key: cord-0966406-w2xaxhkj
authors: Limeres Posse, Jacobo; Diz Dios, Pedro; Scully, Crispian
title: Viral Diseases Transmissible by Kissing
date: 2017-07-31
journal: Saliva Protection and Transmissible Diseases
DOI: 10.1016/b978-0-12-813681-2.00004-4
sha: dc845f9fdcd05760f704f4250fae42c9f29773b0
doc_id: 966406
cord_uid: w2xaxhkj

Viral infections can be transmitted by various routes. At one extreme, airborne or droplet viral infections (e.g., varicella zoster, ebola) are highly contagious. Most viruses can be spread by touching surfaces contaminated by the virus and then touching the mouth or eyes. Mass gatherings, clinical, and chronic care facilities may be hotspots for virus spread when transmission is via aerosols, droplets, or fomites (contaminated surfaces). Environmental factors which are often important for virus survival may include the ambient humidity, temperature, and pH of the environment they are in, so many viruses survive only a few hours in the environment and are often readily inactivated by common hygiene techniques, such as using soap and water, and some detergents, disinfectants, and antiseptics. Sexually transmitted viral infections, such as herpes simplex, are often transmitted by close mucosal contacts.

Viral infections can be transmitted by various routes. At one extreme, airborne or droplet viral infections (e.g., varicella zoster, ebola) are highly contagious. Most viruses can be spread by touching surfaces contaminated by the virus and then touching the mouth or eyes. Mass gatherings, 1 clinical and chronic care facilities may be hotspots for virus spread when transmission is via aerosols, droplets, or fomites (contaminated surfaces). Environmental factors which are often important for virus survival may include the ambient humidity, temperature, and pH of the environment they are in, so many viruses survive only a few hours in the environment and are often readily inactivated by common hygiene techniques, using soap and water, and some detergents, disinfectants, and antiseptics. Sexually transmitted viral infections, such as herpes simplex, are often transmitted by close mucosal contacts.

Virus infections may be seen especially in immunocompromised people and can be life-changing or even lethal. Some viruses, such as herpes simplex viruses, can also cause obvious oral lesions. Some mainly affect animals but can transmit to man (zoonoses), and viruses may mutate.

Various viruses habitually colonize the human mouth and may be present in saliva in quantities sufficient to infect other individuals. 2 Even in instances where ductal saliva might contain no bugs, whole saliva may contain infectious agents from other sites. For example, people who carry respiratory viruses often also have the virus in their saliva 3 as may some who have viral gastroenteritis, and where there is oral bleeding, blood-borne viruses may be present. Humans can be reservoirs of viruses; asymptomatic shedding before clinical disease or where the infection is subclinical (undiagnosed or symptomless) is a major factor in their spread. Host innate or acquired immunity, and saliva can be protective against many infections which may be increased in people It may be difficult or impossible to differentiate saliva transmission from that by body fluids or fomites introduced into the mouth, respiratory droplets, aerosols, or other routes. Reliable studies are needed, designed specifically to clarify which diseases can be transmitted in humans by saliva in order to develop appropriate strategies to control person-to-person spread of infection by this route.

In an ideal world, the implication of viruses in diseases is best achieved using a modification of Koch's postulates 5 as follows:

1. A nucleic acid sequence belonging to a putative pathogen should be present in most cases of an infectious disease. Microbial nucleic acids should be found preferentially in those organs or gross anatomic sites known to be diseased, and not in those organs that lack pathology. 2. Fewer, or no, copy numbers of pathogen-associated nucleic acid sequences should occur in hosts or tissues without disease. 3. With resolution of disease, the copy number of pathogen-associated nucleic acid sequences should decrease or become undetectable. With clinical relapse, the opposite should occur. 4. When sequence detection predates disease, or sequence copy number correlates with severity of disease or pathology, the sequenceÀdisease association is more likely to be a causal relationship. 5. The nature of the microorganism inferred from the available sequence should be consistent with the known biological characteristics of that group of organisms. 6. Tissue-sequence correlates should be sought at the cellular level: efforts should be made to demonstrate specific in situ hybridization of microbial sequence to areas of tissue pathology and to visible infection or to areas where microorganisms are presumed to be located. 7. These sequence-based forms of evidence for microbial causation should be reproducible.

Such data for viruses in saliva are sparse so in the meantime epidemiological data and the presence of virus in saliva, nucleic acid, or antigens of microorganism have to be relied upon as circumstantial evidence. Most evidence for the presence of viruses in saliva comes from salivary culture, or serological responses, but nucleic acid amplification techniques such as Reverse Transcription Polymerase Chain Reaction (RT-PCR) can now be used and have detected many previously undetectable virus infections.

Some of the implications of viruses in oral healthcare are reviewed elsewhere 2,6 and antiviral activities of saliva have been reviewed elsewhere 7,8 but this is an exploding field 9 so here we review viruses classification (Table 4 .1) and the main human viruses detectable in saliva (Table 4 .2).

At least 69 HAdV genotypes are recognized. HAdV are a common cause mainly of respiratory infections and, typically in men who have sex with men, a cause of urethritis and conjunctivitis. 50 Respiratory infection caused by HAdV in immunocompetent people is typically caused by HAdV-3, mild and self-limited. However, more recently HAdV-55 in particular has been found to cause severe communityacquired pneumonia and acute respiratory distress syndrome in immunocompetent adults, 51 mainly from China. HAdV pneumonia typically is found in neonates, immunocompromised people, and school or military camp populations. HAdV infections in immunocompromised individuals can be severe and life-threatening. The past decade has also seen the emergence in resource-rich countries of several other new viruses-often in traveling people-including HAdV-14p1. 52 HAdV can be found in saliva 3 and it is presumed that it can transmit infection though the main routes are through respiratory droplets or touching infected objects. Adenoviruses can survive a long time on objects and spread easily. Adenoviral shedding in saliva and feces has also been reported after p53 adenoviral gene therapy in some patients with esophageal cancer. 53 

CHIKV is a lavivirus transmitted mainly by Aedes aegypti and Aedes albopictus mosquitoes, causing fever and joint pains-similar to Dengue fever.

CHIKV can be present in saliva-confirmed by RT-PCR-and especially associated with oral/nasal hemorrhagic lesions in the viremic period. 10 Since more than 50% of CHIKV-infected people experience gingival bleeding, 54 this could also encourage infection transmission by kissing. Nonvector-based mother-to-child transmission of CHIKV has been reported. 55 The impact of potential CHIKV transmission via saliva needs to be more seriously assessed as it could be highly relevant, especially in immunocompromised patients. 56 

Coronaviruses are common viruses that can infect humans, and animals as diverse as bats and alpacas. There are a number of Human coronaviruses and they usually cause respiratory infections-mostly mild illnesses such as the common cold. However, several coronaviruses including the Middle East Respiratory Syndrome (MERS), especially seen in Saudi Arabia or visitors to that area, and Severe Acute Respiratory Syndrome (SARS), seen mainly in China and travelers from there, can cause more severe and sometimes life-threatening human infections. 52, 57 Coronaviruses that cause severe acute respiratory infections have .50% mortality rates in older and immunosuppressed people. 58 WIV1-CoV, a virus similar to SARS, could also be poised to cause epidemics. 59 People living with or caring for someone with a coronavirus infection are most at risk of developing the infection themselves.

Coronavirus transmission is mainly oralÀfecal and respiratory from small droplets of saliva or on fomites. OralÀurine and saliva transmission of MERS-CoV and SARS-CoV are also highly likely. 11, 12 Salivary cystatin D, a cysteine protease inhibitor, can inhibit replication of some coronaviruses. 60 Although evidence is sparse, SARS-CoV appears to be transmitted primarily through saliva droplets. Kissing could constitute a route for transmission.

DENV, transmitted by Aedes aegypti and Aedes albopictus mosquitoes, is the most important arthropod-borne flavivirus virus affecting humans and, although most infections are asymptomatic or cause only a mild fever, is capable of producing life-threatening hemorrhagic fever, shock syndrome, and systemic complications (e.g., encephalitis and hepatitis).

DENV has been isolated from human saliva and urine. 15,61À63 Human salivary transmission of dengue appears to be most unlikely.

EBOV is a highly lethal flavivirus infection, transmitted via bats and mammalian (monkey and ape) bush meat, causing hemorrhagic fever in humans. EBOV is shed in a wide variety of bodily fluids, including saliva, especially during the acute illness. 16 In a series of eight seriously ill people with Ebola disease, all oral fluid samples obtained 5À10 days after the onset of symptoms were positive for EBOV by RT-PCR. 64 Patients with detectable EBOV in saliva show a higher mortality which likely reflects increased virus shedding in patients with high viremia, an indicator of a poor prognosis. 65 Human-to-human transmission of EBOV is mainly through direct contact with the tissues, blood, secretions, or other body fluids, including saliva, of infected hosts. 66 Particular concern is the frequent presence of EBOV in saliva early in the course of Ebola disease. 16 Moreover, the person-to-person transmission risk increases-bearing in mind that 1À6% of infected individuals are asymptomatic or mildly symptomatic and the incubation period could last up to 21 days. 66 EBOV could be transmitted to others via saliva by sharing food and through intimate contact, although up to date the only documented cases of secondary transmission from recovered patients have been through sexual transmission. 67 No cases of Ebola transmission through deep kissing have been confirmed, although there must surely be a very high potential risk. In West Africa, the kissing of dead bodies is a traditional burial practice and can promote EBOV transmission. 68 

At least 70 serotypes of EV that can infect humans have been identified, including mainly, Coxsackieviruses (groups A and B), ECHOviruses, and polioviruses. Recently, the EV genus has been reclassificated in five species: Human enteroviruses A, B, C, and D and Poliovirus. Enteroviruses are implicated in a range of diseases, some of which may affect the mouth, including herpangina and hand-foot and mouth disease (HFMD) which are common and in which complications including pneumonia, meningitis, or encephalitis are seen but rarely. Animals may be affected by similar conditions (such as foot and mouth disease) but these only rarely transmit to man. 69 Enteroviruses have also been detected by PCR in saliva of asymptomatic children. 17 4.1.6.1 Herpangina Herpangina is typically caused by Coxsackieviruses A1 to 6, 8, 10, and 22. Other cases are caused by Coxsackie group B (strains 1À4), ECHOviruses, and other enteroviruses. Papulovesicular oropharyngeal lesions progress to ulcers and there is usually no rash. 70 Children with Coxsackie A2 infections mostly present with herpangina only, and have fewer central nervous system complications and a better outcome than those with Enterovirus 71 (EV71) infections. 71 4.1.6.2 Hand, Foot, and Mouth Disease Hand, Foot, and Mouth Disease (HFMD) is an exanthem on the hands and feet with associated fever and oral lesions. 70 HFMD, is typically a mild illness, caused mainly by Coxsackievirus A16 or EV71, 72 occasionally by Coxsackieviruses A4À7, A9, A10, B1ÀB3, or B5. Indeed, over 100 serotypes of enterovirus species may cause HFMD. 73 

HPeV types 1 and 2, were previously known as ECHOviruses 22 and 23, respectively, and can be associated with gastrointestinal, respiratory, or meningeal infections. 74 

Poliomyelitis, which is potentially lethal, is now extremely rare. Poliovirus was found in secretions from the upper respiratory tract and salivary swabs of household contacts of patients with virologically proven poliomyelitis. 75 Enteroviruses are highly contagious, spread mainly by oralÀoral and fecalÀoral routes, and typically affect children under 10 years old. It has been speculated that respiratory transmission of enteroviruses by droplets from the oral cavity may also explain the high secondary infection rate within households in some outbreaks. It has been suggested that the primary replication sites for enteroviruses could be in the oral cavity and/or gastrointestinal tract, with person-to-person transmission most commonly occurring via fecalÀoral and oralÀoral routes. 76 It has also been speculated that Coxsackie A16 virus is spread through direct contact with the saliva, mucus, or feces of an infected person, 77 but to date there is no evidence supporting transmission by kissing.

In experimental animal models, Coxsackie B virus was recovered in the whole saliva of rabbits as early as 2 minutes after injection of virus into an ear vein and it was suggested that virus might be transmitted by saliva of viremic animals without infection of the oropharyngeal tissues. 78 EV71 is an important public health problem in Asia as it spreads easily to close contacts 79 and may cause central nervous system involvement, serious illness, or death. 80 ECHOvirus 9 strains have been isolated from the saliva of a mother and daughter, both suffering acute salivary gland swelling, but with negative tests for mumps virus. 81 The evidence suggests that enteroviruses could be transmitted through saliva or via kissing.

Hantaviruses are zoonoses, rodents being the natural hosts.

Hantaviruses cause mainly hemorrhagic fever with renal syndrome (HFRS) and Hantavirus cardiopulmonary syndrome (HCPS) but there are other forms.

Transmission to humans is usually by inhalation of aerosolized viruscontaminated rodent excreta. Hantavirus RNA has also been detected in saliva of patients with HFRS 20 and from Puumala hantavirusÀinfected people.

Human-to-human transmission of hantaviruses appears rare, except in the case of Andes virus (ANDV). 82 It has been speculated that ANDV may be secreted into saliva, which might be a transmission route for ANDV between humans, 83 but there is no reliable evidence, and there is some evidence of salivary inhibitory factors. 84 Hantaan hantavirus appears to be inhibited by salivary mucin-though resistant to histatin 5, lysozyme, lactoferrin, and SLPI. 84 A prospective study of household contacts of patients with HCPS concluded that transmission risks increased in people partaking in deep kissing or sex with an infected individual. 85 The evidence suggests that hantaviruses could be transmitted through deep kissing.

There is a number of hepatotropic viruses, Hepatitis A, B, and C viruses, and others (e.g., EBV) which can cause hepatitis and may be present in saliva as well as blood and other body fluids, such as semen and gastric juices. Hepatitis A is typically transmitted predominantly by the oro-fecal route and causes a transient illness with hepatitis and no serious sequelae. Hepatitis B and C (formerly hepatitis non-A, non-B) virus infections however are transmitted mainly parenterally-blood transfusion and intravenous drug use being the most frequent risk factors, though sexual transmission may also occur. Illness may be prolonged with chronic carriage and can also cause complications such as cirrhosis and hepatocellular carcinoma.

HAV-RNA may be found in oral fluids 86 though it is present in low frequencies in saliva from HAV-infected patients 21 while others failed to detect it in saliva obtained during a Hepatitis A virus outbreak. 87 It seems that saliva can be a potential route of transmission.

HBV-DNA has been detected in saliva from viremic HBV-infected subjects. 88 Transmission has been demonstrated by subcutaneous inoculation of HBV-infected saliva into animals, 89 but the role of saliva in the person-to-person transmission of HBV infection is still not completely defined. Hepatitis B surface antigen (HBsAg) was found in saliva of 76% of patients with severe hepatitis and in 81% of chronic carriers. 90 It has been implied that transmission may be directly from mouth-to-mouth by kissing or by the exchange of saliva on chewed toys and candies 90 but no infections have been confirmed in susceptible persons with an intact oral mucosa who were orally exposed to HBVinfected saliva 91 or students who had oral exposures to HBsAgpositive saliva via contaminated musical instruments. 92 HBV has been transmitted by a human bite, 93 and a case of HBV transmission has been reported in a person who developed hepatitis B presumably after deep kissing with his partner. 94 However, saliva has a HBV load 1000À10,000 times lower than blood, so the possible transmission of HBV by contaminated saliva remains low. 89 ,95À97 There are no reports of HBV transmission during mouth-to-mouth ventilation or cardiopulmonary resuscitation (CPR) training with a mannequim. 98À100

The evidence therefore points to the possible transmission of HBV via saliva being low.

HCV is transmitted primarily through blood-to-blood contact though 62% of chronic carriers may have HCV-positive saliva. 101À103 HCV-RNA can be detected in the saliva of HCV-infected patients, 23 which might provide an argument for the possible transmission of HCV via saliva, but the salivary HCV viral load is significantly lower than the blood viral load. 104 HCV-RNA in saliva is associated with the level of serum viral load but not with periodontal or liver disease severity. 105 No case of transmission by HCV after mouth-to-mouth ventilation has been described. 106 Transmission of HCV in CPR using CPR mannequins has not been reported even when exposed to HCV-contaminated saliva. 107 Saliva may therefore be a source of occasional transmission of HCV, 108 particularly where there is deep kissing and there are oral mucosal lesions 109 though epidemiological studies suggest that the infective capacity of HCV in saliva is only low. 110 

Other hepatotropic viruses, such as Hepatitis G virus (HGV), have been found in saliva both from HGV-infected patients 25 and from nonhepatitis patients with oral diseases, 24 but transmission via saliva has not been demonstrated.

Human herpesvirus (HHV) infections are common, seen especially in younger people subclinically or producing fever and mucocutaneous lesions, and then remain latent but can be reactivated if immunity wanes. Many can be oncogenic. Oral disease associations examined have ranged from carcinogenesis 111, 112 to periodontitis. 113 4.1.9.1 Herpes Simplex Virus Type 1 (HSV-1; HHV-1) Congenital HSV infection may result in fetal abnormalities in the TORCH (Toxoplasmosis, Other agents, Rubella, Cytomegalovirus, and Herpes simplex) syndrome. HSV-1 is typically acquired early in life, usually from direct contact with infected saliva or skin vesicles. 114 HSV can cause oral lesions mainly as gingivostomatitis, with recurrences usually as herpes labialis. HSV type 1 DNA can be found in most cases of recurrent herpes labialis, both before and after the appearance of clinical lesions. 27 Furthermore, viral shedding with viral loads sufficient to be transmitted is more frequent than previously thought, even in otherwise healthy HSV-seronegative individuals. 26 HSV ulceration and recurrences and almost certainly shedding are increased and often more extensive in immunocompromised people such as those with HIV/AIDS or posttransplantation and after oral surgical procedures. 115 HSV can survive up to 88 hours in dry gauze and 1.5 hours on hard surfaces 115 and has the potential to be spread by fomites. 116 From 2% to 10% of adults without clinical signs of disease have HSV-1 in their saliva. 117,118 HSV-1 transmission via saliva is thought to be common and though evidence is sparse it has been transmitted by mouth-tomouth ventilation. 119À121 However, it is more likely that uninfected adults may contract HSV by kissing 122 or sexual practices but there is little hard evidence to confirm this.

HSV-2 typically causes anogenital herpetic lesions and infection is usually transmitted sexually. As with HSV-1, HSV-2 is capable of causing both anogenital and oral disease. Data from a limited number of studies indicate that HSV-2 shedding in saliva is uncommon and symptomless in healthy individuals 28 and usually occurs in the setting of simultaneous anogenital involvement. 123 Men who have sex with men and HIV-positive persons have slightly higher rates of oral HSV-2 shedding than do otherwise healthy individuals. 124, 125 However, some studies showed an incidence of HSV-2 in saliva of HIV-infected patients as low as that detected in controls. 126 On the contrary, high HSV-2 salivary detection rates have been reported among Brazilian HIV-infected and healthy children (4.2% and 8.3%, respectively). 127 HSV-2 may not be detected in the saliva of HIV-seropositive persons undergoing highly active antiretroviral therapy. 128 Based on a study on herpesvirus prevalence among 16-year-old Swedish girls, it was suggested that "transmission of herpesviruses is common in adolescence, and sex, even with regard to its close association with kissing, is one important determinant" 129 ; however, in that series antibodies to HSV-2 were seen only in 1% of participants, and to date kissing transmission has not been reliably demonstrated.

VZV causes mainly varicella (chickenpox) and zoster (shingles) but there can be more serious complications including meningoencephalitis, and occult forms of VZV-induced disease, including zoster sine herpete and enteric zoster. VZV lesions and recurrences are increased and often more extensive in immunocompromised people such as those with HIV/AIDS or posttransplantation. 130 Chickenpox is highly contagious-spread is mainly airborne. 131 VZV-DNA has also been found in the saliva of patients with clinical VZV infections, being detectable before just the varicella rash appears and for 1À2 weeks thereafter. 132 VZV can also be found in saliva in zoster 48 and VZV meningoencephalitis. 133 Saliva samples from individuals aged older than 60 years show VZV in those with a history of zoster, as well as in some healthy older controls with no history of zoster. 134 VZV may also be found in saliva after VZV immunization. 135 Nevertheless, it has been suggested that the detection of VZV-DNA in saliva may be useful in the diagnosis of atypical cases of varicella, zoster sine herpete, neurological syndromes when cerebrospinal fluid is not available and in Bell's palsy, and atypical pain syndromes. 132 It has been suggested that stress favors VZV shedding in saliva, as was shown in a group of asymptomatic astronauts, both during and after space flights. 47 VZV is not detected in saliva from healthy adults. 136 Though there is little reliable evidence of the potential for VZV transmission via saliva, it is highly likely in the scenarios discussed earlier.

Primary EBV infection in young children is usually subclinical. EBV clinical infection-infectious mononucleosis (glandular fever)-is seen mainly in children older than 10 years, adolescents, and young adults, 137 who present mainly with lymphadenopathy and sore throat.

Patients with infectious mononucleosis can shed EBV in saliva for months. 138 EBV-DNA loads in saliva during convalescence are high and associated with continued infectivity. 139 There is a high prevalence of EBV in saliva and throat washings from healthy children and adults in some geographical regions 18 and by adulthood, at least 90% of all people are seropositive to EBV. EBV may particularly be found in saliva when it is reactivated in immunocompromised people such as those with HIV/AIDS or posttransplantation 140, 141 and in oral hairy leukoplakia. 142 EBV replicates in oropharyngeal epithelial cells and can be spread through saliva. 143 EBV can be transmitted by kissing; prospective epidemiological studies in undergraduate university students have confirmed salivary transmission of EBV 19 though some authors criticized the study methods used. 144 EBV is also called "the Kissing Virus." 145 One anecdote is of a man with infectious mononucleosis who, for 12 hours, had shared a train carriage compartment with a women whom he had not met before and whom he never saw again but during the time in the train, they had repeatedly kissed intimately and some weeks later she developed infectious mononucleosis. 146 A large EBV viral load may be acquired during sexual intercourse 147 and presumably it can also be transmitted from carriers who cough. 144 Even so, despite the lack of direct evidence, EBV transmission is most likely from saliva, especially by kissing. 19 4.1.9.5 Cytomegalovirus (CMV; HHV-5) CMV is another cause of "glandular fever" seen mainly before adulthood, and most adults have been previously infected with CMV but the virus may be reactivated in patients with immunocompromising conditions, e.g., HIV infection 148 and posttransplantation. 149 Multiple CMV strains are recognized and, in men who have sex with men coinfected with HIV, infections with several strains may be seen. 150 Infection by CMV B groups, 151 particularly CMV glycoprotein gB1 subtype (gB1) appear to cause most morbidity. 151, 152 CMV is also one of the most important known viral causes of fetal abnormalities (TORCH syndrome). CMV shedding in body fluids is seen in TORCH and also increased where there is reactivation in immunocompromised people. 141 CMV-seropositive children, especially infants, may be a high infective risk to pregnant women, mainly via saliva. Transmission is common in day care centers. 153 Real-time PCR of saliva is the gold-standard diagnostic test for detection of CMV. 14 As well as CMV shedding in body fluids in immunocompromised people, apparently healthy but CMVseropositive children can also shed CMV at high levels in saliva for months, highlighting the potentially high transmission risks posed by saliva, 13 probably the principal postnatal transmission route. 154 Although there is no robust evidence of a risk of CMV transmission associated with kissing, this is a highly probable route. 155 4.1.9.6 Human Herpesvirus 6 (HHV-6) HHV-6 can cause a range of diseases from exanthema subitum (roseola infantum), mononucleosis syndromes, and pneumonitis to encephalitis. 156 Following primary infection, viral genomes may persist in peripheral blood and saliva of most apparently healthy individuals. 30, 157 Serological studies indicate that HHV-6 infects most children by age 2 years and that older siblings serve as a source of transmission. 29 HHV-6 has a number of forms-HHV-6, HHV-6B, and also CiHHV-6, which is chromosomally integrated 158, 159 and can be reactivated.

HHV-6 may be present in saliva from healthy adults 31 but even immunosuppression by AIDS has little effect on HHV-6 shedding in saliva. 160 HHV-6 transmission may occur via an oral route. 161 

HHV-7 infection is usually a benign and self-limited disease of childhood and rarely has complications though it may affect the central nervous system. It has been implicated in pityriasis rosea and, like HHV-6 it can also cause exanthem subitum. HHV-7 DNA has been detected in saliva from practically all patients with pityriasis rosea 32 and frequently from healthy adults, particularly women, with regional variations. 31,162À164 HHV-7 is present in saliva in adults, and immunosuppression increases both frequency of detection and viral load. 160 HHV-7 may well be transmitted person-to-person via saliva. KSHV is detectable in more than 90% of KS lesions, 166, 167 and oral replication is an essential feature of infection. 168 In areas of high HIV prevalence, such as sub-Saharan Africa, the Mediterranean littoral, and the Xinjiang region in China, KSHV can be transmitted sexually or by contaminated blood transfusions and tissue transplants, 169 or via saliva contact. 170 KSHV is found in saliva from some 35%À80% of apparently healthy adults especially from certain geographical regions such as Brazil 33 and also particularly from immunocompromised people. 171 There is a high prevalence of KSHV in the saliva of patients with KS, even in the absence of intraoral lesions. 34 There is consensus that saliva is the main route of KSHV transmission, especially in children in endemic areas, 172 that household exposure increases the risk for early childhood infection, and that specific feeding behaviors probably play a role in some cases. 173 Occupational transmission of KSHV to healthcare workers is uncommon. 174 However, epidemiological evidence points to particular sexual behaviors, including deep kissing, as being significant transmission risk factors for KSHV after childhood. 175 

Human Immunodeficiency Viruses cause HIV disease and the Acquired Immune Deficiency Syndrome (AIDS). The possibility of interpersonal HIV contagion by saliva is often still a common belief 176 and, e.g., some parents fear transmitting HIV to, or catching infection from their children through saliva. 177 However, some 3 decades ago, it was stated that there is no epidemiological evidence that HIV is transmitted by saliva, 178 and, although such transmission is theoretically possible 179 little has changed subsequently.

HIV can indeed be isolated from saliva, but infrequently. 180 Saliva may of course, also contain blood 181 and it has been suggested that HIV may be transmitted after deep kissing, 182 especially if there is blood in the mouth. 183 Hemoglobin concentrations in saliva are higher in HIVpositive intravenous drug abusers (IVDA) than in HIV-negative IVDA and controls, and in AIDS a mean of 1.3 µL blood/mL saliva has been estimated. 183 However, there is only a low level of HIV in saliva even when it is likely contaminated with blood. 184 Transmission to household nonsexual contacts is improbable. 185 HIV transmission is unlikely with normal household contacts 186 and, although it has been stated by the Centers for Disease Control and Prevention (CDC) that deep kissing might result in viral transmission, 187 CDC now declares that HIV is not spread via saliva, considers openmouth kissing a low risk for HIV transmission and yet recommends against engaging in this activity with known HIV-infected persons. 188 Nevertheless, CDC has apparently investigated only a single case attributed to contact with blood in the mouth. 189 Mouth-to-mouth ventilation is not implicated in the transmission of HIV, even though contaminated saliva contacts open wounds. 190 Blood is visible in saliva or vomit in some resuscitations and this with oral microlesions in 50% of healthy rescuers, makes blood-to-blood contact possible. 109 Nevertheless, even after exposure of healthcare workers to bloodcontaminated saliva or blood through accidental needle stick injuries, the risk of infection has been consistently less than 1% and transmission in normal dental practice is improbable. 191 

HPV can cause benign warty lesions on oral and other epithelia, and some oncogenic types are implicated in cervical, anogenital, and oropharyngeal cancers. A number of viruses have been examined for possible roles in oral carcinogenesis. 112,192À194 including HPV. 195 A small but noteworthy proportion of clinically healthy individuals have oral HPV infections, 36, 196, 197 including with HPV types known to cause cancer in the oral region. 198 One HPV reservoir may be in the gingivae. 199 HPV are often latent, lesions may be small or symptomless and often undetected, and virus may be reactivated by immunoincompetence. 200À204 HPV lesions are often more extensive in immunocompromised people such as those with HIV/AIDS or posttransplantation. 205 Some years ago, it was suggested that oral cancer might be a sexually transmitted viral infection. 206, 207 Early focus on herpes simplex virus, turned to HPV. Oropharyngeal cancer in particular has proved to be significantly associated with oral HPV type 16 (an oncogenic HPV) and associated with a high lifetime number of vaginal-sex partners and oral-sex partners with oncogenic HPV-16 DNA being detected in many (72%) of cancers. 208 HPV-DNA in oral cancer biopsy specimens is more frequent among subjects who reported .1 sexual partner or who practiced oral sex. 209 Oropharyngeal cancer, tonsillar in particular, is increased in patients with anogenital cancer 210 and in females with cervical cancer and in their partners. 211 There have been significant increases in tonsil and base of tongue cancers in males, and base of tongue cancer in females with HPV-associated oropharyngeal cancer are increasing. 212 HPV horizontal, nonsexual transmission may be responsible for oral infection in children. 213 Household transmission may occur via saliva and the shared use of contaminated objects. 37 Partners may carry the same oral HPV, and persistent oral HPV infection of the spouse increases the risk of persistent oral HPV infection 10-fold in the other spouse. 214 HPV is particularly common in those with oropharyngeal cancer, 215 though in one study partners of patients with HPV-OPC did not seem to have more oral HPV infection compared with the general population. 216 Sexual behavior may impact on the risk of infection and though some authors consider kissing to be a low-risk activity, 214,217 deep (French) kissing has been associated with the development of oral HPV infection; 218 this finding has been confirmed in epidemiological studies on young adults of both genders 219 and men who have sex with men, 220 but not, in a study based on a questionnaire on sexual behavior of Australian university students, where no significant differences were found in the number of partners for deep kissing, between those with oral HPV infection and HPV-negative students. 221 In summary, some studies imply therefore that oral HPV may be transmitted by deep kissing or by oral sex (mouth-to-genital or mouthto-anus contacts), while others have not. The likelihood of contracting HPV from kissing or having oral sex with a person who carries HPV is not therefore, completely certain. 222 Polyomavirus detection is generally highest among people 15À19 years of age; WUV infections being more frequent between those ages and decreasing later, but BKV excretion peaking and persisting during the third decade of life, and KIV is more common in subjects $ 50 years of age. 42 BKV, JCV, WUV, and KIV are found in the saliva of some healthy individuals 223 and may be transmitted by saliva. 42 Polyomavirus reactivation is more common in immunocompromised people and these viruses may be found in saliva from HIV-positive children 224 and in renal transplant recipients. 225 MCV is widespread in the human body, and in saliva it is more common than in samples from the lung and genitourinary system, so transmission via saliva would seem possible, 43 and MCV may be acquired through close contact between young siblings and between mothers and their children. 226 BKV has also been detected in saliva from apparently healthy individuals, 42 and salivary gland cells may be a site of virus replication, 227 supporting the hypothesis that saliva may be a route for BKV transmission. In contrast, JCV shedding in saliva is rare. 228 Thus although saliva may be a route of transmission for some human polyomaviruses, the possibility that kissing is a significant risk activity remains to be clarified.

There are three main types of Human influenza viruses, types A (IVA), B, and C. All cause severe lower respiratory disease. Nasopharyngeal colonization by Streptococcus pneumoniae (pneumococcus) is thought to be a prerequisite for developing influenza, and in some older people with influenza-like-illnesses pneumococci are plentiful in saliva. 229 Significant decreases in numbers of salivary anaerobic bacterial (CFUs), and neuraminidase and trypsin-like proteases levels after professional oral healthcare suggests that oral hygiene maintenance can be effective in reducing influenza. 230 H1N1 (swine flu) and some other novel strains of Influenza viruses are carried by pigs, poultry, or other birds and several novel viruses have appeared in resource-rich countries mainly in traveling people. 52 Avian influenza A (H5N1) and A (H7N9) viruses which circulate widely in some poultry populations and sporadically infect humans include: in eastern China the H7N9 influenza A virus, and in the United States a Swine-like influenza H3N2 variant virus. Sporadic human cases of avian A (H5N6), A (H10N8), and A (H6N1) have also emerged. 231 Saliva in people with influenza may well contain the virus. About half of the patients with influenza have positive saliva and nasopharyngeal swabs within 24 hours from the onset of symptoms. 232 Saliva sampling for H1N1 is accurate, reliable, and more convenient than a nasopharyngeal swab. 38 It seems that saliva represents an important initial barrier to Influenza virus infection. Consequently, it is unlikely that kissing could constitute a route for transmission.

The Measles virus causes measles, a highly contagious disorder, usually in children manifesting with fever and rash sometimes with more serious complications. 233 Outbreaks of measles communities such as in Gypsy-Travelers are well recognized. 234 Measles virus is found in saliva, 45, 235 where nucleic acid can be amplified by PCR 39 and directly from using a point-of-care test. 236 Measles is usually spread by droplets but kissing may well also transmit the virus.

Human metapneumovirus (hMPV) is a respiratory pathogen that can cause features ranging from asymptomatic infection to severe bronchitis, mainly but by no means exclusively in children, and is therefore clinically similar to infections with Respiratory syncytial virus, Parainfluenza virus type 1, and Human parainfluenza virus type 3.

hMPV is found in saliva, more in children within 3 days of onset of symptoms than later. 3, 237 Although we found no reliable evidence of the virus transmission by saliva, it is highly likely.

Molluscum contagiosum is a benign poxvirus infection of the skin or very occasionally the mucosae. Lesions are seen mainly in children, sexually active adults, and those who are immunocompromised.

We found no reliable evidence of Molluscum contagiosum virus in, or transmission by, saliva.

Mumps virus typically causes acute sialadenitis (usually parotitis) but is a systemic infection with a variety of possible extra-salivary complications. 238 Mumps transmission has occurred despite prompt isolation of cases after the onset of parotitis, indicating viral shedding before the onset of parotitis. 239 Mumps transmission can occur from persons with subclinical or clinical infections and during the prodromal or symptomatic phases of illness and within the subsequent 5 days. 240 The CDC, American Academy of Pediatrics (AAP), and Healthcare Infection Control Practices Advisory Committee (HICPAC) recommend a 5-day period after the onset of parotitis, both for isolation of persons with mumps in either community or healthcare settings and for use of standard infection control precautions and droplet precautions. 240 Mumps virus is transmitted mainly by respiratory droplets but virus can also be found in saliva. 45 Mumps virus can be isolated from saliva and throat swabs from 7 days before to 8 days after the onset of parotitis, isolation rates are much greater closer to parotitis onset, the viral load decreasing substantially over the first 4 days after illness onset and becoming extremely low thereafter. The raised salivary load of mumps virus suggests a risk for transmission. 241 Although we found no reliable evidence of mumps virus transmission by saliva, it is highly likely.

Nipah virus (NiV) is a paramyxovirus, whose main reservoir host is the fruit bat, first identified in Malaysia and Singapore during an outbreak of encephalitis and respiratory illness in farmers and people with close pig contacts. It is potentially lethal. Though uncommon, person-to-person transmission of NiV may occur mainly via respiratory secretions and body fluids, including saliva. 41,242À244 Although we found no reliable evidence of NiV transmission by saliva, it is highly likely.

Noroviruses (NoV or human Nov (HuNov)) are calciviruses which commonly cause acute gastroenteritis (Winter vomiting disease 245 Deaths are usually in the very young, old, or immunosuppressed and are rare in resource-rich communities. 246 Differences in NoV susceptibility relate to factors including histoblood group antigens (HBGAs) (i.e., the ABO blood group, the Lewis phenotype, and the secretor status), FUT2 (FUcosylTransferase 2), and FUT3 genotypes. 247, 248 Noroviruses are extremely contagious, 249 epidemics being seen mainly in closed communities such as cruise ships and long-stay facilities, and some research suggests as few as five virus particles are enough to transmit infection. 250 NoV can survive for long periods outside a host depending on the surface and temperature conditions. One study found NoV on surfaces used for food preparation 7 days after contamination. 251 It can also survive for months in contaminated water, weeks on hard surfaces, and up to 12 days on fabrics. 252 There can be feco-oral transmission of NoV but salivary transmission appears poorly documented. It has been suggested that it is impossible to get infected by kissing someone who is not yet showing symptoms. However, it may be possible to catch it from someone who has recently vomited by kissing them, as viral particles may be in their mouth from vomitus. 253 

Human parainfluenza viruses (HPIVs) are RNA viruses in a group of four distinct serotypes, which commonly cause respiratory illnesses in infants and young children but anyone can suffer HPIV illness of fever, runny nose, and cough. Furthermore, HPIVs can also cause more severe illness, such as croup or pneumonia.

Most children have been infected by HPIV-3 by age 2 years and by HPIV-1 and 2 by age 5, and HPIVs are found in saliva. 3 Transmission is mainly respiratory but probably also by saliva.

Parvovirus B19 infection may cause erythema infectiosum-a mild fever and rash with oral erythema, and sometimes arthralgia or arthritis. However, severe outcomes of Parvovirus B19 infection may occur. During pregnancy, Parvovirus B19 infection of the fetus can cause fetal loss in the first trimester, or extensive hemolysis. In patients with hemolytic anemias, Parvovirus B19 can produce a transient aplastic crisis. In infants, or in immunocompromised patients, Parvovirus B19 can cause serious hemolysis.

Parvovirus transmission is mainly via respiratory droplets 254 but could be through saliva.

Rabies virus expands worldwide, especially in Asia and Africa. Rabies virus can be detected in saliva of rabies patients 255 now with RT-PCR. 44 Rabies virus is present in fluids and tissues during the first 5 weeks of transmission, but there are few well-documented reports of humanto-human transmission-and these invariably are in corneal 256 or organ transplant recipients. 257 Although the infection has never been well-documented, human-tohuman transmission of rabies following saliva exposure remains at least a theoretical possibility.

RSV is a common cause of respiratory illness indistinguishable from the common cold, and seen mainly in young children. It may lead to lower respiratory disease. Secretion of blood group antigens is associated with respiratory virus diseases. 258 RSV can be found in saliva 3, 237 and can remain viable for at least 30 minutes on hands or for up to 5 hours on surfaces.

Although we found no reliable evidence of RSV transmission by saliva, it is highly likely.

Rhinoviruses are a frequent cause of the common cold. 259 Transmission is mainly via droplets, but viruses may persist in moist secretions on fomites.

Communicability of rhinoviruses showed transmission between partners of 41% and 33% for types 16 and 55, respectively, 260,261 but transmission was rare unless the donor spent hours with the partner and had virus on their hands and anterior nares.

Saliva in adults contains neutralizing antibodies to rhinoviruses. 262 Few rhinovirus particles survive in saliva and therefore, though transmission via saliva must be possible, normal kissing is not the usual mode of infection spread.

Rotaviruses are (with noroviruses) the most important causes of acute gastroenteritis, mainly in children. Rotaviruses are highly contagious.

The host secretor status (FUT2 genotype) affects the expression of HBGAs which act as sites for viral attachment to the gastrointestinal, respiratory, and genitourinary tract epithelia. 263 Rotavirus VP4 spike protein (VP8 Ã ) engages sialic acid in the viral binding to cellular receptors, facilitating viral attachment and entry. 264 In newborns and infants immunized against rotavirus, serum and saliva IgA antibodies conceivably assist in protection. 265 Rotaviruses can be found in saliva and other body fluids in infected patients, 266 presumably transmitting infection.

Rubella virus causes infection mainly in children who may be symptomless or develop a rash, fever, and occasionally other symptoms or signs including lymphadenopathy and palatal purpura. Congenital rubella infection may result in TORCH syndrome.

In rubella, the virus RNA can be found in saliva. 45, 267 Although we found no reliable evidence of rubella transmission by saliva, it is highly likely.

TTV was first identified in a patient with non-A-E hepatitis but the viruses are now known to be ubiquitous, 268 with .90% of adults worldwide infected. It has been suggested that TTV infection is associated with many diseases, including some oral disease, 24 with little evidence.

TTV may be detected in saliva. 46 TTV transmission by saliva, though highly likely appears unsupported by reliable evidence.

Yellow Fever virus is, like Dengue and Zika, a flavivirus transmitted by mosquitoes, usually A. aegypti, and is endemic to tropical regions of Africa and the Americas, causing potentially lethal hemorrhagic fever. 269 In Africa, yellow fever occurs in 34 countries and an epidemic in Angola in 2016 caused serious concern and was spread by travelers to at least China, Democratic Republic of Congo, Kenya, and Morocco. At least half of severely affected patients who do not receive treatment die within 14 days.

No humanÀhuman transmission of Yellow fever virus by saliva has been reported, and we found no reliable evidence of salivary transmission.

WNV, a flavivirus, naturally maintained in a cycle between birds and mosquitoes, with occasional spillover by mosquito bites to humans, since isolated first in Uganda, has spread widely including the United States and Europe. 270 As with so many viruses, most WNV infections are asymptomatic, but there is a risk of potentially lethal neurological disease.

Although a case of possible sexual transmission of WNV has been reported, 271 we found no reliable evidence of WNV transmission by saliva.

ZIKV infection is a mosquito-borne, flavivirus disease associated mainly with Guillain-Barre syndrome and fetal microcephaly. 272 The magnitude of the current ZIKV epidemic has led to a declaration of a Public Health Emergency of International Concern by the WHO. 273 ZIKV RNA has been detected in saliva from patients with Zika fever. 49 It has been suggested that the rate of ZIKV detection in saliva samples is higher even than in blood or urine. 49 Saliva and urine samples present higher viral load than serum. 49, 274, 275 Viral RNA is prolonged shedding in saliva for some weeks after symptom onset-with a slightly longer persistence time than in urine, 274, 276 as it has previously been demonstrated for other vector-borne flaviviruses. In consequence, saliva has been recommended to test for ZIKV when drawing blood or processing of blood samples may be difficult. 275, 276 Nonvector-borne ZIKV transmission plays a role in the spread of ZIKV. 277 One American scientist contracted Zika while working in Senegal in 2008, and transmitted ZIKV infection to his wife; a sexual transmission of the virus was suggested, but other possibilities such as exchange of other bodily fluids including saliva could not be ruled out; moreover, aphthous-type oral ulcers were observed in both spouses. 278 Here as yet no reliable evidence to support ZIKV transmission through human saliva, 9, 279, 280 but cytopathic effects have been reported when bringing saliva in contact with Vero cells, which suggests infectious potential. 277 In a case report of ZIKV infection in a 24-year-old woman who was living in Paris and reported sexual contact with a man who had recently returned from Brazil, the authors could not rule out the possibility that transmission occurred through saliva exchanged through deep kissing, 281 but up to date we found here no reliable evidence of Zika transmission by kissing.

The transfer of body fluids might transmit viral infections, many of which are seen especially in immunocompromised people and some can be life-changing or even lethal, as it has happened in a number of catastrophes where viral agents such as Human Immunodeficiency Viruses and hepatitis viruses were transmitted by blood. Any risks of transmission from saliva appear not well-defined, and reliable evidence for virus transmission through kissing is sparse. Nevertheless, this route may be one where the flaviviruses at least may well spread. In this regard, the number of emerging viral diseases has increased dramatically in recent decades. In an ever more global society, the arrival of immigrants requires us to maximise universal barrier measures, in particular to avoid the transmission of pathogenic viruses not recognised by our immune system. Detection of some of these viruses in saliva, such as Ebola virus or Zika virus represent a new challenge for prevention of human to human transmission. Efforts are being made regarding the development of strategies for virus detection _including polymerase chain reaction-based methods, paper-based synthetic gene networks, immunoassays, magnetic nanoparticles-based assays or liposome-based detection assays. However, there is still a need to search for and improve upon more sensitive and specific detection methods for these challenging viruses. Substantial numbers oral viruses are shared amongst genetically unrelated, cohabitating individuals; most of these viruses are bacteriophages and their distribution over time within households indicates that they are frequently transmitted between the microbiomes of household contacts.

Religious mass gatherings: connecting people and infectious agents

Saliva and viral infections

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

Oral sex and the transmission of viral STIs

Sequence-based identification of microbial pathogens: a reconsideration of Koch's postulates

Viral infections affecting periodontal health

Inhibition of herpes simplex virus type 1, respiratory syncytial virus and echovirus type 11 by peroxidase-generated hypothiocyanite

Antiviral activities in human saliva

Check before you travel: Zika virus-another emerging global health threat

Infectious chikungunya virus in the saliva of mice, monkeys and humans

Prediction of intrinsic disorder in MERS-CoV/HCoV-EMC supports a high oral-fecal transmission

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

Repeated measures study of weekly and daily cytomegalovirus shedding patterns in saliva and urine of healthy cytomegalovirus-seropositive children

Comparison of saliva PCR assay versus rapid culture for detection of congenital cytomegalovirus infection

Value of routine dengue diagnostic tests in urine and saliva specimens

Assessment of the risk of Ebola virus transmission from bodily fluids and fomites

Prospective study of enteroviral infections and development of beta-cell autoimmunity. Diabetes autoimmunity study in the young (DAISY)

Detection of EpsteinÀBarr virus in salivas and throat washings in healthy adults and children

Behavioral, virologic, and immunologic factors associated with acquisition and severity of primary EpsteinÀBarr virus infection in university students

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

Exploring the concurrent presence of hepatitis A virus genome in serum, stool, saliva, and urine samples of hepatitis A patients

Saliva as a tool in the detection of hepatitis B surface antigen in patients

Diz Dios P. Detection of HCV RNA in saliva of patients with hepatitis C virus infection by using a highly sensitive test

Investigation of HGV and TTV infection in sera and saliva from non-hepatitis patients with oral diseases

Detection of GBV-C/HGV RNA in saliva and serum, but not in urine of infected patients

Asymptomatic shedding of herpes simplex virus (HSV) in the oral cavity. Oral Surg Oral Med Oral Pathol Oral Radiol Endod

Oral shedding of herpes simplex virus type 1 in immunocompetent persons

Detection of herpes simplex virus (HSV) in the saliva from 1,000 oral surgery outpatients by the polymerase chain reaction (PCR) and virus isolation

A population-based study of primary human herpesvirus 6 infection

Coinfection of human herpesviruses 6A (HHV-6A) and HHV-6B as demonstrated by novel digital droplet PCR assay

Detection of human herpesvirus 6 and 7 DNA in saliva from healthy adults from Rio de Janeiro, Brazil

Pityriasis rosea is associated with systemic active infection with both human herpesvirus-7 and human herpesvirus-6

Human herpesvirus-8 infection and oral shedding in Amerindian and non-Amerindian populations in the Brazilian amazon region

Transmissible Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) in saliva of men with a history of Kaposi's sarcoma

Oral and systemic health correlates of HIV-1 shedding in saliva

Oral human papillomavirus in healthy individuals: a systematic review of the literature

Human papillomavirus 13 in a Mexican Mayan community with multifocal epithelial hyperplasia: could saliva be involved in household transmission?

Salivary detection of H1N1 virus: a clinical feasibility investigation

Use of RT-PCR on oral fluid samples to assist the identification of measles cases during an outbreak

Mumps virus diagnosis and genotyping using a novel single RT-PCR

Transmission of human infection with Nipah virus

Shedding of polyomavirus in the saliva of immunocompetent individuals

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

Intravitam diagnosis of human rabies by PCR using saliva and cerebrospinal fluid

The role of RT-PCR assay of oral fluid for diagnosis and surveillance of measles, mumps and rubella

TT virus prevalence, viral loads and genotypic variability in saliva from healthy Japanese children

Stress-induced subclinical reactivation of varicella zoster virus in astronauts

Varicella-zoster virus in the saliva of patients with herpes zoster

Detection of Zika virus in saliva

Adenovirus urethritis and concurrent conjunctivitis: a case series and review of the literature

Emergence of community-acquired adenovirus type 55 as a cause of community-onset pneumonia

Emerging viral respiratory tract infectionsenvironmental risk factors and transmission

Viral shedding after p53 adenoviral gene therapy in 10 cases of esophageal cancer

Impact of chikungunya virus infection on oral health status: an observational study

Multidisciplinary prospective study of mother-tochild chikungunya virus infections on the Island of La Reunion

Salivary transmission of the chikungunya arbovirus

Emerging respiratory tract infections

Molecular pathology of emerging Coronavirus infections

SARS-like WIV1-CoV poised for human emergence

Cystatin D, a natural salivary cysteine protease inhibitor, inhibits coronavirus replication at its physiologic concentration

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

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

Approach to noninvasive sampling in dengue diagnostics: exploring virus and NS1 antigen detection in saliva and urine of travelers with dengue

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

Rapid diagnosis of ebola hemorrhagic fever by reverse transcription-PCR in an outbreak setting and assessment of patient viral load as a predictor of outcome

Infection control: ebola aware; ebola beware; ebola healthcare

Ebola virus shedding and transmission: review of current evidence

Progress in the diagnosis and control of ebola disease

Human repercussions of foot and mouth disease and other similar viral diseases

Viral exanthems

Comparison of clinical features between coxsackievirus A2 and enterovirus 71 during the enterovirus outbreak in Taiwan, 2008: a children's hospital experience

Coxsackievirus A6 and hand, foot, and mouth disease

Epidemiology of childhood enterovirus infections in Hangzhou, China

Parechoviruses in children: understanding a new infection

Poliovirus in the upper respiratory tract of household contacts

Enteroviruses: polioviruses, coxsackieviruses, echoviruses, and newer enteroviruses

Hand, foot and mouth disease: changing Indian scenario

Salivary excretion of coxsackie b-1 virus in rabbits

Transmission and clinical features of enterovirus 71 infections in household contacts in Taiwan

Diseases caused by enterovirus 71 infection

Isolation of ECHO-9-viruses from the saliva of inflamed salivary glands

Hantavirus pulmonary syndrome: the sound of a mouse roaring

Sensitivity of Andes hantavirus to antiviral effect of human saliva

Antiviral effect of human saliva against hantavirus

Prospective evaluation of household contacts of persons with hantavirus cardiopulmonary syndrome in chile

Detection of hepatitis A virus RNA in saliva

Clinical features and molecular characterization of hepatitis A virus outbreak in a child care center in thailand

Hepatitis B virus DNA in saliva, urine, and seminal fluid of carriers of hepatitis B e antigen

Transmission of hepatitis B virus to gibbons by exposure to human saliva containing hepatitis B surface antigen

Role of saliva, urine and feces in the transmission of type B hepatitis

Epidemiology of hepatitis B in Europe and worldwide

Potential risk of salivary-mediated viral hepatitis type B transmission from oral exposure to fomites

Transmission of hepatitis B by human bite-confirmation by detection of virus in saliva and full genome sequencing

A patient in whom only hepatitis B virus (HBV) was thought to have been contracted, by kissing, from a same-sex partner coinfected with HBV and human immunodeficiency virus-1

Infectious hepatitis. evidence for two distinctive clinical, epidemiological, and immunological types of infection

Letter: hepatitis B not transmissible via faecal-oral route

Experimental transmission of hepatitis B virus by semen and saliva

Lack of transmission of hepatitis B to humans after oral exposure to hepatitis B surface antigen-positive saliva

Hepatitis B virus in a cardiopulmonary resuscitation training course. risk of transmission from a surface antigen-positive participant

Lack of transmission of viral hepatitis type B after oral exposure to HBsAg-positive saliva

Detection of HCV-RNA in saliva of patients with chronic hepatitis C

Demonstration of hepatitis C virus genome in saliva and urine of patients with type C hepatitis: usefulness of the single round polymerase chain reaction method for detection of the HCV genome

Prevalence of hepatitis-C virus RNA in serum and throat washings of children with chronic hepatitis

Hepatitis C virus quantification in serum and saliva of HCV-infected patients

Detection of hepatitis C virus RNA in saliva of patients with active infection not associated with periodontal or liver disease severity

Transmission of infectious diseases through mouth-to-mouth ventilation: evidence-based or emotion-based medicine?

Lack of transmission of hepatitis non-A, non-B by CPR manikins

Evaluation of viral load in saliva from patients with chronic hepatitis C infection

Passionate kissing and microlesions of the oral mucosa: possible role in AIDS transmission

Transmission of hepatitis C virus by saliva?

Detection of RNA complementary to herpes simplex virus in human oral squamous cell carcinoma

Viruses and cancer: herpesviruses and tumors in the head and neck. A review

Association between herpesviruses and chronic periodontitis: a meta-analysis based on case-control studies

The epidemiology and clinical presentation of herpes virus infections

Fomites and herpes simplex virus: the toilet seat revisited

Survival of herpes simplex virus and other selected microorganisms on patient charts: potential source of infection

A prospective study of chronic herpes simplex virus infection and recurrent herpes labialis in humans

Herpes virus in an obstetric hospital. II: Asymptomatic virus excretion in staff members

Herpes simplex infection following cardiopulmonary resuscitation

Primary herpes simplex infection following mouth-to-mouth resuscitation

Transmission of herpes simplex during cardiopulmonary resuscitation training

Oral manifestations of herpes simplex virus infections

Oral shedding of herpes simplex virus type 2

Herpes simplex virus type 2 shedding in human immunodeficiency virus-negative men who have sex with men: frequency, patterns, and risk factors

Saliva can mediate HIV-1-specific antibody-dependent cell-mediated cytotoxicity

Incidence of human herpes virus 1-4 type in saliva of 245 human immunodeficiency virus-infected patients

Lack of association between herpesvirus detection in saliva and gingivitis in HIV-infected children

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

Prevalence of antibodies to herpes simplex virus types 1 and 2, EpsteinÀBarr virus and cytomegalovirus in teenage girls

Pathogenesis and current approaches to control of varicellazoster virus infections

Airborne transmission of chickenpox in a hospital

Varicella zoster virus and virus DNA in the blood and oropharynx of people with latent or active varicella zoster virus infections

Varicellazoster DNA in saliva of patients with meningoencephalitis: a preliminary study

Persistence of varicella zoster virus DNA in saliva after herpes zoster

Varicella zoster virus DNA at inoculation sites and in saliva after zostavax immunization

Search for varicella zoster virus DNA in saliva of healthy individuals aged 20-59 years

Infectious mononucleosis-a "childhood disease" of great medical concern

Infectious mononucleosis. EpsteinÀBarr-virus shedding in saliva and the oropharynx

A prospective follow-up of Epstein-Barr virus LMP1 genotypes in saliva and blood during infectious mononucleosis

Monitoring EBV DNA in saliva for early diagnosis of EBV reactivation in solid tumour patients after allogeneic haematopoietic SCT

Salivary shedding of EpsteinÀBarr virus and cytomegalovirus in people infected or not by human immunodeficiency virus 1

Detection of EpsteinÀBarr virus in oral scrapes in HIV infection, in hairy leukoplakia, and in healthy non-HIV-infected people

Site of EpsteinÀBarr virus replication in the oropharynx

Myths about infectious mononucleosis

Relation of Burkitt's tumor-associated herpes-type virus to infectious mononucleosis

The transmission of infectious mononucleosis

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

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

Cytomegalovirus infection in renal transplant recipients

Identification of multiple cytomegalovirus strains in homosexual men with acquired immunodeficiency syndrome

Cytomegalovirus glycoprotein B groups associated with retinitis in AIDS

Frequency distribution of cytomegalovirus envelope glycoprotein genotypes in bone marrow transplant recipients

Human cytomegalovirus quantification in toddlers saliva from day care centers and emergency unit: a feasibility study

Infectious diseases of the fetus and newborn infant

Cross-sectional study of cytomegalovirus shedding and immunological markers among seropositive children and their mothers

Human herpesvirus 6

Detection of human herpesvirus-6 DNA in peripheral blood and saliva

Herpesviruses and chromosomal integration

Complete genome sequence of germline chromosomally integrated human herpesvirus 6A and analyses integration sites define a new human endogenous virus with potential to reactivate as an emerging infection

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

Human herpesvirus 6 DNA in peripheral blood cells and saliva from immunocompetent individuals

Human herpesvirus 7 is a constitutive inhabitant of adult human saliva

Frequent isolation of human herpesvirus 7 from saliva samples

Variation of human herpesvirus 7 shedding in saliva

Analysis of shedding of 3 betaherpesviruses in saliva from patients with connective tissue diseases

Human herpesvirus 8 and oral health care: an update. Oral Surg Oral Med Oral Pathol Oral Radiol Endod

Human herpesvirus 8 (HHV-8) and the etiopathogenesis of Kaposi's sarcoma

Oral HHV-8 replication among women in Mombasa, Kenya

HHV-8 infection: a model for reactivation and transmission

Transmission of human herpesvirus 8: an update

Presence of human herpes virus-8 in saliva and non-lesional oral mucosa in HIV-infected and oncologic immunocompromised patients

Epidemiology and transmission of Kaposi's sarcoma-associated herpesvirus

Risk factors for early childhood infection of human herpesvirus-8 in Zambian children: the role of early childhood feeding practices

Continuous exposure to Kaposi sarcomaassociated herpesvirus (KSHV) in healthcare workers does not result in KSHV infection

Mucosal shedding of human herpesvirus 8 in men

Approach to sexuality in an AIDS context in Congo

Hugs and kisses: HIV-infected parents' fears about contagion and the effects on parent-child interaction in a nationally representative sample

HIV transmitted by kissing

The biologic possibility of HIV transmission during passionate kissing

Infrequency of isolation of HTLV-III virus from saliva in AIDS

Blood in saliva of patients with acquired immunodeficiency syndrome: possible implication in sexual transmission of the disease

The biologic possibility of HIV transmission during passionate kissing

Blood in saliva of HIV seropositive drug abusers: possible implication in AIDS transmission

Patients infected with human immunodeficiency virus type 1 have low levels of virus in saliva even in the presence of periodontal disease

Lack of transmission of human immunodeficiency virus from infected children to their household contacts

Lack of transmission of HTLV-III/LAV infection to household contacts of patients with AIDS or AIDS-related complex with oral candidiasis

Transmission of HIV possibly associated with exposure of mucous membrane to contaminated blood

Centers for Disease Control and Prevention (CDC). HIV transmission

Kissing reported as possible cause of HIV transmission

Saliva inhibits HIV-1 infectivity

Lack of evidence for patient-to-patient transmission of HIV in a dental practice

Viruses in the aetiology of cancer

Viruses and oral squamous carcinoma

Oral carcinoma: evidence for viral oncogenesis

Human papillomavirus: its identity and controversial role in oral oncogenesis, premalignant and malignant lesions (review)

Detection of human papillomavirus DNA in biopsies of human oral tissue

Detection of human papillomavirus genes in human oral tissue biopsies and cultures by polymerase chain reaction

The epidemiology of oral HPV infection among a multinational sample of healthy men

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

Diseases associated with human papillomavirus infection

Human papillomavirusassociated cancers as acquired immunodeficiency syndrome defining illnesses

Human papillomavirus infection in oral fluids of HIV-1-positive men: prevalence and risk factors

HPV carcinomas in immunocompromised patients

Viral infections associated with oral cancers and diseases in the context of HIV: a workshop report

HPV-related neoplasias in HIV-infected individuals

Oral squamous cell carcinoma; from an hypothesis about a virus, to concern about possible sexual transmission

Oral cancer; the evidence for sexual transmission

Case-control study of human papillomavirus and oropharyngeal cancer

Human papillomavirus and oral cancer: the international agency for research on cancer multicenter study

Aetiological parallel between tonsillar and anogenital squamous-cell carcinomas

Tonsillar and other upper aerodigestive tract cancers among cervical cancer patients and their husbands

Head and neck cancer in Australia between 1982 and 2005 show increasing incidence of potentially HPV-associated oropharyngeal cancers

Prevalence of human papillomavirus in the oral cavity/oropharynx in a large population of children and adolescents

Natural history of oral papillomavirus infections in spouses: a prospective Finnish HPV family study

Concordance of oral HPV prevalence between patients with oropharyngeal cancer and their partners

Oral human papillomavirus (HPV) infection in HPV-positive patients with oropharyngeal cancer and their partners

Adolescent sexual health behavior in Thailand: implications for prevention of cervical cancer

Oral sexual behaviors associated with prevalent oral human papillomavirus infection

The prevalence and incidence of oral human papillomavirus infection among young men and women, aged 18-30 years

Oral human papillomavirus in men having sex with men: risk-factors and sampling

Prevalence and risk factors for oral HPV infection in young Australians

Centers for Disease Control and Prevention (CDC). HPV and oropharyngeal cancer-fact sheet

Seroepidemiology of human polyomaviruses

Polyomavirus in saliva of HIV-infected children

Detection of Merkel cell polyomavirus in oral samples of renal transplant recipients without Merkel cell carcinoma

Merkel cell polyomavirus infection occurs during early childhood and is transmitted between siblings

Replication of oral BK virus in human salivary gland cells

JC virus detection in bodily fluids: clues to transmission

Carriage of Streptococcus pneumoniae in aged adults with influenza-like-illness

Professional oral care reduces influenza infection in elderly

Emerging respiratory tract viral infections

Evaluation of saliva as diagnostic materials for influenza virus infection by PCR-based assays

The burden and impact of measles among the gypsytraveller communities

Atypical measles in a patient twice vaccinated against measles: transmission from an unvaccinated household contact

A point-of-care test for measles diagnosis: detection of measles-specific IgM antibodies and viral nucleic acid

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

Mumps: a resurgent disease with protean manifestations

Mumps transmission in hospitals

Updated recommendations for isolation of persons with mumps

Severity of mumps disease is related to MMR vaccination status and viral shedding

The presence of Nipah virus in respiratory secretions and urine of patients during an outbreak of Nipah virus encephalitis in Malaysia

Genetic characterization of Nipah virus

Person-to-person transmission of Nipah virus in a Bangladeshi community

Norovirus gastroenteritis

Host-pathogen co-evolution and glycan interactions

Characterisation of a household norovirus outbreak occurred in Valencia (Spain)

Norovirus: an overview

Human norovirus as a foodborne pathogen: challenges and developments

Persistence of caliciviruses on environmental surfaces and their transfer to food

Misery-inducing norovirus can survive for months -perhaps years-in drinking water

Norovirus-emetophobia

Infection by parvovirus B 19 during pregnancy: a review

Rabies; a case report with notes on the isolation of the virus from saliva

Is there a risk to contacts of patients with rabies?

Global Alliance for Rabies Control. Exposure, prevention and treatment

Association between secretor status and respiratory viral illness

Literature review: the common cold

Transmission of experimental rhinovirus colds in volunteer married couples

Short-duration exposure and the transmission of rhinoviral colds

Rhinovirus neutralizing antibody in tears, parotid saliva, nasal secretions and serum

Epidemiologic association between FUT2 secretor status and severe rotavirus gastroenteritis in children in the united states

Rotavirus VP8 Ã : phylogeny, host range, and interaction with histo-blood group antigens

Subclasses of IgA antibodies in serum and saliva samples of newborns and infants immunized against rotavirus

Association between norovirus and rotavirus infection and histo-blood group antigen types in Vietnamese children

Detection of rubella virus RNA in clinical material by real time polymerase chain reaction method

Torque teno virus: a ubiquitous virus

Yellow fever: a reemerging threat

The global ecology and epidemiology of West Nile Virus

West Nile Virus meningo-encephalitis: possible sexual transmission

Emerging and changing viral diseases in the new millennium

Zika virus infection: global update on epidemiology and potentially associated clinical manifestations

Isolation of infectious Zika virus from saliva and prolonged viral RNA shedding in a traveller returning from the Dominican Republic to Italy

Potential use of saliva samples to diagnose Zika virus infection

Long-term kinetics of Zika virus RNA and antibodies in body fluids of a vasectomized traveller returning from martinique: a case report

Non-vector-borne transmission of Zika virus: a systematic review

Probable non-vector-borne transmission of Zika virus

Zika virus infection spread through saliva-a truth or myth?

Zika virus: oral healthcare implications

Evidence of sexual transmission of Zika virus