2.1. Prevalence and Transmission

MCV infection is acquired early in life, is near-ubiquitous in adults, is generally asymptomatic, and can result in persistent, life-long infection (Arora et al. 2012a; Chang and Moore 2012; Chen et al. 2011; Chen et al. 2014; Coursaget et al. 2013; IARC 2013; Spurgeon and Lambert 2013).

Age-specific MCV seroprevalence has been reported as 20% in children ages 1 to 5 years, 35% to 50% for those under 10 to 15 years old, and 46% to 87.5% in adults (Chen et al. 2011; IARC 2013; Tolstov et al. 2009; Viscidi et al. 2011). In a study of children with acute lymphoblastic leukemia, neonatal blood spots on filter paper (Guthrie cards) were examined for the presence of polyomaviruses including MCV. All test subjects (N = 50) and controls (N = 100) were found to be MCV negative by real-time PCR assay (Gustafsson et al. 2012). Gustafsson et al. (2012) noted that primers from both the VP1 and LT regions of MCV were used (i.e., coupled LT and VP1 positivity for MCV detection), and all samples were negative for the LT region of MCV; however, 23 of the 150 samples were weakly reactive for the VP1 region of MCV, possibly due to nonspecific amplification or to a very low viral copy number and technical difficulties in amplifying sufficient quantities for sequencing.

U.S. MCV seroprevalence rates have been reported to range from 23% to 88%, indicating that a significant number of people in the United States are exposed to MCV (see Table 2-1) (Carter et al. 2009; Kean et al. 2009; Pastrana et al. 2009; Tolstov et al. 2011; Tolstov et al. 2009; Viscidi et al. 2011). Several test methods are available to determine these levels as described in Section 1.2.1. No analyses of MCV prevalence in blood, serum, or urine specimens from the National Health and Nutrition Examination Survey (NHANES) have been identified.

Table 2-1

U.S. MCV Seroprevalence Rates.

Among 5,548 study participants in a large rural Chinese population, overall MCV seroprevalence was 61.0%; seroprevalence was significantly higher in males than in females (64.5% versus 57.7%, p < 0.001), and showed a trend to increase with age for both genders (male p_trend < 0.001, female p_trend < 0.001) (Zhang et al. 2014). In two study populations in Cameroon, Central Africa, overall seroprevalences of antibodies directed against MCV were 59% (N = 458, 68% of whom were children) and 81% (N = 584, median age = 19 years) (Martel-Jantin et al. 2013). In the study population consisting mostly of children (N = 458), seroprevalence from birth to age 4 months was very similar to seroprevalence in women of childbearing age (approximately 70%). Seroprevalence then decreased with age and reached 0% at age 15 to 16 months, and then increased beginning at age 17 months and reached approximately 60% to 80% at age 4 to 5 years. Martel-Jantin et al. (2013) noted that this seroprevalence pattern in young children is consistent with prevalence of maternal antibodies in very young children, i.e., maternal antibodies progressively disappear, and most children rapidly acquire infection beginning at about age 16 to 18 months.

MCV is found in many different tissues, predominantly on skin surfaces, and healthy individuals have been shown to chronically shed MCV DNA from the skin surface (Pastrana et al. 2012). MCV DNA has been detected in skin samples at up to approximately 28% by polymerase chain reaction (PCR) or nested PCR, up to 40% by rolling circle amplification, and up to 100% by real-time PCR or quantitative PCR (IARC 2013). MCV has also been reported to infect saliva and mouth, esophagus, and colon, as well as the blood and urine; this suggests a systemic distribution (IARC 2013; Loyo et al. 2010). Merkel cell carcinoma has been found to contain up to 0.8 MCV DNA copies per cell (IARC 2013; Shuda et al. 2011). Additionally, MCVs found on one area of skin are genetically identical to the virus found on other areas of skin, further supporting a systemic distribution. It is thought that the viral load is usually higher in the mouth, but that the frequency of detection is higher on the skin where MCV is considered part of normal skin flora.

The mode(s) of transmission of MCV are not fully characterized (IARC 2013). Because MCV has not been detected in fetal autopsy samples, vertical transmission from mother to child does not appear to occur, but the possibility of perinatal transmission at time of delivery has not been excluded. A study of familial aggregation, i.e., the tendency for MCV infection to occur within families, of MCV infection status in Cameroon, Central Africa found statistically significant sib-sib correlation (odds ratio [OR] = 3.2, 95% CI = 1.27 to 9.19, p = 0.014), especially between siblings close together in age (<7 years), and a trend for mother-child correlation (OR = 2.71, 95% CI = 0.86 to 8.44, p = 0.08), suggesting MCV can be transmitted through close personal contact involving saliva or skin, between young siblings, and between mothers and their children (Martel-Jantin et al. 2013). Further, a cross-sectional study of a large rural Chinese population found that poor personal hygiene (e.g., infrequent bathing) may increase risk of cutaneous transmission of MCV, and that among heterosexual couples, MCV seropositivity of one spouse was significantly related to that of the other partner (adjusted OR = 1.32, 95% CI = 1.07 to 1.62, p = 0.009) (Zhang et al. 2014).

MCV DNA detected in the gastrointestinal tract and in urban sewage suggests a possible fecal-oral mode of transmission (Spurgeon and Lambert 2013). MCV has been detected in 85% of environmental surface samples, indicating that transmission from environmental sources to humans is possible (Foulongne et al. 2011; IARC 2013). Because most adults have MCV antibodies, blood transmission is not expected to play a large role in transmission (IARC 2013). MCV DNA has also been detected in nasopharyngeal aspirates (0.6% to 1.3% in children and 2.1% to 8.5% in adults), tonsils (3.5%), lung tissues (6.7%), bronchoalveolar and bronchoaspirates (17.2%), suggesting possible aerodigestive transmission.

MCV seropositivity has not been found to be associated with other chronic viral infections (e.g., human immunodeficiency virus-1, hepatitis B virus, or hepatitis C virus) (IARC 2013; Tolstov et al. 2011) or with sexual activity (Carter et al. 2009; Tolstov et al. 2011; Zhang et al. 2014). However, concordance for MCV seropositivity between heterosexual couples exists and is likely due to increased non-sexual transmission via respiratory, fecal-oral, or cutaneous routes from frequent close contact or shared family environment (Zhang et al. 2014).

2.2. Diseases, Prevention, Treatment

MCV has not been associated with any other disease or symptoms to date (IARC 2013).

Some cancer treatments target MCV oncoproteins (e.g., MCV-specific treatment based on T antigens to manage MCV-positive Merkel cell carcinomas) (Samimi et al. 2015). At this time, there is no vaccine against MCV (CDC 2011; FDA 2015), and limited vaccine development efforts are ongoing (Gomez et al. 2013; Pastrana et al. 2009; Samimi et al. 2015; Zeng et al. 2012).

2.3. Summary

U.S. seroprevalence study data indicate that a significant number of people living in the United States are exposed to Merkel cell polyomavirus. MCV infection is acquired early in life, is near-ubiquitous in adults, is generally asymptomatic, and can result in persistent, life-long infection. The mode(s) of transmission of MCV are not fully characterized. Studies of MCV infection within families suggest that MCV can be transmitted through close personal contact involving saliva or skin, between young siblings, and between mothers and their children. Vertical transmission from mother to child does not appear to occur, but the possibility of perinatal transmission at time of delivery has not been excluded. Based on detections of MCV DNA in the gastrointestinal tract and in urban sewage, a fecal-oral mode of transmission is possible. Detections of MCV in environmental surface samples indicate that transmission from environmental sources to humans is also possible. Poor personal hygiene (e.g., infrequent bathing) may increase risk of cutaneous transmission of MCV. There is currently no vaccine against MCV, although limited vaccine development efforts are ongoing.