Join the 200th Anniversary Celebration

Correspondence

Global Distribution of Transfusion-Transmitted Virus

N Engl J Med 1998; 339:776-777September 10, 1998

Article

To the Editor:

Transfusion-transmitted virus has recently been identified as a potential cause of post-transfusion non-A, non-B, non-C hepatitis.1 The virus has a single-stranded DNA genome whose organization is similar to those of members of the Parvoviridae.2 Transient viremia due to transfusion-transmitted virus was detected by the polymerase chain reaction (PCR) in three patients six to eight weeks after the transfusion of blood components and coincided with modest elevations of alanine aminotransferase. It has been proposed that transfusion-transmitted virus is the chloroform-resistant non-A, non-B agent shown to cause transient alanine aminotransferase elevations in chimpanzees.3

To understand more about the distribution of transfusion-transmitted virus infection, we investigated the prevalence of infection in a wide range of geographically separated human populations and among chimpanzees in Africa. Blood samples were obtained from people inhabiting equatorial forests in Ecuador, northern Brazil, and Papua New Guinea (Karkar Island) and from people living in predominantly rural, farming communities in Gedaref in eastern Sudan, the Lower River Division in the Gambia, around Lagos in Nigeria, and the Kinshasa region in the Democratic Republic of the Congo. Samples were obtained from blood donors in Karachi, Pakistan, and from wild animals in an area extending from Central Africa to West Africa. The samples had originally been collected for studies of other viruses and parasites.

Sequences of transfusion-transmitted virus were amplified by heminested PCR according to previously described conditions.2 Full precautions were taken to prevent contamination of the PCR, with primary and secondary reactions performed in separate laboratories and negative controls included with each set of samples.

We found high frequencies of viremia due to transfusion-transmitted virus in most of the study populations, with values ranging from 16 percent in Pakistan to 83 percent in the Gambia (Table 1Table 1Viremia Due to Frequency of Transfusion-Transmitted Virus on PCR Testing in Various Groups.). Transfusion-transmitted virus DNA sequences were also detected in one of the chimpanzees. Although Nishizawa et al. reported that infection with transfusion-transmitted virus was transient among blood recipients,1 the high frequencies of viremia that we found indicate that the infection can also be persistent. The mechanism by which infection can be maintained at such high frequencies and the routes of transmission are unclear. It is also difficult to assess the clinical significance of the infection and whether it causes disease without detailed clinical assessment or prospective longitudinal studies. However, the finding of transfusion-transmitted virus infection in such a large proportion of the study groups highlights the need for further investigations.

(The international collaborators were Professor D.I. Pritchard, University of Nottingham, Nottingham, United Kingdom; Dr. D.E. Arnot and Dr. E.M. Riley, University of Edinburgh, Edinburgh, United Kingdom; Dr. B.M. Greenwood, Medical Research Council Laboratories, Fajara, the Gambia; Dr. S. Hamid, Aga Khan University, Karachi, Pakistan; Dr. M.O. McClure, St. Mary's Hospital, London; Dr. J.C.M. Lewis, International Zoo Veterinary Group, Keighley, United Kingdom, and Dr. J. Mokili, University of Edinburgh, Edinburgh, United Kingdom.)

Linda E. Prescott, Ph.D.
Peter Simmonds, M.R.C.Path.
University of Edinburgh, Edinburgh, EH8 9AG, United Kingdom

and International Collaborators

4 References
  1. 1

    Nishizawa T, Okamoto H, Konishi K, Yoshizawa H, Miyakawa Y, Mayumi M. A novel DNA virus (TTV) associated with elevated transaminase levels in posttransfusion hepatitis of unknown etiology. Biochem Biophys Res Commun 1997;241:92-97
    CrossRef | Web of Science | Medline

  2. 2

    Okamoto H, Nishizawa T, Kato N, et al. Molecular cloning and characterisation of a novel DNA virus (TTV) associated with posttransfusion hepatitis of unknown aetiology. Hepatol Res 1998;10:1-16
    CrossRef | Web of Science

  3. 3

    Bradley DW, Maynard JE, Popper H, et al. Posttransfusion non-A, non-B hepatitis: physicochemical properties of two distinct agents. J Infect Dis 1983;148:254-265
    CrossRef | Web of Science | Medline

  4. 4

    Simmonds P, Davidson F, Lycett C, et al. Detection of a novel DNA virus (TTV) in blood donors and blood products. Lancet 1998;352:191-195
    CrossRef | Web of Science | Medline

Citing Articles (50)

Citing Articles

  1. 1

    Yasir J Sepah, Masood Umer, Tashfeen Ahmad, Faria Nasim, Muhammad Umer Chaudhry, Muhammad Umar. (2011) Use of Tranexamic acid is a cost effective method in preventing blood loss during and after total knee replacement. Journal of Orthopaedic Surgery and Research 6:1, 22
    CrossRef

  2. 2

    Faissal Tarrass, Jean Louis Koenig, Fanny Leroy, Léandre Mackaya, Henri Colomb. (2006) Le virus transmis par la transfusion (TTV) et insuffisance rénale. Néphrologie & Thérapeutique 2:4, 176-182
    CrossRef

  3. 3

    KUNAL DAS, P KAR, RK GUPTA, BC DAS. (2004) Role of transfusion-transmitted virus in acute viral hepatitis and fulminant hepatic failure of unknown etiology. Journal of Gastroenterology and Hepatology 19:4, 406-412
    CrossRef

  4. 4

    Moslih I. Al-Moslih, Raed O. Abuodeh, Yu-Wen Hu. (2004) Detection and genotyping of TT virus in healthy and subjects with HBV or HCV in different populations in the United Arab Emirates. Journal of Medical Virology 72:3, 502-508
    CrossRef

  5. 5

    Philippe Biagini. (2004) Human circoviruses. Veterinary Microbiology 98:2, 95-101
    CrossRef

  6. 6

    Mary Ersek. (2004) The Continuing Challenge of Assisted Death. Journal of Hospice & Palliative Nursing 6:1, 46-59
    CrossRef

  7. 7

    Priya Abraham, George T. John, Sukanya Raghuraman, Sujatha Radhakrishnan, Paulose P. Thomas, Chacko K. Jacob, Gopalan Sridharan. (2003) GB virus C/hepatitis G virus and TT virus infections among high risk renal transplant recipients in India. Journal of Clinical Virology 28:1, 59-69
    CrossRef

  8. 8

    T. Pollicino, G. Raffa, G. Squadrito, L. Costantino, I. Cacciola, S. Brancatelli, C. Alafaci, M. G. Florio, G Raimondo. (2003) TT virus has a ubiquitous diffusion in human body tissues: analyses of paired serum and tissue samples. Journal of Viral Hepatitis 10:2, 95-102
    CrossRef

  9. 9

    Mária Takács, Katalin Balog, Gábor Tóth, Zsuzsanna Balogh, Katalin N Szomor, Judit Brojnás, Erzsébet Rusvai, János Minárovits, György Berencsi. (2003) TT virus in Hungary: sequence heterogeneity and mixed infections. FEMS Immunology & Medical Microbiology 35:2, 153-157
    CrossRef

  10. 10

    K. V. Narayanan Menon. (2002) Non-A to E hepatitis. Current Opinion in Infectious Diseases 15:5, 529-534
    CrossRef

  11. 11

    Pierre Gallian, Philippe Biagini, Houssam Attoui, Jean-Franois Cantaloube, Bertrand Dussol, Yvon Berland, Philippe de Micco, Xavier de Lamballerie. (2002) High genetic diversity revealed by the study of TLMV infection in French hemodialysis patients. Journal of Medical Virology 67:4, 630-635
    CrossRef

  12. 12

    M. Yazici, M. R. Comert, R. Mas, C. Guney, E. Cinar, I. H. Kocar. (2002) Transfusion-transmitted virus prevalence in subjects at high risk of sexually transmitted infection in Turkey. Clinical Microbiology and Infection 8:6, 363-367
    CrossRef

  13. 13

    P. Grabarczyk, E. Brojer. (2002) Polymorphism of the TT virus and its frequency in Polish blood donors. Vox Sanguinis 82:4, 177-181
    CrossRef

  14. 14

    Sheng Zhong, Winnie Yeo, Mandy Tang, Cuiling Liu, Xiao-rong Lin, Wing M. Ho, Pun Hui, Philip J. Johnson. (2002) Frequent detection of the replicative form of TT virus DNA in peripheral blood mononuclear cells and bone marrow cells in cancer patients. Journal of Medical Virology 66:3, 428-434
    CrossRef

  15. 15

    Laura Krekulova, Vratislav Rehak, Patrick Killoran, Nora Madrigal, Lee W Riley. (2001) Genotypic distribution of TT virus (TTV) in a Czech population: evidence for sexual transmission of the virus. Journal of Clinical Virology 23:1-2, 31-41
    CrossRef

  16. 16

    J. Takamatsu, H. Toyoda, Y. Fukuda, I. Nakano, S. Yokozaki, K. Hayashi, H. Saito. (2001) Effects of HAART on hepatitis C, hepatitis G, and TT virus in multiply coinfected HIV-positive patients with haemophilia. Haemophilia 7:6, 575-581
    CrossRef

  17. 17

    SHENG ZHONG, WINNIE YEO, MANDY W. TANG, XIAO-RONG LIN, FRANKIE MO, WING M. HO, PUN HUI, PHILIP J. JOHNSON. (2001) Gross Elevation of TT Virus Genome Load in the Peripheral Blood Mononuclear Cells of Cancer Patients. Annals of the New York Academy of Sciences 945:1, 84-92
    CrossRef

  18. 18

    Hidenori Toyoda, Yoshihide Fukuda, Isao Nakano, Yoshiaki Katano, Shoichi Yokozaki, Kazuhiko Hayashi, Yoshinori Ito, Koji Suzuki, Hiroshi Nakano, Hidehiko Saito, Junki Takamatsu. (2001) TT virus genotype changes frequently in multiply transfused patients with hemophilia but rarely in patients with chronic hepatitis C and in healthy subjects. Transfusion 41:9, 1130-1135
    CrossRef

  19. 19

    Christian Niel, Elisabeth Lampe. (2001) High detection rates of TTV-like mini virus sequences in sera from Brazilian blood donors. Journal of Medical Virology 65:1, 199-205
    CrossRef

  20. 20

    Philippe Biagini, Pierre Gallian, Houssam Attoui, Jean-François Cantaloube, Mhammed Touinssi, Philippe de Micco, Xavier de Lamballerie. (2001) Comparison of systems performance for TT virus detection using PCR primer sets located in non-coding and coding regions of the viral genome. Journal of Clinical Virology 22:1, 91-99
    CrossRef

  21. 21

    Sheng Zhong, Winnie Yeo, Che Kit Lin, Xiao-Rong Lin, Mandy W. Tang, Philip J. Johnson. (2001) Quantitative and genotypic analysis of TT virusinfection in Chinese blood donors. Transfusion 41:8, 1001-1007
    CrossRef

  22. 22

    Li-Yue Huang, Tom ystein Jonassen, Olav Hungnes, Bjrn Grinde. (2001) High prevalence of TT virus-related DNA (90%) and diverse viral genotypes in norwegian blood donors. Journal of Medical Virology 64:3, 381-386
    CrossRef

  23. 23

    Hideo Ohbayashi, Yujiro Tanaka, Shinya Ohoka, Ryouko Chinzei, Sei Kakinuma, Mieko Goto, Mamoru Watanabe, Fumiaki Marumo, Chifumi Sato. (2001) TT Virus is shown in the liver by in situ hybridization with a PCR-generated probe from the serum TTV-DNA. Journal of Gastroenterology and Hepatology 16:4, 424-428
    CrossRef

  24. 24

    Takao Shibayama, Gohta Masuda, Atsushi Ajisawa, Masaharu Takahashi, Tsutomu Nishizawa, Fumio Tsuda, Hiroaki Okamoto. (2001) Inverse relationship between the titre of TT virus DNA and the CD4 cell count in patients infected with HIV. AIDS 15:5, 563-570
    CrossRef

  25. 25

    Mauro Pistello, Antonietta Morrica, Fabrizio Maggi, Maria Linda Vatteroni, Giulia Freer, Claudia Fornai, Francesca Casula, Santino Marchi, Pietro Ciccorossi, Paolo Rovero, Mauro Bendinelli. (2001) TT virus levels in the plasma of infected individuals with different hepatic and extrahepatic pathology. Journal of Medical Virology 63:2, 189-195
    CrossRef

  26. 26

    Scott Bowden. (2001) New hepatitis viruses: Contenders and pretenders. Journal of Gastroenterology and Hepatology 16:2, 124-131
    CrossRef

  27. 27

    Gianguglielmo Zehender, Aldo Manzin, Chiara De Maddalena, Chiara Colasante, Laura Solforosi, Federica Corsi, Anna Bianchi-Bosisio, Mauro Girotto, Ivan Schirru, Umberto Russo, Massimo Galli, Massimo Clementi. (2001) Molecular epidemiology of TT virus in Italy and phylogenesis of viral isolates from subjects at different risk for parenteral exposure. Journal of Medical Virology 63:1, 76-84
    CrossRef

  28. 28

    Philippe Biagini, Pierre Gallian, Philippe de Micco, Xavier de Lamballerie. (2000) TT virus and TT virus-like mini-virus infection in French blood donors. Transfusion 40:12, 1542-1542
    CrossRef

  29. 29

    Alan D. Kitchen, John A.J. Barbara. (2000) Which agents threaten blood safety in the future?. Best Practice & Research Clinical Haematology 13:4, 601-614
    CrossRef

  30. 30

    Klaus Stark, Gabriele Poggensee, Marina Hhne, Ulrich Bienzle, Ireen Kiwelu, Eckart Schreier. (2000) Seroepidemiology of TT virus, GBC-C/HGV, and hepatitis viruses B, C, and E among women in a rural area of Tanzania. Journal of Medical Virology 62:4, 524-530
    CrossRef

  31. 31

    Akiko Okamura, Mikio Yoshioka, Hideaki Kikuta, Mitsuru Kubota, Xiaoming Ma, Akio Hayashi, Hiroaki Ishiko, Kunihiko Kobayashi. (2000) Detection of TT virus sequences in children with liver disease of unknown etiology. Journal of Medical Virology 62:1, 104-108
    CrossRef

  32. 32

    Philippe Biagini, Houssam Attoui, Pierre Gallian, Mhammed Touinssi, Jean-François Cantaloube, Philippe de Micco, Xavier de Lamballerie. (2000) Complete Sequences of Two Highly Divergent European Isolates of TT Virus. Biochemical and Biophysical Research Communications 271:3, 837-841
    CrossRef

  33. 33

    M. Debiaggi, F. Zara, P. Sacchi, R. Bruno, M. Mazzucco, R. Poma, F. Raffaldi, L. Gerace, M. Perini, A. Pistorio, E. Romero, G. Filice. (2000) Transfusion-transmitted virus infection in HIV-1-seropositive patients. Clinical Microbiology and Infection 6:5, 246-250
    CrossRef

  34. 34

    P. Biagini, P. Gallian, M. Touinssi, J.F. Cantaloube, J.-P. Zapitelli, X. de Lamballerie, P. de Micco. (2000) High prevalence of TT virus infection in French blood donors revealed by the use of three PCR systems. Transfusion 40:5, 590-595
    CrossRef

  35. 35

    Skelton, Kew, Yu, Crookes, Swanevelder, Hodkinson. (2000) Transfusion-transmissible virus and hepatocellular carcinoma: a case-control study. Journal of Viral Hepatitis 7:3, 230-234
    CrossRef

  36. 36

    Yi-Hsiang Huang, Jaw-Ching Wu, Chen-Chun Lin, Wen-Yung Sheng, Pui-Ching Lee, Yuan-Jen Wang, Full-Young Chang, Shou-Dong Lee. (2000) Prevalence and risk factor analysis of TTV infection in prostitutes. Journal of Medical Virology 60:4, 393-395
    CrossRef

  37. 37

    Kanae Tada, Hitoshi Tajiri, Hiroki Kondou, Shunji Mishiro, Shintaro Okada. (2000) Confirmation of mother-to-child transmission of TT virus. The Pediatric Infectious Disease Journal 19:3, 255
    CrossRef

  38. 38

    Carsten Wolff, Andrea Diekmann, Monika Boomgaarden, Michael M. Körner, Knut Kleesiek. (2000) VIREMIA AND EXCRETION OF TT VIRUS IN IMMUNOSUPPRESSED HEART TRANSPLANT RECIPIENTS AND IN IMMUNOCOMPETENT INDIVIDUALS. Transplantation 69:3, 351-356
    CrossRef

  39. 39

    Amal Gad, Eiji Tanaka, Kohji Orii, Todoriki Kafumi, Abed El-Hamid Serwah, Asem El-Sherif, Zohair Nooman, Kendo Kiyosawa. (2000) Clinical significance of TT virus infection in patients with chronic liver disease and volunteer blood donors in Egypt. Journal of Medical Virology 60:2, 177-181
    CrossRef

  40. 40

    A. Handa, B. Dickstein, N.S. Young, K.E. Brown. (2000) Prevalence of the newly described human circovirus, TTV, in United States blood donors. Transfusion 40:2, 245-251
    CrossRef

  41. 41

    Jerome M Teitel. (2000) Viral safety of haemophilia treatment products. Annals of Medicine 32:7, 485-492
    CrossRef

  42. 42

    U. Desselberger. (2000) Emerging and Re-emerging Infectious Diseases. Journal of Infection 40:1, 3-15
    CrossRef

  43. 43

    K. V. Narayanan Menon, Nizar N. Zein. (2000) What do we need to know about nonA—to-E viral hepatitis?. Current Gastroenterology Reports 2:1, 33-39
    CrossRef

  44. 44

    Felipe L. Saback, Selma A. Gomes, Vanessa S. de Paula, Raquel R.S. da Silva, Lia L. Lewis-Ximenez, Christian Niel. (1999) Age-specific prevalence and transmission of TT virus. Journal of Medical Virology 59:3, 318-322
    CrossRef

  45. 45

    Xavier Forns, Patricia Hegerich, Alejandro Darnell, Suzanne U. Emerson, Robert H. Purcell, Jens Bukh. (1999) High prevalence of TT virus (TTV) infection in patients on maintenance hemodialysis: Frequent mixed infections with different genotypes and lack of evidence of associated liver disease. Journal of Medical Virology 59:3, 313-317
    CrossRef

  46. 46

    Thomas P Leary, James C Erker, Michelle L Chalmers, Suresh M Desai, Isa K Mushahwar. (1999) Optimized PCR assay for the detection of TT virus. Journal of Virological Methods 82:2, 109-112
    CrossRef

  47. 47

    Alessandro Tagger, Francesco Donato, Maria Lisa Ribero, Giorgio Binelli, Umberto Gelatti, Giuseppe Portera, Alberto Albertini, Michele Fasola, Roberta Chiesa, Giuseppe Nardi, . (1999) A case-control study on a novel DNA virus (TT virus) infection and hepatocellular carcinoma. Hepatology 30:1, 294-299
    CrossRef

  48. 48

    David J. Brandhagen, John B. Gross, Nizar N. Zein. (1999) Prevalence and Clinical Significance of TT Virus Coinfection in Patients With Chronic Hepatitis C Treated With Interferon. The American Journal of Gastroenterology 94:6, 1715-1716
    CrossRef

  49. 49

    Scott Bowden, Stephen Locarnini. (1999) TT virus: An agent of transfusion-associated hepatitis or yellow herring?. Journal of Gastroenterology and Hepatology 14:4, 299-300
    CrossRef

  50. 50

    Peter Simmonds, Fiona Davidson, Lisa M Jarvis. (1998) Transfusion transmitted virus. The Lancet 352:9136, 1310-1311
    CrossRef