in pooled sample)
Distribution of Bacteroides gingivalis
Levels in Periodontitis Patients
2.0-2.9
3.0-3.9
4.0-4.9
255
2,5.0
B. gingivalis level
(Average % of total cell counts/patient)
Fig. 2 —(a) Distribution of Bacteroides gingivalis levels in Preventive
Dentistry Sample. Two hundred eighty-three patients presenting
to a Preventive Dentistry Clinic mainly corresponding to patients
with little or no periodontal disease, but requiring preventive and
restorative procedures and belonging to the American Dental Association Class I and II were included. B. gingivalis and A. actinomycetemcomitans were assessed by the indirect immunofluorescence
procedure from four subgingival plaque samples taken from the
mesial surfaces of the four first molars. There were no patients
with LJP or severe periodontitis in this patient group, (adapted
from Zambon et al., 1986b)
(b) Distribution of Bacteroides gingivalis levels in periodontitis patients. Seventy subjects with moderate to severe adult periodontitis, ADA Class III and Class IV, referred for periodontal
treatment were assessed for subgingival B. gingivalis by indirect
immunofluorescence techniques. From four to ten subgingival
samples were analyzed for each subject.
Antigenic variation of B. gingivalis has not been reported. The ability of the organism to survive outside
the subgingival site has not been fully evaluated;
however, it can be expected that since B. gingivalis is
highly anaerobic, it may not persist for long periods
of time in an oxygen-rich atmosphere.
No plasmids or phage have been reported in B.
The antimicrobial susceptibility has been described
and reviewed by Genco (1981). B. gingivalis is sensitive to a large number of commonly used antibiotics,
including penicillin and its derivatives, tetracycline,
erythromycin, metronidazole, and clindamycin, as well
as the derivatives of tetracycline, including minocycline, doxycycline, and chlortetracycline. Beta lactamase production by black-pigmented Bacteroides
appears not be to a property of Bacteroides gingivalis',
however, some strains of other black-pigmented Bacteroides have been shown to produce p-lactamase (Slots,
1982).
B. Route of Transmission
B. gingivalis appears to be a periodontal pathogen
in man, and its route of transmission is of considerable interest. However, our present knowledge of the
transmission of B. gingivalis is very limited. We have
some evidence of the reservoir or source of infection.
Since the organism is found in subgingival flora, on
the lateral borders of the tongue, the buccal mucous
membranes, and the tonsils of patients with periodontitis (Zambon et al., 1983a), the human reservoir
may be the subgingival flora and the oral pharynx of
infected adult periodontitis patients. Further study is
necessary for full understanding of the transmission
and acquisition of B. gingivalis. There are at least two
possibilities: One is that B. gingivalis is acquired by
healthy individuals in adolescence or early adulthood
and resides as a member of the indigenous flora. Critical changes occur in the environment or the host
susceptibility such that B. gingivalis overgrows and
causes disease as an opportunistic pathogen. Alternatively, B. gingivalis may be an exogenous pathogen
acquired shortly before the development of periodontal disease.
C. Host Response to B. gingivalis
in Adult Periodontitis
The time of acquisition as well as the site of initial
entrance and colonization of B. gingivalis are unknown. Initial colonization is likely to be in the oral
cavity; however, other sites of colonization of B. gingivalis in the body — including the nasal pharynx,
various levels of the gastro-intestinal tract, and the
genito-urinary tract and skin — remain to be fully
investigated.
Host defense against B. gingivalis has been studied,
particularly the humoral antibody response and cellmediated immunity (see review by Genco and Slots,
1984). Briefly, patients infected with B. gingivalis produce high titers of serum antibody reactive with surface antigens of this organism. A year or so after
treatment, the serum antibody response declines.
Furthermore, early studies by Reed et al. (1980) showed
that B. gingivalis has unique antigens which distinguish this species from other black-pigmented Bac-
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256
Adv Dent Res November 1988
GENCO et al.
teroides, both oral and non-oral. Since (a) the antigens
are unique, (b) there is a significant specific immune
response in adult periodontitis patients, and (c) this
antibody response to B. gingivalis declines after therapy, it is reasonable to hypothesize that the immune
response seen to B. gingivalis in humans with periodontal disease is the result of periodontal infection.
The ability of these antibodies to opsonize or otherwise protect against B. gingivalis infection is unknown, and the role, if any, of antibodies to B.
gingivalis in the tissue destruction seen in periodontitis requires further study.
Treatment of adult periodontitis which results in
the suppression or elimination of the subgingival microbiota has proved to be effective (Christersson et
al., 1988). In these studies, the clinical and microbiological effects of antimicrobial agents as adjuncts
to mechanical periodontal debridement were assessed in 79 adult periodontitis patients. The relationships between subgingival B. gingivalis and changes
in probing attachment levels 12 months after therapy
were sought. In a total of 427 lesions studied, B. gingivalis was detected in 53.1% of the lesions showing
probing attachment loss (>1.5 mm), but in only 4.7%
of lesions showing attachment gain (>1.5 mm). These
results strongly suggest that suppression of subgingival B. gingivalis in adult periodontitis can lead to
clinical success or, at least, the absence of B. gingivalis
correlates well with healing after therapy. Furthermore, persistence of B. gingivalis is consistent with
further periodontal breakdown. It remains to be determined if persistence of B. gingivalis results from
inadequate elimination, repopulation by the organism from the host, or re-infection from another
source.
Since we have very little information on the route
of B. gingivalis transmission or of its reservoir or source,
it is premature to approach the prevention of B. gingivalis-dLSsotiated peridontal disease by means of interfering with the infectious disease chain. However,
if the oral cavity in infected individuals is the reservoir and source of B. gingivalis infection, then
suppression of B. gingivalis may be achieved by the
use of antibiotics such as penicillin and tetracycline,
or through use of topical antiplaque or antimicrobial
agents.
The evaluation of other organisms and their role in
adult periodontitis is important and will likely be directed to evaluation of the chain of infection involving pathogenic agents such as Bacteroides intermedius,
Fusobacterium nucleatum, Wolinella recta, Eikenella corrodens, Bacteroides forsythus, Eubacterium species, and
Peptostreptococcus micros. It will be necessary for researchers to investigate the role of each of these species alone and in combination, keeping in mind the
infectious disease chain and designing experiments
which are directed to identifying the infectious agent,
and to determining whether it is an exogenous pathogen or a member of the indigenous flora which becomes an opportunistic pathogen.
CRITERIA FOR DISTINGUISHING
AN EXOGENOUS FROM
AN OPPORTUNISTIC ORAL PATHOGEN
The following criteria may be useful in distinguishing exogenous periodontal pathogens from bacteria
which are opportunistic oral pathogens:
(1) An exogenous periodontal pathogen is a transient member of the oral flora associated with
periodontal disease. It may also be present in
carriers and those subclinically infected.
(2) An exogenous periodontal pathogen is likely to
be comprised of one or a few clonal types.
(3) An exogenous periodontal pathogen has the
potential to be virulent, acting either singly or
in combination with other members of the periodontal microflora.
In contrast:
(1) An opportunistic periodontal pathogen is a
member of the indigenous oral flora, and
overgrows or expresses its pathogenicity when
a change in the environment or host occurs.
(2) An opportunistic periodontal pathogen is likely
to be comprised of many clonal types.
(3) An opportunistic periodontal pathogen has a
low level of intrinsic virulence, but can cause
disease when it overgrows at the site of the
lesion, or when the host's defense mechanisms
are depressed.
Studies addressing the issue of whether various
periodontal organisms are exogenous or opportunistic pathogens will provide much-needed information on the infectious disease chain in various forms
of periodontal disease, including juvenile periodontitis, adult periodontitis, generalized juvenile periodontitis, rapidly advancing forms of periodontitis,
and periodontitis associated with various systemic
diseases such as diabetes, Down's Syndrome, neutrophil abnormalities, and acquired immune deficiency syndrome. With this information, we are likely
to be better prepared to prevent and manage periodontal disease by interference at a susceptible stage
in the chain of infection.
ACKNOWLEDGMENTS
The authors thank Drs. Per Brandtzaeg, Boris Albini, Jeff Ebersole, Mogens Kilian, and Else Theilade
for critical discussions leading to the definitions of
exogenous and opportunistic pathogens, and the indigenous flora, and to establishing criteria for distinguishing exogenous from opportunistic pathogens.
We thank the staff of the State University of New
York at Buffalo Periodontal Disease Clinical Research
Center for their role in the clinical studies. Special
appreciation is expressed to Mrs. Rose Parkhill for
her expert help in preparing this manuscript.
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Vol. 2 No. 2
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257
Use and Interpretation of Microbiological Assays in Periodontal
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