High rate of TTV infection in multitransfused patients with pediatric malignancy and hematological disorders

Maeda, Miho; Hamada, Hisamitsu; Tsuda, Akio; Kaneko, Kiyoshi; Fukunaga, Yoshitaka

doi:10.1002/1096-8652(200009)65:1<41::aid-ajh7>3.0.co;2-9

Cited by 10 publications

(7 citation statements)

References 12 publications

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“…8,9 TTV may also be disseminated by aerosols, since the virus is present in saliva. 8,10 A high rate of TTV infection was found in patients given multiple transfusions 11 and patients with hemophilia. 5,12-14 TTV sequences are frequently detected in clotting factor concentrates prepared from large plasma pools.…”

Section: Introductionsupporting

confidence: 86%

TT virus contaminates first-generation recombinant factor VIII concentrates

Azzi

Santis

Morfini

et al. 2001

Blood

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Recombinant factor VIII and factor IX concentrates, human-plasma-derived albumin, and samples from previously untreated patients with hemophilia were examined for the presence of TT virus (TTV) by using polymerase chain reaction testing. Blood samples from the patients were obtained prospectively before and every 3 to 6 months after therapy was begun. TTV was detected in 23.5% of the recombinant-product lots and 55.5% of the albumin lots tested. Only first-generation factor VIII recombinant concentrates stabilized with human albumin were positive for TTV, whereas all second-generation (human protein-free) concentrates were negative for the virus. In 59% of patients treated with either first-or second-generation recombinant factor concentrates, TTV infection developed at some point after the initial infusion. Infection with TTV in these patients before and after treatment did not appear to be clinically important. Thus, first-generation recombinant factor VIII concentrates may contain TTV and the source of the viral contamination may be human albumin. IntroductionTT virus (TTV) is a small, naked, single-stranded DNA virus of the Circoviridae family with a circular genome. It was first detected in the serum of patients with posttransfusion hepatitis of unknown cause. 1 It is not known whether TTV is pathogenic. 2-4 TTV may be transmitted parenterally through transfusion of blood products, [5][6][7] by the fecal-oral route, and by pregnant women to fetuses. 8,9 TTV may also be disseminated by aerosols, since the virus is present in saliva. 8,10 A high rate of TTV infection was found in patients given multiple transfusions 11 and patients with hemophilia. 5,12-14 TTV sequences are frequently detected in clotting factor concentrates prepared from large plasma pools. 5,15 First-generation recombinant human factor VIII concentrates stabilized with human-plasma-derived albumin (HPDA) before lyophilization (Recombinate, Baxter, Glendale, CA; and Kogenate, Bayer, Leverkusen, Germany) have been licensed for more than 10 years. They became widely used by patients with hemophilia because of their perceived safety with respect to viral infection. However, parvovirus B19 DNA was detected by polymerase chain reaction (PCR) assay in a few lots of Kogenate, 16 and seroconversion occurred in a few patients with hemophilia who were treated with this product. 17 The source of the B19 virus contamination in recombinant products was thought to be the HPDA used to stabilize the recombinant protein before lyophilization. Second-generation recombinant factor VIII and factor IX concentrates that do not contain albumin (ReFacto and Benefix, Genetics Institute, Cambridge, MA) were recently licensed for the treatment of hemophilia. A prospective study of the viral safety of these concentrates in accordance with International Society on Thrombosis and Haemostasis guidelines has not yet been conducted. To assess the safety of recombinant concentrates regarding TTV transmission, we tested several such products for TTV DNA by using PCR assays. ...

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Section: Introductionsupporting

confidence: 86%

TT virus contaminates first-generation recombinant factor VIII concentrates

Azzi

Santis

Morfini

et al. 2001

Blood

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“…Similarly, in other reports a higher load of TT Virus genomic DNA was detected in PBMCs of patients with cancer compared with healthy controls ( 41 ). In another study a higher prevalence of TT Virus was found in multi-transfused pediatric patients with malignancies ( 12 , 40 ). Similarly, in this study, a significantly higher frequency of TT Virus molecular infection was found in patients with leukemia compared with controls (42.1% and 12%, respectively).…”

Section: Discussionmentioning

confidence: 86%

“…Furthermore, TT Virus infection has been found in 1 - 12% of blood donors reported from different geographical regions. This viral infection was also detected in 18% of patients exposed to blood products and in 4% of patients without parenteral risk factors ( 12 ).…”

Section: Introductionmentioning

confidence: 98%

“…However, a higher prevalence of TT Virus infection has been reported in high-risk patients including: 68% of patients with hemophilia, 46% of patients on hemodialysis, 40% of intravenous drug abusers, and 17.8% of patients with hematological malignancies ( 12 , 13 ). Among these high-risk hematopoietic disorders, associations may exist between TT Virus infection and pathogenesis of different acute and chronic hematologic malignancies ( 2 , 13 , 14 ).…”

Section: Introductionmentioning

confidence: 99%

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Study of the Associations Between TT Virus Single and Mixed Infections With Leukemia

Shaheli

Yaghobi

Rezaeian

et al. 2015

Jundishapur J Microbiol

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Background:The pathogenic association of Transfusion Transmitted Virus or Torque teno Virus (TT Virus) single and mixed infections with leukemia was under evaluation in these years but confront with controversies. This hypothesis is based on the higher prevalence of TT Virus infection in patients with leukemia compared with controls.Objectives:The aim of this study was to determine the frequency of TT Virus, Cytomegalovirus (CMV), Hepatitis B Virus (HBV), and Hepatitis C Virus (HCV) infections in patients with leukemia and healthy controls.Patients and Methods:In this cross sectional study, 95 patients with leukemia and 100 healthy controls who were admitted to the Namazi Hospital affiliated to the Shiraz University of Medical Sciences, Shiraz, Iran, were enrolled between years 2012 and 2013. Blood samples treated with EDTA were collected from each patient with leukemia and controls. The existence of TT Virus infection was analyzed using the semi-nested PCR method. The immunological prevalence of HBV and HCV infections were evaluated using HBs-Ag and HCV-Ab ELISA based protocols, respectively. Active CMV infection was also evaluated using an immunofluorescence method. Also risk factors of leukemia and viral infections were statistically analyzed in patients with leukemia.Results:The TT Virus infection was significantly found in 40 of 95 (42.1%) and 12 of 100 (12%) patients with leukemia and controls, respectively. The HBs-Ag and HCV-Ab were detected in 27 of 95 (28.4%) and 18 of 69 (26.1%) patients with leukemia but were not found in the controls. Active CMV infection was also found in 11 of 69 (16%) patients and none of the controls. Significant co-infection of TT Virus was found with HBV (15 of 40; 37.5%), HCV (14 of 40; 35%) and CMV (7 of 40; 17.5%) in patients with leukemia.Conclusions:Confirmation of the significantly higher frequency of TT Virus, HBV, HCV and CMV single infection and their co-infection in patients with leukemia compared with healthy controls, emphasizes the determinative role of TT Virus pathogenesis in clinical outcomes observed in patients with leukemia, which requires extensive evaluation by further studies.

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“…68 The non-enveloped single stranded DNA virus is particularly prevalent in patients with frequent parenteral exposure. 69 Like HGV virus, TTV is efficiently transmitted from mother to child, 70 with long term persistent infection. TTV is commonly associated with hepatitis B (13%), hepatitis C (16%), hepatitis A (5%), and hepatitis E (20%), but there was no correlation between coinfection, TTV titre, and liver damage, suggesting that TTV may not have a pathological role.…”

Section: Transfusion Transmissable Virus (Ttv)mentioning

confidence: 99%