key: cord-0724094-3d64mso0
authors: Slots, Jørgen; Slots, Henrik
title: Bacterial and viral pathogens in saliva: disease relationship and infectious risk
date: 2010-12-07
journal: Periodontol 2000
DOI: 10.1111/j.1600-0757.2010.00361.x
sha: 923c61c592ba10e2c4a01e2251b001e65f603ead
doc_id: 724094
cord_uid: 3d64mso0

nan

Research on the infectious aspects of dental diseases has focused on the internal development and the pathogenicity of dental biofilms, and comparably little attention has been given to the source of the biofilm microorganisms. Odontopathic bacteria exist in saliva before colonizing dental surfaces, and a better understanding of the acquisition of salivary pathogens may lead to new approaches for managing dental diseases. Human viruses are also frequent inhabitants of the human mouth, and their presence in saliva may be caused by the direct transfer of saliva from infected individuals, a bloodborne infection of the salivary glands, infection of the oral mucosa, or serumal exudates from diseased periodontal sites.

It has long been recognized that saliva can contain potential pathogens in quantities sufficient to infect other individuals (152) . The classic example of a serious infection contracted through saliva is Epstein-Barr virus-induced mononucleosis, which colloquially is termed the Ôkissing diseaseÕ. An example from the past is the ÔNo SpittingÕ signs to prevent inhalation of the tubercle bacillus from spit specimens on street pavements and public floors. Dental clinics implement stringent infection-control measures to protect personnel and patients from pathogens in spatter, mists, aerosols, particulate matter or contaminated instruments (36) and, in the future, may adopt fully automated test systems to identify salivaborne pathogens of oral and medical diseases (72, 144) .

The potential of salivary biomolecules to aid in the diagnosis of various conditions ⁄ diseases is a topic of current interest (209) . Highly sensitive and specific molecular detection methods have greatly facilitated the search for salivary molecules of diagnostic value. Polymerase chain reaction (PCR)-based assays can detect a large array of pathogens in saliva with no interference from PCR inhibitors (139) , and even more efficient identification techniques are rapidly emerging (97, 132) . A major advantage of salivary testing is the ease by which diagnostic samples can be collected by health professionals, by the individuals themselves, or by parents for young children. Salivary sampling is painless and involves fewer health and safety issues than venepuncture, especially in patients with hemorrhagic diseases or virulent bloodborne pathogens. Used as diagnostic aids, salivary biomolecules can identify a variety of cancers, illicit and prescription drug use, hereditary disorders and hormonal irregularities (87) . Salivary testing can also screen for infection with the human immunodeficiency virus (HIV) (206) , herpesviruses (144, 172) , hepatitis viruses (144) , measles virus (70) and other pathogenic viruses and bacteria (discussed later). Some biomarkers in saliva exhibit significant intrasubject fluctuations and may have limited diagnostic utility (189) .

Salivary microbial assays to assess the presence or the risk of dental diseases are premised on the idea that (i) whole saliva is the immediate source of oral biofilm bacteria, and saliva and dental biofilms tend to harbor similar relative levels of odontopathogens, and (ii) high salivary counts of odontopathic bacteria infer a high risk for dental disease and for pathogen transmission between individuals, and a decrease in the salivary count of pathogens can serve as an indicator of therapeutic effectiveness. Periodontal disease severity may be ascertained by the salivary level of periodontal pathogens or host-response markers (67, 130, 146, 193, 214) , and the periodontopathic bacteria may be acquired from the infectious saliva of close family members (17) . Caries risk is assessed by the levels of mutans streptococci and lactobacilli in stimulated saliva (94, 96) , and salivary transmission of cariogenic bacteria frequently occurs from the mother to her child (92, 100) . Yeasts can be part of oral biofilms and cause candidosis and other oral diseases (157, 210) , especially in HIV-infected individuals, and Candida albicans transmission between spouses can take place through saliva (26) . Comparatively few parasites colonize the mouth, but systemic parasitic infections can affect the oral cavity (e.g. leishmaniasis), and oral protozoa may be more common than once thought (21) .

This review article presents evidence that pathogenic bacteria and viruses can be present in saliva at levels that pose a disease risk for individuals with whom saliva is exchanged. Emphasis is placed on the salivary route of transmission of periodontopathic bacteria and herpesviruses, and on the relationship between these infectious agents and periodontitis. The salivary presence of viral pathogens of rare, but serious, medical diseases is also reviewed.

Periodontitis and dental caries are infectious diseases, but the exact causes and their relative importance is still a matter of research. The search for etiological factors is closely connected to the question of how to avoid dental diseases. The consensus viewpoint of the scientific community is that specific bacteria cause both periodontitis and dental caries. This understanding has prompted the pursuit of microbiological methods to diagnose, prevent and treat dental infections.

The periodontopathic microbiota has been studied for the purpose of developing more effective diagnostic tests and treatments (12, 165) . As periodontopathic bacteria also colonize the tongue dorsum and other nondental sites (43, 131) , and can be transferred via saliva to close family members (17) , periodontitis therapeutic measures ought to target periodontal pathogens in the whole mouth, not only in dental biofilms, and may even include entire family units in order to prevent cross-infection. Umeda et al. (193) compared the presence of six species of periodontopathic bacteria in whole saliva and subgingival plaque from 202 subjects. Each study subject contributed a whole saliva sample and a paper point sample pooled from the deepest perio-dontal pocket in each quadrant of the dentition, and the test bacteria were identified using a 16S ribosomal RNA-based PCR assay (15) . A statistical relationship was found between the presence of Porphyromonas gingivalis, Prevotella intermedia, Prevotella nigrescens and Treponema denticola in whole saliva and in periodontal pocket samples, and in the event of disagreement, the organisms were more frequently present in whole saliva than in periodontal pockets (P < 0.01). The oral presence of Aggregatibacter actinomycetemcomitans and Tannerella forsythia was not reliably detected by sampling either whole saliva or periodontal pockets. Other studies also found that a salivary sample alone did not identify all individuals infected with A. actinomycetemcomitans (176, 200) . Taken together, a sample of whole saliva seems to be superior to a pooled periodontal pocket sample for detecting oral P. gingivalis, P. intermedia, P. nigrescens and T. denticola, but samples of both whole saliva and periodontal pockets may be needed in order to detect oral A. actinomycetemcomitans and T. forsythia with reasonably good accuracy. The reason for this is that A. actinomycetemcomitans and T. forsythia can persist in nondental sites, as best demonstrated in fully edentulous individuals (55, 194) . Umeda et al. (192) also investigated risk factors for harboring A. actinomycetemcomitans, P. gingivalis, T. forsythia, P. intermedia, P. nigrescens and T. denticola in periodontal pockets, in whole saliva, or in both sites (i.e. orally). The study subjects included 49 African-Americans, 48 Asian-Americans, 50 Hispanics and 52 Caucasians living in Los Angeles. Periodontal probing depth was positively associated with all six study bacteria. African-Americans were at increased risk (compared with Caucasians) for harboring P. gingivalis in saliva [odds ratio (OR) 2.95] and orally (OR 2.66), and at reduced risk for harboring T. denticola orally (OR 0.34). Asian-Americans showed an increased risk for harboring A. actinomycetemcomitans in periodontal pockets (OR 6.63) and for harboring P. gingivalis in periodontal pockets (OR 5.39), in saliva (OR 5.74) and orally (OR 5.81). Hispanics demonstrated an increased risk for harboring A. actinomycetemcomitans in periodontal pockets (OR 12.27) , and for harboring P. gingivalis in periodontal pockets (OR 6.07), in saliva (OR 8.72) and orally (OR 7.98). Age was positively associated with the prevalence of A. actinomycetemcomitans orally (OR 1.18), and with P. gingivalis in saliva (OR 1.20) and orally (OR 1.20). The male gender was a risk factor for harboring P. intermedia in periodontal pockets (OR 2.40), in saliva (OR 3.31) and orally (OR 4.25) , and for harboring P. nigrescens in saliva (OR 2.85). The longer the subjects had resided in the USA, the greater the decrease in detection of A. actinomycetemcomitans orally (OR 0.82). Former smokers demonstrated a decreased risk for harboring A. actinomycetemcomitans in saliva (OR 0.23), and current smokers displayed an increased risk for harboring T. denticola in periodontal pockets (OR 4.61) . Current and passive smokers revealed less salivary P. nigrescens than nonsmokers (127) . In sum, the study found a relationship between the presence of periodontopathic bacteria in whole saliva and in periodontal pockets, and pointed to the importance of genetic or environmental factors in the colonization of these pathogens. Salivary tests for periodontitis may show increased accuracy if supplementing infectious disease variables with ethnic and social factors and with smoking habits (177) .

Studies have evaluated the salivary route of transmission of periodontopathic bacteria. Transmission of periodontal pathogens from person to person depends on the salivary load of pathogens in the donor subject and various ecological factors in the recipient (16) . An early epidemiologic study found that members of the same family were infected with A. actinomycetemcomitans strains of the same biotype and serotype (213) . However, even in families with individuals heavily infected with A. actinomycetemcomitans, some family members did not harbor the organism, attesting to a relatively poor transmissibility of A. actinomycetemcomitans (213) . A study based on bacterial typing by means of the arbitrarily primed PCR method revealed an interspousal transmission of A. actinomycetemcomitans in 4 ⁄ 11 (36%) of married couples and of P. gingivalis in 2 ⁄ 10 (20%) of married couples (17) . Parent-to-child transmission of A. actinomycetemcomitans took place in 6 ⁄ 19 (32%) families, whereas P. gingivalis was not transmitted from parent to child in any of the families studied (17) . Similarities in the profile of periodontal bacteria have also been shown for 6-to 36-month-old children and their caregivers (186) . A review article described horizontal transmission between spouses to be 14-60% for A. actinomycetemcomitans and 30-75% for P. gingivalis, and vertical transmission to be 30-60% for A. actinomycetemcomitans and to occur only rarely for P. gingivalis (197) . The intrafamilial transmission of A. actinomycetemcomitans and P. gingivalis may in part explain the familial pattern of some types of periodontitis (13) . Also, periodontal treatment and marked suppression of periodontopathic bacteria in members of a periodontitis-prone family may diminish the risk of transferring the pathogens and the disease to uninfected family members.

The major cariogenic bacteria are mutans streptococci in incipient dental caries and lactobacilli in advanced caries lesions (95) , perhaps in combination with other bacteria of the dental biofilm (1, 142) . After adjusting for age and ethnicity, 6-to 36-month-old children with high levels of Streptococcus mutans were found to be five times more likely to have dental caries than children with low levels of the bacterium (117) . Recent large-scale microbiological studies have linked S. mutans to crown caries in children and adolescents (1, 42) and to root caries in elderly patients (142) . Herpesviruses have been statistically associated with severe dental caries, but their role, if any, in the caries process remains obscure (38, 212) .

An intrafamilial transfer of S. mutans was first suggested in the 1980s (23, 47) . Transmission of cariogenic bacteria from the mother to the young child is particularly common, although the organisms also may be acquired from a spouse or from outside the family (98) . More recent studies have found a similar profile of cariogenic bacteria in young children and their caregivers (186) , and molecular typing studies have provided additional evidence of a transmission of mutans streptococci from mother to child (92, 100) . Caries-free twins have a more similar oral microflora than twins that are caries-active, and hereditary factors seem to influence the colonization of oral bacterial species that protect against dental caries (41) .

The finding of a relatively unique cariogenic microflora has a practical implication. Routine testing for elevated caries risk, based on the salivary level of mutans streptococci (>1,000,000 per ml saliva) and lactobacilli (>100,000 per ml saliva), has been performed in Sweden for more than 30 years (46, 94) . Repeat swabbing of teeth of young children with 10% povidone-iodine can reduce the number of mutans streptococci (22) and the incidence of caries (106) . Suppression of high levels of S. mutans in the mother may delay or prevent the establishment of the organism in her child (91) .

A variety of bacterial pathogens of medical diseases can be present in the oral cavity and may be transmitted to individuals in close contact with the host (45) . Medical pathogens are mostly detected in the mouth during the acute phase of the nonoral infection, but the organisms can also occur in the saliva of clinically healthy subjects.

Streptococcus pyogenes (beta-hemolytic group A Streptococcus) is the cause of a variety of human diseases ranging from mild illnesses of the skin or throat (pharyngitis or Ôstrep. throatÕ) to severe invasive infections, including necrotizing fasciitis (flesheating disease), septicemia, toxic shock syndrome, erysipelas, cellulitis, acute postinfectious glomerulonephritis, rheumatic fever and scarlet fever (178) . S. pyogenes normally resides in the throat and is one of the most common medical pathogens in the saliva. An asymptomatic carriage stage of S. pyogenes was detected in approximately 10% of adults and 25% of children, and in as many as 60% of subjects during large outbreaks of streptococcal pharyngotonsillitis (178) . Beta-hemolytic group A streptococci were found in 20% of pharyngeal samples and in 5% of saliva samples of young schoolchildren in New Zealand, with a suggestion of a child-to-child transmission of the organism (185) . Members in the same household of a patient with pharyngotonsillitis frequently harbor the same strain of beta-hemolytic group A Streptococcus, indicating an intrafamilial transmission of the bacterium (58) .

Haemophilus influenzae can cause acute bronchitis and exacerbations of chronic obstructive pulmonary disease, as well as meningitis in children and other serious diseases (124) . Despite the availability of highly effective vaccines since the early 1990s, 100,000s of unvaccinated children die every year from H. influenzae-related disease (208) . The organism resides in the pharynx and is rarely recovered from the saliva of healthy individuals (88) . It can reach quantities of 10 3 -10 8 ⁄ ml in the sputum of patients with lower respiratory tract infections and purulent sputum (61) .

Staphylococcus spp., Pseudomonas spp. and Acinetobacter spp. are also potential pathogens in respiratory (and other) diseases. These bacteria were detected in the oral cavity of 85% of hospitalized patients in Brazil (216) and in subgingival sites of periodontitis patients in the USA (145, 174) . Periodontal staphylococci occurred with highest proportions in younger individuals, and periodontal gram-negative bacilli were found mostly in older subjects (174) . Staphylococci can also be prominent in the microbiota of failing dental implants (78) . Gram-negative bacilli are frequent inhabitants of the oral cavity of individuals in developing countries, where the bacteria are probably acquired through contaminated potable water (8, 79, 175) .

Meningococcal invasive disease (septicemia and ⁄ or meningitis in association with hemorrhagic rash) is a life-threatening condition that primarily affects young children. Meningococcal disease can also occur in teenagers, and is more common in collage ⁄ university students than in the general population (OR 3.4) (190) . Although Neisseria meningitidis resides in the nasopharynx and in the tonsils, and is much less common in saliva (129), intimate kissing, especially with multiple partners, constitutes a risk factor for meningococcal disease (OR 3.7) (190) . Fortunately, the prevalence of meningitis caused by N. meningitidis, H. influenzae type b and Streptococcus pneumoniae has decreased markedly after the introduction of vaccines against these bacteria (89) .

Neisseria gonorrhoeae (which causes gonorrhea) and Treponema pallidum (which causes syphilis) can produce acute and chronic oral infections. Gonorrhea is a widespread disease worldwide, with an estimated 600,000 new cases each year in the USA (103) . Although oral gonorrhea is relatively rare, the literature describes more than 500 cases of oropharyngeal gonorrhea (20) . Syphilis is re-emerging in many countries, especially in HIV-infected individuals and among men who have sex with men, and oral sex is often reported to be the route of T. pallidum transmission (37, 168, 198) . Infants have contracted syphilis by the mouth-to-mouth transfer of prechewed food from actively infected relatives (215) . Dentists can play an important role in the control of sexually transmitted diseases by identifying signs and symptoms of gonorrhea and syphilis and making appropriate referrals for treatment.

Tuberculosis remains a serious disease worldwide (68) . In 2005, there were an estimated 8.8 million new cases of tuberculosis, with 7.4 million occurring in Asia and sub-Saharan Africa, and 1.6 million people died of tuberculosis, including 195,000 with HIV infection (114) . Mycobacterium tuberculosis can be identified in the whole saliva of almost all tuberculosis patients (54) and of some nontuberculous individuals (101) , and has been recovered from alginate dental impressions (140) . The US Centers for Disease Control has identified the personnel of a dental-care facility to be at increased risk for infection with M. tuberculosis (35) and has updated the tuberculosis infection control guidelines for dental clinics (40) .

Helicobacter pylori can cause gastritis, peptic ulcers and gastric adenocarcinoma (143) . The organism resides primarily in the human stomach and may colonize about 50% of the worldÕs population. Large quantities of H. pylori can be recovered from vomitus, and the bacterium can also be detected in saliva, especially in subjects suffering from gastric ulcer. However, published data on the occurrence of H. pylori in the mouth vary greatly (143) , perhaps because the oral carriage of H. pylori is population dependent or is only transient (50) . The transmission route is mainly from the mother, or an older sibling, to younger children. Both gastro-to-oral and oral-tooral transmission are considered important.

Legionella pneumophila is the cause of legionellosis (LegionnaireÕs disease), a severe type of pneumonia with multisystem failure, and of Pontiac fever, a self-limiting influenza-like illness (114) . The natural reservoir for L. pneumophila and other Legionella species is aquatic habitats. Legionellae have been isolated from sputum and other body fluids and sites (123) . L. pneumophila has also been recovered from dental unit water in England, Germany and Austria (184) , and from 8% of dental units in the USA (18) . However, no evidence exists to incriminate dental units as a significant source of legionellosis.

Herpesvirus species comprise the most prevalent viral family in human saliva and are important periodontopathic agents (173) . Eight herpesvirus species, with distinct biological and clinical characteristics, can infect humans: herpes simplex virus-1 and -2, varicella-zoster virus, Epstein-Barr virus, human cytomegalovirus, human herpesvirus-6, human herpesvirus-7 and human herpesvirus-8 (KaposiÕs sarcoma virus) (171) . Herpesviruses establish a lifelong persistent infection, and some herpesvirus species infect as many as 90% of the adult population. The clinical outcome of a herpesvirus infection ranges from subclinical or mild disease to encephalitis, pneumonia and various types of cancer. Herpesviral infections in the oral cavity may give rise to asymptomatic and unrecognized shedding of virions into saliva, or to diseases of the oral mucosa or the periodontium (171, 179) . A recent article reviewed acute herpesviral infections in the oral cavity of children (156) .

Herpesviruses exhibit a biphasic infection cycle involving a lytic, replicative (ÔproductiveÕ) phase and a latent, nonproductive phase (171) . The replicative phase involves expression of viral regulatory and structural proteins, and the formation of infectious virion particles (172) . The ability to switch between replicative and latent states ensures viral transmissibility between individuals as well as a permanent infection of the host. Following the initial infection, herpesviruses preferentially exist in a state of latency in sensory ganglion cells (herpes simplex viruses and varicella-zoster virus), B-lymphocytes (Epstein-Barr virus, herpesvirus-8), or monocytes and T-lymphocytes (cytomegalovirus and herpesviruses-6 and -7).

Herpesvirus conversion from a latent form to lytic replication can occur spontaneously or be caused by environmental stimuli, chemical agents and physical and psychosocial stress events, as found in adults with an abusive early-childhood history, astronauts in space flight, students before important academic exams, elite athletes in intensive training and subjects with work-related fatigue ( Table 1 ). Reactivation of an oral herpesviral infection can be estimated by a rise in herpesvirus salivary counts or a significant increase in herpesvirus-specific salivary antibodies. Immunocompetent individuals usually experience herpesvirus re-activation lasting for only a few hours or days (112) , which is probably too short a time period to initiate or exacerbate clinical disease. However, the egress of herpesvirus virions into saliva poses a risk for infecting individuals in intimate contact.

By contrast, immunosuppressive conditions ⁄ diseases and long-term medications may result in the re-activation of oral herpesviruses that continues for an extended period of time and may pose a pathogenetic risk for the infected individual. The immune system of older persons may fail to control a latent varicella-zoster infection, resulting in herpes zoster outbreaks (29), or may not protect effectively against Epstein-Barr virus and cytomegalovirus re-activation (180) . The herpesvirus infection in such persons may be characterized as chronically re-activated instead of latent.

The great majority of systemically healthy adults continually shed herpesvirus DNA into saliva. Herpes simplex virus-1 DNA was detected in saliva in quantities up to 2.0-2.8 · 10 6 ⁄ ml (102, 118) . Epstein-Barr virus DNA copies in saliva can reach levels of 10 8 ⁄ ml (76), 1.6 · 10 9 ⁄ ml (155), 7.1 · 10 5 ⁄ ml (181) and 2.2 · 10 6 per 0.5 lg of DNA (202) . As the Epstein-Barr virus salivary count only decreased moderately after large-volume mouth gargles and rinses, or after normal swallowing every 2 min, a large quantity of the virus must constantly enter the saliva (76) . However, the salivary Epstein-Barr virus load can vary by as much as 4-5 logs over the course of several months, which complicates the categorizing of (76) . Cytomegalovirus DNA was detected in the saliva of 61% of immunocompetent and immunocompromised subjects (65) , and could reach salivary DNA copy counts of 4.2 · 10 4 ⁄ ml (155) . Herpesvirus-6 and herpesvirus-7 may occur in saliva, with prevalences exceeding 95% and in quantities of several million DNA copies ⁄ ml (118) . Salivary herpesvirus-8 DNA, in quantities of 2.0-7.3 log 10 copies ⁄ ml, was detected in 61% of asymptomatic, immunocompetent men who have sex with men (32) , and in 37% of Zimbabwean women with KaposiÕs sarcoma, but not in women without the disease (99) . Varicella-zoster virus DNA is present at a low prevalence and in quantities of <1,100 copies ⁄ ml in the saliva of both healthy and HIV-infected individuals (205) . Table 2 shows the association between salivary herpesviruses and periodontitis. A periodontal dual infection of herpesviruses and pathogenic bacteria gives rise to enhanced cytokine release and immune signaling dysregulation (27, 104, 187) , and tends to be associated with more severe periodontitis than a periodontal infection involving solely bacteria (172) . Herpes simplex virus-1 may contribute to periodontitis in a subset of individuals (173) , and the virus was identified in whole saliva of 24% of patients with chronic periodontitis (71) . In the same group of patients, herpes simplex virus-1 DNA was present in 16% of subgingival samples and in 8% of peripheral blood samples (71) . Herpes simplex virus DNA was found in the saliva of 84% of patients with overt herpetic lesions (144) . Epstein-Barr virus DNA has been detected in whole saliva of 79% of periodontitis patients and 33% of gingivitis patients (155) , and in 49% of periodontitis patients and 15% of healthy individuals (82) . A correlation was found between salivary and subgingival levels of Epstein-Barr virus in one study (48) but not in another study (84) . As high quantities of salivary Epstein-Barr virus DNA can be recovered from fully edentulous patients (155) , the occurrence of the virus in saliva may not be a reliable indicator of its subgingival level or of the periodontitis disease status. Cytomegalovirus periodontal active infection is closely linked to aggressive periodontitis (173) . Cytomegalovirus DNA was detected in the saliva of 50% of periodontitis patients, but was not found in the saliva of gingivitis patients or complete denture wearers, suggesting that salivary cytomegalovirus originates mainly from periodontitis lesions (155) . Also, cytomegalovirus DNA from infected breast milk appeared in the saliva of infants at 4 months of age, peaked 4-10 months after birth, and thereafter decreased or became undetectable (122) .

To sum up, a great proportion of salivary herpeviruses are shed from periodontal disease sites. As periodontal treatment can markedly reduce subgingival (73, 162) and salivary (82, 162) herpesvirus DNA counts, the establishment of a healthy periodontium may diminish the risk of intersubject herpesvirus transmission and of herpesvirus-related diseases. The close relationship between some herpesvirus species and periodontitis also argues for examining the potential of using herpesvirus salivary counts to indicate periodontal disease risk.

Infectious mononucleosis is caused by a primary infection with Epstein-Barr virus, and predominantly by Epstein-Barr virus type 1 (44) . Approximately 10% of mononucleosis-like disease is attributable to cytomegalovirus. The Epstein-Barr virus infects B-lymphocytes, which gives rise to the strong T-lymphocyte response that is characteristic of mononucleosis. Clinical signs of infectious mononucleosis are long-lasting fever, tonsillopharyngitis, lymphadenopathy, fatigue, and occasionally splenomegaly, liver involvement and pericarditis (199) . Oral signs are sore throat, palatal petechiae and enlarged lymph nodes in the throat and neck. The Epstein-Barr virus is transmitted through direct contact with virus-infected saliva, such as with kissing, and rarely via the air or blood. Young adults with a primary Epstein-Barr virus infection can rapidly clear the virus from the blood but not from the oropharynx (19) . However, individuals who are already infected with the Epstein-Barr virus (and cytomegalovirus) are not at risk for infectious mononucleosis, even when exposed to individuals with the disease.

Other diseases have been linked to salivary herpesviruses (Table 2) . Relationships have been found between BellÕs palsy (idiopathic peripheral facial paralysis) and an active herpes simplex virus-1 infection (3), between oropharyngeal lesions of the Ramsay Hunt syndrome and varicella-zoster virus (62, 144) , and between HIV infection and Epstein-Barr virus (74) and herpesvirus-8 (33) . Young children with exanthem subitum acquired the disease from their mothers who excreted the causative herpesvirus-6 into saliva (121) .

Human immunodeficiency virus infection is a potent herpesvirus re-activator, as demonstrated by a strong correlation between decreasing CD4 cell counts in HIV-infected patients and increasing rates of herpesvirus re-activation (34) . An HIV infection is frequently associated with the salivary presence of several re-activated herpesvirus species (Table 3 ). In the mode of synergism, herpesviruses (196) , P. gingivalis (83) and other periodontal bacteria (81) may resides in the buccal epithelial cells of HIV-infected subjects (134) , and can be transmitted horizontally from an HIV-infected mother to her young children (66, 111) but, despite the possibility of in utero infection (28) , vertical transmission of the virus is uncommon in infants born to an HIV-positive mother (111) . Herpesvirus-8 can also be transmitted by oral sex. Deep kissing was an independent risk factor (odds ratio of 5.4) for transmitting herpesvirus-8 from HIV-seropositive men to HIV-seronegative men, (134) . Taken together, the saliva of HIV-infected persons is a risk factor for the transmission of several virulent herpesvirus species, and patients receiving HAART cannot be assumed to be less infectious for herpesviruses than individuals not receiving HAART. Oral mucositis is an important complication of immunosuppressive radiotherapy, chemotherapy and radiochemotherapy (163) . The mucositis may involve herpesviruses, bacteria and yeasts, individually or in combination (163) . Bone marrow and stem cell transplantation has been associated with oral cytomegalovirus re-activation (148) , and renal allograft transplantation has been associated with oral cytomegalovirus re-activation (128) and oral herpesvirus-8 re-activation (9) . Also, although not studied in the oral cavity, corticosteroid immunosuppressive treatment may trigger the re-activation of herpesvirus species (14, 49, 164, 211) .

Viruses of serious medical diseases can be present in saliva at levels sufficient to be transmitted from person to person through close (within 2 meter) or intimate contact (Table 4) . Moreover, viral pathogens can be transferred to humans by animals or insects (Table 4) , or from humans to animals and then later transferred back into humans (56) . Viruses in saliva may infect the periodontium and exacerbate periodontal disease.

Human papillomaviruses are frequent inhabitants of the oral mucosa of normal adults (188) and have been found to occur in the saliva of 25% of healthy individuals (154) . Papillomavirus DNA was detected in 26% of gingival biopsies from periodontitis lesions (80) , and in as many as 92% of biopsies of cyclosporin-induced gingival hyperplasia from renal transplant recipients (30) . Papillomavirus type 16 is associated with a subset of oropharyngeal squamous cell carcinomas (171) , and quantitative measurement of salivary papillomavirus-16 DNA has shown promise for early detection of recurrence of head and neck squamous cell carcinoma (39) , and for surveillance of premalignant oral disorders (183) . Papillomavirus DNA was identified in the saliva of 10% (5) and 41% (154) of oral squamous cell carcinoma patients, and in the saliva of 35% of HIV-positive individuals (5) . A spouse had a 10-fold higher risk of acquiring a persistent oral papillomavirus infection if the other spouse had a persistent oral papillomavirus infection, a finding that is consistent with the oral route of papillomavirus transmission (149) . The likelihood of contracting an oral papillomavirus infection increases with increasing numbers of open-mouthed kissing partners and oral sex partners (52) , and papillomavirus-positive oral tumors are strongly linked to multiple oral sex partners (53) . The current prophylactic papillomavirus-6 ⁄ 11 ⁄ 16 ⁄ 18 vaccine, designed to prevent cervical cancer, generates an oral antibody response and will probably also reduce the incidence of papillomavirus-related diseases of the mouth (153) .

Human immunodeficiency virus is transmitted through sexual contact or by contaminated needles and blood, but only exceptionally rarely through saliva. A recent study provided compelling evidence that three infants acquired HIV ⁄ acquired immunedeficiency syndrome (AIDS) after receiving prechewed food (64) . The HIV-infected caregivers had bleeding gingiva while masticating food for the infants, and thus blood, not saliva, was probably the vehicle for HIV transmission in the three cases reported. In fact, submandibular ⁄ sublingual gland secretions contain mucin molecules that normally will prevent infection and transmission of HIV by the oral route (75) . Thus, as is the case for HIV and for other viruses, saliva is not merely serving as a passive transport medium, but can significantly affect the efficiency of pathogen transmission and the course of disease. Fortunately, anti-retroviral drugs have turned HIV infection into a manageable condition with a greatly reduced morbidity.

The proviral DNA of human T-cell lymphotropic virus type I, an oncogenic retrovirus, was detected in whole saliva of 77% of Mashhadi-born Iranian Jews with viral myelopathy (4) . This finding may suggest the potential for a salivary transmission of human T-cell lymphotropic virus type I and may possibly help to explain the relatively high rate of myelopathy in the elderly Mashhadi-Jewish population. The human T-cell lymphotropic virus type I can also be present in the saliva of asymptomatic carriers of the virus (4).

Hepatitis viruses (designated A through G) cause the majority of cases of acute and chronic hepatitis and liver damage worldwide. Hepatitis ranges pathologically from asymptomatic or mild disease to fulminant liver failure. Hepatitis A and hepatitis E viruses are transmitted by water contaminated with feces (fecal-oral route), produce acute infections and do not induce a chronic carrier state. A high incidence of hepatitis A and hepatitis E viral infections occurs in countries with poor sanitary standards. Hepatitis A virus RNA was detected in the saliva of 50% of patients during a hepatitis A outbreak (11) . A study in cynomolgus monkeys found that the tonsils and salivary glands acted as extrahepatic sites for early hepatitis A virus replication and constituted potential sources for saliva-transmitted infection (10) . Hepatitis B virus is parenterally transmitted and is frequently associated with chronic viremia. Hepatitis B virus DNA was found at concentrations of >10 5 copies ⁄ ml of saliva in 15% of patients with chronic hepatitis B (195) . That concentration may be sufficient to permit horizontal transmission of the virus, and perhaps some of the 20% of hepatitis B patients, who contract the disease without a known origin of the infection, may have acquired the hepatitis B virus by salivary transfer (195) . Chronic hepatitis C affects more than 170 million people worldwide, and the hepatitis C virus persists in 80% of the infected individuals, where it can give rise to liver inflammation, liver cirrhosis and hepatocellular carcinoma (135) , and perhaps to periodontitis, SjögrenÕs syndrome, oral lichen planus and sialadenitis (171) . Hepatitis C virus RNA was present in the saliva of 39-72% of subjects with chronic hepatitis (113, 133, 144, 204) , and was detected in 59% of gingival crevice fluid specimens from viremic patients (113) . The gingival crevice fluid was identified as the major source for salivary hepatitis C virus (113) . Twenty-seven percent of spouses of individuals with chronic hepatitis C revealed antibodies against Three HIV-positive infants (9-39 months old) were fed with premasticated food: two children by an HIV-infected mother with oral bleeding; and one child by an HIV-positive aunt (the mother was HIV-negative)

The infants were not breastfed and perinatal transmission of HIV was previously ruled out. Viruses of respiratory diseases are usually transmitted through coughs or sneezes that release large quantities of high-velocity droplets into the air, and the risk of cross-infection through salivary exchange is comparatively small. Children with respiratory disease revealed respiratory viruses (respiratory syncytial virus, influenza virus, parainfluenza virus, adenovirus) in 74% of oral specimens and in 77% of nasopharyngeal specimens (150) , and respiratory syncytial virus RNA in 76% of salivary samples (201) . Although present in saliva (150) , influenza virions may not be infectious because of the anti-influenza virus activity of salivary glycoproteins (207) . The severe acute respiratory syndrome (SARS) corona virus, the etiological agent of a highly lethal type of pneumonia, was detected in the saliva of each SARS patient studied, and was present in quantities up to 6.38 · 10 8 copies ⁄ ml (203) . A dental clinic located in a SARS-affected region must institute strict infectioncontrol measures in order to prevent cross-infection with the SARS virus (158) . Measles and rubella are rare diseases in vaccinated populations, but still occur in unvaccinated persons, commonly in developing countries. The causative viruses are spread through respiration, and can be present in saliva in high numbers during disease outbreaks (2, 126) . Ebola is a viral hemorrhagic febrile disease that can cause death in 2-5 days. Ebola virus was detected in the saliva of all 24 patients with a positive Ebola diagnosis (60) , and transmission of the Ebola virus through oral exposure has been demonstrated in nonhuman primates (85) . Merkel cell carcinoma is a highly lethal neuroepithelial tumor of the skin, and at least some Merkel cell carcinomas appear to be caused by a newly discovered polyomavirus. The Merkel cell polyomavirus is found in relatively high numbers in respiratory secretions and in the saliva of patients with Merkel cell carcinoma (107) , possibly exposing close individuals to a risk of infection.

Humans can contract serious viral diseases through zoonotic transfer ( Table 4 ). The rabies virus resides in dogs, foxes, cats, vampire bats and other animals, and is transmitted to humans through the bite of a rabid animal. Rabies virus RNA was identified in 88% of salivary samples from humans with an ante-mortem diagnosis of rabies (125) . Hantaviruses cause hemorrhagic fever with renal syndrome (in Eurasia) or cardiopulmonary syndrome (in the Americas), and rodent-to-human transmission usually occurs by the inhalation of aerozolized viruscontaminated rodent excreta. However, the Andes hantavirus infects the secretory cells of human salivary glands and can be detected in the saliva after onset of disease symptoms, suggesting that the virus also may be transmitted by human-to-human contact (77, 137) . Nipah virus, a paramyxovirus with a reservoir in fruit bats, can cause respiratory disease and severe encephalitis in humans. A study in Bangladesh concluded that 50% of Nipah patients acquired the virus through salivary transmission from person to person (108) .

Some viral diseases in tropical and subtropical parts of the world are acquired through insect bites. Dengue fever, caused by a mosquito-borne flavivirus, afflicts more than 100 million subjects annually. Patients with dengue fever revealed the dengue virus genome in saliva during the acute phase of the infection (120, 141) . Crimean-Congo hemorrhagic fever virus is transmitted by tick bites or by contact with the blood or tissues of infected patients and livestock. The genome of the Crimean-Congo hemorrhagic fever virus was detected in the saliva of five of six patients with confirmed disease (24) , increasing the likelihood of a human-to-human transmission.

Our knowledge of infectious agents in the human oral cavity has expanded greatly in recent years, mainly as a result of molecular techniques that can identify and quantify oral bacteria and viruses with great accuracy. Several oral and medical pathogens occur in saliva at levels that are sufficient to infect close individuals, and contact with saliva may be a more important mode of pathogen transmission than previously realized. The rising awareness of the infectious potential of saliva raises challenging questions about the safety of intimate (ÔdeepÕ or Ôopen mouthedÕ) kissing contact. The risk of cross-infection by salivary transfer may not be trivial and needs to be studied further. The type of pathogenic agents that can retain infectiousness in saliva and that are efficiently spread by saliva needs to be identified and controlled.

Current knowledge of the oral ecology may form the basis for more efficient treatments of bacterial and viral infections around teeth and of the oral mucosa. The finding of major periodontopathic bacteria in nondental sites, especially on the tongue, argues for antimicrobial treatment of the entire oral cavity, not only of dental biofilms (151) . Virtually all periodontal patients can benefit from treatment with antiseptics active against bacteria and herpesviruses, such as sodium hypochlorite and povidone-iodine (169) , and selective patients may benefit from treatment with systemic antibacterial (170) and antiviral (182) medications. Effective periodontal therapy includes professional administration of a battery of well-tolerated antimicrobial agents, each exhibiting high activity against periodontal pathogens and delivered in ways that simultaneously affect pathogens residing in different oral ecological niches [i.e. chlorhexidine or dilute sodium hypochlorite (bleach) for general oral disinfection, povidone-iodine for subgingival irrigation, and systemic antibiotics to reach microorganisms within periodontal tissue and in difficult-to-reach subgingival and extra-dental sites]. The follow-up maintenance program should have a strong anti-infective emphasis, and may include patient-administered subgingival irrigation with dilute sodium hypochlorite and oral rinsing with sodium hypochlorite or chlorhexidine two to three times per week. Full-mouth disinfection may also reduce the risk for cross-infection of oral pathogens between individuals in close contact.

However, in the final analysis, most chronic infectious diseases such as periodontitis and dental caries will be defeated on a mass-scale only by employing effective, safe and inexpensive vaccines. Vaccines may be prophylactic, therapeutic, or a combination of both. Perhaps a vaccine that reduces the infectious load without actually eliminating the infectious agent is sufficient to arrest or prevent dental and other oral diseases. Vaccination studies on herpesviruses and some oral bacteria have yielded occasional successes in animal models, but a number of human trials have failed to show adequate efficacy. Vaccine development has been difficult because of the heterogeneity, variability and poor immunogenicity of the outer surface components of many infectious agents. Nonetheless, despite the setbacks, vaccines against herpes zoster virus and oncogenic papillomaviruses were recently approved for clinical use by the US Food and Drug Administration. Effective and safe vaccines against oral infectious diseases constitute one of the most important needs in dentistry.

Bacteria of dental caries in primary and permanent teeth in children and young adults

Confirmation of rubella within 4 days of rash onset: comparison of rubella virus RNA detection in oral fluid with immunoglobulin M detection in serum or oral fluid

Secretion and dynamics of herpes simplex virus in tears and saliva of patients with BellÕs palsy

Detection of proviral human T-cell lymphotrophic virus type I DNA in mouthwash samples of HAM ⁄ TSP patients and HTLV-I carriers

HPV detection rate in saliva may depend on the immune system efficiency

Hepatitis C virus infection in spouses of patients with type C chronic liver disease

Prevalence and risk factors for intrafamilial transmission of hepatitis C virus in Karachi, Pakistan

Comparative detection frequency of 6 putative periodontal pathogens in Sudanese and Norwegian adult periodontitis patients

Extensive oral shedding of human herpesvirus 8 in a renal allograft recipient

Experimental hepatitis A virus (HAV) infection in cynomolgus monkeys (Macaca fascicularis): evidence of active extrahepatic site of HAV replication

Comparison between serum and saliva for the detection of hepatitis A virus RNA

Comparison of the microbiologic features of chronic and aggressive periodontitis

Comparison of the clinical features of chronic and aggressive periodontitis

Cytomegalovirus disease during severe drug eruptions: report of 2 cases and retrospective study of 18 patients with drug-induced hypersensitivity syndrome

Polymerase chain reaction detection of 8 putative periodontal pathogens in subgingival plaque of gingivitis and advanced periodontitis lesions

Oral ecology and person-to-person transmission of Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis

Likelihood of transmitting Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis in families with periodontitis

Legionella contamination of dental-unit waters

A prospective clinical study of Epstein-Barr virus and host interactions during acute infectious mononucleosis

Gonococcal tonsillar infectiona case report and literature review

Parasitic infections affecting the oral cavity

Adjunctive chemotherapeutic suppression of mutans streptococci in the setting of severe early childhood caries: an exploratory study

Mouth-to-mouth transmission of the bacterium Streptococcus mutans between mother and child

Detection of Crimean-Congo hemorrhagic fever virus genome in saliva and urine

Human polyoma viruses and disease with emphasis on clinical BK and JC

Distribution and hydrolytic enzyme characteristics of Candida albicans strains isolated from diabetic patients and their non-diabetic consorts

Profiling of inflammatory cytokines produced by gingival fibroblasts after human cytomegalovirus infection

Postnatal human herpesvirus 8 and human immunodeficiency virus type 1 infection in mothers and infants from Zambia

Varicella zoster virus: natural history and current therapies of varicella and herpes zoster. Herpes

Human papillomavirus infection in cyclosporin-induced gingival overgrowth in renal allograft recipients

Spread of hepatitis C virus infection within families. Investigators of an Italian multicenter group

Frequent and asymptomatic oropharyngeal shedding of human herpesvirus 8 among immunocompetent men

HIV infection and human herpesvirus-8 oral shedding among men who have sex with men

The interaction between herpes simplex virus and human immunodeficiency virus

Guidelines for preventing the transmission of Mycobacterium tuberculosis in health-care facilities. Notice of final revisions to the ''Guidelines for Preventing the Transmission of Mycobacterium tuberculosis in health-care facilities

Transmission of primary and secondary syphilis by oral sex -Chicago

Herpes simplex virus infection in patients affected by dental caries

Presence of HPV DNA in convalescent salivary rinses is an adverse prognostic marker in head and neck squamous cell carcinoma

Tuberculosis epidemiology, diagnosis and infection control recommendations for dental settings: an update on the Centers for Disease Control and Prevention guidelines

Heritability of oral microbial species in caries-active and caries-free twins

Microbial risk indicators of early childhood caries

Detection of periodontal pathogens in oral mucous membranes of edentulous individuals

A cohort study among university students: identification of risk factors for Epstein-Barr virus seroconversion and infectious mononucleosis

Bacterial infections of the oral mucosa

Multiple types of the bacterium Streptococcus mutans in the human mouth and their intrafamily transmission

Salivary levels of Epstein-Barr virus DNA correlate with subgingival levels, not severity of periodontitis

Cytomegalovirus retinitis following intravitreal injection of triamcinolone: report of two cases

Oral Helicobacter pylori: can we stomach it?

Human herpesviruses 6 and 7 in salivary glands and shedding in saliva of healthy and human immunodeficiency virus positive individuals

Oral sexual behaviors associated with prevalent oral human papillomavirus infection

Case-control study of human papillomavirus and oropharyngeal cancer

PCR method is essential for detecting Mycobacterium tuberculosis in oral cavity samples

Bacterial colonization of oral implants from nondental sources

The significant but understudied impact of pathogen transmission from humans to animals

Investigation of saliva, faeces, urine or semen samples for the presence of GBV-C RNA

The role of household contacts in the transmission of group A streptococci

Salivary cytomegalovirus (CMV) shedding, glycoprotein B genotype distribution, and CMV disease in human immunodeficiency virus-seropositive patients

Detection of Ebola virus in oral fluid specimens during outbreaks of Ebola virus hemorrhagic fever in the Republic of Congo

Ecology of Haemophilus influenzae and Haemophilus parainfluenzae in sputum and saliva and effects of antibiotics on their distribution in patients with lower respiratory tract infections

Varicellazoster virus DNA level and facial paralysis in Ramsay Hunt syndrome

Quantitation of varicella-zoster virus DNA in patients with Ramsay Hunt syndrome and zoster sine herpete

Practice of feeding premasticated food to infants: a potential risk factor for HIV transmission

Detection of human Betaherpesvirinae in saliva and urine from immunocompromised and immunocompetent subjects

Human herpesvirus 8 primary infection occurs during childhood in Cameroon, Central Africa

Saliva as a diagnostic tool for periodontal disease: current state and future directions

Global burden and epidemiology of tuberculosis

Epstein-Barr virus reactivation and upper-respiratory illness in elite swimmers

Oral fluid, a substitute for serum to monitor measles IgG antibody?

Herpes viruses in periodontal compromised sites: comparison between HIV-positive and -negative patients

DentistsÕ attitudes toward chairside screening for medical conditions

Detection of herpetic viruses in gingival crevicular fluid of patients suffering from periodontal diseases: prevalence and effect of treatment

Oral mucosal reactivation rates of herpesviruses among HIV-1 seropositive persons

The role of crude human saliva and purified salivary MUC5B and MUC7 mucins in the inhibition of human immunodeficiency virus type 1 in an inhibition assay

The dynamics of EBV shedding implicate a central role for epithelial cells in amplifying viral output

Sensitivity of Andes hantavirus to antiviral effect of human saliva

Comparative biology of chronic and aggressive periodontitis vs. peri-implantitis

Subgingival microbial profiles in chronic periodontitis patients from Chile, Colombia and Spain

Marginal periodontium as a potential reservoir of human papillomavirus in oral mucosa

Oral bacteria induce a differential activation of HIV-1 promoter in T cells, macrophages, and dendritic cells

Detection of Epstein-Barr virus in saliva by real-time PCR

Reactivation of latent HIV-1 infection by the periodontopathic bacterium Porphyromonas gingivalis involves histone modification

Detection of Epstein-Barr virus and human cytomegalovirus in blood and oral samples: comparison of three sampling methods

Lethal experimental infection of rhesus monkeys with Ebola-Zaire (Mayinga) virus by the oral and conjunctival route of exposure

BK virus has tropism for human salivary gland cells in vitro: implications for transmission

The diagnostic applications of saliva -a review

Haemophili and related bacteria in the human oral cavity

Acute bacterial meningitis in infants and children

Oral herpes simplex virus type 2 reactivation in HIV-positive and -negative men

Preventive measures in mothers influence the establishment of the bacterium Streptococcus mutans in their infants

Longitudinal study of intrafamilial mutans streptococci ribotypes

Caries risk. A practical guide for assessment and control

Specific microorganisms and dental caries in children

Root surface caries: a problem for periodontally compromised patients

Genotyping to distinguish microbial pathogenicity in periodontitis

An investigation into the use of restriction endonuclease analysis for the study of transmission of mutans streptococci

Detection of KaposiÕs sarcoma-associated herpesvirus in oral and genital secretions of Zimbabwean women

Demonstration of mother-to-child transmission of Streptococcus mutans using multilocus sequence typing

Detection of hepatitis B virus and Mycobacterium tuberculosis in Korean dental patients

Asymptomatically shed recombinant herpes simplex virus type 1 strains detected in saliva

Gonorrhea: update. Oral Surg Oral Med Oral Pathol Oral Radiol Endod

Cytokine responses against periodontal infection: protective and destructive roles

Hepatitis C-contamination of toothbrushes: myth or reality?

Topical antimicrobial therapy in the prevention of early childhood caries

Quantitative detection of Merkel cell virus in human tissues and possible mode of transmission

Transmission of human infection with Nipah virus

Epstein-Barr virus (EBV) DNA in saliva and EBV serology of HIV-1-infected persons with and without hairy leukoplakia

Shedding of cytomegalovirus and herpesviruses 6, 7 and 8 in saliva of human immunodeficiency virus type 1-infected patients and healthy controls

Evidence for horizontal and not vertical transmission of human herpesvirus 8 in children born to human immunodeficiency virus-infected mothers

Rapidly cleared episodes of herpes simplex virus reactivation in immunocompetent adults

Detection of hepatitis C virus RNA from gingival crevicular fluid and its relation to virus presence in saliva

Respiratory tract infections and pneumonia

Stress-induced subclinical reactivation of varicella zoster virus in astronauts

Epstein-Barr virus reactivation associated with diminished cell-mediated immunity in antarctic expeditioners

Dental caries and its relationship to bacterial infection, hypoplasia, diet, and oral hygiene in 6-to 36-month-old children

Effect of prophylactic valacyclovir on the presence of human herpesvirus DNA in saliva of healthy individuals after dental treatment

High prevalence of multiple human herpesviruses in saliva from human immunodeficiency virus-infected persons in the era of highly active antiretroviral therapy

Confirmation of dengue virus infection by detection of dengue virus type 1 genome in urine and saliva but not in plasma

Molecular epidemiological studies on human herpesvirus 6 in families

Quantitative detection of HCMV-DNA in saliva from infants and breast milk on real-time polymerase chain reaction

Diagnosis of Legionella infection

Nontypeable Haemophilus influenzae as a pathogen in children

Ante mortem diagnosis of human rabies using saliva samples: comparison of real time and conventional RT-PCR techniques

Measles virus strains circulating in Ethiopia in 1998-1999: molecular characterisation using oral fluid samples and identification of a new genotype

Association between involuntary smoking and salivary markers related to periodontitis: a 2-year longitudinal study

Human cytomegalovirus-associated periodontitis in renal transplant patients

Saliva and meningococcal transmission

Detection of multiple pathogenic species in saliva is associated with periodontal infection in adults

The microbiota on different oral surfaces in healthy children

Molecular microbial diagnosis

Detection of hepatitis C virus-RNA in saliva from chronically HCV-infected patients

Mucosal shedding of human herpesvirus 8 in men

Pathophysiology of hepatitis C virus infection and related liver disease

Incidence of Epstein-Barr virus in astronaut saliva during spaceflight

Hantavirus RNA in saliva from patients with hemorrhagic fever with renal syndrome

Epstein-Barr virus shedding by astronauts during space flight

Clinical evaluation of a quantitative real time polymerase chain reaction assay for diagnosis of primary Epstein-Barr virus infection in children

Incidence of viable mycobacteria tuberculosis on alginate impressions in patients with positive sputum

Detection of dengue virus in saliva and urine by real time RT-PCR

Bacterial profiles of root caries in elderly patients

Infections of the esophagus and the stomach

Reliable detection and quantitation of viral nucleic acids in oral fluid: liquid phase-based sample collection in conjunction with automated and standardized molecular assays

Staphylococci in human periodontal diseases

Giannobile WV. Identification of pathogen and host-response markers correlated with periodontal disease

Quantitation of hepatitis C virus RNA in saliva and serum of patients coinfected with HCV and human immunodeficiency virus

Quantitative determination of CMV-DNA in saliva of patients with bone marrow and stem cell transplantation using TaqMan-PCR

Natural history of oral human papillomasvirus infections in female and male partners: a prospective Finnish HPV Family Study

Use of throat swab or saliva specimens for detection of respiratory viruses in children

The use of PVP-iodine as an adjunct to nonsurgical treatment of chronic periodontitis

Quantitative studies on the salivary flora

Antibody responses in oral fluid after administration of prophylactic human papillomavirus vaccines

Human papillomavirus in saliva of patients with oral squamous cell carcinoma

Periodontitis lesions are the main source of salivary cytomegalovirus

Oral viral infections of children

Oral mucosal fungal infections

Severe acute respiratory syndrome and dentistry: a retrospective view

Epstein-Barr virus specific salivary antibodies as related to stress caused by examinations

Human cytomegalovirus salivary antibodies as related to stress

Academic stress, immunological reaction, and academic performance among students of nursing and physiotherapy

Periodontitis lesions are a source of salivary cytomegalovirus and Epstein-Barr virus

Oral mucositis: a challenging complication of radiotherapy, chemotherapy, and radiochemotherapy: part 1, pathogenesis and prophylaxis of mucositis

Reactivation of human herpesvirus (HHV) family members other than HHV-6 in drug-induced hypersensitivity syndrome

Microbial testing in periodontics: value, limitations and future directions

Investigating the concurrent presence of HCV in serum, oral fluid and urine samples from chronic HCV patients in Faisalabad

Early childhood stress is associated with elevated antibody levels to herpes simplex virus type 1

The re-emergence of syphilis in the United Kingdom: the new epidemic phases

Selection of antimicrobial agents in periodontal therapy

Systemic antibiotics in periodontics

Oral viral infections of adults

Herpesviral-bacterial interactions in periodontal diseases

Human viruses in periodontitis

Age and sex relationships of superinfecting microorganisms in periodontitis patients

Subgingival microflora of advanced periodontitis in the Dominican Republic

Actinobacillus actinomycetemcomitans in human periodontal disease: a crosssectional microbiological investigation

Genetic and environmental risk factors for chronic periodontitis and aggressive periodontitis

Oral herpetic infections (HSV 1-8)

Chronic herpesvirus reactivation occurs in aging

Relationship between Porphyromonas gingivalis, Epstein-Barr virus infection and reactivation in periodontitis

Patient with severe periodontitis and subgingival Epstein-Barr virus treated with antiviral therapy

Progressive increase of human papillomavirus carriage rates in potentially malignant and malignant oral disorders with increasing malignant potential

Risk of exposure to Legionella in dental practice

A longitudinal study of Lancefield group A streptococcus acquisitions by a group of young Dunedin schoolchildren

Similarity of the oral microbiota of pre-school children with that of their caregivers in a population-based study

Cytokine regulation of immune responses to Porphyromonas gingivalis

High prevalence of human papillomaviruses in the normal oral cavity of adults

Within-subject variability in repeated measures of salivary analytes in healthy adults

Risk and protective factors for meningococcal disease in adolescents: matched cohort study

Cytokine secretion and latent herpes virus reactivation with 28 days of horizontal hypokinesia

Risk indicators for harboring periodontal pathogens

The utility of whole saliva to detect the oral presence of periodontopathic bacteria

Do periodontopathogens disappear after full-mouth tooth extraction?

Paired, quantitative measurements of hepatitis B virus DNA in saliva, urine and serum of chronic hepatitis B patients

Herpes simplex virus and HIV-1: deciphering viral synergy

Transmission of periodontal bacteria and models of infection

Syphilis epidemiology in Sweden: re-emergence since 2000 primarily due to spread among men who have sex with men

Infectious mononucleosis and Epstein-Barr virus

Occurrence of Aggregatibacter actinomycetemcomitans in Brazilian indians from Umutina Reservation, Mato Grosso, Brazil

Excretion patterns of human metapneumovirus and respiratory syncytial virus among young children

Multiple Epstein-Barr virus infections in healthy individuals

Detection of SARS-associated coronavirus in throat wash and saliva in early diagnosis

High serum hepatitis C virus (HCV) RNA load predicts the presence of HCV RNA in saliva from individuals with chronic and acute HCV infection

Low prevalence of varicella zoster virus and herpes simplex virus type 2 in saliva from human immunodeficiency virus-infected persons in the era of highly active antiretroviral therapy. Oral Surg Oral Med Oral Pathol Oral Radiol Endod

Post-marketing Surveillance Team. Post-marketing surveillance of OraQuick whole blood and oral fluid rapid HIV testing

Multiple components contribute to ability of saliva to inhibit influenza viruses

Haemophilus influenzae type B (HiB)

Salivary diagnostics powered by nanotechnologies, proteomics and genomics

Candida biofilms and oral candidosis: treatment and prevention

Disseminated varicella infection in a child receiving short-term steroids for asthma

TaqMan real-time quantification of Epstein-Barr virus in severe early childhood caries

Actinobacillus actinomycetemcomitans in human periodontal disease. Prevalence in patient groups and distribution of biotypes and serotypes within families

The clinical value of salivary biomarkers for periodontal disease

Nonvenereal transmission of syphilis in infancy by mouth-to-mouth transfer of prechewed food

Prevalence of potential bacterial respiratory pathogens in the oral cavity of hospitalised individuals