Role of virus in periodontal diseases

Guided by:
Dr. Monica Mahajani
Dr. Chandrahas Goud
Dr. Anup Shelke
Dr. Subodh Gaikwad
Dr. Anup Gore
Dr. Kuldeep Patil
Presented by:
Dr. Chavan Sneha S.
(1ST Year PG)
31-05-2021 1

INTRODUCTION
• Periodontal diseases are multifactorial in nature and many
etiological agents are suggested to play a role in their
etiopathogenesis.
periodontitis
gingivitis
Periodontal disease
31-05-2021 2

• The word virus in Latin refers to poison
and other noxious substances.
• Lwoff’s :definition of viruses in 1957
….“Submicroscopic entities which
reproduce within the specific living cells”
Norrby E.Nobel Prizes and the emerging virus concept. Arch Virol 2008 153 (6): 1109–23
31-05-2021 3

HISTORY
Oldstone MBA (2009). Viruses, Plagues, and History: Past, Present and Future. Oxford University Press, USA. p. 306
Louis Pasteur and Edward Jenner developed the first
vaccines to protect against viral infections he did not
know that viruses existed
The first evidence of the existence of viruses came from
experiments with filters that had pores small enough to
retain bacteria.
In 1892, the Russian biologist Dmitry Ivanovsky (1864–1920)
used a Chamberland filter to study what is now known as the
tobacco mosaic virus. His experiments showed that crushed
leaf extracts from infected tobacco plants remain infectious
after filtration.
31-05-2021 4

Oldstone MBA (2009). Viruses, Plagues, and History: Past, Present and Future. Oxford University Press, USA. p. 306.
FIRST ANIMAL VIRUSES
The second virus discovered was what is now known as
Foot and mouth disease virus (FMDV) of farm and other
animals, in 1898 by the German scientists Friedrich
Loeffler and Paul Frosch.
FIRST HUMAN VIRUS
described was the agent which causes yellow fever: this
probably originated in Africa, but was spread along with its
mosquito vector Aedes aegyptii to the Americas and
neighbouring islands by the slave trade.
31-05-2021 5

CHARACTERISTICS OF VIRUS
• Small, obligate, intracellular parasites.
• Do not have a cellular organization.
• Contain only one type of nucleic acid, either DNA or
RNA but never both.
• Cannot replicate on their own.
• Must infect and take over a host cell in order to
replicate.
• Lack the enzymes necessary for protein & nucleic
acid synthesis.
• Multiply by a complex process and not by binary
fission.
• Unaffected by antibiotic.
Samaranayake L. Virus and Prions. In: Essential Microbiology. 4th ed. Churchill livingstone.2011.P. 28-68.
31-05-2021 6

STRUCTURE OF VIRUS
Virion consists of
mainly nucleic acid
surrounded by a
protein coat
CAPSID
Mithlesh Bhagat et.al. Role of viruses in periodontal diseases Galore International Journal of Health Sciences and Research (www.gijhsr.com) Vol.5; Issue: 1; January-March 2020
31-05-2021 7

Virus symmetry
• HELICAL SYMMETRY
• Nucleic acid and capsomeres are
wound together to form a Helical
tube
• Rod like with capsid proteins
winding around the core in a spiral
• Eg.:TMV
31-05-2021 8

• Icosahedral: polygon with 12 vertices
(corners), 20 facets (Sides)
• Each facet is in shape of a equilateral
triangle
• Capsomeres in icosahedral symmetry are
of two types
• Pentagonal capsomeres at the vertices
• Hexagonal capsomeres in the facets
• E.g.: POLIO VIRUS, RHINOVIRUS &
ADENOVIRUS
ICOSAHEDRAL (CUBICAL)
31-05-2021 9

COMPLEX:
Polyhedral capsid attached to a helical tail.
Eg: Pox virus
31-05-2021 10

Chemical properties
Kapil A. Virology. In: Ananthanarayan and Paniker’s Textbook of Microbiology. 9th ed. United press, Hyderabad. P. 427-588
Proteins
Lipids
Nucleic acid
31-05-2021 11

cultivation virus
Inoculation into animal
Tissue culture
Embryonated egg
31-05-2021
12

Viral pathogenesis
Morse SA, Riedel S, Mietzner TA, Miller S (2019-08-25). Jawetz Melnick & Adelbergs Medical Microbiology 28E. McGraw-Hill Education. ISBN 9781260012033.
31-05-2021
14

Host response to viral infection
Immune Responses to Viruses ; British society for immunology; Kerry Laing, Fred Hutchinson Cancer Research Centre, Seattle, USA
……Via cytotoxic cells, Via interferons & Via antibodies
31-05-2021 15

Periodontology 2000, Vol. 38, 2005, 33–62, Herpesviruses in periodontal diseases Jørgen Slots
31-05-2021 17

Periodontal healthand gingivitis
• Periodontal health is associated with median genome
detection rates of 8% for Epstein–Barr virus and for
cytomegalovirus.
• Gingivitis studies reveal a median genome detection
rate of 20% for Epstein– Barr virus and 33% for
cytomegalovirus.
Periodontology 2000, Vol. 53, 2010, 89–110 Human viruses in periodontitis Jørgen Slots
31-05-2021 18

• Healthy peri-implant sites have demonstrated an absence of
cytomegalovirus.
• Herpesvirus-infected periodontal healthy and gingivitis sites typically
harbor the viruses in a nontranscriptional state (156, 204) and in copy-
counts of only 1,000–20,000.
Nowzari H, Botero JE, DeGiacomo M, Villacres MC, Rich SK. Microbiology and cytokine levels around
healthy dental implants and teeth. Clin Implant Dent Relat Res 2008: 10: 166–173.
31-05-2021 19

Aggressive periodontitis
• Cytomegalovirus and Porphyromonas gingivalis seemed to act
synergistically to influence the risk for both the occurrence and the
extent of disease. Localized aggressive periodontitis was associated
with cytomegalovirus with an odds ratio of 6.6, and with P. gingivalis
with an odds ratio of 8.7.
• The odds of having localized aggressive periodontitis increased
multiplicatively in individuals with a co-infection of cytomegalovirus
and P. gingivalis (odds ratio, 51.4), compared with the odds of
harboring neither of the two infectious agents
31-05-2021 20

Prevalence of subgingival genome-copies of
herpesviruses in aggressive and chronic periodontitis
• Median detection rates for:
• HSV1- 78%
• EBV – 58%
• CMV – 42%
31-05-2021 21

Herpesvirus in localized juvenile
periodontitis
• HCMV, EBV-1 and HSV were detected more frequently in deep
periodontal pockets than in shallow periodontal sites of LJP
patients. Also, using similar detection methods.
• Demonstrated HCMV or EBV-1 in 90% of LJP lesions but only in
40±78% of adult periodontitis lesions.
Ting M, Contreras A, Slots J. Herpesvirus in localized juvenile periodontitis. J Periodontal Res 2000: 35: 17–25.
31-05-2021 22

Pathogenesis of localised aggressive
periodontitis
• Ting et al hypothesis
primary CMV infection at the time of root formation of
permanent incisors and first molars (3-5 years of age)
can disrupt normal cell differentiation , change the morphology of
developing teeth (cemental hypoplasia)
giving rise to a defective periodontium.
31-05-2021 23

Pathogenesis of localised aggressive
periodontitis
• Hormonal changes at the onset of puberty
in suppression of
antibacterial
immune defenses
overgrowth of bacteria,
such as specific
genotypes of A.
actinomycetemcomitans
may re-activate a
periodontal
cytomegalovirus
infection
31-05-2021 24

Chronic periodontitis
• Hochman et al. detected antibodies against Epstein–Barr virus in 32%,
and against cytomegalovirus in 71%, of gingival crevice fluid samples
from 34 study sites.
• Antibodies against the herpesviruses were predominantly of the
immunoglobulin A (IgA) isotype in the gingival crevice fluid and of the
immunoglobulin G (IgG) isotype in serum samples.
• These antibody findings suggest a local synthesis by plasma cells
rather than passive transudation from the blood, and thus provide
further evidence of a close relationship between herpesviruses and
periodontal disease.
31-05-2021 25

• The Epstein–Barr virus nuclear antigen 2 (EBNA2)
genotype 1 occurs more frequently in periodontitis
lesions than the EBNA2 genotype 2.
• Periodontitis lesions can also harbour papillomaviruses,
human immunodeficiency virus (HIV), human T-
lymphotropic virus type 1 , hepatitis B virus, hepatitis C
virus and torquetenovirus.
31-05-2021 26

Periodontal abscess
• Bacteria typically recovered from periodontal abscesses are
Fusobacterium spp. (75% of abscesses studied), Prevotella intermedia
⁄ nigrescens (60%), P. gingivalis (51%) and A. actinomycetemcomitans
(30%).
• Epstein–Barr virus was detected in 72%, cytomegalovirus in 67%, and
co-infection with the two viruses in 56% of 18 abscesses studied, and
the herpesviruses were not identified in healthy periodontium or
after treatment of the periodontal abscess.
31-05-2021 27

• Epstein–Barr virus has also been linked to extra-oral
abscesses in children and young adults, and
cytomegalovirus has been implicated in periodontal and
extra-oral abscesses of HIV-infected individuals.
• It is suggested that re-activation of a periodontal
herpesvirus latent infection impairs the periodontal
host defense, which permits bacterial pathogens to
enter the gingiva and cause abscess formation.
31-05-2021 28

Periodontal diseases in compromised subjects HIV-associated
periodontitis
• Cytomegalovirus infection in neonates and
immunocompromised patients (HIV-infected patients and
transplant recipients) has a high rate of morbidity.
• HIV-induced immunosuppression facilitates herpesvirus re-
activation, but active herpesviruses may also activate latent HIV.
• Re-activation of latent periodontal herpesviruses by HIV may
start a cascade of tissue-destructive events leading to
periodontal breakdown.
31-05-2021 29

• Periodontitis in HIV-infected patients may resemble
periodontitis of nonHIV-infected individuals, or be
associated with profuse gingival bleeding or necrotizing
gingival tissue.
• Herpesvirus-like virions were detected
electronmicroscopically in 56% of gingival tissue from HIV-
seropositive patients with necrotizing ulcerative
periodontitis.
31-05-2021 30

• Epstein–Barr virus type 1 was identified more frequently in
subgingival sites of HIV-positive patients than in subgingival sites of
HIV-negative patients (72 vs. 48%). Epstein–Barr virus type 2, which is
frequently found in HIV-infected subjects, was detected in 57% of
biopsies from HIV-associated periodontitis lesions, but was absent in
non-HIV associated periodontitis biopsies.
• Human herpesvirus-8 was present in periodontitis lesions of 24% of
HIV-infected individuals with no clinical signs of Kaposis sarcoma, but
was not recovered from periodontitis sites of non-HIV-infected
individuals.
31-05-2021 31

• Herpes simplex virus, Epstein–Barr virus,
cytomegalovirus and human herpesvirus-8 genomes
occur frequently in the saliva of HIV-infected
individuals, and have been related to ulcerative oral
lesions, widespread gingival and mucosal
inflammation, and oral cancer.
31-05-2021 32

Necrotizing ulcerative gingivitis ⁄
periodontitis
• Necrotizing ulcerative gingivitis ⁄ periodontitis affects
immunocompromised, malnourished and psychosocially
stressed individuals.
• In developing countries, necrotizing gingivitis may expand
considerably beyond the periodontium and give rise to the life
threatening disease termed noma or cancrum oris.
• Noma affects primarily children and is sometimes preceded by
a viral infection, such as herpetic gingivostomatitis or measles,
or HIV, which may impair host defenses against resident
viruses and pathogenic bacteria.
31-05-2021 33

• Contreras et al. studied necrotizing ulcerative
gingivitis in non HIV-infected malnourished Nigerian
children, 3–14 years of age.
• Necrotizing gingivitis lesions of malnourished children
yielded herpes simplex virus (23% of study lesions),
Epstein–Barr virus (27%) and cytomegalovirus (59%),
whereas periodontal sites of malnourished, but
periodontally normal children revealed.
31-05-2021 34

Human herpesviruses in periodontitis
associated with syndromes
31-05-2021 35

Periodontology 2000, Vol. 49, 2009, 60–86 Oral viral infections of adults Jørgen Slots
31-05-2021 36

31-05-2021 37

31-05-2021 38

31-05-2021 39

CLASSIFICATION OF VIRUS
31-05-2021 40

• Membership in the family Herpesviridae is based on a four-
layered structure of the virion.
• Herpesviruses have
(i) a core containing a large double stranded DNA genome
encased within
(ii) an isosapentahedral capsid containing 162 capsomers,
(iii) an amorphous proteinaceous tegument and, surrounding the
capsid and tegument,
(iv) a lipid bilayer envelope derived from host cell membranes
31-05-2021 42

31-05-2021 43

Pathogenesis of herpesvirus associated
periodontal disease
31-05-2021 44

HUMAN HERPES VIRUSES
• The most wellknown, herpes simplex virus (HSV), exists in 2
types: HSV-1 and HSV-2. The remaining types in the
Herpetoviridae family include varicella zoster virus (VZV),
Epstein-Barr virus (EBV), CMV, HHV-6, HHV-7, and HHV-8.
31-05-2021 46

Herpes Simplex Virus Type 1
• usually acquired during childhood. Its primary mode of
transmission is via infected saliva or direct contact of
mucocutaneous lesions.
• In primary infection,
the virus migrates to the sensory or autonomic ganglia (trigeminal
ganglia) where it remains dormant until reactivation
• secondary or recurrent form,
Reactivation occurs during stress induced states (fever, anxiety,
immune compromised states). Incubation period ranges from
several days to 2 weeks
31-05-2021 47
Neville BW. Oral and maxillofacial pathology. St Louis (MO): Saunders/Elsevier; 2009.
Gladwin M, Trattler B, Mahan CS. Clinical microbiology: made ridiculously simple. Miami (FL): Medmaster; 2014
Woo SB. Oral pathology: a comprehensive atlas and Text. Philadelphia: Elsevier/ Saunders; 2012.

Herpes Simplex Virus Type 2
• has a predilection for genital mucosa lesions.
• Transmission occurs from oral to genital contact Becomes latent
in the autonomic ganglia (lumbosacral region).
• Also capable of causing ocular lesions in newborns. from
infected mothers during the peripartum period owing to
disrupted membranes and/or with direct contact with the
infected mother’s vaginal secretions.
31-05-2021 48
Gladwin M, Trattler B, Mahan CS. Clinical microbiology: made ridiculously simple. Miami (FL): Medmaster; 2014

Clinical features
• Primary herpetic gingivostomatitis
• is an acute onset of the primary form of HSV-1 that occurs
between the ages of 6 months and 5 years.
• Primary herpetic gingivostomatitis commonly presents with flu
like symptoms (fever, chills, and cervical lymphadenopathy),
intraoral mucosal lesions (usually 2–3 mm in size) and skin
lesions.
• Lesions usually take about 7 to 10 days to resolve and heal
without scar formation.
31-05-2021 49

The main features of clinical primary
disease are
• The mouth or oropharynx is sore
• A single episode of oral vesicles
which may be widespread, and break
down to leave oral ulcers. These are
initially pin point but fuse to produce
irregular painful ulcers.
• Acute generalised marginal gingivitis
• Cervical lymph nodes may be
enlarged & tender.
31-05-2021 50

Herpes labialis
• Herpes labialis is secondary or recrudescent
herpes occurring around the perioral region,
characterized by a burning and itching sensation
before the appearance of vesicles.
• They can also appear in keratinized tissue of the
hard palate and gingival tissues owing to the
reactivation of the latent virus during conditions of
stress or immunocompromised states.
31-05-2021 51

• recurrent oral herpes infection consists of
small ulcers usually localized on palatal
mucosa , lesions are observed on the
attached gingiva surrounding the teeth and on
the palate.
• The lesions of intra oral herpes may persist.
31-05-2021 52

Herpetic whitlow
• Herpetic whitlow occurs when the virulent orofacial
lesions come in direct contact with fingers
31-05-2021 53
Woo SB. Oral pathology: a comprehensive atlas and Text.
Philadelphia: Elsevier/ Saunders; 2012.

Histopathology
• Microscopically, HSV contain
intraepithelial cell balloonings,
inflammatory cells, virus infected
epithelial cells, and acantholytic
epithelial cells (Tzanck cells), although
these findings are not specific for
herpes.
31-05-2021 54

Diagnosis
• Diagnosis is based on clinical presentation and virus
cultures. Cultures usually require 2 to 4 days for positive
identification and provide adjunctive confirmation along
with clinical diagnosis.
• Immunologic assays using monoclonal antibodies or DNA in
situ hybridization are also useful tools for positive testing.
31-05-2021 56

Treatment and prevention
• Supportive therapy is indicated (analgesics, nonsteroidal
antiinflammatory drugs, lavage, hydration).
• When symptoms arise, a 5% topical acyclovir ointment applied
5 times a day decreases the duration of herpes labialis.
• 200 to 400 mg acyclovir 5 times a day in adult patients.
• Prophylactic treatment with acyclovir 400 mg twice a day,
valacyclovir 1 g daily, or famciclovir 250 mg twice daily reduces
the prevalence and severity of recurrence.
31-05-2021 57
Regezi JA. Oral pathology: clinical pathologic correlations. 6th edition. St. Louis (MO): Elsevier; 2012.

• The VZV is a highly contagious member of the herpes
virus family its effects on children is more commonly
known as chickenpox.
• it can reactivate in adults as shingles Spreading in
droplet form, recover in a 2- to 3-week span.
• Children, older adults, and immunocompromised
patients face a greater threat.
31-05-2021 59

Clinical Features
• common in children 6 to 11 years of age the
virus remains latent at the dorsal root and
trigeminal ganglia.
• Primary symptoms include low-grade fever,
pruritis, malaise, and rash. Subsequently,
vesicles develop.
• Initial lesions begins on the trunk and face
and spread to the extremities Skin lesions are
preceded typically by oral lesions, which tend
to be painless
31-05-2021 60
Neville BW. Oral and maxillofacial pathology. St Louis (MO): Saunders/Elsevier; 2009

Histopathology
• Microscopically, acantholysis of epithelial cells
results in numerous free-floating Tzank cells, with
margination of chromatin along the nuclear
membrane and occasional multinucleation.
• In simple cases, the epithelium regenerates from
ulcer margins with minimal scar formation.
31-05-2021 61

HERPES ZOSTER/ SHINGLES
31-05-2021 62

• Latent VZV is reactivated Typically, it affects the
sensory nerves of the trunk, head, and neck,
resulting in symptoms of pain or paresthesia in those
dermatomes. Vesicular primary lesions ulcerate and
heal over in 1 to 2 weeks.
31-05-2021 63

Clinical Features
• Vesicular development is distributed in a
unilateral and linear distribution.
• The involvement of the geniculate
ganglion is a rare but reported
complication, also known as Ramsay
Hunt syndrome.
31-05-2021 64

Histopathology
• Vesicles of herpes zoster are indistinguishable
microscopically from vesicles seen in primary varicella
infection.
31-05-2021 65

Treatment
• Primary VZV infections are treated with a high dose of oral
acyclovir, 800 mg 5 times daily for 7 days.
• Treatment should begin within hours of disease onset to
reduce the risk of postherpetic neuralgia.
31-05-2021 66
Woo SB. Oral pathology: a comprehensive atlas and Text. Philadelphia: Elsevier/ Saunders; 2012

INFECTIOUS MONONUCLEOSIS
31-05-2021 67

• INFECTIOUS MONONUCLEOSIS (ALSO KNOWN AS “MONO”
OR “KISSING DISEASE”) Mono is a disease of young adults,
also known as kissing disease owing to its nature of
transmission.
• It is primarily transmitted owing to close contact (sharing of
straws, kissing and other forms of saliva exchange). EBV and
HHV-8 are the causal agents.
31-05-2021 68

Clinical Features
• children affected are asymptomatic young adults symptoms like
fever, lymphadenopathy, pharyngitis, and tonsillitis are noted.
• Prodromal symptoms like malaise, fatigue precede 2 weeks
before the development of fever, which can last 2 to 14 days in
classic infectious mononucleosis cases.
• oral lesions are similar to petechiae on the soft and hard
palates; necrotizing ulcerative gingivitis is also fairly common in
infected patients
31-05-2021 69
Gladwin M, Trattler B, Mahan CS. Clinical microbiology: made ridiculously simple. Miami (FL): Medmaster; 2014.
Woo SB. Oral pathology: a comprehensive atlas and Text. Philadelphia: Elsevier/ Saunders; 2012.

Diagnosis
• Monospot test is a rapid screening test in which
antibodies (hetrophile antibody) against EBV cross-
react and agglutinates with sheep red blood cells.
• Complete blood count reveals elevated leukocytes
and peripheral blood smears shows atypical
lymphocytes
31-05-2021 70

Treatment
• resolves spontaneously within 4 to 6 weeks and
only require treatment of clinical symptoms.
• Nonsteroidal antiinflammatory drugs are used for
fever reduction and bed rest is advised for malaise
and fatigue.
31-05-2021 71

• CMV establishes latency after initial infection in
the salivary glandular cells, endothelium,
macrophages, and lymphocytes.
• The virus can cross the placenta, causing
congenital disease or infect newborns during
delivery.
• Transmission can also occur by exchange of
bodily fluids and blood transfusions.
31-05-2021 73

Clinical Features
• Most infections are asymptomatic.
• less than 10% can present with flulike symptoms.
• In rare cases, other signs like hepatomegaly,
splenomegaly, jaundice, and central nervous system
involvement can occur.
• Oral lesions presenting with chronic mucosal
ulcerations can present with coinfections of HSV.
• Neonatal CMV infections can produce dental
disorders exhibiting diffuse enamel hypoplasia,
enamel hypomaturation, attrition, or discoloration of
dentin.
31-05-2021 74

Diagnosis
• Diagnosis is based on a combination of
clinical features and other testing procedures,
such as polymerase chain reaction or
immunoassays serologic testing
• Biopsy can be performed and should be done in
chronic ulcers for immunocompromised patients
that do not respond to conservative therapy
31-05-2021 75

Treatment
• Intravenous Ganciclovir is recommended
for treatment of CMV infections, although
most resolve spontaneously
31-05-2021 76

• Enterovirus belongs to the family picornavirus
• These infections affect any age group but are
mostly seen in young children or infants.
• The most significant diseases among this group
are herpangina; hand, foot, and mouth disease;
and acute lymphonodular pharyngitis.
31-05-2021 78

HERPANGINA
• Herpangina is transmitted by contaminated
saliva or through contaminated feces.
• Outbreaks are very common in summer or
early autumn.
31-05-2021 79

Clinical Features
• Sore throat, fever, rhinorrhea, myalgia, and dysphagia are
commonly seen with herpangina.
• Most cases are mild and symptoms last for 3 days.
• Clinically, oral lesions appear in the posterior areas of the
mouth, usually the tonsillar pillars or soft palate.
• Small vesicles form but rapidly break down to 2- to 4-mm
ulcers.
31-05-2021 80

Histopathology
• Intracellular edema resulting in subepithelial vesicles
with epithelial necrosis and ulceration are the final
result.
31-05-2021 81

Treatment
• Treatment Herpangina is mild, with minimal
complications and a short duration. Therefore,
supportive therapy is recommended.
• Contact with infected individual should be avoided to
prevent spread of disease.
31-05-2021 82

HAND, FOOT, AND MOUTH SYNDROME
• This most common enterovirus condition mostly affects children
younger than 5 years old, is highly contagious (seasonal mostly
summer), and transmits through airborne Oral Viral Infections
spread or fecal–oral contamination.
• Coxsackie type A16 or enterovirus 71 viruses were linked to
these infections. Hand, foot, and mouth syndrome tends to
occur in epidemic clusters with high transmission rates.
31-05-2021 83

Clinical Features
• Skin rash and oral lesions are associated with flulike symptoms,
accompanied by cough, rhinorrhea, diarrhea, and headaches.
• Oral lesions precede skin lesions, first presenting as vesicles that
rupture and become ulcers.
• Intraorally, these lesions tend to disseminate anywhere in the mouth
although the palate, tongue, and buccal mucosa are favored sites.
31-05-2021 84

• Cutaneous lesions primarily affect ventral surfaces and sides of
the fingers and toes, borders of the palms, and soles of the feet.
• The legs and genitals are rarely affected. Skin lesions start as
erythematous macules that develop central vesicles and heal
without crusting.
31-05-2021 85

Histopathology
• Histologic feature of skin lesions include reticular
and ballooning degeneration of keratinocytes.
31-05-2021 86

Treatment
• Management of hand, foot, and mouth disease is mainly
supportive. Signs and symptoms usually clear up in 7 to 10
days.
• Over-the-counter pain medications such as acetaminophen
(Tylenol, Johnson & Johnson, New Brunswick, NJ) or
ibuprofen with topical oral anesthetics may help pain
control.
31-05-2021 87

ACUTE LYMPHONODULAR PHARYNGITIS
• Acute lymphonodular pharyngitis is a variant of
herpangina that is associated with CVA 10.
31-05-2021 88

Clinical Features
• Sore throat, headache, and a fever, which may last
up to 10 days, are prominent features. Patients will
develop diffuse small yellow to dark-pink nodules
in the area of oropharynx.
31-05-2021 89

Histopathology
• Histopathology Findings include lymphoid
aggregate, which resolve without ulceration or
vesiculation.
31-05-2021 90

Treatment
• No treatment is necessary; the condition is self-limiting
31-05-2021 91

RUBEOLA (MEASLES)
31-05-2021 92

• Rubeola belongs to the family paramyxovirus, an RNA
enveloped virus that is highly contagious. Rubeola is
spread via airborne droplets through the
nasopharyngeal respiratory epithelium.
31-05-2021 93

Clinical Features
• Measles are uncommon in the 21st century owing to
vaccination programs, but is commonly seen in
unvaccinated individuals.
• The incubation period lasts from 10 to 12 days with the
prodromal period lasting 1 to 7 days. There are 3 stages
of measles, each typically lasting 3 days.
• The first stage includes the 3 Cs of coryza, cough, and
conjunctivitis. Oral manifestations, known as Koplik’s
spots, precede cutaneous lesions by 1 to 2 days.
• Koplik’s spots are characterized as red macular lesions
with a blue white center.
31-05-2021 94

• The second stage consists of erythematous maculopapular rashes
that starts from the face and spreads down toward the extremities,
along with a continuing fever.
• The third stage is when the fever resolves and the rashes began to
subside.
31-05-2021 95

Complications
• Complications are rare, but can include encephalitis and
thrombocytopenic purpura. Otitis media and pneumonia
can also occur as secondary infections.
31-05-2021 96

Diagnosis
• Koplik’s spots are a pathognomonic feature and
histologically are seen as focal epithelial
hyperparakeratosis. Diagnosis is clinically based with
laboratory confirmation of rising serologic antibody
titers.
31-05-2021 97

Treatment and Prevention
• Supportive therapy includes adequate rest, fluids, and antipyretic and
analgesics medications. The best therapy is prevention through
vaccination.
• The Centers for Disease Control and Prevention recommends
childhood vaccination with the measles, mumps, and rubella (MMR)
vaccine in 2 doses, first being around 12 to 15 months of age and the
second around 4 to 6 years of age.
• Complete elimination of this disease is possible with a good
vaccination program and requires global cooperation
31-05-2021 98

GERMAN MEASLES (RUBELLA)
31-05-2021 99

• German measles are caused by the Togavirus family.
• It is a contagious disease with clinical features similar to measles.
• German measles are known to causes congenital birth defects in
the developing fetus, especially if infections occur during the first
trimester of pregnancy.
• The classic triad of rubella congenital syndrome includes heart
disease, deafness, and cataracts.
• Prevention is through the MMR vaccines.
31-05-2021 100

• Mumps are no longer common in the United States. Since
the pre-vaccinated era there has been a reduction of 99%
of cases in the United States. Belonging to the
Paramyxoviridae virus family, the mumps virus primarily
infects via salivary secretions or respiratory droplets.
31-05-2021 102

Clinical Features
• One-third of mumps infections are subclinical and the rest have
nonspecific symptoms such as fever, malaise, myalgia, and headache.
• The incubation period usually ranges from 2 to 4 weeks, with the
patient at risk of spreading the virus 1 day before clinical symptoms to
2 weeks after resolution.
• Bilaterally, parotid gland involvement is the most commonly affected
salivary gland; however, the sublingual and submandibular glands can
also be involved. Swelling and pain begin from the ears and extend
down to the mandible posteriorly and inferiorly, with pain during
mastication.
31-05-2021 103

Diagnosis
• Diagnosis is easily made clinically with serologic
confirmation of rising titers of mumps, specifically
immunoglobulin (Ig)G and IgM during the infectious
stages.
31-05-2021 104

Treatment and Prevention
• The recommended treatment is palliative care with
nonsteroidal anti-inflammatory drugs as analgesics,
antipyretics, and bed rest. Hydration and diet
precautions are recommended. Prevention is through
prior MMR vaccinations.
31-05-2021 105

HUMAN PAPILLOMAVIRUS
31-05-2021 106

• HUMAN PAPILLOMAVIRUS Studies have shown that
at least 25 strains of HPV have been associated with
oral lesions. The most frequent lesions include: oral
squamous papilloma and verruca vulgaris (common
wart).
31-05-2021 107

ORAL SQUAMOUS PAPILLOMA
• Clinical Features Intraorally, these lesions
present as small, white, isolated,
exophytic, and pedunculated growths.
• They are commonly found on the hard
and soft palate, uvula, and vermillion of
the lips.
• Lesions are prevalent in middle-aged male
and females with a history of current
sexual activity.
31-05-2021 108

Histopathology
• Exaggerated growth of normal squamous epithelium.
• These lesions are exophytic with fingerlike extensions of the
epithelium supported by connective tissue. This pattern
resembles cutaneous warts.
31-05-2021 109

COMMON WART (VERRUCA VULGARIS)
• Clinical Features Common warts are found commonly on the
skin and are caused by the cutaneous HPV subtypes 2 and 57.
• These warts are similar in appearance to squamous
papillomas and tend to involve the lips, gingivae, and hard
palate.
• Aerosolizing HPV particles should be suspected while locally
excising these lesions with laser or electrocautery
31-05-2021 110

CONDYLOMA ACUMINATUM
31-05-2021 111

Clinical Features
• Condyloma acuminatum is another condition resulting from
a virus-induced proliferation of stratified squamous
epithelium of the genitalia, perianal region, mouth, and
larynx.
• HPV types 6 and 11 are usually detected in these lesions.
Condyloma is regarded as a sexually transmitted disease
with an incubation period of 1 to 2 months from the time of
contact.
31-05-2021 112

• These lesions might indicate sexual abuse
when diagnosed in young children. Studies
suggested vertical transmission from mothers
with genital infections.
• Intraorally, these lesions commonly present
as a group of multiple pink nodules on the
labial mucosa, soft palate, and lingual frenum
The average lesion size is 1.0 to 1.5 cm.
31-05-2021 113

Histopathology
• Papillary projections are covered by stratified squamous
epithelium, often parakeratotic but may be
nonkeratinized.
• The epithelium is differentiated. However, prickle cells
often demonstrate pyknotic nuclei surrounded by clear
margin (Koilocytes).
31-05-2021 114

Treatment
• Surgical excision with cryosurgery, scalpel excision, or
laser ablation is the ultimate approach to manage these
condition.
• Recurrences are common and perhaps are related to
surrounding normal appearing tissue that may be
harboring the infectious agent.
31-05-2021 115

HECK’S DISEASE
(ALSOKNOWNAS FOCAL EPITHELIALHYPERPLASIA/
MULTIFOCALEPITHELIAL HYPERPLASIA)
31-05-2021 116

Clinical Features
• Heck’s disease is characterized by multiple
asymptomatic well-circumscribed, smooth
papules on the tongue and labial mucosa of
children.
• These lesions are frequently seen in children but
they can often be seen in older adults as well.
HPV types 13 and 32 are detected in 75% to
100% of these lesions.
31-05-2021 117

Histopathology
• Histopathologic evaluation reveals prominent acanthosis
of the epithelium with elongated and wide rete ridge
31-05-2021 118

• Coronavirus disease 19 (COVID-19) is the recent
infectious disease that is rapidly spreading
worldwide. COVID-19 is caused by severe acute
respiratory syndrome coronavirus 2 (SARS-CoV-2) and
targets human angiotensin-converting enzyme 2
(ACE2).
31-05-2021 120

• manifestation and generalized erythematous and
edematous gingiva and necrotic interdental papillae in
both the maxillary and mandibular regions.
• Bleeding was seen from the gingival sulcus, and also
there was no detectable attachment loss.
31-05-2021 121

Oral Microbiome in Periodontal Tissue and
COVID-19 Patient
• Firstly, periodontal tissue containing commensals (oral
microbiome) plays an important role in oral physiology. In
oral physiology, some signals are modulated by a network
of microbial and host metabolites.
• Bacteria present in patients with severe COVID-19 infection
are usually organisms in the oral cavity such as Prevotella,
Staphylococcus, and Fusobacterium.
31-05-2021 122
Chen L, Zhao J, Peng J, Li X, Deng X, Geng Z, et al. Detection of 2019-nCoV in saliva and
characterization of oral symptoms in COVID-19 patients. doi:10.2139/ssrn.3556665.
Sampson, V. Oral hygiene risk factor. Br Dent J 2020;228:569

• Common complications of COVID-19 have similarities
to that of diabetes such as biofilms formation and
periodontitis. Moreover, the study showed that 80%
of patients with severe COVID-19 had high bacterial
load.
Xu J, Li Y, Gan F, Du Y, Yao Y. Salivary glands: Potential reservoirs for COVID19 asymptomatic
infection. J Dent Res 2020;99:0022034520918518
31-05-2021 123

• Host immune responses are also a potential risk for disease
mechanism in COVID-19 patients. A recent study found that there is a
“cytokine storm” which exhibited an elevated serum cytokine levels in
COVID-19 patients.
• Higher interleukin levels were found in severe COVID-19 patients.
These conditions were involved in the pulmonary edema and tissue
damage by SARS-CoV-2.
Badran Z., Gaudin A., Struillou X, Amador G, Soueidan A. Periodontal pockets: A potential reservoir for SARS-CoV-
2? Med Hypotheses 2020;143:109907.
31-05-2021 124

• Exaggerated systemic inflammatory responses could result in
disease manifestation in oral cavity, especially in the periodontal
region.
• Periodontal disease is an infectious disease with multifactorial
pathology mediated by immune responses.
• Increasing cytokine levels in periodontal tissue and serum were
shown in patients with periodontal disease compared to healthy
controls.
Madapusi Balaji T, Varadarajan S, Rao USV, Raj AT, Patil S, Arakeri G, et al. Oral cancer and periodontal disease
increase the risk of COVID 19? A mechanism mediated through furin and cathepsin overexpression. Med
Hypotheses 2020;144:109936.
Galván Casas C, Català A, Carretero Hernández G, Rodríguez‐Jiménez P, Fernández Nieto D,
Rodríguez‐Villa Lario A, et al. Classification of the cutaneous manifestations of COVID-19: A rapid prospective
nationwide consensus study in Spain with 375 cases. Br J Dermatol 2020;183:71-7.
31-05-2021 125

Human immunodeficiency virus
(HIV)
31-05-2021 126

• Chronic gingivitis and periodontitis are the most common
forms of gingival and periodontal diseases in Human
immunodeficiency virus (HIV) infected individuals.
• The relationship between periodontal health & prevalence
&severity of chronic gingivitis and periodontitis among
immunosuppressed HIV infected individual remains
controversial.
31-05-2021 127

• Acquired Immunodeficiency Syndrome (AIDS) is a disease of the
immune system due to infection with Human Immunodeficiency
Virus (HIV).
• HIV destroys the CD4 T lymphocytes (CD4 cells) of the immune
system, leaving body vulnerable to life threatening infections and
cancers.
• AIDS is the most advanced stage of HIV infection. To be diagnosed
with AIDS, a person with HIV infection must have an AIDS-
defining condition or have a CD4 count less than 200 cells/mm3
31-05-2021 128
AIDSinfoGlossary: https://aidsinfo.nih.gov/understanding-hiv-aids/glossary/3/acquired-immunodeficiency-syndrome

Highly active antiretroviral therapy (HAART) has significantly changed the
characteristics of chronic periodontitis in HIV infected individuals, but only
little evidence is available about its longterm treatment outcomes.
Mataftsi M, Skoura L, and Sakellari D.HIV infection and periodontal diseases: an overview of the post-HAART
era. Oral Diseases 2011; 17(1): 13–25
While HAART turns HIV into a manageable disease, treatment does not lead
to eradication of the virus. Human immunodeficiency virus is known to
interfere with the host’s immune system at different stages of both cell-
mediated and humoral immune responses.
Ras GJ, EftychisHA, Anderson R and van der Walt I. Mononuclear and polymorphonuclear leucocyte dysfunction in
male homosexuals with the acquired immuno deficiency syndrome (AIDS). South African Med J 1984; 66:806–809.
Therefore, there is potential for a long-term HIVmediated effect on chronic
periodontitis even in spite of HAART.
Burgoyne RW and Tan DH. Prolongation and quality of life for HIV-infected adults treated with highly active
antiretroviral therapy (HAART): a balancing act. J Antimicrobial Chemotherapy 2008;61(3): 469–473.
31-05-2021 129

Oral manifestations
• The majority of these lesions can be detected early or appear during the progression of the
disease. This is the case of a peculiar and uncommon aggressive type of periodontal
disease found in AIDS patients (Swango et al., 1991).
• Although oral manifestations of bacterial origin can be less evident these must be
considered and may lead to periodontal disease, bone pockets and delayed wound healing
(Correa et al., 1994).
• Gingival lesions and alveolar bone loss are clinical features found frequently in HIV
patients, and these lesions often do not respond properly to treatment (Winkler and Robertson, 1992).
• This may be a direct result of changes in the microbial flora and colonization which
reflect a breakdown of the immunologic system. The appearance of stomatitis in AIDS
patients differs from that seen in non-infected patients because in AIDS sufferers the
lesion is chronic and does not obtain complete remission (Melo, 1989).
31-05-2021 130

• Gingivitis associated to HIV (G-HIV) is characterized by the lack of
local irritants, severe erythema of the gum and oral mucosa, and
bleeding. It is highly resistant to conventional local treatments (Winkler and
Robertson, 1992; Langford, 1994; Murray, 1995; Serb, 1995).
• The disease is aggravated by acute necrotizing ulcerative gingivitis or
ANUG (HIV-ANUG), when it assumes a chronic or sub-acute course.
It may initially appear as ulcerations covered by fibrinous exudate
which precedes the disruption of the gingival crest and the formation
of craters. The lesion may also progress quickly to necrotizing
periodontitis (Langford, 1994; Murray, 1995; Serb, 1995).
31-05-2021 131

• Periodontitis associated to HIV (P-HIV) is a very peculiar feature
because HIV-infected patients frequently show a severe increase in the
manifestation of this atypical periodontal disease (Glick et al., 1990).
• Clinically, severe edema, gingival erythema, pain, spontaneous
bleeding, interproximal necrosis, ulcerations, and rapid loss of
periodontal tissue can be observed. This is often followed by severe
necrosis, with the progression of this disease extremely fast not
responding to conventional treatment used in non-infected patients
(Friedman et al., 1991; Klein et al., 1991; Winkler and Robertson, 1992; Serb, 1995).
31-05-2021 132

Rapid progressive periodontitis
• Rapid progressive periodontitis is another periodontal disease which must
be differentiated from the above-mentioned diseases. This disease was
described a century ago and has bimodal peaks (puberty and around 35
years of age) affecting all teeth without limits of destruction.
• Some patients may have a previous history of juvenile periodontites.
Initially there is quick and severe bone destruction which may stop
spontaneously.
• After this acute phase the gum presents signs of inflammation and marginal
hyperplasia and may be extensively covered by residues.
• In approximately 83% of the patients modification in the function of
neutrophils and/or monocytes, weight loss, malaise and depression are
observed. Some patients respond to treatment (Page et al., 1983).
31-05-2021 133

Prevention and treatment
• The natural history of periodontal diseases includes long-term chronic
irritation of the periodontal tissue followed by circumscribed areas of
inflammation of both surface and deep tissues resulting in the
migration of the junction epithelium.
• Later, there is loss of alveolar bone and formation of deep pockets and
consequent pathologic tooth mobility which results in loss of function
and finally exfoliation of the tooth.
• Early preventive measures must be taken to prevent progression of the
disease. Initially, improved conditions for increased resistance of the
periodontal tissues must be sought.
31-05-2021 134

• Specific and direct protection of periodontal health and early diagnosis and
treatment of any disease must be provided. Limitation of damage through
rehabilitation must be carried out .
• Generally the treatment of periodontal lesions requires debridement,
antibiotics and long-term follow-up. Professional oral prophylaxis, plaque
control and debridement of necrotic tissues are essential for the success of
treatment.
• There are other procedures which may be used to improve the results of the
control of plaque and post-surgical treatments must be used according to the
needs of each patient. Fundamentally, the prevention of periodontal disease
must be precocious due to the accumulative characteristic of these
pathologies.
31-05-2021 135

• Up to now there is no treatment for AIDS. Therefore, treatments
available are used to minimize symptoms of associated diseases.
However, many times these treatments may result in severe side
effects which may need multiple medical consultations and
frequent stays in the hospital (De Vita et al., 1991; Winkler and Robertson, 1992).
• Because periodontal diseases associated with AIDS do not respond
well to conventional treatment, the lost of teeth is very common.
Literature has shown that these patients need rigorous and frequent
follow-up in order to assess the use of preventive measures and to
verify the progression of the disease.
• Dental health education and rigid plaque control are essential and
must be associated with the use of antibiotics and chlorhexidine-
based oral mouthrinses (Glick et al., 1990; De Vita et al., 1991; Winkler and Robertson, 1992).
31-05-2021 136

• Oral hygiene of areas of difficult access must be associated with the
use of interproximal cleaning devices and interproximal brushes.
• Long-term need of periodontal treatment varies from patient to patient
and appears to depend on the general conditions of the patient.
• Monthly visits to the Dentist for the assessment of oral hygiene and
professional scaling and tooth polishing are strongly recommended
and must be carried out until the condition is stabilized.
• When the situation is controlled, visits may be at 3-month intervals.
Relapses of HIV-associated lesions are common in patients who are
not able to keep an excellent level of oral hygiene and do not follow a
regular program of visits to their Dentists (Winkler and Robertson, 1992).
31-05-2021 137

LABORATORY DIAGNOSIS OF
VIRAL DISEASES
31-05-2021 138

ELECTRON MICROSCOPY
• Negatively stained by potassium phosphotungstate, scanned under
EM.
• SHAPES:
• Rabies Virus : bullet shaped
• Rotavirus : wheel shape
• Coronavirus : petal shaped
• Adenovirus : space vehicle shaped
31-05-2021 139

• Direct detection from specimens :
Difficult to cultivate- rotavirus, coronavirus, Hepatitis A, Hepatitis E.
• Virus detection in tissue cultures
• Disadvantages:
Expensive
Low sensitivity (107 virions/ml)
Specificity low
31-05-2021 140

IMMUNOELECTRON MICROSCOPE
Improved sensitivity & specificity
Specific antiviral antibody added to the specimen to aggregate viral
particles
Direct –IF-
Specimen mounted on slide
Stained with specific antiviral antibody tagged with flurescent dye
Rabies virus antigen in skin biopsy
31-05-2021 141
FLOURESCENT MICROSCOPE

IMMUNOPEROXIDASE STAINING
• Cells coated with viral antigen
• Stained with Immunoperoxidase tagged specific
antibiodies
• Viewed under light microscope
31-05-2021 142

VIRAL ANTIGEN
• ELISA
• ICT
• FLOW THROUGH ASSAY
• HBsAg & HBeAg detrction
• NS1 antigen detection for dengue
• P24 antigen detection for HIV stool
31-05-2021 143

VIRAL ANTIBODIES
• MC used in diagnostic virology
• IgM antibody
• Four fold rise in titer og IgG antibody (recent infection)
• Hemagglutination Inhibition (HAI) test for influenza virus
• Neutralization test (poliovirus)
• Anti-Hepatitis C antibodies in serum
31-05-2021 144

MOLECULAR METHOD
• Nucleic acid probe
• Polymerase chain reaction
• RT-PCR (reverse transcriptase polymerase chain reaction) –
RNA viruses
• Real time PCR- quantify viral nucleic acid
-monitor the treatment response
-visualized on real time basis
31-05-2021 145

ANTIVIRAL SUSCEPTIBILITY TESTING
31-05-2021 146

• ANTIVIRAL SUSCEPTIBILITY TESTING With an increase of treating
physicians to prescribe antimicrobial medications, it is well
documented that drug resistance is increasing.
• Antiviral susceptibility testing is available not widely and modalities
are not standardized. Antiviral resistance develops as a result of
mutations in viral genes.
• Currently, there are 2 main modalities to test resistance: genotypic
antiviral resistance testing and phenotypic drug susceptibility testing.
31-05-2021 147
Hupp JR, Ferneini EM. Head, neck, and orofacial infections: an interdisciplinary approach. 1 edition. St Louis (MO): Elsevier; 2016.
Storch GA. Diagnostic virology. Clin Infect Dis 2000;31:739–51.

conclusion
• the general dentist will be able to diagnose
these lesions based on clinical features.
They will also be familiarized with details
on basic histopathology, treatment, and
prevention of commonly associated viral
infections of the oral cavity.
31-05-2021 148

References:
31-05-2021 149
• Norrby E.Nobel Prizes and the emerging virus concept. Arch Virol 2008 153 (6): 1109–23
• Oldstone MBA (2009). Viruses, Plagues, and History: Past, Present and Future. Oxford University
Press, USA. p. 306
• Samaranayake L. Virus and Prions. In: Essential Microbiology. 4th ed. Churchill livingstone.2011.P.
28-68.
• Mithlesh Bhagat et.al. Role of viruses in periodontal diseases Galore International Journal of Health Sciences
and Research (www.gijhsr.com) Vol.5; Issue: 1; January-March 2020
• Kapil A. Virology. In: Ananthanarayan and Paniker’s Textbook of Microbiology. 9th ed. United press,
Hyderabad. P. 427-588
• Morse SA, Riedel S, Mietzner TA, Miller S (2019-08-25). Jawetz Melnick & Adelbergs Medical
Microbiology 28E. McGraw-Hill Education. ISBN 9781260012033
• Immune Responses to Viruses ; British society for immunology; Kerry Laing, Fred Hutchinson Cancer
Research Centre, Seattle, USA

• Periodontology 2000, Vol. 38, 2005, 33–62, Herpesviruses in periodontal diseases Jørgen
Slots
• Periodontology 2000, Vol. 53, 2010, 89–110 Human viruses in periodontitis Jørgen Slots
• Periodontology 2000, Vol. 49, 2009, 60–86 Oral viral infections of adults Jørgen Slots
• Ting M, Contreras A, Slots J. Herpesvirus in localized juvenile periodontitis. J Periodontal Res
2000: 35: 17–25.
• Neville BW. Oral and maxillofacial pathology. St Louis (MO): Saunders/Elsevier; 2009.
• Gladwin M, Trattler B, Mahan CS. Clinical microbiology: made ridiculously simple. Miami (FL):
Medmaster; 2014
• Woo SB. Oral pathology: a comprehensive atlas and Text. Philadelphia: Elsevier/ Saunders; 2012.
• Regezi JA. Oral pathology: clinical pathologic correlations. 6th edition. St. Louis (MO): Elsevier;
2012.
31-05-2021 150

• Chen L, Zhao J, Peng J, Li X, Deng X, Geng Z, et al. Detection of 2019-nCoV
in saliva and characterization of oral symptoms in COVID-19 patients.
doi:10.2139/ssrn.3556665.
• Sampson, V. Oral hygiene risk factor. Br Dent J 2020;228:569
• Xu J, Li Y, Gan F, Du Y, Yao Y. Salivary glands: Potential reservoirs for COVID19
asymptomatic infection. J Dent Res 2020;99:0022034520918518
• Badran Z., Gaudin A., Struillou X, Amador G, Soueidan A. Periodontal
pockets: A potential reservoir for SARS-CoV-2? Med Hypotheses
2020;143:109907
• Madapusi Balaji T, Varadarajan S, Rao USV, Raj AT, Patil S, Arakeri G, et al.
Oral cancer and periodontal disease increase the risk of COVID 19?
A mechanism mediated through furin and cathepsin overexpression. Med
Hypotheses 2020;144:109936.
• Galván Casas C, Català A, Carretero Hernández G, Rodríguez‐Jiménez P,
Fernández Nieto D, Rodríguez‐Villa Lario A, et al. Classification of the
cutaneous manifestations of COVID-19: A rapid prospective nationwide
consensus study in Spain with 375 cases. Br J Dermatol 2020;183:71-7.
31-05-2021 151

• AIDSinfoGlossary: https://aidsinfo.nih.gov/understanding-hiv-
aids/glossary/3/acquired-immunodeficiency-syndrome
• Mataftsi M, Skoura L, and Sakellari D.HIV infection and periodontal
diseases: an overview of the post-HAART era. Oral Diseases 2011;
17(1): 13–25.
• Ras GJ, EftychisHA, Anderson R and van der Walt I. Mononuclear and
polymorphonuclear leucocyte dysfunction in male homosexuals with
the acquired immuno deficiency syndrome (AIDS). South African
Med J 1984; 66:806–809.
• Burgoyne RW and Tan DH. Prolongation and quality of life for HIV-
infected adults treated with highly active antiretroviral therapy
(HAART): a balancing act. J Antimicrobial Chemotherapy 2008;61(3):
469–473.
31-05-2021 152

Role of virus in periodontal diseases

Recomendados

Recomendados

Más contenido relacionado

La actualidad más candente

La actualidad más candente (20)

Similar a Role of virus in periodontal diseases

Similar a Role of virus in periodontal diseases (20)

Más de Dr. sneha chavan

Más de Dr. sneha chavan (10)

Último

Último (20)

Role of virus in periodontal diseases

Notas del editor