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Background: Emerging viral infections in humans are appearing at an increasing rate. Recently, we identified a new Marseillevirus, named Giant Blood Marseillevirus (GBM), by performing viral metagenomics on asymptomatic blood donors., Objectives: To study and compare the prevalence of Marseillevirus between asymptomatic blood donors and thalassemia patients., Design: Here, we present a combined molecular and serological study on 174 asymptomatic blood donors and 22 patients with thalassemia who receive repeated blood transfusions to estimate the prevalence of Marseillevirus in these two populations., Results: We identified Marseillevirus genomic DNA in 4% of donors, whereas 9.1% of the thalassemia patients were positive for this virus. Moreover, IgG seropositivity was detected in 22.7% of patients in the thalassemia group, whereas this seropositivity was observed in 12.6% of the blood donor population., Conclusion: These results suggest that Marseillevirus infection is not rare in healthy persons and may be transmitted by transfusion, thus raising speculation regarding the long-term consequences of this viral infection, particularly in patients requiring repeated blood transfusions., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background: SEN virus (SENV) is a newly discovered DNA virus. We conducted this study to evaluate potential modes of SENV transmission and the pathogenic effect of SENV on liver diseases in children., Methods: Polymerase chain reaction was used to detect 2 SENV variant (SENV-D and SENV-H) DNA in sera from healthy individuals and diseased children. Nucleotide sequence of SENV was determined by direct sequencing., Results: SENV infection was assessed in healthy individuals, including 50 newborns (sera collected from the umbilical cord), 24 infants, 46 preschool children (aged 1-6 years), 42 school children of an age before that of the first sexual experience (aged 7-12 years), 62 adolescents (13-18 years), 72 young adults (19-30 years) and 32 adults (>30 years). The prevalence of SENV-D and/or SENV-H (SENV-D/H) viremia in each group was 0%, 17%, 24%, 24%, 27%, 33% and 40%, respectively. The prevalence of SENV-D/H viremia in 18 children with non-A to E hepatitis, 64 thalassemic children, 80 children transfused during cardiac surgery, 30 children with chronic hepatitis B, 9 children with chronic hepatitis C and 32 infants with biliary atresia was 11%, 61%, 80%, 83%, 67% and 50%, respectively. SENV was found more frequently in all patient groups than in 174 age-matched controls (P < 0.01), with the exception of non-A to E hepatitis (11% versus 24% in the control group; P = 0.27). In 2 infants with proven intrauterine hepatitis B viral infection, identical SENV-D nucleotide sequence existed in both the maternal and neonate serum. Elevated alanine aminotransferase concentrations were rarely observed in children who acquired isolated SENV viremia because of transfusion for surgery. Infection with SENV in children with chronic hepatitis C virus or hepatitis B viral infection was not associated with higher peak alanine aminotransferase values., Conclusion: SENV is transmitted mainly via nonparenteral daily contact and frequently occurs early in life. Transfusion can significantly increase the rate of SENV viremia. SENV does not appear to cause hepatitis in children.

Objective: To investigate the rate of infection caused by Torque teno virus (TTV) in United Arab Emirates (UAEs) healthy population as a pilot study in detecting TTV DNA in 100 healthy blood donors., Methods: We randomly choose a total of 100 healthy blood donors who attended Zayed Military Hospital, Abu Dhabi, UAE from January 20 to May 30, 2005. We carried out a real-time polymerase chain reaction (PCR) test to detect TTV DNA., Results: Real-time for TTV was positive in 75 (75%) donors. Eight (73%) non-UAE donors were TTV positive while 67 (75%) were UAEs. Among these donors, 72 (77%) were males and 3 (50%) were females., Conclusion: Our results demonstrated a high prevalence of TTV in UAE.

SEN virus (SEN-V) is a blood-borne, single-stranded, nonenveloped DNA virus. Although its prevalence varies by geographic region, it has been detected in as many as 30 percent of postoperative transfusion recipients, compared to 3 percent of postoperative patients who did not receive transfusions. A significant association has been observed between transfusion volume and the occurrence of SEN-V infection. Transmission by transfusion also has been confirmed by the detection of greater than 99 percent homology between SEN-V in donor and recipient sera. Concurrent infections with SEN-V and hepatitis B virus, hepatitis C virus, or human immunodeficiency virus type 1 have been documented, and these observations probably reflect the blood-borne transmission of these viruses as well as SEN-V. Although SEN-V was discovered as part of a search for causes of posttransfusion hepatitis, there is no firm evidence so far that SEN-V infection either causes hepatitis or worsens the course of coexistent liver disease. Nevertheless, SEN-V appears to be transmitted by transfusion, and further studies may reveal more about its role in the future.

Objective: To determine the prevalence and clinical impact of transfusion-transmitted virus (TTV) DNA in patients with chronic liver diseases in the Southeast Anatolia region of Turkey where hepatitis B and C viral infections are endemic., Subjects and Methods: Patients diagnosed with chronic liver disease by clinical, biochemical and histologic means were enrolled in the study. Serum samples of 60 patients (19 males, 41 females) with chronic liver diseases, and of 45 healthy volunteer blood donors as a control group were collected. The chronic liver disease group consisted of 11 patients with hepatitis B, 44 with hepatitis C and 5 with chronic liver disease of unknown etiology. Presence of TTV DNA was investigated by the polymerase chain reaction. Using a scoring system histological grading of inflammation and staging of fibrosis were performed only in the chronic hepatitis C group., Results: TTV DNA was detected in 47 (78%) patients with chronic liver disease and 5 (11%) volunteers in the control group. The difference was statistically significant (p < 0.001). Ten of the 11 (91%) patients with hepatitis B, 32 of 44 (73%) of those with hepatitis C-related chronic liver disease, and 5 of 5 (100%) of the patients with cryptogenic liver disease were positive for TTV DNA., Conclusion: TTV is highly prevalent in patients with chronic liver diseases in Southeast Anatolia, Turkey but no pathogenic effect attributable to TTV infection was detected., (Copyright 2003 S. Karger AG, Basel)

Aim: To determine the prevalences of TTV and HGV infections among blood donors and patients with chronic liver disease in Korea, to investigate the association of TTV and HGV infections with blood transfusion, and to assess the correlation between TTV and HGV viremia and hepatic damage., Methods: A total of 391 serum samples were examined in this study. Samples were obtained from healthy blood donors (n=110), hepatitis B surface antigen (HBsAg)-positive donors (n=112), anti-hepatitis C virus (anti-HCV)-positive donors (n=69), patients with type B chronic liver disease (n=81), and patients with type C chronic liver disease (n=19). TTV DNA was detected using the hemi-nested PCR. HGV RNA was tested using RT-PCR. A history of blood transfusion and serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were also determined., Results: TTV DNA was detected in 8.2 % of healthy blood donors, 16.1 % of HBsAg-positive donors, 20.3 % of anti-HCV-positive donors, 21.0 % of patients with type B chronic liver disease, and 21.1 % of patients with type C chronic liver disease. HGV RNA was detected in 1.8 % of healthy blood donors, 1.8 % of HBsAg-positive donors, 17.4 % of anti-HCV-positive donors, 13.6 % of patients with type B chronic liver disease, and 10.5 % of patients with type C chronic liver disease. The prevalence of TTV and HGV infections in HBV- or HCV-positive donors and patients was significantly higher than in healthy blood donors (P<0.05), except for the detection rate of HGV in HBsAg-positive donors which was the same as for healthy donors. There was a history of transfusion in 66.7 % of TTV DNA-positive patients and 76.9 % of HGV RNA-positive patients (P<0.05). No significant increase in serum ALT and AST was detected in the TTV- or HGV-positive donors and patients., Conclusion: TTV and HGV infections are more frequently found in donors and patients infected with HBV or HCV than in healthy blood donors. However, there is no significant association between TTV or HGV infections and liver injury.

Serum samples from healthy and diseased children were studied for the presence of TTV DNA by nested PCR using primer sets generated from N-22 region and from the untranslated region (UTR) of the viral genome. N-22 positive TTV DNA was detectable in 33 (27%) of 122 healthy children, 47 (73.4%) of 64 polytransfused thalassemic children, 37 (46.3%) of 80 children who received transfusion during cardiac surgery, 8 (42.1%) of 19 non-A to E hepatitis, 10 (33.3%) of 30 HBV carrier children, and 5 (15.6%) of 32 infants with biliary atresia. A much higher prevalence of TTV DNA with rates varying from 78-100% in the above study groups was observed using the UTR primers. For children with N-22 positive TTV DNA, biochemical assessment of isolated TTV viremia in thalassemic children or children transfused during surgery showed no convincing association between raised ALT levels and TTV viremia. Coinfection with TTV in chronic HCV-infected or HBV-infected children did not result in higher peak ALT levels during follow-up, suggesting that TTV has no synergistic pathogenic effect. The phylogenetic analysis of the N-22 positive TTV DNA isolates revealed that most isolates from healthy children, children transfused during surgery, and non-A to E fulminant hepatitis children were type 1 TTV. These results indicate that TTV infection in children was significantly associated with transfusion. TTV infection is highly prevalent in early childhood in Taiwan but plays a minimal role in the induction of hepatitis in children., (Copyright 2003 Wiley-Liss, Inc.)

Transfusion-transmitted virus (TTV) is a recently discovered transfusion-transmissible DNA virus. Its frequency and clinical impact has not been established in cancer patients in Turkey. In this study, we determined the prevalence of TTV DNA positivity, and its relationship with history of transfusion, amount of transfusion, age and sex in patients with hematological and solid malignancies. Sixty-one patients (35 male and 26 female) followed up for various malignancies and 45 healthy subjects were included in the study. ITV DNA was assayed by the polymerase chain reaction (PCR). TTV DNA was detected in 18 of 61 patients (29.5%) and in 5 of 45 control subjects (11.1%). In cancer patients, the prevalence of TTV DNA positivity was higher to comparison with control group. In addition, the prevalence of TTV DNA positivity was significantly higher in 22 patients who had a history of blood transfusion in the last 6 months than 39 patients who had no current or past history of transfusion (40.9% vs 23.0% respectively). These results suggest that the prevalence of TTV DNA is high and the parenteral route is an important mode of transmission for TTV in cancer patients. In addition, the high prevalence and persistence of TTV in cancer patients with parenteral risk exposure could be related to the immunodeficiency due to cancer and high viral loads by parenteral route.

Transfusion transmitted viruses (TTV) were investigated in cardiac surgery cases who were previously transfused with blood and/or blood products and were suspected of having posttransfusion hepatitis (PTH) based on the results of physical examination, clinical findings, biochemical blood test results and in a smaller number, on radiological results. They were identified as having non-A-C hepatitis based on serological or molecular test methods. In this study, out of 90 cases suspected for PTH and non-A-C, 78 (86.7%) were male, 12 (13.3%) were female and their ages were between 17 and 67. Ninety healthy blood donors, who donated blood for the first time and had never had a transfusion, were selected as the control group. They had alanine aminotransferase (ALT) levels < 40 U, were seronegative for hepatitis B virus (HBV) and hepatitis C virus (HCV). Seventy-seven were immune, and 13 were seronegative for hepatitis A virus (HAV). In this study, TTV-deoxyribonucleic acid (DNA) investigation was performed by the polymerase chain reaction (PCR) method suggested by Takahashi et al. with 5' GCT ACG TCA CTA ACC ACG TG 3' (T801) and 5' CTG CGG TGT GTA AAC TCA CC 3' (T935) primers. TTV-DNA was found to be positive in 21 (23.3%) of the patient group and 4 (4.4%) of the control group (p < 0.05). In the patients determined to be TTV-DNA positive, the admission time following transfusion was a minimum of 3, and a maximum of 15 (average 7) weeks. The average ALT levels detected at the time of admission did not show a difference between TTV-DNA positive and negative cases (p > 0.05). However the ALT levels had a tendency to rise and reached their highest level nine weeks after transfusion in the TTV-DNA positive cases, although in two cases the ALT levels decreased to normal value after the 13th week. During the 24 month follow up of the TTV-DNA positives all cases except one were positive at the end of this period. The results of this study are the same as those reported in the literature suggesting that TTV-DNA, excluding the main viral agents which are known to cause PTH, can be determined in transfused PTH or non-transfused asymptomatic patients in varying ratios. In order to define the epidemiological properties and hepatic-extrahepatic pathologies more clearly we have looked for evidence of the viral agent, which probably contaminates both by transfusion and non-transfusion routes. It is suggested that, in addition to the case groups in this study, new clinical studies are necessary including transfused but non-PTH patients.

Background: TT virus (TTV), a novel DNA virus, was originally thought to be transmitted by transfusion. However, nonparenteral transmission is recently suspected to be a major mode of transmission. To investigate the possibility of reinfection with TTV in multiply transfused patients and to evaluate the significance of transfusion transmission of TTV in patients with hemophilia, serial changes in TTV genotype were investigated in three groups., Study Design and Methods: Serial changes in TTV genotype were investigated in 16 multiply transfused patients with hemophilia, 16 age-matched patients with chronic hepatitis C, and 16 age-matched healthy subjects., Results: Mixed infection with multiple TTV genotypes was common in all groups. However, changes in TTV genotype were frequent in patients with hemophilia (15/16; 93.8%) but rare in patients with chronic hepatitis C and in healthy subjects (each group: 1/16; 6.3%)., Conclusion: Changes in TTV genotype were frequently observed in multiply transfused patients with hemophilia but not in patients with chronic hepatitis or in healthy subjects without risk of transfusion transmission. This difference may suggest that exposure to TTV or even reinfection occurs frequently in patients with hemophilia, which could be evidence of transfusion transmission of TTV in this population.

Objective: To study transfusion transmitted virus (TTV) infection in pregnant women and their newborns, and the route of transmission., Methods: Serum, breast milk from 150 pregnant women and umbilical venous blood from their newborns were collected. TTV DNA was amplified by semi-nested-polymerase chain reaction, and the positive products were sequenced directly., Results: The positive rate of TTV DNA in pregnancy serum was 11.3% (17/150). Among the 17 serum positive cases, TTV DNA was detected in 11 breast milk samples, and none in all the umbilical blood. The homologous of partial nucleotide sequence of TTV DNA between the 3 serum samples and their breast milk were 97.6%-99.2%. Compared the 5 serum positive samples (A1-A5) with N22 segments of Japanese original isolate, the homologous of partial nucleotide and amino acid sequence were 71.5%-92.8%, 71.5%-92.8%, respectively., Conclusion: There exists TTV infection in pregnancy serum and breast milk. Transmission by breast feeding may be one of the main pathway causing TTV infection.

Objective: To clarify the frequency, the routes of transmission from mother to infant, the correlation factors and distribution of genotypes of transfusion transmitted virus (TTV) infection., Methods: Nested-polymerase chain reaction (n-PCR) was performed to detect TTV DNA and genotypes in serums and breast milks from 160 cases of pregnant women., Results: TTV DNA in serum and breast milk was detected in 64 (40.0%) and 60 (37.5%) of 160 cases of pregnant women respectively. The positive rates of TTV DNA from HBV markers (+) and normal groups were 50.0%, 43.1% and 13.6%, 22.7% respectively in serums and breast milk. There were significant difference between the two groups (P < 0.05). The TTV genotypes were type I in all 124 samples of TTV DNA detected., Conclusions: TTV infection is common in the pregnant women and a high prevalence of TTV infection in pregnant women with positive HBV markers has been demonstrated. TTV infection is correlated with HBV. TTV is probably transmitted from mother to their children by breast feeding. All of TTV genotypes detected in pregnant women is genotype I.

The development of new technologies leads to the discovery of new viruses. For each of these new infectious agents, their possible relevance to blood transfusion needs to be assessed. The questions to be answered are transmissibility by transfusion, pathogenicity, prevalence in blood donors, persistence, and the availability of screening assays. Since 1995, three new viruses have been identified and extensively studied.

Objective: To investigate the perinatal infection of transfusion transmitted virus (TTV) in the mother-to-infant transmission and molecular evidence., Methods: TTV was examined in serum from 104 mothers and umbilical blood of their infants by a semi-nested polymerase chain reaction technique. TTV nucleotide sequences isolated from two sets of mother/infant pairs were analyzed., Results: The TTV detection rate was 13.46% (15/104), and it was 4.81% (5/104) in the umbilical blood of their newborns. Homology analysis was done by sequencing between positions 1,915 and 2,185 of the published TTV genome, Analysis of TTV sequences from the 2 pairs of mother and infant both infected confirmed a genetic link between the virus of the infected mother and their infected infants., Conclusions: There is a possibility of vertical maternal-fetal transmission of TTV.

The prevalence of transfusion-transmitted virus (TTV) infection has not been known in patients suffering from pediatric malignancies and hematological disorders who receive blood transfusion and/or blood products during treatment. Blood samples were taken from 75 patients. TTV infection was identified when TTV DNA was detected in serum by a polymerase chain reaction (PCR) assay. Hepatitis C virus (HCV) and hepatitis G virus (HGV) RNA were also assayed by PCR. TTV DNA was detected in 38 of 75 patients (51%). In 4 of 38 patients, the amount of blood transfused was less than 3 units. By time since last transfusion, TTV DNA was detected in 12 of 35 patients after more than 4 years, 12 of 21 between 1 and 4 years, and 14 of 19 within 1 year. Six patients had mixed infection of TTV and HCV, and 12 patients had mixed infection of TTV and HGV. Three different kinds of virus were found simultaneously in serum from 3 patients. Eight out of 75 patients showed abnormal levels of alanine aminotransferase (ALT) (>40 IU/liter), and 3 of them had TTV DNA. All patients who had TTV DNA and elevated ALT levels also were positive for HCV RNA and HGV RNA. The prevalence of TTV infection is high in patients with pediatric malignancies and hematological disorders after episodes of blood transfusion. Transfusion is one of the most important risk factors for TTV infection regardless of the amount of blood transfused., (Copyright 2000 Wiley-Liss, Inc.)

Background: A novel transfusion-transmissible human DNA virus, TT virus (TTV), has been discovered recently. An attempt was made to determine the incidence and clinical outcome of TTV infection in recipients of blood transfusion., Study Design and Methods: Serial serum samples collected as part of a prospective study of posttransfusion hepatitis were examined for TTV DNA by a nested PCR assay., Results: Among 150 adults undergoing cardiac surgery, posttransfusion specimens from 59 individuals were positive for TTV DNA. Pretransfusion sera were found to be positive in 13 of these individuals. Therefore, 46 (33.6%) of the 137 previously uninfected patients developed new TTV viremia after transfusion. Among the 46 patients, 3 were coinfected with HCV, 5 were coinfected with HGV, and 38 were infected with TTV alone. No apparent symptoms or signs were noted in the 38 patients infected by TTV alone or the 5 infected with HGV plus TTV. The average peak serum ALT activity was 31 IU per L, with persistently normal levels in 34 of the 38 patients with TTV infection alone. In 8 other patients who subsequently developed well-documented non-A-G hepatitis, 3 were positive for TTV (3/8 vs. 46/137, p = 0.8). In 12 patients followed for more than 1 year, TTV viremia persisted in every case., Conclusion: In this population, TTV is transmitted by transfusion to approximately 30 percent of patients who undergo cardiac surgery. Most of the infections appear to become persistent. Despite the high prevalence rate, TTV does not appear to cause hepatitis on its own.

Little is known about the natural history and the pathogenicity of the TT virus (TTV). We present our findings of a cross-sectional study based on the TTV DNA screening of 173 multiple-transfused patients and a longitudinal study based on the follow-up of TTV DNA-positive patients. Overall, 48 patients (27.7%) tested positive for TTV DNA. The influence of the number of blood donor exposures on the prevalence of blood-borne viral infection indicates that TTV, hepatitis C virus (HCV), and an RNA virus known as GB virus C/hepatitis G virus (GBV-C/HGV) share a parenteral transmission, but that TTV, in contrast to the 2 other viruses, is also transmitted by at least another efficient means. The patients having a well-defined date of TTV infection were positive for TTV DNA during a mean period of 3.1 years. A chronic infection was observed in 31 cases (86%). TTV carriage appeared clinically benign in all patients. No clinical evidence of a disease potentially linked to the TTV infection was observed in patients with TTV DNA carriage over several years. The majority of TTV carriers had no biochemical evidence of liver disease. The prevalence of elevated serum alanine aminotransferase (ALT) level was higher in the TTV DNA-positive group, even in the absence of HCV infection, but the observed peaks of ALT level were most often transient and very mild. The prevalence of TTV DNA observed in blood recipients is consistent with that of TTV infection observed in blood donors. TTV infection frequently tends to persist. (Blood. 2000;95:347-351)

We evaluated the characteristics and rate of infection with TT virus (TTV), a novel DNA virus, in Japanese haemophiliacs. TTV DNA was measured in 60 haemophiliacs by semi-nested polymerase chain reaction. Co-infection with hepatitis C virus (HCV), hepatitis G virus (HGV) and human immunodeficiency virus (HIV) was also evaluated. In addition, the rate of detection of TTV DNA in blood products was evaluated. TTV DNA was detected in 35/60 haemophiliacs (58.3%). There were no differences in the backgrounds or characteristics between haemophiliacs with and without TTV infection, except for higher levels of IgG and IgM in patients with TTV infection. In patients infected with TTV of types other than type 1, which are rarely detected in Japan, the rate of co-infection with HCV of imported types was high; TTV of types other than type 1 in Japanese haemophiliacs were probably transmitted by imported blood products. TTV DNA was detected in over half of the blood products tested, but TTV DNA concentrations in these products were lower than in the serum of haemophiliacs.

Background: To examine the prevalence of TT virus (TTV) before and after blood transfusion, we retrospectively examined serum samples obtained from 55 patients who received blood transfusions before, during and after resection of hepatocellular carcinoma., Methods: TT virus DNA was extracted from serum samples and detected by nested polymerase chain reaction. Before transfusion, seven (12.7%) were positive for TTV. Patients were transfused whole blood or separated blood components (fresh frozen plasma, platelet and/or red blood cells), the total amount of transfused fresh frozen plasma ranging from 12 to 271 (median 38) units., Results: Seven (14.6%) of the 48 TTV-negative patients became positive for TTV-DNA 1 month after transfusion. Only one of the seven patients, who was already positive for HCV-RNA, exhibited elevation of alanine aminotransferase. Five of the newly infected seven patients become negative for TTV during a 2 year follow up., Conclusions: Our findings suggest that the proportion of patients with TTV was relatively high in this sample, and that the prevalence of TTV transmission by blood components was also relatively high (14.6%). Although TTV persisted for more than 6 months in some patients, infection was not noticeable during the course of chronic liver disease.

Recently, a new single-stranded DNA virus (TT virus, TTV) has been isolated and related to post-transfusion hepatitis. The aim of this study was to investigate the prevalence of TTV in blood donors and blood recipients, and the incidence of TTV transmission by blood transfusion. TTV DNA and serum markers of hepatitis B virus (HBV) and hepatitis C virus (HCV), were examined in 130 blood recipients, and the presence of TTV was studied in their 340 corresponding blood donors. The prevalence of TTV infection was 10.6% (36/340) in donors and 8.5% (11/130) in blood recipients, before transfusion. Eighteen subjects (15.1%) were found to be TTV positive, after transfusion, in the 119 blood recipients without TTV before transfusion; at least one of the corresponding donors was TTV positive. There were 46 subjects with post-transfusion hepatitis virus infection, 45 with HCV infection (including seven co-infected with TTV) and two with HBV infection (including one co-infected with HCV and one co-infected with TTV). The recipient with TTV and HBV co-infection and three of the seven patients with TTV and HCV infection had alanine aminotransferase (ALT) levels higher than 90 Ul-1, but only two of the 10 isolated TTV infections had a mild ALT elevation. These results show that prevalence of TTV was high in blood donors and hospitalized patients, and isolated TTV infection is not related to significant ALT elevation.

To investigate transfusion transmitted virus (TTV) infection in the hepatitis patients and blood donors in Hunan, we used nested polymerase chain reaction (nPCR) assay with primers from TTV genome to detect TTV DNA in seventy clinical hepatitis cases and forty-three blood donors. The results were as follows: TTV DNA was positive in ten of thirty eight patients with hepatitis B(26.3%), and twelve of thirty-two patients with non-A through non-E(37.5%). Elevated transaminase (ALT) was observed in those cases (452 U.L-1 and 582 U.L-1, respectively). On the other hand, TTV DNA was positive in four of forty-three normal blood donors. The data indicate that infectious rates of TTV in hepatitis patients and blood donors in Hunan are similar to those in Japan, and TTV's pathogenicity needs further study.