Periodontology 2000, Voi.
21, 1999, 106-124
Printed in Denmark All rights reserved
Oral mucosal lesions caused by
infective microorganisms
I. Viruses and bacteria
RIVERA-HIDALGO
FRANCISCO & THOMAS
W. STANFORD
The purpose of this chapter is to concisely review
oral lesions that are caused by viruses and bacteria
infecting the oral tissues. In this context we adhere
to the classical concept of infection: the state of in-
jury or damage that results from the process by
which organisms, capable of causing disease, gain
entry to the body and establish colonies.a Oral
lesions may originate from local infections or may
represent the oral manifestations or consequences of
a systemic infection.
The oral mucosal environment is characterized by
the presence of a large complex microbiota that,
under normal circumstances, does not cause pa-
thosis. The health status of the mouth is largely the
result of a balance resulting from the interaction be-
tween microorganisms and the local defensive
mechanisms, and thus, any changes that may alter
this interaction may lead to disease. Factors that may
alter this balance include changes in the integrity of
the epithelium, changes in lubrication of the mucosa
and changes in secretion of saliva.
This oral environmental balance might also be al-
tered by changes in the systemic defensive posture
that result from a compromised immune system.
When the defensive system is temporarily weakened
by stress, smoking and poor oral hygiene, diseases
such as acute necrotizing ulcerative gingivitis can
ensue. Normal microbiota microorganisms can be-
come opportunistic pathogens in an altered oral en-
vironment.
Lesions of infective origin may affect any of the
oral mucosal structures: the masticatory mucosa, the
lining mucosa and the specialized mucosa. The term
infective stomatitis, used as an inclusive term, is pre-
ferred to group these lesions. For the purpose of this
Modified from: Collins dictionary of medicine. Glas-
gow, Harper Collins.
I06
Coavrinht 0 Munksgaard I999
PERIODONTOLOGY 2000
ISSN 0906-6713
-
review, the lesions of infective stomatitis are categor-
ized according to the type of microorganism causing
the infection. The literature reports on bacterial
stomatitis, fungal stomatitis, parasitic stomatitis and
viral stomatitis. This chapter presents reviews of vi-
ruses and bacteria. Part I1 presents reviews of fungi
and parasites.
Incidence of infective stomatitis
Infective stomatitis is infrequently observed in the
healthy individual, but there exists an impression of
an overall increase in incidence during the past few
years due to increased incidence rates of tubercu-
losis (189) and syphilis (55). There have also been
reports of an increased incidence of opportunistic
oral infections (3) and other types of oral infections
(99), especially in human immunodeficiency virus
(HIV)-positivepatients.
One may speculate that the ever-increasing use of
antibiotics, an expanding population of immuno-
suppressed individuals and a more mobile global
society are factors that have contributed to the rise
in the incidence of oral infections. By far, immuno-
suppression represents the major contributing fac-
tor. With the appearance of HIV disease, many of the
previously rare diseases have reappeared and some-
times with a different presentation.
The development of molecular biology techniques
and better understanding of immune mechanisms
have contributed significantly in the detection of
previously unrecognized pathogens in a disease pro-
cess. This is particularly true for virally induced dis-
eases.
It is with this background that we review the
literature for oral infectious diseases.
 Oral mucosal lesions caused bv infectiue microorganisms. I. Viruses and bacteria

Table 1. Oral viral infections

Strains or other names
Infection Causative virus or acronyms
~-
Measles Measles virus
Mumps Mumps virus
Hand, foot and mouth disease Coxsackievirus (A5, A10, A16)
Herpanaina Coxsackievirus (A2-6,A10)

Primary herpetic gingivostomatitis Herpes simplex type 1 (HSV-1) or type 2 virus

Recurrent intraoral herpes HSV-1, HSV-2 (HHV-1, HHV-2)
Recurrent herpes labialis HSV-1, HSV-2 (HHV-1, HHV-2)
Varicella (chickenpox1 Varicella-zoster virus (HHV-3)
Shingles Varicella-zoster virus (HHV-3)
Infectious mononucleosis Epstein-Barr virus (HHV-4)
Hairy leukoplakia Epstein-Barr virus (HHV-4)
(HHV-5)

Roseola (exanthema subitum)" Human herpesvirus 6 (HHV-6)

Heterophil-negative infectious mononucleosis

Kaposi's sarcoma Kaposi's sarcoma herpesvirus (HHV-8)

a Oral lesions have not been reported: this is included from completion. High proportions of oral squamous carcinoma lesions have been shown to be
positive for HHV-6.
A recent report supports a role for HHV-7 in pityriasis rosea.

Infective stomatitis: 1954, preferentially infects monocytes. Measles is a

infections caused by viruses
Oral lesions secondary to viral infections are rela-
tively common during an individual's lifetime. Dis-
eases of the infancy and childhood such as measles
and mumps are caused by an RNA virus (para-
myxoviridae) and may present oral lesions. Coxsacki-
eviruses, a subgroup of the RNA enteroviruses, cause
herpangina and hand, foot and mouth diseases,
which present oral lesions. Oral papillomas, oral ver-
rucous carcinoma and focal epithelial hyperplasia
are caused by a DNA virus (human papillomavirus
of the papovavirus family). Oral lesions are also pro-
duced by the human herpesvirus family, which are
DNA viruses. Viruses belonging to the herpes family
are major pathogens in oral disease. A summary of
oral viral infections appears in Table 1.
Paramyxoviridae
Paramyxoviridae is a family of RNA viruses com-
posed of three genera: Paramyxovirus, Morbillivirus
and Pneumovirus.
Measles. An enveloped RNA virus that belongs to the
Morbillivirus genus causes measles (rubeola) (8, 74).
This virus, which was first isolated in cultures in
highly communicable disease transmitted by inhal-
ation of infective droplets with an incubation period
of 10 to 14 days. Measles remains a major cause of
childhood mortality in developing countries (36).
Measles is one of a group of vaccine-preventable dis-
eases in which vaccination programs have greatly re-
duced its incidence. It is an acute systemic condition
with a prodrome in which the patient suffers from
cough, conjunctivitis, fever, photophobia, rhinitis
and Kopliks spots. Kopliks spots, the bluish-gray
specks on a red base, are pathognomonic for
measles, as they appear approximately 48 hours be-
fore the irregular red-brick maculopapular skin rash.
Kopliks spots appear on the mucosa next to the mo-
lar teeth and may last for 4 days. Shedding of the
measles virus starts during the prodromal stage and
continues through the acute stage. A recent report
has shown that laboratory confirmation of measles
is possible using oral fluids for the detection of
measles-specific immunoglobulin M (IgM) (76). In a
recent report, cases originally diagnosed as measles
or rubella (German measles) were later diagnosed as
primary herpesvirus 6 and herpesvirus 7 infections
(181.
Mumps. Mumps (epidemic parotiditis) (8, 74) is
caused by the mumps virus, an RNA virus that be-

107
Rivera-Hidalgo& Stanford
longs to the Paramyxovirus genus. Parotid salivary
gland infection may occur unilaterally or bilaterally,
and viremia can lead to orchitis, aseptic meningitis,
pancreatitis and oophoritis, especially in unvaccin-
ated individuals. Affected salivary glands may be
swollen and painful and may be accompanied by
erythema and swelling of the parotid (Stensen’s)
duct. Mumps is a highly communicable disease
transmitted by inhalation of infective droplets with
an incubation period of 14 to 21 days. Similar to
measles, the disease is one of a group of vaccine-
preventable diseases, and vaccination programs
have greatly reduced its incidence.
Picornaviridae
Picornaviridae is a family of single-stranded nonen-
veloped RNA viruses composed of three genera: En-
terovirus, Poliovirus and Rhinovirus. The Enterovirus
genus includes the coxsackievirus (A and B), echo-
viruses, enteroviruses and poliovirus (types 1, 2 and
3).
Coxsackieviruses. Coxsackieviruses are antigenically
divided into groups A and B comprising more than
50 serotypes. Infections are more common during
the summer months and are transmitted by con-
taminated aerosol (74). Many of these viruses can
cause oropharyngeal vesiculoulcerative lesions and
are clinically differentiated by the location of the
lesions (47). These viruses are responsible for hand,
foot and mouth disease, herpangina, lymphonodular
pharyngitis and ulcerative oropharyngitis, all pro-
ducing oral lesions. Lymphonodular pharyngitis fea-
tures orange slightly painful papules in the soft pal-
ate while ulcerative pharyngitis produces ulcerations
in the soft palate, lips and buccal mucosa (47).
Hand, foot and mouth disease. Hand, foot and
mouth disease can be caused by coxsackieviruses A5,
A10 and, most commonly, by A16. It is a disease of
children with an incubation period of 3 to 5 days,
but the disease has been reported in adults as well
(97). The lesions appear as ulcerations on buccal
mucosa (rhomboidal vesicles “square blisters” (162))
and soft palate, often in conjunction with ulcers on
the hands and feet. In the largest reported epidemic
in England and Wales during 1994, most of 950 cases
were children 1-4 years of age and disease severity
was associated with the degree of mouth lesions
(14). Treatment with acyclovir has been reported to
be effective (162). The disease is benign and resolves
in 7 to 10 days.
108
Herpangina. Herpangina is caused by coxsackie-
viruses A2, A3, A4, A5, A6 and A10. It features clus-
tered petechiae in the soft palate that become shal-
low ulcers in a few days and then heal. Headache,
high fever, myalgia and sore throat precede soft pal-
ate lesions. Treatment is palliative.
Papovaviridae
Papovaviridae are a family of DNA viruses that are
responsible for producing tumors and capable of
transforming animal cell lines. The family is com-
posed of the Papillomavirus genus and the Polyoma-
virus genus.
Papillomavirus. The human papillomavirus is com-
posed of more than 60 serological types (39). Papil-
lomaviruses cause lesions in many areas of the body,
including genitalia, the nasal cavity, larynx, trachea,
esophagus and the mouth. Diagnosis of papillomavi-
rus lesions is made based on the histopathological ap-
pearance. Characteristic features include koilo-
cytosis, acanthosis and papillomatosis which,
coupled to the clinical appearance, suggest the infec-
tion (39). The classical oral lesions associated with hu-
man papillomavirus are squamous cell papilloma (58,
143, 182), condyloma acuminatum (58, 1431, verruca
vulgaris (58, 143) and focal epithelial hyperplasia (58,
143).
Squamous cell papilloma is a cauliflower-like
lesion with a narrow base. It is a small, pink exophyt-
ic growth of the oral mucosa. The lesion of condylo-
ma acuminatum is similar, presenting multiple
small, soft, pale lesions with a cauliflower-like sur-
face. Histologically, both lesions have the same ap-
pearance, and human papillomavirus types 6 and 11
are involved (135, 197). Treatment is by surgical ex-
cision.
Verruca vulgaris or the common wart is a narrow
exophytic growth, wider at the base, sessile and firm.
The lesion is usually found on the gingiva, labial mu-
cosa, commissure, hard palate or tongue (113, 135,
137). Human papillomavirus types 2 and 57 have
been identified in the lesions (125, 135). Treatment
is by surgical excision.
Focal epithelial hyperplasia (Heck‘s disease)
usually presents as multiple plaque-like or papular
lesions, flat or convex, in the mucosa mostly of
children (34). The color may vary from red to gray to
white (135). Lesions occur on oral mucosa exclus-
ively (135). There may be a genetic predisposition,
and contrary to the initial reports, the condition is
not limited to certain ethnic groups (136). The
 Oral mucosal lesions caused by infective microorganisms. I. Viruses and bacteria
lesions are benign and may resolve spontaneously.
Human papillomavirus types 13 and 32 have been
implicated as causative agents (124, 135).
Other oral lesions (135) that have been associated
with human papillomavirus include erythroplakia
(HPV-16), proliferative verrucous leukoplakia (HPV-
16) (1261, candidal leukoplakia (1881, oral squamous
cell carcinoma (HPV-16 and HPV-19) (9, 109, 135,
188) and lichen planus (HPV-6, HPV-11 and HPV-16)
(87, 135, 179). Overall, HPV types 2, 4, 6, 11, 13 and
32 have been associated with benign oral lesions
while HPV types 16 and 18 have been associated
with malignant lesions (58). Transmission of the vi-
rus can occur with direct contact and from mother
to child during delivery (138).
Herpetoviridae
The Herpetoviridue family contains only one genus:
Herpesvirus. Viruses of the herpes family are double-
stranded DNA viruses transmitted from host to host
by direct contact with saliva or genital secretions,
where they are shed by asymptomatic hosts (67). The
herpes viruses are classified into three groups (30).
The alpha group (subfamilyAlphuherpesvirinue) in-
cludes the herpes simplex virus 1 (HSV-l),the herpes
simplex virus 2 (HSV-2) and the varicellazoster virus.
The beta group (subfamily Betuherpesvirinae) in-
cludes the human cytomegalovirus, while the
gamma group (subfamily Gummuherpesvirinae) in-
cludes the Epstein-Barr virus. The species names
and the acronyms of herpes viruses used in the
literature are as follows: human herpesvirus 1 (HSV-
11, human herpesvirus 2 (HSV-21, human herpesvi-
rus 3 (varicellazoster virus), human herpesvirus 4
(Epstein-Barr virus), human herpesvirus 5 (human
cytomegalovirus), human herpesvirus 6 (HHV-61,
human herpesvirus 7 (HHV-7)and human herpesvi-
rus 8 (HHV-8 or Kaposi’s sarcoma herpesvirus).
Herpesviruses cause a primary infection after
which they remain latent within the host’s cells for
the life of the individual. While latent, the virus may
become reactivated and may cause symptomatic or
asymptomatic recurrent infection (160). Factors that
may trigger reactivation of the virus include trauma,
stress, immunosuppression, immune dysfunction
and radiotherapy (22, 123). Latency is maintained
(67) for HSV-1, HSV-2 and varicellazoster virus in
sensory nerve ganglia; Epstein-Barr virus in B
lymphocytes and salivary gland tissue (1131, human
cytomegalovirus in lymphocytes and salivary gland
tissue, HHV-6 in mononuclear cells in ductal epithel-
ium (192), HHV-7 in salivary gland tissue primarily
the submandibular gland (153) and HHV-8 in sali-
vary gland tissue (102). It has been proposed that the
clinical patterns of reactivation of HSV-1, HSV-2 and
varicellazoster virus are different (170).
Herpes simplex virus types 1 and 2. The primary in-
fection with herpes simplex virus usually occurs in in-
fants or children and may cause a prodrome of fever,
malaise and nausea. The infection may go unnoticed,
be subclinical or produce pharyngitis (67). Usually,
the infection presents vesicles on the mucosa of the
mouth and pharynx that break to produce ulcers. A
generalized marginal gingivitis may occur in conjunc-
tion with ulcers in the alveolar mucosa and gingiva,
and crusting of the lips is a common feature. Lesions
can occur extraorally, while systemic symptoms
usually include fever and chills. This primary herpetic
gingivostomatitis is usually accompanied by cervical
lymphadenopathy, and it may be more severe when
it occurs in adults (47). Disseminated herpes simplex
virus infections have been reported with a flu-like
prodrome and a severe generalized outbreak of vesic-
ulo-ulcerative lesions. The disseminated herpes sim-
plex virus infection can occur during pregnancy, and
infants born during the course of such infection have
a high mortality rate (196).
After the primary infection, the virus goes dor-
mant in the sensory and autonomic trigeminal or
sacral ganglia to be reactivated by certain conditions.
Latent infection exists when the viral genome is
present in the tissue without production of infective
viral particles (169). Recurrent infections affect 20%
to 40% of individuals after the primary infection (67).
Recurrent infections with type 1herpes simplex virus
are classically described as occurring above the
waist, whereas type 2 infections occur below the
waist, but either can appear in the other region.
There is regional preference of reactivation for each
virus; type 1 virus appears to arise more frequently
from the trigeminal ganglia, affecting the oral cavity,
whereas type 2 is most often reactivated from the
sacral ganglia, producing genital lesions (195). The
typical appearance of intraoral recurrent lesions (re-
current intraoral herpes) is of a cluster of small ul-
cers in the attached gingiva. The initially discrete
and usually painful ulcers may coalesce to form
larger lesions that heal in 10 to 12 days. In HIV-posi-
tive patients and other immunocompromised indi-
viduals, atypically deep and large ulcers may occur
that persist for weeks to months.
Herpes labialis (cold sores) is a common express-
ion of recurrent herpes infection. Lesions may affect
the lips and perioral skin as a result of triggering of
109
Rivera-Hidalgo & Stanford
a latent ganglion infection, usually by ultraviolet
radiation (96), other local stimuli, fever, emotional
stress or menstruation (169). Lesions appear as
closely clustered vesicles that tend to reappear in the
same area with each outbreak (170). It is interesting
to note that, even after repeated infection, there ap-
pears to be no sensory loss in the area (65).
Trigeminal neuralgia has been described in con-
junction with episodes of herpes labialis, suggesting
that the neuro-sensory abnormalities may be in-
duced by reactivation of herpes simplex virus (65). In
addition, herpetic reactions may sometimes trigger
unilateral or bilateral facial paralysis (herpetic facial
paralysis), which may be identical to Bell’s palsy
(157). Herpetic infection of the fingers (herpetic
Whitlow) can induce painful locally severe lesions in
which surgical intervention may lead to spread of
the virus and is thus contraindicated (89, 90). Her-
petic Whitlow was an occupational hazard for dental
professionals prior to initiation of universal infection
control measures such as gloving for all patient care
in dental practice. Acyclovir has been recommended
in treatment of the various forms of recurrent HSV-
1 and HSV-2 infections, but the drug appears more
predictably successful in the management of genital
herpes as opposed to oral lesions. Oral lesions are
quite responsive to acyclovir, however, in immuno-
compromised individuals (147).
In HIV-positive patients, herpes simplex virus has
been recovered from persistent oral ulcers in more
than 30% of cases (48). In another report, cultures
from 40 HIV-positive patients with persistent oral ul-
cers yielded herpes simplex virus in 19% of the cases,
cytomegalovirus in 53% and coinfection of herpes
simplex virus and cytomegalovirus in 28% (53). In
this study, treatment with systemic ganciclovir in
conjunction with oral acyclovir resulted in lesion res-
olution in all but one case.
Diagnosis of herpes simplex virus from lesions can
be made using cultures, which take up to 10 days, or
by using enzyme-linked immunosorbent assay (961,
polymerase chain reaction (65, 169) or direct immu-
nofluorescence. Cultures are more predictably diag-
nostic if obtained from an early vesicular lesion
rather than an ulcer.
Varicella zoster virus (HHV-3). The varicella zoster
virus causes varicella (chickenpox) as a primary in-
fection mainly in children and later, in adults, its re-
activation causes herpes zoster (shingles). Varicella
is a highly infectious disease transmitted by inhal-
ation of infective droplets and by direct contact with
lesions. It is self-limiting in children and more severe
110
in adults. The pruritic skin rash progresses through
macules, papules, vesicles, drying vesicles and scabs,
with healing occurring over 2 to 3 weeks. Oral lesions
include vesicles on the lips, hard palate and soft pal-
ate (113). After the primary infection, the virus re-
mains latent in the dorsal root ganglion (it is not
clear whether it resides in neurons or in satellite cells
(156)) to be reactivated later.
Herpes zoster results from reactivation of the lat-
ent virus. Fever and malaise may accompany the ap-
pearance of lesions. Vesicles quickly break to form
ulcerated lesions with prominent red borders, re-
sembling apthae. Lesions are unilaterally distributed
along the infected nerve (113). Paresthesia, pain and
tenderness are the initial symptoms of herpes zoster,
which may appear prodromally 3-5 days before the
lesions (67).The infection is more frequent in elderly
individuals, and it has been suggested that shingles
may signal the presence of systemic disease. When
reactivation occurs from the trigeminal ganglion,
there seems to be a preference for the second or
third divisions (67). It is not known what induces re-
activation, but alterations in cell-mediated immun-
ity have been implicated (91). In most patients, the
infection is self-limiting. Antiviral agents (acyclovir,
valacyclovir and famciclovir (67, 130))are effective in
reducing the course of the disease in varicella and in
reducing the effects of secondary infections. Anti-
viral agents should be used as early as possible in
disease development (113).
Prolonged postherpetic neuralgia is a common af-
termath of herpes zoster (118).It is hypothesized that
the neuralgia results from virally induced lesions in
the neurons (145).Necrosis of alveolar bone followed
by tooth exfoliation has been described as a compli-
cation of intraoral herpes zoster (118).
In immunocompromised individuals, including
those with HIV, there is increased incidence and re-
currence (170) of herpes zoster infection. Chronic
varicella occurs in HIV-positive patients and is an
atypical persistent form of the disease. Treatment
with intravenous acyclovir and foscarnet has been
effective in controlling the infection (27). Clinical
presentation and occurrence of complications of vi-
rus reactivation are related to degree of immuno-
deficiency (178).
Epstein-Barr virus (HHV-4). The Epstein-Barr virus
is transmitted by blood or saliva. Primary infection
can occur at any age. It is often subclinical in
children. Epstein-Barr virus can cause infectious
mononucleosis in adolescents and young adults.
The symptoms of infectious mononucleosis in-
 Oral mucosal lesions caused by infective microorganisnu. I. Viruses and bacteria
clude fever, lymphadenopathy (especially the pos-
terior cervical chain), malaise and sore throat (phar-
yngitis). Oral ulcers, multiple palatal petechia and
infrequently gingival ulcerations have been reported
(67, 113). Diagnostic tests for heterophile antibodies
produced by Epstein-Barr virus are available
(Monospot test). The disease is self-limiting, requir-
ing bed rest and analgesics, with recovery usually oc-
curring in about 4 weeks. Acyclovir has not been ef-
fective in treatment.
Occasionally, a latent infection of Epstein-Barr vi-
rus can be reactivated, leading to viral shedding into
the oral mucosa. It has been hypothesized that con-
stant shedding can lead to infection of epithelial
cells, and this may explain the appearance of oral
hairy leukoplakia in HIV-positive patients (82).
Oral hairy leukoplakia was first described in HIV-
positive homosexual men (69). Clinically, it presents
as a white lesion most often on the ventral-lateral
surface of the tongue that can be unilateral or bilat-
eral (156). Lesions have a corrugated appearance
with keratin projections that look like hair. The his-
tological features include parakeratosis with hair-like
projections, hyperplasia, acanthosis and koilocyte-
like cells within the epithelium and an absence of
inflammation in the connective tissue (156).Langer-
hans cells are also absent (37).There is evidence that
Epstein-Barr virus replicates within epithelial cells
(70). The appearance of oral hairy leukoplakia in
HIV-positive patients may be highly predictive of the
development of AIDS (71). Reports indicate, how-
ever, that in some cases, oral hairy leukoplakia can
appear in the absence of HIV, and oral hairy leuko-
plakia has been reported in patients who are not im-
munosuppressed (102, 113). Additionally, there are
reports of lesions similar to oral hairy leukoplakia in
cases that were Epstein-Barr virus negative (66, 111).
Epstein-Barr virus has also been found in malig-
nancies (nasopharyngeal carcinoma, Burkitt’s
lymphoma, B-cell lymphoma (67) and oral squam-
ous cell carcinoma (52)) and in periodontal disease
(35), although its role in periodontal disease has not
been determined.
Human cytomegalovirus (HHV-5). Human cyto-
megalovirus is found in many of the body secre-
tions (including blood, milk and saliva) of infected
individuals. However, it is one of the least preva-
lent herpesvirus infections (113). Most primary in-
fections are asymptomatic, and it is not clear
where the virus remains latent, although it is re-
coverable from 25% of salivary glands (74). Endo-
thelial and ductal epithelial cells seem to be a tar-
get for human cytomegalovirus (86). Antibody to
human cytomegalovirus is present in the serum of
most homosexual men (74).
Human cytomegalovirus infection produces
three recognizable clinical syndromes (74): peri-
natal disease and human cytornegalovirus in-
clusion disease, acute acquired human cytoineg-
alovirus infection and human cytomegalovirus dis-
ease in immunocompromised hosts. Perinatal
disease is the result of a primary infection while
the mother is pregnant. The infection may affect
the fetus, causing severe consequences. When the
infection is acquired neonatally, it resembles infec-
tious mononucleosis or it may be asymptomatic.
The second syndrome is similar to infectious
mononucleosis except that there is no (or milder)
pharyngitis associated and no production of heter-
ophil antibodies. The third syndrome is observed
in immunocompromised individuals, tissue and
bone marrow transplant patients, and in HIV-in-
fected patients. Human cytomegalovirus infection
in these patients is in itself immunosuppressive
and can worsen HIV opportunistic infections.
Oral lesions in patients infected with human cyto-
megalovirus occur in the latter two syndromes. The
most common manifestation of primary infection is
heterophil-negative infectious mononucleosis (1131,
which occurs in adults (113). Infection can result
from sexual contact and blood transfusions (67).The
disease follows a course similar to that seen with
Epstein-Barr virus infection and is self-limiting.
Oral ulcerations related to human cytomegalo-
virus have been described in immunodepressed pa-
tients (53, 86, 141). It has been reported that, in a
group of HIV-positive patients, more than half (53%)
of persistent ulcers were associated with human
cytomegalovirus, and another 28% were associated
with human cytomegalovirus and herpes simplex vi-
rus coinfection (53).Tissue biopsies of suspected hu-
man cytomegalovirus-induced oral ulcers can be di-
agnosed by a combination of histological and im-
muno cytochemical met hods (53).Treatment with a
combination of oral acyclovir and systemic ganciclo-
vir has proved successful (53).
Human herpesvirus 6 (HHV-6). The originally
named human B-lymphotropic virus (154) has re-
cently been reclassified as a herpesvirus and re-
named HHV-6 (168). In infants, this virus is associ-
ated with roseola (exanthema subitum or sixth dis-
ease), a self-limiting condition that causes a mild
skin exanthem and fever (1). HHV-6 is commonly
isolated from saliva (in mononuclear cells in ductal
111
Rivera-Hidalgo & Stanford
epithelium) and has affinity for CD4 lymphocytes
(192). It is also suspected of causing mononucleosis,
pneumonia, meningitis, encephalitis and as a cofac-
tor in accelerated immunosuppression in HIV-in-
fected individuals. Infection with HHV-6 can induce
the expression of CD4 on CD8+ cells (lymphocytes
and natural killer cells), thus rendering them suscep-
tible to infection by HIV-1 (106). It is believed that
HHV-6 is responsible for short-lived febrile illnesses
and active hepatitis in previously healthy individuals
as well as prolonged febrile illness in patients that
are immunodeficient (168). Two variants have been
identified, A and B (94). The B variant is sensitive to
ganciclovir, and both are sensitive to foscarnet (74).
There are instances where infectious mononu-
cleosis cannot be associated with either Epstein-Barr
virus or human cytomegalovirus infection. There is
evidence that HHV-6 is responsible for some of these
infections, although is not clear whether these repre-
sent primary infections or reactivation of latent virus
(168). There is also evidence that both H W - 6 and
Epstein-Barr virus, as coinfectants, are responsible
for some acute infectious mononucleosis (17).
HHV-6 has been found in oral squamous carci-
noma lesions (191, 192) and in cervical carcinoma
(191). In a study of 51 squamous cell carcinomas, 18
non-malignant lesions and 7 normal mucosa
samples, HHV-6 was found in 79% of malignancies,
67% of lichen planus lesions and leukoplakia and
was not present in normal mucosa (193). In this
study, HHV-6 variant B was found in 60% of the ma-
lignancies.
Human herpesvirus 7 (HHV-7). HHV-7 is a ubiqui-
tous virus, that is very similar to HHV-6 in that it has
serological cross-reactivity with some antibodies to
HHV-6 (102). Infection is usually acquired in child-
hood with most adults being seropositive. The virus
is found in saliva and is secreted for many years after
initial infection (173). Saliva represents the major
mode of transmission, and transmission has been
detected from a grandparent to a parent to a child
(173). In general, initial infection occurs later in life
than with HHV-6 infection. Minor labial salivary
glands have been shown to harbor the virus, and
these glands may sometimes be the sites where rep-
lication occurs (193). In a study of more than 100
specimens from the three salivary glands, HHV-7
was found in 100% of submandibular gland samples,
85% of the parotid gland samples and in 59% of lip
minor salivary gland samples (153). HHV-7 has been
reported to enhance the cytotoxicity of natural killer
cells through induction of interleukin 15 (5).
112
HHV-7 appears to be associated with at least
two conditions: roseola and pityriasis rosea. Pa-
tients recovering from roseola were found to have
sera positive to both HHV-6 and HHV-7, suggesting
a role for both viruses in the disease (120). Patients
with pityriasis rosea showed HHV-7 DNA in
plasma, supporting a role for viral replication and
virulence (42). Pityriasis rosea is a self-limiting ex-
anthem without systemic signs or symptoms char-
acterized by crops of maculopapular pale-red oval
lesions on skin that may last for up to 2 weeks
(60). Oral lesions of the tongue and cheek have
been reported in pityriasis rosea (180). There is
evidence that infections misdiagnosed as measles
and rubella could be caused by primary infections
of HHV-6 or HHV-7 (18).
Human herpesvirus 8 (HHV-8). Newly discovered,
the human herpesvirus 8 is believed to be associated
with the pathogenesis of human lymphomas (22,
30). Originally, the virus was called Kaposi’s sarcoma
herpesvirus and was later renamed HHV-8 (57, 93).
HHV-8 DNA sequences have been identified in body
cavity-based non-Hodgkin’s lymphomas, Castle-
man’s disease, angioimmunoblastic lymphadeno-
pathy and all forms of Kaposi’s sarcoma (102, 105).
Serological evidence indicates that HHV-8 is found
in 25% of the adult population and in up to 8% of
children in the United States (100). It is also evident
that women with AIDS are much less likely to de-
velop Kaposi’s sarcoma than men (63).
Kaposi’s sarcoma was originally described as a
rare vascular malignant tumor occurring in elderly
men of mainly Mediterranean, eastern European or
Middle Eastern origin. The tumor has become more
prevalent with the advent of the AIDS epidemic, al-
though it has been reported in the skin of an HIV-
negative immunosuppressed patient with bullous
pemphigoid (59). These reports suggest that im-
munosuppression may serve to activate a latent
HHV-8 infection. In one study, HHV-8 DNA se-
quences were identified in 53 of 54 AIDS related oral
Kaposi’s sarcoma lesions (54). Palliative treatment of
the oral lesions has been reported using an intrale-
sional injection of vinblastine (46).
Infective stomatitis:
infections caused by bacteria
Bacterial infective stomatitis has been reported in
both immunocompetent and immunocompromised
patients. Some of these infections can become es-
 Oral mucosal lesions caused bv infective microornanisms. I. Viruses and bacteria
tablished as a result of transmission during sexual
activity; others result from a weakening in the host’s
defense posture and are thus opportunistic in na-
ture. In these section we review the reported bac-
terial infections that can present oral lesions. A sum-
mary of oral bacterial infections and responsible or-
ganisms appears in Table 2.
Acute necrotizing ulcerative stomatitis
Acute necrotizing ulcerative gingivitis (or necrotizing
gingivostomatitis or necrotizing ulcerative gingivitis)
is an acute infection of the gingiva that has been
known by different names through the years (78).
Because of its prevalence in the soldiers fighting in
the trenches during World War I, it was called trench
mouth; because of a description of the microorgan-
isms in the lesions by Vincent, it was also called Vin-
cent’s infection. Vincent’s angina refers to an infec-
tion of the tonsils and pharynx usually associated
with acute necrotizing ulcerative gingivitis. Likewise,
noma or cancrum oris or gangrenous stomatitis is
often an extension of acute necrotizing ulcerative
gingivitis into the adjacent tissues. Noma is at best
disfiguring and can be lethal if not treated promptly.
In recent years, the disease has become a common
cause of mortality and disability in children of
underdeveloped areas of Africa, Asia and South
America (2, 38, 174). Noma has been reported in pa-
tients with HW, where local removal of necrotic
tissue along with lavage with providone-iodine has
been effective in controlling the disease (31).
Acute necrotizing ulcerative gingivitis is an infec-
Table 2. Oral bacterial infections
Infection
Acute necrotizing ulcerative gingivitis (necrotizing ulcerative gingivitis,
necrotizing gingivostomatitis,necrotizing stomatitis, noma (cancrum oris),
Vincent’s infection, trench mouth)
Actinomycosis
Bacillary angiomatosis (epithelioid angiomatosis)
__
- ~~~
Gonorrhea
.-
Streptococcal stomatitis
______ ~ . __.
tious disease of the gingiva causing gingival
bleeding, gingival ulceration (that may lead to the
loss of the tissue forming the papilla) and pain. It
has been reported more commonly in young adults,
although recently it has been reported with increas-
ing frequency in children in developing countries.
Factors that may predispose to the initiation of this
disease include episodes of stress, smoking, malnu-
trition and poor oral hygiene (80). These factors sug-
gest that, given the condition where poor oral hy-
giene exists, events that can depress the host’s im-
mune response can precipitate the disease.
A mixed flora of spirochetes (Treportema spp.),
fusobacteria (Fusobacterium n u c l e a t u m ) , Preuotella
intermedia, Veillonella spp. and streptococci and
have been implicated in the disease. Early attempts
to induce the disease by the subcutaneous injection
of cultures from active patients have only produced
abscesses and not the disease (150). From the lesions
created, Fusobacterium fusiforme and Borwlia irin-
centii (a spirochete) can be recovered. However, later
work showed that the spirochete found in the lesion
was not B. vincentii (104). Listgarten showed spiro-
chetes infiltrating healthy tissue ahead of the lesion.
Other bacteria and viruses have been found associ-
ated to the lesions, but no cause-effect relationship
has been established (116).
Acute necrotizing ulcerative gingivitis has been re-
ported in recent years in patients with HIV infection
or AIDS. Acute necrotizing ulcerative gingivitis has
been included in a classification of periodontal dis-
eases associated with HIV infection (43, 112). 1he
classification includes: linear gingival erythema, nec-
Causative bacteria ~ ~~~~
Mixed bacterial flora
including spirochetes and Fusobacteria
__ ~~
Actinomyces israelii
Actinomyces viscosus
Actinomyces odontolyticus
Actinomyces naeslundii
Bartonella quintana
BaronteZlu henselae
__ _ _ _ _ _ _ _ _
~ ~
Neisseria gonorrhoeae
~~ ~~
Mycobacterium tuberculosis
Mycobacterium leprae
rium avium and intracellulare
rium bovis
rium chelonae
__ Mycobacterium--kansasii
-
~
Streptococci
Group A beta-hemolytic streptococci
~~ ~~~ ~ ~~~~ ~.
113
Rivera-Hidalgo & Stanford
rotizing ulcerative gingivitis and necrotizing ulcer-
ative periodontitis. In this classification acute nec-
rotizing ulcerative gingivitis is described as destruc-
tion of one or more gingival papilla, with ulceration,
cratering and necrosis. In a study of naval personnel,
Horning & Cohen reported that acute necrotizing ul-
cerative gingivitis cases in seropositive and in sero-
negative HIV cases were clinically indistinguishable
(80).
Necrotizing ulcerative periodontitis is described as
producing very rapid bone loss in addition to the
findings for acute necrotizing ulcerative gingivitis
(116). Severe deep aching pain with a very rapid rate
of bone destruction is characteristic of necrotizing ul-
cerative periodontitis. It is believed by some that nec-
rotizing ulcerative periodontitis is an extension of
acute necrotizing ulcerative gingivitis.Acute necrotiz-
ing ulcerative gingivitis and necrotizing ulcerative
periodontitis have been correlated with decreased
CD4 counts (<200/mm3). Glick et al. (62) reported
that HIV-seropositive individuals presenting with
necrotizing ulcerative periodontitis were 20.8 times
(odds ratio) more likely to have CD4 counts below 200
cells/mm? compared with HIV-seropositive individ-
uals without necrotizing ulcerative periodontitis. In
this study, the predictive value of a CD4 count below
200 cells/mm3 in patients with necrotizing ulcerative
periodontitis was 95%. Further, the cumulative prob-
ability of death within 24 months of a necrotizing ul-
cerative periodontitis diagnosis was 73%. Necrotizing
ulcerative periodontitis can extend into the alveolar
mucosa and adjacent tissues, in which case it is desig-
nated necrotizing stomatitis (117). Periodontal dis-
ease in HIV-positive patients, like in non-seropositive
patients, seems to be the result of the interaction be-
tween the host’s immune response and the micro-
organisms in dental plaque. There is increased rate of
progression of periodontal disease in HIV patients,
which seems to be modified by the interaction be-
tween typical and atypical microorganisms and the
level of immunocompetence (98).
In treating acute necrotizing ulcerative gingivitis
in both normal and HIV patients, the fundamental
activity must be the debridement of teeth and
affected soft tissue areas. In classical cases of acute
necrotizing ulcerative gingivitis the use of antibiotics
without debridement has only served to suppress
the infection while the medication is being taken.
Actinomycosis
Actinomycosis is a chronic disease characterized by
the formation of abscesses, fibrosis of tissues and
114
~~~
draining sinuses. It is caused by non-spore-forming,
anaerobic or microaerophilic bacterial species of the
genus Actinoinyces. These organisms were once con-
sidered fungi because of their branching, but are
now classified as bacteria (165). The pathogenic ac-
tinomycetes do not exist free in nature but are com-
mensals and normal inhabitants of the oropharyn-
geal cavity and the gastrointestinal tract. The Acti-
nomyces are gram-positive, pleomorphic and
diphtheroidal or, more commonly, filamentous.
Actinomycosis may present in the cervicofacial, tho-
racic and abdominal areas of the body, as well as the
central nervous system. Cervico-facial actinomycosis
is the most common form of this disease, and oral
manifestations are part of this form (99).
Actinomyces organisms access the host tissues
when there is an interruption of the mucosal barrier.
In the oral cavity actinomycosis has been reported
following tooth extraction and may be a compli-
cation of endodontic treatment (49, 79, 183). Acti-
nomyces involving localized atypical gingivitis has
been described, and cases involving most of the oral
tissues including the tongue and palate have been
reported (49, 50, 73, 151, 183). As the Actinomyces
infection spreads into the tissues, a hard, slow grow-
ing, relatively nontender swelling may form. Lesions
of the bone and soft tissues may also show multiple
abscesses that drain to the surface by sinus tracts.
The discharge from the tracts typically contains vis-
ible yellowish colonies of organisms called “sulfur
granules”. In late stages, osteomyelitis with extensive
bone destruction may take place. The disease may
become chronic, with old lesions healing, but new
sinuses and abscesses develop (99, 151, 165). Most
human infections are caused by Actinomyces israelii,
but other species, Actinomyces viscosus, Actinomyces
odontolyticus and Actinomyces naeslundii, have been
identified in occasional cases (15, 23, 50, 64, 152,
183).
Diagnosis is made most accurately by isolation
of Actinomyces species in cultures of clinical speci-
mens. Indirect immunofluorescence microscopy
has also been utilized (64). The demonstration of
actinomycotic granules in exudates or in histologi-
cal sections is strongly supportive of the diagnosis.
The granules consist of tangled filaments of organ-
isms, which are apparent on microscopic examina-
tion of a Gram-stained smear. Histological diag-
nosis is difficult because many specimens contain
only a few granules (165). Nagler et al. (119) re-
cently discussed the diagnostic challenge associ-
ated with actinomycosis infections. In addition to
the wide variety of clinical presentations, the
 Oral mucosal lesions caused by infectiue microorganisms. I. Viruses and bacteria
authors also noted the difficulty associated with
obtaining positive cultures.
Actinomycosis was included in a list of bacterial
diseases with oral manifestations, which have been
reported to be associated with HIV (194) infection.
In 1989, Pindborg noted a single case of actino-
mycosis in an HIV-positive patient (132). Since then,
other cases have been reported, and although rare,
actinomycosis should be carefully considered when
diagnosing infections involving the cervicofacial
areas in patients with AIDS (107, 183).
Bacillary angiomatosis
Bacillary angiomatosis, also called epithelioid angi-
omatosis, is a rare vasoproliferative disorder that oc-
curs almost exclusively in severely immunocom-
promised persons, primarily AIDS and cancer pa-
tients and organ transplant recipients (6, 13, 32, 33,
61, 144, 146, 166, 172). It is known to cause both cu-
taneous and disseminated visceral disease in these
patients. It has, however, also been reported, in im-
munocompetent individuals (128). It was first de-
scribed by Stoler et al. in 1983 (171) as an unusual
subcutaneous vascular infection in a patient with
AIDS. The most common clinical presentation is a
cutaneous vascular lesion similar to that of Kaposi’s
sarcoma.
There have been a limited number of reports of
bacillary angiomatosis involving the oral cavity. The
lesions have been described as bluish or purple mac-
ules, pale bluish patches, and red, edematous lesions
occurring on the palate, buccal mucosa and attached
gingiva (6, 33, 61, 166, 172). Only one report de-
scribes alveolar bone loss associated with the
lesions, and in this patient, two teeth were extracted
without complication (61).
The challenge to the accurate diagnosis of bacil-
lary angiomatosis lies in its clinical similarity to
Kaposi’s sarcoma. Bacillary angiomatosis is treatable,
and in most cases curable with antibiotic therapy.
Biopsy confirmation of cases of suspected Kaposi’s
sarcoma, particularly in patients with AIDS, is con-
sidered essential (32).The histological appearance of
bacillary angiomatosis is one of lobular proliferation
of small round blood vessels with plump endothelial
cells that protrude into the vascular lumen. The ag-
gregates of bacteria appear as variably sized, ampho-
philic granular masses, within the vessels, when
stained with the Warthin-Starry stains (32). The
causative organisms have been identified as Rochali-
maea quintana and Rochalimaea henselae (6, 7, 13,
144, 164, 187) and have recently been reclassified as
members of the genus Bartonella based on ribo-
somal RNA.
Gonorrhea
Gonorrhea is a sexually transmitted infection with a
worldwide distribution. It is caused by Neisseria
gonorrhoeae, a nonmotile, spherical or oval coccus,
which is usually found in pairs. The organism is aer-
obic, gram-negative and stains readily. It cannot
cross intact stratified squamous epithelium, such as
skin and oral mucous membranes, but can invade
columnar and transitional epithelium, such as that
which lines the urinary and respiratory tracts. The
urethra, pharynx, endocervix and conjunctivae may
be infected directly. From these sites, the infection
may spread locally along mucosal surfaces or sys-
temically to produce disseminated disease (72, 159,
163). N. gonorrhoeae has been cultured from saliva
of patients with oropharyngeal infections (81). The
human is the only known host for N. gonorrhoeae
(115).
Gonorrhea continues to be the most frequently re-
ported sexually transmitted disease in the United
States. However, the 392,848 cases reported in 1995
do represent a decline from 439,673 cases reported
in 1993 and reflect a steady reduction that has con-
tinued over the last decade (29). The most frequently
affected population is adolescents between the ages
of 15 and 24, although almost any age group can
be afflicted (28). The most common cause of oral
infections is orogenital contact with an infected sex-
ual partner.
Twenty percent of patients with gonorrhea have
oral, pharyngeal or tonsillar involvement (186). The
tonsils become red and swollen, with a grayish exu-
date, and may include cervical lymphadenitis.
Lesions of the oral mucosa may present as a fiery
red, edematous and occasionally painful ulceration.
Case reports have described single or multiple ulcers
of the tongue, gingiva, and buccal mucosa as well as
the hard and soft palate (161). Diagnosis is made by
culture and identification of N. gonorrhoeae. Sugar
fermentation tests aid in species differentiation, and
rapid identification of gonococci by fluorescent anti-
body techniques is possible (115). Systemic anti-
biotic treatment, usually with penicillin, has been ef-
fective in managing gonococcal infections. Beta-lac-
tamase-producing strains of N. gonorrhoeae resistant
to penicillin and tetracycline have been reported.
More recently, ceftriaxone and ciprofloxacin have
also been used successfully in treating gonorrhea
(163).
115
Mycobacterial infections
The term tuberculosis is usually reserved for infec-
tion with Rlycohacteriurn tuberculosis, just as leprosy
is an infection with Mycobacterium Zeprae. Nontu-
berculous atypical mycobacterial diseases are gener-
ally identified as mycobacterial diseases with a spe-
cific organism - Mycobacteriurn kansasii, Mycobac-
teriiim chelonei and the Mycobacterium avium-
irz tracellu lure complex ( 184).
Most medical mycobacterial infections are not
from M. tuberculosis but from nontuberculous op-
portunistic atypical mycobacteria. Cervical lymph-
adenitis caused by these bacteria can be successfully
treated by surgical excision. These infections are not
communicable from person to person and usually
do not require systemic medication for months, as is
the case with tuberculosis. Mycobacterial infections
are among the most common opportunistic infec-
tions in I-IIV patients.
Tuberculosis - M. tuberculosis. Tuberculosis is a
chronic, infectious disease caused by the bacteria M.
tuberculosis. It most commonly affects the lungs but
may also involve any organ of the body. The disease
is an airborne infection spread almost exclusively by
droplets from a person with active disease (114, 131,
184). It is characterized by the formation of granu-
lomas with caseation necrosis caused by a cell-me-
diated response in infected tissue.
Tuberculosis, an ancient disease, reached its peak
incidence in the United States in the nineteenth cen-
tury, at that time being responsible for up to 25%
of all deaths. Since then, there has been a dramatic
decline, mainly as a result of improvements in living
conditions, nutrition and chemotherapy (114). Re-
cently, however, tuberculosis has resurfaced as a
public health threat, in part because of its associ-
ation with HIV infection. There is particular concern
regarding increasing reports of multi-drug-resistant
tuberculosis in patients with AIDS. This resurgence
has renewed interest in tuberculosis among health
care providers, especially those who treat hospital-
ized patients with AIDS (110, 114, 131, 184).
Primary tuberculosis involves a person who has
no previous exposure and has never established an
iniiiiune response to the tubercle bacilli. The ma-
jority of cases are subclinical, and only about 10% of
people infected develop the disease (131). Secondary
tuberculosis is an infection that arises in a previously
sensitized person, usually because of reactivation of
a primary infection, and may occur months to years
later. Oral lesions of tuberculosis are rare, occurring
116
in less than 1% of all pulmonary cases (110). Most
reported cases have been attributed to secondary in-
fection from pulmonary lesions. Self-inoculation
from infected sputum and hematogenous spread ac-
count for initiation of the lesions.
The most common oral tuberculosis lesion is a
chronic, painless, irregular ulcer, with a vegetating
surface covered by a gray or yellowish exudate. Other
reports describe a nodular, granular or leukoplakic
appearance. The lesion is usually surrounded by
edematous and hyperemic mucosa. The dorsal sur-
face of the tongue is the most common oral site, fol-
lowed by the palate, gingiva, buccal mucosa, and lips.
Tuberculosis of the cervical lymph nodes is called
scrofula and may result in breakdown of the skin over-
lying the nodes and fistula formation (41, 44, 45, 83,
127, 131, 139). Primary oral mucosal infection with
the tubercle bacillus has been reported in patients
treated by a dentist with active tuberculosis after the
dentist performed dental extractions. This occurred
prior to the use of barrier protection for infection con-
trol (149). Other case reports described primary tu-
berculosis and oral lesions in patients with no evi-
dence of disseminated disease (41,56,83,95,185).
Diagnosis of infection with M. tuberculosis is de-
rived from the medical history, demonstration of the
acid-fast mycobacteria in clinical specimens, a posi-
tive delayed hypersensitivity (tuberculin) skin reac-
tion to purified protein derivative and chest radio-
graphs. Mycobacterial culture of the organism from
sputum is the most reliable means of diagnosis;
however, 6-12 weeks is required to isolate and ident-
ify the organism. Recent developments in rapid de-
tection and identification are reducing laboratory
time (44, 114, 131).
Leprosy - M. leprae. Leprosy is a chronic disease
caused by M. Zeprae. The most characteristic feature
of the disease is damage to nerves and skin, which
results in deformities and disabilities. While the glo-
bal prevalence has been reduced, leprosy remains a
major public health problem in most countries of
Africa, Asia and Latin America (85).
M. Zeprae is a gram-positive, acid-fast, non-spore-
forming, nonmotile, pleomorphic bacillus. It has not
been cultivated on artificial medium or in tissue cul-
tures, but it has been grown in armadillos and the
footpads of some mice (85, 155). A relationship has
been demonstrated between the clinical, histopatho-
logical and bacteriological manifestations of the dis-
ease and the degree of cell-mediated immunity of
the patient. The Mitsuda reaction is used to assess
cellular immunity, with a positive test reflecting re-
 Oral rnucosal Lesions caused bv infectiue microornanisms. 1. Viruses and bacteria
sistance to the organism. There are four types of lep-
rosy listed, from least to most involved: indetermi-
nate, tuberculoid, borderline and lepromatous. In
addition to skin and peripheral nerves, the disease
also affects oral and respiratory mucosa, bones and
viscera (85).
Oral lesions have been reported in the tuberculo-
id, borderline, and lepromatous types of leprosy. The
incidence varies from less than 20% in the borderline
type, to as high as 60% in patients with lepromatous
leprosy (4, 24, 77, 155). The lesions present as nod-
ules (lepromas) that progress to necrosis and ulcer-
ation. The ulcers may then heal with scarring, or
progress on to cause further tissue destruction. The
lepromas are filled with M. leprae. The oral lesions
of leprosy occur on the palate, dorsum of the tongue,
gingiva, uvula and the lips, and when untreated, may
cause extensive destruction of the oral tissues (4, 24,
77, 142, 155).
Diagnosis is based on the clinical signs of anes-
thetic skin lesions, enlarged peripheral nerves and
the presence of acid-fast bacilli in smears taken from
skin lesions. Histological examination of biopsy
specimens is occasionally necessary. At this time,
there is no immunological test that is useful in the
diagnosis of leprosy (85).
Mycobacterium avium-intracellulare complex in-
fection. Opportunistic infection by the M. avium-in-
tracellulare complex is a common complication of
the latter stages of AIDS (16, 175). Oral lesions of the
M. avium-intracellulare complex are uncommon
and have been reported only in two patients. The
lesions presented as ulcerations with firm borders
and necrotic centers which extended to bone. They
were located in the incisive papilla and edentulous
maxillary ridge areas of one patient, and in the buc-
cal gingiva of the maxillary premolars and molars of
the other patient. Diagnosis in both cases was made
from histopathological examinations and culture of
the organisms from tissue biopsy. Both patients also
demonstrated widespread disseminated infection
with the M. avium-intracellulare complex (148, 181).
Mycobacterium bovis infection. On rare occasions,
human tuberculosis has been caused by M. bovis,
and infections of the tongue and gingiva have been
reported. The pathogenesis is similar to M. tubercu-
losis except that the primary inoculation occurs in
the mouth, probably the result of ingesting unpas-
teurized or infected milk. Primary lesions of the
tongue without evidence of tuberculosis elsewhere
in the body have been described (41).
Mycobacterium chelonae infection. M. chelonae is
an opportunistic pathogen that causes abscess for-
mation, usually in skin, following trauma or subcuta-
neous injections. The organism is rapidly growing
and resistant to standard antituberculosis agents as
well as to antibiotics. Lesions in immunocompetent
patients heal spontaneously, however surgical ex-
cision, debridement and drainage are recommended
to enhance healing. There have been two case re-
ports of intraoral infections attributed to M.
chelonae. Both cases were diagnosed after biopsy
and laboratory evaluations and healed slowly, but
without incident (21, 129). Cervicofacial infection
with M. chelonae has also been reported with similar
findings (19).
Mycobacterium kansasii infection. Several cases of
disseminated M. kansasii infection have been re-
ported in patients with AIDS (10, 25, 122). Only one
patient, however, has demonstrated oral manifes-
tations associated with the M. kansasii infection.
This consisted of an ulcerated lesion in the area of
the palatoglottic arch in a patient with disseminated
disease. M. kansasii was cultured from the ulcer bi-
opsy. The patient did not demonstrate signs or
symptoms of pneumonia, and the disseminated in-
fection was diagnosed from bone marrow and blood
specimens (122).
Streptococcal stomatitis
Streptococcal stomatitis is a rare condition, usually
characterized by a diffuse erythema of the posterior
areas of the oral mucosa, but sometimes includes
the gingiva. Acute gingival streptococcal infections
have been described as acute streptococcal gingivos-
tomatitis, acute streptococcal gingivitis and strepto-
coccal gingivostomatitis, with only a few case reports
in the literature (20, 26, 104, 121). It is, however, de-
scribed in several periodontal textbooks (26, 121,
133, 134).
Acute streptococcal gingivostomatitis is usually
preceded by tonsillitis, and the patients present clin-
ically with an acutely inflamed, diffuse, red and
swollen gingiva with an increased tendency to bleed.
The gingiva is not ulcerated and necrosis is not pres-
ent (20, 104, 177).Gingival abscesses in the interden-
tal papillae and areas with discrete yellowish or
white plaques were described in a few patients.
When the plaques were wiped off, a bleeding surface
was produced (20, 177). In some patients, the ery-
thema also involved areas of oral mucosa with sub-
mandibular lymph node enlargement. Fever, mal-
117
I? i vem - Hidalgo & Stanford
aise, and gingival pain accompany these symptoms
(20, 104, 177).
‘The causative agent of streptococcal stomatitis
was originally thought to be Streptococcus viriduns,
but microbial analysis in recent reports found group
A beta-hemolytic streptococci as the predominant
culture organisms. All patients were treated with sys-
temic penicillin and healed without complications. A
few patients also received a tetracycline mouthrinse
concurrently (104).
‘The symptoms attributed to streptococcal gingi-
vostomatitis - diffusely swollen, bright red gingiva,
fever, malaise, and lymph node enlargement - may
also be associated with viral infections, and careful
diagnosis is necessary.
Syphilis
Syphilis is a venereal disease that has infected
humans for centuries. It is caused by the spirochete
li.qionernn pallidurn. Syphilis is the fourth most
comrnonly reported infectious disease in the United
States. In 1995, the total number of reported cases
of primary and secondary syphilis was 16,500. This
represented a decrease from the 26,498 reported in
1993 and continues a downward trend in the num-
ber of annually reported cases since the epidemic
proportions during the years 1986 through 1990 (29,
163).
Syphilis has been classified as either congenital or
acquired. Congenital syphilis occurs most frequently
when the fetus becomes infected in utero, although
it is possible for the neonate to acquire the infection
as it passes through the birth canal (176). Acquired
syphilis may be contracted by sexual contact, by
transfusion with fresh human blood or by accidental
direct inoculation. The acquisition of syphilis
through transfusion has become rare due to screen-
ing procedures for blood donors and modern blood
bank procedures. Accidental direct inoculation has
also been reduced by improved laboratory pro-
ceduies for handling infected clinical material and
by the use of infection control and barrier pro-
cedures in clinical settings. There have been no re-
ports of occupationally acquired syphilis in a dental
office since the advent of improved infection control
procedures. The overwhelming majority of syphilis
cases, however, continue to be transmitted by sexual
intercourse (161, 163, 176).
Early congenital syphilis may manifest as papulos-
quanious lesions ot the skin and oral mucous mem-
branes. ‘The lesions at the conimissures of the lips,
the angle of the nose and the eyes may heal with
118
radiating scars called rhagades. Oral manifestation
of late congenital syphilis includes Hutchinson’s
triad of deafness, interstitial keratitis and malformed
incisors. In addition to the malformed incisors (Hut-
chinson’s teeth), other dental anomalies include per-
manent molars with hypoplastic, poorly developed
cusps called mulberry molars, and maxillary incisors
with crowns that are wider towards the cemento-
enamel junction than at the incisal edge, producing
a screwdriver appearance.
Acquired syphilis occurs clinically in three classi-
cal phases (primary, secondary and tertiary). Pri-
mary syphilis features formation of a chancre at the
site of inoculation, usually 3 weeks (3 to 90 days)
after contact. The chancre appears on skin or in the
oral cavity as an asymptomatic, centrally ulcerated
granulomatous papule with a raised indurated bor-
der. Spirochetes are present in large numbers in
these highly infectious lesions. Chancres usually heal
spontaneously in 2-8 weeks but may persist in im-
munocompromised hosts (161, 163, 176). Secondary
syphilis is the systemic or disseminated phase, and
it may occur 2-12 weeks (mean, 6 weeks) after con-
tact. The healing chancre may still be present. Signs
and symptoms of this phase include fever, headache,
malaise, a rash that is usually symmetrical and gen-
eralized painless lymph node involvement. The oral
lesion of this stage is the mucous patch, a character-
istic grayish-white, glistening patch seen on the soft
palate, tongue, buccal mucosa and, rarely, the gin-
giva (11, 51, 88, 108, 140). During this phase, elev-
ated, sessile plaques of the labial commissure (con-
dyloma lata) may also occur. After the secondary
stage subsides, the patient enters a latent period in
which diagnosis can only be made by serological
tests. Tertiary syphilis develops in 30% to 40% of un-
treated patients. This phase includes multiorgan in-
volvement, and most frequently involves the cardio-
vascular and nervous systems. The gumma is the
characteristic lesion of this phase and appears on
skin or mucosa as a localized granuloma. The most
common intraoral location for the gumma is the
hard palate, although the soft palate, lips and tongue
may also be involved (40, 84, 92). Tertiary syphilis is
not infectious (163).
Clinical examination and serological testing
usually diagnose syphilis. Darkfield microscopy and
histopathological examination also assist in diag-
nosis. The serological tests are of two types: trepone-
ma1 and non-treponemal. Non-treponemal (non-
specific) tests are for the nonspecific nontreponemal
reaginic antibody, and include the Venereal Disease
Research Laboratory test, the rapid plasma reagin
 Oral mucosal lesions caused bv infective microorganisms. I. Viruses and bacteria
test and the automated reagin test. Positive Venereal
Disease Research Laboratory tests will occur towards
the end of primary syphilis, remain positive in un-
treated secondary or tertiary syphilis, but is usually
negative in treated syphilis. Treponemal (specific)
tests are for the specific antitreponemal antibody,
and include the Reiter protein complement fixation
test, the fluorescent treponemal antibody (absorbed)
test, the treponemal hemagglutination test and the
treponemal immobilization test. Specific tests be-
come positive during primary syphilis, and remain
positive throughout untreated secondary and ter-
tiary syphilis. In contrast to the Venereal Disease Re-
search Laboratory test, most specific tests remain
positive in treated syphilis (161). Darkfield micro-
scopy can be useful in primary syphilis when serol-
ogy may be negative, and occasionally in secondary
or tertiary syphilis. Histopathological examination
demonstrates an obliterative endarteritis, and with
special stains, the I: pallidurn microorganism. The
gumma demonstrate large areas of necrosis and oc-
casional microorganisms (161, 163, 176).
Penicillin is the pharmaceutical treatment of
choice. Treatment given in any of the three stages of
acquired syphilis can cure the disease (176).
Concomitant HW and syphilis infections are com-
mon, and variations in the clinical presentation and
response to syphilis may be related to the degree of
immunosuppression (40, 51, 176).
Oral infection with enteric organisms
A small number of cases of oral infections with en-
teric bacteria have been reported (12, 68, 158, 167).
Schmidt-Westhausen et al. (158) using oral swabs,
compared the incidence of enteric bacteria in the
oral cavity of 144 HIV patients and 166 controls.
They found enteric bacteria in 5.0% of HW patients
and 4.8% of the controls. The isolation of the enteric
organisms from the oral cavity was not associated
with clinical abnormalities. The bacteria were found
to coexist with yeast (68). Barone et al. (12) reported
on an HIV-seropositive patient with glossitis from
whom Escherichia coli could be isolated. In another
report, Stark et al. (167) reported that, of 14 patients
treated with a combination of antibiotics for Helico-
bacter pylori infection, two patients had colonization
of the oral cavity with Enterobacteriaceae.Heitman &
Brasher (75) reported an oral infection due to Klebsi-
ella pneumoniae, an organism indigenous to the
respiratory tract, in a patient following periodontal
surgery. Culture and antibiotic sensitivity testing, fol-
lowed by treatment with tetracycline resolved this
infection (75). It seems unlikely that oral infection
with enteric organisms is a significant cause of mor-
bidity in people infected with HW.
References
1. Ablashi DV, Salahuddin SZ, Josephs SE Balachandran N,
Krueger GR, Gallo RC. Human herpesvirus-6 (HHV-6).In
Vivo 1991:5: 193-199.
2. Adolph HP, Yugueros P, Woods JE. Noma: a review. Ann
Plast Surg 1996:37: 657-668.
3. AIDS among persons aged 250 years - United States,
1991-1996. MMWR Morb Mortal Wkly Rep 1998: 47: 21-
27.
4. Alferi N, Fleury RN, Opromolla DVA, Ura S, de Campos
I. Oral lesions in borderline and reactional tuberculoid
leprosy. Oral Surg Oral Med Oral Pathol Oral Radiol Endod
1982:55:52-57.
5. Atedzoe BN, Ahamad A, Menezes J. Enhancement of
natural killer cell cytotoxicity by the human herpesvirus-
7 via IL-15induction. J Immunol 1997: 159: 49664972.
6. Axiotis CA, Schwartz R, Jennings TA, Glaser N. AIDS-re-
lated angiomatosis. Am J Dermatopathol 1988: 11: 177-
181.
7. Bachelez H, Oksenhendler E, Lebbe C. Bacillary angi-
omatosis in HIV-infected patients: report of three cases
with different clinical courses and identification of Roch-
alimaea quintana as the etiological agent. Br J Dermatol
1995: 133: 983-989.
8. Bagg J. Common infectious diseases. Dent Clin North Am
1996:40: 385-393.
9. Balaram P, Nalinakumari KR, Abraham E, Balan A,
Hareendran NK, Bernard HU, Chan SY. Human papil-
lomaviruses in 91 oral cancers from Indian betel quid
chewers - high prevalence and multiplicity of infections.
Int J Cancer 1995:61:450454.
10. Bamberger DM, Dirks MR, Gupta MR, O’Connor MC, Jost
PM, Neihart RE, McKinsey DS, Moore LA. Mycobacterium
kansasii among patients infected with human immuno-
deficiency virus in Kansas City. Clin Infect Dis 1994: 18:
395-400.
11. Ban M, Ohtani M, Seishima M. A case of secondary syph-
ilis with mucous patches o n the hard palate. J Dermatol
1995:22: 52-54.
12. Barone R, Ficarra D, Gaglioti A, Orsi A, Mazzotta F. Preva-
lence of oral lesions among HIV-infected intravenous
drug abusers and other risk groups. Oral Surg Oral Med
Oral Pathol Oral Radiol Endod 1966:69: 169-173.
13. Bass JW, Vincent JM, Pearson DA. The expanding spec-
trum of Bartonella infections. 11. Cat-scratch disease. Ped-
iatr Infect Dis J 1997: 16:163-179.
14. Bendig JW, Fleming DM. Epidemiological, virological, and
clinical features of an epidemic of hand, foot, and mouth
disease in England and Wales. Commun Dis Rep CDR Rev
1996:6:R81-86.
15. Bennhoff F. Actinomycosis: diagnostic and therapeutic
considerations and a review of 32 cases. Laryngoscope
1984:94: 1198-1217.
16. Benson CA, Ellner JJ. Mycobacterium avium complex in-
fection and AIDS: advances in theory and practice. Clin
Infect Dis 1993: 17: 7-20.
119
Rivera-Hidalgo & Stanford
17. Bertram G, Dreiner N, Krueger GR, Ramon A, Ablashi DV,
Salahuddin SZ, Balachandram N. Frequent double infec-
tion with Epstein-Barr virus and human herpesvirus-6 in
patients with acute infectious mononucleosis. In Vivo
1991: 5: 271-279.
18. Black JB, Durigon E, Kite-Powell K, de Souza L, Curli SE
Alfonso AM, Theobaldo M, Pellett PE. Seroconversion to
human herpesvirus 6 and human herpesvirus 7 among
Brazilian children with clinical diagnosis of measles or ru-
bella. Clin Infect Dis 1996: 23: 1156-1158.
19. Blake CG, Murray JJ, Lee Kw. Cervico-facial infection with
Mycobacteriurn ckelonei - a case report. Br J Oral Surg
1976: 13: 278-281.
20. Blake GC, Trott JR. Acute streptococcal gingivitis. Dent
Pract Dent Rec 1959: 10: 43-45.
21. Boyd BW. Oral infection with associated lymphadeno-
pathy due to Mycobacteriurn ckelonei. Ala Med 1984: 54:
9-10,
22. Brooks LA, Wilson AJ, Crook T. Kaposi’s sarcoma-associ-
ated herpesvirus (KSVH)/human herpesvirus 8 (HHV8) -
a new human tumour virus. J Pathol 1997: 182: 262-265.
23. Brown J. Human actinomycosis: a study of 181 patients.
Hum Pathol 1973: 4: 319-330.
24. Bucci F, Mesa M, Schwartz RA, McNeil G, Lambert WC.
Oral lesions in lepromatous leprosy. J Oral Med 1987: 42:
4-6.
25. Carpenter JL, Parks JM. Mycobacteriurn kansasii infection
in patients positive for human immunodeficiency virus.
Rev Infect Dis 1991: 13: 789-796.
26. Carranza FA. Acute gingival infections. In: Carranza FA,
Newman MG, ed. Clinical periodontology. 8th edn. Phila-
delphia: Saunders, 1996: 249-258.
27. Castanet J, Rodot S, Lacour JE Van Elslande L, Perrin C,
Durant J, Ortonne JR Chronic varicella presenting as dis-
seminated pinpoint-sized papule in a man infected with
the human immunodeficiency virus. Dermatology 1996:
192: 84-86.
28. Centers for Disease Control. Special focus: surveillance
for sexually transmitted diseases. MMWR Morb Mortal
Wkly Rep 1993: 42(SS-3): 1-39.
29. Centers for Disease Control. Summary notifiable diseases,
United States, 1995. MMWR Morb Mortal Wkly Rep 1996
44: 7-33.
30. Chang Y, Moore PS. Kaposi’s sarcoma (KS)-associated
herpesvirus and its role in KS. Infect Agents Dis 1996: 5:
215-222.
31. Chidzonga MM. Noma (cancrum oris) in human im-
munodeficiency virus/acquired immune deficiency syn-
drome patients: report of eight cases. J Oral Maxillofac
Surg 1996: 5 4 1056-1060.
32. Cockerell CJ, LeBoit PE. Bacillary angiomatosis: a newly
characterized, pseudoneoplastic, infectious, cutaneous
vascular disorder. J Am Acad Dermatol 1990: 22: 501-512.
33. Cockerell CJ, Whitlow MA, Webster GF, Freidman-Kien
AE. Epitheloid angiomatosis: a distinct vascular disorder
in patients with the acquired immunodeficiency syndri-
me or AIDS-related complex. Lancet 1987: 2: 654-656.
34. Cohen PR, Hebert AA, Adler-Storthz K. Focal epithelial hy-
perplasia: Heck disease. Pediatr Dermatol 1993: 10: 245-
251.
35. Contreras A, Slots J. Mammalian viruses in human peri-
odontitis. Oral Microbial Immunol 1996: l l: 381-386.
36. Cutts FT, Clements CJ, Bennet JV Alternative routes of
120
measles immunization: a review. Biologicals 1997: 25:
323-338.
37. Daniels TE, Greenspan D, Greenspan JS, Lennette E,
Schiodt M, Petersen V, de Souza Y. Absence of Langerhans
cells in oral hairy leukoplakia, an AIDS-associated lesion.
J Invest Dermatol 1987: 89: 178-182.
38. Dean JA, Magee W. One-stage reconstruction for defects
caused by cancrum oris (noma). Ann Plast Surg 1997: 38:
29-35.
39. Dhariwal SK, Cubie HA, Southam JC. Detection of human
papillomavirus in oral lesions using commercially de-
veloped typing kits. Oral Microbiol Immunol 1995: 10: 60-
63.
40. Dickenson AJ, Currie WJR,Avery BS. Screening for syphilis
in patients with carcinoma of the tongue. Br J Oral Maxil-
lofac Surg 1995: 33: 319-320.
41. Dimitrakopoulos 1, Zouloumis L, Lazaridis N, Karakasis D,
Trigonidis G, Sichletidis L. Primary tuberculosis of the
oral cavity. Oral Surg Oral Med Oral Pathol Oral Radiol
Endod 1991: 72: 712-715.
42. Drago F, Ranieri E, Malagiti F, Losi E, Rebora A. Human
herpesvirus 7 in pityriasis rosea. Lancet 1997: 349: 1367-
1368.
43. EC Clearinghouse on Oral Problems Related to HIV Infec-
tion and WHO Collaborating Centre on Oral Manifes-
tations of the Human Immunodeficiency Virus. Classifi-
cation and diagnostic criteria for oral lesions in HW infec-
tion. J Oral Pathol Med 1993: 22: 289-291.
44. Ellner PD, Kiehn TE, Cammarata R, Hosmer M. Rapid de-
tection and identification of pathogenic mycobacteria by
combining radiometric and nucleic acid probe methods.
J Clin Microbiol 1988: 26: 1349-1352.
45. Eng HL, Lu SY, Yang CH, Chen WJ. Oral tuberculosis. Oral
Surg Oral Med Oral Pathol Oral Radiol Endod 1996: 81:
415-420.
46. Epstein JB. Treatment of Kaposi’s sarcoma with intrale-
sional vinblastine. Cancer 1993: 71: 1722-1725.
47. Eversole LR. Inflammatory diseases of the mucous mem-
branes. 1. Viral and fungal infections. J Calif Dent Assoc
19984: 22: 52-57.
48. Eversole LR. Cause of ulcers in HIV-infected patients: a
study of 19 cases. Oral Surg Oral Med Oral Pathol Oral
Radiol Endod 1996: 82: 166-172.
49. Feder HM. Actinomycosis manifesting as an acute pain-
less lump of the jaw. Pediatrics 1990: 85: 858-863.
50. Ficarra G, DiLollo S, Pierieoni E Panzoni E. Actinomycosis
of the tongue: a diagnostic challenge. Head Neck 1993:
15: 53-55.
51. Ficarra G, Zaragoza AM, Stendardi L, Parri E Cockerell.
Early oral presentation of lues inaligna in a patient with
HIV infection. A case report. Oral Surg Oral Med Oral
Pathol Oral Radiol Endod 1993: 75: 728-732.
52. Flaitz CM, Nichols CM, Adler-Storthz K, Hicks MJ. Intra-
oral squamous cell carcinoma in human immunodefic-
iency virus infection. Oral Surg Oral Med Oral Pathol Oral
Radiol Endod 1995: 80: 55-62.
53. Flaitz CM, Nichols CM, Hicks MJ. Herpesviridue-associ-
ated persistent mucocutaneous ulcers in acquired im-
munodeficiency syndrome. Oral Surg Oral Med Oral
Pathol Oral Radiol Endod 1996: 81: 433-441.
54. Flaitz CM, Jin YT, Hicks MJ, Nichols CM, Wang W, Su IJ.
Kaposi’s sarcoma-associated herpesvirus-like DNA se-
quences (KSHVIHHV-8) in oral AIDS-Kaposi’s sarcoma: a
 Oral mucosal lesions caused by infective microorganisms. I. Viruses and bacteria
PCR and clinicopathologic study. Oral Surg Oral Med Oral
Pathol Oral Radiol Endod 1997: 83: 259-264.
55. Flores JL. Syphilis. A tale of twisted treponemes. West J
Med 1995: 163: 552-559.
56. Fujimoto T, Morishima T, Ueda M. Probable BCG osteo-
myelitis of the hard palate: a case report. Int J Oral Maxil-
lofac Surg 1996: 25: 145-146.
57. Ganem D. KSHV and Kaposi’s sarcoma: the end of the
beginning? Cell 1997: 91: 157-160.
58. Garlick JA, Taichman LB. Human papillomavirus infection
of the oral mucosa. Am J Dermatopathol 1991: 13: 386-
395.
59. Gaspari AA, Marchese S, Powell D, Rady PL, w i n g SK.
Identification of HHV-8 in the skin lesions of Kaposi’s sar-
coma in an immunosuppressed patient with bullous
pemphigoid. J Am Acad Dermatol 1997: 3 7 843-847.
60. Ginsburg CM. Pityriasis rosea. Pediatr Infect Dis J 1991:
10: 858-859.
61. Glick M, Cleveland DB. Oral mucosal bacillary epitheloid
angiomatosis in a patient with AIDS associated with rapid
alveolar bone loss: case report. J Oral Med 1993: 22: 235-
239.
62. Glick M, Muzyka BC, Salkin LM, Lurie D. Necrotizing ul-
cerative periodontitis: a marker for immune deterioration
and a predictor for the diagnosis of AIDS. J Periodontol
1994: 65: 393-397.
63. Goedert JJ, Kedes DH, Ganem D. Antibodies to human
herpesvirus 8 in women and infants in Haiti and the USA.
Lancet 1997: 349: 1368.
64. Gohean RJ, Pantera EA, Schuster SG. Indirect immunoflu-
orescence microscopy for the identification of Actinomyces
sp. In endodontic disease. J Endod 1990: 16: 318-322.
65. Gominak S, Cross D, Paydafar D. Herpes simplex labialis
and trigeminal neuropathy. Neurology 1990: 40: 151-152.
66. Green TL, Greenspan D, Greenspan JS, de Souza YG. Oral
lesions mimicking hairy leukoplakia: a diagnostic dilema.
Oral Surg Oral Med Oral Pathol Oral Radiol Endod 67:
422-426.
67. Greenberg MS. Herpesvirus infections. Dent Clin North
Am 1996: 40: 359-368.
68. Greenspan D, Greenspan J, Pinborg J, Schiodt M. AIDS
and the mouth. Copenhagen: Munksgaard, 1990.
69. Greenspan D, Greenspan JS, Conant M, Petersen V, Sil-
verman S Jr, De Souza Y. Oral “hairy” leukoplakia in male
homosexuals: evidence of association with both papil-
lomavirus and a herpes-group virus. Lancet 1984: 13: 831-
834.
70. Greenspan JS, Greenspan D, Lennette ET, Abrams DI,
Conant MA, Petersen V, Freese UK. Replication of Epstein-
Barr virus within epithelial cells of oral “hairy” leukoplak-
ia, an AIDS-associated lesion. N Engl J Med 1985: 313:
1564-1571.
71. Greenspan D, Greenspan JS, Hearst NG, Pan LZ,Conant
MA, Abrams DI, Hollander H, Levy JA. Relation of oral
hairy leukoplakia to infection with the human immuno-
deficiency virus and the risk of developing AIDS. J Infect
Dis 1987: 155: 475481.
72. Guinta JL, Fiumara NJ. Facts about gonorrhea and den-
tistry. Oral Surg Oral Med Oral Pathol Oral Radiol Endod
1986: 62: 529-531.
73. Gulabivala K, Briggs PFA. Diagnostic dilemma: an unusual
presentation of an infected nasopalatine duct cyst. Int En-
dod 1992: 25: 107-1 11.
74. Hashmey R, Shandera WX. Infectious diseases: viral and
rickettsial. In: Tierney LM Jr, McPhee SJ, Papadakis MA,
ed. Current medical diagnosis and treatment. 36th edn.
Stamford, CT: Appleton and Lange, 1997: 1203-1237.
75. Heitman KL, Brasher WJ. Oral infection due to Klebsiella
pneumonia microorganism: case report. J Periodontol
1971: 42: 552-554.
76. Helfand RE Kebede S, Alexander JP Jr, Alemu W, Heath JL,
Gary HE Jr, Anderson LJ, Beyene H, Bellini WJ. Compara-
tive detection of measles-specific IgM in oral fluid and
serum from children by a n antibody-capture IgM EM. J
Infect Dis 1996: 173: 1470-1474.
77. High AS, Lansley CV. Labial and gingival enlargement in
leprosy. Br Dent J 1988: 165: 371-372.
78. Hirschfeld I, Beube F, Siege1 EH. The history of Vincent’s
infection. J Periodontol 1940: 11: 89.
79. Holbrook W. Bacterial infections of oral soft tissues. Curr
Opin Dent 1991: 1: 404410.
80. Horning GM, Cohen ME. Necrotizing ulcerative gingivitis,
periodontitis, and stomatitis: clinical staging and predis-
posing factors. J Periodontol 1995: 66: 990-998.
81. Hutt DM, Judson FN. Epidemiology and treatment of oro-
pharyngeal gonorrhea. Ann Intern Med 1986: 104: 655-
658.
82. Itin PH. Oral hairy leukoplakia - 10 years on. Dermatology
1993: 187: 159-163.
83. Jawas J, El-Zuebi E Primary lingual tuberculosis: a case
report. J Laryngol Otol 1996: 110: 177-178.
84. Jefferies SBD, Ord RA. An unusual presentation of oral
syphilis. Br Dent J 1985: 23: 376-380.
85. Ji B, Grosset J. Leprosy. In: Hoeprich PD, Jordan MC, Ron-
ald AR, ed. Infectious diseases. 5th edn. Philadelphia: Lip-
pincott, 1994.
86. Jones AC, Freedman PD, Phelam JA, Baughman RA, Ker-
pel SM. Cytomegalovirus infections of the oral cavity. Oral
Surg Oral Med Oral Pathol Oral Radiol Endod 1993: 75:
76-85.
87. Jontell M, Watts S, Wallstrom M, Levin L, Sloberg K. Hu-
man papilloma virus in erosive lichen planus. J Oral
Pathol 1990: 19: 273-277.
88. Jordaan HE Secondary syphilis: a clinicopathological
study. Am J Dermatopathol 1988: 10: 399409.
89. Juel-Jensen BE. Herpes simplex and zoster. BMJ 1973: 1:
406-410.
90. Juel-JensenBE. Herpetic whitlowes: an occupational risk.
Anesthesia 1973: 28: 324-327.
91. Karlin JD. Herpes zoster ophthalmicus: the virus strikes
back. Ann Opthalmol 1993: 25: 208-215.
92. Kearns G, Pogrel MA, Honda G. Intraoral tertiary syphilis
(gumma) in a human immunodeficiency virus-positive
man: a case report. J Oral Maxillofac Surg 1993: 51: 85-
88.
93. KemCny L, Gyulai R, Kiss M, Nagy F, Dobozy A. Kaposi’s
sarcoma-associated herpesvirus/human herpesvirus-8: a
new virus in human pathology. J Am Acad Dermatoll997:
37: 107-113.
94. Kimberlin DW. Human herpesvirus 6 and 7: identifi-
cation of newly recognized viral pathogens and their as-
sociation with human disease. Pediatr Infect Dis J 1998:
17 59-68.
95. Kolokotronis A, Antonidis D, Trigonidis G, Papanagiotou
F! Oral tuberculosis. Oral Dis 1996: 2: 242-243.
96. Kriesel JD, Pisani PL, McKeough MB, Baringer JR, Spru-
121
Rivera-Hidalzo & Stanford
ance SL. Correlation between detection of herpes simplex
virus in oral secretions by PCR and susceptibility to ex-
perimental UV radiation-induced herpes labialis. J Clin
Microbiol 1994: 32: 3088-3090.
97. Kushner D, Caldwell BD. Hand-foot-and-mouth disease. J
Am Podiatr Med Assoc 1996: 86: 257-259.
98. Lamster IB, Grbic JT, Bucklan RS, Mitchell-Lewis D, Reyn-
olds HS, Zambon JJ. Epidemiology and diagnosis of HIV-
associated periodontal diseases. Oral Dis 1997: 3(suppl):
S141-S148.
99. Laskaris G. Oral manifestations of infectious diseases,
Dent Clin North Am 1996: 40: 395-423.
100. Lennette ET, Blackbourn DJ, Levy JA. Antibodies to hu-
man herpesvirus type 8 in the general population and in
Kaposi’s sarcoma patients. Lancet 1996: 348: 858-881.
101. Levy JA, Ungar AM. Oral hairy leukoplakia in an HIV-
negative renal transplant recipient. J Oral Pathol Med
1989: 18: 32-34.
102. Levy JA. Three new human herpesviruses (HHV6, 7, and
8). Lancet 1997: 349: 558-583.
103. Listgarten MA. Electron microscopy observations on the
bacterial flora of acute necrotizing ulcerative gingivitis. J
Periodontol 1965: 36: 328.
104. Littner MM, Dayan D, Kaffe I, Begleiter A, Gorsky M, Mos-
kana D, Buchner A. Acute streptococcal gingivostomatitis.
Report of five cases. Oral Surg Oral Med Oral Pathol Oral
Radiol Endod 1982: 53: 144-147.
105. Luppi M, Torelli G. Hematologica 1996: 81: 265-281
106. Lusso P, De Maria A, Malnati M, Lori E DeRocco SE, Basel-
er M, Gallo RC. Induction of CD4 and susceptibility to
HIV-1 infection in human CD8+ T lymphocytes by human
herpesvirus 6. Nature 1991: 349: 533-535.
107. Manfredi R, Mazzoni A, Marinacci G, Nanetti A, Chiodo
F. Prograssive intractable actinomycosis in patients with
AIDS. Scand J Infect Dis 1995: 27: 405-407.
108. Manton SL, Egglestone SI, Alexander I, Scully C. Oral
presentation of secondary syphilis. Br Dent J 1986: 160:
237-238.
109. Mao EJ, Schwartz SM, Daling JR, Oda D, Tickman L,
Beckmann AM. Human papilloma viruses and p53 muta-
tions in normal pre-malignant and malignant oral epi-
thelia. Int J Cancer 1996: 69: 152-158.
110. Mattingly G, Rodu B. Differential diagnosis of oral mu-
cosal ulcerations. Compendium Contin Educ Dent 1993:
14: 136-150.
111. McCreary CE, Flint SR, McCartan BE, Shields JA, Mabruk
M, Toner ME. Uremic stomatitis mimicking oral hairy leu-
koplakia: report of a case. Oral Surg Oral Med Oral Pathol
Oral Radiol Endod 1997: 83: 350-353.
112. Mealy BL. Periodontal implications: medically compro-
mised patients. Ann Periodontol 1996: 1: 256-322.
113. Miller CS. Viral infections in the immunocompetent pa-
tient. Dermatol Clin 1996: 14: 225-241.
114. Molinari JA, Cottone JA, Chandrasekar PH. Tuberculosis
in the 1990s: current implications for dentistry. Compen-
dium Contin Educ Dent 1993: 14: 276-292.
115. Morse SA, Holmes KK. Infectious diseases. 5th edn. Phila-
delphia: Lippincott, 1994.
116. Murayama Y, Kurihara H, Nagai A, Dompkowski D, Van
Dyke TE. Acute necrotizing ulcerative gingivitis: risk fac-
tors involving host defense mechanisms. Periodontol
2000 1994: 6: 116-124.
117. Murray PA. Periodontal disease in patients infected by hu-
122
man immunodeficiency virus. Periodontol 2000 1994: 6:
50-67.
118. Muto T, Tsuchiya H, Sat0 K, Kanazawa M. Tooth exfoli-
ation and necrosis of the mandible. A rare complication
following trigeminal herpes zoster. J Oral Maxillofac Surg
1990: 48: 1000-1003.
119. Nagler R, Peled M, Laufer D. Cervicofacial actinomycosis.
Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1997:
83: 652-656.
120. Nakagawa N, Mukai T, Sakamoto J, Hata A, Okunp T, Take-
da K, Yamanishi K. Antigenic analysis of human herpesvi-
rus 7 (HHV-7) and HHV-6 using immune sera and mono-
clonal antibodies against HHV-7. J Gen Virol 1997: 78(part
5): 1131-11377.
121. Newman HN. The classification of periodontal diseases.
In: Newman HN, Rees TD, Kinane DF, ed. Diseases of the
periodontiurn. Northwood: Science Reviews Limited,
1993: 8-26.
122. Nuesch R, Battegay M, Zimmerli W, Thumshirn M, Gilli L,
Itin PH. OraI manifestation of disseminated Mycobuc-
terium kansasii in a patient with AIDS. Dermatology 1996:
192: 183-184.
123. Oakley C, Epstein JB, Sherlock CH. Reactivation of oral
herpes simplex virus recurrence during radiotherapy. Oral
Surg Oral Med Oral Pathol Oral Radiol Endod 1997: 84:
272-278.
124. Obalek S, Janniger C, Jablonska S, Favre M, Orth G. Spor-
adic cases of Heck disease in two polish girls: association
with human papillomavirus type 13. Pediatr Dermatol
1993: 10: 240-244.
125. Padayachee A. Human papillomavirus (HPV) types 2 and
57 in oral verrucae demonstrated by in situ hybridization.
J Oral Pathol Med 1994: 23: 413-417.
126. Palefsky JM, Silverman S Jr, Abdel-Salaam M, Daniels TE,
Greenspan JS. Association between proliferative verru-
cous leukoplakia and infection with human papillomavi-
rus type 16. J Oral Pathol Med 1995: 24: 193-197.
127. Pande TK, Hiran S, Rao VVB, Pani S, Vishwanathan KA.
Primary lingual tuberculosis caused by M. bovis infection.
Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1995:
80: 172-174.
128. Paul MA, Fleischer AB, Wieselthier JS, White WL. Bacillary
angiomatosis in an immunocompetent child: the first re-
ported case. Pediatr Dermatol 1994: 11: 338-341.
129. Pedersen A, Reibel J. Intraoral infection with Mycobac-
terium chelonue. Oral Surg Oral Med Oral Pathol Oral
Radiol Endod 1989: 67: 262-265.
130. Perry CM, Wagstaff AJ. Famciclovir. A review of its phar-
macological properties and therapeutic efficacy in her-
pesvirus infections. Drugs 1995: 50: 396-415.
131. Phalen JA, Jimenez V, Tompkins DC. Tuberculosis. Dent
Clin North Am 1996: 4 0 327-341.
132. Pindborg J. Classification of oral lesions associated with
HIV infection. Oral Surg Oral Med Oral Pathol Oral Radiol
Endod 1989: 67: 292-295.
133. Pindborg JJ. Manifestation of systemic disorders in the
periodontium. In: Lindhe J, ed. Textbook of clinical peri-
odontology. 2nd edn. Copenhagen: Munksgaard, 1989:
282-296.
134. Pindborg JJ. Atlas of diseases of the oral mucosa. 5th edn.
Copenhagen: Munksgaard, 1993: 180.
135. Praetorious E HPV-associated diseases of oral mucosa.
Clin Dermatol 1997: 15: 399413.
 Oral mucosal lesions caused by infective microorganisms. I. Viruses and bacteria
136. Premoli-de-Percoco G, Cisternas JP, Ramirez JL, Galindo
I. Focal epithelial hyperplasia: human papillomavirus-in-
duced disease with a genetic predisposition in a Venezue-
lan family. Hum Genet 1993: 91: 386-388.
137. Premoli-de-Percoco G, Galindo I, Ramirez JL, Perrone M,
Rivera H. Detection of human papillomavirus-related oral
verruca vulgaris among Venezuelans. J Oral Pathol Med
1993: 22: 113-116.
138. Puranen M, Yliskoski M, Saarikoski S, Syrjanen K, Syrjan-
en S. Vertical transmission of human papillomavirus from
infected mothers to their newborn babies and persistence
of the virus in childhood. Am J Obstet Gynecol 1996: 174:
694-699.
139. Purohit SD, Mathur BB, Gupta PR, Agarwal KC, Hathi
HH. Tuberculous fistula of cheek report of a case. Oral
Surg Oral Med Oral Pathol Oral Radiol Endod 1985: 60:
41-42.
140. Ramirez-Amador V, Sierra Madero JG, Esquivel Pedraza
LE, de la Rosa Garcia E, Gonzalez Guevara M, Reyes Guti-
errez E, Reyes-Teran G. Oral secondary syphilis in a pa-
tient with human immunodeficiency virus infection. Oral
Surg Oral Med Oral Pathol Oral Radiol Endod 1996: 81:
652-654.
141. Regezi JA, Eversole LR, Baker BE Rick GM, Silverman S.
Herpes simplex and cytomegalovirus coinfected oral ul-
cers in HIV-positive patients. Oral Surg Oral Med Oral
Pathol Oral Radiol Endod 1996: 81: 55-62.
142. Reichart P, Ananatasan T, Reznik G. Gingiva and peri-
odontium in lepromatous leprosy. J Periodontol 1976: 47:
455460.
143. Reichart PA. Oral manifestations of recently described
viral infections. Curr Opin Dent 1991: 1: 377-383.
144. Relman DA, Loutit JS, Schmidt TM, Falkow S, Tompkins
LS. The agent of bacillary angiomatosis. N Engl J Med
1990: 323: 1573-1580.
145. Rentier B, Piette J, Baudoux L, Debrus S, Defechereux P,
Merville MP, Sadzot-Delvaux C, Schoonbroodt S. Lessons
to be learned from varicella-zoster virus. Vet Microbiol
1996: 53: 55-66.
146. Rhame FS. Acquired immunodeficiency syndrome. In:
Hoeprich PD, Jordan MC, Ronald AR, ed. Infectious dis-
eases. 5th edn. Philadelphia: Lippincott, 1994: 628-632.
147. Robayna MG, Herranz P, Rubio FA, Pena P, Pena JM, Gon-
zalez J, Casado M. Destructive herpetic whitlow in AIDS:
report of three cases. Br J Dermatol 1997: 37: 812-815.
148. Robinson E: Farthing E: Scott GM, Bennett JH. Oral Myco-
bacterium auiurn complex infection in a patient with HIV-
related disease. Oral Surg Oral Med Oral Pathol Oral
Radiol Endod 1996: 81: 177-179.
149. Roderick Smith WHR, Davis D, Mason KD, Onions I€? In-
traoral and pulmonary tuberculosis following dental ma-
nipulation. Lancet 1982: 1: 842-843.
150. Rosebury T. The role of infection in periodontal disease.
Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1952:
5: 363.
151. Rubin MM, Krost BS. Actinomycosis presenting as a mid-
line palatal defect. J Oral Maxillofac Surg 1995: 53: 701-
703.
152. Sa’do B, Yoshiura K, Yuasa K, Ariji Y, Kanda S, Oka M, Kat-
suki T. Multimodality imaging of cervicofacial actino-
mycosis. Oral Surg Oral Med Oral Pathol Oral Radiol En-
dod 1993: 76: 772-782.
153. Sada E, Yasukawa M, Ito C, Takeda A, Shiosaka T, Tanioka
H, Fujita S. Detection of human herpesvirus 6 and human
herpesvirus 7 in the submandibular gland, parotid gland,
and lip salivary gland by PCR. J Clin Microbiol 1996: 34:
2320-2321.
154. Salahuddin SZ, Ablashi D\5 Markharn PD, Josephs SF,
Sturzenegger S, Kaplan M, Halligan G, Biberfeld P, Wong-
Staal F, Kramarsky B. Isolation of a new virus, HBLV, in
patients with lymphoproliferative disorders. Science 1986:
234: 596-601.
155. Sawyer DR, Nwoku AL, Lehnert JF. Facial and oral mani-
festations of leprosy: an evaluation one hundred and four
cases. J Oral Med 1987: 42: 143-149.
156. Schiodt M, Greenspan D, Daniels TE, Greenspan JS. Clin-
ical and histologic spectrum of oral hairy leukoplakia.
Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1987:
64: 716-720.
157. Schirm J, Mulkens PS. Bell’s palsy and herpes simplex vi-
rus. APMIS 1997: 105: 815-823.
158. Schmidt-Westhausen A, Fehrenbach FJ, Reichart PA. Oral
Enterobacteriaceue in patients with HIV infection. J Oral
Pathol Med 1990: 19: 229-231.
159. Sciubba JJ. Oral aspects of sexually-transmitted diseases.
Ann Dent 1978: 37: 1-7.
160. Scott DA, Coulter WA, Biagioni PA, O’Neill H, Lamey P-J.
Detection of herpes simplex virus type 1 shedding in the
oral cavity by polymerase chain reaction and enzyme-
linked immunosorbent assay at the prodromal stage of
recrudescent herpes labialis. J Oral Pathol Med 1997: 26:
305-309.
161. SculIy C. Infectious diseases: review of the literature. In:
Millard HD, Mason DR, ed. 2nd World Workshop on Oral
Medicine. Ann Arbor: University of Michigan, 1995:3:7-16.
162. Shelley WB, Hashim M, Shelley ED. Acyclovir in the treat-
ment of hand-foot-and-mouth disease. Cutis 1996: 57:
232-234.
163. Siege1 MA. Syphilis and gonorrhea. Dent Clin North Am
1996: 40: 369-383.
164. Slater LN, Welch DF, Min Kw. Rochalimaea henselae
causes bacillary angiomatosis and peliosis hepatis. Arch
Intern Med 1992: 152: 602-606.
165. Smego RA. Actinomycosis. In: Hoeprich PD, Jordan MC,
Ronald AR, ed. Infectious diseases. 5th edn. Philadelphia:
Lippincott, 1994: 493497.
166. Speight PM, Fletcher CDM. Epithelioid angiomatosis af-
fecting the oral cavity as a first sign of HlV infection. Br
Dent J 1991: 171: 367-370.
167. Stark CA, Adamsson I, Edlund C, Sjosted S, Seesalu R,
Wikstrom B, Nord CE. Effects of omeprazole and amoxi-
cillin on the human oral and gastrointestinal microflora
in patients with Helicobacter pylori infection. J Anti-
microb Chemother 1996: 38: 927-939.
168. Steeper TA, Horwitz CA, Ablashi DV, Salahuddin SK, Sax-
ingcr C, Saltzman R, Schwartz B. The spectrum of clinical
and laboratory findings resulting from human herpesvi-
rus-6 (HHV-6) in patients with mononucleosis-like ill-
nesses not resulting from Epstein-Barr virus or cytome-
galus. Am J Clin Pathol 1990: 93: 776-783.
169. Steiner I, Kennedy PGE. Herpes simplex virus latent infec-
tion in the nervous system. J Neurovirol 1995: 1: 19-29.
170. Steiner I. Human herpes viruses latent infection in the
nervous system. Jmmunol Rev 1996: 152: 157-173.
171. Stoler MH, Bonfiglio TA, Steigbigel RT, Pereira M. An
atypical subcutaneous infection associated with acquired
123
Rivera-Hidalgo & Stanford
immune deficiency syndrome. Am J Clin Pathol 1983: 80:
7 14-71 8.
172. Szaniawski WK, Don PC, Bitterman SR, Schachner JR. Ep-
itheloid angiomatosis in patients with AIDS. J Am Acad
Dermatol 1990: 23: 41-48.
173. Takahashi Y, Yamada M, Nakamura J, Tsukasaki T, Padilla
J, Kitamura T, Yoshida M, Nii S. Transmission of herpesvi-
rus 7 through multigenerational families in the same
household. Pediatr Infect Dis J 1997: 16: 975-978.
174. Takkal AM, Ionescu G, Becker JH. Noma (cancrum oris)
associated with Kwashiorkor: a case report and review of
the literature. Acta Chir Belg 1996: 96: 179-181.
175. TB diagnosis: new test gives 48-hour result. AIDS Treat-
ment News 1992: 16l(October 16): 1.
176. Tramont EC. Treponerna pallidurn (syphilis). In: Mandell
GL, Douglas RG, Bennett JE, ed. Principles of infectious
disease. 3rd edn. New York Churchill Livingston, 1990:
1794-1808.
177. Qldesley WR. Infections of the oral mucosa. Br Dent J
1973: 135: 449-455.
178. Veenstra J, van Prag RM, Krol A, Wertheim van Dillem PM,
Weigel HM, Schellekens PT, Lange JM, Coutinho RA, van
der Meer JT. Complications of varicella zoster virus reacti-
vation in HIV-infected homosexual men. AIDS 1996: 10:
393-399.
179. Vesper M, Riethdorf S, Christoph E, Ruthke A. Schmelzle
R, Loning T. Detection of human papillomavirus ( H V P ) -
DNA in oral manifestation of lichen planus. Mund Kiefer
Gesichtschir 1997: 1: 146149.
180. Vidimos AT, Camisa C. Tongue and cheek oral lesions in
pityriasis rosea. Cutis 1992: 50: 276-280.
181. Volpe F, Schwimmer A, Barr C. Oral manifestation of dis-
seminated Mycobacterium avium intracellulare in a pa-
tient with AIDS. Oral Surg Oral Med Oral Pathol Oral
Radiol Endod 1985: 60: 567-570.
182. Ward KA, Napier SS, Winter PC, Maw RD, Dinsmore W.
Detection of human papilloma virus DNA sequences in
oral squamous cell papillomas by the polymerase chain
reaction. Oral Surg Oral Med Oral Pathol Oral Radiol En-
dod 1995: 80: 63-66.
183. Watkins W,Richmond AS, Langstein IM. Nonhealing ex-
traction site due to Actinornycetes naeslundii in patient
with AIDS. Oral Surg Oral Med Oral Pathol Oral Radiol
Endod 1991: 71: 675-677.
184. Weg JG. Tuberculosis and other mycobacterial diseases.
Barrier 1988: 3: 1-7.
124
185. Weiner GM. Tuberculous parotitis: limiting the role of
surgery. J Laryngol Otol 1996: 110: 96-97.
186. Weisner PJ, Tronca E, Bonin P, Pedersen AHB, Holmes KK.
Clinical spectrum of pharyngeal gonococcol infection. N
Engl J Med 1973: 288: 181-185.
187. Welch DF, Picket DA, Slater LN, Steigerwalt AG, Brenner
DJ. Rochalimaea hensalae sp. nov., a cause of septicemia,
bacillary angiomatosis, and parenchymal bacillary pe-
liosis. J Clin Microbiol 1991: 30: 275-280.
188. Wen S, Tsuji T, Li X, Mizugaki Y, Hayatsu Y, Shinozaki E
Detection and analysis of human papillomavirus 16 and
18 homologous DNA sequences in oral lesions. Antican-
cer Res 1997: 17: 307-211.
189. West RW, Thompson JR. Modeling the impact of HIV on
the spread of tuberculosis in the United States. Math Bio-
sci 1997: 143: 35-60.
190. Yadav M, Chandrashekran A, Vasudevan DM, Ablashi DV
Frequent detection of human herpesvirus 6 in oral carci-
noma. J Natl Cancer Inst 1994: 86: 1792-1794.
191. Yadav M, Arivanathan M, Kumar S. HHV-6 antigen and
viral DNA detected in cervical cells from archived tissue
using histochemical staining and hybridization. Clin Di-
agn Virol 1996: 7: 23-33.
92. Yadav M, Arivanathan M, Chandrashekran A, Tan BS,
Hashim BY. Human herpesvirus-6 (HHV-6) DNA and vi-
rus-encoded antigen in oral lesions. J Oral Pathol Med
1997: 26: 393-401.
93. Yadav M, Nambiar S, Khoo Sl? Yaacob HB. Detection of
human herpesvirus 7 in salivary glands. Arch Oral Biol
1997: 42: 559-567.
194. Yeager BA, Hoxie J, Weisman RA, Greenberg MS, Bilaniul
LT. Actinomycosis in acquired immunodeficiency syn-
drome-related complex. Arch Otolaryngol Head Neck
Surg 1986: 112: 1293-1295.
195. Yoshikawa T, Hill JM, Stanberry LR, Bourne N, Kurawad-
wala JFj Kause PR. The characteristic site-specific reacti-
vation phenotypes of HSV-1 and HSV-2 depend upon the
latency-associated transcript region. J Exp Med 1996: 184:
659-664.
196. Young EJ, Chafizadeh E, Oliveira VL, Genta RM. Dissemi-
nated herpesvirus infection during pregnancy. Clin Infect
Dis 1996: 22: 51-58.
197. Zeuss MS, Miller CS, White DK. In situ hybridization
analysis of human papillomavirus DNA in oral mucosal
lesions. Oral Surg Oral Med Oral Pathol Oral Radiol Endod
1991: 71: 714-720.